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Sample records for optimised electroporation mediated

  1. Optimised electroporation mediated DNA vaccination for treatment of prostate cancer.

    LENUS (Irish Health Repository)

    Ahmad, Sarfraz

    2010-01-01

    , preventing tumour occurrence in 54% of treated animals. Vaccination with phPSA resulted in anti-hPSA Abs production and a significant production of IFNgamma was observed in immunised animals (p < 0.05). Immune responses were tumour specific and were transferable in adoptive T cell transfer experiments. CONCLUSIONS: This phPSA plasmid electroporation vaccination strategy can effectively activate tumour specific immune responses. Optimisation of the approach indicated that a four-dose regimen provided highest tumour protection. In vivo electroporation mediated vaccination is a safe and effective modality for the treatment of prostate cancer and has a potential to be used as a neo-adjuvant or adjuvant therapy.

  2. Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type.

    Science.gov (United States)

    Prevc, Ajda; Bedina Zavec, Apolonija; Cemazar, Maja; Kloboves-Prevodnik, Veronika; Stimac, Monika; Todorovic, Vesna; Strojan, Primoz; Sersa, Gregor

    2016-10-01

    Bystander effect, a known phenomenon in radiation biology, where irradiated cells release signals which cause damage to nearby, unirradiated cells, has not been explored in electroporated cells yet. Therefore, our aim was to determine whether bystander effect is present in electroporated melanoma cells in vitro, by determining viability of non-electroporated cells exposed to medium from electroporated cells and by the release of microvesicles as potential indicators of the bystander effect. Here, we demonstrated that electroporation of cells induces bystander effect: Cells exposed to electric pulses mediated their damage to the non-electroporated cells, thus decreasing cell viability. We have shown that shedding microvesicles may be one of the ways used by the cells to mediate the death signals to the neighboring cells. The murine melanoma B16F1 cell line was found to be more electrosensitive and thus more prone to bystander effect than the canine melanoma CMeC-1 cell line. In B16F1 cell line, bystander effect was present above the level of electropermeabilization of the cells, with the threshold at 800 V/cm. Furthermore, with increasing electric field intensities and the number of pulses, the bystander effect also increased. In conclusion, electroporation can induce bystander effect which may be mediated by microvesicles, and depends on pulse amplitude, repetition frequency and cell type.

  3. Efficacy of In Vivo Electroporation-Mediated IL-10 Gene Delivery on Survival of Skin Flaps.

    Science.gov (United States)

    Seyed Jafari, S Morteza; Shafighi, Maziar; Beltraminelli, Helmut; Weber, Benedikt; Schmid, Ralph A; Geiser, Thomas; Gazdhar, Amiq; Hunger, Robert E

    2018-04-01

    Despite advances in understanding the underlying mechanisms of flap necrosis and improvement in surgical techniques, skin flap necrosis after reconstructive surgery remains a crucial issue. We investigated the efficacy of electroporation-mediated IL-10 gene transfer to random skin flap with an aim to accelerate wound healing and improve skin flap survival. Nine male Wistar rats (300-330 g) were divided in two groups (a) control group (n = 5), only surgery no gene transfer, and (b) experimental group, received electroporation-mediated IL-10 gene transfer 24 h before the surgery as prophylaxis (n = 4). Random skin flap (McFarlane) was performed in both groups. Planimetry, Laser Doppler imaging, and immunohistochemistry were used to evaluate the effect of IL-10 gene transfer between study groups at day 7. Electroporation-mediated IL-10 gene transfer decreased percentage of flap necrosis (p value = 0.0159) and increased cutaneous perfusion compared to the control group (p value = 0.0159). In addition, Spearman's rank correlation showed a significant negative correlation between percentage of flap necrosis and Laser Index (p value = 0.0083, r -0.83, respectively). Furthermore, significantly higher mean CD31 + vessel density was detected in the experimental group compared to the control group (p value = 0.0159). Additionally, semi-quantitative image analysis showed lower inflammatory cell count in experimental group compared to control group (p value = 0.0317). In vivo electroporation-mediated IL-10 gene transfer reduced necrosis, enhanced survival and vascularity in the ischemic skin flap.

  4. Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.

    Science.gov (United States)

    Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G; Scholler, John; Levine, Bruce L; Albelda, Steven M; June, Carl H

    2010-11-15

    Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week after electroporation. Multiple injections of RNA CAR-electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(-/-) mice. Dramatic tumor reduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been growing in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes showing that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Copyright © 2010 AACR.

  5. Use of electroporation for high-molecular-weight DNA-mediated gene transfer.

    Science.gov (United States)

    Jastreboff, M M; Ito, E; Bertino, J R; Narayanan, R

    1987-08-01

    Electroporation was used to introduce high-molecular-weight DNA into murine hematopoietic cells and NIH3T3 cells. CCRF-CEM cells were stably transfected with SV2NEO plasmid and the genomic DNA from G-418-resistant clones (greater than 65 kb) was introduced into mouse bone marrow and NIH3T3 cells by electroporation. NEO sequences and expression were detected in the hematopoietic tissues of lethally irradiated mice, with 24% of individual spleen colonies expressing NEO. The frequency of genomic DNA transfer into NIH3T3 cells was 0.25 X 10(-3). Electroporation thus offers a powerful mode of gene transfer not only of cloned genes but also of high-molecular-weight DNA into cells.

  6. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha

    2015-01-01

    BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...... efficacy-and normal cell sensitivity. METHODS: Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780......), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p

  7. Electroporation-mediated in vivo gene delivery of the Na+/K+-ATPase pump reduced lung injury in a mouse model of lung contusion.

    Science.gov (United States)

    Machado-Aranda, David A; Suresh, M V; Yu, Bi; Raghavendran, Krishnan

    2012-01-01

    Lung contusion (LC) is an independent risk factor for acute respiratory distress syndrome. The final common pathway in ARDS involves accumulation of fluid in the alveoli. In this study, we demonstrate the application of a potential gene therapy approach by delivering the Na+/K+-ATPase pump subunits in a murine model of LC. We hypothesized that restoring the activity of the pump will result in removal of excess alveolar fluid and additionally reduce inflammation. Under anesthesia, C57/BL6 mice were struck along the right posterior axillary line 1 cm above the costal margin with a cortical contusion impactor. Immediately afterward, 100 μg of plasmid DNA coding for the α,β of the Na+/K+-ATPase pump were instilled into the lungs (LC-electroporation-pump group). Contusion only (LC-only) and a sham saline instillation group after contusion were used as controls (LC-electroporation-sham). By using a BTX 830 electroporator, eight electrical pulses of 200 V/cm field strength were applied transthoracically. Mice were killed at 24 hours, 48 hours, and 72 hours after delivery. Bronchial alveolar lavage was recollected to measure albumin and cytokines by enzyme-linked immunosorbent assay. Pulmonary compliance was measured, and lungs were subject to histopathologic analysis. After the electroporation and delivery of genes coding for the α,β subunits of the Na+/K+-ATPase pump, there was a significant mitigation of acute lung injury as evidenced by reduction in bronchial alveolar lavage levels of albumin, improved pressure volume curves, and reduced inflammation seen on histology. Electroporation-mediated gene transfer of the subunits of the Na+/K+-ATPase pump enhanced recovery from acute inflammatory lung injury after LC.

  8. CRY 1AB trangenic cowpea obtained by nodal electroporation ...

    African Journals Online (AJOL)

    Electroporation-mediated genetic transformation was used to introduce Cry 1 Ab insecticidal gene into cowpea. Nodal buds were electroporated in planta with a plasmid carrying the Cry 1Ab and antibiotic resistance npt II genes driven by a 35S CaMV promoter. T1 seeds derived from electroporated branches were selected ...

  9. Electroporation-mediated transfer of SOX trio genes (SOX-5, SOX-6, and SOX-9) to enhance the chondrogenesis of mesenchymal stem cells.

    Science.gov (United States)

    Kim, Hye-Joung; Im, Gun-Il

    2011-12-01

    The purpose of this study was to test the hypothesis that the SOX trio genes (SOX-5, SOX-6, and SOX-9) have a lower level of expression during the chondrogenic differentiation of mesenchymal stem cells (MSCs) compared with chondrocytes and that the electroporation-mediated gene transfer of SOX trio promotes chondrogenesis from human MSCs. An in vitro pellet culture was carried out using MSCs or chondrocytes at passage 3 and analyzed after 7 and 21 days. Then, MSCs were transfected with SOX trio genes and analyzed for the expression of chondrogenic markers after 21 days of in vitro culture. Without transforming growth factor-β1, the untransfected MSCs had a lower level of SOX trio gene and protein expression than chondrocytes. However, the level of SOX-9 gene expression increased in MSCs when treated with transforming growth factor-β1. GAG level significantly increased 7-fold in MSCs co-transfected with SOX trio, which was corroborated by Safranin-O staining. SOX trio co-transfection significantly increased COL2A1 gene and protein and decreased COL10A1 protein in MSCs. It is concluded that the SOX trio have a significantly lower expression in human MSCs than in chondrocytes and that the electroporation-mediated co-transfection of SOX trio enhances chondrogenesis and suppresses hypertrophy of human MSCs.

  10. Focused transhepatic electroporation mediated by hypersaline infusion through the portal vein in rat model. Preliminary results on differential conductivity

    Directory of Open Access Journals (Sweden)

    Pañella Clara

    2017-11-01

    Full Text Available Spread hepatic tumours are not suitable for treatment either by surgery or conventional ablation methods. The aim of this study was to evaluate feasibility and safety of selectively increasing the healthy hepatic conductivity by the hypersaline infusion (HI through the portal vein. We hypothesize this will allow simultaneous safe treatment of all nodules by irreversible electroporation (IRE when applied in a transhepatic fashion.

  11. Inhibition of TC-1 tumor progression by cotransfection of Saxatilin and IL-12 genes mediated by lipofection or electroporation.

    Science.gov (United States)

    Park, Y S; Kim, K S; Lee, Y K; Kim, J S; Baek, J Y; Huang, L

    2009-01-01

    Recently, a number of reports have demonstrated that coexpression of therapeutic genes having different anticancer mechanisms is a more effective strategy for anticancer gene therapy than single gene expression. Saxatilin, a novel disintegrin from snake venom, has recently been shown to have potent antiangiogenic functions, such as inhibition of platelet aggregation, bFGF-induced proliferation of HUVEC, and vitronectin-induced smooth muscle cell migration. IL-12 is a well-known immune modulator that promotes Thl-type antitumor immune responses and inhibits angiogenesis as well. The saxatilin and/or IL-12 genes were transfected intratumorally into C57BL/6 mice carrying TC-1 transformed mouse lung endothelial cells by either lipofection or electroporation. The plasmids encoding saxatilin and IL-12 were administered to tumor tissues via novel cationic liposomes consisting of dimyristyl-glutamyl-lysine (DMKE). On the other hand, expression of the genes was also induced by electroporation after naked pDNA injection to the tumor tissues. Lipofection of saxatilin and/or IL-12 genes appeared to be slightly more effective in inhibition of tumor growth than electroporation of the same genes. Cotransfection of saxatilin and IL-12 genes was clearly more effective than individual administration of either gene. This result implies that cotransfection of saxatilin and IL-12 genes represents an innovative modality for anticancer gene therapy.

  12. Electroporation driven delivery of both an IL-12 expressing plasmid and cisplatin synergizes to inhibit B16 melanoma tumor growth through an NK cell mediated tumor killing mechanism.

    Science.gov (United States)

    Kim, Ha; Sin, Jeong-Im

    2012-11-01

    Combined therapy using chemotherapeutic drugs and immunotherapeutics offers some promise for treating patients with cancer. In this study, we evaluated whether cisplatin delivered by intratumoral (IT)-electroporation (EP) might enhance antitumor activity against established B16 melanoma and whether further addition of intramuscular (IM)-EP of IL-12 cDNA to IT-EP of cisplatin might augment antitumor therapeutic activity, with a focus on the underlining antitumor mechanism(s). When tumor (7 mm)-bearing animals were treated locally with cisplatin by IT-EP, they showed tumor growth inhibition significantly more than those without IT-EP. Moreover, IL-12 cDNA delivered by IM-EP was also able to inhibit tumor growth significantly more than control vector delivery. This tumor growth inhibition was mediated by NK cells, but not CD4+ T or CD8+ T cells, as determined by immune cell subset depletion and IFN-γ induction. Moreover, concurrent therapy using IT-EP of cisplatin plus IM-EP of IL-12 cDNA displayed antitumor therapeutic synergy. This therapeutic synergy appeared to be mediated by increased sensitivity of cisplatin-treated tumors to NK cell-mediated tumor killing. Taken together, these data support that cisplatin delivery by IT-EP plus IL-12 gene delivery by IM-EP are more effective at inducing antitumor therapeutic responses through increased sensitivity of cisplatin-treated tumors to NK cell-mediated tumor killing. This combined approach might have some implication for treating melanoma in patients.

  13. Focused Transhepatic Electroporation Mediated by Hypersaline Infusion through the Portal Vein in Rat Model. Preliminary Results on Differential Conductivity.

    Science.gov (United States)

    Pañella, Clara; Castellví, Quim; Moll, Xavier; Quesada, Rita; Villanueva, Alberto; Iglesias, Mar; Naranjo, Dolores; Sánchez-Velázquez, Patricia; Andaluz, Anna; Grande, Luís; Ivorra, Antoni; Burdío, Fernando

    2017-12-01

    Spread hepatic tumours are not suitable for treatment either by surgery or conventional ablation methods. The aim of this study was to evaluate feasibility and safety of selectively increasing the healthy hepatic conductivity by the hypersaline infusion (HI) through the portal vein. We hypothesize this will allow simultaneous safe treatment of all nodules by irreversible electroporation (IRE) when applied in a transhepatic fashion. Sprague Dawley (Group A, n = 10) and Athymic rats with implanted hepatic tumour (Group B, n = 8) were employed. HI was performed (NaCl 20%, 3.8 mL/Kg) by trans-splenic puncture. Deionized serum (40 mL/Kg) and furosemide (2 mL/Kg) were simultaneously infused through the jugular vein to compensate hypernatremia. Changes in conductivity were monitored in the hepatic and tumour tissue. The period in which hepatic conductivity was higher than tumour conductivity was defined as the therapeutic window (TW). Animals were monitored during 1-month follow-up. The animals were sacrificed and selective samples were used for histological analysis. The overall survival rate was 82.4% after the HI protocol. The mean maximum hepatic conductivity after HI was 2.7 and 3.5 times higher than the baseline value, in group A and B, respectively. The mean maximum hepatic conductivity after HI was 1.4 times higher than tumour tissue in group B creating a TW to implement selective IRE. HI through the portal vein is safe when the hypersaline overload is compensated with deionized serum and it may provide a TW for focused IRE treatment on tumour nodules.

  14. In vivo real-time monitoring system of electroporation mediated control of transdermal and topical drug delivery.

    Science.gov (United States)

    Blagus, Tanja; Markelc, Bostjan; Cemazar, Maja; Kosjek, Tina; Preat, Veronique; Miklavcic, Damijan; Sersa, Gregor

    2013-12-28

    Electroporation (EP) is a physical method for the delivery of molecules into cells and tissues, including the skin. In this study, in order to control the degree of transdermal and topical drug delivery, EP at different amplitudes of electric pulses was evaluated. A new in vivo real-time monitoring system based on fluorescently labeled molecules was developed, for the quantification of transdermal and topical drug delivery. EP of the mouse skin was performed with new non-invasive multi-array electrodes, delivering different amplitudes of electric pulses ranging from 70 to 570 V, between the electrode pin pairs. Patches, soaked with 4 kDa fluorescein-isothiocyanate labeled dextran (FD), doxorubicin (DOX) or fentanyl (FEN), were applied to the skin before and after EP. The new monitoring system was developed based on the delivery of FD to and through the skin. FD relative quantity was determined with fluorescence microscopy imaging, in the treated region of the skin for topical delivery and in a segment of the mouse tail for transdermal delivery. The application of electric pulses for FD delivery resulted in enhanced transdermal delivery. Depending on the amplitude of electric pulses, it increased up to the amplitude of 360 V, and decreased at higher amplitudes (460 and 570 V). Topical delivery steadily enhanced with increasing the amplitude of the delivered electric pulses, being even higher than after tape stripping used as a positive control. The non-invasive monitoring of the delivery of DOX, a fluorescent chemotherapeutic drug, qualitatively and quantitatively confirmed the effects of EP at 360 and 570 V pulse amplitudes on topical and transdermal drug delivery. Delivery of FEN at 360 and 570 V pulse amplitudes verified the observed effects as obtained with FD and DOX, by the measured physiological responses of the mice as well as FEN plasma concentration. This study demonstrates that with the newly developed non-invasive multi-array electrodes and with the

  15. Perspectives on Transdermal Electroporation

    Science.gov (United States)

    Ita, Kevin

    2016-01-01

    Transdermal drug delivery offers several advantages, including avoidance of erratic absorption, absence of gastric irritation, painlessness, noninvasiveness, as well as improvement in patient compliance. With this mode of drug administration, there is no pre-systemic metabolism and it is possible to increase drug bioavailability and half-life. However, only a few molecules can be delivered across the skin in therapeutic quantities. This is because of the hindrance provided by the stratum corneum. Several techniques have been developed and used over the last few decades for transdermal drug delivery enhancement. These include sonophoresis, iontophoresis, microneedles, and electroporation. Electroporation, which refers to the temporary perturbation of the skin following the application of high voltage electric pulses, has been used to increase transcutaneous flux values by several research groups. In this review, transdermal electroporation is discussed and the use of the technique for percutaneous transport of low and high molecular weight compounds described. This review also examines our current knowledge regarding the mechanisms of electroporation and safety concerns arising from the use of this transdermal drug delivery technique. Safety considerations are especially important because electroporation utilizes high voltage pulses which may have deleterious effects in some cases. PMID:26999191

  16. In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells.

    Science.gov (United States)

    Sales, Natiely S; Silva, Jamile R; Aps, Luana R M M; Silva, Mariângela O; Porchia, Bruna F M M; Ferreira, Luís Carlos S; Diniz, Mariana O

    2017-12-19

    In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8 + T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8 + T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Handbook of electroporation

    CERN Document Server

    2017-01-01

    This major reference work is a one-shot knowledge base on electroporation and the use of pulsed electric fields of high intensity and their use in biology, medicine, biotechnology, and food and environmental technologies. The Handbook offers a widespread and well-structured compilation of 156 chapters ranging from the foundations to applications in industry and hospital. It is edited and written by most prominent researchers in the field. With regular updates and growing in its volume it is suitable for academic readers and researchers regardless of their disciplinary expertise, and will also be accessible to students and serious general readers. The Handbook's 276 authors have established scholarly credentials and come from a wide range of disciplines. This is crucially important in a highly interdisciplinary field of electroporation and the use of pulsed electric fields of high intensity and its applications in different fields from medicine, biology, food proce ssing, agriculture, process engineering, en...

  18. An optimized electroporation approach for efficient CRISPR/Cas9 genome editing in murine zygotes.

    Directory of Open Access Journals (Sweden)

    Simon E Tröder

    Full Text Available Electroporation of zygotes represents a rapid alternative to the elaborate pronuclear injection procedure for CRISPR/Cas9-mediated genome editing in mice. However, current protocols for electroporation either require the investment in specialized electroporators or corrosive pre-treatment of zygotes which compromises embryo viability. Here, we describe an easily adaptable approach for the introduction of specific mutations in C57BL/6 mice by electroporation of intact zygotes using a common electroporator with synthetic CRISPR/Cas9 components and minimal technical requirement. Direct comparison to conventional pronuclear injection demonstrates significantly reduced physical damage and thus improved embryo development with successful genome editing in up to 100% of living offspring. Hence, our novel approach for Easy Electroporation of Zygotes (EEZy allows highly efficient generation of CRISPR/Cas9 transgenic mice while reducing the numbers of animals required.

  19. Electroporation-induced electrosensitization.

    Directory of Open Access Journals (Sweden)

    Olga N Pakhomova

    Full Text Available BACKGROUND: Electroporation is a method of disrupting the integrity of cell membrane by electric pulses (EPs. Electrical modeling is widely employed to explain and study electroporation, but even most advanced models show limited predictive power. No studies have accounted for the biological consequences of electroporation as a factor that alters the cell's susceptibility to forthcoming EPs. METHODOLOGY/PRINCIPAL FINDINGS: We focused first on the role of EP rate for membrane permeabilization and lethal effects in mammalian cells. The rate was varied from 0.001 to 2,000 Hz while keeping other parameters constant (2 to 3,750 pulses of 60-ns to 9-µs duration, 1.8 to 13.3 kV/cm. The efficiency of all EP treatments was minimal at high rates and started to increase gradually when the rate decreased below a certain value. Although this value ranged widely (0.1-500 Hz, it always corresponded to the overall treatment duration near 10 s. We further found that longer exposures were more efficient irrespective of the EP rate, and that splitting a high-rate EP train in two fractions with 1-5 min delay enhanced the effects severalfold. CONCLUSIONS/SIGNIFICANCE: For varied experimental conditions, EPs triggered a delayed and gradual sensitization to EPs. When a portion of a multi-pulse exposure was delivered to already sensitized cells, the overall effect markedly increased. Because of the sensitization, the lethality in EP-treated cells could be increased from 0 to 90% simply by increasing the exposure duration, or the exposure dose could be reduced twofold without reducing the effect. Many applications of electroporation can benefit from accounting for sensitization, by organizing the exposure either to maximize sensitization (e.g., for sterilization or, for other applications, to completely or partially avoid it. In particular, harmful side effects of electroporation-based therapies (electrochemotherapy, gene therapies, tumor ablation include convulsions

  20. ATR-FTIR and Raman spectroscopic investigation of the electroporation-mediated transdermal delivery of a nanocarrier system containing an antitumour drug.

    Science.gov (United States)

    Balázs, Boglárka; Sipos, Péter; Danciu, Corina; Avram, Stefana; Soica, Codruta; Dehelean, Cristina; Varju, Gábor; Erős, Gábor; Budai-Szűcs, Mária; Berkó, Szilvia; Csányi, Erzsébet

    2016-01-01

    The aim of the present work was the optimization of the transdermal delivery of a lyotropic liquid crystal genistein-based formulation (LLC-GEN). LLC was chosen as medium in view of the poor solubility of GEN in water. Membrane diffusion and penetration studies were carried out with a Franz diffusion cell, through a synthetic membrane in vitro, a chick chorioallantoic membrane ex ovo, and ex vivo excised human epidermis. Thereafter, LLC-GEN was combined with electroporation (EP) to enhance the transdermal drug delivery. The synergistic effect of EP was verified by in vivo ATR-FTIR and ex vivo Raman spectroscopy on hairless mouse skin.

  1. Electroporation in food processing and biorefinery.

    Science.gov (United States)

    Mahnič-Kalamiza, Samo; Vorobiev, Eugène; Miklavčič, Damijan

    2014-12-01

    Electroporation is a method of treatment of plant tissue that due to its nonthermal nature enables preservation of the natural quality, colour and vitamin composition of food products. The range of processes where electroporation was shown to preserve quality, increase extract yield or optimize energy input into the process is overwhelming, though not exhausted; e.g. extraction of valuable compounds and juices, dehydration, cryopreservation, etc. Electroporation is--due to its antimicrobial action--a subject of research as one stage of the pasteurization or sterilization process, as well as a method of plant metabolism stimulation. This paper provides an overview of electroporation as applied to plant materials and electroporation applications in food processing, a quick summary of the basic technical aspects on the topic, and a brief discussion on perspectives for future research and development in the field. The paper is a review in the very broadest sense of the word, written with the purpose of orienting the interested newcomer to the field of electroporation applications in food technology towards the pertinent, highly relevant and more in-depth literature from the respective subdomains of electroporation research.

  2. Delineating the cell death mechanisms associated with skin electroporation.

    Science.gov (United States)

    Schultheis, Katherine; Smith, Trevor R F; Kiosses, William B; Kraynyak, Kimberly A; Wong, Amelia; Oh, Janet; Broderick, Kate Elizabeth

    2018-06-28

    The immune responses elicited following delivery of DNA vaccines to the skin has previously been shown to be significantly enhanced by the addition of electroporation (EP) to the treatment protocol. Principally, EP increases the transfection of pDNA into the resident skin cells. In addition to increasing the levels of in vivo transfection, the physical insult induced by EP is associated with activation of innate pathways which are believed to mediate an adjuvant effect, further enhancing DNA vaccine responses. Here, we have investigated the possible mechanisms associated with this adjuvant effect, primarily focusing on the cell death pathways associated with the skin EP procedure independent of pDNA delivery. Using the minimally invasive CELLECTRA®-3P intradermal electroporation device that penetrates the epidermal and dermal layers of the skin, we have investigated apoptotic and necrotic cell death in relation to the vicinity of the electrode needles and electric field generated. Employing the well-established TUNEL assay, we detected apoptosis beginning as early as one hour after EP and peaking at the 4 hour time point. The majority of the apoptotic events were detected in the epidermal region directly adjacent to the electrode needle. Using a novel propidium iodide in vivo necrotic cell death assay, we detected necrotic events concentrated in the epidermal region adjacent to the electrode. Furthermore, we detected up-regulation of calreticulin expression on skin cells after EP, thus labeling these cells for uptake by dendritic cells and macrophages. These results allow us to delineate the cell death mechanisms occurring in the skin following intradermal EP independently of pDNA delivery. We believe these events contribute to the adjuvant effect observed following electroporation at the skin treatment site.

  3. Electroporation-based DNA delivery technology

    DEFF Research Database (Denmark)

    Gothelf, A; Gehl, Julie

    2014-01-01

    DNA delivery to for example skin and muscle can easily be performed with electroporation. The method is efficient, feasible, and inexpensive and the future possibilities are numerous. Here we present our protocol for gene transfection to mouse skin using naked plasmid DNA and electric pulses....

  4. Transformation of group A streptococci by electroporation

    NARCIS (Netherlands)

    Suvorov, Alexander; Kok, Jan; Venema, Gerhardus

    1988-01-01

    The introduction, via electroporation, of free plasmid DNA into three strains of Streptococcus pyogenes is described. The method is very simple and rapid and efficiencies vary from 1 × 10^3 to 4 × 10^4 per µg of DNA. The method was also used to introduce an integrative plasmid and transformants were

  5. Simulation optimisation

    International Nuclear Information System (INIS)

    Anon

    2010-01-01

    Over the past decade there has been a significant advance in flotation circuit optimisation through performance benchmarking using metallurgical modelling and steady-state computer simulation. This benchmarking includes traditional measures, such as grade and recovery, as well as new flotation measures, such as ore floatability, bubble surface area flux and froth recovery. To further this optimisation, Outotec has released its HSC Chemistry software with simulation modules. The flotation model developed by the AMIRA P9 Project, of which Outotec is a sponsor, is regarded by industry as the most suitable flotation model to use for circuit optimisation. This model incorporates ore floatability with flotation cell pulp and froth parameters, residence time, entrainment and water recovery. Outotec's HSC Sim enables you to simulate mineral processes in different levels, from comminution circuits with sizes and no composition, through to flotation processes with minerals by size by floatability components, to full processes with true particles with MLA data.

  6. Non-Invasive Delivery of dsRNA into De-Waxed Tick Eggs by Electroporation

    Science.gov (United States)

    Ruiz, Newton; de Abreu, Leonardo Araujo; Parizi, Luís Fernando; Kim, Tae Kwon; Mulenga, Albert; Braz, Gloria Regina Cardoso; Vaz, Itabajara da Silva; Logullo, Carlos

    2015-01-01

    RNA interference-mediated gene silencing was shown to be an efficient tool for validation of targets that may become anti-tick vaccine components. Here, we demonstrate the application of this approach in the validation of components of molecular signaling cascades, such as the Protein Kinase B (AKT) / Glycogen Synthase Kinase (GSK) axis during tick embryogenesis. It was shown that heptane and hypochlorite treatment of tick eggs can remove wax, affecting corium integrity and but not embryo development. Evidence of AKT and GSK dsRNA delivery into de-waxed eggs of via electroporation is provided. Primers designed to amplify part of the dsRNA delivered into the electroporated eggs dsRNA confirmed its entry in eggs. In addition, it was shown that electroporation is able to deliver the fluorescent stain, 4',6-diamidino-2-phenylindole (DAPI). To confirm gene silencing, a second set of primers was designed outside the dsRNA sequence of target gene. In this assay, the suppression of AKT and GSK transcripts (approximately 50% reduction in both genes) was demonstrated in 7-day-old eggs. Interestingly, silencing of GSK in 7-day-old eggs caused 25% reduction in hatching. Additionally, the effect of silencing AKT and GSK on embryo energy metabolism was evaluated. As expected, knockdown of AKT, which down regulates GSK, the suppressor of glycogen synthesis, decreased glycogen content in electroporated eggs. These data demonstrate that electroporation of de-waxed R. microplus eggs could be used for gene silencing in tick embryos, and improve the knowledge about arthropod embryogenesis. PMID:26091260

  7. Treatment planning of electroporation-based medical interventions: electrochemotherapy, gene electrotransfer and irreversible electroporation

    International Nuclear Information System (INIS)

    Zupanic, Anze; Kos, Bor; Miklavcic, Damijan

    2012-01-01

    In recent years, cancer electrochemotherapy (ECT), gene electrotransfer for gene therapy and DNA vaccination (GET) and tissue ablation with irreversible electroporation (IRE) have all entered clinical practice. We present a method for a personalized treatment planning procedure for ECT, GET and IRE, based on medical image analysis, numerical modelling of electroporation and optimization with the genetic algorithm, and several visualization tools for treatment plan assessment. Each treatment plan provides the attending physician with optimal positions of electrodes in the body and electric pulse parameters for optimal electroporation of the target tissues. For the studied case of a deep-seated tumour, the optimal treatment plans for ECT and IRE require at least two electrodes to be inserted into the target tissue, thus lowering the necessary voltage for electroporation and limiting damage to the surrounding healthy tissue. In GET, it is necessary to place the electrodes outside the target tissue to prevent damage to target cells intended to express the transfected genes. The presented treatment planning procedure is a valuable tool for clinical and experimental use and evaluation of electroporation-based treatments. (paper)

  8. A statistical model describing combined irreversible electroporation and electroporation-induced blood-brain barrier disruption.

    Science.gov (United States)

    Sharabi, Shirley; Kos, Bor; Last, David; Guez, David; Daniels, Dianne; Harnof, Sagi; Mardor, Yael; Miklavcic, Damijan

    2016-03-01

    Electroporation-based therapies such as electrochemotherapy (ECT) and irreversible electroporation (IRE) are emerging as promising tools for treatment of tumors. When applied to the brain, electroporation can also induce transient blood-brain-barrier (BBB) disruption in volumes extending beyond IRE, thus enabling efficient drug penetration. The main objective of this study was to develop a statistical model predicting cell death and BBB disruption induced by electroporation. This model can be used for individual treatment planning. Cell death and BBB disruption models were developed based on the Peleg-Fermi model in combination with numerical models of the electric field. The model calculates the electric field thresholds for cell kill and BBB disruption and describes the dependence on the number of treatment pulses. The model was validated using in vivo experimental data consisting of rats brains MRIs post electroporation treatments. Linear regression analysis confirmed that the model described the IRE and BBB disruption volumes as a function of treatment pulses number (r(2) = 0.79; p disruption, the ratio increased with the number of pulses. BBB disruption radii were on average 67% ± 11% larger than IRE volumes. The statistical model can be used to describe the dependence of treatment-effects on the number of pulses independent of the experimental setup.

  9. Electroporation of Postimplantation Mouse Embryos In Utero.

    Science.gov (United States)

    Huang, Cheng-Chiu; Carcagno, Abel

    2018-02-01

    Gene transfer by electroporation is possible in mouse fetuses within the uterus. As described in this protocol, the pregnant female is anesthetized, the abdominal cavity is opened, and the uterus with the fetuses is exteriorized. A solution of plasmid DNA is injected through the uterine wall directly into the fetus, typically into a cavity like the brain ventricle, guided by fiber optic illumination. Electrodes are positioned on the uterus around the region of the fetus that was injected, and electrical pulses are delivered. The uterus is returned to the abdominal cavity, the body wall is sutured closed, and the female is allowed to recover. The manipulated fetuses can then be collected and analyzed at various times after the electroporation. This method allows experimental access to later-stage developing mouse embryos. © 2018 Cold Spring Harbor Laboratory Press.

  10. DNA Vaccine Electroporation and Molecular Adjuvants

    Science.gov (United States)

    2016-03-16

    Suschak and Schmaljohn DNA Vaccine Electroporation and Molecular Adjuvants 1 Abstract To date, there is no protective vaccine for Ebola virus...the formulation of DNA launched virus-like particles (VLP). In this case, the antigen is encoded in one DNA plasmid, while structural proteins are...Virol, 2010. 155(12): p. 2083-103. 2. Feldmann, H. and T.W. Geisbert, Ebola haemorrhagic fever. Lancet, 2011. 377(9768): p. 849-62. 3. Hart, M.K

  11. Irreversible electroporation: state of the art

    Directory of Open Access Journals (Sweden)

    Wagstaff PGK

    2016-04-01

    Full Text Available Peter GK Wagstaff,1 Mara Buijs,1 Willemien van den Bos,1 Daniel M de Bruin,2 Patricia J Zondervan,1 Jean JMCH de la Rosette,1 M Pilar Laguna Pes1 1Department of Urology, 2Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, the Netherlands Abstract: The field of focal ablative therapy for the treatment of cancer is characterized by abundance of thermal ablative techniques that provide a minimally invasive treatment option in selected tumors. However, the unselective destruction inflicted by thermal ablation modalities can result in damage to vital structures in the vicinity of the tumor. Furthermore, the efficacy of thermal ablation intensity can be impaired due to thermal sink caused by large blood vessels in the proximity of the tumor. Irreversible electroporation (IRE is a novel ablation modality based on the principle of electroporation or electropermeabilization, in which electric pulses are used to create nanoscale defects in the cell membrane. In theory, IRE has the potential of overcoming the aforementioned limitations of thermal ablation techniques. This review provides a description of the principle of IRE, combined with an overview of in vivo research performed to date in the liver, pancreas, kidney, and prostate. Keywords: irreversible electroporation, IRE, tumor, ablation, focal therapy, cancer

  12. A nonlinear electromechanical coupling model for electropore expansion in cell electroporation

    KAUST Repository

    Deng, Peigang; Lee, Yi Kuen; Zhang, Tong Yi

    2014-01-01

    the electroporation (EP) phenomenon. In comparison with previous EP models, the proposed model has the ability to predict the metastable point on the free energy curve that is relevant to the lipid ion channel. In addition, the proposed model can also predict

  13. Tutorial: Electroporation of cells in complex materials and tissue

    Science.gov (United States)

    Rems, L.; Miklavčič, D.

    2016-05-01

    Electroporation is being successfully used in biology, medicine, food processing, and biotechnology, and in some environmental applications. Recent applications also include in addition to classical electroporation, where cells are exposed to micro- or milliseconds long pulses, exposures to extremely short nanosecond pulses, i.e., high-frequency electroporation. Electric pulses are applied to cells in different structural configurations ranging from suspended cells to cells in tissues. Understanding electroporation of cells in tissues and other complex environments is a key to its successful use and optimization in various applications. Thus, explanation will be provided theoretically/numerically with relation to experimental observations by scaling our understanding of electroporation from the molecular level of the cell membrane up to the tissue level.

  14. Optimisation of Surface-Initiated Photoiniferter-Mediated Polymerisation under Confinement, and the Formation of Block Copolymers in Mesoporous Films

    Directory of Open Access Journals (Sweden)

    Jessica C. Tom

    2017-10-01

    Full Text Available Nature as the ultimate inspiration can direct, gate, and selectively transport species across channels to fulfil a specific targeted function. Harnessing such precision over local structure and functionality at the nanoscale is expected to lead to indispensable developments in synthetic channels for application in catalysis, filtration and sensing, and in drug delivery. By combining mesoporous materials with localised charge-switchable poly(2-(dimethylaminoethyl methacrylate (PDMAEMA brushes, precisely controlling pore filling and exploring the possibility of incorporating two different responsive polymers, we hope to approach the precision control of natural systems in the absence of an external force. Here, we report a simple one-step approach to prepare a mesoporous silica thin film with ~8 nm pores functionalised with a photoiniferter by combining sol–gel chemistry and evaporation-induced self-assembly (EISA. We show that surface-initiated photoiniferter-mediated polymerisation (SI-PIMP allows the incorporation of a high polymer content up to geometrical pore blocking by the simple application of UV light in the presence of a monomer and solvent, proceeding in a controlled manner in pore sizes below 10 nm, with the potential to tune the material properties through the formation of surface-grafted block copolymers.

  15. Influence of DMPS on the water retention capacity of electroporated stratum corneum: ATR-FTIR study.

    Science.gov (United States)

    Sckolnick, Maria; Hui, Sek-Wen; Sen, Arindam

    2008-02-28

    Anionic lipids like phosphatidylserine are known to significantly enhance electroporation mediated transepidermal transport of polar solutes of molecular weights up to 10kDa. The underlying mechanism of the effect of anionic lipids on transdermal transport is not fully understood. The main barrier to transdermal transport lies within the intercellular lipid matrix (ILM) of the stratum corneum (SC) and our previous studies indicate that dimyristoyl phosphatidylserine (DMPS) can perturb the packing of this lipid matrix. Here we report on our investigation on water retention in the SC following electroporation in the presence and the absence of DMPS. The water content in the outer most layers of the SC of full thickness porcine skin was determined using ATR-FTIR-spectroscopy. The results show that in the presence of DMPS, the SC remains in a state of enhanced hydration for longer periods after electroporation. This increase in water retention in the SC by DMPS is likely to play an important role in trans-epidermal transport, since improved hydration of the skin barrier can be expected to increase the partitioning of polar solutes and possibly the permeability.

  16. Electroporation - a biophysical method for transferring nano-sized systems and drugs in vitro and in vivo

    International Nuclear Information System (INIS)

    Nikolova, B.; Atanasova, S.; Pehlivanova, V.; Jelev, J.; Tsoneva, Y.; Bakalova, R.; Peycheva, E.

    2017-01-01

    The aim of this study was to investigate the electrostatic internalisation of quinatum dots (QDs) and QDs containing nano-hydrogels in the Colon 26 cell line and their effect on cell viability as well as their passive and electrically mediated delivery in solid murine tumor models. Materials and methods: Colon 26 cancer cell line was used for in vitro experiments, survival was followed by a MTS test, and images were obtained by confocal microscopy. For in vivo experiments, mouse models with implanted Colon 26 cells were used. All in vivo measurements are carried out ~ 9-10 days after the inoculation, when the tumor size is ~ 100 mm 3 . Results: Electroporation facilitates the delivery of nanoparticles - both in vivo and in vitro. We demonstrate that increasing the applied tension leads to increased nanoparticle penetration into the cells without significantly reducing cell survival. The penetration of nano-hydrogels into tumor tissue is visualized by fluorescence imaging and MRI. The highest intensity of the tumor signal was recorded 30 minutes after the combined treatment (electroporation and QDs loaded nano-hydrogels), even 48 hours post electroporation. The data show a more efficient penetration and long retention of nanoparticles in the tumor after electroporation, due to the increased permeability of the cell membranes and local cleavage of the blood vessels. Conclusion: The internalization and retention of nano-hydrogels is a promising tool both in future strategies for the treatment of cancer and nano medicine. [bg

  17. A nonlinear electromechanical coupling model for electropore expansion in cell electroporation

    KAUST Repository

    Deng, Peigang

    2014-10-15

    Under an electric field, the electric tractions acting on a cell membrane containing a pore-nucleus are investigated by using a nonlinear electromechanical coupling model, in which the cell membrane is treated as a hyperelastic material. Iterations between the electric field and the structure field are performed to reveal the electrical forces exerting on the pore region and the subsequent pore expansion process. An explicit exponential decay of the membrane\\'s edge energy as a function of pore radius is defined for a hydrophilic pore and the transition energy as a hydrophobic pore converts to a hydrophilic pore during the initial stage of pore formation is investigated. It is found that the edge energy for the creation of an electropore edge plays an important role at the atomistic scale and it determines the hydrophobic-hydrophilic transition energy barrier. Various free energy evolution paths are exhibited, depending on the applied electric field, which provides further insight towards the electroporation (EP) phenomenon. In comparison with previous EP models, the proposed model has the ability to predict the metastable point on the free energy curve that is relevant to the lipid ion channel. In addition, the proposed model can also predict the critical transmembrane potential for the activation of an effective electroporation that is in a good agreement with previously published experimental data.

  18. Anistropically varying conductivity in irreversible electroporation simulations.

    Science.gov (United States)

    Labarbera, Nicholas; Drapaca, Corina

    2017-11-01

    One recent area of cancer research is irreversible electroporation (IRE). Irreversible electroporation is a minimally invasive procedure where needle electrodes are inserted into the body to ablate tumor cells with electricity. The aim of this paper is to propose a mathematical model that incorporates a tissue's conductivity increasing more in the direction of the electrical field as this has been shown to occur in experiments. It was necessary to mathematically derive a valid form of the conductivity tensor such that it is dependent on the electrical field direction and can be easily implemented into numerical software. The derivation of a conductivity tensor that can take arbitrary functions for the conductivity in the directions tangent and normal to the electrical field is the main contribution of this paper. Numerical simulations were performed for isotropic-varying and anisotropic-varying conductivities to evaluate the importance of including the electrical field's direction in the formulation for conductivity. By starting from previously published experimental results, this paper derived a general formulation for an anistropic-varying tensor for implementation into irreversible electroporation modeling software. The anistropic-varying tensor formulation allows the conductivity to take into consideration both electrical field direction and magnitude, as opposed to previous published works that only took into account electrical field magnitude. The anisotropic formulation predicts roughly a five percent decrease in ablation size for the monopolar simulation and approximately a ten percent decrease in ablation size for the bipolar simulations. This is a positive result as previously reported results found the isotropic formulation to overpredict ablation size for both monopolar and bipolar simulations. Furthermore, it was also reported that the isotropic formulation overpredicts the ablation size more for the bipolar case than the monopolar case. Thus, our

  19. Feasibility of Parylene Coating for Planar Electroporation Copper Electrodes

    Directory of Open Access Journals (Sweden)

    Vitalij NOVICKIJ

    2017-08-01

    Full Text Available This paper is focused on the feasibility study of parylene as a biocompatible coating for planar electroporation microelectrodes. The planar parallel and the circular interdigitated electrodes are applied in the analysis. The electrodes feature 100 μm width with a 300 μm gap between anode and cathode. The parylene coating thickness was varied in the 250 nm – 2 μm range. The resultant electric field distribution evaluation has been performed using the finite element method. The electrodes have been applied in electroporation experiments with Saprolegnia parasitica. For reference the additional experiments using conventional electroporation cuvette (1 mm gap have been performed. It has been determined that the parylene coating with hydrophobic properties has limited applicability for the passivation of the planar electroporation electrodes.DOI: http://dx.doi.org/10.5755/j01.ms.23.2.14953

  20. Nonlinear electro-mechanobiological behavior of cell membrane during electroporation

    KAUST Repository

    Deng, Peigang; Lee, Yi-Kuen; Lin, Ran; Zhang, Tong-Yi

    2012-01-01

    A nonlinear electroporation (EP) model is proposed to study the electro-mechanobiological behavior of cell membrane during EP, by taking the nonlinear large deformation of the membrane into account. The proposed model predicts the critical

  1. Pulsed Electromagnetic Field Assisted in vitro Electroporation: A Pilot Study

    Science.gov (United States)

    Novickij, Vitalij; Grainys, Audrius; Lastauskienė, Eglė; Kananavičiūtė, Rūta; Pamedytytė, Dovilė; Kalėdienė, Lilija; Novickij, Jurij; Miklavčič, Damijan

    2016-09-01

    Electroporation is a phenomenon occurring due to exposure of cells to Pulsed Electric Fields (PEF) which leads to increase of membrane permeability. Electroporation is used in medicine, biotechnology, and food processing. Recently, as an alternative to electroporation by PEF, Pulsed ElectroMagnetic Fields (PEMF) application causing similar biological effects was suggested. Since induced electric field in PEMF however is 2-3 magnitudes lower than in PEF electroporation, the membrane permeabilization mechanism remains hypothetical. We have designed pilot experiments where Saccharomyces cerevisiae and Candida lusitaniae cells were subjected to single 100-250 μs electrical pulse of 800 V with and without concomitant delivery of magnetic pulse (3, 6 and 9 T). As expected, after the PEF pulses only the number of Propidium Iodide (PI) fluorescent cells has increased, indicative of membrane permeabilization. We further show that single sub-millisecond magnetic field pulse did not cause detectable poration of yeast. Concomitant exposure of cells to pulsed electric (PEF) and magnetic field (PMF) however resulted in the increased number PI fluorescent cells and reduced viability. Our results show increased membrane permeability by PEF when combined with magnetic field pulse, which can explain electroporation at considerably lower electric field strengths induced by PEMF compared to classical electroporation.

  2. A theoretical analysis of the feasibility of a singularity-induced micro-electroporation system.

    Directory of Open Access Journals (Sweden)

    Gregory D Troszak

    Full Text Available Electroporation, the permeabilization of the cell membrane lipid bilayer due to a pulsed electric field, has important implications in the biotechnology, medicine, and food industries. Traditional macro and micro-electroporation devices have facing electrodes, and require significant potential differences to induce electroporation. The goal of this theoretical study is to investigate the feasibility of singularity-induced micro-electroporation; an electroporation configuration aimed at minimizing the potential differences required to induce electroporation by separating adjacent electrodes with a nanometer-scale insulator. In particular, this study aims to understand the effect of (1 insulator thickness and (2 electrode kinetics on electric field distributions in the singularity-induced micro-electroporation configuration. A non-dimensional primary current distribution model of the micro-electroporation channel shows that while increasing insulator thickness results in smaller electric field magnitudes, electroporation can still be performed with insulators thick enough to be made with microfabrication techniques. Furthermore, a secondary current distribution model of the singularity-induced micro-electroporation configuration with inert platinum electrodes and water electrolyte indicates that electrode kinetics do not inhibit charge transfer to the extent that prohibitively large potential differences are required to perform electroporation. These results indicate that singularity-induced micro-electroporation could be used to develop an electroporation system that consumes minimal power, making it suitable for remote applications such as the sterilization of water and other liquids.

  3. The effects of metallic implants on electroporation therapies: feasibility of irreversible electroporation for brachytherapy salvage.

    Science.gov (United States)

    Neal, Robert E; Smith, Ryan L; Kavnoudias, Helen; Rosenfeldt, Franklin; Ou, Ruchong; Mclean, Catriona A; Davalos, Rafael V; Thomson, Kenneth R

    2013-12-01

    Electroporation-based therapies deliver brief electric pulses into a targeted volume to destabilize cellular membranes. Nonthermal irreversible electroporation (IRE) provides focal ablation with effects dependent on the electric field distribution, which changes in heterogeneous environments. It should be determined if highly conductive metallic implants in targeted regions, such as radiotherapy brachytherapy seeds in prostate tissue, will alter treatment outcomes. Theoretical and experimental models determine the impact of prostate brachytherapy seeds on IRE treatments. This study delivered IRE pulses in nonanimal, as well as in ex vivo and in vivo tissue, with and in the absence of expired radiotherapy seeds. Electrical current was measured and lesion dimensions were examined macroscopically and with magnetic resonance imaging. Finite-element treatment simulations predicted the effects of brachytherapy seeds in the targeted region on electrical current, electric field, and temperature distributions. There was no significant difference in electrical behavior in tissue containing a grid of expired radiotherapy seeds relative to those without seeds for nonanimal, ex vivo, and in vivo experiments (all p > 0.1). Numerical simulations predict no significant alteration of electric field or thermal effects (all p > 0.1). Histology showed cellular necrosis in the region near the electrodes and seeds within the ablation region; however, there were no seeds beyond the ablation margins. This study suggests that electroporation therapies can be implemented in regions containing small metallic implants without significant changes to electrical and thermal effects relative to use in tissue without the implants. This supports the ability to use IRE as a salvage therapy option for brachytherapy.

  4. Application of Electroporation Technique in Biofuel Processing

    Directory of Open Access Journals (Sweden)

    Yousuf Abu

    2017-01-01

    Full Text Available Biofuels production is mostly oriented with fermentation process, which requires fermentable sugar as nutrient for microbial growth. Lignocellulosic biomass (LCB represents the most attractive, low-cost feedstock for biofuel production, it is now arousing great interest. The cellulose that is embedded in the lignin matrix has an insoluble, highly-crystalline structure, so it is difficult to hydrolyze into fermentable sugar or cell protein. On the other hand, microbial lipid has been studying as substitute of plant oils or animal fat to produce biodiesel. It is still a great challenge to extract maximum lipid from microbial cells (yeast, fungi, algae investing minimum energy.Electroporation (EP of LCB results a significant increase in cell conductivity and permeability caused due to the application of an external electric field. EP is required to alter the size and structure of the biomass, to reduce the cellulose crystallinity, and increase their porosity as well as chemical composition, so that the hydrolysis of the carbohydrate fraction to monomeric sugars can be achieved rapidly and with greater yields. Furthermore, EP has a great potential to disrupt the microbial cell walls within few seconds to bring out the intracellular materials (lipid to the solution. Therefore, this study aims to describe the challenges and prospect of application of EP technique in biofuels processing.

  5. Simple Genome Editing of Rodent Intact Embryos by Electroporation.

    Directory of Open Access Journals (Sweden)

    Takehito Kaneko

    Full Text Available The clustered regularly interspaced short palindromic repeat (CRISPR/CRISPR-associated (Cas system is a powerful tool for genome editing in animals. Recently, new technology has been developed to genetically modify animals without using highly skilled techniques, such as pronuclear microinjection of endonucleases. Technique for animal knockout system by electroporation (TAKE method is a simple and effective technology that produces knockout rats by introducing endonuclease mRNAs into intact embryos using electroporation. Using TAKE method and CRISPR/Cas system, the present study successfully produced knockout and knock-in mice and rats. The mice and rats derived from embryos electroporated with Cas9 mRNA, gRNA and single-stranded oligodeoxynucleotide (ssODN comprised the edited targeted gene as a knockout (67% of mice and 88% of rats or knock-in (both 33%. The TAKE method could be widely used as a powerful tool to produce genetically modified animals by genome editing.

  6. Simulation of micro/nano electroporation for cell transfection

    Science.gov (United States)

    Zhang, Guocheng; Fan, Na; Jiang, Hai; Guo, Jian; Peng, Bei

    2018-03-01

    The 3D micro/nano electroporation for transfection has become a powerful biological cell research technique with the development of micro-nano manufacturing technology. The micro channels connected the cells with transfection reagents on the chip were important to the transmemnbrane potentical, which directly influences the electroporation efficiency. In this study, a two-dimensional model for electroporation of cells was designed to address the effects of channels’ sizes and number on transmembrane potential. The simulation results indicated that the transmembrane potential increased with increasing size of channels’ entrances. Moreover, compared with single channel entrance, the transmembrane potential was higher when the cells located at multiple channels entrances. These results suggest that it IS required to develop higher micro manufacturing technology to create channels as we expected size.

  7. Administration of HPV DNA vaccine via electroporation elicits the strongest CD8+ T cell immune responses compared to intramuscular injection and intradermal gene gun delivery

    Science.gov (United States)

    Best, Simon R.; Peng, Shiwen; Juang, Chi-Mou; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.; Pai, Sara I.

    2009-01-01

    DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC Class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such immunotherapeutic strategies is dependent on the identification of an effective route and method of DNA administration. Electroporation and gene gun-mediated particle delivery are leading methods of DNA vaccine delivery that can generate protective and therapeutic levels of immune responses in experimental models. In this study, we perform a head-to-head comparison of three methods of vaccination – conventional intramuscular injection, electroporation mediated intramuscular delivery, and epidermal gene gun-mediated particle delivery - in the ability to generate antigen specific cytotoxic CD8+ T cell responses as well as anti-tumor immune responses against an HPV-16 E7 expressing tumor cell line using the pNGVL4a-CRT/E7(detox) DNA vaccine. Vaccination via electroporation generated the highest number of E7-specific cytotoxic CD8+ T cells, which correlated to improved outcomes in the treatment of growing tumors. In addition, we demonstrate that electroporation results in significantly higher levels of circulating protein compared to gene gun or intramuscular vaccination, which likely enhances calreticulin’s role as a local tumor anti-angiogenesis agent. We conclude that electroporation is a promising method for delivery of HPV DNA vaccines and should be considered for DNA vaccine delivery in human clinical trials. PMID:19622402

  8. Irreversible Electroporation in a Swine Lung Model

    International Nuclear Information System (INIS)

    Dupuy, Damian E.; Aswad, Bassam; Ng, Thomas

    2011-01-01

    Purpose: This study was designed to evaluate the safety and tissue effects of IRE in a swine lung model. Methods: This study was approved by the institutional animal care committee. Nine anesthetized domestic swine underwent 15 percutaneous irreversible electroporation (IRE) lesion creations (6 with bipolar and 3 with 3–4 monopolar electrodes) under fluoroscopic guidance and with pancuronium neuromuscular blockade and EKG gating. IRE electrodes were placed into the central and middle third of the right mid and lower lobes in all animals. Postprocedure PA and lateral chest radiographs were obtained to evaluate for pneumothorax. Three animals were sacrificed at 2 weeks and six at 4 weeks. Animals underwent high-resolution CT scanning and PA and lateral radiographs 1 h before sacrifice. The treated lungs were removed en bloc, perfused with formalin, and sectioned. Gross pathologic and microscopic changes after standard hematoxylin and eosin staining were analyzed within the areas of IRE lesion creation. Results: No significant adverse events were identified. CT showed focal areas of spiculated high density ranging in greatest diameter from 1.1–2.2 cm. On gross inspection of the sectioned lung, focal areas of tan discoloration and increased density were palpated in the areas of IRE. Histological analysis revealed focal areas of diffuse alveolar damage with fibrosis and inflammatory infiltration that respected the boundaries of the interlobular septae. No pathological difference could be discerned between the 2- and 4-week time points. The bronchioles and blood vessels within the areas of IRE were intact and did not show signs of tissue injury. Conclusion: IRE creates focal areas of diffuse alveolar damage without creating damage to the bronchioles or blood vessels. Short-term safety in a swine model appears to be satisfactory.

  9. Efficiency of cellular delivery of antisense peptide nucleic acid by electroporation depends on charge and electroporation geometry

    DEFF Research Database (Denmark)

    Joergensen, Mette; Agerholm-Larsen, Birgit; Nielsen, Peter E

    2011-01-01

    Electroporation is potentially a very powerful technique for both in vitro cellular and in vivo drug delivery, particularly relating to oligonucleotides and their analogs for genetic therapy. Using a sensitive and quantitative HeLa cell luciferase RNA interference mRNA splice correction assay...... with a functional luciferase readout, we demonstrate that parameters such as peptide nucleic acid (PNA) charge and the method of electroporation have dramatic influence on the efficiency of productive delivery. In a suspended cell electroporation system (cuvettes), a positively charged PNA (+8) was most efficiently...... transferred, whereas charge neutral PNA was more effective in a microtiter plate electrotransfer system for monolayer cells. Surprisingly, a negatively charged (-23) PNA did not show appreciable activity in either system. Findings from the functional assay were corroborated by pulse parameter variations...

  10. Developing a de novo targeted knock-in method based on in utero electroporation into the mammalian brain.

    Science.gov (United States)

    Tsunekawa, Yuji; Terhune, Raymond Kunikane; Fujita, Ikumi; Shitamukai, Atsunori; Suetsugu, Taeko; Matsuzaki, Fumio

    2016-09-01

    Genome-editing technology has revolutionized the field of biology. Here, we report a novel de novo gene-targeting method mediated by in utero electroporation into the developing mammalian brain. Electroporation of donor DNA with the CRISPR/Cas9 system vectors successfully leads to knock-in of the donor sequence, such as EGFP, to the target site via the homology-directed repair mechanism. We developed a targeting vector system optimized to prevent anomalous leaky expression of the donor gene from the plasmid, which otherwise often occurs depending on the donor sequence. The knock-in efficiency of the electroporated progenitors reached up to 40% in the early stage and 20% in the late stage of the developing mouse brain. Furthermore, we inserted different fluorescent markers into the target gene in each homologous chromosome, successfully distinguishing homozygous knock-in cells by color. We also applied this de novo gene targeting to the ferret model for the study of complex mammalian brains. Our results demonstrate that this technique is widely applicable for monitoring gene expression, visualizing protein localization, lineage analysis and gene knockout, all at the single-cell level, in developmental tissues. © 2016. Published by The Company of Biologists Ltd.

  11. Transformation of undomesticated strains of Bacillus subtilis by protoplast electroporation

    NARCIS (Netherlands)

    Romero, Diego; Perez-Garcia, Alejandro; Veening, Jan-Willem; de Vicente, Antonio; Kuipers, Oscar P.; de, Vicente A.

    A rapid method combining the use of protoplasts and electroporation was developed to transform recalcitrant wild strains of Bacillus subtilis. The method described here allows transformation with both replicative and integrative plasmids, as well as with chromosomal DNA, and provides a valuable tool

  12. Theory and in vivo application of electroporative gene delivery.

    Science.gov (United States)

    Somiari, S; Glasspool-Malone, J; Drabick, J J; Gilbert, R A; Heller, R; Jaroszeski, M J; Malone, R W

    2000-09-01

    Efficient and safe methods for delivering exogenous genetic material into tissues must be developed before the clinical potential of gene therapy will be realized. Recently, in vivo electroporation has emerged as a leading technology for developing nonviral gene therapies and nucleic acid vaccines (NAV). Electroporation (EP) involves the application of pulsed electric fields to cells to enhance cell permeability, resulting in exogenous polynucleotide transit across the cytoplasmic membrane. Similar pulsed electrical field treatments are employed in a wide range of biotechnological processes including in vitro EP, hybridoma production, development of transgenic animals, and clinical electrochemotherapy. Electroporative gene delivery studies benefit from well-developed literature that may be used to guide experimental design and interpretation. Both theory and experimental analysis predict that the critical parameters governing EP efficacy include cell size and field strength, duration, frequency, and total number of applied pulses. These parameters must be optimized for each tissue in order to maximize gene delivery while minimizing irreversible cell damage. By providing an overview of the theory and practice of electroporative gene transfer, this review intends to aid researchers that wish to employ the method for preclinical and translational gene therapy, NAV, and functional genomic research.

  13. The optimization of voltage parameter for tissue electroporation in ...

    African Journals Online (AJOL)

    USER

    2010-07-19

    Jul 19, 2010 ... bodies, peptides or pharmaceuticals into the cell. Electro- ... acetic acid; MS, Murashige and Skoog; 2,4-D, 2,4-dichloro- ... sterile water and transferred to each ice-cold 0.4 cm electroporation ... (X-gluc) and 20% methanol.

  14. Low vulnerability of the right phrenic nerve to electroporation ablation

    NARCIS (Netherlands)

    van Driel, Vincent J. H. M.; Neven, KGEJ; van Wessel, Harri; Vink, Aryan; Doevendans, Pieter A. F. M.; Wittkampf, Fred H. M.

    BACKGROUND Circular electroporation ablation is a novel ablation modality for electrical pulmonary vein isolation. With a single 200-3 application, deep circular myocardial lesions can be created. However, the acute and chronic effects of this energy source on phrenic nerve (PN) function are

  15. Computer Based Optimisation Rutines

    DEFF Research Database (Denmark)

    Dragsted, Birgitte; Olsen, Flemmming Ove

    1996-01-01

    In this paper the need for optimisation methods for the laser cutting process has been identified as three different situations. Demands on the optimisation methods for these situations are presented, and one method for each situation is suggested. The adaptation and implementation of the methods...

  16. Optimal Optimisation in Chemometrics

    NARCIS (Netherlands)

    Hageman, J.A.

    2004-01-01

    The use of global optimisation methods is not straightforward, especially for the more difficult optimisation problems. Solutions have to be found for items such as the evaluation function, representation, step function and meta-parameters, before any useful results can be obtained. This thesis aims

  17. The Effects of Irreversible Electroporation on the Achilles Tendon: An Experimental Study in a Rabbit Model.

    Directory of Open Access Journals (Sweden)

    Yue Song

    Full Text Available To evaluate the potential effects of irreversible electroporation ablation on the Achilles tendon in a rabbit model and to compare the histopathological and biomechanical changes between specimens following electroporation ablation and radiofrequency ablation.A total of 140 six-month-old male New Zealand rabbits were used. The animals were randomly divided into two groups, 70 in the radiofrequency ablation group and 70 in the electroporation group. In situ ablations were applied directly to the Achilles tendons of rabbits using typical electroporation (1800 V/cm, 90 pulses and radiofrequency ablation (power control mode protocols. Histopathological and biomechanical evaluations were performed to examine the effects of electroporation ablation and radiofrequency ablation over time.Both electroporation and radiofrequency ablation produced complete cell ablation in the target region. Thermal damage resulted in tendon rupture 3 days post radiofrequency ablation. In contrast, electroporation-ablated Achilles tendons preserved their biomechanical properties and showed no detectable rupture at this time point. The electroporation-ablated tendons exhibited signs of recovery, including tenoblast regeneration and angiogenesis within 2 weeks, and the restoration of their integral structure was evident within 12 weeks.When applying electroporation to ablate solid tumors, major advantage could be that collateral damage to adjacent tendons or ligaments is minimized due to the unique ability of electroporation ablation to target the cell membrane. This advantage could have a significant impact on the field of tumor ablation near vital tendons or ligaments.

  18. The Effects of Irreversible Electroporation on the Achilles Tendon: An Experimental Study in a Rabbit Model.

    Science.gov (United States)

    Song, Yue; Zheng, Jingjing; Yan, Mingwei; Ding, Weidong; Xu, Kui; Fan, Qingyu; Li, Zhao

    2015-01-01

    To evaluate the potential effects of irreversible electroporation ablation on the Achilles tendon in a rabbit model and to compare the histopathological and biomechanical changes between specimens following electroporation ablation and radiofrequency ablation. A total of 140 six-month-old male New Zealand rabbits were used. The animals were randomly divided into two groups, 70 in the radiofrequency ablation group and 70 in the electroporation group. In situ ablations were applied directly to the Achilles tendons of rabbits using typical electroporation (1800 V/cm, 90 pulses) and radiofrequency ablation (power control mode) protocols. Histopathological and biomechanical evaluations were performed to examine the effects of electroporation ablation and radiofrequency ablation over time. Both electroporation and radiofrequency ablation produced complete cell ablation in the target region. Thermal damage resulted in tendon rupture 3 days post radiofrequency ablation. In contrast, electroporation-ablated Achilles tendons preserved their biomechanical properties and showed no detectable rupture at this time point. The electroporation-ablated tendons exhibited signs of recovery, including tenoblast regeneration and angiogenesis within 2 weeks, and the restoration of their integral structure was evident within 12 weeks. When applying electroporation to ablate solid tumors, major advantage could be that collateral damage to adjacent tendons or ligaments is minimized due to the unique ability of electroporation ablation to target the cell membrane. This advantage could have a significant impact on the field of tumor ablation near vital tendons or ligaments.

