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Sample records for generates enhanced therapeutic

  1. Diagnostic and Therapeutic RI Generators

    International Nuclear Information System (INIS)

    Lee, Jong-Sup; Lee, Jun-Sig; Park, Ul-Jae; Han, Hyon-Soo

    2006-01-01

    Different types of generators have been developed for the convenient use of 99m Tc as the demand for this radioisotope is strong. Currently, the demand for 99m Tc is more than 80 % of the total demand for medical isotopes in the world. A 99m Tc generator, in general, is composed of a column packed with ceramic adsorbent, tubing, eluent reservoir or vials, collection vials, and shielding. The key technology to develop a good generator is how to load 99 Mo as much as possible while maintaining the quality of eluted 99 mTc as good as possible. The technology is well developed and already available commercially for the case of the fission 99 Mo/ 99 mTc because loading of few curries of 99 Mo on a conventional adsorbent, i.e. alumina is not a serious task in the chemical point of view. However, the current infrastructure of the supply of 99 Mo to the world market is sturdy as the research reactors are getting aged. In this regard, alternative research activities to develop generators with (n,γ) 99 Mo have been performed by different groups. To develop commercially viable (n,γ) 99 Mo/ 99 mTc generator, the generator column should have high adsorption capacity for molybdenum at least several fold higher than the fission 99 Mo generator column. To achieve such high adsorption capacity, gel generator, PZC, and other technologies have been developed. However, there are still many restrictions to apply these technologies for the commercial production. As one of the latter approaches, several candidate adsorbents have been developed. One of the new adsorbents developed at Korea Atomic Energy Research Institute shows a high adsorption capacity for Mo (∼200 mg/g) and reasonable elution efficiency for 99 mTc (60 (∼ 80%). In addition, (n,γ 99 Mo can be loaded by a column operation just like fission Mo generator production

  2. Optically generated ultrasound for enhanced drug delivery

    Science.gov (United States)

    Visuri, Steven R.; Campbell, Heather L.; Da Silva, Luiz

    2002-01-01

    High frequency acoustic waves, analogous to ultrasound, can enhance the delivery of therapeutic compounds into cells. The compounds delivered may be chemotherapeutic drugs, antibiotics, photodynamic drugs or gene therapies. The therapeutic compounds are administered systemically, or preferably locally to the targeted site. Local delivery can be accomplished through a needle, cannula, or through a variety of vascular catheters, depending on the location of routes of access. To enhance the systemic or local delivery of the therapeutic compounds, high frequency acoustic waves are generated locally near the target site, and preferably near the site of compound administration. The acoustic waves are produced via laser radiation interaction with an absorbing media and can be produced via thermoelastic expansion, thermodynamic vaporization, material ablation, or plasma formation. Acoustic waves have the effect of temporarily permeabilizing the membranes of local cells, increasing the diffusion of the therapeutic compound into the cells, allowing for decreased total body dosages, decreased side effects, and enabling new therapies.

  3. Enhancing Therapeutic Cellular Prostate Cancer Vaccines

    Science.gov (United States)

    2012-06-01

    a cystatin -like molecule, inhibits ERK-dependent lymphocyte proliferation. Mech Ageing Dev 126:1284-91 7. Gomez, C.R., Acuña-Castillo, C ., Nishimura...the development of better prostate cancer cell vaccines 2. Gomez, C.R., Kosari, F., Munz, J.M., Schreiber, C ., Knutson, G., Charlesworth, C ., Karnes...TITLE: Enhancing Therapeutic Cellular Prostate Cancer Vaccines PRINCIPAL INVESTIGATOR: Christian R. Gomez, Ph.D

  4. Enhanced metabolite generation

    Science.gov (United States)

    Chidambaram, Devicharan [Middle Island, NY

    2012-03-27

    The present invention relates to the enhanced production of metabolites by a process whereby a carbon source is oxidized with a fermentative microbe in a compartment having a portal. An electron acceptor is added to the compartment to assist the microbe in the removal of excess electrons. The electron acceptor accepts electrons from the microbe after oxidation of the carbon source. Other transfers of electrons can take place to enhance the production of the metabolite, such as acids, biofuels or brewed beverages.

  5. Enhancer-associated RNAs as therapeutic targets.

    Science.gov (United States)

    Léveillé, Nicolas; Melo, Carlos A; Agami, Reuven

    2015-05-01

    Regulation of gene expression involves a variety of mechanisms driven by a complex regulatory network of factors. Control of transcription is an important step in gene expression regulation, which integrates the function of cis-acting and trans-acting elements. Among cis-regulatory elements, enhancer RNA (eRNA)-producing domains recently emerged as widespread and potent regulators of transcription and cell fate decision. Thus, manipulation of eRNA levels becomes a novel and appealing avenue for the design of new therapeutic treatments. In this review, we focus on eRNA-producing domains. We describe mechanisms involved in their cell-type specific selection and activation as well as their epigenetic features. In addition, we present their function and the growing evidences of their deregulation in human diseases. Finally, we discuss eRNAs as potential therapeutic targets. As key factors in the control of transcription, eRNAs appear to possess a great potential for the establishment of new therapy options. However, thorough testing as well as providing the genetic toolbox to target eRNAs will be needed to fully assess the practical and clinical possibilities.

  6. Therapeutic Radionuclide Generators: 90Sr/90Y and 188W/188Re Generators

    International Nuclear Information System (INIS)

    2009-01-01

    Radionuclide therapy using radiopharmaceuticals has been in existence for over 60 years and offers substantial benefits to cancer patients, in particular, patients suffering from thyroid cancer. Numerous clinical trials for treating other types of cancer using therapeutic radiopharmaceuticals are in progress, and their success will increase the demand for therapeutic radionuclides in the coming years. Those radioisotopes having short physical half-lives ranging from a few hours to a few days are useful for radionuclide therapy. The use of short lived radioisotopes for radionuclide therapy involves important challenges including the transport of the radionuclides and the need for frequent shipments. Radionuclide generators represent an efficient means for making short lived therapeutic radionuclides more widely available throughout the world. To meet the requirements for sustained growth and future expansion of the application of therapeutic radiopharmaceuticals in nuclear medicine, particularly in oncology, it is important to develop and maintain a constant and reliable supply of therapeutic radionuclides of the required quality in the desired quantities. The IAEA has several activities to support programmes that foster the enhanced availability of therapeutic radionuclides and radiopharmaceuticals in Member States. One such activity was the coordinated research project (CRP) on the development of generator technologies for therapeutic radionuclides, which ran from 2004 to 2007, in which participants from 13 countries worked to develop generator technologies for the preparation of 90 Y and 188 Re usable for radionuclide therapy. The objectives of the CRP were: (a) To develop reproducible methodologies for the preparation of 90 Sr/ 90 Y and 188 W/ 188 Re generators; (b) To standardize quality control techniques for generator eluted therapeutic radionuclides; (c) To optimize technologies for post-elution concentration of 188 Re; (d) To prepare chromatography

  7. Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.

    Science.gov (United States)

    Shah, Dhaval K

    2015-10-01

    Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized.

  8. Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

    Science.gov (United States)

    Kelly, Cynthia W

    2008-04-01

    To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

  9. 188W/188Re Generator System and Its Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    A. Boschi

    2014-01-01

    Full Text Available The 188Re radioisotope represents a useful radioisotope for the preparation of radiopharmaceuticals for therapeutic applications, particularly because of its favorable nuclear properties. The nuclide decay pattern is through the emission of a principle beta particle having 2.12 MeV maximum energy, which is enough to penetrate and destroy abnormal tissues, and principle gamma rays (Eγ=155 keV, which can efficiently be used for imaging and calculations of radiation dose. 188Re may be conveniently produced by 188W/188Re generator systems. The challenges related to the double neutron capture reaction route to provide only modest yield of the parent 188W radionuclide indeed have been one of the major issues about the use of 188Re in nuclear medicine. Since the specific activity of 188W used in the generator is relatively low (<185 GBq/g, the eluted Re188O4- can have a low radioactive concentration, often ineffective for radiopharmaceutical preparation. However, several efficient postelution concentration techniques have been developed, which yield clinically useful Re188O4- solutions. This review summarizes the technologies developed for the preparation of 188W/188Re generators, postelution concentration of the 188Re perrhenate eluate, and a brief discussion of new chemical strategies available for the very high yield preparation of 188Re radiopharmaceuticals.

  10. Therapeutic benefits of enhancing permeability barrier for atopic eczema

    Directory of Open Access Journals (Sweden)

    George Man

    2015-06-01

    Full Text Available The regulatory role of epidermal permeability barrier function in cutaneous inflammation has been well appreciated. While barrier disruption induces cutaneous inflammation, improvement of permeability barrier function alleviates inflammation. Studies have demonstrated that improvement of epidermal permeability barrier function not only prevents the development of atopic eczema, but also delays the relapse of these diseases. Moreover, enhancing the epidermal permeability barrier also alleviates atopic eczema. Furthermore, co-applications of barrier enhancing products with glucocorticoids can increase the therapeutic efficacy and reduce the adverse effects of glucocorticoids in the treatment of atopic eczema. Therefore, utilization of permeability barrier enhancing products alone or in combination with glucocorticoids could be a valuable approach in the treatment of atopic eczema. In this review, we discuss the benefits of improving the epidermal permeability barrier in the management of atopic eczema.

  11. Therapeutic enhancement of protective immunity during experimental leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Senad Divanovic

    2011-09-01

    Full Text Available Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+ T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx, a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+ T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.

  12. Pharmacokinetic properties of 2nd-generation fibroblast growth factor-1 mutants for therapeutic application.

    Directory of Open Access Journals (Sweden)

    Xue Xia

    Full Text Available Fibroblast growth factor-1 (FGF-1 is an angiogenic factor with therapeutic potential for the treatment of ischemic disease. FGF-1 has low intrinsic thermostability and is characteristically formulated with heparin as a stabilizing agent. Heparin, however, adds a number of undesirable properties that negatively impact safety and cost. Mutations that increase the thermostability of FGF-1 may obviate the need for heparin in formulation and may prove to be useful "2nd-generation" forms for therapeutic use. We report a pharmacokinetic (PK study in rabbits of human FGF-1 in the presence and absence of heparin, as well as three mutant forms having differential effects upon thermostability, buried reactive thiols, and heparin affinity. The results support the hypothesis that heparan sulfate proteoglycan (HSPG in the vasculature of liver, kidney and spleen serves as the principle peripheral compartment in the distribution kinetics. The addition of heparin to FGF-1 is shown to increase endocrine-like properties of distribution. Mutant forms of FGF-1 that enhance thermostability or eliminate buried reactive thiols demonstrate a shorter distribution half-life, a longer elimination half-life, and a longer mean residence time (MRT in comparison to wild-type FGF-1. The results show how such mutations can produce useful 2nd-generation forms with tailored PK profiles for specific therapeutic application.

  13. Dual pH-sensitive oxidative stress generating micellar nanoparticles as a novel anticancer therapeutic agent.

    Science.gov (United States)

    Park, Sanga; Kwon, Byeongsu; Yang, Wonseok; Han, Eunji; Yoo, Wooyoung; Kwon, Byoung-Mog; Lee, Dongwon

    2014-12-28

    Cancer cells are under oxidative stress due to a large production of reactive oxygen species (ROS), which involve in cell proliferation and cancer promotion and progression. On the other hand, ROS promotes cell death, depending on the rate of ROS production and the activity of antioxidant systems. Recently, "oxidation therapy" has arisen as a promising anticancer strategy, which can be achieved by inducing the generation of cytotoxic level of ROS or inhibiting the antioxidant systems in tumor cells. Here, we report oxidative stress amplifying nanoplatforms as novel anticancer therapeutics, which are able not only to suppress antioxidant but also to generate ROS simultaneously in acidic tumor microenvironments. The oxidative stress amplifying nanoplatforms are composed of dual pH-sensitive PBCAE copolymer, polymeric prodrug of BCA (benzoyloxycinnamaldehyde) and heme oxygenase-1 (HO-1) inhibiting zinc protoporphyrin (ZnPP). PBCAE was designed to incorporate ROS-generating BCA in its backbone via acid-cleavable acetal linkages and self-assemble to form micelles that encapsulate ZnPP. In vitro proof-of-concept studies revealed that ZnPP encapsulated in PBCAE micelles suppressed HO-1 to make cancer cells more vulnerable to BCA-induced ROS, leading to enhanced apoptotic cell death. In addition, ZnPP-loaded PBCAE micelles significantly suppressed the tumor growth in human cancer xenograft mouse models. We believe that oxidative stress amplifying micellar nanoparticles have a great potential as novel redox anticancer therapeutics. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Eugenol nanocapsule for enhanced therapeutic activity against periodontal infections.

    Science.gov (United States)

    Pramod, Kannissery; Aji Alex, M R; Singh, Manisha; Dang, Shweta; Ansari, Shahid H; Ali, Javed

    2016-01-01

    Eugenol is a godsend to dental care due to its analgesic, local anesthetic, and anti-inflammatory and antibacterial effects. The aim of the present research work was to prepare, characterize and evaluate eugenol-loaded nanocapsules (NCs) against periodontal infections. Eugenol-loaded polycaprolactone (PCL) NCs were prepared by solvent displacement method. The nanometric size of the prepared NCs was confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The in vitro drug release was found to follow a biphasic pattern and followed Michaelis-Menten like model. The percentage cell viability values near to 100 in the cell viability assay indicated that the NCs are not cytotoxic. In the in vivo studies, the eugenol NC group displayed significant difference in the continuity of epithelium of the interdental papilla in comparison to the untreated, pure eugenol and placebo groups. The in vivo performance of the eugenol-loaded NCs using ligature-induced periodontitis model in rats indicated that eugenol-loaded NCs could prevent septal bone resorption in periodontitis. On the basis of our research findings it could be concluded that eugenol-loaded PCL NCs could serve as a novel colloidal drug delivery system for enhanced therapeutic activity of eugenol in the treatment of periodontal infections.

  15. Enhancing Secondary School Counseling with a Therapeutic Dog

    Science.gov (United States)

    Daughhetee, Charlotte; Stalls, Laura; Spencer, M. E.

    2006-01-01

    Animals are increasingly being used for emotional support and therapeutic intervention in a variety of settings including, hospitals, nursing homes, schools, and prisons. Therapeutic animals can bring comfort to the ill, bereaved or lonely, and there are indications that owning a pet may positively influence an individual's health and well-being.…

  16. Magnetic nanoparticles: reactive oxygen species generation and potential therapeutic applications

    Science.gov (United States)

    Mai, Trang; Hilt, J. Zach

    2017-07-01

    Magnetic nanoparticles have been demonstrated to produce reactive oxygen species (ROS), which play a major role in various cellular pathways, via Fenton and Haber-Weiss reaction. ROS act as a double-edged sword inside the body. At normal conditions, the generation of ROS is in balance with their elimination by scavenger systems, and they can promote cell proliferation as well as differentiation. However, at an increased level, they can cause damages to protein, lead to cellular apoptosis, and contribute to many diseases including cancer. Many recent studies proposed a variety of strategies to either suppress toxicity of ROS generation or exploit the elevated ROS levels for cancer therapy.

  17. Therapeutic Ultrasound Enhancement of Drug Delivery to Soft Tissues

    Science.gov (United States)

    Lewis, George; Wang, Peng; Lewis, George; Olbricht, William

    2009-04-01

    Effects of exposure to 1.58 MHz focused ultrasound on transport of Evans Blue Dye (EBD) in soft tissues are investigated when an external pressure gradient is applied to induce convective flow through the tissue. The magnitude of the external pressure gradient is chosen to simulate conditions in brain parenchyma during convection-enhanced drug delivery (CED) to the brain. EBD uptake and transport are measured in equine brain, avian muscle and agarose brain-mimicking phantoms. Results show that ultrasound enhances EBD uptake and transport, and the greatest enhancement occurs when the external pressure gradient is applied. The results suggest that exposure of the brain parenchyma to ultrasound could enhance penetration of material infused into the brain during CED therapy.

  18. Using Art in Narrative Therapy: Enhancing Therapeutic Possibilities.

    Science.gov (United States)

    Carlson, Thomas D.

    1997-01-01

    Shows how applying art-therapy techniques to the basic principles of narrative therapy enhances the potential for therapists and families to open the door to externalizing conversations that lead to a new life. (Author/MKA)

  19. How Art Teachers Can Enhance Artmaking as a Therapeutic Experience: Art Therapy and Art Education.

    Science.gov (United States)

    Dunn-Snow, Peggy; D'Amelio, Georgette

    2000-01-01

    Discusses four ways that art teachers can enhance the therapeutic aspects of their lessons: (1) recognize the similarities between the therapeutic and creative processes: (2) empathetically talk with students about their artwork; (3) understand Expressive Therapies Continuum (ETC); and (4) work in collaboration with faculty and staff members. (CMK)

  20. Therapeutic enhancement of newly derived bacteriocins against Giardia lamblia.

    Science.gov (United States)

    Amer, Eglal I; Mossallam, Shereen F; Mahrous, Hoda

    2014-11-01

    Trials for identifying efficient anti-giardial agents are still ongoing. Nowadays, bacteriocins have attracted the attention as potential antimicrobial compounds. For the first time, the current study evaluated the therapeutic efficacy of bacteriocins derived from newly isolated Egyptian strains of probiotics Lactobacilli; L. acidophilus (P106) and L. plantarum (P164) against Giardia lamblia. Bacteriocins' efficacy was evaluated both in vitro; by growth inhibition and adherence assays, and in vivo; through estimation of parasite density, intestinal histopathological examination and ultrastructural analysis of Giardia trophozoites. In vivo bacteriocins' clinical safety was assessed. In vitro results proved that 50 µg of L. acidophilus bacteriocin induced reduction of the mean Giardia lamblia trophozoites by 58.3 ± 4.04%, while at lower concentrations of 10 and 20 µg of both L. acidophilus and L. plantarum, non significant reduction of the mean parasite density was achieved. In vitro trophozoites adherence was susceptible to the tested bacteriocins at all studied concentrations with variable degrees, while the highest adherence reduction was demonstrated using 50 µg of L acidophilus bacteriocin. In vivo, oral inoculation of 50 µg/mouse L. acidophilus bacteriocin for 5 successive days resulted in a noteworthy decline of the intestinal parasite density, along with amelioration of intestinal pathology of infected mice. Ultrastructural examination proved thatfive doses of L. acidophilus bacteriocin showed marked changes in cellular architecture of the trophozoites with evident disorganization of the cell membrane, adhesive disc and cytoplasmic components. This is the first reported study of the safe anti-giardial efficacy of L. acidophilus (P106) derived bacteriocin, hence highlighting its great promise as a potential therapeutic safe alternative to existing commercial drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Multistimulative Nanogels with Enhanced Thermosensitivity for Intracellular Therapeutic Delivery.

    Science.gov (United States)

    Ji, Ping; Zhou, Bingjie; Zhan, Yuan; Wang, Yifeng; Zhang, Yuhong; Li, Yulin; He, Peixin

    2017-11-15

    The flexibility and hydrophilicity of nanogels suggest their potential for the creation of nanocarriers with good colloidal stability and stimulative ability. In the present study, biocompatible AGP and AGPA nanogels with triple-stimulative properties (thermosensitivity, pH sensitivity, and redox sensitivity) were prepared by incorporating poly(N-isopropylacrylamide) (PNIPAM) or poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-AA)) into alginate (AG) emulsion nanodrops, followed by fixation with a disulfide-containing molecule (cystamine dihydrochloride (Cys)). Compared to AG/PNIPAM(AGP) nanogels, AG/P(NIPAM-AA) (AGPA) nanogels exhibited more sensitive volumetric expansion by switching the temperature from 40 to 25 °C under physiological medium. This expansion occurs because P(NIPAM-AA) with -COOH groups can be fixed inside the nanogels via chemical bonding with Cys, whereas PNIPAM was encapsulated in the nanogels through simple physical interactions with the AG matrix. AGPA nanogels carrying an anticancer drug tend to easily enter cells upon heating, thereby exerting toxicity through a cold shock and reverse thermally induced release of an anticancer drug. Upon internalization inside cells, the nanogels use the reducible and acidic intracellular environments to effectively release the drug to the nucleus to impart anticancer activity. These results demonstrate that multifunctional nanogels may be used as a general platform for therapeutic delivery.

  2. Bismuth-213 and actinium-225 -- generator performance and evolving therapeutic applications of two generator-derived alpha-emitting radioisotopes.

    Science.gov (United States)

    Morgenstern, Alfred; Bruchertseifer, Frank; Apostolidis, Christos

    2012-07-01

    The alpha emitters (225)Ac and (213)Bi are promising therapeutic radionuclides for application in targeted alpha therapy of cancer and infectious diseases. Both alpha emitters are available with high specific activity from established radionuclide generators. Their favourable chemical and physical properties have led to the conduction of a large number of preclinical studies and several clinical trials, demonstrating the feasibility, safety and therapeutic efficacy of targeted alpha therapy with (225)Ac and (213)Bi. This review describes methods for the production of (225)Ac and (213)Bi and gives an overview of (225)Ac/(213)Bi radionuclide generator systems. Selected preclinical studies are highlighted and the current clinical experience with (225)Ac and (213)Bi is summarized.

  3. Improving therapeutic outcomes in autism spectrum disorders: Enhancing social communication and sensory processing through the use of interactive robots.

    Science.gov (United States)

    Sartorato, Felippe; Przybylowski, Leon; Sarko, Diana K

    2017-07-01

    For children with autism spectrum disorders (ASDs), social robots are increasingly utilized as therapeutic tools in order to enhance social skills and communication. Robots have been shown to generate a number of social and behavioral benefits in children with ASD including heightened engagement, increased attention, and decreased social anxiety. Although social robots appear to be effective social reinforcement tools in assistive therapies, the perceptual mechanism underlying these benefits remains unknown. To date, social robot studies have primarily relied on expertise in fields such as engineering and clinical psychology, with measures of social robot efficacy principally limited to qualitative observational assessments of children's interactions with robots. In this review, we examine a range of socially interactive robots that currently have the most widespread use as well as the utility of these robots and their therapeutic effects. In addition, given that social interactions rely on audiovisual communication, we discuss how enhanced sensory processing and integration of robotic social cues may underlie the perceptual and behavioral benefits that social robots confer. Although overall multisensory processing (including audiovisual integration) is impaired in individuals with ASD, social robot interactions may provide therapeutic benefits by allowing audiovisual social cues to be experienced through a simplified version of a human interaction. By applying systems neuroscience tools to identify, analyze, and extend the multisensory perceptual substrates that may underlie the therapeutic benefits of social robots, future studies have the potential to strengthen the clinical utility of social robots for individuals with ASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Enhancement Approachof Object Constraint Language Generation

    Science.gov (United States)

    Salemi, Samin; Selamat, Ali

    2018-01-01

    OCL is the most prevalent language to document system constraints that are annotated in UML. Writing OCL specifications is not an easy task due to the complexity of the OCL syntax. Therefore, an approach to help and assist developers to write OCL specifications is needed. There are two approaches to do so: First, creating an OCL specifications by a tool called COPACABANA. Second, an MDA-based approach to help developers in writing OCL specification by another tool called NL2OCLviaSBVR that generates OCL specification automatically. This study presents another MDA-based approach called En2OCL, and its objective is twofold. 1- to improve the precison of the existing works. 2- to present a benchmark of these approaches. The benchmark shows that the accuracy of COPACABANA, NL2OCLviaSBVR, and En2OCL are 69.23, 84.64, and 88.40 respectively.

  5. Report of the 2. research coordination meeting on development of generator technologies for therapeutic radionuclides

    International Nuclear Information System (INIS)

    2006-01-01

    The objectives of this CRP are to evaluate various generator and concentration technologies for 188 W- 188 Re, 99 Mo- 99 mTc and 90 Sr- 90 Y generators, to optimize generator fabrication and use, to standardize quality control techniques for the eluted radionuclides and to provide standardized procedures to participating laboratories. The following issues will be addressed during the CRP. - Development of reproducible methodologies for the preparation of 188 W- 188 Re, 99 Mo- 99 mTc and 90 Sr- 90 Y generators. - Development and evaluation of chromatography adsorbents (Zr/Ti composites) having higher binding capacities and demonstration of their utility in the preparation of column generators for 188 Re and 99 mTc. - Comparison and optimization of technologies for post elution concentration of 188 Re and 99 mTc in order to improve the radioactive concentration. - Development of quality control techniques and specifications for generator eluted therapeutic radionuclides

  6. Next generation diode lasers with enhanced brightness

    Science.gov (United States)

    Ried, S.; Rauch, S.; Irmler, L.; Rikels, J.; Killi, A.; Papastathopoulos, E.; Sarailou, E.; Zimer, H.

    2018-02-01

    High-power diode lasers are nowadays well established manufacturing tools in high power materials processing, mainly for tactile welding, surface treatment and cladding applications. Typical beam parameter products (BPP) of such lasers range from 30 to 50 mm·mrad at several kilowatts of output power. TRUMPF offers a product line of diode lasers to its customers ranging from 150 W up to 6 kW of output power. These diode lasers combine high reliability with small footprint and high efficiency. However, up to now these lasers are limited in brightness due to the commonly used spatial and coarse spectral beam combining techniques. Recently diode lasers with enhanced brightness have been presented by use of dense wavelength multiplexing (DWM). In this paper we report on TRUMPF's diode lasers utilizing DWM. We demonstrate a 2 kW and a 4 kW system ideally suited for fine welding and scanner welding applications. The typical laser efficiency is in the range of 50%. The system offers plug and play exchange of the fiber beam delivery cable, multiple optical outputs and integrated cooling in a very compact package. An advanced control system offers flexible integration in any customer's shop floor environment and includes industry 4.0 capabilities (e.g. condition monitoring and predictive maintenance).

  7. Therapeutic assessment of SEED: a new engineered antibody platform designed to generate mono- and bispecific antibodies.

    Science.gov (United States)

    Muda, Marco; Gross, Alec W; Dawson, Jessica P; He, Chaomei; Kurosawa, Emmi; Schweickhardt, Rene; Dugas, Melanie; Soloviev, Maria; Bernhardt, Anna; Fischer, David; Wesolowski, John S; Kelton, Christie; Neuteboom, Berend; Hock, Bjoern

    2011-05-01

    The strand-exchange engineered domain (SEED) platform was designed to generate asymmetric and bispecific antibody-like molecules, a capability that expands therapeutic applications of natural antibodies. This new protein engineered platform is based on exchanging structurally related sequences of immunoglobulin within the conserved CH3 domains. Alternating sequences from human IgA and IgG in the SEED CH3 domains generate two asymmetric but complementary domains, designated AG and GA. The SEED design allows efficient generation of AG/GA heterodimers, while disfavoring homodimerization of AG and GA SEED CH3 domains. Using a clinically validated antibody (C225), we tested whether Fab derivatives constructed on the SEED platform retain desirable therapeutic antibody features such as in vitro and in vivo stability, favorable pharmacokinetics, ligand binding and effector functions including antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. In addition, we tested SEED with combinations of binder domains (scFv, VHH, Fab). Mono- and bivalent Fab-SEED fusions retain full binding affinity, have excellent biochemical and biophysical stability, and retain desirable antibody-like characteristics conferred by Fc domains. Furthermore, SEED is compatible with different combinations of Fab, scFv and VHH domains. Our assessment shows that the new SEED platform expands therapeutic applications of natural antibodies by generating heterodimeric Fc-analog proteins.

  8. The Secret Life of Exosomes: What Bees Can Teach Us About Next-Generation Therapeutics.

    Science.gov (United States)

    Marbán, Eduardo

    2018-01-16

    Mechanistic exploration has pinpointed nanosized extracellular vesicles, known as exosomes, as key mediators of the benefits of cell therapy. Exosomes appear to recapitulate the benefits of cells and more. As durable azoic entities, exosomes have numerous practical and conceptual advantages over cells. Will cells end up just being used to manufacture exosomes, or will they find lasting value as primary therapeutic agents? Here, a venerable natural process-the generation of honey-serves as an instructive parable. Flowers make nectar, which bees collect and process into honey. Cells make conditioned medium, which laboratory workers collect and process into exosomes. Unlike flowers, honey is durable, compact, and nutritious, but these facts do not negate the value of flowers themselves. The parallels suggest new ways of thinking about next-generation therapeutics. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. Size unbiased representative enzymatically generated RNAi (SURER) library and application for RNAi therapeutic screens.

    Science.gov (United States)

    Li, Tiejun; Zhu, York Yuanyuan; Chen, Li; Sun, Yuncheng; Yuan, Jian; Graham, Michael; French, Peter

    2015-02-01

    RNA interference (RNAi) libraries screens have become widely used for small RNA (sRNA) therapeutic targets development. However, conventional enzymatically libraries, typically prepared using the type 2 restriction enzyme MmeI, produce sRNAs between 18 and 20 bp, much shorter than the usual lengths of 19-23 bp. Here we develop a size unbiased representative enzymatically generated RNAi (SURER) library, which employs type 3 restriction modification enzyme EcoP15I to produce sRNAs ranging from 19 to 23 bp using a group of rationally designed linkers, which can completely mimic the length of sRNAs naturally generated by Dicer enzyme in living cells, and the screening results of SURER libraries showed high recombination rate and knockdown efficiency. SURER library provides a useful tool for RNAi therapeutics screening in a fast and simple way.

  10. Identifying Therapeutics for Platinum-Resistant Ovarian Cancer by Next Generation Mechanotyping

    Science.gov (United States)

    2017-09-01

    impact on other disciplines? The ability to screen cells based on mechanotype opens up possibilities for screens that are relevant to other fields from...Research, 820 Chandler Street , Fort Detrick, MD 21702-5014 Period: 05/01/17 – 04/30/20 Funding: Role: Co-Investigator...therapeutic targets in the tumor stroma by correlating stromal factors with clinical outcomes; 2) Generate a spatiotemporal map of stromal activity

  11. Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC.

    Science.gov (United States)

    Singh, Thangjam Davis; Meitei, Heikrujam Thoihen; Sharma, Adhikarimayum Lakhikumar; Robinson, Asem; Singh, Lisam Shanjukumar; Singh, Thiyam Ramsing

    2015-08-20

    Clinical use of chemotherapeutic drug, cisplatin is limited by its toxicity and drug resistance. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin, to increase efficacy and reduce its toxicity. Here, we screened 16 medicinal plant extracts from Northeast part of India and found that leaf extract of Zanthoxylum armatum DC. (ZALE) induced cytotoxicity as well as an effect on the increasing of the efficiency of chemotherapeutic drugs (cisplatin, mitomycin C and camptothecin). This work shows detail molecular mechanism of anti-cancer activity of ZALE and its potential for combined treatment regimens to enhance the apoptotic response of chemotherapeutic drugs. ZALE induced cytotoxicity, nuclear blebbing and DNA fragmentation in HeLA cells suggesting apoptosis induction in human cervical cell line. However, the apoptosis induced was independent of caspase 3 activation and poly ADP ribose polymerase (PARP) cleavage. Further, ZALE activated Mitogen-activated protein kinases (MAPK) pathway as revealed by increased phosphorylation of extracellular-signal-regulated kinases (ERK), p38 and c-Jun N-terminal kinase (JNK). Inhibition of ERK activation but not p38 or JNK completely blocked the ZALE induced apoptosis suggesting an ERK dependent apoptosis. Moreover, ZALE generated DNA double strand breaks as suggested by the induction γH2AX foci formation. Interestingly, pretreatment of certain cancer cell lines with ZALE, sensitized the cancer cells to cisplatin and other chemotherapeutic drugs. Enhanced caspase activation was observed in the synergistic interaction among chemotherapeutic drugs and ZALE. Purification and identification of the bio-active molecules from the ZALE or as a complementary treatment for a sequential treatment of ZALE with chemotherapeutic drugs might be a new challenger to open a new therapeutic window for the novel anti-cancer treatment.

  12. Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC

    Directory of Open Access Journals (Sweden)

    Thangjam Davis Singh

    2015-01-01

    Full Text Available BACKGROUND: Clinical use of chemotherapeutic drug, cisplatin is limited by its toxicity and drug resistance. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin, to increase efficacy and reduce its toxicity. Here, we screened 16 medicinal plant extracts from Northeast part of India and found that leaf extract of Zanthoxylum armatum DC. (ZALE induced cytotoxicity as well as an effect on the increasing of the efficiency of chemotherapeutic drugs (cisplatin, mitomycin C and camptothecin. This work shows detail molecular mechanism of anti-cancer activity of ZALE and its potential for combined treatment regimens to enhance the apoptotic response of chemotherapeutic drugs. RESULTS: ZALE induced cytotoxicity, nuclear blebbing and DNA fragmentation in HeLA cells suggesting apoptosis induction in human cervical cell line. However, the apoptosis induced was independent of caspase 3 activation and poly ADP ribose polymerase (PARP cleavage. Further, ZALE activated Mitogen-activated protein kinases (MAPK pathway as revealed by increased phosphorylation of extracellular-signal-regulated kinases (ERK, p38 and c-Jun N-ter-minal kinase (JNK. Inhibition of ERK activation but not p38 or JNK completely blocked the ZALE induced apoptosis suggesting an ERK dependent apoptosis. Moreover, ZALE generated DNA double strand breaks as suggested by the induction γH2AX foci formation. Interestingly, pretreatment of certain cancer cell lines with ZALE, sensitized the cancer cells to cisplatin and other chemotherapeutic drugs. Enhanced caspase activation was observed in the synergistic interaction among chemotherapeutic drugs and ZALE. CONCLUSION: Purification and identification of the bio-active molecules from the ZALE or as a complementary treatment for a sequential treatment of ZALE with chemotherapeutic drugs might be a new challenger to open a new therapeutic window for the novel anti-cancer treatment.

  13. Therapeutical radiopharmaceuticals based In vivo generator system [166 Dy] Dy/166 Ho

    International Nuclear Information System (INIS)

    Ferro F, G.; Garcia S, L.; Monroy G, F.; Tendilla, J.I.; Pedraza L, M.; Murphy, C.A. de

    2002-01-01

    At the idea to administer to a patient a molecule containing in it structure a father radionuclide, with a half life enough large which allows to the radiolabelled molecule to take up position specifically in a white tissue and decaying In vivo to the daughter radionuclide with properties potentially therapeutic, it is known as In vivo generator system. In this work the preparation and the preliminary dosimetric valuations of radiopharmaceuticals based In vivo generator system 166 Dy Dy/ 166 Ho for applications in radioimmunotherapy, in the treatment of the rheumatoid arthritis and in the bone marrow ablation (m.o.) for candidates patients to bone marrow transplant are presented. (Author)

  14. Enhancement of cell-based therapeutic angiogenesis using a novel type of injectable scaffolds of hydroxyapatite-polymer nanocomposite microspheres.

    Directory of Open Access Journals (Sweden)

    Yohei Mima

    Full Text Available BACKGROUND: Clinical trials demonstrate the effectiveness of cell-based therapeutic angiogenesis in patients with severe ischemic diseases; however, their success remains limited. Maintaining transplanted cells in place are expected to augment the cell-based therapeutic angiogenesis. We have reported that nano-hydroxyapatite (HAp coating on medical devices shows marked cell adhesiveness. Using this nanotechnology, HAp-coated poly(l-lactic acid (PLLA microspheres, named nano-scaffold (NS, were generated as a non-biological, biodegradable and injectable cell scaffold. We investigate the effectiveness of NS on cell-based therapeutic angiogenesis. METHODS AND RESULTS: Bone marrow mononuclear cells (BMNC and NS or control PLLA microspheres (LA were intramuscularly co-implanted into mice ischemic hindlimbs. When BMNC derived from enhanced green fluorescent protein (EGFP-transgenic mice were injected into ischemic muscle, the muscle GFP level in NS+BMNC group was approximate fivefold higher than that in BMNC or LA+BMNC groups seven days after operation. Kaplan-Meier analysis demonstrated that NS+BMNC markedly prevented hindlimb necrosis (P<0.05 vs. BMNC or LA+BMNC. NS+BMNC revealed much higher induction of angiogenesis in ischemic tissues and collateral blood flow confirmed by three-dimensional computed tomography angiography than those of BMNC or LA+BMNC groups. NS-enhanced therapeutic angiogenesis and arteriogenesis showed good correlations with increased intramuscular levels of vascular endothelial growth factor and fibroblast growth factor-2. NS co-implantation also prevented apoptotic cell death of transplanted cells, resulting in prolonged cell retention. CONCLUSION: A novel and feasible injectable cell scaffold potentiates cell-based therapeutic angiogenesis, which could be extremely useful for the treatment of severe ischemic disorders.

  15. Ultrasonic enhancement of chemical cleaning of steam generators. Final report

    International Nuclear Information System (INIS)

    Scharton, T.

    1983-04-01

    This report presents the results of an investigation into the use of ultrasound to enhance the chemical cleaning of steam generator tube and support crevices. Primary attention was focused on a configuration with ultrasonic transducers in the downcomer region of the steam generator in conjunction with the EPRI Steam Generator Owners Group (SGOG) crevice solvent at 200 0 F. The investigation consisted primarily of experiments conducted in facilities designed to simulate the geometry and acoustics of a steam generator. The largest facility holds approximately 1000 gallons of solvent and simulates a 40 0 sector of a steam generator with two support plates. The testing demonstrated that ultrasonics is indeed an effective means of enhancing the crevice cleaning if sound levels sufficient to cause cavitation can be transmitted to the crevices. The effort focused on the coupling of the transducers to the wrapper plate, on the transmission of sound through the tube bundle, and on the determination of cavitation threshold levels

  16. Emerging Therapeutic Enhancement Enabling Health Technologies and Their Discourses: What Is Discussed within the Health Domain?

    Directory of Open Access Journals (Sweden)

    Gregor Wolbring

    2013-07-01

    Full Text Available So far, the very meaning of health and therefore, treatment and rehabilitation is benchmarked to the normal or species-typical body. We expect certain abilities in members of a species; we expect humans to walk but not to fly, but a bird we expect to fly. However, increasingly therapeutic interventions have the potential to give recipients beyond species-typical body related abilities (therapeutic enhancements, TE. We believe that the perfect storm of TE, the shift in ability expectations toward beyond species-typical body abilities, and the increasing desire of health consumers to shape the health system will increasingly influence various aspects of health care practice, policy, and scholarship. We employed qualitative and quantitative methods to investigate among others how human enhancement, neuro/cognitive enhancement, brain machine interfaces, and social robot discourses cover (a healthcare, healthcare policy, and healthcare ethics, (b disability and (c health consumers and how visible various assessment fields are within Neuro/Cogno/ Human enhancement and within the BMI and social robotics discourse. We found that health care, as such, is little discussed, as are health care policy and ethics; that the term consumers (but not health consumers is used; that technology, impact and needs assessment is absent; and that the imagery of disabled people is primarily a medical one. We submit that now, at this early stage, is the time to gain a good understanding of what drives the push for the enhancement agenda and enhancement-enabling devices, and the dynamics around acceptance and diffusion of therapeutic enhancements.

  17. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2015-10-01

    cell activation assays, respectively (Table 1). In addition, we found that most of these immunogenic epitopes were not related to breast cancer and... HLA - A*02-negative cells, and we plotted the peptides that were derived from these cells in relation to percentile ranks (Fig. 3). Fig. 2. The...1 Award Number: W81XWH-11-1-0549 TITLE: Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer PRINCIPAL INVESTIGATOR

  18. Development of next generation cardiovascular therapeutics through bio-assisted nanotechnology.

    Science.gov (United States)

    Lakshmanan, Rajesh; Maulik, Nilanjana

    2017-09-26

    Cardiovascular diseases (CVDs) rank, next to cancer and stroke, among the deadliest diseases in the world. Among the major CVDs, acute myocardial infarction is a life-threatening disorder resulting from permanent damage to the left ventricular cardiac tissue. The major coronary arteries that supply blood to the functional left ventricle become blocked due to thrombotic plaque occlusion. During myocardial ischemia, oxidative stress and free radicals destroy healthy cardiomyocytes, smooth muscle cells, and endothelial cells, followed by degradation of the extracellular matrix, which results in ventricular wall-thinning and dilation. To protect the left ventricle from further damage and to rescue ischemic cardiac tissue, specially designed scaffolds consisting of biological material and nanomaterials have been developed. At the preclinical level, scaffolds loaded with growth factors and cells have been shown to regenerate ischemic tissue into healthy, functional myocardium. In this review, different therapeutic strategies currently available to treat the disease conditions at various stages are discussed, with special emphasis on biomaterials. Recent advancements in cardiovascular therapeutics using graphene and exosomal nanovesicles are discussed in detail. In addition, future directions for the development of next-generation cardiovascular therapeutics with biological and non-biological materials through nano-assisted technology are explored. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  19. Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity.

    Science.gov (United States)

    Herter, Sylvia; Birk, Martina C; Klein, Christian; Gerdes, Christian; Umana, Pablo; Bacac, Marina

    2014-03-01

    Therapeutic Abs possess several clinically relevant mechanisms of action including perturbation of tumor cell signaling, activation of complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cellular phagocytosis (ADCP), and induction of adaptive immunity. In view of the important role of phagocytic lineage cells in the mechanism of action of therapeutic Abs, we analyzed FcγR receptor-dependent effector functions of monocytes and macrophages triggered by glycoengineered (GE) Abs (having enhanced FcγRIIIa [CD16a] binding affinity) versus their wild-type (WT) counterparts under different experimental conditions. We first defined the precise FcγR repertoire on classical and nonclassical intermediate monocytes--M1 and M2c macrophage populations. We further show that WT and GE Abs display comparable binding and induce similar effector functions (ADCC and ADCP) in the absence of nonspecific, endogenous IgGs. However, in the presence of these IgGs (i.e., in a situation that more closely mimics physiologic conditions), GE Abs display significantly superior binding and promote stronger monocyte and macrophage activity. These data show that in addition to enhancing CD16a-dependent NK cell cytotoxicity, glycoengineering also enhances monocyte and macrophage phagocytic and cytotoxic activities through enhanced binding to CD16a under conditions that more closely resemble the physiologic setting.

  20. Heat-Transfer Enhancement by Artificially Generated Streamwise Vorticity

    Science.gov (United States)

    Ghanem, Akram; Habchi, Charbel; Lemenand, Thierry; Della Valle, Dominique; Peerhossaini, Hassan

    2012-11-01

    Vortex-induced heat transfer enhancement exploits longitudinal and transverse pressure-driven vortices through the deliberate artificial generation of large-scale vortical flow structures. Thermal-hydraulic performance, Nusselt number and friction factor are experimentally investigated in a HEV (high-efficiency vortex) mixer, which is a tubular heat exchanger and static mixer equipped with trapezoidal vortex generators. Pressure gradients are generated on the trapezoidal tab initiating a streamwise swirling motion in the form of two longitudinal counter-rotating vortex pairs (CVP). Due to the Kelvin-Helmholtz instability, the shear layer generated at the tab edges, which is a production site of turbulence kinetic energy (TKE), becomes unstable further downstream from the tabs and gives rise to periodic hairpin vortices. The aim of the study is to quantify the effects of hydrodynamics on the heat- and masstransfer phenomena accompanying such flows for comparison with the results of numerical studies and validate the high efficiency of the intensification process implementing such vortex generators. The experimental results reflect the enhancement expected from the numerical studies and confirm the high status of the HEV heat exchanger and static mixer.

  1. A Polar Sulfamide Spacer Significantly Enhances the Manufacturability, Stability, and Therapeutic Index of Antibody–Drug Conjugates

    Directory of Open Access Journals (Sweden)

    Jorge M. M. Verkade

    2018-02-01

    Full Text Available Despite tremendous efforts in the field of targeted cancer therapy with antibody–drug conjugates (ADCs, attrition rates have been high. Historically, the priority in ADC development has been the selection of target, antibody, and toxin, with little focus on the nature of the linker. We show here that a short and polar sulfamide spacer (HydraSpace™, AE Oss, The Netherland positively impacts ADC properties in various ways: (a efficiency of conjugation; (b stability; and (c therapeutic index. Different ADC formats are explored in terms of drug-to-antibody ratios (DAR2, DAR4 and we describe the generation of a DAR4 ADC by site-specific attachment of a bivalent linker–payload construct to a single conjugation site in the antibody. A head-to-head comparison of HydraSpace™-containing DAR4 ADCs to marketed drugs, derived from the same antibody and toxic payload components, indicated a significant improvement in both the efficacy and safety of several vivo models, corroborated by in-depth pharmacokinetic analysis. Taken together, HydraSpace™ technology based on a polar sulfamide spacer provides significant improvement in manufacturability, stability, and ADC design, and is a powerful platform to enable next-generation ADCs with enhanced therapeutic index.

  2. The Life Threatened Child and the Life Enhancing Clown: Towards a Model of Therapeutic Clowning

    Directory of Open Access Journals (Sweden)

    Donna Koller

    2008-01-01

    Full Text Available In the last decade, there has been a rapid growth in the presence of clowns in hospitals, particularly in pediatric settings. The proliferation of clowns in health care settings has resulted in varying levels of professionalism and accountability. For this reason, there is a need to examine various forms of clowning, in particular therapeutic clowning in pediatric settings. The purpose of this article is to address what therapeutic clowning is and to describe the extent to which it can provide a complementary form of health care. In an attempt to apply theory to practice, the article will draw upon the experiences of a therapeutic clown within a pediatric setting while providing a historical and theoretical account of how clowns came to be in hospitals. Toward this end, a proposed model of therapeutic clowning will be offered which can be adapted for a variety of settings where children require specialized forms of play in order to enhance their coping, development and adjustment to life changes. Finally, current research on clowning in children's hospitals will be reviewed including a summary of findings from surveys administered at the Hospital for Sick Children.

  3. Generation and Characterization of a Defective HIV-1 Virus as an Immunogen for a Therapeutic Vaccine

    Science.gov (United States)

    García-Pérez, Javier; García, Felipe; Blanco, Julia; Escribà-García, Laura; Gatell, Jose Maria; Alcamí, Jose; Plana, Montserrat; Sánchez-Palomino, Sonsoles

    2012-01-01

    Background The generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals. Results Viral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors. Conclusions We propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles. PMID:23144996

  4. Method of generating ploynucleotides encoding enhanced folding variants

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.

    2017-05-02

    The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

  5. A generative model for resolution enhancement of diffusion MRI data.

    Science.gov (United States)

    Yap, Pew-Thian; An, Hongyu; Chen, Yasheng; Shen, Dinggang

    2013-01-01

    The advent of diffusion magnetic resonance imaging (DMRI) presents unique opportunities for the exploration of white matter connectivity in vivo and non-invasively. However, DMRI suffers from insufficient spatial resolution, often limiting its utility to the studying of only major white matter structures. Many image enhancement techniques rely on expensive scanner upgrades and complex time-consuming sequences. We will instead take a post-processing approach in this paper for resolution enhancement of DMRI data. This will allow the enhancement of existing data without re-acquisition. Our method uses a generative model that reflects the image generation process and, after the parameters of the model have been estimated, we can effectively sample high-resolution images from this model. More specifically, we assume that the diffusion-weighted signal at each voxel is an agglomeration of signals from an ensemble of fiber segments that can be oriented and located freely within the voxel. Our model for each voxel therefore consists of an arbitrary number of signal generating fiber segments, and the model parameters that need to be determined are the locations and orientations of these fiber segments. Solving for these parameters is an ill-posed problem. However, by borrowing information from neighboring voxels, we show that this can be solved by using Markov chain Monte Carlo (MCMC) methods such as the Metropolis-Hastings algorithm. Preliminary results indicate that out method substantially increases structural visibility in both subcortical and cortical regions.

  6. The Paramyxovirus Polymerase Complex as a Target for Next-Generation Anti-Paramyxovirus Therapeutics

    Directory of Open Access Journals (Sweden)

    Richard K Plemper

    2015-05-01

    Full Text Available The paramyxovirus family includes major human and animal pathogens, including measles virus, mumps virus, and human respiratory syncytial virus (RSV, as well as the emerging zoonotic Hendra and Nipah viruses. In the United States, RSV is the leading cause of infant hospitalizations due to viral infectious disease. Despite their clinical significance, effective drugs for the improved management of paramyxovirus disease are lacking. The development of novel anti-paramyxovirus therapeutics is therefore urgently needed. Paramyxoviruses contain RNA genomes of negative polarity, necessitating a virus-encoded RNA-dependent RNA polymerase (RdRp complex for replication and transcription. Since an equivalent enzymatic activity is absent in host cells, the RdRp complex represents an attractive druggable target, although structure-guided drug development campaigns are hampered by the lack of high-resolution RdRp crystal structures. Here, we review the current structural and functional insight into the paramyxovirus polymerase complex in conjunction with an evaluation of the mechanism of activity and developmental status of available experimental RdRp inhibitors. Our assessment spotlights the importance of the RdRp complex as a premier target for therapeutic intervention and examines how high-resolution insight into the organization of the complex will pave the path towards the structure-guided design and optimization of much-needed next-generation paramyxovirus RdRp blockers.

  7. Toward a new generation of therapeutics: artificial cell targeted delivery of live cells for therapy.

    Science.gov (United States)

    Prakash, Satya; Martoni, Christopher

    2006-01-01

    Scientific evidence in the prevention and treatment of various disorders is accumulating regarding probiotics. The health benefits supported by adequate clinical data include increased resistance to infectious disease, decreased duration of diarrhea, management of inflammatory bowel disease, reduction of serum cholesterol, prevention of allergy, modulation of cytokine gene expression, and suppression of carcinogen production. Recent ventures in metabolic engineering and heterologous protein expression have enhanced the enzymatic and immunomodulatory effects of probiotics and, with time, may allow more active intervention among critical care patients. In addition, a number of approaches are currently being explored, including the physical and chemical protection of cells, to increase probiotic viability and its health benefits. Traditional immobilization of probiotics in gel matrices, most notably calcium alginate and kappa-carrageenan, has frequently been employed, with noted improvements in viability during freezing and storage. Conflicting reports exist, however, on the protection offered by immobilization from harsh physiologic environments. An alternative approach, microencapsulation in "artificial cells," builds on immobilization technologies by combining enhanced mechanical stability of the capsule membrane with improved mass transport, increased cell loading, and greater control of parameters. This review summarizes the current clinical status of probiotics, examines the promises and challenges of current immobilization technologies, and presents the concept of artificial cells for effective delivery of therapeutic bacterial cells.

  8. Allometry of Factor VIII and informed scaling of next generation therapeutic proteins

    Science.gov (United States)

    Kosloski, Matthew P.; Pisal, Dipak S.; Mager, Donald E.; Balu-Iyer, Sathy V.

    2013-01-01

    Allometric scaling has been applied to the pharmacokinetics (PK) of factor VIII (FVIII), but published relationships are based on relatively small subsets of available data. Numerous next generation forms of FVIII are being developed (e.g. Fc fusion, PEGylated, and liposomal formulations) and traditional pharmacokinetic scaling of these products would not incorporate the wealth of existing knowledge for current FVIII therapy in humans. We conducted a meta-analysis and developed allometric relationships of FVIII from over 100 PK studies collected from literature. Normalized Wajima curves were used to relate mean FVIII profiles between species. An ‘informed scaling’ approach was derived for predicting first-in-human PK parameters and demonstrated with a case study for an Fc fusion FVIII. NCA values for FVIII PK were well described by the allometric equations CL=6.59·W0.85 and Vss=65.0·W0.97. A subset of studies characterized by two compartment modeling showed strong linearity in scaling of total clearance and central volume, but more variability in distributional clearance and peripheral volume. Wajima curves for FVIII superimposed across species and the disposition of Fc fusion FVIII in humans was well predicted by ‘informed scaling.’ This approach might be generally applicable for predicting human PK of next generational therapeutics. PMID:23620343

  9. Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target

    Science.gov (United States)

    Paz, Jeanne T.; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D.; Wang, Gordon; Lemmens, Robin; Tran, Kevin V.; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A.; O’Rourke, Nancy; Smith, Stephen J.; Huguenard, John R.; Bliss, Tonya M.

    2016-01-01

    Abstract Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem’s potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. PMID:26685158

  10. Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy.

    Science.gov (United States)

    Järnum, Sofia; Runström, Anna; Bockermann, Robert; Winstedt, Lena; Crispin, Max; Kjellman, Christian

    2017-09-01

    Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells. Mol Cancer Ther; 16(9); 1887-97. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Enhancing patient-level clinical data access to promote evidence-based practice and incentivize therapeutic innovation.

    Science.gov (United States)

    Fortunato, Alice; Grainger, David W; Abou-El-Enein, Mohamed

    2018-01-31

    Clinical trials are crucial to determining the human safety and efficacy of new therapeutic innovations. Extraordinary amounts of human experiential data are generated over the course of any clinical trial, however, much of these data is never made publicly accessible. Improved, reliable data sharing is essential to inform clinical decisions and incentivize further therapeutic improvements; this need, and the call and concept to enhance patient-level clinical trial data accessibility is not new. Several recent public and private shifts in clinical data sharing policies and procedures promise to improve access and data utility to reduce waste in research and increase efficiency of evidence synthesis. Nonetheless, pharmaceutical industry remain reluctant to share full clinical data sets at some level to protect their commercial interests and avoid misuse of their data. Here, we review the landscape of emerging regulations related to the sharing of patient level data and current clinical data access models of major pharmaceutical companies. We also summarize the different measures that could satisfy both clinical data producers and users in achieving the benefits of accessing patient-level data while mitigating any associated risks. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  13. Multi-Functional Distributed Generation Unit for Power Quality Enhancement

    DEFF Research Database (Denmark)

    Zeng, Zheng; Yang, Huan; Guerrero, Josep M.

    2015-01-01

    A multi-functional distributed generation unit (MFDGU) and its control strategy are proposed in this paper for the purpose of enhancing power quality in low-voltage networks. By using the 3H-bridge converter structure, an MFDGU can be applied in 3-phase 4-wire low-voltage distribution networks...... reference of the MFDGU, which can be easily implemented in three-phase networks. A 15kVA prototype consisting of three full bridge converters has been built and tested. Experimental results show the feasibility of the proposed topology and control strategy....

  14. Biomaterials-based 3D cell printing for next-generation therapeutics and diagnostics.

    Science.gov (United States)

    Jang, Jinah; Park, Ju Young; Gao, Ge; Cho, Dong-Woo

    2018-02-01

    Building human tissues via 3D cell printing technology has received particular attention due to its process flexibility and versatility. This technology enables the recapitulation of unique features of human tissues and the all-in-one manufacturing process through the design of smart and advanced biomaterials and proper polymerization techniques. For the optimal engineering of tissues, a higher-order assembly of physiological components, including cells, biomaterials, and biomolecules, should meet the critical requirements for tissue morphogenesis and vascularization. The convergence of 3D cell printing with a microfluidic approach has led to a significant leap in the vascularization of engineering tissues. In addition, recent cutting-edge technology in stem cells and genetic engineering can potentially be adapted to the 3D tissue fabrication technique, and it has great potential to shift the paradigm of disease modeling and the study of unknown disease mechanisms required for precision medicine. This review gives an overview of recent developments in 3D cell printing and bioinks and provides technical requirements for engineering human tissues. Finally, we propose suggestions on the development of next-generation therapeutics and diagnostics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. The pharmacology of PEGylation: balancing PD with PK to generate novel therapeutics.

    Science.gov (United States)

    Fishburn, C Simone

    2008-10-01

    Conjugation of macromolecules to polyethylene glycol (PEG) has emerged recently as an effective strategy to alter the pharmacokinetic (PK) profiles of a variety of drugs, and thereby to improve their therapeutic potential. PEG conjugation increases retention of drugs in the circulation by protecting against enzymatic digestion, slowing filtration by the kidneys and reducing the generation of neutralizing antibodies. Often, PEGylation leads to a loss in binding affinity due to steric interference with the drug-target binding interaction. This loss in potency is offset by the longer circulating half-life of the drugs, and the resulting change in PK-PD profile has led in some cases to enabling of drugs that otherwise could not be developed, and in others to improvements in existing drugs. Thus, whereas most approaches to drug development seek to increase the activity of drugs directly, the creation of PEGylated drugs seeks to balance the pharmacodynamic (PD) and pharmacokinetic properties to produce novel therapies that will meet with both increased efficacy and greater compliance in the clinical setting. This review examines some of the PEGylated drugs developed in recent years, and highlights some of the different strategies taken to employ PEG to maximize the overall PK-PD profiles of these compounds. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  16. MHC class I antigen presentation and implications for developing a new generation of therapeutic vaccines.

    Science.gov (United States)

    Comber, Joseph D; Philip, Ramila

    2014-05-01

    Major histocompatibility complex class I (MHC-I) presented peptide epitopes provide a 'window' into the changes occurring in a cell. Conventionally, these peptides are generated by proteolysis of endogenously synthesized proteins in the cytosol, loaded onto MHC-I molecules, and presented on the cell surface for surveillance by CD8(+) T cells. MHC-I restricted processing and presentation alerts the immune system to any infectious or tumorigenic processes unfolding intracellularly and provides potential targets for a cytotoxic T cell response. Therefore, therapeutic vaccines based on MHC-I presented peptide epitopes could, theoretically, induce CD8(+) T cell responses that have tangible clinical impacts on tumor eradication and patient survival. Three major methods have been used to identify MHC-I restricted epitopes for inclusion in peptide-based vaccines for cancer: genetic, motif prediction and, more recently, immunoproteomic analysis. Although the first two methods are capable of identifying T cell stimulatory epitopes, these have significant disadvantages and may not accurately represent epitopes presented by a tumor cell. In contrast, immunoproteomic methods can overcome these disadvantages and identify naturally processed and presented tumor associated epitopes that induce more clinically relevant tumor specific cytotoxic T cell responses. In this review, we discuss the importance of using the naturally presented MHC-I peptide repertoire in formulating peptide vaccines, the recent application of peptide-based vaccines in a variety of cancers, and highlight the pros and cons of the current state of peptide vaccines.

  17. Therapeutic Genome Editing and its Potential Enhancement through CRISPR Guide RNA and Cas9 Modifications.

    Science.gov (United States)

    Batzir, Nurit Assia; Tovin, Adi; Hendel, Ayal

    2017-06-01

    Genome editing with engineered nucleases is a rapidly growing field thanks to transformative technologies that allow researchers to precisely alter genomes for numerous applications including basic research, biotechnology, and human gene therapy. The genome editing process relies on creating a site-specific DNA double-strand break (DSB) by engineered nucleases and then allowing the cell's repair machinery to repair the break such that precise changes are made to the DNA sequence. The recent development of CRISPR-Cas systems as easily accessible and programmable tools for genome editing accelerates the progress towards using genome editing as a new approach to human therapeutics. Here we review how genome editing using engineered nucleases works and how using different genome editing outcomes can be used as a tool set for treating human diseases. We then review the major challenges of therapeutic genome editing and we discuss how its potential enhancement through CRISPR guide RNA and Cas9 protein modifications could resolve some of these challenges. Copyright© of YS Medical Media ltd.

  18. Immune disease-associated variants in gene enhancers point to BET epigenetic mechanisms for therapeutic intervention.

    Science.gov (United States)

    Tough, David F; Prinjha, Rab K

    2017-04-01

    Genome-wide association studies have identified thousands of single nucleotide polymorphisms in the human genome that are statistically associated with particular disease traits. In this Perspective, we review emerging data suggesting that most single nucleotide polymorphisms associated with immune-mediated diseases are found in regulatory regions of the DNA - parts of the genome that control expression of the protein encoding genes - rather than causing mutations in proteins. We discuss how the emerging understanding of particular gene regulatory regions, gene enhancers and the epigenetic mechanisms by which they are regulated is opening up new opportunities for the treatment of immune-mediated diseases, focusing particularly on the BET family of epigenetic reader proteins as potential therapeutic targets.

  19. Enhanced Deep Blue Aerosol Retrieval Algorithm: The Second Generation

    Science.gov (United States)

    Hsu, N. C.; Jeong, M.-J.; Bettenhausen, C.; Sayer, A. M.; Hansell, R.; Seftor, C. S.; Huang, J.; Tsay, S.-C.

    2013-01-01

    The aerosol products retrieved using the MODIS collection 5.1 Deep Blue algorithm have provided useful information about aerosol properties over bright-reflecting land surfaces, such as desert, semi-arid, and urban regions. However, many components of the C5.1 retrieval algorithm needed to be improved; for example, the use of a static surface database to estimate surface reflectances. This is particularly important over regions of mixed vegetated and non- vegetated surfaces, which may undergo strong seasonal changes in land cover. In order to address this issue, we develop a hybrid approach, which takes advantage of the combination of pre-calculated surface reflectance database and normalized difference vegetation index in determining the surface reflectance for aerosol retrievals. As a result, the spatial coverage of aerosol data generated by the enhanced Deep Blue algorithm has been extended from the arid and semi-arid regions to the entire land areas.

  20. Knowledge Generation in Technology-Enhanced Health Exhibitions

    DEFF Research Database (Denmark)

    Magnussen, Rikke; Kharlamov, Nikita; Zachariasssen, Maria

    2016-01-01

    This paper presents results from eye-tracking studies of audience interaction and knowledge generation in the technology-enhanced health promotion exhibition PULSE at a science centre in Copenhagen, Denmark. The main purpose of the study was to understand what types of knowledge audiences build...... age 6–12. Health promotion technologies are defined here, as technologies designed specifically for the purpose of health promotion, be they educational or focused on physical activities. The study was conducted in late 2015 and comprised eight families with children in 2nd-6th grade visiting....... Results also showed that the exhibition supported both themes related to discovering new types of physical activity and themes of collaboration and social family activity....

  1. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

    Directory of Open Access Journals (Sweden)

    Claudia P. Miller

    2011-01-01

    Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

  2. Enhanced diffusion weighting generated by selective adiabatic pulse trains

    Science.gov (United States)

    Sun, Ziqi; Bartha, Robert

    2007-09-01

    A theoretical description and experimental validation of the enhanced diffusion weighting generated by selective adiabatic full passage (AFP) pulse trains is provided. Six phantoms (Ph-1-Ph-6) were studied on a 4 T Varian/Siemens whole body MRI system. Phantoms consisted of 2.8 cm diameter plastic tubes containing a mixture of 10 μm ORGASOL polymer beads and 2 mM Gd-DTPA dissolved in 5% agar (Ph-1) or nickel(II) ammonium sulphate hexahydrate doped (56.3-0.8 mM) water solutions (Ph-2-Ph-6). A customized localization by adiabatic selective refocusing (LASER) sequence containing slice selective AFP pulse trains and pulsed diffusion gradients applied in the phase encoding direction was used to measure 1H 2O diffusion. The b-value associated with the LASER sequence was derived using the Bloch-Torrey equation. The apparent diffusion coefficients measured by LASER were comparable to those measured by a conventional pulsed gradient spin-echo (PGSE) sequence for all phantoms. Image signal intensity increased in Ph-1 and decreased in Ph-2-Ph-6 as AFP pulse train length increased while maintaining a constant echo-time. These experimental results suggest that such AFP pulse trains can enhance contrast between regions containing microscopic magnetic susceptibility variations and homogeneous regions in which dynamic dephasing relaxation mechanisms are dominant.

  3. One Step Hydrogen Generation Through Sorption Enhanced Reforming

    Energy Technology Data Exchange (ETDEWEB)

    Mays, Jeff [Gas Technology Inst., Des Plaines, IL (United States)

    2017-08-03

    One-step hydrogen generation, using Sorption Enhanced Reforming (SER) technology, is an innovative means of providing critical energy and environmental improvements to US manufacturing processes. The Gas Technology Institute (GTI) is developing a Compact Hydrogen Generator (CHG) process, based on SER technology, which successfully integrates previously independent process steps, achieves superior energy efficiency by lowering reaction temperatures, and provides pathways to doubling energy productivity with less environmental pollution. GTI’s prior CHG process development efforts have culminated in an operational pilot plant. During the initial pilot testing, GTI identified two operating risks- 1) catalyst coating with calcium aluminate compounds, 2) limited solids handling of the sorbent. Under this contract GTI evaluated alternative materials (one catalyst and two sorbents) to mitigate both risks. The alternate catalyst met performance targets and did not experience coating with calcium aluminate compounds of any kind. The alternate sorbent materials demonstrated viable operation, with one material enabling a three-fold increase in sorbent flow. The testing also demonstrated operation at 90% of its rated capacity. Lastly, a carbon dioxide co-production study was performed to assess the advantage of the solid phase separation of carbon dioxide- inherent in the CHG process. Approximately 70% lower capital cost is achievable compared to SMR-based hydrogen production with CO2 capture, as well as improved operating costs.

  4. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection.

    Science.gov (United States)

    Pinto, Amelia K; Brien, James D; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V; Barrett, Alan D; Shresta, Sujan; Diamond, Michael S

    2015-09-15

    With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre(+) Ifnar(flox/flox) [denoted as Ifnar(f/f) herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre(+) Ifnar(f/f) mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre(+) Ifnar(f/f) mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. Although dengue virus (DENV) infects hundreds of millions of people annually and results in morbidity and mortality on a global scale, there are no approved antiviral treatments or vaccines. Part of the difficulty in evaluating therapeutic candidates is the lack of small animal models that are permissive to DENV and recapitulate the clinical features

  5. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

    Science.gov (United States)

    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  6. Transdermal therapeutic system of enalapril maleate using piperidine as penetration enhancer.

    Science.gov (United States)

    Aqil, M; Bhavna; Chowdhary, I; Sultana, Y; Talegaonkar, S; Ahmad, F J; Ali, M M

    2008-04-01

    The aim of this work was to formulate transdermal therapeutic system (TTS) of an antihypertensive drug, enalapril maleate (EM) using a new penetration enhancer, piperidine hydrochloride (PH), belonging to the class of Dihydropyridines. The TTS of EM was prepared by solvent evaporation technique using polymers Eudragit E100 and polyvinyl pyrrolidone K-30 in varying ratios, 5% w/w dibutylphthalate as plasticizer and 10% w/w PH as penetration enhancer. The TTS was evaluated for in-vitro drug release using paddle over disc method and ex-vivo skin permeation using modified Keshary and Chein diffusion cell. The interaction studies were carried out by comparing the results of assay, UV and TLC analysis for pure drug and medicated and TTS formulation. Skin irritation potential of TTS was assessed by visual examination of treated rat skin. Stability studies were conducted according to ICH guidelines at a temperature of 40+/-0.5 degrees C and 75+/-5% RH. The optimized formulation was evaluated for preclinical bioavailability and antihypertensive efficacy using albino rat model. The optimized formulation provided 87.3% drug release in-vitro and a flux of 380 microg/cm(2)/hr over a period of 48 hours. No chemical interaction was found between the drug and excipients and there were no signs of skin irritation on application of patch. The optimized formulation was stable with a tentative shelf life of two years. Significant fall in BP (p<0.001) was observed in experimental hypertensive rats which was maintained for 2 days. There was 3 fold improvement in bioavailability with TTS vis-à-vis marketed tablet (AUC(0 to t) : 1253.9 ng.h/ml vs. 422.88 ng.h/ml). These preclinicial studies indicate the feasibility of matrix-type TTS of EM for 2 day management of hypertension. Further studies on human beings are warranted to establish clinical utility of the above TTS.

