SU-G-IeP4-10: Microimaging for Different Degrees of Human Cavernous Hemangioma of Liver by Using In-Line Phase-Contrast Imaging CT

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

Duan, J

2016-06-15

Purpose: Cavernous hemangioma of the liver (CHL) is the most common benign solid tumor of the liver. In this study, we quantitative assessment the different degrees of CHL from microscopic viewpoint by using in-line phase-contrast imaging CT (ILPCI-CT). Methods: The experiments were performed at x-ray imaging and biomedical application beamline (BL13W1) of Shanghai Synchrotron Radiation Facility (SSRF) in China. Three typical specimens at different stages, i.e., mild, moderate and severe human CHL were imaged using ILPCI-CT at 16keV without contrast agents. The 3D visualization of different degrees of CHL samples were presented using ILPCI-CT. Additionally, quantitative evaluation of the CHLmore » features, such as the range of hepatic sinusoid equivalent diameters in different degrees of CHL samples, the ratio of the hepatic sinusoid to the CHL tissue, were measured. Results: The planar image clearly displayed the dilated hepatic sinusoids in microns. There was no normal hepatic vascular found in the all CHL samples. Different stages of CHL samples were presented with vivid shapes and stereoscopic effects by using 3D visualization. The equivalent diameters of hepatic sinusoids in three degrees CHL were different. The equivalent diameters of the hepatic sinusoids in mild CHL, range from 60 to 120 µm. The equivalent diameters of the hepatic sinusoids in moderate CHL, range from 65 to 190 µm. The equivalent diameters of the hepatic sinusoids in severe CHL, range from 95 to 215 µm. The ratio of the hepatic sinusoid to the mild, moderate and severe CHL tissue were 3%, 16% and 21%, respectively. Conclusion: The results show that the high degree of sensitivity of the ILPCI-CT technique and demonstrate the feasibility of accurate visualization of different stage human CHL. ILPCI-CT may offers a potential use in non-invasive study and analysis of CHL.« less

Hepatic sinusoidal cells in health and disease: update from the 14th International Symposium.

PubMed

Smedsrød, Bård; Le Couteur, David; Ikejima, Kenichi; Jaeschke, Hartmut; Kawada, Norifumi; Naito, Makoto; Knolle, Percy; Nagy, Laura; Senoo, Haruki; Vidal-Vanaclocha, Fernando; Yamaguchi, Noriko

2009-04-01

This review aims to give an update of the field of the hepatic sinusoid, supported by references to presentations given at the 14th International Symposium on Cells of the Hepatic Sinusoid (ISCHS2008), which was held in Tromsø, Norway, August 31-September 4, 2008. The subtitle of the symposium, 'Integrating basic and clinical hepatology', signified the inclusion of both basal and applied clinical results of importance in the field of liver sinusoidal physiology and pathophysiology. Of nearly 50 oral presentations, nine were invited tutorial lectures. The authors of the review have avoided writing a 'flat summary' of the presentations given at ISCHS2008, and instead focused on important novel information. The tutorial presentations have served as a particularly important basis in the preparation of this update. In this review, we have also included references to recent literature that may not have been covered by the ISCHS2008 programme. The sections of this review reflect the scientific programme of the symposium (http://www.ub.uit.no/munin/bitstream/10037/1654/1/book.pdf): 1. Liver sinusoidal endothelial cells. 2. Kupffer cells. 3. Hepatic stellate cells. 4. Immunology. 5. Tumor/metastasis. Symposium abstracts are referred to by a number preceded by the letter A.

Engineered liquid crystal anchoring energies with nanopatterned surfaces.

PubMed

Gear, Christopher; Diest, Kenneth; Liberman, Vladimir; Rothschild, Mordechai

2015-01-26

The anchoring energy of liquid crystals was shown to be tunable by surface nanopatterning of periodic lines and spaces. Both the pitch and height were varied using hydrogen silsesquioxane negative tone electron beam resist, providing for flexibility in magnitude and spatial distribution of the anchoring energy. Using twisted nematic liquid crystal cells, it was shown that this energy is tunable over an order of magnitude. These results agree with a literature model which predicts the anchoring energy of sinusoidal grooves.

False Operation of Static Random Access Memory Cells under Alternating Current Power Supply Voltage Variation

NASA Astrophysics Data System (ADS)

Sawada, Takuya; Takata, Hidehiro; Nii, Koji; Nagata, Makoto

2013-04-01

Static random access memory (SRAM) cores exhibit susceptibility against power supply voltage variation. False operation is investigated among SRAM cells under sinusoidal voltage variation on power lines introduced by direct RF power injection. A standard SRAM core of 16 kbyte in a 90 nm 1.5 V technology is diagnosed with built-in self test and on-die noise monitor techniques. The sensitivity of bit error rate is shown to be high against the frequency of injected voltage variation, while it is not greatly influenced by the difference in frequency and phase against SRAM clocking. It is also observed that the distribution of false bits is substantially random in a cell array.

Energy storage cell impedance measuring apparatus, methods and related systems

DOEpatents

Morrison, John L.; Morrison, William H.; Christophersen, Jon P.

2017-12-26

Energy storage cell impedance testing devices, circuits, and related methods are disclosed. An energy storage cell impedance measuring device includes a sum of sinusoids (SOS) current excitation circuit including differential current sources configured to isolate a ground terminal of the differential current sources from a positive terminal and a negative terminal of an energy storage cell. A method includes applying an SOS signal comprising a sum of sinusoidal current signals to the energy storage cell with the SOS current excitation circuit, each of the sinusoidal current signals oscillating at a different one of a plurality of different frequencies. The method also includes measuring an electrical signal at a positive terminal and a negative terminal of the energy storage cell, and computing an impedance of the energy storage cell at each of the plurality of different frequencies using the measured electrical signal.

Natural history of hepatic metastases from colorectal cancer--pathobiological pathways with clinical significance.

PubMed

Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

2014-04-14

Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

Changes in receptor-mediated endocytosis in liver sinusoidal cells after partial hepatectomy in the rat.

PubMed

Kamimoto, Y; Tanabe, D; Tashiro, S; Hiraoka, T; Miyauchi, Y

1994-06-01

Liver sinusoidal cells play an important role in host defense by clearing particulate matter and macromolecules from the circulation. In this study, receptor-mediated endocytosis in sinusoidal cells was examined in two-thirds hepatectomized rats using 125I-labeled formaldehyde-treated bovine serum albumin (fBSA) as an endocytable macromolecule. The liver-weight to body-weight ratio in hepatectomized rats returned to the control value 10 days after hepatectomy. The endocytotic index for fBSA in sinusoidal cells decreased significantly to 0.0210 +/- 0.0017 (controls, 0.0598 +/- 0.0019) on the first day, then returned to the control level at 5 days (0.0554 +/- 0.0030). The changes in hepatic uptake for fBSA showed a similar time course of the endocytotic index. A transient increase in the uptake of fBSA per unit weight of liver of 22-39% above control occurred 2 to 3 days after hepatectomy. In contrast to fBSA, the endocytotic index in hepatocytes evaluated with 125I-labeled asialofetuin reached the minimum level on the second day, and then recovered to the control level 10 days after hepatectomy. These results suggest that endocytosis of fBSA by sinusoidal cells decreases after hepatectomy and rapidly recovers to normal before the completion of liver regeneration, whereas endocytosis of asialofetuin by hepatocytes decreases following hepatic resection and returns to normal when regeneration is substantially complete.

Flagellum motion in 2-D: Work rate and efficiency of the non-sinusoidal approach

NASA Astrophysics Data System (ADS)

Viridi, Sparisoma; Nuraini, Nuning; Stephanie, Monica; Rifqi, Ainur; Christina, Dina; Thania, Elsa; Sihite, Erland

2018-03-01

Today microorganisms have been widely used to support human life. Some examples include foodstuffs (Spirulina.sp), to help with medical needs, for mining purposes and more. On the other hand, the development of technology is also very big influence on human life. The combination of technology and health science will be very useful if we can develop it. One is the cancer treatment by utilizing the movement of the flagella to be made a nanorobot used as a carrier of cancer drugs. Movement of flagella that resembles the shape of the arc and straight line can be searched formulation and then applied to the manufacture of nanorobot tail. Then the nanorobot will carry a cancer drug that leads directly to the cancer cells. So hopefully with this nanorobot, can minimize the death of healthy cells around cancer cells. From the results of research and analysis of the movement of flagella, it can be concluded that the smaller the mass of the flagella, the greater the efficiency will be or will be more efficient. So, the energy needed nanorobot will be smaller. Model with non-sinusoidal approach (Brokaw, 1965) is discussed in this work and formulation to get the energy efficiency is proposed and analyzed. Unfortunately, there is a negative value in the formulation.

Frequency tracking and variable bandwidth for line noise filtering without a reference.

PubMed

Kelly, John W; Collinger, Jennifer L; Degenhart, Alan D; Siewiorek, Daniel P; Smailagic, Asim; Wang, Wei

2011-01-01

This paper presents a method for filtering line noise using an adaptive noise canceling (ANC) technique. This method effectively eliminates the sinusoidal contamination while achieving a narrower bandwidth than typical notch filters and without relying on the availability of a noise reference signal as ANC methods normally do. A sinusoidal reference is instead digitally generated and the filter efficiently tracks the power line frequency, which drifts around a known value. The filter's learning rate is also automatically adjusted to achieve faster and more accurate convergence and to control the filter's bandwidth. In this paper the focus of the discussion and the data will be electrocorticographic (ECoG) neural signals, but the presented technique is applicable to other recordings.

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction.