  19. A new equivalent circuit model for micro electroporation systems

    KAUST Repository

    Shagoshtasbi, Hooman

    2011-02-01

    Electroporation (EP) is a unique biotechnique in which intense electric pulses are applied on the cell membrane to temporarily generate nanoscale electropores and to increase the membrane permeability for the delivery of exogenous biomolecules or drugs. We propose a new equivalent circuit model with 8 electric components to predict the electrodynamic response of a micro EP system. As the permeability of the cell membrane increases, the membrane resistance decreases. The numerical simulations of the transmembrane current responses to different applied voltages (1∼6V) are consistent with the experimental results using HeLa cells. Besides, the transmembrane voltage as a function of applied voltages is determined as well. These transmembrane current and voltage responses can be extremely useful for the design of new generation of micro EP systems for transfection of large DNA molecules in the future. © 2011 IEEE.

  20. A new equivalent circuit model for micro electroporation systems

    KAUST Repository

    Shagoshtasbi, Hooman; Lee, Yi-Kuen

    2011-01-01

    Electroporation (EP) is a unique biotechnique in which intense electric pulses are applied on the cell membrane to temporarily generate nanoscale electropores and to increase the membrane permeability for the delivery of exogenous biomolecules or drugs. We propose a new equivalent circuit model with 8 electric components to predict the electrodynamic response of a micro EP system. As the permeability of the cell membrane increases, the membrane resistance decreases. The numerical simulations of the transmembrane current responses to different applied voltages (1∼6V) are consistent with the experimental results using HeLa cells. Besides, the transmembrane voltage as a function of applied voltages is determined as well. These transmembrane current and voltage responses can be extremely useful for the design of new generation of micro EP systems for transfection of large DNA molecules in the future. © 2011 IEEE.

  1. Optimised Renormalisation Group Flows

    CERN Document Server

    Litim, Daniel F

    2001-01-01

    Exact renormalisation group (ERG) flows interpolate between a microscopic or classical theory and the corresponding macroscopic or quantum effective theory. For most problems of physical interest, the efficiency of the ERG is constrained due to unavoidable approximations. Approximate solutions of ERG flows depend spuriously on the regularisation scheme which is determined by a regulator function. This is similar to the spurious dependence on the ultraviolet regularisation known from perturbative QCD. Providing a good control over approximated ERG flows is at the root for reliable physical predictions. We explain why the convergence of approximate solutions towards the physical theory is optimised by appropriate choices of the regulator. We study specific optimised regulators for bosonic and fermionic fields and compare the optimised ERG flows with generic ones. This is done up to second order in the derivative expansion at both vanishing and non-vanishing temperature. An optimised flow for a ``proper-time ren...

  2. A method of combined single-cell electrophysiology and electroporation.

    Science.gov (United States)

    Graham, Lyle J; Del Abajo, Ricardo; Gener, Thomas; Fernandez, Eduardo

    2007-02-15

    This paper describes a method of extracellular recording and subsequent electroporation with the same electrode in single retinal ganglion cells in vitro. We demonstrate anatomical identification of neurons whose receptive fields were measured quantitatively. We discuss how this simple method should also be applicable for the delivery of a variety of intracellular agents, including gene delivery, to physiologically characterized neurons, both in vitro and in vivo.

  3. Single exponential decay waveform; a synergistic combination of electroporation and electrolysis (E2 for tissue ablation

    Directory of Open Access Journals (Sweden)

    Nina Klein

    2017-04-01

    Full Text Available Background Electrolytic ablation and electroporation based ablation are minimally invasive, non-thermal surgical technologies that employ electrical currents and electric fields to ablate undesirable cells in a volume of tissue. In this study, we explore the attributes of a new tissue ablation technology that simultaneously delivers a synergistic combination of electroporation and electrolysis (E2. Method A new device that delivers a controlled dose of electroporation field and electrolysis currents in the form of a single exponential decay waveform (EDW was applied to the pig liver, and the effect of various parameters on the extent of tissue ablation was examined with histology. Results Histological analysis shows that E2 delivered as EDW can produce tissue ablation in volumes of clinical significance, using electrical and temporal parameters which, if used in electroporation or electrolysis separately, cannot ablate the tissue. Discussion The E2 combination has advantages over the three basic technologies of non-thermal ablation: electrolytic ablation, electrochemical ablation (reversible electroporation with injection of drugs and irreversible electroporation. E2 ablates clinically relevant volumes of tissue in a shorter period of time than electrolysis and electroporation, without the need to inject drugs as in reversible electroporation or use paralyzing anesthesia as in irreversible electroporation.

  4. Network for development of electroporation-based technologies and treatments: COST TD1104.

    Science.gov (United States)

    Miklavčič, Damijan

    2012-10-01

    Exposure of biological cells to a sufficiently strong external electric field results in increased permeability of cell membranes, referred to as "electroporation." Since all types of cells (animal, plant and microorganism) can be effectively electroporated, electroporation is considered to be a universal method and a platform technology. Electroporation has become a widely used technology applicable to, e.g., cancer treatment, gene transfection, food and biomass processing and microbial inactivation. However, despite significant progress in electroporation-based applications, there is a lack of coordination and interdisciplinary exchange of knowledge between researchers from different scientific domains. Thus, critical mass for new major breakthroughs is missing. This is why we decided to establish cooperation between research groups working in different fields of electroporation. Cooperation in Science and Technology (COST), which funds networking and capacity-building activities, presents a perfect framework for such scientific cooperation. This COST action aims at (1) providing necessary steps toward EU cooperation of science and technology to foster basic understanding of electroporation; (2) improving communication between research groups, resulting in streamlining European research and development activities; and (3) enabling development of new and further development of existing electroporation-based applications by integrating multidisciplinary research teams, as well as providing comprehensive training for early-stage researchers. Results of this COST action will provide multiple societal, scientific and technological benefits from improving existing electroporation-based applications to adding new ones in the fields of medicine, biotechnology and environmental preservation.

  5. Use of electroporation to study the cytotoxic effects of fluorodeoxyuridylate in intact cells.

    Science.gov (United States)

    Jastreboff, M M; Sokoloski, J A; Bertino, J R; Narayanan, R

    1987-04-15

    The introduction of 2'-deoxyuridine 5'-monophosphate and its analog, 5-fluoro-2'-deoxyuridine 5'-monophosphate, into intact CCRF-CEM and NIH3T3 cells was achieved by electroporation. Following electroporation, cells were shown to be fully functional as monitored by the incorporation of deoxyuridylate, after conversion to thymidylate, into DNA. Pretreatment of cells with fluorodeoxyuridine completely abolished this effect. In contrast, introduction of the fluoro analog into cells by electroporation markedly inhibited both DNA synthesis and cell growth in a time-dependent manner. Thus, electroporation offers a powerful tool to permeabilize cells to a variety of cellular metabolites and antimetabolites.

  6. Electroporation of DC-3F cells is a dual process.

    Science.gov (United States)

    Wegner, Lars H; Frey, Wolfgang; Silve, Aude

    2015-04-07

    Treatment of biological material by pulsed electric fields is a versatile technique in biotechnology and biomedicine used, for example, in delivering DNA into cells (transfection), ablation of tumors, and food processing. Field exposure is associated with a membrane permeability increase usually ascribed to electroporation, i.e., formation of aqueous membrane pores. Knowledge of the underlying processes at the membrane level is predominantly built on theoretical considerations and molecular dynamics (MD) simulations. However, experimental data needed to monitor these processes with sufficient temporal resolution are scarce. The whole-cell patch-clamp technique was employed to investigate the effect of millisecond pulsed electric fields on DC-3F cells. Cellular membrane permeabilization was monitored by a conductance increase. For the first time, to our knowledge, it could be established experimentally that electroporation consists of two clearly separate processes: a rapid membrane poration (transient electroporation) that occurs while the membrane is depolarized or hyperpolarized to voltages beyond so-called threshold potentials (here, +201 mV and -231 mV, respectively) and is reversible within ∼100 ms after the pulse, and a long-term, or persistent, permeabilization covering the whole voltage range. The latter prevailed after the pulse for at least 40 min, the postpulse time span tested experimentally. With mildly depolarizing or hyperpolarizing pulses just above threshold potentials, the two processes could be separated, since persistent (but not transient) permeabilization required repetitive pulse exposure. Conductance increased stepwise and gradually with depolarizing and hyperpolarizing pulses, respectively. Persistent permeabilization could also be elicited by single depolarizing/hyperpolarizing pulses of very high field strength. Experimental measurements of propidium iodide uptake provided evidence of a real membrane phenomenon, rather than a mere

  7. Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

    Directory of Open Access Journals (Sweden)

    Kihyuck Kwak

    Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type

  8. Imaging activity in astrocytes and neurons with genetically encoded calcium indicators following in utero electroporation

    Directory of Open Access Journals (Sweden)

    J. Michael eGee

    2015-04-01

    Full Text Available Complex interactions between networks of astrocytes and neurons are beginning to be appreciated, but remain poorly understood. Transgenic mice expressing fluorescent protein reporters of cellular activity, such as the GCaMP family of genetically encoded calcium indicators, have been used to explore network behavior. However, in some cases, it may be desirable to use long-established rat models that closely mimic particular aspects of human conditions such as Parkinson’s disease and the development of epilepsy following status epilepticus. Methods for expressing reporter proteins in the rat brain are relatively limited. Transgenic rat technologies exist but are fairly immature. Viral-mediated expression is robust but unstable, requires invasive injections, and only works well for fairly small genes (< 5 kb. In utero electroporation offers a valuable alternative. IUE is a proven method for transfecting populations of astrocytes and neurons in the rat brain without the strict limitations on transgene size. We built a toolset of IUE plasmids carrying GCaMP variants 3, 6s or 6f driven by CAG and targeted to the cytosol or the plasma membrane. Because low baseline fluorescence of GCaMP can hinder identification of transfected cells, we included the option of co-expressing a cytosolic tdTomato protein. A binary system consisting of a plasmid carrying a piggyBac inverted terminal repeat-flanked CAG-GCaMP-IRES-tdTomato cassette and a separate plasmid encoding for expression of piggyBac transposase was employed to stably express GCaMP and tdTomato. The plasmids were co-electroporated on embryonic days 13.5-14.5 and astrocytic and neuronal activity was subsequently imaged in acute or cultured brain slices prepared from the cortex or hippocampus. Large spontaneous transients were detected in slices obtained from rats of varying ages up to 127 days. In this report, we demonstrate the utility of this toolset for interrogating astrocytic and neuronal

  9. Transfection of small numbers of human endothelial cells by electroporation and synthetic amphiphiles

    NARCIS (Netherlands)

    van Leeuwen, E B; van der Veen, A Y; Hoekstra, D; Engberts, J B; Halie, M R; van der Meer, J; Ruiters, M H

    OBJECTIVES: This study compared the efficiency of electroporation and synthetic amphiphiles. (SAINT-2pp/DOPE) in transfecting small numbers of human endothelial cells. METHODS AND RESULTS: Optimal transfection conditions were tested and appeared to be 400 V and 960 microF for electroporation and a

  10. Optimising Magnetostatic Assemblies

    DEFF Research Database (Denmark)

    Insinga, Andrea Roberto; Smith, Anders

    theorem. This theorem formulates an energy equivalence principle with several implications concerning the optimisation of objective functionals that are linear with respect to the magnetic field. Linear functionals represent different optimisation goals, e.g. maximising a certain component of the field...... approached employing a heuristic algorithm, which led to new design concepts. Some of the procedures developed for linear objective functionals have been extended to non-linear objectives, by employing iterative techniques. Even though most the optimality results discussed in this work have been derived...

  11. Magnetic resonance electrical impedance tomography for determining electric field distribution during electroporation

    International Nuclear Information System (INIS)

    Kranjc, Matej; Miklavcic, Damijan; Bajd, Franci; Serša, Igor

    2013-01-01

    Electroporation is a phenomenon caused by externally applied electric field to cells that results in an increase of cell membrane permeability to various molecules. Accurate coverage of the tissue with a sufficiently large electric field presents one of the most important conditions for successful membrane permeabilization. Applications based on electroporation would greatly benefit with a method for monitoring the electric field, especially if it could be done in situ. As the membrane electroporation is a consequence of an induced transmembrane potential, which is directly proportional to the local electric field, we have been investigating current density imaging and magnetic resonance electrical impedance tomography techniques to determine the electric field distribution during electroporation. In this paper, we present comparison of current density and electric field distribution in an agar phantom and in a liver tissue exposed to electroporation pulses. As expected, a region of increased electrical conductivity was observed in the liver tissue exposed to sufficiently high electric field but not in agar phantom.

  12. Nonlinear electro-mechanobiological behavior of cell membrane during electroporation

    KAUST Repository

    Deng, Peigang

    2012-01-01

    A nonlinear electroporation (EP) model is proposed to study the electro-mechanobiological behavior of cell membrane during EP, by taking the nonlinear large deformation of the membrane into account. The proposed model predicts the critical transmembrane potential and the activation energy for EP, the equilibrium pore size, and the resealing process of the pore. Single-cell EP experiments using a micro EP chip were conducted on chicken red blood cells at different temperatures to determine the activation energy and the critical transmembrane potential for EP. The experimental results are in good agreement with the theoretical predictions. © 2012 American Institute of Physics.

  13. From Cell to Tissue Properties-Modeling Skin Electroporation With Pore and Local Transport Region Formation.

    Science.gov (United States)

    Dermol-Cerne, Janja; Miklavcic, Damijan

    2018-02-01

    Current models of tissue electroporation either describe tissue with its bulk properties or include cell level properties, but model only a few cells of simple shapes in low-volume fractions or are in two dimensions. We constructed a three-dimensional model of realistically shaped cells in realistic volume fractions. By using a 'unit cell' model, the equivalent dielectric properties of whole tissue could be calculated. We calculated the dielectric properties of electroporated skin. We modeled electroporation of single cells by pore formation on keratinocytes and on the papillary dermis which gave dielectric properties of the electroporated epidermis and papillary dermis. During skin electroporation, local transport regions are formed in the stratum corneum. We modeled local transport regions and increase in their radii or density which affected the dielectric properties of the stratum corneum. The final model of skin electroporation accurately describes measured electric current and voltage drop on the skin during electroporation with long low-voltage pulses. The model also accurately describes voltage drop on the skin during electroporation with short high-voltage pulses. However, our results indicate that during application of short high-voltage pulses additional processes may occur which increase the electric current. Our model connects the processes occurring at the level of cell membranes (pore formation), at the level of a skin layer (formation of local transport region in the stratum corneum) with the tissue (skin layers) and even level of organs (skin). Using a similar approach, electroporation of any tissue can be modeled, if the morphology of the tissue is known.

  14. Optimisation of radiation protection

    International Nuclear Information System (INIS)

    1988-01-01

    Optimisation of radiation protection is one of the key elements in the current radiation protection philosophy. The present system of dose limitation was issued in 1977 by the International Commission on Radiological Protection (ICRP) and includes, in addition to the requirements of justification of practices and limitation of individual doses, the requirement that all exposures be kept as low as is reasonably achievable, taking social and economic factors into account. This last principle is usually referred to as optimisation of radiation protection, or the ALARA principle. The NEA Committee on Radiation Protection and Public Health (CRPPH) organised an ad hoc meeting, in liaison with the NEA committees on the safety of nuclear installations and radioactive waste management. Separate abstracts were prepared for individual papers presented at the meeting

  15. Optimisation by hierarchical search

    Science.gov (United States)

    Zintchenko, Ilia; Hastings, Matthew; Troyer, Matthias

    2015-03-01

    Finding optimal values for a set of variables relative to a cost function gives rise to some of the hardest problems in physics, computer science and applied mathematics. Although often very simple in their formulation, these problems have a complex cost function landscape which prevents currently known algorithms from efficiently finding the global optimum. Countless techniques have been proposed to partially circumvent this problem, but an efficient method is yet to be found. We present a heuristic, general purpose approach to potentially improve the performance of conventional algorithms or special purpose hardware devices by optimising groups of variables in a hierarchical way. We apply this approach to problems in combinatorial optimisation, machine learning and other fields.

  16. Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille

    2012-01-01

    in vivo. Calcium electroporation elicited dramatic antitumor responses in which 89% of treated tumors were eliminated. Histologic analyses indicated complete tumor necrosis. Mechanistically, calcium electroporation caused acute ATP depletion likely due to a combination of increased cellular use of ATP......, decreased production of ATP due to effects on the mitochondria, as well as loss of ATP through the permeabilized cell membrane. Taken together, our findings offer a preclinical proof of concept for the use of electroporation to load cancer cells with calcium as an efficient anticancer treatment...

  17. Advanced optimisation - coal fired power plant operations

    Energy Technology Data Exchange (ETDEWEB)

    Turney, D.M.; Mayes, I. [E.ON UK, Nottingham (United Kingdom)

    2005-03-01

    The purpose of this unit optimization project is to develop an integrated approach to unit optimisation and develop an overall optimiser that is able to resolve any conflicts between the individual optimisers. The individual optimisers have been considered during this project are: on-line thermal efficiency package, GNOCIS boiler optimiser, GNOCIS steam side optimiser, ESP optimisation, and intelligent sootblowing system. 6 refs., 7 figs., 3 tabs.

  18. Optimisation in radiotherapy II: Programmed and inversion optimisation algorithms

    International Nuclear Information System (INIS)

    Ebert, M.

    1997-01-01

    This is the second article in a three part examination of optimisation in radiotherapy. The previous article established the bases of optimisation in radiotherapy, and the formulation of the optimisation problem. This paper outlines several algorithms that have been used in radiotherapy, for searching for the best irradiation strategy within the full set of possible strategies. Two principle classes of algorithm are considered - those associated with mathematical programming which employ specific search techniques, linear programming type searches or artificial intelligence - and those which seek to perform a numerical inversion of the optimisation problem, finishing with deterministic iterative inversion. (author)

  19. Efficient in vivo electroporation of the postnatal rodent forebrain.

    Directory of Open Access Journals (Sweden)

    Camille Boutin

    Full Text Available Functional gene analysis in vivo represents still a major challenge in biomedical research. Here we present a new method for the efficient introduction of nucleic acids into the postnatal mouse forebrain. We show that intraventricular injection of DNA followed by electroporation induces strong expression of transgenes in radial glia, neuronal precursors and neurons of the olfactory system. We present two proof-of-principle experiments to validate our approach. First, we show that expression of a human isoform of the neural cell adhesion molecule (hNCAM-140 in radial glia cells induces their differentiation into cells showing a neural precursor phenotype. Second, we demonstrate that p21 acts as a cell cycle inhibitor for postnatal neural stem cells. This approach will represent an important tool for future studies of postnatal neurogenesis and of neural development in general.

  20. Effects of deformability and thermal motion of lipid membrane on electroporation: By molecular dynamics simulations

    KAUST Repository

    Sun, Sheng; Yin, Guangyao; Lee, Yi-Kuen; Wong, Joseph T.Y.; Zhang, Tong-Yi

    2011-01-01

    Effects of mechanical properties and thermal motion of POPE lipid membrane on electroporation were studied by molecular dynamics simulations. Among simulations in which specific atoms of lipids were artificially constrained at their equilibrium

  1. Effect of electroporation on radiosensitization with cisplatin in two cell lines with different chemo- and radiosensitivity

    International Nuclear Information System (INIS)

    Kranjc, S.; Cemazar, M.; Grosel, A.; Pipan, Z.; Sersa, G.

    2003-01-01

    Aim. Radiosensitization with cisplatin can be enhanced by electroporation of cells and tumours. The aim of this study was to extend our previous studies on two carcinoma tumour models with different chemo- and radiosensitivity in order to evaluate whether this treatment is effective also on less chemo- and radiosensitive tumour cells. Materials and methods. This in vitro study was performed on carcinoma SCK and EAT-E cells. The cytotoxicity of three-modality treatment consisting of cisplatin, electroporation and irradiation was determined by the clonogenic assay. Results. The radiosensitizing effect of cisplatin on the two cell lines was greatly enhanced by electroporation. By this combined treatment, less chemo and radiosensitive EAT-E cells were rendered as sensitive as more chemo and radiosensitive SCK cells. Conclusion. The enhancement of cisplatin-induced radiosensitization of cells by electroporation could be beneficially used in the treatment of intrinsically less chemo- and radiosensitive tumours. (author)

  2. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers.

    Directory of Open Access Journals (Sweden)

    Sandhya Vasan

    Full Text Available DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987.

  3. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  4. Optimisation of monochrome images

    International Nuclear Information System (INIS)

    Potter, R.

    1983-01-01

    Gamma cameras with modern imaging systems usually digitize the signals to allow storage and processing of the image in a computer. Although such computer systems are widely used for the extraction of quantitative uptake estimates and the analysis of time variant data, the vast majority of nuclear medicine images is still interpreted on the basis of an observer's visual assessment of a photographic hardcopy image. The optimisation of hardcopy devices is therefore vital and factors such as resolution, uniformity, noise grey scales and display matrices are discussed. Once optimum display parameters have been determined, routine procedures for quality control need to be established; suitable procedures are discussed. (U.K.)

  5. Electroporation-Induced Cell Modifications Detected with THz Time-Domain Spectroscopy

    Science.gov (United States)

    Romeo, Stefania; Vernier, P. Thomas; Zeni, Olga

    2018-04-01

    Electroporation (electropermeabilization) increases the electrical conductivity of biological cell membranes and lowers transport barriers for normally impermeant materials. Molecular simulations suggest that electroporation begins with the reorganization of water and lipid head group dipoles in the phospholipid bilayer interface, driven by an externally applied electric field, and the evolution of the resulting defects into water-filled, lipid pores. The interior of the electroporated membrane thus contains water, which should provide a signature for detection of the electropermeabilized state. In this feasibility study, we use THz time-domain spectroscopy, a powerful tool for investigating biomolecular systems and their interactions with water, to detect electroporation in human cells subjected to permeabilizing pulsed electric fields (PEFs). The time-domain response of electroporated human monocytes was acquired with a commercial THz, time-domain spectrometer. For each sample, frequency spectra were calculated, and the absorption coefficient and refractive index were extracted in the frequency range between 0.2 and 1.5 THz. This analysis reveals a higher absorption of THz radiation by PEF-exposed cells, with respect to sham-exposed ones, consistent with the intrusion of water into the cell through the permeabilized membrane that is presumed to be associated with electroporation.

  6. Electroporation of cells using EM induction of ac fields by a magnetic stimulator

    International Nuclear Information System (INIS)

    Chen, C; Robinson, M P; Evans, J A; Smye, S W; O'Toole, P

    2010-01-01

    This paper describes a method of effectively electroporating mammalian cell membranes with pulsed alternating-current (ac) electric fields at field strengths of 30-160 kV m -1 . Although many in vivo electroporation protocols entail applying square wave or monotonically decreasing pulses via needles or electrode plates, relatively few have explored the use of pulsed ac fields. Following our previous study, which established the effectiveness of ac fields for electroporating cell membranes, a primary/secondary coil system was constructed to produce sufficiently strong electric fields by electromagnetic induction. The primary coil was formed from the applicator of an established transcranial magnetic stimulation (TMS) system, while the secondary coil was a purpose-built device of a design which could eventually be implanted into tissue. The effects of field strength, pulse interval and cumulative exposure time were investigated using microscopy and flow cytometry. Results from experiments on concentrated cell suspensions showed an optimized electroporation efficiency of around 50%, demonstrating that electroporation can be practicably achieved by inducing such pulsed ac fields. This finding confirms the possibility of a wide range of in vivo applications based on magnetically coupled ac electroporation.

  7. Electroporation of cells using EM induction of ac fields by a magnetic stimulator

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C; Robinson, M P [Department of Electronics, University of York, Heslington, York YO10 5DD (United Kingdom); Evans, J A [Academic Unit of Medical Physics, University of Leeds, Leeds LS2 9JT (United Kingdom); Smye, S W [Department of Medical Physics and Engineering, Leeds Teaching Hospitals, St. James' s University Hospital, Leeds LS9 7TF (United Kingdom); O' Toole, P [Department of Biology, University of York, Heslington, York YO10 5DD (United Kingdom)

    2010-02-21

    This paper describes a method of effectively electroporating mammalian cell membranes with pulsed alternating-current (ac) electric fields at field strengths of 30-160 kV m{sup -1}. Although many in vivo electroporation protocols entail applying square wave or monotonically decreasing pulses via needles or electrode plates, relatively few have explored the use of pulsed ac fields. Following our previous study, which established the effectiveness of ac fields for electroporating cell membranes, a primary/secondary coil system was constructed to produce sufficiently strong electric fields by electromagnetic induction. The primary coil was formed from the applicator of an established transcranial magnetic stimulation (TMS) system, while the secondary coil was a purpose-built device of a design which could eventually be implanted into tissue. The effects of field strength, pulse interval and cumulative exposure time were investigated using microscopy and flow cytometry. Results from experiments on concentrated cell suspensions showed an optimized electroporation efficiency of around 50%, demonstrating that electroporation can be practicably achieved by inducing such pulsed ac fields. This finding confirms the possibility of a wide range of in vivo applications based on magnetically coupled ac electroporation.

  8. Effects of deformability and thermal motion of lipid membrane on electroporation: By molecular dynamics simulations

    International Nuclear Information System (INIS)

    Sun, Sheng; Yin, Guangyao; Lee, Yi-Kuen; Wong, Joseph T.Y.; Zhang, Tong-Yi

    2011-01-01

    Research highlights: → MD simulations show that deformability and thermal motion of membrane affect electroporation. → Stiffer membrane inhibits electroporation and makes water penetrate from both sides. → Higher temperature accelerates electroporation. -- Abstract: Effects of mechanical properties and thermal motion of POPE lipid membrane on electroporation were studied by molecular dynamics simulations. Among simulations in which specific atoms of lipids were artificially constrained at their equilibrium positions using a spring with force constant of 2.0 kcal/(mol A 2 ) in the external electric field of 1.4 kcal/(mol A e), only constraint on lateral motions of lipid tails prohibited electroporation while non-tail parts had little effects. When force constant decreased to 0.2 kcal/(mol A 2 ) in the position constraints on lipid tails in the external electric field of 2.0 kcal/(mol A e), water molecules began to enter the membrane. Position constraints of lipid tails allow water to penetrate from both sides of membrane. Thermal motion of lipids can induce initial defects in the hydrophobic core of membrane, which are favorable nucleation sites for electroporation. Simulations at different temperatures revealed that as the temperature increases, the time taken to the initial pore formation will decrease.

  9. Beam position optimisation for IMRT

    International Nuclear Information System (INIS)

    Holloway, L.; Hoban, P.

    2001-01-01

    Full text: The introduction of IMRT has not generally resulted in the use of optimised beam positions because to find the global solution of the problem a time consuming stochastic optimisation method must be used. Although a deterministic method may not achieve the global minimum it should achieve a superior dose distribution compared to no optimisation. This study aimed to develop and test such a method. The beam optimisation method developed relies on an iterative process to achieve the desired number of beams from a large initial number of beams. The number of beams is reduced in a 'weeding-out' process based on the total fluence which each beam delivers. The process is gradual, with only three beams removed each time (following a small number of iterations), ensuring that the reduction in beams does not dramatically affect the fluence maps of those remaining. A comparison was made between the dose distributions achieved when the beams positions were optimised in this fashion and when the beams positions were evenly distributed. The method has been shown to work quite effectively and efficiently. The Figure shows a comparison in dose distribution with optimised and non optimised beam positions for 5 beams. It can be clearly seen that there is an improvement in the dose distribution delivered to the tumour and a reduction in the dose to the critical structure with beam position optimisation. A method for beam position optimisation for use in IMRT optimisations has been developed. This method although not necessarily achieving the global minimum in beam position still achieves quite a dramatic improvement compared with no beam position optimisation and is very efficiently achieved. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

  10. Electroporation of Mammalian Cells by Nanosecond Electric Field Oscillations and its Inhibition by the Electric Field Reversal

    Science.gov (United States)

    2015-09-08

    Report 3. DATES COVERED (From – To) March 2013 to July 2015 4. TITLE AND SUBTITLE Electroporation of mammalian cells by nanosecond electric field...Prescribed by ANSI Std. Z39.18 1Scientific RepoRts | 5:13818 | DOi: 10.1038/srep13818 www.nature.com/scientificreports Electroporation of mammalian cells...first to demonstrate that mammalian cells can be electroporated by damped sine wave electric stimuli of nanosecond duration. By comparing the

  11. Optimisation of occupational exposure

    International Nuclear Information System (INIS)

    Webb, G.A.M.; Fleishman, A.B.

    1982-01-01

    The general concept of the optimisation of protection of the public is briefly described. Some ideas being developed for extending the cost benefit framework to include radiation workers with full implementation of the ALARA criterion are described. The role of cost benefit analysis in radiological protection and the valuation of health detriment including the derivation of monetary values and practical implications are discussed. Cost benefit analysis can lay out for inspection the doses, the associated health detriment costs and the costs of protection for alternative courses of action. However it is emphasised that the cost benefit process is an input to decisions on what is 'as low as reasonably achievable' and not a prescription for making them. (U.K.)

  12. Effects of in ovo electroporation on endogenous gene expression: genome-wide analysis

    Directory of Open Access Journals (Sweden)

    Chambers David

    2011-04-01

    Full Text Available Abstract Background In ovo electroporation is a widely used technique to study gene function in developmental biology. Despite the widespread acceptance of this technique, no genome-wide analysis of the effects of in ovo electroporation, principally the current applied across the tissue and exogenous vector DNA introduced, on endogenous gene expression has been undertaken. Here, the effects of electric current and expression of a GFP-containing construct, via electroporation into the midbrain of Hamburger-Hamilton stage 10 chicken embryos, are analysed by microarray. Results Both current alone and in combination with exogenous DNA expression have a small but reproducible effect on endogenous gene expression, changing the expression of the genes represented on the array by less than 0.1% (current and less than 0.5% (current + DNA, respectively. The subset of genes regulated by electric current and exogenous DNA span a disparate set of cellular functions. However, no genes involved in the regional identity were affected. In sharp contrast to this, electroporation of a known transcription factor, Dmrt5, caused a much greater change in gene expression. Conclusions These findings represent the first systematic genome-wide analysis of the effects of in ovo electroporation on gene expression during embryonic development. The analysis reveals that this process has minimal impact on the genetic basis of cell fate specification. Thus, the study demonstrates the validity of the in ovo electroporation technique to study gene function and expression during development. Furthermore, the data presented here can be used as a resource to refine the set of transcriptional responders in future in ovo electroporation studies of specific gene function.

  13. Standardised approach to optimisation

    International Nuclear Information System (INIS)

    Warren-Forward, Helen M.; Beckhaus, Ronald

    2004-01-01

    Optimisation of radiographic images is said to have been obtained if the patient has achieved an acceptable level of dose and the image is of diagnostic value. In the near future, it will probably be recommended that radiographers measure patient doses and compare them to reference levels. The aim of this paper is to describe a standardised approach to optimisation of radiographic examinations in a diagnostic imaging department. A three-step approach is outlined with specific examples for some common examinations (chest, abdomen, pelvis and lumbar spine series). Step One: Patient doses are calculated. Step Two: Doses are compared to existing reference levels and the technique used compared to image quality criteria. Step Three: Appropriate action is taken if doses are above the reference level. Results: Average entrance surface doses for two rooms were as follows AP Abdomen (6.3mGy and 3.4mGy); AP Lumbar Spine (6.4mGy and 4.1mGy) for AP Pelvis (4.8mGy and 2.6mGy) and PA chest (0.19mGy and 0.20mGy). Comparison with the Commission of the European Communities (CEC) recommended techniques identified large differences in the applied potential. The kVp values in this study were significantly lower (by up to lOkVp) than the CEC recommendations. The results of this study have indicated that there is a need to monitor radiation doses received by patients undergoing diagnostic radiography examinations. Not only has the assessment allowed valuable comparison with International Diagnostic Reference Levels and Radiography Good Practice but has demonstrated large variations in mean doses being delivered from different rooms of the same radiology department. Following the simple 3-step approach advocated in this paper should either provide evidence that department are practising the ALARA principle or assist in making suitable changes to current practice. Copyright (2004) Australian Institute of Radiography

  14. In situ formation of magnetopolymersomes via electroporation for MRI

    Science.gov (United States)

    Bain, Jennifer; Ruiz-Pérez, Lorena; Kennerley, Aneurin J.; Muench, Stephen P.; Thompson, Rebecca; Battaglia, Giuseppe; Staniland, Sarah S.

    2015-09-01

    As the development of diagnostic/therapeutic (and combined: theranostic) nanomedicine grows, smart drug-delivery vehicles become ever more critical. Currently therapies consist of drugs tethered to, or encapsulated within nanoparticles or vesicles. There is growing interest in functionalising them with magnetic nanoparticles (MNPs) to target the therapeutics by localising them using magnetic fields. An alternating magnetic field induces remote heating of the particles (hyperthermia) triggering drug release or cell death. Furthermore, MNPs are diagnostic MRI contrast agents. There is considerable interest in MNP embedded vehicles for nanomedicine, but their development is hindered by difficulties producing consistently monodisperse MNPs and their reliable loading into vesicles. Furthermore, it is highly advantageous to "trigger" MNP production and to tune the MNP's size and magnetic response. Here we present the first example of a tuneable, switchable magnetic delivery vehicle for nanomedical application. These are comprised of robust, tailored polymer vesicles (polymersomes) embedded with superparamagnetic magnetite MNPs (magnetopolymersomes) which show good MRI contrast (R2* = 148.8 s-1) and have a vacant core for loading of therapeutics. Critically, the magnetopolymersomes are produced by a pioneering nanoreactor method whereby electroporation triggers the in situ formation of MNPs within the vesicle membrane, offering a switchable, tuneable magnetic responsive theranostic delivery vehicle.

  15. The effects of irreversible electroporation (IRE on nerves.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available BACKGROUND: If a critical nerve is circumferentially involved with tumor, radical surgery intended to cure the cancer must sacrifice the nerve. Loss of critical nerves may lead to serious consequences. In spite of the impressive technical advancements in nerve reconstruction, complete recovery and normalization of nerve function is difficult to achieve. Though irreversible electroporation (IRE might be a promising choice to treat tumors near or involved critical nerve, the pathophysiology of the nerve after IRE treatment has not be clearly defined. METHODS: We applied IRE directly to a rat sciatic nerve to study the long term effects of IRE on the nerve. A sequence of 10 square pulses of 3800 V/cm, each 100 µs long was applied directly to rat sciatic nerves. In each animal of group I (IRE the procedure was applied to produce a treated length of about 10 mm. In each animal of group II (Control the electrodes were only applied directly on the sciatic nerve for the same time. Electrophysiological, histological, and functional studies were performed on immediately after and 3 days, 1 week, 3, 5, 7 and 10 weeks following surgery. FINDINGS: Electrophysiological, histological, and functional results show the nerve treated with IRE can attain full recovery after 7 weeks. CONCLUSION: This finding is indicative of the preservation of nerve involving malignant tumors with respect to the application of IRE pulses to ablate tumors completely. In summary, IRE may be a promising treatment tool for any tumor involving nerves.

  16. Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration.

    Science.gov (United States)

    Berkó, Szilvia; Szűcs, Kálmán F; Balázs, Boglárka; Csányi, Erzsébet; Varju, Gábor; Sztojkov-Ivanov, Anita; Budai-Szűcs, Mária; Bóta, Judit; Gáspár, Róbert

    2016-01-01

    Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Both intravenously and EP-administered neostigmine (0.2-66.7 μg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 μg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice.

  17. Intracellular Protein Delivery and Gene Transfection by Electroporation Using a Microneedle Electrode Array

    Science.gov (United States)

    Choi, Seong-O; Kim, Yeu-Chun; Lee, Jeong Woo; Park, Jung-Hwan

    2012-01-01

    The impact of many biopharmaceuticals, including protein- and gene-based therapies, has been limited by the need for better methods of delivery into cells within tissues. Here, we present intracellular delivery of molecules and transfection with plasmid DNA by electroporation using a novel microneedle electrode array designed for targeted treatment of skin and other tissue surfaces. The microneedle array is molded out of polylactic acid. Electrodes and circuitry required for electroporation are applied to the microneedle array surface by a new metal-transfer micromolding method. The microneedle array maintains mechanical integrity after insertion into pig cadaver skin and is able to electroporate human prostate cancer cells in vitro. Quantitative measurements show that increasing electroporation pulse voltage increases uptake efficiency of calcein and bovine serum albumin, whereas increasing pulse length has lesser effects over the range studied. Uptake of molecules by up to 50 % of cells and transfection of 12 % of cells with a gene for green fluorescent protein is demonstrated at high cell viability. We conclude that the microneedle electrode array is able to electroporate cells, resulting in intracellular uptake of molecules, and has potential applications to improve intracellular delivery of proteins, DNA and other biopharmaceuticals. PMID:22328093

  18. Topology optimised wavelength dependent splitters

    DEFF Research Database (Denmark)

    Hede, K. K.; Burgos Leon, J.; Frandsen, Lars Hagedorn

    A photonic crystal wavelength dependent splitter has been constructed by utilising topology optimisation1. The splitter has been fabricated in a silicon-on-insulator material (Fig. 1). The topology optimised wavelength dependent splitter demonstrates promising 3D FDTD simulation results....... This complex photonic crystal structure is very sensitive against small fabrication variations from the expected topology optimised design. A wavelength dependent splitter is an important basic building block for high-performance nanophotonic circuits. 1J. S. Jensen and O. Sigmund, App. Phys. Lett. 84, 2022...

  19. Optimisation of the Laser Cutting Process

    DEFF Research Database (Denmark)

    Dragsted, Birgitte; Olsen, Flemmming Ove

    1996-01-01

    The problem in optimising the laser cutting process is outlined. Basic optimisation criteria and principles for adapting an optimisation method, the simplex method, are presented. The results of implementing a response function in the optimisation are discussed with respect to the quality as well...

  20. Turbulence optimisation in stellarator experiments

    Energy Technology Data Exchange (ETDEWEB)

    Proll, Josefine H.E. [Max-Planck/Princeton Center for Plasma Physics (Germany); Max-Planck-Institut fuer Plasmaphysik, Wendelsteinstr. 1, 17491 Greifswald (Germany); Faber, Benjamin J. [HSX Plasma Laboratory, University of Wisconsin-Madison, Madison, WI 53706 (United States); Helander, Per; Xanthopoulos, Pavlos [Max-Planck/Princeton Center for Plasma Physics (Germany); Lazerson, Samuel A.; Mynick, Harry E. [Plasma Physics Laboratory, Princeton University, P.O. Box 451 Princeton, New Jersey 08543-0451 (United States)

    2015-05-01

    Stellarators, the twisted siblings of the axisymmetric fusion experiments called tokamaks, have historically suffered from confining the heat of the plasma insufficiently compared with tokamaks and were therefore considered to be less promising candidates for a fusion reactor. This has changed, however, with the advent of stellarators in which the laminar transport is reduced to levels below that of tokamaks by shaping the magnetic field accordingly. As in tokamaks, the turbulent transport remains as the now dominant transport channel. Recent analytical theory suggests that the large configuration space of stellarators allows for an additional optimisation of the magnetic field to also reduce the turbulent transport. In this talk, the idea behind the turbulence optimisation is explained. We also present how an optimised equilibrium is obtained and how it might differ from the equilibrium field of an already existing device, and we compare experimental turbulence measurements in different configurations of the HSX stellarator in order to test the optimisation procedure.

  1. Optimisation of load control

    International Nuclear Information System (INIS)

    Koponen, P.

    1998-01-01

    Electricity cannot be stored in large quantities. That is why the electricity supply and consumption are always almost equal in large power supply systems. If this balance were disturbed beyond stability, the system or a part of it would collapse until a new stable equilibrium is reached. The balance between supply and consumption is mainly maintained by controlling the power production, but also the electricity consumption or, in other words, the load is controlled. Controlling the load of the power supply system is important, if easily controllable power production capacity is limited. Temporary shortage of capacity causes high peaks in the energy price in the electricity market. Load control either reduces the electricity consumption during peak consumption and peak price or moves electricity consumption to some other time. The project Optimisation of Load Control is a part of the EDISON research program for distribution automation. The following areas were studied: Optimization of space heating and ventilation, when electricity price is time variable, load control model in power purchase optimization, optimization of direct load control sequences, interaction between load control optimization and power purchase optimization, literature on load control, optimization methods and field tests and response models of direct load control and the effects of the electricity market deregulation on load control. An overview of the main results is given in this chapter

  2. Optimisation of load control

    Energy Technology Data Exchange (ETDEWEB)

    Koponen, P [VTT Energy, Espoo (Finland)

    1998-08-01

    Electricity cannot be stored in large quantities. That is why the electricity supply and consumption are always almost equal in large power supply systems. If this balance were disturbed beyond stability, the system or a part of it would collapse until a new stable equilibrium is reached. The balance between supply and consumption is mainly maintained by controlling the power production, but also the electricity consumption or, in other words, the load is controlled. Controlling the load of the power supply system is important, if easily controllable power production capacity is limited. Temporary shortage of capacity causes high peaks in the energy price in the electricity market. Load control either reduces the electricity consumption during peak consumption and peak price or moves electricity consumption to some other time. The project Optimisation of Load Control is a part of the EDISON research program for distribution automation. The following areas were studied: Optimization of space heating and ventilation, when electricity price is time variable, load control model in power purchase optimization, optimization of direct load control sequences, interaction between load control optimization and power purchase optimization, literature on load control, optimization methods and field tests and response models of direct load control and the effects of the electricity market deregulation on load control. An overview of the main results is given in this chapter

  3. SPS batch spacing optimisation

    CERN Document Server

    Velotti, F M; Carlier, E; Goddard, B; Kain, V; Kotzian, G

    2017-01-01

    Until 2015, the LHC filling schemes used the batch spac-ing as specified in the LHC design report. The maximumnumber of bunches injectable in the LHC directly dependson the batch spacing at injection in the SPS and hence onthe MKP rise time.As part of the LHC Injectors Upgrade project for LHCheavy ions, a reduction of the batch spacing is needed. In thisdirection, studies to approach the MKP design rise time of150ns(2-98%) have been carried out. These measurementsgave clear indications that such optimisation, and beyond,could be done also for higher injection momentum beams,where the additional slower MKP (MKP-L) is needed.After the successful results from 2015 SPS batch spacingoptimisation for the Pb-Pb run [1], the same concept wasthought to be used also for proton beams. In fact, thanksto the SPS transverse feed back, it was already observedthat lower batch spacing than the design one (225ns) couldbe achieved. For the 2016 p-Pb run, a batch spacing of200nsfor the proton beam with100nsbunch spacing wasreque...

  4. Gene delivery by microfluidic flow-through electroporation based on constant DC and AC field.

    Science.gov (United States)

    Geng, Tao; Zhan, Yihong; Lu, Chang

    2012-01-01

    Electroporation is one of the most widely used physical methods to deliver exogenous nucleic acids into cells with high efficiency and low toxicity. Conventional electroporation systems typically require expensive pulse generators to provide short electrical pulses at high voltage. In this work, we demonstrate a flow-through electroporation method for continuous transfection of cells based on disposable chips, a syringe pump, and a low-cost power supply that provides a constant voltage. We successfully transfect cells using either DC or AC voltage with high flow rates (ranging from 40 µl/min to 20 ml/min) and high efficiency (up to 75%). We also enable the entire cell membrane to be uniformly permeabilized and dramatically improve gene delivery by inducing complex migrations of cells during the flow.

  5. Lightning-triggered electroporation and electrofusion as possible contributors to natural horizontal gene transfer.

    Science.gov (United States)

    Kotnik, Tadej

    2013-09-01

    Phylogenetic studies show that horizontal gene transfer (HGT) is a significant contributor to genetic variability of prokaryotes, and was perhaps even more abundant during the early evolution. Hitherto, research of natural HGT has mainly focused on three mechanisms of DNA transfer: conjugation, natural competence, and viral transduction. This paper discusses the feasibility of a fourth such mechanism--cell electroporation and/or electrofusion triggered by atmospheric electrostatic discharges (lightnings). A description of electroporation as a phenomenon is followed by a review of experimental evidence that electroporation of prokaryotes in aqueous environments can result in release of non-denatured DNA, as well as uptake of DNA from the surroundings and transformation. Similarly, a description of electrofusion is followed by a review of experiments showing that prokaryotes devoid of cell wall can electrofuse into hybrids expressing the genes of their both precursors. Under sufficiently fine-tuned conditions, electroporation and electrofusion are efficient tools for artificial transformation and hybridization, respectively, but the quantitative analysis developed here shows that conditions for electroporation-based DNA release, DNA uptake and transformation, as well as for electrofusion are also present in many natural aqueous environments exposed to lightnings. Electroporation is thus a plausible contributor to natural HGT among prokaryotes, and could have been particularly important during the early evolution, when the other mechanisms might have been scarcer or nonexistent. In modern prokaryotes, natural absence of the cell wall is rare, but it is reasonable to assume that the wall has formed during a certain stage of evolution, and at least prior to this, electrofusion could also have contributed to natural HGT. The concluding section outlines several guidelines for assessment of the feasibility of lightning-triggered HGT. © 2013 Elsevier B.V. All rights

  6. Theoretical and experimental study of electroporation of red blood cells using MEMS technology

    KAUST Repository

    Deng, Peigang; Yin, Guangyao; Zhang, Tong Yi; Chang, Donald C.; Lee, Yi Kuen

    2010-01-01

    A theoretical and experimental study of electroporation (EP) of red blood cells (RBCs) was presented in this paper. With additional strain energy, an energy-based model of an electropore induced on a RBC's membrane at different electric fields was proposed to predict the critical EP electric field strength. In addition, EP experiments with red blood cells at single-cell level was carried out on a micro EP chip. The measured critical EP electric field strengths are in agreement with the numerical predictions. ©2010 IEEE.

  7. Theoretical and experimental study of electroporation of red blood cells using MEMS technology

    KAUST Repository

    Deng, Peigang

    2010-01-01

    A theoretical and experimental study of electroporation (EP) of red blood cells (RBCs) was presented in this paper. With additional strain energy, an energy-based model of an electropore induced on a RBC\\'s membrane at different electric fields was proposed to predict the critical EP electric field strength. In addition, EP experiments with red blood cells at single-cell level was carried out on a micro EP chip. The measured critical EP electric field strengths are in agreement with the numerical predictions. ©2010 IEEE.

  8. Vaccine strategies: Optimising outcomes.

    Science.gov (United States)

    Hardt, Karin; Bonanni, Paolo; King, Susan; Santos, Jose Ignacio; El-Hodhod, Mostafa; Zimet, Gregory D; Preiss, Scott

    2016-12-20

    factors that encourage success, which often include strong support from government and healthcare organisations, as well as tailored, culturally-appropriate local approaches to optimise outcomes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells.

    Science.gov (United States)

    Van Tendeloo, V F; Ponsaerts, P; Lardon, F; Nijs, G; Lenjou, M; Van Broeckhoven, C; Van Bockstaele, D R; Berneman, Z N

    2001-07-01

    Designing effective strategies to load human dendritic cells (DCs) with tumor antigens is a challenging approach for DC-based tumor vaccines. Here, a cytoplasmic expression system based on mRNA electroporation to efficiently introduce tumor antigens into DCs is described. Preliminary experiments in K562 cells using an enhanced green fluorescent protein (EGFP) reporter gene revealed that mRNA electroporation as compared with plasmid DNA electroporation showed a markedly improved transfection efficiency (89% versus 40% EGFP(+) cells, respectively) and induced a strikingly lower cell toxicity (15% death rate with mRNA versus 51% with plasmid DNA). Next, mRNA electroporation was applied for nonviral transfection of different types of human DCs, including monocyte-derived DCs (Mo-DCs), CD34(+) progenitor-derived DCs (34-DCs) and Langerhans cells (34-LCs). High-level transgene expression by mRNA electroporation was obtained in more than 50% of all DC types. mRNA-electroporated DCs retained their phenotype and maturational potential. Importantly, DCs electroporated with mRNA-encoding Melan-A strongly activated a Melan-A-specific cytotoxic T lymphocyte (CTL) clone in an HLA-restricted manner and were superior to mRNA-lipofected or -pulsed DCs. Optimal stimulation of the CTL occurred when Mo-DCs underwent maturation following mRNA transfection. Strikingly, a nonspecific stimulation of CTL was observed when DCs were transfected with plasmid DNA. The data clearly demonstrate that Mo-DCs electroporated with mRNA efficiently present functional antigenic peptides to cytotoxic T cells. Therefore, electroporation of mRNA-encoding tumor antigens is a powerful technique to charge human dendritic cells with tumor antigens and could serve applications in future DC-based tumor vaccines.

  10. Efficient transfection of DNA into primarily cultured rat sertoli cells by electroporation.

    Science.gov (United States)

    Li, Fuping; Yamaguchi, Kohei; Okada, Keisuke; Matsushita, Kei; Enatsu, Noritoshi; Chiba, Koji; Yue, Huanxun; Fujisawa, Masato

    2013-03-01

    The expression of exogenous DNA in Sertoli cells is essential for studying its functional genomics, pathway analysis, and medical applications. Electroporation is a valuable tool for nucleic acid delivery, even in primarily cultured cells, which are considered difficult to transfect. In this study, we developed an optimized protocol for electroporation-based transfection of Sertoli cells and compared its efficiency with conventional lipofection. Sertoli cells were transfected with pCMV-GFP plasmid by square-wave electroporation under different conditions. After transfection of plasmid into Sertoli cells, enhanced green fluorescent protein (EGFP) expression could be easily detected by fluorescent microscopy, and cell survival was evaluated by dye exclusion assay using Trypan blue. In terms of both cell survival and the percentage expressing EGFP, 250 V was determined to produce the greatest number of transiently transfected cells. Keeping the voltage constant (250 V), relatively high cell survival (76.5% ± 3.4%) and transfection efficiency (30.6% ± 5.6%) were observed with a pulse length of 20 μm. The number of pulses significantly affected cell survival and EGFP expression (P transfection methods, the transfection efficiency of electroporation (21.5% ± 5.7%) was significantly higher than those of Lipofectamine 2000 (2.9% ± 1.0%) and Effectene (1.9% ± 0.8%) in this experiment (P transfection of Sertoli cells.

  11. Electroporation ablation: A new energy modality for ablation of arrhythmogenic cardiac substrate

    NARCIS (Netherlands)

    van Driel, VJHM

    2016-01-01

    At the very end of the Direct Current (DC) era, low-energy DC ablation was demonstrated to cause myocardial lesions by non-thermal irreversible electroporation (IRE) (permanent formation of pores in the cell membrane, leading to cell death), without arcing and/or barotrauma. To eliminate rather

  12. Scalable Device for Automated Microbial Electroporation in a Digital Microfluidic Platform.

    Science.gov (United States)

    Madison, Andrew C; Royal, Matthew W; Vigneault, Frederic; Chen, Liji; Griffin, Peter B; Horowitz, Mark; Church, George M; Fair, Richard B

    2017-09-15

    Electrowetting-on-dielectric (EWD) digital microfluidic laboratory-on-a-chip platforms demonstrate excellent performance in automating labor-intensive protocols. When coupled with an on-chip electroporation capability, these systems hold promise for streamlining cumbersome processes such as multiplex automated genome engineering (MAGE). We integrated a single Ti:Au electroporation electrode into an otherwise standard parallel-plate EWD geometry to enable high-efficiency transformation of Escherichia coli with reporter plasmid DNA in a 200 nL droplet. Test devices exhibited robust operation with more than 10 transformation experiments performed per device without cross-contamination or failure. Despite intrinsic electric-field nonuniformity present in the EP/EWD device, the peak on-chip transformation efficiency was measured to be 8.6 ± 1.0 × 10 8 cfu·μg -1 for an average applied electric field strength of 2.25 ± 0.50 kV·mm -1 . Cell survival and transformation fractions at this electroporation pulse strength were found to be 1.5 ± 0.3 and 2.3 ± 0.1%, respectively. Our work expands the EWD toolkit to include on-chip microbial electroporation and opens the possibility of scaling advanced genome engineering methods, like MAGE, into the submicroliter regime.

  13. Improvement of in vivo transfer of plasmid DNA in muscle : Comparison of electroporation versus ultrasound

    NARCIS (Netherlands)

    Kusumanto, Yoka H.; Mulder, Nanno H.; Dam, Wendy A.; Losen, Mario H.; Meijer, Coby; Hospers, Geke A. P.

    Plasmid-based gene delivery to muscle is a treatment strategy for many diseases with potential advantages above viral-based gene delivery methods, however, with a relative low transfection efficiency. We compared two physical methods-electroporation and ultrasound-that facilitate DNA uptake into

  14. Irreversible electroporation ablation area enhanced by synergistic high- and low-voltage pulses.

    Directory of Open Access Journals (Sweden)

    Chenguo Yao

    Full Text Available Irreversible electroporation (IRE produced by a pulsed electric field can ablate tissue. In this study, we achieved an enhancement in ablation area by using a combination of short high-voltage pulses (HVPs to create a large electroporated area and long low-voltage pulses (LVPs to ablate the electroporated area. The experiments were conducted in potato tuber slices. Slices were ablated with an array of four pairs of parallel steel electrodes using one of the following four electric pulse protocols: HVP, LVP, synergistic HVP+LVP (SHLVP or LVP+HVP. Our results showed that the SHLVPs more effectively necrotized tissue than either the HVPs or LVPs, even when the SHLVP dose was the same as or lower than the HVP or LVP doses. The HVP and LVP order mattered and only HVPs+LVPs (SHLVPs treatments increased the size of the ablation zone because the HVPs created a large electroporated area that was more susceptible to the subsequent LVPs. Real-time temperature change monitoring confirmed that the tissue was non-thermally ablated by the electric pulses. Theoretical calculations of the synergistic effects of the SHLVPs on tissue ablation were performed. Our proposed SHLVP protocol provides options for tissue ablation and may be applied to optimize the current clinical IRE protocols.

  15. Irreversible electroporation ablation area enhanced by synergistic high- and low-voltage pulses.

    Science.gov (United States)

    Yao, Chenguo; Lv, Yanpeng; Dong, Shoulong; Zhao, Yajun; Liu, Hongmei

    2017-01-01

    Irreversible electroporation (IRE) produced by a pulsed electric field can ablate tissue. In this study, we achieved an enhancement in ablation area by using a combination of short high-voltage pulses (HVPs) to create a large electroporated area and long low-voltage pulses (LVPs) to ablate the electroporated area. The experiments were conducted in potato tuber slices. Slices were ablated with an array of four pairs of parallel steel electrodes using one of the following four electric pulse protocols: HVP, LVP, synergistic HVP+LVP (SHLVP) or LVP+HVP. Our results showed that the SHLVPs more effectively necrotized tissue than either the HVPs or LVPs, even when the SHLVP dose was the same as or lower than the HVP or LVP doses. The HVP and LVP order mattered and only HVPs+LVPs (SHLVPs) treatments increased the size of the ablation zone because the HVPs created a large electroporated area that was more susceptible to the subsequent LVPs. Real-time temperature change monitoring confirmed that the tissue was non-thermally ablated by the electric pulses. Theoretical calculations of the synergistic effects of the SHLVPs on tissue ablation were performed. Our proposed SHLVP protocol provides options for tissue ablation and may be applied to optimize the current clinical IRE protocols.

  16. Electroporation Enhanced Effect of Dystrophin Splice Switching PNA Oligomers in Normal and Dystrophic Muscle

    Directory of Open Access Journals (Sweden)

    Camilla Brolin

    2015-01-01

    Full Text Available Peptide nucleic acid (PNA is a synthetic DNA mimic that has shown potential for discovery of novel splice switching antisense drugs. However, in vivo cellular delivery has been a limiting factor for development, and only few successful studies have been reported. As a possible modality for improvement of in vivo cellular availability, we have investigated the effect of electrotransfer upon intramuscular (i.m. PNA administration in vivo. Antisense PNA targeting exon 23 of the murine dystrophin gene was administered by i.m. injection to the tibialis anterior (TA muscle of normal NMRI and dystrophic mdx mice with or without electroporation. At low, single PNA doses (1.5, 3, or 10 µg/TA, electroporation augmented the antisense exon skipping induced by an unmodified PNA by twofold to fourfold in healthy mouse muscle with optimized electric parameters, measured after 7 days. The PNA splice switching was detected at the RNA level up to 4 weeks after a single-dose treatment. In dystrophic muscles of the MDX mouse, electroporation increased the number of dystrophin-positive fibers about 2.5-fold at 2 weeks after a single PNA administration compared to injection only. In conclusion, we find that electroporation can enhance PNA antisense effects in muscle tissue.

  17. A method of genetically engineering acidophilic, heterotrophic, bacteria by electroporation and conjugation

    Energy Technology Data Exchange (ETDEWEB)

    Roberto, F.F.; Glenn, A.W.; Ward, T.E.

    1990-08-07

    A method of genetically manipulating an acidophilic bacteria is provided by two different procedures. Using electroporation, chimeric and broad-host range plasmids are introduced into Acidiphilium. Conjugation is also employed to introduce broad-host range plasmids into Acidiphilium at neutral pH.

  18. Injection molded chips with integrated conducting polymer electrodes for electroporation of cells

    DEFF Research Database (Denmark)

    Andresen, Kristian; Hansen, Morten; Matschuk, Maria

    2010-01-01

    We present the design-concept for an all polymer injection molded single use microfluidic device. The fabricated devices comprise integrated conducting polymer electrodes and Luer fitting ports to allow for liquid and electrical access. A case study of low voltage electroporation of biological...

  19. Studies on mRNA electroporation of immature and mature dendritic cells

    DEFF Research Database (Denmark)

    Met, Ozcan; Eriksen, Jens; Svane, Inge Marie

    2008-01-01

    Previous studies have shown that mRNA-electroporated dendritic cells (DCs) are able to process and present tumor-associated antigens, leading to the activation of tumor-specific T cells in vitro and in vivo. However, the optimal maturation state of antigen loading and half-life of the mRNA-transl...

  20. Magnetic resonance electrical impedance tomography for measuring electrical conductivity during electroporation

    International Nuclear Information System (INIS)

    Kranjc, M; Miklavčič, D; Bajd, F; Serša, I

    2014-01-01

    The electroporation effect on tissue can be assessed by measurement of electrical properties of the tissue undergoing electroporation. The most prominent techniques for measuring electrical properties of electroporated tissues have been voltage–current measurement of applied pulses and electrical impedance tomography (EIT). However, the electrical conductivity of tissue assessed by means of voltage–current measurement was lacking in information on tissue heterogeneity, while EIT requires numerous additional electrodes and produces results with low spatial resolution and high noise. Magnetic resonance EIT (MREIT) is similar to EIT, as it is also used for reconstruction of conductivity images, though voltage and current measurements are not limited to the boundaries in MREIT, hence it yields conductivity images with better spatial resolution. The aim of this study was to investigate and demonstrate the feasibility of the MREIT technique for assessment of conductivity images of tissues undergoing electroporation. Two objects were investigated: agar phantoms and ex vivo liver tissue. As expected, no significant change of electrical conductivity was detected in agar phantoms exposed to pulses of all used amplitudes, while a considerable increase of conductivity was measured in liver tissue exposed to pulses of different amplitudes. (paper)

  1. Controlled release of optimized electroporation enhances the transdermal efficiency of sinomenine hydrochloride for treating arthritis in vitro and in clinic

    Science.gov (United States)

    Feng, Shun; Zhu, Lijun; Huang, Zhisheng; Wang, Haojia; Li, Hong; Zhou, Hua; Lu, Linlin; Wang, Ying; Liu, Zhongqiu; Liu, Liang

    2017-01-01

    Sinomenine hydrochloride (SH) is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration. PMID:28670109

  2. Multi-Optimisation Consensus Clustering

    Science.gov (United States)

    Li, Jian; Swift, Stephen; Liu, Xiaohui

    Ensemble Clustering has been developed to provide an alternative way of obtaining more stable and accurate clustering results. It aims to avoid the biases of individual clustering algorithms. However, it is still a challenge to develop an efficient and robust method for Ensemble Clustering. Based on an existing ensemble clustering method, Consensus Clustering (CC), this paper introduces an advanced Consensus Clustering algorithm called Multi-Optimisation Consensus Clustering (MOCC), which utilises an optimised Agreement Separation criterion and a Multi-Optimisation framework to improve the performance of CC. Fifteen different data sets are used for evaluating the performance of MOCC. The results reveal that MOCC can generate more accurate clustering results than the original CC algorithm.