  7. Nanodiamonds enhance therapeutic efficacy of doxorubicin in treating metastatic hormone-refractory prostate cancer.

    Science.gov (United States)

    Salaam, Amanee D; Hwang, Patrick T J; Poonawalla, Aliza; Green, Hadiyah N; Jun, Ho-wook; Dean, Derrick

    2014-10-24

    Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer (HRPC). To improve the efficacy of doxorubicin (DOX) for treating chemoresistant disease, the feasibility of using nanodiamond (ND) particles was investigated. Utilizing the pH responsive properties of ND, a novel protocol for complexing NDs and DOX was developed using a pH 8.5 coupling buffer. The DOX loading efficiency, loading on the NDs, and pH responsive release characteristics were determined utilizing UV-Visible spectroscopy. The effects of the ND-DOX on HRPC cell line PC3 were evaluated with MTS and live/dead cell viability assays. ND-DOX displayed exceptional loading efficiency (95.7%) and drug loading on NDs (23.9 wt%) with optimal release at pH 4 (80%). In comparison to treatment with DOX alone, cell death significantly increased when cells were treated with ND-DOX complexes demonstrating a 50% improvement in DOX efficacy. Of the tested treatments, ND-DOX with 2.4 μg mL(-1) DOX exhibited superior efficacy (60% cell death). ND-DOX with 1.2 μg mL(-1) DOX achieved 42% cell death, which was comparable to cell death in response to 2.4 μg mL(-1) of free DOX, suggesting that NDs aid in decreasing the DOX dose necessary to achieve a chemotherapeutic efficacy. Due to its enhanced efficacy, ND-DOX can be used to successfully treat HRPC and potentially decrease the clinical side effects of DOX.

  8. Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma

    Science.gov (United States)

    Tsend-Ayush, Altansukh; Zhu, Xiumei; Ding, Yu; Yao, Jianxu; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-05-01

    Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (˜141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.

  9. Enhanced Component Performance Study. Emergency Diesel Generators 1998–2013

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, John Alton [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-11-01

    This report presents an enhanced performance evaluation of emergency diesel generators (EDGs) at U.S. commercial nuclear power plants. This report evaluates component performance over time using Institute of Nuclear Power Operations (INPO) Consolidated Events Database (ICES) data from 1998 through 2013 and maintenance unavailability (UA) performance data using Mitigating Systems Performance Index (MSPI) Basis Document data from 2002 through 2013. The objective is to present an analysis of factors that could influence the system and component trends in addition to annual performance trends of failure rates and probabilities. The factors analyzed for the EDG component are the differences in failures between all demands and actual unplanned engineered safety feature (ESF) demands, differences among manufacturers, and differences among EDG ratings. Statistical analyses of these differences are performed and results showing whether pooling is acceptable across these factors. In addition, engineering analyses were performed with respect to time period and failure mode. The factors analyzed are: sub-component, failure cause, detection method, recovery, manufacturer, and EDG rating.

  10. Enhanced Component Performance Study: Emergency Diesel Generators 1998–2014

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, John Alton [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2015-11-01

    This report presents an enhanced performance evaluation of emergency diesel generators (EDGs) at U.S. commercial nuclear power plants. This report evaluates component performance over time using (1) Institute of Nuclear Power Operations (INPO) Consolidated Events Database (ICES) data from 1998 through 2014 and (2) maintenance unavailability (UA) performance data from Mitigating Systems Performance Index (MSPI) Basis Document data from 2002 through 2014. The objective is to show estimates of current failure probabilities and rates related to EDGs, trend these data on an annual basis, determine if the current data are consistent with the probability distributions currently recommended for use in NRC probabilistic risk assessments, show how the reliability data differ for different EDG manufacturers and for EDGs with different ratings; and summarize the subcomponents, causes, detection methods, and recovery associated with each EDG failure mode. Engineering analyses were performed with respect to time period and failure mode without regard to the actual number of EDGs at each plant. The factors analyzed are: sub-component, failure cause, detection method, recovery, manufacturer, and EDG rating. Six trends with varying degrees of statistical significance were identified in the data.

  11. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy

    Directory of Open Access Journals (Sweden)

    K. M. Maheswari

    2014-01-01

    Full Text Available The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs of Amlodipine Besylate (AMLO to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC and methyl cellulose (MC along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30, and sodium lauryl sulphate (SLS as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

  12. Use of Xylitol To Enhance the Therapeutic Efficacy of Polymethylmethacrylate-Based Antibiotic Therapy in Treatment of Chronic Osteomyelitis

    Science.gov (United States)

    Beenken, Karen E.; Bradney, Laura; Bellamy, William; Skinner, Robert A.; McLaren, Sandra G.; Gruenwald, M. Johannes; Spencer, Horace J.; Smith, James K.; Haggard, Warren O.

    2012-01-01

    Using a rabbit model of postsurgical osteomyelitis, we demonstrate that incorporation of xylitol into polymethylmethacrylate (PMMA) bone cement enhances the elution of daptomycin under in vivo conditions. We also demonstrate that this can be correlated with an improved therapeutic outcome in the treatment of a chronic bone infection following surgical debridement. PMID:22948866

  13. G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?

    Directory of Open Access Journals (Sweden)

    Takeharu Kanazawa

    2015-08-01

    Full Text Available Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor. In this review, we discuss the roles that galanin receptor type 1 (GALR1 and type 2 (GALR2, tachykinin receptor type 1 (TACR1, and somatostatin receptor type 1 (SST1 play in HNSCC. GALR1 inhibits proliferation of HNSCC cells though ERK1/2-mediated effects on cell cycle control proteins such as p27, p57, and cyclin D1, whereas GALR2 inhibits cell proliferation and induces apoptosis in HNSCC cells. Hypermethylation of GALR1, GALR2, TACR1, and SST1 is associated with significantly reduced disease-free survival and a higher recurrence rate. Although their overall activities varies, each of these GPCRs has value as both a prognostic factor and a therapeutic target. These data indicate that further study of GPCRs is a promising strategy that will enrich pharmacogenomics and prognostic research in HNSCC.

  14. The Use of a Therapeutic Jurisprudence Approach to the Teaching and Learning of Law to a New Generation of Law Students in South Africa

    Directory of Open Access Journals (Sweden)

    E Fourie

    2012-03-01

    Full Text Available In rapidly changing social, economic and intellectual environments it is imperative that teaching and learning should be transformed from being primarily concerned with the transmission of knowledge (learning about to being primarily concerned with the practices of a knowledge domain (learning to be. Law lecturers are faced with a new generation of law students, many of whom may be the first in their families to enter university, and one of the important challenges that we face, when educating law students, is how to enable these students to take their place in a very important profession. To meet this challenge it is necessary to instill skills that will be beneficial to the profession, future clients and the community as a whole. We at the University of Johannesburg are endeavouring to do so through embracing a therapeutic jurisprudence approach that focuses on the well-being of the student, the client and the community. The integration of therapeutic jurisprudence throughout the law student's studies, starting with orientation and continuing through to the final-year clinical experience, will enhance the therapeutic outcomes for all of the parties involved. A therapeutic jurisprudence approach, combined with appropriate teaching and learning methods, will enhance the student's interpersonal skills and writing and reading skills. The teaching methods invoked include role-play to transform formal knowledge into living knowledge, thereby stimulating students' natural practical curiosity and creating a learning environment that supports collaboration and encourages students to act purposefully in such an environment. This article discusses the teaching of first-generation students and how to overcome the existing social, cultural, economic and linguistic barriers by using a therapeutic jurisprudence approach, while upholding the values that should guide legal practice, such as integrity and respect for diversity and human dignity. The

  15. Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging.

    Science.gov (United States)

    Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R

    2013-05-01

    Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

  16. Colon-targeted delivery of piceatannol enhances anti-colitic effects of the natural product: potential molecular mechanisms for therapeutic enhancement.

    Science.gov (United States)

    Yum, Soohwan; Jeong, Seongkeun; Lee, Sunyoung; Nam, Joon; Kim, Wooseong; Yoo, Jin-Wook; Kim, Min-Soo; Lee, Bok Luel; Jung, Yunjin

    2015-01-01

    Piceatannol (PCT), an anti-colitic natural product, undergoes extensive Phase II hepatic metabolism, resulting in very low bioavailability. We investigated whether colon-targeted delivery of PCT could enhance anti-colitic effects and how therapeutic enhancement occurred at the molecular level. Molecular effects of PCT were examined in human colon carcinoma cells and inflamed colons. The anti-colitic effects of PCT in a colon-targeted capsule (colon-targeted PCT) were compared with PCT in a gelatin capsule (conventional PCT) in a trinitrobenzene sulfonic acid-induced rat colitis model. Colon-targeted PCT elicited greatly enhanced recovery of the colonic inflammation. In HCT116 cells, PCT inhibited nuclear factor kappaB while activating anti-colitic transcription factors, nuclear factor-erythroid 2 (NF-E2) p45-related factor 2, and hypoxia-inducible factor-1. Colon-targeted PCT, but not conventional PCT, modulated production of the target gene products of the transcription factors in the inflamed colonic tissues. Rectal administration of PCT, which simulates the therapeutic action of colon-targeted PCT, also ameliorated rat colitis and reproduced the molecular effects in the inflamed colonic tissues. Colon-targeted delivery increased therapeutic efficacy of PCT against colitis, likely resulting from multitargeted effects exerted by colon-targeted PCT. The drug delivery technique may be useful for therapeutic optimization of anti-colitic lead compounds including natural products.

  17. Copper(II)-Graphitic Carbon Nitride Triggered Synergy: Improved ROS Generation and Reduced Glutathione Levels for Enhanced Photodynamic Therapy.

    Science.gov (United States)

    Ju, Enguo; Dong, Kai; Chen, Zhaowei; Liu, Zhen; Liu, Chaoqun; Huang, Yanyan; Wang, Zhenzhen; Pu, Fang; Ren, Jinsong; Qu, Xiaogang

    2016-09-12

    Graphitic carbon nitride (g-C3 N4 ) has been used as photosensitizer to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). However, its therapeutic efficiency was far from satisfactory. One of the major obstacles was the overexpression of glutathione (GSH) in cancer cells, which could diminish the amount of generated ROS before their arrival at the target site. Herein, we report that the integration of Cu(2+) and g-C3 N4 nanosheets (Cu(2+) -g-C3 N4 ) led to enhanced light-triggered ROS generation as well as the depletion of intracellular GSH levels. Consequently, the ROS generated under light irradiation could be consumed less by reduced GSH, and efficiency was improved. Importantly, redox-active species Cu(+) -g-C3 N4 could catalyze the reduction of molecular oxygen to the superoxide anion or hydrogen peroxide to the hydroxyl radical, both of which facilitated the generation of ROS. This synergy of improved ROS generation and GSH depletion could enhance the efficiency of PDT for cancer therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Can Generating Representations Enhance Learning with Dynamic Visualizations?

    Science.gov (United States)

    Zhang, Zhihui Helen; Linn, Marcia C.

    2011-01-01

    This study explores the impact of asking middle school students to generate drawings of their ideas about chemical reactions on integrated understanding. Students explored atomic interactions during hydrogen combustion using a dynamic visualization. The generation group drew their ideas about how the reaction takes place at the molecular level.…

  19. Tapered photonic crystal fibers for blue-enhanced supercontinuum generation

    DEFF Research Database (Denmark)

    Møller, Uffe; Sørensen, Simon Toft; Larsen, Casper

    2012-01-01

    Tapering of photonic crystal fibers is an effective way of shifting the blue edge of a supercontinuum spectrum down in the deep-blue. We discuss the optimum taper profile for enhancing the power in the blue edge....

  20. Therapeutic intraspinal stimulation to generate activity and promote long-term recovery

    Directory of Open Access Journals (Sweden)

    Sarah E. Mondello

    2014-02-01

    Full Text Available Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury. This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

  1. Therapeutic potential of regulatory macrophages generated from peritoneal dialysate in adriamycin nephropathy.

    Science.gov (United States)

    Cao, Qi; Wang, Yiping; Wang, Changqi; Wang, Xin M; Lee, Vincent W S; Zheng, Guoping; Zhao, Ye; Alexander, Stephen I; Harris, David C H

    2018-04-01

    Cell therapy using macrophages requires large amounts of cells, which are difficult to collect from patients. Patients undergoing peritoneal dialysis (PD) discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages can be modulated to become regulatory macrophages, which have shown great promise as a therapeutic strategy in experimental kidney disease and human kidney transplantation. This study aimed to examine the potential of using peritoneal macrophages (PMs) from peritoneal dialysate to treat kidney disease. Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both patients and mice undergoing PD. PMs from patients and mice undergoing PD were more mature than peripheral monocytes/macrophages, as shown by low expression of C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro culture. PMs from patients and mice undergoing PD displayed normal macrophage function and could be modulated into a regulatory (M2) phenotype. In vivo, adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively protected against kidney injury in mice with adriamycin nephropathy (AN). Importantly, the transfused peritoneal M2 macrophages maintained their M2 phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice undergoing PD exhibited conventional macrophage features. Peritoneal M2 macrophages derived from PD mice are able to reduce kidney injury in AN, suggesting that peritoneal macrophages from patients undergoing PD may have the potential for clinical therapeutic application.

  2. Enhanced ultrasonic focusing and temperature elevation via a therapeutic ultrasonic transducer with sub-wavelength periodic structure

    Science.gov (United States)

    Li, Chenghai; Yang, Yanye; Guo, Xiasheng; Tu, Juan; Huang, Pintong; Li, Faqi; Zhang, Dong

    2017-07-01

    In this paper, we report a therapeutic ultrasonic transducer with a sub-wavelength periodic structure, by which ultrasonic focusing and temperature elevation have been significantly enhanced compared to a conventional concave transducer with the same size. Enhanced acoustic focusing was demonstrated by both measuring and simulating acoustic pressure and temperature elevation. Compared to the conventional concave transducer, the proposed transducer exhibited stronger capacity in elevating acoustic pressure and temperature rise in the focal region, in which extraordinary acoustic transmission close to Wood's anomaly could be modulated by the spherically curved surface. This work is believed to possess great clinical potential in the safe and efficient application of ultrasonic therapy.

  3. Evaluation of Therapeutic Tissue Crosslinking (TXL) for Myopia Using Second Harmonic Generation Signal Microscopy in Rabbit Sclera.

    Science.gov (United States)

    Zyablitskaya, Mariya; Takaoka, Anna; Munteanu, Emilia L; Nagasaki, Takayuki; Trokel, Stephen L; Paik, David C

    2017-01-01

    Second harmonic generation signals (SHG) are emitted preferentially from collagenous tissue structures and have been used to evaluate photochemically-induced (CXL) crosslinking changes in the cornea. Since therapeutic tissue crosslinking (TXL) using sodium hydroxymethylglycinate (SMG) of the sclera is a potential treatment for high myopia, we explored the use of SHG microscopy to evaluate the effects. Single sub-Tenon's (sT) injections (400 μL) using SMG (40-400 mM) were made at the equatorial 12 o'clock position of the right eye of cadaveric rabbit heads (n = 16 pairs). After 3.5 hours, confocal microscopy (CM) was performed using 860 nm two-photon excitation and 400 to 450 nm emission. Pixel density and fiber bundle "waviness" analyses were performed on the images. Crosslinking effects were confirmed using thermal denaturation (Tm) temperature. Comparison experiments with riboflavin photochemical crosslinking were done. Therapeutic tissue crosslinking localization studies indicated that crosslinking changes occurred at the site of injection and in adjacent sectors. Second harmonic generation signals revealed large fibrous collagenous bundled structures that displayed various degrees of waviness. Histogram analysis showed a nearly 6-fold signal increase in 400 mM SMG over 40 mM. This corresponded to a ΔTm = 13°C for 400 mM versus ΔTm = 4°C for 40 mM. Waviness analysis indicated increased fiber straightening as a result of SMG CXL. Second harmonic generation signal intensity and fiber bundle waviness is altered by scleral tissue crosslinking using SMG. These changes provide insights into the macromolecular changes that are induced by therapeutic crosslinking technology and may provide a method to evaluate connective tissue protein changes induced by scleral crosslinking therapies.

  4. Environmental enrichment and brain repair: harnessing the therapeutic effects of cognitive stimulation and physical activity to enhance experience-dependent plasticity.

    Science.gov (United States)

    Hannan, A J

    2014-02-01

    Environmental enrichment (EE) increases levels of novelty and complexity, inducing enhanced sensory, cognitive and motor stimulation. In wild-type rodents, EE has been found to have a range of effects, such as enhancing experience-dependent cellular plasticity and cognitive performance, relative to standard-housed controls. Whilst environmental enrichment is of course a relative term, dependent on the nature of control environmental conditions, epidemiological studies suggest that EE has direct clinical relevance to a range of neurological and psychiatric disorders. EE has been demonstrated to induce beneficial effects in animal models of a wide variety of brain disorders. The first evidence of beneficial effects of EE in a genetically targeted animal model was generated using Huntington's disease transgenic mice. Subsequent studies found that EE was also therapeutic in mouse models of Alzheimer's disease, consistent with epidemiological studies of relevant environmental modifiers. EE has also been found to ameliorate behavioural, cellular and molecular deficits in animal models of various neurological and psychiatric disorders, including Parkinson's disease, stroke, traumatic brain injury, epilepsy, multiple sclerosis, depression, schizophrenia and autism spectrum disorders. This review will focus on the effects of EE observed in animal models of neurodegenerative brain diseases, at molecular, cellular and behavioural levels. The proposal that EE may act synergistically with other approaches, such as drug and cell therapies, to facilitate brain repair will be discussed. I will also discuss the therapeutic potential of 'enviromimetics', drugs which mimic or enhance the therapeutic effects of cognitive activity and physical exercise, for both neuroprotection and brain repair. © 2013 British Neuropathological Society.

  5. Novel Receiver-Enhanced Solar Vapor Generation: Review and Perspectives

    Directory of Open Access Journals (Sweden)

    Aikifa Raza

    2018-01-01

    Full Text Available Efficient solar vapor/steam generation is important for various applications ranging from power generation, cooling, desalination systems to compact and portable devices like drinking water purification and sterilization units. However, conventional solar steam generation techniques usually rely on costly and cumbersome optical concentration systems and have relatively low efficiency due to bulk heating of the entire liquid volume. Recently, by incorporating novel light harvesting receivers, a new class of solar steam generation systems has emerged with high vapor generation efficiency. They are categorized in two research streams: volumetric and floating solar receivers. In this paper, we review the basic principles of these solar receivers, the mechanism involving from light absorption to the vapor generation, and the associated challenges. We also highlight the two routes to produce high temperature steam using optical and thermal concentration. Finally, we propose a scalable approach to efficiently harvest solar energy using a semi-spectrally selective absorber with near-perfect visible light absorption and low thermal emittance. Our proposed approach represents a new development in thermally concentrated solar distillation systems, which is also cost-effective and easy to fabricate for rapid industrial deployment.

  6. Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment.

    Science.gov (United States)

    Kintzing, James R; Filsinger Interrante, Maria V; Cochran, Jennifer R

    2016-12-01

    Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell-surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity. In this review we highlight some of these strategies and provide examples of modified and engineered proteins under development as preclinical and clinical-stage drug candidates for the treatment of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy.

    LENUS (Irish Health Repository)

    Wander, Seth A

    2011-04-01

    Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

  8. Molecular Design Properties of OxyVita Hemoglobin, a New Generation Therapeutic Oxygen Carrier: A Review

    Directory of Open Access Journals (Sweden)

    Hanna Wollocko

    2011-12-01

    Full Text Available OxyVita Hb is a new generation hemoglobin based oxygen carrier (HBOC produced through modification of a zero-linked polymerization mechanism using activators which incorporate cross-linked bovine tetramer hemoglobin into “super-polymeric” macromolecules (Average molecular weight = 17 MDa for the purpose of oxygen delivery when whole blood or packed red cells are not available. This molecular design approach was generated in order to address several fundamental biochemical and physiological weaknesses of previous generations of HBOCs. Observation during pre-clinical and clinical studies provided evidence that these early generation acellular HBOCs were directly associated with loss of retention within the circulatory system, extravasation across endothelial tissue membranes due to their small molecular size leading to arterial and venous vasoconstriction with coupled increases in mean arterial pressure (MAP. The inherent increase in molecular size and structural stability of the OxyVita Hb is a direct response to addressing these serious weaknesses that have occurred during the evolution of HBOC development within the past two decades. The nature of the zero-linked synthetic route eliminates any chemical linkers remaining in the product, eliminating side reaction concerns, such as reversibility and decomposition due to weak chemical bonds, dependency on temperature and pressure, and residual toxicity.

  9. Phenotype and functional evaluation of ex vivo generated antigen-specific immune effector cells with potential for therapeutic applications

    Directory of Open Access Journals (Sweden)

    Wang Yichen

    2009-08-01

    Full Text Available Abstract Ex vivo activation and expansion of lymphocytes for adoptive cell therapy has demonstrated great success. To improve safety and therapeutic efficacy, increased antigen specificity and reduced non-specific response of the ex vivo generated immune cells are necessary. Here, using a complete protein-spanning pool of pentadecapeptides of the latent membrane protein 2A (LMP2A of Epstein-Barr virus (EBV, a weak viral antigen which is associated with EBV lymphoproliferative diseases, we investigated the phenotype and function of immune effector cells generated based on IFN-γ or CD137 activation marker selection and dendritic cell (DC activation. These ex vivo prepared immune cells exhibited a donor- and antigen-dependent T cell response; the IFN-γ-selected immune cells displayed a donor-related CD4- or CD8-dominant T cell phenotype; however, the CD137-enriched cells showed an increased ratio of CD4 T cells. Importantly, the pentadecapeptide antigens accessed both class II and class I MHC antigen processing machineries and effectively activated EBV-specific CD4 and CD8 T cells. Phenotype and kinetic analyses revealed that the IFN-γ and the CD137 selections enriched more central memory T (Tcm cells than did the DC-activation approach, and after expansion, the IFN-γ-selected effector cells showed the highest level of antigen-specificity and effector activities. While all three approaches generated immune cells with comparable antigen-specific activities, the IFN-γ selection followed by ex vivo expansion produced high quality and quantity of antigen-specific effector cells. Our studies presented the optimal approach for generating therapeutic immune cells with potential for emergency and routine clinical applications.

  10. Extracellular Histones Increase Tissue Factor Activity and Enhance Thrombin Generation by Human Blood Monocytes.

    Science.gov (United States)

    Gould, Travis J; Lysov, Zakhar; Swystun, Laura L; Dwivedi, Dhruva J; Zarychanski, Ryan; Fox-Robichaud, Alison E; Liaw, Patricia C

    2016-12-01

    Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. Tissue factor (TF) activity assays were performed on histone-treated THP-1 cells and blood monocytes. Exposure of monocytic cells to histones resulted in increases in TF activity, TF antigen, and phosphatidylserine exposure. Histones modulate the procoagulant activity via engagement of Toll-like receptors 2 and 4, and this effect was abrogated with inhibitory antibodies. Increased TF activity of histone-treated cells corresponded to enhanced thrombin generation in plasma determined by calibrated automated thrombography. Finally, TF activity was increased on monocytes exposed to plasma from septic patients, an effect that was attenuated in plasma from patients receiving unfractionated heparin (UFH). Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.

  11. Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications.

    Science.gov (United States)

    Balasubramanyam, M; Koteswari, A Adaikala; Kumar, R Sampath; Monickaraj, S Finny; Maheswari, J Uma; Mohan, V

    2003-12-01

    There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.

  12. Gold nanolenses generated by laser ablation-efficient enhancing structure for surface enhanced Raman scattering analytics and sensing.

    Science.gov (United States)

    Kneipp, Janina; Li, Xiangting; Sherwood, Margaret; Panne, Ulrich; Kneipp, Harald; Stockman, Mark I; Kneipp, Katrin

    2008-06-01

    Nanoaggregates formed by metal spheres of different radii and interparticle distances represent finite, deterministic, self-similar systems that efficiently concentrate optical fields and act as "nanolenses". Here we verify experimentally the theoretical concept of nanolenses and explore their potential as enhancing nanostructures in surface enhanced Raman scattering (SERS). Self-similar structures formed by gold nanospheres of different sizes are generated by laser ablation from solid gold into water. These nanolenses exhibit SERS enhancement factors on the order of 10(9). The "chemically clean" preparation process provides several advantages over chemically prepared nanoaggregates and makes the stable and biocompatible gold nanolenses potent enhancing structures for various analytical and sensing applications.

  13. Enhanced gene expression of systemically administered plasmid DNA inthe liver with therapeutic ultrasound and microbubbles

    NARCIS (Netherlands)

    Raju, B.I.; Leyvi, E.; Seip, R.; Sethuraman, S.; Luo, X.; Bird, A.; Li, S.; Koeberl, D.

    2012-01-01

    Ultrasound mediated delivery (USMD) of novel therapeutic agents in the presence of microbubbles is a potentially safe and effective method for gene therapy offering many desired characteristics such as low toxicity, potential for repeated treatment, and organ specificity.In this study we tested the

  14. 78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

    Science.gov (United States)

    2013-12-23

    ...; nationalized), U.S. Patent Application 7,371,225, European Patent Application 03756863.1, Australian Patent 2003299140, to Medicenna Therapeutics, Inc. having a principle place of business in 1075 West Georgia St... be made available for public inspection, and, to the extent permitted by law, will not be released...

  15. Herb-Herb Combination for Therapeutic Enhancement and Advancement: Theory, Practice and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Christopher Wai Kei Lam

    2013-05-01

    Full Text Available Herb-herb combinations have been used in Chinese medicine practice for thousands of years, yet scientific evidence of their therapeutic benefits is lacking. With increasing interest in shifting from the one-drug-one-target paradigm to combination therapy or polypharmacy to achieve therapeutic benefits for a number of diseases, there is momentum to explore new knowledge by tapping the past empirical experiences of herb-herb combinations. This review presents an overview of the traditional concept and practice of herb-herb combination in Chinese medicine, and highlights the available scientific and clinical evidence to support the combined use of herbs. It is hoped that such information would provide a lead for developing new approaches for future therapeutic advancement and pharmaceutical product development. Very likely modern technologies combined with innovative research for the quality control of herbal products, identification of active components and understanding of the molecular mechanism, followed by well-designed animal and clinical studies would pave the way in advancing the wealth of empirical knowledge from herb-herb combination to new therapeutic modalities.

  16. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential into the Brain using MRI-Guided Focused Ultrasound

    Science.gov (United States)

    Etame, Arnold B.; Diaz, Roberto J.; O’Reilly, Meaghan A.; Smith, Christian A.; Mainprize, Todd G.; Hynynen, Kullervo; Rutka, James T.

    2014-01-01

    The blood brain barrier (BBB) is a major impediment to the delivery of therapeutics into the central nervous system (CNS). Gold nanoparticles (AuNPs) have been successfully employed in multiple potential therapeutic and diagnostic applications outside the CNS. However, AuNPs have very limited biodistribution within the CNS following intravenous administration. Magnetic resonance imaging guided focused ultrasound (MRgFUS) is a novel technique that can transiently increase BBB permeability allowing delivery of therapeutics into the CNS. MRgFUS has not been previously employed for delivery of AuNPs into the CNS. This work represents the first demonstration of focal enhanced delivery of AuNPs into the CNS using MRgFUS in a rat model both safely and effectively. Histologic visualization and analytical quantification of AuNPs within the brain parenchyma suggest BBB transgression. These results suggest a role for MRgFUS in the delivery of AuNPs with therapeutic potential into the CNS for targeting neurological diseases. PMID:22349099

  17. New String Reconfiguration Technique for Residential Photovoltaic System Generation Enhancement

    Directory of Open Access Journals (Sweden)

    CORBA, Z.

    2016-02-01

    Full Text Available Improvement of photovoltaic (PV power plant performance under partial shading conditions aiming to increase electrical energy generation is in the focus of this research. This paper proposes the performance optimization of PV power plant under partial shading conditions by new PV string reconfiguration technique. The Matlab/Simulink model is used to simulate the operation of the PV string under partial shading conditions and with the proposed recombination technique. Simulated operational conditions have experimentally been verified by string characteristics measurement on the existing roof-top PV system at the Faculty of Technical Sciences in Novi Sad. Simulation and experimental results showed a high degree of matching, while the obtained values proved that proposed method leads to output power increase and higher PV system generation in PV string operation under partial shading.

  18. Therapeutic response assessment of percutaneous radiofrequency ablation for hepatocellular carcinoma: Utility of contrast-enhanced agent detection imaging

    International Nuclear Information System (INIS)

    Kim, Chan Kyo; Choi, Dongil; Lim, Hyo K.; Kim, Seung Hoon; Lee, Won Jae; Kim, Min Ju; Lee, Ji Yeon; Jeon, Yong Hwan; Lee, Jongmee; Lee, Soon Jin; Lim, Jae Hoon

    2005-01-01

    Purpose: To assess the utility of contrast-enhanced agent detection imaging (ADI) in the assessment of the therapeutic response to percutaneous radiofrequency (RF) ablation in patients with hepatocellular carcinoma (HCC). Materials and methods: Ninety patients with a total of 97 nodular HCCs (mean, 2.1 ± 1.3 cm; range, 1.0-5.0 cm) treated with percutaneous RF ablation under the ultrasound guidance were evaluated with contrast-enhanced ADI after receiving an intravenous bolus injection of a microbubble contrast agent (SH U 508A). We obtained serial contrast-enhanced ADI images during the time period from 15 to 90 s after the initiation of the bolus contrast injection. All of the patients underwent a follow-up four-phase helical CT at 1 month after RF ablation, which was then repeated at 2-4 month intervals during a period of at least 12 months. The results of the contrast-enhanced ADI were compared with those of the follow-up CT in terms of the presence or absence of residual unablated tumor and local tumor progression in the treated lesions. Results: On contrast-enhanced ADI, technical success was obtained in 94 (97%) of the 97 HCCs, while residual unablated tumors were found in three HCCs (3%). Two of the three tumors that were suspicious (was not proven) for incomplete ablation were subjected to additional RF ablation. The remaining one enhancing lesion that was suspicious of a residual tumor on contrast-enhanced ADI was revealed to be reactive hyperemia at the 1-month follow-up CT. Therefore; the diagnostic concordance between the contrast-enhanced ADI and 1-month follow-up CT was 99%. Of the 94 ablated HCCs without residual tumors on both the contrast-enhanced ADI and 1-month follow-up CT after the initial RF ablation, five (5%) had CT findings of local tumor progression at a subsequent follow-up CT. Conclusion: Despite its limitations in predicting local tumor progression in the treated tumors, contrast-enhanced ADI is potentially useful for evaluating the

  19. Interpreting therapeutic effect in multiple sclerosis via MRI contrast enhancing lesions: now you see them, now you don't.

    Science.gov (United States)

    Leppert, Ilana R; Narayanan, S; Araújo, D; Giacomini, P S; Lapierre, Y; Arnold, D L; Pike, G B

    2014-04-01

    Gadolinium (Gd) enhancement of multiple sclerosis (MS) lesions on MRI scans is a commonly used outcome measure in therapeutic trials. However, enhancement depends on MRI acquisition parameters that might significantly alter detectability. We investigated how the difference in blood-brain barrier (BBB) permeability threshold between MRI protocols affects lesion detection and apparent enhancement time using dynamic-contrast-enhanced (DCE) MRI. We examined fourty-four relapsing-remitting MS patients with two MRI protocols: 'standard sensitivity' (SS) (1.5 T, single-dose Gd) and 'high sensitivity' (HS) (3 T, triple-dose Gd, delayed acquisition). Eleven patients had at least one enhancing lesion and completed the 1-month follow-up. We acquired DCE-MRI during the HS protocol and calculated BBB permeability. Sixty-five lesions were enhanced with the SS vs. 135 with the HS protocol. The detection threshold of the HS was significantly lower than that of the SS protocol (K trans = 2.64 vs. 4.00E-3 min(-1), p effects of anti-inflammatory therapies on MS lesions.

  20. Male emotional intimacy: how therapeutic men's groups can enhance couples therapy.

    Science.gov (United States)

    Garfield, Robert

    2010-03-01

    Men's difficulty with emotional intimacy is a problem that therapists regularly encounter in working with heterosexual couples in therapy. The first part of this article describes historical and cultural factors that contribute to this dilemma in men's marriages and same-sex friendships. Therapeutic men's groups can provide a corrective experience for men, helping them to develop emotional intimacy skills while augmenting their work in couples therapy. A model for such groups is presented, including guidelines for referral, screening, and collaboration with other therapists. Our therapeutic approach encourages relationship-based learning through direct emotional expression and supportive feedback. We emphasize the development of friendship skills, core attributes of friendship (connection, communication, commitment, and cooperation) that contribute to emotional intimacy in men's relationships. Case examples are included to illustrate how this model works in clinical practice, as well as specific suggestions for further study that could lead to a more evidence-based practice.

  1. Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine.

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Wang, Xijun

    2014-04-01

    Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Second-Generation Phenylthiazole Antibiotics with Enhanced Pharmacokinetic Properties.

    Science.gov (United States)

    Seleem, Mohammed A; Disouky, Ahmed M; Mohammad, Haroon; Abdelghany, Tamer M; Mancy, Ahmed S; Bayoumi, Sammar A; Elshafeey, Ahmed; El-Morsy, Ahmed; Seleem, Mohamed N; Mayhoub, Abdelrahman S

    2016-05-26

    A series of second-generation analogues for 2-(1-(2-(4-butylphenyl)-4-methylthiazol-5-yl)ethylidene)aminoguanidine (1) have been synthesized and tested against methicillin-resistant Staphylococcus aureus (MRSA). The compounds were designed with the objective of improving pharmacokinetic properties. This main aim has been accomplished by replacing the rapidly hydrolyzable Schiff-base moiety of first-generation members with a cyclic, unhydrolyzable pyrimidine ring. The hydrazide-containing analogue 17 was identified as the most potent analogue constructed thus far. The corresponding amine 8 was 8 times less active. Finally, incorporating the nitrogenous side chain within an aromatic system completely abolished the antibacterial character. Replacement of the n-butyl group with cyclic bioisosteres revealed cyclohexenyl analogue 29, which showed significant improvement in in vitro anti-MRSA potency. Increasing or decreasing the ring size deteriorated the antibacterial activity. Compound 17 demonstrated a superior in vitro and in vivo pharmacokinetic profile, providing compelling evidence that this particular analogue is a good drug candidate worthy of further analysis.

  3. Photoconductive switch enhancements for use in Blumlein pulse generators

    International Nuclear Information System (INIS)

    Davanloo, F.; Park, H.; Collins, C. B.; Agee, F. J.

    1999-01-01

    Stacked Blumlein pulse generators developed at the University of Texas at Dallas have produced high-power waveforms with risetimes and repetition rates in the range of 0.2-50 ns and 1-300 Hz, respectively, using a conventional thyratron, spark gap or photoconductive switch. Adaptation of the design has enabled the stacked Blumleins to produce 80 MW, nanosecond pulses with risetimes better than 200 ps into nominally matched loads. The device has a compact line geometry and is commutated by a single GaAs photoconductive switch triggered by a low power laser diode array. Our current investigations involve the switch characteristics that affect the broadening of the current channels in the avalanche, pre-avalanche seedings, the switch lifetime and the durability. This report presents the progress toward improving the GaAs switch operation and lifetime in stacked Blumlein pulsers. Advanced switch treatments including diamond film overcoating are implemented and discussed

  4. Transient Stability Enhancement of the Power System with Wind Generation

    Directory of Open Access Journals (Sweden)

    Ashwani Kumar Chandel

    2011-08-01

    Full Text Available Transient stability analysis of a power system with wind generation has been addressed in this paper. The effects of automatic voltage regulators, power system stabilizers, and static synchronous compensators on transient stability of a power system are investigated. Various simulation results show that addition of power system stabilizer and static synchronous compensators reduce the rotor angle oscillations. However, the static synchronous compensator shows better damping characteristics and improves the stability of the wind integrated system. It has been established that the static synchronous compensator damps out the speed oscillations in the shaft of the constant speed wind turbine. A transient impact index has been proposed to prove that the static compensator damps out the rotor oscillations.

  5. Enhancement of on-site emergency diesel generator reliability

    International Nuclear Information System (INIS)

    Boner, G.L.; Hanners, H.W.

    1979-01-01

    The University of Dayton Research Institute has concluded a program designed to provide NRC/DOR with technical assistance in evaluating the factors leading to improved reliability of on-site emergency diesel generator (DG) units. The program consisted of a comprehensive review of DG maintenance and operating experience and a comparative evaluation of the DG manufacturer's recommendations. This information, will enable the NRC to improve the basis on which it makes regulatory decisions. The primary goal of the program is to better identify the main problem areas which decrease the reliability of the DG units and make recommendations. The report has attained the program objectives by identifying and discussing the more significant problems and presenting the recommended corrective actions. The identified problems have been categorized into three groups as a function of their significance

  6. Selective Coupling Enhances Harmonic Generation of Whispering-Gallery Modes

    Science.gov (United States)

    Trainor, Luke S.; Sedlmeir, Florian; Peuntinger, Christian; Schwefel, Harald G. L.

    2018-02-01

    We demonstrate second-harmonic generation (SHG) in an x -cut congruent lithium niobate (LN) whispering-gallery mode (WGM) resonator. First, we show theoretically that independent control of the coupling of the pump and signal modes is optimal for high conversion rates. A coupling scheme based on our earlier work [F. Sedlmeir et al., Phys. Rev. Applied 7, 024029 (2017), 10.1103/PhysRevApplied.7.024029] is then implemented experimentally to verify this improvement. Thereby, we are able to improve on the efficiency of SHG by more than an order of magnitude by selectively outcoupling using a LN prism, utilizing the birefringence of it and the resonator in kind. This method is also applicable to other nonlinear processes in WGM resonators.

  7. Next Generation Sequencing Identifies Five Major Classes of Potentially Therapeutic Enzymes Secreted by Lucilia sericata Medical Maggots.

    Science.gov (United States)

    Franta, Zdeněk; Vogel, Heiko; Lehmann, Rüdiger; Rupp, Oliver; Goesmann, Alexander; Vilcinskas, Andreas

    2016-01-01

    Lucilia sericata larvae are used as an alternative treatment for recalcitrant and chronic wounds. Their excretions/secretions contain molecules that facilitate tissue debridement, disinfect, or accelerate wound healing and have therefore been recognized as a potential source of novel therapeutic compounds. Among the substances present in excretions/secretions various peptidase activities promoting the wound healing processes have been detected but the peptidases responsible for these activities remain mostly unidentified. To explore these enzymes we applied next generation sequencing to analyze the transcriptomes of different maggot tissues (salivary glands, gut, and crop) associated with the production of excretions/secretions and/or with digestion as well as the rest of the larval body. As a result we obtained more than 123.8 million paired-end reads, which were assembled de novo using Trinity and Oases assemblers, yielding 41,421 contigs with an N50 contig length of 2.22 kb and a total length of 67.79 Mb. BLASTp analysis against the MEROPS database identified 1729 contigs in 577 clusters encoding five peptidase classes (serine, cysteine, aspartic, threonine, and metallopeptidases), which were assigned to 26 clans, 48 families, and 185 peptidase species. The individual enzymes were differentially expressed among maggot tissues and included peptidase activities related to the therapeutic effects of maggot excretions/secretions.

  8. New-Generation, Non-SSRI Antidepressants: Therapeutic Drug Monitoring and Pharmacological Interactions. Part 1: SNRIs, SMSs, SARIs.

    Science.gov (United States)

    Mandrioli, Roberto; Protti, Michele; Mercolini, Laura

    2018-01-01

    New-generation antidepressants (NGAs) are the latest additions to the clinician's arsenal in the fight against depression. After the introduction of selective serotonin reuptake inhibitors (SSRIs), a plethora of other groups followed, identified by their main mechanisms of activity: serotonin and norepinephrine reuptake inhibitors (SNRI); serotonin modulators and stimulators (SMS); serotonin antagonists and reuptake inhibitors (SARI); noradrenergic and selective serotonergic antidepressants (NaSSA); norepinephrine reuptake inhibitors (NeRI); serotonin, norepinephrine and dopamine reuptake inhibitors (SNDRI) or triple reuptake inhibitors (TRI); and melatonin and serotonin agonists (MaSA). Although SSRIs are still the most widely used and well known NGAs, the other groups are increasingly being used in the current therapeutic settings obtaining comparable clinical results, and with tolerability and safety profiles that can often provide significant advantages over those of SSRIs. Scopus and PubMed databases were searched for the most significant papers centered on the medicinal chemistry, pharmacodynamics, pharmacokinetics and analysis in human biological fluids of the following antidepressants: venlafaxine, duloxetine, milnacipran, trazodone, vortioxetine, vilazodone. The main characteristics of commercially available non-SSRI NGAs (belonging to the SNRI, SARI and SMS classes) are described, focusing on the role of analytical methods that can be applied to perform therapeutic drug monitoring (TDM), but also including drug pharmacokinetics, metabolism and interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Next Generation Sequencing Identifies Five Major Classes of Potentially Therapeutic Enzymes Secreted by Lucilia sericata Medical Maggots

    Science.gov (United States)

    Franta, Zdeněk; Vogel, Heiko; Lehmann, Rüdiger; Rupp, Oliver; Goesmann, Alexander; Vilcinskas, Andreas

    2016-01-01

    Lucilia sericata larvae are used as an alternative treatment for recalcitrant and chronic wounds. Their excretions/secretions contain molecules that facilitate tissue debridement, disinfect, or accelerate wound healing and have therefore been recognized as a potential source of novel therapeutic compounds. Among the substances present in excretions/secretions various peptidase activities promoting the wound healing processes have been detected but the peptidases responsible for these activities remain mostly unidentified. To explore these enzymes we applied next generation sequencing to analyze the transcriptomes of different maggot tissues (salivary glands, gut, and crop) associated with the production of excretions/secretions and/or with digestion as well as the rest of the larval body. As a result we obtained more than 123.8 million paired-end reads, which were assembled de novo using Trinity and Oases assemblers, yielding 41,421 contigs with an N50 contig length of 2.22 kb and a total length of 67.79 Mb. BLASTp analysis against the MEROPS database identified 1729 contigs in 577 clusters encoding five peptidase classes (serine, cysteine, aspartic, threonine, and metallopeptidases), which were assigned to 26 clans, 48 families, and 185 peptidase species. The individual enzymes were differentially expressed among maggot tissues and included peptidase activities related to the therapeutic effects of maggot excretions/secretions. PMID:27119084

  10. Surface enhanced second harmonic generation from macrocycle, catenane, and rotaxane thin films : Experiments and theory

    NARCIS (Netherlands)

    Arfaoui, I.; Bermudez, V.; Bottari, G.; De Nadai, C.; Jalkanen, J.P.; Kajzar, F.; Leigh, D.A.; Lubomska, M.; Mendoza, S.M.; Niziol, J.; Rudolf, Petra; Zerbetto, F.

    2006-01-01

    Surface enhanced second harmonic generation (SE SHG) experiments on molecular structures, macrocycles, catenanes, and rotaxanes, deposited as monolayers and multilayers by vacuum sublimation on silver, are reported. The measurements show that the molecules form ordered thin films, where the highest

  11. Optimization of Tapered Photonic Crystal Fibers for Blue-Enhanced Supercontinuum Generation

    DEFF Research Database (Denmark)

    Møller, Uffe; Sørensen, Simon Toft; Larsen, Casper

    2012-01-01

    Tapering of photonic crystal fibers is an effective way of shifting the dispersive wavelength edge of a supercontinuum spectrum down in the deep-blue. We discuss the optimum taper profile for blue-enhanced supercontinuum generation....

  12. Metformin and Anti-Cancer Therapeutics: Hopes for a More Enhanced Armamentarium Against Human Neoplasias?

    Science.gov (United States)

    Christodoulou, Maria-Ioanna; Scorilas, Andreas

    2017-01-01

    Metformin, a natural product from Galega officinalis, is an oral drug, now in the forefront of the therapeutic management of type-2 diabetes mellitus. A series of clinical observations of the last decades, support that metformin may contribute to lowering the risk of cancer development in diabetic patients, and also to improvement of response-to-therapy and survival in individuals with certain types of malignancies. Moreover, several preclinical in vitro and in vivo data indicate that metformin indeed exerts anti-proliferative capacities upon tumor cells mediated through a variety of mechanisms. Interestingly, metformin has been shown to act in synergy with certain anti-cancer agents and also to overcome chemo- and/or radio-resistance of various types of tumors, providing a hopeful rationale for novel therapeutic strategies against cancer development and progression. However, this remains an issue of controversy, since significant contradictions exist among the available data. Limitations of preclinical studies and caveats of epidemiological works, together with significant variances among the several types of cancer and the fact that the mode of metformin's action is largely unknown, make longitudinal surveys urgently needed. Now, a plethora of large clinical trials are active worldwide, aiming at determining the effect of metformin in the prevention or prognosis of a variety of human cancers. If encouraging results arise, metformin will be an attractive candidate adjuvant in the management of human neoplasias, due to its safety, tolerability and low-cost, expected to mitigate adverse effects and no-response parameters of current anti-cancer therapeutics, thus improving the quality of life and survival of cancer patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Climate regulation enhances the value of second generation biofuel technology

    Science.gov (United States)

    Hertel, T. W.; Steinbuks, J.; Tyner, W.

    2014-12-01

    Commercial scale implementation of second generation (2G) biofuels has long been 'just over the horizon - perhaps a decade away'. However, with recent innovations, and higher oil prices, we appear to be on the verge of finally seeing commercial scale implementations of cellulosic to liquid fuel conversion technologies. Interest in this technology derives from many quarters. Environmentalists see this as a way of reducing our carbon footprint, however, absent a global market for carbon emissions, private firms will not factor this into their investment decisions. Those interested in poverty and nutrition see this as a channel for lessening the biofuels' impact on food prices. But what is 2G technology worth to society? How valuable are prospective improvements in this technology? And how are these valuations affected by future uncertainties, including climate regulation, climate change impacts, and energy prices? This paper addresses all of these questions. We employ FABLE, a dynamic optimization model for the world's land resources which characterizes the optimal long run path for protected natural lands, managed forests, crop and livestock land use, energy extraction and biofuels over the period 2005-2105. By running this model twice for each future state of the world - once with 2G biofuels technology available and once without - we measure the contribution of the technology to global welfare. Given the uncertainty in how these technologies are likely to evolve, we consider a range cost estimates - from optimistic to pessimistic. In addition to technological uncertainty, there is great uncertainty in the conditions characterizing our baseline for the 21st century. For each of the 2G technology scenarios, we therefore also consider a range of outcomes for key drivers of global land use, including: population, income, oil prices, climate change impacts and climate regulation. We find that the social valuation of 2G technologies depends critically on climate change

  14. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2012-10-01

    P. Rocca -Serra, P. T. Spellman, H. C. Causton, A. Farne, E. Holloway, R. A. Irizarry, J . Liu, D. S. Maier, M. Miller, K. Petersen, J . Quackenbush, G...REFERENCES: [1] A. J . Zajac, K. Murali-Krishna, J . N. Blattman, and R. Ahmed, “Therapeutic vaccination against chronic viral infection: the...importance of cooperation between CD4+ and CD8+ T cells,” Curr. Opin. Immunol., vol. 10, no. 4, pp. 444–449, Aug. 1998. [2] R. J . Simpson

  15. A study on heat transfer enhancement using flow channel inserts for thermoelectric power generation

    International Nuclear Information System (INIS)

    Lesage, Frédéric J.; Sempels, Éric V.; Lalande-Bertrand, Nathaniel

    2013-01-01

    Highlights: • Thermal enhancement in a thermoelectric liquid generator is tested. • Thermal enhancement is brought upon by flow impeding inserts. • CFD simulations attribute thermal enhancement to velocity field alterations. • Thermoelectric power enhancement is measured and discussed. • Power enhancement relative to adverse pressure drop is investigated. - Abstract: Thermoelectric power production has many potential applications that range from microelectronics heat management to large scale industrial waste-heat recovery. A low thermoelectric conversion efficiency of the current state of the art prevents wide spread use of thermoelectric modules. The difficulties lie in material conversion efficiency, module design, and thermal system management. The present study investigates thermoelectric power improvement due to heat transfer enhancement at the channel walls of a liquid-to-liquid thermoelectric generator brought upon by flow turbulating inserts. Care is taken to measure the adverse pressure drop due to the presence of flow impeding obstacles in order to measure the net thermoelectric power enhancement relative to an absence of inserts. The results illustrate the power enhancement performance of three different geometric forms fitted into the channels of a thermoelectric generator. Spiral inserts are shown to offer a minimal improvement in thermoelectric power production whereas inserts with protruding panels are shown to be the most effective. Measurements of the thermal enhancement factor which represents the ratio of heat flux into heat flux out of a channel and numerical simulations of the internal flow velocity field attribute the thermal enhancement resulting in the thermoelectric power improvement to thermal and velocity field synergy

  16. Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington's disease.

    Science.gov (United States)

    Liu, Yanying; Hettinger, Casey L; Zhang, Dong; Rezvani, Khosrow; Wang, Xuejun; Wang, Hongmin

    2014-05-01

    The ubiquitin proteasome system (UPS) is impaired in Huntington's disease, a devastating neurodegenerative disorder. Sulforaphane, a naturally occurring compound, has been shown to stimulate UPS activity in cell cultures. To test whether sulforaphane enhances UPS function in vivo, we treated UPS function reporter mice ubiquitously expressing the green fluorescence protein (GFP) fused to a constitutive degradation signal that promotes its rapid degradation in the conditions of a healthy UPS. The modified GFP is termed GFP UPS reporter (GFPu). We found that both GFPu and ubiquitinated protein levels were significantly reduced and the three peptidase activities of the proteasome were increased in the brain and peripheral tissues of the mice. Interestingly, sulforaphane treatment also enhanced autophagy activity in the brain and the liver. To further examine whether sulforaphane promotes mutant huntingtin (mHtt) degradation, we treated Huntington's disease cells with sulforaphane and found that sulforaphane not only enhanced mHtt degradation but also reduced mHtt cytotoxicity. Sulforaphane-mediated mHtt degradation was mainly through the UPS pathway as the presence of a proteasome inhibitor abolished this effect. Taken together, these data indicate that sulforaphane activates protein degradation machineries in both the brain and peripheral tissues and may be a therapeutic reagent for Huntington's disease and other intractable disorders. Accumulation of mutant huntingtin (mHtt) protein causes Huntington's disease (HD). Sulforaphane (SFN), a naturally occurring compound, increased proteasome and autophagy activities in vivo and enhanced mHtt turnover and cell survival in HD cell models. SFN-mediated mHtt degradation is mainly through the proteasome pathway. These data suggest that SFN can be a therapeutic reagent for treating HD and other intractable disorders. © 2014 International Society for Neurochemistry.

  17. Plasmonic enhancement of High Harmonic Generation revisited: Predominance of Atomic Line Emission

    Directory of Open Access Journals (Sweden)

    Ropers C.

    2013-03-01

    Full Text Available We demonstrate nanostructure-enhanced extreme ultraviolet fluorescence from noble gases driven by low-energy, few-cycle light pulses. Despite sufficient local intensities, plasmon-enhanced high harmonic generation is not observed, which follows from the small, nanometer-size coherent source volume.

  18. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  19. GDNF Enhances Therapeutic Efficiency of Neural Stem Cells-Based Therapy in Chronic Experimental Allergic Encephalomyelitis in Rat.

    Science.gov (United States)

    Gao, Xiaoqing; Deng, Li; Wang, Yun; Yin, Ling; Yang, Chaoxian; Du, Jie; Yuan, Qionglan

    2016-01-01

    Multiple sclerosis (MS) is an autoimmune disease in the CNS. The current immunomodulating drugs for MS do not effectively prevent the progressive neurological decline. Neural stem cells (NSCs) transplantation has been proven to promote repair and functional recovery of experimental allergic encephalomyelitis (EAE) animal model for MS, and glial cell line-derived neurotrophic factor (GDNF) has also been found to have capability of promoting axonal regeneration and remyelination of regenerating axons. In the present study, to assess whether GDNF would enhance therapeutic effect of NSCs for EAE, GDNF gene-modified NSCs (GDNF/NSCs) and native NSCs were transplanted into each lateral ventricle of rats at 10 days and rats were sacrificed at 60 days after EAE immunization. We found that NSCs significantly reduced the clinical signs, and GDNF gene-modification further promoted functional recovery. GDNF/NSCs more profoundly suppressed brain inflammation and improved density of myelin compared with NSCs. The survival of GDNF/NSCs was significantly higher than that of transplanted NSCs. Transplanted GDNF/NSCs, in contrast to NSCs, differentiated into more neurons and oligodendrocytes. Moreover, the mRNA expression of oligodendrocyte lineage cells in rats with GDNF/NSCs was significantly increased compared to rats with NSCs. These results suggest that GDNF enhances therapeutic efficiency of NSCs-based therapy for EAE.

  20. Therapeutic Intervention of Glial-Mediated Enhancement of Neuroinflammation in an Established Model of GWI

    Science.gov (United States)

    2017-06-01

    development of enhanced neuroinflammation in our GWI model,” has been started by increasing animal numbers in our ALDH1L1 bacTRAP transgenic colony...3) The microglial wipeout drug has been obtained and formulated into rodent food . This diet will be fed to the animals and a pilot experiment will

  1. Enhancing the cellular uptake of Py–Im polyamides through next-generation aryl turns

    OpenAIRE

    Meier, Jordan L.; Montgomery, David C.; Dervan, Peter B.

    2012-01-01

    Pyrrole–imidazole (Py–Im) hairpin polyamides are a class of programmable, sequence-specific DNA binding oligomers capable of disrupting protein–DNA interactions and modulating gene expression in living cells. Methods to control the cellular uptake and nuclear localization of these compounds are essential to their application as molecular probes or therapeutic agents. Here, we explore modifications of the hairpin γ-aminobutyric acid turn unit as a means to enhance cellular uptake and biologica...

  2. Ontak reduces the immunosuppressive tumor environment and enhances successful therapeutic vaccination in HER-2/neu-tolerant mice.

    Science.gov (United States)

    Gritzapis, Angelos D; Voutsas, Ioannis F; Baxevanis, Constantin N

    2012-03-01

    Disrupting tumor-mediated mechanisms suppressing host immunity represents a novel approach to tumor immunotherapy. Depletion of regulatory T cells (Tregs) increases endogenous anti-tumor immunity and the efficacy of active immunotherapy in experimental tumor models. HLA-A2.1/HLA-DR1 (A2.1/DR1) × BALB- neuT+ (neuT+) triple transgenic mice represent an improvement over neuT+ mice for evaluating vaccination regimens to overcome tolerance against HER-2/neu. We questioned whether depletion of Tregs with Denileukin diftitox (Ontak) enhances the efficacy of a therapeutic vaccine consisting of HER-2(85-94) (p85) CTL and HER-2(776-790) (p776) Th peptides against the growth of TUBO.A2 transplantable tumor in male A2.1/DR1 × neuT+ Tg mice. While the therapeutic vaccine primed the tumor-reactive CD8+ CTLs and CD4+ effector T lymphocytes (Teffs) compartment, inducing activation, tumor infiltration, and tumor rejection or delay in tumor growth, treatment with Ontak 1 day prior to vaccination resulted in enhanced CD4+ and CD8+ T-cell-mediated vaccine-specific immune responses in the periphery. This was closely associated with greater infiltration and a striking change in the intratumor balance of Tregs and vaccine-specific CTLs/Teffs that directly correlated with markedly enhanced antitumor activity. The data suggest that Tregs control both CD4+ and CD8+ T-cell activity within the tumor, emphasize the importance of the intratumor ratio of vaccine-specific lymphocytes to Tregs, and demonstrate significant inversion of this ratio and correlation with tumor rejection during Ontak/vaccine immunotherapy.

  3. Histone deacetylase inhibitor AR-42 enhances E7-specific CD8⁺ T cell-mediated antitumor immunity induced by therapeutic HPV DNA vaccination.

    Science.gov (United States)

    Lee, Sung Yong; Huang, Zhuomin; Kang, Tae Heung; Soong, Ruey-Shyang; Knoff, Jayne; Axenfeld, Ellen; Wang, Chenguang; Alvarez, Ronald D; Chen, Ching-Shih; Hung, Chien-Fu; Wu, T-C

    2013-10-01

    We have previously created a potent DNA vaccine encoding calreticulin linked to the human papillomavirus (HPV) oncogenic protein E7 (CRT/E7). While treatment with the CRT/E7 DNA vaccine generates significant tumor-specific immune responses in vaccinated mice, the potency with the DNA vaccine could potentially be improved by co-administration of a histone deacetylase inhibitor (HDACi) as HDACi has been shown to increase the expression of MHC class I and II molecules. Thus, we aimed to determine whether co-administration of a novel HDACi, AR-42, with therapeutic HPV DNA vaccines could improve the activation of HPV antigen-specific CD8(+) T cells, resulting in potent therapeutic antitumor effects. To do so, HPV-16 E7-expressing murine TC-1 tumor-bearing mice were treated orally with AR-42 and/or CRT/E7 DNA vaccine via gene gun. Mice were monitored for E7-specific CD8(+) T cell immune responses and antitumor effects. TC-1 tumor-bearing mice treated with AR-42 and CRT/E7 DNA vaccine experienced longer survival, decreased tumor growth, and enhanced E7-specific immune response compared to mice treated with AR-42 or CRT/E7 DNA vaccine alone. Additionally, treatment of TC-1 cells with AR-42 increased the surface expression of MHC class I molecules and increased the susceptibility of tumor cells to the cytotoxicity of E7-specific T cells. This study indicates the ability of AR-42 to significantly enhance the potency of the CRT/E7 DNA vaccine by improving tumor-specific immune responses and antitumor effects. Both AR-42 and CRT/E7 DNA vaccines have been used in independent clinical trials; the current study serves as foundation for future clinical trials combining both treatments in cervical cancer therapy. AR-42, a novel HDAC inhibitor, enhances potency of therapeutic HPV DNA vaccines AR-42 treatment leads to strong E7-specific CD8+ T cell immune responses AR-42 improves tumor-specific immunity and antitumor effects elicited by HPV DNA vaccine AR-42 is more potent than

  4. Enhanced focus steering abilities of multi-element therapeutic arrays operating in nonlinear regimes

    Energy Technology Data Exchange (ETDEWEB)

    Yuldashev, P., E-mail: petr@acs366.phys.msu.ru; Ilyin, S. [Physics Faculty, Moscow State University, Leninskie Gory, 119991 Moscow (Russian Federation); Gavrilov, L. [Andreyev Acoustics Institute, 4 Schvernik Str., 117036 Moscow (Russian Federation); Sapozhnikov, O.; Khokhlova, V. [Physics Faculty, Moscow State University, Leninskie Gory, 119991 Moscow (Russian Federation); Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40" t" h, Street, Seattle, WA 98105 (United States); Kreider, W. [Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 1013 NE 40" t" h, Street, Seattle, WA 98105 (United States)

    2015-10-28

    Steering abilities of a typical HIFU therapeutic array operated in linear and nonlinear regimes were compared using numerical simulation with the 3D Westervelt equation. The array included 256 elements of 1.2 MHz frequency and 6.6 mm diameter distributed in a quasi-random pattern over a spherical shell with a 130 mm aperture and a focal length of 120 mm. In the case of linear focusing, thermal effects are proportional to the intensity level and the criterion for safe array operation is that the intensity in the grating lobes should be less than 10% of the intensity in the main focus. In the case of nonlinear focusing, the heating effect is no longer proportional to intensity; therefore the heat deposition rate was chosen as the relevant metric, using the same 10% threshold for the secondary lobe in comparison with the focal maximum. When steering the focus, the same linearly predicted intensity level at the main focus was maintained by increasing the array power. Numerical simulations of the acoustic field were performed for nonlinear propagation both in water and in tissue. It was shown that for shock-forming conditions in the main focus, the steering range of safe electronic focusing is larger than that for linear propagation conditions. Nonlinear sonication regimes therefore can be used to enlarge tissue volumes that can be sonicated using electronic steering of the focus of HIFU arrays.

  5. Loss of CHD1 causes DNA repair defects and enhances prostate cancer therapeutic responsiveness

    DEFF Research Database (Denmark)

    Kari, Vijayalakshmi; Mansour, Wael Yassin; Raul, Sanjay Kumar

    2016-01-01

    The CHD1 gene, encoding the chromo-domain helicase DNA-binding protein-1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of Ct......-homologous end joining. Together, we provide evidence for a previously unknown role of CHD1 in DNA DSB repair via HR and show that CHD1 depletion sensitizes cells to PARP inhibitors, which has potential therapeutic relevance. Our findings suggest that CHD1 deletion, like BRCA1/2 mutation in ovarian cancer, may......IP to chromatin and subsequent end resection during DNA DSB repair. Our data support a role for CHD1 in opening the chromatin around the DSB to facilitate the recruitment of homologous recombination (HR) proteins. Consequently, depletion of CHD1 specifically affects HR-mediated DNA repair but not non...

  6. Sophisticated Cloning, Fermentation, and Purification Technologies for an Enhanced Therapeutic Protein Production: A Review

    Directory of Open Access Journals (Sweden)

    Sanjeev K. Gupta

    2017-07-01

    Full Text Available The protein productions strategies are crucial towards the development of application based research and elucidating the novel purification strategies for industrial production. Currently, there are few innovative avenues are studies for cloning, upstream, and purification through efficient bioprocess development. Such strategies are beneficial for industries as well as proven to be vital for effectual therapeutic protein development. Though, these techniques are well documented, but, there is scope of addition to current knowledge with novel and new approaches and it will pave new avenues in production of recombinant microbial and non-microbial proteins including secondary metabolites. In this review, we have focussed on the recent development in clone selection, various modern fermentation and purification technologies and future directions in these emerging areas. Moreover, we have also highlighted notable perspectives and challenges involved in the bioengineering of such proteins, including quality by design, gene editing and pioneering ideas. The biopharmaceutical industries continue to shift towards more flexible, automated platforms and economical product development, which in turn can help in developing the cost effective processes and affordable drug development for a large community.

  7. Novel angiogenesis therapeutics by redox injectable hydrogel - Regulation of local nitric oxide generation for effective cardiovascular therapy.

    Science.gov (United States)

    Vong, Long Binh; Bui, Thang Quoc; Tomita, Tsutomu; Sakamoto, Hiroaki; Hiramatsu, Yuji; Nagasaki, Yukio

    2018-06-01

    Nitric oxide (NO) possesses various functions in cardiovascular diseases; however, due to an extremely short half-life and low bioavailability, its therapeutic application is limited. In inflamed tissues, overproduced reactive oxygen species (ROS) rapidly react with the endogenous NO, reducing its bioavailability. Here, we developed a controllable NO-releasing redox injectable hydrogel (NO-RIG) formed by the electrostatic crosslinking between the polyion complex flower-type micelles composing of functional polymers to scavenge overproduced ROS and regulate the local NO expression level simultaneously. After the intracardiac injection to mice, NO-RIG converted to gel via physiological temperature-responsive character, distributed homogeneously, and retained in the myocardial tissue for more than 10 d. Treatment with NO-RIG remarkably decreased the infarction size and improved the heart function after myocardial infarction when compared to control injectable hydrogels, such as a simple NO-releasing or ROS-scavenging injectable gels. We found that NO-RIG treatment significantly enhanced the angiogenesis and new blood vessels formation in mice through the regulation of the NO sustained release and redox equilibrium. NO-RIG presents high potential in preventing and treating cardiovascular diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet.

    Science.gov (United States)

    Lussier, Danielle M; Woolf, Eric C; Johnson, John L; Brooks, Kenneth S; Blattman, Joseph N; Scheck, Adrienne C

    2016-05-13

    Glioblastoma multiforme is a highly aggressive brain tumor with a poor prognosis, and advances in treatment have led to only marginal increases in overall survival. We and others have shown previously that the therapeutic ketogenic diet (KD) prolongs survival in mouse models of glioma, explained by both direct tumor growth inhibition and suppression of pro-inflammatory microenvironment conditions. The aim of this study is to assess the effects of the KD on the glioma reactive immune response. The GL261-Luc2 intracranial mouse model of glioma was used to investigate the effects of the KD on the tumor-specific immune response. Tumor-infiltrating CD8+ T cells, CD4+ T cells and natural killer (NK) cells were analyzed by flow cytometry. The expression of immune inhibitory receptors cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) on CD8+ T cells were also analyzed by flow cytometry. Analysis of intracellular cytokine production was used to determine production of IFN, IL-2 and IFN- in tumor-infiltrating CD8+ T and natural killer (NK) cells and IL-10 production by T regulatory cells. We demonstrate that mice fed the KD had increased tumor-reactive innate and adaptive immune responses, including increased cytokine production and cytolysis via tumor-reactive CD8+ T cells. Additionally, we saw that mice maintained on the KD had increased CD4 infiltration, while T regulatory cell numbers stayed consistent. Lastly, mice fed the KD had a significant reduction in immune inhibitory receptor expression as well as decreased inhibitory ligand expression on glioma cells. The KD may work in part as an immune adjuvant, boosting tumor-reactive immune responses in the microenvironment by alleviating immune suppression. This evidence suggests that the KD increases tumor-reactive immune responses, and may have implications in combinational treatment approaches.

  9. Nose-to-Brain Delivery of Peptide Drugs Enhanced by Coadministration of Cell-penetrating Peptides: Therapeutic Potential for Dementia.

    Science.gov (United States)

    Kamei, Noriyasu

    2017-01-01

    Recent reports suggest that peptide drugs such as insulin have the potential to serve as therapeutics in neurodegenerative diseases such as Alzheimer's disease. However, the transport of these drugs to the therapeutic target, the brain, is significantly hindered by the blood-brain barrier (BBB). Intranasal administration appears to be an ideal solution for drug delivery to the brain, bypassing the BBB, however the entry of peptide drugs into neuronal and epithelial cells in the olfactory mucosa remains low. In this study, we therefore examined whether intranasal coadministration of cell-penetrating peptides (CPPs) could improve nose-to-brain drug transport. In both mice and rats, we found that direct transport of insulin into the brain was significantly facilitated when coadministered with amphipathic CPP penetratin, and eventually insulin reached the deeper regions of the brain such as the hippocampus. In the mouse line senescence-accelerated mouse prone-8 (SAMP8), spatial learning tests demonstrated that long-term intranasal coadministration of insulin with penetratin improved mild memory loss in the early stages of dementia. In contrast, the severe cognitive dysfunction in the aged SAMP8 mice was preserved despite intranasal coadministration of insulin with penetratin. The immunohistological examination of the hippocampus suggested that enhanced nose-to-brain delivery of insulin had a partial neuroprotective effect but unexpectedly increased amyloid β plaque deposition. In conclusion, intranasal coadministration of insulin with CPPs has the potential to serve as a therapeutic for mild cognitive dysfunction. To identify suitable pharmacotherapy for dementia with severe pathology, further studies of nose-to-brain delivery of molecularly appropriate biopharmaceuticals are necessary.

  10. Reflection enhances creativity: Beneficial effects of idea evaluation on idea generation.

    Science.gov (United States)

    Hao, Ning; Ku, Yixuan; Liu, Meigui; Hu, Yi; Bodner, Mark; Grabner, Roland H; Fink, Andreas

    2016-03-01

    The present study aimed to explore the neural correlates underlying the effects of idea evaluation on idea generation in creative thinking. Participants were required to generate original uses of conventional objects (alternative uses task) during EEG recording. A reflection task (mentally evaluating the generated ideas) or a distraction task (object characteristics task) was inserted into the course of idea generation. Behavioral results revealed that participants generated ideas with higher originality after evaluating the generated ideas than after performing the distraction task. The EEG results revealed that idea evaluation was accompanied with upper alpha (10-13 Hz) synchronization, most prominent at frontal cortical sites. Moreover, upper alpha activity in frontal cortices during idea generation was enhanced after idea evaluation. These findings indicate that idea evaluation may elicit a state of heightened internal attention or top-down activity that facilitates efficient retrieval and integration of internal memory representations. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakiba, Camille [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Cornelis, François [Department of Radiology, Pellegrin Hospital, Bordeaux (France); Descat, Edouard [Department of Radiology, Saint-Augustin Clinic, Bordeaux (France); Gross-Goupil, Marine [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Sargos, Paul [Department of Radiotherapy, Bergonié Cancer Institute, Bordeaux (France); Roubaud, Guilhem [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Houédé, Nadine, E-mail: nadine.houede@chu-nimes.fr [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Department of Medical Oncology, Nimes University Hosptital, Nîmes (France)

    2015-06-15

    Highlights: • DCE-MRI parameters could be useful biomarker for patients with localized bladder carcinoma. • Rate of relapse is lower for good responders assessed by DCE-MRI. • The use of DCE-MRI parameters may improve the standardization of patients’ selection before surgery. - Abstract: Objectives: To evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. Methods: From 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI{sub 35s}) and venous phases (rSI{sub 80s}) of each tumour was obtained. Histological response was assessed and outcomes were recorded. Results: Histological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P = 0.03). After treatment, rSI{sub 80s} was significantly different between pCR and non-pCR patients (P = 0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. Conclusion: Our results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery.

