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

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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

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

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

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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.

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.

The effects of irreversible electroporation (IRE on nerves.

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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.

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

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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.

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

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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.

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

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

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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.

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.

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.

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

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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.

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.

BNNT-mediated irreversible electroporatio: its potential on cancer cells

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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

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.

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.

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.

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

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

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

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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.

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.

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.

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.

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.

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.

Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient.

Science.gov (United States)

Garcia, P A; Pancotto, T; Rossmeisl, J H; Henao-Guerrero, N; Gustafson, N R; Daniel, G B; Robertson, J L; Ellis, T L; Davalos, R V

2011-02-01

Non-thermal irreversible electroporation (N-TIRE) has shown promise as an ablative therapy for a variety of soft-tissue neoplasms. Here we describe the therapeutic planning aspects and first clinical application of N-TIRE for the treatment of an inoperable, spontaneous malignant intracranial glioma in a canine patient. The N-TIRE ablation was performed safely, effectively reduced the tumor volume and associated intracranial hypertension, and provided sufficient improvement in neurological function of the patient to safely undergo adjunctive fractionated radiotherapy (RT) according to current standards of care. Complete remission was achieved based on serial magnetic resonance imaging examinations of the brain, although progressive radiation encephalopathy resulted in the death of the dog 149 days after N-TIRE therapy. The length of survival of this patient was comparable to dogs with intracranial tumors treated via standard excisional surgery and adjunctive fractionated external beam RT. Our results illustrate the potential benefits of N-TIRE for in vivo ablation of undesirable brain tissue, especially when traditional methods of cytoreductive surgery are not possible or ideal, and highlight the potential radiosensitizing effects of N-TIRE on the brain.

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.)

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.

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

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

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.

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

Intra-operative navigation of a 3-dimensional needle localization system for precision of irreversible electroporation needles in locally advanced pancreatic cancer.

Science.gov (United States)

Bond, L; Schulz, B; VanMeter, T; Martin, R C G

2017-02-01

Irreversible electroporation (IRE) uses multiple needles and a series of electrical pulses to create pores in cell membranes and cause cell apoptosis. One of the demands of IRE is the precise needle spacing required. Two-dimensional intraoperative ultrasound (2-D iUS) is currently used to measure inter-needle distances but requires significant expertise. This study evaluates the potential of three-dimensional (3-D) image guidance for placing IRE needles and calculating needle spacing. A prospective clinical evaluation of a 3-D needle localization system (Explorer™) was evaluated in consecutive patients from April 2012 through June 2013 for unresectable pancreatic adenocarcinoma. 3-D reconstructions of patients' anatomy were generated from preoperative CT images, which were aligned to the intraoperative space. Thirty consecutive patients with locally advanced pancreatic cancer were treated with IRE. The needle localization system setup added an average of 6.5 min to each procedure. The 3-D needle localization system increased surgeon confidence and ultimately reduced needle placement time. IRE treatment efficacy is highly dependent on accurate needle spacing. The needle localization system evaluated in this study aims to mitigate these issues by providing the surgeon with additional visualization and data in 3-D. The Explorer™ system provides valuable guidance information and inter-needle distance calculations. Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

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

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.

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.

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.

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

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.

Urinary Tract Effects After Multifocal Nonthermal Irreversible Electroporation of the Kidney: Acute and Chronic Monitoring by Magnetic Resonance Imaging, Intravenous Urography and Urinary Cytology

Energy Technology Data Exchange (ETDEWEB)

Wendler, Johann Jakob, E-mail: johann.wendler@med.ovgu.de [University of Magdeburg, Department of Urology (Germany); Pech, Maciej [University of Magdeburg, Department of Radiology and Nuclear Medicine (Germany); Porsch, Markus; Janitzky, Andreas [University of Magdeburg, Department of Urology (Germany); Fischbach, Frank [University of Magdeburg, Department of Radiology and Nuclear Medicine (Germany); Buhtz, Peter; Vogler, Klaus [University of Magdeburg, Institute of Pathology (Germany); Huehne, Sarah [University of Magdeburg, Department of Urology (Germany); Borucki, Katrin [University of Magdeburg, Institute of Clinical Chemistry (Germany); Strang, Christof [University of Magdeburg, Department of Anaesthesiology (Germany); Mahnkopf, Dirk [Institute of Medical Technology and Research (Germany); Ricke, Jens [University of Magdeburg, Department of Radiology and Nuclear Medicine (Germany); Liehr, Uwe-Bernd [University of Magdeburg, Department of Urology (Germany)

2012-08-15

Purpose: The nonthermal irreversible electroporation (NTIRE) is a novel potential ablation modality for renal masses. The aim of this study was the first evaluation of NTIRE's effects on the renal urine-collecting system using intravenous urography (IVU) and urinary cytology in addition to histology and magnetic resonance imaging (MRI). Methods: Eight percutaneous NTIRE ablations of the renal parenchyma, including the calyxes or pelvis, were performed in three male swine. MRI, IVU, histology, and urinary cytology follow-ups were performed within the first 28 days after treatment. Results: MRI and histological analysis demonstrated a localized necrosis 7 days and a localized scarification of the renal parenchyma with complete destruction 28 days after NTIRE. The urine-collecting system was preserved and showed urothelial regeneration. IVU and MRI showed an unaltered normal morphology of the renal calyxes, pelvis, and ureter. A new urinary cytology phenomenon featured a temporary degeneration by individual vacuolization of detached transitional epithelium cells within the first 3 days after NTIRE. Conclusions: This first urographical, urine-cytological, and MRI evaluation after porcine kidney NTIRE shows multifocal parenchyma destruction while protecting the involved urine-collecting system with regenerated urothelial tissue. NTIRE could be used as a targeted ablation method of centrally located renal masses.

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

Irreversible electroporation ablation (IRE of unresectable soft tissue tumors: learning curve evaluation in the first 150 patients treated.

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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

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.

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.

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 ...

MRI and contrast-enhanced ultrasound imaging for evaluation of focal irreversible electroporation treatment: results from a phase I-II study in patients undergoing IRE followed by radical prostatectomy

International Nuclear Information System (INIS)

Bos, Willemien van den; Bruin, D.M. de; Randen, A. van; Engelbrecht, M.R.W.; Postema, A.W.; Muller, B.G.; Zondervan, P.J.; Laguna Pes, M.P.; Reijke, T.M. de; Rosette, J.J.M.C.H. de la; Varkarakis, I.M.; Skolarikos, A.; Savci-Heijink, C.D.; Jurhill, R.R.; Wijkstra, H.

2016-01-01

Irreversible electroporation (IRE) is an ablative therapy with a low side-effect profile in prostate cancer. The objective was: 1) To compare the volumetric IRE ablation zone on grey-scale transrectal ultrasound (TRUS), contrast-enhanced ultrasound (CEUS) and multiparametric MRI (mpMRI) with histopathology findings; 2) To determine a reliable imaging modality to visualize the IRE ablation effects accurately. A prospective phase I-II study was performed in 16 patients scheduled for radical prostatectomy (RP). IRE of the prostate was performed 4 weeks before RP. Prior to, and 4 weeks after the IRE treatment, imaging was performed by TRUS, CEUS, and mpMRI. 3D-analysis of the ablation volumes on imaging and on H and E-stained whole-mount sections was performed. The volumes were compared and the correlation was calculated. Evaluation of the imaging demonstrated that with T2-weighted MRI, dynamic contrast enhanced (DCE) MRI, and CEUS, effects of IRE are visible. T2MRI and CEUS closely match the volumes on histopathology (Pearson correlation r = 0.88 resp. 0.80). However, IRE is not visible with TRUS. mpMRI and CEUS are appropriate for assessing IRE effects and are the most feasible imaging modalities to visualize IRE ablation zone. The imaging is concordant with results of histopathological examination. (orig.)

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.

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.

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...

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

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.

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...

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.

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.

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

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.

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.

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.

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...

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.

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.

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

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.

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.

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

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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.

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....

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.

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

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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

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.

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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.

Simple Genome Editing of Rodent Intact Embryos by Electroporation.

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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.

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

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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

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.

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)

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

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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

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

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.

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

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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.

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.

Multivalent human papillomavirus l1 DNA vaccination utilizing electroporation.

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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

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

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

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...

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

Irreversible social change

NARCIS (Netherlands)

Pols, A.J.K.; Romijn, H.A.; Collste, G.; Reuter, L.

2014-01-01

In this paper we evaluate how irreversible social change should be evaluated from an ethical perspective. First; we analyse the notion of irreversibility in general terms. We define a general notion of what makes a change irreversible; drawing on discussions in ecology and economics. This notion is

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.

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

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.

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

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.

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

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.

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)

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

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

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

Irreversible processes kinetic theory

CERN Document Server

Brush, Stephen G

2013-01-01

Kinetic Theory, Volume 2: Irreversible Processes deals with the kinetic theory of gases and the irreversible processes they undergo. It includes the two papers by James Clerk Maxwell and Ludwig Boltzmann in which the basic equations for transport processes in gases are formulated, together with the first derivation of Boltzmann's ""H-theorem"" and a discussion of this theorem, along with the problem of irreversibility.Comprised of 10 chapters, this volume begins with an introduction to the fundamental nature of heat and of gases, along with Boltzmann's work on the kinetic theory of gases and s

Optimised electroporation mediated DNA vaccination for treatment of prostate cancer.

LENUS (Irish Health Repository)

Ahmad, Sarfraz

2010-01-01

ABSTRACT: BACKGROUND: Immunological therapies enhance the ability of the immune system to recognise and destroy cancer cells via selective killing mechanisms. DNA vaccines have potential to activate the immune system against specific antigens, with accompanying potent immunological adjuvant effects from unmethylated CpG motifs as on prokaryotic DNA. We investigated an electroporation driven plasmid DNA vaccination strategy in animal models for treatment of prostate cancer. METHODS: Plasmid expressing human PSA gene (phPSA) was delivered in vivo by intra-muscular electroporation, to induce effective anti-tumour immune responses against prostate antigen expressing tumours. Groups of male C57 BL\\/6 mice received intra-muscular injections of phPSA plasmid. For phPSA delivery, quadriceps muscle was injected with 50 mug plasmid. After 80 seconds, square-wave pulses were administered in sequence using a custom designed pulse generator and acustom-designed applicator with 2 needles placed through the skin central to the muscle. To determine an optimum treatment regimen, three different vaccination schedules were investigated. In a separate experiment, the immune potential of the phPSA vaccine was further enhanced with co- administration of synthetic CpG rich oligonucleotides. One week after last vaccination, the mice were challenged subcutaneously with TRAMPC1\\/hPSA (prostate cancer cell line stably expressing human PSA) and tumour growth was monitored. Serum from animals was examined by ELISA for anti-hPSA antibodies and for IFNgamma. Histological assessment of the tumours was also carried out. In vivo and in vitro cytotoxicity assays were performed with splenocytes from treated mice. RESULTS: The phPSA vaccine therapy significantly delayed the appearance of tumours and resulted in prolonged survival of the animals. Four-dose vaccination regimen provided optimal immunological effects. Co - administration of the synthetic CpG with phPSA increased anti-tumour responses

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.

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.

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.

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.

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

Multidimensional spectrometer

Science.gov (United States)

Zanni, Martin Thomas; Damrauer, Niels H.

2010-07-20

A multidimensional spectrometer for the infrared, visible, and ultraviolet regions of the electromagnetic spectrum, and a method for making multidimensional spectroscopic measurements in the infrared, visible, and ultraviolet regions of the electromagnetic spectrum. The multidimensional spectrometer facilitates measurements of inter- and intra-molecular interactions.

Irreversibility and self-organization in spin glasses. 1. Origin of irreversibility in spin glasses

International Nuclear Information System (INIS)

Kovrov, V.P.; Kurbatov, A.M.

1989-05-01

The origin of irreversibility in spin glasses is found out on the basis of the analytical study of the well-known TAP equations. Connection between irreversible jumpwise transitions and a positive feedback in spin glasses is discussed. (author). 7 refs, 4 figs

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

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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.

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.

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.

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

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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.

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...

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...

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.

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

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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.

Examination of various postulates of irreversibility

Energy Technology Data Exchange (ETDEWEB)

Salmon, J [Conservatoire National des Arts et Metiers (CNAM), 75 - Paris (France)

1977-01-01

Firstly, it is shown that it is necessary to break the reversible character of the B.B.G.K.Y. system of equations by means of a postulate of irreversibility to obtain a kinetic equation compatible with the second principle of thermodynamics. Next, three postulates of irreversibility are examined: that of molecular chaos, that of linear relaxation and, finally, that of superposition. Then the corresponding kinetic equations and the expressions for the viscosity coefficient to which they lead are determined. Comparison with experiment is made each time. Lastly, an attempt to obtain an irreversible kinetic equation without introducing a postulate of irreversibility in the B.B.G.K.Y. system is realized. This consists in adding a complementary irreversible term to the fundamental equation of the dynamics of a particle. The suggested term is of quantum origin and leads to a kinetic equation of the Fokker-Planck type.

Effect of pulsed electric field treatments on permeabilization and extraction of pigments from Chlorella vulgaris.

Science.gov (United States)

Luengo, Elisa; Condón-Abanto, Santiago; Álvarez, Ignacio; Raso, Javier

2014-12-01

The effect of pulsed electric field (PEF) treatments of different intensities on the electroporation of the cytoplasmatic membrane of Chlorella vulgaris, and on the extraction of carotenoids and chlorophylls were investigated. Staining the cells with propidium iodide before and after the PEF treatment revealed the existence of reversible and irreversible electroporation. Application of PEF treatments in the range of 20-25 kV cm(-1) caused most of the population of C. vulgaris to be irreversibly electroporated even at short treatment times (5 pulses of 3 µs). However, at lower electric field strengths (10 kV cm(-1)), cells that were reversibly electroporated were observed even after 50 pulses of 3 µs. The electroporation of C. vulgaris cells by PEF higher than 15 kV cm(-1) and duration is higher than 15 µs increased significantly the extraction yield of intracellular components of C. vulgaris. The application of a 20 kV cm(-1) for 75 μs increased the extraction yield just after the PEF treatment of the carotenoids, and chlorophylls a and b 0.5, 0.7, and 0.8 times, respectively. However, further increments in electric field strength and treatment time did not cause significant increments in the extraction yield. The extraction of carotenoids from PEF-treated C. vulgaris cells after 1 h of the application of the treatment significantly increased the extraction yield in comparison to the yield obtained from the cells extracted just after the PEF treatment. After PEF treatment at 20 kV cm(-1) for 75 µs, extraction yield for carotenoids, and chlorophylls a and b increased 1.2, 1.6, and 2.1 times, respectively. A high correlation was observed between irreversible electroporation and percentage of yield increase when the extraction was conducted after 1 h of the application of PEF treatment (R: 0.93), but not when the extraction was conducted just after PEF treatment (R: 0.67).

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

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

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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

Ecological optimization for generalized irreversible Carnot refrigerators

International Nuclear Information System (INIS)

Chen Lingen; Zhu Xiaoqin; Sun Fengrui; Wu Chih

2005-01-01

The optimal ecological performance of a Newton's law generalized irreversible Carnot refrigerator with the losses of heat resistance, heat leakage and internal irreversibility is derived by taking an ecological optimization criterion as the objective, which consists of maximizing a function representing the best compromise between the exergy output rate and exergy loss rate (entropy production rate) of the refrigerator. Numerical examples are given to show the effects of heat leakage and internal irreversibility on the optimal performance of generalized irreversible refrigerators

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

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

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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.

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.

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

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

Entropy, Extropy and the Physical Driver of Irreversibility

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Attila Grandpierre

2012-06-01

Full Text Available We point out that the fundamental irreversibility of Nature requires the introduction of a suitable measure for the distance from equilibrium. We show that entropy, which is widely held to be such a measure, suffers from the problem that it does not have a physical meaning, since it is introduced on the basis of mathematical arguments. As a consequence, the basic physics beyond irreversibility has remained obscure. We present here a simple but transparent physical approach for solving the problem of irreversibility. This approach shows that extropy, the fundamental thermodynamic variable introduced by Katalin Martinás, is the suitable measure for the distance from equilibrium, since it corresponds to the actual driver of irreversible processes. Since extropy explicitly contains in its definition all the general thermodynamic forces that drive irreversible processes, extropy is the suitable physical measure of irreversibility.

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

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

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

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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.

Multi-dimensional Fuzzy Euler Approximation

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Yangyang Hao

2017-05-01

Full Text Available Multi-dimensional Fuzzy differential equations driven by multi-dimen-sional Liu process, have been intensively applied in many fields. However, we can not obtain the analytic solution of every multi-dimensional fuzzy differential equation. Then, it is necessary for us to discuss the numerical results in most situations. This paper focuses on the numerical method of multi-dimensional fuzzy differential equations. The multi-dimensional fuzzy Taylor expansion is given, based on this expansion, a numerical method which is designed for giving the solution of multi-dimensional fuzzy differential equation via multi-dimensional Euler method will be presented, and its local convergence also will be discussed.

Irreversible dynamics, Onsager-Casimir symmetry, and an application to turbulence.

Science.gov (United States)

Ottinger, Hans Christian

2014-10-01

Irreversible contributions to the dynamics of nonequilibrium systems can be formulated in terms of dissipative, or irreversible, brackets. We discuss the structure of such irreversible brackets in view of a degeneracy implied by energy conservation, where we consider different types of symmetries of the bracket corresponding to the Onsager and Casimir symmetries of linear irreversible thermodynamics. Slip and turbulence provide important examples of antisymmetric irreversible brackets and offer guidance for the more general modeling of irreversible dynamics without entropy production. Conversely, turbulence modeling could benefit from elucidating thermodynamic structure. The examples suggest constructing antisymmetric irreversible brackets in terms of completely antisymmetric functions of three indices. Irreversible brackets without well-defined symmetry properties can arise for rare events, causing big configurational changes.

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.

Hydraulically irreversible fouling on ceramic MF/UF membranes: comparison of fouling indices, foulant composition and irreversible pore narrowing

KAUST Repository

Shang, Ran; Vuong, Francois; Hu, Jingyi; Li, Sheng; Kemperman, Antoine J.B.; Nijmeijer, Kitty; Cornelissen, Emile R.; Heijman, Sebastiaan G.J.; Rietveld, Luuk C.

2015-01-01

The application of ceramic membranes in water treatment is becoming increasing attractive because of their long life time and excellent chemical, mechanical and thermal stability. However, fouling of ceramic membranes, especially hydraulically irreversible fouling, is still a critical aspect affecting the operational cost and energy consumption in water treatment plants. In this study, four ceramic membranes with pore sizes or molecular weight cut-off (MWCO) of 0.20 μm, 0.14 μm, 300 kDa and 50 kDa were compared during natural surface water filtration with respect to hydraulically irreversible fouling index (HIFI), foulant composition and narrowing of pore size due to the irreversible fouling. Our results showed that the hydraulically irreversible fouling index (HIFI) was proportional to the membrane pore size (r2=0.89) when the same feed water was filtrated. The UF membranes showed lower HIFI values than the MF membranes. Pore narrowing (internal fouling) was found to be a main fouling pattern of the hydraulically irreversible fouling. The internal fouling was caused by monolayer adsorption of foulants with different sizes that is dependent on the size of the membrane pore.

Hydraulically irreversible fouling on ceramic MF/UF membranes: comparison of fouling indices, foulant composition and irreversible pore narrowing

KAUST Repository

Shang, Ran

2015-05-06

The application of ceramic membranes in water treatment is becoming increasing attractive because of their long life time and excellent chemical, mechanical and thermal stability. However, fouling of ceramic membranes, especially hydraulically irreversible fouling, is still a critical aspect affecting the operational cost and energy consumption in water treatment plants. In this study, four ceramic membranes with pore sizes or molecular weight cut-off (MWCO) of 0.20 μm, 0.14 μm, 300 kDa and 50 kDa were compared during natural surface water filtration with respect to hydraulically irreversible fouling index (HIFI), foulant composition and narrowing of pore size due to the irreversible fouling. Our results showed that the hydraulically irreversible fouling index (HIFI) was proportional to the membrane pore size (r2=0.89) when the same feed water was filtrated. The UF membranes showed lower HIFI values than the MF membranes. Pore narrowing (internal fouling) was found to be a main fouling pattern of the hydraulically irreversible fouling. The internal fouling was caused by monolayer adsorption of foulants with different sizes that is dependent on the size of the membrane pore.

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.

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

The new era of minimally invasive interventions for prostate cancer: robot-assisted laparoscopic radical prostatectomy and focal therapy

Directory of Open Access Journals (Sweden)

Schatloff O

2011-10-01

Full Text Available Oscar Schatloff1, Alyssa S Louis2, Uri Lindner21Global Robotics Institute, Florida Hospital Celebration Health, Celebration, FL, USA; 2Division of Urology, Department of Surgical Oncology, University Health Network, Toronto, ON, CanadaAbstract: Prostate cancer remains a common but highly treatable disease. Innovations in prostate cancer treatment have allowed a transition toward minimally invasive approaches in an attempt to avoid treatment-related morbidities. In the middle of the treatment spectrum between radical open surgeries and active surveillance lies robot-assisted laparoscopic radical prostatectomy (RALP and focal therapy (FT. This review sets out the most current information on RALP and FT (including laser ablation, cryotherapy, high-intensity focused ultrasound, photodynamic therapy, and irreversible electroporation.Keywords: PCa, RALP, FT, laser ablation, cryotherapy, high-intensity focused ultrasound, photodynamic therapy, irreversible electroporation

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.

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

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.

Irreversibility and dissipation in finite-state automata

International Nuclear Information System (INIS)

Ganesh, Natesh; Anderson, Neal G.

2013-01-01

Irreversibility and dissipation in finite-state automata (FSA) are considered from a physical-information-theoretic perspective. A quantitative measure for the computational irreversibility of finite automata is introduced, and a fundamental lower bound on the average energy dissipated per state transition is obtained and expressed in terms of FSA irreversibility. The irreversibility measure and energy bound are germane to any realization of a deterministic automaton that faithfully registers abstract FSA states in distinguishable states of a physical system coupled to a thermal environment, and that evolves via a sequence of interactions with an external system holding a physical instantiation of a random input string. The central result, which is shown to follow from quantum dynamics and entropic inequalities alone, can be regarded as a generalization of Landauer's Principle applicable to FSAs and tailorable to specified automata. Application to a simple FSA is illustrated.

Multidimensional Heat Conduction

DEFF Research Database (Denmark)

Rode, Carsten

1998-01-01

Analytical theory of multidimensional heat conduction. General heat conduction equation in three dimensions. Steay state, analytical solutions. The Laplace equation. Method of separation of variables. Principle of superposition. Shape factors. Transient, multidimensional heat conduction....

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.

Extended Irreversible Thermodynamics

CERN Document Server

Jou, David

2010-01-01

This is the 4th edition of the highly acclaimed monograph on Extended Irreversible Thermodynamics, a theory that goes beyond the classical theory of irreversible processes. In contrast to the classical approach, the basic variables describing the system are complemented by non-equilibrium quantities. The claims made for extended thermodynamics are confirmed by the kinetic theory of gases and statistical mechanics. The book covers a wide spectrum of applications, and also contains a thorough discussion of the foundations and the scope of the current theories on non-equilibrium thermodynamics. For this new edition, the authors critically revised existing material while taking into account the most recent developments in fast moving fields such as heat transport in micro- and nanosystems or fast solidification fronts in materials sciences. Several fundamental chapters have been revisited emphasizing physics and applications over mathematical derivations. Also, fundamental questions on the definition of non-equil...

Attribution of irreversible loss to anthropogenic climate change

Science.gov (United States)

Huggel, Christian; Bresch, David; Hansen, Gerrit; James, Rachel; Mechler, Reinhard; Stone, Dáithí; Wallimann-Helmer, Ivo

2016-04-01

The Paris Agreement (2015) under the UNFCCC has anchored loss and damage in a separate article which specifies that understanding and support should be enhanced in areas addressing loss and damage such as early warning, preparedness, insurance and resilience. Irreversible loss is a special category under loss and damage but there is still missing clarity over what irreversible loss actually includes. Many negative impacts of climate change may be handled or mitigated by existing risk management, reduction and absorption approaches. Irreversible loss, however, is thought to be insufficiently addressed by risk management. Therefore, countries potentially or actually affected by irreversible loss are calling for other measures such as compensation, which however is highly contested in international climate policy. In Paris (2015) a decision was adopted that loss and damage as defined in the respective article of the agreement does not involve compensation and liability. Nevertheless, it is likely that some sort of mechanism will eventually need to come into play for irreversible loss due to anthropogenic climate change, which might involve compensation, other forms of non-monetary reparation, or transformation. Furthermore, climate litigation has increasingly been attempted to address negative effects of climate change. In this context, attribution is important to understand the drivers of change, what counts as irreversible loss due to climate change, and, possibly, who or what is responsible. Here we approach this issue by applying a detection and attribution perspective on irreversible loss. We first analyze detected climate change impacts as assessed in the IPCC Fifth Assessment Report. We distinguish between irreversible loss in physical, biological and human systems, and accordingly identify the following candidates of irreversible loss in these systems: loss of glaciers and ice sheets, loss of subsurface ice (permafrost) and related loss of lake systems; loss

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.

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

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.

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...

Multidimensional high harmonic spectroscopy

International Nuclear Information System (INIS)

Bruner, Barry D; Soifer, Hadas; Shafir, Dror; Dudovich, Nirit; Serbinenko, Valeria; Smirnova, Olga

2015-01-01

High harmonic generation (HHG) has opened up a new frontier in ultrafast science where attosecond time resolution and Angstrom spatial resolution are accessible in a single measurement. However, reconstructing the dynamics under study is limited by the multiple degrees of freedom involved in strong field interactions. In this paper we describe a new class of measurement schemes for resolving attosecond dynamics, integrating perturbative nonlinear optics with strong-field physics. These approaches serve as a basis for multidimensional high harmonic spectroscopy. Specifically, we show that multidimensional high harmonic spectroscopy can measure tunnel ionization dynamics with high precision, and resolves the interference between multiple ionization channels. In addition, we show how multidimensional HHG can function as a type of lock-in amplifier measurement. Similar to multi-dimensional approaches in nonlinear optical spectroscopy that have resolved correlated femtosecond dynamics, multi-dimensional high harmonic spectroscopy reveals the underlying complex dynamics behind attosecond scale phenomena. (paper)

Numeric invariants from multidimensional persistence

Energy Technology Data Exchange (ETDEWEB)

Skryzalin, Jacek [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carlsson, Gunnar [Stanford Univ., Stanford, CA (United States)

2017-05-19

In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be used to study data.

Generalized irreversible heat-engine experiencing a complex heat-transfer law

International Nuclear Information System (INIS)

Chen Lingen; Li Jun; Sun Fengrui

2008-01-01

The fundamental optimal relation between optimal power-output and efficiency of a generalized irreversible Carnot heat-engine is derived based on a generalized heat-transfer law, including a generalized convective heat-transfer law and a generalized radiative heat-transfer law, q ∝ (ΔT n ) m . The generalized irreversible Carnot-engine model incorporates several internal and external irreversibilities, such as heat resistance, bypass heat-leak, friction, turbulence and other undesirable irreversibility factors. The added irreversibilities, besides heat resistance, are characterized by a constant parameter and a constant coefficient. The effects of heat-transfer laws and various loss terms are analyzed. The results obtained corroborate those in the literature

Absorption media for irreversibly gettering thionyl chloride

Science.gov (United States)

Buffleben, George; Goods, Steven H.; Shepodd, Timothy; Wheeler, David R.; Whinnery, Jr., LeRoy

2002-01-01

Thionyl chloride is a hazardous and reactive chemical used as the liquid cathode in commercial primary batteries. Contrary to previous thinking, ASZM-TEDA.RTM. carbon (Calgon Corporation) reversibly absorbs thionyl chloride. Thus, several candidate materials were examined as irreversible getters for thionyl chloride. The capacity, rate and effect of temperature were also explored. A wide variety of likely materials were investigated through screening experiments focusing on the degree of heat generated by the reaction as well as the material absorption capacity and irreversibility, in order to help narrow the group of possible getter choices. More thorough, quantitative measurements were performed on promising materials. The best performing getter was a mixture of ZnO and ASZM-TEDA.RTM. carbon. In this example, the ZnO reacts with thionyl chloride to form ZnCl.sub.2 and SO.sub.2. The SO.sub.2 is then irreversibly gettered by ASZM-TEDA.RTM. carbon. This combination of ZnO and carbon has a high capacity, is irreversible and functions effectively above -20.degree. C.

The Value of Fighting Irreversible Demise by Softening the Irreversible Cost

NARCIS (Netherlands)

Magis, P.; Sbuelz, A.

2005-01-01

We study a novel issue in the real-options-based technology innovation literature by means of double barrier contingent claims analysis.We show how much a ¯rm with the monopoly over a project is willing to spend in investment technology innovation that softens the irreversible cost of accessing the

Irreversible work in a thermal medium with colored noise

International Nuclear Information System (INIS)

Ohkuma, Takahiro

2009-01-01

Irreversible work and its fluctuations in a classical system governed by non-Markovian stochastic dynamics are investigated. The production of irreversible work depends not only on the protocol of an operation but also on the details of the non-Markovian memory. We consider a generalized Langevin equation with a memory kernel and derive an expression for the irreversible work in the case of slow operations by carrying out an expansion of this memory kernel in the parameter representing the length of the memory. We apply our formulation to a harmonically trapped system and demonstrate the efficiency of a cycle by evaluating the irreversible work. It is found that a decrease in the irreversible work due to the memory effect can occur for an operation through which the trap is squeezed. The results for this harmonic system are verified exactly in the case that the memory kernel has exponential decay

Irreversible work in a thermal medium with colored noise

Science.gov (United States)

Ohkuma, Takahiro

2009-10-01

Irreversible work and its fluctuations in a classical system governed by non-Markovian stochastic dynamics are investigated. The production of irreversible work depends not only on the protocol of an operation but also on the details of the non-Markovian memory. We consider a generalized Langevin equation with a memory kernel and derive an expression for the irreversible work in the case of slow operations by carrying out an expansion of this memory kernel in the parameter representing the length of the memory. We apply our formulation to a harmonically trapped system and demonstrate the efficiency of a cycle by evaluating the irreversible work. It is found that a decrease in the irreversible work due to the memory effect can occur for an operation through which the trap is squeezed. The results for this harmonic system are verified exactly in the case that the memory kernel has exponential decay.

Irreversible thermodynamic analysis and application for molecular heat engines

Science.gov (United States)

Lucia, Umberto; Açıkkalp, Emin

2017-09-01

Is there a link between the macroscopic approach to irreversibility and microscopic behaviour of the systems? Consumption of free energy keeps the system away from a stable equilibrium. Entropy generation results from the redistribution of energy, momentum, mass and charge. This concept represents the essence of the thermodynamic approach to irreversibility. Irreversibility is the result of the interaction between systems and their environment. The aim of this paper is to determine lost works in a molecular engine and compare results with macro (classical) heat engines. Firstly, irreversible thermodynamics are reviewed for macro and molecular cycles. Secondly, irreversible thermodynamics approaches are applied for a quantum heat engine with -1/2 spin system. Finally, lost works are determined for considered system and results show that macro and molecular heat engines obey same limitations. Moreover, a quantum thermodynamic approach is suggested in order to explain the results previously obtained from an atomic viewpoint.

Exergetic efficiency optimization for an irreversible heat pump ...

Indian Academy of Sciences (India)

side ... For irreversible cycle, the internal irreversibility, i.e., non-isentropic losses in the ... constant thermal capacitance rate (the product of mass flow rate and specific heat), .... reversed Brayton cycle is dependent on the external heat transfer ...

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

The detection of local irreversibility in time series based on segmentation

Science.gov (United States)

Teng, Yue; Shang, Pengjian

2018-06-01

We propose a strategy for the detection of local irreversibility in stationary time series based on multiple scale. The detection is beneficial to evaluate the displacement of irreversibility toward local skewness. By means of this method, we can availably discuss the local irreversible fluctuations of time series as the scale changes. The method was applied to simulated nonlinear signals generated by the ARFIMA process and logistic map to show how the irreversibility functions react to the increasing of the multiple scale. The method was applied also to series of financial markets i.e., American, Chinese and European markets. The local irreversibility for different markets demonstrate distinct characteristics. Simulations and real data support the need of exploring local irreversibility.

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...

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.

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.

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...

General thermodynamic performance of irreversible absorption heat pump

International Nuclear Information System (INIS)

Zhao Xiling; Fu Lin; Zhang Shigang

2011-01-01

The absorption heat pump (AHP) was studied with thermodynamics. A four reservoirs model of absorption heat pump was established considering the heat resistance, heat leak and the internal irreversibility. The reasonable working regions, the performance effects of irreversibility, heat leak and the correlation of four components were studied. When studying the effects of internal irreversibility, two internal irreversibility parameters (I he for generator-absorber assembly and I re for evaporator-condenser assembly) were introduced to distinguish the different effects. When studying the heat transfer relations of four components, a universal relationship between the main parameters were deduced. The results which have more realized meaning show that, the reduction of the friction, heat loss, and internal dissipations of the evaporator-condenser assembly are more important than its reduction of generator-absorber assembly, and lessening the heat leak of generator are more important than its reduction of other components to improve the AHP performance.