  3. Use of electroporation and reverse iontophoresis for extraction of transdermal multibiomarkers

    Directory of Open Access Journals (Sweden)

    Ching CTS

    2012-02-01

    Full Text Available Congo Tak-Shing Ching1,2, Lin-Shien Fu3-5, Tai-Ping Sun1, Tzu-Hsiang Hsu1, Kang-Ming Chang21Department of Electrical Engineering, National Chi Nan University, Puli, Nantou County, 2Department of Photonics and Communication Engineering, Asia University, Wufeng, Taichung, 3Department of Pediatrics, National Yang Ming University, Taipei, 4Institute of Technology, National Chi Nan University, Puli, 5Department of Pediatrics, Taichung Veterans General Hospital, Taichung City, TaiwanBackground: Monitoring of biomarkers, like urea, prostate-specific antigen (PSA, and osteopontin, is very important because they are related to kidney disease, prostate cancer, and ovarian cancer, respectively. It is well known that reverse iontophoresis can enhance transdermal extraction of small molecules, and even large molecules if reverse iontophoresis is used together with electroporation. Electroporation is the use of a high-voltage electrical pulse to create nanochannels within the stratum corneum, temporarily and reversibly. Reverse iontophoresis is the use of a small current to facilitate both charged and uncharged molecule transportation across the skin. The objectives of this in vitro study were to determine whether PSA and osteopontin are extractable transdermally and noninvasively and whether urea, PSA, and osteopontin can be extracted simultaneously by electroporation and reverse iontophoresis.Methods: All in vitro experiments were conducted using a diffusion cell assembled with the stratum corneum of porcine skin. Three different symmetrical biphasic direct currents (SBdc, five various electroporations, and a combination of the two techniques were applied to the diffusion cell via Ag/AgCl electrodes. The three different SBdc had the same current density of 0.3 mA/cm2, but different phase durations of 0 (ie, no current, control group, 30, and 180 seconds. The five different electroporations had the same pulse width of 1 msec and number of pulses per second

  4. Seeing the electroporative uptake of cell-membrane impermeable fluorescent molecules and nanoparticles

    Science.gov (United States)

    Kim, Kisoo; Kim, Jeong Ah; Lee, Soon-Geul; Lee, Won Gu

    2012-07-01

    This paper presents direct visualization of uptake directionality for cell-membrane impermeant fluorescent molecules and fluorescence-doped nanoparticles at a single-cell level during electroporation. To observe directly the uptake direction, we used microchannel-type electroporation that can generate a relatively symmetric and uniform electric field. For all the image frames during electroporation, fluorescence intensities that occurred at cell membranes in both uptake directions toward the electrodes have been sequentially recorded and quantitatively analyzed pixel by pixel. In our experiments, we found that fluorescent molecules, even not labeled to target biomolecules, had their own uptake direction with different intensities. It is also observed that the uptake intensity toward the cell membrane had a maximal value at a certain electric voltage, not at the highest value of voltages applied. The results also imply that the uptake direction of fluorescence-doped nanoparticles can be determined by a net surface charge of uptake materials and sizes in the electroporative environments. In summary, we performed a quantitative screening and direct visualization of uptake directionality for a set of fluorescent molecules and fluorescence-doped nanoparticles using electric-pulsation. Taking a closer look at the uptake direction of exogenous materials will help researchers to understand an unknown uptake phenomenon in which way foreign materials are inclined to move, and furthermore to design functional nanoparticles for electroporative gene delivery.This paper presents direct visualization of uptake directionality for cell-membrane impermeant fluorescent molecules and fluorescence-doped nanoparticles at a single-cell level during electroporation. To observe directly the uptake direction, we used microchannel-type electroporation that can generate a relatively symmetric and uniform electric field. For all the image frames during electroporation, fluorescence intensities

  5. Isogeometric Analysis and Shape Optimisation

    DEFF Research Database (Denmark)

    Gravesen, Jens; Evgrafov, Anton; Gersborg, Allan Roulund

    of the whole domain. So in every optimisation cycle we need to extend a parametrisation of the boundary of a domain to the whole domain. It has to be fast in order not to slow the optimisation down but it also has to be robust and give a parametrisation of high quality. These are conflicting requirements so we...... will explain how the validity of a parametrisation can be checked and we will describe various ways to parametrise a domain. We will in particular study the Winslow functional which turns out to have some desirable properties. Other problems we touch upon is clustering of boundary control points (design...

  6. Flow-through electroporation based on constant voltage for large-volume transfection of cells.

    Science.gov (United States)

    Geng, Tao; Zhan, Yihong; Wang, Hsiang-Yu; Witting, Scott R; Cornetta, Kenneth G; Lu, Chang

    2010-05-21

    Genetic modification of cells is a critical step involved in many cell therapy and gene therapy protocols. In these applications, cell samples of large volume (10(8)-10(9)cells) are often processed for transfection. This poses new challenges for current transfection methods and practices. Here we present a novel flow-through electroporation method for delivery of genes into cells at high flow rates (up to approximately 20 mL/min) based on disposable microfluidic chips, a syringe pump, and a low-cost direct current (DC) power supply that provides a constant voltage. By eliminating pulse generators used in conventional electroporation, we dramatically lowered the cost of the apparatus and improved the stability and consistency of the electroporation field for long-time operation. We tested the delivery of pEFGP-C1 plasmids encoding enhanced green fluorescent protein into Chinese hamster ovary (CHO-K1) cells in the devices of various dimensions and geometries. Cells were mixed with plasmids and then flowed through a fluidic channel continuously while a constant voltage was established across the device. Together with the applied voltage, the geometry and dimensions of the fluidic channel determined the electrical parameters of the electroporation. With the optimal design, approximately 75% of the viable CHO cells were transfected after the procedure. We also generalize the guidelines for scaling up these flow-through electroporation devices. We envision that this technique will serve as a generic and low-cost tool for a variety of clinical applications requiring large volume of transfected cells. Copyright 2010 Elsevier B.V. All rights reserved.

  7. Enhancing Irreversible Electroporation by Manipulating Cellular Biophysics with a Molecular Adjuvant.

    Science.gov (United States)

    Ivey, Jill W; Latouche, Eduardo L; Richards, Megan L; Lesser, Glenn J; Debinski, Waldemar; Davalos, Rafael V; Verbridge, Scott S

    2017-07-25

    Pulsed electric fields applied to cells have been used as an invaluable research tool to enhance delivery of genes or other intracellular cargo, as well as for tumor treatment via electrochemotherapy or tissue ablation. These processes involve the buildup of charge across the cell membrane, with subsequent alteration of transmembrane potential that is a function of cell biophysics and geometry. For traditional electroporation parameters, larger cells experience a greater degree of membrane potential alteration. However, we have recently demonstrated that the nuclear/cytoplasm ratio (NCR), rather than cell size, is a key predictor of response for cells treated with high-frequency irreversible electroporation (IRE). In this study, we leverage a targeted molecular therapy, ephrinA1, known to markedly collapse the cytoplasm of cells expressing the EphA2 receptor, to investigate how biophysical cellular changes resulting from NCR manipulation affect the response to IRE at varying frequencies. We present evidence that the increase in the NCR mitigates the cell death response to conventional electroporation pulsed-electric fields (∼100 μs), consistent with the previously noted size dependence. However, this same molecular treatment enhanced the cell death response to high-frequency electric fields (∼1 μs). This finding demonstrates the importance of considering cellular biophysics and frequency-dependent effects in developing electroporation protocols, and our approach provides, to our knowledge, a novel and direct experimental methodology to quantify the relationship between cell morphology, pulse frequency, and electroporation response. Finally, this novel, to our knowledge, combinatorial approach may provide a paradigm to enhance in vivo tumor ablation through a molecular manipulation of cellular morphology before IRE application. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation

    Directory of Open Access Journals (Sweden)

    Xiaojun Liu

    2017-05-01

    Full Text Available ABSTRACT The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB. The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the co-electroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effective method for generating high-quality T cells for adoptive immunotherapy.

  9. Cogeneration technologies, optimisation and implementation

    CERN Document Server

    Frangopoulos, Christos A

    2017-01-01

    Cogeneration refers to the use of a power station to deliver two or more useful forms of energy, for example, to generate electricity and heat at the same time. This book provides an integrated treatment of cogeneration, including a tour of the available technologies and their features, and how these systems can be analysed and optimised.

  10. For Time-Continuous Optimisation

    DEFF Research Database (Denmark)

    Heinrich, Mary Katherine; Ayres, Phil

    2016-01-01

    Strategies for optimisation in design normatively assume an artefact end-point, disallowing continuous architecture that engages living systems, dynamic behaviour, and complex systems. In our Flora Robotica investigations of symbiotic plant-robot bio-hybrids, we re- quire computational tools...

  11. Acute and Long-Term Effects of Full-Power Electroporation Ablation Directly on the Porcine Esophagus

    NARCIS (Netherlands)

    Neven, Kars; van Es, René; van Driel, Vincent; van Wessel, Harry; Fidder, Herma; Vink, Aryan; Doevendans, Pieter; Wittkampf, Fred

    BACKGROUND: Esophageal ulceration and fistula are complications of pulmonary vein isolation using thermal energy sources. Irreversible electroporation is a novel, nonthermal ablation modality for pulmonary vein isolation. A single 200 J application can create deep myocardial lesions. Acute and

  12. The Effect of Electroporation of a Lyotroic Liquid Crystal Genistein-Based Formulation in the Recovery of Murine Melanoma Lesions.

    Science.gov (United States)

    Danciu, Corina; Berkó, Szilvia; Varju, Gábor; Balázs, Boglárka; Kemény, Lajos; Németh, István Balázs; Cioca, Andreea; Petruș, Alexandra; Dehelean, Cristina; Cosmin, Citu Ioan; Amaricai, Elena; Toma, Claudia Crina

    2015-07-08

    A lamellar lyotropic liquid crystal genistein-based formulation (LLC-Gen) was prepared in order to increase the aqueous solubility of the lipophilic phytocompound genistein. The formulation was applied locally, in a murine model of melanoma, with or without electroporation. The results demonstrated that, when the formulation was applied by electroporation, the tumors appeared later. During the 21 days of the experiment, the LLC-Gen formulation decreased the tumor volume, the amount of melanin and the degree of erythema, but when electroporation was applied, all these parameters indicated a better prognosis even (lower tumor volume, amount of melanin and degree of erythema). Although hematoxylin-eosin (HE) staining confirmed the above events, application of the LLC-Gen formulation by electroporation did not lead to a significant effect in terms of the serum concentrations of the protein S100B and serum neuron specific enolase (NSE), or the tissue expression of the platelet-derived growth factor receptor β (PDGFRβ) antibody.

  13. A ‘suicide’ CRISPR-Cas9 system to promote gene deletion and restoration by electroporation in Cryptococcus neoformans

    Science.gov (United States)

    Wang, Yu; Wei, Dongsheng; Zhu, Xiangyang; Pan, Jiao; Zhang, Ping; Huo, Liang; Zhu, Xudong

    2016-01-01

    Loss-of-function mutagenesis is an important tool used to characterize gene functions, and the CRISPR-Cas9 system is a powerful method for performing targeted mutagenesis in organisms that present low recombination frequencies, such as the serotype D strains of Cryptococcus neoformans. However, when the CRISPR-Cas9 system persists in the host cells, off-target effects and Cas9 cytotoxicity may occur, which might block subsequent genetic manipulation. Here, we report a method of spontaneously eliminating the CRISPR-Cas9 system without impairing its robust editing function. We successfully expressed single guide RNA under the driver of an endogenous U6 promoter and the human codon-optimized Cas9 endonuclease with an ACT1 promoter. This system can effectively generate an indel mutation and efficiently perform targeted gene disruption via homology-directed repair by electroporation in yeast. We then demonstrated the spontaneous elimination of the system via a cis arrangement of the CRISPR-Cas9 expression cassettes to the recombination construct. After a system-mediated double crossover, the CRISPR-Cas9 cassettes were cleaved and degraded, which was validated by Southern blotting. This ‘suicide’ CRISPR-Cas9 system enables the validation of gene functions by subsequent complementation and has the potential to minimize off-target effects. Thus, this technique has the potential for use in functional genomics studies of C. neoformans. PMID:27503169

  14. Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE

    Directory of Open Access Journals (Sweden)

    Kos Bor

    2015-09-01

    Full Text Available Background. Irreversible electroporation (IRE is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated.

  15. Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration

    Directory of Open Access Journals (Sweden)

    Berkó S

    2016-05-01

    Full Text Available Szilvia Berkó,1,* Kálmán F Szűcs,2,* Boglárka Balázs,1,3 Erzsébet Csányi,1 Gábor Varju,4 Anita Sztojkov-Ivanov,2 Mária Budai-Szűcs,1 Judit Bóta,2 Róbert Gáspár2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 2Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, Hungary; 3Gedeon Richter Plc., Budapest, 4Dr Derm Clinic of Anti-Aging Dermatology, Aesthetic Laser and Plastic Surgery, Budapest, Hungary *These authors contributed equally to this work Purpose: Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. Methods: The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. Results: Both intravenously and EP-administered neostigmine (0.2–66.7 µg/kg increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 µg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. Conclusion: The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. Keywords: transdermal

  16. 1st World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food & Environmental Technologies

    CERN Document Server

    Kramar, Peter

    2016-01-01

    This volume presents the proceedings of the 1st World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food & Environmental Technologies (WC2015). The congress took place in Portorož, Slovenia, during the week of September 6th to 10th, 2015. The scientific part of the Congress covered different aspects of electroporation and related technologies and included the following main topics:   ·         Application of pulsed electric fields technology in food: challenges and opportunities ·         Electrical impedance measurement for assessment of electroporation yield ·         Electrochemistry and electroporation ·         Electroporation meets electrostimulation ·         Electrotechnologies for food and biomass treatment ·         Food and biotechnology applications ·         In vitro electroporation - basic mechanisms ·         Interfacial behaviour of lipid-assemblies, membranes and cells in electric f...

  17. Bleomycin--electrical pulse delivery: electroporation therapy-bleomycin--Genetronics; MedPulser-bleomycin--Genetronics.

    Science.gov (United States)

    2004-01-01

    Genetronics Biomedical is using its electroporation therapy technology to deliver bleomycin to tumour cells for the treatment of cancer. Genetronics have developed the MedPulser Electroporation Therapy System, which consists of an electrical pulse generator and disposable electrode applicators. The MedPulser system enables the delivery of large molecules into cells by briefly applying an electric field to the cell. This causes a transient permeability in the cell's outer membrane characterised by the appearance of pores across the membrane. After the field is discontinued, the pores close, trapping the therapeutic molecules inside the target cells. Genetronics is using the MedPulser System in conjunction with bleomycin, an antineoplastic antibiotic that binds to DNA causing strand scissions. Genetronics is seeking a licensing partner for the use of electroporation for the delivery of drugs in chemotherapy. In 1998, Genetronics entered a licensing and development agreement with Ethicon for electroporation and electrofusion. Under the terms of this agreement, Ethicon was to develop and clinically test the Genetronics electroporation delivery system and conduct all regulatory activities throughout the world except Canada. Ethicon would also market the products once regulatory approval has been obtained and Genetronics was to receive a percentage of the net sales and as license fees. However, in July 2000, Ethicon exercised its rights to terminate the agreement without cause. All rights were returned to Genetronics in January 2001. In 1997, Genetronics entered an agreement with Abbott Laboratories for the manufacture of bleomycin for use in the US in its MedPulsar system after regulatory approval had been granted for its use in the treatment of solid tumours. In a separate supply agreement, Faulding Inc. has agreed to manufacture bleomycin for Genetronic for use in Canada after regulatory approval had been granted. The MedPulsar Electroporation Therapy System with

  18. Visualization through Magnetic Resonance Imaging of DNA Internalized Following “In Vivo” Electroporation

    Directory of Open Access Journals (Sweden)

    Simonetta Geninatti Crich

    2005-01-01

    Full Text Available The ability to visualize plasmid DNA entrapment in muscle cells undergoing an “in vivo” electroporation treatment was investigated on BALB/c mice using a 7-T magnetic resonance imaging (MRI scanner using the paramagnetic Gd–DOTA–spd complex as imaging reporter. Gd–DOTA–spd bears a tripositively charged spermidine residue that yields a strong binding affinity toward the negatively charged DNA chain (6.4 kb, Ka = 2.2 × 103 M−1 for approximately 2500 ± 500 binding sites. Cellular colocalization of Gd-DOTA-spd and plasmid DNA has been validated by histological analysis of excised treated muscle. In vivo MRI visualization of Gd-DOTA-spd distribution provides an excellent route to access the cellular entrapment of plasmid DNA upon applying an electroporation pulse.

  19. Optimising Comprehensibility in Interlingual Translation

    DEFF Research Database (Denmark)

    Nisbeth Jensen, Matilde

    2015-01-01

    The increasing demand for citizen engagement in areas traditionally belonging exclusively to experts, such as health, law and technology has given rise to the necessity of making expert knowledge available to the general public through genres such as instruction manuals for consumer goods, patien...... the functional text type of Patient Information Leaflet. Finally, the usefulness of applying the principles of Plain Language and intralingual translation for optimising comprehensibility in interlingual translation is discussed....

  20. TEM turbulence optimisation in stellarators

    Science.gov (United States)

    Proll, J. H. E.; Mynick, H. E.; Xanthopoulos, P.; Lazerson, S. A.; Faber, B. J.

    2016-01-01

    With the advent of neoclassically optimised stellarators, optimising stellarators for turbulent transport is an important next step. The reduction of ion-temperature-gradient-driven turbulence has been achieved via shaping of the magnetic field, and the reduction of trapped-electron mode (TEM) turbulence is addressed in the present paper. Recent analytical and numerical findings suggest TEMs are stabilised when a large fraction of trapped particles experiences favourable bounce-averaged curvature. This is the case for example in Wendelstein 7-X (Beidler et al 1990 Fusion Technol. 17 148) and other Helias-type stellarators. Using this knowledge, a proxy function was designed to estimate the TEM dynamics, allowing optimal configurations for TEM stability to be determined with the STELLOPT (Spong et al 2001 Nucl. Fusion 41 711) code without extensive turbulence simulations. A first proof-of-principle optimised equilibrium stemming from the TEM-dominated stellarator experiment HSX (Anderson et al 1995 Fusion Technol. 27 273) is presented for which a reduction of the linear growth rates is achieved over a broad range of the operational parameter space. As an important consequence of this property, the turbulent heat flux levels are reduced compared with the initial configuration.

  1. Nanochannel Electroporation as a Platform for Living Cell Interrogation in Acute Myeloid Leukemia.

    Science.gov (United States)

    Zhao, Xi; Huang, Xiaomeng; Wang, Xinmei; Wu, Yun; Eisfeld, Ann-Kathrin; Schwind, Sebastian; Gallego-Perez, Daniel; Boukany, Pouyan E; Marcucci, Guido I; Lee, Ly James

    2015-12-01

    A living cell interrogation platform based on nanochannel electroporation is demonstrated with analysis of RNAs in single cells. This minimally invasive process is based on individual cells and allows both multi-target analysis and stimulus-response analysis by sequential deliveries. The unique platform possesses a great potential to the comprehensive and lysis-free nucleic acid analysis on rare or hard-to-transfect cells.

  2. Effects of Circular DNA Length on Transfection Efficiency by Electroporation into HeLa Cells.

    Science.gov (United States)

    Hornstein, Benjamin D; Roman, Dany; Arévalo-Soliz, Lirio M; Engevik, Melinda A; Zechiedrich, Lynn

    2016-01-01

    The ability to produce extremely small and circular supercoiled vectors has opened new territory for improving non-viral gene therapy vectors. In this work, we compared transfection of supercoiled DNA vectors ranging from 383 to 4,548 bp, each encoding shRNA against GFP under control of the H1 promoter. We assessed knockdown of GFP by electroporation into HeLa cells. All of our vectors entered cells in comparable numbers when electroporated with equal moles of DNA. Despite similar cell entry, we found length-dependent differences in how efficiently the vectors knocked down GFP. As vector length increased up to 1,869 bp, GFP knockdown efficiency per mole of transfected DNA increased. From 1,869 to 4,257 bp, GFP knockdown efficiency per mole was steady, then decreased with increasing vector length. In comparing GFP knockdown with equal masses of vectors, we found that the shorter vectors transfect more efficiently per nanogram of DNA transfected. Our results rule out cell entry and DNA mass as determining factors for gene knockdown efficiency via electroporation. The length-dependent effects we have uncovered are likely explained by differences in nuclear translocation or transcription. These data add an important step towards clinical applications of non-viral vector delivery.

  3. Effects of deformability and thermal motion of lipid membrane on electroporation: By molecular dynamics simulations

    KAUST Repository

    Sun, Sheng

    2011-01-01

    Effects of mechanical properties and thermal motion of POPE lipid membrane on electroporation were studied by molecular dynamics simulations. Among simulations in which specific atoms of lipids were artificially constrained at their equilibrium positions using a spring with force constant of 2.0kcal/(molÅ2) in the external electric field of 1.4kcal/(molÅe), only constraint on lateral motions of lipid tails prohibited electroporation while non-tail parts had little effects. When force constant decreased to 0.2kcal/(molÅ2) in the position constraints on lipid tails in the external electric field of 2.0kcal/(molÅe), water molecules began to enter the membrane. Position constraints of lipid tails allow water to penetrate from both sides of membrane. Thermal motion of lipids can induce initial defects in the hydrophobic core of membrane, which are favorable nucleation sites for electroporation. Simulations at different temperatures revealed that as the temperature increases, the time taken to the initial pore formation will decrease. © 2010 Elsevier Inc.

  4. Finite-element modelling and preliminary validation of microneedle-based electrodes for enhanced tissue electroporation.

    Science.gov (United States)

    Houlihan, Ruth; Grygoryev, Konstantin; Zhenfei Ning; Williams, John; Moore, Tom; O'Mahony, Conor

    2017-07-01

    This paper investigates the use of microneedle-based electrodes for enhanced testis electroporation, with specific application to the production of transgenic mice. During the design phase, finite-element software has been used to construct a tissue model and to compare the relative performance of electrodes employing a) conventional flat plates, b) microneedle arrays, and c) invasive needles. Results indicate that microneedle-based electrodes can achieve internal tissue field strengths which are an order of magnitude higher than those generated using conventional flat electrodes, and which are comparable to fields produced using invasive needles. Using a double-sided etching process, conductive microneedle arrays were then fabricated and used in prototype electrodes. In a series of mouse model experiments involving injection of a DNA vector expressing Green Fluorescent Protein (GFP), the performance of flat and microneedle electrodes was compared by measuring GFP expression after electroporation. The main finding, supported by experimental and simulated data, is that use of microneedle-based electrodes significantly enhanced electroporation of testis.

  5. HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Charlotta Nilsson

    Full Text Available We compared safety and immunogenicity of intradermal (ID vaccination with and without electroporation (EP in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers.HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet with (n=16 or without (n=9 ID EP (Dermavax. Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA.The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33% and HIV-DNA ID recipients (1/7, 14%, p=0.6158. The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%. CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients.Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use.International Standard Randomised Controlled Trial Number (ISRCTN 60284968.

  6. HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.

    Science.gov (United States)

    Nilsson, Charlotta; Hejdeman, Bo; Godoy-Ramirez, Karina; Tecleab, Teghesti; Scarlatti, Gabriella; Bråve, Andreas; Earl, Patricia L; Stout, Richard R; Robb, Merlin L; Shattock, Robin J; Biberfeld, Gunnel; Sandström, Eric; Wahren, Britta

    2015-01-01

    We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers. HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg. Twenty-five volunteers received vaccine using a needle-free device (ZetaJet) with (n=16) or without (n=9) ID EP (Dermavax). Five volunteers were placebo recipients. Boosting with recombinant MVA-CMDR expressing HIV-1 Env, Gag, Pol of CRF01_AE (HIV-MVA) or placebo was performed at weeks 24 and 40. Nine of the vaccinees received a subtype C CN54 gp140 protein boost together with HIV-MVA. The ID/EP delivery was very well tolerated. After three HIV-DNA immunizations, no statistically significant difference was seen in the IFN-γ ELISpot response rate to Gag between HIV-DNA ID/EP recipients (5/15, 33%) and HIV-DNA ID recipients (1/7, 14%, p=0.6158). The first HIV-MVA or HIV-MVA+gp140 vaccination increased the IFN-γ ELISpot response rate to 18/19 (95%). CD4+ and/or CD8+ T cell responses to Gag or Env were demonstrable in 94% of vaccinees. A balanced CD4+ and CD8+ T cell response was noted, with 78% and 71% responders, respectively. IFN-γ and IL-2 dominated the CD4+ T cell response to Gag and Env. The CD8+ response to Gag was broader with expression of IFN-γ, IL-2, MIP-1β and/or CD107. No differences were seen between DNA vaccine groups. Binding antibodies were induced after the second HIV-MVA+/-gp140 in 93% of vaccinees to subtype C Env, with the highest titers among EP/gp140 recipients. Intradermal electroporation of HIV-DNA was well tolerated. Strong cell- and antibody-mediated immune responses were elicited by the HIV-DNA prime and HIV-MVA boosting regimen, with or without intradermal electroporation use. International Standard Randomised Controlled Trial Number (ISRCTN) 60284968.

  7. Education on electrical phenomena involved in electroporation-based therapies and treatments: a blended learning approach.

    Science.gov (United States)

    Čorović, Selma; Mahnič-Kalamiza, Samo; Miklavčič, Damijan

    2016-04-07

    Electroporation-based applications require multidisciplinary expertise and collaboration of experts with different professional backgrounds in engineering and science. Beginning in 2003, an international scientific workshop and postgraduate course electroporation based technologies and treatments (EBTT) has been organized at the University of Ljubljana to facilitate transfer of knowledge from leading experts to researches, students and newcomers in the field of electroporation. In this paper we present one of the integral parts of EBTT: an e-learning practical work we developed to complement delivery of knowledge via lectures and laboratory work, thus providing a blended learning approach on electrical phenomena involved in electroporation-based therapies and treatments. The learning effect was assessed via a pre- and post e-learning examination test composed of 10 multiple choice questions (i.e. items). The e-learning practical work session and both of the e-learning examination tests were carried out after the live EBTT lectures and other laboratory work. Statistical analysis was performed to compare and evaluate the learning effect measured in two groups of students: (1) electrical engineers and (2) natural scientists (i.e. medical doctors, biologists and chemists) undergoing the e-learning practical work in 2011-2014 academic years. Item analysis was performed to assess the difficulty of each item of the examination test. The results of our study show that the total score on the post examination test significantly improved and the item difficulty in both experimental groups decreased. The natural scientists reached the same level of knowledge (no statistical difference in total post-examination test score) on the post-course test take, as do electrical engineers, although the engineers started with statistically higher total pre-test examination score, as expected. The main objective of this study was to investigate whether the educational content the e

  8. Particle swarm optimisation classical and quantum perspectives

    CERN Document Server

    Sun, Jun; Wu, Xiao-Jun

    2016-01-01

    IntroductionOptimisation Problems and Optimisation MethodsRandom Search TechniquesMetaheuristic MethodsSwarm IntelligenceParticle Swarm OptimisationOverviewMotivationsPSO Algorithm: Basic Concepts and the ProcedureParadigm: How to Use PSO to Solve Optimisation ProblemsSome Harder Examples Some Variants of Particle Swarm Optimisation Why Does the PSO Algorithm Need to Be Improved? Inertia and Constriction-Acceleration Techniques for PSOLocal Best ModelProbabilistic AlgorithmsOther Variants of PSO Quantum-Behaved Particle Swarm Optimisation OverviewMotivation: From Classical Dynamics to Quantum MechanicsQuantum Model: Fundamentals of QPSOQPSO AlgorithmSome Essential ApplicationsSome Variants of QPSOSummary Advanced Topics Behaviour Analysis of Individual ParticlesConvergence Analysis of the AlgorithmTime Complexity and Rate of ConvergenceParameter Selection and PerformanceSummaryIndustrial Applications Inverse Problems for Partial Differential EquationsInverse Problems for Non-Linear Dynamical SystemsOptimal De...

  9. Biomedical Application of Electroporation: Electrochemotherapy and Electrogene Therapy in Treatment of Cutaneous and Deep Seated Tumors

    International Nuclear Information System (INIS)

    Sersa, G.; Cemazar, M.; Gadzijev, E.; Edhemovic, I.; Brecelj, E.; Snoj, M.

    2011-01-01

    Several novel tumor-targeting and drug delivery approaches in cancer treatment are currently undergoing intensive investigation in order to increase the therapeutic index - among them physical approaches such as tissue electroporation. Electroporation of tissue increases the membrane permeability of cells, specifically in the area that is exposed to the applied electric pulses. Electroporation-based cancer treatment approaches are currently undergoing intensive investigation in the field of drug (electrochemo-therapy) and gene (electrogene therapy) delivery. Electrochemotherapy, since its beginnings in the late 1980s, has evolved into a clinically verified treatment approach for cutaneous and subcutaneous tumor nodules. It is defined as a local treatment which, via cell membrane permeabilising electric pulses, potentiates the cytotoxicity of non-permeant or poorly permeant anticancer drugs with high intrinsic cytotoxicity at the site of electric pulse application. Suitable candidates for electrochemotherapy are limited to those drugs that are hydrophilic and lack transport system in the membrane. Up to date two drugs have been identified as potential candidates for electrochemotherapy: bleomycin, which cytotoxicity in vitro can be potentiated up to several-1000-fold by electroporation of cells, and cisplatin whose cytotoxicity increased by up to 80-fold due to electroporation. High antitumor effectiveness of electrochemotherapy was demonstrated on fibrosarcomas, melanoma, and carcinomas in mice, rats and rabbits; good clinical results were also obtained in veterinary medicine on cats, dogs and horses. In these studies it was demonstrated that with drug doses that have minimal or no antitumor effectiveness, high (up to 75 %) complete responses of the electrochemotherapy-treated tumors were obtained. The drug doses used were so low that they had no systemic toxicity. Also the application of electric pulses to the tumors had no antitumor effectiveness and no systemic

  10. An Optimisation Approach for Room Acoustics Design

    DEFF Research Database (Denmark)

    Holm-Jørgensen, Kristian; Kirkegaard, Poul Henning; Andersen, Lars

    2005-01-01

    This paper discuss on a conceptual level the value of optimisation techniques in architectural acoustics room design from a practical point of view. It is chosen to optimise one objective room acoustics design criterium estimated from the sound field inside the room. The sound field is modeled...... using the boundary element method where absorption is incorporated. An example is given where the geometry of a room is defined by four design modes. The room geometry is optimised to get a uniform sound pressure....

  11. Escherichia coli can be transformed by a liposome-mediated lipofection method.

    Science.gov (United States)

    Kawata, Yoshikazu; Yano, Shin-ichi; Kojima, Hiroyuki

    2003-05-01

    Transformation of Escherichia coli is a basic technique for genetic engineering. We used a liposome-mediated lipofection method to transform electrocompetent E. coli cells which has little natural competence of foreign DNA without electroporation treatment, and got transformants with simple and quick treatment by a plasmid or a transposon and transposase complex.

  12. Optimisation of technical specifications using probabilistic methods

    International Nuclear Information System (INIS)

    Ericsson, G.; Knochenhauer, M.; Hultqvist, G.

    1986-01-01

    During the last few years the development of methods for modifying and optimising nuclear power plant Technical Specifications (TS) for plant operations has received increased attention. Probalistic methods in general, and the plant and system models of probabilistic safety assessment (PSA) in particular, seem to provide the most forceful tools for optimisation. This paper first gives some general comments on optimisation, identifying important parameters and then gives a description of recent Swedish experiences from the use of nuclear power plant PSA models and results for TS optimisation

  13. Layout Optimisation of Wave Energy Converter Arrays

    DEFF Research Database (Denmark)

    Ruiz, Pau Mercadé; Nava, Vincenzo; Topper, Mathew B. R.

    2017-01-01

    This paper proposes an optimisation strategy for the layout design of wave energy converter (WEC) arrays. Optimal layouts are sought so as to maximise the absorbed power given a minimum q-factor, the minimum distance between WECs, and an area of deployment. To guarantee an efficient optimisation......, a four-parameter layout description is proposed. Three different optimisation algorithms are further compared in terms of performance and computational cost. These are the covariance matrix adaptation evolution strategy (CMA), a genetic algorithm (GA) and the glowworm swarm optimisation (GSO) algorithm...

  14. Optimisation of the LHCb detector

    CERN Document Server

    Hierck, R H

    2003-01-01

    This thesis describes a comparison of the LHCb classic and LHCb light concept from a tracking perspective. The comparison includes the detector occupancies, the various pattern recognition algorithms and the reconstruction performance. The final optimised LHCb setup is used to study the physics performance of LHCb for the Bs->DsK and Bs->DsPi decay channels. This includes both the event selection and a study of the sensitivity for the Bs oscillation frequency, delta m_s, the Bs lifetime difference, DGamma_s, and the CP parameter gamma-2delta gamma.

  15. Optimisation combinatoire Theorie et algorithmes

    CERN Document Server

    Korte, Bernhard; Fonlupt, Jean

    2010-01-01

    Ce livre est la traduction fran aise de la quatri me et derni re dition de Combinatorial Optimization: Theory and Algorithms crit par deux minents sp cialistes du domaine: Bernhard Korte et Jens Vygen de l'universit de Bonn en Allemagne. Il met l accent sur les aspects th oriques de l'optimisation combinatoire ainsi que sur les algorithmes efficaces et exacts de r solution de probl mes. Il se distingue en cela des approches heuristiques plus simples et souvent d crites par ailleurs. L ouvrage contient de nombreuses d monstrations, concises et l gantes, de r sultats difficiles. Destin aux tudia

  16. Electroporation-based treatment planning for deep-seated tumors based on automatic liver segmentation of MRI images.

    Science.gov (United States)

    Pavliha, Denis; Mušič, Maja M; Serša, Gregor; Miklavčič, Damijan

    2013-01-01

    Electroporation is the phenomenon that occurs when a cell is exposed to a high electric field, which causes transient cell membrane permeabilization. A paramount electroporation-based application is electrochemotherapy, which is performed by delivering high-voltage electric pulses that enable the chemotherapeutic drug to more effectively destroy the tumor cells. Electrochemotherapy can be used for treating deep-seated metastases (e.g. in the liver, bone, brain, soft tissue) using variable-geometry long-needle electrodes. To treat deep-seated tumors, patient-specific treatment planning of the electroporation-based treatment is required. Treatment planning is based on generating a 3D model of the organ and target tissue subject to electroporation (i.e. tumor nodules). The generation of the 3D model is done by segmentation algorithms. We implemented and evaluated three automatic liver segmentation algorithms: region growing, adaptive threshold, and active contours (snakes). The algorithms were optimized using a seven-case dataset manually segmented by the radiologist as a training set, and finally validated using an additional four-case dataset that was previously not included in the optimization dataset. The presented results demonstrate that patient's medical images that were not included in the training set can be successfully segmented using our three algorithms. Besides electroporation-based treatments, these algorithms can be used in applications where automatic liver segmentation is required.

  17. Direct and efficient transfection of mouse neural stem cells and mature neurons by in vivo mRNA electroporation.

    Science.gov (United States)

    Bugeon, Stéphane; de Chevigny, Antoine; Boutin, Camille; Coré, Nathalie; Wild, Stefan; Bosio, Andreas; Cremer, Harold; Beclin, Christophe

    2017-11-01

    In vivo brain electroporation of DNA expression vectors is a widely used method for lineage and gene function studies in the developing and postnatal brain. However, transfection efficiency of DNA is limited and adult brain tissue is refractory to electroporation. Here, we present a systematic study of mRNA as a vector for acute genetic manipulation in the developing and adult brain. We demonstrate that mRNA electroporation is far more efficient than DNA electroporation, and leads to faster and more homogeneous protein expression in vivo Importantly, mRNA electroporation allows the manipulation of neural stem cells and postmitotic neurons in the adult brain using minimally invasive procedures. Finally, we show that this approach can be efficiently used for functional studies, as exemplified by transient overexpression of the neurogenic factor Myt1l and by stably inactivating Dicer nuclease in vivo in adult born olfactory bulb interneurons and in fully integrated cortical projection neurons. © 2017. Published by The Company of Biologists Ltd.

  18. Electroporated Antigen-Encoding mRNA Is Not a Danger Signal to Human Mature Monocyte-Derived Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Stefanie Hoyer

    2015-01-01

    Full Text Available For therapeutic cancer vaccination, the adoptive transfer of mRNA-electroporated dendritic cells (DCs is frequently performed, usually with monocyte-derived, cytokine-matured DCs (moDCs. However, DCs are rich in danger-sensing receptors which could recognize the exogenously delivered mRNA and induce DC activation, hence influencing the DCs’ immunogenicity. Therefore, we examined whether electroporation of mRNA with a proper cap and a poly-A tail of at least 64 adenosines had any influence on cocktail-matured moDCs. We used 16 different RNAs, encoding tumor antigens (MelanA, NRAS, BRAF, GNAQ, GNA11, and WT1, and variants thereof. None of those RNAs induced changes in the expression of CD25, CD40, CD83, CD86, and CD70 or the secretion of the cytokines IL-8, IL-6, and TNFα of more than 1.5-fold compared to the control condition, while an mRNA encoding an NF-κB-activation protein as positive control induced massive secretion of the cytokines. To determine whether mRNA electroporation had any effect on the whole transcriptome of the DCs, we performed microarray analyses of DCs of 6 different donors. None of 60,000 probes was significantly different between mock-electroporated DCs and MelanA-transfected DCs. Hence, we conclude that no transcriptional programs were induced within cocktail-matured DCs by electroporation of single tumor-antigen-encoding mRNAs.

  19. Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

    Directory of Open Access Journals (Sweden)

    Benencia Fabian

    2008-04-01

    Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

  20. Optimising resource management in neurorehabilitation.

    Science.gov (United States)

    Wood, Richard M; Griffiths, Jeff D; Williams, Janet E; Brouwers, Jakko

    2014-01-01

    To date, little research has been published regarding the effective and efficient management of resources (beds and staff) in neurorehabilitation, despite being an expensive service in limited supply. To demonstrate how mathematical modelling can be used to optimise service delivery, by way of a case study at a major 21 bed neurorehabilitation unit in the UK. An automated computer program for assigning weekly treatment sessions is developed. Queue modelling is used to construct a mathematical model of the hospital in terms of referral submissions to a waiting list, admission and treatment, and ultimately discharge. This is used to analyse the impact of hypothetical strategic decisions on a variety of performance measures and costs. The project culminates in a hybridised model of these two approaches, since a relationship is found between the number of therapy hours received each week (scheduling output) and length of stay (queuing model input). The introduction of the treatment scheduling program has substantially improved timetable quality (meaning a better and fairer service to patients) and has reduced employee time expended in its creation by approximately six hours each week (freeing up time for clinical work). The queuing model has been used to assess the effect of potential strategies, such as increasing the number of beds or employing more therapists. The use of mathematical modelling has not only optimised resources in the short term, but has allowed the optimality of longer term strategic decisions to be assessed.

  1. Single Cell Electroporation Method for Mammalian CNS Neurons in Organotypic Slice Cultures

    Science.gov (United States)

    Uesaka, Naofumi; Hayano, Yasufumi; Yamada, Akito; Yamamoto, Nobuhiko

    Axon tracing is an essential technique to study the projection pattern of neurons in the CNS. Horse radish peroxidase and lectins have contributed to revealing many neural connection patterns in the CNS (Itaya and van Hoesen, 1982; Fabian and Coulter, 1985; Yoshihara, 2002). Moreover, a tracing method with fluorescent dye has enabled the observation of growing axons in living conditions, and demon strated a lot of developmental aspects in axon growth and guidance (Harris et al., 1987; O'Rourke and Fraser, 1990; Kaethner and Stuermer, 1992; Halloran and Kalil, 1994; Yamamoto et al., 1997). More recently, genetically encoded fluores cent proteins can be used as a powerful tool to observe various biological events. Several gene transfer techniques such as microinjection, biolistic gene gun, viral infection, lipofection and transgenic technology have been developed (Feng et al., 2000; Ehrengruber et al., 2001; O'Brien et al., 2001; Ma et al., 2002; Sahly et al., 2003). In particular, the electroporation technique was proved as a valuable tool, since it can be applied to a wide range of tissues and cell types with little toxicity and can be performed with relative technical easiness. Most methods, including a stand ard electroporation technique, are suitable for gene transfer to a large number of cells. However, this is not ideal for axonal tracing, because observation of individ ual axons is occasionally required. To overcome this problem, we have developed an electroporation method using glass micropipettes containing plasmid solutions and small current injection. Here we introduce the method in detail and exemplified results with some example applications and discuss its usefulness.

  2. Enhancement of therapeutic drug and DNA delivery into cells by electroporation

    Energy Technology Data Exchange (ETDEWEB)

    Rabussay, Dietmar [Genetronics, Inc., Department of Research and Development, 11199 Sorrento Valley Road, San Diego, CA (United States); Dev, Nagendu B [Genetronics, Inc., Department of Research and Development, 11199 Sorrento Valley Road, San Diego, CA (United States); Fewell, Jason [Valentis, Inc., 8301 New Trails Drive, The Woodlands, TX (United States); Smith, Louis C [Valentis, Inc., 8301 New Trails Drive, The Woodlands, TX (United States); Widera, Georg [Genetronics, Inc., Department of Research and Development, 11199 Sorrento Valley Road, San Diego, CA (United States); Zhang Lei [Genetronics, Inc., Department of Research and Development, 11199 Sorrento Valley Road, San Diego, CA (United States)

    2003-02-21

    The effectiveness of potentially powerful therapeutics, including DNA, is often limited by their inability to permeate the cell membrane efficiently. Electroporation (EP) also referred to as 'electropermeabilization' of the outer cell membrane renders this barrier temporarily permeable by inducing 'pores' across the lipid bilayer. For in vivo EP, the drug or DNA is delivered into the interstitial space of the target tissue by conventional means, followed by local EP. EP pulses of micro- to millisecond duration and field strengths of 100-1500 V cm{sup -1} generally enhance the delivery of certain chemotherapeutic drugs by three to four orders of magnitude and intracellular delivery of DNA several hundred-fold. We have used EP in clinical studies for human cancer therapy and in animals for gene therapy and DNA vaccination. Late stage squamous cell carcinomas of the head and neck were treated with intratumoural injection of bleomycin and subsequent EP. Of the 69 tumours treated, 25% disappeared completely and another 32% were reduced in volume by more than half. Residence time of bleomycin in electroporated tumours was significantly greater than in non-electroporated lesions. Histological findings and gene expression patterns after bleomycin-EP treatment indicated rapid apoptosis of the majority of tumour cells. In animals, we demonstrated the usefulness of EP for enhanced DNA delivery by achieving normalization of blood clotting times in haemophilic dogs, and by substantially increasing transgene expression in smooth muscle cells of arterial walls using a novel porous balloon EP catheter. Finally, we have found in animal experiments that the immune response to DNA vaccines can be dramatically enhanced and accelerated by EP and co-injection of micron-sized particles. We conclude that EP represents an effective, economical and safe approach to enhance the intracellular delivery, and thus potency, of important drugs and genes for therapeutic purposes

  3. Enhancement of therapeutic drug and DNA delivery into cells by electroporation

    International Nuclear Information System (INIS)

    Rabussay, Dietmar; Dev, Nagendu B; Fewell, Jason; Smith, Louis C; Widera, Georg; Zhang Lei

    2003-01-01

    The effectiveness of potentially powerful therapeutics, including DNA, is often limited by their inability to permeate the cell membrane efficiently. Electroporation (EP) also referred to as 'electropermeabilization' of the outer cell membrane renders this barrier temporarily permeable by inducing 'pores' across the lipid bilayer. For in vivo EP, the drug or DNA is delivered into the interstitial space of the target tissue by conventional means, followed by local EP. EP pulses of micro- to millisecond duration and field strengths of 100-1500 V cm -1 generally enhance the delivery of certain chemotherapeutic drugs by three to four orders of magnitude and intracellular delivery of DNA several hundred-fold. We have used EP in clinical studies for human cancer therapy and in animals for gene therapy and DNA vaccination. Late stage squamous cell carcinomas of the head and neck were treated with intratumoural injection of bleomycin and subsequent EP. Of the 69 tumours treated, 25% disappeared completely and another 32% were reduced in volume by more than half. Residence time of bleomycin in electroporated tumours was significantly greater than in non-electroporated lesions. Histological findings and gene expression patterns after bleomycin-EP treatment indicated rapid apoptosis of the majority of tumour cells. In animals, we demonstrated the usefulness of EP for enhanced DNA delivery by achieving normalization of blood clotting times in haemophilic dogs, and by substantially increasing transgene expression in smooth muscle cells of arterial walls using a novel porous balloon EP catheter. Finally, we have found in animal experiments that the immune response to DNA vaccines can be dramatically enhanced and accelerated by EP and co-injection of micron-sized particles. We conclude that EP represents an effective, economical and safe approach to enhance the intracellular delivery, and thus potency, of important drugs and genes for therapeutic purposes. The safety and pharmaco

  4. Gene therapy by electroporation for the treatment of chronic renal failure in companion animals

    Directory of Open Access Journals (Sweden)

    Pope Melissa A

    2009-01-01

    Full Text Available Abstract Background Growth hormone-releasing hormone (GHRH plasmid-based therapy for the treatment of chronic renal failure and its complications was examined. Companion dogs (13.1 ± 0.8 years, 29.4 ± 5.01 kg and cats (13.2 ± 0.9 years, 8.5 ± 0.37 kg received a single 0.4 mg or 0.1 mg species-specific plasmid injection, respectively, intramuscularly followed by electroporation, and analyzed up to 75 days post-treatment; controls underwent electroporation without plasmid administration. Results Plasmid-treated animals showed an increase in body weight (dogs 22.5% and cats 3.2% compared to control animals, and displayed improved quality of life parameters including significant increases in appetite, activity, mentation and exercise tolerance levels. Insulin-like growth factor I (IGF-I, the downstream effector of GHRH levels were increased in the plasmid treated animals. Hematological parameters were also significantly improved. Protein metabolism changes were observed suggesting a shift from a catabolic to an anabolic state in the treated animals. Blood urea nitrogen and creatinine did not show any significant changes suggesting maintenance of kidney function whereas the control animal's renal function deteriorated. Treated animals survived longer than control animals with 70% of dogs and 80% of cats surviving until study day 75. Only 17% and 40% of the control dogs and cats, respectively, survived to day 75. Conclusion Improved quality of life, survival and general well-being indicate that further investigation is warranted, and show the potential of a plasmid-based therapy by electroporation in preventing and managing complications of renal insufficiency.

  5. Evolutionary programming for neutron instrument optimisation

    Energy Technology Data Exchange (ETDEWEB)

    Bentley, Phillip M. [Hahn-Meitner Institut, Glienicker Strasse 100, D-14109 Berlin (Germany)]. E-mail: phillip.bentley@hmi.de; Pappas, Catherine [Hahn-Meitner Institut, Glienicker Strasse 100, D-14109 Berlin (Germany); Habicht, Klaus [Hahn-Meitner Institut, Glienicker Strasse 100, D-14109 Berlin (Germany); Lelievre-Berna, Eddy [Institut Laue-Langevin, 6 rue Jules Horowitz, BP 156, 38042 Grenoble Cedex 9 (France)

    2006-11-15

    Virtual instruments based on Monte-Carlo techniques are now integral part of novel instrumentation development and the existing codes (McSTAS and Vitess) are extensively used to define and optimise novel instrumental concepts. Neutron spectrometers, however, involve a large number of parameters and their optimisation is often a complex and tedious procedure. Artificial intelligence algorithms are proving increasingly useful in such situations. Here, we present an automatic, reliable and scalable numerical optimisation concept based on the canonical genetic algorithm (GA). The algorithm was used to optimise the 3D magnetic field profile of the NSE spectrometer SPAN, at the HMI. We discuss the potential of the GA which combined with the existing Monte-Carlo codes (Vitess, McSTAS, etc.) leads to a very powerful tool for automated global optimisation of a general neutron scattering instrument, avoiding local optimum configurations.

  6. Evolutionary programming for neutron instrument optimisation

    International Nuclear Information System (INIS)

    Bentley, Phillip M.; Pappas, Catherine; Habicht, Klaus; Lelievre-Berna, Eddy

    2006-01-01

    Virtual instruments based on Monte-Carlo techniques are now integral part of novel instrumentation development and the existing codes (McSTAS and Vitess) are extensively used to define and optimise novel instrumental concepts. Neutron spectrometers, however, involve a large number of parameters and their optimisation is often a complex and tedious procedure. Artificial intelligence algorithms are proving increasingly useful in such situations. Here, we present an automatic, reliable and scalable numerical optimisation concept based on the canonical genetic algorithm (GA). The algorithm was used to optimise the 3D magnetic field profile of the NSE spectrometer SPAN, at the HMI. We discuss the potential of the GA which combined with the existing Monte-Carlo codes (Vitess, McSTAS, etc.) leads to a very powerful tool for automated global optimisation of a general neutron scattering instrument, avoiding local optimum configurations

  7. Efficacy of irreversible electroporation in human pancreatic adenocarcinoma: advanced murine model

    Directory of Open Access Journals (Sweden)

    Prejesh Philips

    Full Text Available Irreversible electroporation (IRE is a promising cell membrane ablative modality for pancreatic cancer. There have been recent concerns regarding local recurrence and the potential use of IRE as a debulking (partial ablation modality. We hypothesize that incomplete ablation leads to early recurrence and a more aggressive biology. We created the first ever heterotopic murine model by inoculating BALB/c nude mice in the hindlimb with a subcutaneous injection of Panc-1 cells, an immortalized human pancreatic adenocarcinoma cell line. Tumors were allowed to grow from 0.75 to 1.5 cm and then treated with the goal of complete ablation or partial ablation using standard IRE settings. Animals were recovered and survived for 2 days (n = 6, 7 (n = 6, 14 (n = 6, 21 (n = 6, 30 (n = 8, and 60 (n = 8 days. All 40 animals/tumors underwent successful IRE under general anesthesia with muscle paralysis. The mean tumor volume of the animals undergoing ablation was 1,447.6 mm3 ± 884. Histologically, in the 14-, 21-, 30-, and 60-day survival groups the entire tumor was nonviable, with a persistent tumor nodule completely replaced fibrosis. In the group treated with partial ablation, incomplete electroporation/recurrences (N = 10 animals were seen, of which 66% had confluent tumors and this was a significant predictor of recurrence (P < 0.001. Recurrent tumors were also significantly larger (mean 4,578 mm3 ± SD 877 versus completed electroporated tumors 925.8 ± 277, P < 0.001. Recurrent tumors had a steeper growth curve (slope = 0.73 compared with primary tumors (0.60, P = 0.02. Recurrent tumors also had a significantly higher percentage of EpCAM expression, suggestive of stem cell activation. Tumors that recur after incomplete electroporation demonstrate a biologically aggressive tumor that could be more resistant to standard of care chemotherapy. Clinical correlation of this data is limited, but should be considered when IRE of pancreatic cancer is being

  8. Synthesis of ABA Tri-Block Co-Polymer Magnetopolymersomes via Electroporation for Potential Medical Application

    Directory of Open Access Journals (Sweden)

    Jennifer Bain

    2015-12-01

    Full Text Available The ABA tri-block copolymer poly(2-methyloxazoline–poly(dimethylsiloxane–poly(2-methyloxazoline (PMOXA–PDMS–PMOXA is known for its capacity to mimic a bilayer membrane in that it is able to form vesicular polymersome structures. For this reason, it is the subject of extensive research and enables the development of more robust, adaptable and biocompatible alternatives to natural liposomes for biomedical applications. However, the poor solubility of this polymer renders published methods for forming vesicles unreproducible, hindering research and development of these polymersomes. Here we present an adapted, simpler method for the production of PMOXA–PDMS–PMOXA polymersomes of a narrow polydispersity (45 ± 5.8 nm, via slow addition of aqueous solution to a new solvent/polymer mixture. We then magnetically functionalise these polymersomes to form magnetopolymersomes via in situ precipitation of iron-oxide magnetic nanoparticles (MNPs within the PMOXA–PDMS–PMOXA polymersome core and membrane. This is achieved using electroporation to open pores within the membrane and to activate the formation of MNPs. The thick PMOXA–PDMS–PMOXA membrane is well known to be relatively non-permeable when compared to more commonly used di-block polymer membranes due a distinct difference in both size and chemistry and therefore very difficult to penetrate using standard biological methods. This paper presents for the first time the application of electroporation to an ABA tri-block polymersome membrane (PMOXA–PDMS–PMOXA for intravesicular in situ precipitation of uniform MNPs (2.6 ± 0.5 nm. The electroporation process facilitates the transport of MNP reactants across the membrane yielding in situ precipitation of MNPs. Further to differences in length and chemistry, a tri-block polymersome membrane structure differs from a natural lipid or di-block polymer membrane and as such the application and effects of electroporation on this type of

  9. Percutaneous Irreversible Electroporation of Unresectable Hilar Cholangiocarcinoma (Klatskin Tumor): A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Melenhorst, Marleen C. A. M., E-mail: m.melenhorst@vumc.nl; Scheffer, Hester J., E-mail: hj.scheffer@vumc.nl; Vroomen, Laurien G. P. H., E-mail: la.vroomen@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands); Kazemier, Geert, E-mail: g.kazemier@vumc.nl; Tol, M. Petrousjka van den, E-mail: mp.vandentol@vumc.nl [VU University Medical Center, Department of Surgery (Netherlands); Meijerink, Martijn R., E-mail: mr.meijerink@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands)

    2016-01-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant tumors located near large vessels or bile ducts. The presence of metal objects in the ablation zone, such as Wallstents, is generally considered a contraindication for IRE, because tissue heating due to power conduction may lead to thermal complications. This report describes a 66-year-old female with a Bismuth–Corlette stage IV unresectable cholangiocarcinoma with a metallic Wallstent in the common bile duct, who was safely treated with percutaneous IRE with no signs for relapse 1 year after the procedure.

  10. Construction of insertion and deletion mxa mutants of Methylobacterium extorquens AM1 by electroporation.

    Science.gov (United States)

    Toyama, H; Anthony, C; Lidstrom, M E

    1998-09-01

    Methylobacterium extorquens AM1 is a pink-pigmented facultative methylotroph which is widely used for analyzing pathways of C1 metabolism with biochemical and molecular biological techniques. To facilitate this approach, we have applied a new method to construct insertion or disruption mutants with drug resistance genes by electroporation. By using this method, mutants were obtained in four genes present in the mxa methylotrophy gene cluster for which the functions were unknown, mxaR, mxaS, mxaC and mxaD. These mutants were unable to grow on methanol except the mutant of mxaD, which showed reduced growth on methanol.

  11. Dose optimisation in computed radiography

    International Nuclear Information System (INIS)

    Schreiner-Karoussou, A.

    2005-01-01

    After the installation of computed radiography (CR) systems in three hospitals in Luxembourg a patient dose survey was carried out for three radiographic examinations, thorax, pelvis and lumbar spine. It was found that the patient doses had changed in comparison with the patient doses measured for conventional radiography in the same three hospitals. A close collaboration between the manufacturers of the X-ray installations, the CR imaging systems and the medical physicists led to the discovery that the speed class with which each radiographic examination was to be performed, had been ignored, during installation of the digital imaging systems. A number of procedures were carried out in order to calibrate and program the X-ray installations in conjunction with the CR systems. Following this optimisation procedure, a new patient dose survey was carried out for the three radiographic examinations. It was found that patient doses for the three hospitals were reduced. (authors)

  12. Optimising costs in WLCG operations

    CERN Document Server

    Pradillo, Mar; Flix, Josep; Forti, Alessandra; Sciabà, Andrea

    2015-01-01

    The Worldwide LHC Computing Grid project (WLCG) provides the computing and storage resources required by the LHC collaborations to store, process and analyse the 50 Petabytes of data annually generated by the LHC. The WLCG operations are coordinated by a distributed team of managers and experts and performed by people at all participating sites and from all the experiments. Several improvements in the WLCG infrastructure have been implemented during the first long LHC shutdown to prepare for the increasing needs of the experiments during Run2 and beyond. However, constraints in funding will affect not only the computing resources but also the available effort for operations. This paper presents the results of a detailed investigation on the allocation of the effort in the different areas of WLCG operations, identifies the most important sources of inefficiency and proposes viable strategies for optimising the operational cost, taking into account the current trends in the evolution of the computing infrastruc...

  13. Avoiding neuromuscular stimulation in liver irreversible electroporation using radiofrequency electric fields

    Science.gov (United States)

    Castellví, Quim; Mercadal, Borja; Moll, Xavier; Fondevila, Dolors; Andaluz, Anna; Ivorra, Antoni

    2018-02-01

    Electroporation-based treatments typically consist of the application of high-voltage dc pulses. As an undesired side effect, these dc pulses cause electrical stimulation of excitable tissues such as motor nerves. The present in vivo study explores the use of bursts of sinusoidal voltage in a frequency range from 50 kHz to 2 MHz, to induce irreversible electroporation (IRE) whilst avoiding neuromuscular stimulation. A series of 100 dc pulses or sinusoidal bursts, both with an individual duration of 100 µs, were delivered to rabbit liver through thin needles in a monopolar electrode configuration, and thoracic movements were recorded with an accelerometer. Tissue samples were harvested three hours after treatment and later post-processed to determine the dimensions of the IRE lesions. Thermal damage due to Joule heating was ruled out via computer simulations. Sinusoidal bursts with a frequency equal to or above 100 kHz did not cause thoracic movements and induced lesions equivalent to those obtained with conventional dc pulses when the applied voltage amplitude was sufficiently high. IRE efficacy dropped with increasing frequency. For 100 kHz bursts, it was estimated that the electric field threshold for IRE is about 1.4 kV cm-1 whereas that of dc pulses is about 0.5 kV cm-1.

  14. In vivo non-thermal irreversible electroporation impact on rat liver galvanic apparent internal resistance

    International Nuclear Information System (INIS)

    Golberg, A; Laufer, S; Rabinowitch, H D; Rubinsky, B

    2011-01-01

    Non-thermal irreversible electroporation (NTIRE) is a biophysical phenomenon which involves application of electric field pulses to cells or tissues, causing certain rearrangements in the membrane structure leading to cell death. The treated tissue ac impedance changes induced by electroporation were shown to be the indicators for NTIRE efficiency. In a previous study we characterized in vitro tissue galvanic apparent internal resistance (GAIR) changes due to NTIRE. Here we describe an in vivo study in which we monitored the GAIR changes of a rat liver treated by NTIRE. Electrical pulses were delivered through the same Zn/Cu electrodes by which GAIR was measured. GAIR was measured before and for 3 h after the treatment at 15 min intervals. The results were compared to the established ac bioimpedance measurement method. A decrease of 33% was measured immediately after the NTIRE treatment and a 40% decrease was measured after 3 h in GAIR values; in the same time 40% and 47% decrease respectively were measured by ac bioimpedance analyses. The temperature increase due to the NTIRE was only 0.5 deg. C. The results open the way for an inexpensive, self-powered in vivo real-time NTIRE effectiveness measurement.

  15. Induction of rat liver tumor using the Sleeping Beauty transposon and electroporation.

    Science.gov (United States)

    Park, June-Shine; Kim, Bae-Hwan; Park, Sung Goo; Jung, Sun Young; Lee, Do Hee; Son, Woo-Chan

    2013-05-10

    The Sleeping Beauty (SB) transposon system has been receiving much attention as a gene transfer method of choice since it allows permanent gene expression after insertion into the host chromosome. However, low transposition frequency in higher eukaryotes limits its use in commonly-used mammalian species. Researchers have therefore attempted to modify gene delivery and expression to overcome this limitation. In mouse liver, tumor induction using SB introduced by the hydrodynamic method has been successfully accomplished. Liver tumor in rat models using SB could also be of great use; however, dose of DNA, injection volume, rate of injection and achieving back pressure limit the use of the hydrodynamics-based gene delivery. In the present study, we combined the electroporation, a relatively simple and easy gene delivery method, with the SB transposon system and as a result successfully induced tumor in rat liver by directly injecting the c-Myc, HRAS and shp53 genes. The tumor phenotype was determined as a sarcomatoid carcinoma. To our knowledge, this is the first demonstration of induction of tumor in the rat liver using the electroporation-enhanced SB transposon system. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Comparison of membrane electroporation and protein denature in response to pulsed electric field with different durations.

    Science.gov (United States)

    Huang, Feiran; Fang, Zhihui; Mast, Jason; Chen, Wei

    2013-05-01

    In this paper, we compared the minimum potential differences in the electroporation of membrane lipid bilayers and the denaturation of membrane proteins in response to an intensive pulsed electric field with various pulse durations. Single skeletal muscle fibers were exposed to a pulsed external electric field. The field-induced changes in the membrane integrity (leakage current) and the Na channel currents were monitored to identify the minimum electric field needed to damage the membrane lipid bilayer and the membrane proteins, respectively. We found that in response to a relatively long pulsed electric shock (longer than the membrane intrinsic time constant), a lower membrane potential was needed to electroporate the cell membrane than for denaturing the membrane proteins, while for a short pulse a higher membrane potential was needed. In other words, phospholipid bilayers are more sensitive to the electric field than the membrane proteins for a long pulsed shock, while for a short pulse the proteins become more vulnerable. We can predict that for a short or ultrashort pulsed electric shock, the minimum membrane potential required to start to denature the protein functions in the cell plasma membrane is lower than that which starts to reduce the membrane integrity. Copyright © 2013 Wiley Periodicals, Inc.

  17. In vivo non-thermal irreversible electroporation impact on rat liver galvanic apparent internal resistance

    Energy Technology Data Exchange (ETDEWEB)

    Golberg, A; Laufer, S [Center for Bioengineering in the Service of Humanity and Society, School of Computer Science and Engineering, Hebrew University of Jerusalem, Jerusalem 91904 (Israel); Rabinowitch, H D [Robert H Smith Faculty of Agriculture, Food and Environment, Robert H Smith Institute of Plant Science and Genetics in Agriculture, Hebrew University of Jerusalem, Rehovot 76 100 (Israel); Rubinsky, B, E-mail: Rabin@agri.huji.ac.il [Department of Mechanical Engineering, Graduate Program in Biophysics, University of California at Berkeley, Berkeley, CA 84720 (United States)

    2011-02-21

    Non-thermal irreversible electroporation (NTIRE) is a biophysical phenomenon which involves application of electric field pulses to cells or tissues, causing certain rearrangements in the membrane structure leading to cell death. The treated tissue ac impedance changes induced by electroporation were shown to be the indicators for NTIRE efficiency. In a previous study we characterized in vitro tissue galvanic apparent internal resistance (GAIR) changes due to NTIRE. Here we describe an in vivo study in which we monitored the GAIR changes of a rat liver treated by NTIRE. Electrical pulses were delivered through the same Zn/Cu electrodes by which GAIR was measured. GAIR was measured before and for 3 h after the treatment at 15 min intervals. The results were compared to the established ac bioimpedance measurement method. A decrease of 33% was measured immediately after the NTIRE treatment and a 40% decrease was measured after 3 h in GAIR values; in the same time 40% and 47% decrease respectively were measured by ac bioimpedance analyses. The temperature increase due to the NTIRE was only 0.5 deg. C. The results open the way for an inexpensive, self-powered in vivo real-time NTIRE effectiveness measurement.

  18. Genetic transformation of intact Lactococcus lactis subsp. lactis by high-voltage electroporation

    Energy Technology Data Exchange (ETDEWEB)

    McIntyre, D.A.; Harlander, S.K. (Univ. of Minnesota, St. Paul (USA))

    1989-03-01

    The objective of this study was to develop a system for electroporating intact cells of Lactococcus lactis subsp. lactis LM0230 (previously designated Streptococcus lactis LM0230) with a commercially available electroporation unit. Parameters which influenced the efficiency of transformation included growth phase and final concentration of cells, ionic strength of the suspending medium, concentration of plasmid DNA, and the amplitude and duration of the pulse. Washed suspensions of intact cells suspended in deionized distilled water were subjected to one high-voltage electric pulse varying in voltage (300 to 900 V corresponding to field strengths of 5 to 17 kV/cm) and duration (100 {mu}s to 1 s). Transformation efficiencies of 10{sup 3} transformants per {mu}g of DNA were obtained when dense suspensions (final concentration, 5 {times} 10{sup 10} CFU/ml) of stationary-phase cells were subjected to one pulse with a peak voltage of 900 V (field strength, 17 kV/cm) and a pulse duration of 5 ms in the presence of plasmid DNA. Dilution of porated cells in broth medium followed by an expression period of 2 h at 30{degree}C was beneficial in enhancing transformation efficiencies. Plasmids ranging in size from 9.8 to 30.0 kilobase pairs could be transformed by this procedure.