PubMed

Sakurai, Kentaro; Miyashita, Tomoharu; Okazaki, Mitsuyoshi; Yamaguchi, Takahisa; Ohbatake, Yoshinao; Nakanuma, Shinichi; Okamoto, Koichi; Sakai, Seisho; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Hayashi, Hironori; Oyama, Katsunobu; Tajima, Hidehiro; Takamura, Hiroyuki; Ninomiya, Itasu; Fushida, Sachio; Harada, Kenichi; Harmon, John W; Ohta, Tetsuo

2017-01-01

Severe sepsis is associated with high morbidity and mortality rates. Inflammation and coagulation play pivotal roles in the pathogenesis of sepsis leading to multiple organ failure, especially in the liver. The aim of the present study was to assess the mechanism from sepsis to liver damage in a mouse model. We created a sepsis model by injecting lipopolysaccharide (LPS) intraperitoneally in mice. At 0, 6, 12, and 24 h following intraperitoneal injection of LPS, mice were euthanised and analyzed. Primary antibodies against myeloperoxidase (MPO), hepatic sinusoidal endothelial cells (SE-1), and P-selectin (CD62p) were used. Expression and localization in neutrophil, sinusoidal endothelial, and platelet cells were assessed by immunohistochemistry. Immunohistochemical analyses revealed a positive staining for MPO, most abundantly in neutrophil granulocytes, within the hepatic sinusoids immediately after injection. Neutrophil extracellular trap (NET)-like structures stained for MPO, indicating the presence of neutrophils undergoing NETosis, were confirmed at 6 h after LPS administration. SE-1 staining for liver sinusoidal endothelial cells was significantly reduced at 12 h post-LPS administration through sinusoidal endothelial injury or detachment. Furthermore, the presence of extravasated platelets was confirmed in the space of Disse at 24 h after LPS administration. Blood sample analyses showed that white blood cell counts and platelet counts decreased gradually, while MPO amounts increased until 12 h after LPS administration. We conclude that NET formation and intravasated platelet aggregation are the first steps from sepsis to liver damage, and that extravasated platelet aggregation promoted by NET-facilitated detachment of sinusoidal endothelial cells is the origin of sepsis-induced liver dysfunction. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Basement membrane of mouse bone marrow sinusoids shows distinctive structure and proteoglycan composition: a high resolution ultrastructural study.

PubMed

Inoue, S; Osmond, D G

2001-11-01

Venous sinusoids in bone marrow are the site of a large-scale traffic of cells between the extravascular hemopoietic compartment and the blood stream. The wall of the sinusoids consists solely of a basement membrane interposed between a layer of endothelial cells and an incomplete covering of adventitial cells. To examine its possible structural specialization, the basement membrane of bone marrow sinusoids has now been examined by high resolution electron microscopy of perfusion-fixed mouse bone marrow. The basement membrane layer was discontinuous, consisting of irregular masses of amorphous material within a uniform 60-nm-wide space between apposing endothelial cells and adventitial cell processes. At maximal magnifications, the material was resolved as a random arrangement of components lacking the "cord network" formation seen in basement membranes elsewhere. Individual components exhibited distinctive ultrastructural features whose molecular identity has previously been established. By these morphological criteria, the basement membrane contained unusually abundant chondroitin sulfate proteoglycan (CSPG) revealed by 3-nm-wide "double tracks," and moderate amounts of both laminin as dense irregular coils and type IV collagen as 1-1.5-nm-wide filaments, together with less conspicuous amounts of amyloid P forming pentagonal frames. In contrast, 4.5-5-nm-wide "double tracks" characteristic of heparan sulfate proteoglycan (HSPG) were absent. The findings demonstrate that, in comparison with "typical" basement membranes in other tissues, the bone marrow sinusoidal basement membrane is uniquely specialized in several respects. Its discontinuous nature, lack of network organization, and absence of HSPG, a molecule that normally helps to maintain membrane integrity, may facilitate disassembly and reassembly of basement membrane material in concert with movements of adventitial cell processes as maturing hemopoietic cells pass through the sinusoidal wall: the exceptionally large quantity of CSPG may represent a reservoir of CD44 receptor for use in hemopoiesis. Copyright 2001 Wiley-Liss, Inc.

Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver.

PubMed

Narita, Masato; Hatano, Etsuro; Tamaki, Nobuyuki; Yamanaka, Kenya; Yanagida, Atsuko; Nagata, Hiromitsu; Asechi, Hiroyuki; Takada, Yasutsugu; Ikai, Iwao; Uemoto, Shinji

2009-06-01

Sinusoidal obstruction syndrome (SOS) is drug-induced liver injury that occurs in patients who receive hematopoietic cell transplantation and oxaliplatin-contained chemotherapy. The aim of study was to investigate the pharmacological treatment of SOS using a traditional Japanese medicine, Dai-kenchu-to (DKT). Male Sprague-Dawley rats were treated with monocrotaline (MCT) to induce SOS. The rats were divided into three groups: control, MCT and MCT+DKT groups. In the MCT+DKT group, DKT was gavaged at 12 h after MCT treatment and given every 12 h until the end of the protocol. The rats of MCT group were treated with water instead of DKT. At 48 h after MCT treatment, blood and liver samples were collected. In the MCT+DKT group, the macroscopic and histological findings revealed liver congestion, sinusoidal alteration and the destruction of sinusoidal lining, which were comparable with those of the MCT group. However, the area of hepatic necrosis and serum AST levels significantly decreased in the MCT+DKT group compared with those of the MCT group. Treatment with DKT resulted in the reduction of neutrophil accumulation, myeloperoxidase activity and the expression of cytokine-induced neutrophil chemoattractant (CINC) and intracellular adhesion molecule-1 (ICAM-1) mRNA in the liver compared with those of the MCT group. Treatment with processed ginger, one of the ingredients in DKT, resulted in similar effects to those shown by DKT. Dai-kenchu-to attenuates MCT-induced liver injury by preventing neutrophil-induced liver injury through blockage of upregulation of CINC and ICAM-1 mRNA level.

Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report.

PubMed

Behre, Gerhard; Theurich, Sebastian; Christopeit, Maximilian; Weber, Thomas

2009-03-10

We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report

PubMed Central

2009-01-01

Introduction We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. Case presentation A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. Conclusion As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure. PMID:19830097

SNOM and AFM microscopy techniques to study the effect of non-ionizing radiation on the morphological and biochemical properties of human keratinocytes cell line (HaCaT).

PubMed

Rieti, S; Manni, V; Lisi, A; Giuliani, L; Sacco, D; D'Emilia, E; Cricenti, A; Generosi, R; Luce, M; Grimaldi, S

2004-01-01

In this study we have employed atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM) techniques to study the effect of the interaction between human keratinocytes (HaCaT) and electromagnetic fields at low frequency. HaCaT cells were exposed to a sinusoidal magnetic field at a density of 50 Hz, 1 mT. AFM analysis revealed modification in shape and morphology in exposed cells with an increase in the areas of adhesion between cells. This latter finding was confirmed by SNOM indirect immunofluorescence analysis performed with a fluorescent antibody against the adhesion marker beta4 integrin, which revealed an increase of beta4 integrin segregation in the cell membrane of 50-Hz exposed cells, suggesting that a higher percentage of these cells shows a modified pattern of this adhesion marker.

Phase-contrast CT: Qualitative and Quantitative Evaluation of Capillarized Sinusoids and Trabecular Structure in Human Hepatocellular Carcinoma Tissues.

PubMed

Jian, Jianbo; Zhang, Wenxue; Yang, Hao; Zhao, Xinyan; Xuan, Ruijiao; Li, Dongyue; Hu, Chunhong

2017-01-01

Capillarization of sinusoids and change of trabecular thickness are the main histologic features in hepatocellular carcinoma (HCC). Of particular interest are the three-dimensional (3D) visualization and quantitative evaluation of such alterations in the HCC progression. X-ray phase-contrast computed tomography (PCCT) is an emerging imaging method that provides excellent image contrast for soft tissues. This study aimed to explore the potential of in-line PCCT in microstructure imaging of capillarized sinusoids and trabecular structure in human HCC tissues and to quantitatively evaluate the alterations of those fine structures during the development of HCC. This project was designed as an ex vivo experimental study. The study was approved by the institutional review board, and informed consent was obtained from the patients. Eight human resected HCC tissue samples were imaged using in-line PCCT. After histologic processing, PCCT images and histopathologic data were matched. Fine structures in HCC tissues were revealed. Quantitative analyses of capillarized sinusoids (ie, percentage of sinusoidal area [PSA], sinusoidal volume) and trabecular structure (ie, trabecular thickness, surface-area-to-volume ratio [SA/V]) in low-grade (well or moderately differentiated) and high-grade (poorly differentiated) HCC groups were performed. Using PCCT, the alterations of capillarized sinusoids and trabecular structure were clearly observed in 3D geometry, which was confirmed by the corresponding histologic sections. The 3D qualitative analyses of sinusoids in the high-grade HCC group were significantly different (P < 0.05) in PSA (7.8 ± 2.5%) and sinusoidal volume (2.9 ± 0.6 × 10 7  µm 3 ) from those in the low-grade HCC group (PSA, 12.9 ± 2.2%; sinusoidal volume, 2.4 ± 0.3 × 10 7  µm 3 ). Moreover, the 3D quantitative evaluation of the trabecular structure in the high-grade HCC group showed a significant change (P < 0.05) in the trabecular thickness (87.8 ± 15.6 µm) and SA/V (2.2 ± 1.3 × 10 3  µm - 1 ) compared to the low-grade HCC group (trabecular thickness, 75.9 ± 7.1 µm; SA/V, 7.5 ± 1.3 × 10 3  µm - 1 ). This study provides insights into the 3D alterations of microstructures such as capillarized sinusoids and the trabecular structure at a micrometer level, which might allow for an improved understanding of the development of HCC. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Fibronectin Extra Domain A Promotes Liver Sinusoid Repair following Hepatectomy.

PubMed

Sackey-Aboagye, Bridget; Olsen, Abby L; Mukherjee, Sarmistha M; Ventriglia, Alexander; Yokosaki, Yasuyuki; Greenbaum, Linda E; Lee, Gi Yun; Naga, Hani; Wells, Rebecca G

2016-01-01

Liver sinusoidal endothelial cells (LSECs) are the main endothelial cells in the liver and are important for maintaining liver homeostasis as well as responding to injury. LSECs express cellular fibronectin containing the alternatively spliced extra domain A (EIIIA-cFN) and increase expression of this isoform after liver injury, although its function is not well understood. Here, we examined the role of EIIIA-cFN in liver regeneration following partial hepatectomy. We carried out two-thirds partial hepatectomies in mice lacking EIIIA-cFN and in their wild type littermates, studied liver endothelial cell adhesion on decellularized, EIIIA-cFN-containing matrices and investigated the role of cellular fibronectins in liver endothelial cell tubulogenesis. We found that liver weight recovery following hepatectomy was significantly delayed and that sinusoidal repair was impaired in EIIIA-cFN null mice, especially females, as was the lipid accumulation typical of the post-hepatectomy liver. In vitro, we found that liver endothelial cells were more adhesive to cell-deposited matrices containing the EIIIA domain and that cellular fibronectin enhanced tubulogenesis and vascular cord formation. The integrin α9β1, which specifically binds EIIIA-cFN, promoted tubulogenesis and adhesion of liver endothelial cells to EIIIA-cFN. Our findings identify a role for EIIIA-cFN in liver regeneration and tubulogenesis. We suggest that sinusoidal repair is enhanced by increased LSEC adhesion, which is mediated by EIIIA-cFN.