  12. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection

    Science.gov (United States)

    Pinto, Amelia K.; Brien, James D.; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V.; Barrett, Alan D.; Shresta, Sujan

    2015-01-01

    ABSTRACT With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre+ Ifnarflox/flox [denoted as Ifnarf/f herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre+ Ifnarf/f mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre+ Ifnarf/f mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. PMID:26374123

  13. Expanded therapeutic potential in activity space of next-generation 5-nitroimidazole antimicrobials with broad structural diversity

    Science.gov (United States)

    Miyamoto, Yukiko; Kalisiak, Jarosław; Korthals, Keith; Lauwaet, Tineke; Cheung, Dae Young; Lozano, Ricardo; Cobo, Eduardo R.; Upcroft, Peter; Upcroft, Jacqueline A.; Berg, Douglas E.; Gillin, Frances D.; Fokin, Valery V.; Sharpless, K. Barry; Eckmann, Lars

    2013-01-01

    Metronidazole and other 5-nitroimidazoles (5-NI) are among the most effective antimicrobials available against many important anaerobic pathogens, but evolving resistance is threatening their long-term clinical utility. The common 5-NIs were developed decades ago, yet little 5-NI drug development has since taken place, leaving the true potential of this important drug class unexplored. Here we report on a unique approach to the modular synthesis of diversified 5-NIs for broad exploration of their antimicrobial potential. Many of the more than 650 synthesized compounds, carrying structurally diverse functional groups, have vastly improved activity against a range of microbes, including the pathogenic protozoa Giardia lamblia and Trichomonas vaginalis, and the bacterial pathogens Helicobacter pylori, Clostridium difficile, and Bacteroides fragilis. Furthermore, they can overcome different forms of drug resistance, and are active and nontoxic in animal infection models. These findings provide impetus to the development of structurally diverse, next-generation 5-NI drugs as agents in the antimicrobial armamentarium, thus ensuring their future viability as primary therapeutic agents against many clinically important infections. PMID:24101497

  14. Therapeutic response assessment of high intensity focused ultrasound therapy for uterine fibroid: Utility of contrast-enhanced ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Xiaodong [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China)]. E-mail: zhouxd@fmmu.edu.cn; Ren Xiaolong [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China)]. E-mail: renxiaolong70@hotmail.com; Zhang Jun [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); He Guangbin [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Zheng Minjuan [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Tian Xue [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Li Li [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Zhu Ting [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Zhang Min [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Wang Lei [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Luo Wen [Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China)

    2007-05-15

    Purpose: To assess the utility of contrast-enhanced ultrasonography (ceUS) in the assessment of the therapeutic response to high intensity focused ultrasound (HIFU) ablation in patients with uterine fibroid. Materials and methods: Sixty-four patients with a total of 64 uterine fibroids (mean: 5.3 {+-} 1.2 cm; range: 3.2-8.9 cm) treated with HIFU ablation under the ultrasound guidance were evaluated with ceUS after receiving an intravenous bolus injection of a microbubble contrast agent (SonoVue) within 1 week after intervention. We obtained serial ceUS images during the time period from beginning to 5 min after the initiation of the bolus contrast injection. All of the patients underwent a contrast enhanced MRI (ceMRI) and ultrasound guided needle puncture biopsy within 1 week after HIFU ablation. And as a follow-up, all of the patients underwent US at 1, 3, 6 and 12 months after HIFU treatment. The volume change was observed and compared to pre- and post-HIFU ablation. The results of the ceUS were compared with those of the ceMRI in terms of the presence or absence of residual unablated tumor and pathologic change in the treated lesions. Results: On ceUS, diagnostic accuracy was 100%, while residual unablated tumors were found in three uterine fibroids (4.7%) and failed treatment was found in eight uterine fibroids (12.5%). All the 11 fibroids were subjected to additional HIFU ablation. Of the 58 ablated fibroids without residual tumors on both the ceUS and ceMRI after the HIFU ablation, the volumes of all the fibroids decreased in different degrees during the 1 year follow-up USs. And histologic examinations confirmed findings of necrotic and viable tumor tissue, respectively. Conclusion: CEUS is potentially useful for evaluating the early therapeutic effect of percutaneous HIFU ablation for uterine fibroids.

  15. Therapeutic response assessment of high intensity focused ultrasound therapy for uterine fibroid: Utility of contrast-enhanced ultrasonography

    International Nuclear Information System (INIS)

    Zhou Xiaodong; Ren Xiaolong; Zhang Jun; He Guangbin; Zheng Minjuan; Tian Xue; Li Li; Zhu Ting; Zhang Min; Wang Lei; Luo Wen

    2007-01-01

    Purpose: To assess the utility of contrast-enhanced ultrasonography (ceUS) in the assessment of the therapeutic response to high intensity focused ultrasound (HIFU) ablation in patients with uterine fibroid. Materials and methods: Sixty-four patients with a total of 64 uterine fibroids (mean: 5.3 ± 1.2 cm; range: 3.2-8.9 cm) treated with HIFU ablation under the ultrasound guidance were evaluated with ceUS after receiving an intravenous bolus injection of a microbubble contrast agent (SonoVue) within 1 week after intervention. We obtained serial ceUS images during the time period from beginning to 5 min after the initiation of the bolus contrast injection. All of the patients underwent a contrast enhanced MRI (ceMRI) and ultrasound guided needle puncture biopsy within 1 week after HIFU ablation. And as a follow-up, all of the patients underwent US at 1, 3, 6 and 12 months after HIFU treatment. The volume change was observed and compared to pre- and post-HIFU ablation. The results of the ceUS were compared with those of the ceMRI in terms of the presence or absence of residual unablated tumor and pathologic change in the treated lesions. Results: On ceUS, diagnostic accuracy was 100%, while residual unablated tumors were found in three uterine fibroids (4.7%) and failed treatment was found in eight uterine fibroids (12.5%). All the 11 fibroids were subjected to additional HIFU ablation. Of the 58 ablated fibroids without residual tumors on both the ceUS and ceMRI after the HIFU ablation, the volumes of all the fibroids decreased in different degrees during the 1 year follow-up USs. And histologic examinations confirmed findings of necrotic and viable tumor tissue, respectively. Conclusion: CEUS is potentially useful for evaluating the early therapeutic effect of percutaneous HIFU ablation for uterine fibroids

  16. Dynamic contrast enhanced ultrasound assessment of the vascular effects of novel therapeutics in early stage trials.

    Science.gov (United States)

    Leen, Edward; Averkiou, Michalakis; Arditi, Marcel; Burns, Peter; Bokor, Daniela; Gauthier, Thomas; Kono, Yuko; Lucidarme, Olivier

    2012-07-01

    Imaging is key in the accurate monitoring of response to cancer therapies targeting tumour vascularity to inhibit its growth and dissemination. Dynamic contrast enhanced ultrasound (DCE ultrasound) is a quantitative method with the advantage of being non-invasive, widely available, portable, cost effective, highly sensitive and reproducible using agents that are truly intravascular. Under the auspices of the initiative of the Experimental Cancer Medicine Centre Imaging Network, bringing together experts from the UK, Europe and North America for a 2-day workshop in May 2010, this consensus paper aims to provide guidance on the use of DCE ultrasound in the measurement of tumour vascular support in clinical trials. Key Points • DCE ultrasound can quantify and extract specific blood flow parameters, such as flow velocity, relative vascular volume and relative blood flow rate. • DCE ultrasound can be performed repeatedly and is therefore ideally suited for pharmacokinetic and pharmacodynamic studies evaluating vascular-targeted drugs. • DCE ultrasound provides a reproducible method of assessing the vascular effects of therapy in pre-clinical and early clinical trials, which is easily translatable into routine clinical practice.

  17. Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

    Science.gov (United States)

    Barua, Neil U; Gill, Steven S; Love, Seth

    2014-03-01

    Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD). © 2013 International Society of Neuropathology.

  18. Intrapulmonary shear stress enhancement: a new therapeutic approach in acute myocardial ischemia.

    Science.gov (United States)

    Nour, Sayed; Yang, Daya; Dai, Gong; Wang, Qinmei; Feng, Minze; Lila, Nermine; Chachques, Juan Carlos; Wu, Guifu

    2013-10-09

    Ischemic heart disease (IHD) is a leading cause of mortality with insufficient results of current therapies, most probably due to maintained endothelial dysfunction conditions. Alternatively, we propose a new treatment that promotes endothelial shear stress (ESS) enhancement using an intrapulmonary pulsatile catheter. Twelve piglets, divided in equal groups of 6: pulsatile (P) and non-pulsatile (NP), underwent permanent left anterior descending coronary artery ligation through sternotomy. After 1 h of ischemia and heparin injection (150 IU/kg): in P group, a pulsatile catheter was introduced into the pulmonary trunk and pulsated intermittently over 1 h, and irrespective of heart rate (110 bpm). In NP group, nitrates were given (7 ± 2 mg/kg/min) for 1 h. In P group all 6 animals survived ischemia for 120 min, but in NP group only 2 animals survived. The 4 animals that died during the experiment in NP group survived for 93 ± 14 min. Hemodynamics and cardiac output (CO) were significantly improved in P group compared with NP group: CO was 0.92 ± 0.15 vs. 0.52 ± 0.08 in NP group (L/min; p p P group versus NP group: pulmonary resistance was 119 ± 13 vs. 400 ± 42 and systemic resistance was 319 ± 43 vs. 1857 ± 326, respectively. Myocardial apoptosis was significantly (p P group (0.66 ± 0.07) vs. (4.18 ± 0.27) in NP group. Myocardial endothelial NO synthase mRNA expression was significantly (p P group (0.90 ± 0.09) vs. (0.25 ± 0.04) in NP group. Intrapulmonary pulsatile catheter could improve hemodynamics and myocardial contractility in acute myocardial ischemia. This represents a cost-effective method, suitable for emergency setting as a first priority, regardless of classical coronary reperfusion. © 2013.

  19. Mobile applications as solutions to enhance sustainable travel behaviour among Generation Y

    OpenAIRE

    Kiilunen, Olga

    2013-01-01

    The aim of this thesis was to investigate the possibility and the best ways of using mobile applications to enhance sustainable travel behavior among Generation Y. The development of Information and Communication Technology (ICT) brings the new opportunities in tourism and travel industry. At the same time, widely accepted as currently most significant segment both in travel industry and global sustainable development, Generation Y is know for their high expertise and passion for using techno...

  20. Enhancement of third-order harmonic generation by interaction of two IR femtosecond filaments

    International Nuclear Information System (INIS)

    Liu, Z Y; Ding, P J; Shi, Y C; Lu, X; Liu, Q C; Sun, S H; Ding, B W; Hu, B T; Liu, X L

    2012-01-01

    Three orders of magnitude in the enhancement of the third-order harmonic (TH) generation induced by the interaction of two femtosecond filaments crossing with small angles in the air is achieved. The dependences of the TH generation on the time delay, the relative polarization, the input laser intensity ratios between the probe and pump beam are measured with the crossing angle of 3.5deg , and the results with quasi-vertical crossing angle are also shown for comparison

  1. Potential therapeutic application of gold nanoparticles in B-chronic lymphocytic leukemia (BCLL: enhancing apoptosis

    Directory of Open Access Journals (Sweden)

    Lu Lichun

    2007-05-01

    Full Text Available Abstract B-Chronic Lymphocytic Leukemia (CLL is an incurable disease predominantly characterized by apoptosis resistance. We have previously described a VEGF signaling pathway that generates apoptosis resistance in CLL B cells. We found induction of significantly more apoptosis in CLL B cells by co-culture with an anti-VEGF antibody. To increase the efficacy of these agents in CLL therapy we have focused on the use of gold nanoparticles (GNP. Gold nanoparticles were chosen based on their biocompatibility, very high surface area, ease of characterization and surface functionalization. We attached VEGF antibody (AbVF to the gold nanoparticles and determined their ability to kill CLL B cells. Gold nanoparticles and their nanoconjugates were characterized using UV-Visible spectroscopy (UV-Vis, transmission electron microscopy (TEM, thermogravimetric analysis (TGA and X-ray photoelectron spectroscopy (XPS. All the patient samples studied (N = 7 responded to the gold-AbVF treatment with a dose dependent apoptosis of CLL B cells. The induction of apoptosis with gold-AbVF was significantly higher than the CLL cells exposed to only AbVF or GNP. The gold-AbVF treated cells showed significant down regulation of anti-apoptotic proteins and exhibited PARP cleavage. Gold-AbVF treated and GNP treated cells showed internalization of the nanoparticles in early and late endosomes and in multivesicular bodies. Non-coated gold nanoparticles alone were able to induce some levels of apoptosis in CLL B cells. This paper opens up new opportunities in the treatment of CLL-B using gold nanoparticles and integrates nanoscience with therapy in CLL. In future, potential opportunities exist to harness the optoelectronic properties of gold nanoparticles in the treatment of CLL.

  2. An enhanced geometry-independent mesh weight window generator for MCNP

    International Nuclear Information System (INIS)

    Evans, T.M.; Hendricks, J.S.

    1997-01-01

    A new, enhanced, weight window generator suite has been developed for MCNP trademark. The new generator correctly estimates importances in either an user-specified, geometry-independent orthogonal grid or in MCNP geometric cells. The geometry-independent option alleviates the need to subdivide the MCNP cell geometry for variance reduction purposes. In addition, the new suite corrects several pathologies in the existing MCNP weight window generator. To verify the correctness of the new implementation, comparisons are performed with the analytical solution for the cell importance. Using the new generator, differences between Monte Carlo generated and analytical importances are less than 0.1%. Also, assumptions implicit in the original MCNP generator are shown to be poor in problems with high scattering media. The new generator is fully compatible with MCNP's AVATAR trademark automatic variance reduction method. The new generator applications, together with AVATAR, gives MCNP an enhanced suite of variance reduction methods. The flexibility and efficacy of this suite is demonstrated in a neutron porosity tool well-logging problem

  3. Effect of loss on slow-light-enhanced second-harmonic generation in periodic nanostructures

    DEFF Research Database (Denmark)

    Saravi, Sina; Quintero-Bermudez, Rafael; Setzpfandt, Frank

    2016-01-01

    We theoretically analyze the dependence of second-harmonic generation efficiency on the group index in periodic optical waveguides with loss. We investigate different possible scenarios of using slow light to enhance the efficiency of this process and show that in some cases there exists a maxima...

  4. A composite generator film impregnated with cellulose nanocrystals for enhanced triboelectric performance

    Science.gov (United States)

    Jun Peng; Huilong Zhang; Qifeng Zheng; Craig M. Clemons; Ronald C. Sabo; Shaoqin Gong; Zhenqiang Ma; Lih-Sheng Turng

    2017-01-01

    A novel polydimethylsiloxane (PDMS)/cellulose nanocrystal flake (CNCF) composite triboelectric nanogenerator (CTG) using CNCFs as effective dielectrics a 10-times-enhanced triboelectric performance compared with its pure PDMS counterpart. Positive charges generated on the surface of the CNCFs during cyclic compression boosted electron transfer and induced extra charges...

  5. Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease.

    Science.gov (United States)

    Schaeffer, Evelin L; Forlenza, Orestes V; Gattaz, Wagner F

    2009-01-01

    Alzheimer disease (AD) is the leading cause of dementia in the elderly and has no known cure. Evidence suggests that reduced activity of specific subtypes of intracellular phospholipases A2 (cPLA2 and iPLA2) is an early event in AD and may contribute to memory impairment and neuropathology in the disease. The objective of this study was to review the literature focusing on the therapeutic role of PLA2 stimulation by cognitive training and positive modulators, or of supplementation with arachidonic acid (PLA2 product) in facilitating memory function and synaptic transmission and plasticity in either research animals or human subjects. MEDLINE database was searched (no date restrictions) for published articles using the keywords Alzheimer disease (mild, moderate, severe), mild cognitive impairment, healthy elderly, rats, mice, phospholipase A(2), phospholipid metabolism, phosphatidylcholine, arachidonic acid, cognitive training, learning, memory, long-term potentiation, protein kinases, dietary lipid compounds, cell proliferation, neurogenesis, and neuritogenesis. Reference lists of the identified articles were checked to select additional studies of interest. Overall, the data suggest that PLA2 activation is induced in the healthy brain during learning and memory. Furthermore, learning seems to regulate endogenous neurogenesis, which has been observed in AD brains. Finally, PLA2 appears to be implicated in homeostatic processes related to neurite outgrowth and differentiation in both neurodevelopmental processes and response to neuronal injury. The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.

  6. Transient stability enhancement of electric power generating systems by 120-degree phase rotation

    Science.gov (United States)

    Cresap, Richard L.; Taylor, Carson W.; Kreipe, Michael J.

    1982-01-01

    A method and system for enhancing the transient stability of an intertied three-phase electric power generating system. A set of power exporting generators (10) is connected to a set of power importing generators (20). When a transient cannot be controlled by conventional stability controls, and imminent loss of synchronism is detected (such as when the equivalent rotor angle difference between the two generator sets exceeds a predetermined value, such as 150 degrees), the intertie is disconnected by circuit breakers. Then a switch (30) having a 120-degree phase rotation, or a circuit breaker having a 120-degree phase rotation is placed in the intertie. The intertie is then reconnected. This results in a 120-degree reduction in the equivalent rotor angle difference between the two generator sets, making the system more stable and allowing more time for the conventional controls to stabilize the transient.

  7. Stability Enhancement of a Power System Containing High-Penetration Intermittent Renewable Generation

    Directory of Open Access Journals (Sweden)

    Jorge Morel

    2015-06-01

    Full Text Available This paper considers the transient stability enhancement of a power system containing large amounts of solar and wind generation in Japan. Following the Fukushima Daiichi nuclear disaster there has been an increasing awareness on the importance of a distributed architecture, based mainly on renewable generation, for the Japanese power system. Also, the targets of CO2 emissions can now be approached without heavily depending on nuclear generation. Large amounts of renewable generation leads to a reduction in the total inertia of the system because renewable generators are connected to the grid by power converters, and transient stability becomes a significant issue. Simulation results show that sodium-sulfur batteries can keep the system in operation and stable after strong transient disturbances, especially for an isolated system. The results also show how the reduction of the inertia in the system can be mitigated by exploiting the kinetic energy of wind turbines.

  8. Cuckoo search based optimal mask generation for noise suppression and enhancement of speech signal

    Directory of Open Access Journals (Sweden)

    Anil Garg

    2015-07-01

    Full Text Available In this paper, an effective noise suppression technique for enhancement of speech signals using optimized mask is proposed. Initially, the noisy speech signal is broken down into various time–frequency (TF units and the features are extracted by finding out the Amplitude Magnitude Spectrogram (AMS. The signals are then classified based on quality ratio into different classes to generate the initial set of solutions. Subsequently, the optimal mask for each class is generated based on Cuckoo search algorithm. Subsequently, in the waveform synthesis stage, filtered waveforms are windowed and then multiplied by the optimal mask value and summed up to get the enhanced target signal. The experimentation of the proposed technique was carried out using various datasets and the performance is compared with the previous techniques using SNR. The results obtained proved the effectiveness of the proposed technique and its ability to suppress noise and enhance the speech signal.

  9. A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy.

    Science.gov (United States)

    Tung, Frank Y; Tung, Jack K; Pallikkuth, Suresh; Pahwa, Savita; Fischl, Margaret A

    2016-04-27

    HIV-1 specific cellular immunity plays an important role in controlling viral replication. In this first-in-human therapeutic vaccination study, a replication-defective HIV-1 vaccine (HIVAX) was tested in HIV-1 infected participants undergoing highly active antiretroviral therapy (HAART) to enhance anti-HIV immunity (Clinicaltrials.gov, identifier NCT01428596). A010 was a randomized, placebo-controlled trial to evaluate the safety and the immunogenicity of a replication defective HIV-1 vaccine (HIVAX) given as a subcutaneous injection to HIV-1 infected participants who were receiving HAART with HIV-1 viral load 500 cells/mm(3). HIV-1 specific immune responses were monitored by INF-γ enzyme linked immunospot (Elispot) and intracellular cytokine staining (ICS) assay after vaccination. Following the randomized placebo-controlled vaccination phase, subjects who received HIVAX vaccine and who met eligibility underwent a 12-week analytical antiretroviral treatment interruption (ATI). Viral load was monitored throughout the study. HIVAX was well tolerated in trial participants. Transient grade 1 to 2 (mild to moderate) injection site reactions occurred in 8 of 10 vaccinated participants. HIVAX was immunogenic in all vaccinated participants. The functionality of T cells was significantly enhanced after vaccination. Median viral load (3.45 log10 copies/ml, range of 96-12,830 copies/ml) at the end of the 12-week treatment interruption in HIVAX vaccinated group was significantly lower than the pre-treatment levels. Three vaccinated participants extended ATI for up to 2 years with stable CD4 cells and low viral loads. HIVAX vaccine is generally safe, elicits strong anti-HIV-1 immune responses, and may play an important role in controlling viral load during treatment interruption in HIV-1 infected participants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase.

    Science.gov (United States)

    Inoue, Minoru; Yoshimura, Michio; Kobayashi, Minoru; Morinibu, Akiyo; Itasaka, Satoshi; Hiraoka, Masahiro; Harada, Hiroshi

    2015-10-27

    The cytotoxicity of ionizing radiation depends on the cell cycle phase; therefore, its pharmacological manipulation, especially the induction of cell cycle arrest at the radiosensitive mitotic-phase (M-phase), has been attempted for effective radiation therapy. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that functions in mitotic progression, and is now recognized as a potential target for radiosensitization. We herein investigated whether PLK1 blockade enhanced the cytotoxic effects of radiation by modulating cell cycle phases of cancer cells using the novel small molecule inhibitor of PLK1, TAK-960. The TAK-960 treatment exhibited radiosensitizing effects in vitro, especially when it increased the proportion of M-phase cells. TAK-960 did not sensitize cancer cells to radiation when an insufficient amount of time was provided to induce mitotic arrest. The overexpression of a PLK1 mutant, PLK1-R136G&T210D, which was confirmed to cancel the TAK-960-mediated increase in the proportion of mitotic cells, abrogated the radiosensitizing effects of TAK-960. A tumor growth delay assay also demonstrated that the radiosensitizing effects of TAK-960 depended on an increase in the proportion of M-phase cells. These results provide a rational basis for targeting PLK1 for radiosensitization when considering the therapeutic time window for M-phase arrest as the best timing for radiation treatments.

  11. Evaluation of therapeutically induced hypertension in patients with delayed cerebral vasospasm by xenon-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Touho, Hajime; Karasawa, Jun; Ohnishi, Hideyuki; Shishido, Hisashi; Yamada, Keisuke; Shibamoto, Keiji (Osaka Neurological Inst., Toyonaka (Japan))

    1992-08-01

    Serial cerebral blood flow (CBF) measurement were made with stable xenon-enhanced computed tomography in 20 patients with angiographically confirmed reputerd intracranial aneurysms, before and during induced hypertension with continuous infusion of dopamine. All patients showed angiogaphic vasospasm during their course. Twelve patients without symptomatic vasospasm (Group 1) had the lowest hemispheric CBF on the craniotomy side of 31.6[+-]6.8 ml/100 gm/min on days 4-9 (control value, 40.1[+-]2.0 ml/100 gm/min), while the other eight patients with symptomatic vasopsasm (Group 2) had the lowest hemispheric CBF on the craniotomy side of 25.0[+-]7.6 ml/100 gm/min on days 10-14. The critical hemispheric CBF inducing neurological deficits was about 20 ml/ 100 gm/min in Group 2. Dysautoregulation was usually present in Groups 1 and 2, but therapeutically induced hypertension could reverse the delayed neurological deficits, it begun early at the stage of delayed vasospasm. (author).

  12. Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

    Energy Technology Data Exchange (ETDEWEB)

    Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad, E-mail: amtamadon@gmail.com [Shiraz University of Medical Sciences, Department of Pharmaceutics, School of Pharmacy (Iran, Islamic Republic of)

    2016-05-15

    Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and {sup 1}H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (<50 µg/ml) depending on the dendrimer generation and cholesterol/amine mole ratio. Cholesterol conjugation resulted in higher resistance of the condensed plasmid DNA in a competition assay with heparin sulfate. Also, the transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol{sub 40 %}) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

  13. Therapeutic miRNA and siRNA: Moving from Bench to Clinic as Next Generation Medicine

    Directory of Open Access Journals (Sweden)

    Chiranjib Chakraborty

    2017-09-01

    Full Text Available In the past few years, therapeutic microRNA (miRNA and small interfering RNA (siRNA are some of the most important biopharmaceuticals that are in commercial space as future medicines. This review summarizes the patents of miRNA- and siRNA-based new drugs, and also provides a snapshot about significant biopharmaceutical companies that are investing for the therapeutic development of miRNA and siRNA molecules. An insightful view about individual siRNA and miRNA drugs has been depicted with their present status, which is gaining attention in the therapeutic landscape. The efforts of the biopharmaceuticals are discussed with the status of their preclinical and/or clinical trials. Here, some of the setbacks have been highlighted during the biopharmaceutical development of miRNA and siRNA as individual therapeutics. Finally, a snapshot is illustrated about pharmacokinetics, pharmacodynamics with absorption, distribution, metabolism, and excretion (ADME, which is the fundamental development process of these therapeutics, as well as the delivery system for miRNA- and siRNA-based drugs. Keywords: miRNA, siRNA, drug development

  14. Plasmonic Structure Enhanced Exciton Generation at the Interface between the Perovskite Absorber and Copper Nanoparticles

    Directory of Open Access Journals (Sweden)

    Sheng Hsiung Chang

    2014-01-01

    Full Text Available The refractive index and extinction coefficient of a triiodide perovskite absorber (TPA were obtained by fitting the transmittance spectra of TPA/PEDOT:PSS/ITO/glass using the transfer matrix method. Cu nanoplasmonic structures were designed to enhance the exciton generation in the TPA and to simultaneously reduce the film thickness of the TPA. Excitons were effectively generated at the interface between TPA and Cu nanoparticles, as observed through the 3D finite-difference time-domain method. The exciton distribution is advantageous for the exciton dissociation and carrier transport.

  15. Enhanced structural color generation in aluminum metamaterials coated with a thin polymer layer.

    Science.gov (United States)

    Cheng, Fei; Yang, Xiaodong; Rosenmann, Daniel; Stan, Liliana; Czaplewski, David; Gao, Jie

    2015-09-21

    A high-resolution and angle-insensitive structural color generation platform is demonstrated based on triple-layer aluminum-silica-aluminum metamaterials supporting surface plasmon resonances tunable across the entire visible spectrum. The color performances of the fabricated aluminum metamaterials can be strongly enhanced by coating a thin transparent polymer layer on top. The results show that the presence of the polymer layer induces a better impedance matching for the plasmonic resonances to the free space so that strong light absorption can be obtained, leading to the generation of pure colors in cyan, magenta, yellow and black (CMYK) with high color saturation.

  16. Plasmonic Structure Enhanced Exciton Generation at the Interface between the Perovskite Absorber and Copper Nanoparticles

    Science.gov (United States)

    Lin, Kuen-Feng; Chiang, Chien-Hung; Wu, Chun-Guey

    2014-01-01

    The refractive index and extinction coefficient of a triiodide perovskite absorber (TPA) were obtained by fitting the transmittance spectra of TPA/PEDOT:PSS/ITO/glass using the transfer matrix method. Cu nanoplasmonic structures were designed to enhance the exciton generation in the TPA and to simultaneously reduce the film thickness of the TPA. Excitons were effectively generated at the interface between TPA and Cu nanoparticles, as observed through the 3D finite-difference time-domain method. The exciton distribution is advantageous for the exciton dissociation and carrier transport. PMID:25295290

  17. Poly(ethylene glycol-block-poly(ε-caprolactone– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

    Directory of Open Access Journals (Sweden)

    He XD

    2015-03-01

    Full Text Available Xiaodan He,1 Li Li,2 Hong Su,1 Dinglun Zhou,3 Hongmei Song,4 Ling Wang,1 Xuehua Jiang1 1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China School of Public Health, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4HitGen Ltd., Chengdu, Sichuan, People’s Republic of China Background: Effective anticancer drug delivery to the tumor site without rapid body clearance is a prerequisite for successful chemotherapy. 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-(methoxy[polyethyleneglycol]-2000 (DSPE-PEG2000 has been widely used in the preparation of stealth liposomes. Although PEG chains can efficiently preserve liposomes from rapid clearance by the reticuloendothelial system (RES, its application has been hindered by poor cellular uptake and unsatisfactory therapeutic effect.Methods: To address the dilemma, we presented a facile approach to fabricate novel stealth nanoparticles generated by poly(ethylene glycol-block-poly(ε-caprolactone (PEG-b-PCL, soybean phosphatidylcholine (SPC, and cholesterol, namely LPPs (L represented lipid and PP represented PEG-b-PCL, for the delivery of anticancer drug paclitaxel (PTX. LPPs were prepared using the thin film hydration method. Two PEG-b-PCL polymers with different molecular weights (MW; PEG2000-b-PCL2000, MW: 4,000 Da and PEG5000-b-PCL5000, MW: 10,000 Da were used to fabricate stealth nanoparticles. Conventional PEGylated liposome (LDP2000, L represented lipid and DP2000 represented DSPE-PEG2000 composed of SPC, cholesterol, and DSPE-PEG2000 was used as the control. The physical properties, cellular uptake, endocytosis pathway, cytotoxicity, pharmacokinetics, tumor accumulation, and anticancer efficacy of free PTX, PTX-loaded LPPs, and LDP2000 were systemically investigated after injection into 4T1

  18. Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro.

    Science.gov (United States)

    Bansal, Savita; Siddarth, Manushi; Chawla, Diwesh; Banerjee, Basu D; Madhu, S V; Tripathi, Ashok K

    2012-02-01

    Increased oxidative stress (OS) in diabetes mellitus is one of the major factors leading to diabetic pathology. However, the mediators and mechanism that provoke OS in diabetes is not fully understood, and it is possible that accumulation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions may incite circulating polymorphonuclear neutrophils (PMN) to generate reactive oxygen species (ROS). In this report, we aim to investigate the effect of AGE on reactive oxygen and nitrogen species generation and subsequent OS in PMN. AGE-HSA exert dose- and time-dependent enhancement of ROS and reactive nitrogen intermediates (RNI) generation by PMN. Increased ROS and RNI generation were found to be mediated through the upregulation of NADPH oxidase and inducible nitric oxide synthase (iNOS), respectively, as evident from the fact that AGE-treated neutrophils failed to generate ROS and RNI in presence of diphenyleneiodonium, a flavoprotein inhibitor for both enzymes. Further increased generation of ROS and RNI ceased when the cells were incubated with anti-RAGE antibody suggesting the involvement of AGE-RAGE interaction. Also increased malondialdehyde (MDA) and protein carbonyl formation in AGE-exposed PMN suggest induction of OS by AGE. This study provides evidence that AGEs may play a key role in the induction of oxidative stress through the augmentation of PMN-mediated ROS and RNI generation and this may be in part responsible for development of AGE-induced diabetic pathology.

  19. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    Directory of Open Access Journals (Sweden)

    Domenico F Galati

    2016-09-01

    Full Text Available Abstract Brain-derived neurotrophic factor (BDNF regulates both action potential (AP generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.

  20. New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies

    Directory of Open Access Journals (Sweden)

    Laetitia Devy

    2011-01-01

    Full Text Available MMP intervention strategies have met with limited clinical success due to severe toxicities. In particular, treatment with broad-spectrum MMP-inhibitors (MMPIs caused musculoskeletal pain and inflammation. Selectivity may be essential for realizing the clinical potential of MMPIs. Here we review discoveries pinpointing membrane-bound MMPs as mediators of mechanisms underlying cancer and inflammation and as possible therapeutic targets for prevention/treatment of these diseases. We discuss strategies to target these therapeutic proteases using highly selective inhibitory agents (i.e., human blocking antibodies against individual membrane-bound MMPs.

  1. "Straight up": enhancing rapport and therapeutic alliance with previously-detained youth in the delivery of mental health services.

    Science.gov (United States)

    Brown, James R; Holloway, Evan D; Akakpo, Tohoro F; Aalsma, Matthew C

    2014-02-01

    A strong therapeutic alliance has been shown to improve mental health treatment outcomes in adults, but this topic has not been fully explored with youth. Adolescents, particularly justice-involved youth, stand to benefit greatly from an improved treatment experience. One quality which can improve treatment is mental health providers' interpersonal skills when attempting to build a therapeutic rapport with adolescent clients. Semi-structured interviews were conducted with 19 youth who screened positive for mental health concerns while in juvenile detention. Four themes were identified as important to improving the therapeutic alliance: Empathy, client-directed care, sequencing, and positive rapport. Suggestions for strengthening a therapeutic alliance are provided.

  2. Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

    Science.gov (United States)

    Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad

    2016-05-01

    Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and 1H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol40 %) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

  3. Enhancement and electric charge-assisted tuning of nonlinear light generation in bipolar plasmonics.

    Science.gov (United States)

    Ding, Wei; Zhou, Liangcheng; Chou, Stephen Y

    2014-05-14

    We propose and experimentally demonstrate a new plasmonic nonlinear light generation (NLG) structure, termed plasmonic-enhanced, charge-assisted second-harmonic generator (p-CASH), that not only achieves high second-harmonic generation (SHG) enhancement (76-fold), large SHG tunability by bias (8%/V), wide tuning range (280%), 7.8 × 10(-9) conversion efficiency, and high stability but also exhibits a SHG tuning, that is bipolar rather than unipolar, not due to the third-order nonlinear polarization term, hence fundamentally different from the classic electric field induced SHG-tuning (EFISH). We propose a new SHG tuning mechanism: the second-order nonlinear polarization term enhanced by plasmonic effects, changed by charge injection and negative oxygen vacancies movement, and is nearly 3 orders of magnitude larger than EFISH. p-CASH is a bipolar parallel-plate capacitor with thin layers of plasmonic nanostructures, a TiOx (semiconductor and nonlinear) and a SiO2 (insulator) sandwiched between two electrodes. Fabrication of p-CASH used nanoimprint on 4″ wafer and is scalable to wallpaper-sized areas. The new structure, new properties, and new understanding should open up various new designs and applications of NLG in various fields.

  4. Highly penetrative liposome nanomedicine generated by a biomimetic strategy for enhanced cancer chemotherapy.

    Science.gov (United States)

    Jia, Yali; Sheng, Zonghai; Hu, Dehong; Yan, Fei; Zhu, Mingting; Gao, Guanhui; Wang, Pan; Liu, Xin; Wang, Xiaobing; Zheng, Hairong

    2018-04-25

    Liposome nanomedicine has been successfully applied for cancer chemotherapy in patients. However, in general, the therapeutic efficacy is confined by its limited accumulation and penetration in solid tumors. Here, we established a biomimetic strategy for the preparation of highly penetrative liposome nanomedicine for enhanced chemotherapeutic efficacy. By applying this unique type of nanomedicine, membrane proteins on the cancer cells are used as highly penetrative targeting ligands. Biomimetic liposomes are highly stable, exhibiting a superior in vitro homologous targeting ability, and a 2.25-fold deeper penetration in 3D tumor spheroids when compared to conventional liposome nanomedicine. The fluorescence/photoacoustic dual-modal imaging approach demonstrated enhanced tumor accumulation and improved tumor penetration of the biomimetic liposome in C6 glioma tumor-bearing nude mice. Following the intravenous administration of biomimetic liposome nanomedicine, the tumor inhibition rate reached up to 93.3%, which was significantly higher when compared to that of conventional liposome nanomedicine (69.3%). Moreover, histopathological analyses demonstrated that biomimetic liposome nanomedicine has limited side effects. Therefore, these results suggested that a cancer cell membrane-based biomimetic strategy may provide a breakthrough approach for enhancing drug penetration and improving treatment efficacy, holding a great promise for further clinical studies.

  5. A novel peptide enhances therapeutic efficacy of liposomal anti-cancer drugs in mice models of human lung cancer.

    Directory of Open Access Journals (Sweden)

    De-Kuan Chang

    Full Text Available Lung cancer is the leading cause of cancer-related mortality worldwide. The lack of tumor specificity remains a major drawback for effective chemotherapies and results in dose-limiting toxicities. However, a ligand-mediated drug delivery system should be able to render chemotherapy more specific to tumor cells and less toxic to normal tissues. In this study, we isolated a novel peptide ligand from a phage-displayed peptide library that bound to non-small cell lung cancer (NSCLC cell lines. The targeting phage bound to several NSCLC cell lines but not to normal cells. Both the targeting phage and the synthetic peptide recognized the surgical specimens of NSCLC with a positive rate of 75% (27 of 36 specimens. In severe combined immunodeficiency (SCID mice bearing NSCLC xenografts, the targeting phage specifically bound to tumor masses. The tumor homing ability of the targeting phage was inhibited by the cognate synthetic peptide, but not by a control or a WTY-mutated peptide. When the targeting peptide was coupled to liposomes carrying doxorubicin or vinorelbine, the therapeutic index of the chemotherapeutic agents and the survival rates of mice with human lung cancer xenografts markedly increased. Furthermore, the targeting liposomes increased drug accumulation in tumor tissues by 5.7-fold compared with free drugs and enhanced cancer cell apoptosis resulting from a higher concentration of bioavailable doxorubicin. The current study suggests that this tumor-specific peptide may be used to create chemotherapies specifically targeting tumor cells in the treatment of NSCLC and to design targeted gene transfer vectors or it may be used one in the diagnosis of this malignancy.

  6. [Oxygen enhancement ratio (OER) and therapeutic gain factor (GF) for low-dose irradiation with californium-252].

    Science.gov (United States)

    Wambersie, A; Van Dam, J; Octave-Prignot, M; Dutreix, A

    1982-01-01

    The potential benefit of the introduction of californium-252 in interstitial and intracavitary therapy is related to the greater efficiency of its neutron emission against anoxic cancer cells. In that respect, the oxygen enhancement ratio (OER) of the 252Cf emission has been determined for a continuous low dose rate irradiation. The biological system is growth inhibition in Vicia faba bean roots. A new Vicia faba "BelB" strain has been used, which better tolerates long periods (up to about 10 hours) of anoxia. In a first series of experiments, for a 252Cf (Dn + gamma) dose rate of 0.11 Gy . h-1, an OER of 1.4 +/- 0.1 was observed (the gamma contribution of D gamma to the total absorbed dose Dn + gamma was 0.35 at the position of the root tips). In a second series of experiments, in somewhat different geometrical conditions with a 252Cf (Dn + gamma) dose rate of 0.13 Gy . h-1, an OER of 1.5 +/- 0.1 was observed (D gamma/Dn + gamma = 0.42). The OER values observed for similar irradiation times, with iridium-192 gamma-rays, were 2.3 +/- 0.2 and 2.6 +/- 0.1 respectively, which leads to therapeutic gain factors (GF) of 1.6 and 1.7 respectively. These GF values are slightly lower than those previously obtained (GF = 1.8) on the same system, with d(50)-Be, p(75)-Be and 15 MeV neutron beams.

  7. Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats.

    Science.gov (United States)

    Tang, Wei-Ping; Akahoshi, Tomohiko; Piao, Jing-Shu; Narahara, Sayoko; Murata, Masaharu; Kawano, Takahito; Hamano, Nobuhito; Ikeda, Tetsuo; Hashizume, Makoto

    2016-08-01

    Clinical studies suggest that splenectomy improves liver function in cirrhotic patients, but the influence of splenectomy on stem cell transplantation is poorly understood. This study investigated the effect of splenectomy on stem cell infusion and elucidated its mechanism. Rat adipose tissue-derived mesenchymal stem cells were infused into cirrhosis rats with or without splenectomy, followed by the assessment of the in vivo distribution of stem cells and pathological changes. Stromal cell-derived factor-1 and hepatocyte growth factor expression were also investigated in splenectomized cirrhosis patients and rats. Splenectomy, prior to cell infusion, improved liver function and suppressed fibrosis progression more efficiently than cell infusion alone in the experimental cirrhosis model. Stromal cell-derived factor-1 and hepatocyte growth factor levels after splenectomy were increased in patients and rats. These upregulated cytokines significantly facilitated stem cell motility, migration and proliferation in vitro. C-X-C chemokine receptor type 4 neutralization weakened the promotion of cell migration by these cytokines. The infused cells integrated into liver fibrosis septa and participated in regeneration more efficiently in splenectomized rats. Direct coculture with stem cells led to inhibition of hepatic stellate cell proliferation. In addition, hepatocyte growth factor induced hepatic stellate cell apoptosis via the c-jun N-terminal kinase-p53 pathway. Splenectomy prior to cell infusion enhanced the therapeutic effect of stem cells on cirrhosis, which involved upregulation of stromal cell-derived factor-1 and hepatocyte growth factor after splenectomy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Urea removal coupled with enhanced electricity generation in single-chambered microbial fuel cells.

    Science.gov (United States)

    Wang, Luguang; Xie, Beizhen; Gao, Ningshengjie; Min, Booki; Liu, Hong

    2017-09-01

    High concentration of total ammonia nitrogen (TAN) in the form of urea is known to inhibit the performance of many biological wastewater treatment processes. Microbial fuel cells (MFCs) have great potential for TAN removal due to its unique oxic/anoxic environment. In this study, we demonstrated that increased urea (TAN) concentration up to 3940 mg/L did not inhibit power output of single-chambered MFCs, but enhanced power generation by 67% and improved coulombic efficiency by 78% compared to those obtained at 80 mg/L of TAN. Over 80% of nitrogen removal was achieved at TAN concentration of 2630 mg/L. The increased nitrogen removal coupled with significantly enhanced coulombic efficiency, which was observed for the first time, indicates the possibility of a new electricity generation mechanism in MFCs: direct oxidation of ammonia for power generation. This study also demonstrates the great potential of using one MFC reactor to achieve simultaneous electricity generation and urea removal from wastewater.

  9. Technique for enhancing the power output of an electrostatic generator employing parametric resonance

    Science.gov (United States)

    Post, Richard F.

    2016-02-23

    A circuit-based technique enhances the power output of electrostatic generators employing an array of axially oriented rods or tubes or azimuthal corrugated metal surfaces for their electrodes. During generator operation, the peak voltage across the electrodes occurs at an azimuthal position that is intermediate between the position of minimum gap and maximum gap. If this position is also close to the azimuthal angle where the rate of change of capacity is a maximum, then the highest rf power output possible for a given maximum allowable voltage at the minimum gap can be attained. This rf power output is then coupled to the generator load through a coupling condenser that prevents suppression of the dc charging potential by conduction through the load. Optimized circuit values produce phase shifts in the rf output voltage that allow higher power output to occur at the same voltage limit at the minimum gap position.

  10. CAR models: next-generation CAR modifications for enhanced T-cell function

    Directory of Open Access Journals (Sweden)

    Daniel Abate-Daga

    2016-01-01

    Full Text Available T cells genetically targeted with a chimeric antigen receptor (CAR to B-cell malignancies have demonstrated tremendous clinical outcomes. With the proof in principle for CAR T cells as a therapy for B-cell malignancies being established, current and future research is being focused on adapting CAR technology to other cancers, as well as enhancing its efficacy and/or safety. The modular nature of the CAR, extracellular antigen-binding domain fused to a transmembrane domain and intracellular T-cell signaling domains, allows for optimization by replacement of the various components. These modifications are creating a whole new class of therapeutic CARs. In this review, we discuss the recent major advances in CAR design and how these modifications will impact its clinical application.

  11. Enhanced therapeutic effect of multiple injections of HSV-TK + GCV gene therapy in combination with ionizing radiation in a mouse mammary tumor model

    International Nuclear Information System (INIS)

    Vlachaki, Maria T.; Chhikara, Madhu; Aguilar, Laura; Zhu Xiaohong; Chiu, Kam J.; Woo, Shiao; Teh, Bin S.; Thompson, Timothy C.; Butler, E. Brian; Aguilar-Cordova, Estuardo

    2001-01-01

    Purpose: Standard therapies for breast cancer lack tumor specificity and have significant risk for recurrence and toxicities. Herpes simplex virus-thymidine kinase (HSV-tk) gene therapy combined with radiation therapy (XRT) may be effective because of complementary mechanisms and distinct toxicity profiles. HSV-tk gene therapy followed by systemic administration of ganciclovir (GCV) enhances radiation-induced DNA damage by generating high local concentrations of phosphorylated nucleotide analogs that increase radiation-induced DNA breaks and interfere with DNA repair mechanisms. In addition, radiation-induced membrane damage enhances the 'bystander effect' by facilitating transfer of nucleotide analogs to neighboring nontransduced cells and by promoting local and systemic immune responses. This study assesses the effect of single and multiple courses of HSV-tk gene therapy in combination with ionizing radiation in a mouse mammary cancer model. Methods and Materials: Mouse mammary TM40D tumors transplanted s.c. in syngeneic immunocompetent BALB-c mice were treated with either adenoviral-mediated HSV-tk gene therapy or local radiation or the combination of gene and radiation therapy. A vector consisting of a replication-deficient (E1-deleted) adenovirus type 5 was injected intratumorally to administer the HSV-tk gene, and GCV was initiated 24 h later for a total of 6 days. Radiation was given as a single dose of 5 Gy 48 h after the HSV-tk injection. A metastatic model was developed by tail vein injection of TM40D cells on the same day that the s.c. tumors were established. Systemic antitumor effect was evaluated by counting the number of lung nodules after treating only the primary tumors with gene therapy, radiation, or the combination of gene and radiation therapy. To assess the therapeutic efficacy of multiple courses of this combinatorial approach, one, two, and three courses of HSV-tk + GCV gene therapy, in combination with radiation, were compared to HSV-tk or

  12. Dynamic contrast enhancement in widefield microscopy using projector-generated illumination patterns

    International Nuclear Information System (INIS)

    Samson, Edward Carlo; Blanca, Carlo Mar

    2007-01-01

    We present a simple and cost-effective optical protocol to realize contrast-enhancement imaging (such as dark-field, optical-staining and oblique illumination microscopy) of transparent samples on a conventional widefield microscope using commercial multimedia projectors. The projector functions as both light source and mask generator implemented by creating slideshows of the filters projected along the illumination planes of the microscope. The projected optical masks spatially modulate the distribution of the incident light to selectively enhance structures within the sample according to spatial frequency thereby increasing the image contrast of translucent biological specimens. Any amplitude filter can be customized and dynamically controlled so that switching from one imaging modality to another involves a simple slide transition and can be executed at a keystroke with no physical filters and no moving optical parts. The method yields an image contrast of 89-96% comparable with standard enhancement techniques. The polarization properties of the projector are then utilized to discriminate birefringent and non-birefringent sites on the sample using single-shot, simultaneous polarization and optical-staining microscopy. In addition to dynamic pattern generation and polarization, the projector also provides high illumination power and spectral excitation selectivity through its red-green-blue (RGB) channels. We exploit this last property to explore the feasibility of using video projectors to selectively excite stained samples and perform fluorescence imaging in tandem with reflectance and polarization reflectance microscopy

  13. Chain of evidence generation for contrast enhancement in digital image forensics

    Science.gov (United States)

    Battiato, Sebastiano; Messina, Giuseppe; Strano, Daniela

    2010-01-01

    The quality of the images obtained by digital cameras has improved a lot since digital cameras early days. Unfortunately, it is not unusual in image forensics to find wrongly exposed pictures. This is mainly due to obsolete techniques or old technologies, but also due to backlight conditions. To extrapolate some invisible details a stretching of the image contrast is obviously required. The forensics rules to produce evidences require a complete documentation of the processing steps, enabling the replication of the entire process. The automation of enhancement techniques is thus quite difficult and needs to be carefully documented. This work presents an automatic procedure to find contrast enhancement settings, allowing both image correction and automatic scripting generation. The technique is based on a preprocessing step which extracts the features of the image and selects correction parameters. The parameters are thus saved through a JavaScript code that is used in the second step of the approach to correct the image. The generated script is Adobe Photoshop compliant (which is largely used in image forensics analysis) thus permitting the replication of the enhancement steps. Experiments on a dataset of images are also reported showing the effectiveness of the proposed methodology.

  14. Greener corona discharge for enhanced wind generation with a simple dip-coated carbon nanotube decoration

    Science.gov (United States)

    Wu, Yishan; Li, Jun; Ye, Jianchun; Chen, Xiaohong; Li, Huili; Huang, Sumei; Zhao, Ran; Ou-Yang, Wei

    2017-10-01

    Corona discharge-induced wind (CDIW) has been widely utilized in production lines in the food and semiconductor industries and in indoor devices such as electrostatic precipitators. Some ozone is inevitably emitted, posing serious health risks to respiratory system and lung function of a human being. In this work, a greener corona discharge with enhanced wind generation for a needle-to-cylinder discharge structure is demonstrated using a simple dip-coating method to attach carbon nanotubes (CNTs) to the discharge electrode of a stainless steel needle. Compared with a conventional discharge electrode without CNT decoration, the velocity of the CDIW is greatly enhanced, the onset voltage is lowered, the energy conversion efficiency is greatly improved and the concentration of generated ozone is much reduced, making this easy method of CNT decoration a promising candidate for greener corona discharge systems. In addition, several impact factors for improved performance are discussed mathematically and phenomenologically, providing an insight into the corona discharge and wind generation.

  15. Spanish language generation engine to enhance the syntactic quality of AAC systems

    Science.gov (United States)

    Narváez A., Cristian; Sastoque H., Sebastián.; Iregui G., Marcela

    2015-12-01

    People with Complex Communication Needs (CCN) face difficulties to communicate their ideas, feelings and needs. Augmentative and Alternative Communication (AAC) approaches aim to provide support to enhance socialization of these individuals. However, there are many limitations in current applications related with systems operation, target scenarios and language consistency. This work presents an AAC approach to enhance produced messages by applying elements of Natural Language Generation. Specifically, a Spanish language engine, composed of a grammar ontology and a set of linguistic rules, is proposed to improve the naturalness in the communication process, when persons with CCN tell stories about their daily activities to non-disabled receivers. The assessment of the proposed method confirms the validity of the model to improve messages quality.

  16. High order harmonic generation in noble gases using plasmonic field enhancement

    International Nuclear Information System (INIS)

    Ciappina, Marcelo F.; Shaaran, Tahir; Lewenstein, Maciej

    2013-01-01

    Theoretical studies of high-order harmonic generation (HHG) in rare gases driven by plasmonic field enhancement are presented. This kind of fields appears when plasmonic nanostructures are illuminated by an intense few-cycle laser and have a particular spatial dependency, depending on the geometrical shape of the nanostructure. It is demonstrated that the strong nonhomogeneous character of the laser enhanced field plays an important role in the HHG process and significantly extends the harmonic cutoff. The models are based on numerical solution of the time dependent Schroedinger equation (TDSE) and supported by classical and semiclassical calculations. (copyright 2012 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  17. Nonresonant Local Fields Enhance Second-Harmonic Generation from Metal Nanoislands with Dielectric Cover

    Science.gov (United States)

    Chervinskii, Semyon; Koskinen, Kalle; Scherbak, Sergey; Kauranen, Martti; Lipovskii, Andrey

    2018-03-01

    We study second-harmonic generation from gold nanoislands covered with amorphous titanium oxide (TiO2 ) films. As the TiO2 thickness increases, the plasmon resonance of the nanoislands shifts away from the second-harmonic wavelength of 532 nm, diminishing the resonant enhancement of the process at this wavelength. Nevertheless, the second-harmonic signal is enhanced by up to a factor of 45 with increasing TiO2 thickness. This unexpected effect arises from the scaling of local fields at the fundamental wavelength of 1064 nm—which is at the far tail of the resonance—due to a change in the dielectric environment of the nanoislands.

  18. Fin-and-tube heat exchanger enhancement with a combined herringbone and vortex generator design

    DEFF Research Database (Denmark)

    Välikangas, Turo; Singh, Shobhana; Sørensen, Kim

    2018-01-01

    Vortex generators (VGs) are the most commonly investigated enhancement methods in the field of improved heat exchangers. The aim of present work is to study the effect of VGs in a fin-and-tube heat exchanger (FTHE) with herringbone fin shape. The delta winglet VG design with length (s) and height...... (H) is selected based on previous studies. The investigated VG design is simple and considered realistic from the manufacturing point of view. The combined enhancement with herringbone fin and the VG is evaluated by simulating the conjugate heat transfer and the air flow. The structured mesh...... transfer in the herringbone fin but also decrease the pressure drop. The highest and longest investigated VG design is found to perform the best because of its ability to delay the flow detachment from the tube, to feed high kinetic energy flow to the recirculation zone and to create longitudinal vortices...

  19. Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

    International Nuclear Information System (INIS)

    Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke; Kajikawa, Shu-hei; Uesato, Shin-ichi; Watanabe, Kazushi; Tanimura, Susumu; Koji, Takehiko; Kohno, Michiaki

    2013-01-01

    Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showed that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients

  20. Phase chaos generation and security enhancement by introducing fine-controllable dispersion

    Science.gov (United States)

    Yi, Lilin; Ke, Junxiang; Xia, Guangqiong; Hu, Weisheng

    2018-01-01

    For the first time, we experimentally demonstrate phase chaos generation by introducing a fine-controllable dispersion module into the feedback-delayed loop. To study the effect of this specific nonlinearity, we demonstrate the nonlinear dynamics evolution route in terms of the dependence of dispersion and feedback gain parameters by both experiment and simulation, which show good agreement. We also investigate the synchronization error variation with the dispersion mismatch to evaluate the security level of the proposed phase chaos system. The results show that the proposed approach can simultaneously simplify the phase chaos synchronization and enhance the key space, which has potential to be used in high-speed chaotic optical communications.

  1. Enhancements to Constrained Novelty Search: Two-Population Novelty Search for Generating Game Content

    DEFF Research Database (Denmark)

    Liapis, Antonios; Yannakakis, Georgios N.; Togelius, Julian

    2013-01-01

    pop genetic algorithm. These algorithms are applied to the problem of creating diverse and feasible game levels, representative of a large class of important problems in procedural content generation for games. Results show that the new algorithms under certain conditions can produce larger and more...... diverse sets of feasible strategy game maps than existing algorithms. However, the best algorithm is contingent on the particularities of the search space and the genetic operators used. It is also shown that the proposed enhancement of offspring boosting increases performance in all cases....

  2. RFID of next generation network for enhancing customer relationship management in healthcare industries.

    Science.gov (United States)

    Alzahrani, Ahmed; Qureshi, Muhammad Shuaib; Thayananthan, Vijey

    2017-10-23

    This paper aims to analyze possible next generation of networked radio frequency identification (NGN-RFID) system for customer relationship management (CRM) in healthcare industries. Customer relationship and its management techniques in a specific healthcare industry are considered in this development. The key objective of using NGN-RFID scheme is to enhance the handling of patients' data to improve the CRM efficiency in healthcare industries. The proposed NGN-RFID system is one of the valid points to improve the ability of CRM by analyzing different prior and current traditional approaches. The legacy of customer relationship management will be improved by using this modern NGN-RFID technology without affecting the novelty.

  3. Enhanced vanadium (V) reduction and bioelectricity generation in microbial fuel cells with biocathode

    Science.gov (United States)

    Qiu, Rui; Zhang, Baogang; Li, Jiaxin; Lv, Qing; Wang, Song; Gu, Qian

    2017-08-01

    Microbial fuel cells (MFCs) represent a promising approach for remediation of toxic vanadium (V) contaminated environment. Herein, enhanced V(V) reduction and bioelectricity generation are realized in MFCs with biocathode. Synergistically electrochemical and microbial reductions result in the nearly complete removals of V(V) within 7 d operation with initial concentration of 200 mg L-1. Maximum power density of 529 ± 12 mW m-2 is obtained. Electrochemical tests reveal that biocathode promotes electron transfers and reduces charge transfer resistance. XPS analysis confirms that V(IV) is the main reduction product, which precipitates naturally under neutral conditions. High-throughput 16S rRNA gene sequencing analysis indicates that the newly appeared Dysgonomonas is responsible for V(V) reduction and Klebsiella contributes mainly to bioelectricity generation in MFCs with biocathode. This study further improves the performance of remediating V(V) contaminated environment based on MFC technology.

  4. Generation of Binary Off-axis Digital Fresnel Hologram with Enhanced Quality

    Directory of Open Access Journals (Sweden)

    Peter Wai Ming Tsang

    2015-06-01

    Full Text Available The emergence of high resolution printer and digital micromirror device (DMD has enabled real, off-axis holograms to be printed, or projected onto a screen. As most printers and DMD can only reproduce binary dots, the pixels in a hologram have to be truncated to 2 levels. However, direct binarizing a hologram will lead to severe degradation on its reconstructed image. In this paper, a method for generating binary off-axis digital Fresnel hologram is reported. A hologram generated with the proposed method is referred to as the "Enhanced Sampled Binary Hologram" (ESBH. The reconstructed image of the ESBH is superior in visual quality as compare with the one obtained with existing technique, and also resistant to noise contamination.

  5. PANI/NaTaO3 composite photocatalyst for enhanced hydrogen generation under UV light irradiation

    Directory of Open Access Journals (Sweden)

    Zielińska Beata

    2017-09-01

    Full Text Available A PANI/NaTaO3 composite was successfully synthesized by an oxidative polymerization of aniline monomer in hydrochloric acid solution containing sodium tantalate. NaTaO3 at a monoclinic structure was produced via hydrothermal method. The photocatalytic activities of the unmodified NaTaO3 and PANI/NaTaO3 were evaluated for hydrogen generation from an aqueous HCOOH solution and under UV light irradiation. The results showed that the evolution rate of H2 increased significantly when NaTaO3 was modified with PANI. The enhancement of the photocatalytic activity of PANI/NaTaO3 composite was ascribed to the effective charge transfer and separation between NaTaO3 and PANI, which reduced their recombination. This indicates that PANI modification of tantalate photocatalysts may open up a new way to prepare highly efficient catalytic materials for H2 generation.

  6. Enhancement of spatial resolution of terahertz imaging systems based on terajet generation by dielectric cube

    Directory of Open Access Journals (Sweden)

    Hai Huy Nguyen Pham

    2017-05-01

    Full Text Available The terahertz (THz, 0.1–10 THz region has been attracting tremendous research interest owing to its potential in practical applications such as biomedical, material inspection, and nondestructive imaging. Those applications require enhancing the spatial resolution at a specific frequency of interest. A variety of resolution-enhancement techniques have been proposed, such as near-field scanning probes, surface plasmons, and aspheric lenses. Here, we demonstrate for the first time that a mesoscale dielectric cube can be exploited as a novel resolution enhancer by simply placing it at the focused imaging point of a continuous wave THz imaging system. The operating principle of this enhancer is based on the generation—by the dielectric cuboid—of the so-called terajet, a photonic jet in the THz region. A subwavelength hotspot is obtained by placing a Teflon cube, with a 1.46 refractive index, at the imaging point of the imaging system, regardless of the numerical aperture (NA. The generated terajet at 125 GHz is experimentally characterized, using our unique THz-wave visualization system. The full width at half maximum (FWHM of the hotspot obtained by placing the enhancer at the focal point of a mirror with a measured NA of 0.55 is approximately 0.55λ, which is even better than the FWHM obtained by a conventional focusing device with the ideal maximum numerical aperture (NA = 1 in air. Nondestructive subwavelength-resolution imaging demonstrations of a Suica integrated circuit card, which is used as a common fare card for trains in Japan, and an aluminum plate with 0.63λ trenches are presented. The amplitude and phase images obtained with the enhancer at 125 GHz can clearly resolve both the air-trenches on the aluminum plate and the card’s inner electronic circuitry, whereas the images obtained without the enhancer are blurred because of insufficient resolution. An increase of the image contrast by a factor of 4.4 was also obtained using

  7. Prediction of municipal solid waste generation using artificial neural network approach enhanced by structural break analysis.

    Science.gov (United States)

    Adamović, Vladimir M; Antanasijević, Davor Z; Ristić, Mirjana Đ; Perić-Grujić, Aleksandra A; Pocajt, Viktor V

    2017-01-01

    This paper presents the development of a general regression neural network (GRNN) model for the prediction of annual municipal solid waste (MSW) generation at the national level for 44 countries of different size, population and economic development level. Proper modelling of MSW generation is essential for the planning of MSW management system as well as for the simulation of various environmental impact scenarios. The main objective of this work was to examine the potential influence of economy crisis (global or local) on the forecast of MSW generation obtained by the GRNN model. The existence of the so-called structural breaks that occur because of the economic crisis in the studied period (2000-2012) for each country was determined and confirmed using the Chow test and Quandt-Andrews test. Two GRNN models, one which did not take into account the influence of the economic crisis (GRNN) and another one which did (SB-GRNN), were developed. The novelty of the applied method is that it uses broadly available social, economic and demographic indicators and indicators of sustainability, together with GRNN and structural break testing for the prediction of MSW generation at the national level. The obtained results demonstrate that the SB-GRNN model provide more accurate predictions than the model which neglected structural breaks, with a mean absolute percentage error (MAPE) of 4.0 % compared to 6.7 % generated by the GRNN model. The proposed model enhanced with structural breaks can be a viable alternative for a more accurate prediction of MSW generation at the national level, especially for developing countries for which a lack of MSW data is notable.

  8. Field-enhanced route to generating anti-Frenkel pairs in HfO2

    Science.gov (United States)

    Schie, Marcel; Menzel, Stephan; Robertson, John; Waser, Rainer; De Souza, Roger A.

    2018-03-01

    The generation of anti-Frenkel pairs (oxygen vacancies and oxygen interstitials) in monoclinic and cubic HfO2 under an applied electric field is examined. A thermodynamic model is used to derive an expression for the critical field strength required to generate an anti-Frenkel pair. The critical field strength of EaFcr˜101GVm-1 obtained for HfO2 exceeds substantially the field strengths routinely employed in the forming and switching operations of resistive switching HfO2 devices, suggesting that field-enhanced defect generation is negligible. Atomistic simulations with molecular static (MS) and molecular dynamic (MD) approaches support this finding. The MS calculations indicated a high formation energy of Δ EaF≈8 eV for the infinitely separated anti-Frenkel pair, and only a decrease to Δ EaF≈6 eV for the adjacent anti-Frenkel pair. The MD simulations showed no defect generation in either phase for E <3 GVm-1 , and only sporadic defect generation in the monoclinic phase (at E =3 GVm-1 ) with fast (trec<4 ps ) recombination. At even higher E but below EaFcr both monoclinic and cubic structures became unstable as a result of field-induced deformation of the ionic potential wells. Further MD investigations starting with preexisting anti-Frenkel pairs revealed recombination of all pairs within trec<1 ps , even for the case of neutral vacancies and charged interstitials, for which formally there is no electrostatic attraction between the defects. In conclusion, we find no physically reasonable route to generating point-defects in HfO2 by an applied field.

  9. BODIPY-doped silica nanoparticles with reduced dye leakage and enhanced singlet oxygen generation.

    Science.gov (United States)

    Wang, Zhuyuan; Hong, Xuehua; Zong, Shenfei; Tang, Changquan; Cui, Yiping; Zheng, Qingdong

    2015-07-27

    Photodynamic therapy (PDT) is a promising modality for cancer treatment. The essential element in PDT is the photosensitizer, which can be excited by light of a specific wavelength to generate cytotoxic oxygen species (ROS) capable of killing tumor cells. The effectiveness of PDT is limited in part by the low yield of ROS from existing photosensitizers and the unwanted side effects induced by the photosensitizers toward normal cells. Thus the design of nanoplatforms with enhanced PDT is highly desirable but remains challenging. Here, we developed a heavy atom (I) containing dipyrromethene boron difluoride (BODIPY) dye with a silylated functional group, which can be covalently incorporated into a silica matrix to form dye-doped nanoparticles. The incorporated heavy atoms can enhance the generation efficiency of ROS. Meanwhile, the covalently dye-encapsulated nanoparticles can significantly reduce dye leakage and subsequently reduce unwanted side effects. The nanoparticles were successfully taken up by various tumor cells and showed salient phototoxicity against these cells upon light irradiation, demonstrating promising applications in PDT. Moreover, the incorporated iodine atom can be replaced by a radiolabeled iodine atom (e.g., I-124, I-125). The resulting nanoparticles will be good contrast agents for positron emission tomography (PET) imaging with their PDT functionality retained.

  10. Enhancing biodegradation and energy generation via roughened surface graphite electrode in microbial desalination cell.

    Science.gov (United States)

    Ebrahimi, Atieh; Yousefi Kebria, Daryoush; Najafpour Darzi, Ghasem

    2017-09-01

    The microbial desalination cell (MDC) is known as a newly developed technology for water and wastewater treatment. In this study, desalination rate, organic matter removal and energy production in the reactors with and without desalination function were compared. Herein, a new design of plain graphite called roughened surface graphite (RSG) was used as the anode electrode in both microbial fuel cell (MFC) and MDC reactors for the first time. Among the three type of anode electrodes investigated in this study, RSG electrode produced the highest power density and salt removal rate of 10.81 W/m 3 and 77.6%, respectively. Such a power density was 2.33 times higher than the MFC reactor due to the junction potential effect. In addition, adding the desalination function to the MFC reactor enhanced columbic efficiency from 21.8 to 31.4%. These results provided a proof-of-concept that the use of MDC instead of MFC would improve wastewater treatment efficiency and power generation, with an added benefit of water desalination. Furthermore, RSG can successfully be employed in an MDC or MFC, enhancing the bio-electricity generation and salt removal.

  11. A highly efficient method for generation of therapeutic quality human pluripotent stem cells by using naive induced pluripotent stem cells nucleus for nuclear transfer

    Directory of Open Access Journals (Sweden)

    Madhusudana Girija Sanal

    2014-09-01

    Full Text Available Even after several years since the discovery of human embryonic stem cells and induced pluripotent stem cells (iPSC, we are still unable to make any significant therapeutic benefits out of them such as cell therapy or generation of organs for transplantation. Recent success in somatic cell nuclear transfer (SCNT made it possible to generate diploid embryonic stem cells, which opens up the way to make high-quality pluripotent stem cells. However, the process is highly inefficient and hence expensive compared to the generation of iPSC. Even with the latest SCNT technology, we are not sure whether one can make therapeutic quality pluripotent stem cell from any patient’s somatic cells or by using oocytes from any donor. Combining iPSC technology with SCNT, that is, by using the nucleus of the candidate somatic cell which got reprogrammed to pluripotent state instead that of the unmodified nucleus of the candidate somatic cell, would boost the efficiency of the technique, and we would be able to generate therapeutic quality pluripotent stem cells. Induced pluripotent stem cell nuclear transfer (iPSCNT combines the efficiency of iPSC generation with the speed and natural reprogramming environment of SCNT. The new technique may be called iPSCNT. This technique could prove to have very revolutionary benefits for humankind. This could be useful in generating organs for transplantation for patients and for reproductive cloning, especially for childless men and women who cannot have children by any other techniques. When combined with advanced gene editing techniques (such as CRISPR-Cas system this technique might also prove useful to those who want to have healthy children but suffer from inherited diseases. The current code of ethics may be against reproductive cloning. However, this will change with time as it happened with most of the revolutionary scientific breakthroughs. After all, it is the right of every human to have healthy offspring and it is

  12. Theory of enhanced second-harmonic generation by the quadrupole-dipole hybrid exciton

    International Nuclear Information System (INIS)

    Roslyak, Oleksiy; Birman, Joseph L

    2008-01-01

    We report calculated substantial enhancement of the second-harmonic generation (SHG) in cuprous oxide crystals, resonantly hybridized with an appropriate organic material (DCM2:CA:PS 'solid state solvent'). The quadrupole origin of the inorganic part of the quadrupole-dipole hybrid provides inversion symmetry breaking and the organic part contributes to the oscillator strength of the hybrid. We show that the enhancement of the SHG, compared to the bulk cuprous oxide crystal, is proportional to the ratio of the DCM2 dipole moment and the effective dipole moment of the quadrupole transitions in the cuprous oxide. It is also inversely proportional to the line-width of the hybrid and bulk excitons. The enhancement may be regulated by adjusting the organic blend (mutual concentration of the DCM2 and CA part of the solvent) and pumping conditions (varying the angle of incidence in the case of optical pumping or populating the minimum of the lower branch of the hybrid in the case of electrical pumping)

  13. Selectively Plasmon-Enhanced Second-Harmonic Generation from Monolayer Tungsten Diselenide on Flexible Substrates

    KAUST Repository

    Wang, Zhuo

    2018-01-04

    Monolayer two-dimensional transition metal dichalcogenides (2D TMDCs) exhibit promising characteristics in miniaturized nonlinear optical frequency converters, due to their inversion asymmetry and large second-order nonlinear susceptibility. However, these materials usually have a very short light interaction lengths with the pump laser because they are atomically thin, such that second-harmonic generation (SHG) is generally inefficient. In this paper, we fabricate a judiciously structured 150-nm-thick planar surface consisting of monolayer tungsten diselenide and sub-20-nm-wide gold trenches on flexible substrates, reporting ~7000-fold SHG enhancement without peak broadening or background in the spectra as compared to WSe2 on as-grown sapphire substrates. Our proof-of-concept experiment yields effective second-order nonlinear susceptibility of 2.1 × 104 pm/V. Three orders of magnitude enhancement is maintained with pump wavelength ranging from 800 nm to 900 nm, breaking the limitation of narrow pump wavelength range for cavity-enhanced SHG. In addition, SHG amplitude can be dynamically controlled via selective excitation of the lateral gap plasmon by rotating the laser polarization. Such fully open, flat and ultrathin profile enables a great variety of functional samples with high SHG from one patterned silicon substrate, favoring scalable production of nonlinear converters. The surface accessibility also enables integration with other optical components for information processing in an ultrathin and flexible form.