  19. CT-guided Irreversible Electroporation in an Acute Porcine Liver Model: Effect of Previous Transarterial Iodized Oil Tissue Marking on Technical Parameters, 3D Computed Tomographic Rendering of the Electroporation Zone, and Histopathology

    International Nuclear Information System (INIS)

    Sommer, C. M.; Fritz, S.; Vollherbst, D.; Zelzer, S.; Wachter, M. F.; Bellemann, N.; Gockner, T.; Mokry, T.; Schmitz, A.; Aulmann, S.; Stampfl, U.; Pereira, P.; Kauczor, H. U.; Werner, J.; Radeleff, B. A.

    2015-01-01

    PurposeTo evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance.MethodsAfter Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann–Whitney test. Histopathological differences were assessed.ResultsMean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm 3 , and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm 3 , and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone.ConclusionThere is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver

  20. CT-guided Irreversible Electroporation in an Acute Porcine Liver Model: Effect of Previous Transarterial Iodized Oil Tissue Marking on Technical Parameters, 3D Computed Tomographic Rendering of the Electroporation Zone, and Histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, C. M., E-mail: christof.sommer@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Fritz, S., E-mail: stefan.fritz@med.uni-heidelberg.de [University Hospital Heidelberg, Department of General Visceral and Transplantation Surgery (Germany); Vollherbst, D., E-mail: dominikvollherbst@web.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Zelzer, S., E-mail: s.zelzer@dkfz-heidelberg.de [German Cancer Research Center (dkfz), Medical and Biological Informatics (Germany); Wachter, M. F., E-mail: fredericwachter@googlemail.com; Bellemann, N., E-mail: nadine.bellemann@med.uni-heidelberg.de; Gockner, T., E-mail: theresa.gockner@med.uni-heidelberg.de; Mokry, T., E-mail: theresa.mokry@med.uni-heidelberg.de; Schmitz, A., E-mail: anne.schmitz@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Aulmann, S., E-mail: sebastian.aulmann@mail.com [University Hospital Heidelberg, Department of General Pathology (Germany); Stampfl, U., E-mail: ulrike.stampfl@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Pereira, P., E-mail: philippe.pereira@slk-kliniken.de [SLK Kliniken Heilbronn GmbH, Clinic for Radiology, Minimally-invasive Therapies and Nuclear Medicine (Germany); Kauczor, H. U., E-mail: hu.kauczor@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany); Werner, J., E-mail: jens.werner@med.uni-heidelberg.de [University Hospital Heidelberg, Department of General Visceral and Transplantation Surgery (Germany); Radeleff, B. A., E-mail: boris.radeleff@med.uni-heidelberg.de [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (Germany)

    2015-02-15

    PurposeTo evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance.MethodsAfter Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann–Whitney test. Histopathological differences were assessed.ResultsMean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm{sup 3}, and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm{sup 3}, and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone.ConclusionThere is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver.

  1. Predicting electroporation of cells in an inhomogeneous electric field based on mathematical modeling and experimental CHO-cell permeabilization to propidium iodide determination.

    Science.gov (United States)

    Dermol, Janja; Miklavčič, Damijan

    2014-12-01

    High voltage electric pulses cause electroporation of the cell membrane. Consequently, flow of the molecules across the membrane increases. In our study we investigated possibility to predict the percentage of the electroporated cells in an inhomogeneous electric field on the basis of the experimental results obtained when cells were exposed to a homogeneous electric field. We compared and evaluated different mathematical models previously suggested by other authors for interpolation of the results (symmetric sigmoid, asymmetric sigmoid, hyperbolic tangent and Gompertz curve). We investigated the density of the cells and observed that it has the most significant effect on the electroporation of the cells while all four of the mathematical models yielded similar results. We were able to predict electroporation of cells exposed to an inhomogeneous electric field based on mathematical modeling and using mathematical formulations of electroporation probability obtained experimentally using exposure to the homogeneous field of the same density of cells. Models describing cell electroporation probability can be useful for development and presentation of treatment planning for electrochemotherapy and non-thermal irreversible electroporation. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Efficient large volume electroporation of dendritic cells through micrometer scale manipulation of flow in a disposable polymer chip

    DEFF Research Database (Denmark)

    Selmeczi, David; Hansen, Thomas; Met, Özcan

    2011-01-01

    We present a hybrid chip of polymer and stainless steel designed for high-throughput continuous electroporation of cells in suspension. The chip is constructed with two parallel stainless steel mesh electrodes oriented perpendicular to the liquid flow. The relatively high hydrodynamic resistance ...

  3. The Effect of Electroporation of a Lyotroic Liquid Crystal Genistein-Based Formulation in the Recovery of Murine Melanoma Lesions

    Directory of Open Access Journals (Sweden)

    Corina Danciu

    2015-07-01

    Full Text Available A lamellar lyotropic liquid crystal genistein-based formulation (LLC-Gen was prepared in order to increase the aqueous solubility of the lipophilic phytocompound genistein. The formulation was applied locally, in a murine model of melanoma, with or without electroporation. The results demonstrated that, when the formulation was applied by electroporation, the tumors appeared later. During the 21 days of the experiment, the LLC-Gen formulation decreased the tumor volume, the amount of melanin and the degree of erythema, but when electroporation was applied, all these parameters indicated a better prognosis even (lower tumor volume, amount of melanin and degree of erythema. Although hematoxylin–eosin (HE staining confirmed the above events, application of the LLC-Gen formulation by electroporation did not lead to a significant effect in terms of the serum concentrations of the protein S100B and serum neuron specific enolase (NSE, or the tissue expression of the platelet-derived growth factor receptor β (PDGFRβ antibody.

  4. Ca2+ uptake and cellular integrity in rat EDL muscle exposed to electrostimulation, electroporation, or A23187

    DEFF Research Database (Denmark)

    Gissel, Hanne; Clausen, Torben

    2003-01-01

    We tested the hypothesis that increased Ca2+ uptake in rat extensor digitorum longus (EDL) muscle elicits cell membrane damage as assessed from release of the intracellular enzyme lactate dehydrogenase (LDH). This was done by using 1) electrostimulation, 2) electroporation, and 3) the Ca2+ ionoph...

  5. Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille

    2013-01-01

    offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium...

  6. Transfection of HeLa-cells with pEGFP plasmid by impedance power-assisted electroporation

    DEFF Research Database (Denmark)

    Glahder, Jacob; Norrild, Bodil; Persson, Mikael B

    2005-01-01

    Bioimpedance spectrometry was applied to study cell viability and pEGFP plasmid-transfection efficiency in electroporation (EP) of 20,000 HeLa cells with 0.3 microg DNA in 90 microl low conductivity 0.32 M sucrose medium of pH 7.5. Monopolar rectangular pulses, of field strength 75 V/mm, and puls...

  7. Studies on mRNA electroporation of immature and mature dendritic cells: Effects on their immunogenic potential

    DEFF Research Database (Denmark)

    Met, O.; Eriksen, J.; Svane, Inge Marie

    2008-01-01

    Previous studies have shown that mRNA-electroporated dendritic cells (DCs) are able to process and present tumor-associated antigens, leading to the activation of tumor-specific T cells in vitro and in vivo. However, the optimal maturation state of antigen loading and half-life of the mRNA-transl...

  8. Combining simulation and multi-objective optimisation for equipment quantity optimisation in container terminals

    OpenAIRE

    Lin, Zhougeng

    2013-01-01

    This thesis proposes a combination framework to integrate simulation and multi-objective optimisation (MOO) for container terminal equipment optimisation. It addresses how the strengths of simulation and multi-objective optimisation can be integrated to find high quality solutions for multiple objectives with low computational cost. Three structures for the combination framework are proposed respectively: pre-MOO structure, integrated MOO structure and post-MOO structure. The applications of ...

  9. Layout Optimisation of Wave Energy Converter Arrays

    Directory of Open Access Journals (Sweden)

    Pau Mercadé Ruiz

    2017-08-01

    Full Text Available This paper proposes an optimisation strategy for the layout design of wave energy converter (WEC arrays. Optimal layouts are sought so as to maximise the absorbed power given a minimum q-factor, the minimum distance between WECs, and an area of deployment. To guarantee an efficient optimisation, a four-parameter layout description is proposed. Three different optimisation algorithms are further compared in terms of performance and computational cost. These are the covariance matrix adaptation evolution strategy (CMA, a genetic algorithm (GA and the glowworm swarm optimisation (GSO algorithm. The results show slightly higher performances for the latter two algorithms; however, the first turns out to be significantly less computationally demanding.

  10. Topology optimisation of natural convection problems

    DEFF Research Database (Denmark)

    Alexandersen, Joe; Aage, Niels; Andreasen, Casper Schousboe

    2014-01-01

    This paper demonstrates the application of the density-based topology optimisation approach for the design of heat sinks and micropumps based on natural convection effects. The problems are modelled under the assumptions of steady-state laminar flow using the incompressible Navier-Stokes equations...... coupled to the convection-diffusion equation through the Boussinesq approximation. In order to facilitate topology optimisation, the Brinkman approach is taken to penalise velocities inside the solid domain and the effective thermal conductivity is interpolated in order to accommodate differences...... in thermal conductivity of the solid and fluid phases. The governing equations are discretised using stabilised finite elements and topology optimisation is performed for two different problems using discrete adjoint sensitivity analysis. The study shows that topology optimisation is a viable approach...

  11. Topology Optimisation for Coupled Convection Problems

    DEFF Research Database (Denmark)

    Alexandersen, Joe

    This thesis deals with topology optimisation for coupled convection problems. The aim is to extend and apply topology optimisation to steady-state conjugate heat transfer problems, where the heat conduction equation governs the heat transfer in a solid and is coupled to thermal transport...... in a surrounding uid, governed by a convection-diffusion equation, where the convective velocity field is found from solving the isothermal incompressible steady-state Navier-Stokes equations. Topology optimisation is also applied to steady-state natural convection problems. The modelling is done using stabilised...... finite elements, the formulation and implementation of which was done partly during a special course as prepatory work for this thesis. The formulation is extended with a Brinkman friction term in order to facilitate the topology optimisation of fluid flow and convective cooling problems. The derived...

  12. Benchmarks for dynamic multi-objective optimisation

    CSIR Research Space (South Africa)

    Helbig, M

    2013-06-01

    Full Text Available When algorithms solve dynamic multi-objective optimisation problems (DMOOPs), benchmark functions should be used to determine whether the algorithm can overcome specific difficulties that can occur in real-world problems. However, for dynamic multi...

  13. Credit price optimisation within retail banking

    African Journals Online (AJOL)

    2014-02-14

    Feb 14, 2014 ... cost based pricing, where the price of a product or service is based on the .... function obtained from fitting a logistic regression model .... Note that the proposed optimisation approach below will allow us to also incorporate.

  14. User perspectives in public transport timetable optimisation

    DEFF Research Database (Denmark)

    Jensen, Jens Parbo; Nielsen, Otto Anker; Prato, Carlo Giacomo

    2014-01-01

    The present paper deals with timetable optimisation from the perspective of minimising the waiting time experienced by passengers when transferring either to or from a bus. Due to its inherent complexity, this bi-level minimisation problem is extremely difficult to solve mathematically, since tim...... on the large-scale public transport network in Denmark. The timetable optimisation approach yielded a yearly reduction in weighted waiting time equivalent to approximately 45 million Danish kroner (9 million USD)....

  15. Methodological principles for optimising functional MRI experiments

    International Nuclear Information System (INIS)

    Wuestenberg, T.; Giesel, F.L.; Strasburger, H.

    2005-01-01

    Functional magnetic resonance imaging (fMRI) is one of the most common methods for localising neuronal activity in the brain. Even though the sensitivity of fMRI is comparatively low, the optimisation of certain experimental parameters allows obtaining reliable results. In this article, approaches for optimising the experimental design, imaging parameters and analytic strategies will be discussed. Clinical neuroscientists and interested physicians will receive practical rules of thumb for improving the efficiency of brain imaging experiments. (orig.) [de

  16. Optimisation: how to develop stake holder involvement

    International Nuclear Information System (INIS)

    Weiss, W.

    2003-01-01

    The Precautionary Principle is an internationally recognised approach for dealing with risk situations characterised by uncertainties and potential irreversible damages. Since the late fifties, ICRP has adopted this prudent attitude because of the lack of scientific evidence concerning the existence of a threshold at low doses for stochastic effects. The 'linear, no-threshold' model and the 'optimisation of protection' principle have been developed as a pragmatic response for the management of the risk. The progress in epidemiology and radiobiology over the last decades have affirmed the initial assumption and the optimisation remains the appropriate response for the application of the precautionary principle in the context of radiological protection. The basic objective of optimisation is, for any source within the system of radiological protection, to maintain the level of exposure as low as reasonably achievable, taking into account social and economical factors. Methods tools and procedures have been developed over the last two decades to put into practice the optimisation principle with a central role given to the cost-benefit analysis as a means to determine the optimised level of protection. However, with the advancement in the implementation of the principle more emphasis was progressively given to good practice, as well as on the importance of controlling individual levels of exposure through the optimisation process. In the context of the revision of its present recommendations, the Commission is reenforcing the emphasis on protection of the individual with the adoption of an equity-based system that recognizes individual rights and a basic level of health protection. Another advancement is the role that is now recognised to 'stakeholders involvement' in the optimisation process as a mean to improve the quality of the decision aiding process for identifying and selecting protection actions considered as being accepted by all those involved. The paper

  17. Dose optimisation in single plane interstitial brachytherapy

    DEFF Research Database (Denmark)

    Tanderup, Kari; Hellebust, Taran Paulsen; Honoré, Henriette Benedicte

    2006-01-01

    patients,       treated for recurrent rectal and cervical cancer, flexible catheters were       sutured intra-operatively to the tumour bed in areas with compromised       surgical margin. Both non-optimised, geometrically and graphically       optimised CT -based dose plans were made. The overdose index...... on the       regularity of the implant, such that the benefit of optimisation was       larger for irregular implants. OI and HI correlated strongly with target       volume limiting the usability of these parameters for comparison of dose       plans between patients. CONCLUSIONS: Dwell time optimisation significantly......BACKGROUND AND PURPOSE: Brachytherapy dose distributions can be optimised       by modulation of source dwell times. In this study dose optimisation in       single planar interstitial implants was evaluated in order to quantify the       potential benefit in patients. MATERIAL AND METHODS: In 14...

  18. Thermal performance monitoring and optimisation

    International Nuclear Information System (INIS)

    Sunde, Svein; Berg; Oeyvind

    1998-01-01

    Monitoring of the thermal efficiency of nuclear power plants is expected to become increasingly important as energy-market liberalisation exposes plants to increasing availability requirements and fiercer competition. The general goal in thermal performance monitoring is straightforward: to maximise the ratio of profit to cost under the constraints of safe operation. One may perceive this goal to be pursued in two ways, one oriented towards fault detection and cost-optimal predictive maintenance, and another determined at optimising target values of parameters in response to any component degradation detected, changes in ambient conditions, or the like. Annual savings associated with effective thermal-performance monitoring are expected to be in the order of $ 100 000 for power plants of representative size. A literature review shows that a number of computer systems for thermal-performance monitoring exists, either as prototypes or commercially available. The characteristics and needs of power plants may vary widely, however, and decisions concerning the exact scope, content and configuration of a thermal-performance monitor may well follow a heuristic approach. Furthermore, re-use of existing software modules may be desirable. Therefore, we suggest here the design of a flexible workbench for easy assembly of an experimental thermal-performance monitor at the Halden Project. The suggested design draws heavily on our extended experience in implementing control-room systems featured by assets like high levels of customisation, flexibility in configuration and modularity in structure, and on a number of relevant adjoining activities. The design includes a multi-computer communication system and a graphical user's interface, and aims at a system adaptable to any combination of in-house or end user's modules, as well as commercially available software. (author)

  19. Approaches and challenges to optimising primary care teams’ electronic health record usage

    Directory of Open Access Journals (Sweden)

    Nancy Pandhi

    2014-07-01

    Full Text Available Background Although the presence of an electronic health record (EHR alone does not ensure high quality, efficient care, few studies have focused on the work of those charged with optimising use of existing EHR functionality.Objective To examine the approaches used and challenges perceived by analysts supporting the optimisation of primary care teams’ EHR use at a large U.S. academic health care system.Methods A qualitative study was conducted. Optimisation analysts and their supervisor were interviewed and data were analysed for themes.Results Analysts needed to reconcile the tension created by organisational mandates focused on the standardisation of EHR processes with the primary care teams’ demand for EHR customisation. They gained an understanding of health information technology (HIT leadership’s and primary care team’s goals through attending meetings, reading meeting minutes and visiting with clinical teams. Within what was organisationally possible, EHR education could then be tailored to fit team needs. Major challenges were related to organisational attempts to standardise EHR use despite varied clinic contexts, personnel readiness and technical issues with the EHR platform. Forcing standardisation upon clinical needs that current EHR functionality could not satisfy was difficult.Conclusions Dedicated optimisation analysts can add value to health systems through playing a mediating role between HIT leadership and care teams. Our findings imply that EHR optimisation should be performed with an in-depth understanding of the workflow, cognitive and interactional activities in primary care.

  20. DNA transfection of bone marrow mesenchymal stem cells using micro electroporation chips

    KAUST Repository

    Deng, Peigang

    2011-02-01

    Experimental study of electroporation of bone marrow mesenchymal stem cells (MSCs) at the single-cell level was carried out on a micro EP chip by using single electric rectangular pulse. The threshold values of the electrode potential and pulse width for gas bubble generation on the micro electrodes due to electrolysis of water were revealed as 4.5 volt and 100 μs, respectively. Quantitative EP study was performed with various electric field strengths for various pulse widths, ranging from 20μs to 15ms. Over 1,000 single-cell EP results were used to construct an EP "phase diagram", which delineates the boundaries for (1) effective EP of MSCs and (2) electric cell lysis of MSCs. Finally, the micro EP chip showed successful transfection of the pEGFP-C1 plasmid into the MSCs by properly choosing the electric parameters from the EP "phase diagram". © 2011 IEEE.

  1. Electroporation Enhanced Effect of Dystrophin Splice Switching PNA Oligomers in Normal and Dystrophic Muscle

    DEFF Research Database (Denmark)

    Hjortkjær, Camilla Brolin; Shiraishi, Takehiko; Hojman, Pernille

    2015-01-01

    for improvement of in vivo cellular availability, we have investigated the effect of electrotransfer upon intramuscular (i.m.) PNA administration in vivo. Antisense PNA targeting exon 23 of the murine dystrophin gene was administered by i.m. injection to the tibialis anterior (TA) muscle of normal NMRI......Peptide nucleic acid (PNA) is a synthetic DNA mimic that has shown potential for discovery of novel splice switching antisense drugs. However, in vivo cellular delivery has been a limiting factor for development, and only few successful studies have been reported. As a possible modality...... switching was detected at the RNA level up to 4 weeks after a single-dose treatment. In dystrophic muscles of the MDX mouse, electroporation increased the number of dystrophin-positive fibers about 2.5-fold at 2 weeks after a single PNA administration compared to injection only. In conclusion, we find...

  2. Detection of electroporation-induced membrane permeabilization states in the brain using diffusion-weighted MRI

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Hansen, Rasmus H; Agerholm-Larsen, Birgit

    2015-01-01

    BACKGROUND: Tissue permeabilization by electroporation (EP) is a promising technique to treat certain cancers. Non-invasive methods for verification of induced permeabilization are important, especially in deep-seated cancers. In this study we evaluated diffusion-weighted magnetic resonance imaging...... (NP), transient membrane permeabilization (TMP), and permanent membrane permeabilization (PMP), respectively. DW-MRI was acquired 5 minutes, 2 hours, 24 hours and 48 hours after EP. Histology was performed for validation of the permeabilization states. Tissue content of water, Na+, K+, Ca2...... minutes after EP, compared to NP. Kurtosis was also significantly higher at 24 hours (pstates, supporting the DW-MRI findings. We conclude that DW-MRI is capable of detecting EP...

  3. DNA transfection of bone marrow mesenchymal stem cells using micro electroporation chips

    KAUST Repository

    Deng, Peigang; Chang, Donald C.; Lee, Yi Kuen; Zhou, Junwei; Li, Gang

    2011-01-01

    Experimental study of electroporation of bone marrow mesenchymal stem cells (MSCs) at the single-cell level was carried out on a micro EP chip by using single electric rectangular pulse. The threshold values of the electrode potential and pulse width for gas bubble generation on the micro electrodes due to electrolysis of water were revealed as 4.5 volt and 100 μs, respectively. Quantitative EP study was performed with various electric field strengths for various pulse widths, ranging from 20μs to 15ms. Over 1,000 single-cell EP results were used to construct an EP "phase diagram", which delineates the boundaries for (1) effective EP of MSCs and (2) electric cell lysis of MSCs. Finally, the micro EP chip showed successful transfection of the pEGFP-C1 plasmid into the MSCs by properly choosing the electric parameters from the EP "phase diagram". © 2011 IEEE.

  4. Electric field computation and measurements in the electroporation of inhomogeneous samples

    Science.gov (United States)

    Bernardis, Alessia; Bullo, Marco; Campana, Luca Giovanni; Di Barba, Paolo; Dughiero, Fabrizio; Forzan, Michele; Mognaschi, Maria Evelina; Sgarbossa, Paolo; Sieni, Elisabetta

    2017-12-01

    In clinical treatments of a class of tumors, e.g. skin tumors, the drug uptake of tumor tissue is helped by means of a pulsed electric field, which permeabilizes the cell membranes. This technique, which is called electroporation, exploits the conductivity of the tissues: however, the tumor tissue could be characterized by inhomogeneous areas, eventually causing a non-uniform distribution of current. In this paper, the authors propose a field model to predict the effect of tissue inhomogeneity, which can affect the current density distribution. In particular, finite-element simulations, considering non-linear conductivity against field relationship, are developed. Measurements on a set of samples subject to controlled inhomogeneity make it possible to assess the numerical model in view of identifying the equivalent resistance between pairs of electrodes.

  5. Clonal and Widespread Gene Transfer by Proviral Electroporation for Analysis of Brain Laminar Formation

    Science.gov (United States)

    Sugiyama, Sayaka; Nakamura, Harukazu

    An essential approach to understanding the mechanisms of development is to alter a gene function/expression. In vivo electroporation has been adapted as one such technique (Muramatsu et al., 1997). It is a very useful tool to achieve a gain- and loss-of-function (by using RNAi or morpholinos) of a gene of interest (Funahashi et al., 1999; Fukuchi-Shimogori and Grove, 2001; Kos et al., 2001; Katahira and Nakamura, 2003; Sugiyama and Nakamura, 2003). The technique has allowed the altering of gene expression temporally and spatially. Pulse-labeling technique is an approach to manipulate a specific cell population temporally, depending on its birthday, as this chapter describes. This technique is more advantageous over the BrdU application, as it can reveal cell lineage; it also has the ability to manipulate a gain- and loss-of-function into specific precursor cells (Tabata and Nakajima, 2001; Sugiyama and Nakamura, 2003; Huber et al., 2008).

  6. The second phase of bipolar, nanosecond-range electric pulses determines the electroporation efficiency.

    Science.gov (United States)

    Pakhomov, Andrei G; Grigoryev, Sergey; Semenov, Iurii; Casciola, Maura; Jiang, Chunqi; Xiao, Shu

    2018-03-29

    Bipolar cancellation refers to a phenomenon when applying a second electric pulse reduces ("cancels") cell membrane damage by a preceding electric pulse of the opposite polarity. Bipolar cancellation is a reason why bipolar nanosecond electric pulses (nsEP) cause weaker electroporation than just a single unipolar phase of the same pulse. This study was undertaken to explore the dependence of bipolar cancellation on nsEP parameters, with emphasis on the amplitude ratio of two opposite polarity phases of a bipolar pulse. Individual cells (CHO, U937, or adult mouse ventricular cardiomyocytes (VCM)) were exposed to either uni- or bipolar trapezoidal nsEP, or to nanosecond electric field oscillations (NEFO). The membrane injury was evaluated by time-lapse confocal imaging of the uptake of propidium (Pr) or YO-PRO-1 (YP) dyes and by phosphatidylserine (PS) externalization. Within studied limits, bipolar cancellation showed little or no dependence on the electric field intensity, pulse repetition rate, chosen endpoint, or cell type. However, cancellation could increase for larger pulse numbers and/or for longer pulses. The sole most critical parameter which determines bipolar cancellation was the phase ratio: maximum cancellation was observed with the 2nd phase of about 50% of the first one, whereas a larger 2nd phase could add a damaging effect of its own. "Swapping" the two phases, i.e., delivering the smaller phase before the larger one, reduced or eliminated cancellation. These findings are discussed in the context of hypothetical mechanisms of bipolar cancellation and electroporation by nsEP. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Cation selectivity of the plasma membrane of tobacco protoplasts in the electroporated state.

    Science.gov (United States)

    Wegner, Lars H

    2013-08-01

    Cation selectivity of the cellular membrane of tobacco culture cells (cell line 'bright yellow-2') exposed to pulsed electric fields in the millisecond range was investigated. The whole cell configuration of the patch clamp technique was established on protoplasts prepared from these cells. Ion selectivity of the electroporated membrane was investigated by measuring the reversal potential of currents passing through field-induced pores. To this end the membrane was hyper- or depolarized for 10ms (prepulse); subsequently the voltage was driven to opposite polarity at a constant rate (+40 or -40mV/ms, respectively). The experiment was started by polarizing the membrane to moderately negative or positive voltages (prepulse potential ±150mV) that would not induce pore formation. Subsequently, an extended voltage range was scanned in the porated state of the membrane (prepulse potential ±600mV). IV curves in the porated and the non-porated state (obtained at the same prepulse polarity) were superimposed to determine the voltage at which both curves intersected ('Intersection potential'). Using a modified version of the Goldmann-Hodgkin-Katz equation relative permeabilities to Ca(2+) and various monovalent alkali and organic cations were calculated. Pores were found to be fairly cation selective, with a selectivity sequence determined to be Ca(2+)>Li(+)>Rb(+)≈K(+)≈Na(+)>TEA(+)≈TBA(+)>Cl(-). Relative permeability to monovalent cations was inversely related to the ionic diameter. By fitting a formalism suggested by Dwyer at al. (J. Gen. Physiol. 75 (1980), 469-492) the effective average diameter of field induced pores was estimated to be about 1.8nm. Implications of these results for biotechnology and electroporation theory are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Irreversible electroporation of locally advanced solid pseudopapillary carcinoma of the pancreas: A case report

    Directory of Open Access Journals (Sweden)

    Luciano Tarantino

    2018-04-01

    Full Text Available Introduction: Solid pseudopapillary Carcinoma (SPC is a rare pancreatic Tumor with variable, usually low, malignancy potential. Howewer, several SPC are associated with aggressive behavior, local vascular infiltration, organ invasion, distant metastasis, and can be unresectable. Irreversible Electroporation (IRE is an emerging non-thermal ablation technique for the treatment of locally advanced pancreatic carcinoma. We report the results of four year disease-free follow-up in a case of locally advanced unresectable SPC treated with IRE. Presentation of case: A 24-year female patient with SPC of the pancreas underwent IRE during laparotomy under general anesthesia with intubation. Computed Tomography (CT showed complete tumor thrombosis of splenic vein, encasement of celiac artery and mesenteric vein. Six insertions of 3–4 electrodes per insertion were performed. One month-CT-control showed shrinkage of the tumor. 6 months-post-treatment imaging showed complete regression of the mass, patent Splenic/mesenteric veins, absence of local recurrence or distant metastasis. Post treatment CTs at 12-18-24-30-36-42-48 months follow-up confirmed absence of local or distant recurrence. Discussion: Surgery is the first choice curative treatment of SPC. Howewer aggressive surgery (duodeno-pancreasectomy in unresectable cases, may have a high risk of recurrences, morbidities and death, and bring concerns about endocrine and exocrine insufficiency in a young patient. In these cases, IRE could be a safe and effective alternative treatment and could realize, in selected cases, the condition for a radical surgery, and a bridge to R-0 resection. Conclusions: IRE could represent an effective alternative therapy to surgery in local advanced, unresectable SPC. Keywords: Pancreatic neoplasm, Solid papillary carcinoma, Intraoperative ultrasound, Irreversible electroporation, Case report

  9. Optimisation of Investment Resources at Small Enterprises

    Directory of Open Access Journals (Sweden)

    Shvets Iryna B.

    2014-03-01

    Full Text Available The goal of the article lies in the study of the process of optimisation of the structure of investment resources, development of criteria and stages of optimisation of volumes of investment resources for small enterprises by types of economic activity. The article characterises the process of transformation of investment resources into assets and liabilities of the balances of small enterprises and conducts calculation of the structure of sources of formation of investment resources in Ukraine at small enterprises by types of economic activity in 2011. On the basis of the conducted analysis of the structure of investment resources of small enterprises the article forms main groups of criteria of optimisation in the context of individual small enterprises by types of economic activity. The article offers an algorithm and step-by-step scheme of optimisation of investment resources at small enterprises in the form of a multi-stage process of management of investment resources in the context of increase of their mobility and rate of transformation of existing resources into investments. The prospect of further studies in this direction is development of a structural and logic scheme of optimisation of volumes of investment resources at small enterprises.

  10. Multicriteria Optimisation in Logistics Forwarder Activities

    Directory of Open Access Journals (Sweden)

    Tanja Poletan Jugović

    2007-05-01

    Full Text Available Logistics forwarder, as organizer and planner of coordinationand integration of all the transport and logistics chains elements,uses adequate ways and methods in the process of planningand decision-making. One of these methods, analysed inthis paper, which could be used in optimisation of transportand logistics processes and activities of logistics forwarder, isthe multicriteria optimisation method. Using that method, inthis paper is suggested model of multicriteria optimisation of logisticsforwarder activities. The suggested model of optimisationis justified in keeping with method principles of multicriteriaoptimization, which is included in operation researchmethods and it represents the process of multicriteria optimizationof variants. Among many different processes of multicriteriaoptimization, PROMETHEE (Preference Ranking OrganizationMethod for Enrichment Evaluations and Promcalc& Gaia V. 3.2., computer program of multicriteria programming,which is based on the mentioned process, were used.

  11. Noise aspects at aerodynamic blade optimisation projects

    International Nuclear Information System (INIS)

    Schepers, J.G.

    1997-06-01

    The Netherlands Energy Research Foundation (ECN) has often been involved in industrial projects, in which blade geometries are created automatic by means of numerical optimisation. Usually, these projects aim at the determination of the aerodynamic optimal wind turbine blade, i.e. the goal is to design a blade which is optimal with regard to energy yield. In other cases, blades have been designed which are optimal with regard to cost of generated energy. However, it is obvious that the wind turbine blade designs which result from these optimisations, are not necessarily optimal with regard to noise emission. In this paper an example is shown of an aerodynamic blade optimisation, using the ECN-program PVOPT. PVOPT calculates the optimal wind turbine blade geometry such that the maximum energy yield is obtained. Using the aerodynamic optimal blade design as a basis, the possibilities of noise reduction are investigated. 11 figs., 8 refs

  12. In Vivo Production of Monoclonal Antibodies by Gene Transfer via Electroporation Protects against Lethal Influenza and Ebola Infections

    Directory of Open Access Journals (Sweden)

    Chasity D. Andrews

    2017-12-01

    Full Text Available Monoclonal antibodies (mAbs have wide clinical utility, but global access is limited by high costs and impracticalities associated with repeated passive administration. Here, we describe an optimized electroporation-based DNA gene transfer platform technology that can be utilized for production of functional mAbs in vivo, with the potential to reduce costs and administration burdens. We demonstrate that multiple mAbs can be simultaneously expressed at protective concentrations for a protracted period of time using DNA doses and electroporation conditions that are feasible clinically. The expressed mAbs could also protect mice against lethal influenza or Ebola virus challenges. Our findings suggest that this DNA gene transfer platform technology could be a game-changing advance that expands access to effective mAb therapeutics globally.

  13. Preliminary study of steep pulse irreversible electroporation technology in human large cell lung cancer cell lines L9981

    Directory of Open Access Journals (Sweden)

    Song Zuoqing

    2013-01-01

    Full Text Available Our aim was to validate the effectiveness of steep pulse irreversible electroporation technology in human large cell lung cancer cells and to screen the optimal treatment of parameters for human large cell lung cancer cells. Three different sets of steep pulse therapy parameters were applied on the lung cancer cell line L9981. The cell line L9981 inhibition rate and proliferation capacity were detected by Vi-Cell vitality analysis and MTT. Steep pulsed irreversible electroporation technology for large cell lung cancer L9981 presents killing effects with various therapy parameters. The optimal treatment parameters are at a voltage amplitude of 2000V/cm, pulse width of 100μs, pulse frequency of 1 Hz, pulse number 10. With this group of parameters, steep pulse could have the best tumor cell-killing effects.

  14. Topology Optimisation of Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Thike Aye Min

    2016-01-01

    Full Text Available Wireless sensor networks are widely used in a variety of fields including industrial environments. In case of a clustered network the location of cluster head affects the reliability of the network operation. Finding of the optimum location of the cluster head, therefore, is critical for the design of a network. This paper discusses the optimisation approach, based on the brute force algorithm, in the context of topology optimisation of a cluster structure centralised wireless sensor network. Two examples are given to verify the approach that demonstrate the implementation of the brute force algorithm to find an optimum location of the cluster head.

  15. A review of electroporation-based antitumor skin therapies and investigation of betulinic acid-loaded ointment.

    Science.gov (United States)

    Bakonyi, Monika; Berko, Szilvia; Eros, Gabor; Varju, Gabor; Dehelean, Cristina; Szucs, Maria Budai; Csanyi, Erzsebet

    2017-11-13

    Electrochemotherapy is a novel treatment for cutaneous and subcutaneous tumors utilizing the combination of electroporation and chemotherapeutic agents. Since tumors have an increasing incidence nowadays as a result of environmental and genetic factors, electrochemotherapy could be a promising treatment for cancer patients. The aim of this article is to summarize the novel knowledge about the use of electroporation for antitumor treatments and to present a new application of electrochemotherapy with a well-known plant derived antitumor drug betulinic acid. For the review we have searched the databases of scientific and medical research to collect the available publications about the use of electrochemotherapy in the treatment of various types of cancer. By the utilization of the available knowledge, we investigated the effect of electroporation on the penetration of a topically applied betulinic acid formulation into the skin by ex vivo Raman spectroscopy on hairless mouse skin Results: Raman measurements have demonstrated that the penetration depth of betulinic acid can be remarkably ameliorated by the use of electroporation, so this protocol can be a possibility for the treatment of deeper localized cancer nodules. Furthermore, it proved the influence of various treatment times, since they caused different spatial distributions of the drug in the skin. The review demonstrates that electrochemotherapy is a promising tool to treat different kinds of tumors with high efficiency and with only a few moderate adverse effects. Moreover, it presents a non-invasive method to enhance the penetration of antitumor agents, which can offer novel prospects for antitumor therapies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Careful treatment planning enables safe ablation of liver tumors adjacent to major blood vessels by percutaneous irreversible electroporation (IRE).

    Science.gov (United States)

    Kos, Bor; Voigt, Peter; Miklavcic, Damijan; Moche, Michael

    2015-09-01

    Irreversible electroporation (IRE) is a tissue ablation method, which relies on the phenomenon of electroporation. When cells are exposed to a sufficiently electric field, the plasma membrane is disrupted and cells undergo an apoptotic or necrotic cell death. Although heating effects are known IRE is considered as non-thermal ablation technique and is currently applied to treat tumors in locations where thermal ablation techniques are contraindicated. The manufacturer of the only commercially available pulse generator for IRE recommends a voltage-to-distance ratio of 1500 to 1700 V/cm for treating tumors in the liver. However, major blood vessels can influence the electric field distribution. We present a method for treatment planning of IRE which takes the influence of blood vessels on the electric field into account; this is illustrated on a treatment of 48-year-old patient with a metastasis near the remaining hepatic vein after a right side hemi-hepatectomy. Output of the numerical treatment planning method shows that a 19.9 cm3 irreversible electroporation lesion was generated and the whole tumor was covered with at least 900 V/cm. This compares well with the volume of the hypodense lesion seen in contrast enhanced CT images taken after the IRE treatment. A significant temperature raise occurs near the electrodes. However, the hepatic vein remains open after the treatment without evidence of tumor recurrence after 6 months. Treatment planning using accurate computer models was recognized as important for electrochemotherapy and irreversible electroporation. An important finding of this study was, that the surface of the electrodes heat up significantly. Therefore the clinical user should generally avoid placing the electrodes less than 4 mm away from risk structures when following recommendations of the manufacturer.

  17. Electroporation increases antitumoral efficacy of the bcl-2 antisense G3139 and chemotherapy in a human melanoma xenograft

    Directory of Open Access Journals (Sweden)

    Baldi Alfonso

    2011-07-01

    Full Text Available Abstract Background Nucleic acids designed to modulate the expression of target proteins remain a promising therapeutic strategy in several diseases, including cancer. However, clinical success is limited by the lack of efficient intracellular delivery. In this study we evaluated whether electroporation could increase the delivery of antisense oligodeoxynucleotides against bcl-2 (G3139 as well as the efficacy of combination chemotherapy in human melanoma xenografts. Methods Melanoma-bearing nude mice were treated i.v. with G3139 and/or cisplatin (DDP followed by the application of trains of electric pulses to tumors. Western blot, immunohistochemistry and real-time PCR were performed to analyze protein and mRNA expression. The effect of electroporation on muscles was determined by histology, while tumor apoptosis and the proliferation index were analyzed by immunohistochemistry. Antisense oligodeoxynucleotides tumor accumulation was measured by FACS and confocal microscopy. Results The G3139/Electroporation combined therapy produced a significant inhibition of tumor growth (TWI, more than 50% accompanied by a marked tumor re-growth delay (TRD, about 20 days. The efficacy of this treatment was due to the higher G3139 uptake in tumor cells which led to a marked down-regulation of bcl-2 protein expression. Moreover, the G3139/EP combination treatment resulted in an enhanced apoptotic index and a decreased proliferation rate of tumors. Finally, an increased tumor response was observed after treatment with the triple combination G3139/DDP/EP, showing a TWI of about 75% and TRD of 30 days. Conclusions These results demonstrate that electroporation is an effective strategy to improve the delivery of antisense oligodeoxynucleotides within tumor cells in vivo and it may be instrumental in optimizing the response of melanoma to chemotherapy. The high response rate observed in this study suggest to apply this strategy for the treatment of melanoma patients.

  18. Single cell electroporation for longitudinal imaging of synaptic structure and function in the adult mouse neocortex in vivo

    Directory of Open Access Journals (Sweden)

    Stephane ePages

    2015-04-01

    Full Text Available Longitudinal imaging studies of neuronal structures in vivo have revealed rich dynamics in dendritic spines and axonal boutons. Spines and boutons are considered to be proxies for synapses. This implies that synapses display similar dynamics. However, spines and boutons do not always bear synapses, some may contain more than one, and dendritic shaft synapses have no clear structural proxies. In addition, synaptic strength is not always accurately revealed by just the size of these structures. Structural and functional dynamics of synapses could be studied more reliably using fluorescent synaptic proteins as markers for size and function. These proteins are often large and possibly interfere with circuit development, which renders them less suitable for conventional transfection or transgenesis methods such as viral vectors, in utero electroporation and germline transgenesis. Single cell electroporation has been shown to be a potential alternative for transfection of recombinant fluorescent proteins in adult cortical neurons. Here we provide proof of principle for the use of single cell electroporation to express and subsequently image fluorescently tagged synaptic proteins over days to weeks in vivo.

  19. Application of Surpac and Whittle Software in Open Pit Optimisation ...

    African Journals Online (AJOL)

    Application of Surpac and Whittle Software in Open Pit Optimisation and Design. ... This paper studies the Surpac and Whittle software and their application in designing an optimised pit. ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  20. (MBO) algorithm in multi-reservoir system optimisation

    African Journals Online (AJOL)

    A comparative study of marriage in honey bees optimisation (MBO) algorithm in ... A practical application of the marriage in honey bees optimisation (MBO) ... to those of other evolutionary algorithms, such as the genetic algorithm (GA), ant ...

  1. Extending Particle Swarm Optimisers with Self-Organized Criticality

    DEFF Research Database (Denmark)

    Løvbjerg, Morten; Krink, Thiemo

    2002-01-01

    Particle swarm optimisers (PSOs) show potential in function optimisation, but still have room for improvement. Self-organized criticality (SOC) can help control the PSO and add diversity. Extending the PSO with SOC seems promising reaching faster convergence and better solutions.......Particle swarm optimisers (PSOs) show potential in function optimisation, but still have room for improvement. Self-organized criticality (SOC) can help control the PSO and add diversity. Extending the PSO with SOC seems promising reaching faster convergence and better solutions....

  2. Operational Radiological Protection and Aspects of Optimisation

    International Nuclear Information System (INIS)

    Lazo, E.; Lindvall, C.G.

    2005-01-01

    Since 1992, the Nuclear Energy Agency (NEA), along with the International Atomic Energy Agency (IAEA), has sponsored the Information System on Occupational Exposure (ISOE). ISOE collects and analyses occupational exposure data and experience from over 400 nuclear power plants around the world and is a forum for radiological protection experts from both nuclear power plants and regulatory authorities to share lessons learned and best practices in the management of worker radiation exposures. In connection to the ongoing work of the International Commission on Radiological Protection (ICRP) to develop new recommendations, the ISOE programme has been interested in how the new recommendations would affect operational radiological protection application at nuclear power plants. Bearing in mind that the ICRP is developing, in addition to new general recommendations, a new recommendation specifically on optimisation, the ISOE programme created a working group to study the operational aspects of optimisation, and to identify the key factors in optimisation that could usefully be reflected in ICRP recommendations. In addition, the Group identified areas where further ICRP clarification and guidance would be of assistance to practitioners, both at the plant and the regulatory authority. The specific objective of this ISOE work was to provide operational radiological protection input, based on practical experience, to the development of new ICRP recommendations, particularly in the area of optimisation. This will help assure that new recommendations will best serve the needs of those implementing radiation protection standards, for the public and for workers, at both national and international levels. (author)

  3. Optimisation of surgical care for rectal cancer

    NARCIS (Netherlands)

    Borstlap, W.A.A.

    2017-01-01

    Optimisation of surgical care means weighing the risk of treatment related morbidity against the patients’ potential benefits of a surgical intervention. The first part of this thesis focusses on the anaemic patient undergoing colorectal surgery. Hypothesizing that a more profound haemoglobin

  4. On optimal development and becoming an optimiser

    NARCIS (Netherlands)

    de Ruyter, D.J.

    2012-01-01

    The article aims to provide a justification for the claim that optimal development and becoming an optimiser are educational ideals that parents should pursue in raising their children. Optimal development is conceptualised as enabling children to grow into flourishing persons, that is persons who

  5. Particle Swarm Optimisation with Spatial Particle Extension

    DEFF Research Database (Denmark)

    Krink, Thiemo; Vesterstrøm, Jakob Svaneborg; Riget, Jacques

    2002-01-01

    In this paper, we introduce spatial extension to particles in the PSO model in order to overcome premature convergence in iterative optimisation. The standard PSO and the new model (SEPSO) are compared w.r.t. performance on well-studied benchmark problems. We show that the SEPSO indeed managed...

  6. OPTIMISATION OF COMPRESSIVE STRENGTH OF PERIWINKLE ...

    African Journals Online (AJOL)

    In this paper, a regression model is developed to predict and optimise the compressive strength of periwinkle shell aggregate concrete using Scheffe's regression theory. The results obtained from the derived regression model agreed favourably with the experimental data. The model was tested for adequacy using a student ...

  7. An efficient optimisation method in groundwater resource ...

    African Journals Online (AJOL)

    DRINIE

    2003-10-04

    Oct 4, 2003 ... theories developed in the field of stochastic subsurface hydrology. In reality, many ... Recently, some researchers have applied the multi-stage ... Then a robust solution of the optimisation problem given by Eqs. (1) to (3) is as ...

  8. Water distribution systems design optimisation using metaheuristics ...

    African Journals Online (AJOL)

    The topic of multi-objective water distribution systems (WDS) design optimisation using metaheuristics is investigated, comparing numerous modern metaheuristics, including several multi-objective evolutionary algorithms, an estimation of distribution algorithm and a recent hyperheuristic named AMALGAM (an evolutionary ...

  9. Optimisation of efficiency of axial fans

    NARCIS (Netherlands)

    Kruyt, Nicolaas P.; Pennings, P.C.; Faasen, R.

    2014-01-01

    A three-stage research project has been executed to develop ducted axial-fans with increased efficiency. In the first stage a design method has been developed in which various conflicting design criteria can be incorporated. Based on this design method, an optimised design has been determined

  10. Thermodynamic optimisation of a heat exchanger

    NARCIS (Netherlands)

    Cornelissen, Rene; Hirs, Gerard

    1999-01-01

    The objective of this paper is to show that for the optimal design of an energy system, where there is a trade-off between exergy saving during operation and exergy use during construction of the energy system, exergy analysis and life cycle analysis should be combined. An exergy optimisation of a

  11. Self-optimising control of sewer systems

    DEFF Research Database (Denmark)

    Mauricio Iglesias, Miguel; Montero-Castro, Ignacio; Mollerup, Ane Loft

    2013-01-01

    . The definition of an optimal performance was carried out by through a two-stage optimisation (stochastic and deterministic) to take into account both the overflow during the current rain event as well as the expected overflow, given the probability of a future rain event. The methodology is successfully applied...

  12. High-frequency irreversible electroporation (H-FIRE for non-thermal ablation without muscle contraction

    Directory of Open Access Journals (Sweden)

    Arena Christopher B

    2011-11-01

    Full Text Available Abstract Background Therapeutic irreversible electroporation (IRE is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death. Methods A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE. A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for in vivo treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for in vivo experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation. Results No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain. Conclusions H-FIRE is a feasible technique for

  13. Optimising Shovel-Truck Fuel Consumption using Stochastic ...

    African Journals Online (AJOL)

    Optimising the fuel consumption and truck waiting time can result in significant fuel savings. The paper demonstrates that stochastic simulation is an effective tool for optimising the utilisation of fossil-based fuels in mining and related industries. Keywords: Stochastic, Simulation Modelling, Mining, Optimisation, Shovel-Truck ...

  14. Design of optimised backstepping controller for the synchronisation ...

    Indian Academy of Sciences (India)

    Ehsan Fouladi

    2017-12-18

    Dec 18, 2017 ... for the proposed optimised method compared to PSO optimised controller or any non-optimised backstepping controller. Keywords. Colpitts oscillator; backstepping controller; chaos synchronisation; shark smell algorithm; particle .... The velocity model is based on the gradient of the objective function, tilting ...

  15. Efficient topology optimisation of multiscale and multiphysics problems

    DEFF Research Database (Denmark)

    Alexandersen, Joe

    The aim of this Thesis is to present efficient methods for optimising high-resolution problems of a multiscale and multiphysics nature. The Thesis consists of two parts: one treating topology optimisation of microstructural details and the other treating topology optimisation of conjugate heat...

  16. Ex vivo electroporation of retinal cells: a novel, high efficiency method for functional studies in primary retinal cultures.

    Science.gov (United States)

    Vergara, M Natalia; Gutierrez, Christian; O'Brien, David R; Canto-Soler, M Valeria

    2013-04-01

    Primary retinal cultures constitute valuable tools not only for basic research on retinal cell development and physiology, but also for the identification of factors or drugs that promote cell survival and differentiation. In order to take full advantage of the benefits of this system it is imperative to develop efficient and reliable techniques for the manipulation of gene expression. However, achieving appropriate transfection efficiencies in these cultures has remained challenging. The purpose of this work was to develop and optimize a technique that would allow the transfection of chick retinal cells with high efficiency and reproducibility for multiple applications. We developed an ex vivo electroporation method applied to dissociated retinal cell cultures that offers a significant improvement over other currently available transfection techniques, increasing efficiency by five-fold. In this method, eyes were enucleated, devoid of RPE, and electroporated with GFP-encoding plasmids using custom-made electrodes. Electroporated retinas were then dissociated into single cells and plated in low density conditions, to be analyzed after 4 days of incubation. Parameters such as voltage and number of electric pulses, as well as plasmid concentration and developmental stage of the animal were optimized for efficiency. The characteristics of the cultures were assessed by morphology and immunocytochemistry, and cell viability was determined by ethidium homodimer staining. Cell imaging and counting was performed using an automated high-throughput system. This procedure resulted in transfection efficiencies in the order of 22-25% of cultured cells, encompassing both photoreceptors and non-photoreceptor neurons, and without affecting normal cell survival and differentiation. Finally, the feasibility of the technique for cell-autonomous studies of gene function in a biologically relevant context was tested by carrying out gain and loss-of-function experiments for the

  17. Electroporation of micro-droplet encapsulated HeLa cells in oil phase

    KAUST Repository

    Xiao, Kang

    2010-08-27

    Electroporation (EP) is a method widely used to introduce foreign genes, drugs or dyes into cells by permeabilizing the plasma membrane with an external electric field. A variety of microfluidic EP devices have been reported so far. However, further integration of prior and posterior EP processes turns out to be very complicated, mainly due to the difficulty of developing an efficient method for precise manipulation of cells in microfluidics. In this study, by means of a T-junction structure within a delicate microfluidic device, we encapsulated HeLa cells in micro-droplet of poration medium in oil phase before EP, which has two advantages: (i) precise control of cell-encapsulating droplets in oil phase is much easier than the control of cell populations or individuals in aqueous buffers; (ii) this can minimize the electrochemical reactions on the electrodes. Finally, we successfully introduced fluorescent dyes into the micro-droplet encapsulated HeLa cells in oil phase. Our results reflected a novel way to realize the integrated biomicrofluidic system for EP. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

  18. Electrokinetic transport of nanoparticles to opening of nanopores on cell membrane during electroporation

    Energy Technology Data Exchange (ETDEWEB)

    Movahed, Saeid [University of Toronto, Department of Chemistry (Canada); Li Dongqing, E-mail: dongqing@mme.uwaterloo.ca [University of Waterloo, Department of Mechanical and Mechatronics Engineering (Canada)

    2013-04-15

    Nanoparticle transport to the opening of the single nanopore created on the cell membrane during the electroporation is studied. First, the permeabilization of a single cell located in a microchannel is investigated. When the nanopores are created, the transport of the nanoparticles from the surrounding liquid to the opening of one of the created nanopores is examined. It was found that the negatively charged nanoparticles preferably move into the nanopores from the side of the cell membrane that faces the negative electrode. Opposite to the electro-osmotic flow effect, the electrophoretic force tends to draw the negatively charged nanoparticles into the opening of the nanopores. The effect of the Brownian force is negligible in comparison with the electro-osmosis and the electrophoresis. Smaller nanoparticles with stronger surface charge transport more easily to the opening of the nanopores. Positively charged nanoparticles preferably enter the nanopores from the side of the cell membrane that faces the positive electrode. On this side, both the electrophoretic and the electro-osmotic forces are in the same directions and contribute to bring the positively charged particles into the nanopores.

  19. Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ

    Directory of Open Access Journals (Sweden)

    Kaustuv Banerjee

    2013-08-01

    Full Text Available Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA, and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA.

  20. Electroporation of micro-droplet encapsulated HeLa cells in oil phase

    KAUST Repository

    Xiao, Kang; Zhang, Mengying; Chen, Shuyu; Wang, Limu; Chang, Donald Choy; Wen, Weijia

    2010-01-01

    Electroporation (EP) is a method widely used to introduce foreign genes, drugs or dyes into cells by permeabilizing the plasma membrane with an external electric field. A variety of microfluidic EP devices have been reported so far. However, further integration of prior and posterior EP processes turns out to be very complicated, mainly due to the difficulty of developing an efficient method for precise manipulation of cells in microfluidics. In this study, by means of a T-junction structure within a delicate microfluidic device, we encapsulated HeLa cells in micro-droplet of poration medium in oil phase before EP, which has two advantages: (i) precise control of cell-encapsulating droplets in oil phase is much easier than the control of cell populations or individuals in aqueous buffers; (ii) this can minimize the electrochemical reactions on the electrodes. Finally, we successfully introduced fluorescent dyes into the micro-droplet encapsulated HeLa cells in oil phase. Our results reflected a novel way to realize the integrated biomicrofluidic system for EP. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

  1. Local Control of Perivascular Malignant Liver Lesions Using Percutaneous Irreversible Electroporation: Initial Experiences

    Energy Technology Data Exchange (ETDEWEB)

    Eller, Achim, E-mail: Achim.Eller@uk-erlangen.de; Schmid, Axel, E-mail: axel.schmid@uk-erlangen.de [University Hospital Erlangen, University of Erlangen-Nuremberg, Department of Radiology (Germany); Schmidt, Joachim, E-mail: joachim.schmidt@kfa.imed.uni-erlangen.de [University Hospital Erlangen, University of Erlangen-Nuremberg, Department of Anesthesiology (Germany); May, Matthias, E-mail: matthias.may@uk-erlangen.de; Brand, Michael, E-mail: michael.brand@uk-erlangen.de; Saake, Marc, E-mail: marc.saake@uk-erlangen.de; Uder, Michael, E-mail: michael.uder@uk-erlangen.de; Lell, Michael, E-mail: michael.lell@uk-erlangen.de [University Hospital Erlangen, University of Erlangen-Nuremberg, Department of Radiology (Germany)

    2015-02-15

    PurposeThis study was designed to assess efficacy and safety in the treatment of perivascular malignant liver lesions using percutaneous, computed tomography (CT)-guided irreversible electroporation (IRE).MethodsFourteen patients (mean age 58 ± 11 years) with 18 malignant liver lesions were consecutively enrolled in this study. IRE was performed in patients not eligible for surgery and lesions abutting large vessels or bile ducts. Follow-up exams were performed using multislice-CT (MS-CT) or MRI.ResultsMedium lesion diameter was 20 ± 5 mm. Ten of 14 (71 %) were successfully treated with no local recurrence to date (mean follow-up 388 ± 160 days). One case left initial tumor control unclear and additional RFA was performed 4 weeks after IRE. Complications occurred in 4 of 14 (29 %) cases. In one case, intervention was terminated and abdominal bleeding required laparotomy. In two cases, a postinterventional hematothorax required intervention. In another case, abdominal bleeding could be managed conservatively. No complications related to the bile ducts occurred.ConclusionsPercutaneous IRE seems to be effective in perivascular lesions but is associated with a higher complication rate compared with thermoablative techniques.

  2. Electroporation and use of hepatitis B virus envelope L proteins as bionanocapsules.

    Science.gov (United States)

    Yamada, Tadanori; Jung, Joohee; Seno, Masaharu; Kondo, Akihiko; Ueda, Masakazu; Tanizawa, Katsuyuki; Kuroda, Shun'ichi

    2012-06-01

    Hepatitis B virus (HBV) envelope L proteins, when synthesized in yeast cells, form a hollow bionanocapsule (BNC) in which genes (including large plasmids up to 40 kbp), small interfering RNA (siRNA), drugs, and proteins can be enclosed by electroporation. BNCs made from L proteins have several advantages as a delivery system: Because they display a human liver-specific receptor (the pre-S region of the L protein) on their surface, BNCs can efficiently and specifically deliver their contents to human liver-derived cells and tissues ex vivo (in cell culture) and in vivo (in a mouse xenograft model). Retargeting can be achieved simply by substituting other biorecognition molecules such as antibodies, ligands, receptors, and homing peptides for the pre-S region. In addition, BNCs have already been proven to be safe for use in humans during their development as an immunogen of hepatitis B vaccine. This protocol describes the loading of BNCs and their use in cell culture and in vivo.

  3. Irreversible electroporation of the pancreas is feasible and safe in a porcine survival model.

    Science.gov (United States)

    Fritz, Stefan; Sommer, Christof M; Vollherbst, Dominik; Wachter, Miguel F; Longerich, Thomas; Sachsenmeier, Milena; Knapp, Jürgen; Radeleff, Boris A; Werner, Jens

    2015-07-01

    Use of thermal tumor ablation in the pancreatic parenchyma is limited because of the risk of pancreatitis, pancreatic fistula, or hemorrhage. This study aimed to evaluate the feasibility and safety of irreversible electroporation (IRE) in a porcine model. Ten pigs were divided into 2 study groups. In the first group, animals received IRE of the pancreatic tail and were killed after 60 minutes. In the second group, animals received IRE at the head of the pancreas and were followed up for 7 days. Clinical parameters, computed tomography imaging, laboratory results, and histology were obtained. All animals survived IRE ablation, and no cardiac adverse effects were noted. Sixty minutes after IRE, a hypodense lesion on computed tomography imaging indicated the ablation zone. None of the animals developed clinical signs of acute pancreatitis. Only small amounts of ascites fluid, with a transient increase in amylase and lipase levels, were observed, indicating that no pancreatic fistula occurred. This porcine model shows that IRE is feasible and safe in the pancreatic parenchyma. Computed tomography imaging reveals significant changes at 60 minutes after IRE and therefore might serve as an early indicator of therapeutic success. Clinical studies are needed to evaluate the efficacy of IRE in pancreatic cancer.

  4. Real-time optimisation of the Hoa Binh reservoir, Vietnam

    DEFF Research Database (Denmark)

    Richaud, Bertrand; Madsen, Henrik; Rosbjerg, Dan

    2011-01-01

    -time optimisation. First, the simulation-optimisation framework is applied for optimising reservoir operating rules. Secondly, real-time and forecast information is used for on-line optimisation that focuses on short-term goals, such as flood control or hydropower generation, without compromising the deviation...... in the downstream part of the Red River, and at the same time to increase hydropower generation and to save water for the dry season. The real-time optimisation procedure further improves the efficiency of the reservoir operation and enhances the flexibility for the decision-making. Finally, the quality......Multi-purpose reservoirs often have to be managed according to conflicting objectives, which requires efficient tools for trading-off the objectives. This paper proposes a multi-objective simulation-optimisation approach that couples off-line rule curve optimisation with on-line real...

  5. Acoustic Resonator Optimisation for Airborne Particle Manipulation

    Science.gov (United States)

    Devendran, Citsabehsan; Billson, Duncan R.; Hutchins, David A.; Alan, Tuncay; Neild, Adrian

    Advances in micro-electromechanical systems (MEMS) technology and biomedical research necessitate micro-machined manipulators to capture, handle and position delicate micron-sized particles. To this end, a parallel plate acoustic resonator system has been investigated for the purposes of manipulation and entrapment of micron sized particles in air. Numerical and finite element modelling was performed to optimise the design of the layered acoustic resonator. To obtain an optimised resonator design, careful considerations of the effect of thickness and material properties are required. Furthermore, the effect of acoustic attenuation which is dependent on frequency is also considered within this study, leading to an optimum operational frequency range. Finally, experimental results demonstrated good particle levitation and capture of various particle properties and sizes ranging to as small as 14.8 μm.

  6. Techno-economic optimisation of energy systems

    International Nuclear Information System (INIS)

    Mansilla Pellen, Ch.

    2006-07-01

    The traditional approach currently used to assess the economic interest of energy systems is based on a defined flow-sheet. Some studies have shown that the flow-sheets corresponding to the best thermodynamic efficiencies do not necessarily lead to the best production costs. A method called techno-economic optimisation was proposed. This method aims at minimising the production cost of a given energy system, including both investment and operating costs. It was implemented using genetic algorithms. This approach was compared to the heat integration method on two different examples, thus validating its interest. Techno-economic optimisation was then applied to different energy systems dealing with hydrogen as well as electricity production. (author)

  7. Pre-operative optimisation of lung function

    Directory of Open Access Journals (Sweden)

    Naheed Azhar

    2015-01-01

    Full Text Available The anaesthetic management of patients with pre-existing pulmonary disease is a challenging task. It is associated with increased morbidity in the form of post-operative pulmonary complications. Pre-operative optimisation of lung function helps in reducing these complications. Patients are advised to stop smoking for a period of 4–6 weeks. This reduces airway reactivity, improves mucociliary function and decreases carboxy-haemoglobin. The widely used incentive spirometry may be useful only when combined with other respiratory muscle exercises. Volume-based inspiratory devices have the best results. Pharmacotherapy of asthma and chronic obstructive pulmonary disease must be optimised before considering the patient for elective surgery. Beta 2 agonists, inhaled corticosteroids and systemic corticosteroids, are the main drugs used for this and several drugs play an adjunctive role in medical therapy. A graded approach has been suggested to manage these patients for elective surgery with an aim to achieve optimal pulmonary function.

  8. Electrical pulse – mediated enhanced delivery of silver nanoparticles into living suspension cells for surface enhanced Raman spectroscopy

    International Nuclear Information System (INIS)

    Lin, J; Li, B; Feng, S; Chen, G; Li, Y; Huang, Z; Chen, R; Yu, Y; Huang, H; Lin, S; Li, C; Su, Y; Zeng, H

    2012-01-01

    Electrical pulse-mediated enhanced silver nanoparticles delivery is a much better method for intracellular surface-enhanced Raman spectroscopy (SERS) measurements of suspension cells. Robust and high-quality SERS spectra of living suspension cells were obtained based on an electroporation-SERS method, which can overcomes the shortcoming of non-uniform distribution of silver nanoparticles localized in the cell cytoplasm after electroporation and reduces the amount variance of silver nanoparticles delivered into different cells. The electroporation parameters include three 150 V (375 V/cm) electric pulses of 1, 5, and 5 ms durations respectively. Our results indicate that considerable amount of silver nanoparticles can be rapidly delivered into the human promyelocytic leukemia HL60 cells, and the satisfied SERS spectra were obtained while the viability of the treated cells was highly maintained (91.7%). The electroporation-SERS method offers great potential approach in delivering silver nanoparticles into living suspension cells, which is useful for widely biomedical applications including the real-time intracellular SERS analysis of living cells

  9. Optimised dipper fine tunes shovel performance

    Energy Technology Data Exchange (ETDEWEB)

    Fiscor, S.

    2005-06-01

    Joint efforts between mine operators, OEMs, and researchers yields unexpected benefits from dippers for shovels for coal, oil, or hardrock mining that can now be tailored to meet site-specific conditions. The article outlines a process being developed by CRCMining and P & H MIning Equipment to optimise the dipper that involves rapid prototyping and scale modelling of the dipper and the mine conditions. Scale models have been successfully field tested. 2 photos.