Fibronectin Extra Domain A Promotes Liver Sinusoid Repair following Hepatectomy

PubMed Central

Sackey-Aboagye, Bridget; Olsen, Abby L.; Mukherjee, Sarmistha M.; Ventriglia, Alexander; Yokosaki, Yasuyuki; Greenbaum, Linda E.; Lee, Gi Yun; Naga, Hani

2016-01-01

Liver sinusoidal endothelial cells (LSECs) are the main endothelial cells in the liver and are important for maintaining liver homeostasis as well as responding to injury. LSECs express cellular fibronectin containing the alternatively spliced extra domain A (EIIIA-cFN) and increase expression of this isoform after liver injury, although its function is not well understood. Here, we examined the role of EIIIA-cFN in liver regeneration following partial hepatectomy. We carried out two-thirds partial hepatectomies in mice lacking EIIIA-cFN and in their wild type littermates, studied liver endothelial cell adhesion on decellularized, EIIIA-cFN-containing matrices and investigated the role of cellular fibronectins in liver endothelial cell tubulogenesis. We found that liver weight recovery following hepatectomy was significantly delayed and that sinusoidal repair was impaired in EIIIA-cFN null mice, especially females, as was the lipid accumulation typical of the post-hepatectomy liver. In vitro, we found that liver endothelial cells were more adhesive to cell-deposited matrices containing the EIIIA domain and that cellular fibronectin enhanced tubulogenesis and vascular cord formation. The integrin α9β1, which specifically binds EIIIA-cFN, promoted tubulogenesis and adhesion of liver endothelial cells to EIIIA-cFN. Our findings identify a role for EIIIA-cFN in liver regeneration and tubulogenesis. We suggest that sinusoidal repair is enhanced by increased LSEC adhesion, which is mediated by EIIIA-cFN. PMID:27741254

"Artificial micro organs"--a microfluidic device for dielectrophoretic assembly of liver sinusoids.

PubMed

Schütte, Julia; Hagmeyer, Britta; Holzner, Felix; Kubon, Massimo; Werner, Simon; Freudigmann, Christian; Benz, Karin; Böttger, Jan; Gebhardt, Rolf; Becker, Holger; Stelzle, Martin

2011-06-01

In order to study possible toxic side effects of potential drug compounds in vitro a reliable test system is needed. Predicting liver toxicity presents a major challenge of particular importance as liver cells grown in a cell culture suffer from a rapid loss of their liver specific functions. Therefore we are developing a new microfluidic test system for liver toxicity. This test system is based on an organ-like liver 3D co-culture of hepatocytes and endothelial cells. We devised a microfluidic chip featuring cell culture chambers with integrated electrodes for the assembly of liver sinusoids by dielectrophoresis. Fluid channels enable an organ-like perfusion with culture media and test compounds. Different chamber designs were studied and optimized with regard to dielectrophoretic force distribution, hydrodynamic flow profile, and cell trapping rate using numeric simulations. Based on simulation results a microchip was injection-moulded from COP. This chip allowed the assembly of viable hepatocytes and endothelial cells in a sinusoid-like fashion.

Long term studies of the rat reticuloendothelial system and endocrine gland responses to foreign particles

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

Frankel, Howard H.; Patek, Paul R.; Bernick, Sol

1962-03-01

Changes in morphology and responses of macrophages to a single intravenous injection of carbon or thorium dioxide (Thorotrast) were studied in rats. Localization of C particles is described in detail, although an identical response of macrophages to ThO 2 was observed. In lever, C particles were observed in Kupffer cells lining the sinusoids of the hepatic lobule 24 hr after injection. At 48 hr the concentration of C increased within the hepatic lobule. The increased uptake of C by individual Kupffer cells eventually led to conglomeration of these macrophages and apparent sinusoidal occlusion. Only a minimal amount of C particlesmore » was observed in the lungs at one month, but migration of Claden macrophages to lung from liver began one month after the injection and quickly ceased shortly afterward. There was a relative increase in the particles demonstrated in the spleen as the experiment progressed. Administration of the reticuloendothelial blocking agents resulted in morphological changes in the thyroid gland, anterior pituitary, and adrenals. Both C and ThO 2 produced a hyperplasia of the thyroid follicles. Concomitantly, there was a marked increase in the number of thyrotrophic cells of the anterior pituitary, suggesting thyrotropin production or release. There was also an increased infiltration of a sudanophilic positive substance into all the zones of the adrenal cortex. (H.H.D.)« less

Morphologic differentiation of colon carcinoma cell lines HT-29 and HT-29KM in rotating-wall vessels

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; Jessup, J. M.; Wolf, D. A.

1992-01-01

A new low shear stress microcarrier culture system has been developed at NASA's Johnson Space Center that permits three-dimensional tissue culture. Two established human colon adenocarcinoma cell lines, HT-29, an undifferentiated, and HT-29KM, a stable, moderately differentiated subline of HT-29, were grown in new tissue culture bioreactors called Rotating-Wall Vessels (RWVs). RWVs are used in conjunction with multicellular cocultivation to develop a unique in vitro tissue modeling system. Cells were cultivated on Cytodex-3 microcarrier beads, with and without mixed normal human colonic fibroblasts, which served as the mesenchymal layer. Culture of the tumor lines in the absence of fibroblasts produced spheroidlike growth and minimal differentiation. In contrast, when tumor lines were co-cultivated with normal colonic fibroblasts, initial growth was confined to the fibroblast population until the microcarriers were covered. The tumor cells then commenced proliferation at an accelerated rate, organizing themselves into three-dimensional tissue masses that achieved 1.0- to 1.5-cm diameters. The masses displayed glandular structures, apical and internal glandular microvilli, tight intercellular junctions, desmosomes, cellular polarity, sinusoid development, internalized mucin, and structural organization akin to normal colon crypt development. Differentiated samples were subjected to transmission and scanning electron microscopy and histologic analysis, revealing embryoniclike mesenchymal cells lining the areas around the growth matrices. Necrosis was minimal throughout the tissue masses. These data suggest that the RWV affords a new model for investigation and isolation of growth, regulatory, and structural processes within neoplastic and normal tissue.

Sinusoidal nanotextures for light management in silicon thin-film solar cells.

PubMed

Köppel, G; Rech, B; Becker, C

2016-04-28

Recent progresses in liquid phase crystallization enabled the fabrication of thin wafer quality crystalline silicon layers on low-cost glass substrates enabling conversion efficiencies up to 12.1%. Because of its indirect band gap, a thin silicon absorber layer demands for efficient measures for light management. However, the combination of high quality crystalline silicon and light trapping structures is still a critical issue. Here, we implement hexagonal 750 nm pitched sinusoidal and pillar shaped nanostructures at the sun-facing glass-silicon interface into 10 μm thin liquid phase crystallized silicon thin-film solar cell devices on glass. Both structures are experimentally studied regarding their optical and optoelectronic properties. Reflection losses are reduced over the entire wavelength range outperforming state of the art anti-reflective planar layer systems. In case of the smooth sinusoidal nanostructures these optical achievements are accompanied by an excellent electronic material quality of the silicon absorber layer enabling open circuit voltages above 600 mV and solar cell device performances comparable to the planar reference device. For wavelengths smaller than 400 nm and higher than 700 nm optical achievements are translated into an enhanced quantum efficiency of the solar cell devices. Therefore, sinusoidal nanotextures are a well-balanced compromise between optical enhancement and maintained high electronic silicon material quality which opens a promising route for future optimizations in solar cell designs for silicon thin-film solar cells on glass.

Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

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

Straub, Adam C.; Stolz, Donna B.; Vin, Harina

2007-08-01

The vascular effects of arsenic in drinking water are global health concerns contributing to human disease worldwide. Arsenic targets the endothelial cells lining blood vessels, and endothelial cell activation or dysfunction may underlie the pathogenesis of both arsenic-induced vascular diseases and arsenic-enhanced tumorigenesis. The purpose of the current studies was to demonstrate that exposing mice to drinking water containing environmentally relevant levels of arsenic promoted endothelial cell dysfunction and pathologic vascular remodeling. Increased angiogenesis, neovascularization, and inflammatory cell infiltration were observed in Matrigel plugs implanted in C57BL/6 mice following 5-week exposures to 5-500 ppb arsenic [Soucy, N.V., Mayka, D., Klei,more » L.R., Nemec, A.A., Bauer, J.A., Barchowsky, A., 2005. Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice. Cardiovasc.Toxicol 5, 29-42]. Therefore, functional in vivo effects of arsenic on endothelial cell function and vessel remodeling in an endogenous vascular bed were investigated in the liver. Liver sinusoidal endothelial cells (LSEC) became progressively defenestrated and underwent capillarization to decrease vessel porosity following exposure to 250 ppb arsenic for 2 weeks. Sinusoidal expression of PECAM-1 and laminin-1 proteins, a hallmark of capillarization, was also increased by 2 weeks of exposure. LSEC caveolin-1 protein and caveolae expression were induced after 2 weeks of exposure indicating a compensatory change. Likewise, CD45/CD68-positive inflammatory cells did not accumulate in the livers until after LSEC porosity was decreased, indicating that inflammation is a consequence and not a cause of the arsenic-induced LSEC phenotype. The data demonstrate that the liver vasculature is an early target of pathogenic arsenic effects and that the mouse liver vasculature is a sensitive model for investigating vascular health effects of arsenic.« less

The effect of intermediate-scale motions on line formation. [sawtooth and sine motions in solar atmosphere

NASA Technical Reports Server (NTRS)

Shine, R. A.

1975-01-01

The problem of LTE and non-LTE line formation in the presence of nonthermal velocity fields with geometric scales between the microscopic and macroscopic limits is investigated in the cases of periodic sinusoidal and sawtooth waves. For a fixed source function (the LTE case), it is shown that time-averaged line profiles progress smoothly from the microscopic to the macroscopic limits as the geometric scale of the motions increases, that the sinusoidal motions produce symmetric time-averaged profiles, and that the sawtooth motions cause a redshift. In several idealized non-LTE cases, it is found that intermediate-scale velocity fields can significantly increase the surface source functions and line-core intensities. Calculations are made for a two-level atom in an isothermal atmosphere for a range of velocity scales and non-LTE coupling parameters and also for a two-level atom and a four-level representation of Na I line formation in the Harvard-Smithsonian Reference Atmosphere (1971) solar model. It is found that intermediate-scale velocity fields in the solar atmosphere could explain the central intensities of the Na I D lines and other strong absorption lines without invoking previously suggested high electron densities.

Peliosis hepatis and sinusoidal dilation during infection by the human immunodeficiency virus (HIV). An ultrastructural study.

PubMed Central

Scoazec, J. Y.; Marche, C.; Girard, P. M.; Houtmann, J.; Durand-Schneider, A. M.; Saimot, A. G.; Benhamou, J. P.; Feldmann, G.