Stochastic dynamics and irreversibility

CERN Document Server

Tomé, Tânia

2015-01-01

This textbook presents an exposition of stochastic dynamics and irreversibility. It comprises the principles of probability theory and the stochastic dynamics in continuous spaces, described by Langevin and Fokker-Planck equations, and in discrete spaces, described by Markov chains and master equations. Special concern is given to the study of irreversibility, both in systems that evolve to equilibrium and in nonequilibrium stationary states. Attention is also given to the study of models displaying phase transitions and critical phenomema both in thermodynamic equilibrium and out of equilibrium. These models include the linear Glauber model, the Glauber-Ising model, lattice models with absorbing states such as the contact process and those used in population dynamic and spreading of epidemic, probabilistic cellular automata, reaction-diffusion processes, random sequential adsorption and dynamic percolation. A stochastic approach to chemical reaction is also presented.The textbook is intended for students of ...

Irreversible stochastic processes on lattices

International Nuclear Information System (INIS)

Nord, R.S.

1986-01-01

Models for irreversible random or cooperative filling of lattices are required to describe many processes in chemistry and physics. Since the filling is assumed to be irreversible, even the stationary, saturation state is not in equilibrium. The kinetics and statistics of these processes are described by recasting the master equations in infinite hierarchical form. Solutions can be obtained by implementing various techniques: refinements in these solution techniques are presented. Programs considered include random dimer, trimer, and tetramer filling of 2D lattices, random dimer filling of a cubic lattice, competitive filling of two or more species, and the effect of a random distribution of inactive sites on the filling. Also considered is monomer filling of a linear lattice with nearest neighbor cooperative effects and solve for the exact cluster-size distribution for cluster sizes up to the asymptotic regime. Additionally, a technique is developed to directly determine the asymptotic properties of the cluster size distribution. Finally cluster growth is considered via irreversible aggregation involving random walkers. In particular, explicit results are provided for the large-lattice-size asymptotic behavior of trapping probabilities and average walk lengths for a single walker on a lattice with multiple traps. Procedures for exact calculation of these quantities on finite lattices are also developed

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.

Irreversible thermodynamics of Poisson processes with reaction.

Science.gov (United States)

Méndez, V; Fort, J

1999-11-01

A kinetic model is derived to study the successive movements of particles, described by a Poisson process, as well as their generation. The irreversible thermodynamics of this system is also studied from the kinetic model. This makes it possible to evaluate the differences between thermodynamical quantities computed exactly and up to second-order. Such differences determine the range of validity of the second-order approximation to extended irreversible thermodynamics.

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...

Thermodynamic Analysis of an Irreversible Maisotsenko Reciprocating Brayton Cycle

Directory of Open Access Journals (Sweden)

Fuli Zhu

2018-03-01

Full Text Available An irreversible Maisotsenko reciprocating Brayton cycle (MRBC model is established using the finite time thermodynamic (FTT theory and taking the heat transfer loss (HTL, piston friction loss (PFL, and internal irreversible losses (IILs into consideration in this paper. A calculation flowchart of the power output (P and efficiency (η of the cycle is provided, and the effects of the mass flow rate (MFR of the injection of water to the cycle and some other design parameters on the performance of cycle are analyzed by detailed numerical examples. Furthermore, the superiority of irreversible MRBC is verified as the cycle and is compared with the traditional irreversible reciprocating Brayton cycle (RBC. The results can provide certain theoretical guiding significance for the optimal design of practical Maisotsenko reciprocating gas turbine plants.

Antibiotic use for irreversible pulpitis.

Science.gov (United States)

Agnihotry, Anirudha; Fedorowicz, Zbys; van Zuuren, Esther J; Farman, Allan G; Al-Langawi, Jassim Hasan

2016-02-17

Irreversible pulpitis, which is characterised by acute and intense pain, is one of the most frequent reasons that patients attend for emergency dental care. Apart from removal of the tooth, the customary way of relieving the pain of irreversible pulpitis is by drilling into the tooth, removing the inflamed pulp (nerve) and cleaning the root canal. However, a significant number of dentists continue to prescribe antibiotics to stop the pain of irreversible pulpitis.This review updates the previous version published in 2013. To assess the effects of systemic antibiotics for irreversible pulpitis. We searched the Cochrane Oral Health Group's Trials Register (to 27 January 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 12); MEDLINE via Ovid (1946 to 27 January 2016); EMBASE via Ovid (1980 to 27 January 2016), ClinicalTrials.gov (to 27 January 2016) and the WHO International Clinical Trials Registry Platform (to 27 January 2016). There were no language restrictions in the searches of the electronic databases. Randomised controlled trials which compared pain relief with systemic antibiotics and analgesics, against placebo and analgesics in the acute preoperative phase of irreversible pulpitis. Two review authors screened studies and extracted data independently. We assessed the quality of the evidence of included studies using GRADEpro software. Pooling of data was not possible and a descriptive summary is presented. One trial assessed at low risk of bias, involving 40 participants was included in this update of the review. The quality of the body of evidence was rated low for the different outcomes. There was a close parallel distribution of the pain ratings in both the intervention and placebo groups over the seven-day study period. There was insufficient evidence to claim or refute a benefit for penicillin for pain intensity. There was no significant difference in the mean total number of ibuprofen tablets over the

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.

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

Optimization of an irreversible Stirling regenerative cycle

International Nuclear Information System (INIS)

Aragón-González, G; Cano-Bianco, M; León-Galicia, A; Rivera-Camacho, J M

2015-01-01

In this work a Stirling regenerative cycle with some irreversibilities is analyzed. The analyzed irreversibilities are located at the heat exchangers. They receive a finite amount of heat and heat leakage occurs between both reservoirs. Using this model, power and the efficiency at maximum power are obtained. Some optimal design parameters for the exchanger heat areas and thermal conductances are presented. The relation between the power, efficiency and the results obtained are shown graphically

Multidimensional Models of Information Need

OpenAIRE

Yun-jie (Calvin) Xu; Kai Huang (Joseph) Tan

2009-01-01

User studies in information science have recognised relevance as a multidimensional construct. An implication of multidimensional relevance is that a user's information need should be modeled by multiple data structures to represent different relevance dimensions. While the extant literature has attempted to model multiple dimensions of a user's information need, the fundamental assumption that a multidimensional model is better than a uni-dimensional model has not been addressed. This study ...

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 ...

Reversible and irreversible heat engine and refrigerator cycles

Science.gov (United States)

Leff, Harvey S.

2018-05-01

Although no reversible thermodynamic cycles exist in nature, nearly all cycles covered in textbooks are reversible. This is a review, clarification, and extension of results and concepts for quasistatic, reversible and irreversible processes and cycles, intended primarily for teachers and students. Distinctions between the latter process types are explained, with emphasis on clockwise (CW) and counterclockwise (CCW) cycles. Specific examples of each are examined, including Carnot, Kelvin and Stirling cycles. For the Stirling cycle, potentially useful task-specific efficiency measures are proposed and illustrated. Whether a cycle behaves as a traditional refrigerator or heat engine can depend on whether it is reversible or irreversible. Reversible and irreversible-quasistatic CW cycles both satisfy Carnot's inequality for thermal efficiency, η ≤ η C a r n o t . Irreversible CCW cycles with two reservoirs satisfy the coefficient of performance inequality K ≤ K C a r n o t . However, an arbitrary reversible cycle satisfies K ≥ K C a r n o t when compared with a reversible Carnot cycle operating between its maximum and minimum temperatures, a potentially counterintuitive result.

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)

Formation of Irreversible H-bonds in Cellulose Materials

Science.gov (United States)

Umesh P. Agarwal; Sally A. Ralph; Rick S. Reiner; Nicole M. Stark

2015-01-01

Understanding of formation of irreversible Hbonds in cellulose is important in a number of fields. For example, fields as diverse as pulp and paper and enzymatic saccharification of cellulose are affected. In the present investigation, the phenomenon of formation of irreversible H-bonds is studied in a variety of celluloses and under two different drying conditions....

Irreversible climate change due to carbon dioxide emissions

Science.gov (United States)

Solomon, Susan; Plattner, Gian-Kasper; Knutti, Reto; Friedlingstein, Pierre

2009-01-01

The severity of damaging human-induced climate change depends not only on the magnitude of the change but also on the potential for irreversibility. This paper shows that the climate change that takes place due to increases in carbon dioxide concentration is largely irreversible for 1,000 years after emissions stop. Following cessation of emissions, removal of atmospheric carbon dioxide decreases radiative forcing, but is largely compensated by slower loss of heat to the ocean, so that atmospheric temperatures do not drop significantly for at least 1,000 years. Among illustrative irreversible impacts that should be expected if atmospheric carbon dioxide concentrations increase from current levels near 385 parts per million by volume (ppmv) to a peak of 450–600 ppmv over the coming century are irreversible dry-season rainfall reductions in several regions comparable to those of the “dust bowl” era and inexorable sea level rise. Thermal expansion of the warming ocean provides a conservative lower limit to irreversible global average sea level rise of at least 0.4–1.0 m if 21st century CO2 concentrations exceed 600 ppmv and 0.6–1.9 m for peak CO2 concentrations exceeding ≈1,000 ppmv. Additional contributions from glaciers and ice sheet contributions to future sea level rise are uncertain but may equal or exceed several meters over the next millennium or longer. PMID:19179281

Intrinsic irreversibility in quantum theory

International Nuclear Information System (INIS)

Prigogine, I.; Petrosky, T.Y.

1987-01-01

Quantum theory has a dual structure: while solutions of the Schroedinger equation evolve in a deterministic and time reversible way, measurement introduces irreversibility and stochasticity. This presents a contrast to Bohr-Sommerfeld-Einstein theory, in which transitions between quantum states are associated with spontaneous and induced transitions, defined in terms of stochastic processes. A new form of quantum theory is presented here, which contains an intrinsic form of irreversibility, independent of observation. This new form applies to situations corresponding to a continuous spectrum and to quantum states with finite life time. The usual non-commutative algebra associated to quantum theory is replaced by more general algebra, in which operators are also non-distributive. Our approach leads to a number of predictions, which hopefully may be verified or refuted in the next years. (orig.)

Irreversibility and self-organization in spin glasses. 2. Irreversibility and the problem of configuration averaging

International Nuclear Information System (INIS)

Kovrov, V.P.; Kurbatov, A.M.

1989-05-01

The generalization of a configuration averaging to a system displaying irreversible effects is suggested. The properties of the ''pathological'' equilibrium state at low temperatures are determined and discussed. (author). 16 refs, 3 figs

Optimization at different loads by minimization of irreversibilities

International Nuclear Information System (INIS)

Wong, K.F.V.; Niu, Z.

1991-01-01

This paper reports that the irreversibility of the power cycle was chosen as the objective function as this function can successfully measure both the quality and quantity of energy flow in the cycle. Minimization of the irreversibility ensures that the power cycle will operate more efficiently. One feature of the present work is that the boiler, turbine, condenser and heaters are treated as one system for the purpose of optimization. In the optimization model, nine regression formulae are used, which are obtained from the measured test data. From the results of the present work, it can be seen that the optimization model developed can represent the effect of operational parameters on the power plant first and second law efficiency. Some of the results can be used to provide guidance for the optimal operation of the power plant. When the power cycle works at full load, the main steam temperature and pressure should be at the upper limit for minimal irreversibility of the system. If the load is less than 65% of its design capacity, the steam temperature and pressure should be decreased for a lower irreversibility of the system

Applied multidimensional systems theory

CERN Document Server

Bose, Nirmal K

2017-01-01

Revised and updated, this concise new edition of the pioneering book on multidimensional signal processing is ideal for a new generation of students. Multidimensional systems or m-D systems are the necessary mathematical background for modern digital image processing with applications in biomedicine, X-ray technology and satellite communications. Serving as a firm basis for graduate engineering students and researchers seeking applications in mathematical theories, this edition eschews detailed mathematical theory not useful to students. Presentation of the theory has been revised to make it more readable for students, and introduce some new topics that are emerging as multidimensional DSP topics in the interdisciplinary fields of image processing. New topics include Groebner bases, wavelets, and filter banks.

SQL and Multidimensional Data

Directory of Open Access Journals (Sweden)

Mihaela MUNTEAN

2006-01-01

Full Text Available Using SQL you can manipulate multidimensional data and extract that data into a relational table. There are many PL/SQL packages that you can use directly in SQL*Plus or indirectly in Analytic Workspace Manager and OLAP Worksheet. In this article I discussed about some methods that you can use for manipulating and extracting multidimensional data.

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.

Focal irreversible electroporation as primary treatment for localized prostate cancer

NARCIS (Netherlands)

van den Bos, Willemien; Scheltema, Matthijs J.; Siriwardana, Amila R.; Kalsbeek, Anton M. F.; Thompson, James E.; Ting, Francis; Böhm, Maret; Haynes, Anne-Maree; Shnier, Ron; Delprado, Warick; Stricker, Phillip D.

2017-01-01

To determine the safety, quality of life (QoL) and short-term oncological outcomes of primary focal IRE for the treatment of localized prostate cancer. To identify potential risk factors for oncological failure. Patients that met both the consensus guidelines on patient criteria and selection

Multidimensional Databases and Data Warehousing

CERN Document Server

Jensen, Christian

2010-01-01

The present book's subject is multidimensional data models and data modeling concepts as they are applied in real data warehouses. The book aims to present the most important concepts within this subject in a precise and understandable manner. The book's coverage of fundamental concepts includes data cubes and their elements, such as dimensions, facts, and measures and their representation in a relational setting; it includes architecture-related concepts; and it includes the querying of multidimensional databases.The book also covers advanced multidimensional concepts that are considered to b

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.

The necessity-concerns framework: a multidimensional theory benefits from multidimensional analysis.

Science.gov (United States)

Phillips, L Alison; Diefenbach, Michael A; Kronish, Ian M; Negron, Rennie M; Horowitz, Carol R

2014-08-01

Patients' medication-related concerns and necessity-beliefs predict adherence. Evaluation of the potentially complex interplay of these two dimensions has been limited because of methods that reduce them to a single dimension (difference scores). We use polynomial regression to assess the multidimensional effect of stroke-event survivors' medication-related concerns and necessity beliefs on their adherence to stroke-prevention medication. Survivors (n = 600) rated their concerns, necessity beliefs, and adherence to medication. Confirmatory and exploratory polynomial regression determined the best-fitting multidimensional model. As posited by the necessity-concerns framework (NCF), the greatest and lowest adherence was reported by those necessity weak concerns and strong concerns/weak Necessity-Beliefs, respectively. However, as could not be assessed using a difference-score model, patients with ambivalent beliefs were less adherent than those exhibiting indifference. Polynomial regression allows for assessment of the multidimensional nature of the NCF. Clinicians/Researchers should be aware that concerns and necessity dimensions are not polar opposites.

Multi-dimensional imaging

CERN Document Server

Javidi, Bahram; Andres, Pedro

2014-01-01

Provides a broad overview of advanced multidimensional imaging systems with contributions from leading researchers in the field Multi-dimensional Imaging takes the reader from the introductory concepts through to the latest applications of these techniques. Split into 3 parts covering 3D image capture, processing, visualization and display, using 1) a Multi-View Approach and 2.) a Holographic Approach, followed by a 3rd part addressing other 3D systems approaches, applications and signal processing for advanced 3D imaging. This book describes recent developments, as well as the prospects and

Substance P and CGRP expression in dental pulps with irreversible pulpitis.

Science.gov (United States)

Sattari, Mandana; Mozayeni, Mohammad Ali; Matloob, Arash; Mozayeni, Maryam; Javaheri, Homan H

2010-08-01

The purpose of this study was to compare substance P (SP) and calcitonin gene-related peptide (CGRP) expression in pulp tissue with clinically diagnosed symptomatic and asymptomatic irreversible pulpitis. Healthy pulps acted as controls. Five normal pulps and 40 with irreversible pulpitis (20 symptomatic and 20 asymptomatic) were obtained from 45 different patients. SP and CGRP expression was determined by competition binding assays using enzyme immunoassay. anova and Mann-Whitney tests were used to ascertain if there were statistically significant differences between the groups. The results showed that neuropeptides were found in all pulp samples. The highest and the lowest expressions for SP and CGRP were found in symptomatic irreversible pulpitis and healthy pulps groups, respectively. The differences between healthy pulps and the groups of pulps having irreversible pulpitis were significant (P pulpitis groups (P pulpitis groups were not significant. This study demonstrated that the expression of CGRP and SP is significantly higher in pulps with irreversible pulpitis compared with healthy pulps.

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.

Guinea pig ductus arteriosus. II - Irreversible closure after birth.

Science.gov (United States)

Fay, F. S.; Cooke, P. H.

1972-01-01

To investigate the mechanism underlying irreversibility of ductal closure after birth, studies were undertaken to determine the exact time course for the onset of irreversible closure of the guinea pig ductus arteriosus. Parallel studies of the reactivity of ductal smooth muscle to oxygen and studies of the postpartum cellular changes within the vessel were also carried out.

Multiscale time irreversibility of heart rate and blood pressure variability during orthostasis

International Nuclear Information System (INIS)

Chladekova, L; Czippelova, B; Turianikova, Z; Tonhajzerova, I; Calkovska, A; Javorka, M; Baumert, M

2012-01-01

Time irreversibility is a characteristic feature of non-equilibrium, complex systems such as the cardiovascular control mediated by the autonomic nervous system (ANS). Time irreversibility analysis of heart rate variability (HRV) and blood pressure variability (BPV) represents a new approach to assess cardiovascular regulatory mechanisms. The aim of this paper was to assess the changes in HRV and BPV irreversibility during the active orthostatic test (a balance of ANS shifted towards sympathetic predominance) in 28 healthy young subjects. We used three different time irreversibility indices—Porta’s, Guzik's and Ehler's indices (P%, G% and E, respectively) derived from data segments containing 1000 beat-to-beat intervals on four timescales. We observed an increase in the HRV and a decrease in the BPV irreversibility during standing compared to the supine position. The postural change in irreversibility was confirmed by surrogate data analysis. The differences were more evident in G% and E than P% and for higher scale factors. Statistical analysis showed a close relationship between G% and E. Contrary to this, the association between P% and G% and P% and E was not proven. We conclude that time irreversibility of beat-to-beat HRV and BPV is significantly altered during orthostasis, implicating involvement of the autonomous nervous system in its generation. (paper)

Irreversibility and conditional probability

International Nuclear Information System (INIS)

Stuart, C.I.J.M.

1989-01-01

The mathematical entropy - unlike physical entropy - is simply a measure of uniformity for probability distributions in general. So understood, conditional entropies have the same logical structure as conditional probabilities. If, as is sometimes supposed, conditional probabilities are time-reversible, then so are conditional entropies and, paradoxically, both then share this symmetry with physical equations of motion. The paradox is, of course that probabilities yield a direction to time both in statistical mechanics and quantum mechanics, while the equations of motion do not. The supposed time-reversibility of both conditionals seems also to involve a form of retrocausality that is related to, but possibly not the same as, that described by Costa de Beaurgard. The retrocausality is paradoxically at odds with the generally presumed irreversibility of the quantum mechanical measurement process. Further paradox emerges if the supposed time-reversibility of the conditionals is linked with the idea that the thermodynamic entropy is the same thing as 'missing information' since this confounds the thermodynamic and mathematical entropies. However, it is shown that irreversibility is a formal consequence of conditional entropies and, hence, of conditional probabilities also. 8 refs. (Author)

Performance Optimization of Irreversible Air Heat Pumps Considering Size Effect

Science.gov (United States)

Bi, Yuehong; Chen, Lingen; Ding, Zemin; Sun, Fengrui

2018-06-01

Considering the size of an irreversible air heat pump (AHP), heating load density (HLD) is taken as thermodynamic optimization objective by using finite-time thermodynamics. Based on an irreversible AHP with infinite reservoir thermal-capacitance rate model, the expression of HLD of AHP is put forward. The HLD optimization processes are studied analytically and numerically, which consist of two aspects: (1) to choose pressure ratio; (2) to distribute heat-exchanger inventory. Heat reservoir temperatures, heat transfer performance of heat exchangers as well as irreversibility during compression and expansion processes are important factors influencing on the performance of an irreversible AHP, which are characterized with temperature ratio, heat exchanger inventory as well as isentropic efficiencies, respectively. Those impacts of parameters on the maximum HLD are thoroughly studied. The research results show that HLD optimization can make the size of the AHP system smaller and improve the compactness of system.

Kinetic theory of nonequilibrium ensembles, irreversible thermodynamics, and generalized hydrodynamics

CERN Document Server

Eu, Byung Chan

2016-01-01

This book presents the fundamentals of irreversible thermodynamics for nonlinear transport processes in gases and liquids, as well as for generalized hydrodynamics extending the classical hydrodynamics of Navier, Stokes, Fourier, and Fick. Together with its companion volume on relativistic theories, it provides a comprehensive picture of the kinetic theory formulated from the viewpoint of nonequilibrium ensembles in both nonrelativistic and, in Vol. 2, relativistic contexts. Theories of macroscopic irreversible processes must strictly conform to the thermodynamic laws at every step and in all approximations that enter their derivation from the mechanical principles. Upholding this as the inviolable tenet, the author develops theories of irreversible transport processes in fluids (gases or liquids) on the basis of irreversible kinetic equations satisfying the H theorem. They apply regardless of whether the processes are near to or far removed from equilibrium, or whether they are linear or nonlinear with respe...

Discovering Multidimensional Structure in Relational Data

DEFF Research Database (Denmark)

Jensen, Mikael Rune; Holmgren, Thomas; Pedersen, Torben Bach

2004-01-01

On-Line Analytical Processing (OLAP) systems based on multidimensional databases are essential elements of decision support. However, most existing data is stored in “ordinary” relational OLTP databases, i.e., data has to be (re-) modeled as multidimensional cubes before the advantages of OLAP to...... algorithms for discovering multidimensional schemas from relational databases. The algorithms take a wide range of available metadata into account in the discovery process, including functional and inclusion dependencies, and key and cardinality information....... tools are available. In this paper we present an approach for the automatic construction of multidimensional OLAP database schemas from existing relational OLTP databases, enabling easy OLAP design and analysis for most existing data sources. This is achieved through a set of practical and effective...

Transition to Clean Capital, Irreversible Investment and Stranded Assets

OpenAIRE

Rozenberg, Julie; Vogt-Schilb, Adrien; Hallegatte, Stephane

2014-01-01

This paper uses a Ramsey model with two types of capital to analyze the optimal transition to clean capital when polluting investment is irreversible. The cost of climate mitigation decomposes as a technical cost of using clean instead of polluting capital and a transition cost from the irreversibility of pre-existing polluting capital. With a carbon price, the transition cost can be limit...

Spectral line intensity irreversibility in circulatory plasma magnetization processes

Science.gov (United States)

Qu, Z. Q.; Dun, G. T.

2012-01-01

Spectral line intensity variation is found to be irreversible in circulatory plasma magnetization process by experiments described in this paper, i.e., the curves illustrating spectral line photon fluxes irradiated from a light source immerged in a magnetic field by increasing the magnetic induction cannot be reproduced by decreasing the magnetic induction within the errors. There are two plasma magnetization patterns found. One shows that the intensities are greater at the same magnetic inductions during the magnetic induction decreasing process after the increasing, and the other gives the opposite effect. This reveals that the magneto-induced excitation and de-excitation process is irreversible like ferromagnetic magnetization. But the two irreversible processes are very different in many aspects stated in the text.

The Necessity-Concerns-Framework: A Multidimensional Theory Benefits from Multidimensional Analysis

Science.gov (United States)

Phillips, L. Alison; Diefenbach, Michael; Kronish, Ian M.; Negron, Rennie M.; Horowitz, Carol R.

2014-01-01

Background Patients’ medication-related concerns and necessity-beliefs predict adherence. Evaluation of the potentially complex interplay of these two dimensions has been limited because of methods that reduce them to a single dimension (difference scores). Purpose We use polynomial regression to assess the multidimensional effect of stroke-event survivors’ medication-related concerns and necessity-beliefs on their adherence to stroke-prevention medication. Methods Survivors (n=600) rated their concerns, necessity-beliefs, and adherence to medication. Confirmatory and exploratory polynomial regression determined the best-fitting multidimensional model. Results As posited by the Necessity-Concerns Framework (NCF), the greatest and lowest adherence was reported by those with strong necessity-beliefs/weak concerns and strong concerns/weak necessity-beliefs, respectively. However, as could not be assessed using a difference-score model, patients with ambivalent beliefs were less adherent than those exhibiting indifference. Conclusions Polynomial regression allows for assessment of the multidimensional nature of the NCF. Clinicians/Researchers should be aware that concerns and necessity dimensions are not polar opposites. PMID:24500078

Ecological optimization and parametric study of irreversible Stirling and Ericsson heat pumps

International Nuclear Information System (INIS)

Tyagi, S.K.; Kaushik, S.C.; Salohtra, R.

2002-01-01

This communication presents the ecological optimization and parametric study of irreversible Stirling and Ericsson heat pump cycles, in which the external irreversibility is due to finite temperature difference between working fluid and external reservoirs while the internal irreversibilities are due to regenerative heat loss and other entropy generations within the cycle. The ecological function is defined as the heating load minus the irreversibility (power loss) which is ambient temperature times the entropy generation. The ecological function is optimized with respect to working fluid temperatures, and the expressions for various parameters at the optimal operating condition are obtained. The effects of different operating parameters on the performance of these cycles have been studied. It is found that the effect of internal irreversibility parameter is more pronounced than the other parameters on the performance of these cycles. (author)

Ictal time-irreversible intracranial EEG signals as markers of the epileptogenic zone.

Science.gov (United States)

Schindler, Kaspar; Rummel, Christian; Andrzejak, Ralph G; Goodfellow, Marc; Zubler, Frédéric; Abela, Eugenio; Wiest, Roland; Pollo, Claudio; Steimer, Andreas; Gast, Heidemarie

2016-09-01

To show that time-irreversible EEG signals recorded with intracranial electrodes during seizures can serve as markers of the epileptogenic zone. We use the recently developed method of mapping time series into directed horizontal graphs (dHVG). Each node of the dHVG represents a time point in the original intracranial EEG (iEEG) signal. Statistically significant differences between the distributions of the nodes' number of input and output connections are used to detect time-irreversible iEEG signals. In 31 of 32 seizure recordings we found time-irreversible iEEG signals. The maximally time-irreversible signals always occurred during seizures, with highest probability in the middle of the first seizure half. These signals spanned a large range of frequencies and amplitudes but were all characterized by saw-tooth like shaped components. Brain regions removed from patients who became post-surgically seizure-free generated significantly larger time-irreversibilities than regions removed from patients who still had seizures after surgery. Our results corroborate that ictal time-irreversible iEEG signals can indeed serve as markers of the epileptogenic zone and can be efficiently detected and quantified in a time-resolved manner by dHVG based methods. Ictal time-irreversible EEG signals can help to improve pre-surgical evaluation in patients suffering from pharmaco-resistant epilepsies. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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.

Irreversible properties of YBCO coated conductors

International Nuclear Information System (INIS)

Vostner, A.

2001-02-01

Over the past few years substantial efforts were made to optimize the fabrication techniques of various high temperature superconductors for commercial applications. In addition to Bi-2223 tapes, Y-123 coated conductors have the potential for large-scale production and are considered as the second generation of superconducting 'wires' for high current applications. This work reports on magnetic and transport current investigations of Y-123 thick films deposited on either single crystalline substrates by liquid phase epitaxy (LPE) or on metallic substrates by pulsed laser deposition (PLD). At the beginning, a short introduction of the general idea of a coated conductor and of the different production techniques is presented, followed by a description of the different experimental set-ups and the evaluation methods. The main part starts with the results obtained from SQUID magnetometry and ac-susceptibility measurements including the transition temperatures T c , the field dependence of the magnetic critical current densities and the irreversibility lines. In addition, some issues concerning the granular structure and the inter- and intragranular current distribution of the superconducting films are discussed. The investigations by transport currents are focused on the behavior of the application relevant irreversible parameters. These are the angular and the field dependence of the critical transport current densities at 77 and 60 K, as well as the temperature dependence of the irreversibility fields up to 6 T. To gain more insight into the defect structure of the films, neutron irradiation studies were performed on some samples. The introduction of these artificial pinning centers causes large enhancements of the magnetic J c in LPE specimens for the field parallel to the c-axis (H//c) at higher temperatures and magnetic fields. The granular structure of the samples does not change up to the highest neutron fluences. However, the enhancements of the transport J c

Irreversibility analysis in the process of solar distillation

International Nuclear Information System (INIS)

Chávez, S; Terres, H; Lizardi, A; López, R; Lara, A

2017-01-01

In this work an irreversibility analysis for the thermal process of solar distillation of three different substances is presented, for which it employs a solar still of a slope where three experimental tests with 5.5 L of brine, river water and MgCl 2 were performed. Temperature data principally in the glass cover, absorber plate, fluid, environment and the incident solar radiation on the device were obtained. With measurements of temperature, solar radiation and exergetic balance, irreversibilities are found on the device. The results show that the highest values of irreversibilities are concentrated in the absorber plate with an average of 321 W, 342 W and 276 W, followed by the cover glass with an average of 75.8 W, 80.4 W and 86.7 W and finally the fluid with 15.3 W, 15.9 W and 16 W, for 5.5 L of brine, river water and MgCl 2 . (paper)

Performance of an irreversible quantum Ericsson cooler at low temperature limit

International Nuclear Information System (INIS)

Wu Feng; Chen Lingen; Wu Shuang; Sun Fengrui

2006-01-01

The purpose of this paper is to investigate the effect of quantum properties of the working medium on the performance of an irreversible quantum Ericsson cooler with spin-1/2. The cooler is studied with the losses of heat resistance, heat leakage and internal irreversibility. The optimal relationship between the dimensionless cooling load R * versus the coefficient of performance ε for the irreversible quantum Ericsson cooler is derived. In particular, the performance characteristics of the cooler at the low temperature limit are discussed

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.

Reversible and Irreversible Binding of Nanoparticles to Polymeric Surfaces

Directory of Open Access Journals (Sweden)

Wolfgang H. Binder

2009-01-01

Full Text Available Reversible and irreversible binding of CdSe-nanoparticles and nanorods to polymeric surfaces via a strong, multiple hydrogen bond (= Hamilton-receptor/barbituric acid is described. Based on ROMP-copolymers, the supramolecular interaction on a thin polymer film is controlled by living polymerization methods, attaching the Hamilton-receptor in various architectures, and concentrations. Strong binding is observed with CdSe-nanoparticles and CdSe-nanorods, whose surfaces are equipped with matching barbituric acid-moieties. Addition of polar solvents, able to break the hydrogen bonds leads to the detachment of the nanoparticles from the polymeric film. Irreversible binding is observed if an azide/alkine-“click”-reaction is conducted after supramolecular recognition of the nanoparticles on the polymeric surface. Thus reversible or irreversible attachment of the nanosized objects can be achieved.

Multidimensional singular integrals and integral equations

CERN Document Server

Mikhlin, Solomon Grigorievich; Stark, M; Ulam, S

1965-01-01

Multidimensional Singular Integrals and Integral Equations presents the results of the theory of multidimensional singular integrals and of equations containing such integrals. Emphasis is on singular integrals taken over Euclidean space or in the closed manifold of Liapounov and equations containing such integrals. This volume is comprised of eight chapters and begins with an overview of some theorems on linear equations in Banach spaces, followed by a discussion on the simplest properties of multidimensional singular integrals. Subsequent chapters deal with compounding of singular integrals

The thermomechanics of nonlinear irreversible behaviors an introduction

CERN Document Server

Maugin, Gérard A

1999-01-01

In this invaluable book, macroscopic irreversible thermodynamics is presented in its realm and its splendor by appealing to the notion of internal variables of state. This applies to both fluids and solids with or without microstructures of mechanical or electromagnetic origin. This unmatched richness of essentially nonlinear behaviors is the result of the use of modern mathematical techniques such as convex analysis in a clear-cut framework which allows one to put under the umbrella of "irreversible thermodynamics" behaviors which until now have been commonly considered either not easily cove

Time in Science: Reversibility vs. Irreversibility

Science.gov (United States)

Pomeau, Yves

To discuss properly the question of irreversibility one needs to make a careful distinction between reversibility of the equations of motion and the choice of the initial conditions. This is also relevant for the rather confuse philosophy of the wave packet reduction in quantum mechanics. The explanation of this reduction requires also to make precise assumptions on what initial data are accessible in our world. Finally I discuss how a given (and long) time record can be shown in an objective way to record an irreversible or reversible process. Or: can a direction of time be derived from its analysis? This leads quite naturally to examine if there is a possible spontaneous breaking of the time reversal symmetry in many body systems, a symmetry breaking that would be put in evidence objectively by looking at certain specific time correlations.