  14. Affinity improvement of a therapeutic antibody by structure-based computational design: generation of electrostatic interactions in the transition state stabilizes the antibody-antigen complex.

    Directory of Open Access Journals (Sweden)

    Masato Kiyoshi

    Full Text Available The optimization of antibodies is a desirable goal towards the development of better therapeutic strategies. The antibody 11K2 was previously developed as a therapeutic tool for inflammatory diseases, and displays very high affinity (4.6 pM for its antigen the chemokine MCP-1 (monocyte chemo-attractant protein-1. We have employed a virtual library of mutations of 11K2 to identify antibody variants of potentially higher affinity, and to establish benchmarks in the engineering of a mature therapeutic antibody. The most promising candidates identified in the virtual screening were examined by surface plasmon resonance to validate the computational predictions, and to characterize their binding affinity and key thermodynamic properties in detail. Only mutations in the light-chain of the antibody are effective at enhancing its affinity for the antigen in vitro, suggesting that the interaction surface of the heavy-chain (dominated by the hot-spot residue Phe101 is not amenable to optimization. The single-mutation with the highest affinity is L-N31R (4.6-fold higher affinity than wild-type antibody. Importantly, all the single-mutations showing increase affinity incorporate a charged residue (Arg, Asp, or Glu. The characterization of the relevant thermodynamic parameters clarifies the energetic mechanism. Essentially, the formation of new electrostatic interactions early in the binding reaction coordinate (transition state or earlier benefits the durability of the antibody-antigen complex. The combination of in silico calculations and thermodynamic analysis is an effective strategy to improve the affinity of a matured therapeutic antibody.

  15. Effect of problem solving support and cognitive style on idea generation: Implications for Technology-Enhanced-Learning

    OpenAIRE

    Stoyanov, Slavi; Kirschner, Paul A.

    2008-01-01

    Stoyanov, S., & Kirschner, P. (2007). Effect of problem solving support and cognitive style on idea generation: Implications for Technology-Enhanced-Learning. Journal of Research on Technology in Education, 40(1), 49-63.

  16. Therapeutic efficacy of antibodies lacking Fcγ receptor binding against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies [corrected].

    Directory of Open Access Journals (Sweden)

    Katherine L Williams

    2013-02-01

    Full Text Available Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV. At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel in vitro suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease in vivo. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.

  17. Numerical and Experimental Investigation for Heat Transfer Enhancement by Dimpled Surface Heat Exchanger in Thermoelectric Generator

    Science.gov (United States)

    Wang, Yiping; Li, Shuai; Yang, Xue; Deng, Yadong; Su, Chuqi

    2016-03-01

    For vehicle thermoelectric exhaust energy recovery, the temperature difference between the heat exchanger and the coolant has a strong influence on the electric power generation, and ribs are often employed to enhance the heat transfer of the heat exchanger. However, the introduction of ribs will result in a large unwanted pressure drop in the exhaust system which is unfavorable for the engine's efficiency. Therefore, how to enhance the heat transfer and control the pressure drop in the exhaust system is quite important for thermoelectric generators (TEG). In the current study, a symmetrical arrangement of dimpled surfaces staggered in the upper and lower surfaces of the heat exchanger was proposed to augment heat transfer rates with minimal pressure drop penalties. The turbulent flow characteristics and heat transfer performance of turbulent flow over the dimpled surface in a flat heat exchanger was investigated by numerical simulation and temperature measurements. The heat transfer capacity in terms of Nusselt number and the pressure loss in terms of Fanning friction factors of the exchanger were compared with those of the flat plate. The pressure loss and heat transfer characteristics of dimples with a depth-to-diameter ratio ( h/D) at 0.2 were investigated. Finally, a quite good heat transfer performance with minimal pressure drop heat exchanger in a vehicle TEG was obtained. And based on the area-averaged surface temperature of the heat exchanger and the Seeback effect, the power generation can be improved by about 15% at Re = 25,000 compared to a heat exchanger with a flat surface.

  18. Enhanced microbial coalbed methane generation: A review of research, commercial activity, and remaining challenges

    Science.gov (United States)

    Ritter, Daniel J.; Vinson, David S.; Barnhart, Elliott P.; Akob, Denise M.; Fields, Matthew W.; Cunningham, Al B.; Orem, William H.; McIntosh, Jennifer C.

    2015-01-01

    Coalbed methane (CBM) makes up a significant portion of the world’s natural gas resources. The discovery that approximately 20% of natural gas is microbial in origin has led to interest in microbially enhanced CBM (MECoM), which involves stimulating microorganisms to produce additional CBM from existing production wells. This paper reviews current laboratory and field research on understanding processes and reservoir conditions which are essential for microbial CBM generation, the progress of efforts to stimulate microbial methane generation in coal beds, and key remaining knowledge gaps. Research has been primarily focused on identifying microbial communities present in areas of CBM generation and attempting to determine their function, in-situ reservoir conditions that are most favorable for microbial CBM generation, and geochemical indicators of metabolic pathways of methanogenesis (i.e., acetoclastic or hydrogenotrophic methanogenesis). Meanwhile, researchers at universities, government agencies, and companies have focused on four primary MECoM strategies: 1) microbial stimulation (i.e., addition of nutrients to stimulate native microbes); 2) microbial augmentation (i.e., addition of microbes not native to or abundant in the reservoir of interest); 3) physically increasing microbial access to coal and distribution of amendments; and 4) chemically increasing the bioavailability of coal organics. Most companies interested in MECoM have pursued microbial stimulation: Luca Technologies, Inc., successfully completed a pilot scale field test of their stimulation strategy, while two others, Ciris Energy and Next Fuel, Inc., have undertaken smaller scale field tests. Several key knowledge gaps remain that need to be addressed before MECoM strategies can be implemented commercially. Little is known about the bacterial community responsible for coal biodegradation and how these microorganisms may be stimulated to enhance microbial methanogenesis. In addition, research

  19. Generation and tunable enhancement of a sum-frequency signal in lithium niobate nanowires

    Science.gov (United States)

    Sergeyev, Anton; Reig Escalé, Marc; Grange, Rachel

    2017-02-01

    Recent developments in the fabrication of lithium niobate (LiNbO3) structures down to the nanoscale opens up novel applications of this versatile material in nonlinear optics. Current nonlinear optical studies in sub-micron waveguides are mainly restricted to the generation of second and third harmonics. In this work, we demonstrate the generation and waveguiding of the sum-frequency generation (SFG) signal in a single LiNbO3 nanowire with a cross-section of 517 nm  ×  654 nm. Furthermore, we enhance the guided SFG signal 17.9 times by means of modal phase matching. We also display tuning of the phase-matched wavelength by varying the nanowire cross-section and changing the polarization of the incident laser. The results prove that LiNbO3 nanowires can be successfully used for nonlinear wave-mixing applications and assisting the miniaturization of optical devices. , which features invited work from the best early-career researchers working within the scope of J Phys D. This project is part of the Journal of Physics series’ 50th anniversary celebrations in 2017. Rachel Grange was selected by the Editorial Board of J Phys D as an Emerging Leader.

  20. Phase-merging enhanced harmonic generation free-electron laser with a normal modulator.

    Science.gov (United States)

    Zhao, Zhouyu; Li, Heting; Jia, Qika

    2017-09-01

    A phase-merging enhanced harmonic generation free-electron laser (FEL) was proposed to increase the harmonic conversion efficiency of seeded FELs and promote the radiation wavelength towards the X-ray spectral region. However, this requires a specially designed transverse gradient undulator (TGU) as the modulator to couple the transverse and longitudinal phase space of the electron beam. In this paper, the generation of the phase-merging effect is explored using the natural field gradient of a normal planar undulator. In this method, a vertical dispersion on the electron beam is introduced and then the dispersed beam travels through a normal modulator in a vertical off-axis orbit where the vertical field gradient is selected properly in terms of the vertical dispersion strength and modulation amplitude. The phase-merging effect will be generated after passing through the dispersive chicane. Theoretical analysis and numerical simulations for a seeded soft X-ray FEL based on parameters of the Shanghai Soft X-ray FEL project are presented. Compared with a TGU modulator, using the natural gradient of a normal planar modulator has the distinct advantage that the gradient can be conveniently tuned in quite a large range by adjusting the beam orbit offset.

  1. Enhanced protein loading on a planar Si(111)-H surface with second generation NTA

    Science.gov (United States)

    Liu, Xiang; Han, Huan-Mei; Liu, Hong-Bo; Xiao, Shou-jun

    2010-08-01

    A Si(111)-H surface was modified via a direct reaction between Si-H and 1-undecylenic acid (UA) under microwave irradiation to form molecular monolayers with terminal carboxyl groups. After esterifying carboxylic acid being esterified with N-hydroxysuccinimide (NHS), aminobutyl nitrilotriacetic acid (ANTA) was bound to the silicon surface through amidation (pH = 8.0) between its primary amino group and NHS-ester, producing nitrilotriacetic acid (NTA) anions. Then hexa-histidine tagged thioredoxin-urodilatin (his-tagged protein) and FITC-labeled hexa-histidine tagged thioredoxin-urodilatin (FITC-his-tagged protein) can be anchored after NTA was coordinated with Ni 2+. Furthermore, the NTA-terminated chip was acidified with 0.1 M HCl and subsequently esterified with NHS and then amidated with ANTA again to produce a second generation NTA. Thus the surface density of nitrilotriacetic acid anions was improved and resultantly that of anchored proteins was also enhanced through the iterative reactions. Both multiple transmission-reflection infrared spectroscopy (MTR-IR) and fluorescence scanning measurements demonstrated a proximate 1.63 times of anchored proteins on the second generation NTA/Ni 2+ as that on the first generation NTA/Ni 2+ monolayer.

  2. Enhancing Sensor Array Intelligence by Bayesian Fusion of Information Multiplicity Generated by Multiple Processors

    Directory of Open Access Journals (Sweden)

    Prabha VERMA

    2014-11-01

    Full Text Available The paper presents a new data processing method for sensor array based pattern recognition problem. The primary motivation is to improve the odor recognition efficiency of electronic nose systems. The method creates a set of virtual experts in which individual expert members are defined by a different combination of a feature extractor and a radial basis function (RBF neural network classifier. In this work the outputs from five different linear feature extraction methods: principal component analysis (PCA, independent component analysis (ICA, singular value decomposition (SVD, linear discriminant analysis (LDA and partial-least-square regression (PLSR, are fed separately as inputs to five different RBF neural networks. The parameters defining each RBF network are optimized separately by training them as independent decision makers. Since a given feature extractor processes raw data with specific perspective about the data structure, and RBF network generates a set of class likelihood values, the set of virtual experts generate alternate sets of class likelihood values. Bayesian product rule for fusion is then applied for combining these class likelihood values into class posterior probabilities. The class declaration is finally done by maximum posterior probability. The method has been validated by analyzing 9 chemical and 7 non-chemical data sets. The enhancement in classification rate up to 33.3 % has been found. The reason for system performance improvement is that the multiple feature extractors generate varied representations of raw data by exploring diversity of hidden attributes, and Bayesian fusion works on the extended information provided by several experts.

  3. A Selection Method for Power Generation Plants Used for Enhanced Geothermal Systems (EGS

    Directory of Open Access Journals (Sweden)

    Kaiyong Hu

    2016-07-01

    Full Text Available As a promising and advanced technology, enhanced geothermal systems (EGS can be used to generate electricity using deep geothermal energy. In order to better utilize the EGS to produce electricity, power cycles’ selection maps are generated for people to choose the best system based on the geofluids’ temperature and dryness conditions. Optimizations on double-flash system (DF, flash-organic Rankine cycle system (FORC, and double-flash-organic Rankine cycle system (DFORC are carried out, and the single-flash (SF system is set as a reference system. The results indicate that each upgraded system (DF, FORC, and DFORC can produce more net power output compared with the SF system and can reach a maximum net power output under a given geofluid condition. For an organic Rankine cycle (ORC using R245fa as working fluid, the generated selection maps indicate that using the FORC system can produce more power than using other power cycles when the heat source temperature is below 170 °C. Either DF or DFORC systems could be an option if the heat source temperature is above 170 °C, but the DF system is more attractive under a relatively lower geofluid’s dryness and a higher temperature condition.

  4. Transcranial Cerebellar Direct Current Stimulation Enhances Verb Generation but Not Verb Naming in Poststroke Aphasia.

    Science.gov (United States)

    Marangolo, Paola; Fiori, Valentina; Caltagirone, Carlo; Pisano, Francesca; Priori, Alberto

    2018-02-01

    Although the role of the cerebellum in motor function is well recognized, its involvement in the lexical domain remains to be further elucidated. Indeed, it has not yet been clarified whether the cerebellum is a language structure per se or whether it contributes to language processing when other cognitive components (e.g., cognitive effort, working memory) are required by the language task. Neuromodulation studies on healthy participants have suggested that cerebellar transcranial direct current stimulation (tDCS) is a valuable tool to modulate cognitive functions. However, so far, only a single case study has investigated whether cerebellar stimulation enhances language recovery in aphasic individuals. In a randomized, crossover, double-blind design, we explored the effect of cerebellar tDCS coupled with language treatment for verb improvement in 12 aphasic individuals. Each participant received cerebellar tDCS (20 min, 2 mA) in four experimental conditions: (1) right cathodal and (2) sham stimulation during a verb generation task and (3) right cathodal and (4) sham stimulation during a verb naming task. Each experimental condition was run in five consecutive daily sessions over 4 weeks. At the end of treatment, a significant improvement was found after cathodal stimulation only in the verb generation task. No significant differences were present for verb naming among the two conditions. We hypothesize that cerebellar tDCS is a viable tool for recovery from aphasia but only when the language task, such as verb generation, also demands the activation of nonlinguistic strategies.

  5. Connected: Recommendations and Techniques in Order to Employ Internet Tools for the Enhancement of Online Therapeutic Relationships. Experiences from Italy.

    Science.gov (United States)

    Manfrida, Gianmarco; Albertini, Valentina; Eisenberg, Erica

    2017-01-01

    The article explores the different types of therapeutic relationship that can evolve both on- and offline, thanks to the use of tools, such as software and applications, which enable therapists and patients contact outside of the traditional setting. Given the premise that it is practically impossible today to maintain a relationship without the use of internet and telephones, it becomes necessary to question the ways in which the online space can become a useful extension of the therapeutic setting. The authors, starting from a consideration regarding the specificity of the online therapeutic relationship, analyze the best ways to use text and email messaging with patients. Furthermore, specific interactions via group chats are presented, for example, to coordinate a therapeutic team involving several professionals. Further, video chat settings are discussed through a clinical case presentation. Lastly, the therapist's management of social networks is debated, underscoring the importance for the therapists that his or her online identity be consistent with the offline image which patients are introduced to in the traditional setting of the therapy room.

  6. Enhanced therapeutic agent delivery through magnetic resonance imaging-monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status.

    Science.gov (United States)

    Liu, Hao-Li; Yang, Hung-Wei; Hua, Mu-Yi; Wei, Kuo-Chen

    2012-01-01

    Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

  7. Enhanced Control for a Direct-driven Permanent Synchronous Generator Wind-power Generation System with Flywheel Energy Storage Unit Under Unbalanced Grid Fault

    DEFF Research Database (Denmark)

    Yao, Jun; Zhou, Te; Hu, Weihao

    2015-01-01

    This article presents an enhanced control strategy for a direct-driven permanent synchronous generator based wind-power generation system with a flywheel energy storage unit. The behaviors of the direct-driven permanent magnet synchronous generator system with a flywheel energy storage unit under......, the DC-link voltage oscillations can be effectively suppressed during the unbalanced grid fault by controlling the flywheel energy storage unit. Furthermore, a proportional–integral-resonant controller is designed for the flywheel motor to eliminate the oscillations in the DC-link voltage. Finally......, the proposed coordinated control strategy for the direct-driven permanent magnet synchronous generator system with a flywheel energy storage unit has been validated by the simulation results of a 1-MW direct-driven permanent magnet synchronous generator wind power generation system with a flywheel energy...

  8. Substrate-enhanced microbial fuel cells for improved remote power generation from sediment-based systems.

    Science.gov (United States)

    Rezaei, Farzaneh; Richard, Tom L; Brennan, Rachel A; Logan, Bruce E

    2007-06-01

    A sediment microbial fuel cell (MFC) produces electricity through the bacterial oxidation of organic matter contained in the sediment. The power density is limited, however, due in part to the low organic matter content of most marine sediments. To increase power generation from these devices, particulate substrates were added to the anode compartment. Three materials were tested: two commercially available chitin products differing in particle size and biodegradability (Chitin 20 and Chitin 80) and cellulose powder. Maximum power densities using chitin in this substrate-enhanced sediment MFC (SEM) were 76 +/- 25 and 84 +/- 10 mW/m2 (normalized to cathode projected surface area) for Chitin 20 and Chitin 80, respectively, versus less than 2 mW/m2 for an unamended control. Power generation over a 10 day period averaged 64 +/- 27 mW/ m2 (Chitin 20) and 76 +/- 15 mW/m2 (Chitin 80). With cellulose, a similar maximum power was initially generated (83 +/- 3 mW/m2), but power rapidly decreased after only 20 h. Maximum power densities over the next 5 days varied substantially among replicate cellulose-fed reactors, ranging from 29 +/- 12 to 62 +/- 23 mW/m2. These results suggest a new approach to power generation in remote areas based on the use of particulate substrates. While the longevity of the SEM was relatively short in these studies, it is possible to increase operation times by controlling particle size, mass, and type of material needed to achieve desired power levels that could theoretically be sustained over periods of years or even decades.

  9. How music training enhances working memory: a cerebrocerebellar blending mechanism that can lead equally to scientific discovery and therapeutic efficacy in neurological disorders.

    Science.gov (United States)

    Vandervert, Larry

    2015-01-01

    Following in the vein of studies that concluded that music training resulted in plastic changes in Einstein's cerebral cortex, controlled research has shown that music training (1) enhances central executive attentional processes in working memory, and (2) has also been shown to be of significant therapeutic value in neurological disorders. Within this framework of music training-induced enhancement of central executive attentional processes, the purpose of this article is to argue that: (1) The foundational basis of the central executive begins in infancy as attentional control during the establishment of working memory, (2) In accordance with Akshoomoff, Courchesne and Townsend's and Leggio and Molinari's cerebellar sequence detection and prediction models, the rigors of volitional control demands of music training can enhance voluntary manipulation of information in thought and movement, (3) The music training-enhanced blending of cerebellar internal models in working memory as can be experienced as intuition in scientific discovery (as Einstein often indicated) or, equally, as moments of therapeutic advancement toward goals in the development of voluntary control in neurological disorders, and (4) The blending of internal models as in (3) thus provides a mechanism by which music training enhances central executive processes in working memory that can lead to scientific discovery and improved therapeutic outcomes in neurological disorders. Within the framework of Leggio and Molinari's cerebellar sequence detection model, it is determined that intuitive steps forward that occur in both scientific discovery and during therapy in those with neurological disorders operate according to the same mechanism of adaptive error-driven blending of cerebellar internal models. It is concluded that the entire framework of the central executive structure of working memory is a product of the cerebrocerebellar system which can, through the learning of internal models

  10. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Cação-Benedini, L.O.; Ribeiro, P.G. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Prado, C.M.; Chesca, D.L. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Mattiello-Sverzut, A.C. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Medicina e Reabilitação do Aparelho Locomotor, Departamento de Biomecânica, Ribeirão Preto, SP, Brasil, Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

  11. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

    Directory of Open Access Journals (Sweden)

    L.O. Cação-Benedini

    2014-06-01

    Full Text Available Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68 and Western blot analysis (dystrophin/laminin. Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days, an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

  12. Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle.

    Science.gov (United States)

    Cação-Benedini, L O; Ribeiro, P G; Prado, C M; Chesca, D L; Mattiello-Sverzut, A C

    2014-06-01

    Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

  13. Carbon quantum dots coated BiVO{sub 4} inverse opals for enhanced photoelectrochemical hydrogen generation

    Energy Technology Data Exchange (ETDEWEB)

    Nan, Feng; Shen, Mingrong; Fang, Liang, E-mail: zhkang@suda.edu.cn, E-mail: lfang@suda.edu.cn [College of Physics, Optoelectronics and Energy and Jiangsu Key Laboratory of Thin Films, Soochow University, Suzhou 215006 (China); Kang, Zhenhui, E-mail: zhkang@suda.edu.cn, E-mail: lfang@suda.edu.cn [Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006 (China); Wang, Junling [School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

    2015-04-13

    Carbon quantum dots (CQDs) coated BiVO{sub 4} inverse opal (io-BiVO{sub 4}) structure that shows dramatic improvement of photoelectrochemical hydrogen generation has been fabricated using electrodeposition with a template. The io-BiVO{sub 4} maximizes photon trapping through slow light effect, while maintaining adequate surface area for effective redox reactions. CQDs are then incorporated to the io-BiVO{sub 4} to further improve the photoconversion efficiency. Due to the strong visible light absorption property of CQDs and enhanced separation of the photoexcited electrons, the CQDs coated io-BiVO{sub 4} exhibit a maximum photo-to-hydrogen conversion efficiency of 0.35%, which is 6 times higher than that of the pure BiVO{sub 4} thin films. This work is a good example of designing composite photoelectrode by combining quantum dots and photonic crystal.

  14. Control technique for enhancing the stable operation of distributed generation units within a microgrid

    International Nuclear Information System (INIS)

    Mehrasa, Majid; Pouresmaeil, Edris; Mehrjerdi, Hasan; Jørgensen, Bo Nørregaard; Catalão, João P.S.

    2015-01-01

    Highlights: • A control technique for enhancing the stable operation of distributed generation units is proposed. • Passivity-based control technique is considered to analyze the dynamic and steady-state behaviors. • The compensation of instantaneous variations in the reference current components is considered. • Simulation results confirm the performance of the control scheme within the microgrid. - Abstract: This paper describes a control technique for enhancing the stable operation of distributed generation (DG) units based on renewable energy sources, during islanding and grid-connected modes. The Passivity-based control technique is considered to analyze the dynamic and steady-state behaviors of DG units during integration and power sharing with loads and/or power grid, which is an appropriate tool to analyze and define a stable operating condition for DG units in microgrid technology. The compensation of instantaneous variations in the reference current components of DG units in ac-side, and dc-link voltage variations in dc-side of interfaced converters, are considered properly in the control loop of DG units, which is the main contribution and novelty of this control technique over other control strategies. By using the proposed control technique, DG units can provide the continuous injection of active power from DG sources to the local loads and/or utility grid. Moreover, by setting appropriate reference current components in the control loop of DG units, reactive power and harmonic current components of loads can be supplied during the islanding and grid-connected modes with a fast dynamic response. Simulation results confirm the performance of the control scheme within the microgrid during dynamic and steady-state operating conditions

  15. A Polar Sulfamide Spacer Significantly Enhances the Manufacturability, Stability, and Therapeutic Index of Antibody–Drug Conjugates

    OpenAIRE

    Jorge M. M. Verkade; Marloes A. Wijdeven; Remon van Geel; Brian M. G. Janssen; Sander S. van Berkel; Floris L. van Delft

    2018-01-01

    Despite tremendous efforts in the field of targeted cancer therapy with antibody–drug conjugates (ADCs), attrition rates have been high. Historically, the priority in ADC development has been the selection of target, antibody, and toxin, with little focus on the nature of the linker. We show here that a short and polar sulfamide spacer (HydraSpace™, AE Oss, The Netherland) positively impacts ADC properties in various ways: (a) efficiency of conjugation; (b) stability; and (c) therapeutic inde...

  16. Identification of enhanced cytokine generation following sepsis. Dream of magic bullet for mortality prediction and therapeutic evaluation

    Directory of Open Access Journals (Sweden)

    H Hamishehkar

    2010-09-01

    Full Text Available "n  "nBackground and the purpose of the study: sepsis is one of the most widespread and lethal disease in Intensive Care Units (ICU. Based on pathophisyology of sepsis, it seems that routine laboratory tests combined with analysis of pro-inflammatory cytokines plasma levels, help clinicians to have more information about disease progress and its correct management. "nMethods:This was a prospective observational study to determine the predictive role of Tumor Necrosis Factor alpha (TNF-α, Interleukin (IL-1β and IL-6 as three main pro-inflammatory cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II and Sequential Organ Failure Assessment (SOFA as two scoring systems in mortality of critically ill patients with severe sepsis. Fifty and five patients with criteria of severe sepsis were included in this study. An exclusion criterion was post Cardiopulmonary Resuscitation (CPR status. Cytokines (TNF-α, IL-1β and IL-6 were assayed in the first, third and seventh days in blood of patients. Results and major conclusion:Among three measured cytokines, sequential levels of TNF-α and IL-6 showed significant differences between survivors and nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during the period of this study. The areas under the receiver operating characteristic (AUROC curve indicated that APACHE II (0.858, 0.848, 0.861 and IL-6 (0.797, 0.799, 0.899 had discriminative power in prediction of mortality during sequental measured days. Multiple logestic regression analysis identified that evaluation of APACHE II and TNF-α in the first day and APACHE II and IL-6 in the third and seventh days of severe septic patients are independent outcome predictors. Results of this study suggest that IL-6 and APACHE II are useful cytokine and scoring systems respectively in prediction of mortality and clinical evaluation of severe septic patients.

  17. Brief Communication: Contrast-stretching- and histogram-smoothness-based synthetic aperture radar image enhancement for flood map generation

    Science.gov (United States)

    Nazir, F.; Riaz, M. M.; Ghafoor, A.; Arif, F.

    2015-02-01

    Synthetic-aperture-radar-image-based flood map generation is usually a challenging task (due to degraded contrast). A three-step approach (based on adaptive histogram clipping, histogram remapping and smoothing) is proposed for generation of a more visualized flood map image. The pre- and post-flood images are adaptively histogram equalized. The hidden details in difference image are enhanced using contrast-based enhancement and histogram smoothing. A fast-ready flood map is then generated using equalized pre-, post- and difference images. Results (evaluated using different data sets) show significance of the proposed technique.

  18. Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin.

    Science.gov (United States)

    Masadeh, Majed M; Alzoubi, Karem H; Al-Azzam, Sayer I; Al-Buhairan, Ahlam M

    2017-01-01

    The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923). The antibacterial activity of ciprofloxacin, with or without pretreatment of bacterial cells by vorinostat, was examined using the disc diffusion procedure and determination of the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared to those treated with ciprofloxacin alone. In correlation, generation of reactive oxygen species (ROS) induced by the antibacterial action of ciprofloxacin was enhanced by treatment of bacterial cells with vorinostat. Results showed the possible agonistic properties of vorinostat when used together with ciprofloxacin. This could be related to the ability of these agents to enhance oxidative stress in bacterial cells.

  19. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

    Science.gov (United States)

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

  20. Position of nuclear power generation in the public and further enhancement of safe and stable operation

    International Nuclear Information System (INIS)

    Miyazaki, Yozo

    1996-01-01

    In Japan, the first commercial light water reactor (LWR) started operation in 1970 when the International Exposition was held in Osaka, and now 50 nuclear power plants supply about 30 % of the total electricity and nuclear power plays the important role as a 'major power source'. Meanwhile, with the international transportation of plutonium and return shipment of vitrified HLW reprocessed abroad, nuclear power has closer relationship with the public in these days. We will review the history of nuclear power generation in Japan from the viewpoint of the safety culture and consider the safety culture under the present situation. The team of 'safety Charlotte's fixed its position since the occurrence of Chernobyl accident though the concept existed as expressed in words such as 'safety-first principle' and 'enhancement of morale'. The safety culture is a concept: high level 'safety Culture' cab be expected when 'the management of the organization' and 'individual consciousness concerning safety' are well balanced. The 'safety culture' has experienced various changes along with the development of nuclear power in Japan: at the initial period of the development, the management side invested excellent talents and funds to the nuclear division based on the 'safety-first principle' from the beginning. At the same time, the world of atom filled with dream appealed to those who had enthusiasm as pioneers and they were engaged in the development with enhanced morale

  1. Atom-Dependent Edge-Enhanced Second-Harmonic Generation on MoS2Monolayers.

    Science.gov (United States)

    Lin, Kuang-I; Ho, Yen-Hung; Liu, Shu-Bai; Ciou, Jian-Jhih; Huang, Bo-Ting; Chen, Christopher; Chang, Han-Ching; Tu, Chien-Liang; Chen, Chang-Hsiao

    2018-02-14

    Edge morphology and lattice orientation of single-crystal molybdenum disulfide (MoS 2 ) monolayers, a transition metal dichalcogenide (TMD), possessing a triangular shape with different edges grown by chemical vapor deposition are characterized by atomic force microscopy and transmission electron microscopy. Multiphoton laser scanning microscopy is utilized to study one-dimensional atomic edges of MoS 2 monolayers with localized midgap electronic states, which result in greatly enhanced optical second-harmonic generation (SHG). Microscopic S-zigzag edge and S-Mo Klein edge (bare Mo atoms protruding from a S-zigzag edge) terminations and the edge-atom dependent resonance energies can therefore be deduced based on SHG images. Theoretical calculations based on density functional theory clearly explain the lower energy of the S-zigzag edge states compared to the corresponding S-Mo Klein edge states. Characterization of the atomic-scale variation of edge-enhanced SHG is a step forward in this full-optical and high-yield technique of atomic-layer TMDs.

  2. Microwave generation enhancement of X-band CRBWO by use of coaxial dual annular cathodes

    Directory of Open Access Journals (Sweden)

    Yan Teng

    2013-07-01

    Full Text Available This paper presents an approach that greatly enhances both the output power and the conversion efficiency of the coaxial relativistic backward wave oscillator (CRBWO by using coaxial dual annular cathodes, which increases the diode current rather than the diode voltage. The reasons for the maladjustment of CRBWO under a high diode voltage are analyzed theoretically. It is found that by optimization of the diode structure, the shielding effect of the space charge of the outer beams on the inner cathode can be alleviated effectively and dual annular beams with the same kinetic energy can be explosively emitted in parallel. The coaxial reflector can enhance the conversion efficiency by improving the premodulation of the beams. The electron dump on the inner conductor ensures that the electron beams continue to provide kinetic energy to the microwave output until they vanish. Particle-in-cell (PIC simulation results show that generation can be enhanced up to an output power level of 3.63 GW and conversion efficiency of 45% at 8.97 GHz under a diode voltage of 659 kV and current of 12.27 kA. The conversion efficiency remains above 40% and the output frequency variation is less than 100 MHz over a voltage range of more than 150 kV. Also, the application of the coaxial dual annular cathodes means that the diode impedance is matched to that of the transmission line of the accelerators. This impedance matching can effectively eliminate power reflection at the diode, and thus increase the energy efficiency of the entire system.

  3. Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

    Directory of Open Access Journals (Sweden)

    Manasi Das

    Full Text Available Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined and single or dual drug loaded nanoparticles (unconjugated/folate conjugated. The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.

  4. Modeling and characterization of field-enhanced corona discharge in ozone-generator diode

    Science.gov (United States)

    Patil, Jagadish G.; Vijayan, T.

    2010-02-01

    Electric field enhanced corona plasma discharge in ozone generator diode of axial symmetry has been investigated and characterized in theory. The cathode K of diode is made of a large number of sharpened nozzles arranged on various radial planes on the axial mast and pervaded in oxygen gas inside the anode cup A, produces high fields over MV/m and aids in the formation of a corona plume of dense ozone cloud over the cathode surface. An r-z finite difference scheme has been devised and employed to numerically determine the potential and electric field distributions inside the diode. The analyses of cathode emissions revealed a field emission domain conformed to modified Child-Langmuir diode-current. Passage of higher currents (over μA) in shorter A-K gaps d gave rise to cathode heated plasma extending from the corona to Saha regimes depending on local temperature. Plasma densities of order 102-106 m-3 are predicted in these. For larger d however, currents are smaller and heating negligible and a negative corona favoring ozone formation is attained. High ozone yields about 20 per cent of oxygen input is predicted in this domain. The generator so developed will be applied to various important applications such as, purification of ambient air /drinking water, ozone therapy, and so on.

  5. Modeling and characterization of field-enhanced corona discharge in ozone-generator diode

    International Nuclear Information System (INIS)

    Patil, Jagadish G; Vijayan, T

    2010-01-01

    Electric field enhanced corona plasma discharge in ozone generator diode of axial symmetry has been investigated and characterized in theory. The cathode K of diode is made of a large number of sharpened nozzles arranged on various radial planes on the axial mast and pervaded in oxygen gas inside the anode cup A, produces high fields over MV/m and aids in the formation of a corona plume of dense ozone cloud over the cathode surface. An r-z finite difference scheme has been devised and employed to numerically determine the potential and electric field distributions inside the diode. The analyses of cathode emissions revealed a field emission domain conformed to modified Child-Langmuir diode-current. Passage of higher currents (over μA) in shorter A-K gaps d gave rise to cathode heated plasma extending from the corona to Saha regimes depending on local temperature. Plasma densities of order 10 2 -10 6 m -3 are predicted in these. For larger d however, currents are smaller and heating negligible and a negative corona favoring ozone formation is attained. High ozone yields about 20 per cent of oxygen input is predicted in this domain. The generator so developed will be applied to various important applications such as, purification of ambient air /drinking water, ozone therapy, and so on.

  6. Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential.

    Science.gov (United States)

    El-Andaloussi, Nazim; Bonifati, Serena; Kaufmann, Johanna K; Mailly, Laurent; Daeffler, Laurent; Deryckère, François; Nettelbeck, Dirk M; Rommelaere, Jean; Marchini, Antonio

    2012-10-01

    In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1- and E3-deleted Ad5 vector genome. As we found that parvoviral NS expression inhibited Ad-PV chimera production, we engineered the parvoviral P4 early promoter, which governs NS expression, by inserting into its sequence tetracycline operator elements. As a result of these modifications, P4-driven expression was blocked in the packaging T-REx-293 cells, which constitutively express the tetracycline repressor, allowing high-yield chimera production. The chimera effectively delivered the PV genome into cancer cells, from which fully infectious replication-competent parvovirus particles were generated. Remarkably, the Ad-PV chimera exerted stronger cytotoxic activities against various cancer cell lines, compared with the PV and Ad parental viruses, while being still innocuous to a panel of tested healthy primary human cells. This Ad-PV chimera represents a novel versatile anticancer agent which can be subjected to further genetic manipulations in order to reinforce its enhanced oncolytic capacity through arming with transgenes or retargeting into tumor cells.

  7. Scaling law and enhancement of lift generation of an insect-size hovering flexible wing

    Science.gov (United States)

    Kang, Chang-kwon; Shyy, Wei

    2013-01-01

    We report a comprehensive scaling law and novel lift generation mechanisms relevant to the aerodynamic functions of structural flexibility in insect flight. Using a Navier–Stokes equation solver, fully coupled to a structural dynamics solver, we consider the hovering motion of a wing of insect size, in which the dynamics of fluid–structure interaction leads to passive wing rotation. Lift generated on the flexible wing scales with the relative shape deformation parameter, whereas the optimal lift is obtained when the wing deformation synchronizes with the imposed translation, consistent with previously reported observations for fruit flies and honeybees. Systematic comparisons with rigid wings illustrate that the nonlinear response in wing motion results in a greater peak angle compared with a simple harmonic motion, yielding higher lift. Moreover, the compliant wing streamlines its shape via camber deformation to mitigate the nonlinear lift-degrading wing–wake interaction to further enhance lift. These bioinspired aeroelastic mechanisms can be used in the development of flapping wing micro-robots. PMID:23760300

  8. Enhanced performance of dispenser printed MA n-type Bi₂Te₃ composite thermoelectric generators.

    Science.gov (United States)

    Madan, Deepa; Wang, Zuoqian; Chen, Alic; Juang, Rei-Cheng; Keist, Jay; Wright, Paul K; Evans, Jim W

    2012-11-01

    This work presents performance advancements of dispenser printed composite thermoelectric materials and devices. Dispenser printed thick films allow for low-cost and scalable manufacturing of microscale energy harvesting devices. A maximum ZT value of 0.31 has been achieved for mechanically alloyed (MA) n-type Bi₂Te₃-epoxy composite films with 1 wt % Se cured at 350 °C. The enhancement of ZT is a result of increase in the electrical conductivity through the addition of Se, which ultimately lowers the sintering temperature (350 °C). A 62 single-leg thermoelectric generator (TEG) prototype with 5 mm ×700 μm × 120 μm printed element dimensions was fabricated on a custom designed polyimide substrate with thick metal contacts. The prototype device produced a power output of 25 μW at 0.23 mA current and 109 mV voltage for a temperature difference of 20 °C, which is sufficient for low power generation for autonomous microsystem applications.

  9. ENHANCEMENT OF STEREO IMAGERY BY ARTIFICIAL TEXTURE PROJECTION GENERATED USING A LIDAR

    Directory of Open Access Journals (Sweden)

    J. Veitch-Michaelis

    2016-06-01

    Full Text Available Passive stereo imaging is capable of producing dense 3D data, but image matching algorithms generally perform poorly on images with large regions of homogenous texture due to ambiguous match costs. Stereo systems can be augmented with an additional light source that can project some form of unique texture onto surfaces in the scene. Methods include structured light, laser projection through diffractive optical elements, data projectors and laser speckle. Pattern projection using lasers has the advantage of producing images with a high signal to noise ratio. We have investigated the use of a scanning visible-beam LIDAR to simultaneously provide enhanced texture within the scene and to provide additional opportunities for data fusion in unmatched regions. The use of a LIDAR rather than a laser alone allows us to generate highly accurate ground truth data sets by scanning the scene at high resolution. This is necessary for evaluating different pattern projection schemes. Results from LIDAR generated random dots are presented and compared to other texture projection techniques. Finally, we investigate the use of image texture analysis to intelligently project texture where it is required while exploiting the texture available in the ambient light image.

  10. Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation Cephalosporin.

    Directory of Open Access Journals (Sweden)

    Lindsey Chambers

    Full Text Available Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. β-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3 relative to control cows (n = 3. However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with "phages, prophages, transposable elements, and plasmids", suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle, along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria. This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored.

  11. Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation Cephalosporin.

    Science.gov (United States)

    Chambers, Lindsey; Yang, Ying; Littier, Heather; Ray, Partha; Zhang, Tong; Pruden, Amy; Strickland, Michael; Knowlton, Katharine

    2015-01-01

    Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs) to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. β-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3) relative to control cows (n = 3). However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with "phages, prophages, transposable elements, and plasmids", suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle), along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria). This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored.

  12. Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation Cephalosporin

    Science.gov (United States)

    Ray, Partha; Zhang, Tong; Pruden, Amy; Strickland, Michael; Knowlton, Katharine

    2015-01-01

    Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs) to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. β-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3) relative to control cows (n = 3). However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with “phages, prophages, transposable elements, and plasmids”, suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle), along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria). This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored. PMID:26258869

  13. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions

    International Nuclear Information System (INIS)

    Hammerstingl, Renate; Vogl, Thomas J.; Huppertz, Alexander; Breuer, Josy; Balzer, Thomas; Blakeborough, Anthony; Carter, Rick; Castells Fuste, Lluis; Heinz-Peer, Gertraud; Judmaier, Werner; Laniado, Michael; Manfredi, Riccardo M.; Mathieu, Didier G.; Mueller, Dieter; Mortele, Koenraad; Reimer, Peter; Reiser, Maximilian F.; Robinson, Philip J.; Shamsi, Kohkan; Strotzer, Michael; Taupitz, Matthias; Tombach, Bernd; Valeri, Gianluca; Beers, Bernhard E. van

    2008-01-01

    A multicenter study has been employed to evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) using the new liver-specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic spiral computed tomography (CT), in the diagnosis of focal liver lesions, compared with a standard of reference (SOR). One hundred and sixty-nine patients with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined with intraoperative ultrasound established the SOR. Data sets were evaluated on-site (14 investigators) and off-site (three independent blinded readers). Gd-EOB-DTPA was well tolerated. Three hundred and two lesions were detected in 131 patients valid for analysis by SOR. The frequency of correctly detected lesions was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB-DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19 of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI was superior in the diagnosis and therapeutic management of focal liver lesions compared with CT. (orig.)

  14. Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions

    Energy Technology Data Exchange (ETDEWEB)

    Hammerstingl, Renate; Vogl, Thomas J. [Johann Wolfgang Goethe-Univ., Inst. of Diagnostic and Interventional Radiology, Frankfurt am Main (Germany); Huppertz, Alexander [Imaging Science Inst., Charite - Siemens, Berlin (Germany); Breuer, Josy; Balzer, Thomas [Gobal Clinical Development Diagnostics, Bayer Schering Pharma AG, Berlin (Germany); Blakeborough, Anthony [Royal Hallamshire Hospital, Dept. of Radiology, Sheffield (United Kingdom); Carter, Rick [Bayer Health Care Ltd., Burgess Hill, West Sussex (United Kingdom); Castells Fuste, Lluis [Hospital Vall d' Hebron, Liver Unit, Dept. of Internal Medicine, Barcelona (Spain); Heinz-Peer, Gertraud [Universitaetsklinik fuer Radiodiagnostik, Allg. Krankenhaus der Stadt Wien, Wien (Germany); Judmaier, Werner [Univ. Hospital Innsbruck, Dept. of Magnetic Resonance Imaging and Spectroscopy, Innsbruck (Austria); Laniado, Michael [Universitaetsklinikum Carl Gustav Carus, Technische Univ. Dresden, Inst. for Diagnostic Radiology, Dresden (Germany); Manfredi, Riccardo M. [Univ. of Verona, Dept. of Radiology, Verona (Italy); Mathieu, Didier G. [Centre d' Imagerie, Aix en Provence (France); Mueller, Dieter [Georg-August Univ., Dept. of Radiology, Goettingen (Germany); Mortele, Koenraad [Brigham and Women' s Hospital, Dept. of Radiology (L1), Boston, MA (United States); Reimer, Peter [Klinikum Karlsruhe, Dept. of Radiology, Karlsruhe (Germany); Reiser, Maximilian F. [Ludwig-Maximilians-Univ. Munich - Klinikum Grosshadern, Inst. of Clinical Radiology, Munich (Germany); Robinson, Philip J. [St James' s Univ. Hospital, Dept. of Clinical Radiology, Leeds (United Kingdom); Shamsi, Kohkan [Berlex Labs. Inc., Montville, NJ (United States); Strotzer, Michael [Univ. Hospital, Dept. of Diagnostic Radiology, Regensburg (Germany); Taupitz, Matthias [Universitaetsklinikum Charite, Med. Fakultaet der Humboldt-Univ., Dept. of Radiology, Berlin (Germany); Tombach, Bernd; Valeri, Gianluca; Beers, Bernhard E. van [and others

    2008-03-15

    A multicenter study has been employed to evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) using the new liver-specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic spiral computed tomography (CT), in the diagnosis of focal liver lesions, compared with a standard of reference (SOR). One hundred and sixty-nine patients with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined with intraoperative ultrasound established the SOR. Data sets were evaluated on-site (14 investigators) and off-site (three independent blinded readers). Gd-EOB-DTPA was well tolerated. Three hundred and two lesions were detected in 131 patients valid for analysis by SOR. The frequency of correctly detected lesions was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB-DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19 of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI was superior in the diagnosis and therapeutic management of focal liver lesions compared with CT. (orig.)

  15. Therapeutic Drug Monitoring of Second-Generation Antipsychotics for the Estimation of Early Drug Effect in First-Episode Psychosis: A Cross-sectional Assessment.

    Science.gov (United States)

    Bustillo, Mariana; Zabala, Arantzazu; Querejeta, Imanol; Carton, Jaione I; Mentxaka, Oiane; González-Pinto, Ana; García, Sainza; Meana, J Javier; Eguiluz, J Ignacio; Segarra, Rafael

    2018-04-01

    Studies on therapeutic drug monitoring (TDM) of second-generation antipsychotics (SGAs) have provided conflicting results regarding the association between dose, plasma concentrations, and drug effect and have focused rather on analyzing how individual drugs work. No study has attempted to process data from different SGAs globally to offer a panoramic view of the utility of TDM in clinical practice, and data on patients with first-episode psychosis (FEP) are lacking. This study aimed to assess the relationship between dose, plasma concentrations, and drug effect in a sample of patients with FEP, regardless of the SGA prescribed. Data from 64 compliant patients treated with the same SGA during a 2-month follow-up were recorded. Clinical symptoms were assessed using the Positive and Negative Symptoms Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg für Kliniske Undersogelser scale. SGA doses were standardized to chlorpromazine equivalents, and patients were classified into 3 different ranges according to their plasma concentrations (subtherapeutic, therapeutic, and supratherapeutic). Plasma concentration ranges were proportionally related to dose. Patients with supratherapeutic plasma concentrations were treated with doses significantly higher than those with subtherapeutic concentrations. Dose and plasma concentrations were not associated with early drug effect. TDM seems unable to accurately estimate the early effects of SGAs in FEP. Ours is the first study to categorize plasma concentrations of SGAs into ranges for joint processing of data from a larger number of patients.

  16. A new concept of efficient therapeutic drug monitoring using the high-resolution continuum source absorption spectrometry and the surface enhanced Raman spectroscopy

    Science.gov (United States)

    Xing, Yanlong; Fuss, Harald; Lademann, Jürgen; Huang, Mao Dong; Becker-Ross, Helmut; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora; Esser, Norbert

    2018-04-01

    In this study, a new therapeutic drug monitoring approach has been tested based on the combination of CaF molecular absorption using high-resolution continuum source absorption spectrometry (HR-CSAS) and surface enhanced Raman spectroscopy (SERS). HR-CSAS with mini graphite tube was successfully tested for clinical therapeutic drug monitoring of the fluorine-containing drug capecitabine in sweat samples of cancer patients: It showed advantageous features of high selectivity (no interference from Cl), high sensitivity (characteristic mass of 0.1 ng at CaF 583.069 nm), low sample consumption (down to 30 nL) and fast measurement (no sample pretreatment and less than 1 min of responding time) in tracing the fluorine signal out of capecitabine. However, this technique has the disadvantage of the total loss of the drug's structure information after burning the sample at very high temperature. Therefore, a new concept of combining HR-CSAS with a non-destructive spectroscopic method (SERS) was proposed for the sensitive sensing and specific identification of capecitabine. We tested and succeed in obtaining the molecular characteristics of the metabolite of capecitabine (named 5-fluorouracil) by the non-destructive SERS technique. With the results shown in this work, it is demonstrated that the combined spectroscopic technique of HR-CSAS and SERS will be very useful in efficient therapeutic drug monitoring in the future.

  17. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum.

    Science.gov (United States)

    Ziegler, Anja; Everett, Helen; Hamza, Eman; Garbani, Mattia; Gerber, Vinzenz; Marti, Eliane; Steinbach, Falko

    2016-11-15

    Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including horses. Currently, the gold standard protocol for generating dendritic cells from monocytes across various species relies upon a combination of GM-CSF and IL-4 added to cell culture medium which is supplemented with FBS. The aim of this study was to substitute FBS with heterologous horse serum. For this purpose, equine monocyte-derived dendritic cells (eqMoDC) were generated in the presence of horse serum or FBS and analysed for the effect on morphology, phenotype and immunological properties. Changes in the expression of phenotypic markers (CD14, CD86, CD206) were assessed during dendritic cell maturation by flow cytometry. To obtain a more complete picture of the eqMoDC differentiation and assess possible differences between FBS- and horse serum-driven cultures, a transcriptomic microarray analysis was performed. Lastly, immature eqMoDC were primed with a primary antigen (ovalbumin) or a recall antigen (tetanus toxoid) and, after maturation, were co-cultured with freshly isolated autologous CD5 + T lymphocytes to assess their T cell stimulatory capacity. The microarray analysis demonstrated that eqMoDC generated with horse serum were indistinguishable from those generated with FBS. However, eqMoDC incubated with horse serum-supplemented medium exhibited a more characteristic dendritic cell morphology during differentiation from monocytes. A significant increase in cell viability was also observed in eqMoDC cultured with horse serum. Furthermore, eqMoDC generated in the presence of horse serum

  18. Defective dendritic cell generation from monocytes is a potential reason for poor therapeutic efficacy of interferon α2b (IFNα2b) in cervical cancer.

    Science.gov (United States)

    Roy, Soumyabrata; Goswami, Shyamal; Bose, Anamika; Goswami, Kuntal Kanti; Sarkar, Koustav; Chakraborty, Krishnendu; Chakraborty, Tathagata; Pal, Smarajit; Haldar, Atanu; Basu, Parthasarathi; Biswas, Jaydip; Baral, Rathindranath

    2011-10-01

    Despite being a pleiotropic cytokine, the therapeutic potential of interferon α2b (IFNα2b) is debatable. Thus, the need for identifying predictive marker(s) for patients who are most likely to benefit from the treatment is pivotal for avoiding the exposure of nonresponsive patients to the toxicity of the treatment. To account for the attenuated efficacy of the drug, we have verified its dendritic cell (DC) maturating ability from monocytes of cervical cancer stage IIIB (CaCx-IIIB) patients. First, we evaluated the status of monocytes from CaCx-IIIB and healthy women by conducting flow cytometric studies of various activation markers and a cytokine analysis by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Immature DCs were then generated from these monocytes and matured with low-dose IFNα2b (1500 units/mL). A functional and phenotypic comparative analysis of these matured DCs was performed by flow cytometric, proliferative, cytotoxic, and enzyme-linked immunosorbent assays. Our study shows that monocytes isolated from CaCx-IIIB are impaired, and in vitro maturation with IFNα2b did not significantly improve the functional repertoire of DCs generated from these monocytes in comparison with healthy controls. This impairment of monocytes might be a plausible reason for the attenuated efficacy of this drug alone in treating CaCx-IIIB patients, and this imbalance of immune parameters associated with the stage of malignancy might be considered an effective marker to design a proper therapeutic regimen. Copyright © 2011 Mosby, Inc. All rights reserved.

  19. Next Generation Safeguards Initiative Workshop on Enhanced Recruiting for International Safeguards

    International Nuclear Information System (INIS)

    Pepper, S.E.; Rosenthal, M.D.; Fishbone, L.G.; Occhogrosso, D.M.; Lockwood, D.; Carroll, C.J.; Dreicer, M.; Wallace, R.; Fankhauser, J.

    2009-01-01

    Brookhaven National Laboratory (BNL) hosted a Workshop on Enhanced Recruiting for International Safeguards October 22 and 23, 2008. The workshop was sponsored by DOE/NA-243 under the Next Generation Safeguards Initiative (NGSI). Placing well-qualified Americans in sufficient number and in key safeguards positions within the International Atomic Energy Agency's (IAEA's) Department of Safeguards is an important U.S. non-proliferation objective. The goal of the NGSI Workshop on Enhanced Recruiting for International Safeguards was to improve U.S. efforts to recruit U.S. citizens for IAEA positions in the Department of Safeguards. The participants considered the specific challenges of recruiting professional staff, safeguards inspectors, and managers. BNL's International Safeguards Project Office invited participants from the U.S. Department of Energy, the IAEA, U.S. national laboratories, private industry, academia, and professional societies who are either experts in international safeguards or who understand the challenges of recruiting for technical positions. A final report for the workshop will be finalized and distributed in early 2009. The main finding of the workshop was the need for an integrated recruitment plan to take into account pools of potential candidates, various government and private agency stakeholders, the needs of the IAEA, and the NGSI human capital development plan. There were numerous findings related to and recommendations for maximizing the placement of U.S. experts in IAEA Safeguards positions. The workshop participants offered many ideas for increasing the pool of candidates and increasing the placement rate. This paper will provide details on these findings and recommendations

  20. Next Generation Safeguards Initiative Workshop on Enhanced Recruiting for International Safeguards

    Energy Technology Data Exchange (ETDEWEB)

    Pepper,S.E.; Rosenthal, M.D.; Fishbone, L.G.; Occhogrosso, D.M.; Lockwood, D.; Carroll, C.J.; Dreicer, M.; Wallace, R.; Fankhauser, J.

    2009-07-12

    Brookhaven National Laboratory (BNL) hosted a Workshop on Enhanced Recruiting for International Safeguards October 22 and 23, 2008. The workshop was sponsored by DOE/NA-243 under the Next Generation Safeguards Initiative (NGSI). Placing well-qualified Americans in sufficient number and in key safeguards positions within the International Atomic Energy Agency’s (IAEA’s) Department of Safeguards is an important U.S. non-proliferation objective. The goal of the NGSI Workshop on Enhanced Recruiting for International Safeguards was to improve U.S. efforts to recruit U.S. citizens for IAEA positions in the Department of Safeguards. The participants considered the specific challenges of recruiting professional staff, safeguards inspectors, and managers. BNL’s International Safeguards Project Office invited participants from the U.S. Department of Energy, the IAEA, U.S. national laboratories, private industry, academia, and professional societies who are either experts in international safeguards or who understand the challenges of recruiting for technical positions. A final report for the workshop will be finalized and distributed in early 2009. The main finding of the workshop was the need for an integrated recruitment plan to take into account pools of potential candidates, various government and private agency stakeholders, the needs of the IAEA, and the NGSI human capital development plan. There were numerous findings related to and recommendations for maximizing the placement of U.S. experts in IAEA Safeguards positions. The workshop participants offered many ideas for increasing the pool of candidates and increasing the placement rate. This paper will provide details on these findings and recommendations

  1. Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin

    Directory of Open Access Journals (Sweden)

    Masadeh MM

    2017-10-01

    Full Text Available Majed M Masadeh,1 Karem H Alzoubi,2 Sayer I Al-azzam,2 Ahlam M Al-buhairan3 1Department of Pharmaceutical Technology, 2Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia Abstract: The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA (ATCC 43300, and Streptococcus pneumoniae (ATCC 25923. The antibacterial activity of ciprofloxacin, with or without pretreatment of bacterial cells by vorinostat, was examined using the disc diffusion procedure and determination of the minimum inhibitory concentration (MIC and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared to those treated with ciprofloxacin alone. In correlation, generation of reactive oxygen species (ROS induced by the antibacterial action of ciprofloxacin was enhanced by treatment of bacterial cells with vorinostat. Results showed the possible agonistic properties of vorinostat when used together with ciprofloxacin. This could be related to the

  2. Tumor Therapeutics Work as Stress Inducers to Enhance Tumor Sensitivity to Natural Killer (NK) Cell Cytolysis by Up-regulating NKp30 Ligand B7-H6.

    Science.gov (United States)

    Cao, Guoshuai; Wang, Jian; Zheng, Xiaodong; Wei, Haiming; Tian, Zhigang; Sun, Rui

    2015-12-11

    Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia, and cytokine injection. One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis. Further studies showed that treatment of tumor cells with almost all standard tumor therapeutics, including chemotherapy (cisplatin, 5-fluorouracil), radiation therapy, non-lethal heat shock, and cytokine therapy (TNF-α), could up-regulate the expression of B7-H6 in tumor cells and enhance tumor sensitivity to NK cell cytolysis. B7-H6 shRNA treatment effectively dampened sensitization of tumor cells to NK-mediated lysis. Our study not only reveals the possibility that tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis but also suggests that B7-H6 could be a potential target for tumor therapy in the future. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Powerful Swirl Generation of Flow-driven Rotating Mixing Vane for Enhancing CHF

    International Nuclear Information System (INIS)

    Seo, Han; Seo, Seok Bin; Heo, Hyo; Bang, In Cheol

    2014-01-01

    Mixing vanes are utilized to improve CHF and heat transfer performance in the rod bundle during normal operation. Experimental measurement of the swirling flow from a split vane pair was conducted using particle image velocimetry (PIV) and boroscope. The lateral velocity fields show that the swirling flow was initially centered in the subchannel and the computational fluid dynamics (CFD) analysis was performed based on the experiment. To visualize flow patterns in the 5Χ5 subchannel using PIV, matching the refraction between the working fluid and the structure was considered and the experiment aimed to develop the experimental data for providing fundamental information of the CFD analysis. The fixed split vane is the main mixing inducer in the fuel assembly. In a heat exchanger research, propeller type swirl generates at several pitch ratios and different blades angles were used to enhance heat transfer rate. Significant improvements of the heat transfer rate using the propellers were confirmed due to creation of tangential flow. In the present study, the mixing effect of rotation vane which has a shape of propeller was studied using PIV. A split vane was considered in the experiment to show the effect of rotation vane. Vertical and horizontal flow analyses were conducted to show the possible use of rotation vane in a subchannel. In the present work, the study of flow visualization using three types of vanes is conducted to show the mixing effect. The vertical flow and the horizontal flow distributions were analyzed in the two experimental facilities. For the vertical flow facility, flow distributions, flow profiles, and the turbulence kinetic energy are analyzed at the centerline of the channel. The results show that the rotation vane has the highest flow and turbulence kinetic intensity at the centerline of the channel. For the horizontal flow facility, the results indicate that lateral flow of the rotation vane is generated and maintained along with the flow

  4. Design and Implementation of Quantum Dot Enhanced Next Generation Photovoltaic Devices

    Science.gov (United States)

    Polly, Stephen Jade

    Photovoltaics are an essential enabling technology providing power both where it would be impractical to deliver otherwise and where sustainably produced--and recently, economically competitive--energy is demanded. Significant effort has gone into increasing the efficiency of these devices since their initial development in the 1950s. The most dramatic enhancements have been from the judicious choice of material used for photon collection, with current state of the art (SOA) conversion efficiencies reaching 46%. Further improvements may be engineered through exploration of next-generation methodologies, such as the incorporation of quantum dots (QDs), to maximally exploit the solar spectrum and develop solar cells producing both large current densities and large voltages compared to current SOA. In this work, the electrical, optical, and mechanical properties of GaAs solar cells incorporating nanostructured InAs QDs, strain balanced with GaP, were studied. QDs allow for an increase in the current generation capabilities of the bulk GaAs semiconductor through absorption of sub-bandgap photons via bound states in the low-bandgap, low-dimensional material. QDs alter the recombination dynamics of charge carriers in the photovoltaic device, which typically led to an undesirable reduction in voltage of more than 200 mV. The addition of dopant, necessary to explore the effects of an intermediate band solar cell, showed a voltage recovery of 121 mV, with no positive or negative effects on sub-bandgap collection. Advanced characterization and data analysis techniques were developed, combining photoreflectance and temperature-dependent photoluminescence, to investigate the activation energy of bound states in the QD, which were shown to undesirably decrease by 34 meV to 40 meV with the addition of doping. Simulation of alternative structures that may help to increase this activation energy were performed using alternative strain balancing designs, and a general strain

  5. Investigation of advanced nanostructured multijunction photoanodes for enhanced solar hydrogen generation via water splitting

    Science.gov (United States)

    Ishihara, Hidetaka

    As the worldwide demand for fossil-based fuel increases every day and the fossil reserve continues to be depleted, the need for alternative/renewable energy sources has gained momentum. Electric, hybrid, and hydrogen cars have been at the center of discussion lately among consumers, automobile manufacturers, and politicians, alike. The development of a fuel-cell based engine using hydrogen has been an ambitious research area over the last few decades-ever since Fujishima showed that hydrogen can be generated via the solar-energy driven photo-electrolytic splitting of water. Such solar cells are known as Photo-Electro-Chemical (PEC) solar cells. In order to commercialize this technology, various challenges associated with photo-conversion efficiency, chemical corrosion resistance, and longevity need to be overcome. In general, metal oxide semiconductors such as titanium dioxide (TiO 2, titania) are excellent candidates for PEC solar cells. Titania nanotubes have several advantages, including biocompatibility and higher chemical stability. Nevertheless, they can absorb only 5-7% of the solar spectrum which makes it difficult to achieve the higher photo-conversion efficiency required for successful commercial applications. A two-prong approach was employed to enhance photo-conversion efficiency: 1) surface modification of titania nanotubes using plasma treatment and 2) nano-capping of the titania nanotubes using titanium disilicide. The plasma surface treatment with N2 was found to improve the photo-current efficiency of titania nanotubes by 55%. Similarly, a facile, novel approach of nano-capping titania nanotubes to enhance their photocurrent response was also investigated. Electrochemically anodized titania nanotubes were capped by coating a 25 nm layer of titanium disilicide using RF magnetron sputtering technique. The optical properties of titania nanotubes were not found to change due to the capping; however, a considerable increase (40%) in the photocurrent

  6. Histatin 5-spermidine conjugates have enhanced fungicidal activity and efficacy as a topical therapeutic for oral candidiasis.

    Science.gov (United States)

    Tati, Swetha; Li, Rui; Puri, Sumant; Kumar, Rohitashw; Davidow, Peter; Edgerton, Mira

    2014-01-01

    Oropharyngeal candidiasis (OPC) is caused by the opportunistic fungi Candida albicans and is prevalent in immunocompromised patients, individuals with dry mouth, or patients with prolonged antibiotic therapies that reduce oral commensal bacteria. Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. However, Hsts are rapidly degraded in vivo, limiting their usefulness as therapeutic agents despite their lack of toxicity. We constructed a conjugate peptide using spermidine (Spd) linked to the active fragment of Hst 5 (Hst 54-15), based upon our findings that C. albicans spermidine transporters are required for Hst 5 uptake and fungicidal activity. We found that Hst 54-15-Spd was significantly more effective in killing C. albicans and Candida glabrata than Hst 5 alone in both planktonic and biofilm growth and that Hst 54-15-Spd retained high activity in both serum and saliva. Hst 54-15-Spd was not bactericidal against streptococcal oral commensal bacteria and had no hemolytic activity. We tested the effectiveness of Hst 54-15-Spd in vivo by topical application to tongue surfaces of immunocompromised mice with OPC. Mice treated with Hst 54-15-Spd had significant clearance of candidal tongue lesions macroscopically, which was confirmed by a 3- to 5-log fold reduction of C. albicans colonies recovered from tongue tissues. Hst 54-15-Spd conjugates are a new class of peptide-based drugs with high selectivity for fungi and potential as topical therapeutic agents for oral candidiasis.

  7. A highly stable monolithic enhancement cavity for second harmonic generation in the ultraviolet

    Science.gov (United States)

    Hannig, S.; Mielke, J.; Fenske, J. A.; Misera, M.; Beev, N.; Ospelkaus, C.; Schmidt, P. O.

    2018-01-01

    We present a highly stable bow-tie power enhancement cavity for critical second harmonic generation (SHG) into the UV using a Brewster-cut β-BaB2O4 (BBO) nonlinear crystal. The cavity geometry is suitable for all UV wavelengths reachable with BBO and can be modified to accommodate anti-reflection coated crystals, extending its applicability to the entire wavelength range accessible with non-linear frequency conversion. The cavity is length-stabilized using a fast general purpose digital PI controller based on the open source STEMlab 125-14 (formerly Red Pitaya) system acting on a mirror mounted on a fast piezo actuator. We observe 130 h uninterrupted operation without decay in output power at 313 nm. The robustness of the system has been confirmed by exposing it to accelerations of up to 1 g with less than 10% in-lock output power variations. Furthermore, the cavity can withstand 30 min of acceleration exposure at a level of 3 grms without substantial change in the SHG output power, demonstrating that the design is suitable for transportable setups.

  8. Bioelectrochemically-assisted anaerobic composting process enhancing compost maturity of dewatered sludge with synchronous electricity generation.

    Science.gov (United States)

    Yu, Hang; Jiang, Junqiu; Zhao, Qingliang; Wang, Kun; Zhang, Yunshu; Zheng, Zhen; Hao, Xiaodi

    2015-10-01

    Bioelectrochemically-assisted anaerobic composting process (AnCBE) with dewatered sludge as the anode fuel was constructed to accelerate composting of dewatered sludge, which could increase the quality of the compost and harvest electric energy in comparison with the traditional anaerobic composting (AnC). Results revealed that the AnCBE yielded a voltage of 0.60 ± 0.02 V, and total COD (TCOD) removal reached 19.8 ± 0.2% at the end of 35 d. The maximum power density was 5.6 W/m(3). At the end of composting, organic matter content (OM) reduction rate increased to 19.5 ± 0.2% in AnCBE and to 12.9 ± 0.1% in AnC. The fuzzy comprehensive assessment (FCA) result indicated that the membership degree of class I of AnCBE compost (0.64) was higher than that of AnC compost (0.44). It was demonstrated that electrogenesis in the AnCBE could improve the sludge stabilization degree, accelerate anaerobic composting process and enhance composting maturity with bioelectricity generation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Image Encryption Using Stream Cipher Based on Nonlinear Combination Generator with Enhanced Security

    Directory of Open Access Journals (Sweden)

    Belmeguenaï Aîssa

    2013-03-01

    Full Text Available The images are very largely used in our daily life; the security of their transfer became necessary. In this work a novel image encryption scheme using stream cipher algorithm based on nonlinear combination generator is developed. The main contribution of this work is to enhance the security of encrypted image. The proposed scheme is based on the use the several linear feedback shifts registers whose feedback polynomials are primitive and of degrees are all pairwise coprimes combined by resilient function whose resiliency order, algebraic degree and nonlinearity attain Siegenthaler’s and Sarkar, al.’s bounds. This proposed scheme is simple and highly efficient. In order to evaluate performance, the proposed algorithm was measured through a series of tests. These tests included visual test and histogram analysis, key space analysis, correlation coefficient analysis, image entropy, key sensitivity analysis, noise analysis, Berlekamp-Massey attack, correlation attack and algebraic attack. Experimental results demonstrate the proposed system is highly key sensitive, highly resistance to the noises and shows a good resistance against brute-force, statistical attacks, Berlekamp-Massey attack, correlation attack, algebraic attack and a robust system which makes it a potential candidate for encryption of image.

  10. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum

    OpenAIRE

    Ziegler, Anja; Everett, Helen; Hamza, Eman; Garbani, Mattia; Gerber, Vinzenz; Marti, Eliane; Steinbach, Falko

    2016-01-01

    BACKGROUND: Dendritic cells are professional antigen-presenting cells that play an essential role in the initiation and modulation of T cell responses. They have been studied widely for their potential clinical applications, but for clinical use to be successful, alternatives to xenogeneic substances like fetal bovine serum (FBS) in cell culture need to be found. Protocols for the generation of dendritic cells ex vivo from monocytes are well established for several species, including hor...