1988-01-01

The description of hepatic sinusoidal lesions in a significant number of acquired immunodeficiency syndrome (AIDS) patients prompted the authors to undertake an ultrastructural study of the sinusoidal barrier abnormalities during human immunodeficiency virus (HIV) infection, in order to compare these lesions with those described in other conditions and to discuss their possible origin. In a series of 29 patients with serologic evidence of HIV infection and liver abnormalities, 8 (28%) had sinusoidal lesions. Peliosis hepatis was present in 2 cases, and sinusoidal dilatation in 6. These patients were classified as follows: 3 AIDS, 4 AIDS-related complex, 1 unclassifiable. Ultrastructural lesions of the sinusoidal barrier were observed in all the cases. They closely mimicked the changes previously reported in peliotic and peliotic-like changes of various origins. A striking particularity was, however, the presence of numerous and hyperplastic sinusoidal macrophages. This work suggests that an injury of the endothelial cells, directly or indirectly related to the presence of HIV, may be incriminated in the pathogenesis of sinusoidal lesions during HIV infection. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3354642

Platelets: No longer bystanders in liver disease

PubMed Central

Adams, David H.; Watson, Steve P.; Lalor, Patricia F.

2016-01-01

Growing lines of evidence recognize that platelets play a central role in liver homeostasis and pathobiology. Platelets have important roles at every stage during the continuum of liver injury and healing. These cells contribute to the initiation of liver inflammation by promoting leukocyte recruitment through sinusoidal endothelium. They can activate effector cells, thus amplifying liver damage, and by modifying the hepatic cellular and cytokine milieu drive both hepatoprotective and hepatotoxic processes. Conclusion: In this review we summarize how platelets drive such pleiotropic actions and attempt to reconcile the paradox of platelets being both deleterious and beneficial to liver function; with increasingly novel methods of manipulating platelet function at our disposal, we highlight avenues for future therapeutic intervention in liver disease. (Hepatology 2016;64:1774‐1784) PMID:26934463

Advanced Method for Isolation of Mouse Hepatocytes, Liver Sinusoidal Endothelial Cells, and Kupffer Cells.

PubMed

Liu, Jia; Huang, Xuan; Werner, Melanie; Broering, Ruth; Yang, Dongliang; Lu, Mengji

2017-01-01

Separation of pure cell populations from the liver is a prerequisite to study the role of hepatic parenchymal and non-parenchymal cells in liver physiology, pathophysiology, and immunology. Traditional methods for hepatic cell separation usually purify only single cell types from liver specimens. Here, we describe an efficient method that can simultaneously purify populations of hepatocytes (HCs), liver sinusoidal endothelial cells (LSECs), and Kupffer cells (KCs) from a single mouse liver specimen. A liberase-based perfusion technique in combination with a low-speed centrifugation and magnetic-activated cell sorting (MACS) led to the isolation and purification of HCs, KCs, and LSECs with high yields and purity.

Immunohistochemical localization of D-aspartate oxidase in porcine peripheral tissues.

PubMed

Yamamoto, Atsushi; Tanaka, Hiroyuki; Ishida, Tetsuo; Horiike, Kihachiro

2011-07-01

D-Aspartate (D-Asp) is an endogenous substance in mammals. Degradation of D-Asp is carried out only by D-aspartate oxidase (DDO). We measured DDO activity in porcine tissues, and produced an anti-porcine DDO antibody to examine the cellular localization of DDO. All the tissues examined showed DDO activities, whereas the substrate D-Asp was not detected in kidney cortex, liver, heart, and gastric mucosa. In the kidney, intensive immunohistochemical staining for DDO was found in the epithelial cells of the proximal tubules. In the liver, the epithelial cells of interlobular bile ducts, liver sinusoid-lining cells with cytoplasmic processes, and the smooth muscle cells of arterioles were strongly stained for DDO. In the heart, cardiomyocytes and the smooth muscle cells of arterioles showed DDO-immunoreactivity. In the gastric mucosa, only the chief cells were DDO-positive. These newly identified DDO-positive cells seem to actively degrade D-Asp to prevent an excess of D-Asp from exerting harmful effects on the respective functions of porcine tissues.

Human liver-resident CD56(bright)/CD16(neg) NK cells are retained within hepatic sinusoids via the engagement of CCR5 and CXCR6 pathways.

PubMed

Hudspeth, Kelly; Donadon, Matteo; Cimino, Matteo; Pontarini, Elena; Tentorio, Paolo; Preti, Max; Hong, Michelle; Bertoletti, Antonio; Bicciato, Silvio; Invernizzi, Pietro; Lugli, Enrico; Torzilli, Guido; Gershwin, M Eric; Mavilio, Domenico

2016-01-01

The liver-specific natural killer (NK) cell population is critical for local innate immune responses, but the mechanisms that lead to their selective homing and the definition of their functionally relevance remain enigmatic. We took advantage of the availability of healthy human liver to rigorously define the mechanisms regulating the homing of NK cells to liver and the repertoire of receptors that distinguish liver-resident NK (lr-NK) cells from circulating counterparts. Nearly 50% of the entire liver NK cell population is composed of functionally relevant CD56(bright) lr-NK cells that localize within hepatic sinusoids. CD56(bright) lr-NK cells express CD69, CCR5 and CXCR6 and this unique repertoire of chemokine receptors is functionally critical as it determines selective migration in response to the chemotactic stimuli exerted by CCL3, CCL5 and CXCL16. Here, we also show that hepatic sinusoids express CCL3(pos) Kupffer cells, CXCL16(pos) endothelial cells and CCL5(pos) T and NK lymphocytes. The selective presence of these chemokines in sinusoidal spaces creates a unique tissue niche for lr-CD56(bright) NK cells that constitutively express CCR5 and CXCR6. CD56(bright) lr-NK cells co-exist with CD56(dim) conventional NK (c-NK) cells that are, interestingly, transcriptionally and phenotypically similar to their peripheral circulating counterparts. Indeed, CD56(dim) c-NK cells lack expression of CD69, CCR5, and CXCR6 but express selectins, integrins and CX3CR1. Our findings disclosing the phenotypic and functional differences between lr-Nk cells and c-NK cells are critical to distinguish liver-specific innate immune responses. Hence, any therapeutic attempts at modifying the large population of CD56(bright) lr-NK cells will require modification of hepatic CCR5 and CXCR6. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human liver-resident CD56bright/CD16neg NK cells are retained within hepatic sinusoids via the engagement of CCR5 and CXCR6 pathways

PubMed Central

Hudspeth, Kelly; Donadon, Matteo; Cimino, Matteo; Pontarini, Elena; Tentorio, Paolo; Preti, Max; Hong, Michelle; Bertoletti, Antonio; Bicciato, Silvio; Invernizzi, Pietro; Lugli, Enrico; Torzilli, Guido; Gershwin, M. Eric; Mavilio, Domenico

2015-01-01

Rationale The liver-specific natural killer (NK) cell population is critical for local innate immune responses, but the mechanisms that lead to their selective homing and the definition of their functionally relevance remain enigmatic. Objectives We took advantage of the availability of healthy human liver to rigorously define the mechanisms regulating the homing of NK cells to liver and the repertoire of receptors that distinguish liver-resident NK (lr-NK) cells from circulating counterparts. Findings Nearly 50% of the entire liver NK cell population is composed of functionally relevant CD56bright lr-NK cells that localize within hepatic sinusoids. Further, CD56bright lr-NK cells express CD69, CCR5 and CXCR6 and this unique repertoire of chemokine receptors is functionally critical as it determines selective migration in response to the chemotactic stimuli exerted by CCL3, CCL5 and CXCL16. In addition, hepatic sinusoids express CCL3pos Kupffer cells, CXCL16pos endothelial cells and CCL5pos T and NK lymphocytes. The selective presence of these chemokines in sinusoidal spaces creates a tissue niche for lr-CD56bright NK cells that constitutively express CCR5 and CXCR6. CD56bright lr-NK cells co-exist with CD56dim conventional NK (c-NK) cells that are, interestingly, transcriptionally and phenotypically similar to their peripheral circulating counterparts. Indeed, CD56dim c-NK cells lack expression of CD69, CCR5, and CXCR6 but express selectins, integrins and CX3CR1. Conclusion Our findings disclosing the phenotypic and functional differences between lr-Nk cells and c-NK cells are critical to distinguish liver-specific innate immune responses. Hence, any therapeutic attempts at modifying the large population of CD56bright lr-NK cells will require modification of hepatic CCR5 and CXCR6. PMID:26330348

Age-related Changes in the Hepatic Microcirculation in Mice

PubMed Central

Ito, Yoshiya; Sørensen, Karen K.; Bethea, Nancy W.; Svistounov, Dmitri; McCuskey, Margaret K.; Smedsrød, Bård H.; McCuskey, Robert S.

2007-01-01

Aging of the liver is associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins. Since reduced hepatic blood flow is suspected to contribute this impairment, we examined age-related alterations in hepatic microcirculation.. Livers of C57Bl/6 mice were examined at 0.8 (pre-pubertal), 3 (young adult), 14 (middle-aged) and 27 (senescent) months of age using in vivo and electron microscopic methods. The results demonstrated a 14% reduction in the numbers of perfused sinusoids between 0.8 and 27 month mice associated with 35% reduction in sinusoidal blood flow. This was accompanied by an inflammatory response evidenced by a 5-fold increase in leukocyte adhesion in 27 month mice, up-regulated expression of ICAM-1, and increases in intrahepatic macrophages. Sinusoidal diameter decreased 6-10%. Liver sinusoidal endothelial cell (LSEC) dysfunction was seen as early as 14 months when there was a 3-fold increase in the numbers of swollen LSEC. The endocytotic capacity of LSEC also was found to be reduced in older animals. The sinusoidal endothelium in 27 month old mice exhibited pseudocapillarization. In conclusion, the results suggest that leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarization and dysfunction of LSEC reduce sinusoidal blood flow in aged livers. PMID:17582718

Corrigendum to "Sinusoidal potential cycling operation of a direct ethanol fuel cell to improving carbon dioxide yields" [J. Power Sources 268 (5 December 2014) 439-442

NASA Astrophysics Data System (ADS)

Majidi, Pasha; Pickup, Peter G.

2016-09-01

The authors regret that Equation (5) is incorrect and has resulted in errors in Fig. 4 and the efficiencies stated on p. 442. The corrected equation, figure and text are presented below. In addition, the title should be 'Sinusoidal potential cycling operation of a direct ethanol fuel cell to improve carbon dioxide yields', and the reversible cell potential quoted on p. 441 should be 1.14 V. The authors would like to apologise for any inconvenience caused.