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.

Multidimensional Riemann problem with self-similar internal structure - part III - a multidimensional analogue of the HLLI Riemann solver for conservative hyperbolic systems

Science.gov (United States)

Balsara, Dinshaw S.; Nkonga, Boniface

2017-10-01

Just as the quality of a one-dimensional approximate Riemann solver is improved by the inclusion of internal sub-structure, the quality of a multidimensional Riemann solver is also similarly improved. Such multidimensional Riemann problems arise when multiple states come together at the vertex of a mesh. The interaction of the resulting one-dimensional Riemann problems gives rise to a strongly-interacting state. We wish to endow this strongly-interacting state with physically-motivated sub-structure. The fastest way of endowing such sub-structure consists of making a multidimensional extension of the HLLI Riemann solver for hyperbolic conservation laws. Presenting such a multidimensional analogue of the HLLI Riemann solver with linear sub-structure for use on structured meshes is the goal of this work. The multidimensional MuSIC Riemann solver documented here is universal in the sense that it can be applied to any hyperbolic conservation law. The multidimensional Riemann solver is made to be consistent with constraints that emerge naturally from the Galerkin projection of the self-similar states within the wave model. When the full eigenstructure in both directions is used in the present Riemann solver, it becomes a complete Riemann solver in a multidimensional sense. I.e., all the intermediate waves are represented in the multidimensional wave model. The work also presents, for the very first time, an important analysis of the dissipation characteristics of multidimensional Riemann solvers. The present Riemann solver results in the most efficient implementation of a multidimensional Riemann solver with sub-structure. Because it preserves stationary linearly degenerate waves, it might also help with well-balancing. Implementation-related details are presented in pointwise fashion for the one-dimensional HLLI Riemann solver as well as the multidimensional MuSIC Riemann solver.

Multidimensional Data Model and Query Language for Informetrics.

Science.gov (United States)

Niemi, Timo; Hirvonen, Lasse; Jarvelin, Kalervo

2003-01-01

Discusses multidimensional data analysis, or online analytical processing (OLAP), which offer a single subject-oriented source for analyzing summary data based on various dimensions. Develops a conceptual/logical multidimensional model for supporting the needs of informetrics, including a multidimensional query language whose basic idea is to…

Irreversibility and Action of the Heat Conduction Process

Directory of Open Access Journals (Sweden)

Yu-Chao Hua

2018-03-01

Full Text Available Irreversibility (that is, the “one-sidedness” of time of a physical process can be characterized by using Lyapunov functions in the modern theory of stability. In this theoretical framework, entropy and its production rate have been generally regarded as Lyapunov functions in order to measure the irreversibility of various physical processes. In fact, the Lyapunov function is not always unique. In the represent work, a rigorous proof is given that the entransy and its dissipation rate can also serve as Lyapunov functions associated with the irreversibility of the heat conduction process without the conversion between heat and work. In addition, the variation of the entransy dissipation rate can lead to Fourier’s heat conduction law, while the entropy production rate cannot. This shows that the entransy dissipation rate, rather than the entropy production rate, is the unique action for the heat conduction process, and can be used to establish the finite element method for the approximate solution of heat conduction problems and the optimization of heat transfer processes.

Irreversible investments revisited

DEFF Research Database (Denmark)

Sandal, Leif K.; Steinshamn, Stein I.; Hoff, Ayoe

2007-01-01

A multi-dimensional, non-linear dynamic model in continuous time is presented for the purpose of finding the optimal combination of exploitation and capital investment in optimal renewable resource management. Non-malleability of capital is incorporated in the model through an asymmetric cost......-function of investment, and investments can be both positive and negative. Exploitation is controlled through the utilisation rate of available capital. A novel feature in this model is that there are costs associated with the available capital whether it is utilised or not. And, in contrast to most of the previous...

Multiscale Analysis of Time Irreversibility Based on Phase-Space Reconstruction and Horizontal Visibility Graph Approach

Science.gov (United States)

Zhang, Yongping; Shang, Pengjian; Xiong, Hui; Xia, Jianan

Time irreversibility is an important property of nonequilibrium dynamic systems. A visibility graph approach was recently proposed, and this approach is generally effective to measure time irreversibility of time series. However, its result may be unreliable when dealing with high-dimensional systems. In this work, we consider the joint concept of time irreversibility and adopt the phase-space reconstruction technique to improve this visibility graph approach. Compared with the previous approach, the improved approach gives a more accurate estimate for the irreversibility of time series, and is more effective to distinguish irreversible and reversible stochastic processes. We also use this approach to extract the multiscale irreversibility to account for the multiple inherent dynamics of time series. Finally, we apply the approach to detect the multiscale irreversibility of financial time series, and succeed to distinguish the time of financial crisis and the plateau. In addition, Asian stock indexes away from other indexes are clearly visible in higher time scales. Simulations and real data support the effectiveness of the improved approach when detecting time irreversibility.

A kinetic equation for irreversible aggregation

International Nuclear Information System (INIS)

Zanette, D.H.

1990-09-01

We introduce a kinetic equation for describing irreversible aggregation in the ballistic regime, including velocity distributions. The associated evolution for the macroscopic quantities is studied, and the general solution for Maxwell interaction models is obtained in the Fourier representation. (author). 23 refs

Anisotropic shift of the irreversibility line by neutron irradiation

International Nuclear Information System (INIS)

Sauerzopf, F.M.; Wiesinger, H.P.; Weber, H.W.; Crabtree, G.W.; Frischherz, M.C.; Kirk, M.A.

1991-09-01

The irreversibility line of high-T c superconductors is shifted considerably by irradiating the material with fast neutrons. The anisotropic and non-monotonous shift is qualitatively explained by a simple model based on an interaction between three pinning mechanisms, the intrinsic pinning by the ab-planes, the weak pinning by the pre-irradiation defect structure, and strong pinning by neutron induced defect cascades. A correlation between the cascade density and the position of the irreversibility line is observed

Measures of thermodynamic irreversibility in deterministic and stochastic dynamics

International Nuclear Information System (INIS)

Ford, Ian J

2015-01-01

It is generally observed that if a dynamical system is sufficiently complex, then as time progresses it will share out energy and other properties amongst its component parts to eliminate any initial imbalances, retaining only fluctuations. This is known as energy dissipation and it is closely associated with the concept of thermodynamic irreversibility, measured by the increase in entropy according to the second law. It is of interest to quantify such behaviour from a dynamical rather than a thermodynamic perspective and to this end stochastic entropy production and the time-integrated dissipation function have been introduced as analogous measures of irreversibility, principally for stochastic and deterministic dynamics, respectively. We seek to compare these measures. First we modify the dissipation function to allow it to measure irreversibility in situations where the initial probability density function (pdf) of the system is asymmetric as well as symmetric in velocity. We propose that it tests for failure of what we call the obversibility of the system, to be contrasted with reversibility, the failure of which is assessed by stochastic entropy production. We note that the essential difference between stochastic entropy production and the time-integrated modified dissipation function lies in the sequence of procedures undertaken in the associated tests of irreversibility. We argue that an assumed symmetry of the initial pdf with respect to velocity inversion (within a framework of deterministic dynamics) can be incompatible with the Past Hypothesis, according to which there should be a statistical distinction between the behaviour of certain properties of an isolated system as it evolves into the far future and the remote past. Imposing symmetry on a velocity distribution is acceptable for many applications of statistical physics, but can introduce difficulties when discussing irreversible behaviour. (paper)

Multi-Dimensional Path Queries

DEFF Research Database (Denmark)

Bækgaard, Lars

1998-01-01

to create nested path structures. We present an SQL-like query language that is based on path expressions and we show how to use it to express multi-dimensional path queries that are suited for advanced data analysis in decision support environments like data warehousing environments......We present the path-relationship model that supports multi-dimensional data modeling and querying. A path-relationship database is composed of sets of paths and sets of relationships. A path is a sequence of related elements (atoms, paths, and sets of paths). A relationship is a binary path...

CAMS: OLAPing Multidimensional Data Streams Efficiently

Science.gov (United States)

Cuzzocrea, Alfredo

In the context of data stream research, taming the multidimensionality of real-life data streams in order to efficiently support OLAP analysis/mining tasks is a critical challenge. Inspired by this fundamental motivation, in this paper we introduce CAMS (C ube-based A cquisition model for M ultidimensional S treams), a model for efficiently OLAPing multidimensional data streams. CAMS combines a set of data stream processing methodologies, namely (i) the OLAP dimension flattening process, which allows us to obtain dimensionality reduction of multidimensional data streams, and (ii) the OLAP stream aggregation scheme, which aggregates data stream readings according to an OLAP-hierarchy-based membership approach. We complete our analytical contribution by means of experimental assessment and analysis of both the efficiency and the scalability of OLAPing capabilities of CAMS on synthetic multidimensional data streams. Both analytical and experimental results clearly connote CAMS as an enabling component for next-generation Data Stream Management Systems.

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.

Fundamental economic irreversibilities influence policies for enhancing international forest phytosanitary security

Science.gov (United States)

Thomas P. Holmes; Will Allen; Robert G. Haight; E. Carina H. Keskitalo; Mariella Marzano; Maria Pettersson; Christopher P. Quine; E. R. Langer

2017-01-01

National and international efforts to manage forest biosecurity create tension between opposing sources of ecological and economic irreversibility. Phytosanitary policies designed to protect national borders from biological invasions incur sunk costs deriving from economic and political irreversibilities that incentivizes wait-and-see decision-making. However, the...

The use of TiO2 nanoparticles to reduce refrigerator ir-reversibility

International Nuclear Information System (INIS)

Padmanabhan, Venkataramana Murthy V.; Palanisamy, Senthilkumar

2012-01-01

Highlights: ► COP of hydrocarbons mixture VCRSs increases less when compared to R134a. ► Compressor ir-reversibility of VCRSs decreases by 33% (R134a), 14% (R436A and R436B). ► Total ir-reversibility of selected VCRSs decreases. ► Exergy efficiency of R134a is exceptionally low at lower reference temperature. ► Exergy efficiency of selected VCRSs increases. - Abstract: The ir-reversibility at the process of a vapour-compression refrigeration system (VCRS) with nanoparticles in the working fluid was investigated experimentally. Mineral oil (MO) with 0.1 g L −1 TiO 2 nanoparticles mixture were used as the lubricant instead of Polyol-ester (POE) oil in the R134a, R436A (R290/R600a-56/44-wt.%) and R436B (R290/R600a-52/48-wt.%)VCRSs. The VCRS ir-reversibility at the process with the nanoparticles was investigated using second law of thermodynamics. The results indicate that R134a, R436A and R436B and MO with TiO 2 nanoparticles work normally and safely in the VCRS. The VCRSs total ir-reversibility (529, 588 and 570 W) at different process was better than the R134a, R436A and R436B and POE oil system (777, 697 and 683 W). The same tests with Al 2 O 3 nanoparticles showed that the different nanoparticles properties have little effect on the VCRS ir-reversibility. Thus, TiO 2 nanoparticles can be used in VCRS with reciprocating compressor to considerably reduce ir-reversibility at the process.

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.

Irreversible Local Markov Chains with Rapid Convergence towards Equilibrium

Science.gov (United States)

Kapfer, Sebastian C.; Krauth, Werner

2017-12-01

We study the continuous one-dimensional hard-sphere model and present irreversible local Markov chains that mix on faster time scales than the reversible heat bath or Metropolis algorithms. The mixing time scales appear to fall into two distinct universality classes, both faster than for reversible local Markov chains. The event-chain algorithm, the infinitesimal limit of one of these Markov chains, belongs to the class presenting the fastest decay. For the lattice-gas limit of the hard-sphere model, reversible local Markov chains correspond to the symmetric simple exclusion process (SEP) with periodic boundary conditions. The two universality classes for irreversible Markov chains are realized by the totally asymmetric SEP (TASEP), and by a faster variant (lifted TASEP) that we propose here. We discuss how our irreversible hard-sphere Markov chains generalize to arbitrary repulsive pair interactions and carry over to higher dimensions through the concept of lifted Markov chains and the recently introduced factorized Metropolis acceptance rule.

A Fingerprint Encryption Scheme Based on Irreversible Function and Secure Authentication

Directory of Open Access Journals (Sweden)

Yijun Yang

2015-01-01

Full Text Available A fingerprint encryption scheme based on irreversible function has been designed in this paper. Since the fingerprint template includes almost the entire information of users’ fingerprints, the personal authentication can be determined only by the fingerprint features. This paper proposes an irreversible transforming function (using the improved SHA1 algorithm to transform the original minutiae which are extracted from the thinned fingerprint image. Then, Chinese remainder theorem is used to obtain the biokey from the integration of the transformed minutiae and the private key. The result shows that the scheme has better performance on security and efficiency comparing with other irreversible function schemes.

Multidimensional poverty, household environment and short-term morbidity in India.

Science.gov (United States)

Dehury, Bidyadhar; Mohanty, Sanjay K

2017-01-01

Using the unit data from the second round of the Indian Human Development Survey (IHDS-II), 2011-2012, which covered 42,152 households, this paper examines the association between multidimensional poverty, household environmental deprivation and short-term morbidities (fever, cough and diarrhoea) in India. Poverty is measured in a multidimensional framework that includes the dimensions of education, health and income, while household environmental deprivation is defined as lack of access to improved sanitation, drinking water and cooking fuel. A composite index combining multidimensional poverty and household environmental deprivation has been computed, and households are classified as follows: multidimensional poor and living in a poor household environment, multidimensional non-poor and living in a poor household environment, multidimensional poor and living in a good household environment and multidimensional non-poor and living in a good household environment. Results suggest that about 23% of the population belonging to multidimensional poor households and living in a poor household environment had experienced short-term morbidities in a reference period of 30 days compared to 20% of the population belonging to multidimensional non-poor households and living in a poor household environment, 19% of the population belonging to multidimensional poor households and living in a good household environment and 15% of the population belonging to multidimensional non-poor households and living in a good household environment. Controlling for socioeconomic covariates, the odds of short-term morbidity was 1.47 [CI 1.40-1.53] among the multidimensional poor and living in a poor household environment, 1.28 [CI 1.21-1.37] among the multidimensional non-poor and living in a poor household environment and 1.21 [CI 1.64-1.28] among the multidimensional poor and living in a good household environment compared to the multidimensional non-poor and living in a good household

Optima and bounds for irreversible thermodynamic processes

International Nuclear Information System (INIS)

Hoffmann, K.H.

1990-01-01

In this paper bounds and optima for irreversible thermodynamic processes and their application in different fields are discussed. The tools of finite time thermodynamics are presented and especially optimal control theory is introduced. These methods are applied to heat engines, including models of the Diesel engine and a light-driven engine. Further bounds for irreversible processes are introduced, discussing work deficiency and its relation to thermodynamic length. Moreover the problem of dissipation in systems composed of several subsystems is studied. Finally, the methods of finite time thermodynamics are applied to thermodynamic processes described on a more microscopic level. The process used as an example is simulated annealing. It is shown how optimal control theory is applied to find the optimal cooling schedule for this important stochastic optimization method

A minimal dissipation type-based classification in irreversible thermodynamics and microeconomics

Science.gov (United States)

Tsirlin, A. M.; Kazakov, V.; Kolinko, N. A.

2003-10-01

We formulate the problem of finding classes of kinetic dependencies in irreversible thermodynamic and microeconomic systems for which minimal dissipation processes belong to the same type. We show that this problem is an inverse optimal control problem and solve it. The commonality of this problem in irreversible thermodynamics and microeconomics is emphasized.

Optimization of the performance characteristics in an irreversible magnetic Brayton refrigeration cycle

International Nuclear Information System (INIS)

Wang Hao; Liu Sanqiu

2008-01-01

An irreversible cycle model of magnetic Brayton refrigerators is established, in which the thermal resistance and irreversibility in the two adiabatic processes are taken into account. Expressions for several important performance parameters, such as the coefficient of performance, cooling rate and power input are derived. Moreover, the optimal performance parameters are obtained at the maximum coefficient of performance. The optimization region (or criteria) for an irreversible magnetic Brayton refrigerator is obtained. The results obtained here have general significance and will be helpful to understand deeply the performance of a magnetic Brayton refrigeration cycle

Multidimensional quantum entanglement with large-scale integrated optics.

Science.gov (United States)

Wang, Jianwei; Paesani, Stefano; Ding, Yunhong; Santagati, Raffaele; Skrzypczyk, Paul; Salavrakos, Alexia; Tura, Jordi; Augusiak, Remigiusz; Mančinska, Laura; Bacco, Davide; Bonneau, Damien; Silverstone, Joshua W; Gong, Qihuang; Acín, Antonio; Rottwitt, Karsten; Oxenløwe, Leif K; O'Brien, Jeremy L; Laing, Anthony; Thompson, Mark G

2018-04-20

The ability to control multidimensional quantum systems is central to the development of advanced quantum technologies. We demonstrate a multidimensional integrated quantum photonic platform able to generate, control, and analyze high-dimensional entanglement. A programmable bipartite entangled system is realized with dimensions up to 15 × 15 on a large-scale silicon photonics quantum circuit. The device integrates more than 550 photonic components on a single chip, including 16 identical photon-pair sources. We verify the high precision, generality, and controllability of our multidimensional technology, and further exploit these abilities to demonstrate previously unexplored quantum applications, such as quantum randomness expansion and self-testing on multidimensional states. Our work provides an experimental platform for the development of multidimensional quantum technologies. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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.

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.

Multidimensional Poverty and Child Survival in India

Science.gov (United States)

Mohanty, Sanjay K.

2011-01-01

Background Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations) and included in the development agenda, its measurement and application are still limited. Objectives and Methodology Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses. Results The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed. Conclusion Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population. PMID:22046384

Multidimensional poverty and child survival in India.

Directory of Open Access Journals (Sweden)

Sanjay K Mohanty

Full Text Available Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations and included in the development agenda, its measurement and application are still limited. OBJECTIVES AND METHODOLOGY: Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses.The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed.Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population.

Multidimensional poverty and child survival in India.

Science.gov (United States)

Mohanty, Sanjay K

2011-01-01

Though the concept of multidimensional poverty has been acknowledged cutting across the disciplines (among economists, public health professionals, development thinkers, social scientists, policy makers and international organizations) and included in the development agenda, its measurement and application are still limited. OBJECTIVES AND METHODOLOGY: Using unit data from the National Family and Health Survey 3, India, this paper measures poverty in multidimensional space and examine the linkages of multidimensional poverty with child survival. The multidimensional poverty is measured in the dimension of knowledge, health and wealth and the child survival is measured with respect to infant mortality and under-five mortality. Descriptive statistics, principal component analyses and the life table methods are used in the analyses. The estimates of multidimensional poverty are robust and the inter-state differentials are large. While infant mortality rate and under-five mortality rate are disproportionately higher among the abject poor compared to the non-poor, there are no significant differences in child survival among educationally, economically and health poor at the national level. State pattern in child survival among the education, economical and health poor are mixed. Use of multidimensional poverty measures help to identify abject poor who are unlikely to come out of poverty trap. The child survival is significantly lower among abject poor compared to moderate poor and non-poor. We urge to popularize the concept of multiple deprivations in research and program so as to reduce poverty and inequality in the population.

The emergence and evolution of the multidimensional organization

OpenAIRE

Strikwerda, J.; Stoelhorst, J.W.

2009-01-01

The article discusses multidimensional organizations and the evolution of complex organizations. The six characteristics of multidimensional organizations, disadvantages of the successful organizational structure that is categorized as a multidivisional, multi-unit or M-form, research by the Foundation for Management Studies which suggests that synergies across business divisions can be exploited by the M-form, a team approach to creating economic value, examples of multidimensional firms suc...

Fluctuation theorems in feedback-controlled open quantum systems: Quantum coherence and absolute irreversibility

Science.gov (United States)

Murashita, Yûto; Gong, Zongping; Ashida, Yuto; Ueda, Masahito

2017-10-01

The thermodynamics of quantum coherence has attracted growing attention recently, where the thermodynamic advantage of quantum superposition is characterized in terms of quantum thermodynamics. We investigate the thermodynamic effects of quantum coherent driving in the context of the fluctuation theorem. We adopt a quantum-trajectory approach to investigate open quantum systems under feedback control. In these systems, the measurement backaction in the forward process plays a key role, and therefore the corresponding time-reversed quantum measurement and postselection must be considered in the backward process, in sharp contrast to the classical case. The state reduction associated with quantum measurement, in general, creates a zero-probability region in the space of quantum trajectories of the forward process, which causes singularly strong irreversibility with divergent entropy production (i.e., absolute irreversibility) and hence makes the ordinary fluctuation theorem break down. In the classical case, the error-free measurement ordinarily leads to absolute irreversibility, because the measurement restricts classical paths to the region compatible with the measurement outcome. In contrast, in open quantum systems, absolute irreversibility is suppressed even in the presence of the projective measurement due to those quantum rare events that go through the classically forbidden region with the aid of quantum coherent driving. This suppression of absolute irreversibility exemplifies the thermodynamic advantage of quantum coherent driving. Absolute irreversibility is shown to emerge in the absence of coherent driving after the measurement, especially in systems under time-delayed feedback control. We show that absolute irreversibility is mitigated by increasing the duration of quantum coherent driving or decreasing the delay time of feedback control.

Application of Electroporation Technique in Biofuel Processing

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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.

Irreversible adsorption of phenolic compounds by activated carbons

Energy Technology Data Exchange (ETDEWEB)

Grant, T.M.; King, C.J.

1988-12-01

Studies were undertaken to determine the reasons why phenolic sorbates can be difficult to remove and recover from activated carbons. The chemical properties of the sorbate and the adsorbent surface, and the influences of changes in the adsorption and desorption conditions were investigated. Comparison of isotherms established after different contact times or at different temperatures indicated that phenolic compounds react on carbon surfaces. The reaction rate is a strong function of temperature. Regeneration of carbons by leaching with acetone recovered at least as much phenol as did regeneration with other solvents or with displacers. The physiochemical properties of adsorbents influences irreversible uptakes. Sorbates differed markedly in their tendencies to undergo irreversible adsorption. 64 refs., 47 figs., 32 tabs.

Irreversible adsorption of phenolic compounds by activated carbons

International Nuclear Information System (INIS)

Grant, T.M.; King, C.J.

1988-12-01

Studies were undertaken to determine the reasons why phenolic sorbates can be difficult to remove and recover from activated carbons. The chemical properties of the sorbate and the adsorbent surface, and the influences of changes in the adsorption and desorption conditions were investigated. Comparison of isotherms established after different contact times or at different temperatures indicated that phenolic compounds react on carbon surfaces. The reaction rate is a strong function of temperature. Regeneration of carbons by leaching with acetone recovered at least as much phenol as did regeneration with other solvents or with displacers. The physiochemical properties of adsorbents influences irreversible uptakes. Sorbates differed markedly in their tendencies to undergo irreversible adsorption. 64 refs., 47 figs., 32 tabs

Port contact systems for irreversible thermodynamical systems

NARCIS (Netherlands)

Eberard, D.; Maschke, B.M.; Schaft, A.J. van der

2005-01-01

In this paper we propose a definition of control contact systems, generalizing input-output Hamiltonian systems, to cope with models arising from irreversible Thermodynamics. We exhibit a particular subclass of these systems, called conservative, that leaves invariant some Legendre submanifold (the

Classical many-body theory with retarded interactions: Dynamical irreversibility and determinism without probabilities

Energy Technology Data Exchange (ETDEWEB)

Zakharov, A.Yu., E-mail: Anatoly.Zakharov@novsu.ru; Zakharov, M.A., E-mail: ma_zakharov@list.ru

2016-01-28

The exact equations of motion for microscopic density of classical many-body system with account of inter-particle retarded interactions is derived. It is shown that interactions retardation leads to irreversible behavior of many-body systems. - Highlights: • A new form of equation of motion of classical many-body system is proposed. • Interactions retardation as one of the mechanisms of many-body system irreversibility. • Irreversibility and determinism without probabilities. • The possible way to microscopic foundation of thermodynamics.

β-characterization by irreversibility analysis: A thermoeconomic diagnosis method

International Nuclear Information System (INIS)

Zaleta-Aguilar, Alejandro; Olivares-Arriaga, Abraham; Cano-Andrade, Sergio; Rodriguez-Alejandro, David A.

2016-01-01

This paper presents a reconciliation methodology for the diagnosis of energy systems. The methodology is based on the characterization of irreversibilities in the components of an energy system. These irreversibilities can be attributed to malfunctions or dysfunctions. The characterization of irreversibilities as presented here makes possible to reconcile the Actual Operating Condition (AOC) versus the Reference Operating Condition (ROC) of the energy system in a real-time manner. The diagnosis methodology introduces a parameter β, which represents the total exergy or useful work of a component in terms of its inlet and output streams at either design (full-load) or off-design (partial-load) conditions. The methodology is applied to the diagnosis of an actual Natural Gas Combined Cycle (NGCC) power plant. Data for the model is obtained directly from the plant by monitoring its performance at every time; thus, a real-time thermodynamic diagnosis for the system is obtained. Results show that the methodology presented here is able to detect and quantify the deviations on the performance of the NGCC power plant during its real-time operation. Based on the detection and quantification of these deviations, the user is able to make recommendations to schedule maintenance on the components where the irreversibilities are present. - Highlights: • A new methodology for thermoeconomic diagnosis of energy systems is presented. • A parameter β is defined for characterization of the components of an energy system. • The β characterization methodology is tested in a real 420 MW NGCC power plant. • Results show that the complexity of a diagnosis analysis is reduced substantially.

Variability of Irreversible Poleward Transport in the Lower Stratosphere

Science.gov (United States)

Olsen, Mark; Douglass, Anne; Newman, Paul; Nash, Eric; Witte, Jacquelyn; Ziemke, Jerry

2011-01-01

The ascent and descent of the Brewer-Dobson circulation plays a large role in determining the distributions of many constituents in the extratropical lower stratosphere. However, relatively fast, quasi-horizontal transport out of the tropics and polar regions also significantly contribute to determining these distributions. The tropical tape recorder signal assures that there must be outflow from the tropics into the extratropical lower stratosphere. The phase of the quasi-biennial oscillation (QBO) and state of the polar vortex are known to modulate the transport from the tropical and polar regions, respectively. In this study we examine multiple years of ozone distributions in the extratropical lower stratosphere observed by the Aura Microwave Limb Sounder (MLS) and the Aura High Resolution Dynamic Limb Sounder (HIRDLS). The distributions are compared with analyses of irreversible, meridional isentropic transport. We show that there is considerable year-to-year seasonal variability in the amount of irreversible transport from the tropics, which is related to both the phase of the QBO and the state of the polar vortex. The reversibility of the transport is consistent with the number of observed breaking waves. The variability of the atmospheric index of refraction in the lower stratosphere is shown to be significantly correlated with the wave breaking and amount of irreversible transport. Finally, we will show that the seasonal extratropical stratosphere to troposphere transport of ozone can be substantially modulated by the amount of irreversible meridional transport in the lower stratosphere and we investigate how observable these differences are in data of tropospheric ozone.

Tumour Cell Membrane Poration and Ablation by Pulsed Low-Intensity Electric Field with Carbon Nanotubes

Directory of Open Access Journals (Sweden)

Lijun Wang

2015-03-01

Full Text Available Electroporation is a physical method to increase permeabilization of cell membrane by electrical pulses. Carbon nanotubes (CNTs can potentially act like “lighting rods” or exhibit direct physical force on cell membrane under alternating electromagnetic fields thus reducing the required field strength. A cell poration/ablation system was built for exploring these effects of CNTs in which two-electrode sets were constructed and two perpendicular electric fields could be generated sequentially. By applying this system to breast cancer cells in the presence of multi-walled CNTs (MWCNTs, the effective pulse amplitude was reduced to 50 V/cm (main field/15 V/cm (alignment field at the optimized pulse frequency (5 Hz of 500 pulses. Under these conditions instant cell membrane permeabilization was increased to 38.62%, 2.77-fold higher than that without CNTs. Moreover, we also observed irreversible electroporation occurred under these conditions, such that only 39.23% of the cells were viable 24 h post treatment, in contrast to 87.01% cell viability without presence of CNTs. These results indicate that CNT-enhanced electroporation has the potential for tumour cell ablation by significantly lower electric fields than that in conventional electroporation therapy thus avoiding potential risks associated with the use of high intensity electric pulses.

Quantum thermodynamics: Microscopic foundations of entropy and of entropy generation by irreversibility

Directory of Open Access Journals (Sweden)

Beretta, Gian Paolo

2008-02-01

Full Text Available What is the physical significance of entropy? What is the physical origin of irreversibility? Do entropy and irreversibility exist only for complex and macroscopic systems? Most physicists still accept and teach that the rationalization of these fundamental questions is given by Statistical Mechanics. Indeed, for everyday laboratory physics, the mathematical formalism of Statistical Mechanics (canonical and grand-canonical, Boltzmann, Bose-Einstein and Fermi-Dirac distributions allows a successful description of the thermodynamic equilibrium properties of matter, including entropy values. However, as already recognized by Schrodinger in 1936, Statistical Mechanics is impaired by conceptual ambiguities and logical inconsistencies, both in its explanation of the meaning of entropy and in its implications on the concept of state of a system. An alternative theory has been developed by Gyftopoulos, Hatsopoulos and the present author to eliminate these stumbling conceptual blocks while maintaining the mathematical formalism so successful in applications. To resolve both the problem of the meaning of entropy and that of the origin of irreversibility we have built entropy and irreversibility into the laws of microscopic physics. The result is a theory, that we call Quantum Thermodynamics, that has all the necessary features to combine Mechanics and Thermodynamics uniting all the successful results of both theories, eliminating the logical inconsistencies of Statistical Mechanics and the paradoxes on irreversibility, and providing an entirely new perspective on the microscopic origin of irreversibility, nonlinearity (therefore including chaotic behavior and maximal-entropy-generation nonequilibrium dynamics. In this paper we discuss the background and formalism of Quantum Thermodynamics including its nonlinear equation of motion and the main general results. Our objective is to show in a not-too-technical manner that this theory provides indeed a

A new approach to irreversibility in deep inelastic collisions

International Nuclear Information System (INIS)

Nemes, M.C.

1982-01-01

We use concepts of statistical mechanics to discuss the irreversible character of the experimental data in deep inelastic collisions. A definition of irreversibility proposed by Ruch permits a unified overview on current theories which describe these reactions. An information theoretical analysis of the data leads to a Fokker-Planck equation for the collective variables (excitation energy, charge and mass). The concept of mixing distance can serve as a quantitative measure to characterize the 'approach to equilibrium'. We apply it to the brownian motion as an illustration and also to the phenomenological analysis of deep inelastic scattering data with interesting results. (orig.)

Multidimensional fatigue and its correlates in hospitalised advanced cancer patients.

NARCIS (Netherlands)

Echteld, M.A.; Passchier, J.; Teunissen, S.; Claessen, S.; Wit, R. de; Rijt, C.C.D. van der

2007-01-01

Although fatigue is a multidimensional concept, multidimensional fatigue is rarely investigated in hospitalised cancer patients. We determined the levels and correlates of multidimensional fatigue in 100 advanced cancer patients admitted for symptom control. Fatigue dimensions were general fatigue

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.

Intuitionistic fuzzy (IF) evaluations of multidimensional model

International Nuclear Information System (INIS)

Valova, I.

2012-01-01

There are different logical methods for data structuring, but no one is perfect enough. Multidimensional model-MD of data is presentation of data in a form of cube (referred also as info-cube or hypercube) with data or in form of 'star' type scheme (referred as multidimensional scheme), by use of F-structures (Facts) and set of D-structures (Dimensions), based on the notion of hierarchy of D-structures. The data, being subject of analysis in a specific multidimensional model is located in a Cartesian space, being restricted by D-structures. In fact, the data is either dispersed or 'concentrated', therefore the data cells are not distributed evenly within the respective space. The moment of occurrence of any event is difficult to be predicted and the data is concentrated as per time periods, location of performed business event, etc. To process such dispersed or concentrated data, various technical strategies are needed. The basic methods for presentation of such data should be selected. The approaches of data processing and respective calculations are connected with different options for data representation. The use of intuitionistic fuzzy evaluations (IFE) provide us new possibilities for alternative presentation and processing of data, subject of analysis in any OLAP application. The use of IFE at the evaluation of multidimensional models will result in the following advantages: analysts will dispose with more complete information for processing and analysis of respective data; benefit for the managers is that the final decisions will be more effective ones; enabling design of more functional multidimensional schemes. The purpose of this work is to apply intuitionistic fuzzy evaluations of multidimensional model of data. (authors)

Extremum principles for irreversible processes

International Nuclear Information System (INIS)

Hillert, M.; Agren, J.