  11. Tb/s physical random bit generation with bandwidth-enhanced chaos in three-cascaded semiconductor lasers.

    Science.gov (United States)

    Sakuraba, Ryohsuke; Iwakawa, Kento; Kanno, Kazutaka; Uchida, Atsushi

    2015-01-26

    We experimentally demonstrate fast physical random bit generation from bandwidth-enhanced chaos by using three-cascaded semiconductor lasers. The bandwidth-enhanced chaos is obtained with the standard bandwidth of 35.2 GHz, the effective bandwidth of 26.0 GHz and the flatness of 5.6 dB, whose waveform is used for random bit generation. Two schemes of single-bit and multi-bit extraction methods for random bit generation are carried out to evaluate the entropy rate and the maximum random bit generation rate. For single-bit generation, the generation rate at 20 Gb/s is obtained for physical random bit sequences. For multi-bit generation, the maximum generation rate at 1.2 Tb/s ( = 100 GS/s × 6 bits × 2 data) is equivalently achieved for physical random bit sequences whose randomness is verified by using both NIST Special Publication 800-22 and TestU01.

  12. Therapeutic ultrasound

    International Nuclear Information System (INIS)

    Crum, Lawrence A

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  13. Combination of a Flipped Classroom Format and a Virtual Patient Case to Enhance Active Learning in a Required Therapeutics Course.

    Science.gov (United States)

    Lichvar, Alicia Beth; Hedges, Ashley; Benedict, Neal J; Donihi, Amy C

    2016-12-25

    Objective. To design and evaluate the integration of a virtual patient activity in a required therapeutics course already using a flipped-classroom teaching format. Design. A narrative-branched, dynamic virtual-patient case was designed to replace the static written cases that students worked through during the class, which was dedicated to teaching the complications of liver disease. Students completed pre- and posttests before and after completing the virtual patient case. Examination scores were compared to those in the previous year. Assessment. Students' posttest scores were higher compared to pretest scores (33% vs 50%). Overall median examination scores were higher compared to the historical control group (70% vs 80%), as well as scores on questions assessing higher-level learning (67% vs 83%). A majority of students (68%) felt the virtual patient helped them apply knowledge gained in the pre-class video lecture. Students preferred this strategy to usual in-class activities (33%) or indicated it was of equal value (37%). Conclusion. The combination of a pre-class video lecture with an in-class virtual patient case is an effective active-learning strategy.

  14. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Naeem M

    2015-07-01

    Full Text Available Muhammad Naeem, Jiafu Cao, Moonjeong Choi, Woo Seong Kim, Hyung Ryong Moon, Bok Luel Lee, Min-Soo Kim, Yunjin Jung, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. Keywords: azo-polyurethane, methacrylate copolymer, budesonide, colon-targeted nanoparticles, colitis

  15. Benzimidazoles Promote Anti-TNF Mediated Induction of Regulatory Macrophages and Enhance Therapeutic Efficacy in a Murine Model.

    Science.gov (United States)

    Wildenberg, Manon E; Levin, Alon D; Ceroni, Alessandro; Guo, Zhen; Koelink, Pim J; Hakvoort, Theodorus B M; Westera, Liset; Bloemendaal, Felicia M; Brandse, Johannan F; Simmons, Alison; D'Haens, Geert R; Ebner, Daniel; van den Brink, Gijs R

    2017-12-04

    Regulatory macrophages play a critical role in tissue repair, and we have previously shown that anti-tumour necrosis factor [TNF] antibodies induce these macrophages in vitro and in vivo in IBD patients. The induction of regulatory macrophages can be potentiated using the combination of anti-TNF and thiopurines, consistent with the enhanced efficacy of this combination therapy described in clinical trials. As thiopurines are unfortunately associated with significant side effects, we here aimed to identify alternatives for combination therapy with anti-TNF, using the macrophage induction model as a screening tool. Mixed lymphocyte reactions were treated with anti-TNF and a library of 1600 drug compounds. Induction of CD14+CD206+ macrophages was analysed by flow cytometry. Positive hits were validated in vitro and in the T cell transfer model of colitis. Among the 98 compounds potentiating the induction of regulatory macrophages by anti-TNF were six benzimidazoles, including albendazole. Albendazole treatment in the presence of anti-TNF resulted in alterations in the tubulin skeleton and signalling though AMPK, which was required for the enhanced induction. Combination therapy also increased expression levels of the immunoregulatory cytokine IL-10. In vivo, albendazole plus anti-TNF combination therapy was superior to monotherapy in a model of colitis, in terms of both induction of regulatory macrophages and improvement of clinical symptoms. Albendazole enhances the induction of regulatory macrophages by anti-TNF and potentiates clinical efficacy in murine colitis. Given its favourable safety profile, these data indicate that the repurposing of albendazole may be a novel option for anti-TNF combination therapy in IBD.

  16. Enhanced therapeutic efficacy of an adenovirus-PEI-bile-acid complex in tumors with low coxsackie and adenovirus receptor expression.

    Science.gov (United States)

    Lee, Cho-Hee; Kasala, Dayananda; Na, Youjin; Lee, Min Sang; Kim, Sung Wan; Jeong, Ji Hoon; Yun, Chae-Ok

    2014-07-01

    Adenovirus (Ad) is a potential vehicle for cancer gene therapy. However, cells that express low levels of the coxsackie and adenovirus receptor (CAR) demonstrate poor Ad infection efficiency. We developed a bile acid-conjugated poly(ethyleneimine) (DA3)-coated Ad complex (Ad/DA3) to enhance Ad transduction efficiency. The size distribution and zeta potential of Ad/DA3 increased to 324 ± 3.08 nm and 10.13 ± 0.21 mV, respectively, compared with those of naked Ad (108 ± 2.26 nm and -17.7 ± 1.5 mV). The transduction efficiency of Ad/DA3 increased in a DA3 polymer concentration-dependent manner. Enhanced gene transfer by Ad/DA3 was more evident in CAR-moderate and CAR-negative cancer cells. Competition assays with a CAR-specific antibody revealed that internalization of Ad/DA3 was not mediated primarily by CAR but involved clathrin-, caveolae-, and macropinocytosis-mediated endocytosis. Cancer cell death was significantly increased when oncolytic Ad and DA3 were complexed (RdB-KOX/DA3) compared to that of naked oncolytic Ad and was inversely proportional to CAR levels. Importantly, RdB-KOX/DA3 significantly enhanced apoptosis, reduced angiogenesis, reduced proliferation, and increased active viral replication in human tumor xenografts compared to that of naked Ad. These results demonstrate that a hybrid vector system can increase the efficacy of oncolytic Ad virotherapy, particularly in CAR-limited tumors. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Next Generation Safeguards Initiative Workshop on Enhanced Recruiting for International Safeguards

    Energy Technology Data Exchange (ETDEWEB)

    Pepper,S.; Rosenthal, M.; Fishbone, L.; Occhiogrosso, D.; Carroll, C.; Dreicer, M.; Wallace, R.; Rankhauser, J.

    2008-10-22

    In 2007, the National Nuclear Security Administration's Office of Nonproliferation and International Security (NA-24) completed a yearlong review of the challenges facing the international safeguards system today and over the next 25 years. The study found that without new investment in international safeguards, the U.S. safeguards technology base, and our ability to support International Atomic Energy Agency (IAEA) safeguards, will continue to erode and soon may be at risk. To reverse this trend, the then U.S. Secretary of Energy, Samuel Bodman, announced at the 2007 IAEA General Conference that the Department of Energy (DOE) would launch the Next Generation Safeguards Initiative (NGSI). He stated 'IAEA safeguards must be robust and capable of addressing proliferation threats. Full confidence in IAEA safeguards is essential for nuclear power to grow safely and securely. To this end, the U.S. Department of Energy will seek to ensure that modern technology, the best scientific expertise, and adequate resources are available to keep pace with expanding IAEA responsibilities.' To meet this goal, the NGSI objectives include the recruitment of international safeguards experts to work at the U.S. national laboratories and to serve at the IAEA's headquarters. Part of the latter effort will involve enhancing our existing efforts to place well-qualified Americans in a sufficient number of key safeguards positions within the IAEA's Department of Safeguards. Accordingly, the International Safeguards Project Office (ISPO) at Brookhaven National Laboratory (BNL) hosted a Workshop on Enhanced Recruiting for International Safeguards (ERIS) on October 22 and 23, 2008. The ISPO used a workshop format developed earlier with Sonalysts, Inc., that was followed at the U.S. Support Program's (USSP's) technology road-mapping sessions. ISPO invited participants from the U.S. DOE, the IAEA, the U.S. national laboratories, private industry, academia, and

  18. HPV integration hijacks and multimerizes a cellular enhancer to generate a viral-cellular super-enhancer that drives high viral oncogene expression

    Science.gov (United States)

    Redmond, Catherine J.; Dooley, Katharine E.; Fu, Haiqing; Gillison, Maura L.; Akagi, Keiko; Symer, David E.; Aladjem, Mirit I.

    2018-01-01

    Integration of human papillomavirus (HPV) genomes into cellular chromatin is common in HPV-associated cancers. Integration is random, and each site is unique depending on how and where the virus integrates. We recently showed that tandemly integrated HPV16 could result in the formation of a super-enhancer-like element that drives transcription of the viral oncogenes. Here, we characterize the chromatin landscape and genomic architecture of this integration locus to elucidate the mechanisms that promoted de novo super-enhancer formation. Using next-generation sequencing and molecular combing/fiber-FISH, we show that ~26 copies of HPV16 are integrated into an intergenic region of chromosome 2p23.2, interspersed with 25 kb of amplified, flanking cellular DNA. This interspersed, co-amplified viral-host pattern is frequent in HPV-associated cancers and here we designate it as Type III integration. An abundant viral-cellular fusion transcript encoding the viral E6/E7 oncogenes is expressed from the integration locus and the chromatin encompassing both the viral enhancer and a region in the adjacent amplified cellular sequences is strongly enriched in the super-enhancer markers H3K27ac and Brd4. Notably, the peak in the amplified cellular sequence corresponds to an epithelial-cell-type specific enhancer. Thus, HPV16 integration generated a super-enhancer-like element composed of tandem interspersed copies of the viral upstream regulatory region and a cellular enhancer, to drive high levels of oncogene expression. PMID:29364907

  19. Next generation of CO2 enhanced water recovery with subsurface energy storage in China

    Science.gov (United States)

    Li, Qi; Kühn, Michael; Ma, Jianli; Niu, Zhiyong

    2017-04-01

    Carbon dioxide (CO2) utilization and storage (CCUS) is very popular in comparison with traditional CO2 capture and storage (CCS) in China. In particular, CO2 storage in deep saline aquifers with enhanced water recovery (CO2-EWR) [1] is gaining more and more attention as a cleaner production technology. The CO2-EWR was written into the "U.S.-China Joint Announcement on Climate Change" released November 11, 2014. "Both sides will work to manage climate change by demonstrating a new frontier for CO2 use through a carbon capture, use, and sequestration (CCUS) project that will capture and store CO2 while producing fresh water, thus demonstrating power generation as a net producer of water instead of a water consumer. This CCUS project with enhanced water recovery will eventually inject about 1.0 million tonnes of CO2 and create approximately 1.4 million cubic meters of freshwater per year." In this article, at first we reviewed the history of the CO2-EWR and addressed its current status in China. Then, we put forth a new generation of the CO2-EWR with emphasizing the collaborative solutions between carbon emission reductions and subsurface energy storage or renewable energy cycle [2]. Furthermore, we figured out the key challenging problems such as water-CCUS nexus when integrating the CO2-EWR with the coal chemical industry in the Junggar Basin, Xinjiang, China [3-5]. Finally, we addressed some crucial problems and strategic consideration of the CO2-EWR in China with focuses on its technical bottleneck, relative advantage, early opportunities, environmental synergies and other related issues. This research is not only very useful for the current development of CCUS in the relative "cold season" but also beneficial for the energy security and clean production in China. [1] Li Q, Wei Y-N, Liu G, Shi H (2015) CO2-EWR: a cleaner solution for coal chemical industry in China. Journal of Cleaner Production 103:330-337. doi:10.1016/j.jclepro.2014.09.073 [2] Streibel M

  20. MEK inhibitors enhance therapeutic response towards ATRA in NF1 associated malignant peripheral nerve sheath tumors (MPNST in-vitro.

    Directory of Open Access Journals (Sweden)

    Susan Fischer-Huchzermeyer

    Full Text Available Neurofibromatosis type 1 (NF1 is a hereditary tumor syndrome characterized by an increased risk of malignant peripheral nerve sheath tumors (MPNST. Chemotherapy of MPNST is still insufficient. In this study, we investigated whether human tumor Schwann cells derived from NF1 associated MPNST respond to all-trans retinoic acid (ATRA. We analyzed effects of ATRA and MEK inhibitor (MEKi combination therapy.MPNST cell lines S462, T265, NSF1 were treated with ATRA and MEKi U0126 and PD0325901. We assessed cell viability, proliferation, migration, apoptosis and differentiation as well as mRNA expression of RAR and RXR subtypes and ATRA target genes such as CRABP2, CYP26A1, RARB and PDK1. We also analyzed CRABP2 methylation in cell lines and performed immunohistochemistry of human MPNST specimens.ATRA therapy reduced viability and proliferation in S462 and T265 cells, accompanied by differentiation, apoptosis and reduced migration. NSF1 cells which lacked RXRG expression did not respond to ATRA. We furthermore demonstrated that ATRA signaling was functional for common targets, and that mRNA expression of CRABP2 and its targets was raised by ATRA therapy, whereas alternative pathways via FABP5 were not induced. Finally, combination of ATRA and MEKi demonstrated additively reduced viability of T265 and S462 cells.We observed therapeutic effects in two of three MPNST cell lines pronounced by combination therapy. These data point to a potentially successful treatment of MPNST by combined application of ATRA and MEK inhibitors such as U0126 or PD0325901.

  1. Studying the effect of photodynamic therapy (PDT) to enhance healing of femur fractures using polarimetric second-harmonic generation microscopy

    Science.gov (United States)

    Golaraei, Ahmad; Raja, Vaishnavi; Akens, Margarete K.; Wilson, Brian C.; Barzda, Virginijus

    2017-07-01

    Linear polarization-in, polarization-out second-harmonic generation microscopy was used to study the effect of Photodynamic therapy treatment on enhancing the healing of femur fracture by investigating the ultrastructure of collagen as a major component of bone matrix.

  2. Knock-in of Enhanced Green Fluorescent Protein or/and Human Gene into Gene Locus in the Porcine Fibroblasts to Produce Therapeutic Protein

    Directory of Open Access Journals (Sweden)

    Sang Mi Lee

    2014-11-01

    Full Text Available Transgenic animals have become important tools for the production of therapeutic proteins in the domestic animal. Production efficiencies of transgenic animals by conventional methods as microinjection and retrovirus vector methods are low, and the foreign gene expression levels are also low because of their random integration in the host genome. In this study, we investigated the homologous recombination on the porcine β-casein gene locus using a knock-in vector for the β-casein gene locus. We developed the knock-in vector on the porcine β-casein gene locus and isolated knock-in fibroblast for nuclear transfer. The knock-in vector consisted of the neomycin resistance gene (neo as a positive selectable marker gene, diphtheria toxin-A gene as negative selection marker, and 5′ arm and 3′ arm from the porcine β-casein gene. The secretion of enhanced green fluorescent protein (EGFP was more easily detected in the cell culture media than it was by western blot analysis of cell extract of the HC11 mouse mammary epithelial cells transfected with EGFP knock-in vector. These results indicated that a knock-in system using β-casein gene induced high expression of transgene by the gene regulatory sequence of endogenous β-casein gene. These fibroblasts may be used to produce transgenic pigs for the production of therapeutic proteins via the mammary glands.

  3. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction

    Directory of Open Access Journals (Sweden)

    Xiaodong Xue

    2015-01-01

    Full Text Available Objectives. Low survival rate of mesenchymal stem cells (MSCs severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI. Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs or empty vector (vector-MSCs. MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF, insulin-like growth factor-1 (IGF-1, and plate-derived growth factor (PDGF increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  4. Efficient enhancement of below-threshold harmonic generation by laser-driven excited states of Cs atom

    Science.gov (United States)

    Guo, Qiao-Ling; Li, Peng-Cheng; Zhou, Xiao-Xin; Chu, Shih-I.

    2018-03-01

    We propose an efficient method for the enhancement of below-threshold harmonic generation (BTHG) by mid-infrared laser-driven excited states of a Cs atom. The BTHG is calculated by solving three-dimensional time-dependent Schrödinger equation accurately and efficiently using the time-dependent generalized pseudospectral method. We adopt an excited state as the initial state of a Cs atom. As a result, the BTHG is significantly enhanced by two orders of magnitude compared with the case of the initial ground state. Furthermore, we find that a single vacuum-ultraviolet pulse can be generated by mid-infrared laser-driven excited states by superposing several below-threshold harmonics of a Cs atom. Our finding suggests that the generation of below-threshold harmonics by laser-driven excited states of an atom can provide a powerful methodology for the production of intense vacuum-ultraviolet pulses.

  5. 4-1BB Aptamer-Based Immunomodulation Enhances the Therapeutic Index of Radiation Therapy in Murine Tumor Models

    Energy Technology Data Exchange (ETDEWEB)

    Benaduce, Ana Paula; Brenneman, Randall; Schrand, Brett; Pollack, Alan; Gilboa, Eli; Ishkanian, Adrian, E-mail: aishkanian@med.miami.edu

    2016-10-01

    Purpose: To report a novel strategy using oligonucleotide aptamers to 4-1BB as an alternate method for costimulation, and show that combinatorial therapy with radiation improves the therapeutic ratio over equivalent monoclonal antibodies. Methods and Materials: Subcutaneous 4T1 (mouse mammary carcinoma) tumors were established (approximately 100 mm{sup 3}), and a radiation therapy (RT) dose/fractionation schedule that optimally synergizes with 4-1BB monoclonal antibody (mAb) was identified. Comparable tumor control and animal survival was observed when either 4-1BB antibody or aptamer were combined with RT using models of breast cancer and melanoma (4T1 and B16-F10). Off-target CD8{sup +} T-cell toxicity was evaluated by quantification of CD8{sup +} T cells in livers and spleens of treated animals. Results: When combined with 4-1BB mAb, significant differences in tumor control were observed by varying RT dose and fractionation schedules. Optimal synergy between RT and 4-1BB mAb was observed at 5 Gy × 6. Testing 4-1BB mAb and aptamer independently using the optimal RT (5 Gy × 6 for 4T1/Balb/c and 12 Gy × 1 for B16/C57BL6J mouse models) revealed equivalent tumor control using 4-1BB aptamer and 4-1BB mAb. 4-1BB mAb, but not 4-1BB aptamer-treated animals, exhibited increased lymphocytic liver infiltrates and increased splenic and liver CD8{sup +} T cells. Conclusions: Radiation therapy synergizes with 4-1BB mAb, and this effect is dependent on RT dose and fractionation. Tumor control by 4-1BB aptamer is equivalent to 4-1BB mAb when combined with optimal RT dose, without eliciting off-target liver and spleen CD8{sup +} expansion. 4-1BB aptamer-based costimulation affords a comparable and less toxic strategy to augment RT-mediated tumor control.

  6. Multi-Modality Therapeutics with Potent Anti-Tumor Effects: Photochemical Internalization Enhances Delivery of the Fusion Toxin scFvMEL/rGel

    Science.gov (United States)

    Selbo, Pål K.; Rosenblum, Michael G.; Cheung, Lawrence H.; Zhang, Wendy; Berg, Kristian

    2009-01-01

    Background There is a need for drug delivery systems (DDS) that can enhance cytosolic delivery of anti-cancer drugs trapped in the endo-lysosomal compartments. Exposure of cells to specific photosensitizers followed by light exposure (photochemical internalization, PCI) results in transfer of agents from the endocytic compartment into the cytosol. Methodology and Principal Findings The recombinant single-chain fusion construct scFvMEL/rGel is composed of an antibody targeting the progenitor marker HMW-MAA/NG2/MGP/gp240 and the highly effective toxin gelonin (rGel). Here we demonstrate enhanced tumor cell selectivity, cytosolic delivery and anti-tumor activity by applying PCI of scFvMEL/rGel. PCI performed by light activation of cells co-incubated with scFvMEL/rGel and the endo-lysosomal targeting photosensitizers AlPcS2a or TPPS2a resulted in enhanced cytotoxic effects against antigen-positive cell lines, while no differences in cytotoxicity between the scFvMEL/rGel and rGel were observed in antigen-negative cells. Mice bearing well-developed melanoma (A-375) xenografts (50–100 mm3) were treated with PCI of scFvMEL/rGel. By 30 days after injection, ∼100% of mice in the control groups had tumors>800 mm3. In contrast, by day 40, 50% of mice in the PCI of scFvMEL/rGel combination group had tumorsmodality approach combining a recombinant, targeted therapeutic such as scFvMEL/rGel and PCI act in concert to provide potent in vivo efficacy without sacrificing selectivity or enhancing toxicity. The present DDS warrants further evaluation of its clinical potential. PMID:19690617

  7. Malignant hepatic tumors treated with percutaneous radio-frequency ablation: Comparison between contrast-enhanced color Doppler ultrasound and spiral CT in evaluating the therapeutic efficacy

    International Nuclear Information System (INIS)

    Yoon, Jung Hee; Han, Sang Suk; Cha, Sung Sook

    2002-01-01

    To compare contrast-enhanced color Doppler ultrasound (CECDUS) with spiral CT in the evaluation of the therapeutic efficacy of malignant hepatic tumors after radio-frequency ablation (RFA). During a recent 2 year period (April 1999 to March 2001). One hundred fifteen hepatic tumors (95 hepatocellular carcinomas and 20 metastases; mean diameter, 2.7 cm) from 83 consecutive patients (60 men and 23 women; mean age, 57 years) that were treated with RFA were included in this study. Both CECDUS and two-or three phase spiral CT were performed a day after RFA as the immediate follow-up study in most cases. Afterward, both imaging studies were alternatively performed on monthly basis, but when incomplete ablation was suspected on one follow-up imaging study, the other imaging study was performed within a week for comparison. For ultrasound contrast agent, a suspension of 2.5 g or 4.0 g Levovist (Schering AG, Berlin, Germany) with a concentration of 300 mg/mL was used. For evaluating the therapeutic efficacy, the presence of viable portion, either residual or recurrent, within the ablated tumor was determined on each imaging study. The criteria for viable portion were defined as focal or irregular enhancement at the periphery of the ablated tumor on the arterial or portal phase spiral CT images and intratumoral vascularities on CECDUS. The correspondence rate between both imaging studies was assessed to compare the diagnostic accuracy of both studies in evaluating a residual or recurrent tumor. In addition, their imaging findings were analyzed. Analyzing both imaging findings of 116 malignant hepatic tumors, the correspondence rate between CECDUS and CT obtained after 116 times of imaging studies was 91.4% (106/116). For the diagnosis of residual or recurrent tumors, the sensitivity, specificity and diagnostic accuracy of spiral CT were 71%, 99%, and 94%, respectively, while those of CECDUS were 87%, 99%, and 97%, respectively. As the immediate follow-up study, CECDUS seemed

  8. Enhanced output voltage generation via ZnO nanowires (50 nm): Effect of diameter thinning on voltage enhancement

    Science.gov (United States)

    Ahmad, Mansoor; Iqbal, Muhammad Azhar; Kiely, Janice; Luxton, Richard; Jabeen, Musarrat

    2017-05-01

    50 nm ZnO nanowires were grown on indium tin oxide (ITO) coated poly ethylene terephthalate (PET) substrates by adapting facile aqueous growth technique using low temperature and vacuum conditions. Prior to growth of ZnO nanowires, pure hexagonal wurtzite structured seed layer was grown on flexible substrates. Surface morphology of nanostructure has been examined by scanning electron microscopy (SEM). Vertical growth orientation has been evidenced in XRD patterns. Minute external mechanical force ( 50 nN) has produced periodic voltage peaks. 2.5 nm and 7.5 nm thick sputtered Pt electrode have been tested to obtain output voltages. 50 nm ZnO nanowires has produced a maximum output voltage of 2.717 volts having an output power density of 397.1 mW/cm2. By squeezing the diameter, we have reduced reverse leakage current through nanowires and enhanced output voltage.

  9. Safety enhancement concept for NPP of new generation with VVER reactors

    International Nuclear Information System (INIS)

    Bezlepkin, V.; Kukhtevich, I.; Semashko, S.; Svetlov, S.; Solodovnikov, A.

    2004-01-01

    With the present day conditions, in order to successfully promote new NPP designs in the electric power markets, it is necessary to ensure enhanced technical/economic performances provided that international safety requirements are properly adhered to. When compared with high-powered nuclear power plants, NPP VVER-640 design (medium powered) possesses a number of advantages for the regions with undeveloped energy systems. Reduced specific energy intensity of the core adopted in this type of reactor allows to ensure the emergency cooldown of the reactor plant by passive means and to minimize the 'human factor' risk and external effects and provide sound substantiations as to how to retain corium inside RPV in case of severe accidents. At the same time, high-powered NPPs seem to be promising for regions with developed energy systems. Among such designs, NPP VVER-1000 and VVER-1500 designs are the most desirable. Configuration of new generation NPP with VVER-1500 is to be selected based on the gained experience in designing NPPs of previous generations considering the latest safety requirements and situation in the domestic and global energy markets for the time being and in the short run. Recent IAEA publications and latest EUR requirements insist that the following key safety indices should be established for new NPP designs: - aggregated frequency of core melting is 10 -6 (1/year); - frequency of maximum accident release is 10 -7 (1/year). To meet the aforementioned criteria, it is necessary to implement some safety assurance principles recommended by IAEA (in-depth defence, single failure, redundancy, diversity, etc.), application of deterministic and probabilistic methods for selection of safety assurance activities and means and use of reasonable combination of active and passive systems. Application of VVER-640 concept to high-powered NPPs seems to be a formidable task due to a number of reasons, namely, it is quite difficult to carry out cooldown process

  10. Can trans-generational experiments be used to enhance species resilience to ocean warming and acidification?

    Science.gov (United States)

    Chakravarti, Leela J; Jarrold, Michael D; Gibbin, Emma M; Christen, Felix; Massamba-N'Siala, Gloria; Blier, Pierre U; Calosi, Piero

    2016-10-01

    Human-assisted, trans-generational exposure to ocean warming and acidification has been proposed as a conservation and/or restoration tool to produce resilient offspring. To improve our understanding of the need for and the efficacy of this approach, we characterized life-history and physiological responses in offspring of the marine polychaete Ophryotrocha labronica exposed to predicted ocean warming (OW: + 3°C), ocean acidification (OA: pH -0.5) and their combination (OWA: + 3°C, pH -0.5), following the exposure of their parents to either control conditions ( within-generational exposure ) or the same conditions ( trans-generational exposure ). Trans-generational exposure to OW fully alleviated the negative effects of within-generational exposure to OW on fecundity and egg volume and was accompanied by increased metabolic activity. While within-generational exposure to OA reduced juvenile growth rates and egg volume, trans-generational exposure alleviated the former but could not restore the latter. Surprisingly, exposure to OWA had no negative impacts within- or trans-generationally. Our results highlight the potential for trans-generational laboratory experiments in producing offspring that are resilient to OW and OA. However, trans-generational exposure does not always appear to improve traits and therefore may not be a universally useful tool for all species in the face of global change.

  11. Does Gadoxetic acid-enhanced 3.0T MRI in addition to 64-detector-row contrast-enhanced CT provide better diagnostic performance and change the therapeutic strategy for the preoperative evaluation of colorectal liver metastases?

    Science.gov (United States)

    Sofue, Keitaro; Tsurusaki, Masakatsu; Murakami, Takamichi; Onoe, Shunsuke; Tokue, Hiroyuki; Shibamoto, Kentaro; Arai, Yasuaki; Sugimura, Kazuro

    2014-10-01

    To compare diagnostic performance in the detection of colorectal liver metastases between 64-detector-row contrast-enhanced CT (CE-CT) alone and the combination of CE-CT and gadoxetic acid-enhanced MRI (EOB-MRI) at 3.0T, and to assess whether EOB-MRI in addition to CE-CT results in a change to initially planned operative strategy. A total of 39 patients (27 men, mean age 65 years) with 85 histopathologically confirmed liver metastases were included. At EOB-MRI, unenhanced (T1- and T2-weighted), dynamic, and hepatocyte-phase images were obtained. At CE-CT, four-phase dynamic contrast-enhanced images were obtained. One on-site reader and three off-site readers independently reviewed both CE-CT alone and the combination of CE-CT and EOB-MRI. Sensitivity, positive predictive value, and alternative free-response receiver operating characteristic (AFROC) method were calculated. Differences in therapeutic strategy before and after the EOB-MRI examination were also evaluated. Sensitivity and area under the AFROC curve with the combination of CE-CT and EOB-MRI were significantly superior to those with CE-CT alone. Changes in surgical therapy were documented in 13 of 39 patients. The combination of CE-CT and EOB-MRI may provide better diagnostic performance than CE-CT alone for the detection of colorectal liver metastases, and EOB-MRI in addition to CE-CT resulted in changes to the planned operative strategy in one-third of the patients. • Accurate preoperative imaging is essential for surgical planning and successful hepatic resection. • Combination of CE-CT and EOB-MRI is useful to detect colorectal liver metastases. • EOB-MRI combined with CE-CT contributes to determine the correct therapeutic strategy.

  12. Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement

    DEFF Research Database (Denmark)

    Czermak, B J; Lentsch, A B; Bless, N M

    1999-01-01

    demonstrated synergistic production of C-X-C (macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant) and C-C (macrophage inflammatory protein-1alpha and monocyte chemoattractant-1) chemokines. In the absence of the costimulus, C5a or MAC did not induce chemokine generation....... In in vivo studies, C5a and MAC alone caused limited or no intrapulmonary generation of chemokines, but in the presence of a costimulus (IgG immune complexes) C5a and MAC caused synergistic intrapulmonary generation of C-X-C and C-C chemokines but not of tumor necrosis factor alpha. Under these conditions...... increased neutrophil accumulation occurred, as did lung injury. These observations suggest that C5a and MAC function synergistically with a costimulus to enhance chemokine generation and the intensity of the lung inflammatory response....

  13. Learning Technology through Three Generations of Technology Enhanced Distance Education Pedagogy

    Science.gov (United States)

    Anderson, Terry; Dron, Jon

    2012-01-01

    This paper updates earlier work in which we defined three generations of distance education pedagogy. We then describe emerging technologies that are most conducive to instructional designs that evolve with each generation. Finally we discuss matching the pedagogies with learning outcomes. (Contains 3 figures.)

  14. Harnessing Alternative Energy Sources to Enhance the Design of a Wave Generator

    Science.gov (United States)

    Bravo, A.

    2017-12-01

    Wave energy has the power to replace a non-renewable source of electricity for a home near the ocean. I built a small-scale wave generator capable of producing approximately 5 volts of electricity. The generator is an array of 16 small generators, each consisting of 200 feet of copper wire, 12 magnets, and a buoy. I tested my design in the Pacific Ocean and was able to power a string of lights I had attached to the generator. While the waves in the ocean moved my buoys, my design was powered by the vertical motion of the waves. My generator was hit with significant horizontal wave motion, and I realized I wasn't taking advantage of that direction of motion. To make my generator produce more electricity, I experimented with capturing the energy of the horizontal motion of water and incorporated that into my generator design. My generator, installed in the ocean, is also exposed to sun and wind, and I am exploring the potential of solar and wind energy collection in my design to increase the electricity output. Once I have maximized my electricity output, I would like to explore scaling up my design.

  15. A Preclinical Assessment of Early Continuous Passive Motion and Treadmill Therapeutic Exercises for Generating Chondroprotective Effects After Anterior Cruciate Ligament Rupture.

    Science.gov (United States)

    Chang, Nai-Jen; Lee, Kuan-Wei; Chu, Chih-Jou; Shie, Ming-You; Chou, Pei-Hsi; Lin, Chih-Chan; Liang, Peir-In

    2017-08-01

    Anterior cruciate ligament (ACL) injury is a well-known risk factor for the development of posttraumatic osteoarthritis (PTOA). However, whether using continuous passive motion (CPM) with or without additional treadmill exercise (TRE) in early ACL injury might provide chondroprotective effects and further decrease the risk of PTOA has yet to be determined. CPM may offer an enhanced chondroprotective effect, but TRE may attenuate that effect due to the mechanical stress on the joint and inflammatory cytokines in the joint. Controlled laboratory study. Thirty adult New Zealand White male rabbits were randomly allocated to sedentary (SED), CPM, TRE, or CPM+TRE groups. Each rabbit underwent an ACL transection (ACLT) on the right knee, with the contralateral knee used as an internal control (sham). The 4 joint surfaces (ie, medial and lateral femoral condyles and tibial plateaus) were evaluated 4 weeks after surgery for gross appearance, histological characteristics, and quantitative osteoarthritis (OA) scores. Overall, at the end of testing, the CPM group experienced the best protective therapeutic effects in all compartments. In gross appearance, CPM resulted in normal articular surfaces, while the TRE and SED groups exhibited surface abrasion. Histological analysis showed significant differences in articular cartilage status. The CPM group had significantly better histological OA scores ( P exercise may contribute to osteoarthritis. The sham treatment showed no difference in the changes in all compartments between groups. Immediate CPM therapy produces a superior in situ microenvironment for reducing the occurrence of PTOA after ACL injury without reconstruction in rabbits. These data suggest that immediate application of CPM therapy may be necessary to create a sound microenvironment in joints and possibly to decrease the risk of PTOA without or while awaiting ACL reconstruction. In contrast, both early active loading exercise and inactivity lead to the development

  16. Simulation of Terahertz Frequency Sources. Polar-Optical Phonon Enhancement of Harmonic Generation in Schottky Diodes

    National Research Council Canada - National Science Library

    Gelmont, Boris

    2002-01-01

    ... polar optical vibration frequency When a high frequency input signal is applied to a frequency multiplier device polar-optical phonons can enhance the non-linearities inherent in this device, enabling...

  17. Enhancement of ATP generation capacity, antioxidant activity and immunomodulatory activities by Chinese Yang and Yin tonifying herbs

    Directory of Open Access Journals (Sweden)

    Leung Hoi

    2007-03-01

    Full Text Available Abstract Chinese tonifying herbs such as Herba Cistanche, Ganoderma and Cordyceps, which possess antioxidant and/or immunomodulatory activities, can be useful in the prevention and treatment of age-related diseases. Pharmacological studies on Yang and Yin tonifying herbs suggest that Yang tonifying herbs stimulate mitochondrial adenosine triphosphate (ATP generation, presumably through the intermediacy of reactive oxidant species, leading to the enhancement of cellular/mitochondrial antioxidant status. Yin tonifying herbs, however, apart from possessing antioxidant properties, exert mainly immunomodulatory functions that may boost a weak immune system and may also suppress overreactive immune responses. The abilities of Yang and Yin Chinese tonifying herbs to enhance ATP generation and to exhibit antioxidant and/or immunomodulatory actions are the pharmacological basis for their beneficial effects on the retardation of aging.

  18. Plasmonic enhancement of second harmonic generation from nonlinear RbTiOPO4 crystals by aggregates of silver nanostructures

    DEFF Research Database (Denmark)

    Sánchez-García, Laura; Tserkezis, Christos; Ramírez, Mariola O

    2016-01-01

    We demonstrate a 60–fold enhancement of the second harmonic generation (SHG) response at the nanoscale in a hybrid metal-dielectric system. By using complex silver nanostructures photochemically deposited on the polar surface of a ferroelectric crystal, we tune the plasmonic resonances from...... the visible to the near-infrared (NIR) spectral region, matching either the SH or the fundamental frequency. In both cases the SHG signal at the metal-dielectric interface is enhanced, although with substantially different enhancement values: around 5 times when the plasmonic resonance is at the SH frequency...... or up to 60 times when it matches the fundamental NIR radiation. The results are consistent with the more spatially-extended near-field response of complex metallic nanostructures and can be well explained by taking into account the quadratic character of the SHG process. The work points out...

  19. Plasmon-enhanced second harmonic generation in semiconductor quantum dots close to metal nanoparticles

    Directory of Open Access Journals (Sweden)

    Andrea V. Bragas

    2011-03-01

    Full Text Available We report the enhancement of the optical second harmonic signal in non-centrosymmetric semiconductor CdS quantum dots, when they are placed in close contact with isolated silver nanoparticles. The intensity enhancement is about 1000. We also show that the enhancement increases when the incoming laser frequency $omega$ is tuned toward the spectral position of the silver plasmon at $2omega$, proving that the silver nanoparticle modifies the nonlinear emission.Received: 8 March 2011, Accepted: 30 May 2011; Edited by: L. Viña; Reviewed by: R. Gordon, Department of Electrical and Computer Engineering, University of Victoria, British Columbia, Canada; DOI: 10.4279/PIP.030002Cite as: P. M. Jais, C. von Bilderling, A. V. Bragas, Papers in Physics 3, 030002 (2011

  20. Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection.

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2014-01-01

    Full Text Available Hepatitis B virus (HBV persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1. Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1 interaction. In this study, we examined whether in vivo blockade of the PD-1 pathway enhances virus-specific T cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. The woodchuck PD-1 was first cloned, characterized, and its expression patterns on T cells from woodchucks with acute or chronic woodchuck hepatitis virus (WHV infection were investigated. Woodchucks chronically infected with WHV received a combination therapy with nucleoside analogue entecavir (ETV, therapeutic DNA vaccination and woodchuck PD-L1 antibody treatment. The gain of T cell function and the suppression of WHV replication by this therapy were evaluated. We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. Moreover, the combination therapy potently suppressed WHV replication, leading to sustained immunological control of viral infection, anti-WHs antibody development and complete viral clearance in some woodchucks. Our results provide a new approach to improve T cell function in chronic hepatitis B infection, which may be used to design new immunotherapeutic strategies in patients.

  1. Method and apparatus for enhanced heat recovery from steam generators and water heaters

    Science.gov (United States)

    Knight, Richard A.; Rabovitser, Iosif K.; Wang, Dexin

    2006-06-27

    A heating system having a steam generator or water heater, at least one economizer, at least one condenser and at least one oxidant heater arranged in a manner so as to reduce the temperature and humidity of the exhaust gas (flue gas) stream and recover a major portion of the associated sensible and latent heat. The recovered heat is returned to the steam generator or water heater so as to increase the quantity of steam generated or water heated per quantity of fuel consumed. In addition, a portion of the water vapor produced by combustion of fuel is reclaimed for use as feed water, thereby reducing the make-up water requirement for the system.

  2. Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: Implications for WT1-based cancer therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Borbulevych, Oleg Y.; Do, Priscilla; Baker, Brian M. (Notre)

    2010-09-07

    Presentation of peptides by class I or class II major histocompatibility complex (MHC) molecules is required for the initiation and propagation of a T cell-mediated immune response. Peptides from the Wilms Tumor 1 transcription factor (WT1), upregulated in many hematopoetic and solid tumors, can be recognized by T cells and numerous efforts are underway to engineer WT1-based cancer vaccines. Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding. The R1Y variant, a potential vaccine candidate, alters the positions of MHC charged side chains near the peptide N-terminus and significantly reduces the peptide/MHC electrostatic surface potential. These alterations indicate that the R1Y variant is an imperfect mimic of the native WT1 peptide, and suggest caution in its use as a therapeutic vaccine. Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.

  3. Enhanced neuro-therapeutic potential of Wharton's Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture.

    Science.gov (United States)

    Drela, Katarzyna; Lech, Wioletta; Figiel-Dabrowska, Anna; Zychowicz, Marzena; Mikula, Michał; Sarnowska, Anna; Domanska-Janik, Krystyna

    2016-04-01

    Substantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton's Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors. The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type "pre-MSC," where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration-associated potency. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  4. Enhancement of the efficacy of therapeutic proteins by formulation with PEGylated liposomes; a case of FVIII, FVIIa and G-CSF.

    Science.gov (United States)

    Yatuv, Rivka; Robinson, Micah; Dayan, Inbal; Baru, Moshe

    2010-02-01

    Improving the pharmacodynamics of protein drugs has the potential to improve the care and the quality of life of patients suffering from a variety of diseases. Four approaches to improve protein drugs are described: PEGylation, amino acid substitution, fusion to carrier proteins and encapsulation. A new platform technology based on the binding of proteins/peptides to the outer surface of PEGylated liposomes (PEGLip) is then presented. Binding of proteins to PEGLip is non-covalent, highly specific and dependent on an amino acid consensus sequence within the proteins. Association of proteins with PEGLip results in substantial enhancement of the pharmacodynamic properties of proteins following administration. This has been demonstrated in preclinical studies and clinical trials with coagulation factors VIII and VIIa. It has also been demonstrated in preclinical studies with granulocyte colony-stimulating factor. A mechanism is presented that explains the improvements in hemostatic efficacy of PEGLip-formulated coagulation factors VIII and VIIa. The reader will gain an understanding of the advantages and disadvantages of each of the approaches discussed. PEGLip formulation is an important new approach to improve the pharmacodynamics of protein drugs. This approach may be applied to further therapeutic proteins in the future.

  5. Genotoxic and cytotoxic damage by the therapeutic radiopharmaceutical [166Dy]Dy/166Ho-EDTMP as in vivo generator system

    International Nuclear Information System (INIS)

    Pedraza L, M.; Piedras R, J.; Ferro F, G.; Morales R, P.; Murphy S, E.; Hernandez O, O.

    2005-01-01

    In patients with leukemias and multiple myeloma, the cure can be obtained to inclination of a bone marrow transplant (m.o.), for that which one is used a combination of external radiotherapy and chemotherapy with the consequent toxicity to healthy organs. The complex [ 166 Dy]Dy/ 166 Ho-ethylenediaminetetramethylenephosphonate ([ 166 Dy]Dy/ 166 Ho-EDTMP) it forms a generator system in vivo stable with bony selective likeness in mice therefore, this it could work as a therapeutic radiopharmaceutical for bone marrow ablation. The objective of this original work was to determine the genotoxic and cytotoxic damage produced by the [ 166 Dy]Dy/ 166 Ho-EDTMP like a generator system in vivo by means of the reticulocytes reduction (RET) and micronucleus elevation in reticulocytes (RET-MN) in peripheral blood and to evaluate its myeloablative potential for histopathologic studies. It was irradiated 166 Dy 2 O 3 enriched and it was add in form 166 DyCI 3 to the EDTMP in a softening media of phosphates (pH 8), the optimal molar relationship 166 Dy: EDTMP was 1.7:1 and the radiochemical purity was evaluated by ITLC. The Dy:EDTMP complexes, non radioactive, its were prepared in the same way with non irradiated dysprosium oxide. A group of BALB/c mice was injected intraperitoneally with the radiopharmaceutical and two groups of control mice were injected with the non radioactive complex and with sodium chloride 0.9% respectively. Before injecting each one of the solutions it was take a basal sample of peripheral blood of the mouse tail and each 48 h post-injection during 12 d. The animals were sacrificed to obtain the organs of interest and to determine the radioactivity in each one. The femur was used for the histopathologic studies. The quantification of the frequency of RET and RET-MN was carried out by flow cytometry of the sanguine samples and the Monte Carlo code MCNP4B for the dosimetry calculations was used. The radiochemical purity was 99% and in average the specific

  6. Student-Generated Content: Enhancing Learning through Sharing Multiple-Choice Questions

    Science.gov (United States)

    Hardy, Judy; Bates, Simon P.; Casey, Morag M.; Galloway, Kyle W.; Galloway, Ross K.; Kay, Alison E.; Kirsop, Peter; McQueen, Heather A.

    2014-01-01

    The relationship between students' use of PeerWise, an online tool that facilitates peer learning through student-generated content in the form of multiple-choice questions (MCQs), and achievement, as measured by their performance in the end-of-module examinations, was investigated in 5 large early-years science modules (in physics, chemistry and…

  7. Chemical vapour generation of silver: reduced palladium as permanent reaction modifier for enhanced performance

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Tomáš; Sturgeon, R. E.

    2004-01-01

    Roč. 19, č. 8 (2004), s. 1014-1017 ISSN 0267-9477 R&D Projects: GA ČR GA203/01/0453 Institutional research plan: CEZ:AV0Z4031919 Keywords : chemical vapour generation * chemical modification * silver Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.926, year: 2004

  8. Capacitive mixing power production from salinity gradient energy enhanced through exoelectrogen-generated ionic currents

    KAUST Repository

    Hatzell, Marta C.

    2014-01-01

    Several approaches to generate electrical power directly from salinity gradient energy using capacitive electrodes have recently been developed, but power densities have remained low. By immersing the capacitive electrodes in ionic fields generated by exoelectrogenic microorganisms in bioelectrochemical reactors, we found that energy capture using synthetic river and seawater could be increased ∼65 times, and power generation ∼46 times. Favorable electrochemical reactions due to microbial oxidation of organic matter, coupled to oxygen reduction at the cathode, created an ionic flow field that enabled more effective passive charging of the capacitive electrodes and higher energy capture. This ionic-based approach is not limited to the use of river water-seawater solutions. It can also be applied in industrial settings, as demonstrated using thermolytic solutions that can be used to capture waste heat energy as salinity gradient energy. Forced charging of the capacitive electrodes, using energy generated by the bioelectrochemical system and a thermolytic solution, further increased the maximum power density to 7 W m -2 (capacitive electrode). © 2014 The Royal Society of Chemistry.

  9. Peripheral ligands as electron storage reservoirs and their role in enhancement of photocatalytic hydrogen generation

    NARCIS (Netherlands)

    Pan, Qing; Freitag, Leon; Kowacs, Tanja; Falgenhauer, Jane C.; Korterik, Jeroen P.; Schlettwein, Derck; Browne, Wesley R.; Pryce, Mary T.; Rau, Sven; Gonzalez, Leticia; Vos, Johannes G.; Huijser, Jannetje Maria

    2016-01-01

    The contrasting early-time photodynamics of two related Ru/Pt photocatalysts with very different photocatalytic H2 generation capabilities are reported. Ultrafast equilibration (535 ± 17 fs) creates an electron reservoir on the peripheral ligands of the ester substituted complex, allowing a dramatic

  10. Obestatin enhances in vitro generation of pancreatic islets through regulation of developmental pathways.

    Directory of Open Access Journals (Sweden)

    Alessandra Baragli

    Full Text Available Availability of large amounts of in vitro generated β-cells may support replacement therapy in diabetes. However, methods to obtain β-cells from stem/progenitor cells are limited by inefficient endocrine differentiation. We have recently shown that the ghrelin gene product obestatin displays beneficial effects on pancreatic β-cell survival and function. Obestatin prevents β-cell apoptosis, preserves β-cell mass and stimulates insulin secretion in vitro and in vivo, in both normal and diabetic conditions. In the present study, we investigated whether obestatin may promote in vitro β-cell generation from mouse pancreatic islet-derived precursor cells. Treatment of cultured islets of Langerhans with obestatin (i enriched cells expressing the mesenchymal/neuronal marker nestin, which is associated with pancreatic precursors; (ii increased cell survival and reduced apoptosis during precursor selection; (iii promoted the generation of islet-like cell clusters (ICCs with increased insulin gene expression and C-peptide secretion. Furthermore, obestatin modulated the expression of fibroblast growth factor receptors (FGFRs, Notch receptors and neurogenin 3 (Ngn3 during islet-derived precursor cell selection and endocrine differentiation. These results indicate that obestatin improves the generation of functional β-cells/ICCs in vitro, suggesting implications for cell-based replacement therapy in diabetes. Moreover, obestatin may play a role in regulating pathways involved in pancreas development and regeneration.

  11. Functionalizing carbon nitride with heavy atom-free spin converters for enhanced 1 O 2 generation

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Wenting; Han, Congcong; Zhang, Qinhua; Zhang, Qinggang; Li, Zhongtao; Gosztola, David J.; Wiederrecht, Gary P.; Wu, Mingbo

    2018-05-01

    advanced photosensitizers for singlet oxygen (1O2) generation. However, the intersystem crossing (ISC) process is quite insufficient in carbon nitride, limiting the 1O2 generation. Here, we report a facile and general strategy to confined benzophenone as a heavy atom-free spin converter dopant in carbon nitride via the facile copolymerization. With proper energy level matching between the heavy atom-free spin converter and various ligands based on carbon nitride precursors, the proper combination can decrease the singlet-triplet energy gap (DEST) and hence generate 1O2 effectively. Due to its significant and selectivity for 1O2 generation, the as-prepared carbon nitride-based photosensitizer shows a high selective photooxidation activity for 1,5-dihydroxy-naphthalene (1,5-DHN). The product yield reached 71.8% after irradiation for 60 min, which was higher than that of cyclometalated PtII complexes (53.6%) in homogeneous photooxidation. This study can broaden the application of carbon nitride in the field of selective heterogeneous photooxidation due to simple operation, low cost, and high efficiency, making it a strong candidate for future industrialization.

  12. New generation main control room of enhanced safety NPP with MKER reactor

    International Nuclear Information System (INIS)

    Golovanev, V.E.; Gorelov, A.I.; Proshin, V.A.

    1994-01-01

    Russia is planning to begin the gradual substitution RMBK NPP units, whose resources were worked out itself, to NPP units with a 800 MW multiloop boiling water power reactor (MKER-800) enhanced safety at next ten-year period. Main drawbacks of RBMK Reactor were completely removed in design of MKER-800 reactor. Moreover some special decisions were made to give MKER-800 self-safety properties. The proposed design of the MKER-800 enhanced safety reactor is not only fully free from the drawbacks of the RBMK reactors, but also show a number of advantages of channel-type reactors. This Paper presents some preliminary proposals of MCR Design, that developed Research and Development Institute of Power Energy (RDIPE). 6 refs, 2 figs

  13. Enhancement of the Number of Fast Electrons Generated in a Laser Inverse Cone Interaction

    International Nuclear Information System (INIS)

    Yan-Ling, Ji; Gang, Jiang; Wei-Dong, Wu; Ji-Cheng, Zhang; Yong-Jian, Tang

    2010-01-01

    Enhancement of the energy-conversion efficiency from laser to target electrons is demonstrated by two-dimensional particle-in-cell simulations in a laser-inverse cone interaction. When an intense short-pulse laser illuminates the inverse cone target, the electrons at the cone end are accelerated by the ponderomotive force. Then these electrons are guided and confined to transport along the inverse cone walls by the induced electromagnetic fields. A device consisting of inverse hollow-cone and multihole array plasma is proposed in order to increase the energy-conversion efficiency from laser to electrons. Particle-in-cell simulations present that the multiholes transpiercing the cone end help to enhance the number of fast electrons and the maximum electron energy significantly. (physics of gases, plasmas, and electric discharges)

  14. Microwave generation enhancement of X-band CRBWO by use of coaxial dual annular cathodes

    OpenAIRE

    Yan Teng; Jun Sun; Changhua Chen; Hao Shao

    2013-01-01

    This paper presents an approach that greatly enhances both the output power and the conversion efficiency of the coaxial relativistic backward wave oscillator (CRBWO) by using coaxial dual annular cathodes, which increases the diode current rather than the diode voltage. The reasons for the maladjustment of CRBWO under a high diode voltage are analyzed theoretically. It is found that by optimization of the diode structure, the shielding effect of the space charge of the outer beams on the inn...

  15. A Visible-Light-Active Heterojunction with Enhanced Photocatalytic Hydrogen Generation.

    Science.gov (United States)

    Adhikari, Shiba P; Hood, Zachary D; More, Karren L; Chen, Vincent W; Lachgar, Abdou

    2016-07-21

    A visible-light-active carbon nitride (CN)/strontium pyroniobate (SNO) heterojunction photocatalyst was fabricated by deposition of CN over hydrothermally synthesized SNO nanoplates by a simple thermal decomposition process. The microscopic study revealed that nanosheets of CN were anchored to the surface of SNO resulting in an intimate contact between the two semiconductors. Diffuse reflectance UV/Vis spectra show that the resulting CN/SNO heterojunction possesses intense absorption in the visible region. The structural and spectral properties endowed the CN/SNO heterojunction with remarkably enhanced photocatalytic activity. Specifically, the photocatalytic hydrogen evolution rate per mole of CN was found to be 11 times higher for the CN/SNO composite compared to pristine CN. The results clearly show that the composite photocatalyst not only extends the light absorption range of SNO but also restricts photogenerated charge-carrier recombination, resulting in significant enhancement in photocatalytic activity compared to pristine CN. The relative band positions of the composite allow the photogenerated electrons in the conduction band of CN to migrate to that of SNO. This kind of charge migration and separation leads to the reduction in the overall recombination rate of photogenerated charge carriers, which is regarded as one of the key factors for the enhanced activity. A plausible mechanism for the enhanced photocatalytic activity of the heterostructured composite is proposed based on observed activity, photoluminescence, time-resolved fluorescence emission decay, electrochemical impedance spectroscopy, and band position calculations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. External CO2 and water supplies for enhancing electrical power generation of air-cathode microbial fuel cells.

    Science.gov (United States)

    Ishizaki, So; Fujiki, Itto; Sano, Daisuke; Okabe, Satoshi

    2014-10-07

    Alkalization on the cathode electrode limits the electrical power generation of air-cathode microbial fuel cells (MFCs), and thus external proton supply to the cathode electrode is essential to enhance the electrical power generation. In this study, the effects of external CO2 and water supplies to the cathode electrode on the electrical power generation were investigated, and then the relative contributions of CO2 and water supplies to the total proton consumption were experimentally evaluated. The CO2 supply decreased the cathode pH and consequently increased the power generation. Carbonate dissolution was the main proton source under ambient air conditions, which provides about 67% of total protons consumed for the cathode reaction. It is also critical to adequately control the water content on the cathode electrode of air-cathode MFCs because the carbonate dissolution was highly dependent on water content. On the basis of these experimental results, the power density was increased by 400% (143.0 ± 3.5 mW/m(2) to 575.0 ± 36.0 mW/m(2)) by supplying a humid gas containing 50% CO2 to the cathode chamber. This study demonstrates that the simultaneous CO2 and water supplies to the cathode electrode were effective to increase the electrical power generation of air-cathode MFCs for the first time.

  17. Enhancing Photocatalytic Activity of Graphitic Carbon Nitride by Codoping with P and C for Efficient Hydrogen Generation.

    Science.gov (United States)

    Wang, Hao; Wang, Bo; Bian, Yaru; Dai, Liming

    2017-07-05

    The generation of clean hydrogen gas from photocatalytic water splitting by using graphitic carbon nitride (g-C 3 N 4 ) as the photocatalyst has attracted considerable research interest. For practical applications, however, the photocatalytic activity of g-C 3 N 4 needs to be further improved by, for example, band gap engineering through heteroatom doping. In this study, we found that doping of carbon nitride with carbon and phosphorus (P) could tune energy level of the conduction band. Subsequent hydrothermal treatment led to an increase in the specific surface area from 24.9 up to 141.1 m 2 g -1 , which was accompanied by increasing C concentration of the resultant C, P-doped g-C 3 N 4 to reduce the hole-electron recombination and enhance the conductivity. Consequently, the C, P-codoped g-C 3 N 4 (i.e., CPCN-1*) exhibited a much enhanced photocatalytic activity for efficient generation of H 2 by photocatalytic water splitting under visible-light irradiation (1493.3 μmol g -1 h -1 -about 9.7 times enhancement from that of bulk g-C 3 N 4 ).

  18. Generating structured light with phase helix and intensity helix using reflection-enhanced plasmonic metasurface at 2 μm

    Science.gov (United States)

    Zhao, Yifan; Du, Jing; Zhang, Jinrun; Shen, Li; Wang, Jian

    2018-04-01

    Mid-infrared (2-20 μm) light has been attracting great attention in many areas of science and technology. Beyond the extended wavelength range from visible and near-infrared to mid-infrared, shaping spatial structures may add opportunities to grooming applications of mid-infrared photonics. Here, we design and fabricate a reflection-enhanced plasmonic metasurface and demonstrate efficient generation of structured light with the phase helix and intensity helix at 2 μm. This work includes two distinct aspects. First, structured light (phase helix, intensity helix) generation at 2 μm, which is far beyond the ability of conventional spatial light modulators, is enabled by the metasurface with sub-wavelength engineered structures. Second, the self-referenced intensity helix against environmental noise is generated without using a spatially separated light. The demonstrations may open up advanced perspectives to structured light applications at 2 μm, such as phase helix for communications and non-communications (imaging, sensing) and intensity helix for enhanced microscopy and advanced metrology.

  19. Enhanced piezoelectric operation of NiO/GaN heterojunction generator by suppressed internal carrier screening

    International Nuclear Information System (INIS)

    Jeong, Dae Kyung; Kang, Jin-Ho; Ryu, Sang-Wan; Ha, Jun-Seok

    2017-01-01

    A NiO/GaN heterojunction piezoelectric generator was fabricated, and the improvement in device performance was analyzed. The electrical properties of NiO were varied by regulating the gas environment during sputtering. An optimized NiO layer was adopted for high piezoelectric voltage generation. Internal carrier screening was revealed to be the dominant mechanism degrading the piezoelectric performance, necessitating the suppression of carrier screening. The highly resistive NiO layer was advantageous in the suppression of carrier transport across the junction that screened the piezoelectric field. The maximum piezoelectric voltage and current density values obtained were 7.55 V and 1.14 µ A cm −2 , respectively. The power obtained was sufficient to operate a light-emitting diode combined with a charging circuit. (paper)

  20. Enhancement of the vacuum ultraviolet emission from excimer laser-generated plasmas by ambient gas atoms

    Science.gov (United States)

    Mehlman, G.; Chrisey, D. B.; Horwitz, J. S.; Burkhalter, P. G.; Auyeung, R. C. Y.; Newman, D. A.

    1993-11-01

    We have measured the axial (z) and radial (x) distribution of the vacuum ultraviolet emission from excimer laser generated aluminum plasmas in vacuum and in 300 mTorr of argon. The ratio of the radiated line intensities (emission in a gas versus vacuum) on the z axis (i.e., x=0) increased exponentially with distance from the target surface for plasmas generated in a 300 mTorr argon ambient. The absolute line intensities increased linearly with the argon pressure and approximately linearly with the ambient gas atomic cross section when other rare gases were substituted. The line intensity radial distribution was broader for plasmas in argon than in vacuum and the magnitude of the effect increased monotonically with z. The spectral data obtained from plasmas in a gas ambient are discussed in terms of the diffusion of plasma electrons in an ionized gas.

  1. High gain harmonic generation free electron lasers enhanced by pseudoenergy bands

    Directory of Open Access Journals (Sweden)

    Takashi Tanaka

    2017-08-01

    Full Text Available We propose a new scheme for high gain harmonic generation free electron lasers (HGHG FELs, which is seeded by a pair of intersecting laser beams to interact with an electron beam in a modulator undulator located in a dispersive section. The interference of the laser beams gives rise to a two-dimensional modulation in the energy-time phase space because of a strong correlation between the electron energy and the position in the direction of dispersion. This eventually forms pseudoenergy bands in the electron beam, which result in efficient harmonic generation in HGHG FELs in a similar manner to the well-known scheme using the echo effects. The advantage of the proposed scheme is that the beam quality is less deteriorated than in other existing schemes.

  2. Evaluation of power conditioning architectures for energy production enhancement in thermoelectric generator systems

    DEFF Research Database (Denmark)

    Wu, Hongfei; Sun, Kai; Chen, Min

    2014-01-01

    of implementing high MPPT efficiency and high conversion efficiency simultaneously. A 50-W TEG system composed of two TEG modules is built and tested. Experimental results show that the proposed hybrid power conditioning architecture generates up to 5% more energy for a temperature difference between the two......A large-scale thermoelectric generator (TEG) system has an unbalanced temperature distribution among the TEG modules, which leads to power mismatch among the modules and decreases the power output of the TEG system. To maximize the power output and minimize the power conversion loss, a centralized......- distributed hybrid power conditioning architecture is presented, analyzed, and evaluated for a TEG system. The novel architecture is a combination of a conventional centralized architecture and a fully distributed architecture. By using the proposed architecture, most of the harvested power is processed...

  3. Self-generated mnemonics for enhancing free recall performance in older learners.

    Science.gov (United States)

    Hill, R D; Allen, C; Gregory, K

    1990-01-01

    The effectiveness of self-generated mnemonic strategies for free-recall list learning was examined in 94 older community-dwelling adults. Participants were presented with a list of 19 nouns and were given seven minutes to commit the list to memory with three minutes for recall. Performance was measured immediately following recall and after a 2-day delay. Forty-five percent of the participants reported using a specific organizational mnemonic encoding strategy to facilitate recall. At both immediate and delayed recall, those individuals who reported using a well-articulated mnemonic outperformed those reporting the use of repetition or making simple associations. The results suggest that many older adults can spontaneously generate specific elaborative encoding strategies and that pre-existing encoding skills should be assessed prior to remedial memory training for older adults.

  4. Enhanced boron removal by electricity generation in a microbial fuel cell

    OpenAIRE

    Ping, Qingyun; Abu-Reesh, Ibrahim M.; He, Zhen

    2016-01-01

    Boron needs to be removed during desalination, because excessive boron in the product water for irrigation can deteriorate plant growth. In this study, a microbial fuel cell (MFC) equipped with anion exchange membrane (AEM) was proposed and investigated to remove boron via two successive steps: boric acid is ionized to borate ions in the presence of high pH as a result of cathode reaction, and borate ions are transported across AEM driven by electricity generation. Two scenarios were examined...

  5. Large enhancement of fully resonant sum-frequency generation through quantum control via continuum states

    Science.gov (United States)

    Popov, A. K.; Kimberg, V. V.; George, Thomas F.

    2004-04-01

    A theory of quantum control of short-wavelength sum-frequency generation, which employs the continuum states, is developed. The proposed scheme employs all-resonant coupling and trade-off optimization of the accompanying constructive and destructive quantum interference effects in the lower-order and higher-order polarizations controlled by the overlap of two autoionizinglike laser-induced continuum structures. The scheme does not rely on adiabatic passage, coherent population trapping or maximum atomic coherence as a means to facilitate maximum output. The opportunities for manipulating transparency of the medium and refractive index for the fundamental and generated radiations, as well as nonlinear polarization in the multiple-resonant medium, are shown. This opens the feasibility of creating frequency-tunable narrowband filters, polarization rotators, and dispersive elements for vacuum ultraviolet radiation. The features specific for quantum interference in Doppler-broadened media are investigated. The feasibility of almost complete conversion of long-wavelength fundamental radiation into generated short-wavelength radiation, and of a dramatic decrease in the intensity of required fundamental radiations, is shown.

  6. Enhanced Efficiency of Thermoelectric Generator by Optimizing Mechanical and Electrical Structures

    Directory of Open Access Journals (Sweden)

    Jinlong Chen

    2017-09-01

    Full Text Available Much attention has been paid to the application of low temperature thermal resources, especially for power generation in recent years. Most of the current commercialized thermal (including geothermal power-generation technologies convert thermal energy to electric energy indirectly, that is, making mechanical work before producing electricity. Technology using a thermoelectric generator (TEG, however, can directly transform thermal energy into electricity through the Seebeck effect. TEG technology has many advantages such as compactness, quietness, and reliability because there are no moving parts. One of the biggest disadvantages of TEGs is the low efficiency from thermal to electric energy. For this reason, we redesigned and modified our previous 1 KW (at a temperature difference of around 120 °C TEG system. The output power of the system was improved significantly, about 34.6% greater; the instantaneous efficiency of the TEG system could reach about 6.5%. Laboratory experiments have been conducted to measure the output power at different conditions: different connection modes between TEG modules, different mechanical structures, and different temperature differences between hot and cold sides. The TEG apparatus has been tested and the data have been presented. This kind of TEG power system can be applied in many thermal and geothermal sites with low temperature resources, including oil fields where fossil and geothermal energies are coproduced.

  7. Enhanced Solar-to-Hydrogen Generation with Broadband Epsilon-Near-Zero Nanostructured Photocatalysts

    KAUST Repository

    Tian, Yi

    2017-05-08

    The direct conversion of solar energy into fuels or feedstock is an attractive approach to address increasing demand of renewable energy sources. Photocatalytic systems relying on the direct photoexcitation of metals have been explored to this end, a strategy that exploits the decay of plasmonic resonances into hot carriers. An efficient hot carrier generation and collection requires, ideally, their generation to be enclosed within few tens of nanometers at the metal interface, but it is challenging to achieve this across the broadband solar spectrum. Here the authors demonstrate a new photocatalyst for hydrogen evolution based on metal epsilon-near-zero metamaterials. The authors have designed these to achieve broadband strong light confinement at the metal interface across the entire solar spectrum. Using electron energy loss spectroscopy, the authors prove that hot carriers are generated in a broadband fashion within 10 nm in this system. The resulting photocatalyst achieves a hydrogen production rate of 9.5 µmol h-1  cm-2 that exceeds, by a factor of 3.2, that of the best previously reported plasmonic-based photocatalysts for the dissociation of H2 with 50 h stable operation.

  8. ‘Trans-generational immune priming’: specific enhancement of the antimicrobial immune response in the mealworm beetle, Tenebrio molitor

    Science.gov (United States)

    Moret, Yannick

    2006-01-01

    Encounters with parasites and pathogens are often unpredictable in time. However, experience of an infection may provide the host with reliable cues about the future risk of infection for the host itself or for its progeny. If the parental environment predicts the quality of the progeny's environment, then parents may further enhance their net reproductive success by differentially providing their offspring with phenotypes to cope with potential hazards such as pathogen infection. Here, I test for the occurrence of such an adaptive transgenerational phenotypic plasticity in the mealworm beetle, Tenebrio molitor. A pathogenic environment was mimicked by injection of bacterial lipopolysaccharides for two generations of insects. I found that parental challenge enhanced offspring immunity through the inducible production of antimicrobial peptides in the haemolymph. PMID:16777729

  9. "Trans-generational immune priming": specific enhancement of the antimicrobial immune response in the mealworm beetle, Tenebrio molitor.

    Science.gov (United States)

    Moret, Yannick

    2006-06-07

    Encounters with parasites and pathogens are often unpredictable in time. However, experience of an infection may provide the host with reliable cues about the future risk of infection for the host itself or for its progeny. If the parental environment predicts the quality of the progeny's environment, then parents may further enhance their net reproductive success by differentially providing their offspring with phenotypes to cope with potential hazards such as pathogen infection. Here, I test for the occurrence of such an adaptive transgenerational phenotypic plasticity in the mealworm beetle, Tenebrio molitor. A pathogenic environment was mimicked by injection of bacterial lipopolysaccharides for two generations of insects. I found that parental challenge enhanced offspring immunity through the inducible production of antimicrobial peptides in the haemolymph.

  10. Runaway electron generation as possible trigger for enhancement of magnetohydrodynamic plasma activity and fast changes in runaway beam behavior

    International Nuclear Information System (INIS)

    Pankratov, I. M.; Zhou, R. J.; Hu, L. Q.