Nematic liquid crystals on sinusoidal channels: the zigzag instability.

PubMed

Silvestre, Nuno M; Romero-Enrique, Jose M; Telo da Gama, Margarida M

2017-01-11

Substrates which are chemically or topographically patterned induce a variety of liquid crystal textures. The response of the liquid crystal to competing surface orientations, typical of patterned substrates, is determined by the anisotropy of the elastic constants and the interplay of the relevant lengths scales, such as the correlation length and the surface geometrical parameters. Transitions between different textures, usually with different symmetries, may occur under a wide range of conditions. We use the Landau-de Gennes free energy to investigate the texture of nematics in sinusoidal channels with parallel anchoring bounded by nematic-air interfaces that favour perpendicular (hometropic) anchoring. In micron size channels 5CB was observed to exhibit a non-trivial texture characterized by a disclination line, within the channel, which is broken into a zigzag pattern. Our calculations reveal that when the elastic anisotropy of the nematic does not favour twist distortions the defect is a straight disclination line that runs along the channel, which breaks into a zigzag pattern with a characteristic period, when the twist elastic constant becomes sufficiently small when compared to the splay and bend constants. The transition occurs through a twist instability that drives the defect line to rotate from its original position. The interplay between the energetically favourable twist distortions that induce the defect rotation and the liquid crystal anchoring at the surfaces leads to the zigzag pattern. We investigate in detail the dependence of the periodicity of the zigzag pattern on the geometrical parameters of the sinusoidal channels, which in line with the experimental results is found to be non-linear.

The discovery of pulsed iron line emission from Centaurus X-3

NASA Technical Reports Server (NTRS)

Day, C. S. R.; Nagase, F.; Asai, K.; Takeshima, T.

1993-01-01

We present the first discovery of pulsed iron line emission from an X-ray binary, namely Cen X-3. Compared with the continuum pulsations, the iron line pulsations are shallow (50 percent change in amplitude), smeared (the profile is a single-peaked sinusoid) and phase-shifted (by about half a cycle). We also discuss the constraints on the origin of the line imposed by this discovery and by other observations.

Extravasated platelet aggregation in liver zone 3 may correlate with the progression of sinusoidal obstruction syndrome following living donor liver transplantation: A case report

PubMed Central

NAKANUMA, SHINICHI; MIYASHITA, TOMOHARU; HAYASHI, HIRONORI; TAJIMA, HIDEHIRO; TAKAMURA, HIROYUKI; TSUKADA, TOMOYA; OKAMOTO, KOICHI; SAKAI, SEISHO; MAKINO, ISAMU; KINOSHITA, JUN; NAKAMURA, KEISHI; OYAMA, KATSUNOBU; INOKUCHI, MASAFUMI; NAKAGAWARA, HISATOSHI; NINOMIYA, ITASU; KITAGAWA, HIROHISA; FUSHIDA, SACHIO; FUJIMURA, TAKASHI; OHTA, TETSUO

2015-01-01

Sinusoidal obstruction syndrome (SOS), previously known as veno-occlusive disease, is relatively rare subsequent to liver transplantation (LT). SOS refractory to medical therapy, however, can result in centrilobular fibrosis, portal hypertension and liver failure. Although sinusoidal endothelial cell damage around central venules (zone 3) occurs early in the development of SOS, the detailed mechanism of SOS development and its association with thrombocytopenia are not yet completely understood. The present report describes a patient who experienced SOS with unexplained thrombocytopenia following living donor LT. The progression of SOS resulted in graft dysfunction and the patient succumbed. The presence of platelets in the liver allograft was assayed immunohistochemically using antibody to the platelet marker cluster of differentiation 42b (platelet glycoprotein Ib). Platelet aggregates were found attached to hepatocytes along the sinusoid and within the cytoplasm of hepatocytes, particularly in zone 3. By contrast, no staining was observed in zone 1. These findings suggested that extravasated platelet aggregation in the space of Disse and the phagocytosis of platelets by hepatocytes were initiated by sinusoidal endothelial cell damage due to the toxicity of the immunosuppressant tacrolimus or a corticosteroid pulse, and that platelet activation and degranulation may be at least partially involved in the mechanism responsible for SOS. PMID:25780397

Hyperthermia heating apparatus. [cancer therapy

NASA Technical Reports Server (NTRS)

Gammell, P. M. (Inventor)

1982-01-01

Electromagnetic energy is delivered to a localized area of a patient's body in a hyperthermic treatment so that it provides a uniform distribution of electromagnetic flux lines within the localized area of the patient's body and produces a uniform and localized heating gradient. An electrode array includes a number of electrodes which are arranged in pair, with the electrodes in each pair being spaced a particular distance apart. The array is driven by a balanced line system which is electromagnetically coupled to each pair of electrodes and which is shielded by a ground coaxial shield which itself is ground to the body of the patient. Each electrode is embedded in a Teflon stand-off in order to move the region of strong field, from the body, produced by rapidly changing potentials. The two pairs of electrodes forming a cross-like geometry are used with the balanced line systems. The electrical power is either multiplexed among the electrodes or the second pair is driven by a potential which is sinusoidal and which is 90% out of phase with the first balanced line system which is also sinusoidal.

Expression of a monocarboxylate transporter in reticular cells of the mouse lymph node and its involvement in the uptake of exogenous particles.

PubMed

Zheng, Miao; Ishiguro-Oonuma, Toshina; Iwanaga, Toshihiko

2014-01-01

The monocarboxylate transporter (MCT)-1 plays an important role in the transfer of monocarboxylate metabolites such as lactate, ketone bodies, and acetic acid. The present study revealed the selective localization of MCT1 in reticular cells of the murine lymph node. An intense MCT1 immunoreactivity was found in the reticular cells forming a cellular network together with sinus-lining cells in the medullary sinuses and in cells covering the inside of subcapsular sinuses.Electron-microscopically, MCT1 was localized along the plasma membrane of the reticular cells.The medullary reticular cells vigorously ingested carboxylate-modified latex particles, but any reticular cells within the cortical lymphoid follicles and medullary cords neither expressed MCT1 nor incorporated latex particles. MCT1-immunoreactive reticular cells also expressed LYVE-1,which is a hyaluronan receptor abundant in both the lymphatic endothelium and hepatic sinusoidal epithelium. The selective localization of MCT1 and LYVE-1 suggests a high level of activity for lymphoid reticular cells in the uptake of carboxylate-modified and hyaluronate waste substances circulating in the body.

Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion

PubMed Central

Kim, Min-Sik

2016-01-01

Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine. PMID:27551151

Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion.

PubMed

Cha, Sung-Jae; Kim, Min-Sik; Pandey, Akhilesh; Jacobs-Lorena, Marcelo

2016-09-19

Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine. © 2016 Cha et al.

Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells

PubMed Central

Zhang, Feng; Zhang, Zili; Chen, Li; Kong, Desong; Zhang, Xiaoping; Lu, Chunfeng; Lu, Yin; Zheng, Shizhong

2014-01-01

Hepatic fibrosis is concomitant with sinusoidal pathological angiogenesis, which has been highlighted as novel therapeutic targets for the treatment of chronic liver disease. Our prior studies have demonstrated that curcumin has potent antifibrotic activity, but the mechanisms remain to be elucidated. The current work demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of a number of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells and rat aortic ring angiogenesis were not impaired by curcumin. These results indicated that hepatic stellate cells (HSCs) that are characterized as liver-specific pericytes could be potential target cells for curcumin. Further investigations showed that curcumin inhibited VEGF expression in HSCs associated with disrupting platelet-derived growth factor-β receptor (PDGF-βR)/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin associated with blocking PDGF-βR/focal adhesion kinase/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPAR-γ activation-dependent mechanism. PPAR-γ could be a target molecule for reducing pathological angiogenesis during liver fibrosis. PMID:24779927

The basic helix-loop-helix transcription factor, heart and neural crest derivatives expressed transcript 2, marks hepatic stellate cells in zebrafish: analysis of stellate cell entry into the developing liver.

PubMed

Yin, Chunyue; Evason, Kimberley J; Maher, Jacquelyn J; Stainier, Didier Y R

2012-11-01

Hepatic stellate cells (HSCs) are liver-specific mesenchymal cells that play vital roles in liver development and injury. Our knowledge of HSC biology is limited by the paucity of in vivo data. HSCs and sinusoidal endothelial cells (SECs) reside in close proximity, and interactions between these two cell types are potentially critical for their development and function. Here, we introduce a transgenic zebrafish line, Tg(hand2:EGFP), that labels HSCs. We find that zebrafish HSCs share many similarities with their mammalian counterparts, including morphology, location, lipid storage, gene-expression profile, and increased proliferation and matrix production, in response to an acute hepatic insult. Using the Tg(hand2:EGFP) line, we conducted time-course analyses during development to reveal that HSCs invade the liver after SECs do. However, HSCs still enter the liver in mutants that lack most endothelial cells, including SECs, indicating that SECs are not required for HSC differentiation or their entry into the liver. In the absence of SECs, HSCs become abnormally associated with hepatic biliary cells, suggesting that SECs influence HSC localization during liver development. We analyzed factors that regulate HSC development and show that inhibition of vascular endothelial growth factor signaling significantly reduces the number of HSCs that enter the liver. We also performed a pilot chemical screen and identified two compounds that affect HSC numbers during development. Our work provides the first comprehensive description of HSC development in zebrafish and reveals the requirement of SECs in HSC localization. The Tg(hand2:EGFP) line represents a unique tool for in vivo analysis and molecular dissection of HSC behavior. Copyright © 2012 American Association for the Study of Liver Diseases.

3-O sulfation of heparin leads to hepatotropism and longer circulatory half-life.