  10. Public transport optimisation emphasising passengers’ travel behaviour.

    OpenAIRE

    Jensen, Jens Parbo; Nielsen, Otto Anker; Prato, Carlo Giacomo

    2015-01-01

    Passengers in public transport complaining about their travel experiences are not uncommon. This might seem counterintuitive since several operators worldwide are presenting better key performance indicators year by year. The present PhD study focuses on developing optimisation algorithms to enhance the operations of public transport while explicitly emphasising passengers’ travel behaviour and preferences. Similar to economic theory, interactions between supply and demand are omnipresent in ...

  11. ATLAS software configuration and build tool optimisation

    Science.gov (United States)

    Rybkin, Grigory; Atlas Collaboration

    2014-06-01

    ATLAS software code base is over 6 million lines organised in about 2000 packages. It makes use of some 100 external software packages, is developed by more than 400 developers and used by more than 2500 physicists from over 200 universities and laboratories in 6 continents. To meet the challenge of configuration and building of this software, the Configuration Management Tool (CMT) is used. CMT expects each package to describe its build targets, build and environment setup parameters, dependencies on other packages in a text file called requirements, and each project (group of packages) to describe its policies and dependencies on other projects in a text project file. Based on the effective set of configuration parameters read from the requirements files of dependent packages and project files, CMT commands build the packages, generate the environment for their use, or query the packages. The main focus was on build time performance that was optimised within several approaches: reduction of the number of reads of requirements files that are now read once per package by a CMT build command that generates cached requirements files for subsequent CMT build commands; introduction of more fine-grained build parallelism at package task level, i.e., dependent applications and libraries are compiled in parallel; code optimisation of CMT commands used for build; introduction of package level build parallelism, i. e., parallelise the build of independent packages. By default, CMT launches NUMBER-OF-PROCESSORS build commands in parallel. The other focus was on CMT commands optimisation in general that made them approximately 2 times faster. CMT can generate a cached requirements file for the environment setup command, which is especially useful for deployment on distributed file systems like AFS or CERN VMFS. The use of parallelism, caching and code optimisation significantly-by several times-reduced software build time, environment setup time, increased the efficiency of

  12. Natural Erosion of Sandstone as Shape Optimisation.

    Science.gov (United States)

    Ostanin, Igor; Safonov, Alexander; Oseledets, Ivan

    2017-12-11

    Natural arches, pillars and other exotic sandstone formations have always been attracting attention for their unusual shapes and amazing mechanical balance that leave a strong impression of intelligent design rather than the result of a stochastic process. It has been recently demonstrated that these shapes could have been the result of the negative feedback between stress and erosion that originates in fundamental laws of friction between the rock's constituent particles. Here we present a deeper analysis of this idea and bridge it with the approaches utilized in shape and topology optimisation. It appears that the processes of natural erosion, driven by stochastic surface forces and Mohr-Coulomb law of dry friction, can be viewed within the framework of local optimisation for minimum elastic strain energy. Our hypothesis is confirmed by numerical simulations of the erosion using the topological-shape optimisation model. Our work contributes to a better understanding of stochastic erosion and feasible landscape formations that could be found on Earth and beyond.

  13. Exploration of automatic optimisation for CUDA programming

    KAUST Repository

    Al-Mouhamed, Mayez

    2014-09-16

    © 2014 Taylor & Francis. Writing optimised compute unified device architecture (CUDA) program for graphic processing units (GPUs) is complex even for experts. We present a design methodology for a restructuring tool that converts C-loops into optimised CUDA kernels based on a three-step algorithm which are loop tiling, coalesced memory access and resource optimisation. A method for finding possible loop tiling solutions with coalesced memory access is developed and a simplified algorithm for restructuring C-loops into an efficient CUDA kernel is presented. In the evaluation, we implement matrix multiply (MM), matrix transpose (M-transpose), matrix scaling (M-scaling) and matrix vector multiply (MV) using the proposed algorithm. We present the analysis of the execution time and GPU throughput for the above applications, which favourably compare to other proposals. Evaluation is carried out while scaling the problem size and running under a variety of kernel configurations. The obtained speedup is about 28-35% for M-transpose compared to NVIDIA Software Development Kit, 33% speedup for MV compared to general purpose computation on graphics processing unit compiler, and more than 80% speedup for MM and M-scaling compared to CUDA-lite.

  14. Exploration of automatic optimisation for CUDA programming

    KAUST Repository

    Al-Mouhamed, Mayez; Khan, Ayaz ul Hassan

    2014-01-01

    © 2014 Taylor & Francis. Writing optimised compute unified device architecture (CUDA) program for graphic processing units (GPUs) is complex even for experts. We present a design methodology for a restructuring tool that converts C-loops into optimised CUDA kernels based on a three-step algorithm which are loop tiling, coalesced memory access and resource optimisation. A method for finding possible loop tiling solutions with coalesced memory access is developed and a simplified algorithm for restructuring C-loops into an efficient CUDA kernel is presented. In the evaluation, we implement matrix multiply (MM), matrix transpose (M-transpose), matrix scaling (M-scaling) and matrix vector multiply (MV) using the proposed algorithm. We present the analysis of the execution time and GPU throughput for the above applications, which favourably compare to other proposals. Evaluation is carried out while scaling the problem size and running under a variety of kernel configurations. The obtained speedup is about 28-35% for M-transpose compared to NVIDIA Software Development Kit, 33% speedup for MV compared to general purpose computation on graphics processing unit compiler, and more than 80% speedup for MM and M-scaling compared to CUDA-lite.

  15. Optimisation and symmetry in experimental radiation physics

    International Nuclear Information System (INIS)

    Ghose, A.

    1988-01-01

    The present monograph is concerned with the optimisation of geometric factors in radiation physics experiments. The discussions are essentially confined to those systems in which optimisation is equivalent to symmetrical configurations of the measurement systems. They include, measurements of interaction cross section of diverse types, determination of polarisations, development of detectors with almost ideal characteristics, production of radiations with continuously variable energies and development of high efficiency spectrometers etc. The monograph is intended for use by experimental physicists investigating primary interactions of radiations with matter and associated technologies. We have illustrated the various optimisation procedures by considering the cases of the so-called ''14 MeV'' on d-t neutrons and gamma rays with energies less than 3 MeV. Developments in fusion technology are critically dependent on the availability accurate cross sections of nuclei for fast neutrons of energies at least as high as d-t neutrons. In this monograph we have discussed various techniques which can be used to improve the accuracy of such measurements and have also presented a method for generating almost monoenergetic neutrons in the 8 MeV to 13 MeV energy range which can be used to measure cross sections in this sparingly investigated region

  16. Cholesterol Induced Changes in the Characteristics of the Time Series From Planar Lipid Bilayer Membrane during Electroporation

    International Nuclear Information System (INIS)

    Kotulska, M.; Koronkiewicz, S.; Kalinowski, S.

    2002-01-01

    The electroporation can be used as a non-toxic method for introducing exogenous macromolecules, especially DNA and drugs, into various types of cells. Research in to new therapeutic methods based on Long Duration Electroporation (LDE) is of special interest. A new current-clamp method makes possible the electroporation of very long duration with no damage to bio-membranes. In this paper we compare responses of lipid planar bilayer membranes at physiological concentration of KCl, with lipid membranes formed at higher ionic strength, and membranes containing cholesterol. A longer lifespan of the membranes with cholesterol and membranes with increased ionic strength could be observed. Sensitivity of the power spectrum response to the presence of cholesterol, ionic strength, current intensity, and membrane ageing was examined. The membrane memory was analyzed by means of autocorrelation function and rescaled range analysis. We showed that the memory of the system decreases for higher current intensities and this relation is pronounced better at higher ionic strength. At low current intensities all membranes showed slightly persistent type of noise behavior with crossover to Brownian type of noise for higher current value. The transition w as much faster for higher ionic strength, where the next transition to anti-persistent response was observed for relatively low currents. Very interesting results were obtained from power spectrum analysis. At low current intensity, all membranes exhibited 1/f noise, which disappeared for higher currents, maintaining f β type with rising value of β. Membranes formed at lower ionic strength and with cholesterol showed a pronounced tendency to lose flicker noise while ageing, also with rising β value. (author)

  17. Electroporation of Skin Stratum Corneum Lipid Bilayer and Molecular Mechanism of Drug Transport: A Molecular Dynamics Study.

    Science.gov (United States)

    Gupta, Rakesh; Rai, Beena

    2018-04-30

    Skin electroporation has been used significantly to increase the drug permeation. However, molecular mechanism, which resulted in enhancement of flux through skin, is still not known. In this study, extensive atomistic molecular dynamics simulation of skin lipids (made up of ceramide (CER), cholesterol (CHOL) and free fatty acid (FFA)) have been performed at various external electric field. We show for the first time the pore formation in the skin lipid bilayer during the electroporation. We show the effect of applied external electrical field on the pore formation dynamics in lipid bilayer of different size and composition. The pore formation and resealing kinetics were different and was found to be highly dependent on the composition of skin lipid bilayer. The pore formation time decreased with increase in the bilayer size. The pore sustaining electric field was found to be in the range of 0.20-0.25 V/nm for equimolar CER, CHOL and FFA lipid bilayer. The skin lipid bilayer (1:1:1), sealed itself within 20 ns after the removal of external electric field. We also present the molecular mechanism of enhancement of drug permeation in the presence of external field as compared to the passive diffusion. The molecular level understanding obtained here could help in optimizing/designing the electroporation experiments for effective drug delivery. For a given skin composition and size of drug molecule, the combination of pore formation time and pore growth model can be used to know aproiri the desired electric field and time for application of electric field.

  18. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    International Nuclear Information System (INIS)

    Wendler, J. J.; Porsch, M.; Hühne, S.; Baumunk, D.; Buhtz, P.; Fischbach, F.; Pech, M.; Mahnkopf, D.; Kropf, S.; Roessner, A.; Ricke, J.; Schostak, M.; Liehr, U.-B.

    2013-01-01

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  19. Assessment of Chronological Effects of Irreversible Electroporation on Hilar Bile Ducts in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae Woong, E-mail: cooljay@korea.ac.kr; Lu, David S. K., E-mail: dlu@mednet.ucla.edu; Osuagwu, Ferdnand, E-mail: fosuagwu@mednet.ucla.edu; Raman, Steven, E-mail: sraman@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Department of Radiology (United States); Lassman, Charles, E-mail: classman@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Department of Pathology (United States)

    2013-11-07

    PurposeTo evaluate the chronological effects of irreversible electroporation (IRE) on large hilar bile ducts in an in vivo porcine model correlated with computed tomography (CT) cholangiography and histopathology.Materials and MethodsTwelve IRE zones were made along hilar bile ducts intraoperatively under ultrasound (US)-guidance in 11 pigs. Paired electrodes were placed either on opposing sides of the bile duct (straddle [STR]) or both on one side of the bile duct (one-sided [OSD]). The shortest electrode-to-duct distance was classified as periductal (≤2 mm) or nonperiductal (>2 mm). CT cholangiography and laboratory tests were performed before IRE and again at 2 days, 4 weeks, and 8 weeks after IRE. Degree of bile duct injury were graded as follows: grade 0 = no narrowing; grade 1 = ≤50 % duct narrowing; grade 2 = >50 % narrowing without proximal duct dilatation; grade 3 = grade 2 with proximal duct dilatation; and grade 4 = grade 3 with enzyme elevation. Pigs were selected for killing and histopathology at 2 days, 4, and 8 weeks.ResultsNonperiductal electrode placement produced no long-term strictures in 5 of 5 ducts. Periductal electrode placement produced mild narrowing in 6 of 7 ducts: 5 grade 1 and 1 grade 2. None showed increased enzymes. There was no significant difference between STR versus OSD electrode placement. Histopathology showed minor but relatively greater ductal mural changes in narrowed ducts.ConclusionIn the larger hilar ducts, long-term patency and mural integrity appear resistant to IRE damage with the energy deposition used, especially if the electrode is not immediately periductal in position.

  20. Assessment of Chronological Effects of Irreversible Electroporation on Hilar Bile Ducts in a Porcine Model

    International Nuclear Information System (INIS)

    Choi, Jae Woong; Lu, David S. K.; Osuagwu, Ferdnand; Raman, Steven; Lassman, Charles

    2014-01-01

    PurposeTo evaluate the chronological effects of irreversible electroporation (IRE) on large hilar bile ducts in an in vivo porcine model correlated with computed tomography (CT) cholangiography and histopathology.Materials and MethodsTwelve IRE zones were made along hilar bile ducts intraoperatively under ultrasound (US)-guidance in 11 pigs. Paired electrodes were placed either on opposing sides of the bile duct (straddle [STR]) or both on one side of the bile duct (one-sided [OSD]). The shortest electrode-to-duct distance was classified as periductal (≤2 mm) or nonperiductal (>2 mm). CT cholangiography and laboratory tests were performed before IRE and again at 2 days, 4 weeks, and 8 weeks after IRE. Degree of bile duct injury were graded as follows: grade 0 = no narrowing; grade 1 = ≤50 % duct narrowing; grade 2 = >50 % narrowing without proximal duct dilatation; grade 3 = grade 2 with proximal duct dilatation; and grade 4 = grade 3 with enzyme elevation. Pigs were selected for killing and histopathology at 2 days, 4, and 8 weeks.ResultsNonperiductal electrode placement produced no long-term strictures in 5 of 5 ducts. Periductal electrode placement produced mild narrowing in 6 of 7 ducts: 5 grade 1 and 1 grade 2. None showed increased enzymes. There was no significant difference between STR versus OSD electrode placement. Histopathology showed minor but relatively greater ductal mural changes in narrowed ducts.ConclusionIn the larger hilar ducts, long-term patency and mural integrity appear resistant to IRE damage with the energy deposition used, especially if the electrode is not immediately periductal in position

  1. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    Energy Technology Data Exchange (ETDEWEB)

    Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.; Baumunk, D. [University of Magdeburg, Department of Urology (Germany); Buhtz, P. [Institute of Pathology, University of Magdeburg (Germany); Fischbach, F.; Pech, M. [University of Magdeburg, Department of Radiology (Germany); Mahnkopf, D. [Institute of Medical Technology and Research (Germany); Kropf, S. [Institute of Biometry, University of Magdeburg (Germany); Roessner, A. [Institute of Pathology, University of Magdeburg (Germany); Ricke, J. [University of Magdeburg, Department of Radiology (Germany); Schostak, M.; Liehr, U.-B. [University of Magdeburg, Department of Urology (Germany)

    2013-04-15

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  2. Irreversible Electroporation of the Pancreas Using Parallel Plate Electrodes in a Porcine Model: A Feasibility Study.

    Science.gov (United States)

    Rombouts, Steffi J E; Nijkamp, Maarten W; van Dijck, Willemijn P M; Brosens, Lodewijk A A; Konings, Maurits; van Hillegersberg, R; Borel Rinkes, Inne H M; Hagendoorn, Jeroen; Wittkampf, Fred H; Molenaar, I Quintus

    2017-01-01

    Irreversible electroporation (IRE) with needle electrodes is being explored as treatment option in locally advanced pancreatic cancer. Several studies have shown promising results with IRE needles, positioned around the tumor to achieve tumor ablation. Disadvantages are the technical difficulties for needle placement, the time needed to achieve tumor ablation, the risk of needle track seeding and most important the possible occurrence of postoperative pancreatic fistula via the needle tracks. The aim of this experimental study was to evaluate the feasibility of a new IRE-technique using two parallel plate electrodes, in a porcine model. Twelve healthy pigs underwent laparotomy. The pancreas was mobilized to enable positioning of the paddles. A standard monophasic external cardiac defibrillator was used to perform an ablation in 3 separate parts of the pancreas; either a single application of 50 or 100J or a serial application of 4x50J. After 6 hours, pancreatectomy was performed for histology and pigs were terminated. Histology showed necrosis of pancreatic parenchyma with neutrophil influx in 5/12, 11/12 and 12/12 of the ablated areas at 50, 100, and 4x50J respectively. The electric current density threshold to achieve necrosis was 4.3, 5.1 and 3.4 A/cm2 respectively. The ablation threshold was significantly lower for the serial compared to the single applications (p = 0.003). The content of the ablated areas differed between the applications: areas treated with a single application of 50 J often contained vital areas without obvious necrosis, whereas half of the sections treated with 100 J showed small islands of normal looking cells surrounded by necrosis, while all sections receiving 4x 50 J showed a homogeneous necrotic lesion. Pancreatic tissue can be successfully ablated using two parallel paddles around the tissue. A serial application of 4x50J was most effective in creating a homogeneous necrotic lesion.

  3. Irreversible Electroporation of the Pancreas Using Parallel Plate Electrodes in a Porcine Model: A Feasibility Study.

    Directory of Open Access Journals (Sweden)

    Steffi J E Rombouts

    Full Text Available Irreversible electroporation (IRE with needle electrodes is being explored as treatment option in locally advanced pancreatic cancer. Several studies have shown promising results with IRE needles, positioned around the tumor to achieve tumor ablation. Disadvantages are the technical difficulties for needle placement, the time needed to achieve tumor ablation, the risk of needle track seeding and most important the possible occurrence of postoperative pancreatic fistula via the needle tracks. The aim of this experimental study was to evaluate the feasibility of a new IRE-technique using two parallel plate electrodes, in a porcine model.Twelve healthy pigs underwent laparotomy. The pancreas was mobilized to enable positioning of the paddles. A standard monophasic external cardiac defibrillator was used to perform an ablation in 3 separate parts of the pancreas; either a single application of 50 or 100J or a serial application of 4x50J. After 6 hours, pancreatectomy was performed for histology and pigs were terminated.Histology showed necrosis of pancreatic parenchyma with neutrophil influx in 5/12, 11/12 and 12/12 of the ablated areas at 50, 100, and 4x50J respectively. The electric current density threshold to achieve necrosis was 4.3, 5.1 and 3.4 A/cm2 respectively. The ablation threshold was significantly lower for the serial compared to the single applications (p = 0.003. The content of the ablated areas differed between the applications: areas treated with a single application of 50 J often contained vital areas without obvious necrosis, whereas half of the sections treated with 100 J showed small islands of normal looking cells surrounded by necrosis, while all sections receiving 4x 50 J showed a homogeneous necrotic lesion.Pancreatic tissue can be successfully ablated using two parallel paddles around the tissue. A serial application of 4x50J was most effective in creating a homogeneous necrotic lesion.

  4. Experimental study on ablating goat liver tissue with ultrasound imaging guided percutaneous irreversible electroporation

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2011-03-01

    Full Text Available Objective To investigate the proper method of percutaneous irreversible electroporation(IRE to ablate goat liver tissue under ultrasonic guidance,and observe the features of ultrasound imaging and histological changes.Methods The pulse electric fields(PEFs with permanent duration(100 μs,frequency(1Hz,voltage(2000V and pulses(120 pieces were applied to the electrodes,and the electrodes were placed into goats’ liver under ultrasound guidance through the animal skin to the target area.The treated area was observed by real-time ultrasound scanning,and the histopathological changes were assessed by hematoxylin and eosin(HE staining under light microscope at the time of 0h and 24h after IRE ablation.The circumscribed ablated area was compared with that of finite element modeling(FEM calculation method.Results Ultrasound imaging guidance was accurate in focusing on the target area.Imaging captured by the ultrasound after IRE procedure was quite different from that of the normal liver imaging.Complete hepatic cell death with a sharp demarcation between the ablated zone and the non-ablated zone was well visualized 24 hours after the procedure.Necrospy-based measurement demonstrated a high consistence with FEM-anticipated ablation zones.Conclusion With real-time monitoring by ultrasonography and well-controlled ablation of the target tissue,percutaneous IRE can provide a novel and unique ablative method for cancer treatment.The present paper provides a fundamental experimental work for future studies on clinical application of IRE.

  5. Planning Irreversible Electroporation in the Porcine Kidney: Are Numerical Simulations Reliable for Predicting Empiric Ablation Outcomes?

    International Nuclear Information System (INIS)

    Wimmer, Thomas; Srimathveeravalli, Govindarajan; Gutta, Narendra; Ezell, Paula C.; Monette, Sebastien; Maybody, Majid; Erinjery, Joseph P.; Durack, Jeremy C.; Coleman, Jonathan A.; Solomon, Stephen B.

    2015-01-01

    PurposeNumerical simulations are used for treatment planning in clinical applications of irreversible electroporation (IRE) to determine ablation size and shape. To assess the reliability of simulations for treatment planning, we compared simulation results with empiric outcomes of renal IRE using computed tomography (CT) and histology in an animal model.MethodsThe ablation size and shape for six different IRE parameter sets (70–90 pulses, 2,000–2,700 V, 70–100 µs) for monopolar and bipolar electrodes was simulated using a numerical model. Employing these treatment parameters, 35 CT-guided IRE ablations were created in both kidneys of six pigs and followed up with CT immediately and after 24 h. Histopathology was analyzed from postablation day 1.ResultsAblation zones on CT measured 81 ± 18 % (day 0, p ≤ 0.05) and 115 ± 18 % (day 1, p ≤ 0.09) of the simulated size for monopolar electrodes, and 190 ± 33 % (day 0, p ≤ 0.001) and 234 ± 12 % (day 1, p ≤ 0.0001) for bipolar electrodes. Histopathology indicated smaller ablation zones than simulated (71 ± 41 %, p ≤ 0.047) and measured on CT (47 ± 16 %, p ≤ 0.005) with complete ablation of kidney parenchyma within the central zone and incomplete ablation in the periphery.ConclusionBoth numerical simulations for planning renal IRE and CT measurements may overestimate the size of ablation compared to histology, and ablation effects may be incomplete in the periphery

  6. Pain Analysis in Patients with Hepatocellular Carcinoma: Irreversible Electroporation versus Radiofrequency Ablation-Initial Observations

    Energy Technology Data Exchange (ETDEWEB)

    Narayanan, Govindarajan, E-mail: gnarayanan@med.miami.edu; Froud, Tatiana, E-mail: tfroud@med.miami.edu [Miller School of Medicine, University of Miami, Department of Vascular and Interventional Radiology (United States); Lo, Kaming, E-mail: KLo@biostat.med.miami.edu [Miller School of Medicine, University of Miami, Department of Epidemiology and Public Health (United States); Barbery, Katuska J., E-mail: kbarbery@med.miami.edu; Perez-Rojas, Evelyn, E-mail: eprojas@med.miami.edu; Yrizarry, Jose, E-mail: jyrizarr@med.miami.edu [Miller School of Medicine, University of Miami, Department of Vascular and Interventional Radiology (United States)

    2013-02-15

    To retrospectively compare the postprocedure pain of hepatocellular carcinoma treated with irreversible electroporation (IRE) with radiofrequency ablation (RFA). This Health Insurance Portability and Accountability Act-compliant, institutional review board-approved study compared postprocedure pain in 21 patients (15 men, six women; mean age 61.5 years) who underwent IRE of 29 intrahepatic lesions (mean size 2.20 cm) in 28 IRE sessions with 22 patients (16 men, six women; mean age 60.2 years) who underwent RFA of 27 lesions (mean size 3.38 cm) in 25 RFA sessions. Pain was determined by patient-disclosed scores with an 11-point numerical rating scale and 24 h cumulative hydromorphone use from patient-controlled analgesia pump. Complications were noted. Statistical significance was evaluated by Fisher's exact test, the Chi-square test, and Student's t test. There was no significant difference in the cumulative hydromorphone dose (1.54 mg (IRE) vs. 1.24 mg (RFA); P = 0.52) and in the mean pain score (1.96 (IRE) vs. 2.25 (RFA); P = 0.70). In nine (32.14 %) of 28 IRE sessions and 11 (44.0 %) of 25 RFA sessions, patients reported no pain. Complications occurred in three (10.7 %) of 28 IRE treatments and included pneumothorax (n = 1), pleural effusion (n = 1), and bleeding in the form of hemothorax (n = 1); one (4 %) of 25 RFA treatments included burn. IRE is comparable to RFA in the amount of pain that patients experience and the amount of pain medication self-administered. Both modalities were well tolerated by patients. Prospective, randomized trials are necessary to further evaluate these findings.

  7. Pain Analysis in Patients with Hepatocellular Carcinoma: Irreversible Electroporation versus Radiofrequency Ablation—Initial Observations

    International Nuclear Information System (INIS)

    Narayanan, Govindarajan; Froud, Tatiana; Lo, Kaming; Barbery, Katuska J.; Perez-Rojas, Evelyn; Yrizarry, Jose

    2013-01-01

    To retrospectively compare the postprocedure pain of hepatocellular carcinoma treated with irreversible electroporation (IRE) with radiofrequency ablation (RFA). This Health Insurance Portability and Accountability Act–compliant, institutional review board–approved study compared postprocedure pain in 21 patients (15 men, six women; mean age 61.5 years) who underwent IRE of 29 intrahepatic lesions (mean size 2.20 cm) in 28 IRE sessions with 22 patients (16 men, six women; mean age 60.2 years) who underwent RFA of 27 lesions (mean size 3.38 cm) in 25 RFA sessions. Pain was determined by patient-disclosed scores with an 11-point numerical rating scale and 24 h cumulative hydromorphone use from patient-controlled analgesia pump. Complications were noted. Statistical significance was evaluated by Fisher’s exact test, the Chi-square test, and Student’s t test. There was no significant difference in the cumulative hydromorphone dose (1.54 mg (IRE) vs. 1.24 mg (RFA); P = 0.52) and in the mean pain score (1.96 (IRE) vs. 2.25 (RFA); P = 0.70). In nine (32.14 %) of 28 IRE sessions and 11 (44.0 %) of 25 RFA sessions, patients reported no pain. Complications occurred in three (10.7 %) of 28 IRE treatments and included pneumothorax (n = 1), pleural effusion (n = 1), and bleeding in the form of hemothorax (n = 1); one (4 %) of 25 RFA treatments included burn. IRE is comparable to RFA in the amount of pain that patients experience and the amount of pain medication self-administered. Both modalities were well tolerated by patients. Prospective, randomized trials are necessary to further evaluate these findings.

  8. Percutaneous Irreversible Electroporation Lung Ablation: Preliminary Results in a Porcine Model

    International Nuclear Information System (INIS)

    Deodhar, Ajita; Monette, Sébastien; Single, Gordon W.; Hamilton, William C.; Thornton, Raymond H.; Sofocleous, Constantinos T.; Maybody, Majid; Solomon, Stephen B.

    2011-01-01

    Objective: Irreversible electroporation (IRE) uses direct electrical pulses to create permanent “pores” in cell membranes to cause cell death. In contrast to conventional modalities, IRE has a nonthermal mechanism of action. Our objective was to study the histopathological and imaging features of IRE in normal swine lung. Materials and Methods: Eleven female swine were studied for hyperacute (8 h), acute (24 h), subacute (96 h), and chronic (3 week) effects of IRE ablation in lung. Paired unipolar IRE applicators were placed under computed tomography (CT) guidance. Some applicators were deliberately positioned near bronchovascular structures. IRE pulse delivery was synchronized with the cardiac rhythm only when ablation was performed within 2 cm of the heart. Contrast-enhanced CT scan was performed immediately before and after IRE and at 1 and 3 weeks after IRE ablation. Representative tissue was stained with hematoxylin and eosin for histopathology. Results: Twenty-five ablations were created: ten hyperacute, four acute, and three subacute ablations showed alveolar edema and necrosis with necrosis of bronchial, bronchiolar, and vascular epithelium. Bronchovascular architecture was maintained. Chronic ablations showed bronchiolitis obliterans and alveolar interstitial fibrosis. Immediate post-procedure CT images showed linear or patchy density along the applicator tract. At 1 week, there was consolidation that resolved partially or completely by 3 weeks. Pneumothorax requiring chest tube developed in two animals; no significant cardiac arrhythmias were noted. Conclusion: Our preliminary porcine study demonstrates the nonthermal and extracellular matrix sparing mechanism of action of IRE. IRE is a potential alternative to thermal ablative modalities.

  9. Evaluating Electroporation and Lipofectamine Approaches for Transient and Stable Transgene Expressions in Human Fibroblasts and Embryonic Stem Cells

    Science.gov (United States)

    Sharifi Tabar, Mehdi; Hesaraki, Mahdi; Esfandiari, Fereshteh; Sahraneshin Samani, Fazel; Vakilian, Haghighat; Baharvand, Hossein

    2015-01-01

    Objective Genetic modification of human embryonic stem cells (hESCs) is critical for their extensive use as a fundamental tool for cell therapy and basic research. Despite the fact that various methods such as lipofection and electroporation have been applied to transfer the gene of interest (GOI) into the target cell line, however, there are few re- ports that compare all parameters, which influence transfection efficiency. In this study, we examine all parameters that affect the efficiency of electroporation and lipofection for transient and long-term gene expression in three different cell lines to introduce the best method and determinant factor. Materials and Methods In this experimental study, both electroporation and lipofection approaches were employed for genetic modification. pCAG-EGFP was applied for tran- sient expression of green fluorescent protein in two genetically different hESC lines, Roy- an H5 (XX) and Royan H6 (XY), as well as human foreskin fibroblasts (hFF). For long-term EGFP expression VASA and OLIG2 promoters (germ cell and motoneuron specific genes, respectively), were isolated and subsequently cloned into a pBluMAR5 plasmid backbone to drive EGFP expression. Flow cytometry analysis was performed two days after trans- fection to determine transient expression efficiency. Differentiation of drug resistant hESC colonies toward primordial germ cells (PGCs) was conducted to confirm stable integration of the transgene. Results Transient and stable expression suggested a variable potential for different cell lines against transfection. Analysis of parameters that influenced gene transformation ef- ficiency revealed that the vector concentrations from 20-60 μg and the density of the sub- jected cells (5×105and 1×106cells) were not as effective as the genetic background and voltage rate. The present data indicated that in contrast to the circular form, the linearized vector generated more distinctive drug resistant colonies. Conclusion

  10. Electroporation and microinjection successfully deliver single-stranded and duplex DNA into live cells as detected by FRET measurements.

    Directory of Open Access Journals (Sweden)

    Rosemary A Bamford

    Full Text Available Förster resonance energy transfer (FRET technology relies on the close proximity of two compatible fluorophores for energy transfer. Tagged (Cy3 and Cy5 complementary DNA strands forming a stable duplex and a doubly-tagged single strand were shown to demonstrate FRET outside of a cellular environment. FRET was also observed after transfecting these DNA strands into fixed and live cells using methods such as microinjection and electroporation, but not when using lipid based transfection reagents, unless in the presence of the endosomal acidification inhibitor bafilomycin. Avoiding the endocytosis pathway is essential for efficient delivery of intact DNA probes into cells.

  11. Methods for Optimisation of the Laser Cutting Process

    DEFF Research Database (Denmark)

    Dragsted, Birgitte

    This thesis deals with the adaptation and implementation of various optimisation methods, in the field of experimental design, for the laser cutting process. The problem in optimising the laser cutting process has been defined and a structure for at Decision Support System (DSS......) for the optimisation of the laser cutting process has been suggested. The DSS consists of a database with the currently used and old parameter settings. Also one of the optimisation methods has been implemented in the DSS in order to facilitate the optimisation procedure for the laser operator. The Simplex Method has...... been adapted in two versions. A qualitative one, that by comparing the laser cut items optimise the process and a quantitative one that uses a weighted quality response in order to achieve a satisfactory quality and after that maximises the cutting speed thus increasing the productivity of the process...

  12. Mechatronic System Design Based On An Optimisation Approach

    DEFF Research Database (Denmark)

    Andersen, Torben Ole; Pedersen, Henrik Clemmensen; Hansen, Michael Rygaard

    The envisaged objective of this paper project is to extend the current state of the art regarding the design of complex mechatronic systems utilizing an optimisation approach. We propose to investigate a novel framework for mechatronic system design. The novelty and originality being the use...... of optimisation techniques. The methods used to optimise/design within the classical disciplines will be identified and extended to mechatronic system design....

  13. Analysis and optimisation of heterogeneous real-time embedded systems

    DEFF Research Database (Denmark)

    Pop, Paul; Eles, Petru; Peng, Zebo

    2005-01-01

    . The success of such new design methods depends on the availability of analysis and optimisation techniques. Analysis and optimisation techniques for heterogeneous real-time embedded systems are presented in the paper. The authors address in more detail a particular class of such systems called multi...... of application messages to frames. Optimisation heuristics for frame packing aimed at producing a schedulable system are presented. Extensive experiments and a real-life example show the efficiency of the frame-packing approach....

  14. Analysis and optimisation of heterogeneous real-time embedded systems

    DEFF Research Database (Denmark)

    Pop, Paul; Eles, Petru; Peng, Zebo

    2006-01-01

    . The success of such new design methods depends on the availability of analysis and optimisation techniques. Analysis and optimisation techniques for heterogeneous real-time embedded systems are presented in the paper. The authors address in more detail a particular class of such systems called multi...... of application messages to frames. Optimisation heuristics for frame packing aimed at producing a schedulable system are presented. Extensive experiments and a real-life example show the efficiency of the frame-packing approach....

  15. Flotation process control optimisation at Prominent Hill

    International Nuclear Information System (INIS)

    Lombardi, Josephine; Muhamad, Nur; Weidenbach, M.

    2012-01-01

    OZ Minerals' Prominent Hill copper- gold concentrator is located 130 km south east of the town of Coober Pedy in the Gawler Craton of South Australia. The concentrator was built in 2008 and commenced commercial production in early 2009. The Prominent Hill concentrator is comprised of a conventional grinding and flotation processing plant with a 9.6 Mtpa ore throughput capacity. The flotation circuit includes six rougher cells, an IseMill for regrinding the rougher concentrate and a Jameson cell heading up the three stage conventional cell cleaner circuit. In total there are four level controllers in the rougher train and ten level controllers in the cleaning circuit for 18 cells. Generic proportional — integral and derivative (PID) control used on the level controllers alone propagated any disturbances downstream in the circuit that were generated from the grinding circuit, hoppers, between cells and interconnected banks of cells, having a negative impact on plant performance. To better control such disturbances, FloatStar level stabiliser was selected for installation on the flotation circuit to account for the interaction between the cells. Multivariable control was also installed on the five concentrate hoppers to maintain consistent feed to the cells and to the IsaMill. An additional area identified for optimisation in the flotation circuit was the mass pull rate from the rougher cells. FloatStar flow optimiser was selected to be installed subsequent to the FloatStar level stabiliser. This allowed for a unified, consistent and optimal approach to running the rougher circuit. This paper describes the improvement in the stabilisation of the circuit achieved by the FloatStar level stabiliser by using the interaction matrix between cell level controllers and the results and benefits of implementing the FloatStar flow optimiser on the rougher train.

  16. Risk based test interval and maintenance optimisation - Application and uses

    International Nuclear Information System (INIS)

    Sparre, E.

    1999-10-01

    The project is part of an IAEA co-ordinated Research Project (CRP) on 'Development of Methodologies for Optimisation of Surveillance Testing and Maintenance of Safety Related Equipment at NPPs'. The purpose of the project is to investigate the sensitivity of the results obtained when performing risk based optimisation of the technical specifications. Previous projects have shown that complete LPSA models can be created and that these models allow optimisation of technical specifications. However, these optimisations did not include any in depth check of the result sensitivity with regards to methods, model completeness etc. Four different test intervals have been investigated in this study. Aside from an original, nominal, optimisation a set of sensitivity analyses has been performed and the results from these analyses have been compared to the original optimisation. The analyses indicate that the result of an optimisation is rather stable. However, it is not possible to draw any certain conclusions without performing a number of sensitivity analyses. Significant differences in the optimisation result were discovered when analysing an alternative configuration. Also deterministic uncertainties seem to affect the result of an optimisation largely. The sensitivity of failure data uncertainties is important to investigate in detail since the methodology is based on the assumption that the unavailability of a component is dependent on the length of the test interval

  17. Improving Vector Evaluated Particle Swarm Optimisation by incorporating nondominated solutions.

    Science.gov (United States)

    Lim, Kian Sheng; Ibrahim, Zuwairie; Buyamin, Salinda; Ahmad, Anita; Naim, Faradila; Ghazali, Kamarul Hawari; Mokhtar, Norrima

    2013-01-01

    The Vector Evaluated Particle Swarm Optimisation algorithm is widely used to solve multiobjective optimisation problems. This algorithm optimises one objective using a swarm of particles where their movements are guided by the best solution found by another swarm. However, the best solution of a swarm is only updated when a newly generated solution has better fitness than the best solution at the objective function optimised by that swarm, yielding poor solutions for the multiobjective optimisation problems. Thus, an improved Vector Evaluated Particle Swarm Optimisation algorithm is introduced by incorporating the nondominated solutions as the guidance for a swarm rather than using the best solution from another swarm. In this paper, the performance of improved Vector Evaluated Particle Swarm Optimisation algorithm is investigated using performance measures such as the number of nondominated solutions found, the generational distance, the spread, and the hypervolume. The results suggest that the improved Vector Evaluated Particle Swarm Optimisation algorithm has impressive performance compared with the conventional Vector Evaluated Particle Swarm Optimisation algorithm.

  18. Improving Vector Evaluated Particle Swarm Optimisation by Incorporating Nondominated Solutions

    Directory of Open Access Journals (Sweden)

    Kian Sheng Lim

    2013-01-01

    Full Text Available The Vector Evaluated Particle Swarm Optimisation algorithm is widely used to solve multiobjective optimisation problems. This algorithm optimises one objective using a swarm of particles where their movements are guided by the best solution found by another swarm. However, the best solution of a swarm is only updated when a newly generated solution has better fitness than the best solution at the objective function optimised by that swarm, yielding poor solutions for the multiobjective optimisation problems. Thus, an improved Vector Evaluated Particle Swarm Optimisation algorithm is introduced by incorporating the nondominated solutions as the guidance for a swarm rather than using the best solution from another swarm. In this paper, the performance of improved Vector Evaluated Particle Swarm Optimisation algorithm is investigated using performance measures such as the number of nondominated solutions found, the generational distance, the spread, and the hypervolume. The results suggest that the improved Vector Evaluated Particle Swarm Optimisation algorithm has impressive performance compared with the conventional Vector Evaluated Particle Swarm Optimisation algorithm.

  19. Optimising end of generation of Magnox reactors

    International Nuclear Information System (INIS)

    Hall, D.; Hopper, E.D.A.

    2014-01-01

    Designing, justifying and gaining regulatory approval for optimised, terminal fuel cycles for the last 4 of the 13 strong Magnox Fleet is described, covering: - constraints set by the plant owner's integrated closure plan, opportunities for innovative fuel cycles while preserving flexibility to respond to business changes; - methods of collectively determining best options for each site; - selected strategies including lower fuel element retention and inter-reactor transfer of fuel; - the required work scope, its technical, safety case and resource challenges and how they were met; - achieving additional electricity generation worth in excess of Pound 1 b from 4 sites (a total of 8 reactors); - the keys to success. (authors)

  20. Advanced manufacturing: optimising the factories of tomorrow

    International Nuclear Information System (INIS)

    Philippon, Patrick

    2013-01-01

    Faced with competition Patrick Philippon - Les Defis du CEA no.179 - April 2013 from the emerging countries, the competitiveness of the industrialised nations depends on the ability of their industries to innovate. This strategy necessarily entails the reorganisation and optimisation of the production systems. This is the whole challenge for 'advanced manufacturing', which relies on the new information and communication technologies. Interactive robotics, virtual reality and non-destructive testing are all technological building blocks developed by CEA, now approved within a cross-cutting programme, to meet the needs of industry and together build the factories of tomorrow. (author)

  1. Biorefinery plant design, engineering and process optimisation

    DEFF Research Database (Denmark)

    Holm-Nielsen, Jens Bo; Ehimen, Ehiazesebhor Augustine

    2014-01-01

    Before new biorefinery systems can be implemented, or the modification of existing single product biomass processing units into biorefineries can be carried out, proper planning of the intended biorefinery scheme must be performed initially. This chapter outlines design and synthesis approaches...... applicable for the planning and upgrading of intended biorefinery systems, and includes discussions on the operation of an existing lignocellulosic-based biorefinery platform. Furthermore, technical considerations and tools (i.e., process analytical tools) which could be applied to optimise the operations...... of existing and potential biorefinery plants are elucidated....

  2. Specification, Verification and Optimisation of Business Processes

    DEFF Research Database (Denmark)

    Herbert, Luke Thomas

    is extended with stochastic branching, message passing and reward annotations which allow for the modelling of resources consumed during the execution of a business process. Further, it is shown how this structure can be used to formalise the established business process modelling language Business Process...... fault tree analysis and the automated optimisation of business processes by means of an evolutionary algorithm. This work is motivated by problems that stem from the healthcare sector, and examples encountered in this field are used to illustrate these developments....

  3. Topology Optimisation for Coupled Convection Problems

    DEFF Research Database (Denmark)

    Alexandersen, Joe; Andreasen, Casper Schousboe; Aage, Niels

    stabilised finite elements implemented in a parallel multiphysics analysis and optimisation framework DFEM [1], developed and maintained in house. Focus is put on control of the temperature field within the solid structure and the problems can therefore be seen as conjugate heat transfer problems, where heat...... conduction governs in the solid parts of the design domain and couples to convection-dominated heat transfer to a surrounding fluid. Both loosely coupled and tightly coupled problems are considered. The loosely coupled problems are convection-diffusion problems, based on an advective velocity field from...

  4. Cost optimisation studies of high power accelerators

    Energy Technology Data Exchange (ETDEWEB)

    McAdams, R.; Nightingale, M.P.S.; Godden, D. [AEA Technology, Oxon (United Kingdom)] [and others

    1995-10-01

    Cost optimisation studies are carried out for an accelerator based neutron source consisting of a series of linear accelerators. The characteristics of the lowest cost design for a given beam current and energy machine such as power and length are found to depend on the lifetime envisaged for it. For a fixed neutron yield it is preferable to have a low current, high energy machine. The benefits of superconducting technology are also investigated. A Separated Orbit Cyclotron (SOC) has the potential to reduce capital and operating costs and intial estimates for the transverse and longitudinal current limits of such machines are made.

  5. Introduction of exogenous DNA into gonads of chick embryos by lipofection and electroporation of stage X blastoderms in vivo.

    Science.gov (United States)

    Sano, A; Tagami, T; Harumi, T; Matsubara, Y; Naito, M

    2003-03-01

    1. In order to introduce exogenous DNA into gonads of chick embryos, stage X blastoderms of freshly laid and unincubated eggs were transfected by lipofection and electroporation in vivo. 2. The introduced DNA, green fluorescence protein (GFP) gene, was efficiently expressed in the blastoderms incubated for 24 h (78.8%, 78/99). 3. The GFP gene was present in most of the embryonic bodies and extra-embryonic membranes died by d 10 of incubation, when analysed by polymerase chain reaction. On d 16 to 20 of incubation, the GFP gene was detected in 7.0 to 20.9% of embryos in the heart, liver, stomach and brain, but not in the sartorius muscle. For the gonads, the GFP gene was detected in 22.2% (6/27) of the testes and 6.3% (1/18) of the ovaries examined. 4. These results suggest that it is possible to introduce exogenous DNA into gonads of chick embryos by lipofection and electroporation of stage X blastoderms in vivo.

  6. A high efficiency gene disruption strategy using a positive-negative split selection marker and electroporation for Fusarium oxysporum.

    Science.gov (United States)

    Liang, Liqin; Li, Jianqiang; Cheng, Lin; Ling, Jian; Luo, Zhongqin; Bai, Miao; Xie, Bingyan

    2014-11-01

    The Fusarium oxysporum species complex consists of fungal pathogens that cause serial vascular wilt disease on more than 100 cultivated species throughout the world. Gene function analysis is rapidly becoming more and more important as the whole-genome sequences of various F. oxysporum strains are being completed. Gene-disruption techniques are a common molecular tool for studying gene function, yet are often a limiting step in gene function identification. In this study we have developed a F. oxysporum high-efficiency gene-disruption strategy based on split-marker homologous recombination cassettes with dual selection and electroporation transformation. The method was efficiently used to delete three RNA-dependent RNA polymerase (RdRP) genes. The gene-disruption cassettes of three genes can be constructed simultaneously within a short time using this technique. The optimal condition for electroporation is 10μF capacitance, 300Ω resistance, 4kV/cm field strength, with 1μg of DNA (gene-disruption cassettes). Under these optimal conditions, we were able to obtain 95 transformants per μg DNA. And after positive-negative selection, the transformants were efficiently screened by PCR, screening efficiency averaged 85%: 90% (RdRP1), 85% (RdRP2) and 77% (RdRP3). This gene-disruption strategy should pave the way for high throughout genetic analysis in F. oxysporum. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. Targeted electroporation of defined lateral ventricular walls: a novel and rapid method to study fate specification during postnatal forebrain neurogenesis

    Directory of Open Access Journals (Sweden)

    Cremer Harold

    2011-04-01

    Full Text Available Abstract Background Postnatal olfactory bulb (OB neurogenesis involves the generation of granule and periglomerular cells by neural stem cells (NSCs located in the walls of the lateral ventricle (LV. Recent studies show that NSCs located in different regions of the LV give rise to different types of OB neurons. However, the molecular mechanisms governing neuronal specification remain largely unknown and new methods to approach these questions are needed. Results In this study, we refine electroporation of the postnatal forebrain as a technique to perform precise and accurate delivery of transgenes to NSCs located in distinct walls of the LV in the mouse. Using this method, we confirm and expand previous studies showing that NSCs in distinct walls of the LV produce neurons that invade different layers of the OB. Fate mapping of the progeny of radial glial cells located in these distinct LV walls reveals their specification into defined subtypes of granule and periglomerular neurons. Conclusions Our results provide a baseline with which future studies aiming at investigating the role of factors in postnatal forebrain neuronal specification can be compared. Targeted electroporation of defined LV NSC populations will prove valuable to study the genetic factors involved in forebrain neuronal specification.

  8. Development of a statistical model for cervical cancer cell death with irreversible electroporation in vitro.

    Science.gov (United States)

    Yang, Yongji; Moser, Michael A J; Zhang, Edwin; Zhang, Wenjun; Zhang, Bing

    2018-01-01

    The aim of this study was to develop a statistical model for cell death by irreversible electroporation (IRE) and to show that the statistic model is more accurate than the electric field threshold model in the literature using cervical cancer cells in vitro. HeLa cell line was cultured and treated with different IRE protocols in order to obtain data for modeling the statistical relationship between the cell death and pulse-setting parameters. In total, 340 in vitro experiments were performed with a commercial IRE pulse system, including a pulse generator and an electric cuvette. Trypan blue staining technique was used to evaluate cell death after 4 hours of incubation following IRE treatment. Peleg-Fermi model was used in the study to build the statistical relationship using the cell viability data obtained from the in vitro experiments. A finite element model of IRE for the electric field distribution was also built. Comparison of ablation zones between the statistical model and electric threshold model (drawn from the finite element model) was used to show the accuracy of the proposed statistical model in the description of the ablation zone and its applicability in different pulse-setting parameters. The statistical models describing the relationships between HeLa cell death and pulse length and the number of pulses, respectively, were built. The values of the curve fitting parameters were obtained using the Peleg-Fermi model for the treatment of cervical cancer with IRE. The difference in the ablation zone between the statistical model and the electric threshold model was also illustrated to show the accuracy of the proposed statistical model in the representation of ablation zone in IRE. This study concluded that: (1) the proposed statistical model accurately described the ablation zone of IRE with cervical cancer cells, and was more accurate compared with the electric field model; (2) the proposed statistical model was able to estimate the value of electric

  9. HVAC system optimisation-in-building section

    Energy Technology Data Exchange (ETDEWEB)

    Lu, L.; Cai, W.; Xie, L.; Li, S.; Soh, Y.C. [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore (Singapore)

    2004-07-01

    This paper presents a practical method to optimise in-building section of centralised Heating, Ventilation and Air-Conditioning (HVAC) systems which consist of indoor air loops and chilled water loops. First, through component characteristic analysis, mathematical models associated with cooling loads and energy consumption for heat exchangers and energy consuming devices are established. By considering variation of cooling load of each end user, adaptive neuro-fuzzy inference system (ANFIS) is employed to model duct and pipe networks and obtain optimal differential pressure (DP) set points based on limited sensor information. A mix-integer nonlinear constraint optimization of system energy is formulated and solved by a modified genetic algorithm. The main feature of our paper is a systematic approach in optimizing the overall system energy consumption rather than that of individual component. A simulation study for a typical centralized HVAC system is provided to compare the proposed optimisation method with traditional ones. The results show that the proposed method indeed improves the system performance significantly. (author)

  10. Optimisation of milling parameters using neural network

    Directory of Open Access Journals (Sweden)

    Lipski Jerzy

    2017-01-01

    Full Text Available The purpose of this study was to design and test an intelligent computer software developed with the purpose of increasing average productivity of milling not compromising the design features of the final product. The developed system generates optimal milling parameters based on the extent of tool wear. The introduced optimisation algorithm employs a multilayer model of a milling process developed in the artificial neural network. The input parameters for model training are the following: cutting speed vc, feed per tooth fz and the degree of tool wear measured by means of localised flank wear (VB3. The output parameter is the surface roughness of a machined surface Ra. Since the model in the neural network exhibits good approximation of functional relationships, it was applied to determine optimal milling parameters in changeable tool wear conditions (VB3 and stabilisation of surface roughness parameter Ra. Our solution enables constant control over surface roughness parameters and productivity of milling process after each assessment of tool condition. The recommended parameters, i.e. those which applied in milling ensure desired surface roughness and maximal productivity, are selected from all the parameters generated by the model. The developed software may constitute an expert system supporting a milling machine operator. In addition, the application may be installed on a mobile device (smartphone, connected to a tool wear diagnostics instrument and the machine tool controller in order to supply updated optimal parameters of milling. The presented solution facilitates tool life optimisation and decreasing tool change costs, particularly during prolonged operation.

  11. Noise aspects at aerodynamic blade optimisation projects

    Energy Technology Data Exchange (ETDEWEB)

    Schepers, J.G. [Netherlands Energy Research Foundation, Petten (Netherlands)

    1997-12-31

    This paper shows an example of an aerodynamic blade optimisation, using the program PVOPT. PVOPT calculates the optimal wind turbine blade geometry such that the maximum energy yield is obtained. Using the aerodynamic optimal blade design as a basis, the possibilities of noise reduction are investigated. The aerodynamic optimised geometry from PVOPT is the `real` optimum (up to the latest decimal). The most important conclusion from this study is, that it is worthwhile to investigate the behaviour of the objective function (in the present case the energy yield) around the optimum: If the optimum is flat, there is a possibility to apply modifications to the optimum configuration with only a limited loss in energy yield. It is obvious that the modified configurations emits a different (and possibly lower) noise level. In the BLADOPT program (the successor of PVOPT) it will be possible to quantify the noise level and hence to assess the reduced noise emission more thoroughly. At present the most promising approaches for noise reduction are believed to be a reduction of the rotor speed (if at all possible), and a reduction of the tip angle by means of low lift profiles, or decreased twist at the outboard stations. These modifications were possible without a significant loss in energy yield. (LN)

  12. Immobilization of Electroporated Cells for Fabrication of Cellular Biosensors: Physiological Effects of the Shape of Calcium Alginate Matrices and Foetal Calf Serum

    Directory of Open Access Journals (Sweden)

    Nikos Katsanakis

    2009-01-01

    Full Text Available In order to investigate the physiological effect of transfected cell immobilization in calcium alginate gels, we immobilized electroporated Vero cells in gels shaped either as spherical beads or as thin membrane layers. In addition, we investigated whether serum addition had a positive effect on cell proliferation and viability in either gel configuration. The gels were stored for four weeks in a medium supplemented or not with 20% (v/v foetal calf serum. Throughout a culture period of four weeks, cell proliferation and cell viability were assayed by optical microscopy after provision of Trypan Blue. Non-elaborate culture conditions (room temperature, non-CO2 enriched culture atmosphere were applied throughout the experimental period in order to evaluate cell viability under less than optimal storage conditions. Immobilization of electroporated cells was associated with an initially reduced cell viability, which was gradually increased. Immobilization was associated with maintenance of cell growth for the duration of the experimental period, whereas electroporated cells essentially died after a week in suspension culture. Considerable proliferation of immobilized cells was observed in spherical alginate beads. In both gel configurations, addition of serum was associated with increased cell proliferation. The results of the present study could contribute to an improvement of the storability of biosensors based on electroporated, genetically or membrane-engineered cells.

  13. Optimising polarised neutron scattering measurements--XYZ and polarimetry analysis

    International Nuclear Information System (INIS)

    Cussen, L.D.; Goossens, D.J.

    2002-01-01

    The analytic optimisation of neutron scattering measurements made using XYZ polarisation analysis and neutron polarimetry techniques is discussed. Expressions for the 'quality factor' and the optimum division of counting time for the XYZ technique are presented. For neutron polarimetry the optimisation is identified as analogous to that for measuring the flipping ratio and reference is made to the results already in the literature

  14. Optimising polarised neutron scattering measurements--XYZ and polarimetry analysis

    CERN Document Server

    Cussen, L D

    2002-01-01

    The analytic optimisation of neutron scattering measurements made using XYZ polarisation analysis and neutron polarimetry techniques is discussed. Expressions for the 'quality factor' and the optimum division of counting time for the XYZ technique are presented. For neutron polarimetry the optimisation is identified as analogous to that for measuring the flipping ratio and reference is made to the results already in the literature.

  15. Application of ant colony optimisation in distribution transformer sizing

    African Journals Online (AJOL)

    This study proposes an optimisation method for transformer sizing in power system using ant colony optimisation and a verification of the process by MATLAB software. The aim is to address the issue of transformer sizing which is a major challenge affecting its effective performance, longevity, huge capital cost and power ...

  16. Multi-objective evolutionary optimisation for product design and manufacturing

    CERN Document Server

    2011-01-01

    Presents state-of-the-art research in the area of multi-objective evolutionary optimisation for integrated product design and manufacturing Provides a comprehensive review of the literature Gives in-depth descriptions of recently developed innovative and novel methodologies, algorithms and systems in the area of modelling, simulation and optimisation

  17. Design Optimisation and Conrol of a Pilot Operated Seat Valve

    DEFF Research Database (Denmark)

    Nielsen, Brian; Andersen, Torben Ole; Hansen, Michael Rygaard

    2004-01-01

    The paper gives an approach for optimisation of the bandwidth of a pilot operated seat valve for mobile applications. Physical dimensions as well as parameters of the implemented control loop are optimised simultaneously. The frequency response of the valve varies as a function of the pressure drop...

  18. DACIA LOGAN LIVE AXLE OPTIMISATION USING COMPUTER GRAPHICS

    Directory of Open Access Journals (Sweden)

    KIRALY Andrei

    2017-05-01

    Full Text Available The paper presents some contributions to the calculus and optimisation of a live axle used at Dacia Logan using computer graphics software for creating the model and afterwards using FEA evaluation to determine the effectiveness of the optimisation. Thus using specialized computer software, a simulation is made and the results were compared to the measured real prototype.

  19. Spatial-structural interaction and strain energy structural optimisation

    NARCIS (Netherlands)

    Hofmeyer, H.; Davila Delgado, J.M.; Borrmann, A.; Geyer, P.; Rafiq, Y.; Wilde, de P.

    2012-01-01

    A research engine iteratively transforms spatial designs into structural designs and vice versa. Furthermore, spatial and structural designs are optimised. It is suggested to optimise a structural design by evaluating the strain energy of its elements and by then removing, adding, or changing the

  20. Adjoint Optimisation of the Turbulent Flow in an Annular Diffuser

    DEFF Research Database (Denmark)

    Gotfredsen, Erik; Agular Knudsen, Christian; Kunoy, Jens Dahl

    2017-01-01

    In the present study, a numerical optimisation of guide vanes in an annular diffuser, is performed. The optimisation is preformed for the purpose of improving the following two parameters simultaneously; the first parameter is the uniformity perpen-dicular to the flow direction, a 1/3 diameter do...

  1. Optimising of Steel Fiber Reinforced Concrete Mix Design | Beddar ...

    African Journals Online (AJOL)

    Optimising of Steel Fiber Reinforced Concrete Mix Design. ... as a result of the loss of mixture workability that will be translated into a difficult concrete casting in site. ... An experimental study of an optimisation method of fibres in reinforced ...

  2. GAOS: Spatial optimisation of crop and nature within agricultural fields

    NARCIS (Netherlands)

    Bruin, de S.; Janssen, H.; Klompe, A.; Lerink, P.; Vanmeulebrouk, B.

    2010-01-01

    This paper proposes and demonstrates a spatial optimiser that allocates areas of inefficient machine manoeuvring to field margins thus improving the use of available space and supporting map-based Controlled Traffic Farming. A prototype web service (GAOS) allows farmers to optimise tracks within

  3. Selective effect of irreversible electroporation on parenchyma of the pancreas and its vascular structures - an in vivo experiment on a porcine model

    Directory of Open Access Journals (Sweden)

    Roman Svatoň

    2016-01-01

    Full Text Available Irreversible electroporation is a local, non-thermal ablation method, where short electrical pulses of high voltage lead to changes in cell membrane permeability and cell death. Recent experimental studies have shown that it does not lead to damage of blood vessels, nerves, bile duct or ureters. The aim of our experimental study was to evaluate the negative effect of irreversible electroporation regarding damage to the vascular wall and porcine pancreatic tissue. Irreversible electroporation of the pancreas was performed in 6 pigs after medial laparotomy. Irreversible electroporation was applied to each pig to the splenic lobe of the pancreas in order to assess damage to the pancreatic tissue and to the duodenal lobe of the pancreas to assess damage to the vascular structure of the pancreatic tissue. Higher ablation electric intensity (minimum 500 V/cm – maximum 1,750 V/cm, step 250 V/cm in 90 μs pulses was utilized on each pig. After 7 days, macroscopic and microscopic evaluations of en bloc resected specimen (pancreas with duodenum were performed. During 7 post-ablation days, no deaths or clinical worsening occurred in any of the pigs. Necrotic changes in the pancreatic tissue were recorded at an electric intensity of 750 V/cm. Changes in the outer layers of the wall of the arteries and veins occurred at 1,000 V/cm. Transmural vascular wall damage was not recorded in any case. Irreversible electroporation allows for relatively efficient cell death in the target tissues. Our independent experimental work confirms the safety of this method towards vascular structures located in the ablation zone.

  4. Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy – spatial and time dependent distribution

    Directory of Open Access Journals (Sweden)

    Dachs Gabi U

    2004-11-01

    Full Text Available Abstract Background Electroporation is currently receiving much attention as a way to increase drug and DNA delivery. Recent studies demonstrated the feasibility of electrogene therapy using a range of therapeutic genes for the treatment of experimental tumors. However, the transfection efficiency of electroporation-assisted DNA delivery is still low compared to viral methods and there is a clear need to optimize this approach. In order to optimize treatment, knowledge about spatial and time dependency of gene expression following delivery is of utmost importance in order to improve gene delivery. Intravital microscopy of tumors growing in dorsal skin fold window chambers is a useful method for monitoring gene transfection, since it allows non-invasive dynamic monitoring of gene expression in tumors in a live animal. Methods Intravital microscopy was used to monitor real time spatial distribution of the green fluorescent protein (GFP and time dependence of transfection efficiency in syngeneic P22 rat tumor model. DNA alone, liposome-DNA complexes and electroporation-assisted DNA delivery using two different sets of electric pulse parameters were compared. Results Electroporation-assisted DNA delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz was superior to other methods and resulted in 22% increase in fluorescence intensity in the tumors up to 6 days post-transfection, compared to the non-transfected area in granulation tissue. Functional GFP was detected within 5 h after transfection. Cells expressing GFP were detected throughout the tumor, but not in the surrounding tissue that was not exposed to electric pulses. Conclusions Intravital microscopy was demonstrated to be a suitable method for monitoring time and spatial distribution of gene expression in experimental tumors and provided evidence that electroporation-assisted gene delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz is an effective method, resulting in early onset and homogenous

  5. Direct visualization of electroporation-assisted in vivo gene delivery to tumors using intravital microscopy – spatial and time dependent distribution

    International Nuclear Information System (INIS)

    Cemazar, Maja; Wilson, Ian; Dachs, Gabi U; Tozer, Gillian M; Sersa, Gregor

    2004-01-01

    Electroporation is currently receiving much attention as a way to increase drug and DNA delivery. Recent studies demonstrated the feasibility of electrogene therapy using a range of therapeutic genes for the treatment of experimental tumors. However, the transfection efficiency of electroporation-assisted DNA delivery is still low compared to viral methods and there is a clear need to optimize this approach. In order to optimize treatment, knowledge about spatial and time dependency of gene expression following delivery is of utmost importance in order to improve gene delivery. Intravital microscopy of tumors growing in dorsal skin fold window chambers is a useful method for monitoring gene transfection, since it allows non-invasive dynamic monitoring of gene expression in tumors in a live animal. Intravital microscopy was used to monitor real time spatial distribution of the green fluorescent protein (GFP) and time dependence of transfection efficiency in syngeneic P22 rat tumor model. DNA alone, liposome-DNA complexes and electroporation-assisted DNA delivery using two different sets of electric pulse parameters were compared. Electroporation-assisted DNA delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz was superior to other methods and resulted in 22% increase in fluorescence intensity in the tumors up to 6 days post-transfection, compared to the non-transfected area in granulation tissue. Functional GFP was detected within 5 h after transfection. Cells expressing GFP were detected throughout the tumor, but not in the surrounding tissue that was not exposed to electric pulses. Intravital microscopy was demonstrated to be a suitable method for monitoring time and spatial distribution of gene expression in experimental tumors and provided evidence that electroporation-assisted gene delivery using 8 pulses, 600 V/cm, 5 ms, 1 Hz is an effective method, resulting in early onset and homogenous distribution of gene expression in the syngeneic P22 rat tumor model

  6. Modified cuckoo search: A new gradient free optimisation algorithm

    International Nuclear Information System (INIS)

    Walton, S.; Hassan, O.; Morgan, K.; Brown, M.R.

    2011-01-01

    Highlights: → Modified cuckoo search (MCS) is a new gradient free optimisation algorithm. → MCS shows a high convergence rate, able to outperform other optimisers. → MCS is particularly strong at high dimension objective functions. → MCS performs well when applied to engineering problems. - Abstract: A new robust optimisation algorithm, which can be regarded as a modification of the recently developed cuckoo search, is presented. The modification involves the addition of information exchange between the top eggs, or the best solutions. Standard optimisation benchmarking functions are used to test the effects of these modifications and it is demonstrated that, in most cases, the modified cuckoo search performs as well as, or better than, the standard cuckoo search, a particle swarm optimiser, and a differential evolution strategy. In particular the modified cuckoo search shows a high convergence rate to the true global minimum even at high numbers of dimensions.