2006-01-01

Hamilton's extremum principle is a powerful mathematical tool in classical mechanics. Onsager's extremum principle may play a similar role in irreversible thermodynamics and may also become a valuable tool. His principle may formally be regarded as a principle of maximum rate of entropy production but does not have a clear physical interpretation. Prigogine's principle of minimum rate of entropy production has a physical interpretation when it applies, but is not strictly valid except for a very special case

Irreversible performance of a quantum harmonic heat engine

Science.gov (United States)

Rezek, Yair; Kosloff, Ronnie

2006-05-01

The unavoidable irreversible loss of power in a heat engine is found to be of quantum origin. Following thermodynamic tradition, a model quantum heat engine operating in an Otto cycle is analysed, where the working medium is composed of an ensemble of harmonic oscillators and changes in volume correspond to changes in the curvature of the potential well. Equations of motion for quantum observables are derived for the complete cycle of operation. These observables are sufficient to determine the state of the system and with it all thermodynamical variables. Once the external controls are set, the engine settles to a limit cycle. Conditions for optimal work, power and entropy production are derived. At high temperatures and quasistatic operating conditions, the efficiency at maximum power coincides with the endoreversible result \\eta_q=1-\\sqrt{{T_c}/{T_h}} . The optimal compression ratio varies from {\\cal C} =\\sqrt{T_h/T_c} in the quasistatic limit where the irreversibility is dominated by heat conductance to {\\cal C} =(T_h/T_c)^{1/4} in the sudden limit when the irreversibility is dominated by friction. When the engine deviates from adiabatic conditions, the performance is subject to friction. The origin of this friction can be traced to the noncommutability of the kinetic and potential energy of the working medium.

Symbolic Multidimensional Scaling

NARCIS (Netherlands)

P.J.F. Groenen (Patrick); Y. Terada

2015-01-01

markdownabstract__Abstract__ Multidimensional scaling (MDS) is a technique that visualizes dissimilarities between pairs of objects as distances between points in a low dimensional space. In symbolic MDS, a dissimilarity is not just a value but can represent an interval or even a histogram. Here,

Risk Aversion, Price Uncertainty and Irreversible Investments

NARCIS (Netherlands)

van den Goorbergh, R.W.J.; Huisman, K.J.M.; Kort, P.M.

2003-01-01

This paper generalizes the theory of irreversible investment under uncertainty by allowing for risk averse investors in the absence of com-plete markets.Until now this theory has only been developed in the cases of risk neutrality, or risk aversion in combination with complete markets.Within a

An Improved Multidimensional MPA Procedure for Bidirectional Earthquake Excitations

OpenAIRE

Wang, Feng; Sun, Jian-Gang; Zhang, Ning

2014-01-01

Presently, the modal pushover analysis procedure is extended to multidimensional analysis of structures subjected to multidimensional earthquake excitations. an improved multidimensional modal pushover analysis (IMMPA) method is presented in the paper in order to estimate the response demands of structures subjected to bidirectional earthquake excitations, in which the unidirectional earthquake excitation applied on equivalent SDOF system is replaced by the direct superposition of two compone...

The emergence and evolution of the multidimensional organization

NARCIS (Netherlands)

Strikwerda, J.; Stoelhorst, J.W.

2009-01-01

The article discusses multidimensional organizations and the evolution of complex organizations. The six characteristics of multidimensional organizations, disadvantages of the successful organizational structure that is categorized as a multidivisional, multi-unit or M-form, research by the

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

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...

How to account for irreversibility in integrated assessment of climate change?

International Nuclear Information System (INIS)

Ha Duong, M.

1998-04-01

How to account for irreversibility in integrated assessment of climate change? This Ph. D. thesis in Economics balances discounting, technical progress and the inertia of existing capital stock against uncertainty and the inertia of socio-economic systems to examine the issue of near term limitations of greenhouse gases emissions. After a general overview in chapter 2, and a more historical presentation of the debates in chapter 3, chapter 4 proceeds to review a large number of integrated assessment models. Chapter 5 introduces a Model on the Dynamics of Inertia and Adaptability of energy systems: DIAM, used to discuss how much previous studies might have overestimated the long term costs of CO 2 limitations and underestimated adjustment costs. It shows that, given a target date for atmospheric CO 2 concentration stabilisation, a higher inertia implies a lower optimal concentration trajectory. In a sequential decision framework, chapter 6 shows that current uncertainties about which CO 2 concentration ceiling would not present dangerous interference with the climate system justifies precautionary action. Finally, chapter 7 uses the irreversibility effect theory to define formally situations of decision under controversy and compare the irreversibility of CO 2 accumulation with the irreversibility of investments needed to moderate it. An option value for greenhouse gases emissions limitations is computed. (author)

Perceptual Salience and Children's Multidimensional Problem Solving

Science.gov (United States)

Odom, Richard D.; Corbin, David W.

1973-01-01

Uni- and multidimensional processing of 6- to 9-year olds was studied using recall tasks in which an array of stimuli was reconstructed to match a model array. Results indicated that both age groups were able to solve multidimensional problems, but that solution rate was retarded by the unidimensional processing of highly salient dimensions.…

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.

Canonical formalism, fundamental equation, and generalized thermomechanics for irreversible fluids with heat transfer

International Nuclear Information System (INIS)

Sieniutycz, S.; Berry, R.S.

1993-01-01

A Lagrangian with dissipative (e.g., Onsager's) potentials is constructed for the field description of irreversible heat-conducting fluids, off local equilibrium. Extremum conditions of action yield Clebsch representations of temperature, chemical potential, velocities, and generalized momenta, including a thermal momentum introduced recently [R. L. Selinger and F. R. S. Whitham, Proc. R. Soc. London, Ser. A 302, 1 (1968); S. Sieniutycz and R. S. Berry, Phys. Rev. A 40, 348 (1989)]. The basic question asked is ''To what extent may irreversibility, represented by a given form of the entropy source, influence the analytical form of the conservation laws for the energy and momentum?'' Noether's energy for a fluid with heat flow is obtained, which leads to a fundamental equation and extended Hamiltonian dynamics obeying the second law of thermodynamics. While in the case of the Onsager potentials this energy coincides numerically with the classical energy E, it contains an extra term (vanishing along the path) still contributing to an irreversible evolution. Components of the energy-momentum tensor preserve all terms regarded standardly as ''irreversible'' (heat, tangential stresses, etc.) generalized to the case when thermodynamics includes the state gradients and the so-called thermal phase, which we introduce here. This variable, the Lagrange multiplier of the entropy generation balance, is crucial for consistent treatment of irreversible processes via an action formalism. We conclude with the hypothesis that embedding the first and second laws in the context of the extremal behavior of action under irreversible conditions may imply accretion of an additional term to the classical energy

A Conceptual Model for Multidimensional Analysis of Documents

Science.gov (United States)

Ravat, Franck; Teste, Olivier; Tournier, Ronan; Zurlfluh, Gilles

Data warehousing and OLAP are mainly used for the analysis of transactional data. Nowadays, with the evolution of Internet, and the development of semi-structured data exchange format (such as XML), it is possible to consider entire fragments of data such as documents as analysis sources. As a consequence, an adapted multidimensional analysis framework needs to be provided. In this paper, we introduce an OLAP multidimensional conceptual model without facts. This model is based on the unique concept of dimensions and is adapted for multidimensional document analysis. We also provide a set of manipulation operations.

Multidimensional Measurement of Poverty among Women in Sub-Saharan Africa

Science.gov (United States)

Batana, Yele Maweki

2013-01-01

Since the seminal work of Sen, poverty has been recognized as a multidimensional phenomenon. The recent availability of relevant databases renewed the interest in this approach. This paper estimates multidimensional poverty among women in fourteen Sub-Saharan African countries using the Alkire and Foster multidimensional poverty measures, whose…

Application of multidimensional IRT models to longitudinal data

NARCIS (Netherlands)

te Marvelde, J.M.; Glas, Cornelis A.W.; Van Landeghem, Georges; Van Damme, Jan

2006-01-01

The application of multidimensional item response theory (IRT) models to longitudinal educational surveys where students are repeatedly measured is discussed and exemplified. A marginal maximum likelihood (MML) method to estimate the parameters of a multidimensional generalized partial credit model

Health Technology Assessment of CEM Pulpotomy in Permanent Molars with Irreversible Pulpitis

Science.gov (United States)

Yazdani, Shahram; Jadidfard, Mohammad-Pooyan; Tahani, Bahareh; Kazemian, Ali; Dianat, Omid; Alim Marvasti, Laleh

2014-01-01

Introduction: Teeth with irreversible pulpitis usually undergo root canal therapy (RCT). This treatment modality is often considered disadvantageous as it removes vital pulp tissue and weakens the tooth structure. A relatively new concept has risen which suggests vital pulp therapy (VPT) for irreversible pulpitis. VPT with calcium enriched mixture (VPT/CEM) has demonstrated favorable treatment outcomes when treating permanent molars with irreversible pulpitis. This study aims to compare patient related factors, safety and organizational consideration as parts of health technology assessment (HTA) of the new VPT/CEM biotechnology when compared with RCT. Materials and Methods: Patient related factors were assessed by looking at short- and long-term clinical success; safety related factors were evaluated by a specialist committee and discussion board involved in formulating healthcare policies. Organizational evaluation was performed and the social implications were assessed by estimating the costs, availability, accessibility and acceptability. The impact of VPT/CEM biotechnology was assessed by investigating the incidence of irreversible pulpitis and the effect of this treatment on reducing the burden of disease. Results: VPT/CEM biotechnology was deemed feasible and acceptable like RCT; however, it was more successful, accessible, affordable, available and also safer than RCT. Conclusion: When considering socioeconomic implications on oral health status and oral health-related quality of life of VPT/CEM, the novel biotechnology can be more effective and more efficient than RCT in mature permanent molars with irreversible pulpitis. PMID:24396372

Multidimensional sexual perfectionism.

Science.gov (United States)

Stoeber, Joachim; Harvey, Laura N; Almeida, Isabel; Lyons, Emma

2013-11-01

Perfectionism is a multidimensional personality characteristic that can affect all areas of life. This article presents the first systematic investigation of multidimensional perfectionism in the domain of sexuality exploring the unique relationships that different forms of sexual perfectionism show with positive and negative aspects of sexuality. A sample of 272 university students (52 male, 220 female) completed measures of four forms of sexual perfectionism: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. In addition, they completed measures of sexual esteem, sexual self-efficacy, sexual optimism, sex life satisfaction (capturing positive aspects of sexuality) and sexual problem self-blame, sexual anxiety, sexual depression, and negative sexual perfectionism cognitions during sex (capturing negative aspects). Results showed unique patterns of relationships for the four forms of sexual perfectionism, suggesting that partner-prescribed and socially prescribed sexual perfectionism are maladaptive forms of sexual perfectionism associated with negative aspects of sexuality whereas self-oriented and partner-oriented sexual perfectionism emerged as ambivalent forms associated with positive and negative aspects.

Onsager's reciprocity theorem in extended irreversible thermodynamics

International Nuclear Information System (INIS)

Garcia-Colin, L.S.; Velasco, R.M.

1992-01-01

In this paper we shall discuss the Onsager relations for the transport coefficients in a dilute monatomic gas described by the extended irreversible thermodynamics. Our discussion is based on a 26 variables description of the system and its corresponding comparison with the kinetic reciprocity between coefficients is shown (Author)

Multidimensional real analysis I differentiation

CERN Document Server

Duistermaat, J J; van Braam Houckgeest, J P

2004-01-01

Part one of the authors' comprehensive and innovative work on multidimensional real analysis. This book is based on extensive teaching experience at Utrecht University and gives a thorough account of differential analysis in multidimensional Euclidean space. It is an ideal preparation for students who wish to go on to more advanced study. The notation is carefully organized and all proofs are clean, complete and rigorous. The authors have taken care to pay proper attention to all aspects of the theory. In many respects this book presents an original treatment of the subject and it contains man

Multidimensional First-Order Dominance Comparisons of Population Wellbeing

DEFF Research Database (Denmark)

Siersbæk, Nikolaj; Østerdal, Lars Peter Raahave; Arndt, Thomas Channing

2017-01-01

This chapter conveys the concept of first-order dominance (FOD) with particular focus on applications to multidimensional population welfare comparisons. It gives an account of the fundamental equivalent definitions of FOD both in the one-dimensional and multidimensional setting, illustrated...

Lie-admissible invariant treatment of irreversibility for matter and antimatter at the classical and operator levels

International Nuclear Information System (INIS)

Santilli, R.M.

2006-01-01

It was generally believed throughout the 20th century that irreversibility is a purely classical event without operator counterpart. however, a classical irreversible system cannot be consistently decomposed into a finite number of reversible quantum particles (and. vive versa), thus establishing that the origin of irreversibility is basically unknown at the dawn of the 21-st century. To resolve this problem. we adopt the historical analytical representation of irreversibility by Lagrange and Hamilton, that with external terms in their analytic equations; we show that, when properly written, the brackets of the time evolution characterize covering Lie-admissible algebras; we prove that the formalism has fully consistent operator counterpart given by the Lie-admissible branch of hadronic mechanics; we identify mathematical and physical inconsistencies when irreversible formulations are treated with the conventional mathematics used for reversible systems; we show that when the dynamical equations are treated with a novel irreversible mathematics, Lie-admissible formulations are fully consistent because invariant at both the classical and operator levels; and we complete our analysis with a number of explicit applications to irreversible processes in classical mechanics, particle physics and thermodynamics. The case of closed-isolated systems verifying conventional total conservation laws, yet possessing an irreversible structure, is treated via the simpler Lie-isotopic branch of hadronic mechanics. The analysis is conducted for both matter and antimatter at the classical and operator levels to prevent insidious inconsistencies occurring for the sole study of matter or, separately, antimatter

Spectral deformation techniques applied to the study of quantum statistical irreversible processes

International Nuclear Information System (INIS)

Courbage, M.

1978-01-01

A procedure of analytic continuation of the resolvent of Liouville operators for quantum statistical systems is discussed. When applied to the theory of irreversible processes of the Brussels School, this method supports the idea that the restriction to a class of initial conditions is necessary to obtain an irreversible behaviour. The general results are tested on the Friedrichs model. (Auth.)

Articaine for supplemental intraosseous anesthesia in patients with irreversible pulpitis.

Science.gov (United States)

Bigby, Jason; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel

2006-11-01

The purpose of this study was to determine the anesthetic efficacy and heart rate effect of 4% articaine with 1:100,000 epinephrine for supplemental intraosseous injection in mandibular posterior teeth diagnosed with irreversible pulpitis. Thirty-seven emergency patients, diagnosed with irreversible pulpitis of a mandibular posterior tooth, received an inferior alveolar nerve block and had moderate-to-severe pain upon endodontic access. The Stabident system was used to administer 1.8 ml of 4% articaine with 1:100,000 epinephrine. Success of the intraosseous injection was defined as none or mild pain upon endodontic access or initial instrumentation. The results demonstrated that anesthetic success was obtained in 86% (32 of 37) of the patients. Maximum mean heart rate was increased 32 beats/minute during the intraosseous injection. We can conclude that when the inferior alveolar nerve block fails to provide profound pulpal anesthesia, the intraosseous injection of 4% articaine with 1:100,000 epinephrine would be successful 86% of the time in achieving pulpal anesthesia in mandibular posterior teeth of patients presenting with irreversible pulpitis.

A multidimensional subdiffusion model: An arbitrage-free market

International Nuclear Information System (INIS)

Li Guo-Hua; Zhang Hong; Luo Mao-Kang

2012-01-01

To capture the subdiffusive characteristics of financial markets, the subordinated process, directed by the inverse α-stale subordinator S α (t) for 0 < α < 1, has been employed as the model of asset prices. In this article, we introduce a multidimensional subdiffusion model that has a bond and K correlated stocks. The stock price process is a multidimensional subdiffusion process directed by the inverse α-stable subordinator. This model describes the period of stagnation for each stock and the behavior of the dependency between multiple stocks. Moreover, we derive the multidimensional fractional backward Kolmogorov equation for the subordinated process using the Laplace transform technique. Finally, using a martingale approach, we prove that the multidimensional subdiffusion model is arbitrage-free, and also gives an arbitrage-free pricing rule for contingent claims associated with the martingale measure. (interdisciplinary physics and related areas of science and technology)

FINITE TIME THERMODYNAMIC MODELING AND ANALYSIS FOR AN IRREVERSIBLE ATKINSON CYCLE

Directory of Open Access Journals (Sweden)

Yanlin Ge

2010-01-01

Full Text Available Performance of an air-standard Atkinson cycle is analyzed by using finite-time thermodynamics. The irreversible cycle model which is more close to practice is founded. In this model, the non-linear relation between the specific heats of working fluid and its temperature, the friction loss computed according to the mean velocity of the piston, the internal irreversibility described by using the compression and expansion efficiencies, and heat transfer loss are considered. The relations between the power output and the compression ratio, between the thermal efficiency and the compression ratio, as well as the optimal relation between power output and the efficiency of the cycle are derived by detailed numerical examples. Moreover, the effects of internal irreversibility, heat transfer loss and friction loss on the cycle performance are analyzed. The results obtained in this paper may provide guidelines for the design of practical internal combustion engines.

Ecological optimization and performance study of irreversible Stirling and Ericsson heat engines

International Nuclear Information System (INIS)

Tyagi, S K; Kaushik, S C; Salhotra, R

2002-01-01

The concept of finite time thermodynamics is used to determine the ecological function of irreversible Stirling and Ericsson heat engine cycles. The ecological function is defined as the power output minus power loss (irreversibility), which is the ambient temperature times, the entropy generation rate. The ecological function is maximized with respect to cycle temperature ratio and the expressions for the corresponding power output and thermal efficiency are derived at the optimal operating conditions. The effect of different operating parameters, the effectiveness on the hot, cold and the regenerative side heat exchangers, the cycle temperature ratio, heat capacitance ratio and the internal irreversibility parameter on the maximum ecological function are studied. It is found that the effect of regenerator effectiveness is more than the hot and cold side heat exchangers and the effect of the effectiveness on cold side heat exchanger is more than the effectiveness on the hot side heat exchanger on the maximum ecological function. It is also found that the effect of internal irreversibility parameter is more than the other parameters not only on the maximum ecological function but also on the corresponding power output and the thermal efficiency

Performance characteristics and parametric optimization of an irreversible magnetic Ericsson heat-pump

International Nuclear Information System (INIS)

Wei Fang; Lin Guoxing; Chen Jincan; Brueck, Ekkes

2011-01-01

Taking into account the finite-rate heat transfer in the heat-transfer processes, heat leak between the two external heat reservoirs, regenerative loss, regeneration time, and internal irreversibility due to dissipation of the cycle working substance, an irreversible magnetic Ericsson heat-pump cycle is presented. On the basis of the thermodynamic properties of magnetic materials, the performance characteristics of the irreversible magnetic Ericsson heat-pump are investigated and the relationship between the optimal heating load and the coefficient of performance (COP) is derived. Moreover, the maximum heating load and the corresponding COP as well as the maximum COP and the corresponding heating load are obtained. Furthermore, the other optimal performance characteristics are discussed in detail. The results obtained here may provide some new information for the optimal parameter design and the development of real magnetic Ericsson heat-pumps. -- Research Highlights: →The effects of multi-irreversibilities on the performance of a magnetic heat-pump are revealed. →Mathematical expressions of the heating load and the COP are derived and the optimal performance and operating parameters are analyzed and discussed. →Several important performance bounds are determined.

Ecological optimization and performance study of irreversible Stirling and Ericsson heat engines

Science.gov (United States)

Tyagi, S. K.; Kaushik, S. C.; Salhotra, R.

2002-10-01

The concept of finite time thermodynamics is used to determine the ecological function of irreversible Stirling and Ericsson heat engine cycles. The ecological function is defined as the power output minus power loss (irreversibility), which is the ambient temperature times, the entropy generation rate. The ecological function is maximized with respect to cycle temperature ratio and the expressions for the corresponding power output and thermal efficiency are derived at the optimal operating conditions. The effect of different operating parameters, the effectiveness on the hot, cold and the regenerative side heat exchangers, the cycle temperature ratio, heat capacitance ratio and the internal irreversibility parameter on the maximum ecological function are studied. It is found that the effect of regenerator effectiveness is more than the hot and cold side heat exchangers and the effect of the effectiveness on cold side heat exchanger is more than the effectiveness on the hot side heat exchanger on the maximum ecological function. It is also found that the effect of internal irreversibility parameter is more than the other parameters not only on the maximum ecological function but also on the corresponding power output and the thermal efficiency.

Multi-dimensional Laplace transforms and applications

International Nuclear Information System (INIS)

Mughrabi, T.A.

1988-01-01

In this dissertation we establish new theorems for computing certain types of multidimensional Laplace transform pairs from known one-dimensional Laplace transforms. The theorems are applied to the most commonly used special functions and so we obtain many two and three dimensional Laplace transform pairs. As applications, some boundary value problems involving linear partial differential equations are solved by the use of multi-dimensional Laplace transformation. Also we establish some relations between the Laplace transformation and other integral transformation in two variables

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.

Ecological optimization of an irreversible quantum Carnot heat engine with spin-1/2 systems

International Nuclear Information System (INIS)

Liu Xiaowei; Chen Lingen; Wu Feng; Sun Fengrui

2010-01-01

A model of a quantum heat engine with heat resistance, internal irreversibility and heat leakage and many non-interacting spin-1/2 systems is established in this paper. The quantum heat engine cycle is composed of two isothermal processes and two irreversible adiabatic processes and is referred to as a spin quantum Carnot heat engine. Based on the quantum master equation and the semi-group approach, equations of some important performance parameters, such as power output, efficiency, entropy generation rate and ecological function (a criterion representing the optimal compromise between exergy output rate and exergy loss rate), for the irreversible spin quantum Carnot heat engine are derived. The optimal ecological performance of the heat engine in the classical limit is analyzed with numerical examples. The effects of internal irreversibility and heat leakage on ecological performance are discussed in detail.

Contributions to multidimensional quadrature formulas

International Nuclear Information System (INIS)

Guenther, C.

1976-11-01

The general objective of this paper is to construct multidimensional quadrature formulas similar to the Gaussian Quadrature Formulas in one dimension. The correspondence between these formulas and orthogonal and nonnegative polynomials is established. One part of the paper considers the construction of multidimensional quadrature formulas using only methods of algebraic geometry, on the other part it is tried to obtain results on quadrature formulas with real nodes and, if possible, with positive weights. The results include the existence of quadrature formulas, information on the number resp. on the maximum possible number of points in the formulas for given polynomial degree N and the construction of formulas. (orig.) [de

Profit rate performance optimization for a generalized irreversible ...

Indian Academy of Sciences (India)

fer law system generalized irreversible combined refrigeration cycle model with finite-rate heat ...... Chen L, Sun F, Wu C 2004b Optimum allocation of heat exchanger area for refrigeration and air conditioning plants. Appl. Energy 77(3): 339– ...

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.

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.

Irreversible investments revisited

DEFF Research Database (Denmark)

Sandal, Leif K.; Steinshamn, Stein I.; Hoff, Ayoe

2007-01-01

A multi-dimensional, non-linear dynamic model in continuous time is presented for the purpose of finding the optimal combination of exploitation and capital investment in optimal renewable resource management. Non-malleability of capital is incorporated in the model through an asymmetric cost......-function of investment, and investments can be both positive and negative. Exploitation is controlled through the utilisation rate of available capital. A novel feature in this model is that there are costs associated with the available capital whether it is utilised or not. And, in contrast to most of the previous...... literature, the state variables, namely the physical capital and the biological resource, enter the objective function. Due to the nonlinearities in this model some of the results are in sharp contrast to previous literature....

Supervised and Unsupervised Learning of Multidimensional Acoustic Categories

Science.gov (United States)

Goudbeek, Martijn; Swingley, Daniel; Smits, Roel

2009-01-01

Learning to recognize the contrasts of a language-specific phonemic repertoire can be viewed as forming categories in a multidimensional psychophysical space. Research on the learning of distributionally defined visual categories has shown that categories defined over 1 dimension are easy to learn and that learning multidimensional categories is…

Nanosecond electric pulses modulate skeletal muscle calcium dynamics and contraction

Science.gov (United States)

Valdez, Chris; Jirjis, Michael B.; Roth, Caleb C.; Barnes, Ronald A.; Ibey, Bennett L.

2017-02-01

Irreversible electroporation therapy is utilized to remove cancerous tissues thru the delivery of rapid (250Hz) and high voltage (V) (1,500V/cm) electric pulses across microsecond durations. Clinical research demonstrated that bipolar (BP) high voltage microsecond pulses opposed to monophasic waveforms relieve muscle contraction during electroporation treatment. Our group along with others discovered that nanosecond electric pulses (nsEP) can activate second messenger cascades, induce cytoskeletal rearrangement, and depending on the nsEP duration and frequency, initiate apoptotic pathways. Of high interest across in vivo and in vitro applications, is how nsEP affects muscle physiology, and if nuances exist in comparison to longer duration electroporation applications. To this end, we exposed mature skeletal muscle cells to monopolar (MP) and BP nsEP stimulation across a wide range of electric field amplitudes (1-20 kV/cm). From live confocal microscopy, we simultaneously monitored intracellular calcium dynamics along with nsEP-induced muscle movement on a single cell level. In addition, we also evaluated membrane permeability with Yo-PRO-1 and Propidium Iodide (PI) across various nsEP parameters. The results from our findings suggest that skeletal muscle calcium dynamics, and nsEP-induced contraction exhibit exclusive responses to both MP and BP nsEP exposure. Overall the results suggest in vivo nsEP application may elicit unique physiology and field applications compared to longer pulse duration electroporation.

The degree of irreversibility in deterministic finite automata

DEFF Research Database (Denmark)

Axelsen, Holger Bock; Holzer, Markus; Kutrib, Martin

2016-01-01

the language, and show that the degree induces a strict infinite hierarchy of languages. We examine how the degree of irreversibility behaves under the usual language operations union, intersection, complement, concatenation, and Kleene star, showing tight bounds (some asymptotically) on the degree....

Exergetic efficiency optimization for an irreversible heat pump ...

Indian Academy of Sciences (India)

This paper deals with the performance analysis and optimization for irreversible heat pumps working on reversed Brayton cycle with constant-temperature heat reservoirs by taking exergetic efficiency as the optimization objective combining exergy concept with finite-time thermodynamics (FTT). Exergetic efficiency is ...

Peptide Drug Release Behavior from Biodegradable Temperature-Responsive Injectable Hydrogels Exhibiting Irreversible Gelation

Directory of Open Access Journals (Sweden)

Kazuyuki Takata

2017-10-01

Full Text Available We investigated the release behavior of glucagon-like peptide-1 (GLP-1 from a biodegradable injectable polymer (IP hydrogel. This hydrogel shows temperature-responsive irreversible gelation due to the covalent bond formation through a thiol-ene reaction. In vitro sustained release of GLP-1 from an irreversible IP formulation (F(P1/D+PA40 was observed compared with a reversible (physical gelation IP formulation (F(P1. Moreover, pharmaceutically active levels of GLP-1 were maintained in blood after subcutaneous injection of the irreversible IP formulation into rats. This system should be useful for the minimally invasive sustained drug release of peptide drugs and other water-soluble bioactive reagents.

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.

Irreversible denaturation of maltodextrin glucosidase studied by differential scanning calorimetry, circular dichroism, and turbidity measurements.

Science.gov (United States)

Goyal, Megha; Chaudhuri, Tapan K; Kuwajima, Kunihiro

2014-01-01

Thermal denaturation of Escherichia coli maltodextrin glucosidase was studied by differential scanning calorimetry, circular dichroism (230 nm), and UV-absorption measurements (340 nm), which were respectively used to monitor heat absorption, conformational unfolding, and the production of solution turbidity. The denaturation was irreversible, and the thermal transition recorded at scan rates of 0.5-1.5 K/min was significantly scan-rate dependent, indicating that the thermal denaturation was kinetically controlled. The absence of a protein-concentration effect on the thermal transition indicated that the denaturation was rate-limited by a mono-molecular process. From the analysis of the calorimetric thermograms, a one-step irreversible model well represented the thermal denaturation of the protein. The calorimetrically observed thermal transitions showed excellent coincidence with the turbidity transitions monitored by UV-absorption as well as with the unfolding transitions monitored by circular dichroism. The thermal denaturation of the protein was thus rate-limited by conformational unfolding, which was followed by a rapid irreversible formation of aggregates that produced the solution turbidity. It is thus important to note that the absence of the protein-concentration effect on the irreversible thermal denaturation does not necessarily means the absence of protein aggregation itself. The turbidity measurements together with differential scanning calorimetry in the irreversible thermal denaturation of the protein provided a very effective approach for understanding the mechanisms of the irreversible denaturation. The Arrhenius-equation parameters obtained from analysis of the thermal denaturation were compared with those of other proteins that have been reported to show the one-step irreversible thermal denaturation. Maltodextrin glucosidase had sufficiently high kinetic stability with a half-life of 68 days at a physiological temperature (37°C).

Anesthetic Efficacy in Irreversible Pulpitis: A Randomized Clinical Trial.

Science.gov (United States)

Allegretti, Carlos E; Sampaio, Roberta M; Horliana, Anna C R T; Armonia, Paschoal L; Rocha, Rodney G; Tortamano, Isabel Peixoto

2016-01-01

Inferior alveolar nerve block has a high failure rate in the treatment of mandibular posterior teeth with irreversible pulpitis. The aim of this study was to compare the anesthetic efficacy of 4% articaine, 2% lidocaine and 2% mepivacaine, all in combination with 1:100,000 epinephrine, in patients with irreversible pulpitis of permanent mandibular molars during a pulpectomy procedure. Sixty-six volunteers from the Emergency Center of the School of Dentistry, University of São Paulo, randomly received 3.6 mL of local anesthetic as a conventional inferior alveolar nerve block (IANB). The subjective signal of lip numbness, pulpal anesthesia and absence of pain during the pulpectomy procedure were evaluated respectively, by questioning the patient, stimulation using an electric pulp tester and a verbal analogue scale. All patients reported the subjective signal of lip numbness. Regarding pulpal anesthesia success as measured with the pulp tester, the success rate was respectively 68.2% for mepivacaine, 63.6% for articaine and 63.6% for lidocaine. Regarding patients who reported no pain or mild pain during the pulpectomy, the success rate was, respectively 72.7% for mepivacaine, 63.6% for articaine and 54.5% for lidocaine. These differences were not statistically significant. Neither of the solutions resulted in 100% anesthetic success in patients with irreversible pulpitis of mandibular molars.

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.

Sample size effect on the determination of the irreversibility line of high-Tc superconductors

International Nuclear Information System (INIS)

Li, Q.; Suenaga, M.; Li, Q.; Freltoft, T.

1994-01-01

The irreversibility lines of a high-J c superconducting Bi 2 Sr 2 Ca 2 Cu 3 O x /Ag tape were systematically measured upon a sequence of subdivisions of the sample. The irreversibility field H r (T) (parallel to the c axis) was found to change approximately as L 0.13 , where L is the effective dimension of the superconducting tape. Furthermore, it was found that the irreversibility line for a grain-aligned Bi 2 Sr 2 Ca 2 Cu 3 O x specimen can be approximately reproduced by the extrapolation of this relation down to a grain size of a few tens of micrometers. The observed size effect could significantly obscure the real physical meaning of the irreversibility lines. In addition, this finding surprisingly indicated that the Bi 2 Sr 2 Ca 2 Cu 2 O x /Ag tape and grain-aligned specimen may have similar flux line pinning strength

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.

Irreversible absorption heat-pump and its optimal performance

International Nuclear Information System (INIS)

Chen Lingen; Qin Xiaoyong; Sun Fengrui; Wu Chih

2005-01-01

On the basis of an endoreversible absorption heat-pump cycle, a generalized irreversible four-heat-reservoir absorption heat-pump cycle model is established by taking account of the heat resistances, heat leak and irreversibilities due to the internal dissipation of the working substance. The heat transfer between the heat reservoir and the working substance is assumed to obey the linear (Newtonian) heat-transfer law, and the overall heat-transfer surface area of the four heat-exchangers is assumed to be constant. The fundamental optimal relations between the coefficient of performance (COP) and the heating-load, the maximum COP and the corresponding heating-load, the maximum heating load and the corresponding COP, as well as the optimal temperatures of the working substance and the optimal heat-transfer surface areas of the four heat-exchangers are derived by using finite-time thermodynamics. Moreover, the effects of the cycle parameters on the characteristics of the cycle are studied by numerical examples

Quantum mechanical irreversibility and measurement

CERN Document Server

Grigolini, P

1993-01-01

This book is intended as a tutorial approach to some of the techniques used to deal with quantum dissipation and irreversibility, with special focus on their applications to the theory of measurements. The main purpose is to provide readers without a deep expertise in quantum statistical mechanics with the basic tools to develop a critical judgement on whether the major achievements in this field have to be considered a satisfactory solution of quantum paradox, or rather this ambitious achievement has to be postponed to when a new physics, more general than quantum and classical physics, will

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.