PubMed

Miller, Colton M; Xu, Yongmei; Kudrna, Katrina M; Hass, Blake E; Kellar, Brianna M; Egger, Andrew W; Liu, Jian; Harris, Edward N

2018-05-17

Heparins are common blood anticoagulants that are critical for many surgical and biomedical procedures used in modern medicine. In contrast to natural heparin derived from porcine gut mucosa, synthetic heparins are homogenous by mass, polymer length, and chemistry. Stable cell lines expressing the human and mouse Stabilin receptors were used to evaluate endocytosis of natural and synthetic heparin. We chemoenzymatically produced synthetic heparin consisting of 12 sugars (dodecamers) containing 14 sulfate groups resulting in a non-3-O sulfated structure (n12mer). Half of the n12mer was modified with a 3-O sulfate on a single GlcNS sugar producing the 3-O sulfated heparin (12mer). Wildtype (WT), Stabilin-1 knock-out (KO), and Stabilin-2 KO C57BL/6 mice were developed and used for metabolic studies and provided as a source for primary liver sinusoidal endothelial cells. Human and mouse Stabilin-2 receptors had very similar endocytosis rates of both the 12mer and n12mer, suggesting that they are functionally similar in primary cells. Subcutaneous injections of the n12mer and 12mer revealed that the 12mer had a much longer half-life in circulation and a higher accumulation in liver. The n12mer never accumulated in circulation and was readily excreted by the kidneys before liver accumulation could occur. Liver sinusoidal endothelial cells from the Stabilin-2 KO mice had lower uptake rates for both dodecamers, whereas, the Stabilin-1 KO mice had lower endocytosis rates for the 12mer than the n12mer. 3-O sulfation of heparin is correlated to both a longer circulatory half-life and hepatotropism which is largely performed by the Stabilin receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Experimental Investigation of Hydrodynamic Forces on Circular Cylinders in Sinusoidal and Random Oscillating Flow

NASA Astrophysics Data System (ADS)

Longoria, Raul Gilberto

An experimental apparatus has been developed which can be used to generate a general time-dependent planar flow across a cylinder. A mass of water enclosed with no free surface within a square cross-section tank and two spring pre-loaded pistons is oscillated using a hydraulic actuator. A circular cylinder is suspended horizontally in the tank by two X-Y force transducers used to simultaneously measure the total in-line and transverse forces. Fluid motion is measured using a differential pressure transducer for instantaneous acceleration and an LVDT for displacement. This investigation provides measurement of forces on cylinders subjected to planar fluid flow velocity with a time (and frequency) dependence which more accurately represent the random conditions encountered in a natural ocean environment. The use of the same apparatus for both sinusoidal and random experiments provides a quantified assessment of the applicability of sinusoidal planar oscillatory flow data in offshore structure design methods. The drag and inertia coefficients for a Morison equation representation of the inline force are presented for both sinusoidal and random flow. Comparison of the sinusoidal results is favorable with those of previous investigations. The results from random experiments illustrates the difference in the force mechanism by contrasting the force transfer coefficients for the inline and transverse forces. It is found that application of sinusoidal results to random hydrodynamic inline force prediction using the Morison equation wrongly weighs the drag and inertia components, and the transverse force is overpredicted. The use of random planar oscillatory flow in the laboratory, contrasted with sinusoidal planar oscillatory flow, quantifies the accepted belief that the force transfer coefficients from sinusoidal flow experiments are conservative for prediction of forces on cylindrical structures subjected to random sea waves and the ensuing forces. Further analysis of data is conducted in the frequency domain to illustrate models used for predicting the power spectral density of the inline force including a nonlinear describing function method. It is postulated that the large-scale vortex activity prominent in sinusoidal oscillatory flow is subdued in random flow conditions.

Intravital Observation of Plasmodium berghei Sporozoite Infection of the Liver

PubMed Central

Engelmann, Sabine; Zougbédé, Sergine; Stange, Jörg; Ng, Bruce; Matuschewski, Kai; Liebes, Leonard; Yee, Herman

2005-01-01

Plasmodium sporozoite invasion of liver cells has been an extremely elusive event to study. In the prevailing model, sporozoites enter the liver by passing through Kupffer cells, but this model was based solely on incidental observations in fixed specimens and on biochemical and physiological data. To obtain direct information on the dynamics of sporozoite infection of the liver, we infected live mice with red or green fluorescent Plasmodium berghei sporozoites and monitored their behavior using intravital microscopy. Digital recordings show that sporozoites entering a liver lobule abruptly adhere to the sinusoidal cell layer, suggesting a high-affinity interaction. They glide along the sinusoid, with or against the bloodstream, to a Kupffer cell, and, by slowly pushing through a constriction, traverse across the space of Disse. Once inside the liver parenchyma, sporozoites move rapidly for many minutes, traversing several hepatocytes, until ultimately settling within a final one. Migration damage to hepatocytes was confirmed in liver sections, revealing clusters of necrotic hepatocytes adjacent to structurally intact, sporozoite-infected hepatocytes, and by elevated serum alanine aminotransferase activity. In summary, malaria sporozoites bind tightly to the sinusoidal cell layer, cross Kupffer cells, and leave behind a trail of dead hepatocytes when migrating to their final destination in the liver. PMID:15901208

The Integrity bare-metal stent made by continuous sinusoid technology.

PubMed

Turco, Mark A

2011-05-01

The Integrity Coronary Stent System (Medtronic Vascular, CA, USA) is a low-profile, open-cell, cobalt-chromium-alloy advanced bare-metal iteration of the well-known Driver/Micro-Driver Coronary Stent System (Medtronic Vascular). The Integrity stent is made with a process called continuous sinusoid technology. This process allows stent construction via wrapping a single thin strand of wire around a mandrel in a sinusoid configuration, with laser fusion of adjacent crowns. The wire-forming process and fusion pattern provide the stent with a continuous preferential bending plane, intended to allow easier access to, and smoother tracking within, distal and tortuous vessels while radial strength is maintained. Continuous sinusoid technology represents innovation in the design of stent platforms and will provide a future stent platform for newer technology, including drug-eluting stent platforms, drug-filled stents and core wire stents.

Rebound spiking in layer II medial entorhinal cortex stellate cells: Possible mechanism of grid cell function

PubMed Central

Shay, Christopher F.; Ferrante, Michele; Chapman, G. William; Hasselmo, Michael E.

2015-01-01

Rebound spiking properties of medial entorhinal cortex (mEC) stellate cells induced by inhibition may underlie their functional properties in awake behaving rats, including the temporal phase separation of distinct grid cells and differences in grid cell firing properties. We investigated rebound spiking properties using whole cell patch recording in entorhinal slices, holding cells near spiking threshold and delivering sinusoidal inputs, superimposed with realistic inhibitory synaptic inputs to test the capacity of cells to selectively respond to specific phases of inhibitory input. Stellate cells showed a specific phase range of hyperpolarizing inputs that elicited spiking, but non-stellate cells did not show phase specificity. In both cell types, the phase range of spiking output occurred between the peak and subsequent descending zero crossing of the sinusoid. The phases of inhibitory inputs that induced spikes shifted earlier as the baseline sinusoid frequency increased, while spiking output shifted to later phases. Increases in magnitude of the inhibitory inputs shifted the spiking output to earlier phases. Pharmacological blockade of h-current abolished the phase selectivity of hyperpolarizing inputs eliciting spikes. A network computational model using cells possessing similar rebound properties as found in vitro produces spatially periodic firing properties resembling grid cell firing when a simulated animal moves along a linear track. These results suggest that the ability of mEC stellate cells to fire rebound spikes in response to a specific range of phases of inhibition could support complex attractor dynamics that provide completion and separation to maintain spiking activity of specific grid cell populations. PMID:26385258

[Defibrotide therapy for patients with sinusoidal obstruction syndrome after hematopoietic stem cell transplantation].

PubMed

Yakushijin, Kimikazu; Okamura, Atsuo; Ono, Kanako; Kawano, Yuko; Kawano, Hiroki; Funakoshi, Yohei; Kawamori, Yuriko; Nishikawa, Shinichiro; Minagawa, Kentaro; Sada, Akiko; Shimoyama, Manabu; Yamamoto, Katsuya; Katayama, Yoshio; Matsui, Toshimitsu

2009-01-01

Sinusoidal obstruction syndrome (SOS) is one of the life-threatening complications caused by endothelial damage to the hepatic sinusoids after hematopoietic stem cell transplantation. However, a satisfactory treatment for SOS has not yet been established. Defibrotide has anti-thrombotic, anti-ischemic, anti-inflammatory, and thrombolytic properties without systemic anticoagulant effects. We treated eight post-transplant SOS patients with defibrotide. Three patients responded to the therapy and the initial response was observed within a week. In addition to the improvement of liver function, rapid recovery of response to diuretic drugs followed by the improvement of renal function was observed. All of the five patients with respiratory dysfunction died despite administration of defibrotide, suggesting that early treatment might lead to better outcomes. There were no severe adverse effects directly due to defibrotide administration. Defibrotide seems to be a promising treatment for SOS, and the initiation of a clinical study in Japan would be important.

Vascular endothelial growth factor increases fenestral permeability in hepatic sinusoidal endothelial cells.

PubMed

Yokomori, Hiroaki; Oda, Masaya; Yoshimura, Kazunori; Nagai, Toshihiro; Ogi, Mariko; Nomura, Masahiko; Ishii, Hiromasa

2003-12-01

Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis and vascular permeability. Hepatic sinusoidal endothelial cells (SECs) possess sieve-like pores that form an anastomosing labyrinth structure by the deeply invaginated plasma membrane. Caveolin is the principal structural protein in caveolae. In this study, we examined the role of VEGF on the fenestration and permeability of SECs and the relation with caveolin-1. SECs isolated from rat livers by collagenase infusion method were cultured for 24 h with (10 or 100 ng/ml) or without VEGF. The cells were then examined by transmission and scanning electron microscopy (EM). The expression of caveolin was investigated by confocal immunofluorescence, immunogold EM, and Western blot. Endocytosis and intracellular traffic was studied using horseradish peroxidase (HRP) reaction as a marker of fluid phase transport in SECs. Both transmission and scanning EM showed an increased number of sinusoidal endothelial fenestrae (SEF) in SECs cultured with VEGF. By confocal immunofluorescence, SECs cultured with VEGF displayed prominent caveolin-l-positive aggregates in the cytoplasm, especially surrounding the nucleus region. Immunogold EM depicted increased caveolin-1 reactivity on vesicles and vacuoles of VEGF-treated SECs compared with VEGF-nontreated cells. However, there was no change in the level of caveolin-1 protein expression on Western blot. After HRP injection, an increase of electron-dense tracer filled the SEF in cells treated with VEGF. Our results suggested that VEGF induced fenestration in SECs, accompanied by an increased number of caveolae-like vesicles. Increased caveolin-1 might be associated with vesicle formation but not with fenestration. Increased fenestration may augment hepatic sinusoidal permeability and transendothelial transport.