  7. Results of the 2010 IGSC Topical Session on Optimisation

    International Nuclear Information System (INIS)

    Bailey, Lucy

    2014-01-01

    Document available in abstract form only. Full text follows: The 2010 IGSC topical session on optimisation explored a wide range of issues concerning optimisation throughout the radioactive waste management process. Philosophical and ethical questions were discussed, such as: - To what extent is the process of optimisation more important than the end result? - How do we balance long-term environmental safety with near-term operational safety? - For how long should options be kept open? - In balancing safety and excessive cost, when is BAT achieved and who decides on this? * How should we balance the needs of current society with those of future generations? It was clear that optimisation is about getting the right balance between a range of issues that cover: radiation protection, environmental protection, operational safety, operational requirements, social expectations and cost. The optimisation process will also need to respect various constraints, which are likely to include: regulatory requirements, site restrictions, community-imposed requirements or restrictions and resource constraints. These issues were explored through a number of presentations that discussed practical cases of optimisation occurring at different stages of international radioactive waste management programmes. These covered: - Operations and decommissioning - management of large disused components, from the findings of an international study, presented by WPDD; - Concept option selection, prior to site selection - upstream and disposal system optioneering in the UK; - Siting decisions - examples from both Germany and France, explaining how optimisation is being used to support site comparisons and communicate siting decisions; - Repository design decisions - comparison of KBS-3 horizontal and vertical deposition options in Finland; and - On-going optimisation during repository operation - operational experience from WIPP in the US. The variety of the remarks and views expressed during the

  8. Work management to optimise occupational radiological protection

    International Nuclear Information System (INIS)

    Ahier, B.

    2009-01-01

    Although work management is no longer a new concept, continued efforts are still needed to ensure that good performance, outcomes and trends are maintained in the face of current and future challenges. The ISOE programme thus created an Expert Group on Work Management in 2007 to develop an updated report reflecting the current state of knowledge, technology and experience in the occupational radiological protection of workers at nuclear power plants. Published in 2009, the new ISOE report on Work Management to Optimise Occupational Radiological Protection in the Nuclear Power Industry provides up-to-date practical guidance on the application of work management principles. Work management measures aim at optimising occupational radiological protection in the context of the economic viability of the installation. Important factors in this respect are measures and techniques influencing i) dose and dose rate, including source- term reduction; ii) exposure, including amount of time spent in controlled areas for operations; and iii) efficiency in short- and long-term planning, worker involvement, coordination and training. Equally important due to their broad, cross-cutting nature are the motivational and organisational arrangements adopted. The responsibility for these aspects may reside in various parts of an installation's organisational structure, and thus, a multi-disciplinary approach must be recognised, accounted for and well-integrated in any work. Based on the operational experience within the ISOE programme, the following key areas of work management have been identified: - regulatory aspects; - ALARA management policy; - worker involvement and performance; - work planning and scheduling; - work preparation; - work implementation; - work assessment and feedback; - ensuring continuous improvement. The details of each of these areas are elaborated and illustrated in the report through examples and case studies arising from ISOE experience. They are intended to

  9. A comparison of forward planning and optimised inverse planning

    International Nuclear Information System (INIS)

    Oldham, Mark; Neal, Anthony; Webb, Steve

    1995-01-01

    A radiotherapy treatment plan optimisation algorithm has been applied to 48 prostate plans and the results compared with those of an experienced human planner. Twelve patients were used in the study, and a 3, 4, 6 and 8 field plan (with standard coplanar beam angles for each plan type) were optimised by both the human planner and the optimisation algorithm. The human planner 'optimised' the plan by conventional forward planning techniques. The optimisation algorithm was based on fast-simulated-annealing. 'Importance factors' assigned to different regions of the patient provide a method for controlling the algorithm, and it was found that the same values gave good results for almost all plans. The plans were compared on the basis of dose statistics and normal-tissue-complication-probability (NTCP) and tumour-control-probability (TCP). The results show that the optimisation algorithm yielded results that were at least as good as the human planner for all plan types, and on the whole slightly better. A study of the beam-weights chosen by the optimisation algorithm and the planner will be presented. The optimisation algorithm showed greater variation, in response to individual patient geometry. For simple (e.g. 3 field) plans it was found to consistently achieve slightly higher TCP and lower NTCP values. For more complicated (e.g. 8 fields) plans the optimisation also achieved slightly better results with generally less numbers of beams. The optimisation time was always ≤5 minutes; a factor of up to 20 times faster than the human planner

  10. Automatic optimisation of gamma dose rate sensor networks: The DETECT Optimisation Tool

    DEFF Research Database (Denmark)

    Helle, K.B.; Müller, T.O.; Astrup, Poul

    2014-01-01

    of the EU FP 7 project DETECT. It evaluates the gamma dose rates that a proposed set of sensors might measure in an emergency and uses this information to optimise the sensor locations. The gamma dose rates are taken from a comprehensive library of simulations of atmospheric radioactive plumes from 64......Fast delivery of comprehensive information on the radiological situation is essential for decision-making in nuclear emergencies. Most national radiological agencies in Europe employ gamma dose rate sensor networks to monitor radioactive pollution of the atmosphere. Sensor locations were often...... source locations. These simulations cover the whole European Union, so the DOT allows evaluation and optimisation of sensor networks for all EU countries, as well as evaluation of fencing sensors around possible sources. Users can choose from seven cost functions to evaluate the capability of a given...

  11. VEHICLE DRIVING CYCLE OPTIMISATION ON THE HIGHWAY

    Directory of Open Access Journals (Sweden)

    Zinoviy STOTSKO

    2016-06-01

    Full Text Available This paper is devoted to the problem of reducing vehicle energy consumption. The authors consider the optimisation of highway driving cycle a way to use the kinetic energy of a car more effectively at various road conditions. The model of a vehicle driving control at the highway which consists of elementary cycles, such as accelerating, free rolling and deceleration under forces of external resistance, was designed. Braking, as an energy dissipation regime, was not included. The influence of the various longitudinal profiles of the road was taken into consideration and included in the model. Ways to use the results of monitoring road and traffic conditions are presented. The method of non-linear programming is used to design the optimal vehicle control function and phase trajectory. The results are presented by improved typical driving cycles that present energy saving as a subject of choice at a specified schedule.

  12. Optimisation algorithms for ECG data compression.

    Science.gov (United States)

    Haugland, D; Heber, J G; Husøy, J H

    1997-07-01

    The use of exact optimisation algorithms for compressing digital electrocardiograms (ECGs) is demonstrated. As opposed to traditional time-domain methods, which use heuristics to select a small subset of representative signal samples, the problem of selecting the subset is formulated in rigorous mathematical terms. This approach makes it possible to derive algorithms guaranteeing the smallest possible reconstruction error when a bounded selection of signal samples is interpolated. The proposed model resembles well-known network models and is solved by a cubic dynamic programming algorithm. When applied to standard test problems, the algorithm produces a compressed representation for which the distortion is about one-half of that obtained by traditional time-domain compression techniques at reasonable compression ratios. This illustrates that, in terms of the accuracy of decoded signals, existing time-domain heuristics for ECG compression may be far from what is theoretically achievable. The paper is an attempt to bridge this gap.

  13. Optimisation and constraints - a view from ICRP

    International Nuclear Information System (INIS)

    Dunster, H.J.

    1994-01-01

    The optimisation of protection has been the major policy underlying the recommendations of the International Commission on Radiological Protection for more than 20 years. In earlier forms, the concept can be traced back to 1951. Constraints are more recent, appearing in their present form only in the 1990 recommendations of the Commission. The requirement to keep all exposures as low as reasonably achievable applies to both normal and potential exposures. The policy and the techniques are well established for normal exposures, i.e. exposures that are certain to occur. The application to potential exposures, i.e. exposures that have a probability of occurring that is less than unity, is more difficult and is still under international discussion. Constraints are needed to limit the inequity associated with the use of collective dose in cost-benefit analysis and to provide a margin to protect individuals who may be exposed to more than one source. (author)

  14. Optimising Impact in Astronomy for Development Projects

    Science.gov (United States)

    Grant, Eli

    2015-08-01

    Positive outcomes in the fields of science education and international development are notoriously difficult to achieve. Among the challenges facing projects that use astronomy to improve education and socio-economic development is how to optimise project design in order to achieve the greatest possible benefits. Over the past century, medical scientists along with statisticians and economists have progressed an increasingly sophisticated and scientific approach to designing, testing and improving social intervention and public health education strategies. This talk offers a brief review of the history and current state of `intervention science'. A similar framework is then proposed for astronomy outreach and education projects, with applied examples given of how existing evidence can be used to inform project design, predict and estimate cost-effectiveness, minimise the risk of unintended negative consequences and increase the likelihood of target outcomes being achieved.

  15. Optimisation of Multilayer Insulation an Engineering Approach

    CERN Document Server

    Chorowski, M; Parente, C; Riddone, G

    2001-01-01

    A mathematical model has been developed to describe the heat flux through multilayer insulation (MLI). The total heat flux between the layers is the result of three distinct heat transfer modes: radiation, residual gas conduction and solid spacer conduction. The model describes the MLI behaviour considering a layer-to-layer approach and is based on an electrical analogy, in which the three heat transfer modes are treated as parallel thermal impedances. The values of each of the transfer mode vary from layer to layer, although the total heat flux remains constant across the whole MLI blanket. The model enables the optimisation of the insulation with regard to different MLI parameters, such as residual gas pressure, number of layers and boundary temperatures. The model has been tested with experimental measurements carried out at CERN and the results revealed to be in a good agreement, especially for insulation vacuum between 10-5 Pa and 10-3 Pa.

  16. Public transport optimisation emphasising passengers’ travel behaviour

    DEFF Research Database (Denmark)

    Jensen, Jens Parbo

    to the case where the two problems are solved sequentially without taking into account interdependencies. Figure 1 - Planning public transport The PhD study develops a metaheuristic algorithm to adapt the line plan configuration in order better to match passengers’ travel demand in terms of transfers as well......Passengers in public transport complaining about their travel experiences are not uncommon. This might seem counterintuitive since several operators worldwide are presenting better key performance indicators year by year. The present PhD study focuses on developing optimisation algorithms...... to enhance the operations of public transport while explicitly emphasising passengers’ travel behaviour and preferences. Similar to economic theory, interactions between supply and demand are omnipresent in the context of public transport operations. In public transport, the demand is represented...

  17. Value Chain Optimisation of Biogas Production

    DEFF Research Database (Denmark)

    Jensen, Ida Græsted

    economically feasible. In this PhD thesis, the focus is to create models for investigating the profitability of biogas projects by: 1) including the whole value chain in a mathematical model and considering mass and energy changes on the upstream part of the chain; and 2) including profit allocation in a value......, the costs on the biogas plant has been included in the model using economy of scale. For the second point, a mathematical model considering profit allocation was developed applying three allocation mechanisms. This mathematical model can be applied as a second step after the value chain optimisation. After...... in the energy systems model to find the optimal end use of each type of gas and fuel. The main contributions of this thesis are the methods developed on plant level. Both the mathematical model for the value chain and the profit allocation model can be generalised and used in other industries where mass...

  18. Expect systems and optimisation in process control

    Energy Technology Data Exchange (ETDEWEB)

    Mamdani, A.; Efstathiou, J. (eds.)

    1986-01-01

    This report brings together recent developments both in expert systems and in optimisation, and deals with current applications in industry. Part One is concerned with Artificial Intellegence in planning and scheduling and with rule-based control implementation. The tasks of control maintenance, rescheduling and planning are each discussed in relation to new theoretical developments, techniques available, and sample applications. Part Two covers model based control techniques in which the control decisions are used in a computer model of the process. Fault diagnosis, maintenance and trouble-shooting are just some of the activities covered. Part Three contains case studies of projects currently in progress, giving details of the software available and the likely future trends. One of these, on qualitative plant modelling as a basis for knowledge-based operator aids in nuclear power stations is indexed separately.

  19. Expert systems and optimisation in process control

    International Nuclear Information System (INIS)

    Mamdani, A.; Efstathiou, J.

    1986-01-01

    This report brings together recent developments both in expert systems and in optimisation, and deals with current applications in industry. Part One is concerned with Artificial Intellegence in planning and scheduling and with rule-based control implementation. The tasks of control maintenance, rescheduling and planning are each discussed in relation to new theoretical developments, techniques available, and sample applications. Part Two covers model based control techniques in which the control decisions are used in a computer model of the process. Fault diagnosis, maintenance and trouble-shooting are just some of the activities covered. Part Three contains case studies of projects currently in progress, giving details of the software available and the likely future trends. One of these, on qualitative plant modelling as a basis for knowledge-based operator aids in nuclear power stations is indexed separately. (author)

  20. Improving and optimising road pricing in Copenhagen

    DEFF Research Database (Denmark)

    Nielsen, Otto Anker; Larsen, Marie Karen

    2008-01-01

    though quite a number of proposed charging systems have been examined only a few pricing strategies have been investigated. This paper deals with the optimisation of different designs for a road pricing system in the Greater Copenhagen area with respect to temporal and spatial differentiation......The question whether to introduce toll rings or road pricing in Copenhagen has been discussed intensively during the last 10 years. The main results of previous analyses are that none of the systems would make a positive contribution at present, when considered from a socio-economic view. Even...... of the pricing levels. A detailed transport model was used to describe the demand effects. The model was based on data from a real test of road pricing on 500 car drivers. The paper compares the price systems with regard to traffic effects and generalised costs for users and society. It is shown how important...

  1. A code for optimising triplet layout

    CERN Document Server

    AUTHOR|(CDS)2141109; Seryi, Andrei; Abelleira, Jose; Cruz Alaniz, Emilia

    2017-01-01

    One of the main challenges when designing final focus systems of particle accelerators is maximising the beam stay clear in the strong quadrupole magnets of the inner triplet. Moreover it is desirable to keep the quadrupoles in the inner triplet as short as possible for space and costs reasons but also to reduce chromaticity and simplify corrections schemes. An algorithm that explores the triplet parameter space to optimise both these aspects was written. It uses thin lenses as a first approximation for a broad parameter scan and MADX for more precise calculations. The thin lens algorithm is significantly faster than a full scan using MADX and relatively precise at indicating the approximate area where the optimum solution lies.

  2. Optimising Signalised Intersection Using Wireless Vehicle Detectors

    DEFF Research Database (Denmark)

    Adjin, Daniel Michael Okwabi; Torkudzor, Moses; Asare, Jack

    Traffic congestion on roads wastes travel times. In this paper, we developed a vehicular traffic model to optimise a signalised intersection in Accra, using wireless vehicle detectors. Traffic volume gathered was extrapolated to cover 2011 and 2016 and were analysed to obtain the peak hour traffic...... volume causing congestion. The intersection was modelled and simulated in Synchro7 as an actuated signalised model using results from the analysed data. The model for morning peak periods gave optimal cycle lengths of 100s and 150s with corresponding intersection delay of 48.9s and 90.6s in 2011 and 2016...... respectively while that for the evening was 55s giving delay of 14.2s and 16.3s respectively. It is shown that the model will improve traffic flow at the intersection....

  3. Dynamic optimisation of an industrial web process

    Directory of Open Access Journals (Sweden)

    M Soufian

    2008-09-01

    Full Text Available An industrial web process has been studied and it is shown that theunderlying physics of such processes governs by the Navier-Stokes partialdifferential equations with moving boundary conditions, which in turn have tobe determined by the solution of the thermodynamics equations. Thedevelopment of a two-dimensional continuous-discrete model structurebased on this study is presented. Other models are constructed based onthis model for better identification and optimisation purposes. Theparameters of the proposed models are then estimated using real dataobtained from the identification experiments with the process plant. Varioussimulation tests for validation are accompanied with the design, developmentand real-time industrial implementation of an optimal controller for dynamicoptimisation of this web process. It is shown that in comparison with thetraditional controller, the new controller resulted in a better performance, animprovement in film quality and saving in raw materials. This demonstrates theefficiency and validation of the developed models.

  4. Recent perspectives on optimisation of radiological protection

    International Nuclear Information System (INIS)

    Robb, J.D.; Croft, J.R.

    1992-01-01

    The ALARA principle as a requirement in radiological protection has evolved from its theoretical roots. Based on several years work, this paper provides a backdrop to practical approaches to ALARA for the 1990s. The key step, developing ALARA thinking so that it becomes an integral part of radiological protection programmes, is discussed using examples from the UK and France, as is the role of tools to help standardise judgements for decision-making. In its latest recommendations, ICRP have suggested that the optimisation of protection should be constrained by restrictions on the doses to individuals. This paper also considers the function of such restrictions for occupational, public and medical exposure, and in the design process. (author)

  5. Optimisation of parameters of DCD for PHWRs

    International Nuclear Information System (INIS)

    Velmurugan, S.; Sathyaseelan, V.S.; Narasimhan, S.V.; Mathur, P.K.

    1991-01-01

    Decontamination formulation based on EDTA, Oxalic acid, Citric acid was evaluated for its efficacy in removing oxide layers of PHWR. An ion exchange system which was specifically suitable for fission product dominated contamination in PHWRs was optimised for the reagent regeneration stage of the decontamination process. An analysis of the nature of the complexed metal species formed in the dissolution process and Electrochemical measurements were employed as a tool to follow the course of oxide removal during the dissolution process. An attempt was made to understand the redeposition behaviour of various isotopes during the decontamination process. SEM and ESCA studies of metal coupons before and after the dissolution process were used to analyse the deposits in the above context. The pick up of DCD reagents on the ion exchangers and material compatibility tests on Carbon steel, Monel-400 and Zircaloy-2 with the decontaminant under the conditions of decontamination experiment are reported. (author)

  6. Optimisation of Inulinase Production by Kluyveromyces bulgaricus

    Directory of Open Access Journals (Sweden)

    Darija Vranešić

    2002-01-01

    Full Text Available The present work is based on observation of the effects of pH and temperature of fermentation on the production of microbial enzyme inulinase by Kluyveromyces marxianus var. bulgaricus. Inulinase hydrolyzes inulin, a polysaccharide which can be isolated from plants such as Jerusalem artichoke, chicory or dahlia, and transformed into pure fructose or fructooligosaccharides. Fructooligosaccharides have great potential in food industry because they can be used as calorie-reduced compounds and noncariogenic sweeteners as well as soluble fibre and prebiotic compounds. Fructose formation from inulin is a single step enzymatic reaction and yields are up to 95 % the fructose. On the contrary, conventional fructose production from starch needs at least three enzymatic steps, yielding only 45 % of fructose. The process of inulinase production was optimised by using experimental design method. pH value of the cultivation medium showed to be the most significant variable and it should be maintained at optimum value of 3.6. The effect of temperature was slightly lower and optimal values were between 30 and 33 °C. At a low pH value of the cultivation medium, the microorganism was not able to producem enough enzyme and enzyme activities were low. Similar effect was caused by high temperature. The highest values of enzyme activities were achieved at optimal fermentation conditions and the values were: 100.16–124.36 IU/mL (with sucrose as substrate for determination of enzyme activity or 8.6–11.6 IU/mL (with inulin as substrate, respectively. The method of factorial design and response surface analysis makes it possible to study several factors simultaneously, to quantify the individual effect of each factor and to investigate their possible interactions. As a comparison to this method, optimisation of a physiological enzyme activity model depending on pH and temperature was also studied.

  7. Optimisation on processing parameters for minimising warpage on side arm using response surface methodology (RSM) and particle swarm optimisation (PSO)

    Science.gov (United States)

    Rayhana, N.; Fathullah, M.; Shayfull, Z.; Nasir, S. M.; Hazwan, M. H. M.; Sazli, M.; Yahya, Z. R.

    2017-09-01

    This study presents the application of optimisation method to reduce the warpage of side arm part. Autodesk Moldflow Insight software was integrated into this study to analyse the warpage. The design of Experiment (DOE) for Response Surface Methodology (RSM) was constructed and by using the equation from RSM, Particle Swarm Optimisation (PSO) was applied. The optimisation method will result in optimised processing parameters with minimum warpage. Mould temperature, melt temperature, packing pressure, packing time and cooling time was selected as the variable parameters. Parameters selection was based on most significant factor affecting warpage stated by previous researchers. The results show that warpage was improved by 28.16% for RSM and 28.17% for PSO. The warpage improvement in PSO from RSM is only by 0.01 %. Thus, the optimisation using RSM is already efficient to give the best combination parameters and optimum warpage value for side arm part. The most significant parameters affecting warpage are packing pressure.

  8. Percutaneous Irreversible Electroporation of a Large Centrally Located Hepatocellular Adenoma in a Woman with a Pregnancy Wish

    Energy Technology Data Exchange (ETDEWEB)

    Scheffer, Hester J., E-mail: hj.scheffer@vumc.nl; Melenhorst, Marleen C. A. M., E-mail: m.melenhorst@vumc.nl; Tilborg, Aukje A. J. M. van, E-mail: a.vantilborg@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands); Nielsen, Karin, E-mail: k.nielsen@vumc.nl [Department of Surgery (Netherlands); Nieuwkerk, Karin M. van, E-mail: cmj.vannieuwkerk@vumc.nl; Vries, Richard A. de, E-mail: ra.devries@vumc.nl [VU University Medical Center, Department of Gastroenterology and Hepatology (Netherlands); Tol, Petrousjka van den [Department of Surgery (Netherlands); Meijerink, Martijn R., E-mail: mr.meijerink@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands)

    2015-08-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant liver tumors located near large vessels or bile ducts. We describe a 28-year-old female patient with a 5 cm large, centrally located hepatocellular adenoma who wished to get pregnant. Regarding the risk of growth and rupture of the adenoma caused by hormonal changes during pregnancy, treatment of the tumor was advised prior to pregnancy. However, due to its central location, the tumor was considered unsuitable for resection and thermal ablation. Percutaneous CT-guided IRE was performed without complications and led to rapid and impressive tumor shrinkage. Subsequent pregnancy and delivery went uncomplicated. This case report suggests that the indication for IRE may extend to the treatment of benign liver tumors that cannot be treated safely otherwise.

  9. Percutaneous Irreversible Electroporation of a Large Centrally Located Hepatocellular Adenoma in a Woman with a Pregnancy Wish

    International Nuclear Information System (INIS)

    Scheffer, Hester J.; Melenhorst, Marleen C. A. M.; Tilborg, Aukje A. J. M. van; Nielsen, Karin; Nieuwkerk, Karin M. van; Vries, Richard A. de; Tol, Petrousjka van den; Meijerink, Martijn R.

    2015-01-01

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is rapidly gaining popularity in the treatment of malignant liver tumors located near large vessels or bile ducts. We describe a 28-year-old female patient with a 5 cm large, centrally located hepatocellular adenoma who wished to get pregnant. Regarding the risk of growth and rupture of the adenoma caused by hormonal changes during pregnancy, treatment of the tumor was advised prior to pregnancy. However, due to its central location, the tumor was considered unsuitable for resection and thermal ablation. Percutaneous CT-guided IRE was performed without complications and led to rapid and impressive tumor shrinkage. Subsequent pregnancy and delivery went uncomplicated. This case report suggests that the indication for IRE may extend to the treatment of benign liver tumors that cannot be treated safely otherwise

  10. Detecting electroporation by assessing the time constants in the exponential response of human skin to voltage controlled impulse electrical stimulation.

    Science.gov (United States)

    Bîrlea, Sinziana I; Corley, Gavin J; Bîrlea, Nicolae M; Breen, Paul P; Quondamatteo, Fabio; OLaighin, Gearóid

    2009-01-01

    We propose a new method for extracting the electrical properties of human skin based on the time constant analysis of its exponential response to impulse stimulation. As a result of this analysis an adjacent finding has arisen. We have found that stratum corneum electroporation can be detected using this analysis method. We have observed that a one time-constant model is appropriate for describing the electrical properties of human skin at low amplitude applied voltages (30V). Higher voltage amplitudes (>30V) have been proven to create pores in the skin's stratum corneum which offer a new, lower resistance, pathway for the passage of current through the skin. Our data shows that when pores are formed in the stratum corneum they can be detected, in-vivo, due to the fact that a second time constant describes current flow through them.

  11. An "Off-the-Shelf" System for Intraprocedural Electrical Current Evaluation and Monitoring of Irreversible Electroporation Therapy.

    Science.gov (United States)

    Neal, Robert E; Kavnoudias, Helen; Thomson, Kenneth R

    2015-06-01

    Irreversible electroporation (IRE) ablation uses a series of brief electric pulses to create nanoscale defects in cell membranes, killing the cells. It has shown promise in numerous soft-tissue tumor applications. Larger voltages between electrodes will increase ablation volume, but exceeding electrical limits may risk damage to the patient, cause ineffective therapy delivery, or require generator restart. Monitoring electrical current for these conditions in real-time enables managing these risks. This capacity is not presently available in clinical IRE generators. We describe a system using a Tektronix TCP305 AC/DC Current Probe connected to a TCPA300 AC/DC Current Probe Amplifier, which is read on a computer using a Protek DSO-2090 USB computer-interfacing oscilloscope. Accuracy of the system was tested with a resistor circuit and by comparing measured currents with final outputs from the NanoKnife clinical electroporation pulse generator. Accuracy of measured currents was 1.64 ± 2.4 % relative to calculations for the resistor circuit and averaged 0.371 ± 0.977 % deviation from the NanoKnife. During clinical pulse delivery, the system offers real-time evaluation of IRE procedure progress and enables a number of methods for identifying approaching issues from electrical behavior of therapy delivery, facilitating protocol changes before encountering therapy delivery issues. This system can monitor electrical currents in real-time without altering the electric pulses or modifying the pulse generator. This facilitates delivering electric pulse protocols that remain within the optimal range of electrical currents-sufficient strength for clinically relevant ablation volumes, without the risk of exceeding safe electric currents or causing inadequate ablation.

  12. Development of plasmid vector and electroporation condition for gene transfer in sporogenic lactic acid bacterium, Bacillus coagulans.

    Science.gov (United States)

    Rhee, Mun Su; Kim, Jin-Woo; Qian, Yilei; Ingram, L O; Shanmugam, K T

    2007-07-01

    Bacillus coagulans is a sporogenic lactic acid bacterium that ferments glucose and xylose, major components of plant biomass, a potential feedstock for cellulosic ethanol. The temperature and pH for optimum rate of growth of B. coagulans (50 to 55 degrees C, pH 5.0) are very similar to that of commercially developed fungal cellulases (50 degrees C; pH 4.8). Due to this match, simultaneous saccharification and fermentation (SSF) of cellulose to products by B. coagulans is expected to require less cellulase than needed if the SSF is conducted at a sub-optimal temperature, such as 30 degrees C, the optimum for yeast, the main biocatalyst used by the ethanol industry. To fully exploit B. coagulans as a platform organism, we have developed an electroporation method to transfer plasmid DNA into this genetically recalcitrant bacterium. We also constructed a B. coagulans/E. coli shuttle vector, plasmid pMSR10 that contains the rep region from a native plasmid (pMSR0) present in B. coagulans strain P4-102B. The native plasmid, pMSR0 (6823bp), has 9 ORFs, and replicates by rolling-circle mode of replication. Plasmid pNW33N, developed for Geobacillus stearothermophilus, was also transformed into this host and stably maintained while several other Bacillus/Escherichia coli shuttle vector plasmids were not transformed into B. coagulans. The transformation efficiency of B. coagulans strain P4-102B using the plasmids pNW33N or pMSR10 was about 1.5x10(16) per mole of DNA. The availability of shuttle vectors and an electroporation method is expected to aid in genetic and metabolic engineering of B. coagulans.

  13. Evaluation of Soft Tissue Sarcoma Tumors Electrical Conductivity Anisotropy Using Diffusion Tensor Imaging for Numerical Modeling on Electroporation

    Directory of Open Access Journals (Sweden)

    Ghazikhanlou-sani K.

    2016-06-01

    Full Text Available Introduction: There is many ways to assessing the electrical conductivity anisotropy of a tumor. Applying the values of tissue electrical conductivity anisotropy is crucial in numerical modeling of the electric and thermal field distribution in electroporation treatments. This study aims to calculate the tissues electrical conductivity anisotropy in patients with sarcoma tumors using diffusion tensor imaging technique. Materials and Method: A total of 3 subjects were involved in this study. All of patients had clinically apparent sarcoma tumors at the extremities. The T1, T2 and DTI images were performed using a 3-Tesla multi-coil, multi-channel MRI system. The fractional anisotropy (FA maps were performed using the FSL (FMRI software library software regarding the DTI images. The 3D matrix of the FA maps of each area (tumor, normal soft tissue and bone/s was reconstructed and the anisotropy matrix was calculated regarding to the FA values. Result: The mean FA values in direction of main axis in sarcoma tumors were ranged between 0.475–0.690. With assumption of isotropy of the electrical conductivity, the FA value of electrical conductivity at each X, Y and Z coordinate axes would be equal to 0.577. The gathered results showed that there is a mean error band of 20% in electrical conductivity, if the electrical conductivity anisotropy not concluded at the calculations. The comparison of FA values showed that there is a significant statistical difference between the mean FA value of tumor and normal soft tissues (P<0.05. Conclusion: DTI is a feasible technique for the assessment of electrical conductivity anisotropy of tissues. It is crucial to quantify the electrical conductivity anisotropy data of tissues for numerical modeling of electroporation treatments.

  14. Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens.

    Directory of Open Access Journals (Sweden)

    Dominick J Laddy

    Full Text Available BACKGROUND: The persistent evolution of highly pathogenic avian influenza (HPAI highlights the need for novel vaccination techniques that can quickly and effectively respond to emerging viral threats. We evaluated the use of optimized consensus influenza antigens to provide broad protection against divergent strains of H5N1 influenza in three animal models of mice, ferrets, and non-human primates. We also evaluated the use of in vivo electroporation to deliver these vaccines to overcome the immunogenicity barrier encountered in larger animal models of vaccination. METHODS AND FINDINGS: Mice, ferrets and non-human primates were immunized with consensus plasmids expressing H5 hemagglutinin (pH5HA, N1 neuraminidase (pN1NA, and nucleoprotein antigen (pNP. Dramatic IFN-gamma-based cellular immune responses to both H5 and NP, largely dependent upon CD8+ T cells were seen in mice. Hemaggutination inhibition titers classically associated with protection (>1:40 were seen in all species. Responses in both ferrets and macaques demonstrate the ability of synthetic consensus antigens to induce antibodies capable of inhibiting divergent strains of the H5N1 subtype, and studies in the mouse and ferret demonstrate the ability of synthetic consensus vaccines to induce protection even in the absence of such neutralizing antibodies. After challenge, protection from morbidity and mortality was seen in mice and ferrets, with significant reductions in viral shedding and disease progression seen in vaccinated animals. CONCLUSIONS: By combining several consensus influenza antigens with in vivo electroporation, we demonstrate that these antigens induce both protective cellular and humoral immune responses in mice, ferrets and non-human primates. We also demonstrate the ability of these antigens to protect from both morbidity and mortality in a ferret model of HPAI, in both the presence and absence of neutralizing antibody, which will be critical in responding to the

  15. An “Off-the-Shelf” System for Intraprocedural Electrical Current Evaluation and Monitoring of Irreversible Electroporation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Neal, Robert E., E-mail: Robert.Neal@alfred.org.au; Kavnoudias, Helen; Thomson, Kenneth R. [The Alfred Hospital, Radiology Research Unit, Department of Radiology (Australia)

    2015-06-15

    IntroductionIrreversible electroporation (IRE) ablation uses a series of brief electric pulses to create nanoscale defects in cell membranes, killing the cells. It has shown promise in numerous soft-tissue tumor applications. Larger voltages between electrodes will increase ablation volume, but exceeding electrical limits may risk damage to the patient, cause ineffective therapy delivery, or require generator restart. Monitoring electrical current for these conditions in real-time enables managing these risks. This capacity is not presently available in clinical IRE generators.MethodsWe describe a system using a Tektronix TCP305 AC/DC Current Probe connected to a TCPA300 AC/DC Current Probe Amplifier, which is read on a computer using a Protek DSO-2090 USB computer-interfacing oscilloscope. Accuracy of the system was tested with a resistor circuit and by comparing measured currents with final outputs from the NanoKnife clinical electroporation pulse generator.ResultsAccuracy of measured currents was 1.64 ± 2.4 % relative to calculations for the resistor circuit and averaged 0.371 ± 0.977 % deviation from the NanoKnife. During clinical pulse delivery, the system offers real-time evaluation of IRE procedure progress and enables a number of methods for identifying approaching issues from electrical behavior of therapy delivery, facilitating protocol changes before encountering therapy delivery issues.ConclusionsThis system can monitor electrical currents in real-time without altering the electric pulses or modifying the pulse generator. This facilitates delivering electric pulse protocols that remain within the optimal range of electrical currents—sufficient strength for clinically relevant ablation volumes, without the risk of exceeding safe electric currents or causing inadequate ablation.

  16. Design optimisation of a flywheel hybrid vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Kok, D.B.

    1999-11-04

    This thesis describes the design optimisation of a flywheel hybrid vehicle with respect to fuel consumption and exhaust gas emissions. The driveline of this passenger car uses two power sources: a small spark ignition internal combustion engine with three-way catalyst, and a highspeed flywheel system for kinetic energy storage. A custom-made continuously variable transmission (CVT) with so-called i{sup 2} control transports energy between these power sources and the vehicle wheels. The driveline includes auxiliary systems for hydraulic, vacuum and electric purposes. In this fully mechanical driveline, parasitic energy losses determine the vehicle's fuel saving potential to a large extent. Practicable energy loss models have been derived to quantify friction losses in bearings, gearwheels, the CVT, clutches and dynamic seals. In addition, the aerodynamic drag in the flywheel system and power consumption of auxiliaries are charted. With the energy loss models available, a calculation procedure is introduced to optimise the flywheel as a subsystem in which the rotor geometry, the safety containment, and the vacuum system are designed for minimum energy use within the context of automotive applications. A first prototype of the flywheel system was tested experimentally and subsequently redesigned to improve rotordynamics and safety aspects. Coast-down experiments with the improved version show that the energy losses have been lowered significantly. The use of a kinetic energy storage device enables the uncoupling of vehicle wheel power and engine power. Therefore, the engine can be smaller and it can be chosen to operate in its region of best efficiency in start-stop mode. On a test-rig, the measured engine fuel consumption was reduced with more than 30 percent when the engine is intermittently restarted with the aid of the flywheel system. Although the start-stop mode proves to be advantageous for fuel consumption, exhaust gas emissions increase temporarily

  17. Profile control studies for JET optimised shear regime

    Energy Technology Data Exchange (ETDEWEB)

    Litaudon, X.; Becoulet, A.; Eriksson, L.G.; Fuchs, V.; Huysmans, G.; How, J.; Moreau, D.; Rochard, F.; Tresset, G.; Zwingmann, W. [Association Euratom-CEA, CEA/Cadarache, Dept. de Recherches sur la Fusion Controlee, DRFC, 13 - Saint-Paul-lez-Durance (France); Bayetti, P.; Joffrin, E.; Maget, P.; Mayorat, M.L.; Mazon, D.; Sarazin, Y. [JET Abingdon, Oxfordshire (United Kingdom); Voitsekhovitch, I. [Universite de Provence, LPIIM, Aix-Marseille 1, 13 (France)

    2000-03-01

    This report summarises the profile control studies, i.e. preparation and analysis of JET Optimised Shear plasmas, carried out during the year 1999 within the framework of the Task-Agreement (RF/CEA/02) between JET and the Association Euratom-CEA/Cadarache. We report on our participation in the preparation of the JET Optimised Shear experiments together with their comprehensive analyses and the modelling. Emphasis is put on the various aspects of pressure profile control (core and edge pressure) together with detailed studies of current profile control by non-inductive means, in the prospects of achieving steady, high performance, Optimised Shear plasmas. (authors)

  18. Weight Optimisation of Steel Monopile Foundations for Offshore Windfarms

    DEFF Research Database (Denmark)

    Fog Gjersøe, Nils; Bouvin Pedersen, Erik; Kristensen, Brian

    2015-01-01

    The potential for mass reduction of monopiles in offshore windfarms using current design practice is investigated. Optimisation by sensitivity analysis is carried out for the following important parameters: wall thickness distribution between tower and monopile, soil stiffness, damping ratio...

  19. Protection against natural radiation: Optimisation and decision exercises

    International Nuclear Information System (INIS)

    O'Riordan, M.C.

    1984-02-01

    Six easy exercises are presented in which cost-benefit analysis is used to optimise protection against natural radiation or to decide whether protection is appropriate. The exercises are illustrative only and do not commit the Board. (author)

  20. Optimisation of wheat-sprouted soybean flour bread using response ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-11-16

    Nov 16, 2009 ... Full Length Research Paper. Optimisation of ... Victoria A. Jideani1* and Felix C. Onwubali2. 1Department of Food Technology, Cape Peninsula University of Technology, P. O. Box 652, Cape Town 8000, South. Africa.

  1. Optimised intake stroke analysis for flat and dome head pistons ...

    African Journals Online (AJOL)

    Optimised intake stroke analysis for flat and dome head pistons. ... in understanding the performance characteristics optioned between flat head and dome head pistons in engine design. ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  2. Distributed optimisation problem with communication delay and external disturbance

    Science.gov (United States)

    Tran, Ngoc-Tu; Xiao, Jiang-Wen; Wang, Yan-Wu; Yang, Wu

    2017-12-01

    This paper investigates the distributed optimisation problem for the multi-agent systems (MASs) with the simultaneous presence of external disturbance and the communication delay. To solve this problem, a two-step design scheme is introduced. In the first step, based on the internal model principle, the internal model term is constructed to compensate the disturbance asymptotically. In the second step, a distributed optimisation algorithm is designed to solve the distributed optimisation problem based on the MASs with the simultaneous presence of disturbance and communication delay. Moreover, in the proposed algorithm, each agent interacts with its neighbours through the connected topology and the delay occurs during the information exchange. By utilising Lyapunov-Krasovskii functional, the delay-dependent conditions are derived for both slowly and fast time-varying delay, respectively, to ensure the convergence of the algorithm to the optimal solution of the optimisation problem. Several numerical simulation examples are provided to illustrate the effectiveness of the theoretical results.

  3. Shape optimisation and performance analysis of flapping wings

    KAUST Repository

    Ghommem, Mehdi; Collier, Nathan; Niemi, Antti; Calo, Victor M.

    2012-01-01

    optimised shapes produce efficient flapping flights, the wake pattern and its vorticity strength are examined. This work described in this paper should facilitate better guidance for shape design of engineered flying systems.

  4. Share-of-Surplus Product Line Optimisation with Price Levels

    Directory of Open Access Journals (Sweden)

    X. G. Luo

    2014-01-01

    Full Text Available Kraus and Yano (2003 established the share-of-surplus product line optimisation model and developed a heuristic procedure for this nonlinear mixed-integer optimisation model. In their model, price of a product is defined as a continuous decision variable. However, because product line optimisation is a planning process in the early stage of product development, pricing decisions usually are not very precise. In this research, a nonlinear integer programming share-of-surplus product line optimization model that allows the selection of candidate price levels for products is established. The model is further transformed into an equivalent linear mixed-integer optimisation model by applying linearisation techniques. Experimental results in different market scenarios show that the computation time of the transformed model is much less than that of the original model.

  5. Optimising a fall out dust monitoring sampling programme at a ...

    African Journals Online (AJOL)

    GREG

    Key words: Fall out dust monitoring, cement plant, optimising, air pollution sampling, fall out dust sampler locations. .... applied for those areas where controls are in place. Sampling ..... mass balance in the total cement manufacturing process.

  6. Issues with performance measures for dynamic multi-objective optimisation

    CSIR Research Space (South Africa)

    Helbig, M

    2013-06-01

    Full Text Available Symposium on Computational Intelligence in Dynamic and Uncertain Environments (CIDUE), Mexico, 20-23 June 2013 Issues with Performance Measures for Dynamic Multi-objective Optimisation Mard´e Helbig CSIR: Meraka Institute Brummeria, South Africa...

  7. Optimisation Study on the Production of Anaerobic Digestate ...

    African Journals Online (AJOL)

    DR. AMIN

    optimise the production of ADC from organic fractions of domestic wastes and the effects of ADC amendments on soil .... (22%), cooked meat (9%), lettuce (11%), carrots. (3%), potato (44%) ... seed was obtained from a mesophilic anaerobic.

  8. Algorithm for optimisation of paediatric chest radiography

    International Nuclear Information System (INIS)

    Kostova-Lefterova, D.

    2016-01-01

    The purpose of this work is to assess the current practice and patient doses in paediatric chest radiography in a large university hospital. The X-ray unit is used in the paediatric department for respiratory diseases. Another purpose was to recommend and apply optimized protocols to reduce patient dose while maintaining diagnostic image quality for the x-ray images. The practice of two different radiographers was studied. The results were compared with the existing practice in paediatric chest radiography and the opportunities for optimization were identified in order to reduce patient doses. A methodology was developed for optimization of the x-ray examinations by grouping children in age groups or according to other appropriate indication and creating an algorithm for proper selection of the exposure parameters for each group. The algorithm for the optimisation of paediatric chest radiography reduced patient doses (PKA, organ dose, effective dose) between 1.5 and 6 times for the different age groups, the average glandular dose up to 10 times and the dose for the lung between 2 and 5 times. The resulting X-ray images were of good diagnostic quality. The subjectivity in the choice of exposure parameters was reduced and standardization has been achieved in the work of the radiographers. The role of the radiologist, the medical physicist and radiographer in the process of optimization was shown. It was proven the effect of teamwork in reducing patient doses at keeping adequate image quality. Key words: Chest Radiography. Paediatric Radiography. Optimization. Radiation Exposure. Radiation Protection

  9. Optimising preterm nutrition: present and future

    LENUS (Irish Health Repository)

    Brennan, Ann-Marie

    2016-04-01

    The goal of preterm nutrition in achieving growth and body composition approximating that of the fetus of the same postmenstrual age is difficult to achieve. Current nutrition recommendations depend largely on expert opinion, due to lack of evidence, and are primarily birth weight based, with no consideration given to gestational age and\\/or need for catch-up growth. Assessment of growth is based predominately on anthropometry, which gives insufficient attention to the quality of growth. The present paper provides a review of the current literature on the nutritional management and assessment of growth in preterm infants. It explores several approaches that may be required to optimise nutrient intakes in preterm infants, such as personalising nutritional support, collection of nutrient intake data in real-time, and measurement of body composition. In clinical practice, the response to inappropriate nutrient intakes is delayed as the effects of under- or overnutrition are not immediate, and there is limited nutritional feedback at the cot-side. The accurate and non-invasive measurement of infant body composition, assessed by means of air displacement plethysmography, has been shown to be useful in assessing quality of growth. The development and implementation of personalised, responsive nutritional management of preterm infants, utilising real-time nutrient intake data collection, with ongoing nutritional assessments that include measurement of body composition is required to help meet the individual needs of preterm infants.

  10. Optimising Boltzmann codes for the PLANCK era

    International Nuclear Information System (INIS)

    Hamann, Jan; Lesgourgues, Julien; Balbi, Amedeo; Quercellini, Claudia

    2009-01-01

    High precision measurements of the Cosmic Microwave Background (CMB) anisotropies, as can be expected from the PLANCK satellite, will require high-accuracy theoretical predictions as well. One possible source of theoretical uncertainty is the numerical error in the output of the Boltzmann codes used to calculate angular power spectra. In this work, we carry out an extensive study of the numerical accuracy of the public Boltzmann code CAMB, and identify a set of parameters which determine the error of its output. We show that at the current default settings, the cosmological parameters extracted from data of future experiments like Planck can be biased by several tenths of a standard deviation for the six parameters of the standard ΛCDM model, and potentially more seriously for extended models. We perform an optimisation procedure that leads the code to achieve sufficient precision while at the same time keeping the computation time within reasonable limits. Our conclusion is that the contribution of numerical errors to the theoretical uncertainty of model predictions is well under control—the main challenges for more accurate calculations of CMB spectra will be of an astrophysical nature instead

  11. Geometrical exploration of a flux-optimised sodium receiver through multi-objective optimisation

    Science.gov (United States)

    Asselineau, Charles-Alexis; Corsi, Clothilde; Coventry, Joe; Pye, John

    2017-06-01

    A stochastic multi-objective optimisation method is used to determine receiver geometries with maximum second law efficiency, minimal average temperature and minimal surface area. The method is able to identify a set of Pareto optimal candidates that show advantageous geometrical features, mainly in being able to maximise the intercepted flux within the geometrical boundaries set. Receivers with first law thermal efficiencies ranging from 87% to 91% are also evaluated using the second law of thermodynamics and found to have similar efficiencies of over 60%, highlighting the influence that the geometry can play in the maximisation of the work output of receivers by influencing the distribution of the flux from the concentrator.

  12. Intelligent Support for a Computer Aided Design Optimisation Cycle

    OpenAIRE

    B. Dolšak; M. Novak; J. Kaljun

    2006-01-01

    It is becoming more and more evident that  adding intelligence  to existing computer aids, such as computer aided design systems, can lead to significant improvements in the effective and reliable performance of various engineering tasks, including design optimisation. This paper presents three different intelligent modules to be applied within a computer aided design optimisation cycle to enable more intelligent and less experience-dependent design performance. 

  13. A supportive architecture for CFD-based design optimisation

    Science.gov (United States)

    Li, Ni; Su, Zeya; Bi, Zhuming; Tian, Chao; Ren, Zhiming; Gong, Guanghong

    2014-03-01

    Multi-disciplinary design optimisation (MDO) is one of critical methodologies to the implementation of enterprise systems (ES). MDO requiring the analysis of fluid dynamics raises a special challenge due to its extremely intensive computation. The rapid development of computational fluid dynamic (CFD) technique has caused a rise of its applications in various fields. Especially for the exterior designs of vehicles, CFD has become one of the three main design tools comparable to analytical approaches and wind tunnel experiments. CFD-based design optimisation is an effective way to achieve the desired performance under the given constraints. However, due to the complexity of CFD, integrating with CFD analysis in an intelligent optimisation algorithm is not straightforward. It is a challenge to solve a CFD-based design problem, which is usually with high dimensions, and multiple objectives and constraints. It is desirable to have an integrated architecture for CFD-based design optimisation. However, our review on existing works has found that very few researchers have studied on the assistive tools to facilitate CFD-based design optimisation. In the paper, a multi-layer architecture and a general procedure are proposed to integrate different CFD toolsets with intelligent optimisation algorithms, parallel computing technique and other techniques for efficient computation. In the proposed architecture, the integration is performed either at the code level or data level to fully utilise the capabilities of different assistive tools. Two intelligent algorithms are developed and embedded with parallel computing. These algorithms, together with the supportive architecture, lay a solid foundation for various applications of CFD-based design optimisation. To illustrate the effectiveness of the proposed architecture and algorithms, the case studies on aerodynamic shape design of a hypersonic cruising vehicle are provided, and the result has shown that the proposed architecture

  14. OPTIMISATION OF A DRIVE SYSTEM AND ITS EPICYCLIC GEAR SET

    OpenAIRE

    Bellegarde , Nicolas; Dessante , Philippe; Vidal , Pierre; Vannier , Jean-Claude

    2007-01-01

    International audience; This paper describes the design of a drive consisting of a DC motor, a speed reducer, a lead screw transformation system, a power converter and its associated DC source. The objective is to reduce the mass of the system. Indeed, the volume and weight optimisation of an electrical drive is an important issue for embedded applications. Here, we present an analytical model of the system in a specific application and afterwards an optimisation of the motor and speed reduce...

  15. Multiobjective optimisation of bogie suspension to boost speed on curves

    Science.gov (United States)

    Milad Mousavi-Bideleh, Seyed; Berbyuk, Viktor

    2016-01-01

    To improve safety and maximum admissible speed on different operational scenarios, multiobjective optimisation of bogie suspension components of a one-car railway vehicle model is considered. The vehicle model has 50 degrees of freedom and is developed in multibody dynamics software SIMPACK. Track shift force, running stability, and risk of derailment are selected as safety objective functions. The improved maximum admissible speeds of the vehicle on curves are determined based on the track plane accelerations up to 1.5 m/s2. To attenuate the number of design parameters for optimisation and improve the computational efficiency, a global sensitivity analysis is accomplished using the multiplicative dimensional reduction method (M-DRM). A multistep optimisation routine based on genetic algorithm (GA) and MATLAB/SIMPACK co-simulation is executed at three levels. The bogie conventional secondary and primary suspension components are chosen as the design parameters in the first two steps, respectively. In the last step semi-active suspension is in focus. The input electrical current to magnetorheological yaw dampers is optimised to guarantee an appropriate safety level. Semi-active controllers are also applied and the respective effects on bogie dynamics are explored. The safety Pareto optimised results are compared with those associated with in-service values. The global sensitivity analysis and multistep approach significantly reduced the number of design parameters and improved the computational efficiency of the optimisation. Furthermore, using the optimised values of design parameters give the possibility to run the vehicle up to 13% faster on curves while a satisfactory safety level is guaranteed. The results obtained can be used in Pareto optimisation and active bogie suspension design problems.

  16. Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation

    Directory of Open Access Journals (Sweden)

    Niranjan Y. Sardesai

    2013-07-01

    Full Text Available Lassa virus (LASV causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC that expressed the LASV glycoprotein precursor gene (GPC. This plasmid was used to vaccinate guinea pigs (GPs using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6 with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development.

  17. Site-targeted non-viral gene delivery by direct DNA injection into the pancreatic parenchyma and subsequent in vivo electroporation in mice.

    Science.gov (United States)

    Sato, Masahiro; Inada, Emi; Saitoh, Issei; Ohtsuka, Masato; Nakamura, Shingo; Sakurai, Takayuki; Watanabe, Satoshi

    2013-11-01

    The pancreas is considered an important gene therapy target because the organ is the site of several high burden diseases, including diabetes mellitus, cystic fibrosis, and pancreatic cancer. We aimed to develop an efficient in vivo gene delivery system using non-viral DNA. Direct intra-parenchymal injection of a solution containing circular plasmid pmaxGFP DNA was performed on adult anesthetized ICR female mice. The injection site was sandwiched with a pair of tweezer-type electrode disks, and electroporated using a square-pulse generator. Green fluorescent protein (GFP) expression within the injected pancreatic portion was observed one day after gene delivery. GFP expression reduced to baseline within a week of transfection. Application of voltages over 40 V resulted in tissue damage during electroporation. We demonstrate that electroporation is effective for safe and efficient transfection of pancreatic cells. This novel gene delivery method to the pancreatic parenchyma may find application in gene therapy strategies for pancreatic diseases and in investigation of specific gene function in situ. © 2013 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptions are made.

  18. Design of optimised backstepping controller for the synchronisation of chaotic Colpitts oscillator using shark smell algorithm

    Science.gov (United States)

    Fouladi, Ehsan; Mojallali, Hamed

    2018-01-01

    In this paper, an adaptive backstepping controller has been tuned to synchronise two chaotic Colpitts oscillators in a master-slave configuration. The parameters of the controller are determined using shark smell optimisation (SSO) algorithm. Numerical results are presented and compared with those of particle swarm optimisation (PSO) algorithm. Simulation results show better performance in terms of accuracy and convergence for the proposed optimised method compared to PSO optimised controller or any non-optimised backstepping controller.

  19. Optimisation of the formulation of a bubble bath by a chemometric approach market segmentation and optimisation.

    Science.gov (United States)

    Marengo, Emilio; Robotti, Elisa; Gennaro, Maria Carla; Bertetto, Mariella

    2003-03-01

    The optimisation of the formulation of a commercial bubble bath was performed by chemometric analysis of Panel Tests results. A first Panel Test was performed to choose the best essence, among four proposed to the consumers; the best essence chosen was used in the revised commercial bubble bath. Afterwards, the effect of changing the amount of four components (the amount of primary surfactant, the essence, the hydratant and the colouring agent) of the bubble bath was studied by a fractional factorial design. The segmentation of the bubble bath market was performed by a second Panel Test, in which the consumers were requested to evaluate the samples coming from the experimental design. The results were then treated by Principal Component Analysis. The market had two segments: people preferring a product with a rich formulation and people preferring a poor product. The final target, i.e. the optimisation of the formulation for each segment, was obtained by the calculation of regression models relating the subjective evaluations given by the Panel and the compositions of the samples. The regression models allowed to identify the best formulations for the two segments ofthe market.

  20. Optimisation of integrated energy and materials systems

    International Nuclear Information System (INIS)

    Gielen, D.J.; Okken, P.A.

    1994-06-01

    To define cost-effective long term CO2 reduction strategies an integrated energy and materials system model for the Netherlands for the period 2000-2040 is developed. The model is based upon the energy system model MARKAL, which configures an optimal mix of technologies to satisfy the specified energy and product/materials service demands. This study concentrates on CO 2 emission reduction in the materials system. For this purpose, the energy system model is enlarged with a materials system model including all steps 'from cradle to grave'. The materials system model includes 29 materials, 20 product groups and 30 waste materials. The system is divided into seven types of technologies; 250 technologies are modeled. The results show that the integrated optimisation of the energy system and the materials system can significantly reduce the emission reduction costs, especially at higher reduction percentages. The reduction is achieved through shifts in materials production and waste handling and through materials substitution in products. Shifts in materials production and waste management seem cost-effective, while the cost-effectiveness of shifts in product composition is sensitive due to the cost structure of products. For the building sector, transportation applications and packaging, CO 2 policies show a significant impact on prices, and shifts in product composition could occur. For other products, the reduction through materials substitution seems less promising. The impact on materials consumption seems most significant for cement (reduced), timber and aluminium (both increased). For steel and plastics, the net effect is balanced, but shifts between applications do occur. The MARKAL-approach is feasible to study integrated energy and materials systems. The progress compared to other environmental system analysis instruments is much more insight in the interaction of technologies on a national scale and in time

  1. An approach to next step device optimisation

    International Nuclear Information System (INIS)

    Salpietro, E.

    2000-01-01

    The requirements for ITER EDA were to achieve ignition with a good safety margin, and controlled long inductive burn. These requirements lead to a big device, which requested a too ambitious step to be undertaken by the world fusion community. More realistic objectives for a next step device shall be to demonstrate the net production of energy with a high energy gain factor (Q) and a high boot strap current fraction (>60%) which is required for a Fusion Power Plant (FPP). The Next Step Device (NSD) shall also allow operation flexibility in order to explore a large range of plasma parameters to find out the optimum concept for the fusion power plant prototype. These requirements could be too demanding for one single device and could probably be better explored in a strongly integrated world programme. The cost of one or more devices is the decisive factor for the choice of the fusion power development programme strategy. The plasma elongation and triangularity have a strong impact in the cost of the device and are limited by the plasma vertical position control issue. The distance between plasma separatrix and the toroidal field conductor does not vary a lot between devices. It is determined by the sum of the distance between first wall-plasma sepratrix and the thickness of the nuclear shield required to protect the toroidal field coil insultation. The thickness of the TF coil is determined by the allowable stresses and superconducting characteristics. The outer radius of the central solenoid is the result of an optimisation to provide the magnetic flux to inductively drive the plasma. Therefore, in order to achieve the objectives for Q and boot-strap current fractions at the minimum cost, the plasma aspect ratio and magnetic field value shall be determined. The paper will present the critical issues for the next device and will make considerations on the optimal way to proceed towards the realisation of the fusion power plant

  2. Optimisation of material discrimination using spectral CT

    International Nuclear Information System (INIS)

    Nik, S.J.; Meyer, J.; Watts, R.

    2010-01-01

    Full text: Spectral computed tomography (CT) using novel X-ray photon counting detectors (PCDs) with energy resolving capabilities is capable of providing energy-selective images. This extra energy information may allow materials such as iodine and calcium, or water and fat to be distinguished. PCDs have energy thresholds, enabling the classification of photons into multiple energy bins. The inform tion content of spectral CT images depends on how the photons are grouped together. [n this work, a method is presented to optimise energy windows for maximum material discrimination. Given a combination of thicknesses, the reference number of expected photons in each energy bin is computed using the Bee Lambert equation. A similar calculation is performed for an exhaustive range of thicknesses and the number of photons in each case is com pared to the reference, allowing a statistical map of the uncertainty in thickness parameters to be constructed. The 63%-confidence region in the two-dimensional thickness space is a representation of how optimal the bins are for material separation. The model is demonstrated with 0.1 mm of iodine and 2.2 mm of calcium using two adjacent bins encompassing the entire energy range. Bins bordering at the iodine k-edge of 33.2 keY are found to be optimal. When compared to two abutted energy bins with equal incident counts as used in the literature (bordering at 54 keY), the thickness uncertainties are reduced from approximately 4% to less than I % (see Figure). This approach has been developed for two materials and is expandable to an arbitrary number of materials and bins.

  3. BNNT-mediated irreversible electroporatio: its potential on cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Vittoria Raffa, Cristina Riggio, Michael W. Smith, Kevin C. Jordan, Wei Cao, Alfred Cuschieri

    2012-10-01

    Tissue ablation, i.e., the destruction of undesirable tissues, has become an important minimally invasive technique alternative to resection surgery for the treatment of tumours. Several methods for tissue ablation are based on thermal techniques using cold, e.g. cryosurgery [1] or heat, e.g. radiofrequency [2] or high-intensity focused ultrasound [3] or nanoparticle-mediated irradiation [4]. Alternatively, irreversible electroporation (IRE) has been proposed as non thermal technique for minimally invasive tissue ablation based on the use of electrical pulses. When the electric field is applied to a cell, a change in transmembrane potential is induced, which can cause biochemical and physiological changes of the cell. When the threshold value of the transmembrane potential is exceeded, the cell membrane becomes permeable, thus allowing entrance of molecules that otherwise cannot cross the membrane [5]. A further increase in the electric field intensity may cause irreversible membrane permeabilization and cell death. These pulses create irreversible defects (pores) in the cell membrane lipid bilayer, causing cell death through loss of cell homeostasis [6]. This is desirable in tumour ablation in order to produce large cell death, without the use of cytostatic drugs. A study of Davalos, Mir and Rubinsky showed that IRE can ablate substantial volumes of tissue without inducing a thermal effect and therefore serve as an independent and new tissue ablation modality; this opened the way to the use of IRE in surgery [7]. Their finding was subsequently confirmed in studies on cells [8], small animal models [9] and in large animal models in the liver [10] and the heart [11]. The most important finding in these papers is that irreversible electroporation produces precisely delineated ablation zones with cell scale resolution between ablated and non-ablated areas, without zones in which the extent of damage changes gradually as during thermal ablation. Furthermore, it is

  4. A methodological approach to the design of optimising control strategies for sewer systems

    DEFF Research Database (Denmark)

    Mollerup, Ane Loft; Mikkelsen, Peter Steen; Sin, Gürkan

    2016-01-01

    This study focuses on designing an optimisation based control for sewer system in a methodological way and linking itto a regulatory control. Optimisation based design is found to depend on proper choice of a model, formulation of objective function and tuning of optimisation parameters. Accordin......This study focuses on designing an optimisation based control for sewer system in a methodological way and linking itto a regulatory control. Optimisation based design is found to depend on proper choice of a model, formulation of objective function and tuning of optimisation parameters....... Accordingly, two novel optimisation configurations are developed, where the optimisation either acts on the actuators or acts on the regulatory control layer. These two optimisation designs are evaluated on a sub-catchment of the sewer system in Copenhagen, and found to perform better than the existing...

  5. Transmit Power Optimisation in Wireless Network

    Directory of Open Access Journals (Sweden)

    Besnik Terziu

    2011-09-01

    Full Text Available Transmit power optimisation in wireless networks based on beamforming have emerged as a promising technique to enhance the spectrum efficiency of present and future wireless communication systems. The aim of this study is to minimise the access point power consumption in cellular networks while maintaining a targeted quality of service (QoS for the mobile terminals. In this study, the targeted quality of service is delivered to a mobile station by providing a desired level of Signal to Interference and Noise Ratio (SINR. Base-stations are coordinated across multiple cells in a multi-antenna beamforming system. This study focuses on a multi-cell multi-antenna downlink scenario where each mobile user is equipped with a single antenna, but where multiple mobile users may be active simultaneously in each cell and are separated via spatial multiplexing using beamforming. The design criteria is to minimize the total weighted transmitted power across the base-stations subject to SINR constraints at the mobile users. The main contribution of this study is to define an iterative algorithm that is capable of finding the joint optimal beamformers for all basestations, based on a correlation-based channel model, the full-correlation model. Among all correlated channel models, the correlated channel model used in this study is the most accurate, giving the best performance in terms of power consumption. The environment here in this study is chosen to be Non-Light of- Sight (NLOS condition, where a signal from a wireless transmitter passes several obstructions before arriving at a wireless receiver. Moreover there are many scatterers local to the mobile, and multiple reflections can occur among them before energy arrives at the mobile. The proposed algorithm is based on uplink-downlink duality using the Lagrangian duality theory. Time-Division Duplex (TDD is chosen as the platform for this study since it has been adopted to the latest technologies in Fourth

  6. MR and CT imaging characteristics and ablation zone volumetry of locally advanced pancreatic cancer treated with irreversible electroporation

    Energy Technology Data Exchange (ETDEWEB)

    Vroomen, Laurien G.P.H.; Scheffer, Hester J.; Melenhorst, Marleen C.A.M.; Jong, Marcus C. de; Bergh, Janneke E. van den; Kuijk, Cornelis van; Meijerink, Martijn R. [VU University Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Delft, Foke van [VU University Medical Center, Department of Gastroenterology and Hepatology, Amsterdam (Netherlands); Kazemier, Geert [VU University Medical Center, Department of Surgery, Amsterdam (Netherlands)

    2017-06-15

    To assess specific imaging characteristics after irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) with contrast-enhanced (ce)MRI and ceCT, and to explore the correlation of these characteristics with the development of recurrence. Qualitative and quantitative analyses of imaging data were performed on 25 patients treated with percutaneous IRE for LAPC. Imaging characteristics of the ablation zone on ceCT and ceMRI were assessed over a 6-month follow-up period. Contrast ratio scores between pre- and post-treatment were compared. To detect early imaging markers for treatment failure, attenuation characteristics at 6 weeks were linked to the area of recurrence within 6 months. Post-IRE, diffusion-weighted imaging (DWI)-b800 signal intensities decreased in all cases (p < 0.05). Both ceMRI and ceCT revealed absent or decreased contrast enhancement, with a hyperintense rim on ceMRI. Ablation zone volume increase was noted on both modalities in the first 6 weeks, followed by a decrease (p < 0.05). In the patients developing tumour recurrence (5/25), a focal DWI-b800 hyperintense spot at 6 weeks predated unequivocal recurrence on CT. The most remarkable signal alterations after pancreatic IRE were shown by DWI-b800 and ceMRI. These early imaging characteristics may be useful to establish technical success and predict treatment outcome. (orig.)