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.

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.

Improving personality facet scores with multidimensional computer adaptive testing

DEFF Research Database (Denmark)

Makransky, Guido; Mortensen, Erik Lykke; Glas, Cees A W

2013-01-01

personality tests contain many highly correlated facets. This article investigates the possibility of increasing the precision of the NEO PI-R facet scores by scoring items with multidimensional item response theory and by efficiently administering and scoring items with multidimensional computer adaptive...

Reversing the irreversible: From limit cycles to emergent time symmetry

Science.gov (United States)

Cortês, Marina; Smolin, Lee

2018-01-01

In 1979 Penrose hypothesized that the arrows of time are explained by the hypothesis that the fundamental laws are time irreversible [R. Penrose, in General Relativity: An Einstein Centenary Survey (1979)]. That is, our reversible laws, such as the standard model and general relativity are effective, and emerge from an underlying fundamental theory which is time irreversible. In [M. Cortês and L. Smolin, Phys. Rev. D 90, 084007 (2014), 10.1103/PhysRevD.90.084007; 90, 044035 (2014), 10.1103/PhysRevD.90.044035; 93, 084039 (2016), 10.1103/PhysRevD.93.084039] we put forward a research program aiming at realizing just this. The aim is to find a fundamental description of physics above the Planck scale, based on irreversible laws, from which will emerge the apparently reversible dynamics we observe on intermediate scales. Here we continue that program and note that a class of discrete dynamical systems are known to exhibit this very property: they have an underlying discrete irreversible evolution, but in the long term exhibit the properties of a time reversible system, in the form of limit cycles. We connect this to our original model proposal in [M. Cortês and L. Smolin, Phys. Rev. D 90, 084007 (2014), 10.1103/PhysRevD.90.084007], and show that the behaviors obtained there can be explained in terms of the same phenomenon: the attraction of the system to a basin of limit cycles, where the dynamics appears to be time reversible. Further than that, we show that our original models exhibit the very same feature: the emergence of quasiparticle excitations obtained in the earlier work in the space-time description is an expression of the system's convergence to limit cycles when seen in the causal set description.

Nonequilibrium and irreversibility

CERN Document Server

Gallavotti, Giovanni

2014-01-01

This book concentrates on the properties of the stationary states in chaotic systems of particles or fluids, leaving aside the theory of the way they can be reached. The stationary states of particles or of fluids (understood as probability distributions on microscopic configurations or on the fields describing continua) have received important new ideas and data from numerical simulations and reviews are needed. The starting point is to find out which time invariant distributions come into play in physics. A special feature of this book is the historical approach. To identify the problems the author analyzes the papers of the founding fathers Boltzmann, Clausius and Maxwell including translations of the relevant (parts of ) historical documents. He also establishes a close link between treatment of irreversible phenomena in statistical mechanics and the theory of chaotic systems at and beyond the onset of turbulence as developed by Sinai, Ruelle, Bowen (SRB) and others: the author gives arguments intending t...

Investment Irreversibility and Precautionary Savings in General Equilibrium

DEFF Research Database (Denmark)

Ejarque, João

than irreversibility effects. If shocks are idiosyncratic and affect a cross section of agents over capital, an increase in their variance may induce an increase in aggregate investment even if all agents have an incentive to invest less, because zero investment is now an active lower bound for part...

Multi-Dimensional Aggregation for Temporal Data

DEFF Research Database (Denmark)

Böhlen, M. H.; Gamper, J.; Jensen, Christian Søndergaard

2006-01-01

Business Intelligence solutions, encompassing technologies such as multi-dimensional data modeling and aggregate query processing, are being applied increasingly to non-traditional data. This paper extends multi-dimensional aggregation to apply to data with associated interval values that capture...... that the data holds for each point in the interval, as well as the case where the data holds only for the entire interval, but must be adjusted to apply to sub-intervals. The paper reports on an implementation of the new operator and on an empirical study that indicates that the operator scales to large data...

Executive Information Systems' Multidimensional Models

Directory of Open Access Journals (Sweden)

2007-01-01

Full Text Available Executive Information Systems are design to improve the quality of strategic level of management in organization through a new type of technology and several techniques for extracting, transforming, processing, integrating and presenting data in such a way that the organizational knowledge filters can easily associate with this data and turn it into information for the organization. These technologies are known as Business Intelligence Tools. But in order to build analytic reports for Executive Information Systems (EIS in an organization we need to design a multidimensional model based on the business model from the organization. This paper presents some multidimensional models that can be used in EIS development and propose a new model that is suitable for strategic business requests.

Linear irreversible thermodynamics and Onsager reciprocity for information-driven engines

Science.gov (United States)

Yamamoto, Shumpei; Ito, Sosuke; Shiraishi, Naoto; Sagawa, Takahiro

2016-11-01

In the recent progress in nonequilibrium thermodynamics, information has been recognized as a kind of thermodynamic resource that can drive thermodynamic current without any direct energy injection. In this paper, we establish the framework of linear irreversible thermodynamics for a broad class of autonomous information processing. In particular, we prove that the Onsager reciprocity holds true with information: The linear response matrix is well-defined and is shown symmetric with both of the information affinity and the conventional thermodynamic affinity. As an application, we derive a universal bound for the efficiency at maximum power for information-driven engines in the linear regime. Our result reveals the fundamental role of information flow in linear irreversible thermodynamics.

The Tunneling Method for Global Optimization in Multidimensional Scaling.

Science.gov (United States)

Groenen, Patrick J. F.; Heiser, Willem J.

1996-01-01

A tunneling method for global minimization in multidimensional scaling is introduced and adjusted for multidimensional scaling with general Minkowski distances. The method alternates a local search step with a tunneling step in which a different configuration is sought with the same STRESS implementation. (SLD)

A study of multidimensional modeling approaches for data warehouse

Science.gov (United States)

Yusof, Sharmila Mat; Sidi, Fatimah; Ibrahim, Hamidah; Affendey, Lilly Suriani

2016-08-01

Data warehouse system is used to support the process of organizational decision making. Hence, the system must extract and integrate information from heterogeneous data sources in order to uncover relevant knowledge suitable for decision making process. However, the development of data warehouse is a difficult and complex process especially in its conceptual design (multidimensional modeling). Thus, there have been various approaches proposed to overcome the difficulty. This study surveys and compares the approaches of multidimensional modeling and highlights the issues, trend and solution proposed to date. The contribution is on the state of the art of the multidimensional modeling design.

Mathematical models and equilibrium in irreversible microeconomics

Directory of Open Access Journals (Sweden)

Anatoly M. Tsirlin

2010-07-01

Full Text Available A set of equilibrium states in a system consisting of economic agents, economic reservoirs, and firms is considered. Methods of irreversible microeconomics are used. We show that direct sale/purchase leads to an equilibrium state which depends upon the coefficients of supply/demand functions. To reach the unique equilibrium state it is necessary to add either monetary exchange or an intermediate firm.

Fatigue and multidimensional disease severity in chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

Inal-Ince Deniz

2010-06-01

Full Text Available Abstract Background and aims Fatigue is associated with longitudinal ratings of health in patients with chronic obstructive pulmonary disease (COPD. Although the degree of airflow obstruction is often used to grade disease severity in patients with COPD, multidimensional grading systems have recently been developed. The aim of this study was to investigate the relationship between perceived and actual fatigue level and multidimensional disease severity in patients with COPD. Materials and methods Twenty-two patients with COPD (aged 52-74 years took part in the study. Multidimensional disease severity was measured using the SAFE and BODE indices. Perceived fatigue was assessed using the Fatigue Severity Scale (FSS and the Fatigue Impact Scale (FIS. Peripheral muscle endurance was evaluated using the number of sit-ups, squats, and modified push-ups that each patient could do. Results Thirteen patients (59% had severe fatigue, and their St George's Respiratory Questionnaire scores were significantly higher (p Conclusions Peripheral muscle endurance and fatigue perception in patients with COPD was related to multidimensional disease severity measured with both the SAFE and BODE indices. Improvements in perceived and actual fatigue levels may positively affect multidimensional disease severity and health status in COPD patients. Further research is needed to investigate the effects of fatigue perception and exercise training on patients with different stages of multidimensional COPD severity.

Multidimensional nonlinear descriptive analysis

CERN Document Server

Nishisato, Shizuhiko

2006-01-01

Quantification of categorical, or non-numerical, data is a problem that scientists face across a wide range of disciplines. Exploring data analysis in various areas of research, such as the social sciences and biology, Multidimensional Nonlinear Descriptive Analysis presents methods for analyzing categorical data that are not necessarily sampled randomly from a normal population and often involve nonlinear relations. This reference not only provides an overview of multidimensional nonlinear descriptive analysis (MUNDA) of discrete data, it also offers new results in a variety of fields. The first part of the book covers conceptual and technical preliminaries needed to understand the data analysis in subsequent chapters. The next two parts contain applications of MUNDA to diverse data types, with each chapter devoted to one type of categorical data, a brief historical comment, and basic skills peculiar to the data types. The final part examines several problems and then concludes with suggestions for futu...

Ecological optimization for an irreversible magnetic Ericsson refrigeration cycle

International Nuclear Information System (INIS)

Wang Hao; Wu Guo-Xing

2013-01-01

An irreversible Ericsson refrigeration cycle model is established, in which multi-irreversibilities such as finite-rate heat transfer, regenerative loss, heat leakage, and the efficiency of the regenerator are taken into account. Expressions for several important performance parameters, such as the cooling rate, coefficient of performance (COP), power input, exergy output rate, entropy generation rate, and ecological function are derived. The influences of the heat leakage and the time of the regenerative processes on the ecological performance of the refrigerator are analyzed. The optimal regions of the ecological function, cooling rate, and COP are determined and evaluated. Furthermore, some important parameter relations of the refrigerator are revealed and discussed in detail. The results obtained here have general significance and will be helpful in gaining a deep understanding of the magnetic Ericsson refrigeration cycle. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Detailed Modeling and Irreversible Transfer Process Analysis of a Multi-Element Thermoelectric Generator System

Science.gov (United States)

Xiao, Heng; Gou, Xiaolong; Yang, Suwen

2011-05-01

Thermoelectric (TE) power generation technology, due to its several advantages, is becoming a noteworthy research direction. Many researchers conduct their performance analysis and optimization of TE devices and related applications based on the generalized thermoelectric energy balance equations. These generalized TE equations involve the internal irreversibility of Joule heating inside the thermoelectric device and heat leakage through the thermoelectric couple leg. However, it is assumed that the thermoelectric generator (TEG) is thermally isolated from the surroundings except for the heat flows at the cold and hot junctions. Since the thermoelectric generator is a multi-element device in practice, being composed of many fundamental TE couple legs, the effect of heat transfer between the TE couple leg and the ambient environment is not negligible. In this paper, based on basic theories of thermoelectric power generation and thermal science, detailed modeling of a thermoelectric generator taking account of the phenomenon of energy loss from the TE couple leg is reported. The revised generalized thermoelectric energy balance equations considering the effect of heat transfer between the TE couple leg and the ambient environment have been derived. Furthermore, characteristics of a multi-element thermoelectric generator with irreversibility have been investigated on the basis of the new derived TE equations. In the present investigation, second-law-based thermodynamic analysis (exergy analysis) has been applied to the irreversible heat transfer process in particular. It is found that the existence of the irreversible heat convection process causes a large loss of heat exergy in the TEG system, and using thermoelectric generators for low-grade waste heat recovery has promising potential. The results of irreversibility analysis, especially irreversible effects on generator system performance, based on the system model established in detail have guiding significance for

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.

Multidimensional Physical Self-Concept of Athletes with Physical Disabilities

Science.gov (United States)

Shapiro, Deborah R.; Martin, Jeffrey J.

2010-01-01

The purposes of this investigation were first to predict reported PA (physical activity) behavior and self-esteem using a multidimensional physical self-concept model and second to describe perceptions of multidimensional physical self-concept (e.g., strength, endurance, sport competence) among athletes with physical disabilities. Athletes (N =…

Irreversible JPEG 2000 compression of abdominal CT for primary interpretation: assessment of visually lossless threshold

International Nuclear Information System (INIS)

Lee, Kyoung Ho; Kim, Young Hoon; Kim, Bo Hyoung; Kim, Kil Joong; Kim, Tae Jung; Kim, Hyuk Jung; Hahn, Seokyung

2007-01-01

To estimate the visually lossless threshold for Joint Photographic Experts Group (JPEG) 2000 compression of contrast-enhanced abdominal computed tomography (CT) images, 100 images were compressed to four different levels: a reversible (as negative control) and irreversible 5:1, 10:1, and 15:1. By alternately displaying the original and the compressed image on the same monitor, six radiologists independently determined if the compressed image was distinguishable from the original image. For each reader, we compared the proportion of the compressed images being rated distinguishable from the original images between the reversible compression and each of the three irreversible compressions using the exact test for paired proportions. For each reader, the proportion was not significantly different between the reversible (0-1%, 0/100 to 1/100) and irreversible 5:1 compression (0-3%). However, the proportion significantly increased with the irreversible 10:1 (95-99%) and 15:1 compressions (100%) versus reversible compression in all readers (P < 0.001); 100 and 95% of the 5:1 compressed images were rated indistinguishable from the original images by at least five of the six readers and all readers, respectively. Irreversibly 5:1 compressed abdominal CT images are visually lossless and, therefore, potentially acceptable for primary interpretation. (orig.)

Development of Multidimensional Gap Conductance model using Virtual Link Gap Element

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyo Chan; Yang, Yong Sik; Kim, Dae Ho; Bang, Je Geon; Kim, Sun Ki; Koo, Yang Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-10-15

The gap conductance that determines temperature gradient between pellet and cladding can be quite sensitive to gap thickness. For instance, once the gap size increases up to several micrometers in certain region, difference of pellet surface temperatures increases up to 100 Kelvin. Therefore, iterative thermo-mechanical coupled analysis is required to solve temperature distribution throughout pellet and cladding. Recently, multidimensional fuel performance codes have been being developed in the advanced countries to evaluate thermal behavior of fuel for off normal conditions and DBA(design based accident) conditions using the Finite Element Method (FEM). FRAPCON-FRAPTRAN code system, which is well known as the verified and reliable code, incorporates 1D thermal module and multidimensional mechanical module. In this code, multidimensional gap conductance model is not applied. ALCYONE developed by CEA introduces equivalent heat convection coefficient that represents multidimensional gap conductance as a function of gap thickness. BISON, which is multidimensional fuel performance code developed by INL, owns multidimensional gap conductance model using projected thermal contact. In general, thermal contact algorithm is nonlinear calculation which is expensive approach numerically. The gap conductance model for multi-dimension is difficult issue in terms of convergence and nonlinearity because gap conductance is function of gap thickness which depends on mechanical analysis at each iteration step. In this paper, virtual link gap (VLG) element has been proposed to resolve convergence issue and nonlinear characteristic of multidimensional gap conductance. In terms of calculation accuracy and convergence efficiency, the proposed VLG model was evaluated. LWR fuel performance codes should incorporate thermo-mechanical loop to solve gap conductance problem, iteratively. However, gap conductance in multidimensional model is difficult issue owing to its nonlinearity and

Conservative Initial Mapping For Multidimensional Simulations of Stellar Explosions

International Nuclear Information System (INIS)

Chen, Ke-Jung; Heger, Alexander; Almgren, Ann

2012-01-01

Mapping one-dimensional stellar profiles onto multidimensional grids as initial conditions for hydrodynamics calculations can lead to numerical artifacts, one of the most severe of which is the violation of conservation laws for physical quantities such as energy and mass. Here we introduce a numerical scheme for mapping one-dimensional spherically-symmetric data onto multidimensional meshes so that these physical quantities are conserved. We validate our scheme by porting a realistic 1D Lagrangian stellar profile to the new multidimensional Eulerian hydro code CASTRO. Our results show that all important features in the profiles are reproduced on the new grid and that conservation laws are enforced at all resolutions after mapping.

Antimicrobial activity and properties of irreversible hydrocolloid impression materials incorporated with silver nanoparticles.

Science.gov (United States)

Ginjupalli, Kishore; Alla, Rama Krishna; Tellapragada, Chaitanya; Gupta, Lokendra; Upadhya Perampalli, Nagaraja

2016-06-01

Conventional spray and the immersion disinfection of irreversible hydrocolloid impression materials may lead to dimensional changes. The purpose of this in vitro study was to investigate the antimicrobial activity and properties of irreversible hydrocolloid impression materials incorporated with silver nanoparticles. The antimicrobial activity and properties of 2 commercially available irreversible hydrocolloid impression materials were evaluated after incorporating varying concentrations of silver nanoparticles. Antimicrobial activity was determined using the disk diffusion method. The gel strength, permanent deformation, flow, and gelation time were measured according to American Dental Association specification #18. Analysis of variance was used to identify the significant differences within and across the groups (α=.05). Adding silver nanoparticles to irreversible hydrocolloid impression materials resulted in superior antimicrobial activity without adversely affecting their properties. Adding silver nanoparticles to Zelgan significantly increased the gel strength compared with the control group, except at 5 wt%. However, the gel strength of Tropicalgin was unaffected except at 5 wt%. An increase in the permanent deformation was found with the incorporation of silver nanoparticles in both Zelgan and Tropicalgin. The flow of Zelgan increased with the incorporation of silver nanoparticles, whereas a decrease in the flow of Tropicalgin was observed at 1 wt% and 2 wt%. An increase in the gelation time of both Zelgan and Tropicalgin was observed with the incorporation of silver nanoparticles. Based on this in vitro study, silver nanoparticles can be incorporated into irreversible hydrocolloid impression materials as antimicrobial agents without adversely affecting their properties. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

A Comparative Study on the Effects of Millisecond- and Microsecond-Pulsed Electric Field Treatments on the Permeabilization and Extraction of Pigments from Chlorella vulgaris.

Science.gov (United States)

Luengo, Elisa; Martínez, Juan Manuel; Coustets, Mathilde; Álvarez, Ignacio; Teissié, Justin; Rols, Marie-Pierre; Raso, Javier

2015-10-01

The interdependencies of the two main processing parameters affecting "electroporation" (electric field strength and pulse duration) while using pulse duration in the range of milliseconds and microseconds on the permeabilization, inactivation, and extraction of pigments from Chlorella vulgaris was compared. While irreversible "electroporation" was observed above 4 kV/cm in the millisecond range, electric field strengths of ≥10 kV/cm were required in the microseconds range. However, to cause the electroporation of most of the 90 % of the population of C. vulgaris in the millisecond (5 kV/cm, 20 pulses) or microsecond (15 kV/cm, 25 pulses) range, the specific energy that was delivered was lower for microsecond treatments (16.87 kJ/L) than in millisecond treatments (150 kJ/L). In terms of the specific energy required to cause microalgae inactivation, treatments in the microsecond range also resulted in greater energy efficiency. The comparison of extraction yields in the range of milliseconds (5 kV, 20 ms) and microseconds (20, 25 pulses) under the conditions in which the maximum extraction was observed revealed that the improvement in the carotenoid extraction was similar and chlorophyll a and b extraction was slightly higher for treatments in the microsecond range. The specific energy that was required for the treatment in the millisecond range (150 kJ/L) was much higher than those required in the microsecond range (30 kJ/L). The comparison of the efficacy of both types of pulses on the extraction enhancement just after the treatment and after a post-pulse incubation period seemed to indicate that PEF in the millisecond range created irreversible alterations while, in the microsecond range, the defects were a dynamic structure along the post-pulse time that caused a subsequent increment in the extraction yield.

Prostaglandin E2 to diagnose between reversible and irreversible pulpitis.

Science.gov (United States)

Petrini, M; Ferrante, M; Ciavarelli, L; Brunetti, L; Vacca, M; Spoto, G

2012-01-01

The aim of this work is to verify a correlation between the grade of inflammation and the concentration of PGE2 in human dental pulp. A total of 25 human dental pulps were examined by histological analysis and radioimmunologic dosage of PGE2. The pulps used in this experiment were from healthy and symptomatic teeth; the first ones were collected from teeth destined to be extracted for orthodontic reasons. An increase was observed of PGE2 in reversible pulpitis compared with healthy pulps and with the irreversible pulpitis and the clear decrease of these when NSAIDs are taken. This study demonstrates that PGE2 level is correlated to histological analysis thus allowing to distinguish symptomatic teeth in reversible and irreversible pulpitis.

Balanced sensitivity functions for tuning multi-dimensional Bayesian network classifiers

NARCIS (Netherlands)

Bolt, J.H.; van der Gaag, L.C.

Multi-dimensional Bayesian network classifiers are Bayesian networks of restricted topological structure, which are tailored to classifying data instances into multiple dimensions. Like more traditional classifiers, multi-dimensional classifiers are typically learned from data and may include

Direct and irreversible inhibition of cyclooxygenase-1 by nitroaspirin (NCX 4016).

Science.gov (United States)

Corazzi, Teresa; Leone, Mario; Maucci, Raffaella; Corazzi, Lanfranco; Gresele, Paolo

2005-12-01

Benzoic acid, 2-(acetyl-oxy)-3-[(nitrooxy)methyl]phenyl ester (NCX 4016), a new drug made by an aspirin molecule linked, through a spacer, to a nitric oxide (NO)-donating moiety, is now under clinical testing for the treatment of atherothrombotic conditions. Aspirin exerts its antithrombotic activity by irreversibly inactivating platelet cyclooxygenase (COX)-1. NCX 4016 in vivo undergoes metabolism into deacetylated and/or denitrated metabolites, and it is not known whether NCX 4016 needs to liberate aspirin to inhibit COX-1, or whether it can block it as a whole molecule. The aim of our study was to evaluate the effects of NCX 4016 and its analog or metabolites on platelet COX-1 and whole blood COX-2 and on purified ovine COX (oCOX)-1 and oCOX-2. In particular, we have compared the mechanism by which NCX 4016 inhibits purified oCOX enzymes with that of aspirin using a spectrophotometric assay. All the NCX 4016 derivatives containing acetylsalicylic acid inhibited the activity of oCOX-1 and oCOX-2, whereas the deacetylated metabolites and the nitric oxide-donating moiety were inactive. Dialysis experiments showed that oCOX-1 inhibition by NCX 4016, similar to aspirin, is irreversible. Reversible COX inhibitors (indomethacin) or salicylic acid incubated with the enzyme before NCX 4016 prevent the irreversible inhibition of oCOX-1 by NCX 4016 as well as by aspirin. In conclusion, our data show that NCX 4016 acts as a direct and irreversible inhibitor of COX-1 and that the presence of a spacer and NO-donating moiety in the molecule slows the kinetics of COX-1 inhibition by NCX 4016, compared with aspirin.

Cluster Oriented Spatio Temporal Multidimensional Data Visualization of Earthquakes in Indonesia

Directory of Open Access Journals (Sweden)

Mohammad Nur Shodiq

2016-03-01

Full Text Available Spatio temporal data clustering is challenge task. The result of clustering data are utilized to investigate the seismic parameters. Seismic parameters are used to describe the characteristics of earthquake behavior. One of the effective technique to study multidimensional spatio temporal data is visualization. But, visualization of multidimensional data is complicated problem. Because, this analysis consists of observed data cluster and seismic parameters. In this paper, we propose a visualization system, called as IES (Indonesia Earthquake System, for cluster analysis, spatio temporal analysis, and visualize the multidimensional data of seismic parameters. We analyze the cluster analysis by using automatic clustering, that consists of get optimal number of cluster and Hierarchical K-means clustering. We explore the visual cluster and multidimensional data in low dimensional space visualization. We made experiment with observed data, that consists of seismic data around Indonesian archipelago during 2004 to 2014. Keywords: Clustering, visualization, multidimensional data, seismic parameters.

Multidimensional filter banks and wavelets research developments and applications

CERN Document Server

Levy, Bernard

1997-01-01

Multidimensional Filter Banks and Wavelets: Reserach Developments and Applications brings together in one place important contributions and up-to-date research results in this important area. Multidimensional Filter Banks and Wavelets: Research Developments and Applications serves as an excellent reference, providing insight into some of the most important research issues in the field.

On new physics searches with multidimensional differential shapes

Science.gov (United States)

Ferreira, Felipe; Fichet, Sylvain; Sanz, Veronica

2018-03-01

In the context of upcoming new physics searches at the LHC, we investigate the impact of multidimensional differential rates in typical LHC analyses. We discuss the properties of shape information, and argue that multidimensional rates bring limited information in the scope of a discovery, but can have a large impact on model discrimination. We also point out subtleties about systematic uncertainties cancellations and the Cauchy-Schwarz bound on interference terms.

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...

Multidimensional human dynamics in mobile phone communications.

Science.gov (United States)

Quadri, Christian; Zignani, Matteo; Capra, Lorenzo; Gaito, Sabrina; Rossi, Gian Paolo

2014-01-01

In today's technology-assisted society, social interactions may be expressed through a variety of techno-communication channels, including online social networks, email and mobile phones (calls, text messages). Consequently, a clear grasp of human behavior through the diverse communication media is considered a key factor in understanding the formation of the today's information society. So far, all previous research on user communication behavior has focused on a sole communication activity. In this paper we move forward another step on this research path by performing a multidimensional study of human sociality as an expression of the use of mobile phones. The paper focuses on user temporal communication behavior in the interplay between the two complementary communication media, text messages and phone calls, that represent the bi-dimensional scenario of analysis. Our study provides a theoretical framework for analyzing multidimensional bursts as the most general burst category, that includes one-dimensional bursts as the simplest case, and offers empirical evidence of their nature by following the combined phone call/text message communication patterns of approximately one million people over three-month period. This quantitative approach enables the design of a generative model rooted in the three most significant features of the multidimensional burst - the number of dimensions, prevalence and interleaving degree - able to reproduce the main media usage attitude. The other findings of the paper include a novel multidimensional burst detection algorithm and an insight analysis of the human media selection process.

Multidimensional human dynamics in mobile phone communications.

Directory of Open Access Journals (Sweden)

Christian Quadri

Full Text Available In today's technology-assisted society, social interactions may be expressed through a variety of techno-communication channels, including online social networks, email and mobile phones (calls, text messages. Consequently, a clear grasp of human behavior through the diverse communication media is considered a key factor in understanding the formation of the today's information society. So far, all previous research on user communication behavior has focused on a sole communication activity. In this paper we move forward another step on this research path by performing a multidimensional study of human sociality as an expression of the use of mobile phones. The paper focuses on user temporal communication behavior in the interplay between the two complementary communication media, text messages and phone calls, that represent the bi-dimensional scenario of analysis. Our study provides a theoretical framework for analyzing multidimensional bursts as the most general burst category, that includes one-dimensional bursts as the simplest case, and offers empirical evidence of their nature by following the combined phone call/text message communication patterns of approximately one million people over three-month period. This quantitative approach enables the design of a generative model rooted in the three most significant features of the multidimensional burst - the number of dimensions, prevalence and interleaving degree - able to reproduce the main media usage attitude. The other findings of the paper include a novel multidimensional burst detection algorithm and an insight analysis of the human media selection process.

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

On the existence of physiological age based on functional hierarchy: a formal definition related to time irreversibility.

Science.gov (United States)

Chauvet, Gilbert A

2006-09-01

The present approach of aging and time irreversibility is a consequence of the theory of functional organization that I have developed and presented over recent years (see e.g., Ref. 11). It is based on the effect of physically small and numerous perturbations known as fluctuations, of structural units on the dynamics of the biological system during its adult life. Being a highly regulated biological system, a simple realistic hypothesis, the time-optimum regulation between the levels of organization, leads to the existence of an internal age for the biological system, and time-irreversibility associated with aging. Thus, although specific genes are controlling aging, time-irreversibility of the system may be shown to be due to the degradation of physiological functions. In other words, I suggest that for a biological system, the nature of time is specific and is an expression of the highly regulated integration. An internal physiological age reflects the irreversible course of a living organism towards death because of the irreversible course of physiological functions towards dysfunction, due to the irreversible changes in the regulatory processes. Following the works of Prigogine and his colleagues in physics, and more generally in the field of non-integrable dynamical systems (theorem of Poincaré-Misra), I have stated this problem in terms of the relationship between the macroscopic irreversibility of the functional organization and the basic mechanisms of regulation at the lowest "microscopic" level, i.e., the molecular, lowest level of organization. The neuron-neuron elementary functional interaction is proposed as an illustration of the method to define aging in the nervous system.

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

Image matrix processor for fast multi-dimensional computations

Science.gov (United States)

Roberson, George P.; Skeate, Michael F.

1996-01-01

An apparatus for multi-dimensional computation which comprises a computation engine, including a plurality of processing modules. The processing modules are configured in parallel and compute respective contributions to a computed multi-dimensional image of respective two dimensional data sets. A high-speed, parallel access storage system is provided which stores the multi-dimensional data sets, and a switching circuit routes the data among the processing modules in the computation engine and the storage system. A data acquisition port receives the two dimensional data sets representing projections through an image, for reconstruction algorithms such as encountered in computerized tomography. The processing modules include a programmable local host, by which they may be configured to execute a plurality of different types of multi-dimensional algorithms. The processing modules thus include an image manipulation processor, which includes a source cache, a target cache, a coefficient table, and control software for executing image transformation routines using data in the source cache and the coefficient table and loading resulting data in the target cache. The local host processor operates to load the source cache with a two dimensional data set, loads the coefficient table, and transfers resulting data out of the target cache to the storage system, or to another destination.

Pinning and irreversibility in superconducting bulk MgB{sub 2} with added nanodiamonds

Energy Technology Data Exchange (ETDEWEB)

Gupta, Anurag [Superconductivity and Cryogenics Division, National Physical Laboratory (CSIR), New Delhi-110012 (India); Narlikar, A V, E-mail: anurag@mail.nplindia.ernet.i [UGC-DAE Consortium for Scientific Research, University Campus, Khandwa Road, Indore-452017, MP (India)

2009-12-15

Resistance, R(T), and magnetization, M(B), studies on superconducting bulk MgB{sub 2} samples containing nanodiamonds (ND) as additives (wt% of ND: x = 0%, 1%, 3%, 5%, 7% and 10%) were recently published in two articles (Vajpayee et al 2007 Supercond. Sci. Technol. 20 S155, Vajpayee et al 2008 J. Appl. Phys. 103 07C708). The main observations reported were significant improvements in the critical current density J{sub c}(B), irreversibility line B{sub irr}(T) and upper critical field B{sub c2}(T) with ND addition. However, a closer look shows that as regards the potential of this technologically important material at higher magnetic fields and temperatures, there is still a lot of room for improvement. With that in mind we revisit the R(T) and M(B) data and analyze them, in the present work. We show that, despite ND addition, J{sub c} depends strongly on B in the high field region and tends to vanish at irreversibility lines that lie deep, i.e. at around 0.3 B{sub c2}(T), in the B-T phase diagram. The irreversibility lines, determined by R(T){yields}0 in the presence of B, are found to lie at around 0.5 B{sub c2}(T) in the phase diagram. These results for pinning and irreversibility lines are discussed in the light of various models such as those of surface sheath superconductivity, magnetically introduced percolation in polycrystalline MgB{sub 2}, thermally assisted flux motion (TAFM) and a modified flux line shear mechanism. Our analysis hints at TAFM and weak pinning channels with distributed superconducting properties percolating in our samples determining the irreversibility and pinning properties.

Two multi-dimensional uncertainty relations

International Nuclear Information System (INIS)

Skala, L; Kapsa, V

2008-01-01

Two multi-dimensional uncertainty relations, one related to the probability density and the other one related to the probability density current, are derived and discussed. Both relations are stronger than the usual uncertainty relations for the coordinates and momentum

Antibacterial efficacy and effect of chlorhexidine mixed with irreversible hydrocolloid for dental impressions: a randomized controlled trial.

Science.gov (United States)

Cubas, Glória; Valentini, Fernanda; Camacho, Guilherme Brião; Leite, Fábio; Cenci, Maximiliano Sérgio; Pereira-Cenci, Tatiana

2014-01-01

This study aimed to evaluate whether chlorhexidine mixed with irreversible hydrocolloid powder decreases microbial contamination during impression taking without affecting the resulting casts. Twenty volunteers were randomly divided into two groups (n = 10) according to the liquid used for impression taking in conjunction with irreversible hydrocolloid: 0.12% chlorhexidine or water. Surface roughness and dimensional stability of the casts were evaluated. Chlorhexidine mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P impression quality.

Benefits of Multidimensional Measures of Child Well Being in China.

Science.gov (United States)

Gatenio Gabel, Shirley; Zhang, Yiwei

2017-11-06

In recent decades, measures of child well-being have evolved from single dimension to multidimensional measures. Multi-dimensional measures deepen and broaden our understanding of child well-being and inform us of areas of neglect. Child well-being in China today is measured through proxy measures of household need. This paper discusses the evolution of child well-being measures more generally, explores the benefits of positive indicators and multiple dimensions in formulating policy, and then reviews efforts to date by the Chinese government, researchers, and non-governmental and intergovernmental organizations to develop comprehensive multidimensional measures of child well-being in China. The domains and their potential interactions, as well as data sources and availability, are presented. The authors believe that child well-being in China would benefit from the development of a multidimensional index and that there is sufficient data to develop such an index.