    2015-01-01

    Peculiar phenomena were observed during experiments with runaway electrons: rapid changes in the synchrotron spot and its intensity that coincided with stepwise increases in the electron cyclotron emission (ECE) signal (cyclotron radiation of suprathermal electrons). These phenomena were initially observed in TEXTOR (Tokamak Experiment for Technology Oriented Research), where these events only occurred in the current decay phase or in discharges with thin stable runaway beams at a q = 1 drift surface. These rapid changes in the synchrotron spot were interpreted by the TEXTOR team as a fast pitch angle scattering event. Recently, similar rapid changes in the synchrotron spot and its intensity that coincided with stepwise increases in the non-thermal ECE signal were observed in the EAST (Experimental Advanced Superconducting Tokamak) runaway discharge. Runaway electrons were located around the q = 2 rational magnetic surface (ring-like runaway electron beam). During the EAST runaway discharge, stepwise ECE signal increases coincided with enhanced magnetohydrodynamic (MHD) activity. This behavior was peculiar to this shot. In this paper, we show that these non-thermal ECE step-like jumps were related to the abrupt growth of suprathermal electrons induced by bursting electric fields at reconnection events during this MHD plasma activity. Enhancement of the secondary runaway electron generation also occurred simultaneously. Local changes in the current-density gradient appeared because of local enhancement of the runaway electron generation process. These current-density gradient changes are considered to be a possible trigger for enhancement of the MHD plasma activity and the rapid changes in runaway beam behavior

  11. Runaway electron generation as possible trigger for enhancement of magnetohydrodynamic plasma activity and fast changes in runaway beam behavior

    Science.gov (United States)

    Pankratov, I. M.; Zhou, R. J.; Hu, L. Q.

    2015-07-01

    Peculiar phenomena were observed during experiments with runaway electrons: rapid changes in the synchrotron spot and its intensity that coincided with stepwise increases in the electron cyclotron emission (ECE) signal (cyclotron radiation of suprathermal electrons). These phenomena were initially observed in TEXTOR (Tokamak Experiment for Technology Oriented Research), where these events only occurred in the current decay phase or in discharges with thin stable runaway beams at a q = 1 drift surface. These rapid changes in the synchrotron spot were interpreted by the TEXTOR team as a fast pitch angle scattering event. Recently, similar rapid changes in the synchrotron spot and its intensity that coincided with stepwise increases in the non-thermal ECE signal were observed in the EAST (Experimental Advanced Superconducting Tokamak) runaway discharge. Runaway electrons were located around the q = 2 rational magnetic surface (ring-like runaway electron beam). During the EAST runaway discharge, stepwise ECE signal increases coincided with enhanced magnetohydrodynamic (MHD) activity. This behavior was peculiar to this shot. In this paper, we show that these non-thermal ECE step-like jumps were related to the abrupt growth of suprathermal electrons induced by bursting electric fields at reconnection events during this MHD plasma activity. Enhancement of the secondary runaway electron generation also occurred simultaneously. Local changes in the current-density gradient appeared because of local enhancement of the runaway electron generation process. These current-density gradient changes are considered to be a possible trigger for enhancement of the MHD plasma activity and the rapid changes in runaway beam behavior.

  12. Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to BAFF in treating human papillomavirus-associated cancer.

    Science.gov (United States)

    Wu, Chao-Chih; Wu, Fang-Cih; Hsu, Yun-Tin; Hsiao, Yu-Chia; Yang, Yuh-Cheng; Chang, C Allen; Chang, Chih-Long

    2017-05-16

    B-cell-activating factor (BAFF) belongs to the tumor necrosis factor family that not only stimulates B and T cells but also counteracts immune tolerance. BAFF is also a type II membrane protein, which is secreted through the endoplasmic reticulum (ER)-Golgi apparatus pathway. Fusing an antigen to BAFF might enhance the presentation of major histocompatibility complex class I molecules. These characteristics represent an opportunity to enhance the antitumor effects of DNA vaccines. Therefore, we fused BAFF to human papillomavirus type 16 E7 as a DNA vaccine and evaluated its antitumor effects. We found that this vaccine increased E7-specific CD8+ T-cell immune responses, engendered major antitumor effects against E7-expressing tumors, and prolonged the survival of the immunized mice. Interestingly, vaccinating B-cell-deficient mice with BAFF-E7 revealed considerable E7-specific CD8+ T-cell immune responses, suggesting that B cells do not contribute to this immune response. Image analysis through confocal fluorescence microscopy revealed that fusing BAFF to E7 targeted the protein to the ER, but not BAFF lacking 128 N-terminal residues that generated a lower number of E7-specific CD8+ T cells in the vaccinated mice. Our data indicated that the ER-targeting characteristic of BAFF is the main factor improving the potency of DNA vaccines.

  13. Field localization and enhancement of phase-locked second- and third-order harmonic generation in absorbing semiconductor cavities

    International Nuclear Information System (INIS)

    Roppo, V.; Cojocaru, C.; Trull, J.; Vilaseca, R.; Raineri, F.; Halioua, Y.; Raj, R.; Sagnes, I.; D'Aguanno, G.; Scalora, M.

    2009-01-01

    We predict and experimentally observe the enhancement by three orders of magnitude of phase mismatched second and third harmonic generation in a GaAs cavity at 650 and 433 nm, respectively, well above the absorption edge. Phase locking between the pump and the harmonics changes the effective dispersion of the medium and inhibits absorption. Despite hostile conditions the harmonics resonate inside the cavity and become amplified leading to relatively large conversion efficiencies. Field localization thus plays a pivotal role despite the presence of absorption, and ushers in a new class of semiconductor-based devices in the visible and uv ranges.

  14. Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

    Science.gov (United States)

    Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

    2013-02-01

    Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

  15. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin; Kim, Jung Hoon; Lee, Jeong Min; Choi, Jin Woo; Han, Joon Koo; Choi, Byung Ihn [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-03-15

    To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

  16. Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI.

    Science.gov (United States)

    Chen, Yi-Fang; Yuan, Ang; Cho, Kuan-Hung; Lu, Yi-Chien; Kuo, Mark Yen-Ping; Chen, Jyh-Horng; Chang, Yeun-Chung

    2017-01-01

    This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive) and HCC827R (gefitinib resistant) to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE) and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (Ktrans, kep, and iAUC90) and apparent diffusion coefficient (ADC) were significantly correlated with tumor size. Ktrans and iAUC90 significantly decreased at week 2 in the groups receiving erlotinib alone and in combination with bevacizumab, whereas kep decreased at week 1 and 2 in both treatment groups. In addition, there was a significant difference in iAUC90 between the treatment groups at week 1. Compared to the control group of HCC827, there was a significant reduction in microvessel density and increased tumor apoptosis in the two treatment group. ADC value increased in the erlotinib alone group at week 1 and week 2, and in the erlotinib combined with bevacizumab group at week 2. Enlarged areas of central tumor necrosis were associated with a higher ADC value. However, progressive enlargement of the tumors but no significant differences in DCE parameters or ADC were noted in the HCC827R model. These results showed that both erlotinib alone and in combination with bevacizumab could effectively inhibit tumor growth in the gefitinib-sensitive lung cancer mice model, and that this was associated with decreased vascular perfusion, increased ADC percentage, decreased microvessel density, and increased tumor apoptosis with a two-week treatment cycle.

  17. Functional evaluation of therapeutic response of HCC827 lung cancer to bevacizumab and erlotinib targeted therapy using dynamic contrast-enhanced and diffusion-weighted MRI.

    Directory of Open Access Journals (Sweden)

    Yi-Fang Chen

    Full Text Available This study aimed to investigate the therapeutic responses of lung cancer mice models with adenocarcinoma HCC827 (gefitinib sensitive and HCC827R (gefitinib resistant to the epidermal growth factor receptor-tyrosine kinase inhibitor erlotinib alone and in combination with the anti-angiogenesis agent bevacizumab using dynamic contrast enhanced (DCE and diffusion-weighted MRI. In the HCC827 model, temporal changes in DCE-MRI derived parameters (Ktrans, kep, and iAUC90 and apparent diffusion coefficient (ADC were significantly correlated with tumor size. Ktrans and iAUC90 significantly decreased at week 2 in the groups receiving erlotinib alone and in combination with bevacizumab, whereas kep decreased at week 1 and 2 in both treatment groups. In addition, there was a significant difference in iAUC90 between the treatment groups at week 1. Compared to the control group of HCC827, there was a significant reduction in microvessel density and increased tumor apoptosis in the two treatment group. ADC value increased in the erlotinib alone group at week 1 and week 2, and in the erlotinib combined with bevacizumab group at week 2. Enlarged areas of central tumor necrosis were associated with a higher ADC value. However, progressive enlargement of the tumors but no significant differences in DCE parameters or ADC were noted in the HCC827R model. These results showed that both erlotinib alone and in combination with bevacizumab could effectively inhibit tumor growth in the gefitinib-sensitive lung cancer mice model, and that this was associated with decreased vascular perfusion, increased ADC percentage, decreased microvessel density, and increased tumor apoptosis with a two-week treatment cycle.

  18. Entomopathogenic fungus generated Nanoparticles for enhancement of efficacy in Culex quinquefasciatus and Anopheles stephensi

    Directory of Open Access Journals (Sweden)

    N. SONI, S. PRAKASH

    2012-05-01

    Full Text Available Objective: To evaluate to efficacy of silver and gold generated larvicide with the help of entomopathogenic fungus Chrysosporium tropicum against the Culex quinquefasciatus and Anopheles stephensi larvae. Methods: The silver and gold nanoparticles were quantified and observed by the Micro-scan reader and X-ray diffraction technique. The micrographs of silver and gold nanoparticles were obtained by the Transmission electron microscope and Scanning electron microscope. The larvicidal efficacy was then performed at six different log concentrations by the probit analysis. Results: The characterization study confirmed the spherical shaped and sized (20-50 and 2-15 nm of silver and gold nanoparticles. The all larval stages of Cx. quinquefasciatus were found more susceptible to the synthesized silver nanoparticles. Whereas, the larvae of An. stephensi were found more susceptible to larvicide synthesized with gold nanoparticles. Conclusions: The results suggested that the silver and gold nanoparticles generated by the entomopathogenic fungus C. tropicum is an environmentally safer and greener approach for mosquito control and new possibility in vector control strategy.

  19. Evaluation of Power Conditioning Architectures for Energy Production Enhancement in Thermoelectric Generator Systems

    Science.gov (United States)

    Wu, Hongfei; Sun, Kai; Chen, Min; Xing, Yan

    2014-06-01

    A large-scale thermoelectric generator (TEG) system has an unbalanced temperature distribution among the TEG modules, which leads to power mismatch among the modules and decreases the power output of the TEG system. To maximize the power output and minimize the power conversion loss, a centralized-distributed hybrid power conditioning architecture is presented, analyzed, and evaluated for a TEG system. The novel architecture is a combination of a conventional centralized architecture and a fully distributed architecture. By using the proposed architecture, most of the harvested power is processed by the centralized stage while only the mismatched power among the TEG modules is processed by the distributed stages. As a result, accurate and distributed maximum-power-point tracking (MPPT) for each TEG module and single-stage power conversion between the modules and load can be achieved. It offers the benefit of implementing high MPPT efficiency and high conversion efficiency simultaneously. A 50-W TEG system composed of two TEG modules is built and tested. Experimental results show that the proposed hybrid power conditioning architecture generates up to 5% more energy for a temperature difference between the two modules of only 10°C.

  20. Porosity-enhanced solar powered hydrogen generation in GaN photoelectrodes

    Science.gov (United States)

    Hou, Y.; Ahmed Syed, Z.; Jiu, L.; Bai, J.; Wang, T.

    2017-11-01

    Two types of GaN based photoelectrodes using either horizontally aligned or vertically aligned nanopores have been fabricated by means of using an electrochemical etching approach. The photoelectrodes based on such nanostructures have demonstrated an up to 5-fold enhancement in applied bias photon-to-current efficiency and incident photon-to-current efficiency in comparison with their planar counterpart, leading to a high Faradaic conversion efficiency which approaches 1. The GaN photoelectrodes with these nanopores also show excellent chemical stability in HBr solution as an electrolyte. The results presented reveal that the gas diffusion in the nanopores plays an important role in water splitting processes, which should be taken into account when designing a GaN photoelectrode with a nanopore structure.

  1. Generation and preservation of field enhancement for organic-plasmonic devices

    DEFF Research Database (Denmark)

    Kostiučenko, Oksana

    of this PhD thesis. First, the optimum size and shape of nanostructured substrates have been estimated via numerical simulations. Following the optimum parameters found via simulation, gold nanostructures have been fabricated by means of lift-off and high resolution electron beam lithography techniques....... The optical response of fabricated nanostructures has been characterized using a recently developed “imprint” technique, where a polymer film, deposited on the nanostructures is ablated by the structure-enhanced electric near-field. The improvement of mechanical durability of gold nanostructures coated...... with optically transparent and hard diamond-like carbon thin films has been investigated by means of atomic-force microscopy. The following optical characterizations of nanostructures with different coating thicknesses allow one to find the optimum balance between their optical and mechanical properties. Finally...

  2. Carbon Nanotube Enhanced Aerospace Composite Materials A New Generation of Multifunctional Hybrid Structural Composites

    CERN Document Server

    Kostopoulos, V

    2013-01-01

    The well documented increase in the use of high performance composites as structural materials in aerospace components is continuously raising the demands in terms of dynamic performance, structural integrity, reliable life monitoring systems and adaptive actuating abilities. Current technologies address the above issues separately; material property tailoring and custom design practices aim to the enhancement of dynamic and damage tolerance characteristics, whereas life monitoring and actuation is performed with embedded sensors that may be detrimental to the structural integrity of the component. This publication explores the unique properties of carbon nanotubes (CNT) as an additive in the matrix of Fibre Reinforced Plastics (FRP), for producing structural composites with improved mechanical performance as well as sensing/actuating capabilities. The successful combination of the CNT properties and existing sensing actuating technologies leads to the realization of a multifunctional FRP structure. The curre...

  3. Therapeutical radiopharmaceuticals based In vivo generator system [{sup 166} Dy] Dy/{sup 166} Ho; Radiofarmacos terapeuticos basados en un sistema de generador In vivo [{sup 166}Dy] Dy/{sup 166}Ho

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Garcia S, L.; Monroy G, F.; Tendilla, J.I. [Gerencia de Aplicaciones Nucleares en la Salud, ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico); Pedraza L, M.; Murphy, C.A. de [Departamento de Medicina Nuclear, Instituto Nacional de Pediatria, Mexico D.F. (Mexico)

    2002-07-01

    At the idea to administer to a patient a molecule containing in it structure a father radionuclide, with a half life enough large which allows to the radiolabelled molecule to take up position specifically in a white tissue and decaying In vivo to the daughter radionuclide with properties potentially therapeutic, it is known as In vivo generator system. In this work the preparation and the preliminary dosimetric valuations of radiopharmaceuticals based In vivo generator system {sup 166} Dy Dy/{sup 166} Ho for applications in radioimmunotherapy, in the treatment of the rheumatoid arthritis and in the bone marrow ablation (m.o.) for candidates patients to bone marrow transplant are presented. (Author)

  4. Enhancement of carboxylic acid degradation with sulfate radical generated by persulfate activation.

    Science.gov (United States)

    Criquet, J; Nebout, P; Karpel Vel Leitner, N

    2010-01-01

    The aim of this work was to investigate the generation of sulfate radical for the removal of two carboxylic acids in aqueous solution: acetic and citric acids. From photochemical and radiolytic processes, kinetics of the degradation of these two carboxylic acids was studied as a function of the pH of the solution. It was shown that the maximum of acetic acid degradation occurred at pH 5. Above this pH, competitive reactions with the carbon mineralized inhibit the reaction of with the solute. In the case of citric acid, pH has only a little effect on the kinetic of citric acid degradation. The determination of mineralization yields shows several differences depending on carboxylic acids and pH. The degradation of both carboxylic acids was also studied in the radiolysis process whether with or without persulfate addition. A comparison of the processes of sulfate radical production is presented.

  5. Hierarchical Coordinated Control of Distributed Generators and Active Power Filters to Enhance Power Quality of Microgrids

    DEFF Research Database (Denmark)

    Savaghebi, Mehdi; Hashempour, Mohammad M.; Guerrero, Josep M.

    2014-01-01

    This paper addresses the coordinated control of distributed generators (DGs) inverters and active power filters (APFs) to compensate voltage harmonics in microgrids. For this, a hierarchical control system is proposed to mitigate voltage harmonic distortion. The hierarchical control structure...... includes two control levels: primary control and secondary control. Primary control consists of power controllers, selective virtual impedance loops and proportional-resonant (PR) voltage/current controllers. Secondary control manages the compensation of voltage harmonic distortion of sensitive load bus...... (SLB). Compensation of SLB harmonics by control of DGs may cause excessive voltage harmonics at the terminal of one or more of DGs interface inverters and/or overloading of the inverters. After occurrence of each of these cases, active power filter (APF) participates in harmonic compensation...

  6. Enhanced electrohydrodynamic force generation in a two-stroke cycle dielectric-barrier-discharge plasma actuator

    Science.gov (United States)

    Sato, Shintaro; Takahashi, Masayuki; Ohnishi, Naofumi

    2017-05-01

    An approach for electrohydrodynamic (EHD) force production is proposed with a focus on a charge cycle on a dielectric surface. The cycle, consisting of positive-charging and neutralizing strokes, is completely different from the conventional methodology, which involves a negative-charging stroke, in that the dielectric surface charge is constantly positive. The two-stroke charge cycle is realized by applying a DC voltage combined with repetitive pulses. Simulation results indicate that the negative pulse eliminates the surface charge accumulated during constant voltage phase, resulting in repetitive EHD force generation. The time-averaged EHD force increases almost linearly with increasing repetitive pulse frequency and becomes one order of magnitude larger than that driven by the sinusoidal voltage, which has the same peak-to-peak voltage.

  7. Oxygen-generating hybrid nanoparticles to enhance fluorescent/photoacoustic/ultrasound imaging guided tumor photodynamic therapy.

    Science.gov (United States)

    Gao, Shi; Wang, Guohao; Qin, Zainen; Wang, Xiangyu; Zhao, Guoqing; Ma, Qingjie; Zhu, Lei

    2017-01-01

    Photodynamic therapy (PDT) is a promising tumor treatment modality that can convert oxygen into cytotoxic singlet oxygen (SO) via photosensitizer to ablate tumor growth. However, the uncontrolled cancer cell proliferation during tumor development and the oxygen consumption during PDT always result in an insufficient oxygen level in tumors, which can adversely affect the PDT efficiency in turn. We designed an oxygen-generating PDT nanocomplex by encapsulating a manganese dioxide nanoparticle (MnO 2 NP) in an indocyanine green (ICG) modified hyaluronic acid nanoparticle (HANP) to overcome this limitation. Because of the excellent fluorescent and photoacoustic properties, the tumor accumulation of the ICG-HANP/MnO 2 (IHM) nanocomplex was monitored by fluorescent imaging and photoacoustic imaging after intravenous administration into the SCC7 tumor-bearing mouse model. Both high fluorescent and photoacoustic signals were detected and found peak at 6 h post-injection (tumor-muscle ratio: 4.03 ± 0.36 for fluorescent imaging and 2.93 ± 0.13 for photoacoustic imaging). In addition, due to the high reactivity of MnO 2 NP to H 2 O 2 , an unfavorable tumor cell metabolic, the oxygen content in the tumor is elevated 2.25 ± 0.07 times compared to that without IHM treatment as ultrasound imaging confirmed. After laser irradiation, significant tumor growth inhibition was observed in the IHM-treated group compared to the ICG-HANP-treated group, attributed to the beneficial oxygen-generating property of IHM for PDT. It is expected that the design of IHM will provide an alternative way of improving clinical PDT efficacy and will be widely applied in cancer theranostics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Enhancing Next-Generation Sequencing-Guided Cancer Care Through Cognitive Computing.

    Science.gov (United States)

    Patel, Nirali M; Michelini, Vanessa V; Snell, Jeff M; Balu, Saianand; Hoyle, Alan P; Parker, Joel S; Hayward, Michele C; Eberhard, David A; Salazar, Ashley H; McNeillie, Patrick; Xu, Jia; Huettner, Claudia S; Koyama, Takahiko; Utro, Filippo; Rhrissorrakrai, Kahn; Norel, Raquel; Bilal, Erhan; Royyuru, Ajay; Parida, Laxmi; Earp, H Shelton; Grilley-Olson, Juneko E; Hayes, D Neil; Harvey, Stephen J; Sharpless, Norman E; Kim, William Y

    2018-02-01

    Using next-generation sequencing (NGS) to guide cancer therapy has created challenges in analyzing and reporting large volumes of genomic data to patients and caregivers. Specifically, providing current, accurate information on newly approved therapies and open clinical trials requires considerable manual curation performed mainly by human "molecular tumor boards" (MTBs). The purpose of this study was to determine the utility of cognitive computing as performed by Watson for Genomics (WfG) compared with a human MTB. One thousand eighteen patient cases that previously underwent targeted exon sequencing at the University of North Carolina (UNC) and subsequent analysis by the UNCseq informatics pipeline and the UNC MTB between November 7, 2011, and May 12, 2015, were analyzed with WfG, a cognitive computing technology for genomic analysis. Using a WfG-curated actionable gene list, we identified additional genomic events of potential significance (not discovered by traditional MTB curation) in 323 (32%) patients. The majority of these additional genomic events were considered actionable based upon their ability to qualify patients for biomarker-selected clinical trials. Indeed, the opening of a relevant clinical trial within 1 month prior to WfG analysis provided the rationale for identification of a new actionable event in nearly a quarter of the 323 patients. This automated analysis took potentially improve patient care by providing a rapid, comprehensive approach for data analysis and consideration of up-to-date availability of clinical trials. The results of this study demonstrate that the interpretation and actionability of somatic next-generation sequencing results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing can significantly improve patient care by providing a fast, cost-effective, and comprehensive approach for data analysis in the delivery of precision medicine. Patients and physicians who

  9. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid

    Directory of Open Access Journals (Sweden)

    Sanie-Jahromi Fatemeh

    2012-04-01

    Full Text Available Abstract Background Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers during treatment of human retinal pigment epithelium (RPE cells with amniotic fluid (AF, RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Results Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1 confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Conclusion Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  10. Generated carrier dynamics in V-pit enhanced InGaN/GaN light emitting diode

    KAUST Repository

    Ajia, Idris A.

    2017-12-18

    We investigate the effects of V-pits on the optical properties of a state-of-the art highly efficient, blue InGaN/GaN multi-quantum-well (MQW) light emitting diode (LED) with high internal quantum efficiency (IQE) of > 80%. The LED is structurally enhanced by incorporating pre-MQW InGaN strain-relief layer with low InN content and patterned sapphire substrate. For comparison, a conventional (unenhanced) InGaN/GaN MQW LED (with IQE of 46%) grown under similar conditions was subjected to the same measurements. Scanning transmission electron microscopy (STEM) reveals the absence of V-pits in the unenhanced LED, whereas in the enhanced LED, V-pits with {10-11} facets, emerging from threading dislocations (TDs) were prominent. Cathodoluminescence mapping reveals the luminescence properties near the V-pits, showing that the formation of V-pit defects can encourage the growth of defect-neutralizing barriers around TD defect states. The diminished contribution of TDs in the MQWs allows indium-rich localization sites to act as efficient recombination centers. Photoluminescence and time-resolved spectroscopy measurements suggest that the V-pits play a significant role in the generated carrier rate and droop mechanism, showing that the quantum confined Stark effect is suppressed at low generated carrier density, after which the carrier dynamics and droop are governed by the carrier overflow effect.

  11. Enhanced output performance of a lead-free nanocomposite generator using BaTiO3 nanoparticles and nanowires filler

    Science.gov (United States)

    Baek, Changyeon; Yun, Jong Hyuk; Wang, Hee Seung; Wang, Ji Eun; Park, Hyeonbin; Park, Kwi-Il; Kim, Do Kyung

    2018-01-01

    Flexible nanocomposite generators based on piezoelectric nanoparticles (NPs)-polymeric matrix have been attracted attention as the energy harvesting device converted the electricity from the mechanical deformations. To enhance the piezo-potential difference introduced inside the piezoelectric nanocomposite, one-dimensional nanostructures such as CNTs, copper nanorods, and Ag nanowires (NWs) should be used inevitably as a dispersing agent for achieving well-distributed piezoelectric nanoparticles in an elastomer. These non-piezoelectric additives showed versatile roles; however, their toxicity to living organism has been an obstacle to realize the bio-eco-friendly flexible energy harvesters. Replacing them with piezoelectric NWs with non-toxic can be a challengeable approach to achieve not only the original purposes of additives but also the improvement of output performance. Here, we synthesized well-crystallized BaTiO3 spherical and acicular NPs via a simple hydrothermal reaction and the two-step hydrothermal reactions, respectively and produced piezoelectric nanocomposite made of piezoelectric BaTiO3 NPs and NWs without toxic dispersion enhancers. Output performance of the fabricated flexible energy harvesters with varying the composition of NPs and NWs were investigated by the well-optimized measurement system during the periodical bending and unbending. A nanocomposite-based energy harvester with 4:1 wt ratio generated the maximum open-circuit voltage and short-circuit current of 60 V and 1.1 μA, respectively.

  12. Graphene controlled H- and J-stacking of perylene dyes into highly stable supramolecular nanostructures for enhanced photocurrent generation

    Science.gov (United States)

    Gan, Shiyu; Zhong, Lijie; Engelbrekt, Christian; Zhang, Jingdong; Han, Dongxue; Ulstrup, Jens; Chi, Qijin; Niu, Li

    2014-08-01

    We report a new method for controlling H- and J-stacking in supramolecular self-assembly. Graphene nanosheets act as structure inducers to direct the self-assembly of a versatile organic dye, perylene into two distinct types of functional nanostructures, i.e. one-dimensional nanotubes via J-stacking and two-dimensional branched nanobuds through H-stacking. Graphene integrated supramolecular nanocomposites are highly stable and show significant enhancement of photocurrent generation in these two configurations of photosensing devices, i.e. solid-state optoelectronic constructs and liquid-junction solar cells.We report a new method for controlling H- and J-stacking in supramolecular self-assembly. Graphene nanosheets act as structure inducers to direct the self-assembly of a versatile organic dye, perylene into two distinct types of functional nanostructures, i.e. one-dimensional nanotubes via J-stacking and two-dimensional branched nanobuds through H-stacking. Graphene integrated supramolecular nanocomposites are highly stable and show significant enhancement of photocurrent generation in these two configurations of photosensing devices, i.e. solid-state optoelectronic constructs and liquid-junction solar cells. Electronic supplementary information (ESI) available: Material and methods, spectroscopic data, AFM and TEM images, materials functional tests and supplementary discussions. See DOI: 10.1039/c4nr02308k

  13. Enhancing organic matter removal, biopolymer recovery and electricity generation from distillery wastewater by combining fungal fermentation and microbial fuel cell.

    Science.gov (United States)

    Ghosh Ray, S; Ghangrekar, M M

    2015-01-01

    For enhancing organic matter removal from cereal-based distillery stillage two-stage treatment consisting of fermentation by Aspergillus awamori followed by microbial fuel cell (MFC) is proposed. Considerable reduction in total and soluble chemical oxygen demand (COD) up to 70% and 40%, respectively, along with 98% reduction of suspended solids (SS) has been achieved during fungal pretreatment. The process generated chitosan, a useful fermentation byproduct from fungal mycelia, as 0.6-0.7g/l of settled sludge with mycelium (3.8% solids). Prior treatment of wastewater with fungal strain enhanced the power generation in MFC by 2.9 times at an organic loading rate of 1.5kgCOD/m(3)day, demonstrating soluble COD reduction of 92% in MFC. While treating distillery wastewater, this two-stage integrated biological process demonstrated overall 99% COD removal and almost complete removal of SS, delivering ample scope for scale-up and industrial application to offer effective solution for distillery wastewater treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Toward enhanced hydrogen generation from water using oxygen permeating LCF membranes

    KAUST Repository

    Wu, Xiao-Yu

    2015-01-01

    © the Owner Societies. Hydrogen production from water thermolysis can be enhanced by the use of perovskite-type mixed ionic and electronic conducting (MIEC) membranes, through which oxygen permeation is driven by a chemical potential gradient. In this work, water thermolysis experiments were performed using 0.9 mm thick La0.9Ca0.1FeO3-δ (LCF-91) perovskite membranes at 990 °C in a lab-scale button-cell reactor. We examined the effects of the operating conditions such as the gas species concentrations and flow rates on the feed and sweep sides on the water thermolysis rate and oxygen flux. A single step reaction mechanism is proposed for surface reactions, and three-resistance permeation models are derived. Results show that water thermolysis is facilitated by the LCF-91 membrane especially when a fuel is added to the sweep gas. Increasing the gas flow rate and water concentration on the feed side or the hydrogen concentration on the sweep side enhances the hydrogen production rate. In this work, hydrogen is used as the fuel by construction, so that a single-step surface reaction mechanism can be developed and water thermolysis rate parameters can be derived. Both surface reaction rate parameters for oxygen incorporation/dissociation and hydrogen-oxygen reactions are fitted at 990 °C. We compare the oxygen fluxes in water thermolysis and air separation experiments, and identify different limiting steps in the processes involving various oxygen sources and sweep gases for this 0.9 mm thick LCF-91 membrane. In the air feed-inert sweep case, the bulk diffusion and sweep side surface reaction are the two limiting steps. In the water feed-inert sweep case, surface reaction on the feed side dominates the oxygen permeation process. Yet in the water feed-fuel sweep case, surface reactions on both the feed and sweep sides are rate determining when hydrogen concentration in the sweep side is in the range of 1-5 vol%. Furthermore, long term studies show that the surface

  15. A System to Generate SignWriting for Video Tracks Enhancing Accessibility of Deaf People

    Directory of Open Access Journals (Sweden)

    Elena Verdú

    2017-12-01

    Full Text Available Video content has increased much on the Internet during last years. In spite of the efforts of different organizations and governments to increase the accessibility of websites, most multimedia content on the Internet is not accessible. This paper describes a system that contributes to make multimedia content more accessible on the Web, by automatically translating subtitles in oral language to SignWriting, a way of writing Sign Language. This system extends the functionality of a general web platform that can provide accessible web content for different needs. This platform has a core component that automatically converts any web page to a web page compliant with level AA of WAI guidelines. Around this core component, different adapters complete the conversion according to the needs of specific users. One adapter is the Deaf People Accessibility Adapter, which provides accessible web content for the Deaf, based on SignWritting. Functionality of this adapter has been extended with the video subtitle translator system. A first prototype of this system has been tested through different methods including usability and accessibility tests and results show that this tool can enhance the accessibility of video content available on the Web for Deaf people.

  16. Pressurized air cathodes for enhanced stability and power generation by microbial fuel cells

    KAUST Repository

    He, Weihua

    2016-09-30

    Large differences between the water and air pressure in microbial fuel cells (MFCs) can deform and damage cathodes. To avoid deformation, the cathode air pressure was controlled to balance pressure differences between the air and water. Raising the air pressures from 0 to 10 kPa at a set cathode potential of −0.3 V (versus Ag/AgCl) enhanced cathode performance by 17%, but pressures ≥25 kPa decreased current and resulted in air leakage into the solution. Matching the air pressure with the water pressure avoided cathode deformation and improved performance. The maximum power density increased by 15%, from 1070 ± 20 to 1230 ± 70 mW m, with balanced air and water pressures of 10–25 kPa. Oxygen partial pressures ≥12.5 kPa in the cathode compartment maintained the oxygen reduction rate to be within 92 ± 1% of that in ambient air. The use of pressurized air flow through the cathode compartments can enable closer spacing of the cathodes compared to passive gas transfer systems, which could make the reactor design more compact. The energy cost of pressurizing the cathodes was estimated to be smaller than the increase in power that resulted from the use of pressurized cathodes.

  17. Optimal battery sizing in photovoltaic based distributed generation using enhanced opposition-based firefly algorithm for voltage rise mitigation.

    Science.gov (United States)

    Wong, Ling Ai; Shareef, Hussain; Mohamed, Azah; Ibrahim, Ahmad Asrul

    2014-01-01

    This paper presents the application of enhanced opposition-based firefly algorithm in obtaining the optimal battery energy storage systems (BESS) sizing in photovoltaic generation integrated radial distribution network in order to mitigate the voltage rise problem. Initially, the performance of the original firefly algorithm is enhanced by utilizing the opposition-based learning and introducing inertia weight. After evaluating the performance of the enhanced opposition-based firefly algorithm (EOFA) with fifteen benchmark functions, it is then adopted to determine the optimal size for BESS. Two optimization processes are conducted where the first optimization aims to obtain the optimal battery output power on hourly basis and the second optimization aims to obtain the optimal BESS capacity by considering the state of charge constraint of BESS. The effectiveness of the proposed method is validated by applying the algorithm to the 69-bus distribution system and by comparing the performance of EOFA with conventional firefly algorithm and gravitational search algorithm. Results show that EOFA has the best performance comparatively in terms of mitigating the voltage rise problem.

  18. Distributed Generation Planning using Peer Enhanced Multi-objective Teaching-Learning based Optimization in Distribution Networks

    Science.gov (United States)

    Selvam, Kayalvizhi; Vinod Kumar, D. M.; Siripuram, Ramakanth

    2017-04-01

    In this paper, an optimization technique called peer enhanced teaching learning based optimization (PeTLBO) algorithm is used in multi-objective problem domain. The PeTLBO algorithm is parameter less so it reduced the computational burden. The proposed peer enhanced multi-objective based TLBO (PeMOTLBO) algorithm has been utilized to find a set of non-dominated optimal solutions [distributed generation (DG) location and sizing in distribution network]. The objectives considered are: real power loss and the voltage deviation subjected to voltage limits and maximum penetration level of DG in distribution network. Since the DG considered is capable of injecting real and reactive power to the distribution network the power factor is considered as 0.85 lead. The proposed peer enhanced multi-objective optimization technique provides different trade-off solutions in order to find the best compromise solution a fuzzy set theory approach has been used. The effectiveness of this proposed PeMOTLBO is tested on IEEE 33-bus and Indian 85-bus distribution system. The performance is validated with Pareto fronts and two performance metrics (C-metric and S-metric) by comparing with robust multi-objective technique called non-dominated sorting genetic algorithm-II and also with the basic TLBO.

  19. Optimal Battery Sizing in Photovoltaic Based Distributed Generation Using Enhanced Opposition-Based Firefly Algorithm for Voltage Rise Mitigation

    Directory of Open Access Journals (Sweden)

    Ling Ai Wong

    2014-01-01

    Full Text Available This paper presents the application of enhanced opposition-based firefly algorithm in obtaining the optimal battery energy storage systems (BESS sizing in photovoltaic generation integrated radial distribution network in order to mitigate the voltage rise problem. Initially, the performance of the original firefly algorithm is enhanced by utilizing the opposition-based learning and introducing inertia weight. After evaluating the performance of the enhanced opposition-based firefly algorithm (EOFA with fifteen benchmark functions, it is then adopted to determine the optimal size for BESS. Two optimization processes are conducted where the first optimization aims to obtain the optimal battery output power on hourly basis and the second optimization aims to obtain the optimal BESS capacity by considering the state of charge constraint of BESS. The effectiveness of the proposed method is validated by applying the algorithm to the 69-bus distribution system and by comparing the performance of EOFA with conventional firefly algorithm and gravitational search algorithm. Results show that EOFA has the best performance comparatively in terms of mitigating the voltage rise problem.

  20. IR-Driven Ultrafast Transfer of Plasmonic Hot Electrons in Nonmetallic Branched Heterostructures for Enhanced H2Generation.

    Science.gov (United States)

    Zhang, Zhenyi; Jiang, Xiaoyi; Liu, Benkang; Guo, Lijiao; Lu, Na; Wang, Li; Huang, Jindou; Liu, Kuichao; Dong, Bin

    2018-03-01

    The ultrafast transfer of plasmon-induced hot electrons is considered an effective kinetics process to enhance the photoconversion efficiencies of semiconductors through strong localized surface plasmon resonance (LSPR) of plasmonic nanostructures. Although this classical sensitization approach is widely used in noble-metal-semiconductor systems, it remains unclear in nonmetallic plasmonic heterostructures. Here, by combining ultrafast transient absorption spectroscopy with theoretical simulations, IR-driven transfer of plasmon-induced hot electron in a nonmetallic branched heterostructure is demonstrated, which is fabricated through solvothermal growth of plasmonic W 18 O 49 nanowires (as branches) onto TiO 2 electrospun nanofibers (as backbones). The ultrafast transfer of hot electron from the W 18 O 49 branches to the TiO 2 backbones occurs within a timeframe on the order of 200 fs with very large rate constants ranging from 3.8 × 10 12 to 5.5 × 10 12 s -1 . Upon LSPR excitation by low-energy IR photons, the W 18 O 49 /TiO 2 branched heterostructure exhibits obviously enhanced catalytic H 2 generation from ammonia borane compared with that of W 18 O 49 nanowires. Further investigations by finely controlling experimental conditions unambiguously confirm that this plasmon-enhanced catalytic activity arises from the transfer of hot electron rather than from the photothermal effect. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Beyond the Lambertian limit: Novel low-symmetry gratings for ultimate light trapping enhancement in next-generation photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Birkmire, Robert [Univ. of Delaware, Newark, DE (United States); Hu, Juejun [Univ. of Delaware, Newark, DE (United States); Richardson, Kathleen [Univ. of Central Florida, Orlando, FL (United States). College of Optics and Photonics, Center for Research and Education in Optics and Lasers (CREOL)

    2016-05-20

    This project aims at addressing the efficiency limit and high fabrication cost of current light trapping methods by developing novel low-symmetry gratings (LSG) for next-generation thin c-Si photovoltaic (PV) cells. The LSG design achieves light trapping enhancement exceeding the 4n2 Lambertian limit and can be fabricated over large areas using low-cost, single-step nanoimprint techniques. We further explored the use of deposited high-refractive-index glass materials for low-temperature LSG processing, which enables direct imprint sculpting of even complex grating geometries in glass without requiring an additional pattern transfer step, which minimizes processing cost and surface damage to PV cells. In the project, we have demonstrated fabrication and integration of sub-wavelength LSG with thin c-Si wafers and bifacial solar cells with low defect density. Optical absorption measurements indicate that LSGs demonstrated superior absorption enhancement compared to their traditional symmetric counterparts as predicted by our simulations. Efficiency enhancement was observed in solar cells integrated with LSGs although fabrication yield of the LSG-integrated cells remains a challenge

  2. Persistent attenuation and enhancement of the earthworm main muscle contraction generator response induced by repeated stimulation of a peripheral neuron

    Directory of Open Access Journals (Sweden)

    Y.C. Chang

    1998-10-01

    Full Text Available Responses evoked in the earthworm, Amynthas hawayanus, main muscle contraction generator M-2 (postsynaptic mechanical-stimulus-sensitive neuron by threshold mechanical stimuli in 2-s intertrial intervals (ITI were used as the control or unconditioned responses (UR. Their attenuation induced by decreasing these intervals in non-associative conditioning and their enhancement induced by associating the unconditioned stimuli (US to a train of short (0.1 s hyperpolarizing electrical substitutive conditioning stimuli (SCS in the Peri-Kästchen (PK neuron were measured in four parameters, i.e., peak numbers (N and amplitude (averaged from 120 responses, sum of these amplitudes (SAMP and the highest peak amplitude (V over a period of 4 min. Persistent attenuation similar to habituation was induced by decreasing the control ITI to 0.5 s and 2.0 s in non-associative conditioning within less than 4 min. Dishabituation was induced by randomly pairing one of these habituated US to an electrical stimulus in the PK neuron. All four parameters of the UR were enhanced by forward (SCS-US, but not backward (US-SCS, association of the US with 25, 100 and 250-Hz trains of SCS with 40-ms interstimulus intervals (ISI for 4 min and persisted for another 4 min after turning off the SCS. The enhancement of these parameters was proportional to the SCS frequencies in the train. No UR was evoked by the SCS when the US was turned off after 4 min of classical conditioning.

  3. SURF imaging beams in an aberrative medium: Generation and postprocessing enhancement.

    Science.gov (United States)

    Näsholm, Sven Peter; Angelsen, Bjørn A J

    2012-11-01

    This paper presents numerical simulations of dual-frequency second-order ultrasound field (SURF) reverberation suppression transmit-pulse complexes. Such propagation was previously studied in a homogeneous medium. In this work, the propagation path includes a strongly aberrating body wall modeled by a sequence of delay screens. Each of the applied SURF transmit pulse complexes consists of a high-frequency 3.5-MHz imaging pulse combined with a low-frequency 0.5-MHz sound speed manipulation pulse. Furthermore, the feasibility of two signal postprocessing methods are investigated using the aberrated transmit SURF beams. These methods have previously been shown to adjust the depth of maximum SURF reverberation suppression within a homogeneous medium. The need for this study arises because imaging situations in which reverberation suppression is useful are also likely to produce pulse wave front distortion (aberration). Such distortions could potentially produce time delays that cancel the accumulated propagation time delay needed for the SURF reverberation suppression technique. Results show that both the generation of synthetic SURF reverberation suppression imaging transmit beams and the following postprocessing adjustments are attainable even when a body wall introduces time delays which are larger than previously reported delays measured on human body wall specimens.

  4. Laser beam shaping for enhanced Zero-Group Velocity Lamb modes generation.

    Science.gov (United States)

    Bruno, François; Laurent, Jérôme; Jehanno, Paul; Royer, Daniel; Prada, Claire

    2016-10-01

    Optimization of Lamb modes induced by laser can be achieved by adjusting the spatial source distribution to the mode wavelength (λ). The excitability of Zero-Group Velocity (ZGV) resonances in isotropic plates is investigated both theoretically and experimentally for axially symmetric sources. Optimal parameters and amplitude gains are derived analytically for spot and annular sources of either Gaussian or rectangular energy profiles. For a Gaussian spot source, the optimal radius is found to be λ ZGV /π. Annular sources increase the amplitude by at least a factor of 3 compared to the optimal Gaussian source. Rectangular energy profiles provide higher gain than Gaussian ones. These predictions are confirmed by semi-analytical simulation of the thermoelastic generation of Lamb waves, including the effect of material attenuation. Experimentally, Gaussian ring sources of controlled width and radius are produced with an axicon-lens system. Measured optimal geometric parameters obtained for Gaussian and annular beams are in good agreement with theoretical predictions. A ZGV resonance amplification factor of 2.1 is obtained with the Gaussian ring. Such source should facilitate the inspection of highly attenuating plates made of low ablation threshold materials like composites.

  5. A large enhancement of photoinduced second harmonic generation in CdI2--Cu layered nanocrystals.

    Science.gov (United States)

    Miah, M Idrish

    2009-02-12

    Photoinduced second harmonic generation (PISHG) in undoped as well as in various Cu-doped (0.05-1.2% Cu) CdI2 nanocrystals was measured at liquid nitrogen temperature (LNT). It was found that the PISHG increases with increasing Cu doping up to approximately 0.6% and then decreases almost to that for the undoped CdI2 for doping higher than approximately 1%. The values of the second-order susceptibility ranged from 0.50 to 0.67 pm V(-1) for the Cu-doped nanocrystals with a thickness of 0.5 nm. The Cu-doping dependence shown in a parabolic fashion suggests a crucial role of the Cu agglomerates in the observed effects. The PISHG in crystals with various nanosizes was also measured at LNT. The size dependence demonstrated the quantum-confined effect with a maximum PISHG for 0.5 nm and with a clear increase in the PISHG with decreasing thickness of the nanocrystal. The Raman scattering spectra at different pumping powers were taken for thin nanocrystals, and the phonon modes originating from interlayer phonons were observed in the spectra. The results were discussed within a model of photoinduced electron-phonon anharmonicity.

  6. Flapping foil power generator performance enhanced with a spring-connected tail

    Science.gov (United States)

    Liu, Zhengliang; Tian, Fang-Bao; Young, John; Lai, Joseph C. S.

    2017-12-01

    The flexibility effects on the performance of a flapping foil power generator are numerically studied by using the immersed boundary-lattice Boltzmann method at a Reynolds number of 1100. The flapping foil system consists of a rigid NACA0015 foil undergoing harmonic pitch and plunge motions and a passively actuated flat plate pinned to the trailing edge of the rigid foil. The flexibility is modeled by a torsional spring model at the conjuncture of the rigid foil and the tail. Here, a parametric study on mass density and natural frequency is conducted under the optimum kinematic condition of the rigid system identified from the literature and numerical simulations made for reduced frequency f* = 0.04-0.24 and pitch amplitude θ0 = 40°-90°. Four typical cases are discussed in detail by considering time histories of hydrodynamic loads and tail deformations under the optimal and non-optimal kinematic conditions. Results show that under the rigid-system optimal kinematic condition, a tail with appropriate mass density (μ = 0.60) and resonant frequency ( fr*=1.18 ) can improve the maximum efficiency by 7.24% accompanied by an increase of 6.63% in power compared to those of a rigid foil with a rigid tail. This is because the deflection of the tail reduces the low pressure region on the pressure surface (i.e., the lower surface during the upstroke or the upper surface during the downstroke) caused by the leading edge vortex after the stroke reversal, resulting in a higher efficiency. At high flapping frequencies, a spring-connected tail ( fr*=0.13 ) eliminates the large spike in the moment observed in high stiffness cases, reducing the power required for the pitch motion, resulting in 117% improvement in efficiency over that with a rigid tail at a reduced frequency of 0.24.

  7. Radiofrequency ablation for hepatocellular carcinoma: utility of conventional ultrasound and contrast-enhanced ultrasound in guiding and assessing early therapeutic response and short-term follow-up results.

    Science.gov (United States)

    Du, Jing; Li, Hong-Li; Zhai, Bo; Chang, Samuel; Li, Feng-Hua

    2015-09-01

    The purpose of this study was to assess the efficacy of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in guiding and assessing early therapeutic response to radiofrequency (RF) ablation for hepatocellular carcinomas (HCCs; up to 3 lesions, each ≤3 cm in diameter) and to report the short-term follow-up results. Between September 2011 and January 2013, 63 patients with 78 HCCs (≤3 cm) underwent conventional US- and CEUS-guided percutaneous RF ablation. CEUS was repeated after 20-30 min to assess therapeutic response, and local efficacy was further confirmed by contrast-enhanced magnetic resonance imaging (MRI) 1 mo after tumor ablation. Patients were followed periodically to look for local tumor or disease progression. Survival probability was estimated with the Kaplan-Meier method. Complete ablation was achieved for 76 (97.4%) of 78 HCCs in one (n = 73) or two (n = 3) sessions. No major complications were observed in any patient. The overall concordance in assessment of therapeutic efficacy of RF ablation between CEUS and MRI was 97.4% (76/78 tumors). The concordance test gave a value of κ = 0.74 (p therapeutic response to RF ablation. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  8. Therapeutic radionuclides

    International Nuclear Information System (INIS)

    Choi, Sun Ju; Hong, Young Don; Lee, So Young

    2006-01-01

    Since the development of sophisticated molecular carriers such as octereotides for peptide receptor targeting and monoclonal antibodies against various associated with specific tumor types, radionuclide therapy (RNT) employing open sources of therapeutic agents is promising modality for treatment of tumors. Furthermore, the emerging of new therapeutic regimes and new approaches for tumor treatment using radionuclide are anticipated in near future. In targeted radiotherapy using peptides and other receptor based carrier molecules, the use of radionuclide with high specific activity in formulating the radiopharmaceutical is essential in order to deliver sufficient number of radionuclides to the target site without saturating the target. In order to develop effective radiopharmaceuticals for therapeutic applications, it is crucial to carefully consider the choice of appropriate radionuclides as well as the carrier moiety with suitable pharmacokinetic properties that could result in good in vivo localization and desired excretion. Up to date, only a limited number of radionuclides have been applied in radiopharmaceutical development due to the constraints in compliance with their physical half-life, decay characteristics, cost and availability in therapeutic applications. In this review article, we intend to provide with the improved understanding of the factors of importance of appropriate radionuclide for therapy with respect to their physical properties and therapeutic applications

  9. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    International Nuclear Information System (INIS)

    Camats, Nuria; Garcia, Francisca; Parrilla, Juan Jose; Calaf, Joaquim; Martin, Miguel; Caldes, Montserrat Garcia

    2008-01-01

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p ≤ 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p ≤ 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells

  10. Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

    Energy Technology Data Exchange (ETDEWEB)

    Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

    2008-04-02

    Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

  11. Hot water generation for oil sands processing from enhanced geothermal systems: Process simulation for different hydraulic fracturing scenarios

    International Nuclear Information System (INIS)

    Hofmann, Hannes; Babadagli, Tayfun; Zimmermann, Günter

    2014-01-01

    Highlights: • Low enthalpy Enhanced Geothermal Systems (EGS) can provide hot water for oil sands processing. • A 5 km deep EGS can generate hot water at temperatures above 60 °C over a period of 30 years. • The cost is competitive as compared to the burning of natural gas. • The cost effective way to create an EGS in granitic basement rocks was the stimulation of complex natural fracture systems. • The savings in greenhouse gas emissions as compared to the burning of natural gas are enormous. - Abstract: The oil sands in northern Alberta, Canada are home to one of the largest hydrocarbon deposits on earth. Huge amounts of hot water—around 50–60 °C—are needed for the current extraction procedure and processing technology. The current practice of obtaining water from the Athabasca River and heating it by the burning of natural gas creates severe economic and environmental costs. In fact, 6% of Canada’s gas consumption is used for this purpose. As seen, the generation of huge amounts of fossil energy through oil sands extraction requires a substantial amount of fossil energy consumption (natural gas). Geothermal energy has the potential to significantly reduce natural gas consumption and greenhouse gas emissions at competitive costs. In this paper, we investigate how and whether or not the required hot water can be generated from the granitic basement rocks beneath the oil sands mining areas near Fort (Ft.) McMurray, located in the north east of Alberta. Hydraulic fracturing and resulting reservoir scenarios were simulated for different expected conditions in the region in order to find suitable fracturing strategies and conditions for an Enhanced Geothermal System (EGS). The simulations show that suitable fracturing treatments can increase the hydraulic performance of the system and that EGS heat generation can significantly reduce the environmental impact at comparable costs associated with the current processing technology. With this effort

  12. Graphene controlled H- and J-stacking of perylene dyes into highly stable supramolecular nanostructures for enhanced photocurrent generation

    DEFF Research Database (Denmark)

    Gan, Shiyu; Zhong, Lijie; Engelbrekt, Christian

    2014-01-01

    We report a new method for controlling H- and J-stacking in supramolecular self-assembly. Graphene nanosheets act as structure inducers to direct the self-assembly of a versatile organic dye, perylene into two distinct types of functional nanostructures, i.e. one-dimensional nanotubes via J-stack......-junction solar cells.......We report a new method for controlling H- and J-stacking in supramolecular self-assembly. Graphene nanosheets act as structure inducers to direct the self-assembly of a versatile organic dye, perylene into two distinct types of functional nanostructures, i.e. one-dimensional nanotubes via J......-stacking and two-dimensional branched nanobuds through H-stacking. Graphene integrated supramolecular nanocomposites are highly stable and show significant enhancement of photocurrent generation in these two configurations of photosensing devices, i.e. solid-state optoelectronic constructs and liquid...

  13. Anolyte recycling enhanced bioelectricity generation of the buffer-free single-chamber air-cathode microbial fuel cell.

    Science.gov (United States)

    Ren, Yueping; Chen, Jinli; Shi, Yugang; Li, Xiufen; Yang, Na; Wang, Xinhua

    2017-11-01

    Anolyte acidification is an inevitable restriction for the bioelectricity generation of buffer-free microbial fuel cells (MFCs). In this work, acidification of the buffer-free KCl anolyte has been thoroughly eliminated through anolyte recycling. The accumulated HCO 3 - concentration in the recycled KCl anolyte was above 50mM, which played as natural buffer and elevated the anolyte pH to above 8. The maximum power density (P max ) increased from 322.9mWm -2 to 527.2mWm -2 , which is comparable with the phosphate buffered MFC. Besides Geobacter genus, the gradually increased anolyte pH and conductivity induced the growing of electrochemically active Geoalkalibacter genus, in the anode biofilm. Anolyte recycling is a feasible strategy to strengthen the self-buffering capacity of buffer-free MFCs, thoroughly eliminate the anolyte acidification and prominently enhance the electric power. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Constructing ternary polyaniline-graphene-TiO{sub 2} hybrids with enhanced photoelectrochemical performance in photo-generated cathodic protection

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weiwei, E-mail: vivizhg@yahoo.com [College of Material Science and Engineering, Shandong University of Science and Technology, Qingdao 266590 (China); State Key Laboratory of Mining Disaster Prevention and Control Co-founded by Shandong Province and the Ministry of Science and Technology, Shandong University of Science and Technology, Qingdao, 266590 (China); Guo, Hanlin; Sun, Haiqing [College of Material Science and Engineering, Shandong University of Science and Technology, Qingdao 266590 (China); Zeng, Rongchang [College of Material Science and Engineering, Shandong University of Science and Technology, Qingdao 266590 (China); State Key Laboratory of Mining Disaster Prevention and Control Co-founded by Shandong Province and the Ministry of Science and Technology, Shandong University of Science and Technology, Qingdao, 266590 (China)

    2017-07-15

    Highlights: • Ternary polyaniline-graphene-TiO{sub 2} hybrids were synthesized. • Flat band potential shift facilitates electron injection to the coupled metal. • Electrons and holes transfer in the hybrids promotes electron–hole separation. • Synergistic effects of the ternary components make the hybrids photo-chargeable. - Abstract: Ternary polyaniline-graphene-TiO{sub 2} nanocomposites were constructed through a stepwise synthetic route. The hybrids exhibit remarkable enhancement in photoelectrochemical performance. The transfer of photo-excited carriers in the ternary composites facilitates the photo-induced electron-hole separation. Meanwhile, the flat band potential shift of the hybrids increases the inner electric field intensity that drives the photo-excited electron migration from the composites to the coupled metal. Furthermore, the ternary hybrids were found firstly to be photo-chargeable, which shows application potentials in photo-generated cathodic protection in dark.

  15. Neural Network based Control of SG based Standalone Generating System with Energy Storage for Power Quality Enhancement

    Science.gov (United States)

    Nayar, Priya; Singh, Bhim; Mishra, Sukumar

    2017-08-01

    An artificial intelligence based control algorithm is used in solving power quality problems of a diesel engine driven synchronous generator with automatic voltage regulator and governor based standalone system. A voltage source converter integrated with a battery energy storage system is employed to mitigate the power quality problems. An adaptive neural network based signed regressor control algorithm is used for the estimation of the fundamental component of load currents for control of a standalone system with load leveling as an integral feature. The developed model of the system performs accurately under varying load conditions and provides good dynamic response to the step changes in loads. The real time performance is achieved using MATLAB along with simulink/simpower system toolboxes and results adhere to an IEEE-519 standard for power quality enhancement.

  16. Novel scheme for enhancement of fault ride-through capability of doubly fed induction generator based wind farms

    International Nuclear Information System (INIS)

    Vinothkumar, K.; Selvan, M.P.

    2011-01-01

    Research highlights: → Proposed Fault ride-through (FRT) scheme for DFIG is aimed at energy conservation. → The input mechanical energy is stored during fault and utilized at fault clearance. → Enhanced Rotor speed stability of DFIG. → Reduced Reactive power requirement and rapid voltage recovery at fault clearance. → Improved post fault performance of DFIG at fault clearance. -- Abstract: Enhancement of fault ride-through (FRT) capability and subsequent improvement of rotor speed stability of wind farms equipped with doubly fed induction generator (DFIG) is the objective of this paper. The objective is achieved by employing a novel FRT scheme with suitable control strategy. The proposed FRT scheme, which is connected between the rotor circuit and dc link capacitor in parallel with Rotor Side Converter, consists of an uncontrolled rectifier, two sets of IGBT switches, a diode and an inductor. In this scheme, the input mechanical energy of the wind turbine during grid fault is stored and utilized at the moment of fault clearance, instead of being dissipated in the resistors of the crowbar circuit as in the existing FRT schemes. Consequently, torque balance between the electrical and mechanical quantities is achieved and hence the rotor speed deviation and electromagnetic torque fluctuations are reduced. This results in reduced reactive power requirement and rapid reestablishment of terminal voltage on fault clearance. Furthermore, the stored electromagnetic energy in the inductor is transferred into the dc link capacitor on fault clearance and hence the grid side converter is relieved from charging the dc link capacitor, which is very crucial at this moment, and this converter can be utilized to its full capacity for rapid restoration of terminal voltage and normal operation of DFIG. Extensive simulation study carried out employing PSCAD/EMTDC software vividly demonstrates the potential capabilities of the proposed scheme in enhancing the performance of

  17. Orthogonal Test Analysis on Conditions Affecting Electricity Generation Performance of an Enhanced Geothermal System at Yangbajing Geothermal Field

    Directory of Open Access Journals (Sweden)

    Yuchao Zeng

    2017-12-01

    Full Text Available The main conditions affecting electricity generation performance of an enhanced geothermal system (EGS include reservoir porosity, reservoir permeability, rock heat conductivity, water production rate and injection temperature. Presently there is lack of systematic research the relative importance of the five aforementioned conditions. The orthogonal test method is a statistical approach to analyze multi-factor and multi-level influence on system performance. In this work, based on the geological data at Yangbajing geothermal field, we analyzed the five conditions affecting the electricity generation performance of EGS, and ranked the relative importance of the five factors. The results show that the order of the relative importance of the conditions on electric power is water production rate > injection temperature > reservoir porosity > rock heat conductivity > reservoir permeability; the order of the relative importance of the conditions on reservoir impedance is reservoir permeability > injection temperature > water production rate > reservoir porosity > rock heat conductivity; the order of the relative importance of the conditions on pump power is water production rate > reservoir permeability > injection temperature > reservoir porosity > rock heat conductivity, and; the order of the relative importance of the conditions on energy efficiency is water production rate > reservoir permeability > reservoir porosity > injection temperature > rock heat conductivity. The construction of an EGS reservoir should be located at a formation with higher reservoir porosity or rock heat conductivity, while the determination of reservoir permeability, water production rate and injection temperature should be based on the comprehensive target.

  18. Enhancing performance of LCoS-SLM as adaptive optics by using computer-generated holograms modulation software

    Science.gov (United States)

    Tsai, Chun-Wei; Lyu, Bo-Han; Wang, Chen; Hung, Cheng-Chieh

    2017-05-01

    We have already developed multi-function and easy-to-use modulation software that was based on LabVIEW system. There are mainly four functions in this modulation software, such as computer generated holograms (CGH) generation, CGH reconstruction, image trimming, and special phase distribution. Based on the above development of CGH modulation software, we could enhance the performance of liquid crystal on silicon - spatial light modulator (LCoSSLM) as similar as the diffractive optical element (DOE) and use it on various adaptive optics (AO) applications. Through the development of special phase distribution, we are going to use the LCoS-SLM with CGH modulation software into AO technology, such as optical microscope system. When the LCOS-SLM panel is integrated in an optical microscope system, it could be placed on the illumination path or on the image forming path. However, LCOS-SLM provides a program-controllable liquid crystal array for optical microscope. It dynamically changes the amplitude or phase of light and gives the obvious advantage, "Flexibility", to the system

  19. Proportional-Resonant Control of Doubly-Fed Induction Generator Wind Turbines for Low-Voltage Ride-Through Enhancement

    Directory of Open Access Journals (Sweden)

    Zhan-Feng Song

    2012-11-01

    Full Text Available A novel control strategy is proposed in this paper for the rotor side converter (RSC of doubly-fed induction generator (DFIG-based wind power generation systems. It is supposed to enhance the low-voltage ride-through (LVRT capability of DFIGs during great-level grid voltage dips. The strategy consists of a proportional-resonant (PR controller and auxiliary PR controllers. The auxiliary controllers compensate the output voltage of the RSC in case of grid faults, thus limiting the rotor inrush current of DFIG and meeting the requirements of LVRT. Sequential-component decompositions of current are not required in the control system to improve the response of system. Since the resonant compensator is a double-side integrator, the auxiliary controllers can be simplified through coordinate transformation. The feasibility of the control strategy is validated by simulation on a 1.5 MW wind-turbine driven DFIG system. The impact of the RSC converter voltage rating on the LVRT capability of DFIG is investigated. Meanwhile, the influence of angular frequency detection and control parameters are also discussed. Compared with traditional vector control schemes based on PI current controllers, the presented control strategy effectively suppress rotor current and reduce oscillations of DFIG power and torque under grid faults.

  20. Gene expression, neurogenesis, and healing: psychosocial genomics of therapeutic hypnosis.

    Science.gov (United States)

    Rossi, Ernest L

    2003-01-01

    The historical lineage of therapeutic hypnosis in James Braid's "psychophysiology", Pierre Janet's "physiological modification", and Milton Erickson's "neuro-psycho-physiology" is extended to include current neuroscience research on activity-dependent gene expression, neurogenesis, and stem cells in memory, learning, behavior change, and healing. Three conditions that optimize gene expression and neurogenesis--novelty, environmental enrichment, and exercise--could integrate fundamentals of the theory, research, and practice of therapeutic hypnosis. Continuing research on immediate-early, activity-dependent, behavior state-related, and clock gene expression could enhance our understanding of how relaxation, sleep, dreaming, consciousness, arousal, stress and trauma are modulated by therapeutic hypnosis. It is speculated that therapeutic and post-hypnotic suggestion could be focused more precisely with the time parameters of gene expression and neurogenesis that range from minutes and hours for synthesizing new synapses to weeks and months for the generation and maturation of new, functioning neurons in the adult brain.

  1. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  2. Therapeutic Gardening

    OpenAIRE

    Turner, Phyllis; Fox, Laurie; Parkhurst, James A. (James Albert)

    2013-01-01

    Gardening can be therapeutic for anyone and has been used as therapy for those with physical, emotional and social disabilities, for children, and for those who are elderly. Through careful adaptations to the garden, the gardener and the plants, almost anyone can benefit from the activity of gardening

  3. Fabrication of A/R-TiO2 composite for enhanced photoelectrochemical performance: Solar hydrogen generation and dye degradation

    Science.gov (United States)

    Mahadik, Mahadeo A.; An, Gil Woo; David, Selvaraj; Choi, Sun Hee; Cho, Min; Jang, Jum Suk

    2017-12-01

    Anatase/rutile TiO2 nanorods composites were prepared by a facile hydrothermal method followed by dip coating method using titanium isopropoxide in acetic acid and ethanol solvent. The effects of the titanium isopropoxide precursor concentration, on the formation of dip coated anatase/rutile TiO2 nanorods composite were systematically explored. The growth of anatase on rutile TiO2 nanorods can be controlled by varying the titanium isopropoxide concentration. The morphological study reveals that anatase TiO2 nanograins formed on the surface of rutile TiO2 nanorod arrays through dip coating method. Photoelectrochemical analyses showed that the enhancement of the photocatalytic activities of the samples is affected by the anatase nanograins present on the rutile TiO2 nanorods, which can induce the separation of electrons and holes. To interpret the photoelectrochemical behaviors, the prepared photoelectrodes were applied in photoelectrochemical solar hydrogen generation and orange II dye degradation. The optimized photocurrent density of 1.8 mA cm-2 and the 625 μmol hydrogen generation was observed for 10 mM anatase/rutile TiO2 NRs composites. Additionally, 96% removal of the orange II dye was achieved within 5 h during oxidative degradation under solar light irradiation. One of the benefits of high specific surface area and the efficient photogenerated charge transport in the anatase/rutile TiO2 nanorod composite improves the photoelectrochemical hydrogen generation and orange dye degradation compared to the rutile TiO2. Thus, our strategy provides a promising, stable, and low cost alternative to existing photocatalysts and is expected to attract considerable attention for industrial applications.

  4. Real-World Use of 3rd Line Therapy for Multiple Myeloma in Austria: An Austrian Myeloma Registry (AMR Analysis of the Therapeutic Landscape and Clinical Outcomes prior to the Use of Next Generation Myeloma Therapeutics.

    Directory of Open Access Journals (Sweden)

    Ella Willenbacher

    Full Text Available Clinical trials demonstrate improving survival in patients with multiple myeloma (MM after treatment. However, it is unclear whether increased survival translates to a similar benefit in a real world setting.We analyzed the overall survival of 347 multiple myeloma patients in Austria by means of a national registry (AMR, focused on results from 3rd and later lines of therapy. This benchmark was chosen to define a baseline prior to the broad application of upcoming 2nd generation drugs (carfilzomib, pomalidomide.Projected 10 years survival for patients with MM in Austria is estimated to be 56% in patients diagnosed in between the years 2011-2014, 21% in patients with a diagnosis made between 2000-2005, and 39% in those with a diagnosis made between 2006-2010. For the same intervals a significant increase in the use of both bortezomib, lenalidomide and thalidomide-so called IMiDs (from 2005 onwards and their simultaneous use in combination therapies (from 2010 onwards could be shown. The use of autologous transplantation (ASCT remained more or less constant at ~ 35% of patients in the 1st line setting over the whole period, comparing well to international practice patterns, while the use of 2nd line ASCT increased from 5.5% to 18.7% of patients. Patients in 3rd or later line treatment (n = 105, showed that even in relapsed and refractory disease median survival was 27 months with a considerable proportion of long-term survivors (~20%.With the expected emergence of additional active anti-myeloma compounds, we aim to assess survival in patients with relapsed and refractory MM.

  5. Irradiation enhances the tumor tropism and therapeutic potential of tumor necrosis factor-related apoptosis-inducing ligand-secreting human umbilical cord blood-derived mesenchymal stem cells in glioma therapy.

    Science.gov (United States)

    Kim, Seong Muk; Oh, Ji Hyeon; Park, Soon A; Ryu, Chung Heon; Lim, Jung Yeon; Kim, Dal-Soo; Chang, Jong Wook; Oh, Wonil; Jeun, Sin-Soo

    2010-12-01

    Irradiation is a standard therapy for gliomas and many other cancers. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for cancer gene therapy. Here, we show that tumor irradiation enhances the tumor tropism of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and the therapeutic effect of TRAIL delivered by UCB-MSCs. The sequential treatment with irradiation followed by TRAIL-secreting UCB-MSCs (MSC-TRAIL) synergistically enhanced apoptosis in either TRAIL-sensitive or TRAIL-resistant glioma cells by upregulating the death receptor 5 and by inducing caspase activation. Migration assays showed greater MSC migration toward irradiated glioma cells and the tumor site in glioma-bearing mice compared with unirradiated tumors. Irradiated glioma cells had increased expression of interleukin-8 (IL-8), which leads to the upregulation of the IL-8 receptor on MSCs. This upregulation, which is involved in the migratory capacity of UCB-MSCs, was confirmed by siRNA inhibition and an antibody-neutralizing assay. In vivo survival experiments in orthotopic xenografted mice showed that MSC-based TRAIL gene delivery to irradiated tumors had greater therapeutic efficacy than a single treatment. These results suggest that clinically relevant tumor irradiation increases the therapeutic efficacy of MSC-TRAIL by increasing tropism of MSCs and TRAIL-induced apoptosis, which may be a more useful strategy for cancer gene therapy.

  6. Improving Vortex Generators to Enhance the Performance of Air-Cooled Condensers in a Geothermal Power Plant

    Energy Technology Data Exchange (ETDEWEB)

    Manohar S. Sohal

    2005-09-01

    Colburn j-factor) associated with deployment of the winglets with circular as well as oval tubes. In general, toe-in (common flow up) type winglets appear to have better performance than the toe-out (common flow down) type winglets. Comparisons of heat transfer and pressure drop results for the elliptical tube versus a circular tube with and without winglets are provided. During the course of their independent research, all of the researchers have established that about 10 to 30% enhancement in Colburn j-factor is expected. However, actual increase in heat transfer rate from a heat exchanger employing finned tubes with winglets may be smaller, perhaps on the order of 2 to 5%. It is also concluded that for any specific application, more full-size experimentation is needed to optimize the winglet design for a specific heat exchanger application. If in place of a circular tube, an oval tube can be economically used in a bundle, it is expected that the pressure drop across the tube bundle with the application of vortex generators (winglets) will be similar to that in a conventional circular tube bundle. It is hoped that the results of this research will demonstrate the benefits of applying vortex generators (winglets) on the fins to improve the heat transfer from the air-side of the tube bundle.