Extracorporeal continuous portal diversion plus temporal plasmapheresis for “small-for-size” syndrome

PubMed Central

Hou, Peng; Chen, Chao; Tu, Yu-Liang; Zhu, Zi-Man; Tan, Jing-Wang

2013-01-01

AIM: To investigate the effect of plasmapheresis via the portal vein for “small-for-size” syndrome (SFSS) aided by extracorporeal continuous portal diversion (ECPD). METHODS: Extensive or total hepatectomy in the pig is usually adopted as a postoperative liver failure (PLF) or SFSS model. In this study, animals which underwent 85%-90% hepatectomy were randomized into either the Systemic group (n = 7) or the Portal group (n = 7). In the Systemic group, all pigs received temporal plasmapheresis (PP) via the extracorporeal catheter circuit (systemic to systemic circulation) from 24 to 30 h post-hepatectomy (PH); in the Portal group, all pigs received ECPD to divert partial portal vein flow (PVF) to the systemic circulation after hepatectomy, then converted to temporal PP from 24 to 30 h PH, and subsequently converted to ECPD again until 48 h PH. In the Portal group, the PVF was preserved at 3.0-3.3 times that of the baseline value, similar to that following 70% hepatectomy, which was regarded as the optimal PVF to the hypertrophic liver remnant. At 48 h PH, all pigs were re-opened and the portal vein pressure (PVP), PVF, and HAF (hepatic artery flow) were measured, and then diversion of the portal venous flow was terminated. After 1 h the PVP, PVF, and HAF were re-measured. The portal hemodynamic changes, liver injury, liver regeneration and bacterial/lipopolysaccharide (LPS) translocation were evaluated in the two groups. RESULTS: The PVP in the Portal group was significantly lower than that in the Systemic group during the time period from 2 to 49 h PH (P < 0.05). Serum alanine aminotransferase (ALT), total bilirubin (TB) and ammonia were significantly reduced in the Portal group compared with the Systemic group from 24 to 48 h PH (P < 0.05). The Portal group may have attenuated sinusoidal endothelial injury and decreased the level of HA compared with the Systemic group. In the Systemic group, there was significant sinusoidal dilation, hydropic changes in hepatocytes and hemorrhage into the hepatic parenchyma, and the sinusoidal endothelial lining was partially destroyed and detached into the sinusoidal space. CD31 immunostaining revealed significant destruction of the endothelial lining. In the Portal group, there was no intraparenchymal hemorrhage and the sinusoidal endothelial cells and hepatocytes were well preserved. CD31 immunostaining was mild which indicated less destruction of the endothelial lining. HA was significantly decreased in the Portal group compared with the Systemic group from 2 to 48 h PH. The rate of liver remnant regeneration was elevated, while apoptosis was attenuated in the Portal group compared with the Systemic group. Thymidine kinase activity was much higher in the Portal group than in the Systemic group at 48 h PH. The PCNA index was significantly increased and the apoptotic index was significantly decreased in the Portal group compared with the Systemic group. Bacterial translocation and endotoxin, as well as the inflammatory response, were significantly attenuated in the Portal group compared with the Systemic group. LPS, tumor necrosis factor-α and interleukin-6 levels were all significantly decreased in the Portal group compared with the Systemic group from 24 to 48 h PH, while bacterial DNA level was significantly decreased from 2 to 48 h PH. CONCLUSION: PP plus ECPD via the portal vein can attenuate toxic load and hyperperfusion injury, and should be undertaken instead of PP via the systemic circulation in SFSS or PLF. PMID:24023489

Sinusoidal potential cycling operation of a direct ethanol fuel cell to improving carbon dioxide yields

NASA Astrophysics Data System (ADS)

Majidi, Pasha; Pickup, Peter G.

2014-12-01

A direct ethanol fuel cell has been operated under sinusoidal (AC) potential cycling conditions in order to increase the yield of carbon dioxide and thereby increase cell efficiency relative to operation at a fixed potential. At 80 °C, faradaic yields of CO2 as high as 25% have been achieved with a PtRu anode catalyst, while the maximum CO2 production at constant potential was 13%. The increased yields under cycling conditions have been attributed to periodic oxidative stripping of adsorbed CO. These results will be important in the optimization of operating conditions for direct ethanol fuel cells, where the benefits of potential cycling are projected to increase as catalysts that produce CO2 more efficiently are implemented.

Photomask CD and LER characterization using Mueller matrix spectroscopic ellipsometry

NASA Astrophysics Data System (ADS)

Heinrich, A.; Dirnstorfer, I.; Bischoff, J.; Meiner, K.; Ketelsen, H.; Richter, U.; Mikolajick, T.

2014-10-01

Critical dimension and line edge roughness on photomask arrays are determined with Mueller matrix spectroscopic ellipsometry. Arrays with large sinusoidal perturbations are measured for different azimuth angels and compared with simulations based on rigorous coupled wave analysis. Experiment and simulation show that line edge roughness leads to characteristic changes in the different Mueller matrix elements. The influence of line edge roughness is interpreted as an increase of isotropic character of the sample. The changes in the Mueller matrix elements are very similar when the arrays are statistically perturbed with rms roughness values in the nanometer range suggesting that the results on the sinusoidal test structures are also relevant for "real" mask errors. Critical dimension errors and line edge roughness have similar impact on the SE MM measurement. To distinguish between both deviations, a strategy based on the calculation of sensitivities and correlation coefficients for all Mueller matrix elements is shown. The Mueller matrix elements M13/M31 and M34/M43 are the most suitable elements due to their high sensitivities to critical dimension errors and line edge roughness and, at the same time, to a low correlation coefficient between both influences. From the simulated sensitivities, it is estimated that the measurement accuracy has to be in the order of 0.01 and 0.001 for the detection of 1 nm critical dimension error and 1 nm line edge roughness, respectively.

Interaction between hyaluronan and CD44 in the development of dimethylnitrosamine-induced liver cirrhosis.

PubMed

Satoh, T; Ichida, T; Matsuda, Y; Sugiyama, M; Yonekura, K; Ishikawa, T; Asakura, H

2000-04-01

A significant increase in serum hyaluronan (HA) levels has been reported in patients with liver cirrhosis. This mechanism is not yet clear, and receptors for HA have not been characterized. In this study, we examined the expression of both HA and its receptors, CD44 and intercellular adhesion molecule-1 (ICAM-1), in dimethylnitrosamine-induced liver cirrhosis. Using biotinylated HA binding protein, HA was detected in the area of periportal fibrosis and around the sinusoidal wall where hepatic fibrosis was developing. Electron microscopy revealed that HA was localized on Ito cells and sinusoidal endothelial cells (SEC). Conversely, CD44, which was only expressed weakly in normal liver, was present in large amounts in cirrhotic liver. The distribution pattern of CD44 was similar to that of HA, however, CD44 was mainly localized on the infiltrating lymphocytes and Kupffer cells. Moreover, CD44 was detected on part of factor VIII-positive SEC. Intercellular adhesion molecule-1, another receptor for HA, was detected on the surface of hepatocytes and around the sinusoidal wall in cirrhotic liver, but its distribution was not accompanied by expression of HA. With respect to CD44 isoforms, the standard form m-RNA predominated in both normal and cirrhotic liver. Variant pMeta-1 mRNA was detected at low levels. An interaction between HA and CD44 may play a role in the recruitment of numerous infiltrating cells and HA accumulation in hepatic sinusoids. Together with phenotypic changes in the SEC, these results may lead to a disturbance in the elimination of HA during the progression of liver cirrhosis.

Combined Multidimensional Microscopy as a Histopathology Imaging Tool.

PubMed

Shami, Gerald J; Cheng, Delfine; Braet, Filip

2017-02-01

Herein, we present a highly versatile bioimaging workflow for the multidimensional imaging of biological structures across vastly different length scales. Such an approach allows for the optimised preparation of samples in one go for consecutive X-ray micro-computed tomography, bright-field light microscopy and backscattered scanning electron microscopy, thus, facilitating the disclosure of combined structural information ranging from the gross tissue or cellular level, down to the nanometre scale. In this current study, we characterize various aspects of the hepatic vasculature, ranging from such large vessels as branches of the hepatic portal vein and hepatic artery, down to the smallest sinusoidal capillaries. By employing high-resolution backscattered scanning electron microscopy, we were able to further characterize the subcellular features of a range of hepatic sinusoidal cells including, liver sinusoidal endothelial cells, pit cells and Kupffer cells. Above all, we demonstrate the capabilities of a specimen manipulation workflow that can be applied and adapted to a plethora of functional and structural investigations and experimental models. Such an approach harnesses the fundamental advantages inherent to the various imaging modalities presented herein, and when combined, offers information not currently available by any single imaging platform. J. Cell. Physiol. 232: 249-256, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The Relationship between Fenestrations, Sieve Plates and Rafts in Liver Sinusoidal Endothelial Cells

PubMed Central

McNerney, Gregory P.; Owen, Dylan M.; Zencak, Dusan; Zykova, Svetlana N.; Crane, Harry; Huser, Thomas; Quinn, Ronald J.; Smedsrød, Bård; Le Couteur, David G.; Cogger, Victoria C.

2012-01-01

Fenestrations are transcellular pores in endothelial cells that facilitate transfer of substrates between blood and the extravascular compartment. In order to understand the regulation and formation of fenestrations, the relationship between membrane rafts and fenestrations was investigated in liver sinusoidal endothelial cells where fenestrations are grouped into sieve plates. Three dimensional structured illumination microscopy, scanning electron microscopy, internal reflectance fluorescence microscopy and two-photon fluorescence microscopy were used to study liver sinusoidal endothelial cells isolated from mice. There was an inverse distribution between sieve plates and membrane rafts visualized by structured illumination microscopy and the fluorescent raft stain, Bodipy FL C5 ganglioside GM1. 7-ketocholesterol and/or cytochalasin D increased both fenestrations and lipid-disordered membrane, while Triton X-100 decreased both fenestrations and lipid-disordered membrane. The effects of cytochalasin D on fenestrations were abrogated by co-administration of Triton X-100, suggesting that actin disruption increases fenestrations by its effects on membrane rafts. Vascular endothelial growth factor (VEGF) depleted lipid-ordered membrane and increased fenestrations. The results are consistent with a sieve-raft interaction, where fenestrations form in non-raft lipid-disordered regions of endothelial cells once the membrane-stabilizing effects of actin cytoskeleton and membrane rafts are diminished. PMID:23029409

Defibrotide Stimulates Angiogenesis and Protects Endothelial Cells from Calcineurin Inhibitor-Induced Apoptosis via Upregulation of AKT/Bcl-xL.