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.

Inequalities for trace anomalies, length of the RG flow, distance between the fixed points and irreversibility

International Nuclear Information System (INIS)

Anselmi, Damiano

2004-01-01

I discuss several issues about the irreversibility of the RG flow and the trace anomalies c, a and a'. First I argue that in quantum field theory: (i) the scheme-invariant area Δ a' of the graph of the effective beta function between the fixed points defines the length of the RG flow; (ii) the minimum of Δ a' in the space of flows connecting the same UV and IR fixed points defines the (oriented) distance between the fixed points and (iii) in even dimensions, the distance between the fixed points is equal to Δ a = a UV - a IR . In even dimensions, these statements imply the inequalities 0 ≤ Δ a ≤ Δ a' and therefore the irreversibility of the RG flow. Another consequence is the inequality a ≤ c for free scalars and fermions (but not vectors), which can be checked explicitly. Secondly, I elaborate a more general axiomatic set-up where irreversibility is defined as the statement that there exist no pairs of non-trivial flows connecting interchanged UV and IR fixed points. The axioms, based on the notions of length of the flow, oriented distance between the fixed points and certain 'oriented-triangle inequalities', imply the irreversibility of the RG flow without a global a function. I conjecture that the RG flow is also irreversible in odd dimensions (without a global a function). In support of this, I check the axioms of irreversibility in a class of d = 3 theories where the RG flow is integrable at each order of the large N expansion

Irreversible thermodynamics, parabolic law and self-similar state in grain growth

International Nuclear Information System (INIS)

Rios, P.R.

2004-01-01

The formalism of the thermodynamic theory of irreversible processes is applied to grain growth to investigate the nature of the self-similar state and its corresponding parabolic law. Grain growth does not reach a steady state in the sense that the entropy production remains constant. However, the entropy production can be written as a product of two factors: a scale factor that tends to zero for long times and a scaled entropy production. It is suggested that the parabolic law and the self-similar state may be associated with the minimum of this scaled entropy production. This result implies that the parabolic law and the self-similar state have a sound irreversible thermodynamical basis

Visual modeling in an analysis of multidimensional data

Science.gov (United States)

Zakharova, A. A.; Vekhter, E. V.; Shklyar, A. V.; Pak, A. J.

2018-01-01

The article proposes an approach to solve visualization problems and the subsequent analysis of multidimensional data. Requirements to the properties of visual models, which were created to solve analysis problems, are described. As a perspective direction for the development of visual analysis tools for multidimensional and voluminous data, there was suggested an active use of factors of subjective perception and dynamic visualization. Practical results of solving the problem of multidimensional data analysis are shown using the example of a visual model of empirical data on the current state of studying processes of obtaining silicon carbide by an electric arc method. There are several results of solving this problem. At first, an idea of possibilities of determining the strategy for the development of the domain, secondly, the reliability of the published data on this subject, and changes in the areas of attention of researchers over time.

Multidimensional Scaling Localization Algorithm in Wireless Sensor Networks

Directory of Open Access Journals (Sweden)

Zhang Dongyang

2014-02-01

Full Text Available Due to the localization algorithm in large-scale wireless sensor network exists shortcomings both in positioning accuracy and time complexity compared to traditional localization algorithm, this paper presents a fast multidimensional scaling location algorithm. By positioning algorithm for fast multidimensional scaling, fast mapping initialization, fast mapping and coordinate transform can get schematic coordinates of node, coordinates Initialize of MDS algorithm, an accurate estimate of the node coordinates and using the PRORUSTES to analysis alignment of the coordinate and final position coordinates of nodes etc. There are four steps, and the thesis gives specific implementation steps of the algorithm. Finally, compared with stochastic algorithms and classical MDS algorithm experiment, the thesis takes application of specific examples. Experimental results show that: the proposed localization algorithm has fast multidimensional scaling positioning accuracy in ensuring certain circumstances, but also greatly improves the speed of operation.

The universal power and efficiency characteristics for irreversible reciprocating heat engine cycles

CERN Document Server

Qin Xiao Yong; Sun Feng Rui; Wu Chih

2003-01-01

The performance of irreversible reciprocating heat engine cycles with heat transfer loss and friction-like term loss is analysed using finite-time thermodynamics. The universal relations between the power output and the compression ratio, between the thermal efficiency and the compression ratio, and the optimal relation between power output and the efficiency of the cycles are derived. Moreover, analysis and optimization of the model were carried out in order to investigate the effect of cycle processes on the performance of the cycle using numerical examples. The results obtained herein include the performance characteristics of irreversible reciprocating Diesel, Otto, Atkinson and Brayton cycles.

A general nonlinear evolution equation for irreversible conservative approach to stable equilibrium

International Nuclear Information System (INIS)

Beretta, G.P.

1986-01-01

This paper addresses a mathematical problem relevant to the question of nonequilibrium and irreversibility, namely, that of ''designing'' a general evolution equation capable of describing irreversible but conservative relaxtion towards equilibrium. The objective is to present an interesting mathematical solution to this design problem, namely, a new nonlinear evolution equation that satisfies a set of very stringent relevant requirements. Three different frameworks are defined from which the new equation could be adopted, with entirely different interpretations. Some useful well-known mathematics involving Gram determinants are presented and a nonlinear evolution equation is given which meets the stringent design specifications

Development of multi-dimensional body image scale for malaysian female adolescents.

Science.gov (United States)

Chin, Yit Siew; Taib, Mohd Nasir Mohd; Shariff, Zalilah Mohd; Khor, Geok Lin

2008-01-01

The present study was conducted to develop a Multi-dimensional Body Image Scale for Malaysian female adolescents. Data were collected among 328 female adolescents from a secondary school in Kuantan district, state of Pahang, Malaysia by using a self-administered questionnaire and anthropometric measurements. The self-administered questionnaire comprised multiple measures of body image, Eating Attitude Test (EAT-26; Garner & Garfinkel, 1979) and Rosenberg Self-esteem Inventory (Rosenberg, 1965). The 152 items from selected multiple measures of body image were examined through factor analysis and for internal consistency. Correlations between Multi-dimensional Body Image Scale and body mass index (BMI), risk of eating disorders and self-esteem were assessed for construct validity. A seven factor model of a 62-item Multi-dimensional Body Image Scale for Malaysian female adolescents with construct validity and good internal consistency was developed. The scale encompasses 1) preoccupation with thinness and dieting behavior, 2) appearance and body satisfaction, 3) body importance, 4) muscle increasing behavior, 5) extreme dieting behavior, 6) appearance importance, and 7) perception of size and shape dimensions. Besides, a multidimensional body image composite score was proposed to screen negative body image risk in female adolescents. The result found body image was correlated with BMI, risk of eating disorders and self-esteem in female adolescents. In short, the present study supports a multi-dimensional concept for body image and provides a new insight into its multi-dimensionality in Malaysian female adolescents with preliminary validity and reliability of the scale. The Multi-dimensional Body Image Scale can be used to identify female adolescents who are potentially at risk of developing body image disturbance through future intervention programs.

Multidimensional Computerized Adaptive Testing for Indonesia Junior High School Biology

Science.gov (United States)

Kuo, Bor-Chen; Daud, Muslem; Yang, Chih-Wei

2015-01-01

This paper describes a curriculum-based multidimensional computerized adaptive test that was developed for Indonesia junior high school Biology. In adherence to the Indonesian curriculum of different Biology dimensions, 300 items was constructed, and then tested to 2238 students. A multidimensional random coefficients multinomial logit model was…

Irreversibility analysis for gravity driven non-Newtonian liquid film along an inclined isothermal plate

International Nuclear Information System (INIS)

Makinde, O.D.

2005-10-01

In this paper, the first and second law of thermodynamics are employed in order to study the inherent irreversibility for a gravity driven non-Newtonian Ostwald-de Waele power law liquid film along an inclined isothermal plate. Based on some simplified assumptions, the governing equations are obtained and solved analytically. Expressions for fluid velocity, temperature, volumetric entropy generation numbers, irreversibility distribution ratio and the Bejan number are also determined. (author)

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.

Analysis of Local Dependence and Multidimensionality in Graphical Loglinear Rasch Models

DEFF Research Database (Denmark)

Kreiner, Svend; Christensen, Karl Bang

2004-01-01

Local independence; Multidimensionality; Differential item functioning; Uniform local dependence and DIF; Graphical Rasch models; Loglinear Rasch model......Local independence; Multidimensionality; Differential item functioning; Uniform local dependence and DIF; Graphical Rasch models; Loglinear Rasch model...

Treatise on irreversible and statistical thermodynamics an introduction to nonclassical thermodynamics

CERN Document Server

Yourgrau, Wolfgang; Raw, Gough

2002-01-01

Extensively revised edition of a much-respected work examines thermodynamics of irreversible processes, general principles of statistical thermodynamics, assemblies of noninteracting structureless particles, and statistical theory. 1966 edition.

Influence of delayed pouring on irreversible hydrocolloid properties

Directory of Open Access Journals (Sweden)

Stéfani Becker Rodrigues

2012-10-01

Full Text Available The aim of this study was to evaluate the physical properties of irreversible hydrocolloid materials poured immediately and after different storage periods. Four alginates were tested: Color Change (Cavex; Hydrogum (Zhermack; Hydrogum 5 (Zhermack; and Hydro Print Premium (Coltene. Their physical properties, including the recovery from deformation (n = 3, compressive strength (n = 3, and detail reproduction and gypsum compatibility (n = 3, were analyzed according to ANSI/ADA specification no. 18. Specimens were stored at 23ºC and humidity and were then poured with gypsum immediately and after 1, 2, 3, 4, and 5 days. The data were analyzed by two-way analysis of variance (ANOVA and Tukey's test at p < 0.05. All of the alginate impression materials tested exhibited detail reproduction and gypsum compatibility at all times. Hydro Print Premium and Hydrogum 5 showed recovery from deformation, as established by ANSI/ADA specification no. 18, after 5 days of storage. As the storage time increased, the compressive strength values also increased. Considering the properties of compounds' recovery from deformation, compressive strength, and detail reproduction and gypsum compatibility, irreversible hydrocolloids should be poured immediately.

Irreversible entropy model for damage diagnosis in resistors

Energy Technology Data Exchange (ETDEWEB)

Cuadras, Angel, E-mail: angel.cuadras@upc.edu; Crisóstomo, Javier; Ovejas, Victoria J.; Quilez, Marcos [Instrumentation, Sensor and Interfaces Group, Electronic Engineering Department, Escola d' Enginyeria de Telecomunicació i Aeronàutica de Castelldefels EETAC, Universitat Politècnica de Catalunya, Barcelona Tech (UPC), Castelldefels-Barcelona (Spain)

2015-10-28

We propose a method to characterize electrical resistor damage based on entropy measurements. Irreversible entropy and the rate at which it is generated are more convenient parameters than resistance for describing damage because they are essentially positive in virtue of the second law of thermodynamics, whereas resistance may increase or decrease depending on the degradation mechanism. Commercial resistors were tested in order to characterize the damage induced by power surges. Resistors were biased with constant and pulsed voltage signals, leading to power dissipation in the range of 4–8 W, which is well above the 0.25 W nominal power to initiate failure. Entropy was inferred from the added power and temperature evolution. A model is proposed to understand the relationship among resistance, entropy, and damage. The power surge dissipates into heat (Joule effect) and damages the resistor. The results show a correlation between entropy generation rate and resistor failure. We conclude that damage can be conveniently assessed from irreversible entropy generation. Our results for resistors can be easily extrapolated to other systems or machines that can be modeled based on their resistance.

Irreversible entropy model for damage diagnosis in resistors

International Nuclear Information System (INIS)

Cuadras, Angel; Crisóstomo, Javier; Ovejas, Victoria J.; Quilez, Marcos

2015-01-01

We propose a method to characterize electrical resistor damage based on entropy measurements. Irreversible entropy and the rate at which it is generated are more convenient parameters than resistance for describing damage because they are essentially positive in virtue of the second law of thermodynamics, whereas resistance may increase or decrease depending on the degradation mechanism. Commercial resistors were tested in order to characterize the damage induced by power surges. Resistors were biased with constant and pulsed voltage signals, leading to power dissipation in the range of 4–8 W, which is well above the 0.25 W nominal power to initiate failure. Entropy was inferred from the added power and temperature evolution. A model is proposed to understand the relationship among resistance, entropy, and damage. The power surge dissipates into heat (Joule effect) and damages the resistor. The results show a correlation between entropy generation rate and resistor failure. We conclude that damage can be conveniently assessed from irreversible entropy generation. Our results for resistors can be easily extrapolated to other systems or machines that can be modeled based on their resistance

Advanced Caries Microbiota in Teeth with Irreversible Pulpitis.

Science.gov (United States)

Rôças, Isabela N; Lima, Kenio C; Assunção, Isauremi V; Gomes, Patrícia N; Bracks, Igor V; Siqueira, José F

2015-09-01

Bacterial taxa in the forefront of caries biofilms are candidate pathogens for irreversible pulpitis and are possibly the first ones to invade the pulp and initiate endodontic infection. This study examined the microbiota of the most advanced layers of dentinal caries in teeth with irreversible pulpitis. DNA extracted from samples taken from deep dentinal caries associated with pulp exposures was analyzed for the presence and relative levels of 33 oral bacterial taxa by using reverse-capture checkerboard hybridization assay. Quantification of total bacteria, streptococci, and lactobacilli was also performed by using real-time quantitative polymerase chain reaction. Associations between the target bacterial taxa and clinical signs/symptoms were also evaluated. The most frequently detected taxa in the checkerboard assay were Atopobium genomospecies C1 (53%), Pseudoramibacter alactolyticus (37%), Streptococcus species (33%), Streptococcus mutans (33%), Parvimonas micra (13%), Fusobacterium nucleatum (13%), and Veillonella species (13%). Streptococcus species, Dialister invisus, and P. micra were significantly associated with throbbing pain, S. mutans with pain to percussion, and Lactobacillus with continuous pain (P pulpitis is suspected. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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.

Multidimensional Databases and Data Warehousing

DEFF Research Database (Denmark)

Jensen, Christian S.; Pedersen, Torben Bach; Thomsen, Christian

The present book's subject is multidimensional data models and data modeling concepts as they are applied in real data warehouses. The book aims to present the most important concepts within this subject in a precise and understandable manner. The book's coverage of fundamental concepts includes...

Background elimination methods for multidimensional coincidence γ-ray spectra

International Nuclear Information System (INIS)

Morhac, M.

1997-01-01

In the paper new methods to separate useful information from background in one, two, three and multidimensional spectra (histograms) measured in large multidetector γ-ray arrays are derived. The sensitive nonlinear peak clipping algorithm is the basis of the methods for estimation of the background in multidimensional spectra. The derived procedures are simple and therefore have a very low cost in terms of computing time. (orig.)

Multidimensional Poverty and Health Status as a Predictor of Chronic Income Poverty.

Science.gov (United States)

Callander, Emily J; Schofield, Deborah J

2015-12-01

Longitudinal analysis of Wave 5 to 10 of the nationally representative Household, Income and Labour Dynamics in Australia dataset was undertaken to assess whether multidimensional poverty status can predict chronic income poverty. Of those who were multidimensionally poor (low income plus poor health or poor health and insufficient education attainment) in 2007, and those who were in income poverty only (no other forms of disadvantage) in 2007, a greater proportion of those in multidimensional poverty continued to be in income poverty for the subsequent 5 years through to 2012. People who were multidimensionally poor in 2007 had 2.17 times the odds of being in income poverty each year through to 2012 than those who were in income poverty only in 2005 (95% CI: 1.23-3.83). Multidimensional poverty measures are a useful tool for policymakers to identify target populations for policies aiming to improve equity and reduce chronic disadvantage. Copyright © 2014 John Wiley & Sons, Ltd.

Towards Optimal Multi-Dimensional Query Processing with BitmapIndices

Energy Technology Data Exchange (ETDEWEB)

Rotem, Doron; Stockinger, Kurt; Wu, Kesheng

2005-09-30

Bitmap indices have been widely used in scientific applications and commercial systems for processing complex, multi-dimensional queries where traditional tree-based indices would not work efficiently. This paper studies strategies for minimizing the access costs for processing multi-dimensional queries using bitmap indices with binning. Innovative features of our algorithm include (a) optimally placing the bin boundaries and (b) dynamically reordering the evaluation of the query terms. In addition, we derive several analytical results concerning optimal bin allocation for a probabilistic query model. Our experimental evaluation with real life data shows an average I/O cost improvement of at least a factor of 10 for multi-dimensional queries on datasets from two different applications. Our experiments also indicate that the speedup increases with the number of query dimensions.

Microbiome of Deep Dentinal Caries Lesions in Teeth with Symptomatic Irreversible Pulpitis.

Science.gov (United States)

Rôças, Isabela N; Alves, Flávio R F; Rachid, Caio T C C; Lima, Kenio C; Assunção, Isauremi V; Gomes, Patrícia N; Siqueira, José F

2016-01-01

This study used a next-generation sequencing approach to identify the bacterial taxa occurring in the advanced front of caries biofilms associated with pulp exposure and irreversible pulpitis. Samples were taken from the deepest layer of dentinal caries lesions associated with pulp exposure in 10 teeth diagnosed with symptomatic irreversible pulpitis. DNA was extracted and the microbiome was characterized on the basis of the V4 hypervariable region of the 16S rRNA gene by using paired-end sequencing on Illumina MiSeq device. Bacterial taxa were mapped to 14 phyla and 101 genera composed by 706 different OTUs. Three phyla accounted for approximately 98% of the sequences: Firmicutes, Actinobacteria and Proteobacteria. These phyla were also the ones with most representatives at the species level. Firmicutes was the most abundant phylum in 9/10 samples. As for genera, Lactobacillus accounted for 42.3% of the sequences, followed by Olsenella (13.7%), Pseudoramibacter (10.7%) and Streptococcus (5.5%). Half of the samples were heavily dominated by Lactobacillus, while in the other half lactobacilli were in very low abundance and the most dominant genera were Pseudoramibacter, Olsenella, Streptococcus, and Stenotrophomonas. High bacterial diversity occurred in deep dentinal caries lesions associated with symptomatic irreversible pulpitis. The microbiome could be classified according to the relative abundance of Lactobacillus. Except for Lactobacillus species, most of the highly prevalent and abundant bacterial taxa identified in this study have been commonly detected in infected root canals. The detected taxa can be regarded as candidate pathogens for irreversible pulpitis and possibly the pioneers in pulp invasion to initiate endodontic infection.

Microbiome of Deep Dentinal Caries Lesions in Teeth with Symptomatic Irreversible Pulpitis.

Directory of Open Access Journals (Sweden)

Isabela N Rôças

Full Text Available This study used a next-generation sequencing approach to identify the bacterial taxa occurring in the advanced front of caries biofilms associated with pulp exposure and irreversible pulpitis. Samples were taken from the deepest layer of dentinal caries lesions associated with pulp exposure in 10 teeth diagnosed with symptomatic irreversible pulpitis. DNA was extracted and the microbiome was characterized on the basis of the V4 hypervariable region of the 16S rRNA gene by using paired-end sequencing on Illumina MiSeq device. Bacterial taxa were mapped to 14 phyla and 101 genera composed by 706 different OTUs. Three phyla accounted for approximately 98% of the sequences: Firmicutes, Actinobacteria and Proteobacteria. These phyla were also the ones with most representatives at the species level. Firmicutes was the most abundant phylum in 9/10 samples. As for genera, Lactobacillus accounted for 42.3% of the sequences, followed by Olsenella (13.7%, Pseudoramibacter (10.7% and Streptococcus (5.5%. Half of the samples were heavily dominated by Lactobacillus, while in the other half lactobacilli were in very low abundance and the most dominant genera were Pseudoramibacter, Olsenella, Streptococcus, and Stenotrophomonas. High bacterial diversity occurred in deep dentinal caries lesions associated with symptomatic irreversible pulpitis. The microbiome could be classified according to the relative abundance of Lactobacillus. Except for Lactobacillus species, most of the highly prevalent and abundant bacterial taxa identified in this study have been commonly detected in infected root canals. The detected taxa can be regarded as candidate pathogens for irreversible pulpitis and possibly the pioneers in pulp invasion to initiate endodontic infection.

Extended irreversible thermodynamics and the Jeffreys type constitutive equations

International Nuclear Information System (INIS)

Serdyukov, S.I.

2003-01-01

A postulate of extended irreversible thermodynamics is considered, according to which the entropy density is a function of the internal energy, the specific volume, and their material time derivatives. On the basis of this postulate, entropy balance equations and phenomenological equations are obtained, which directly lead to the Jeffreys type constitutive equations

Bifactor Approach to Modeling Multidimensionality of Physical Self-Perception Profile

Science.gov (United States)

Chung, ChihMing; Liao, Xiaolan; Song, Hairong; Lee, Taehun

2016-01-01

The multi-dimensionality of Physical Self-Perception Profile (PSPP) has been acknowledged by the use of correlated-factor model and second-order model. In this study, the authors critically endorse the bifactor model, as a substitute to address the multi-dimensionality of PSPP. To cross-validate the models, analyses are conducted first in…

Multidimensional quantum entanglement with large-scale integrated optics

DEFF Research Database (Denmark)

Wang, Jianwei; Paesani, Stefano; Ding, Yunhong

2018-01-01

-dimensional entanglement. A programmable bipartite entangled system is realized with dimension up to 15 × 15 on a large-scale silicon-photonics quantum circuit. The device integrates more than 550 photonic components on a single chip, including 16 identical photon-pair sources. We verify the high precision, generality......The ability to control multidimensional quantum systems is key for the investigation of fundamental science and for the development of advanced quantum technologies. We demonstrate a multidimensional integrated quantum photonic platform able to generate, control and analyze high...

Effects of irreversibility and economics on the performance of a heat engine

International Nuclear Information System (INIS)

Ibrahim, O.M.; Klein, S.A.; Mitchell, J.W.

1992-01-01

In this paper, optimization of the power output of an internally irreversible heat engine is considered for finite capacitance rates of the external fluid streams. The method of Lagrange multipliers is used to solve for working fluid temperatures which yield maximum power. Analytical expressions for the maximum power and the cycle efficiency at miximum power are obtained. The effects of irreversibility and economics on the performance of a heat engine are investigated. A relationship between the maximum power point and economically optimum design is identified. It is demonstrated that, with certain reasonable economic assumptions, the maximum power point of a heat engine corresponds to a point of minimum life-cycle costs

Simulation of a Multidimensional Input Quantum Perceptron

Science.gov (United States)

Yamamoto, Alexandre Y.; Sundqvist, Kyle M.; Li, Peng; Harris, H. Rusty

2018-06-01

In this work, we demonstrate the improved data separation capabilities of the Multidimensional Input Quantum Perceptron (MDIQP), a fundamental cell for the construction of more complex Quantum Artificial Neural Networks (QANNs). This is done by using input controlled alterations of ancillary qubits in combination with phase estimation and learning algorithms. The MDIQP is capable of processing quantum information and classifying multidimensional data that may not be linearly separable, extending the capabilities of the classical perceptron. With this powerful component, we get much closer to the achievement of a feedforward multilayer QANN, which would be able to represent and classify arbitrary sets of data (both quantum and classical).

On multidimensional item response theory -- a coordinate free approach

OpenAIRE

Antal, Tamás

2007-01-01

A coordinate system free definition of complex structure multidimensional item response theory (MIRT) for dichotomously scored items is presented. The point of view taken emphasizes the possibilities and subtleties of understanding MIRT as a multidimensional extension of the ``classical'' unidimensional item response theory models. The main theorem of the paper is that every monotonic MIRT model looks the same; they are all trivial extensions of univariate item response theory.

An Analysis of Multi-dimensional Gender Inequality in Pakistan

OpenAIRE

Abdul Hamid; Aisha M. Ahmed

2011-01-01

Women make almost half of the population of Pakistan. They also contribute significantly to economic and social growth. However, in developing countries like Pakistan, women usually suffer from multidimensional inequality of opportunities leading to multidimensional poverty. The dimensions of family, women identity, health, education and women access to economic resources and employment contribute significantly to the discrimination of women. The provision of more opportunities to women in th...

Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer.

Science.gov (United States)

Liu, Bing; Huang, XinPing; Hu, YunLong; Chen, TingTing; Peng, BoYa; Gao, NingNing; Jin, ZhenChao; Jia, TieLiu; Zhang, Na; Wang, ZhuLin; Jin, GuangYi

2016-09-06

Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer.

Positive Feedback of NDT80 Expression Ensures Irreversible Meiotic Commitment in Budding Yeast

Science.gov (United States)

Tsuchiya, Dai; Yang, Yang; Lacefield, Soni

2014-01-01

In budding yeast, meiotic commitment is the irreversible continuation of the developmental path of meiosis. After reaching meiotic commitment, cells finish meiosis and gametogenesis, even in the absence of the meiosis-inducing signal. In contrast, if the meiosis-inducing signal is removed and the mitosis-inducing signal is provided prior to reaching meiotic commitment, cells exit meiosis and return to mitosis. Previous work has shown that cells commit to meiosis after prophase I but before entering the meiotic divisions. Since the Ndt80 transcription factor induces expression of middle meiosis genes necessary for the meiotic divisions, we examined the role of the NDT80 transcriptional network in meiotic commitment. Using a microfluidic approach to analyze single cells, we found that cells commit to meiosis in prometaphase I, after the induction of the Ndt80-dependent genes. Our results showed that high-level expression of NDT80 is important for the timing and irreversibility of meiotic commitment. A modest reduction in NDT80 levels delayed meiotic commitment based on meiotic stages, although the timing of each meiotic stage was similar to that of wildtype cells. A further reduction of NDT80 resulted in the surprising finding of inappropriately uncommitted cells: withdrawal of the meiosis-inducing signal and addition of the mitosis-inducing signal to cells at stages beyond metaphase I caused return to mitosis, leading to multi-nucleate cells. Since Ndt80 enhances its own transcription through positive feedback, we tested whether positive feedback ensured the irreversibility of meiotic commitment. Ablating positive feedback in NDT80 expression resulted in a complete loss of meiotic commitment. These findings suggest that irreversibility of meiotic commitment is a consequence of the NDT80 transcriptional positive feedback loop, which provides the high-level of Ndt80 required for the developmental switch of meiotic commitment. These results also illustrate the

Dimensional Stability of Color-Changing Irreversible Hydrocolloids after Disinfection

Directory of Open Access Journals (Sweden)

Khaledi AAR

2015-03-01

Full Text Available Statement of Problem: Disinfection of dental impressions is a weak point in the dental hygiene chain. In addition, dental office personnel and dental technicians are endangered by cross-contamination. Objectives: This study aimed to investigate the dimensional stability of two color-changing irreversible hydrocolloid materials (IH after disinfection with glutaraldehyde. Materials and Methods: In this in vitro study, impressions were made of a master maxillary arch containing three reference inserts on the occlucal surface of the left and right maxillary second molars and in the incisal surface of the maxillary central incisors. Two types of color-changing irreversible hydrocolloid (tetrachrom, cavex were used. Glutaraldehyde 2% was used in two methods of spraying and immersion to disinfect the impressions. The control group was not disinfected. Casts were made of type IV gypsum. The linear dimensional change of the stone casts was measured with a profile projector. For statistical analysis, Kruskall-Wallis and Mann-Witney tests were used (α=0.05. Results: By immersion method, the casts fabricated from tetrachrom were 0.36% larger in the anteroposterior (AP and 0.05% smaller in cross arch (CA dimensions; however, the casts prepared after spraying of tetrachrom were 0.44% larger in the AP and 0.10% smaller in CA dimensions. The casts made from Cavex were 0.05% smaller in the AP and 0.02% smaller in CA dimensions after spraying and 0.01% smaller in the AP and 0.003% smaller in CA dimensions after immersion. Generally there were not significant differences in AP and CA dimensions of the experimental groups compared to the control (p > 0.05. Conclusions: Disinfection of the tested color-changing irreversible hydrocolloids by glutaraldahyde 2% did not compromise the accuracy of the obtained casts.

Behavior of the irreversibility line in the new superconductor La1.5+xBa1.5+x-yCayCu3Oz

International Nuclear Information System (INIS)

Parra Vargas, C.A.; Pimentel, J.L.; Pureur, P.; Landínez Téllez, D.A.; Roa-Rojas, J.

2012-01-01

The irreversibility properties of high-T c superconductors are of major importance for technological applications. For example, a high irreversibility magnetic field is a more desirable quality for a superconductor . The irreversibility line in the H-T plane is constituted by experimental points, which divides the irreversible and reversible behavior of the magnetization. The irreversibility lines for series of La 1.5+x Ba 1.5+x-y Ca y Cu 3 O z polycrystalline samples with different doping were investigated. The samples were synthesized using the usual solid estate reaction method. Rietveld-type refinement of x-ray diffraction patterns permitted to determine the crystallization of material in a tetragonal structure. Curves of magnetization ZFC-FC for the system La 1.5+x Ba 1.5+x-y Ca y Cu 3 O z , were measured in magnetic fields of the 10-20,000 Oe, and allowed to obtain the values for the irreversibility and critical temperatures. The data of irreversibility temperature allowed demarcating the irreversibility line, T irr (H). Two main lines are used for the interpretation of the irreversibility line: one of those which suppose that the vortexes are activated thermally and the other proposes that associated to T irr a phase transition occurs. The irreversibility line is described by a power law. The obtained results allow concluding that in the system La 1.5+x Ba 1.5+x-y Ca y Cu 3 O z a characteristic bend of the Almeida-Thouless (AT) tendency is dominant for low fields and a bend Gabay-Toulouse (GT) behavior for high magnetic fields. This feature of the irreversibility line has been reported as a characteristic of granular superconductors and it corroborates the topological effects of vortexes mentioned by several authors .

A Multidimensional Software Engineering Course

Science.gov (United States)

Barzilay, O.; Hazzan, O.; Yehudai, A.

2009-01-01

Software engineering (SE) is a multidimensional field that involves activities in various areas and disciplines, such as computer science, project management, and system engineering. Though modern SE curricula include designated courses that address these various subjects, an advanced summary course that synthesizes them is still missing. Such a…

Magnetic irreversibility in granular superconductors: ac susceptibility study

International Nuclear Information System (INIS)

Perez, F.; Obradors, X.; Fontcuberta, J.; Vallet, M.; Gonzalez-Calbet, J.

1991-01-01

Ac susceptibility measurements of a ceramic weak-coupled superconductor in very low ac fields (2mG, 111Hz) are reported. We present evidence for the observation of the magnetic irreversibility following a ZFC-FC thermal cycling by means of ac susceptibilty measurements. It is shown that this technique also reflect local magnetic field effects in granular superconductors, as previously suggested in microwave surface resistance and I-V characteristics. (orig.)

Effect of disinfection on irreversible hydrocolloid and alternative impression materials and the resultant gypsum casts.

Science.gov (United States)

Suprono, Montry S; Kattadiyil, Mathew T; Goodacre, Charles J; Winer, Myron S

2012-10-01

Many new products have been introduced and marketed as alternatives to traditional irreversible hydrocolloid materials. These alternative materials have the same structural formula as addition reaction silicone, also known as vinyl polysiloxane (VPS), impression materials. Currently, there is limited in vitro and in vivo research on these products, including on the effects of chemical disinfectants on the materials. The purpose of this study was to compare the effects of a spray disinfecting technique on a traditional irreversible hydrocolloid and 3 new alternative impression materials in vitro. The tests were performed in accordance with the American National Standards Institute/American Dental Association (ANSI/ADA) Specification Nos. 18 and 19. Under standardized conditions, 100 impressions were made of a ruled test block with an irreversible hydrocolloid and 3 alternative impression materials. Nondisinfected irreversible hydrocolloid was used as the control. The impressions were examined for surface detail reproduction before and after disinfection with a chloramine-T product. Type III and Type V dental stone casts were evaluated for linear dimensional change and gypsum compatibility. Comparisons of linear dimensional change were analyzed with 2-way ANOVA of mean ranks with the Scheffé post hoc comparisons (α=.05). Data for surface detail reproduction were analyzed with the Wilcoxon Signed-Rank procedure and gypsum compatibility with the Kruskal-Wallis Rank procedure (α=.05). The alternative impression materials demonstrated significantly better outcomes with all 3 parameters tested. Disinfection with chloroamine-T did not have any effect on the 3 alternative impression materials. The irreversible hydrocolloid groups produced the most variability in the measurements of linear dimensional change. All of the tested materials were within the ADA's acceptable limit of 1.0% for linear dimensional change, except for the disinfected irreversible hydrocolloid

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.