  7. Enhanced visible light generation in an active microcavity via third-harmonic conversion beyond the non-depletion approximation

    Science.gov (United States)

    Yu, Rong; Ding, Chunling; Wang, Jiangpeng; Zhang, Duo

    2017-12-01

    We explore the possibility of using an active doubly resonant microtoroid resonator to produce high-efficiency third-harmonic generation (THG) by exploiting optical third-order nonlinearity. In a microresonator, the active fundamental mode is coherently driven with a continuous-wave input laser at the telecommunication wavelength (1550 nm), and then, the visible THG signal (517 nm) is monitored via an individual bus waveguide. We thoroughly compare our results with those obtained from the conventional passive (i.e., loss) microtoroid resonator by a systematic analysis and detailed numerical simulations based on the Heisenberg-Langevin equations of motion. It is shown that the achievable THG spectrum features an ultralow critical input power. The THG power transmission can be significantly enhanced by about three orders of magnitude at a low input power of 0.1 μ W as compared with the obtained results in the passive microtoroid resonator THG system. Moreover, the THG efficiency can reach up to 100% with optical critical input power as low as a few microwatts. In turn, the analytical expressions of the critical intracavity intensity of the light in the microcavity, the critical input pump power, and the maximum THG efficiency are obtained. The enhanced THG power transmission and high conversion efficiency are attributed to a gain-induced loss compensation in the microtoroid resonator, reducing the effective loss felt by the resonator photons. With state-of-the art technologies in the field of solid-state resonators, including but not limited to microtoroids, the proposed THG scheme is experimentally realizable.

  8. [Nuclear transfer and therapeutic cloning].

    Science.gov (United States)

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  9. Enhancement of efficiencies for tandem green phosphorescent organic light-emitting devices with a p-type charge generation layer

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Byung Soo; Jeon, Young Pyo; Lee, Dae Uk; Kim, Tae Whan, E-mail: twk@hanayng.ac.kr

    2014-10-15

    The operating voltage of the tandem green phosphorescent organic light-emitting device with a 1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile layer was improved by 3% over that of the organic light-emitting device with a molybdenum trioxide layer. The maximum brightness of the tandem green phosphorescent organic light-emitting device at 21.9 V was 26,540 cd/m{sup 2}. The dominant peak of the electroluminescence spectra for the devices was related to the fac-tris(2-phenylpyridine) iridium emission. - Highlights: • Tandem OLEDs with CGL were fabricated to enhance their efficiency. • The operating voltage of the tandem OLED with a HAT-CN layer was improved by 3%. • The efficiency and brightness of the tandem OLED were 13.9 cd/A and 26,540 cd/m{sup 2}. • Efficiency of the OLED with a HAT-CN layer was lower than that with a MoO{sub 3} layer. - Abstract: Tandem green phosphorescent organic light-emitting devices with a 1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile or a molybdenum trioxide charge generation layer were fabricated to enhance their efficiency. Current density–voltage curves showed that the operating voltage of the tandem green phosphorescent organic light-emitting device with a 1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile layer was improved by 3% over that of the corresponding organic light-emitting device with a molybdenum trioxide layer. The efficiency and the brightness of the tandem green phosphorescent organic light-emitting device were 13.9 cd/A and 26,540 cd/m{sup 2}, respectively. The current efficiency of the tandem green phosphorescent organic light-emitting device with a 1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile layer was lower by 1.1 times compared to that of the corresponding organic light-emitting device with molybdenum trioxide layer due to the decreased charge generation and transport in the 1,4,5,8,9,11-hexaazatriphenylene-hexacarbonitrile layer resulting from triplet–triplet exciton annihilation.

  10. Enhanced electrical power generation using flame-oxidized stainless steel anode in microbial fuel cells and the anodic community structure.

    Science.gov (United States)

    Yamashita, Takahiro; Ishida, Mitsuyoshi; Asakawa, Shiho; Kanamori, Hiroyuki; Sasaki, Harumi; Ogino, Akifumi; Katayose, Yuichi; Hatta, Tamao; Yokoyama, Hiroshi

    2016-01-01

    Carbon-based materials are commonly used as anodes in microbial fuel cells (MFCs), whereas metal and metal-oxide-based materials are not used frequently because of low electrical output. Stainless steel is a low-cost material with high conductivity and physical strength. In this study, we investigated the power generation using flame-oxidized (FO) stainless steel anodes (SSAs) in single-chambered air-cathode MFCs. The FO-SSA performance was compared to the performance of untreated SSA and carbon cloth anode (CCA), a common carbonaceous electrode. The difference in the anodic community structures was analyzed using high-throughput sequencing of the V4 region in 16S rRNA gene. Flame oxidation of SSA produced raised node-like sites, predominantly consisting of hematite (Fe2O3), on the surface, as determined by X-ray diffraction spectroscopy. The flame oxidation enhanced the maximum power density (1063 mW/m(2)) in MFCs, which was 184 and 24 % higher than those for untreated SSA and CCA, respectively. The FO-SSA exhibited 8.75 and 2.71 times higher current production than SSA and CCA, respectively, under potentiostatic testing conditions. Bacteria from the genus Geobacter were detected at a remarkably higher frequency in the biofilm formed on the FO-SSA (8.8-9.2 %) than in the biofilms formed on the SSA and CCA (0.7-1.4 %). Bacterial species closely related to Geobacter metallireducens (>99 % identity in the gene sequence) were predominant (93-96 %) among the genus Geobacter in the FO-SSA biofilm, whereas bacteria with a 100 % identity to G. anodireducens were abundant (>55 %) in the SSA and CCA biofilms. This is the first demonstration of power generation using an FO-SSA in MFCs. Flame oxidation of the SSA enhances electricity production in MFCs, which is higher than that with the common carbonaceous electrode, CCA. The FO-SSA is not only inexpensive but also can be prepared using a simple method. To our knowledge, this study reveals, for the first time, that

  11. Membrane-Based Osmotic Heat Engine with Organic Solvent for Enhanced Power Generation from Low-Grade Heat

    Energy Technology Data Exchange (ETDEWEB)

    Shaulsky, E; Boo, C; Lin, SH; Elimelech, M

    2015-05-05

    We present a hybrid osmotic heat engine (OHE) system that uses draw solutions with an organic solvent for enhanced thermal separation efficiency. The hybrid OHE system produces sustainable energy by combining pressure-retarded osmosis (PRO) as a power generation stage and membrane distillation (MD) utilizing low-grade heat as a separation stage. While previous OHE systems employed aqueous electrolyte draw solutions, using methanol as a solvent is advantageous because methanol is highly volatile and has a lower heat capacity and enthalpy of vaporization than water. Hence, the thermal separation efficiency of a draw solution with methanol would be higher than that of an aqueous draw solution. In this study, we evaluated the performance of LiCl-methanol as a potential draw solution for a PRO-MD hybrid OHE system. The membrane transport properties as well as performance with LiCl methanol draw solution were evaluated using thin-film composite (TFC) PRO membranes and compared to the results obtained with a LiCl water draw solution. Experimental PRO methanol flux and maximum projected power density of 47.1 L m(-2) h(-1) and 72.1 W m(-2), respectively, were achieved with a 3 M LiCl-methanol draw solution. The overall efficiency of the hybrid OHE system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages under conditions with and without heat recovery. The modeling results demonstrate higher ORE energy efficiency with the LiCl methanol draw solution compared to that with the LiCl water draw solution under practical operating conditions (i.e., heat recovery <90%). We discuss the implications of the results for converting low-grade heat to power.

  12. Gas Production Generated from Crude Oil Biodegradation: Preliminary Study on its Aplication in Microbial Enhanced Oil Recovery (MEOR

    Directory of Open Access Journals (Sweden)

    Astri Nugroho

    2009-11-01

    Full Text Available Gas Production Generated from Crude Oil Biodegradation: Preliminary Study on its Aplication in MicrobialEnhanced Oil Recovery (MEOR. The objective of this study is to observe the capacity of gas production generatedfrom crude oil degradation by the isolated bacteria. The gas in the MEOR could increase pressure in the reservoir,decrease oil viscosity, increase oil permeability-due to the increase of the porosity and viscosity, and also increase oilvolume due to the amount of dissolved gas. A research on gas analysis of oil degradation by 6 isolated bacteria has beenconducted. The bacteria isolates including Bacillus badius (A, Bacillus circulans (B, Bacillus coagulans (C, Bacillusfirmus (D, Pasteurella avium (E and Streptobacillus moniliformis (F. The trial on gas production, gas analysis and oildegradation analysis, was carried out by using SMSS medium. The test of gas production was done by usingmicrorespirometer at 40°C. The result shows that B, C, D, E produce more gas than A and F. Gas of CO2, O2, CO, N2,CH4, and H2 were analyzed by using GC. The results show that only three gases were detected by GC i.e. CO2, N2, andO2. The concentration of CO2 and N2 gas increased while the concentration of O2 decreased over an 8th day ofobservation. CO2 gas producted by mix culture was higher than by the pure culture. On the 8th day of incubation, theproduction of CO2 gas by mix culture was 4,0452% while pure culture C and D only produced 2,4543% and 2,8729%.The mix culture increase simple hydrocarbon by 12.03% and the formation of a complex hydrocarbon by 3.07%. Themix culture (C-D generated the highest concentration of CO2 gas as well as a synergistic concortium that has ability todegrade crude oil.

  13. Membrane-based osmotic heat engine with organic solvent for enhanced power generation from low-grade heat.

    Science.gov (United States)

    Shaulsky, Evyatar; Boo, Chanhee; Lin, Shihong; Elimelech, Menachem

    2015-05-05

    We present a hybrid osmotic heat engine (OHE) system that uses draw solutions with an organic solvent for enhanced thermal separation efficiency. The hybrid OHE system produces sustainable energy by combining pressure-retarded osmosis (PRO) as a power generation stage and membrane distillation (MD) utilizing low-grade heat as a separation stage. While previous OHE systems employed aqueous electrolyte draw solutions, using methanol as a solvent is advantageous because methanol is highly volatile and has a lower heat capacity and enthalpy of vaporization than water. Hence, the thermal separation efficiency of a draw solution with methanol would be higher than that of an aqueous draw solution. In this study, we evaluated the performance of LiCl-methanol as a potential draw solution for a PRO-MD hybrid OHE system. The membrane transport properties as well as performance with LiCl-methanol draw solution were evaluated using thin-film composite (TFC) PRO membranes and compared to the results obtained with a LiCl-water draw solution. Experimental PRO methanol flux and maximum projected power density of 47.1 L m(-2) h(-1) and 72.1 W m(-2), respectively, were achieved with a 3 M LiCl-methanol draw solution. The overall efficiency of the hybrid OHE system was modeled by coupling the mass and energy flows between the thermal separation (MD) and power generation (PRO) stages under conditions with and without heat recovery. The modeling results demonstrate higher OHE energy efficiency with the LiCl-methanol draw solution compared to that with the LiCl-water draw solution under practical operating conditions (i.e., heat recovery<90%). We discuss the implications of the results for converting low-grade heat to power.

  14. Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

    Directory of Open Access Journals (Sweden)

    Owain Thomas

    Full Text Available Low molecular weight heparins (LMWH's are used to prevent and treat thrombosis. Tests for monitoring LMWH's include anti-factor Xa (anti-FXa, activated partial thromboplastin time (aPTT and thrombin generation. Anti-FXa is the current gold standard despite LMWH's varying affinities for FXa and thrombin.To examine the effects of two different LMWH's on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests' concordance.Enoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR and Hemochron Jr (HCJ and an optical plasma method using two different reagents (ActinFSL and PTT-Automat. Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.Methods' mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11 and 69s (SD 14 for enoxaparin and between 101s (SD 21 and 140s (SD 28 for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62-0.87, whereas the other aPTT methods had similar correlation coefficients (Rs0.80-0.92.aPTT displays a linear dose-response to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa's present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH's.

  15. Development of 90Sr/90Y Generator Systems Based on SLM Techniques for Radiolabelling of Therapeutic Biomolecules with 90Y. Chapter 14

    International Nuclear Information System (INIS)

    Thu, N.T.; Van Dong, D.; Van Cuong, B.; Van Khoa, C.; Cam Hoa, V.T.

    2015-01-01

    Yttrium-90 is one of the most useful radionuclides for radioimmunotherapeutic applications, especially for labelling peptides and antibodies. Studies were carried out to develop a 90 Sr/ 90 Y generator system based on the SLM technique. Two stages of 90 Sr/ 90 Y generator systems were developed at different activity levels of 5, 20, 50 and 100 mCi and operated with semiautomation in sequential mode. In the first stage of the system, PC88A based SLM was used, which transported 90 Y from a nitric acid medium containing 0.01–4M HNO 3 . In the second stage, the 90 Y from the first stage was transferred to the first compartment of the second stage using carbamoylmethyl phosphine oxide (CMPO) based SLM where 1M acetic acid was used as the receiving phase for 90 Y. Quality control was carried out for the products of 90 Y using EPC with paper chromatography and Tec control chromatography. Peptides and antibodies were labelled using the 90 Y product obtained from the generator developed in house. (author)

  16. Enhanced hydroxyl radical generation in the combined ozonation and electrolysis process using carbon nanotubes containing gas diffusion cathode.

    Science.gov (United States)

    Wu, Donghai; Lu, Guanghua; Zhang, Ran; Lin, Qiuhong; Yan, Zhenhua; Liu, Jianchao; Li, Yi

    2015-10-01

    Combination of ozone together with electrolysis (ozone-electrolysis) is a promising wastewater treatment technology. This work investigated the potential use of carbon nanotube (CNT)-based gas diffusion cathode (GDC) for ozone-electrolysis process employing hydroxyl radicals (·OH) production as an indicator. Compared with conventional active carbon (AC)-polytetrafluoroethylene (PTFE) and carbon black (CB)-PTFE cathodes, the production of ·OH in the coupled process was improved using CNTs-PTFE GDC. Appropriate addition of acetylene black (AB) and pore-forming agent Na2SO4 could enhance the efficiency of CNTs-PTFE GDC. The optimum GDC composition was obtained by response surface methodology (RSM) analysis and was determined as CNTs 31.2 wt%, PTFE 60.6 wt%, AB 3.5 wt%, and Na2SO4 4.7 wt%. Moreover, the optimized CNT-based GDC exhibited much more effective than traditional Ti and graphite cathodes in Acid Orange 7 (AO7) mineralization and possessed the desirable stability without performance decay after ten times reaction. The comparison tests revealed that peroxone reaction was the main pathway of ·OH production in the present system, and cathodic reduction of ozone could significantly promote ·OH generation. These results suggested that application of CNT-based GDC offers considerable advantages in ozone-electrolysis of organic wastewater.

  17. (Gold core)/(titania shell) nanostructures for plasmon-enhanced photon harvesting and generation of reactive oxygen species

    KAUST Repository

    Fang, Caihong

    2014-01-01

    Integration of gold and titania in a nanoscale core/shell architecture can offer large active metal/semiconductor interfacial areas and avoid aggregation and reshaping of the metal nanocrystal core. Such hybrid nanostructures are very useful for studying plasmon-enhanced/enabled processes and have great potential in light-harvesting applications. Herein we report on a facile route to (gold nanocrystal core)/(titania shell) nanostructures with their plasmon band synthetically variable from ∼700 nm to over 1000 nm. The coating method has also been applied to other mono- and bi-metallic Pd, Pt, Au nanocrystals. The gold/titania nanostructures have been employed as the scattering layer in dye-sensitized solar cells, with the resultant cells exhibiting a 13.3% increase in the power conversion efficiency and a 75% decrease in the scattering-layer thickness. Moreover, under resonant excitation, the gold/titania nanostructures can efficiently utilize low-energy photons to generate reactive oxygen species, including singlet oxygen and hydroxyl radicals.

  18. Antibody-enhanced dengue disease generates a marked CNS inflammatory response in the black-tufted marmoset Callithrix penicillata.

    Science.gov (United States)

    Vasconcelos, Barbara Cristina Baldez; Vieira, Juliana Almeida; Silva, Geane Oliveira; Fernandes, Taiany Nogueira; Rocha, Luciano Chaves; Viana, André Pereira; Serique, Cássio Diego Sá; Filho, Carlos Santos; Bringel, Raissa Aires Ribeiro; Teixeira, Francisco Fernando Dacier Lobato; Ferreira, Milene Silveira; Casseb, Samir Mansour Moraes; Carvalho, Valéria Lima; de Melo, Karla Fabiane Lopes; de Castro, Paulo Henrique Gomes; Araújo, Sanderson Corrêa; Diniz, José Antonio Picanço; Demachki, Samia; Anaissi, Ana Karyssa Mendes; Sosthenes, Marcia Consentino Kronka; Vasconcelos, Pedro Fernando da Costa; Anthony, Daniel Clive; Diniz, Cristovam Wanderley Picanço; Diniz, Daniel Guerreiro

    2016-02-01

    Severe dengue disease is often associated with long-term neurological impairments, but it is unclear what mechanisms are associated with neurological sequelae. Previously, we demonstrated antibody-enhanced dengue disease (ADE) dengue in an immunocompetent mouse model with a dengue virus 2 (DENV2) antibody injection followed by DENV3 virus infection. Here we migrated this ADE model to Callithrix penicillata. To mimic human multiple infections of endemic zones where abundant vectors and multiple serotypes co-exist, three animals received weekly subcutaneous injections of DENV3 (genotype III)-infected supernatant of C6/36 cell cultures, followed 24 h later by anti-DENV2 antibody for 12 weeks. There were six control animals, two of which received weekly anti-DENV2 antibodies, and four further animals received no injections. After multiple infections, brain, liver, and spleen samples were collected and tissue was immunolabeled for DENV3 antigens, ionized calcium binding adapter molecule 1, Ki-67, TNFα. There were marked morphological changes in the microglial population of ADE monkeys characterized by more highly ramified microglial processes, higher numbers of trees and larger surface areas. These changes were associated with intense TNFα-positive immunolabeling. It is unclear why ADE should generate such microglial activation given that IgG does not cross the blood-brain barrier, but this study reveals that in ADE dengue therapy targeting the CNS host response is likely to be important. © 2015 Japanese Society of Neuropathology.

  19. Brain-generated estradiol drives long-term optimization of auditory coding to enhance the discrimination of communication signals.

    Science.gov (United States)

    Tremere, Liisa A; Pinaud, Raphael

    2011-03-02

    Auditory processing and hearing-related pathologies are heavily influenced by steroid hormones in a variety of vertebrate species, including humans. The hormone estradiol has been recently shown to directly modulate the gain of central auditory neurons, in real time, by controlling the strength of inhibitory transmission via a nongenomic mechanism. The functional relevance of this modulation, however, remains unknown. Here we show that estradiol generated in the songbird homolog of the mammalian auditory association cortex, rapidly enhances the effectiveness of the neural coding of complex, learned acoustic signals in awake zebra finches. Specifically, estradiol increases mutual information rates, coding efficiency, and the neural discrimination of songs. These effects are mediated by estradiol's modulation of both the rate and temporal coding of auditory signals. Interference with the local action or production of estradiol in the auditory forebrain of freely behaving animals disrupts behavioral responses to songs, but not to other behaviorally relevant communication signals. Our findings directly show that estradiol is a key regulator of auditory function in the adult vertebrate brain.

  20. Bifunctional Modification of Graphitic Carbon Nitride with MgFe2O4 for Enhanced Photocatalytic Hydrogen Generation.

    Science.gov (United States)

    Chen, Jie; Zhao, Daming; Diao, Zhidan; Wang, Miao; Guo, Liejin; Shen, Shaohua

    2015-08-26

    To gain high photocatalytic activity for hydrogen evolution, both charge separation efficiency and surface reaction kinetics must be improved, and together would be even better. In this study, the visible light photocatalytic hydrogen production activity of graphitic carbon nitride (g-C3N4) was greatly enhanced with MgFe2O4 modification. It was demonstrated that MgFe2O4 could not only extract photoinduced holes from g-C3N4, leading to efficient charge carrier separation at the g-C3N4/MgFe2O4 interface, but also act as an oxidative catalyst accelerating the oxidation reaction kinetics at g-C3N4 surface. This dual function of MgFe2O4 thus contributed to the great improvement (up to three-fold) in photocatalytic activity for hydrogen generation over g-C3N4/MgFe2O4 as compared to pristine g-C3N4, after loading Pt by photoreduction method. It was revealed that in the Pt/g-C3N4/MgFe2O4 system, the photoinduced electrons and holes were entrapped by Pt and MgFe2O4, respectively, giving rise to the promoted charge separation; moreover, as evidenced by electrochemical analysis, the electrocatalysis effect of MgFe2O4 benefited the oxidation reaction at g-C3N4 surface.

  1. Surface Area Expansion of Electrodes with Grass-like Nanostructures to Enhance Electricity Generation in Microbial Fuel Cells

    DEFF Research Database (Denmark)

    Al Atraktchi, Fatima Al-Zahraa; Zhang, Yifeng; Noori, Jafar Safaa

    2012-01-01

    of plain silicium showed a maximum power density of 86.0 mW/m2. Further expanding the surface area of carbon paper electrodes with gold nanoparticles resulted in a maximum stable power density of 346.9 mW/m2 which is 2.9 times higher than that achieved with conventional carbon paper. These results show......Microbial fuel cells (MFCs) have applications possibilities for wastewater treatment, biotransformation, and biosensor, but the development of highly efficient electrode materials is critical for enhancing the power generation. Two types of electrodes modified with nanoparticles or grass......-like nanostructure (termed nanograss) were used. A two-chamber MFC with plain silicium electrodes achieved a maximum power density of 0.002 mW/m2, while an electrode with nanograss of titanium and gold deposited on one side gave a maximum power density of 2.5 mW/m2. Deposition of titanium and gold on both sides...

  2. The small-molecule TNF-alpha modulator, UTL-5g, reduces side effects induced by cisplatin and enhances the therapeutic effect of cisplatin in vivo.

    Science.gov (United States)

    Shaw, JiaJiu; Chen, Ben; Huang, Wen-Hsin; Lee, An-Rong; Media, Joseph; Valeriote, Frederick A

    2011-01-01

    We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by cisplatin treatment. The levels of both aspartate transaminase (AST) and alanine transaminase (ALT) in these animals were also reduced by UTL-5g. Pretreatment of UTL-5g did not significantly affect the number of white blood cells (WBC) under current experimental conditions, yet it markedly increased blood platelet counts by more than threefold. Therapeutic assessment in SCID mice inoculated with human HCT-15 tumor cells showed that UTL-5g did not attenuate the anti-tumor effect of cisplatin but increased the therapeutic efficacy of cisplatin. The LD50 of UTL-5g was determined to be > 2,000 mg/kg by an acute toxicity study. In summary, our studies showed that 1) UTL-5g significantly reduces nephrotoxicity and hepatotoxicity induced by cisplatin in mice, presumably by lowering the levels of TNF-alpha, 2) UTL-5g markedly increased blood platelet counts in mice and 3) UTL-5g treatment increased the therapeutic efficacy of cisplatin against HCT-15 cells inoculated in SCID mice.

  3. Stochastic Prediction of Wind Generating Resources Using the Enhanced Ensemble Model for Jeju Island’s Wind Farms in South Korea

    OpenAIRE

    Deockho Kim; Jin Hur

    2017-01-01

    Due to the intermittency of wind power generation, it is very hard to manage its system operation and planning. In order to incorporate higher wind power penetrations into power systems that maintain secure and economic power system operation, an accurate and efficient estimation of wind power outputs is needed. In this paper, we propose the stochastic prediction of wind generating resources using an enhanced ensemble model for Jeju Island’s wind farms in South Korea. When selecting the poten...

  4. Radargrammetric DSM generation in mountainous areas through adaptive-window least squares matching constrained by enhanced epipolar geometry

    Science.gov (United States)

    Dong, Yuting; Zhang, Lu; Balz, Timo; Luo, Heng; Liao, Mingsheng

    2018-03-01

    Radargrammetry is a powerful tool to construct digital surface models (DSMs) especially in heavily vegetated and mountainous areas where SAR interferometry (InSAR) technology suffers from decorrelation problems. In radargrammetry, the most challenging step is to produce an accurate disparity map through massive image matching, from which terrain height information can be derived using a rigorous sensor orientation model. However, precise stereoscopic SAR (StereoSAR) image matching is a very difficult task in mountainous areas due to the presence of speckle noise and dissimilar geometric/radiometric distortions. In this article, an adaptive-window least squares matching (AW-LSM) approach with an enhanced epipolar geometric constraint is proposed to robustly identify homologous points after compensation for radiometric discrepancies and geometric distortions. The matching procedure consists of two stages. In the first stage, the right image is re-projected into the left image space to generate epipolar images using rigorous imaging geometries enhanced with elevation information extracted from the prior DEM data e.g. SRTM DEM instead of the mean height of the mapped area. Consequently, the dissimilarities in geometric distortions between the left and right images are largely reduced, and the residual disparity corresponds to the height difference between true ground surface and the prior DEM. In the second stage, massive per-pixel matching between StereoSAR epipolar images identifies the residual disparity. To ensure the reliability and accuracy of the matching results, we develop an iterative matching scheme in which the classic cross correlation matching is used to obtain initial results, followed by the least squares matching (LSM) to refine the matching results. An adaptively resizing search window strategy is adopted during the dense matching step to help find right matching points. The feasibility and effectiveness of the proposed approach is demonstrated using

  5. Enhancement of force generated by individual myosin heads in skinned rabbit psoas muscle fibers at low ionic strength.

    Science.gov (United States)

    Sugi, Haruo; Abe, Takahiro; Kobayashi, Takakazu; Chaen, Shigeru; Ohnuki, Yoshiki; Saeki, Yasutake; Sugiura, Seiryo

    2013-01-01

    Although evidence has been presented that, at low ionic strength, myosin heads in relaxed skeletal muscle fibers form linkages with actin filaments, the effect of low ionic strength on contraction characteristics of Ca(2+)-activated muscle fibers has not yet been studied in detail. To give information about the mechanism of muscle contraction, we have examined the effect of low ionic strength on the mechanical properties and the contraction characteristics of skinned rabbit psoas muscle fibers in both relaxed and maximally Ca(2+)-activated states. By progressively decreasing KCl concentration from 125 mM to 0 mM (corresponding to a decrease in ionic strength μ from 170 mM to 50 mM), relaxed fibers showed changes in mechanical response to sinusoidal length changes and ramp stretches, which are consistent with the idea of actin-myosin linkage formation at low ionic strength. In maximally Ca(2+)-activated fibers, on the other hand, the maximum isometric force increased about twofold by reducing KCl concentration from 125 to 0 mM. Unexpectedly, determination of the force-velocity curves indicated that, the maximum unloaded shortening velocity Vmax, remained unchanged at low ionic strength. This finding indicates that the actin-myosin linkages, which has been detected in relaxed fibers at low ionic strength, are broken quickly on Ca(2+) activation, so that the linkages in relaxed fibers no longer provide any internal resistance against fiber shortening. The force-velocity curves, obtained at various levels of steady Ca(2+)-activated isometric force, were found to be identical if they are normalized with respect to the maximum isometric force. The MgATPase activity of muscle fibers during isometric force generation was found not to change appreciably at low ionic strength despite the two-fold increase in Ca(2+)-activated isometric force. These results can be explained in terms of enhancement of force generated by individual myosin heads, but not by any changes in

  6. Enhancement of force generated by individual myosin heads in skinned rabbit psoas muscle fibers at low ionic strength.

    Directory of Open Access Journals (Sweden)

    Haruo Sugi

    Full Text Available Although evidence has been presented that, at low ionic strength, myosin heads in relaxed skeletal muscle fibers form linkages with actin filaments, the effect of low ionic strength on contraction characteristics of Ca(2+-activated muscle fibers has not yet been studied in detail. To give information about the mechanism of muscle contraction, we have examined the effect of low ionic strength on the mechanical properties and the contraction characteristics of skinned rabbit psoas muscle fibers in both relaxed and maximally Ca(2+-activated states. By progressively decreasing KCl concentration from 125 mM to 0 mM (corresponding to a decrease in ionic strength μ from 170 mM to 50 mM, relaxed fibers showed changes in mechanical response to sinusoidal length changes and ramp stretches, which are consistent with the idea of actin-myosin linkage formation at low ionic strength. In maximally Ca(2+-activated fibers, on the other hand, the maximum isometric force increased about twofold by reducing KCl concentration from 125 to 0 mM. Unexpectedly, determination of the force-velocity curves indicated that, the maximum unloaded shortening velocity Vmax, remained unchanged at low ionic strength. This finding indicates that the actin-myosin linkages, which has been detected in relaxed fibers at low ionic strength, are broken quickly on Ca(2+ activation, so that the linkages in relaxed fibers no longer provide any internal resistance against fiber shortening. The force-velocity curves, obtained at various levels of steady Ca(2+-activated isometric force, were found to be identical if they are normalized with respect to the maximum isometric force. The MgATPase activity of muscle fibers during isometric force generation was found not to change appreciably at low ionic strength despite the two-fold increase in Ca(2+-activated isometric force. These results can be explained in terms of enhancement of force generated by individual myosin heads, but not by any

  7. Using a fourth-generation cavity enhanced spectrometer to isotopically investigate nitrous oxide emissions from biochar amended soils.

    Science.gov (United States)

    Grabenhofer, Jutta; Dercon, Gerd; Heiling, Maria; Mayr, Leo; Resch, Christian; Hood-Nowotny, Rebecca

    2016-04-01

    Research into the impacts of biochar on key processes in the nitrogen cycle is important to understand biochar's potential role in sustainable agriculture. There is conflicting evidence that biochar can reduce globally significant greenhouse gas emissions, especially N2O, one of the most important greenhouse gases in agriculture. However to date there is little information on the mechanisms involved. The source of N2O is dependent on the physical, chemical and biological status of the soil at a microbial scale and we need to understand how biochar influences it. Using the 15N2O gas flux method combined with gross rate measurements of nitrification and modelling, it should be possible to determine the parameters which drive N2O emissions and to evaluate the specific impact of biochar on these important N loss processes. To date the scope of isotopic studies on nitrous oxide emissions have been limited, due in part to technical and infrastructural access to complex and expensive mass spectrometry. With the advent of laser based systems these logistical and analytical constraints could be overcome and allow for a deeper and geographically more representative, understanding and assessment of the role of biochar in reducing nitrous oxide emissions from soil. In this study we have developed a simple method for investigated nitrous oxide emissions from soils amended with biochar, employing state of the art stable isotope techniques, using a fourth-generation cavity enhanced absorption technique a variant of conventional Cavity Ringdown Spectroscopy (CRDS) for measurement of isotopes of nitrous oxide. We will present methodologies used and results from these experiments, techniques that should path the way for a greater global understand nitrous oxide emissions from soils.

  8. Enhanced Electricity Generation by Using Cheese Whey Wastewater in A Single-chamber Membrane Less Microbial Fuel Cell

    Directory of Open Access Journals (Sweden)

    Hassan A.Z. Al-Fetlawi

    2018-02-01

    Full Text Available Microbial fuel cells (MFCs are biochemical-catalyzed systems in which electricity is produced by oxidizing  biodegradable organic matters in presence of  bacteria. Many places suffer from lack of electricity infrastructure or even existence" ,"but in the same area  there is wastewater that can be used to generate clean energy". "A batch system single chamber  and  membrane-less microbial fuel cell is designed with wastewater as inoculum and fuel in the same time(before adding cheese whey at pH =7±0.4 and an operating temperature of 30 0C ". Wastewater samples are collected from the Al-Delmaj marsh site at an initial chemical oxygen demand concentration of 862 mg/l and pH of 7.8 (reduced to 7±0.4 in all experiments by adding HCL acid. Rectangular sheets of graphite and smooth surface carbon fiber of 42 cm2 surface area used for anode and cathode electrodes. The obtained results indicated that the cell performance for the cell using graphite for anode and cathode electrodes is better than that using the carbon fiber of smooth surface .the obtained  open circuit voltage and power per unit surface area (for graphite  were" 190 mV and 5.95 mW/m2 respectively ."Cheese whey as substrate was used to enhance the performance of cell to  439 mV OCV and 121.9mW/m2  maximum power density" .

  9. Electrochemotherapy with cisplatin enhances local control after surgical ablation of fibrosarcoma in cats: an approach to improve the therapeutic index of highly toxic chemotherapy drugs

    Directory of Open Access Journals (Sweden)

    Cardelli Pierluigi

    2011-09-01

    Full Text Available Abstract Background Cancer is one of the most difficult current health challenges, being responsible for millions of deaths yearly. Systemic chemotherapy is the most common therapeutic approach, and the prevailing orientation calls for the administration of the maximum tolerated dose; however, considerable limitations exist including toxicities to healthy tissues and low achievable drug concentrations at tumor sites. Electrochemotherapy (ECT is a tumor treatment that combines the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses. In this article we evaluate the capability of ECT to allow the use of cisplatin despite its high toxicity in a spontaneous feline model of soft tissue sarcoma. Methods A cohort of sixty-four cats with incompletely excised sarcomas were treated with cisplatin-based adjuvant ECT and monitored for side effects. Their response was compared to that of fourteen cats treated with surgery alone. Results The toxicities were minimal and mostly treated symptomatically. ECT resulted in increased local control (median not reached at the time of writing with a mean time to recurrence of 666 days versus 180 of controls. Conclusions We conclude that ECT is a safe and efficacious therapy for solid tumors; its use may be considered as part of strategies for the reintroduction of drugs with a narrow therapeutic index in the clinical protocols.

  10. Fabrication, Physicochemical Characterization, and Performance Evaluation of Biodegradable Polymeric Microneedle Patch System for Enhanced Transcutaneous Flux of High Molecular Weight Therapeutics.

    Science.gov (United States)

    Shah, Viral; Choudhury, Bijaya Krushna

    2017-11-01

    A revolutionary paradigm shift is being observed currently, towards the use of therapeutic biologics for disease management. The present research was focused on designing an efficient dosage form for transdermal delivery of α-choriogonadotropin (high molecular weight biologic), through biodegradable polymeric microneedles. Polyvinylpyrrolidone-based biodegradable microneedle arrays loaded with high molecular weight polypeptide, α-choriogonadotropin, were fabricated for its systemic delivery via transdermal route. Varied process and formulation parameters were optimized for fabricating microneedle array, which in turn was expected to temporally rupture the stratum corneum layer of the skin, acting as a major barrier to drug delivery through transdermal route. The developed polymeric microneedles were optimized on the basis of quality attributes like mechanical strength, axial strength, insertion ratio, and insertion force analysis. The optimized polymeric microneedle arrays were characterized for in vitro drug release studies, ex vivo drug permeation studies, skin resealing studies, and in vivo pharmacokinetic studies. Results depicted that fabricated polymeric microneedle arrays with mechanical strength of above 5 N and good insertion ratio exhibited similar systemic bioavailability of α-choriogonadotropin in comparison to marketed subcutaneous injection formulation of α-choriogonadotropin. Thus, it was ultimately concluded that the designed drug delivery system can serve as an efficient tool for systemic delivery of therapeutic biologics, with an added benefit of overcoming the limitations of parenteral delivery, achieving better patient acceptability and compliance.

  11. Acotiamide Hydrochloride, a Therapeutic Agent for Functional Dyspepsia, Enhances Acetylcholine-induced Contraction via Inhibition of Acetylcholinesterase Activity in Circular Muscle Strips of Guinea Pig Stomach.

    Science.gov (United States)

    Ito, K; Kawachi, M; Matsunaga, Y; Hori, Y; Ozaki, T; Nagahama, K; Hirayama, M; Kawabata, Y; Shiraishi, Y; Takei, M; Tanaka, T

    2016-04-01

    Acotiamide is a first-in-class prokinetic drug approved in Japan for the treatment of functional dyspepsia. Given that acotiamide enhances gastric motility in conscious dogs and rats, we assessed the in vitro effects of this drug on the contraction of guinea pig stomach strips and on acetylcholinesterase (AChE) activity in stomach homogenate following fundus removal. We also investigated the serotonin 5-HT4 receptor agonist mosapride, dopamine D2 receptor and AChE inhibitor itopride, and representative AChE inhibitor neostigmine. Acotiamide (0.3 and 1 μM) and itopride (1 and 3 μM) significantly enhanced the contraction of gastric body strips induced by electrical field stimulation (EFS), but mosapride (1 and 10 μM) did not. Acotiamide and itopride significantly enhanced the contraction of gastric body and antrum strips induced by acetylcholine (ACh), but not that induced by carbachol (CCh). Neostigmine also significantly enhanced the contraction of gastric body strips induced by ACh, but not that by CCh. In contrast, mosapride failed to enhance contractions induced by either ACh or CCh in gastric antrum strips. Acotiamide exerted mixed inhibition of AChE, and the percentage inhibition of acotiamide (100 μM) against AChE activity was markedly reduced after the reaction mixture was dialyzed. In contrast, itopride exerted noncompetitive inhibition on AChE activity. These results indicate that acotiamide enhances ACh-dependent contraction in gastric strips of guinea pigs via the inhibition of AChE activity, and that it exerts mixed and reversible inhibition of AChE derived from guinea pig stomach. © Georg Thieme Verlag KG Stuttgart · New York.

  12. A solar PV augmented hybrid scheme for enhanced wind power generation through improved control strategy for grid connected doubly fed induction generator

    Directory of Open Access Journals (Sweden)

    Adikanda Parida

    2016-12-01

    Full Text Available In this paper, a wind power generation scheme using a grid connected doubly fed induction generator (DFIG augmented with solar PV has been proposed. A reactive power-based rotor speed and position estimation technique with reduced machine parameter sensitivity is also proposed to improve the performance of the DFIG controller. The estimation algorithm is based on model reference adaptive system (MRAS, which uses the air gap reactive power as the adjustable variable. The overall generation reliability of the wind energy conversion system can be considerably improved as both solar and wind energy can supplement each other during lean periods of either of the sources. The rotor-side DC-link voltage and active power generation at the stator terminals of the DFIG are maintained constant with minimum storage battery capacity using single converter arrangement without grid-side converter (GSC. The proposed scheme has been simulated and experimentally validated with a practical 2.5 kW DFIG using dSPACE CP1104 module which produced satisfactory results.

  13. Transplantation of storm-generated coral fragments to enhance Caribbean coral reefs: A successful method but not a solution

    Directory of Open Access Journals (Sweden)

    Virginia H. Garrison

    2012-03-01

    Full Text Available In response to dramatic losses of reef-building corals and ongoing lack of recovery, a small-scale coral transplant project was initiated in the Caribbean (U.S. Virgin Islands in 1999 and was followed for 12 years. The primary objectives were to (1 identify a source of coral colonies for transplantation that would not result in damage to reefs, (2 test the feasibility of transplanting storm-generated coral fragments, and (3 develop a simple, inexpensive method for transplanting fragments that could be conducted by the local community. The ultimate goal was to enhance abundance of threatened reef-building species on local reefs. Storm-produced coral fragments of two threatened reef-building species [Acropora palmata and A. cervicornis (Acroporidae] and another fast-growing species [Porites porites (Poritidae] were collected from environments hostile to coral fragment survival and transplanted to degraded reefs. Inert nylon cable ties were used to attach transplanted coral fragments to dead coral substrate. Survival of 75 reference colonies and 60 transplants was assessed over 12 years. Only 9% of colonies were alive after 12 years: no A. cervicornis; 3% of A. palmata transplants and 18% of reference colonies; and 13% of P. porites transplants and 7% of reference colonies. Mortality rates for all species were high and were similar for transplant and reference colonies. Physical dislodgement resulted in the loss of 56% of colonies, whereas 35% died in place. Only A. palmata showed a difference between transplant and reference colony survival and that was in the first year only. Location was a factor in survival only for A. palmata reference colonies and after year 10. Even though the tested methods and concepts were proven effective in the field over the 12-year study, they do not present a solution. No coral conservation strategy will be effective until underlying intrinsic and/or extrinsic factors driving high mortality rates are understood and

  14. Transplantation of storm-generated coral fragments to enhance Caribbean coral reefs: A successful method but not a solution

    Science.gov (United States)

    Garrison, Virginia H.; Ward, Greg A.

    2012-01-01

    In response to dramatic losses of reef-building corals and ongoing lack of recovery, a small-scale coral transplant project was initiated in the Caribbean (U.S. Virgin Islands) in 1999 and was followed for 12 years. The primary objectives were to (1) identify a source of coral colonies for transplantation that would not result in damage to reefs, (2) test the feasibility of transplanting storm-generated coral fragments, and (3) develop a simple, inexpensive method for transplanting fragments that could be conducted by the local community.  The ultimate goal was to enhance abundance of threatened reef-building species on local reefs.  Storm-produced coral fragments of two threatened reef-building species [Acropora palmata and A. cervicornis (Acroporidae)] and another fast-growing species [Porites porites (Poritidae)] were collected from environments hostile to coral fragment survival and transplanted to degraded reefs.  Inert nylon cable ties were used to attach transplanted coral fragments to dead coral substrate.  Survival of 75 reference colonies and 60 transplants was assessed over 12 years. Only 9% of colonies were alive after 12 years: no A. cervicornis; 3% of A. palmata transplants and 18% of reference colonies; and 13% of P. porites transplants and 7% of reference colonies. Mortality rates for all species were high and were similar for transplant and reference colonies. Physical dislodgement resulted in the loss of 56% of colonies, whereas 35% died in place.  Only A. palmata showed a difference between transplant and reference colony survival and that was in the first year only.  Location was a factor in survival only for A. palmata reference colonies and after year 10.  Even though the tested methods and concepts were proven effective in the field over the 12-year study, they do not present a solution. No coral conservation strategy will be effective until underlying intrinsic and/or extrinsic factors driving high mortality rates are

  15. Enhanced Control of a DFIG-Based Wind-Power Generation System With Series Grid-Side Converter Under Unbalanced Grid Voltage Conditions

    DEFF Research Database (Denmark)

    Yao, Jun; Li, Hui; Chen, Zhe

    2013-01-01

    This paper presents an enhanced control method for a doubly fed induction generator (DFIG)-based wind-power generation system with series grid-side converter (SGSC) under unbalanced grid voltage conditions. The behaviors of the DFIG system with SGSC during network unbalance are described....... By injecting a series control voltage generated from the SGSC to balance the stator voltage, the adverse effects of voltage unbalance upon the DFIG, such as stator and rotor current unbalances, electromagnetic torque, and power pulsations, can be removed, and then the conventional vector control strategy...... to the grid. Furthermore, a precise current reference generation strategy for the PGSC has been proposed for the PGSC to further improve the operation performance of the whole system. Finally, the proposed coordinated control strategy for the DFIG system with SGSC has been validated by the simulation results...

  16. Amine bridges grafted mesoporous silica, as a prolonged/controlled drug release system for the enhanced therapeutic effect of short life drugs

    International Nuclear Information System (INIS)

    Rehman, Fozia; Ahmed, Khalid; Airoldi, Claudio; Gaisford, Simon; Buanz, Asma; Rahim, Abdur; Muhammad, Nawshad; Volpe, Pedro L.O.

    2017-01-01

    Hybrid mesoporous silica SBA-15, with surface incorporated cross-linked long hydrophobic organic bridges was synthesized using stepwise synthesis. The synthesized materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-rays diffraction, thermogravimetry and scanning and transmission electron microscopy. The functionalized material showed highly ordered mesoporous network with a surface area of 629.0 m 2 g −1 . The incorporation of long hydrophobic amine chains on silica surface resulted in high drug loading capacity (21% Mass/Mass) and prolonged release of ibuprofen up till 75.5 h. The preliminary investigations suggests that the synthesized materials could be proposed as controlled release devices to prolong the therapeutic effect of short life drugs such as ibuprofen to increase its efficacy and to reduce frequent dosage. - Highlights: • Silica SBA-15 was synthesized and modified with long hydrophobic amine linkers. • These materials were characterized using different techniques. • The modified material showed high drug loading capacity and control ibuprofen release in biological fluids.

  17. Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects.

    Science.gov (United States)

    Song, Zhiwang; Lin, Yun; Zhang, Xia; Feng, Chan; Lu, Yonglin; Gao, Yong; Dong, Chunyan

    2017-01-01

    Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin α v β 3 and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer.

  18. Gene expression of hematoregulatory cytokines is elevated endogenously after sublethal gamma irradiation and is differentially enhanced by therapeutic administration of biologic response modifiers

    International Nuclear Information System (INIS)

    Peterson, V.M.; Adamovicz, J.J.; Madonna, G.S.; Gause, W.C.; Elliott, T.B.; Moore, M.M.; Ledney, G.D.; Jackson, W.E. III

    1994-01-01

    Prompt, cytokine-mediated restoration of hematopoiesis is a prerequisite for survival after irradiation. Therapy with biologic response modifiers (BRMs), such as LPS, 3D monophosphoryl lipid A (MPL), and synthetic trehalose dicrynomycolate (S-TDCM) presumably accelerates hematopoietic recovery after irradiation are poorly defined. One hour after sublethal (7.0 Gy) 60 Co gamma irradiation, B6D2F1/J female mice received a single i.p. injection of LPS, MPL, S-TDCM, an extract from Serratia marcescens (Sm-BRM), or Tween 80 in saline (TS). Five hours later, a quantitative reverse transcription-PCR assay demonstrated marked splenic gene expression for IL-1β, IL-3, IL-6, and granulocyte-CSF (G-CSF). Enhanced gene expression for TNF-α, macrophage-CSF (M-CSF), and stem cell factor (SCF) was not detected. Injection of any BRM further enhanced cytokine gene expression and plasma levels of CSF activity within 24 h after irradiation and hastened bone marrow recovery. Mice injected with S-TDCM or Sm-BRM sustained expression of the IL-6 gene for at least 24 h after irradiation. Sm-BRM-treated mice exhibited greater gene expression for IL-1β, IL-3, TNF-α, and G-CSF at day 1 than any other BRM. When challenged with 2 LD 50/30 of Klebsiella pneumoniae 4 days after irradiation, 100% of Sm-BRM-treated mice and 70% of S-TDCM-treated mice survived, whereas ≤30% of mice treated with LPS, MPL, or TS survived. Thus, sublethal irradiation induces transient, splenic cytokine gene expression that can be differentially amplified and prolonged by BRMs. BRMs that sustained and/or enhanced irradiation-induced expression of specific cytokine genes improved survival after experimental infection. 67 refs., 7 figs., 1 tab

  19. Therapeutic misadventure.

    Science.gov (United States)

    Langford, N J

    2010-10-01

    Therapeutic misadventure can be defined as an injury or an adverse event caused by medical management rather than by an underlying disease. Within the National Health Service there were over 86,000 reported adverse incidents in 2007. In the USA medication errors have been rated as the fourth highest cause of death. Unfortunately one of the greatest contributors to iatrogenic injury is human error. The potential types of misadventure are infinite. Medication errors are a major part of this, being responsible for over 70% of cases that cause serious harm. However, many medication errors caused by slips, lapses, technical errors and mistakes are preventable; intentional violations of safe operating procedures are not. While medication errors were tolerated by society in the past, the readiness to institute criminal proceedings against health-care professionals has increased greatly in the UK over the last decade. The medication process consists of writing prescriptions, dispensing the product, administering it and monitoring its effects. Prescription errors arise owing to incomplete information, lack of appropriate labelling, environmental factors and human blunders. Even with a perfect prescription the right medication must be dispensed and appropriately labelled. Dispensing errors are not uncommon and may be compounded by non-clinical considerations. Administration of a drug by injection is one of the most dangerous aspects of the medication process, especially in inexperienced hands. The final component of medication supply is monitoring the effect of the medication. With short courses of medication such monitoring is easy, but with long-term medication, particularly with potent drugs where the margin between efficacy and toxicity is small, active procedures may be required to ensure toxicity does not ensue. Despite the endeavour of health-care professions to stick to the rule of 'first, do no harm', in reality this is difficult to achieve all of the time. When

  20. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fogg, Mark [Department of Medicine, Brigham and Women' s Hospital (United States); Murphy, John R. [Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, MA 02118 (United States); Lorch, Jochen; Posner, Marshall [Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Wang, Fred, E-mail: fwang@research.bwh.harvard.edu [Department of Medicine, Brigham and Women' s Hospital (United States); Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 (United States)

    2013-07-05

    Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients.

  1. Phosphorylation within the cysteine-rich region of dystrophin enhances its association with β-dystroglycan and identifies a potential novel therapeutic target for skeletal muscle wasting.

    Science.gov (United States)

    Swiderski, Kristy; Shaffer, Scott A; Gallis, Byron; Odom, Guy L; Arnett, Andrea L; Scott Edgar, J; Baum, Dale M; Chee, Annabel; Naim, Timur; Gregorevic, Paul; Murphy, Kate T; Moody, James; Goodlett, David R; Lynch, Gordon S; Chamberlain, Jeffrey S

    2014-12-20

    Mutations in dystrophin lead to Duchenne muscular dystrophy, which is among the most common human genetic disorders. Dystrophin nucleates assembly of the dystrophin-glycoprotein complex (DGC), and a defective DGC disrupts an essential link between the intracellular cytoskeleton and the basal lamina, leading to progressive muscle wasting. In vitro studies have suggested that dystrophin phosphorylation may affect interactions with actin or syntrophin, yet whether this occurs in vivo or affects protein function remains unknown. Utilizing nanoflow liquid chromatography mass spectrometry, we identified 18 phosphorylated residues within endogenous dystrophin. Mutagenesis revealed that phosphorylation at S3059 enhances the dystrophin-dystroglycan interaction and 3D modeling utilizing the Rosetta software program provided a structural model for how phosphorylation enhances this interaction. These findings demonstrate that phosphorylation is a key mechanism regulating the interaction between dystrophin and the DGC and reveal that posttranslational modification of a single amino acid directly modulates the function of dystrophin. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. In situ generated CdS nanostructure induced enhanced photoluminescence from Dy{sup 3+} ions doped dielectric nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Dey, Chirantan; Karmakar, Basudeb [Glass Science and Technology Section, Glass Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India)

    2017-08-15

    We report CdS nanostructure induced enhanced photoluminescence (PL) from Dy{sup +3}:CdS co-doped dielectric-nanocomposites synthesized by the conventional melt-quench technique. CdS nanocrystals (NCs) were synthesized as in situ within the dielectric medium and their growth was controlled by heat treatment duration. Nanoparticles were investigated with absorption spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and Raman spectroscopy. The experimentally obtained sizes of the NCs are found to increase from 5-11 nm to 50-80 nm. Bandgap enhancement for the carrier confinement was found to alter within the range of 0.20-0.38 eV. Phonon confinement effect has been confirmed by blue shifting of Raman peak for CdS NCs at 303 cm{sup -1}. Enhanced highly intense sharp PL peak at 576 nm was detected, and different parameters associated with the PL enhancement including energy transfer from CdS NCs to Dy{sup 3+} ions have been studied. This PL enhancement was steered by varying CdS NC sizes. Enhanced PL of these nanocomposites finds their potential applications as gain medium in the field of solid state lasers. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  3. Histone Deacetylase Inhibitor AR-42 Enhances E7-Specific CD8+ T Cell-Mediated Antitumor Immunity Induced by Therapeutic HPV DNA Vaccination

    OpenAIRE

    Lee, Sung Yong; Huang, Zhuomin; Kang, Tae Heung; Soong, Ruey-Shyang; Knoff, Jayne; Axenfeld, Ellen; Wang, Chenguang; Alvarez, Ronald D.; Chen, Ching-Shih; Hung, Chien-Fu; Wu, T.-C.

    2013-01-01

    We have previously created a potent DNA vaccine encoding calreticulin linked to the HPV oncogenic protein E7 (CRT/E7). While treatment of the CRT/E7 DNA vaccine generates significant tumor-specific immune responses in vaccinated mice, the potency of the DNA vaccine could potentially be improved by co-administration of a histone deacetylase inhibitor (HDACi) as HDACi have been shown to increase the expression of MHC class I and II molecules. Thus, we aimed to determine whether co-administratio...

  4. Stepwise targeted drug delivery to liver cancer cells for enhanced therapeutic efficacy by galactose-grafted, ultra-pH-sensitive micelles.

    Science.gov (United States)

    Yan, Guoqing; Wang, Jun; Hu, Liefeng; Wang, Xin; Yang, Guanqing; Fu, Shengxiang; Cheng, Xu; Zhang, Panpan; Tang, Rupei

    2017-03-15

    To promote drug accumulation and cell-killing ability at tumor tissue, we have prepared a stepwise targeted drug delivery system that can remain stealthy and long-circulating in the blood vessels, improve drug retention at extracellular stimuli, enhance cellular uptake through special targeting ligands, and then achieve rapid drug release to improve toxicity to tumor cells at intracellular stimuli. Herein, galactose-grafted, ultra-pH-sensitive drug carriers (POEAd-g-LA-DOX micelles), which could respond to both extracellular and intracellular pH, and combine with galactose-receptors in cell membrane, were constructed by a facile method, therefore achieving: (i) remaining stable at pH 7.4; (ii) responding to tumoral extracellular pH following gradually larger nanoparticles (NPs); (iii) conjugating receptors in the cell membrane of liver cancer through surface galactose-ligands of micelles; (iv) being sensitive to tumoral intracellular pH following further swelling for rapid drug release. In vitro cytotoxicity and cellular uptake measurement showed that POEAd-g-LA20-DOX micelle was more easily internalized and more toxic effect on tumor cells than free DOX. Moreover, in vivo biodistribution and tumor inhibition examinations demonstrated that POEAd-g-LA20-DOX formulation had more superior efficacy to significantly enhance drug accumulation in tumor, and then restrain tumor growth while decreasing drug concentration in heart. Chemotherapeutic efficacy is limited by poor tumor selectivity, which also causes severe toxicity in normal tissues and organs, although many targeted drug delivery systems have been developed by passive targeting strategies or active targeting strategies with specific targeting ligands in recent years. Herein, galactose-grafted, ultra-pH-sensitive, ortho ester-based drug carriers, which can respond to both extracellular and intracellular pH, and target to galactose-receptors in cell membrane, have been successfully constructed by facile method

  5. Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe (Japan); Fujisawa, Yasuko [Toshiba Medical Systems Corporation, Otawara (Japan); Koyama, Hisanobu; Kishida, Yuji; Seki, Shinichiro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Sugihara, Naoki [Toshiba Medical Systems Corporation, Otawara (Japan); Yoshikawa, Takeshi [Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe (Japan); Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe (Japan)

    2017-01-15

    Purpose: To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Materials and methods: Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR + PR) and 2) stable or progressive disease (SD + PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV{sub max}, and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. Results: The step-wise regression test showed that therapeutic effect (r{sup 2} = 0.63, p = 0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV{sub max}. Mean overall survival showed a significant difference for total perfusion (p = 0.003) and systemic arterial perfusion (p = 0.04). Conclusion: Dynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy.

  6. Female genital mutilation/cutting in Italy: an enhanced estimation for first generation migrant women based on 2016 survey data

    OpenAIRE

    Ortensi, Livia Elisa; Farina, Patrizia; Leye, Els

    2018-01-01

    Background Migration flows of women from Female Genital Mutilation/Cutting practicing countries have generated a need for data on women potentially affected by Female Genital Mutilation/Cutting. This paper presents enhanced estimates for foreign-born women and asylum seekers in Italy in 2016, with the aim of supporting resource planning and policy making, and advancing the methodological debate on estimation methods. Methods The estimates build on the most recent methodological development in...

  7. Therapeutic mechanisms of Mindfulness-Oriented Recovery Enhancement for internet gaming disorder: Reducing craving and addictive behavior by targeting cognitive processes.

    Science.gov (United States)

    Li, Wen; Garland, Eric L; Howard, Matthew O

    2018-03-22

    Internet gaming disorder (IGD) is characterized by signs and symptoms similar to substance use and gambling disorders, and associated with psychosocial impairments. Research suggests that maladaptive gaming-related cognitions and coping may be implicated in IGD; therefore, interventions for IGD need to target these underlying mechanisms. Mindfulness-based treatment is effective in changing maladaptive cognitive processes and increasing adaptive coping among people with addictions. This study used data from an RCT of Mindfulness-Oriented Recovery Enhancement (MORE) for IGD to further examine changes in maladaptive gaming-related cognitions and positive reappraisal as mediators of the effects of MORE on IGD signs/symptoms. Participants (N = 30, Age M = 25.0, SD  = 5.4) were randomized to 8-weekly sessions of MORE or a support group (SG) control condition. IGD severity, levels of craving for video game playing, maladaptive gaming-related cognitions, and positive reappraisal were measured at pre-and posttreatment, and 3-month follow-up. Multivariate path analyses revealed that effects of MORE in reducing IGD and craving were statistically mediated by changes in maladaptive gaming-related cognitions. Though changes in positive reappraisal did not significantly mediate effects of MORE on IGD or craving, MORE enhanced positive reappraisal to a significantly greater extent than the SG at posttreatment. Findings suggest that effects of mindfulness treatment in reducing maladaptive gaming-related cognitions might lead to reductions in IGD severity and cravings for video game playing. This cognitive mechanism should be evaluated in a future, full-scale RCT.

  8. Next-Generation Therapeutics for IBD

    NARCIS (Netherlands)

    Löwenberg, Mark; D'Haens, Geert

    2015-01-01

    Various novel drugs have recently been evaluated in clinical trials showing promising effects in patients with inflammatory bowel disease (IBD). Here, we summarize the recent literature in the area of emerging therapies in the field of IBD, with specific focus on anti-integrin antibodies, such as

  9. Therapeutic Versatility of Resveratrol Derivatives

    OpenAIRE

    Waqas Nawaz; Zhongqin Zhou; Sa Deng; Xiaodong Ma; Xiaochi Ma; Chuangang Li; Xiaohong Shu

    2017-01-01

    Resveratrol, a natural phytoalexin, exhibits a remarkable range of biological activities, such as anticancer, cardioprotective, neuroprotective and antioxidant properties. However, the therapeutic application of resveratrol was encumbered for its low bioavailability. Therefore, many researchers focused on designing and synthesizing the derivatives of resveratrol to enhance the bioavailability and the pharmacological activity of resveratrol. During the past decades, a large number of natural a...

  10. Experimental Investigation on the Feasibility of Using a Fresnel Lens as a Solar-Energy Collection System for Enhancing On-Orbit Power Generation Performance

    Directory of Open Access Journals (Sweden)

    Tae-Yong Park

    2017-01-01

    Full Text Available Cube satellites have a limitation for generating power because of their cubic structure and extremely small size. In addition, the incidence angle between the sun and the solar panels continuously varies owing to the revolution and rotation of the satellite according to the attitude control strategy. This angle is an important parameter for determining the power generation performance of the cube satellite. In this study, we performed an experimental feasibility study that uses a Fresnel lens as a solar-energy collection system for cube satellite applications, so that the power generation efficiency can be enhanced under the worst incidence angle condition between the sun and solar panels by concentrating and redirecting solar energy onto the solar panels with a commercial Fresnel lens. To verify the effectiveness of the proposed system, we conducted a power-measurement test using a solar simulator and Fresnel lenses at various angles to the light source. In addition, we predicted the on-orbit power-generation enhancement achieved by employing the solar-energy collection system with various attitude control strategies.

  11. Enhancing Brain Pregnenolone May Protect Cannabis Intoxication but Should Not Be Considered as an Anti-addiction Therapeutic: Hypothesizing Dopaminergic Blockade and Promoting Anti-Reward

    Science.gov (United States)

    Blum, Kenneth; Oscar-Berman, Marlene; Braverman, Eric R.; Febo, Marcelo; Li, Mona; Gold, Mark S.

    2015-01-01

    Many US states now embrace the medical and recreational use of Cannabis. Changes in the laws have heightened interest and encouraged research into both cannabinoid products and the potential harms of Cannabis use, addiction, and intoxication. Some research into those harms will be reviewed here and misgivings about the use of Pregnenolone, to treat cannabis addiction and intoxication explained. Pregnenolone considered the inactive precursor of all steroid hormones, has recently been shown to protect the brain from Cannabis intoxication. The major active ingredient of Cannabis sativa (marijuana), Δ9-tetrahydrocannabinol (THC) enhances Pregnenolone synthesis in the brain via stimulation of the type-1 cannabinoid (CB1) receptor. This steroid has been shown to inhibit the activity of the CB1 receptor thereby reducing many of the effects of THC. While this mechanism seems correct, in our opinion, Vallee et al., incorrectly suggest that blocking CB1 receptors could open unforeseen approaches to the treatment of cannabis intoxication and addiction. In this hypothesis, we caution the scientific community that, other CB1 receptor blockers, such as, Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB1 receptor blockers were rejected by the FDA due to mood changes including suicide ideation. Blocking CB1 receptors would result in reduced neuronal release of Dopamine by disinhibition of GABA signaling. Long-term blockade of cannabinoid receptors could occur with raising Pregnenolone brain levels, may induce a hypodopaminergic state, and lead to aberrant substance and non-substance (behavioral) addictions. PMID:26306328

  12. PirB is a novel potential therapeutic target for enhancing axonal regeneration and synaptic plasticity following CNS injury in mammals.

    Science.gov (United States)

    Gou, Zhaoyu; Mi, Yajing; Jiang, Fengliang; Deng, Bin; Yang, Jun; Gou, Xingchun

    2014-06-01

    A major barrier to axonal regeneration in mammals is the unfavorable extracellular environment that develops following injury to the central nervous system (CNS). In particular, three myelin-associated inhibitory proteins (MAIs) - Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp) - are known to inhibit axonal regeneration and functional recovery. These MAIs share a common receptor, glycosylphosphatidylinositol-anchored Nogo receptor (NgR). However, paired immunoglobulin-like receptor B (PirB) - which was originally identified as a receptor for class I major histocompatibility complex (MHCI) in the immune system - is also expressed in neurones and plays a similarly inhibitory role in axonal regeneration and synaptic plasticity following CNS injury through its association with MAIs. Importantly, suppression of PirB activity through antibody antagonism or genetic means can partially relieve the inhibition of neurite outgrowth in vitro and in vivo. In this review, we present the molecular features, expression patterns and known signaling pathways of PirB, and we specifically focus on putative roles for PirB in the CNS and its potential as a target of molecular therapies for enhancing axonal regeneration and synaptic plasticity following CNS injury.

  13. Therapeutic tests on methylcholanthrene-induced fibrosarcoma and transplanted fibrosarcoma of the mouse - clostridial oncolysis and its enhancement by high-frequency hyperthermia and X-rays

    International Nuclear Information System (INIS)

    Pirlet, T.

    1982-01-01

    Tests aimed at a conditioning of tumours by means of x-ray irradiation and high-frequency hyperthermia. Methyl cholanthrene-induced fibrosarcoma (IMCM) and its transplant version (T-IMCM) produced at the neck of NMRI-mice at a critical localization immediately next to vital organs, served as a test system since it is almost resistant to simple oncolysis. Individual therapy components were compared for their mutual enhancement of efficacy in 16 test groups, and the triple combination (Cl + X-ray + HFH) was tested in relapse application as well. A 2000-R-x-ray irradiation was followed by almost simultaneous 4 min HF heating and i.v. spore administration at 12 h intervals. Assessment criteria were tumour growth, survival rates and times, absence of recidivity and healing, analysis of post-mortem findings and dimension or duration of lyses. In addition, the two tumour types of induction and transplant tumour were compared. The typical course of clostridial oncolysis can be confirmed in principle. Results show that it is possible by means of additional physical methods as were applied, to increase the systemically apathogenic and selective therapy principle of rather negligible oncolysis to over 80% (IMCM) or 97% (T-IMCM). Concerning the MCA fibrosarcoma which is very resistant to clostridial oncolysis in this mouse-tumour model, marked prolongations of survival or healing are possible even in extremely critical localization. In principle, this provides the preconditions for including oncolysis in clinical studies in human medicine. (orig./MG) [de

  14. Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma.

    Science.gov (United States)

    Marconato, L; Stefanello, D; Sabattini, S; Comazzi, S; Riondato, F; Laganga, P; Frayssinet, P; Pizzoni, S; Rouquet, N; Aresu, L

    2015-09-22

    The aim of this non-randomized controlled trial was to compare time to progression (TTP), lymphoma-specific survival (LSS), and safety of an autologous vaccine (consisting of hydroxyapatite ceramic powder and Heat Shock Proteins purified from the dogs' tumors, HSPPCs-HA) plus chemotherapy versus chemotherapy alone in dogs with newly diagnosed, clinically advanced, histologically confirmed, multicentric indolent B-cell lymphoma. The vaccine was prepared from dogs' resected lymph nodes and administered as an intradermal injection. Forty-five client-owned dogs were enrolled: 20 dogs were treated with dose-intense chemotherapy, and 25 received concurrent immunotherapy. Both treatment arms were well tolerated, with no exacerbated toxicity in dogs also receiving the vaccine. TTP was significantly longer for dogs treated with chemo-immunotherapy versus those receiving chemotherapy only (median, 209 versus 85 days, respectively, P=0.015). LSS was not significantly different between groups: dogs treated with chemo-immunotherapy had a median survival of 349 days, and those treated with chemotherapy only had a median survival of 200 days (P=0.173). Among vaccinated dogs, those mounting an immune response had a significantly longer TTP and LSS than those with no detectable response (P=0.012 and P=0.003, respectively). Collectively these results demonstrate that vaccination with HSPPCs-HA may produce clinical benefits with no increased toxicity, thereby providing a strategy for enhancing chemotherapy in dogs with advanced indolent lymphoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Development of sodium acetate trihydrate-ethylene glycol composite phase change materials with enhanced thermophysical properties for thermal comfort and therapeutic applications.

    Science.gov (United States)

    Kumar, Rohitash; Vyas, Sumita; Kumar, Ravindra; Dixit, Ambesh

    2017-07-12

    The heat packs using phase change materials (PCMs) are designed for possible applications such as body comfort and medical applications under adverse situations. The development and performance of such heat packs rely on thermophysical properties of PCMs such as latent heat, suitable heat releasing temperature, degree of supercooling, effective heat releasing time, crystallite size, stability against spontaneous nucleation in metastable supercooled liquid state and thermal stability during heating and cooling cycles. Such PCMs are rare and the available PCMs do not exhibit such properties simultaneously to meet the desired requirements. The present work reports a facile approach for the design and development of ethylene glycol (EG) and aqueous sodium acetate trihydrate (SAT) based composite phase change materials, showing these properties simultaneously. The addition of 2-3 wt% EG in aqueous SAT enhances the softness of SAT crystallites, its degree of supercooling and most importantly the effective heat releasing time by ~10% with respect to aqueous SAT material. In addition, the maximum heat releasing temperature of aqueous SAT has been tailored from 56.5 °C to 55 °C, 54.9 °C, 53.5 °C, 51.8 °C and 43.2 °C using 2%, 3%, 5%, 7% and 10 wt% EG respectively, making the aqueous SAT-EG composite PCMs suitable for desired thermal applications.