  7. Two doses of bovine viral diarrhea virus DNA vaccine delivered by electroporation induce long-term protective immune responses.

    Science.gov (United States)

    van Drunen Littel-van den Hurk, Sylvia; Lawman, Zoe; Snider, Marlene; Wilson, Don; van den Hurk, Jan V; Ellefsen, Barry; Hannaman, Drew

    2013-02-01

    Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

  8. Clinical and pathological outcomes after irreversible electroporation of the pancreas using two parallel plate electrodes: a porcine model.

    Science.gov (United States)

    Rombouts, Steffi J E; van Dijck, Willemijn P M; Nijkamp, Maarten W; Derksen, Tyche C; Brosens, Lodewijk A A; Hoogwater, Frederik J H; van Leeuwen, Maarten S; Borel Rinkes, Inne H M; van Hillegersberg, Richard; Wittkampf, Fred H; Molenaar, Izaak Q

    2017-12-01

    Irreversible electroporation (IRE) by inserting needles around the tumor as treatment for locally advanced pancreatic cancer entails several disadvantages, such as incomplete ablation due to field inhomogeneity, technical difficulties in needle placement and a risk of pancreatic fistula development. This experimental study evaluates outcomes of IRE using paddles in a porcine model. Six healthy pigs underwent laparotomy and were treated with 2 separate ablations (in head and tail of the pancreas). Follow-up consisted of clinical and laboratory parameters and contrast-enhanced computed tomography (ceCT) imaging. After 2 weeks, pancreatoduodenectomy was performed for histology and the pigs were terminated. All animals survived 14 days. None of the animals developed signs of infection or significant abdominal distention. Serum amylase and lipase peaked at day 1 postoperatively in all pigs, but normalized without signs of pancreatitis. On ceCT-imaging the ablation zone was visible as an ill-defined, hypodense lesion. No abscesses, cysts or ascites were seen. Histology showed a homogenous fibrotic lesion in all pigs. IRE ablation of healthy porcine pancreatic tissue using two plate electrodes is feasible and safe and creates a homogeneous fibrotic lesion. IRE-paddles should be tested on pancreatic adenocarcinoma to determine the effect in cancer tissue. Copyright © 2017. Published by Elsevier Ltd.

  9. Real-time ultrasound imaging of irreversible electroporation in a porcine liver model adequately characterizes the zone of cellular necrosis.

    Science.gov (United States)

    Schmidt, Carl R; Shires, Peter; Mootoo, Mary

    2012-02-01

      Irreversible electroporation (IRE) is a largely non-thermal method for the ablation of solid tumours. The ability of ultrasound (US) to measure the size of the IRE ablation zone was studied in a porcine liver model.   Three normal pig livers were treated in vivo with a total of 22 ablations using IRE. Ultrasound was used within minutes after ablation and just prior to liver harvest at either 6 h or 24 h after the procedure. The area of cellular necrosis was measured after staining with nitroblue tetrazolium and the percentage of cell death determined by histomorphometry.   Visible changes in the hepatic parenchyma were apparent by US after all 22 ablations using IRE. The mean maximum diameter of the ablation zone measured by US during the procedure was 20.1 ± 2.7 mm. This compared with a mean cellular necrosis zone maximum diameter of 20.3 ± 2.9 mm as measured histologically. The mean percentage of dead cells within the ablation zone was 77% at 6 h and 98% at 24 h after ablation.   Ultrasound is a useful modality for measuring the ablation zone within minutes of applying IRE to normal liver tissue. The area of parenchymal change measured by US correlates with the area of cellular necrosis. © 2011 International Hepato-Pancreato-Biliary Association.

  10. Mutual information-based LPI optimisation for radar network

    Science.gov (United States)

    Shi, Chenguang; Zhou, Jianjiang; Wang, Fei; Chen, Jun

    2015-07-01

    Radar network can offer significant performance improvement for target detection and information extraction employing spatial diversity. For a fixed number of radars, the achievable mutual information (MI) for estimating the target parameters may extend beyond a predefined threshold with full power transmission. In this paper, an effective low probability of intercept (LPI) optimisation algorithm is presented to improve LPI performance for radar network. Based on radar network system model, we first provide Schleher intercept factor for radar network as an optimisation metric for LPI performance. Then, a novel LPI optimisation algorithm is presented, where for a predefined MI threshold, Schleher intercept factor for radar network is minimised by optimising the transmission power allocation among radars in the network such that the enhanced LPI performance for radar network can be achieved. The genetic algorithm based on nonlinear programming (GA-NP) is employed to solve the resulting nonconvex and nonlinear optimisation problem. Some simulations demonstrate that the proposed algorithm is valuable and effective to improve the LPI performance for radar network.

  11. Robustness analysis of bogie suspension components Pareto optimised values

    Science.gov (United States)

    Mousavi Bideleh, Seyed Milad

    2017-08-01

    Bogie suspension system of high speed trains can significantly affect vehicle performance. Multiobjective optimisation problems are often formulated and solved to find the Pareto optimised values of the suspension components and improve cost efficiency in railway operations from different perspectives. Uncertainties in the design parameters of suspension system can negatively influence the dynamics behaviour of railway vehicles. In this regard, robustness analysis of a bogie dynamics response with respect to uncertainties in the suspension design parameters is considered. A one-car railway vehicle model with 50 degrees of freedom and wear/comfort Pareto optimised values of bogie suspension components is chosen for the analysis. Longitudinal and lateral primary stiffnesses, longitudinal and vertical secondary stiffnesses, as well as yaw damping are considered as five design parameters. The effects of parameter uncertainties on wear, ride comfort, track shift force, stability, and risk of derailment are studied by varying the design parameters around their respective Pareto optimised values according to a lognormal distribution with different coefficient of variations (COVs). The robustness analysis is carried out based on the maximum entropy concept. The multiplicative dimensional reduction method is utilised to simplify the calculation of fractional moments and improve the computational efficiency. The results showed that the dynamics response of the vehicle with wear/comfort Pareto optimised values of bogie suspension is robust against uncertainties in the design parameters and the probability of failure is small for parameter uncertainties with COV up to 0.1.

  12. A conceptual optimisation strategy for radiography in a digital environment

    International Nuclear Information System (INIS)

    Baath, M.; Haakansson, M.; Hansson, J.; Maansson, L. G.

    2005-01-01

    Using a completely digital environment for the entire imaging process leads to new possibilities for optimisation of radiography since many restrictions of screen/film systems, such as the small dynamic range and the lack of possibilities for image processing, do not apply any longer. However, at the same time these new possibilities lead to a more complicated optimisation process, since more freedom is given to alter parameters. This paper focuses on describing an optimisation strategy that concentrates on taking advantage of the conceptual differences between digital systems and screen/film systems. The strategy can be summarised as: (a) always include the anatomical background during the optimisation, (b) perform all comparisons at a constant effective dose and (c) separate the image display stage from the image collection stage. A three-step process is proposed where the optimal setting of the technique parameters is determined at first, followed by an optimisation of the image processing. In the final step the optimal dose level - given the optimal settings of the image collection and image display stages - is determined. (authors)

  13. Establishing Local Reference Dose Values and Optimisation Strategies

    International Nuclear Information System (INIS)

    Connolly, P.; Moores, B.M.

    2000-01-01

    The revised EC Patient Directive 97/43 EURATOM introduces the concepts of clinical audit, diagnostic reference levels and optimisation of radiation protection in diagnostic radiology. The application of reference dose levels in practice involves the establishment of reference dose values as actual measurable operational quantities. These values should then form part of an ongoing optimisation and audit programme against which routine performance can be compared. The CEC Quality Criteria for Radiographic Images provides guidance reference dose values against which local performance can be compared. In many cases these values can be improved upon quite considerably. This paper presents the results of a local initiative in the North West of the UK aimed at establishing local reference dose values for a number of major hospital sites. The purpose of this initiative is to establish a foundation for both optimisation strategies and clinical audit as an ongoing and routine practice. The paper presents results from an ongoing trial involving patient dose measurements for several radiological examinations upon the sites. The results of an attempt to establish local reference dose values from measured dose values and to employ them in optimisation strategies are presented. In particular emphasis is placed on the routine quality control programmes necessary to underpin this strategy including the effective data management of results from such programmes and how they can be employed to optimisation practices. (author)

  14. Data for TROTS – The Radiotherapy Optimisation Test Set

    Directory of Open Access Journals (Sweden)

    Sebastiaan Breedveld

    2017-06-01

    Full Text Available The Radiotherapy Optimisation Test Set (TROTS is an extensive set of problems originating from radiotherapy (radiation therapy treatment planning. This dataset is created for 2 purposes: (1 to supply a large-scale dense dataset to measure performance and quality of mathematical solvers, and (2 to supply a dataset to investigate the multi-criteria optimisation and decision-making nature of the radiotherapy problem. The dataset contains 120 problems (patients, divided over 6 different treatment protocols/tumour types. Each problem contains numerical data, a configuration for the optimisation problem, and data required to visualise and interpret the results. The data is stored as HDF5 compatible Matlab files, and includes scripts to work with the dataset.

  15. CLIC crab cavity design optimisation for maximum luminosity

    Energy Technology Data Exchange (ETDEWEB)

    Dexter, A.C., E-mail: a.dexter@lancaster.ac.uk [Lancaster University, Lancaster, LA1 4YR (United Kingdom); Cockcroft Institute, Daresbury, Warrington, WA4 4AD (United Kingdom); Burt, G.; Ambattu, P.K. [Lancaster University, Lancaster, LA1 4YR (United Kingdom); Cockcroft Institute, Daresbury, Warrington, WA4 4AD (United Kingdom); Dolgashev, V. [SLAC, Menlo Park, CA 94025 (United States); Jones, R. [University of Manchester, Manchester, M13 9PL (United Kingdom)

    2011-11-21

    The bunch size and crossing angle planned for CERN's compact linear collider CLIC dictate that crab cavities on opposing linacs will be needed to rotate bunches of particles into alignment at the interaction point if the desired luminosity is to be achieved. Wakefield effects, RF phase errors between crab cavities on opposing linacs and unpredictable beam loading can each act to reduce luminosity below that anticipated for bunches colliding in perfect alignment. Unlike acceleration cavities, which are normally optimised for gradient, crab cavities must be optimised primarily for luminosity. Accepting the crab cavity technology choice of a 12 GHz, normal conducting, travelling wave structure as explained in the text, this paper develops an analytical approach to optimise cell number and iris diameter.

  16. Cultural-based particle swarm for dynamic optimisation problems

    Science.gov (United States)

    Daneshyari, Moayed; Yen, Gary G.

    2012-07-01

    Many practical optimisation problems are with the existence of uncertainties, among which a significant number belong to the dynamic optimisation problem (DOP) category in which the fitness function changes through time. In this study, we propose the cultural-based particle swarm optimisation (PSO) to solve DOP problems. A cultural framework is adopted incorporating the required information from the PSO into five sections of the belief space, namely situational, temporal, domain, normative and spatial knowledge. The stored information will be adopted to detect the changes in the environment and assists response to the change through a diversity-based repulsion among particles and migration among swarms in the population space, and also helps in selecting the leading particles in three different levels, personal, swarm and global levels. Comparison of the proposed heuristics over several difficult dynamic benchmark problems demonstrates the better or equal performance with respect to most of other selected state-of-the-art dynamic PSO heuristics.

  17. The principle of optimisation: reasons for success and legal criticism

    International Nuclear Information System (INIS)

    Fernandez Regalado, Luis

    2008-01-01

    The International Commission on Radiological Protection (ICRP) has adopted new recommendations in 2007. In broad outlines they fundamentally continue the recommendations already approved in 1990 and later on. The principle of optimisation of protection, together with the principles of justification and dose limits, remains playing a key role of the ICRP recommendations, and it has so been for the last few years. This principle, somehow reinforced in the 2007 ICRP recommendations, has been incorporated into norms and legislation which have peacefully been in force in many countries all over the world. There are three main reasons to explain the success in the application of the principle of optimisation in radiological protection: First, the subjectivity of the sentence that embraces the principle of optimisation, 'As low as reasonably achievable' (ALARA), that allows different valid interpretations under different circumstances. Second, the pragmatism and adaptability of ALARA to all exposure situations. And third, the scientific humbleness which is behind the principle of optimisation, which makes a clear contrast with the old fashioned scientific positivism that enshrined scientist opinions. Nevertheless, from a legal point of view, there is some criticism cast over the principle of optimisation in radiological protection, where it has been transformed in compulsory norm. This criticism is based on two arguments: The lack of democratic participation in the process of elaboration of the norm, and the legal uncertainty associated to its application. Both arguments are somehow known by the ICRP which, on the one hand, has broadened the participation of experts, associations and the professional radiological protection community, increasing the transparency on how decisions on recommendations have been taken, and on the other hand, the ICRP has warned about the need for authorities to specify general criteria to develop the principle of optimisation in national

  18. Optimisation in X-ray and Molecular Imaging 2015

    International Nuclear Information System (INIS)

    Baath, Magnus; Hoeschen, Christoph; Mattsson, Soeren; Mansson, Lars Gunnar

    2016-01-01

    This issue of Radiation Protection Dosimetry is based on contributions to Optimisation in X-ray and Molecular Imaging 2015 - the 4. Malmoe Conference on Medical Imaging (OXMI 2015). The conference was jointly organised by members of former and current research projects supported by the European Commission EURATOM Radiation Protection Research Programme, in cooperation with the Swedish Society for Radiation Physics. The conference brought together over 150 researchers and other professionals from hospitals, universities and industries with interests in different aspects of the optimisation of medical imaging. More than 100 presentations were given at this international gathering of medical physicists, radiologists, engineers, technicians, nurses and educational researchers. Additionally, invited talks were offered by world-renowned experts on radiation protection, spectral imaging and medical image perception, thus covering several important aspects of the generation and interpretation of medical images. The conference consisted of 13 oral sessions and a poster session, as reflected by the conference title connected by their focus on the optimisation of the use ionising radiation in medical imaging. The conference included technology-specific topics such as computed tomography and tomosynthesis, but also generic issues of interest for the optimisation of all medical imaging, such as image perception and quality assurance. Radiation protection was covered by e.g. sessions on patient dose benchmarking and occupational exposure. Technically-advanced topics such as modelling, Monte Carlo simulation, reconstruction, classification, and segmentation were seen taking advantage of recent developments of hardware and software, showing that the optimisation community is at the forefront of technology and adapts well to new requirements. These peer-reviewed proceedings, representing a continuation of a series of selected reports from meetings in the field of medical imaging

  19. Numerical optimisation of friction stir welding: review of future challenges

    DEFF Research Database (Denmark)

    Tutum, Cem Celal; Hattel, Jesper Henri

    2011-01-01

    During the last decade, the combination of increasingly more advanced numerical simulation software with high computational power has resulted in models for friction stir welding (FSW), which have improved the understanding of the determining physical phenomena behind the process substantially....... This has made optimisation of certain process parameters possible and has in turn led to better performing friction stir welded products, thus contributing to a general increase in the popularity of the process and its applications. However, most of these optimisation studies do not go well beyond manual...

  20. Alternatives for optimisation of rumen fermentation in ruminants

    Directory of Open Access Journals (Sweden)

    T. Slavov

    2017-06-01

    Full Text Available Abstract. The proper knowledge on the variety of events occurring in the rumen makes possible their optimisation with respect to the complete feed conversion and increasing the productive performance of ruminants. The inclusion of various dietary additives (supplements, biologically active substances, nutritional antibiotics, probiotics, enzymatic preparations, plant extracts etc. has an effect on the intensity and specific pathway of fermentation, and thus, on the general digestion and systemic metabolism. The optimisation of rumen digestion is a method with substantial potential for improving the efficiency of ruminant husbandry, increasing of quality of their produce and health maintenance.

  1. Separative power of an optimised concurrent gas centrifuge

    Energy Technology Data Exchange (ETDEWEB)

    Bogovalov, Sergey; Boman, Vladimir [National Research Nuclear University (MEPHI), Moscow (Russian Federation)

    2016-06-15

    The problem of separation of isotopes in a concurrent gas centrifuge is solved analytically for an arbitrary binary mixture of isotopes. The separative power of the optimised concurrent gas centrifuges for the uranium isotopes equals to δU = 12.7 (V/700 m/s)2(300 K/T)(L/1 m) kg·SWU/yr, where L and V are the length and linear velocity of the rotor of the gas centrifuge and T is the temperature. This equation agrees well with the empirically determined separative power of optimised counter-current gas centrifuges.

  2. MANAGEMENT OPTIMISATION OF MASS CUSTOMISATION MANUFACTURING USING COMPUTATIONAL INTELLIGENCE

    Directory of Open Access Journals (Sweden)

    Louwrens Butler

    2018-05-01

    Full Text Available Computational intelligence paradigms can be used for advanced manufacturing system optimisation. A static simulation model of an advanced manufacturing system was developed in order to simulate a manufacturing system. The purpose of this advanced manufacturing system was to mass-produce a customisable product range at a competitive cost. The aim of this study was to determine whether this new algorithm could produce a better performance than traditional optimisation methods. The algorithm produced a lower cost plan than that for a simulated annealing algorithm, and had a lower impact on the workforce.

  3. Optimising a shaft's geometry by applying genetic algorithms

    Directory of Open Access Journals (Sweden)

    María Alejandra Guzmán

    2005-05-01

    Full Text Available Many engnieering design tasks involve optimising several conflicting goals; these types of problem are known as Multiobjective Optimisation Problems (MOPs. Evolutionary techniques have proved to be an effective tool for finding solutions to these MOPs during the last decade, Variations on the basic generic algorithm have been particulary proposed by different researchers for finding rapid optimal solutions to MOPs. The NSGA (Non-dominated Sorting Generic Algorithm has been implemented in this paper for finding an optimal design for a shaft subjected to cyclic loads, the conflycting goals being minimum weight and minimum lateral deflection.

  4. The optimisation study of tbp synthesis process by phosphoric acid

    International Nuclear Information System (INIS)

    Amedjkouh, A.; Attou, M.; Azzouz, A.; Zaoui, B.

    1995-07-01

    The present work deals with the optimisation study of TBP synthesis process by phosphoric acid. This way of synthesis is more advantageous than POCL3 or P2O5 as phosphatant agents. these latters are toxic and dangerous for the environnement. The optimisation study is based on a series of 16 experiences taking into account the range of variation of the following parameters : temperature, pressure, reagents mole ratio, promoter content. the yield calculation is based on the randomisation of an equation including all parameters. the resolution of this equation gave a 30% TBP molar ratio. this value is in agreement with that of experimental data

  5. Optimisation of BPMN Business Models via Model Checking

    DEFF Research Database (Denmark)

    Herbert, Luke Thomas; Sharp, Robin

    2013-01-01

    We present a framework for the optimisation of business processes modelled in the business process modelling language BPMN, which builds upon earlier work, where we developed a model checking based method for the analysis of BPMN models. We define a structure for expressing optimisation goals...... for synthesized BPMN components, based on probabilistic computation tree logic and real-valued reward structures of the BPMN model, allowing for the specification of complex quantitative goals. We here present a simple algorithm, inspired by concepts from evolutionary algorithms, which iteratively generates...

  6. The optimisation of wedge filters in radiotherapy of the prostate

    International Nuclear Information System (INIS)

    Oldham, Mark; Neal, Anthony J.; Webb, Steve

    1995-01-01

    A treatment plan optimisation algorithm has been applied to 12 patients with early prostate cancer in order to determine the optimum beam-weights and wedge angles for a standard conformal three-field treatment technique. The optimisation algorithm was based on fast-simulated-annealing using a cost function designed to achieve a uniform dose in the planning-target-volume (PTV) and to minimise the integral doses to the organs-at-risk. The algorithm has been applied to standard conformal three-field plans created by an experienced human planner, and run in three PLAN MODES: (1) where the wedge angles were fixed by the human planner and only the beam-weights were optimised; (2) where both the wedge angles and beam-weights were optimised; and (3) where both the wedge angles and beam-weights were optimised and a non-uniform dose was prescribed to the PTV. In the latter PLAN MODE, a uniform 100% dose was prescribed to all of the PTV except for that region that overlaps with the rectum where a lower (e.g., 90%) dose was prescribed. The resulting optimised plans have been compared with those of the human planner who found beam-weights by conventional forward planning techniques. Plans were compared on the basis of dose statistics, normal-tissue-complication-probability (NTCP) and tumour-control-probability (TCP). The results of the comparison showed that all three PLAN MODES produced plans with slightly higher TCP for the same rectal NTCP, than the human planner. The best results were observed for PLAN MODE 3, where an average increase in TCP of 0.73% (± 0.20, 95% confidence interval) was predicted by the biological models. This increase arises from a beneficial dose gradient which is produced across the tumour. Although the TCP gain is small it comes with no increase in treatment complexity, and could translate into increased cures given the large numbers of patients being referred. A study of the beam-weights and wedge angles chosen by the optimisation algorithm revealed

  7. Time varying acceleration coefficients particle swarm optimisation (TVACPSO): A new optimisation algorithm for estimating parameters of PV cells and modules

    International Nuclear Information System (INIS)

    Jordehi, Ahmad Rezaee

    2016-01-01

    Highlights: • A modified PSO has been proposed for parameter estimation of PV cells and modules. • In the proposed modified PSO, acceleration coefficients are changed during run. • The proposed modified PSO mitigates premature convergence problem. • Parameter estimation problem has been solved for both PV cells and PV modules. • The results show that proposed PSO outperforms other state of the art algorithms. - Abstract: Estimating circuit model parameters of PV cells/modules represents a challenging problem. PV cell/module parameter estimation problem is typically translated into an optimisation problem and is solved by metaheuristic optimisation problems. Particle swarm optimisation (PSO) is considered as a popular and well-established optimisation algorithm. Despite all its advantages, PSO suffers from premature convergence problem meaning that it may get trapped in local optima. Personal and social acceleration coefficients are two control parameters that, due to their effect on explorative and exploitative capabilities, play important roles in computational behavior of PSO. In this paper, in an attempt toward premature convergence mitigation in PSO, its personal acceleration coefficient is decreased during the course of run, while its social acceleration coefficient is increased. In this way, an appropriate tradeoff between explorative and exploitative capabilities of PSO is established during the course of run and premature convergence problem is significantly mitigated. The results vividly show that in parameter estimation of PV cells and modules, the proposed time varying acceleration coefficients PSO (TVACPSO) offers more accurate parameters than conventional PSO, teaching learning-based optimisation (TLBO) algorithm, imperialistic competitive algorithm (ICA), grey wolf optimisation (GWO), water cycle algorithm (WCA), pattern search (PS) and Newton algorithm. For validation of the proposed methodology, parameter estimation has been done both for

  8. Agent-Based Decision Control—How to Appreciate Multivariate Optimisation in Architecture

    DEFF Research Database (Denmark)

    Negendahl, Kristoffer; Perkov, Thomas Holmer; Kolarik, Jakub

    2015-01-01

    , the method is applied to a multivariate optimisation problem. The aim is specifically to demonstrate optimisation for entire building energy consumption, daylight distribution and capital cost. Based on the demonstrations Moth’s ability to find local minima is discussed. It is concluded that agent-based...... in the early design stage. The main focus is to demonstrate the optimisation method, which is done in two ways. Firstly, the newly developed agent-based optimisation algorithm named Moth is tested on three different single objective search spaces. Here Moth is compared to two evolutionary algorithms. Secondly...... optimisation algorithms like Moth open up for new uses of optimisation in the early design stage. With Moth the final outcome is less dependent on pre- and post-processing, and Moth allows user intervention during optimisation. Therefore, agent-based models for optimisation such as Moth can be a powerful...

  9. Multigrid Implementation of Cellular Automata for Topology Optimisation of Continuum Structures with Design Dependent loads

    NARCIS (Netherlands)

    Zakhama, R.

    2009-01-01

    Topology optimisation of continuum structures has become mature enough to be often applied in industry and continues to attract the attention of researchers and software companies in various engineering fields. Traditionally, most available algorithms for solving topology optimisation problems are

  10. Solving dynamic multi-objective problems with vector evaluated particle swarm optimisation

    CSIR Research Space (South Africa)

    Greeff, M

    2008-06-01

    Full Text Available Many optimisation problems are multi-objective and change dynamically. Many methods use a weighted average approach to the multiple objectives. This paper introduces the usage of the vector evaluated particle swarm optimiser (VEPSO) to solve dynamic...

  11. Electroporation of mRNA as Universal Technology Platform to Transfect a Variety of Primary Cells with Antigens and Functional Proteins.

    Science.gov (United States)

    Gerer, Kerstin F; Hoyer, Stefanie; Dörrie, Jan; Schaft, Niels

    2017-01-01

    Electroporation (EP) of mRNA into human cells is a broadly applicable method to transiently express proteins of choice in a variety of different cell types. We have spent more than a decade to optimize and adapt this method, first for antigen-loading of dendritic cells (DCs), and subsequently for T cells, B cells, bulk PBMCs, and several cell lines. In this regard, antigens were introduced, processed, and presented in context of MHC class I and II. Next to that, functional proteins like adhesion receptors, T-cell receptors (TCRs), chimeric antigen receptors (CARs), constitutively active signal transducers, and others were successfully expressed. We have also established this protocol under full GMP compliance as part of a manufacturing license to produce mRNA-electroporated DCs for therapeutic vaccination in clinical trials. Therefore, we here want to share our universal mRNA electroporation protocol and the experience we have gathered with this method. The advantages of the transfection method presented here are: (1) easy adaptation to different cell types, (2) scalability from 10 6 to approximately 10 8 cells per shot, (3) high transfection efficiency (80-99 %), (4) homogenous protein expression, (5) GMP compliance if the EP is performed in a class A clean room, and (6) no transgene integration into the genome. The provided protocol involves: Opti-MEM® as EP medium, a square-wave pulse with 500 V, and 4 mm cuvettes. To adapt the protocol to differently sized cells, simply the pulse time is altered. Next to the basic protocol, we also provide an extensive list of hints and tricks, which in our opinion are of great value for everyone who intends to use this transfection technique.

  12. Superior induction of T cell responses to conserved HIV-1 regions by electroporated alphavirus replicon DNA compared to that with conventional plasmid DNA vaccine.

    Science.gov (United States)

    Knudsen, Maria L; Mbewe-Mvula, Alice; Rosario, Maximillian; Johansson, Daniel X; Kakoulidou, Maria; Bridgeman, Anne; Reyes-Sandoval, Arturo; Nicosia, Alfredo; Ljungberg, Karl; Hanke, Tomás; Liljeström, Peter

    2012-04-01

    Vaccination using "naked" DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also, in vivo electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that in vivo electroporation increases CD8(+) T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8(+) T cells comparable to those induced by 1 μg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20-fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation.

  13. Irreversible Electroporation (IRE) Fails to Demonstrate Efficacy in a Prospective Multicenter Phase II Trial on Lung Malignancies: The ALICE Trial

    Energy Technology Data Exchange (ETDEWEB)

    Ricke, Jens, E-mail: jens.ricke@med.ovgu.de; Jürgens, Julian H. W., E-mail: julian.juergens@med.ovgu.de [University of Magdeburg, Department of Radiology and Nuclear Medicine (Germany); Deschamps, Frederic; Tselikas, Lambros [Institut de Cancérologie Gustave Roussy, Department of Image Guided Therapy (France); Uhde, Katja; Kosiek, Ortrud [University of Magdeburg, Department of Radiology and Nuclear Medicine (Germany); Baere, Thierry De [Institut de Cancérologie Gustave Roussy, Department of Image Guided Therapy (France)

    2015-04-15

    PurposeTo assess safety and efficacy of irreversible electroporation (IRE) of lung malignancies.Materials and MethodsPatients with primary and secondary lung malignancies and preserved lung function were included in this prospective single arm trial. Primary and secondary endpoints were safety and efficacy. Recruitment goal was 36 subjects in 2 centers. Patients underwent IRE under general anesthesia with probe placement performed in Fluoroscopy-CT. The IRE system employed was NanoKnife{sup ®} (Angiodynamics). System settings for the ablation procedure followed the manufacturer’s recommendations. The Mann–Whitney U test was used to evaluate the correlation of nine technical parameters with local tumor control. Median follow up was 12 months.ResultsThe expected efficacy was not met at interim analysis and the trial was stopped prematurely after inclusion of 23 patients (13/10 between both centers). The dominant tumor entity was colorectal (n = 13). The median tumor diameter was 16 mm (8–27 mm). Pneumothoraces were observed in 11 of 23 patients with chest tubes required in 8 (35 %). Frequently observed alveolar hemorrhage never led to significant hemoptysis. 14/23 showed progressive disease (61 %). Stable disease was found in 1 (4 %), partial remission in 1 (4 %) and complete remission in 7 (30 %) patients. The relative increase of the current during ablation was significantly higher in the group treated successfully as compared to the group presenting local recurrence (p < 0.05). Needle tract seeding was found in three cases (13 %).ConclusionsIRE is not effective for the treatment of lung malignancies. We hypothesize that the energy deposition with current IRE probes is highly sensitive to air exposure.

  14. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  15. Gene transfer to pre-hematopoietic and committed hematopoietic precursors in the early mouse Yolk Sac: a comparative study between in situ electroporation and retroviral transduction

    Directory of Open Access Journals (Sweden)

    Lécluse Yann

    2007-07-01

    Full Text Available Abstract Background Hematopoietic development in vertebrate embryos results from the sequential contribution of two pools of precursors independently generated. While intra-embryonic precursors harbour the features of hematopoietic stem cells (HSC, precursors formed earlier in the yolk sac (YS display limited differentiation and self-renewal potentials. The mechanisms leading to the generation of the precursors in both sites are still largely unknown, as are the molecular basis underlying their different potential. A possible approach to assess the role of candidate genes is to transfer or modulate their expression/activity in both sites. We thus designed and compared transduction protocols to target either native extra-embryonic precursors, or hematopoietic precursors. Results One transduction protocol involves transient modification of gene expression through in situ electroporation of the prospective blood islands, which allows the evolution of transfected mesodermal cells in their "normal" environment, upon organ culture. Following in situ electroporation of a GFP reporter construct into the YS cavity of embryos at post-streak (mesodermal/pre-hematopoietic precursors or early somite (hematopoietic precursors stages, high GFP expression levels as well as a good preservation of cell viability is observed in YS explants. Moreover, the erythro-myeloid progeny typical of the YS arises from GFP+ mesodermal cells or hematopoietic precursors, even if the number of targeted precursors is low. The second approach, based on retroviral transduction allows a very efficient transduction of large precursor numbers, but may only be used to target 8 dpc YS hematopoietic precursors. Again, transduced cells generate a progeny quantitatively and qualitatively similar to that of control YS. Conclusion We thus provide two protocols whose combination may allow a thorough study of both early and late events of hematopoietic development in the murine YS. In situ

  16. Comparative evaluation of transmembrane ion transport due to monopolar and bipolar nanosecond, high-intensity electroporation pulses based on full three-dimensional analyses

    Science.gov (United States)

    Hu, Q.; Joshi, R. P.

    2017-07-01

    Electric pulse driven membrane poration finds applications in the fields of biomedical engineering and drug/gene delivery. Here we focus on nanosecond, high-intensity electroporation and probe the role of pulse shape (e.g., monopolar-vs-bipolar), multiple electrode scenarios, and serial-versus-simultaneous pulsing, based on a three-dimensional time-dependent continuum model in a systematic fashion. Our results indicate that monopolar pulsing always leads to higher and stronger cellular uptake. This prediction is in agreement with experimental reports and observations. It is also demonstrated that multi-pronged electrode configurations influence and increase the degree of cellular uptake.

  17. SINGLE FIXED CRANE OPTIMISATION WITHIN A DISTRIBUTION CENTRE

    Directory of Open Access Journals (Sweden)

    J. Matthews

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT: This paper considersthe optimisation of the movement of a fixed crane operating in a single aisle of a distribution centre. The crane must move pallets in inventory between docking bays, storage locations, and picking lines. Both a static and a dynamic approach to the problem are presented. The optimisation is performed by means of tabu search, ant colony metaheuristics,and hybrids of these two methods. All these solution approaches were tested on real life data obtained from an operational distribution centre. Results indicate that the hybrid methods outperform the other approaches.

    AFRIKAANSE OPSOMMING: Die optimisering van die beweging van 'n vaste hyskraan in 'n enkele gang van 'n distribusiesentrum word in hierdie artikel beskou. Die hyskraan moet pallette vervoer tussen dokhokke, stoorposisies, en opmaaklyne. Beide 'n statiese en 'n dinamiese benadering tot die probleem word aangebied. Die optimisering word gedoen met behulp van tabu-soektogte, mierkolonieoptimisering,en hibriede van hierdie twee metodes. Al die oplossingsbenaderings is getoets met werklike data wat van 'n operasionele distribusiesentrum verkry is. Die resultate toon aan dat die hibriedmetodes die beste oplossings lewer.

  18. Formulation des betons autopla~ants : Optimisation du squelette ...

    African Journals Online (AJOL)

    Formulation des betons autopla~ants : Optimisation du squelette granulaire par la methode graphique de Dreux - Gorisse. Fatiha Boumaza - Zeraoulia* & Mourad Behim. Laboratoire Materiaux, Geo - Materiaux et Environnement - Departement de Genie Civil. Universite Badji Mokhtar Annaba - BP 12, 23000 Annaba - ...

  19. Parameter Optimisation for the Behaviour of Elastic Models over Time

    DEFF Research Database (Denmark)

    Mosegaard, Jesper

    2004-01-01

    Optimisation of parameters for elastic models is essential for comparison or finding equivalent behaviour of elastic models when parameters cannot simply be transferred or converted. This is the case with a large range of commonly used elastic models. In this paper we present a general method tha...

  20. Development of an Optimised Losartan Potassium Press-Coated ...

    African Journals Online (AJOL)

    The optimised formulation was further characterized with Fourier-transform infrared spectroscopy (FTIR) and powder X-ray diffractometry (PXRD) to investigate any drug/excipient modifications/interactions. Results: The tensile strength values of all the PCT were between 1.12 and 1.23MNm-2 and friability was < 0.36 %.

  1. Statistical Optimisation of Fermentation Conditions for Citric Acid ...

    African Journals Online (AJOL)

    This study investigated the optimisation of fermentation conditions during citric acid production via solid state fermentation (SSF) of pineapple peels using Aspergillus niger. A three-variable, three-level Box-Behnken design (BBD) comprising 17 experimental runs was used to develop a statistical model for the fermentation ...

  2. Optimising the Blended Learning Environment: The Arab Open University Experience

    Science.gov (United States)

    Hamdi, Tahrir; Abu Qudais, Mohammed

    2018-01-01

    This paper will offer some insights into possible ways to optimise the blended learning environment based on experience with this modality of teaching at Arab Open University/Jordan branch and also by reflecting upon the results of several meta-analytical studies, which have shown blended learning environments to be more effective than their face…

  3. Comparing and Optimising Parallel Haskell Implementations for Multicore Machines

    DEFF Research Database (Denmark)

    Berthold, Jost; Marlow, Simon; Hammond, Kevin

    2009-01-01

    In this paper, we investigate the differences and tradeoffs imposed by two parallel Haskell dialects running on multicore machines. GpH and Eden are both constructed using the highly-optimising sequential GHC compiler, and share thread scheduling, and other elements, from a common code base. The ...

  4. Larval feeding inhibition assay – need for optimisation

    DEFF Research Database (Denmark)

    Azuhnwi, Blasius; Desrues, O.; Hoste, H.

    2013-01-01

    for this observed variation in results include: parasite (species/strain); material tested; or season. There is thus need to optimise LFIA to permit intra and inter-laboratory comparison of results. We investigate here, if changes in EC50 values occur over the patency phase of a nematode species using two test...

  5. A comparative study of marriage in honey bees optimisation (MBO ...

    African Journals Online (AJOL)

    2012-02-15

    Feb 15, 2012 ... In a typical mating, the queen mates with 7 to 20 drones. Each time the .... Honey bee mating optimisation model's pseudo-code ... for this analysis, which consists of 47 years of monthly time ... tive of Karkheh Reservoir is to control and regulate the flow of ..... Masters thesis, Maastricht University, Maastricht.

  6. Analysing the performance of dynamic multi-objective optimisation algorithms

    CSIR Research Space (South Africa)

    Helbig, M

    2013-06-01

    Full Text Available and the goal of the algorithm is to track a set of tradeoff solutions over time. Analysing the performance of a dynamic multi-objective optimisation algorithm (DMOA) is not a trivial task. For each environment (before a change occurs) the DMOA has to find a set...

  7. Optimisation of dialysate flow in on-line hemodiafiltration

    Directory of Open Access Journals (Sweden)

    Francisco Maduell

    2015-09-01

    Conclusion: Qd variations in OL-HDF do not change convective volume. A higher Qd was associated to a slightly increased urea clearance with no change being observed for medium and large molecules. Qd optimisation to the minimal level assuring an adequate dialysis dose and allowing water and dialysate use to be rationalised should be recommended.

  8. Day-ahead economic optimisation of energy storage

    NARCIS (Netherlands)

    Lampropoulos, I.; Garoufalis, P.; Bosch, van den P.P.J.; Groot, de R.J.W.; Kling, W.L.

    2014-01-01

    This article addresses the day-ahead economic optimisation of energy storage systems within the setting of electricity spot markets. The case study is about a lithium-ion battery system integrated in a low voltage distribution grid with residential customers and photovoltaic generation in the

  9. Optimisation of the image resolution of a positron emission tomograph

    International Nuclear Information System (INIS)

    Ziemons, K.

    1993-10-01

    The resolution and the respective signal-to-noise ratios of reconstructed pictures were a point of main interest of the work for optimisation of PET systems. Monte-Carlo modelling calculations were applied to derive possible improvements of the technical design or performance of the PET system. (DG) [de

  10. FISHRENT; Bio-economic simulation and optimisation model

    NARCIS (Netherlands)

    Salz, P.; Buisman, F.C.; Soma, K.; Frost, H.; Accadia, P.; Prellezo, R.

    2011-01-01

    Key findings: The FISHRENT model is a major step forward in bio-economic model-ling, combining features that have not been fully integrated in earlier models: 1- Incorporation of any number of species (or stock) and/or fleets 2- Integration of simulation and optimisation over a period of 25 years 3-

  11. Design of optimised backstepping controller for the synchronisation

    Indian Academy of Sciences (India)

    In this paper, an adaptive backstepping controller has been tuned to synchronise two chaotic Colpitts oscillators in a master–slave configuration. The parameters of the controller are determined using shark smell optimisation (SSO) algorithm. Numerical results are presented and compared with those of particle swarm ...

  12. Plant-wide performance optimisation – The refrigeration system case

    DEFF Research Database (Denmark)

    Green, Torben; Razavi-Far, Roozbeh; Izadi-Zamanabadi, Roozbeh

    2012-01-01

    applicationsin the process industry. The paper addresses the fact that dynamic performance of the system is important, to ensure optimal changes between different operation conditions. To enable optimisation of the dynamic controller behaviour a method for designing the required excitation signal is presented...

  13. Preconditioned stochastic gradient descent optimisation for monomodal image registration

    NARCIS (Netherlands)

    Klein, S.; Staring, M.; Andersson, J.P.; Pluim, J.P.W.; Fichtinger, G.; Martel, A.; Peters, T.

    2011-01-01

    We present a stochastic optimisation method for intensity-based monomodal image registration. The method is based on a Robbins-Monro stochastic gradient descent method with adaptive step size estimation, and adds a preconditioning matrix. The derivation of the pre-conditioner is based on the

  14. Optimisation of Hidden Markov Model using Baum–Welch algorithm

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Earth System Science; Volume 126; Issue 1. Optimisation of Hidden Markov Model using Baum–Welch algorithm for prediction of maximum and minimum temperature over Indian Himalaya. J C Joshi Tankeshwar Kumar Sunita Srivastava Divya Sachdeva. Volume 126 Issue 1 February 2017 ...

  15. optimisation of compressive strength of periwinkle shell aggregate

    African Journals Online (AJOL)

    user

    2017-01-01

    Jan 1, 2017 ... In this paper, a regression model is developed to predict and optimise the compressive strength of periwinkle shell aggregate concrete using Scheffe's regression theory. The results obtained from the derived regression model agreed favourably with the experimental data. The model was tested for ...

  16. Smart optimisation and sensitivity analysis in water distribution systems

    CSIR Research Space (South Africa)

    Page, Philip R

    2015-12-01

    Full Text Available optimisation of a water distribution system by keeping the average pressure unchanged as water demands change, by changing the speed of the pumps. Another application area considered, using the same mathematical notions, is the study of the sensitivity...

  17. Estimators for initial conditions for optimisation in learning hydraulic systems

    NARCIS (Netherlands)

    Post, W.J.A.E.M.; Burrows, C.R.; Edge, K.A.

    1998-01-01

    In Learning Hydraulic Systems (LHS1. developed at the Eindhoven University of Technology, a specialised optimisation routine is employed In order to reduce energy losses in hydraulic systems. Typical load situations which can be managed by LHS are variable cyclic loads, as can be observed In many

  18. An optimised portfolio management model, incorporating best practices

    OpenAIRE

    2015-01-01

    M.Ing. (Engineering Management) Driving sustainability, optimising return on investments and cultivating a competitive market advantage, are imperative for organisational success and growth. In order to achieve the business objectives and value proposition, effective management strategies must be efficiently implemented, monitored and controlled. Failure to do so ultimately result in; financial loss due to increased capital and operational expenditure, schedule slippages, substandard deliv...

  19. Optimisation of searches for Supersymmetry with the ATLAS detector

    Energy Technology Data Exchange (ETDEWEB)

    Zvolsky, Milan

    2012-01-15

    The ATLAS experiment is one of the four large experiments at the Large Hadron Collider which is specifically designed to search for the Higgs boson and physics beyond the Standard Model. The aim of this thesis is the optimisation of searches for Supersymmetry in decays with two leptons and missing transverse energy in the final state. Two different optimisation studies have been performed for two important analysis aspects: The final signal region selection and the choice of the trigger selection. In the first part of the analysis, a cut-based optimisation of signal regions is performed, maximising the signal for a minimal background contamination. By this, the signal yield can in parts be more than doubled. The second approach is to introduce di-lepton triggers which allow to lower the lepton transverse momentum threshold, thus enhancing the number of selected signal events significantly. The signal region optimisation was considered for the choice of the final event selection in the ATLAS di-lepton analyses. The trigger study contributed to the incorporation of di-lepton triggers to the ATLAS trigger menu. (orig.)

  20. Optimisation Study on the Production of Anaerobic Digestate ...

    African Journals Online (AJOL)

    Organic fraction of municipal solid waste (OFMSW) is a rich substrate for biogas and compost production. Anaerobic Digestate compost (ADC) is an organic fertilizer produced from stabilized residuals of anaerobic digestion of OFMSW. This paper reports the result of studies carried out to optimise the production of ADC from ...

  1. Optimising performance in steady state for a supermarket refrigeration system

    DEFF Research Database (Denmark)

    Green, Torben; Kinnaert, Michel; Razavi-Far, Roozbeh

    2012-01-01

    Using a supermarket refrigeration system as an illustrative example, the paper postulates that by appropriately utilising knowledge of plant operation, the plant wide performance can be optimised based on a small set of variables. Focusing on steady state operations, the total system performance...

  2. A Bayesian Approach for Sensor Optimisation in Impact Identification

    Directory of Open Access Journals (Sweden)

    Vincenzo Mallardo

    2016-11-01

    Full Text Available This paper presents a Bayesian approach for optimizing the position of sensors aimed at impact identification in composite structures under operational conditions. The uncertainty in the sensor data has been represented by statistical distributions of the recorded signals. An optimisation strategy based on the genetic algorithm is proposed to find the best sensor combination aimed at locating impacts on composite structures. A Bayesian-based objective function is adopted in the optimisation procedure as an indicator of the performance of meta-models developed for different sensor combinations to locate various impact events. To represent a real structure under operational load and to increase the reliability of the Structural Health Monitoring (SHM system, the probability of malfunctioning sensors is included in the optimisation. The reliability and the robustness of the procedure is tested with experimental and numerical examples. Finally, the proposed optimisation algorithm is applied to a composite stiffened panel for both the uniform and non-uniform probability of impact occurrence.

  3. Optimisation of selective breeding program for Nile tilapia (Oreochromis niloticus)

    NARCIS (Netherlands)

    Trong, T.Q.

    2013-01-01

    The aim of this thesis was to optimise the selective breeding program for Nile tilapia in the Mekong Delta region of Vietnam. Two breeding schemes, the “classic” BLUP scheme following the GIFT method (with pair mating) and a rotational mating scheme with own performance selection and

  4. Optimised cantilever biosensor with piezoresistive read-out

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Thaysen, J.; Hansen, Ole

    2003-01-01

    We present a cantilever-based biochemical sensor with piezoresistive read-out which has been optimised for measuring surface stress. The resistors and the electrical wiring on the chip are encapsulated in low-pressure chemical vapor deposition (LPCVD) silicon nitride, so that the chip is well sui...

  5. Optimisation of Heterogeneous Migration Paths to High Bandwidth Home Connections

    NARCIS (Netherlands)

    Phillipson, F.

    2017-01-01

    Operators are building architectures and systems for delivering voice, audio, and data services at the required speed for now and in the future. For fixed access networks, this means in many countries a shift from copper based to fibre based access networks. This paper proposes a method to optimise

  6. Optimisation of wort production from rice malt using enzymes and ...

    African Journals Online (AJOL)

    Commercially, rice malt has never been successfully used in brewing because of its low free α-amino nitrogen (FAN) content. This study was designed to optimise rice malt replacement for barley malt in wort production and to improve FAN by adding α-amylase and protease. The response surface methodology (RSM) ...

  7. Transformation of Botrytis cinerea by direct hyphal blasting or by wound-mediated transformation of sclerotia

    Directory of Open Access Journals (Sweden)

    Ish - Shalom Shahar

    2011-12-01

    Full Text Available Abstract Background Botrytis cinerea is a haploid necrotrophic ascomycete which is responsible for 'grey mold' disease in more than 200 plant species. Broad molecular research has been conducted on this pathogen in recent years, resulting in the sequencing of two strains, which has generated a wealth of information toward developing additional tools for molecular transcriptome, proteome and secretome investigations. Nonetheless, transformation protocols have remained a significant bottleneck for this pathogen, hindering functional analysis research in many labs. Results In this study, we tested three different transformation methods for B. cinerea: electroporation, air-pressure-mediated and sclerotium-mediated transformation. We demonstrate successful transformation with three different DNA constructs using both air-pressure- and sclerotium-mediated transformation. Conclusions These transformation methods, which are fast, simple and reproducible, can expedite functional gene analysis of B. cinerea.

  8. Optimisation of a novel trailing edge concept for a high lift device

    CSIR Research Space (South Africa)

    Botha, JDM

    2014-09-01

    Full Text Available A novel concept (referred to as the flap extension) is implemented on the leading edge of the flap of a three element high lift device. The concept is optimised using two optimisation approaches based on Genetic Algorithm optimisations. A zero order...

  9. Coil optimisation for transcranial magnetic stimulation in realistic head geometry.

    Science.gov (United States)

    Koponen, Lari M; Nieminen, Jaakko O; Mutanen, Tuomas P; Stenroos, Matti; Ilmoniemi, Risto J

    Transcranial magnetic stimulation (TMS) allows focal, non-invasive stimulation of the cortex. A TMS pulse is inherently weakly coupled to the cortex; thus, magnetic stimulation requires both high current and high voltage to reach sufficient intensity. These requirements limit, for example, the maximum repetition rate and the maximum number of consecutive pulses with the same coil due to the rise of its temperature. To develop methods to optimise, design, and manufacture energy-efficient TMS coils in realistic head geometry with an arbitrary overall coil shape. We derive a semi-analytical integration scheme for computing the magnetic field energy of an arbitrary surface current distribution, compute the electric field induced by this distribution with a boundary element method, and optimise a TMS coil for focal stimulation. Additionally, we introduce a method for manufacturing such a coil by using Litz wire and a coil former machined from polyvinyl chloride. We designed, manufactured, and validated an optimised TMS coil and applied it to brain stimulation. Our simulations indicate that this coil requires less than half the power of a commercial figure-of-eight coil, with a 41% reduction due to the optimised winding geometry and a partial contribution due to our thinner coil former and reduced conductor height. With the optimised coil, the resting motor threshold of abductor pollicis brevis was reached with the capacitor voltage below 600 V and peak current below 3000 A. The described method allows designing practical TMS coils that have considerably higher efficiency than conventional figure-of-eight coils. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice

    International Nuclear Information System (INIS)

    Tobinaga, Shuichi; Matsumoto, Keitaro; Nagayasu, Takeshi; Furukawa, Katsuro; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Koji, Takehiko

    2015-01-01

    Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO 2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema

  11. The systematic study of the electroporation and electrofusion of B16-F1 and CHO cells in isotonic and hypotonic buffer.

    Science.gov (United States)

    Usaj, Marko; Kanduser, Masa

    2012-09-01

    The fusogenic state of the cell membrane can be induced by external electric field. When two fusogenic membranes are in close contact, cell fusion takes place. An appropriate hypotonic treatment of cells before the application of electric pulses significantly improves electrofusion efficiency. How hypotonic treatment improves electrofusion is still not known in detail. Our results indicate that at given induced transmembrane potential electroporation was not affected by buffer osmolarity. In contrast to electroporation, cells' response to hypotonic treatment significantly affects their electrofusion. High fusion yield was observed when B16-F1 cells were used; this cell line in hypotonic buffer resulted in 41 ± 9 % yield, while in isotonic buffer 32 ± 11 % yield was observed. Based on our knowledge, these fusion yields determined in situ by dual-color fluorescence microscopy are among the highest in electrofusion research field. The use of hypotonic buffer was more crucial for electrofusion of CHO cells; the fusion yield increased from below 1 % in isotonic buffer to 10 ± 4 % in hypotonic buffer. Since the same degree of cell permeabilization was achieved in both buffers, these results indicate that hypotonic treatment significantly improves fusion yield. The effect could be attributed to improved physical contact of cell membranes or to enhanced fusogenic state of the cell membrane itself.

  12. The effects of different concentrations of ccBA-GFP promoter with electroporation methods on the quality of koi sperm (Cyprinus carpio var. koi)

    Science.gov (United States)

    Soeprijanto, A.; Aisyah, D.

    2018-04-01

    The effectiveness of the use of promoter concentration which will be inserted into the Koi sperm as the medium of gene transfer is important. The objective of this research is to find out the influence of the adding of different concentrations of the ccBA-GFP promoter with electroporation methods to the motility, viability and the fertilization rate of the Koi sperm. This study was conducted at Central Lab of Life Sciences Brawijaya University in April 2017. Electroporation methods were conducted by using 30-volt voltage, 4 times shocks with 0.5 seconds per shock. The treatment of different concentration was done through 3 types of ccBA-GFP promoter concentration, namely: 10 ng/µl, 30 ng/µl, and 50 ng/µl. The best motility percentage with the score of 4 is at the treatment A (10ng/µl concentration), the best viability percentage is 77.83 % at the treatment A (10 ng/µl concentration) and the best fertilization rate is 73.09 % at the treatment A (10 ng/µl concentration). The result shows that there is a relationship between the treatment given to the motility and viability of the Koi sperm, at which, the higher the shocks, the lower the percentage of the motility and viability of the Koi sperm.

  13. Optimisation of X-ray examinations: General principles and an Irish perspective

    International Nuclear Information System (INIS)

    Matthews, Kate; Brennan, Patrick C.

    2009-01-01

    In Ireland, the European Medical Exposures Directive [Council Directive 97/43] was enacted into national law in Statutory Instrument 478 of 2002. This series of three review articles discusses the status of justification and optimisation of X-ray examinations nationally, and progress with the establishment of Irish diagnostic reference levels. In this second article, literature relating to optimisation issues arising in SI 478 of 2002 is reviewed. Optimisation associated with X-ray equipment and optimisation during day-to-day practice are considered. Optimisation proposals found in published research are summarised, and indicate the complex nature of optimisation. A paucity of current, research-based guidance documentation is identified. This is needed in order to support a range of professional staff in their practical implementation of optimisation.

  14. Mesh dependence in PDE-constrained optimisation an application in tidal turbine array layouts

    CERN Document Server

    Schwedes, Tobias; Funke, Simon W; Piggott, Matthew D

    2017-01-01

    This book provides an introduction to PDE-constrained optimisation using finite elements and the adjoint approach. The practical impact of the mathematical insights presented here are demonstrated using the realistic scenario of the optimal placement of marine power turbines, thereby illustrating the real-world relevance of best-practice Hilbert space aware approaches to PDE-constrained optimisation problems. Many optimisation problems that arise in a real-world context are constrained by partial differential equations (PDEs). That is, the system whose configuration is to be optimised follows physical laws given by PDEs. This book describes general Hilbert space formulations of optimisation algorithms, thereby facilitating optimisations whose controls are functions of space. It demonstrates the importance of methods that respect the Hilbert space structure of the problem by analysing the mathematical drawbacks of failing to do so. The approaches considered are illustrated using the optimisation problem arisin...

  15. Irreversible electroporation ablation (IRE of unresectable soft tissue tumors: learning curve evaluation in the first 150 patients treated.

    Directory of Open Access Journals (Sweden)

    Prejesh Philips

    Full Text Available BACKGROUND: Irreversible electroporation (IRE is a novel technology that uses peri-target discrete probes to deliver high-voltage localized electric current to induce cell death without thermal-induced coagulative necrosis. "Learnability" and consistently effective results by novice practitioners is essential for determining acceptance of novel techniques. This multi-center prospectively-collected database study evaluates the learning curve of IRE. METHODS: Analysis of 150 consecutive patients over 7 institutions from 9/2010-7/2012 was performed with patients treated divided into 3 groups A (1(st 50 patients treated, B (2(nd 50 and C (3(rd 50 patients treated chronologically and analyzed for outcomes. RESULTS: A total of 167 IRE procedures were performed, with a majority being liver(39.5% and pancreatic(35.5% lesions. The three groups were similar with respect to co-morbidities and demographics. Group C had larger lesions (3.9 vs 3 cm,p=0.001, more numerous lesions (3.2 vs 2.2,p=0.07, more vascular invasion(p=0.001, underwent more associated procedures(p=0.001 and had longer operative times(p<0.001. Despite this, they had similar complication and high-grade complication rates(p=0.24. Attributable morbidity rate was 13.3%(total 29.3% and high-grade complications were seen in 4.19%(total 12.6%. Pancreatic lesions(p=0.001 and laparotomy(p=0.001 were associated with complications. CONCLUSION: The review represents that single largest review of IRE soft tissue ablation demonstrating initial patient selection and safety. Over time, complex treatments of larger lesions and lesions with greater vascular involvement were performed without a significant increase in adverse effects or impact on local relapse free survival. This evolution demonstrates the safety profile of IRE and speed of graduation to more complex lesions, which was greater than 5 cases by institution. IRE is a safe and effective alternative to conventional ablation with a demonstrable

  16. Current NRPB recommendations on optimisation of protection of workers

    International Nuclear Information System (INIS)

    Wrixon, A.D.

    1994-01-01

    The National Radiological Protection Board is required by Ministerial Direction to provide advice on the relevance of the recommendations of the International Commission on Radiological Protection to the UK. Its advice was published in the Spring of 1993 after a period of consultation. In this article, which formed the basis of a presentation at an SRP Meeting on 29 April 1994, the Board's advice on the optimisation of protection of workers is explored and presented in the context of the developments in the understanding of the principle that have taken place in recent years. The most significant developments are the realisation that implementation of the principle is an essential function of good management and the recognition that the interests of the individual are not sufficiently taken into account by the dose limits alone but doses to individuals should be both constrained and optimised. (author)

  17. Optimised Design and Analysis of All-Optical Networks

    DEFF Research Database (Denmark)

    Glenstrup, Arne John

    2002-01-01

    through various experiments and is shown to produce good results and to be able to scale up to networks of realistic sizes. A novel method, subpath wavelength grouping, for routing connections in a multigranular all-optical network where several wavelengths can be grouped and switched at band and fibre......This PhD thesis presents a suite of methods for optimising design and for analysing blocking probabilities of all-optical networks. It thus contributes methodical knowledge to the field of computer assisted planning of optical networks. A two-stage greenfield optical network design optimiser...... is developed, based on shortest-path algorithms and a comparatively new metaheuristic called simulated allocation. It is able to handle design of all-optical mesh networks with optical cross-connects, considers duct as well as fibre and node costs, and can also design protected networks. The method is assessed...

  18. Optimised mounting conditions for poly (ether sulfone) in radiation detection.

    Science.gov (United States)

    Nakamura, Hidehito; Shirakawa, Yoshiyuki; Sato, Nobuhiro; Yamada, Tatsuya; Kitamura, Hisashi; Takahashi, Sentaro

    2014-09-01

    Poly (ether sulfone) (PES) is a candidate for use as a scintillation material in radiation detection. Its characteristics, such as its emission spectrum and its effective refractive index (based on the emission spectrum), directly affect the propagation of light generated to external photodetectors. It is also important to examine the presence of background radiation sources in manufactured PES. Here, we optimise the optical coupling and surface treatment of the PES, and characterise its background. Optical grease was used to enhance the optical coupling between the PES and the photodetector; absorption by the grease of short-wavelength light emitted from PES was negligible. Diffuse reflection induced by surface roughening increased the light yield for PES, despite the high effective refractive index. Background radiation derived from the PES sample and its impurities was negligible above the ambient, natural level. Overall, these results serve to optimise the mounting conditions for PES in radiation detection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Optimisation of patient and staff exposure in interventional cardiology

    International Nuclear Information System (INIS)

    Padovani, R.; Malisan, M.R.; Bernardi, G.; Vano, E.; Neofotistou, V.

    2001-01-01

    The Council Directive of the European Community 97/43/Euratom (MED) deals with the health protection of individuals against dangers of ionising radiation in relation to medical exposure, and also focuses attention on some special practices (Art. 9), including interventional radiology, a technique involving high doses to the patient. The paper presents the European approach to optimisation of exposure in interventional cardiology. The DIMOND research consortium (DIMOND: Digital Imaging: Measures for Optimising Radiological Information Content and Dose) is working to develop quality criteria for cineangiographic images, to develop procedures for the classification of complexity of therapeutic and diagnostic procedures and to derive reference levels, related also to procedure complexity. DIMOND project also includes aspects of equipment characteristics and performance and content of training in radiation protection of personnel working in interventional radiology field. (author)

  20. Biomass supply chain optimisation for Organosolv-based biorefineries.

    Science.gov (United States)

    Giarola, Sara; Patel, Mayank; Shah, Nilay

    2014-05-01

    This work aims at providing a Mixed Integer Linear Programming modelling framework to help define planning strategies for the development of sustainable biorefineries. The up-scaling of an Organosolv biorefinery was addressed via optimisation of the whole system economics. Three real world case studies were addressed to show the high-level flexibility and wide applicability of the tool to model different biomass typologies (i.e. forest fellings, cereal residues and energy crops) and supply strategies. Model outcomes have revealed how supply chain optimisation techniques could help shed light on the development of sustainable biorefineries. Feedstock quality, quantity, temporal and geographical availability are crucial to determine biorefinery location and the cost-efficient way to supply the feedstock to the plant. Storage costs are relevant for biorefineries based on cereal stubble, while wood supply chains present dominant pretreatment operations costs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Optimisation of VSC-HVDC Transmission for Wind Power Plants

    DEFF Research Database (Denmark)

    Silva, Rodrigo Da

    Connection of Wind Power Plants (WPP), typically oshore, using VSCHVDC transmission is an emerging solution with many benefits compared to the traditional AC solution, especially concerning the impact on control architecture of the wind farms and the grid. The VSC-HVDC solution is likely to meet...... more stringent grid codes than a conventional AC transmission connection. The purpose of this project is to analyse how HVDC solution, considering the voltage-source converter based technology, for grid connection of large wind power plants can be designed and optimised. By optimisation, the project...... the robust control technique is applied is compared with the classical proportional-integral (PI) performance, by means of time domain simulation in a point-to-point HVDC connection. The three main parameters in the discussion are the wind power delivered from the offshore wind power plant, the variation...

  2. Computed tomography dose optimisation in cystic fibrosis: A review.

    LENUS (Irish Health Repository)

    Ferris, Helena

    2016-04-28

    Cystic fibrosis (CF) is the most common autosomal recessive disease of the Caucasian population worldwide, with respiratory disease remaining the most relevant source of morbidity and mortality. Computed tomography (CT) is frequently used for monitoring disease complications and progression. Over the last fifteen years there has been a six-fold increase in the use of CT, which has lead to a growing concern in relation to cumulative radiation exposure. The challenge to the medical profession is to identify dose reduction strategies that meet acceptable image quality, but fulfil the requirements of a diagnostic quality CT. Dose-optimisation, particularly in CT, is essential as it reduces the chances of patients receiving cumulative radiation doses in excess of 100 mSv, a dose deemed significant by the United Nations Scientific Committee on the Effects of Atomic Radiation. This review article explores the current trends in imaging in CF with particular emphasis on new developments in dose optimisation.

  3. Energy balance of the optimised CVT-hybrid-driveline

    Energy Technology Data Exchange (ETDEWEB)

    Hoehn, Bernd-Robert; Pflaum, Hermann; Lechner, Claus [Forschungsstelle fuer Zahnraeder und Getriebebau, Technische Univ. Muenchen, Garching (Germany)

    2009-07-01

    Funded by the DFG (German Research Foundation) and some industry partners like GM Powertrain Europe, ZF, EPCOS the Optimised CVT-Hybrid was developed at Technische Universitaet Muenchen in close collaboration with the industry and is currently under scientific investigation. Designed as a parallel hybrid vehicle the Optimised CVT-Hybrid combines a series-production diesel engine with a small electric motor. The core element of the driveline is a two range continuously variable transmission (i{radical}i-transmission), which is based on a chain variator. By a special shifting process without interruption of traction force the ratio range of the chain variator is used twice; thereby a wide transmission-ratio spread is achieved by low complexity. Thus the transmission provides a large pull-away ratio for the small electric motor and a fuel-efficient overdrive ratio for the ic-engine. Instead of heavy and space-consuming accumulators a small efficient package of double layer capacitors (UltraCaps) is used for electric energy and power storage. The driveline management is done by an optimised vehicle controller. Within the scope of the research project two prototype drivelines were manufactured. One driveline is integrated into an Opel Vectra Caravan and is available for investigations at the roller dynamometer and in the actual road traffic. The second hybrid driveline is assembled at the powertrain test rig of the FZG for detailed analysis of system behaviour and fuel consumption. Based on measurements of standardised driving cycles system behaviour, fuel consumption and a detailed energy balance of the Optimised CVT-Hybrid are presented. In comparison to the series-production vehicle the fuel savings are shown. (orig.)