A review of snapshot multidimensional optical imaging: Measuring photon tags in parallel

Energy Technology Data Exchange (ETDEWEB)

Gao, Liang, E-mail: gaol@illinois.edu [Department of Electrical and Computer Engineering, University of Illinois at Urbana–Champaign, 306 N. Wright St., Urbana, IL 61801 (United States); Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana–Champaign, 405 North Mathews Avenue, Urbana, IL 61801 (United States); Wang, Lihong V., E-mail: lhwang@wustl.edu [Optical imaging laboratory, Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Dr., MO, 63130 (United States)

2016-02-29

Multidimensional optical imaging has seen remarkable growth in the past decade. Rather than measuring only the two-dimensional spatial distribution of light, as in conventional photography, multidimensional optical imaging captures light in up to nine dimensions, providing unprecedented information about incident photons’ spatial coordinates, emittance angles, wavelength, time, and polarization. Multidimensional optical imaging can be accomplished either by scanning or parallel acquisition. Compared with scanning-based imagers, parallel acquisition–also dubbed snapshot imaging–has a prominent advantage in maximizing optical throughput, particularly when measuring a datacube of high dimensions. Here, we first categorize snapshot multidimensional imagers based on their acquisition and image reconstruction strategies, then highlight the snapshot advantage in the context of optical throughput, and finally we discuss their state-of-the-art implementations and applications.

Irreversible dilation of NaCl contaminated lime-cement mortar due to crystallization cycles

International Nuclear Information System (INIS)

Lubelli, B.; Hees, R.P.J. van; Huinink, H.P.; Groot, C.J.W.P.

2006-01-01

The mechanism of damage occurring in NaCl contaminated materials has not been clarified yet. Apart from crystallization pressure, other hypotheses have been proposed to explain the cause of decay. Irreversible dilation has been observed in a few cases but has never been studied in a more systematic way. The aim of the research is to contribute to the modeling of this phenomenon. In the present paper the effect of NaCl on the hydric and hygric behavior of a lime-cement mortar is extensively studied. The results indicate that NaCl influences the hydric and hygric dilation behavior of the material. The material contaminated with NaCl shrinks during dissolution and dilates during crystallization of the salt. This dilation is irreversible and sufficient to damage the material after few dissolution/crystallization cycles. This behavior is not restricted to NaCl, but is observed in the presence of other salts as well (NaNO 3 and KCl). Outcomes of electron microscopy studies suggest that salts causing irreversible dilation tend to crystallize as layers on the pore wall

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).

Unifying principles of irreversibility minimization for efficiency maximization in steady-flow chemically-reactive engines

International Nuclear Information System (INIS)

Ramakrishnan, Sankaran; Edwards, Christopher F.

2014-01-01

Systems research has led to the conception and development of various steady-flow, chemically-reactive, engine cycles for stationary power generation and propulsion. However, the question that remains unanswered is: What is the maximum-efficiency steady-flow chemically-reactive engine architecture permitted by physics? On the one hand the search for higher-efficiency cycles continues, often involving newer processes and devices (fuel cells, carbon separation, etc.); on the other hand the design parameters for existing cycles are continually optimized in response to improvements in device engineering. In this paper we establish that any variation in engine architecture—parametric change or process-sequence change—contributes to an efficiency increase via one of only two possible ways to minimize total irreversibility. These two principles help us unify our understanding from a large number of parametric analyses and cycle-optimization studies for any steady-flow chemically-reactive engine, and set a framework to systematically identify maximum-efficiency engine architectures. - Highlights: • A unified thermodynamic model to study chemically-reactive engine architectures is developed. • All parametric analyses of efficiency are unified by two irreversibility-minimization principles. • Variations in internal energy transfers yield a net work increase that is greater than engine irreversibility reduced. • Variations in external energy transfers yield a net work increase that is lesser than engine irreversibility reduced

Antibacterial efficacy and effect of Morinda citrifolia L. mixed with irreversible hydrocolloid for dental impressions: A randomized controlled trial.

Science.gov (United States)

Ahmed, A Shafath; Charles, P David; Cholan, R; Russia, M; Surya, R; Jailance, L

2015-08-01

This study aimed to evaluate whether the extract of Morinda citrifolia L. mixed with irreversible hydrocolloid powder decreases microbial contamination during impression making without affecting the resulting casts. Twenty volunteers were randomly divided into two groups (n = 10). Group A 30 ml extract of M. citrifolia L diluted in 30 ml of water was mixed to make the impression with irreversible hydrocolloid material. Group B 30 ml deionized water was mixed with irreversible hydrocolloid material to make the impressions following which the surface roughness and dimensional stability of casts were evaluated. Extract of M. citrifolia L. mixed with irreversible hydrocolloid decreased the percentage of microorganisms when compared with water (P impression quality.

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

Phase control of light amplification with dynamically irreversible pathways of population transfer in a Λ system

International Nuclear Information System (INIS)

Yuan Shi; Wu Jinhui; Gao Jinyue; Pan Chunliu

2002-01-01

We use the relative phase of two coherent fields for the control of light amplification with dynamically irreversible pathways of population transfer in a Λ system. The population inversion and gain with dynamically irreversible pathways of population transfer are shown as the relative phase is varied. We support our results by numerical calculation and analytical explanation

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.

Logic reversibility and thermodynamic irreversibility demonstrated by DNAzyme-based Toffoli and Fredkin logic gates.

Science.gov (United States)

Orbach, Ron; Remacle, Françoise; Levine, R D; Willner, Itamar

2012-12-26

The Toffoli and Fredkin gates were suggested as a means to exhibit logic reversibility and thereby reduce energy dissipation associated with logic operations in dense computing circuits. We present a construction of the logically reversible Toffoli and Fredkin gates by implementing a library of predesigned Mg(2+)-dependent DNAzymes and their respective substrates. Although the logical reversibility, for which each set of inputs uniquely correlates to a set of outputs, is demonstrated, the systems manifest thermodynamic irreversibility originating from two quite distinct and nonrelated phenomena. (i) The physical readout of the gates is by fluorescence that depletes the population of the final state of the machine. This irreversible, heat-releasing process is needed for the generation of the output. (ii) The DNAzyme-powered logic gates are made to operate at a finite rate by invoking downhill energy-releasing processes. Even though the three bits of Toffoli's and Fredkin's logically reversible gates manifest thermodynamic irreversibility, we suggest that these gates could have important practical implication in future nanomedicine.

Health, Wealth and Wisdom: Exploring Multidimensional Inequality in a Developing Country

Science.gov (United States)

Nilsson, Therese

2010-01-01

Despite a broad theoretical literature on multidimensional inequality and a widespread belief that welfare is not synonymous to income--not the least in a developing context--empirical inequality examinations rarely includes several welfare attributes. We explore three techniques on how to evaluate multidimensional inequality using Zambian…

Extended irreversible thermodynamics and non-equilibrium temperature

Directory of Open Access Journals (Sweden)

Casas-Vazquez, Jose'

2008-02-01

Full Text Available We briefly review the concept of non-equilibrium temperature from the perspectives of extended irreversible thermodynamics, fluctuation theory, and statistical mechanics. The relations between different proposals are explicitly examined in two especially simple systems: an ideal gas in steady shear flow and a forced harmonic oscillator in a thermal bath. We examine with special detail temperatures related to the average molecular kinetic energy along different spatial directions, to the average configurational energy, to the derivative of the entropy with respect to internal energy, to fluctuation-dissipation relation and discuss their measurement.

Statistical mechanics out of equilibrium the irreversibility

International Nuclear Information System (INIS)

Alvarez Estrada, R. F.

2001-01-01

A Round Table about the issue of Irreversibility and related matters has taken place during the last (20th) Statistical Mechanics Conference, held in Paris (July 1998). This article tries to provide a view (necessarily limited, and hence, uncompleted) of some approaches to the subject: the one based upon deterministic chaos (which is currently giving rise to a very active research) and the classical interpretation due to Boltzmann. An attempt has been made to write this article in a self-contained way, and to avoid a technical presentation wherever possible. (Author) 29 refs

Transition from reversible to irreversible magnetic exchange-spring processes in antiferromagnetically exchange-coupled hard/soft/hard trilayer structures

International Nuclear Information System (INIS)

Wang Xiguang; Guo Guanghua; Zhang Guangfu

2011-01-01

The demagnetization processes of antiferromagnetically exchange-coupled hard/soft/hard trilayer structures have been studied based on the discrete one-dimensional atomic chain model and the linear partial domain-wall model. It is found that, when the magnetic anisotropy of soft layer is taken into account, the changes of the soft layer thickness and the interfacial exchange coupling strength may lead a transition of demagnetization process in soft layer from the reversible to the irreversible magnetic exchange-spring process. For the trilayer structures with very thin soft layer, the demagnetization process exhibits typical reversible exchange-spring behavior. However, as the thickness of soft layer is increased, there is a crossover point t c , after which the process becomes irreversible. Similarly, there is also a critical interfacial exchange coupling constant A sh c , above which the exchange-spring process is reversible. When A sh sh c , the irreversible exchange-spring process is achieved. The phase diagram of reversible and irreversible exchange-spring processes is mapped in the plane of the interfacial exchange coupling A sh and soft layer thickness N s . - Research highlights: → A differing magnetic exchange-spring process is found in antiferromagnetically exchange-coupled hard/soft/hard trilayers if the magnetic anisotropy of the soft layers is taken into account. → The change of the soft layer thickness may lead to a transition of demagnetization process in soft layer from the reversible to the irreversible exchange-spring process. → The change of the soft-hard interfacial exchange coupling strength may lead a transition of demagnetization process in soft layer from the reversible to the irreversible exchange-spring process. → The phase diagram of reversible and irreversible exchange-spring processes is mapped in the plane of the interfacial exchange coupling and soft layer thickness.

Recycling Behavior: A Multidimensional Approach

Science.gov (United States)

Meneses, Gonzalo Diaz; Palacio, Asuncion Beerli

2005-01-01

This work centers on the study of consumer recycling roles to examine the sociodemographic and psychographic profile of the distribution of recycling tasks and roles within the household. With this aim in mind, an empirical work was carried out, the results of which suggest that recycling behavior is multidimensional and comprises the undertaking…

Understanding Irreversible Degradation of Nb3Sn Wires with Fundamental Fracture Mechanics

Energy Technology Data Exchange (ETDEWEB)

Zhai, Yuhu [PPPL; Calzolaio, Ciro [Univ of Geneva; Senatore, Carmine [Univ of Geneva

2014-08-01

Irreversible performance degradation of advanced Nb3Sn superconducting wires subjected to transverse or axial mechanical loading is a critical issue for the design of large-scale fusion and accelerator magnets such as ITER and LHC. Recent SULTAN tests indicate that most cable-in-conduit conductors for ITER coils made of Nb3Sn wires processed by various fabrication techniques show similar performance degradation under cyclic loading. The irreversible degradation due to filament fracture and local strain accumulation in Nb3Sn wires cannot be described by the existing strand scaling law. Fracture mechanic modeling combined with X-ray diffraction imaging of filament micro-crack formation inside the wires under mechanical loading may reveal exciting insights to the wire degradation mechanisms. We apply fundamental fracture mechanics with a singularity approach to study influence of wire filament microstructure of initial void size and distribution to local stress concentration and potential crack propagation. We report impact of the scale and density of the void structure on stress concentration in the composite wire materials for crack initiation. These initial defects result in an irreversible degradation of the critical current beyond certain applied stress. We also discuss options to minimize stress concentration in the design of the material microstructure for enhanced wire performance for future applications.

Cationic peptide exposure enhances pulsed-electric-field-mediated membrane disruption.

Science.gov (United States)

Kennedy, Stephen M; Aiken, Erik J; Beres, Kaytlyn A; Hahn, Adam R; Kamin, Samantha J; Hagness, Susan C; Booske, John H; Murphy, William L

2014-01-01

The use of pulsed electric fields (PEFs) to irreversibly electroporate cells is a promising approach for destroying undesirable cells. This approach may gain enhanced applicability if the intensity of the PEF required to electrically disrupt cell membranes can be reduced via exposure to a molecular deliverable. This will be particularly impactful if that reduced PEF minimally influences cells that are not exposed to the deliverable. We hypothesized that the introduction of charged molecules to the cell surfaces would create regions of enhanced transmembrane electric potential in the vicinity of each charged molecule, thereby lowering the PEF intensity required to disrupt the plasma membranes. This study will therefore examine if exposure to cationic peptides can enhance a PEF's ability to disrupt plasma membranes. We exposed leukemia cells to 40 μs PEFs in media containing varying concentrations of a cationic peptide, polyarginine. We observed the internalization of a membrane integrity indicator, propidium iodide (PI), in real time. Based on an individual cell's PI fluorescence versus time signature, we were able to determine the relative degree of membrane disruption. When using 1-2 kV/cm, exposure to >50 μg/ml of polyarginine resulted in immediate and high levels of PI uptake, indicating severe membrane disruption, whereas in the absence of peptide, cells predominantly exhibited signatures indicative of no membrane disruption. Additionally, PI entered cells through the anode-facing membrane when exposed to cationic peptide, which was theoretically expected. Exposure to cationic peptides reduced the PEF intensity required to induce rapid and irreversible membrane disruption. Critically, peptide exposure reduced the PEF intensities required to elicit irreversible membrane disruption at normally sub-electroporation intensities. We believe that these cationic peptides, when coupled with current advancements in cell targeting techniques will be useful tools in

A MULTIDIMENSIONAL AND MULTIPHYSICS APPROACH TO NUCLEAR FUEL BEHAVIOR SIMULATION

Energy Technology Data Exchange (ETDEWEB)

R. L. Williamson; J. D. Hales; S. R. Novascone; M. R. Tonks; D. R. Gaston; C. J. Permann; D. Andrs; R. C. Martineau

2012-04-01

Important aspects of fuel rod behavior, for example pellet-clad mechanical interaction (PCMI), fuel fracture, oxide formation, non-axisymmetric cooling, and response to fuel manufacturing defects, are inherently multidimensional in addition to being complicated multiphysics problems. Many current modeling tools are strictly 2D axisymmetric or even 1.5D. This paper outlines the capabilities of a new fuel modeling tool able to analyze either 2D axisymmetric or fully 3D models. These capabilities include temperature-dependent thermal conductivity of fuel; swelling and densification; fuel creep; pellet fracture; fission gas release; cladding creep; irradiation growth; and gap mechanics (contact and gap heat transfer). The need for multiphysics, multidimensional modeling is then demonstrated through a discussion of results for a set of example problems. The first, a 10-pellet rodlet, demonstrates the viability of the solution method employed. This example highlights the effect of our smeared cracking model and also shows the multidimensional nature of discrete fuel pellet modeling. The second example relies on our the multidimensional, multiphysics approach to analyze a missing pellet surface problem. As a final example, we show a lower-length-scale simulation coupled to a continuum-scale simulation.

Determining the complex modulus of alginate irreversible hydrocolloid dental material.

Science.gov (United States)

King, Shalinie; See, Howard; Thomas, Graham; Swain, Michael

2008-11-01

The aim of the study is to investigate the visco-elastic response of an alginate irreversible hydrocolloid dental impression material during setting. A novel squeeze film Micro-Fourier Rheometer (MFR, GBC Scientific Equipment, Australia) was used to determine the complex modulus of an alginate irreversible hydrocolloid dental impression material (Algident, ISO 1563 Class A Type 1, Dentalfarm Australia Pty. Ltd.) during setting after mixing. Data was collected every 30s for 10 min in one study and every 10 min for a total of 60 min in another study. A high level of repeatability was observed. The results indicate that the MFR is capable of recording the complex shear modulus of alginate irreversible hydrocolloid for 60 min from the start of mixing and to simultaneously report the changing visco-elastic parameters at all frequencies between 1 Hz and 100 Hz. The storage modulus shows a dramatic increase to 370% of its starting value after 6 min and then reduces to 55% after 60 min. The loss modulus increases to a maximum of 175% of its starting value after 10 min and then reduces to 94% after 60 min. The MFR enables the changes in the complex modulus through the complete setting process to be followed. It is anticipated this approach may provide a better method to compare the visco-elastic properties of impression materials and assist with identification of optimum types for different clinical requirements. The high stiffness of the instrument and the use of band-limited pseudo-random noise as the input signal are the main advantages of this technique over conventional rheometers for determining the changes in alginate visco-elasticity.

Irreversibility analysis for optimization design of plate fin heat exchangers using a multi-objective cuckoo search algorithm

International Nuclear Information System (INIS)

Wang, Zhe; Li, Yanzhong

2015-01-01

Highlights: • The first application of IMOCS for plate-fin heat exchanger design. • Irreversibility degrees of heat transfer and fluid friction are minimized. • Trade-off of efficiency, total cost and pumping power is achieved. • Both EGM and EDM methods have been compared in the optimization of PFHE. • This study has superiority over other single-objective optimization design. - Abstract: This paper introduces and applies an improved multi-objective cuckoo search (IMOCS) algorithm, a novel met-heuristic optimization algorithm based on cuckoo breeding behavior, for the multi-objective optimization design of plate-fin heat exchangers (PFHEs). A modified irreversibility degree of the PFHE is separated into heat transfer and fluid friction irreversibility degrees which are adopted as two initial objective functions to be minimized simultaneously for narrowing the search scope of the design. The maximization efficiency, minimization of pumping power, and total annual cost are considered final objective functions. Results obtained from a two dimensional normalized Pareto-optimal frontier clearly demonstrate the trade-off between heat transfer and fluid friction irreversibility. Moreover, a three dimensional Pareto-optimal frontier reveals a relationship between efficiency, total annual cost, and pumping power in the PFHE design. Three examples presented here further demonstrate that the presented method is able to obtain optimum solutions with higher accuracy, lower irreversibility, and fewer iterations as compared to the previous methods and single-objective design approaches

Anesthetic efficacy of articaine for inferior alveolar nerve blocks in patients with symptomatic versus asymptomatic irreversible pulpitis.

Science.gov (United States)

Argueta-Figueroa, Liliana; Arzate-Sosa, Gabriel; Mendieta-Zeron, Hugo

2012-01-01

This study sought to determine the anesthetic efficacy of 4% articaine with 1:100,000 epinephrine in patients with symptomatic and asymptomatic irreversible pulpitis in mandibular posterior teeth and if individual patient factors, pulpal disease characteristics, and previous medication are correlated to local anesthetic success. A second objective was to determine the specificity and sensibility of a cold test for prediction of anesthetic success prior to endodontic treatment. Seventy patients diagnosed with irreversible pulpitis in mandibular posterior teeth received 1.6 mL of 4% articaine with 1:100,000 epinephrine for an inferior alveolar nerve block (IANB) using a metal guide. The anesthetic solution was injected with a computer-preprogrammed delivery system for local anesthesia. Endodontic access was begun 15 minutes after solution deposition; later, patients rated their discomfort using the visual analog scale (VAS). The success rate for the IA NB using articaine was 64.2% in patients with symptomatic irreversible pulpitis and 86.9% in patients with asymptomatic irreversible pulpitis. Cold test prior to root canal treatment had a specificity and sensibility of 12.5% and 87.1%, respectively. The anesthetic efficacy of articaine in irreversible pulpitis is moderately acceptable, and anesthetic success increases when the patient has been premedicated with NSAIDs. The cold test appears to be a favorable indicator for predicting anesthetic success.

Lagrangian formulation of irreversible thermodynamics and the second law of thermodynamics.

Science.gov (United States)

Glavatskiy, K S

2015-05-28

We show that the equations which describe irreversible evolution of a system can be derived from a variational principle. We suggest a Lagrangian, which depends on the properties of the normal and the so-called "mirror-image" system. The Lagrangian is symmetric in time and therefore compatible with microscopic reversibility. The evolution equations in the normal and mirror-imaged systems are decoupled and describe therefore independent irreversible evolution of each of the systems. The second law of thermodynamics follows from a symmetry of the Lagrangian. Entropy increase in the normal system is balanced by the entropy decrease in the mirror-image system, such that there exists an "integral of evolution" which is a constant. The derivation relies on the property of local equilibrium, which states that the local relations between the thermodynamic quantities in non-equilibrium are the same as in equilibrium.

The analysis of irreversibility, uncertainty and dynamic technical inefficiency on the investment decision in the Spanish olive sector

NARCIS (Netherlands)

Lambarraa, Fatima; Stefanou, Spiro; Gil, José M.

2016-01-01

This study addresses irreversible investment decision-making in the context of uncertainty when allowing for inefficiency to be transmitted over time. Both irreversibility and persistence in technical inefficiency can lead to sluggish adjustment of quasi-fixed factors of production. The context

Revisiting the Glansdorff–Prigogine criterion for stability within irreversible thermodynamics

Czech Academy of Sciences Publication Activity Database

Maes, C.; Netočný, Karel

2015-01-01

Roč. 159, č. 6 (2015), s. 1286-1299 ISSN 0022-4715 R&D Projects: GA ČR GAP204/12/0897 Institutional support: RVO:68378271 Keywords : irreversible processes * thermodynamic stability * excess entropy production * nonequilibrium free energy * Clausius heat theorem Subject RIV: BE - Theoretical Physics Impact factor: 1.537, year: 2015

Multidimensional poverty: an alternative measurement approach for the United States?

Science.gov (United States)

Waglé, Udaya R

2008-06-01

International poverty research has increasingly underscored the need to use multidimensional approaches to measure poverty. Largely embraced in Europe and elsewhere, this has not had much impact on the way poverty is measured in the United States. In this paper, I use a comprehensive multidimensional framework including economic well-being, capability, and social inclusion to examine poverty in the US. Data from the 2004 General Social Survey support the interconnectedness among these poverty dimensions, indicating that the multidimensional framework utilizing a comprehensive set of information provides a compelling value added to poverty measurement. The suggested demographic characteristics of the various categories of the poor are somewhat similar between this approach and other traditional approaches. But the more comprehensive and accurate measurement outcomes from this approach help policymakers target resources at the specific groups.

A new multidimensional model with text dimensions: definition and implementation

Directory of Open Access Journals (Sweden)

MariaJ. Martin-Bautista

2013-02-01

Full Text Available We present a new multidimensional model with textual dimensions based on a knowledge structure extracted from the texts, where any textual attribute in a database can be processed, and not only XML texts. This dimension allows to treat the textual data in the same way as the non-textual one in an automatic way, without user's intervention, so all the classical operations in the multidimensional model can been defined for this textual dimension. While most of the models dealing with texts that can be found in the literature are not implemented, in this proposal, the multidimensional model and the OLAP system have been implemented in a software tool, so it can be tested on real data. A case study with medical data is included in this work.

Multi-dimensional simulations of core-collapse supernova explosions with CHIMERA

Science.gov (United States)

Messer, O. E. B.; Harris, J. A.; Hix, W. R.; Lentz, E. J.; Bruenn, S. W.; Mezzacappa, A.

2018-04-01

Unraveling the core-collapse supernova (CCSN) mechanism is a problem that remains essentially unsolved despite more than four decades of effort. Spherically symmetric models with otherwise high physical fidelity generally fail to produce explosions, and it is widely accepted that CCSNe are inherently multi-dimensional. Progress in realistic modeling has occurred recently through the availability of petascale platforms and the increasing sophistication of supernova codes. We will discuss our most recent work on understanding neutrino-driven CCSN explosions employing multi-dimensional neutrino-radiation hydrodynamics simulations with the Chimera code. We discuss the inputs and resulting outputs from these simulations, the role of neutrino radiation transport, and the importance of multi-dimensional fluid flows in shaping the explosions. We also highlight the production of 48Ca in long-running Chimera simulations.

Multi-dimensional quasitoeplitz Markov chains

Directory of Open Access Journals (Sweden)

Alexander N. Dudin

1999-01-01

Full Text Available This paper deals with multi-dimensional quasitoeplitz Markov chains. We establish a sufficient equilibrium condition and derive a functional matrix equation for the corresponding vector-generating function, whose solution is given algorithmically. The results are demonstrated in the form of examples and applications in queues with BMAP-input, which operate in synchronous random environment.

Multidimensional integral representations problems of analytic continuation

CERN Document Server

Kytmanov, Alexander M

2015-01-01

The monograph is devoted to integral representations for holomorphic functions in several complex variables, such as Bochner-Martinelli, Cauchy-Fantappiè, Koppelman, multidimensional logarithmic residue etc., and their boundary properties. The applications considered are problems of analytic continuation of functions from the boundary of a bounded domain in C^n. In contrast to the well-known Hartogs-Bochner theorem, this book investigates functions with the one-dimensional property of holomorphic extension along complex lines, and includes the problems of receiving multidimensional boundary analogs of the Morera theorem.   This book is a valuable resource for specialists in complex analysis, theoretical physics, as well as graduate and postgraduate students with an understanding of standard university courses in complex, real and functional analysis, as well as algebra and geometry.

Quantum degeneracy effect on performance of irreversible Otto cycle with ideal Bose gas

International Nuclear Information System (INIS)

Wu Feng; Chen Lingen; Sun Fengrui; Wu Chih; Guo Fangzhong; Li Qing

2006-01-01

An Otto cycle working with an ideal Bose gas is called a Bose Otto cycle. The internal irreversibility of the cycle is included in the factors of internal irreversibility degree. The quantum degeneracy effect on the performance of the cycle is investigated based on quantum statistical mechanics and thermodynamics. Variations of the maximum work output ratio R W and the efficiency ratio y with temperature ratio τ are examined, which reveal the influence of the quantum degeneracy of the working substance on the performance of a Bose Otto cycle. It is shown that the results obtained herein are valid under both classical and quantum ideal gas conditions

Using the Andrews Plotss to Visualize Multidimensional Data in Multi-criteria Optimization

Directory of Open Access Journals (Sweden)

S. V. Groshev

2015-01-01

Full Text Available Currently, issues on processing of large data volumes are of great importance. Initially, the Andrews plots have been proposed to show multidimensional statistics on the plane. But as the Andrews plots retain information on the average values of the represented values, distances, and dispersion, the distances between the plots linearly indicate distances between the data points, and it becomes possible to use the plots under consideration for the graphical representation of multi-dimensional data of various kinds. The paper analyses a diversity of various mathematical apparatus for Andrews plotting to visualize multi-dimensional data.The first section provides basic information about the Andrews plots, as well as about a test set of multidimensional data in Iris Fischer’s literature. Analysis of the Andrews plot properties shows that they provide a limitlessly many one-dimensional projections on the vectors and, furthermore, the plots, which are nearer to each other, correspond to nearly points. All this makes it possible to use the plots under consideration for multi-dimensional data representation. The paper considers the Andrews plot formation based on Fourier transform functions, and from the analysis results of plotting based on a set of the test, it draws a conclusion that in this way it is possible to provide clustering of multidimensional data.The second section of the work deals with research of different ways to modify the Andrews plots in order to improve the perception of the graphical representation of multidimensional data. Different variants of the Andrews plot projections on the coordinate planes and arbitrary subspaces are considered. In addition, the paper studies an effect of the Andrews plot scaling on the visual perception of multidimensional data.The paper’s third section describes Andrews plotting based on different polynomials, in particular, Chebyshev and Legendre polynomials. It is shown that the resulting image is

Evaluation of properties of irreversible hydrocolloid impression materials mixed with disinfectant liquids

Directory of Open Access Journals (Sweden)

Arul Amalan

2013-01-01

Conclusion: Chlorhexidine solution can be used to mix irreversible hydrocolloid impression materials in regular dental practice as it did not significantly alter the properties. This may ensure effective disinfection of impressions.

Development and application of computer codes for multidimensional thermalhydraulic analyses of nuclear reactor components

International Nuclear Information System (INIS)

Carver, M.B.

1983-01-01

Components of reactor systems and related equipment are identified in which multidimensional computational thermal hydraulics can be used to advantage to assess and improve design. Models of single- and two-phase flow are reviewed, and the governing equations for multidimensional analysis are discussed. Suitable computational algorithms are introduced, and sample results from the application of particular multidimensional computer codes are given

Pathways into chronic multidimensional poverty amongst older people: a longitudinal study.

Science.gov (United States)

Callander, Emily J; Schofield, Deborah J

2016-03-07

The use of multidimensional poverty measures is becoming more common for measuring the living standards of older people. However, the pathways into poverty are relatively unknown, nor is it known how this affects the length of time people are in poverty for. Using Waves 1 to 12 of the nationally representative Household, Income and Labour Dynamics in Australia (HILDA) survey, longitudinal analysis was undertaken to identify the order that key forms of disadvantage develop - poor health, low income and insufficient education attainment - amongst Australians aged 65 years and over in multidimensional poverty, and the relationship this has with chronic poverty. Path analysis and linear regression models were used. For all older people with at least a Year 10 level of education attainment earlier mental health was significantly related to later household income (p = 0.001) and wealth (p = 0.017). For all older people with at less than a Year 10 level of education attainment earlier household income was significantly related to later mental health (p = 0.021). When limited to those in multidimensional poverty who were in income poverty and also had poor health, older people generally fell into income poverty first and then developed poor health. The order in which income poverty and poor health were developed had a significant influence on the length of time older people with less than a Year 10 level of education attainment were in multidimensional poverty for. Those who developed poor health first then fell into income poverty spend significantly less time in multidimensional poverty (-4.90, p poverty then developed poor health. Knowing the order that different forms of disadvantage develop, and the influence this has on poverty entrenchment, is of use to policy makers wishing to provide interventions to prevent older people being in long-term multidimensional poverty.

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.

Multi-dimensional database design and implementation of dam safety monitoring system

Directory of Open Access Journals (Sweden)

Zhao Erfeng

2008-09-01

Full Text Available To improve the effectiveness of dam safety monitoring database systems, the development process of a multi-dimensional conceptual data model was analyzed and a logic design was achieved in multi-dimensional database mode. The optimal data model was confirmed by identifying data objects, defining relations and reviewing entities. The conversion of relations among entities to external keys and entities and physical attributes to tables and fields was interpreted completely. On this basis, a multi-dimensional database that reflects the management and analysis of a dam safety monitoring system on monitoring data information has been established, for which factual tables and dimensional tables have been designed. Finally, based on service design and user interface design, the dam safety monitoring system has been developed with Delphi as the development tool. This development project shows that the multi-dimensional database can simplify the development process and minimize hidden dangers in the database structure design. It is superior to other dam safety monitoring system development models and can provide a new research direction for system developers.

Multi-dimensional indoor location information model

NARCIS (Netherlands)

Xiong, Q.; Zhu, Q.; Zlatanova, S.; Huang, L.; Zhou, Y.; Du, Z.

2013-01-01

Aiming at the increasing requirements of seamless indoor and outdoor navigation and location service, a Chinese standard of Multidimensional Indoor Location Information Model is being developed, which defines ontology of indoor location. The model is complementary to 3D concepts like CityGML and

Irreversibility in room temperature current–voltage characteristics of NiFe_2O_4 nanoparticles: A signature of electrical memory effect

International Nuclear Information System (INIS)

Dey, P.; Debnath, Rajesh; Singh, Swati; Mandal, S.K.; Roy, J.N.

2017-01-01

Room temperature I–V characteristics study, both in presence and absence of magnetic field (1800 Oe), has been performed on NiFe_2O_4 nanoparticles, having different particle size (φ~14, 21 and 31 nm). Our experiments on these nanoparticles provide evidences for: (1) electrical irreversibility or hysteretic behaviour; (2) positive magnetoresistance and (3) magnetic field dependent electrical irreversibility or hysteresis in the sample. “Hysteretic” nature of I–V curve reveals the existence of electrical memory effect in the sample. Significantly, such hysteresis has been found to be tuned by magnetic field. In order to explain the observed electrical irreversibility, we have proposed a phenomenological model on the light of induced polarization in the sample. Both the positive magnetoresistance and the observed magnetic field dependence of electrical irreversibility have been explained through magnetostriction phenomenon. Interestingly, such effects are found to get reduced with increasing particle size. For NiFe_2O_4 nanoparticles having φ=31 nm, we did not observe any irreversibility effect. This feature has been attributed to the enhanced grain surface effect that in turn gives rise to the residual polarization and hence electrical memory effect in NiFe_2O_4 nanoparticles, having small nanoscopic particle size. - Highlights: • I-V characteristics study of NiFe_2O_4 nanoparticles with varying particle sizes. • Experiments evident electrical hysteretic behaviour, i.e., electrical memory effect. • Magnetic field dependent electrical irreversibility is due to magnetostriction. • A phenomenological model has been proposed on the light of induced polarization. • Such electrical irreversibility decreases with increasing particle sizes.

Frost Multidimensional Perfectionism Scale: the portuguese version

Directory of Open Access Journals (Sweden)

Ana Paula Monteiro Amaral

2013-01-01

Full Text Available BACKGROUND: The Frost Multidimensional Perfectionism Scale is one of the most world widely used measures of perfectionism. OBJECTIVE: To analyze the psychometric properties of the Portuguese version of the Frost Multidimensional Perfectionism Scale. METHODS: Two hundred and seventeen (178 females students from two Portuguese Universities filled in the scale, and a subgroup (n = 166 completed a retest with a four weeks interval. RESULTS: The scale reliability was good (Cronbach alpha = .857. Corrected item-total correlations ranged from .019 to .548. The scale test-retest reliability suggested a good temporal stability with a test-retest correlation of .765. A principal component analysis with Varimax rotation was performed and based on the Scree plot, two robust factorial structures were found (four and six factors. The principal component analyses, using Monte Carlo PCA for parallel analyses confirmed the six factor solution. The concurrent validity with Hewitt and Flett MPS was high, as well as the discriminant validity of positive and negative affect (Profile of Mood Stats-POMS. DISCUSSION: The two factorial structures (of four and six dimensions of the Portuguese version of Frost Multidimensional Perfectionism Scale replicate the results from different authors, with different samples and cultures. This suggests this scale is a robust instrument to assess perfectionism, in several clinical and research settings as well as in transcultural studies.