  16. Restructuring reward processing with Mindfulness-Oriented Recovery Enhancement: novel therapeutic mechanisms to remediate hedonic dysregulation in addiction, stress, and pain

    Science.gov (United States)

    Garland, Eric

    2016-01-01

    Though valuation processes are fundamental to survival of the human species, hedonic dysregulation is at the root of an array of clinical disorders, including addiction, stress, and chronic pain, as evidenced by the allostatic shift in the relative salience of natural reward to drug reward observed among persons with severe substance use disorders. To address this crucial clinical issue, novel interventions are needed to restore hedonic regulatory processes gone awry in persons exhibiting addictive behaviors. This article describes a theoretical rationale and empirical evidence for the effects of one such new intervention, mindfulness-oriented recovery enhancement (MORE), on top-down and bottom-up mechanisms implicated in cognitive control and hedonic regulation. MORE is innovative and distinct from extant mindfulness-based interventions in that in unites traditional mindfulness meditation with reappraisal and savoring strategies designed to reverse the downward shift in salience of natural reward relative to drug reward, representing a crucial tipping point to disrupt the progression of addiction, which no other behavioral intervention has been designed to do. Though additional studies are needed, clinical and biobehavioral data from several completed and ongoing trials suggest that MORE may exert salutary effects on addictive behaviors and the neurobiological processes that underpin them. PMID:27037786

  17. OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine both in vitro and in vivo.

    Science.gov (United States)

    Zhi, Xiao; Chen, Wei; Xue, Fei; Liang, Chao; Chen, Bryan Wei; Zhou, Yue; Wen, Liang; Hu, Liqiang; Shen, Jian; Bai, Xueli; Liang, Tingbo

    2015-09-22

    Despite its relative rarity, pancreatic ductal adenocarcinoma (PDAC) accounts for a large percentage of cancer deaths. In this study, we investigated the in vitro efficacy of OSI-027, a selective inhibitor of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2, to treat PDAC cell lines alone, and in combination with gemcitabine (GEM). Similarly, we tested the efficacy of these two compounds in a xenograft mouse model of PDAC. OSI-027 significantly arrested cell cycle in G0/G1 phase, inhibited the proliferation of Panc-1, BxPC-3, and CFPAC-1 cells, and downregulated mTORC1, mTORC2, phospho-Akt, phospho-p70S6K, phospho-4E-BP1, cyclin D1, and cyclin-dependent kinase 4 (CDK4) in these cells. Moreover, OSI-027 also downregulated multidrug resistance (MDR)-1, which has been implicated in chemotherapy resistance in PDAC cells and enhanced apoptosis induced by GEM in the three PDAC cell lines. When combined, OSI-027 with GEM showed synergistic cytotoxic effects both in vitro and in vivo. This is the first evidence of the efficacy of OSI-027 in PDAC and may provide the groundwork for a new clinical PDAC therapy.

  18. Research on vitrification technology to immobilize radioactive sludge generated from Fukushima Daiichi power plant. Enhanced glass medium

    International Nuclear Information System (INIS)

    Amamoto, Ippei; Kobayashi, Hidekazu; Kitamura, Naoto; Takebe, Hiromichi; Mitamura, Naoki; Tsuzuki, Tatsuya; Fukayama, Daigen; Nagano, Yuichi; Jantzen, Tatjana; Hack, Klaus

    2016-01-01

    The search for an enhanced glass medium to immobilize the sludge at the Fukushima Daiichi Nuclear Power Plant is our main purpose. The iron phosphate glass (IPG) is a potential candidate as we set about assessing it by means of theoretical and experimental investigation. Based on the results of this study, the IPG showed favorable characteristics as a vitrification medium for the sludge. (author)

  19. A novel chimeric DNA vaccine: enhancement of preventive and therapeutic efficacy of DNA vaccine by fusion of Mucin 1 to a heat shock protein 70 gene.

    Science.gov (United States)

    Choi, Dae-Han; Woo, Jong Kyu; Choi, Yun; Seo, Hye-Sook; Kim, Chul-Woo

    2011-01-01

    Intensive efforts to improve vaccines against cancer are currently outgoing. Mucin 1 (Muc1) is a tumor-specific antigen that is overexpressed and heavily glycosylated in a variety of adenocarcinomas. In the present study, the efficacy of an anticancer DNA vaccination strategy was demonstrated using Muc1 fusion vaccines. To enhance antigen presentation and tumor-suppressive efficacy, a chimeric Muc1 vaccine was designed, encoding the transmembrane- and C-terminal domain-deleted Muc1 gene (∆TM) fused to the human HSP70 gene. To confirm the expression and secretion of fusion protein, cell culture supernatants were subjected to Western blotting. We found secreted Muc1 ΔTM-HSP0 fusion protein in the supernatants. These results demonstrate that the Muc1 ΔTM-HSP0 construct can be efficiently expressed and secreted from transfected cells. When the chimeric Muc1 vaccine was administered to mice, antigen-specific cellular immune responses were observed. Notably, we observed that antigen-specific lymphocyte proliferation and cytotoxic responses were effectively induced only in the group of mice that had been vaccinated with the chimeric Muc1 vaccine. Concurrent with the Muc1-specific tumor-suppressive effect, the growth of established Muc1-expressing B16 mouse melanoma cells was also significantly inhibited by vaccination with the chimeric Muc1 vaccine. The growth of B16 mouse melanoma cells expressing human Muc1 in C57BL/6 mice was effectively suppressed by the Muc1-HSP70 chimeric DNA vaccine. Our results reveal that the antitumor efficacy of the chimeric DNA vaccine was improved by the presence of HSP/70.

  20. Enhanced Cherenkov phase matching terahertz wave generation via a magnesium oxide doped lithium niobate ridged waveguide crystal

    Directory of Open Access Journals (Sweden)

    K. Takeya

    2017-01-01

    Full Text Available When combined with a nonlinear waveguide crystal, Cherenkov phase matching allows for highly effective generation of high power and broadband terahertz (THz waves. Using a ridged Lithium Niobate (LiNbO3 waveguide coupled with a specially designed silicon lens, we successfully generated THz waves with intensity of approximately three orders of magnitude stronger than those from conventional photoconductive antenna. The broadband spectrum was from 0.1 THz to 7 THz with a maximum dynamic range of 80 dB. The temporal shape of time domain pulse is a regular single cycle which could be used for high depth resolution time of flight tomography. The generated THz wave can also be easily monitored by compact room-temperature THz camera, enabling us to determine the spatial characteristics of the THz propagation.

  1. Enhanced hydrogen generation by hydrolysis of Mg doped with flower-like MoS2 for fuel cell applications

    Science.gov (United States)

    Huang, Minghong; Ouyang, Liuzhang; Liu, Jiangwen; Wang, Hui; Shao, Huaiyu; Zhu, Min

    2017-10-01

    In this work, flower-like MoS2 spheres are synthesized via a hydrothermal method and the catalytic activity of the as-prepared and bulk MoS2 on hydrolysis of Mg is systematically investigated for the first time. The Mg-MoS2 composites are prepared by ball milling and the hydrogen generation performances of the composites are investigated in 3.5% NaCl solution. The experimental results suggest that the as-prepared MoS2 exhibits better catalytic effect on hydrolysis of Mg compared to bulk MoS2. In particular, Mg-10 wt% MoS2 (as-prepared) composite milled for 1 h shows the best hydrogen generation properties and releases 90.4% of theoretical hydrogen generation capacity within 1 min at room temperature. The excellent catalytic effect of as-prepared MoS2 may be attributed to the following aspects: three-dimensional flower-like MoS2 architectures improve its dispersibility on Mg particles; make the composite more reactive; hamper the generated Mg(OH)2 from adhering to the surface of Mg; and increase the galvanic corrosion of Mg. In addition, a hydrogen generator based on the hydrolysis reaction of Mg-0.2 wt% MoS2 composite is manufactured and it can supply a maximum hydrogen flow rate of 2.5 L/min. The findings here demonstrate the as-prepared flower-like MoS2 can be a promising catalyst for hydrogen generation from Mg.

  2. Transplantation of storm-generated coral fragments to enhance Caribbean coral reefs: A successful method but not a solution

    Directory of Open Access Journals (Sweden)

    Virginia H. Garrison

    2012-03-01

    Full Text Available In response to dramatic losses of reef-building corals and ongoing lack of recovery, a small-scale coral transplant project was initiated in the Caribbean (U.S. Virgin Islands in 1999 and was followed for 12 years. The primary objectives were to (1 identify a source of coral colonies for transplantation that would not result in damage to reefs, (2 test the feasibility of transplanting storm-generated coral fragments, and (3 develop a simple, inexpensive method for transplanting fragments that could be conducted by the local community. The ultimate goal was to enhance abundance of threatened reef-building species on local reefs. Storm-produced coral fragments of two threatened reef-building species [Acropora palmata and A. cervicornis (Acroporidae] and another fast-growing species [Porites porites (Poritidae] were collected from environments hostile to coral fragment survival and transplanted to degraded reefs. Inert nylon cable ties were used to attach transplanted coral fragments to dead coral substrate. Survival of 75 reference colonies and 60 transplants was assessed over 12 years. Only 9% of colonies were alive after 12 years: no A. cervicornis; 3% of A. palmata transplants and 18% of reference colonies; and 13% of P. porites transplants and 7% of reference colonies. Mortality rates for all species were high and were similar for transplant and reference colonies. Physical dislodgement resulted in the loss of 56% of colonies, whereas 35% died in place. Only A. palmata showed a difference between transplant and reference colony survival and that was in the first year only. Location was a factor in survival only for A. palmata reference colonies and after year 10. Even though the tested methods and concepts were proven effective in the field over the 12-year study, they do not present a solution. No coral conservation strategy will be effective until underlying intrinsic and/or extrinsic factors driving high mortality rates are understood and

  3. Comparing the therapeutic efficacies of third-generation cephalosporins and broader-spectrum β-lactams as appropriate empirical therapy in adults with community-onset monomicrobial Enterobacteriaceae bacteraemia: a propensity score matched analysis.

    Science.gov (United States)

    Lee, Chung-Hsun; Hsieh, Chih-Chia; Hong, Ming-Yuan; Hung, Yuan-Pin; Ko, Wen-Chien; Lee, Ching-Chi

    2017-05-01

    In this study, the therapeutic efficacy of third-generation cephalosporins (3GCs) was compared with that of broader-spectrum β-lactams (BSBLs) [fourth-generation cephalosporins (4GCs) and carbapenems] as empirical therapy in adults with community-onset monomicrobial Enterobacteriaceae bacteraemia. Compared with those in the 3GC group (n = 477), a significantly higher proportion of patients in the BSBL group (n = 141) had initial presentation with severe sepsis or septic shock, critical illness (Pitt bacteraemia score ≥4) at bacteraemia onset and fatal co-morbidities (McCabe classification). For propensity score matching, 318 of the 477 patients in the 3GC group were matched with 106 patients in the BSBL group with the closest propensity scores on the basis of five independent predictors of 28-day mortality. After appropriate matching, no significant differences were observed in major baseline characteristics between the 3GC and BSBL groups in terms of causative micro-organism, bacteraemia severity, major source of bacteraemia, major co-morbidities and severity of co-morbidity. Consequently, the early clinical failure rate (12.9% vs. 12.3%; P = 0.87), bacteraemia severity (Pitt bacteraemia score ≥4; 4.6% vs. 8.2%; P = 0.17) at Day 3, and 3-day (3.8% vs. 7.5%; P = 0.11) and 28-day (13.2% vs. 17.0%; P = 0.33) crude mortality rates between the two groups were similar. These data suggest that the efficacy of 3GCs is similar to that of 4GCs or carbapenems when used as empirical antimicrobial therapy for community-onset Enterobacteriaceae bacteraemia. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  4. Mitochondrial superoxide generation enhances P2X7R-mediated loss of cell surface CD62L on naive human CD4+ T lymphocytes.

    Science.gov (United States)

    Foster, John G; Carter, Edward; Kilty, Iain; MacKenzie, Amanda B; Ward, Stephen G

    2013-02-15

    Migration of naive CD4(+) T lymphocytes into lymphoid tissue is essential for their activation and subsequent roles in adaptive immunity. The adhesion molecule L-selectin (CD62L), critical for this process, is highly expressed on naive CD4(+) T lymphocytes and is downregulated upon T lymphocyte activation. We demonstrate protein expression of P2X7R on naive CD4(+) T lymphocytes and show functional channel activity in whole-cell patch clamp recordings. CD62L downregulation occurs rapidly in response to extracellular ATP, a process that is blocked by selective antagonists of P2X7R. This loss of surface CD62L expression was not associated with externalization of phosphatidylserine. While investigating the mechanisms for this process, we revealed that pharmacological modulation of mitochondrial complex I or III, but not inhibition of NADPH oxidase, enhanced P2X7R-dependent CD62L downregulation by increasing ATP potency. Enhanced superoxide generation in the mitochondria of rotenone- and antimycin A-treated cells was observed and may contribute to the enhanced sensitivity of P2X7R to ATP. P2X7R-dependent exposure of phosphatidylserine was also revealed by preincubation with mitochondrial uncouplers prior to ATP treatment. This may present a novel mechanism whereby P2X7R-dependent phosphatidylserine exposure occurs only when cells have enhanced mitochondrial reactive oxygen species generation. The clearance of apoptotic cells may therefore be enhanced by this mechanism which requires functional P2X7R expression.

  5. DNA molecules and human therapeutics

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-29

    Dec 29, 2009 ... Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors ...

  6. Ensuring the Criminological Skills of the Next Generation: A Case Study on the Importance of Enhanced Quantitative Method Teaching Provision

    Science.gov (United States)

    Chamberlain, John Martyn

    2017-01-01

    Against the backdrop of contemporary debates surrounding the public role of criminology, this article argues that a key barrier to ensuring that the next generation of criminologists is equipped with the skills necessary to engage in critical forms of citizenship, is the quantitative "skills gap" that undergraduate students possess as a…

  7. A single bout of dynamic exercise by healthy adults enhances the generation of monocyte-derived-dendritic cells

    NARCIS (Netherlands)

    LaVoy, E.C.P.; Bollard, C.M.; Hanley, P.J.; O'Connor, D.P.; Lowder, T.W.; Bosch, J.A.; Simpson, R.J.

    2015-01-01

    The ex vivo generation of monocyte-derived-dendritic cells (mo-DCs) has facilitated the use of DCs in immunotherapy research. However, low blood monocyte numbers frequently limit the manufacture of sufficient numbers of mo-DCs for subsequent experimental and clinical procedures. Because exercise

  8. The 2nd Generation Street Children (SGSC) in Accra: Developing Teaching Strategies to Enhance Positive Learning Outcomes in Schools

    Science.gov (United States)

    Kuyini, Alhassan Abdul-Razak; Abosi, Okechuwu

    2011-01-01

    Ghana is witnessing an increasing number of 2nd generation street children (SGSC) living in the street of Accra, the capital city as a result of many factors including teenage pregnancy among street girls, ethnic conflicts and rural-urban migration. Street presents enormous risks to street children; they are excluded from safe-family environment,…

  9. Time-Resolved Study of the Surface-Enhanced Raman Scattering Effect of Silver Nanoparticles Generated in Voltammetry Experiments

    OpenAIRE

    Ibáñez, David; Fernández Blanco, Ana Cristina; Heras, Aránzazu; Colina, Álvaro

    2014-01-01

    UV–vis absorption and Raman spectroelectrochemistry have been used to study silver nanoparticle (AgNP) electrodeposition, allowing a better understanding about the metal nanoparticle (NP) formation process and its influence on the surface-enhanced Raman scattering (SERS) effect. These techniques have provided in situ information related to the synthesis of AgNPs by cyclic voltammetry. With a marker, such as cyanide anion (CN–), Raman spectroscopy has allowed us to study all changes that take ...

  10. Recombinant modified vaccinia virus Ankara generating excess early double-stranded RNA transiently activates protein kinase R and triggers enhanced innate immune responses.

    Science.gov (United States)

    Wolferstätter, Michael; Schweneker, Marc; Späth, Michaela; Lukassen, Susanne; Klingenberg, Marieken; Brinkmann, Kay; Wielert, Ursula; Lauterbach, Henning; Hochrein, Hubertus; Chaplin, Paul; Suter, Mark; Hausmann, Jürgen

    2014-12-01

    Double-stranded RNA (dsRNA) is an important molecular pattern associated with viral infection and is detected by various extra- and intracellular recognition molecules. Poxviruses have evolved to avoid producing dsRNA early in infection but generate significant amounts of dsRNA late in infection due to convergent transcription of late genes. Protein kinase R (PKR) is activated by dsRNA and triggers major cellular defenses against viral infection, including protein synthesis shutdown, apoptosis, and type I interferon (IFN-I) production. The poxviral E3 protein binds and sequesters viral dsRNA and is a major antagonist of the PKR pathway. We found that the highly replication-restricted modified vaccinia virus Ankara (MVA) engineered to produce excess amounts of dsRNA early in infection showed enhanced induction of IFN-β in murine and human cells in the presence of an intact E3L gene. IFN-β induction required a minimum overlap length of 300 bp between early complementary transcripts and was strongly PKR dependent. Excess early dsRNA produced by MVA activated PKR early but transiently in murine cells and induced enhanced systemic levels of IFN-α, IFN-γ, and other cytokines and chemokines in mice in a largely PKR-dependent manner. Replication-competent chorioallantois vaccinia virus Ankara (CVA) generating excess early dsRNA also enhanced IFN-I production and was apathogenic in mice even at very high doses but showed no in vitro host range defect. Thus, genetically adjuvanting MVA and CVA to generate excess early dsRNA is an effective method to enhance innate immune stimulation by orthopoxvirus vectors and to attenuate replicating vaccinia virus in vivo. Efficient cellular sensing of pathogen-specific components, including double-stranded RNA (dsRNA), is an important prerequisite of an effective antiviral immune response. The prototype poxvirus vaccinia virus (VACV) and its derivative modified vaccinia virus Ankara (MVA) produce dsRNA as a by-product of viral

  11. Enhanced red emission of 808 nm excited upconversion nanoparticles by optimizing the composition of shell for efficient generation of singlet oxygen

    Science.gov (United States)

    Liu, Jinxue; Zhang, Tingbin; Song, Xiaoyan; Xing, Jinfeng

    2018-01-01

    With the aim to enhance the upconversion luminescence (UCL) intensity, much attention was paid to reduce the energy-back transfer from Er3+ ions to Nd3+ ions by constructing various kinds of multilayer upconversion nanoparticles (UCNPs). However, the energy-back transfer was difficult to be completely eliminated. Also, the thick shell of multilayer UCNPs is not favourable for effective Förster resonance energy transfer (FRET) in photodynamic therapy (PDT) system. Herein, an effective and facile method was applied to prepare UCNPs by optimizing the composition to largely enhance the red emission (at 660 nm) for efficient generation of singlet oxygen (1O2). In detail, the concentrations of Nd3+ ions and Yb3+ ions doped in the sensitizing shell were systematically researched to balance the energy back-transfer and the light harvest ability. The optimal emission and a relatively high Red/Green (R/G) ratio of NaYF4:Yb,Er,Nd@NaYF4:Yb0.1Nd0.2 UCNPs were obtained simultaneously. Furthermore, the emission under 980 nm excitation demonstrated the energy back-transfer from Er3+ to Yb3+ ions was also notable which was largely ignored previously. Then, UCNPs were encapsulated into mesoporous silica shell, and the photosensitizer Chlorin e6 (Ce6) was covalently conjugated to form a non-leaking nanoplatform. The efficiency of 1O2 generation obviously increased with the enhanced emission of UCNPs.

  12. Linac-augmented light sources an incremental concept for enhancing the capabilities of existing 3rd-generation storage rings.

    CERN Document Server

    Lewellen, J W

    2003-01-01

    Planned and proposed 4th-generation x-ray sources, such as energy-recovery linacs (ERLs) and single-pass x-ray free-electron lasers (X-FELs) offer a number of potential advantages, including small source size, higher peak brightness, ultrashort pulses, and potentially temporally and transversely coherent pulses. While offering unique capabilities, such facilities will also offer several important limitations, including limited numbers of user beamlines (for FELs) and a pulse-repetition rate that may be too high for many dynamics experiments (ERLs). In addition, there are many technical challenges associated with both types of facilities. A third type of facility, exemplified by the Short Pulse Photon Source (SPPS) at SLAC [1], would support neither a large number of users simultaneously nor generate coherent pulses, but would generate very intense, short x-ray pulses. Such a facility could serve as the starting point for either an ERL or an X-FEL, or a combined, hybrid machine. For the foreseeable future, how...

  13. Repeated exposure to enhanced UV-B radiation in successive generations increases developmental instability (leaf fluctuating asymmetry) in a desert annual

    International Nuclear Information System (INIS)

    Midgley, G.F.; Wand, S.J.E.; Musil, C.F.

    1998-01-01

    Populations of the desert annual Dimorphotheca sinuata, derived from a common seed stock, were exposed concurrently over four successive generations to either ambient (representing no stratospheric ozone depletion) or elevated (representing 20% stratospheric ozone depletion) UV-B levels during their complete life cycle. Leaf fluctuating asymmetry (FA) was measured in populations of plants grown from seeds of selected generations which had experienced different UV-B exposure histories, and from seeds collected from a wild population of this species which grows in a naturally enhanced UV-B environment. These measured plants had been grown in a greenhouse under essentially UV-B-free conditions. Leaf FA was significantly increased by greater numbers of enhanced UV-B exposures in the parentage of the seed. There was a linear to exponential dose–response relationship between number of UV-B exposure iterations in seed parentage and leaf FA, suggesting that damage to DNA caused by UV-B exposure during plant development may not be fully repaired, and thus be inherited by offspring and accumulated over successive generations in this species. Leaf FA of plants grown from seed from the wild population was not significantly greater than that of control plants whose parentage experienced only ambient UV-B exposures, although this negative result may have been due to low sampling intensity and measurement resolution, and the relatively low UV-B enhancement experienced by the wild population. We conclude that leaf FA may constitute a relatively sensitive yet inexpensive means of quantifying UV-B damage to plants. (author)

  14. Hardware-efficient signal generation of layered/enhanced ACO-OFDM for short-haul fiber-optic links.

    Science.gov (United States)

    Wang, Qibing; Song, Binhuang; Corcoran, Bill; Boland, David; Zhu, Chen; Zhuang, Leimeng; Lowery, Arthur J

    2017-06-12

    Layered/enhanced ACO-OFDM is a promising candidate for intensity modulation and direct-detection based short-haul fiber-optic links due to its both power and spectral efficiency. In this paper, we firstly demonstrate a hardware-efficient real-time 9.375 Gb/s QPSK-encoded layered/enhanced asymmetrical clipped optical OFDM (L/E-ACO-OFDM) transmitter using a Virtex-6 FPGA. This L/E-ACO-OFDM signal is successfully transmitted over 20-km uncompensated standard single-mode fiber (S-SMF) using a directly modulated laser. Several methods are explored to reduce the FPGA's logic resource utilization by taking advantage of the L/E-ACO-OFDM's signal characteristics. We show that the logic resource occupation of L/E-ACO-OFDM transmitter is almost the same as that of DC-biased OFDM transmitter when they achieve the same spectral efficiency, proving its great potential to be used in a real-time short-haul optical transmission link.

  15. A new generation approach in enzyme immobilization: Organic-inorganic hybrid nanoflowers with enhanced catalytic activity and stability.

    Science.gov (United States)

    Altinkaynak, Cevahir; Tavlasoglu, Sureyya; Özdemir, Nalan; Ocsoy, Ismail

    2016-11-01

    Many different micro and nano sized materials have been used for enzymes immobilization in order to increase their catalytic activity and stability. Generally, immobilized enzymes with conventional immobilization techniques exhibit improved stability while their activity is lowered compared to free enzymes. Recently, an elegant immobilization approach was discovered in synthesis of flower-like organic-inorganic hybrid nanostructures with extraordinary catalytic activity and stability. In this novel immobilization strategy, proteins (enzymes) and metal ions acted as organic and inorganic components, respectively to form hybrid nanoflowers (hNFs). It is demonstrated that the hNFs highly enhanced catalytic activities and stability in a wide range of experimental conditions (pHs, temperatures and salt concentration, etc.) compared to free and conventionally immobilized enzymes. This review mainly discussed the synthesis, characterization, development and applications of organic-inorganic hybrid nanoflowers formed of various enzymes and metal ions and explained potential mechanism underlying enhanced catalytic activity and stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Mechanisms of Plasma Therapeutics

    Science.gov (United States)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  17. Enhanced electricity generation by triclosan and iron anodes in the three-chambered membrane bio-chemical reactor (TC-MBCR).

    Science.gov (United States)

    Song, Jing; Liu, Lifen; Yang, Fenglin; Ren, Nanqi; Crittenden, John

    2013-11-01

    A three-chambered membrane bio-chemical reactor (TC-MBCR) was developed. The stainless steel membrane modules were used as cathodes and iron plates in the middle chamber served as the anode. The TC-MBCR was able to reduce fouling, remove triclosan (TCS) from a synthetic wastewater treatment and enhance electricity generation by ~60% compared with the cell voltage before TCS addition. The TC-MBCR system generated a relatively stable power output (cell voltage ~0.2V) and the corrosion of iron plates contributed to electricity generation together with microbes on iron anode. The permeation flow from anode to cathode chamber was considered important in electricity generation. In addition, the negatively charged cathode membrane and Fe(2+)/Fe(3+) released by iron plates mitigated membrane fouling by approximately 30%, as compared with the control. The removal of COD and total phosphorus was approximately 99% and 90%. The highest triclosan removal rate reached 97.9%. Copyright © 2013. Published by Elsevier Ltd.

  18. Therapeutic angiogenesis for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    D'Amore Patricia A

    2001-10-01

    Full Text Available Abstract The identification of angiogenic growth factors, such as vascular endothelial growth factor and fibroblast growth factor, has fueled interest in using such factors to induce therapeutic angiogenesis. The results of numerous animal studies and clinical trials have offered promise for new treatment strategies for various ischemic diseases. Increased understanding of the cellular and molecular biology of vessel growth has, however, prompted investigators and clinicians alike to reconsider the complexity of therapeutic angiogenesis. The realization that formation of a stable vessel is a complex, multistep process may provide useful insights into the design of the next generation of angiogenesis therapy.

  19. T cell Activation Is Driven by an ADP-Dependent Glucokinase Linking Enhanced Glycolysis with Mitochondrial Reactive Oxygen Species Generation

    Directory of Open Access Journals (Sweden)

    Marcin M. Kamiński

    2012-11-01

    Full Text Available Mitochondria-originating reactive oxygen species (ROS control T cell receptor (TCR-induced gene expression. Here, we show that TCR-triggered activation of ADP-dependent glucokinase (ADPGK, an alternative, glycolytic enzyme typical for Archaea, mediates generation of the oxidative signal. We also show that ADPGK is localized in the endoplasmic reticulum and suggest that its active site protrudes toward the cytosol. The ADPGK-driven increase in glycolytic metabolism coincides with TCR-induced glucose uptake, downregulation of mitochondrial respiration, and deviation of glycolysis toward mitochondrial glycerol-3-phosphate dehydrogenase (GPD shuttle; i.e., a metabolic shift to aerobic glycolysis similar to the Warburg effect. The activation of respiratory-chain-associated GPD2 results in hyperreduction of ubiquinone and ROS release from mitochondria. In parallel, mitochondrial bioenergetics and ultrastructure are altered. Downregulation of ADPGK or GPD2 abundance inhibits oxidative signal generation and induction of NF-κB-dependent gene expression, whereas overexpression of ADPGK potentiates them.

  20. Optimal Controller Design of a Wind Turbine with Doubly Fed Induction Generator for Small Signal Stability Enhancement

    DEFF Research Database (Denmark)

    Yang, Lihui; Yang, Guangya; Xu, Zhao

    2010-01-01

    Multi-objective optimal controller design of a doubly fed induction generator (DFIG) wind turbine system using Differential Evolution (DE) is presented in this chapter. A detailed mathematical model of DFIG wind turbine with a close loop vector control system is developed. Based on this, objectiv......-objective problem and the constraint with DE. Eigenvalue analysis and simulation are performed on the single machine infinite bus (SMIB) system to demonstrate the control performance of the system with the optimized controller parameters.......Multi-objective optimal controller design of a doubly fed induction generator (DFIG) wind turbine system using Differential Evolution (DE) is presented in this chapter. A detailed mathematical model of DFIG wind turbine with a close loop vector control system is developed. Based on this, objective...... functions, addressing the steady state stability and dynamic performance at different operating conditions are implemented to optimize the controller parameters of both the rotor and grid side converters. A superior ε-constraint method and method of adaptive penalties are applied to handle the multi...

  1. Enhanced Second-Order Nonlinearity for THz Generation by Resonant Interaction of Exciton-Polariton Rabi Oscillations with Optical Phonons

    Science.gov (United States)

    Rojan, Katharina; Léger, Yoan; Morigi, Giovanna; Richard, Maxime; Minguzzi, Anna

    2017-09-01

    Semiconductor microcavities in the strong-coupling regime exhibit an energy scale in the terahertz (THz) frequency range, which is fixed by the Rabi splitting between the upper and lower exciton-polariton states. While this range can be tuned by several orders of magnitude using different excitonic media, the transition between both polaritonic states is dipole forbidden. In this work, we show that, in cadmium telluride microcavities, the Rabi-oscillation-driven THz radiation is actually active without the need for any change in the microcavity design. This feature results from the unique resonance condition which is achieved between the Rabi splitting and the phonon-polariton states and leads to a giant enhancement of the second-order nonlinearity.

  2. Hot compressed water pretreatment of oil palm fronds to enhance glucose recovery for production of second generation bio-ethanol.

    Science.gov (United States)

    Goh, Chun Sheng; Lee, Keat Teong; Bhatia, Subhash

    2010-10-01

    This work presents the pretreatment of oil palm fronds (OPF) using hot compressed water (HCW) to enhance sugar recovery in enzymatic hydrolysis. A central, composite rotatable design was used to optimize the effect of reaction temperature, reaction time and liquid-solid ratio on the pretreatment process. All variables were found to significantly affect the glucose yield. A quadratic polynomial equation was used to model glucose yield by multiple regression analysis, using response surface methodology (RSM). Using a 10 bar pressurized reactor, the optimum conditions for pretreatment of OPF were found at 178 degrees C, 11.1 min and a liquid-solid ratio of 9.6. The predicted glucose yield was 92.78 wt.% at the optimum conditions. Experimental verification of the optimum conditions gave a glucose yield in good agreement with the estimated value of the model. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Optimal controller design of a doubly fed induction generator wind turbine system for small signal stability enhancement

    DEFF Research Database (Denmark)

    Yang, Lihui; Yang, Guang-Ya; Xu, Zhao

    2010-01-01

    Multi-objective optimal controller design of a doubly-fed induction generator (DFIG) wind turbine system using differential evolution (DE) is presented. A detailed mathematical model of DFIG wind turbine with a closed-loop vector control system is developed. Based on this, objective functions...... and the constraint with DE, respectively. Eigenvalue analysis and time-domain simulations are performed on a single machine infinite bus system as well as a nine-bus multi-machine system with two DFIG wind turbines to illustrate the control performance of the DFIG wind turbine with the optimised controller...... parameters. The electric energy productions of the studied DFIG wind turbine system with and without optimised controller parameters under turbulent wind speed are also demonstrated....

  4. Enhanced hot-electron production and strong-shock generation in hydrogen-rich ablators for shock ignition

    Science.gov (United States)

    Theobald, W.; Bose, A.; Yan, R.; Betti, R.; Lafon, M.; Mangino, D.; Christopherson, A. R.; Stoeckl, C.; Seka, W.; Shang, W.; Michel, D. T.; Ren, C.; Nora, R. C.; Casner, A.; Peebles, J.; Beg, F. N.; Ribeyre, X.; Llor Aisa, E.; Colaïtis, A.; Tikhonchuk, V.; Wei, M. S.

    2017-12-01

    Experiments were performed with CH, Be, C, and SiO2 ablators interacting with high-intensity UV laser radiation (5 × 1015 W/cm2, λ = 351 nm) to determine the optimum material for hot-electron production and strong-shock generation. Significantly more hot electrons are produced in CH (up to ˜13% instantaneous conversion efficiency), while the amount is a factor of ˜2 to 3 lower in the other ablators. A larger hot-electron fraction is correlated with a higher effective ablation pressure. The higher conversion efficiency in CH is attributed to stronger damping of ion-acoustic waves because of the presence of light H ions.

  5. Archaeal lipids in oral delivery of therapeutic peptides

    DEFF Research Database (Denmark)

    Jacobsen, Ann-Christin; Jensen, Sara M; Fricker, Gert

    2017-01-01

    tetraether lipids. The inherent chemical stability and unique membrane-spanning characteristics of tetraether lipids render them interesting for oral drug delivery purposes. Archaeal lipids form liposomes spontaneously (archaeosomes) and may be incorporated in conventional liposomes (mixed vesicles). Both...... types of liposomes are promising to protect their drug cargo, such as therapeutic peptides, against the acidic environment of the stomach and proteolytic degradation in the intestine. They appear to withstand lipolytic enzymes and bile salts and may thus deliver orally administered therapeutic peptides...... to distant sections of the intestine or to the colon, where they may be absorbed, eventually by the help of absorption enhancers. Archaeal lipids and their semisynthetic derivatives may thus serve as biological source for the next generation oral drug delivery systems. The aim of this review is to present...

  6. Enhancement of efficacy of process water monitors in detecting heavy water leak in steam generator blow down lines

    International Nuclear Information System (INIS)

    Mitra, S.R.; Kohale, S.D.; Parida, B.K.; Gathe, G.D.; Pati, C.K.; Mudgal, B.K.; Niraj; Pawar, S.K.

    2006-01-01

    The Steam Generator (SG) serves as an interface between primary and secondary cycle in Pressurized Heavy Water Reactor (PHWR). Failure of steam generator tubes result in leaking of active heavy water in the secondary closed loop. In Tarapur Atomic Power Station-3 and 4 (TAPS- 3 and 4), Scintillator detectors are provided to detect on line heavy water leakages in SG and moderator heat exchangers by monitoring Nitrogen-16 ( 16 N) and Oxygen-19 ( 19 O) activities. Efficacy of detection of these activities at designed detector position on SG blow down line in presence of background radiation field is analysed theoretically. The count rate of 19 O and 16 N estimated at the detector position inside Reactor Building (RB) shows that detectors only respond to very high leak rates due to presence of high ambient radiation level even though sensitivity is appreciably good. For detector position in RB in the accessible areas and out side the RE containment, the travel time for the blow down feed water becomes moderately and very long respectively resulting in poor sensitivity. However the results show that wherever background levels is low, the efficacy of leak detection becomes considerably better than the results obtained when detector is placed inside RB. The study was validated during the reactor operation by recording the detector count rates due to prevalent ambient radiation level near to the detectors. Subsequently the detectors were relocated in an area inside RB where relocation was feasible, travel time of the blow down feed water was moderate and the area had an relatively low ambient radiation level. This paper discusses the methodology adopted during the study and results obtained during theoretical estimation and practical validation. (author)

  7. Enhancing Therapeutic Cellular Prostate Cancer Vaccines

    Science.gov (United States)

    2013-06-01

    Renaissance Eden Roc Beach Resort & Spa Miami Beach, FL Conference Co-Chairpersons: Olivera J. Finn University of Pittsburgh School of Medicine, Pittsburgh...150- pair case-control cohort. The cases (progression to systemic disease within five years of surgery ) and controls (no progression within seven...Loyola University Chicago, Stritch School of Medicine, Department of Cell Biology, Neurobiology and Anatomy and Department of Surgery , Maywood, IL

  8. Generation of chimeric minipigs by aggregating 4- to 8-cell-stage blastomeres from somatic cell nuclear transfer with the tracing of enhanced green fluorescent protein.

    Science.gov (United States)

    Ji, Huili; Long, Chuan; Feng, Chong; Shi, Ningning; Jiang, Yingdi; Zeng, Guomin; Li, Xirui; Wu, Jingjing; Lu, Lin; Lu, Shengsheng; Pan, Dengke

    2017-05-01

    Blastocyst complementation is an important technique for generating chimeric organs in organ-deficient pigs, which holds great promise for solving the problem of a shortage of organs for human transplantation procedures. Porcine chimeras have been generated using embryonic germ cells, embryonic stem cells, and induced pluripotent stem cells; however, there are no authentic pluripotent stem cells for pigs. In previous studies, blastomeres from 4- to 8-cell-stage parthenogenetic embryos were able to generate chimeric fetuses efficiently, but the resulting fetuses did not produce live-born young. Here, we used early-stage embryos from somatic cell nuclear transfer (SCNT) to generate chimeric piglets by the aggregation method. Then, the distribution of chimerism in various tissues and organs was observed through the expression of enhanced green fluorescent protein (EGFP). Initially, we determined whether 4- to 8- or 8- to 16-cell-stage embryos were more suitable to generate chimeric piglets. Chimeras were produced by aggregating two EGFP-tagged Wuzhishan minipig (WZSP) SCNT embryos and two Bama minipig (BMP) SCNT embryos. The chimeric piglets were identified by coat color and microsatellite and swine leukocyte antigen analyses. Moreover, the distribution of chimerism in various tissues and organs of the piglets was evaluated by EGFP expression. We found that more aggregated embryos were produced using 4- to 8-cell-stage embryos (157/657, 23.9%) than 8- to 16-cell-stage embryos (100/499, 20.0%). Thus, 4- to 8-cell-stage embryos were used for the generation of chimeras. The rate of blastocysts development after aggregating WZSP with BMP embryos was 50.6%. Transfer of 391 blastocysts developed from 4- to 8-cell-stage embryos to five recipients gave rise to 18 piglets, of which two (11.1%) were confirmed to be chimeric by their coat color and microsatellite examination of the skin. One of the chimeric piglets died at 35 days and was subsequently autopsied, whereas the

  9. Enhanced Emission by Accumulated Charges at Organic/Metal Interfaces Generated during the Reverse Bias of Organic Light Emitting Diodes

    Directory of Open Access Journals (Sweden)

    Soichiro Nozoe

    2017-10-01

    Full Text Available A high frequency rectangular alternating voltage was applied to organic light emitting diodes (OLEDs with the structure ITO/TPD/Alq3/Al and ITO/CoPc/Alq3/Al, where ITO is indium-tin-oxide, TPD is 4,4′-bis[N-phenyl-N-(m-tolylamino]biphenyl, CoPc is cobalt phthalocyanine, and Alq3 is Tris(8-quinolinolatoaluminum, and the effect on emission of the reverse bias was examined. The results reveal that the emission intensity under an alternating reverse-forward bias is greater than that under an alternating zero-forward bias. The difference in the emission intensity (∆I increased both for decreasing frequency and increasing voltage level of the reverse bias. In particular, the change in emission intensity was proportional to the voltage level of the reverse bias given the same frequency. To understand ΔI, this paper proposes a model in which an OLED works as a capacitor under reverse bias, where positive and negative charges accumulate on the metal/organic interfaces. In this model, the emission enhancement that occurs during the alternating reverse-forward bias is rationalized as a result of the charge accumulation at the organic/metal interfaces during the reverse bias, which possibly modulates the vacuum level shifts at the organic/metal interfaces to reduce both the hole injection barrier at the organic/ITO interface and the electron injection barrier at the organic/Al interface under forward bias.

  10. Enhanced power generation in annular single-chamber microbial fuel cell via optimization of electrode spacing using chocolate industry wastewater.

    Science.gov (United States)

    Noori, Parisa; Najafpour Darzi, Ghasem

    2016-05-01

    Development and practical application of microbial fuel cell (MFC) is restricted because of the limitations such as low power output. To overcome low power limitation, the optimization of specific parameters including electrode materials and surface area, electrode spacing, and MFC's cell shape was investigated. To the best of our knowledge, no investigation has been reported in the literature to implement an annular single-chamber microbial fuel cell (ASCMFC) using chocolate industry wastewater. ASCMFC was fabricated via optimization of the stated parameters. The aspects of ASCMFC were comprehensively examined. In this study, the optimization of electrode spacing and its impact on performance of the ASCMFC were conducted. Reduction of electrode spacing by 46.15% (1.3-0.7 cm) resulted in a decrease in internal resistance from 100 to 50 Ω, which enhanced the power density and current output to 22.898 W/m(3) and 6.42 mA, respectively. An optimum electrode spacing of 0.7 cm was determined. Through this paper, the effects of these parameters and the performance of ASCMFC are also evaluated. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  11. Ion beam enhancement in magnetically insulated ion diodes for high-intensity pulsed ion beam generation in non-relativistic mode

    Science.gov (United States)

    Zhu, X. P.; Zhang, Z. C.; Pushkarev, A. I.; Lei, M. K.

    2016-01-01

    High-intensity pulsed ion beam (HIPIB) with ion current density above Child-Langmuir limit is achieved by extracting ion beam from anode plasma of ion diodes with suppressing electron flow under magnetic field insulation. It was theoretically estimated that with increasing the magnetic field, a maximal value of ion current density may reach nearly 3 times that of Child-Langmuir limit in a non-relativistic mode and close to 6 times in a highly relativistic mode. In this study, the behavior of ion beam enhancement by magnetic insulation is systematically investigated in three types of magnetically insulated ion diodes (MIDs) with passive anode, taking into account the anode plasma generation process on the anode surface. A maximal enhancement factor higher than 6 over the Child-Langmuir limit can be obtained in the non-relativistic mode with accelerating voltage of 200-300 kV. The MIDs differ in two anode plasma formation mechanisms, i.e., surface flashover of a dielectric coating on the anode and explosive emission of electrons from the anode, as well as in two insulation modes of external-magnetic field and self-magnetic field with either non-closed or closed drift of electrons in the anode-cathode (A-K) gap, respectively. Combined with ion current density measurement, energy density characterization is employed to resolve the spatial distribution of energy density before focusing for exploring the ion beam generation process. Consistent results are obtained on three types of MIDs concerning control of neutralizing electron flows for the space charge of ions where the high ion beam enhancement is determined by effective electron neutralization in the A-K gap, while the HIPIB composition of different ion species downstream from the diode may be considerably affected by the ion beam neutralization during propagation.

  12. Ion beam enhancement in magnetically insulated ion diodes for high-intensity pulsed ion beam generation in non-relativistic mode

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, X. P. [Key Laboratory of Materials Modification by Laser, Ion, and Electron Beams, Ministry of Education, Dalian University of Technology, Dalian 116024 (China); Surface Engineering Laboratory, School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024 (China); Zhang, Z. C.; Lei, M. K., E-mail: surfeng@dlut.edu.cn [Surface Engineering Laboratory, School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024 (China); Pushkarev, A. I. [Surface Engineering Laboratory, School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024 (China); Laboratory of Beam and Plasma Technology, High Technologies Physics Institute, Tomsk Polytechnic University, 30, Lenin Ave, 634050 Tomsk (Russian Federation)

    2016-01-15

    High-intensity pulsed ion beam (HIPIB) with ion current density above Child-Langmuir limit is achieved by extracting ion beam from anode plasma of ion diodes with suppressing electron flow under magnetic field insulation. It was theoretically estimated that with increasing the magnetic field, a maximal value of ion current density may reach nearly 3 times that of Child-Langmuir limit in a non-relativistic mode and close to 6 times in a highly relativistic mode. In this study, the behavior of ion beam enhancement by magnetic insulation is systematically investigated in three types of magnetically insulated ion diodes (MIDs) with passive anode, taking into account the anode plasma generation process on the anode surface. A maximal enhancement factor higher than 6 over the Child-Langmuir limit can be obtained in the non-relativistic mode with accelerating voltage of 200–300 kV. The MIDs differ in two anode plasma formation mechanisms, i.e., surface flashover of a dielectric coating on the anode and explosive emission of electrons from the anode, as well as in two insulation modes of external-magnetic field and self-magnetic field with either non-closed or closed drift of electrons in the anode-cathode (A-K) gap, respectively. Combined with ion current density measurement, energy density characterization is employed to resolve the spatial distribution of energy density before focusing for exploring the ion beam generation process. Consistent results are obtained on three types of MIDs concerning control of neutralizing electron flows for the space charge of ions where the high ion beam enhancement is determined by effective electron neutralization in the A-K gap, while the HIPIB composition of different ion species downstream from the diode may be considerably affected by the ion beam neutralization during propagation.

  13. Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

    Science.gov (United States)

    Chen, Kuan-Ju

    Over the past decades, significant efforts have been devoted to explore the use of various nanoparticle-based systems in the field of nanomedicine, including molecular imaging and therapy. Supramolecular synthetic approaches have attracted lots of attention due to their flexibility, convenience, and modularity for producing nanoparticles. In this dissertation, the developmental story of our size-controllable supramolecular nanoparticles (SNPs) will be discussed, as well as their use in specific biomedical applications. To achieve the self-assembly of SNPs, the well-characterized molecular recognition system (i.e., cyclodextrin/adamantane recognition) was employed. The resulting SNPs, which were assembled from three molecular building blocks, possess incredible stability in various physiological conditions, reversible size-controllability and dynamic disassembly that were exploited for various in vitro and in vivo applications. An advantage of using the supramolecular approach is that it enables the convenient incorporation of functional ligands onto SNP surface that confers functionality ( e.g., targeting, cell penetration) to SNPs. We utilized SNPs for molecular imaging such as magnetic resonance imaging (MRI) and positron emission tomography (PET) by introducing reporter systems (i.e., radio-isotopes, MR contrast agents, and fluorophores) into SNPs. On the other hand, the incorporation of various payloads, including drugs, genes and proteins, into SNPs showed improved delivery performance and enhanced therapeutic efficacy for these therapeutic agents. Leveraging the powers of (i) a combinatorial synthetic approach based on supramolecular assembly and (ii) a digital microreactor, a rapid developmental pathway was developed that is capable of screening SNP candidates for the ideal structural and functional properties that deliver optimal performance. Moreover, SNP-based theranostic delivery systems that combine reporter systems and therapeutic payloads into a

  14. In situ generation of steam and alkaline surfactant for enhanced oil recovery using an exothermic water reactant (EWR)

    Science.gov (United States)

    Robertson, Eric P

    2011-05-24

    A method for oil recovery whereby an exothermic water reactant (EWR) encapsulated in a water soluble coating is placed in water and pumped into one or more oil wells in contact with an oil bearing formation. After the water carries the EWR to the bottom of the injection well, the water soluble coating dissolves and the EWR reacts with the water to produce heat, an alkali solution, and hydrogen. The heat from the EWR reaction generates steam, which is forced into the oil bearing formation where it condenses and transfers heat to the oil, elevating its temperature and decreasing the viscosity of the oil. The aqueous alkali solution mixes with the oil in the oil bearing formation and forms a surfactant that reduces the interfacial tension between the oil and water. The hydrogen may be used to react with the oil at these elevated temperatures to form lighter molecules, thus upgrading to a certain extent the oil in situ. As a result, the oil can flow more efficiently and easily through the oil bearing formation towards and into one or more production wells.

  15. Control of threshold enhancements in harmonic generation by atoms in a two-color laser field with orthogonal polarizations

    Science.gov (United States)

    Starace, Anthony F.; Frolov, M. V.; Manakov, N. L.; Sarantseva, T. S.; Silaev, A. A.; Vvedenskii, N. V.

    2017-04-01

    Threshold phenomena (or channel-closing effects) are analyzed in high-order harmonic generation (HHG) by atoms in a two-color laser field with orthogonal linearly polarized components of a fundamental field and its second harmonic. We show that the threshold behavior of HHG rates for the case of a weak second harmonic component is sensitive to the parity of a closing multiphoton ionization channel and the spatial symmetry of the initial bound state of the target atom, while for the case of comparable intensities of both components, suppression of threshold phenomena is observed as the relative phase between the components of a two-color field varies. A quantum orbit analysis as well as phenomenological considerations in terms of Baz' theory of threshold phenomena are presented in order to describe and explain the major features of threshold phenomena in HHG by a two-color field. Work supported in part by NSF Grant No. PHYS-1505492 (AFS), by Russian Science Foundation Grant No. 15-12-10033 (MVF, TSS, AAS, NVV), and by the Ministry of Education & Science of the Russian Federation Project No. 1019 (NLM).

  16. Mixed Domains Enhance Charge Generation and Extraction in Bulk-Heterojunction Solar Cells with Small-Molecule Donors

    KAUST Repository

    Alqahtani, Obaid

    2018-03-25

    The interplay between nanomorphology and efficiency of polymer-fullerene bulk-heterojunction (BHJ) solar cells has been the subject of intense research, but the generality of these concepts for small-molecule (SM) BHJs remains unclear. Here, the relation between performance; charge generation, recombination, and extraction dynamics; and nanomorphology achievable with two SM donors benzo[1,2-b:4,5-b]dithiophene-pyrido[3,4-b]-pyrazine BDT(PPTh), namely SM1 and SM2, differing by their side-chains, are examined as a function of solution additive composition. The results show that the additive 1,8-diiodooctane acts as a plasticizer in the blends, increases domain size, and promotes ordering/crystallinity. Surprisingly, the system with high domain purity (SM1) exhibits both poor exciton harvesting and severe charge trapping, alleviated only slightly with increased crystallinity. In contrast, the system consisting of mixed domains and lower crystallinity (SM2) shows both excellent exciton harvesting and low charge recombination losses. Importantly, the onset of large, pure crystallites in the latter (SM2) system reduces efficiency, pointing to possible differences in the ideal morphologies for SM-based BHJ solar cells compared with polymer-fullerene devices. In polymer-based systems, tie chains between pure polymer crystals establish a continuous charge transport network, whereas SM-based active layers may in some cases require mixed domains that enable both aggregation and charge percolation to the electrodes.

  17. Nanophasic biodegradation enhances the durability and biocompatibility of magnesium alloys for the next-generation vascular stents

    Science.gov (United States)

    Mao, Lin; Shen, Li; Niu, Jialin; Zhang, Jian; Ding, Wenjiang; Wu, Yu; Fan, Rong; Yuan, Guangyin

    2013-09-01

    Biodegradable metal alloys emerge as a new class of biomaterials for tissue engineering and medical devices such as cardiovascular stents. Deploying biodegradable materials to fabricate stents not only obviates a second surgical intervention for implant removal but also circumvents the long-term foreign body effect of permanent implants. However, these materials for stents suffer from an un-controlled degradation rate, acute toxic responses, and rapid structural failure presumably due to a non-uniform, fast corrosion process. Here we report that highly uniform, nanophasic degradation is achieved in a new Mg alloy with unique interstitial alloying composition as the nominal formula Mg-2.5Nd-0.2Zn-0.4Zr (wt%, hereafter, denoted as JDBM). This material exhibits highly homogeneous nanophasic biodegradation patterns as compared to other biodegradable metal alloy materials. Consequently it has significantly reduced degradation rate determined by electrochemical characterization. The in vitro cytotoxicity test using human vascular endothelial cells indicates excellent biocompatibility and potentially minimal toxic effect on arterial vessel walls. Finally, we fabricated a cardiovascular stent using JDBM and performed in vivo long-term assessment via implantation of this stent in an animal model. The results confirmed the reduced degradation rate in vivo, excellent tissue compatibility and long-term structural and mechanical durability. Thus, this new Mg-alloy with highly uniform nanophasic biodegradation represents a major breakthrough in the field and a promising material for manufacturing the next generation biodegradable vascular stents.

  18. Next generation enhancement of cements by the addition of industrial wastes and subsequent treatment with supercritical CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, C.M.V.; Rubin, J.B.; Carey, J.W. [Los Alamos National Lab., NM (United States); Jones, R. [Materials Technology Ltd., Reno, NV (United States); Baglin, F.G. [Univ. of Nevada, Reno, NV (United States). Chemical Physics Program

    1997-09-01

    The natural curing reactions which occur in a standard portland cement involve the formation of portlandite, Ca(OH){sub 2}, and calcium silicate hydrates, CSH. Over time, the cured cement abstracts carbon dioxide, CO{sub 2}, from the air, converting the portlandite and CSH to calcium carbonate, CaCO{sub 3}. It turns out, however, that this secondary conversion results in the blockage and/or closure of pores, drastically slowing the reaction rate with time. By exposing a portland cement to supercritical CO{sub 2} (SCCO{sub 2}), it is found that the carbonation reaction can be greatly accelerated. This acceleration is due to (1) the ability of the supercritical fluid to penetrate into the pores of the cement, providing continuous availability of fresh reactant, in hyper-stoichiometric concentrations; and (2) the solubility of the reaction product in the supercritical fluid, facilitating its removal. By accelerating the natural aging reactions, a chemically stable product is formed having reduced porosity, permeability and pH, while at the same time significantly enhancing the mechanical strength. The supercritical CO{sub 2} treatment process also removes a majority of the hydrogenous material from the cement, and sequesters large amounts of carbon dioxide, permanently removing it from the environment. The authors describe the general features of supercritical fluids, as well as the application of these fluids to the treatment of cements containing industrial waste. Some of the issues concerning the economic feasibility of industrial scale-up will be addressed. Finally, some initial results of physical property measurements made on portland cements before and after supercritical fluid CO{sub 2} treatment will be presented.

  19. Phosphate Shifted Oxygen Reduction Pathway on Fe@Fe2O3Core-Shell Nanowires for Enhanced Reactive Oxygen Species Generation and Aerobic 4-Chlorophenol Degradation.

    Science.gov (United States)

    Mu, Yi; Ai, Zhihui; Zhang, Lizhi

    2017-07-18

    Phosphate ions widely exist in the environment. Previous studies revealed that the adsorption of phosphate ions on nanoscale zerovalent iron would generate a passivating oxide shell to block reactive sites and thus decrease the direct pollutant reduction reactivity of zerovalent iron. Given that molecular oxygen activation process is different from direct pollutant reduction with nanoscale zerovalent iron, it is still unclear how phosphate ions will affect molecular oxygen activation and reactive oxygen species generation with nanoscale zerovalent iron. In this study, we systematically studied the effect of phosphate ions on molecular oxygen activation with Fe@Fe 2 O 3 nanowires, a special nanoscale zerovalent iron, taking advantages of rotating ring disk electrochemical analysis. It was interesting to find that the oxygen reduction pathway on Fe@Fe 2 O 3 nanowires was gradually shifted from a four-electron reduction pathway to a sequential one-electron reduction one, along with increasing the phosphate ions concentration from 0 to 10 mmol·L -1 . This oxygen reduction pathway change greatly enhanced the molecular oxygen activation and reactive oxygen species generation performances of Fe@Fe 2 O 3 nanowires, and thus increased their aerobic 4-chlorophenol degradation rate by 10 times. These findings shed insight into the possible roles of widely existed phosphate ions in molecular oxygen activation and organic pollutants degradation with nanoscale zerovalent iron.

  20. Coordinated Control of Superconducting Fault Current Limiter and Superconducting Magnetic Energy Storage for Transient Performance Enhancement of Grid-Connected Photovoltaic Generation System

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2017-01-01

    Full Text Available In regard to the rapid development of renewable energy sources, more and more photovoltaic (PV generation systems have been connected to main power networks, and it is critical to enhance their transient performance under short-circuit faults conditions. This paper proposes and studies the coordinated control of a flux-coupling-type superconducting fault current limiter (SFCL and a superconducting magnetic energy storage (SMES, to improve the fault ride through (FRT capability and smooth the power fluctuation of a grid-connected PV generation system. Theoretical analyses of the device structure, operating principle and control strategy are conducted, and a detailed simulation model of 100 kW class PV generation system is built in MATLAB/SIMULINK. During the simulations of the symmetrical and asymmetrical faults, the maximum power point tracking (MPPT control is disabled, and four different cases including without auxiliary, with SFCL, with SMES, and with SFCL-SMES, are compared. From the demonstrated results, the combination of without MPPT and with SFCL-SMES can more efficiently improve the point of common coupling (PCC voltage sag, inhibit the DC-link overvoltage and alleviate the power fluctuation. Finally, a preliminary parameter optimization method is suggested for the SFCL and the SMES, and it is helpful to promote their future application in the real PV projects.

  1. One-dimensional Z-scheme TiO{sub 2}/WO{sub 3}/Pt heterostructures for enhanced hydrogen generation

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Hongqing [School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001 (China); State Centre for International Cooperation on Designer Low-carbon and Environmental Materials (SCICDLCEM), Zhengzhou University, Zhengzhou 450001, Henan (China); Zhang, Peng, E-mail: Zhangp@zzu.edu.cn [School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001 (China); State Centre for International Cooperation on Designer Low-carbon and Environmental Materials (SCICDLCEM), Zhengzhou University, Zhengzhou 450001, Henan (China); Hu, Junhua, E-mail: Hujh@zzu.edu.cn [School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001 (China); State Centre for International Cooperation on Designer Low-carbon and Environmental Materials (SCICDLCEM), Zhengzhou University, Zhengzhou 450001, Henan (China); Pan, Jimin [School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001 (China); Fan, Jiajie [School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001 (China); State Centre for International Cooperation on Designer Low-carbon and Environmental Materials (SCICDLCEM), Zhengzhou University, Zhengzhou 450001, Henan (China); Shao, Guosheng [School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001 (China); State Centre for International Cooperation on Designer Low-carbon and Environmental Materials (SCICDLCEM), Zhengzhou University, Zhengzhou 450001, Henan (China); Institute for Renewable Energy and Environmental Technologies, University of Bolton, Bolton BL35AB (United Kingdom)

    2017-01-01

    Graphical abstract: We reported one-dimensional solid-state Z-scheme photosynthetic heterojunction system with Pt nanoparticle as an electron collector and WO{sub 3} as a hole collector, leading to effective charge separation. - Highlights: • The composite nanofibers were fabricated by facile electrospinning technique. • The composite nanofibers exhibited enhanced activity for H{sub 2} evolution. • Enhanced activity is due to the formation of Z-scheme TiO{sub 2}/WO{sub 3}/Pt heterojunction. - Abstract: One-dimensional Z-scheme TiO{sub 2}/WO{sub 3}/Pt heterostructures were fabricated by integrating a facile electrospinning technique and subsequent annealing in air. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and UV–vis diffuse reflectance spectroscopy, were used to characterize the as-fabricated samples. The results showed that the H{sub 2}-generation of the as-fabricated one-dimensional Z-scheme TiO{sub 2}/WO{sub 3}/Pt heterostructures (S2) was greatly enhanced compared with pure TiO{sub 2} nanofibers (S0) and TiO{sub 2}/WO{sub 3} nanofibers (S1). The enhanced photocatalyst activities were mainly attributed to the solid-state Z-scheme photosynthetic heterojunction system with Pt nanoparticle as an electron collector and WO{sub 3} as a hole collector, leading to effective charge separation on these semiconductors, which were evidenced by electrochemical impedance spectroscopy (EIS) and photocurrent analysis.

  2. Thymic Atrophy: Experimental Studies and Therapeutic Interventions.

    Science.gov (United States)

    Majumdar, S; Nandi, D

    2018-01-01

    The thymus is essential for T cell development and maturation. It is extremely sensitive to atrophy, wherein loss in cellularity of the thymus and/or disruption of the thymic architecture occur. This may lead to lower naïve T cell output and limited TCR diversity. Thymic atrophy is often associated with ageing. What is less appreciated is that proper functioning of the thymus is critical for reduction in morbidity and mortality associated with various clinical conditions including infections and transplantation. Therefore, therapeutic interventions which possess thymopoietic potential and lower thymic atrophy are required. These treatments enhance thymic output, which is a vital factor in generating favourable outcomes in clinical conditions. In this review, experimental studies on thymic atrophy in rodents and clinical cases where the thymus atrophies are discussed. In addition, mechanisms leading to thymic atrophy during ageing as well as during various stress conditions are reviewed. Therapies such as zinc supplementation, IL7 administration, leptin treatment, keratinocyte growth factor administration and sex steroid ablation during thymic atrophy involving experiments in animals and various clinical scenarios are reviewed. Interventions that have been used across different scenarios to reduce the extent of thymic atrophy and enhance its output are discussed. This review aims to speculate on the roles of combination therapies, which by acting additively or synergistically may further alleviate thymic atrophy and boost its function, thereby strengthening cellular T cell responses. © 2017 The Foundation for the Scandinavian Journal of Immunology.

  3. Formation of SiO2 film by chemical vapor deposition enhanced by atomic species extracted from a surface-wave generated plasma

    Science.gov (United States)

    Okada, H.; Baba, M.; Furukawa, M.; Yamane, K.; Sekiguchi, H.; Wakahara, A.

    2017-01-01

    In this study, we have investigated SiO2 deposition by chemical vapor deposition enhanced by neutral oxygen at the ground state extracted from a surface-wave generated plasma proposed by our group at 350°C using hexamethyldisilane (HMDS) as a precursor. Good properties of deposited SiO2 having refractive index of n = 1.45-1.46 have been confirmed by ellipsometry. Stoichiometric SiO2 was also confirmed by X-ray photoelectron spectroscopy (XPS) with single peak of Si 2p and O 1s. High quality SiO2 film deposition was also confirmed by Fourier transform infrared spectrometer (FT-IR) analysis indicating formation of chemical bonding in SiO2 with no unwanted bonds due to -OH or -CH3 groups.

  4. Dynamic transcriptional control of macrophage miRNA signature via inflammation responsive enhancers revealed using a combination of next generation sequencing-based approaches.

    Science.gov (United States)

    Czimmerer, Zsolt; Horvath, Attila; Daniel, Bence; Nagy, Gergely; Cuaranta-Monroy, Ixchelt; Kiss, Mate; Kolostyak, Zsuzsanna; Poliska, Szilard; Steiner, Laszlo; Giannakis, Nikolas; Varga, Tamas; Nagy, Laszlo

    2018-01-01

    MicroRNAs are important components of the post-transcriptional fine-tuning of macrophage gene expression in physiological and pathological conditions. However, the mechanistic underpinnings and the cis-acting genomic factors of how macrophage polarizing signals induce miRNA expression changes are not well characterized. Therefore, we systematically evaluated the transcriptional basis underlying the inflammation-mediated regulation of macrophage microRNome using the combination of different next generation sequencing datasets. We investigated the LPS-induced expression changes at mature miRNA and pri-miRNA levels in mouse macrophages utilizing a small RNA-seq method and publicly available GRO-seq dataset, respectively. Next, we identified an enhancer set associated with LPS-responsive pri-miRNAs based on publicly available H3K4 mono-methylation-specific ChIP-seq and GRO-seq datasets. This enhancer set was further characterized by the combination of publicly available ChIP and ATAC-seq datasets. Finally, direct interactions between the miR-155-coding genomic region and its distal regulatory elements were identified using a 3C-seq approach. Our analysis revealed 15 robustly LPS-regulated miRNAs at the transcriptional level. In addition, we found that these miRNA genes are associated with an inflammation-responsive enhancer network. Based on NFκB-p65 and JunB transcription factor binding, we showed two distinct enhancer subsets associated with LPS-activated miRNAs that possess distinct epigenetic characteristics and LPS-responsiveness. Finally, our 3C-seq analysis revealed the LPS-induced extensive reorganization of the pri-miR-155-associated functional chromatin domain as well as chromatin loop formation between LPS-responsive enhancers and the promoter region. Our genomic approach successfully combines various genome-wide datasets and allows the identification of the putative regulatory elements controlling miRNA expression in classically activated macrophages

  5. Generation of knock-in mice that express nuclear enhanced green fluorescent protein and tamoxifen-inducible Cre recombinase in the notochord from Foxa2 and T loci.

    Science.gov (United States)

    Imuta, Yu; Kiyonari, Hiroshi; Jang, Chuan-Wei; Behringer, Richard R; Sasaki, Hiroshi

    2013-03-01

    The node and the notochord are important embryonic signaling centers that control embryonic pattern formation. Notochord progenitor cells present in the node and later in the posterior end of the notochord move anteriorly to generate the notochord. To understand the dynamics of cell movement during notochord development and the molecular mechanisms controlling this event, analyses of cell movements using time-lapse imaging and conditional manipulation of gene activities are required. To achieve this goal, we generated two knock-in mouse lines that simultaneously express nuclear enhanced green fluorescent protein (EGFP) and tamoxifen-inducible Cre, CreER(T2) , from two notochord gene loci, Foxa2 and T (Brachury). In Foxa2(nEGFP-CreERT2/+) and T(nEGFP-CreERT2/+) embryos, nuclei of the Foxa2 or T-expressing cells, which include the node, notochord, and endoderm (Foxa2) or wide range of posterior mesoderm (T), were labeled with EGFP at intensities that can be used for live imaging. Cre activity was also induced in cells expressing Foxa2 and T 1 day after tamoxifen administration. These mice are expected to be useful tools for analyzing the mechanisms of notochord development. Copyright © 2013 Wiley Periodicals, Inc.

  6. Numerical Simulation and Optimization of Enhanced Oil Recovery by the In Situ Generated CO2 Huff-n-Puff Process with Compound Surfactant

    Directory of Open Access Journals (Sweden)

    Yong Tang

    2016-01-01

    Full Text Available This paper presents the numerical investigation and optimization of the operating parameters of the in situ generated CO2 Huff-n-Puff method with compound surfactant on the performance of enhanced oil recovery. First, we conducted experiments of in situ generated CO2 and surfactant flooding. Next, we constructed a single-well radial 3D numerical model using a thermal recovery chemical flooding simulator to simulate the process of CO2 Huff-n-Puff. The activation energy and reaction enthalpy were calculated based on the reaction kinetics and thermodynamic models. The interpolation parameters were determined through history matching a series of surfactant core flooding results with the simulation model. The effect of compound surfactant on the Huff-n-Puff CO2 process was demonstrated via a series of sensitivity studies to quantify the effects of a number of operation parameters including the injection volume and mole concentration of the reagent, the injection rate, the well shut-in time, and the oil withdrawal rate. Based on the daily production rate during the period of Huff-n-Puff, a desirable agreement was shown between the field applications and simulated results.

  7. Nonlinear Observer-Based Robust Passive Control of Doubly-Fed Induction Generators for Power System Stability Enhancement via Energy Reshaping

    Directory of Open Access Journals (Sweden)

    Jun Dong

    2017-07-01

    Full Text Available The large-scale penetration of wind power might lead to degradation of the power system stability due to its inherent feature of randomness. Hence, proper control designs which can effectively handle various uncertainties become very crucial. This paper designs a novel robust passive control (RPC scheme of a doubly-fed induction generator (DFIG for power system stability enhancement. The combinatorial effect of generator nonlinearities and parameter uncertainties, unmodelled dynamics, wind speed randomness, is aggregated into a perturbation, which is rapidly estimated by a nonlinear extended state observer (ESO in real-time. Then, the perturbation estimate is fully compensated by a robust passive controller to realize a globally consistent control performance, in which the energy of the closed-loop system is carefully reshaped through output feedback passification, such that a considerable system damping can be injected to improve the transient responses of DFIG in various operation conditions of power systems. Six case studies are carried out while simulation results verify that RPC can rapidly stabilize the disturbed DFIG system much faster with less overshoot, as well as supress power oscillations more effectively compared to that of linear proportional-integral-derivative (PID control and nonlinear feedback linearization control (FLC.

  8. TN trademark FLEX: a new generation of fluorocarbon o-rings developed by COGEMA logistics with enhanced characteristics at low temperature (-40 C)

    International Nuclear Information System (INIS)

    Issard, H.; Andre, R.

    2004-01-01

    Three main types of elastomers are used for the sealing of radioactive material transport casks with elastomeric gaskets: EPDM, fluorocarbons type Viton registered (standard designation: FKM) and silicon rubbers. Each rubber has specific characteristics in terms of temperature range, permeability, coefficient of expansion.. For the casks where high temperatures can be reached (200 C in continuous using), FKM gaskets are generally used. The problem is that this type of gasket does not guarantee the leaktightness at -40 C, which is a regulatory requirement. Two solutions are generally used: to specify a minimum heat load or a minimum ambient temperature. The direct consequence is that it is impossible to get B(U) approvals on the new concepts when FKM gaskets are used but only B(M) approvals, which generate significant additional justification costs (multiple submittals of Safety Analysis Reports, calculation of the minimum heat load or of the minimum ambient temperature..). Thus, it is important to develop gaskets with the same performance as FKM gaskets at high temperature but with enhanced performance at low temperature (and mainly, which guarantee the leaktightness at -40 C). COGEMA LOGISTICS has qualified a new generation of fluorocarbon O-rings (TN trademark FLEX gaskets) which can be used in continuous service on a -47 C/+200 C temperature range. TN trademark FLEX gaskets will be implemented on new casks designs

  9. Reactor-produced therapeutic radioisotopes

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.

    2002-01-01

    The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

  10. Anaerobic Coculture of Microalgae with Thermosipho globiformans and Methanocaldococcus jannaschii at 68°C Enhances Generation of n-Alkane-Rich Biofuels after Pyrolysis

    Science.gov (United States)

    Matsuyama, Shigeru; Igarashi, Kensuke; Utsumi, Motoo; Shiraiwa, Yoshihiro; Kuwabara, Tomohiko

    2013-01-01

    We tested different alga-bacterium-archaeon consortia to investigate the production of oil-like mixtures, expecting that n-alkane-rich biofuels might be synthesized after pyrolysis. Thermosipho globiformans and Methanocaldococcus jannaschii were cocultured at 68°C with microalgae f