  4. Optimising metadata workflows in a distributed information environment

    OpenAIRE

    Robertson, R. John; Barton, Jane

    2005-01-01

    The different purposes present within a distributed information environment create the potential for repositories to enhance their metadata by capitalising on the diversity of metadata available for any given object. This paper presents three conceptual reference models required to achieve this optimisation of metadata workflow: the ecology of repositories, the object lifecycle model, and the metadata lifecycle model. It suggests a methodology for developing the metadata lifecycle model, and ...

  5. Optimising training data for ANNs with Genetic Algorithms

    OpenAIRE

    Kamp , R. G.; Savenije , H. H. G.

    2006-01-01

    International audience; Artificial Neural Networks (ANNs) have proved to be good modelling tools in hydrology for rainfall-runoff modelling and hydraulic flow modelling. Representative datasets are necessary for the training phase in which the ANN learns the model's input-output relations. Good and representative training data is not always available. In this publication Genetic Algorithms (GA) are used to optimise training datasets. The approach is tested with an existing hydraulic model in ...

  6. Optimising training data for ANNs with Genetic Algorithms

    OpenAIRE

    R. G. Kamp; R. G. Kamp; H. H. G. Savenije

    2006-01-01

    Artificial Neural Networks (ANNs) have proved to be good modelling tools in hydrology for rainfall-runoff modelling and hydraulic flow modelling. Representative datasets are necessary for the training phase in which the ANN learns the model's input-output relations. Good and representative training data is not always available. In this publication Genetic Algorithms (GA) are used to optimise training datasets. The approach is tested with an existing hydraulic model in The Netherlands. An...

  7. A study of certain Monte Carlo search and optimisation methods

    International Nuclear Information System (INIS)

    Budd, C.

    1984-11-01

    Studies are described which might lead to the development of a search and optimisation facility for the Monte Carlo criticality code MONK. The facility envisaged could be used to maximise a function of k-effective with respect to certain parameters of the system or, alternatively, to find the system (in a given range of systems) for which that function takes a given value. (UK)

  8. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  9. Module detection in complex networks using integer optimisation

    Directory of Open Access Journals (Sweden)

    Tsoka Sophia

    2010-11-01

    Full Text Available Abstract Background The detection of modules or community structure is widely used to reveal the underlying properties of complex networks in biology, as well as physical and social sciences. Since the adoption of modularity as a measure of network topological properties, several methodologies for the discovery of community structure based on modularity maximisation have been developed. However, satisfactory partitions of large graphs with modest computational resources are particularly challenging due to the NP-hard nature of the related optimisation problem. Furthermore, it has been suggested that optimising the modularity metric can reach a resolution limit whereby the algorithm fails to detect smaller communities than a specific size in large networks. Results We present a novel solution approach to identify community structure in large complex networks and address resolution limitations in module detection. The proposed algorithm employs modularity to express network community structure and it is based on mixed integer optimisation models. The solution procedure is extended through an iterative procedure to diminish effects that tend to agglomerate smaller modules (resolution limitations. Conclusions A comprehensive comparative analysis of methodologies for module detection based on modularity maximisation shows that our approach outperforms previously reported methods. Furthermore, in contrast to previous reports, we propose a strategy to handle resolution limitations in modularity maximisation. Overall, we illustrate ways to improve existing methodologies for community structure identification so as to increase its efficiency and applicability.

  10. Modulation aware cluster size optimisation in wireless sensor networks

    Science.gov (United States)

    Sriram Naik, M.; Kumar, Vinay

    2017-07-01

    Wireless sensor networks (WSNs) play a great role because of their numerous advantages to the mankind. The main challenge with WSNs is the energy efficiency. In this paper, we have focused on the energy minimisation with the help of cluster size optimisation along with consideration of modulation effect when the nodes are not able to communicate using baseband communication technique. Cluster size optimisations is important technique to improve the performance of WSNs. It provides improvement in energy efficiency, network scalability, network lifetime and latency. We have proposed analytical expression for cluster size optimisation using traditional sensing model of nodes for square sensing field with consideration of modulation effects. Energy minimisation can be achieved by changing the modulation schemes such as BPSK, 16-QAM, QPSK, 64-QAM, etc., so we are considering the effect of different modulation techniques in the cluster formation. The nodes in the sensing fields are random and uniformly deployed. It is also observed that placement of base station at centre of scenario enables very less number of modulation schemes to work in energy efficient manner but when base station placed at the corner of the sensing field, it enable large number of modulation schemes to work in energy efficient manner.

  11. Statistical optimisation techniques in fatigue signal editing problem

    International Nuclear Information System (INIS)

    Nopiah, Z. M.; Osman, M. H.; Baharin, N.; Abdullah, S.

    2015-01-01

    Success in fatigue signal editing is determined by the level of length reduction without compromising statistical constraints. A great reduction rate can be achieved by removing small amplitude cycles from the recorded signal. The long recorded signal sometimes renders the cycle-to-cycle editing process daunting. This has encouraged researchers to focus on the segment-based approach. This paper discusses joint application of the Running Damage Extraction (RDE) technique and single constrained Genetic Algorithm (GA) in fatigue signal editing optimisation.. In the first section, the RDE technique is used to restructure and summarise the fatigue strain. This technique combines the overlapping window and fatigue strain-life models. It is designed to identify and isolate the fatigue events that exist in the variable amplitude strain data into different segments whereby the retention of statistical parameters and the vibration energy are considered. In the second section, the fatigue data editing problem is formulated as a constrained single optimisation problem that can be solved using GA method. The GA produces the shortest edited fatigue signal by selecting appropriate segments from a pool of labelling segments. Challenges arise due to constraints on the segment selection by deviation level over three signal properties, namely cumulative fatigue damage, root mean square and kurtosis values. Experimental results over several case studies show that the idea of solving fatigue signal editing within a framework of optimisation is effective and automatic, and that the GA is robust for constrained segment selection

  12. Statistical optimisation techniques in fatigue signal editing problem

    Energy Technology Data Exchange (ETDEWEB)

    Nopiah, Z. M.; Osman, M. H. [Fundamental Engineering Studies Unit Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, 43600 UKM (Malaysia); Baharin, N.; Abdullah, S. [Department of Mechanical and Materials Engineering Faculty of Engineering and Built Environment, Universiti Kebangsaan Malaysia, 43600 UKM (Malaysia)

    2015-02-03

    Success in fatigue signal editing is determined by the level of length reduction without compromising statistical constraints. A great reduction rate can be achieved by removing small amplitude cycles from the recorded signal. The long recorded signal sometimes renders the cycle-to-cycle editing process daunting. This has encouraged researchers to focus on the segment-based approach. This paper discusses joint application of the Running Damage Extraction (RDE) technique and single constrained Genetic Algorithm (GA) in fatigue signal editing optimisation.. In the first section, the RDE technique is used to restructure and summarise the fatigue strain. This technique combines the overlapping window and fatigue strain-life models. It is designed to identify and isolate the fatigue events that exist in the variable amplitude strain data into different segments whereby the retention of statistical parameters and the vibration energy are considered. In the second section, the fatigue data editing problem is formulated as a constrained single optimisation problem that can be solved using GA method. The GA produces the shortest edited fatigue signal by selecting appropriate segments from a pool of labelling segments. Challenges arise due to constraints on the segment selection by deviation level over three signal properties, namely cumulative fatigue damage, root mean square and kurtosis values. Experimental results over several case studies show that the idea of solving fatigue signal editing within a framework of optimisation is effective and automatic, and that the GA is robust for constrained segment selection.

  13. Numerical optimisation of an axial turbine; Numerische Optimierung einer Axialturbine

    Energy Technology Data Exchange (ETDEWEB)

    Welzel, B.

    1998-12-31

    The author presents a method for automatic shape optimisation of components with internal or external flow. The method combines a program for numerical calculation of frictional turbulent flow with an optimisation algorithm. Algorithms are a simplex search strategy and an evolution strategy. The shape of the component to be optimized is variable due to shape parameters modified by the algorithm. For each shape, a flow calculation is carried out on whose basis a functional value like performance, loss, lift or resistivity is calculated. For validation, the optimisation method is used in simple examples with known solutions. It is applied. It is applied to the components of a slow-running axial turbine. Components with accelerated and delayed rotationally symmetric flow and 2D blade profiles are optimized. [Deutsch] Es wird eine Methode zur automatischen Formoptimierung durchstroemter oder umstroemter Bauteile vorgestellt. Diese koppelt ein Programm zur numerischen Berechnung reibungsbehafteter turbulenter Stroemungen mit einem Optimierungsalgorithmus. Dabei kommen als Algorithmen eine Simplex-Suchstrategie und eine Evolutionsstrategie zum Einsatz. Die Form des zu optimierenden Koerpers ist durch Formparameter, die vom Algorithmus veraendert werden, variabel. Fuer jede Form wird eine Stroemungsberechnung durchgefuehrt und mit dieser ein Funktionswert wie Wirkungsgrad, Verlust, Auftrieb oder Widerstandskraft berechnet. Die Optimierungsmethode wird zur Validierung in einfachen Beispielen mit bekannter Loesung eingesetzt. Zur Anwendung kommt sie in den einzelnen Komponenten einer langsamlaeufigen Axialturbine. Es werden Bauteile mit beschleunigter und verzoegerter rotationssymmetrischer Stroemung und 2D-Schaufelprofile optimiert. (orig.)

  14. Optimising the Target and Capture Sections of the Neutrino Factory

    CERN Document Server

    Hansen, Ole Martin; Stapnes, Steinar

    The Neutrino Factory is designed to produce an intense high energy neutrino beam from stored muons. The majority of the muons are obtained from the decay of pions, produced by a proton beam impinging on a free-flowing mercury-jet target and captured by a high magnetic field. It is important to capture a large fraction of the produced pions to maximize the intensity of the neutrino beam. Various optimisation studies have been performed with the aim of maximising the muon influx to the accelerator and thus the neutrino beam intensity. The optimisation studies were performed with the use of Monte Carlo simulation tools. The production of secondary particles, by interactions between the incoming proton beam and the mercury target, was optimised by varying the proton beam impact position and impact angles on the target. The proton beam and target interaction region was studied and showed to be off the central axis of the capture section in the baseline configuration. The off-centred interaction region resulted in ...

  15. Crystal structure optimisation using an auxiliary equation of state

    Science.gov (United States)

    Jackson, Adam J.; Skelton, Jonathan M.; Hendon, Christopher H.; Butler, Keith T.; Walsh, Aron

    2015-11-01

    Standard procedures for local crystal-structure optimisation involve numerous energy and force calculations. It is common to calculate an energy-volume curve, fitting an equation of state around the equilibrium cell volume. This is a computationally intensive process, in particular, for low-symmetry crystal structures where each isochoric optimisation involves energy minimisation over many degrees of freedom. Such procedures can be prohibitive for non-local exchange-correlation functionals or other "beyond" density functional theory electronic structure techniques, particularly where analytical gradients are not available. We present a simple approach for efficient optimisation of crystal structures based on a known equation of state. The equilibrium volume can be predicted from one single-point calculation and refined with successive calculations if required. The approach is validated for PbS, PbTe, ZnS, and ZnTe using nine density functionals and applied to the quaternary semiconductor Cu2ZnSnS4 and the magnetic metal-organic framework HKUST-1.

  16. Crystal structure optimisation using an auxiliary equation of state

    International Nuclear Information System (INIS)

    Jackson, Adam J.; Skelton, Jonathan M.; Hendon, Christopher H.; Butler, Keith T.; 3 Institute and Department of Materials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of))" data-affiliation=" (Centre for Sustainable Chemical Technologies and Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom); Global E3 Institute and Department of Materials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of))" >Walsh, Aron

    2015-01-01

    Standard procedures for local crystal-structure optimisation involve numerous energy and force calculations. It is common to calculate an energy–volume curve, fitting an equation of state around the equilibrium cell volume. This is a computationally intensive process, in particular, for low-symmetry crystal structures where each isochoric optimisation involves energy minimisation over many degrees of freedom. Such procedures can be prohibitive for non-local exchange-correlation functionals or other “beyond” density functional theory electronic structure techniques, particularly where analytical gradients are not available. We present a simple approach for efficient optimisation of crystal structures based on a known equation of state. The equilibrium volume can be predicted from one single-point calculation and refined with successive calculations if required. The approach is validated for PbS, PbTe, ZnS, and ZnTe using nine density functionals and applied to the quaternary semiconductor Cu 2 ZnSnS 4 and the magnetic metal-organic framework HKUST-1

  17. Crystal structure optimisation using an auxiliary equation of state

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, Adam J.; Skelton, Jonathan M.; Hendon, Christopher H.; Butler, Keith T. [Centre for Sustainable Chemical Technologies and Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom); Walsh, Aron, E-mail: a.walsh@bath.ac.uk [Centre for Sustainable Chemical Technologies and Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom); Global E" 3 Institute and Department of Materials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2015-11-14

    Standard procedures for local crystal-structure optimisation involve numerous energy and force calculations. It is common to calculate an energy–volume curve, fitting an equation of state around the equilibrium cell volume. This is a computationally intensive process, in particular, for low-symmetry crystal structures where each isochoric optimisation involves energy minimisation over many degrees of freedom. Such procedures can be prohibitive for non-local exchange-correlation functionals or other “beyond” density functional theory electronic structure techniques, particularly where analytical gradients are not available. We present a simple approach for efficient optimisation of crystal structures based on a known equation of state. The equilibrium volume can be predicted from one single-point calculation and refined with successive calculations if required. The approach is validated for PbS, PbTe, ZnS, and ZnTe using nine density functionals and applied to the quaternary semiconductor Cu{sub 2}ZnSnS{sub 4} and the magnetic metal-organic framework HKUST-1.

  18. Optimisation of Oil Production in Two – Phase Flow Reservoir Using Simultaneous Method and Interior Point Optimiser

    DEFF Research Database (Denmark)

    Lerch, Dariusz Michal; Völcker, Carsten; Capolei, Andrea

    2012-01-01

    in the reservoir. A promising decrease of these remained resources can be provided by smart wells applying water injections to sustain satisfactory pressure level in the reservoir throughout the whole process of oil production. Basically to enhance secondary recovery of the remaining oil after drilling, water...... is injected at the injection wells of the down-hole pipes. This sustains the pressure in the reservoir and drives oil towards production wells. There are however, many factors contributing to the poor conventional secondary recovery methods e.g. strong surface tension, heterogeneity of the porous rock...... fields, or closed loop optimisation, can be used for optimising the reservoir performance in terms of net present value of oil recovery or another economic objective. In order to solve an optimal control problem we use a direct collocation method where we translate a continuous problem into a discrete...

  19. Techno-economic optimisation of energy systems; Contribution a l'optimisation technico-economique de systemes energetiques

    Energy Technology Data Exchange (ETDEWEB)

    Mansilla Pellen, Ch

    2006-07-15

    The traditional approach currently used to assess the economic interest of energy systems is based on a defined flow-sheet. Some studies have shown that the flow-sheets corresponding to the best thermodynamic efficiencies do not necessarily lead to the best production costs. A method called techno-economic optimisation was proposed. This method aims at minimising the production cost of a given energy system, including both investment and operating costs. It was implemented using genetic algorithms. This approach was compared to the heat integration method on two different examples, thus validating its interest. Techno-economic optimisation was then applied to different energy systems dealing with hydrogen as well as electricity production. (author)

  20. Shape optimisation and performance analysis of flapping wings

    KAUST Repository

    Ghommem, Mehdi

    2012-09-04

    In this paper, shape optimisation of flapping wings in forward flight is considered. This analysis is performed by combining a local gradient-based optimizer with the unsteady vortex lattice method (UVLM). Although the UVLM applies only to incompressible, inviscid flows where the separation lines are known a priori, Persson et al. [1] showed through a detailed comparison between UVLM and higher-fidelity computational fluid dynamics methods for flapping flight that the UVLM schemes produce accurate results for attached flow cases and even remain trend-relevant in the presence of flow separation. As such, they recommended the use of an aerodynamic model based on UVLM to perform preliminary design studies of flapping wing vehicles Unlike standard computational fluid dynamics schemes, this method requires meshing of the wing surface only and not of the whole flow domain [2]. From the design or optimisation perspective taken in our work, it is fairly common (and sometimes entirely necessary, as a result of the excessive computational cost of the highest fidelity tools such as Navier-Stokes solvers) to rely upon such a moderate level of modelling fidelity to traverse the design space in an economical manner. The objective of the work, described in this paper, is to identify a set of optimised shapes that maximise the propulsive efficiency, defined as the ratio of the propulsive power over the aerodynamic power, under lift, thrust, and area constraints. The shape of the wings is modelled using B-splines, a technology used in the computer-aided design (CAD) field for decades. This basis can be used to smoothly discretize wing shapes with few degrees of freedom, referred to as control points. The locations of the control points constitute the design variables. The results suggest that changing the shape yields significant improvement in the performance of the flapping wings. The optimisation pushes the design to "bird-like" shapes with substantial increase in the time

  1. Pathological study on the testis of mice irradiated by γ-rays after transfecting pprI gene by in vivo electroporation

    International Nuclear Information System (INIS)

    Lian Lixia; Chen Tingting; Zhang Yongqin; Wang Xiuzhen; Yang Zhanshan

    2011-01-01

    To investigate the effects of pprI gene from Deinococcus radiodurans transferred by in vivo electroporation on γ-ray injury of mice, the morphological changes of testis in the mice were observed. The pCMV-HA-pprI plasmid containing pprI gene was injected into the muscle of mice. The pprI gene was transfected into the cells by in vivo gene electroporation technology. Then the control group and the transferred pCMV-HA-pprI group were exposed to γ-ray radiation of 6 Gy. The muscle tissue at the site of the injection and the testis tissue were taken on days 1, 7, 14, 28 and 35 after radiation. Then total protein was extracted and used to test the expression of PprI with western blotting technology. The testis specimen prepared by hematoxylin-eosin staining was then examined by light microscopy. The expression of PprI is remarkable on the 1 st day after irradiation to prove that the pprI gene was successfully transfected into the mice. On the 1 st day after irradiation there was no obvious pathological change of the testis tissue of the control group. On the 7th day there was degeneration and necrosis of some spermatogonia and spermatocytes in sections of tubules. On the 14th day, the reduction of spermatogonia was generally marked, and there was considerable reduction in the number of primary spermatocytes associated with atrophy of the seminiferous tubules. On the 28th day there was complete depletion of spermatogenic epithelium when spermatocytes and spermatids had largely disappeared, with no regeneration of spermatogonia and only sertoli cells nuclei remaining along the basement membrane. On the 35th day, spermatogonia were actively regenerating in some of the tubules. Compared with the control group, there was also no significant difference on the 1 st after irradiation in the transgenic animal. On the 7th day the degeneration and necrosis of some spermatogonia and spermatocytes in sections of tubules was less than that of the control group. On the 14th day the

  2. Warpage optimisation on the moulded part with straight-drilled and conformal cooling channels using response surface methodology (RSM) and glowworm swarm optimisation (GSO)

    Science.gov (United States)

    Hazwan, M. H. M.; Shayfull, Z.; Sharif, S.; Nasir, S. M.; Zainal, N.

    2017-09-01

    In injection moulding process, quality and productivity are notably important and must be controlled for each product type produced. Quality is measured as the extent of warpage of moulded parts while productivity is measured as a duration of moulding cycle time. To control the quality, many researchers have introduced various of optimisation approaches which have been proven enhanced the quality of the moulded part produced. In order to improve the productivity of injection moulding process, some of researches have proposed the application of conformal cooling channels which have been proven reduced the duration of moulding cycle time. Therefore, this paper presents an application of alternative optimisation approach which is Response Surface Methodology (RSM) with Glowworm Swarm Optimisation (GSO) on the moulded part with straight-drilled and conformal cooling channels mould. This study examined the warpage condition of the moulded parts before and after optimisation work applied for both cooling channels. A front panel housing have been selected as a specimen and the performance of proposed optimisation approach have been analysed on the conventional straight-drilled cooling channels compared to the Milled Groove Square Shape (MGSS) conformal cooling channels by simulation analysis using Autodesk Moldflow Insight (AMI) 2013. Based on the results, melt temperature is the most significant factor contribute to the warpage condition and warpage have optimised by 39.1% after optimisation for straight-drilled cooling channels and cooling time is the most significant factor contribute to the warpage condition and warpage have optimised by 38.7% after optimisation for MGSS conformal cooling channels. In addition, the finding shows that the application of optimisation work on the conformal cooling channels offers the better quality and productivity of the moulded part produced.

  3. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  4. Optimisation of logistics processes of energy grass collection

    Science.gov (United States)

    Bányai, Tamás.

    2010-05-01

    The collection of energy grass is a logistics-intensive process [1]. The optimal design and control of transportation and collection subprocesses is a critical point of the supply chain. To avoid irresponsible decisions by right of experience and intuition, the optimisation and analysis of collection processes based on mathematical models and methods is the scientific suggestible way. Within the frame of this work, the author focuses on the optimisation possibilities of the collection processes, especially from the point of view transportation and related warehousing operations. However the developed optimisation methods in the literature [2] take into account the harvesting processes, county-specific yields, transportation distances, erosion constraints, machinery specifications, and other key variables, but the possibility of more collection points and the multi-level collection were not taken into consideration. The possible areas of using energy grass is very wide (energetically use, biogas and bio alcohol production, paper and textile industry, industrial fibre material, foddering purposes, biological soil protection [3], etc.), so not only a single level but also a multi-level collection system with more collection and production facilities has to be taken into consideration. The input parameters of the optimisation problem are the followings: total amount of energy grass to be harvested in each region; specific facility costs of collection, warehousing and production units; specific costs of transportation resources; pre-scheduling of harvesting process; specific transportation and warehousing costs; pre-scheduling of processing of energy grass at each facility (exclusive warehousing). The model take into consideration the following assumptions: (1) cooperative relation among processing and production facilties, (2) capacity constraints are not ignored, (3) the cost function of transportation is non-linear, (4) the drivers conditions are ignored. The

  5. Articular chondrocyte network mediated by gap junctions: role in metabolic cartilage homeostasis

    Science.gov (United States)

    Mayan, Maria D; Gago-Fuentes, Raquel; Carpintero-Fernandez, Paula; Fernandez-Puente, Patricia; Filgueira-Fernandez, Purificacion; Goyanes, Noa; Valiunas, Virginijus; Brink, Peter R; Goldberg, Gary S; Blanco, Francisco J

    2017-01-01

    Objective This study investigated whether chondrocytes within the cartilage matrix have the capacity to communicate through intercellular connections mediated by voltage-gated gap junction (GJ) channels. Methods Frozen cartilage samples were used for immunofluorescence and immunohistochemistry assays. Samples were embedded in cacodylate buffer before dehydration for scanning electron microscopy. Co-immunoprecipitation experiments and mass spectrometry (MS) were performed to identify proteins that interact with the C-terminal end of Cx43. GJ communication was studied through in situ electroporation, electrophysiology and dye injection experiments. A transwell layered culture system and MS were used to identify and quantify transferred amino acids. Results Microscopic images revealed the presence of multiple cellular projections connecting chondrocytes within the matrix. These projections were between 5 and 150 μm in length. MS data analysis indicated that the C-terminus of Cx43 interacts with several cytoskeletal proteins implicated in Cx trafficking and GJ assembly, including α-tubulin and β-tubulin, actin, and vinculin. Electrophysiology experiments demonstrated that 12-mer oligonucleotides could be transferred between chondrocytes within 12 min after injection. Glucose was homogeneously distributed within 22 and 35 min. No transfer was detected when glucose was electroporated into A549 cells, which have no GJs. Transwell layered culture systems coupled with MS analysis revealed connexins can mediate the transfer of L-lysine and L-arginine between chondrocytes. Conclusions This study reveals that intercellular connections between chondrocytes contain GJs that play a key role in cell-cell communication and a metabolic function by exchange of nutrients including glucose and essential amino acids. A three-dimensional cellular network mediated through GJs might mediate metabolic and physiological homeostasis to maintain cartilage tissue. PMID:24225059

  6. Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

    Science.gov (United States)

    Wendler, J J; Ganzer, R; Hadaschik, B; Blana, A; Henkel, T; Köhrmann, K U; Machtens, S; Roosen, A; Salomon, G; Sentker, L; Witzsch, U; Schlemmer, H P; Baumunk, D; Köllermann, J; Schostak, M; Liehr, U B

    2017-01-01

    Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.

  7. Dose-dependent ATP depletion and cancer cell death following calcium electroporation, relative effect of calcium concentration and electric field strength

    DEFF Research Database (Denmark)

    Hansen, Emilie Louise; Sozer, Esin Bengisu; Romeo, Stefania

    2015-01-01

    death and could be a novel cancer treatment. This study aims at understanding the relationship between applied electric field, calcium concentration, ATP depletion and efficacy. METHODS: In three human cell lines--H69 (small-cell lung cancer), SW780 (bladder cancer), and U937 (leukaemia), viability...... was observed with fluorescence confocal microscopy of quinacrine-labelled U937 cells. RESULTS: Both H69 and SW780 cells showed dose-dependent (calcium concentration and electric field) decrease in intracellular ATP (p...-dependently reduced cell survival and intracellular ATP. Increasing extracellular calcium allows the use of a lower electric field. GENERAL SIGNIFICANCE: This study supports the use of calcium electroporation for treatment of cancer and possibly lowering the applied electric field in future trials....

  8. Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity.

    Science.gov (United States)

    Bissa, Massimiliano; Quaglino, Elena; Zanotto, Carlo; Illiano, Elena; Rolih, Valeria; Pacchioni, Sole; Cavallo, Federica; De Giuli Morghen, Carlo; Radaelli, Antonia

    2016-10-01

    The control of smallpox was achieved using live vaccinia virus (VV) vaccine, which successfully eradicated the disease worldwide. As the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. However, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated VV strains. Considering the closely related animal poxviruses that also arise as zoonoses, and the increasing number of unvaccinated or immunocompromised people, a safer and more effective vaccine is still required. With this aim, new vectors based on avian poxviruses that cannot replicate in mammals should improve the safety of conventional vaccines, and protect from zoonotic orthopoxvirus diseases, such as cowpox and monkeypox. In this study, DNA and fowlpox (FP) recombinants that expressed the VV L1R, A27L, A33R, and B5R genes were generated (4DNAmix, 4FPmix, respectively) and tested in mice using novel administration routes. Mice were primed with 4DNAmix by electroporation, and boosted with 4FPmix applied intranasally. The lethal VV IHD-J strain was then administered by intranasal challenge. All of the mice receiving 4DNAmix followed by 4FPmix, and 20% of the mice immunized only with 4FPmix, were protected. The induction of specific humoral and cellular immune responses directly correlated with this protection. In particular, higher anti-A27 antibodies and IFNγ-producing T lymphocytes were measured in the blood and spleen of the protected mice, as compared to controls. VV IHD-J neutralizing antibodies in sera from the protected mice suggest that the prime/boost vaccination regimen with 4DNAmix plus 4FPmix may be an effective and safe mode to induce protection against smallpox and poxvirus zoonotic infections. The electroporation/intranasal administration routes contributed to effective immune responses and mouse survival. Copyright

  9. The effects of magnetite (Fe3O4 nanoparticles on electroporation-induced inward currents in pituitary tumor (GH3 cells and in RAW 264.7 macrophages

    Directory of Open Access Journals (Sweden)

    Liu YC

    2012-03-01

    Full Text Available Yen-Chin Liu1, Ping-Ching Wu2, Dar-Bin Shieh2–5, Sheng-Nan Wu3,6,71Department of Anesthesiology, 2Institute of Oral Medicine and Department of Stomatology, 3Department of Physiology, National Cheng Kung University Hospital, College of Medicine, 4Advanced Optoelectronic Technology Center, 5Center for Micro/Nano Science and Technology, National Cheng Kung University, 6Innovation Center for Advanced Medical Device Technology, National Cheng Kung University, 7Department of Anatomy and Cell Biology, National Cheng Kung University Medical College, Tainan, TaiwanAims: Fe3O4 nanoparticles (NPs have been known to provide a distinct image contrast effect for magnetic resonance imaging owing to their super paramagnetic properties on local magnetic fields. However, the possible effects of these NPs on membrane ion currents that concurrently induce local magnetic field perturbation remain unclear.Methods: We evaluated whether amine surface-modified Fe3O4 NPs have any effect on ion currents in pituitary tumor (GH3 cells via voltage clamp methods.Results: The addition of Fe3O4 NPs decreases the amplitude of membrane electroporation-induced currents (IMEP with a half-maximal inhibitory concentration at 45 µg/mL. Fe3O4 NPs at a concentration of 3 mg/mL produced a biphasic response in the amplitude of IMEP, ie, an initial decrease followed by a sustained increase. A similar effect was also noted in RAW 264.7 macrophages.Conclusion: The modulation of magnetic electroporation-induced currents by Fe3O4 NPs constitutes an important approach for cell tracking under various imaging modalities or facilitated drug delivery.Keywords: iron oxide, ion current, free radical

  10. Web-based tool for visualization of electric field distribution in deep-seated body structures and planning of electroporation-based treatments.

    Science.gov (United States)

    Marčan, Marija; Pavliha, Denis; Kos, Bor; Forjanič, Tadeja; Miklavčič, Damijan

    2015-01-01

    Treatments based on electroporation are a new and promising approach to treating tumors, especially non-resectable ones. The success of the treatment is, however, heavily dependent on coverage of the entire tumor volume with a sufficiently high electric field. Ensuring complete coverage in the case of deep-seated tumors is not trivial and can in best way be ensured by patient-specific treatment planning. The basis of the treatment planning process consists of two complex tasks: medical image segmentation, and numerical modeling and optimization. In addition to previously developed segmentation algorithms for several tissues (human liver, hepatic vessels, bone tissue and canine brain) and the algorithms for numerical modeling and optimization of treatment parameters, we developed a web-based tool to facilitate the translation of the algorithms and their application in the clinic. The developed web-based tool automatically builds a 3D model of the target tissue from the medical images uploaded by the user and then uses this 3D model to optimize treatment parameters. The tool enables the user to validate the results of the automatic segmentation and make corrections if necessary before delivering the final treatment plan. Evaluation of the tool was performed by five independent experts from four different institutions. During the evaluation, we gathered data concerning user experience and measured performance times for different components of the tool. Both user reports and performance times show significant reduction in treatment-planning complexity and time-consumption from 1-2 days to a few hours. The presented web-based tool is intended to facilitate the treatment planning process and reduce the time needed for it. It is crucial for facilitating expansion of electroporation-based treatments in the clinic and ensuring reliable treatment for the patients. The additional value of the tool is the possibility of easy upgrade and integration of modules with new

  11. Effects of transgenic sterilization constructs and their repressor compounds on hatch, developmental rate and early survival of electroporated channel catfish embryos and fry.

    Science.gov (United States)

    Su, Baofeng; Shang, Mei; Li, Chao; Perera, Dayan A; Pinkert, Carl A; Irwin, Michael H; Peatman, Eric; Grewe, Peter; Patil, Jawahar G; Dunham, Rex A

    2015-04-01

    Channel catfish (Ictalurus punctatus) embryos were electroporated with sterilization constructs targeting primordial germ cell proteins or with buffer. Some embryos then were treated with repressor compounds, cadmium chloride, copper sulfate, sodium chloride or doxycycline, to prevent expression of the transgene constructs. Promoters included channel catfish nanos and vasa, salmon transferrin (TF), modified yeast Saccharomyces cerevisiae copper transport protein (MCTR) and zebrafish racemase (RM). Knock-down systems were the Tet-off (nanos and vasa constructs), MCTR, RM and TF systems. Knock-down genes included shRNAi targeting 5' nanos (N1), 3' nanos (N2) or dead end (DND), or double-stranded nanos RNA (dsRNA) for overexpression of nanos mRNA. These constructs previously were demonstrated to knock down nanos, vasa and dead end, with the repressors having variable success. Exogenous DNA affected percentage hatch (% hatch), as all 14 constructs, except for the TF dsRNA, TF N1 (T), RM DND (C), vasa DND (C), vasa N1 (C) and vasa N2 (C), had lower % hatch than the control electroporated with buffer. The MCTR and RM DND (T) constructs resulted in delayed hatch, and the vasa and nanos constructs had minimal effects on time of hatch (P nanos constructs, doxycycline greatly delayed hatch (P < 0.05). Adverse effects of the transgenes and repressors continued for several treatments for the first 6 days after hatch, but only in a few treatments during the next 10 days. Repressors and gene expression impacted the yield of putative transgenic channel catfish fry, and need to be considered and accounted for in the hatchery phase of producing transgenically sterilized catfish fry and their fertile counterparts. This fry output should be considered to ensure that sufficient numbers of transgenic fish are produced for future applications and for defining repressor systems that are the most successful.

  12. Optimised performance of industrial high resolution computerised tomography

    International Nuclear Information System (INIS)

    Maangaard, M.

    2000-01-01

    The purpose of non-destructive evaluation (NDE) is to acquire knowledge of the investigated sample. Digital x-ray imaging techniques such as radiography or computerised tomography (CT) produce images of the interior of a sample. The obtained image quality determines the possibility of detecting sample related features, e.g. details and flaws. This thesis presents a method of optimising the performance of industrial X-ray equipment for the imaging task at issue in order to obtain images with high quality. CT produces maps of the X-ray linear attenuation of the sample's interior. CT can produce two dimensional cross-section images or three-dimensional images with volumetric information on the investigated sample. The image contrast and noise depend on both the investigated sample and the equipment and settings used (X-ray tube potential, X-ray filtration, exposure time, etc.). Hence, it is vital to find the optimal equipment settings in order to obtain images of high quality. To be able to mathematically optimise the image quality, it is necessary to have a model of the X-ray imaging system together with an appropriate measure of image quality. The optimisation is performed with a developed model for an X-ray image-intensifier-based radiography system. The model predicts the mean value and variance of the measured signal level in the collected radiographic images. The traditionally used measure of physical image quality is the signal-to-noise ratio (SNR). To calculate the signal-to-noise ratio, a well-defined detail (flaw) is required. It was found that maximising the SNR leads to ambiguities, the optimised settings found by maximising the SNR were dependent on the material in the detail. When CT is performed on irregular shaped samples containing density and compositional variations, it is difficult to define which SNR to use for optimisation. This difficulty is solved by the measures of physical image quality proposed here, the ratios geometry

  13. Satellite Vibration Testing: Angle optimisation method to Reduce Overtesting

    Science.gov (United States)

    Knight, Charly; Remedia, Marcello; Aglietti, Guglielmo S.; Richardson, Guy

    2018-06-01

    Spacecraft overtesting is a long running problem, and the main focus of most attempts to reduce it has been to adjust the base vibration input (i.e. notching). Instead this paper examines testing alternatives for secondary structures (equipment) coupled to the main structure (satellite) when they are tested separately. Even if the vibration source is applied along one of the orthogonal axes at the base of the coupled system (satellite plus equipment), the dynamics of the system and potentially the interface configuration mean the vibration at the interface may not occur all along one axis much less the corresponding orthogonal axis of the base excitation. This paper proposes an alternative testing methodology in which the testing of a piece of equipment occurs at an offset angle. This Angle Optimisation method may have multiple tests but each with an altered input direction allowing for the best match between all specified equipment system responses with coupled system tests. An optimisation process that compares the calculated equipment RMS values for a range of inputs with the maximum coupled system RMS values, and is used to find the optimal testing configuration for the given parameters. A case study was performed to find the best testing angles to match the acceleration responses of the centre of mass and sum of interface forces for all three axes, as well as the von Mises stress for an element by a fastening point. The angle optimisation method resulted in RMS values and PSD responses that were much closer to the coupled system when compared with traditional testing. The optimum testing configuration resulted in an overall average error significantly smaller than the traditional method. Crucially, this case study shows that the optimum test campaign could be a single equipment level test opposed to the traditional three orthogonal direction tests.

  14. Reflections on the juridicial roots of the principle of optimisation

    International Nuclear Information System (INIS)

    Lochard, J.; Boehler, M.C.

    1992-01-01

    The disciplines of jurisprudence tend in general towards a rationalisation and stabilisation of social or economic practice and are oriented towards concepts or practices which belong to the field of the determinate. When it comes to the principle of optimising radiological protection, however, the classical juridical technique of administrative law does not exactly answer the problems of implementing this. From the obligations of performance traditionally imposed by the government, a transition to obligation of behaviour by those involved seems to be called for, and this is what makes the optimisation principle difficult to qualify juridically. Instead of a law of command, exemption and control the government must essentially put its trust in the operators of nuclear installations by issuing a standard which sets an objective rather than a standard with the force of a regulation as in the past. Does the future of the juridical sciences in fact lie in the development of an administrative law of the indeterminate which would oblige the government to recognise that, even in the field of the determinate, it is not always government which knows best? While our classical administrative law is a law of command and control, the administrative law of the indeterminate will be that of the law of common effort, framed in collective acts and based on trust, consultation, and obligations of behaviour, all under the control of a judge who intervenes when there is a manifest contradiction between the acts and the promised behaviour. In French law optimisation has remained a general principle unaccompanied by specific provisions for its implementation. The object of our paper is to examine on what juridical foundations it would be possible to apply this principle at practical level without betraying its spirit. (author)

  15. Analysis and optimisation of a mixed fluid cascade (MFC) process

    Science.gov (United States)

    Ding, He; Sun, Heng; Sun, Shoujun; Chen, Cheng

    2017-04-01

    A mixed fluid cascade (MFC) process that comprises three refrigeration cycles has great capacity for large-scale LNG production, which consumes a great amount of energy. Therefore, any performance enhancement of the liquefaction process will significantly reduce the energy consumption. The MFC process is simulated and analysed by use of proprietary software, Aspen HYSYS. The effect of feed gas pressure, LNG storage pressure, water-cooler outlet temperature, different pre-cooling regimes, liquefaction, and sub-cooling refrigerant composition on MFC performance are investigated and presented. The characteristics of its excellent numerical calculation ability and the user-friendly interface of MATLAB™ and powerful thermo-physical property package of Aspen HYSYS are combined. A genetic algorithm is then invoked to optimise the MFC process globally. After optimisation, the unit power consumption can be reduced to 4.655 kW h/kmol, or 4.366 kW h/kmol on condition that the compressor adiabatic efficiency is 80%, or 85%, respectively. Additionally, to improve the process further, with regards its thermodynamic efficiency, configuration optimisation is conducted for the MFC process and several configurations are established. By analysing heat transfer and thermodynamic performances, the configuration entailing a pre-cooling cycle with three pressure levels, liquefaction, and a sub-cooling cycle with one pressure level is identified as the most efficient and thus optimal: its unit power consumption is 4.205 kW h/kmol. Additionally, the mechanism responsible for the weak performance of the suggested liquefaction cycle configuration lies in the unbalanced distribution of cold energy in the liquefaction temperature range.

  16. Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene knock down.

    Directory of Open Access Journals (Sweden)

    Dag Heinemann

    Full Text Available Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types.

  17. Gold nanoparticle mediated laser transfection for efficient siRNA mediated gene knock down.

    Science.gov (United States)

    Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Murua Escobar, Hugo; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

    2013-01-01

    Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types.

  18. Gold Nanoparticle Mediated Laser Transfection for Efficient siRNA Mediated Gene Knock Down

    Science.gov (United States)

    Heinemann, Dag; Schomaker, Markus; Kalies, Stefan; Schieck, Maximilian; Carlson, Regina; Escobar, Hugo Murua; Ripken, Tammo; Meyer, Heiko; Heisterkamp, Alexander

    2013-01-01

    Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on gold nanoparticles unspecifically attached to the cell membrane to evoke transient and spatially defined cell membrane permeabilization. In this study, we explore the parameter regime for gold nanoparticle mediated laser transfection for the delivery of molecules into cell lines and prove its suitability for siRNA mediated gene knock down. The developed setup allows easy usage and safe laser operation in a normal lab environment. We applied a 532 nm Nd:YAG microchip laser emitting 850 ps pulses at a repetition rate of 20.25 kHz. Scanning velocities of the laser spot over the sample of up to 200 mm/s were tested without a decline in perforation efficiency. This velocity leads to a process speed of ∼8 s per well of a 96 well plate. The optimal particle density was determined to be ∼6 particles per cell using environmental scanning electron microscopy. Applying the optimized parameters transfection efficiencies of 88% were achieved in canine pleomorphic adenoma ZMTH3 cells using a fluorescent labeled siRNA while maintaining a high cell viability of >90%. Gene knock down of d2-EGFP was demonstrated and validated by fluorescence repression and western blot analysis. On basis of our findings and established mathematical models we suppose a mixed transfection mechanism consisting of thermal and multiphoton near field effects. Our findings emphasize that gold nanoparticle mediated laser transfection provides an excellent tool for molecular delivery for both, high throughput purposes and the transfection of sensitive cells types. PMID:23536802

  19. Optimising medication for Parkinson's disease patients with dysphagia.

    Science.gov (United States)

    Patel, Krupa

    2015-07-01

    In addition to movement disorders, Parkinson's disease (PD) is associated with several nonmotor symptoms, including dysphagia (swallowing difficulties). Dysphagia can make the consumption of solid medicines difficult, which potentially contributes to the poor adherence that is common among people with PD. However, patients may be reluctant to admit that they experience dysphagia. Community nurses should actively enquire into swallowing difficulties among all patients, not only those with PD, and should work with pharmacists and other members of the multidisciplinary team to help optimise medication management to help improve adherence.

  20. Optimisation of strain selection in evolutionary continuous culture

    Science.gov (United States)

    Bayen, T.; Mairet, F.

    2017-12-01

    In this work, we study a minimal time control problem for a perfectly mixed continuous culture with n ≥ 2 species and one limiting resource. The model that we consider includes a mutation factor for the microorganisms. Our aim is to provide optimal feedback control laws to optimise the selection of the species of interest. Thanks to Pontryagin's Principle, we derive optimality conditions on optimal controls and introduce a sub-optimal control law based on a most rapid approach to a singular arc that depends on the initial condition. Using adaptive dynamics theory, we also study a simplified version of this model which allows to introduce a near optimal strategy.

  1. Optimisation of a parallel ocean general circulation model

    Science.gov (United States)

    Beare, M. I.; Stevens, D. P.

    1997-10-01

    This paper presents the development of a general-purpose parallel ocean circulation model, for use on a wide range of computer platforms, from traditional scalar machines to workstation clusters and massively parallel processors. Parallelism is provided, as a modular option, via high-level message-passing routines, thus hiding the technical intricacies from the user. An initial implementation highlights that the parallel efficiency of the model is adversely affected by a number of factors, for which optimisations are discussed and implemented. The resulting ocean code is portable and, in particular, allows science to be achieved on local workstations that could otherwise only be undertaken on state-of-the-art supercomputers.

  2. Optimisation of test and maintenance based on probabilistic methods

    International Nuclear Information System (INIS)

    Cepin, M.

    2001-01-01

    This paper presents a method, which based on models and results of probabilistic safety assessment, minimises the nuclear power plant risk by optimisation of arrangement of safety equipment outages. The test and maintenance activities of the safety equipment are timely arranged, so the classical static fault tree models are extended with the time requirements to be capable to model real plant states. A house event matrix is used, which enables modelling of the equipment arrangements through the discrete points of time. The result of the method is determination of such configuration of equipment outages, which result in the minimal risk. Minimal risk is represented by system unavailability. (authors)

  3. Generation of safe optimised execution strategies for uml models

    DEFF Research Database (Denmark)

    Herbert, Luke Thomas; Herbert-Hansen, Zaza Nadja Lee

    When designing safety critical systems there is a need for verification of safety properties while ensuring system operations have a specific performance profile. We present a novel application of model checking to derive execution strategies, sequences of decisions at workflow branch points...... which optimise a set of reward variables, while simultaneously observing constraints which encode any required safety properties and accounting for the underlying stochastic nature of the system. By evaluating quantitative properties of the generated adversaries we are able to construct an execution...

  4. Parametric studies and optimisation of pumped thermal electricity storage

    International Nuclear Information System (INIS)

    McTigue, Joshua D.; White, Alexander J.; Markides, Christos N.

    2015-01-01

    Highlights: • PTES is modelled by cycle analysis and a Schumann-style model of the thermal stores. • Optimised trade-off surfaces show a flat efficiency vs. energy density profile. • Overall roundtrip efficiencies of around 70% are not inconceivable. - Abstract: Several of the emerging technologies for electricity storage are based on some form of thermal energy storage (TES). Examples include liquid air energy storage, pumped heat energy storage and, at least in part, advanced adiabatic compressed air energy storage. Compared to other large-scale storage methods, TES benefits from relatively high energy densities, which should translate into a low cost per MW h of storage capacity and a small installation footprint. TES is also free from the geographic constraints that apply to hydro storage schemes. TES concepts for electricity storage rely on either a heat pump or refrigeration cycle during the charging phase to create a hot or a cold storage space (the thermal stores), or in some cases both. During discharge, the thermal stores are depleted by reversing the cycle such that it acts as a heat engine. The present paper is concerned with a form of TES that has both hot and cold packed-bed thermal stores, and for which the heat pump and heat engine are based on a reciprocating Joule cycle, with argon as the working fluid. A thermodynamic analysis is presented based on traditional cycle calculations coupled with a Schumann-style model of the packed beds. Particular attention is paid to the various loss-generating mechanisms and their effect on roundtrip efficiency and storage density. A parametric study is first presented that examines the sensitivity of results to assumed values of the various loss factors and demonstrates the rather complex influence of the numerous design variables. Results of an optimisation study are then given in the form of trade-off surfaces for roundtrip efficiency, energy density and power density. The optimised designs show a

  5. Optimisation of key performance measures in air cargo demand management

    OpenAIRE

    Alexander May; Adrian Anslow; Udechukwu Ojiako; Yue Wu; Alasdair Marshall; Maxwell Chipulu

    2014-01-01

    This article sought to facilitate the optimisation of key performance measures utilised for demand management in air cargo operations. The focus was on the Revenue Management team at Virgin Atlantic Cargo and a fuzzy group decision-making method was used. Utilising intelligent fuzzy multi-criteria methods, the authors generated a ranking order of ten key outcome-based performance indicators for Virgin Atlantic air cargo Revenue Management. The result of this industry-driven study showed that ...

  6. Optimising and Predicting Performance of Industrial Filtrations using Process Data

    DEFF Research Database (Denmark)

    David Bähner, Franz; Santacoloma, Paloma A.; Abildskov, Jens

    2017-01-01

    Industrial cake filtration is non-trivial from an operational point of view. Discrete events such as the removal of filter cake occur on a frequent but irregular basis. These events tend to upset the steady state of the incorporating line, which may constrain plantwide optimisation. A case study...... has been carried out with an industrial partner where changes in the biological feedstock act as strong disturbances on a series of manually reinitialised dead-end pressure leaf filters. This renders production planning a challenging task which,so far, is carried out by experienced operators. We look...

  7. Stochastic Automata for Outdoor Semantic Mapping using Optimised Signal Quantisation

    DEFF Research Database (Denmark)

    Caponetti, Fabio; Blas, Morten Rufus; Blanke, Mogens

    2011-01-01

    Autonomous robots require many types of information to obtain intelligent and safe behaviours. For outdoor operations, semantic mapping is essential and this paper proposes a stochastic automaton to localise the robot within the semantic map. For correct modelling and classi¯cation under...... uncertainty, this paper suggests quantising robotic perceptual features, according to a probabilistic description, and then optimising the quantisation. The proposed method is compared with other state-of-the-art techniques that can assess the con¯dence of their classi¯cation. Data recorded on an autonomous...

  8. Operation, optimisation, and performance of the DELPHI RICH detectors

    CERN Document Server

    Albrecht, E; Augustinus, A; Baillon, Paul; Battaglia, Marco; Bloch, D; Boudinov, E; Brunet, J M; Carrié, P; Cavalli, P; Christophel, E; Davenport, M; Dracos, M; Eklund, L; Erzen, B; Fischer, P A; Fokitis, E; Fontanelli, F; Gracco, Valerio; Hallgren, A; Joram, C; Juillot, P; Kjaer, N J; Kluit, P M; Lenzen, G; Liko, D; Mahon, J R; Maltezos, S; Markou, A; Neufeld, N; Nielsen, B S; Petrolini, A; Podobnik, T; Polok, G; Sajot, G; Sannino, M; Schyns, E; Strub, R; Tegenfeldt, F; Thadome, J; Tristram, G; Ullaland, O; Vulpen, I V

    1999-01-01

    The Ring Imaging Cherenkov detectors of DELPHI represent a large-scale particle identification system which covers almost the full angular acceptance of DELPHI. The combination of liquid and gas radiators (C sub 4 F sub 1 sub 0 , C sub 5 F sub 1 sub 2 , and C sub 6 F sub 1 sub 4) provides particle identification over the whole secondary particle momentum spectrum at LEP I and LEP II. Continuing optimisation on the hardware as well as on the online and offline software level have resulted in a stable operation of the complete detector system for more than five years at full physics performance.

  9. Optimisation of trawl energy efficiency under fishing effort constraint

    OpenAIRE

    Priour, Daniel; Khaled, Ramez

    2009-01-01

    Trawls energy efficiency is greatly affected by the drag, as well as by the swept area. The drag results in an increase of the energy consumption and the sweeping influences the catch. Methods of optimisation of the trawl design have been developed in order to reduce the volume of carburant per kg of caught fish and consequently the drag per swept area of the trawl. Based on a finite element method model for flexible netting structures, the tool modifies step by step a reference design. For e...

  10. Design and manufacture of Portland cement - application of sensitivity analysis in exploration and optimisation Part II. Optimisation

    DEFF Research Database (Denmark)

    Svinning, K.; Høskuldsson, Agnar

    2006-01-01

    A program for a model-based optimisation has been developed. The program contains two subprograms. The first one does minimising or maximising constrained by one original PLS-component or one equal to a combination of several. The second one does searching for the optimal combination of PLS-compo......-components, which gives max or min y. The program has proved to be applicable for achieving realistic results for implementation in the design of Portland cement with respect to performance and in the quality control during production....

  11. Radiation protection optimisation techniques and their application in industry

    Energy Technology Data Exchange (ETDEWEB)

    Lefaure, C

    1997-12-31

    Since the International Commission on Radiation Protection (ICRP) recommendation 60, the optimisation principle appears to be the core of the radiation protection system. In practice applying it, means implementing an approach both predictive and evolutionary - that relies essentially on a prudent and responsible state of mind. the formal expression of this process, called optimization procedure, implies and indispensable tool for its implementation: the system of monetary values for the unit of collective dose. During the last few years, feed ALARA principle means that a global work management approach must be adopted, considering together all factors contributing to radiation dose. In the nuclear field, the ALARA approach appears to be more successful when implemented in the framework of a managerial approach through structure ALARA programmes. Outside the nuclear industry it is necessary to clearly define priorities through generic optimisation studies and ALARA audits. At the international level much efforts remain to be done to expand efficiently the ALARA process to internal exposure as well as to public exposure. (author) 2 graphs, 5 figs., 3 tabs.

  12. Concepts of optimisation and justification consequences for radiological mass screening

    International Nuclear Information System (INIS)

    Carmichael, J.H.E.

    1987-01-01

    Mass radiological screening campaigns have been mounted in many countries for different conditions and the needs of one country are not necessarily those of another. However, in the European community there is a reasonable uniformity about disease patterns and therefore, a mass screening situation applicable to one country is probably equally applicable throughout the Community. In radiation protection terms, all these potential surveys must be looked at under the same factors. In radiation protection, one thinks first of all justification of the practice. Then one follows it by optimisation of the technique used, so as to obtain the best balance between benefit and detriment, and at this point one must remember that the radiation protection concept of optimisation includes a financial element as well as a purely clinical element and this must lead us on eventually to touch on cost effectiveness. The last portion of the ICRP system is the actual setting of dose limits. Now these are really only applicable to workers not to patients. One cannot set an upper limit on the dose one is prepared to use in a diagnostic radiological examination, but one can say that the dose per examination, should be examined and that the dose range of that examination between various institutions should be ascertained. This should enable any one institution to see where their dose range lies in the larger dose range, and to see that their radiological practice is giving as low a dose as is reasonably achievable

  13. Optimisation Of Volvariella volvacea Spawn Production For High Mycelia Growth

    International Nuclear Information System (INIS)

    Nie, H.J.; Azhar Mohamad; Joyce, Y.S.M.; Muhamad Najmi Moin

    2016-01-01

    Volvariella volvacea is a tropical mushroom cultivated throughout the world mostly in Asia and Europe for its taste, nutrition, fast growing nature and simple method of cultivation. It is also widely cultivated in Malaysia and known locally as Paddy Straw Mushroom. Growers strive to obtain high quality mushroom spawn to achieve high production. High quality spawn with fast mycelia growth are achieved through strain selection and optimisation of seedling production conditions. This study aims to optimise spawn production through 3 studies along the production main stages. Firstly, comparisons were made between agar media. Mycelia grown on Malt Extract Agar (MEA) covered the agar plates 2 days faster than Potato Dextrose Agar (PDA) grown mycelia. The next stage is of mother grain spawn production by inoculating a bag of grains from mycelia agar plugs. Bags are then sealed with caps. The amount of aeration for grain spawn were studied by using two types of caps. Caps with hole allowed more aeration compared to caps without holes. Study determined bags with more aeration colonised grains 2 days faster than bags with lesser aeration. For the final stage of producing planting spawn, the growth on paddy straw substrate with and without kapok (10 %) were evaluated. Results revealed mycelia fully colonised the substrate bags without kapok 1-2 days faster than substrate bags with kapok. These findings contribute in achieving production of high quality Volvariella volvacea spawn. (author)

  14. Performance characterisation and optimisation of the HIPOS positron generator setup

    Energy Technology Data Exchange (ETDEWEB)

    Tucek, K., E-mail: kamil.tucek@ec.europa.eu [European Commission, Joint Research Centre, Institute for Energy and Transport, P.O. Box 2, NL-1755 ZG Petten (Netherlands); Zeman, A.; Daquino, G.; Debarberis, L. [European Commission, Joint Research Centre, Institute for Energy and Transport, P.O. Box 2, NL-1755 ZG Petten (Netherlands); Hogenbirk, A. [Nuclear Research and Consultancy Group (NRG), P.O. Box 25, NL-1755 ZG Petten (Netherlands)

    2012-01-01

    As part of an Exploratory Research Project at the Institute for Energy and Transport (Joint Research Centre of the European Commission), a feasibility assessment was performed for the construction and placement of a high-intensity positron facility (HIPOS) in a beam tube, HB9, at the High flux reactor (HFR) in Petten. This paper reports on the results of Monte Carlo simulations to optimise the concept of the HIPOS positron generator and to determine the performance characteristics of the chosen generator design. In the first step, a detailed model of the HFR reactor core, reflector, instrumentation and HB9 beam tube was prepared, and coupled neutron and photon transport calculations were carried out with the MCNP4C3 code to establish neutron and photon source terms on boundary surfaces of the HB9 beam tube. These sources were subsequently used with the MCNPX code to optimise the positron generator concept and geometry. The results showed that the positron beam can reach an integral intensity of 10{sup 13} e{sup +}/s before the moderation stage, easily meeting the specified target and confirming the hypothesis that very high positron yields can be obtained by using combined neutron and gamma radiation sources from a high flux reactor. Full details of the research work are reported in this study.

  15. Nuclear power plant maintenance optimisation SENUF network activity

    International Nuclear Information System (INIS)

    Ahlstrand, R.; Bieth, M.; Pla, P.; Rieg, C.; Trampus, P.

    2004-01-01

    During providing scientific and technical support to TACIS and PHARE nuclear safety programs a large amount of knowledge related to Russian design reactor systems has accumulated and led to creation of a new Network concerning Nuclear Safety in Central and Eastern Europe called ''Safety of Eastern European type Nuclear Facilities'' (SENUF). SENUF contributes to bring together all stakeholders of TACIS and PHARE: beneficiaries, end users, Eastern und Western nuclear industries, and thus, to favour fruitful technical exchanges and feedback of experience. At present the main focus of SENUF is the nuclear power plant maintenance as substantial element of plant operational safety as well as life management. A Working Group has been established on plant maintenance. One of its major tasks in 2004 is to prepare a status report on advanced strategies to optimise maintenance. Optimisation projects have an interface with the plant's overall life management program. Today, almost all plants involved in SENUF network have an explicit policy to extend their service life, thus, component ageing management, modernization and refurbishment actions became much more important. A database is also under development, which intends to help sharing the available knowledge and specific equipment and tools. (orig.)

  16. Power and delay optimisation in multi-hop wireless networks

    KAUST Repository

    Xia, Li

    2014-02-05

    In this paper, we study the optimisation problem of transmission power and delay in a multi-hop wireless network consisting of multiple nodes. The goal is to determine the optimal policy of transmission rates at various buffer and channel states in order to minimise the power consumption and the queueing delay of the whole network. With the assumptions of interference-free links and independently and identically distributed (i.i.d.) channel states, we formulate this problem using a semi-open Jackson network model for data transmission and a Markov model for channel states transition. We derive a difference equation of the system performance under any two different policies. The necessary and sufficient condition of optimal policy is obtained. We also prove that the system performance is monotonic with respect to (w.r.t.) the transmission rate and the optimal transmission rate can be either maximal or minimal. That is, the ‘bang-bang’ control is an optimal control. This optimality structure greatly reduces the problem complexity. Furthermore, we develop an iterative algorithm to find the optimal solution. Finally, we conduct the simulation experiments to demonstrate the effectiveness of our approach. We hope our work can shed some insights on solving this complicated optimisation problem.

  17. Water distribution systems design optimisation using metaheuristics and hyperheuristics

    Directory of Open Access Journals (Sweden)

    DN Raad

    2011-06-01

    Full Text Available The topic of multi-objective water distribution systems (WDS design optimisation using metaheuristics is investigated, comparing numerous modern metaheuristics, including sev- eral multi-objective evolutionary algorithms, an estimation of distribution algorithm and a recent hyperheuristic named AMALGAM (an evolutionary framework for the simultaneous incorporation of multiple metaheuristics, in order to determine which approach is most capa- ble with respect to WDS design optimisation. Novel metaheuristics and variants of existing algorithms are developed, for a total of twenty-three algorithms examined. Testing with re- spect to eight small-to-large-sized WDS benchmarks from the literature reveal that the four top-performing algorithms are mutually non-dominated with respect to the various perfor- mance metrics used. These algorithms are NSGA-II, TAMALGAMJndu , TAMALGAMndu and AMALGAMSndp (the last three being novel variants of AMALGAM. However, when these four algorithms are applied to the design of a very large real-world benchmark, the AMALGAM paradigm outperforms NSGA-II convincingly, with AMALGAMSndp exhibiting the best performance overall.

  18. ICT for whole life optimisation of residential buildings

    Energy Technology Data Exchange (ETDEWEB)

    Haekkinen, T.; Vares, S.; Huovila, P.; Vesikari, E.; Porkka, J. (VTT Technical Research Centre of Finland, Espoo (FI)); Nilsson, L.-O.; Togeroe, AA. (Lund University (SE)); Jonsson, C.; Suber, K. (Skanska Sverige AB (SE)); Andersson, R.; Larsson, R. (Cementa, Malmoe (SE)); Nuorkivi, I. (Skanska Oyj, Helsinki (FI))

    2007-08-15

    The research project 'ICT for whole life optimisation of residential buildings' (ICTWLORB) developed and tested the whole life design and optimisation methods for residential buildings. The objective of the ICTWLORB project was to develop and implement an ICT based tool box for integrated life cycle design of residential building. ICTWLORB was performed in cooperation with Swedish and Finnish partners. The ICTWLORB project defined as a premise that an industrialised building process is characterised by two main elements: a building concept based approach and efficient information management. Building concept based approach enables (1) the product development of the end product, (2) repetition of the basic elements of the building from one project to others and (3) customisation of the end-product considering the specific needs of the case and the client. Information management enables (1) the consideration of wide spectrum of aspects including building performance, environmental aspects, life cycle costs and service life, and (2) rapid adapting of the design to the specific requirements of the case. (orig.)

  19. Fractures in sport: Optimising their management and outcome

    Science.gov (United States)

    Robertson, Greg AJ; Wood, Alexander M

    2015-01-01

    Fractures in sport are a specialised cohort of fracture injuries, occurring in a high functioning population, in which the goals are rapid restoration of function and return to play with the minimal symptom profile possible. While the general principles of fracture management, namely accurate fracture reduction, appropriate immobilisation and timely rehabilitation, guide the treatment of these injuries, management of fractures in athletic populations can differ significantly from those in the general population, due to the need to facilitate a rapid return to high demand activities. However, despite fractures comprising up to 10% of all of sporting injuries, dedicated research into the management and outcome of sport-related fractures is limited. In order to assess the optimal methods of treating such injuries, and so allow optimisation of their outcome, the evidence for the management of each specific sport-related fracture type requires assessment and analysis. We present and review the current evidence directing management of fractures in athletes with an aim to promote valid innovative methods and optimise the outcome of such injuries. From this, key recommendations are provided for the management of the common fracture types seen in the athlete. Six case reports are also presented to illustrate the management planning and application of sport-focussed fracture management in the clinical setting. PMID:26716081

  20. Nuclear power plant maintenance optimisation SENUF network activity

    Energy Technology Data Exchange (ETDEWEB)

    Ahlstrand, R.; Bieth, M.; Pla, P.; Rieg, C.; Trampus, P. [Inst. for Energy, EC DG Joint Research Centre, Petten (Netherlands)

    2004-07-01

    During providing scientific and technical support to TACIS and PHARE nuclear safety programs a large amount of knowledge related to Russian design reactor systems has accumulated and led to creation of a new Network concerning Nuclear Safety in Central and Eastern Europe called ''Safety of Eastern European type Nuclear Facilities'' (SENUF). SENUF contributes to bring together all stakeholders of TACIS and PHARE: beneficiaries, end users, Eastern und Western nuclear industries, and thus, to favour fruitful technical exchanges and feedback of experience. At present the main focus of SENUF is the nuclear power plant maintenance as substantial element of plant operational safety as well as life management. A Working Group has been established on plant maintenance. One of its major tasks in 2004 is to prepare a status report on advanced strategies to optimise maintenance. Optimisation projects have an interface with the plant's overall life management program. Today, almost all plants involved in SENUF network have an explicit policy to extend their service life, thus, component ageing management, modernization and refurbishment actions became much more important. A database is also under development, which intends to help sharing the available knowledge and specific equipment and tools. (orig.)