Model for an irreversible bias current in the superconducting qubit measurement process

International Nuclear Information System (INIS)

Hutchinson, G. D.; Williams, D. A.; Holmes, C. A.; Stace, T. M.; Spiller, T. P.; Barrett, S. D.; Milburn, G. J.; Hasko, D. G.

2006-01-01

The superconducting charge-phase ''quantronium'' qubit is considered in order to develop a model for the measurement process used in the experiment of Vion et al. [Science 296, 886 (2002)]. For this model we propose a method for including the bias current in the readout process in a fundamentally irreversible way, which to first order is approximated by the Josephson junction tilted-washboard potential phenomenology. The decohering bias current is introduced in the form of a Lindblad operator and the Wigner function for the current-biased readout Josephson junction is derived and analyzed. During the readout current pulse used in the quantronium experiment we find that the coherence of the qubit initially prepared in a symmetric superposition state is lost at a time of 0.2 ns after the bias current pulse has been applied, a time scale that is much shorter than the experimental readout time. Additionally we look at the effect of Johnson-Nyquist noise with zero mean from the current source during the qubit manipulation and show that the decoherence due to the irreversible bias current description is an order of magnitude smaller than that found through adding noise to the reversible tilted-washboard potential model. Our irreversible bias current model is also applicable to persistent-current-based qubits where the state is measured according to its flux via a small-inductance direct-current superconducting quantum interference device

How Effective Is Supplemental Intraseptal Anesthesia in Patients with Symptomatic Irreversible Pulpitis?

Science.gov (United States)

Webster, Stephen; Drum, Melissa; Reader, Al; Fowler, Sara; Nusstein, John; Beck, Mike

2016-10-01

Previous studies have reported high levels of success with intraseptal injection for various dental procedures but provide limited information on the use of the injection during endodontic treatment. Therefore, the purpose of this prospective study was to determine the anesthetic efficacy of the supplemental intraseptal technique in mandibular posterior teeth diagnosed with symptomatic irreversible pulpitis when the conventional inferior alveolar nerve (IAN) block failed. One hundred patients with a diagnosis of symptomatic irreversible pulpitis in a mandibular posterior tooth were recruited. Following profound lip numbness after the administration of the conventional IAN block, endodontic treatment was initiated. Patients still experiencing moderate to severe pain during treatment were administered mesial and distal supplemental intraseptal injections using 0.7 mL 4% articaine with 1:000,000 epinephrine administered with a computer-controlled local anesthetic delivery unit. Success was defined as the ability to perform endodontic access and instrumentation with mild to no pain. Success with the IAN block was achieved in 25% of patients. Supplemental intraseptal injections provided success in 29% of patients. Supplemental intraseptal injections achieved profound pulpal anesthesia in 29% of patients when the IAN block failed. This low level of success would not provide predictable levels of anesthesia for patients requiring emergency endodontic treatment for symptomatic irreversible pulpitis in mandibular posterior teeth. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The multidimensional nucleon structure

Directory of Open Access Journals (Sweden)

Pasquini Barbara

2016-01-01

Full Text Available We discuss different kinds of parton distributions, which allow one to obtain a multidimensional picture of the internal structure of the nucleon. We use the concept of generalized transverse momentum dependent parton distributions and Wigner distributions, which combine the features of transverse-momentum dependent parton distributions and generalized parton distributions. We show examples of these functions within a phenomenological quark model, with focus on the role of the spin-spin and spin-orbit correlations of quarks.

Multi-Dimensional Customer Data Analysis in Online Auctions

Institute of Scientific and Technical Information of China (English)

LAO Guoling; XIONG Kuan; QIN Zheng

2007-01-01

In this paper, we designed a customer-centered data warehouse system with five subjects: listing, bidding, transaction,accounts, and customer contact based on the business process of online auction companies. For each subject, we analyzed its fact indexes and dimensions. Then take transaction subject as example,analyzed the data warehouse model in detail, and got the multi-dimensional analysis structure of transaction subject. At last, using data mining to do customer segmentation, we divided customers into four types: impulse customer, prudent customer, potential customer, and ordinary customer. By the result of multi-dimensional customer data analysis, online auction companies can do more target marketing and increase customer loyalty.

Multidimensional artificial field embedding with spatial sensitivity

CSIR Research Space (South Africa)

Lunga, D

2013-06-01

Full Text Available Multidimensional embedding is a technique useful for characterizing spectral signature relations in hyperspectral images. However, such images consist of disjoint similar spectral classes that are spatially sensitive, thus presenting challenges...

Assessment of health surveys: fitting a multidimensional graded response model.

Science.gov (United States)

Depaoli, Sarah; Tiemensma, Jitske; Felt, John M

The multidimensional graded response model, an item response theory (IRT) model, can be used to improve the assessment of surveys, even when sample sizes are restricted. Typically, health-based survey development utilizes classical statistical techniques (e.g. reliability and factor analysis). In a review of four prominent journals within the field of Health Psychology, we found that IRT-based models were used in less than 10% of the studies examining scale development or assessment. However, implementing IRT-based methods can provide more details about individual survey items, which is useful when determining the final item content of surveys. An example using a quality of life survey for Cushing's syndrome (CushingQoL) highlights the main components for implementing the multidimensional graded response model. Patients with Cushing's syndrome (n = 397) completed the CushingQoL. Results from the multidimensional graded response model supported a 2-subscale scoring process for the survey. All items were deemed as worthy contributors to the survey. The graded response model can accommodate unidimensional or multidimensional scales, be used with relatively lower sample sizes, and is implemented in free software (example code provided in online Appendix). Use of this model can help to improve the quality of health-based scales being developed within the Health Sciences.

MCMC estimation of multidimensional IRT models

NARCIS (Netherlands)

Beguin, Anton; Glas, Cornelis A.W.

1998-01-01

A Bayesian procedure to estimate the three-parameter normal ogive model and a generalization to a model with multidimensional ability parameters are discussed. The procedure is a generalization of a procedure by J. Albert (1992) for estimating the two-parameter normal ogive model. The procedure will

Implementation of multidimensional databases in column-oriented NoSQL systems

OpenAIRE

Chevalier, Max; El Malki, Mohammed; Kopliku, Arlind; Teste, Olivier; Tournier, Ronan

2015-01-01

International audience; NoSQL (Not Only SQL) systems are becoming popular due to known advantages such as horizontal scalability and elasticity. In this paper, we study the implementation of multidimensional data warehouses with columnoriented NoSQL systems. We define mapping rules that transform the conceptual multidimensional data model to logical column-oriented models. We consider three different logical models and we use them to instantiate data warehouses. We focus on data loading, mode...

Portable laser synthesizer for high-speed multi-dimensional spectroscopy

Science.gov (United States)

Demos, Stavros G [Livermore, CA; Shverdin, Miroslav Y [Sunnyvale, CA; Shirk, Michael D [Brentwood, CA

2012-05-29

Portable, field-deployable laser synthesizer devices designed for multi-dimensional spectrometry and time-resolved and/or hyperspectral imaging include a coherent light source which simultaneously produces a very broad, energetic, discrete spectrum spanning through or within the ultraviolet, visible, and near infrared wavelengths. The light output is spectrally resolved and each wavelength is delayed with respect to each other. A probe enables light delivery to a target. For multidimensional spectroscopy applications, the probe can collect the resulting emission and deliver this radiation to a time gated spectrometer for temporal and spectral analysis.

Synergetcs - a field beyond irreversible thermodynamics

International Nuclear Information System (INIS)

Haken, H.

1978-01-01

This lecture introduces the reader to synergetics, a very young field of interdisciplinary research, which is devoted to the question of self-organization and, quite generally, to the birth of new qualities. After comparing the role of thermodynamics, irreversible thermodynamics and synergetics in the description of phenomena we give a few examples for self-oragnizing systems. Next we outline the mathematical approach and consider the generalized Ginzburg-Landau equations for non equilibrium phase transitions. We continue by applying these equations to the problem of morphogenesis in biology. We close our lecture by extending the formalism to spatially inhomogeneous or oscillating systems and arrive at order-parameter equations which are capable of describing new large classes of higher bifurcation schemes. (HJ)

Capital dissipation minimization for a class of complex irreversible resource exchange processes

Science.gov (United States)

Xia, Shaojun; Chen, Lingen

2017-05-01

A model of a class of irreversible resource exchange processes (REPes) between a firm and a producer with commodity flow leakage from the producer to a competitive market is established in this paper. The REPes are assumed to obey the linear commodity transfer law (LCTL). Optimal price paths for capital dissipation minimization (CDM) (it can measure economic process irreversibility) are obtained. The averaged optimal control theory is used. The optimal REP strategy is also compared with other strategies, such as constant-firm-price operation and constant-commodity-flow operation, and effects of the amount of commodity transferred and the commodity flow leakage on the optimal REP strategy are also analyzed. The commodity prices of both the producer and the firm for the CDM of the REPes with commodity flow leakage change with the time exponentially.

Irreversible thermodynamics of dark energy on the entropy-corrected apparent horizon

Energy Technology Data Exchange (ETDEWEB)

Karami, K; Sahraei, N [Department of Physics, University of Kurdistan, Pasdaran Street, Sanandaj (Iran, Islamic Republic of); Jamil, M, E-mail: KKarami@uok.ac.i, E-mail: mjamil@camp.nust.edu.p [Center for Advanced Mathematics and Physics (CAMP), National University of Sciences and Technology (NUST), Islamabad (Pakistan)

2010-10-15

We study the irreversible (non-equilibrium) thermodynamics of the Friedmann-Robertson-Walker (FRW) universe containing only dark energy. Using the modified entropy-area relation that is motivated by loop quantum gravity, we calculate the entropy-corrected form of the apparent horizon of the FRW universe.

Pulpitis irreversible como forma de presentación de un odontoma

OpenAIRE

Berástegui, Esther; Buenechea Imaz, Ramón

1997-01-01

Se presenta un caso de odontoma compuesto que provocó pulpitis irreversible en el incisivo central superior derecho (1,1) en una joven de 20 años. El tratamiento fue la biopulpectomía total y extirpación quirúrgica del tumor.

Exploring and linking biomedical resources through multidimensional semantic spaces.

Science.gov (United States)

Berlanga, Rafael; Jiménez-Ruiz, Ernesto; Nebot, Victoria

2012-01-25

The semantic integration of biomedical resources is still a challenging issue which is required for effective information processing and data analysis. The availability of comprehensive knowledge resources such as biomedical ontologies and integrated thesauri greatly facilitates this integration effort by means of semantic annotation, which allows disparate data formats and contents to be expressed under a common semantic space. In this paper, we propose a multidimensional representation for such a semantic space, where dimensions regard the different perspectives in biomedical research (e.g., population, disease, anatomy and protein/genes). This paper presents a novel method for building multidimensional semantic spaces from semantically annotated biomedical data collections. This method consists of two main processes: knowledge and data normalization. The former one arranges the concepts provided by a reference knowledge resource (e.g., biomedical ontologies and thesauri) into a set of hierarchical dimensions for analysis purposes. The latter one reduces the annotation set associated to each collection item into a set of points of the multidimensional space. Additionally, we have developed a visual tool, called 3D-Browser, which implements OLAP-like operators over the generated multidimensional space. The method and the tool have been tested and evaluated in the context of the Health-e-Child (HeC) project. Automatic semantic annotation was applied to tag three collections of abstracts taken from PubMed, one for each target disease of the project, the Uniprot database, and the HeC patient record database. We adopted the UMLS Meta-thesaurus 2010AA as the reference knowledge resource. Current knowledge resources and semantic-aware technology make possible the integration of biomedical resources. Such an integration is performed through semantic annotation of the intended biomedical data resources. This paper shows how these annotations can be exploited for

Testlet-Based Multidimensional Adaptive Testing.

Science.gov (United States)

Frey, Andreas; Seitz, Nicki-Nils; Brandt, Steffen

2016-01-01

Multidimensional adaptive testing (MAT) is a highly efficient method for the simultaneous measurement of several latent traits. Currently, no psychometrically sound approach is available for the use of MAT in testlet-based tests. Testlets are sets of items sharing a common stimulus such as a graph or a text. They are frequently used in large operational testing programs like TOEFL, PISA, PIRLS, or NAEP. To make MAT accessible for such testing programs, we present a novel combination of MAT with a multidimensional generalization of the random effects testlet model (MAT-MTIRT). MAT-MTIRT compared to non-adaptive testing is examined for several combinations of testlet effect variances (0.0, 0.5, 1.0, and 1.5) and testlet sizes (3, 6, and 9 items) with a simulation study considering three ability dimensions with simple loading structure. MAT-MTIRT outperformed non-adaptive testing regarding the measurement precision of the ability estimates. Further, the measurement precision decreased when testlet effect variances and testlet sizes increased. The suggested combination of the MTIRT model therefore provides a solution to the substantial problems of testlet-based tests while keeping the length of the test within an acceptable range.

Testlet-based Multidimensional Adaptive Testing

Directory of Open Access Journals (Sweden)

Andreas Frey

2016-11-01

Full Text Available Multidimensional adaptive testing (MAT is a highly efficient method for the simultaneous measurement of several latent traits. Currently, no psychometrically sound approach is available for the use of MAT in testlet-based tests. Testlets are sets of items sharing a common stimulus such as a graph or a text. They are frequently used in large operational testing programs like TOEFL, PISA, PIRLS, or NAEP. To make MAT accessible for such testing programs, we present a novel combination of MAT with a multidimensional generalization of the random effects testlet model (MAT-MTIRT. MAT-MTIRT compared to non-adaptive testing is examined for several combinations of testlet effect variances (0.0, 0.5, 1.0, 1.5 and testlet sizes (3 items, 6 items, 9 items with a simulation study considering three ability dimensions with simple loading structure. MAT-MTIRT outperformed non-adaptive testing regarding the measurement precision of the ability estimates. Further, the measurement precision decreased when testlet effect variances and testlet sizes increased. The suggested combination of the MTIRT model therefore provides a solution to the substantial problems of testlet-based tests while keeping the length of the test within an acceptable range.

Effect Size Measures for Differential Item Functioning in a Multidimensional IRT Model

Science.gov (United States)

Suh, Youngsuk

2016-01-01

This study adapted an effect size measure used for studying differential item functioning (DIF) in unidimensional tests and extended the measure to multidimensional tests. Two effect size measures were considered in a multidimensional item response theory model: signed weighted P-difference and unsigned weighted P-difference. The performance of…

Development and assessment of multi-dimensional flow model in MARS compared with the RPI air-water experiment

International Nuclear Information System (INIS)

Lee, Seok Min; Lee, Un Chul; Bae, Sung Won; Chung, Bub Dong

2004-01-01

The Multi-Dimensional flow models in system code have been developed during the past many years. RELAP5-3D, CATHARE and TRACE has its specific multi-dimensional flow models and successfully applied it to the system safety analysis. In KAERI, also, MARS(Multi-dimensional Analysis of Reactor Safety) code was developed by integrating RELAP5/MOD3 code and COBRA-TF code. Even though COBRA-TF module can analyze three-dimensional flow models, it has a limitation to apply 3D shear stress dominant phenomena or cylindrical geometry. Therefore, Multi-dimensional analysis models are newly developed by implementing three-dimensional momentum flux and diffusion terms. The multi-dimensional model has been assessed compared with multi-dimensional conceptual problems and CFD code results. Although the assessment results were reasonable, the multi-dimensional model has not been validated to two-phase flow using experimental data. In this paper, the multi-dimensional air-water two-phase flow experiment was simulated and analyzed

Implementation of the Multidimensional Modeling Concepts into Object-Relational Databases

Directory of Open Access Journals (Sweden)

2007-01-01

Full Text Available A key to survival in the business world is being able to analyze, plan and react to changing business conditions as fast as possible. With multidimensional models the managers can explore information at different levels of granularity and the decision makers at all levels can quickly respond to changes in the business climate-the ultimate goal of business intelligence. This paper focuses on the implementation of the multidimensional concepts into object-relational databases.

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.

Is thermodynamic irreversibility a consequence of the expansion of the Universe?

Science.gov (United States)

Osváth, Szabolcs

2018-02-01

This paper explains thermodynamic irreversibility by applying the expansion of the Universe to thermodynamic systems. The effect of metric expansion is immeasurably small on shorter scales than intergalactic distances. Multi-particle systems, however, are chaotic, and amplify any small disturbance exponentially. Metric expansion gives rise to time-asymmetric behaviour in thermodynamic systems in a short time (few nanoseconds in air, few ten picoseconds in water). In contrast to existing publications, this paper explains without any additional assumptions the rise of thermodynamic irreversibility from the underlying reversible mechanics of particles. Calculations for the special case which assumes FLRW metric, slow motions (v ≪ c) and approximates space locally by Euclidean space show that metric expansion causes entropy increase in isolated systems. The rise of time-asymmetry, however, is not affected by these assumptions. Any influence of the expansion of the Universe on the local metric causes a coupling between local mechanics and evolution of the Universe.

Time irreversibility and intrinsics revealing of series with complex network approach

Science.gov (United States)

Xiong, Hui; Shang, Pengjian; Xia, Jianan; Wang, Jing

2018-06-01

In this work, we analyze time series on the basis of the visibility graph algorithm that maps the original series into a graph. By taking into account the all-round information carried by the signals, the time irreversibility and fractal behavior of series are evaluated from a complex network perspective, and considered signals are further classified from different aspects. The reliability of the proposed analysis is supported by numerical simulations on synthesized uncorrelated random noise, short-term correlated chaotic systems and long-term correlated fractal processes, and by the empirical analysis on daily closing prices of eleven worldwide stock indices. Obtained results suggest that finite size has a significant effect on the evaluation, and that there might be no direct relation between the time irreversibility and long-range correlation of series. Similarity and dissimilarity between stock indices are also indicated from respective regional and global perspectives, showing the existence of multiple features of underlying systems.

Linear Dimensional Stability of Irreversible Hydrocolloid Materials Over Time.

Science.gov (United States)

Garrofé, Analía B; Ferrari, Beatriz A; Picca, Mariana; Kaplan, Andrea E

2015-12-01

The aim of this study was to evaluate the linear dimensional stability of different irreversible hydrocolloid materials over time. A metal mold was designed with custom trays made of thermoplastic sheets (Sabilex, sheets 0.125 mm thick). Perforations were made in order to improve retention of the material. Five impressions were taken with each of the following: Kromopan 100 (LASCOD) [AlKr], which has dimensional stability of 100 hours, and Phase Plus (ZHERMACK) [AlPh], which has dimensional stability of 48 hours. Standardized digital photographs were taken at different time intervals (0, 15, 30, 45, 60, 120 minutes; 12, 24 and 96 hours), using an "ad-hoc" device. The images were analyzed with software (UTHSCSA Image Tool) by measuring the distance between intersection of the lines previously made at the top of the mold. The results were analyzed by ANOVA for repeated measures. Initial and final values were (mean and standard deviation): AlKr: 16.44 (0.22) and 16.34 (0.11), AlPh: 16.40 (0.06) and 16.18 (0.06). Statistical evaluation showed significant effect of material and time factors. Under the conditions in this study, time significantly affects the linear dimensional stability of irreversible hydrocolloid materials. Sociedad Argentina de Investigación Odontológica.

Multi-dimensional Bin Packing Problems with Guillotine Constraints

DEFF Research Database (Denmark)

Amossen, Rasmus Resen; Pisinger, David

2010-01-01

The problem addressed in this paper is the decision problem of determining if a set of multi-dimensional rectangular boxes can be orthogonally packed into a rectangular bin while satisfying the requirement that the packing should be guillotine cuttable. That is, there should exist a series of face...... parallel straight cuts that can recursively cut the bin into pieces so that each piece contains a box and no box has been intersected by a cut. The unrestricted problem is known to be NP-hard. In this paper we present a generalization of a constructive algorithm for the multi-dimensional bin packing...... problem, with and without the guillotine constraint, based on constraint programming....

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

Irreversible membrane fouling abatement through pre-deposited layer of hierarchical porous carbons

KAUST Repository

Hamad, Juma; Dua, Rubal; Kurniasari, Novita; Kennedy, Maria Dolores; Wang, Peng; Amy, Gary L.

2014-01-01

In this work, dual-templated hierarchical porous carbons (HPCs), produced from a coupled ice-hard templating approach, are shown to be a highly effective solution to the commonly occurring problem of irreversible fouling of low-pressure membranes

Deriving Multidimensional Poverty Indicators: Methodological Issues and an Empirical Analysis for Italy

Science.gov (United States)

Coromaldi, Manuela; Zoli, Mariangela

2012-01-01

Theoretical and empirical studies have recently adopted a multidimensional concept of poverty. There is considerable debate about the most appropriate degree of multidimensionality to retain in the analysis. In this work we add to the received literature in two ways. First, we derive indicators of multiple deprivation by applying a particular…

Multi-objective optimization and exergetic-sustainability of an irreversible nano scale Braysson cycle operating with Ma

Directory of Open Access Journals (Sweden)

Mohammad H. Ahmadi

2016-06-01

Full Text Available Nano technology is developed in this decade and changes the way of life. Moreover, developing nano technology has effect on the performance of the materials and consequently improves the efficiency and robustness of them. So, nano scale thermal cycles will be probably engaged in the near future. In this paper, a nano scale irreversible Braysson cycle is studied thermodynamically for optimizing the performance of the Braysson cycle. In the aforementioned cycle an ideal Maxwell–Boltzmann gas is used as a working fluid. Furthermore, three different plans are used for optimizing with multi-objectives; though, the outputs of the abovementioned plans are assessed autonomously. Throughout the first plan, with the purpose of maximizing the ecological coefficient of performance and energy efficiency of the system, multi-objective optimization algorithms are used. Furthermore, in the second plan, two objective functions containing the ecological coefficient of performance and the dimensionless Maximum available work are maximized synchronously by utilizing multi-objective optimization approach. Finally, throughout the third plan, three objective functions involving the dimensionless Maximum available work, the ecological coefficient of performance and energy efficiency of the system are maximized synchronously by utilizing multi-objective optimization approach. The multi-objective evolutionary approach based on the non-dominated sorting genetic algorithm approach is used in this research. Making a decision is performed by three different decision makers comprising linear programming approaches for multidimensional analysis of preference and an approach for order of preference by comparison with ideal answer and Bellman–Zadeh. Lastly, analysis of error is employed to determine deviation of the outcomes gained from each plan.

Measures for a multidimensional multiverse

Science.gov (United States)

Chung, Hyeyoun

2015-04-01

We explore the phenomenological implications of generalizing the causal patch and fat geodesic measures to a multidimensional multiverse, where the vacua can have differing numbers of large dimensions. We consider a simple model in which the vacua are nucleated from a D -dimensional parent spacetime through dynamical compactification of the extra dimensions, and compute the geometric contribution to the probability distribution of observations within the multiverse for each measure. We then study how the shape of this probability distribution depends on the time scales for the existence of observers, for vacuum domination, and for curvature domination (tobs,tΛ , and tc, respectively.) In this work we restrict ourselves to bubbles with positive cosmological constant, Λ . We find that in the case of the causal patch cutoff, when the bubble universes have p +1 large spatial dimensions with p ≥2 , the shape of the probability distribution is such that we obtain the coincidence of time scales tobs˜tΛ˜tc . Moreover, the size of the cosmological constant is related to the size of the landscape. However, the exact shape of the probability distribution is different in the case p =2 , compared to p ≥3 . In the case of the fat geodesic measure, the result is even more robust: the shape of the probability distribution is the same for all p ≥2 , and we once again obtain the coincidence tobs˜tΛ˜tc . These results require only very mild conditions on the prior probability of the distribution of vacua in the landscape. Our work shows that the observed double coincidence of time scales is a robust prediction even when the multiverse is generalized to be multidimensional; that this coincidence is not a consequence of our particular Universe being (3 +1 )-dimensional; and that this observable cannot be used to preferentially select one measure over another in a multidimensional multiverse.

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

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.

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.

Multidimensional HAM-conditions

DEFF Research Database (Denmark)

Hansen, Ernst Jan de Place

Heat, Air and Moisture (HAM) conditions, experimental data are needed. Tests were performed in the large climate simulator at SBi involving full-scale wall elements. The elements were exposed for steady-state conditions, and temperature cycles simulating April and September climate in Denmark....... The effect on the moisture and temperature conditions of the addition of a vapour barrier and an outer cladding on timber frame walls was studied. The report contains comprehensive appendices documenting the full-scale tests. The tests were performed as a part of the project 'Model for Multidimensional Heat......, Air and Moisture Conditions in Building Envelope Components' carried out as a co-project between DTU Byg and SBi....

Anomalies, Unitarity and Quantum Irreversibility

CERN Document Server

Anselmi, D

1999-01-01

The trace anomaly in external gravity is the sum of three terms at criticality: the square of the Weyl tensor, the Euler density and Box R, with coefficients, properly normalized, called c, a and a', the latter being ambiguously defined by an additive constant. Unitarity and positivity properties of the induced actions allow us to show that the total RG flows of a and a' are equal and therefore the a'-ambiguity can be consistently removed through the identification a'=a. The picture that emerges clarifies several long-standing issues. The interplay between unitarity and renormalization implies that the flux of the renormalization group is irreversible. A monotonically decreasing a-function interpolating between the appropriate values is naturally provided by a'. The total a-flow is expressed non-perturbatively as the invariant (i.e. scheme-independent) area of the graph of the beta function between the fixed points. We test this prediction to the fourth loop order in perturbation theory, in QCD with Nf ~< ...

Irreversible pulpitis and achieving profound anesthesia: Complexities and managements

OpenAIRE

Modaresi, Jalil; Davoudi, Amin; Badrian, Hamid; Sabzian, Roya

2016-01-01

Dental pain management is one of the most critical aspects of modern dentistry. Irreversible pulpitis and further root canal therapy might cause an untolerated pain to the patients. The improvements in anesthetic agents and techniques were one of the advantages of studying nerve biology and stimulation. This article tried to overview of the nerve activities in inflammatory environments or induced pain. Furthermore, the proper advises, and supplementary techniques were reviewed for better pain...

Irreversibility and multiplicity: two criteria for the disposal of nuclear wastes

International Nuclear Information System (INIS)

Rochlin, G.

1976-01-01

Two criteria are suggested for comparing waste management methods: technical irreversibility and site multiplicity. These criteria can be used to reduce future risk in the face of inherent uncertainty and to provide for safe disposal without requiring guaranteed future ability to recognize, detect or repair areas of failure

SM4MQ: A Semantic Model for Multidimensional Queries

DEFF Research Database (Denmark)

Varga, Jovan; Dobrokhotova, Ekaterina; Romero, Oscar

2017-01-01

On-Line Analytical Processing (OLAP) is a data analysis approach to support decision-making. On top of that, Exploratory OLAP is a novel initiative for the convergence of OLAP and the Semantic Web (SW) that enables the use of OLAP techniques on SW data. Moreover, OLAP approaches exploit different......, sharing, and reuse on the SW. As OLAP is based on the underlying multidimensional (MD) data model we denote such queries as MD queries and define SM4MQ: A Semantic Model for Multidimensional Queries. Furthermore, we propose a method to automate the exploitation of queries by means of SPARQL. We apply...

Modelling of multidimensional quantum systems by the numerical functional integration

International Nuclear Information System (INIS)

Lobanov, Yu.Yu.; Zhidkov, E.P.

1990-01-01

The employment of the numerical functional integration for the description of multidimensional systems in quantum and statistical physics is considered. For the multiple functional integrals with respect to Gaussian measures in the full separable metric spaces the new approximation formulas exact on a class of polynomial functionals of a given summary degree are constructed. The use of the formulas is demonstrated on example of computation of the Green function and the ground state energy in multidimensional Calogero model. 15 refs.; 2 tabs

Exactly solvable irreversible processes on one-dimensional lattices

International Nuclear Information System (INIS)

Wolf, N.O.; Evans, J.W.; Hoffman, D.K.

1984-01-01

We consider the kinetics of a process where the sites of an infinite 1-D lattice are filled irreversibly and, in general, cooperatively by N-mers (taking N consecutive sites at a time). We extend the previously available exact solution for nearest neighbor cooperative effects to range N cooperative effects. Connection with the continuous ''cooperative car parking problem'' is indicated. Both uniform and periodic lattices, and empty and certain partially filled lattice initial conditions are considered. We also treat monomer ''filling in stages'' for certain highly autoinhibitory cooperative effects of arbitrary range

Multidimensional poverty and catastrophic health spending in the mountainous regions of Myanmar, Nepal and India.

Science.gov (United States)

Mohanty, Sanjay K; Agrawal, Nand Kishor; Mahapatra, Bidhubhusan; Choudhury, Dhrupad; Tuladhar, Sabarnee; Holmgren, E Valdemar

2017-01-18

Economic burden to households due to out-of-pocket expenditure (OOPE) is large in many Asian countries. Though studies suggest increasing household poverty due to high OOPE in developing countries, studies on association of multidimensional poverty and household health spending is limited. This paper tests the hypothesis that the multidimensionally poor are more likely to incur catastrophic health spending cutting across countries. Data from the Poverty and Vulnerability Assessment (PVA) Survey carried out by the International Center for Integrated Mountain Development (ICIMOD) has been used in the analyses. The PVA survey was a comprehensive household survey that covered the mountainous regions of India, Nepal and Myanmar. A total of 2647 households from India, 2310 households in Nepal and 4290 households in Myanmar covered under the PVA survey. Poverty is measured in a multidimensional framework by including the dimensions of education, income and energy, water and sanitation using the Alkire and Foster method. Health shock is measured using the frequency of illness, family sickness and death of any family member in a reference period of one year. Catastrophic health expenditure is defined as 40% above the household's capacity to pay. Results suggest that about three-fifths of the population in Myanmar, two-fifths of the population in Nepal and one-third of the population in India are multidimensionally poor. About 47% of the multidimensionally poor in India had incurred catastrophic health spending compared to 35% of the multidimensionally non-poor and the pattern was similar in both Nepal and Myanmar. The odds of incurring catastrophic health spending was 56% more among the multidimensionally poor than among the multidimensionally non-poor [95% CI: 1.35-1.76]. While health shocks to households are consistently significant predictors of catastrophic health spending cutting across country of residence, the educational attainment of the head of the household is

Quantum and Multidimensional Explanations in a Neurobiological Context of Mind.

Science.gov (United States)

Korf, Jakob

2015-08-01

This article examines the possible relevance of physical-mathematical multidimensional or quantum concepts aiming at understanding the (human) mind in a neurobiological context. Some typical features of the quantum and multidimensional concepts are briefly introduced, including entanglement, superposition, holonomic, and quantum field theories. Next, we consider neurobiological principles, such as the brain and its emerging (physical) mind, evolutionary and ontological origins, entropy, syntropy/neg-entropy, causation, and brain energy metabolism. In many biological processes, including biochemical conversions, protein folding, and sensory perception, the ubiquitous involvement of quantum mechanisms is well recognized. Quantum and multidimensional approaches might be expected to help describe and model both brain and mental processes, but an understanding of their direct involvement in mental activity, that is, without mediation by molecular processes, remains elusive. More work has to be done to bridge the gap between current neurobiological and physical-mathematical concepts with their associated quantum-mind theories. © The Author(s) 2014.

Almost-sure identifiability of multidimensional harmonic retrieval

NARCIS (Netherlands)

Jiang, T; Sidiropoulos, ND; ten Berge, JMF

Two-dimensional (2-D) and, more generally, multidimensional harmonic retrieval is of interest in a variety of applications, including transmitter localization and joint time and frequency offset estimation in wireless communications. The associated identifiability problem is key in understanding the

Origin of the irreversibility line in thin YBa2Cu3O7-δ films with and without columnar defects

International Nuclear Information System (INIS)

Prozorov, R.; Konczykowski, M.; Schmidt, B.; Yeshurun, Y.; Shaulov, A.; Villard, C.; Koren, G.

1996-01-01

We report on measurements of the angular dependence of the irreversibility temperature T irr (θ) in YBa 2 Cu 3 O 7-δ thin films, defined by the onset of a third-harmonic signal and measured by a miniature Hall probe. From the functional form of T irr (θ) we conclude that the origin of the irreversibility line in unirradiated films is a dynamic crossover from an unpinned to a pinned vortex liquid. In irradiated films the irreversibility temperature is determined by the trapping angle. copyright 1996 The American Physical Society