PubMed

Wang, Xiangmin; Pan, Bin; Hashimoto, Yuko; Ohkawara, Hiroshi; Xu, Kailin; Zeng, Lingyu; Ikezoe, Takayuki

2018-01-01

Sinusoidal obstruction syndrome is a life-threatening complication that can occur after haematopoietic stem cell transplantation. Defibrotide (DF) has been approved for the treatment of individuals with severe sinusoidal obstruction syndrome following haematopoietic stem cell transplantation in the European Union and the United States. However, the precise mechanisms by which DF protects endothelial cells remain to be elucidated. In this study, we found that DF stimulated angiogenesis in vitro and in vivo as assessed by vascular tube formation, scratch-wound repair and Matrigel plug assays. These effects were associated with an activation of pro-survival signalling pathways, including AKT (protein kinase B), ERK (extracellular signal-regulated kinases) and p38. More importantly, DF alleviated calcineurin inhibitor-induced growth inhibition and apoptosis of human umbilical vein endothelial cells and human hepatic sinusoidal endothelial cells in parallel with upregulation of anti-apoptotic protein B-cell lymphoma-extra-large (Bcl-xL), which was mediated by AKT (protein kinase B). Notably, these effects were abrogated when Bcl-xL was depleted by small interfering RNA (ribonucleic acid). In addition, DF counteracted calcineurin inhibitor-induced activation of nuclear factor-κB and Janus kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signalling and production of cytokines in vascular endothelial cell-derived EA.hy926 cells. Taken together, DF has pro-angiogenic, anti-apoptotic and anti-inflammatory effects on endothelial cells. DF is a potentially useful agent to prevent the development of, and treat individuals with, endothelial cell injury-related complications after haematopoietic stem cell transplantation. Schattauer GmbH Stuttgart.

Roles of ON Cone Bipolar Cell Subtypes in Temporal Coding in the Mouse Retina

PubMed Central

Fyk-Kolodziej, Bozena; Cohn, Jesse

2014-01-01

In the visual system, diverse image processing starts with bipolar cells, which are the second-order neurons of the retina. Thirteen subtypes of bipolar cells have been identified, which are thought to encode different features of image signaling and to initiate distinct signal-processing streams. Although morphologically identified, the functional roles of each bipolar cell subtype in visual signal encoding are not fully understood. Here, we investigated how ON cone bipolar cells of the mouse retina encode diverse temporal image signaling. We recorded bipolar cell voltage changes in response to two different input functions: sinusoidal light and step light stimuli. Temporal tuning in ON cone bipolar cells was diverse and occurred in a subtype-dependent manner. Subtypes 5s and 8 exhibited low-pass filtering property in response to a sinusoidal light stimulus, and responded with sustained fashion to step-light stimulation. Conversely, subtypes 5f, 6, 7, and XBC exhibited bandpass filtering property in response to sinusoidal light stimuli, and responded transiently to step-light stimuli. In particular, subtypes 7 and XBC were high-temporal tuning cells. We recorded responses in different ways to further examine the underlying mechanisms of temporal tuning. Current injection evoked low-pass filtering, whereas light responses in voltage-clamp mode produced bandpass filtering in all ON bipolar cells. These findings suggest that cone photoreceptor inputs shape bandpass filtering in bipolar cells, whereas intrinsic properties of bipolar cells shape low-pass filtering. Together, our results demonstrate that ON bipolar cells encode diverse temporal image signaling in a subtype-dependent manner to initiate temporal visual information-processing pathways. PMID:24966376

Sinusoidal obstruction syndrome.

PubMed

Valla, Dominique-Charles; Cazals-Hatem, Dominique

2016-09-01

Sinusoidal obstruction syndrome (SOS) is characterized by damage to small hepatic vessels affecting particularly sinusoidal endothelium. Damaged sinusoids can be associated with a partial or complete occlusion of small hepatic veins, hence the previous denomination of hepatic veno-occlusive disease (VOD). Exposure to certain exogenous toxins appears to be specific to this condition and is frequently included in its definition. Typical histopathological features of SOS in a liver biopsy specimen are presented in the text. The purpose of this article is to provide an overview on the different entities corresponding to this general definition. Such entities include: (i) liver disease related to pyrrolizidine alcaloids; (ii) liver injury related to conditioning for hematopoietic stem cell transplantation; (iii) vascular liver disease occurring in patients treated with chemotherapy for liver metastasis of colorectal cancer; and (iv) other liver diseases related to toxic agents. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Giant mediastinal haemangiopericytoma: an uncommon case.

PubMed

Agrawal, D; Lahiri, T K; Lakhotia, S; Singh, Deepak

2014-01-01

Haemangiopericytoma is a rare soft tissue tumour characterised by tightly packed tumour cells situated around thin walled endothelial lined vascular channels, ranging from capillary sized vessels to large gaping sinusoidal spaces. The tumour cells are surrounded by reticulin and are negative for muscle, nerve and epithelial markers. The diagnosis of extra-pulmonary intra-thoracic, extra-pleural mediastinal mass is difficult. It constitutes only 6% of all primary tumours and cysts of the mediastinum. We report the rare occurrence of primary intra-thoracic, extra-pulmonary mediastinal haemangiopericytoma of mesenchymal origin with perivascular localisation. The patient underwent right postero-lateral thoracotomy and post-operatively received chemotherapy with adriamycin (60 mg/m2) on day 1 and ifosfamide (1.5 g/m2) on day 1 to 3. Thirty-seven months after the operation, the patient has been well with evidence of a single recurrence in the left lower lobe.

Characterization of Lift and Drag on Two Dimensional Airfoils with and without Sinusoidal Leading Edges

NASA Astrophysics Data System (ADS)

Acosta, Gregorio I.

An experimental investigation was taken on a 63-021 NACA airfoil, to characterize lift and drag and how the effects of sinusoidal leading edges affect the aerodynamic properties. A theoretical model is also purposed by implementing a perturbation on thin-airfoil theory. Two sets of airfoils were machined and tested inside a low-speed open circuit wind tunnel. Data from a pressure scanner and particle image velocity will give an insight of how the modified leading edges affect the aerodynamic properties. A Fourier series expansion was used to solve for the lifting-line model, by use of thin-airfoil theory and complex number theory.

Electromotile hearing: Acoustic tones mask psychophysical response to high-frequency electrical stimulation of intact guinea pig cochleaea)

PubMed Central

Le Prell, Colleen G.; Kawamoto, Kohei; Raphael, Yehoash; Dolan, David F.

2011-01-01

When sinusoidal electric stimulation is applied to the intact cochlea, a frequency-specific acoustic emission can be recorded in the ear canal. Acoustic emissions are produced by basilar membrane motion, and have been used to suggest a corresponding acoustic sensation termed “electromotile hearing.” Electromotile hearing has been specifically attributed to electric stimulation of outer hair cells in the intact organ of Corti. To determine the nature of the auditory perception produced by electric stimulation of a cochlea with intact outer hair cells, we tested guinea pigs in a psychophysical task. First, subjects were trained to report detection of sinusoidal acoustic stimuli and dynamic range was assessed using response latency. Subjects were then implanted with a ball electrode placed into scala tympani. Following the surgical implant procedure, subjects were transferred to a task in which acoustic signals were replaced by sinusoidal electric stimulation, and dynamic range was assessed again. Finally, the ability of acoustic pure-tone stimuli to mask the detection of the electric signals was assessed. Based on the masking effects, we conclude that sinusoidal electric stimulation of the intact cochlea results in perception of a tonal (rather than a broad-band or noisy) sound at a frequency of 8 kHz or above. PMID:17225416

Sinusoidal obstruction syndrome (SOS): A light and electron microscopy study in human liver.

PubMed

Vreuls, C P H; Driessen, A; Olde Damink, S W M; Koek, G H; Duimel, H; van den Broek, M A J; Dejong, C H C; Braet, F; Wisse, E

2016-05-01

Oxaliplatin is an important chemotherapeutic agent, used in the treatment of hepatic colorectal metastases, and known to induce the sinusoidal obstruction syndrome (SOS). Pathophysiological knowledge concerning SOS is based on a rat model. Therefore, the aim was to perform a comprehensive study of the features of human SOS, using both light microscopy (LM) and electron microscopy (EM). Included were all patients of whom wedge liver biopsies were collected during a partial hepatectomy for colorectal liver metastases, in a 4-year period. The wedge biopsy were perfusion fixated and processed for LM and EM. The SOS lesions were selected by LM and details were studied using EM. Material was available of 30 patients, of whom 28 patients received neo-adjuvant oxaliplatin. Eighteen (64%) of the 28 patients showed SOS lesions, based on microscopy. The lesions consisted of sinusoidal endothelial cell detachment from the space of Disse on EM. In the enlarged space of Disse a variable amount of erythrocytes were located. Sinusoidal endothelial cell detachment was present in human SOS, accompanied by enlargement of the space of Disse and erythrocytes in this area. These findings, originally described in a rat model, were now for the first time confirmed in human livers under clinically relevant settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Observation of Sinusoidal Voltage Behaviour in Silver Doped YBCO

NASA Astrophysics Data System (ADS)

Altinkok, Atilgan; Olutas, Murat; Kilic, Kivilcim; Kilic, Atilla

The influence of bi-directional square wave (BSW) current was investigated on the evolution of the V - t curves at different periods (P) , temperatures and external magnetic fields. It was observed that slow transport relaxation measurements result in regular sinusoidal voltage oscillations which were discussed mainly in terms of the dynamic competition between pinning and depinning.The symmetry in the voltage oscillations was attributed to the elastic coupling between the flux lines and the pinning centers along grain boundaries and partly inside the grains. This case was also correlated to the equality between flux entry and exit along the YBCO/Ag sample during regular oscillations. It was shown that the voltage oscillations can be described well by an empirical expression V (t) sin(wt + φ) . We found that the phase angle φgenerally takes different values for the repetitive oscillations. Fast Fourier Transform analysis of the V - t oscillations showed that the oscillation period is comparable to that (PI) of the BSW current. This finding suggests a physical mechanism associated with charge density waves (CDWs), and, indeed, the weakly pinned flux line system in YBCO/Ag resembles the general behavior of CDWs. At certain values of PI, amplitude of BSW current, H and T, the YBCO/Ag sample behaves like a double-integrator, since it converts the BSW current to sinusoidal voltage oscillations in time.

Multilevel cascade voltage source inverter with seperate DC sources

DOEpatents

Peng, Fang Zheng; Lai, Jih-Sheng

1997-01-01

A multilevel cascade voltage source inverter having separate DC sources is described herein. This inverter is applicable to high voltage, high power applications such as flexible AC transmission systems (FACTS) including static VAR generation (SVG), power line conditioning, series compensation, phase shifting and voltage balancing and fuel cell and photovoltaic utility interface systems. The M-level inverter consists of at least one phase wherein each phase has a plurality of full bridge inverters equipped with an independent DC source. This inverter develops a near sinusoidal approximation voltage waveform with only one switching per cycle as the number of levels, M, is increased. The inverter may have either single-phase or multi-phase embodiments connected in either wye or delta configurations.

Multilevel cascade voltage source inverter with seperate DC sources

DOEpatents

Peng, Fang Zheng; Lai, Jih-Sheng

2002-01-01

A multilevel cascade voltage source inverter having separate DC sources is described herein. This inverter is applicable to high voltage, high power applications such as flexible AC transmission systems (FACTS) including static VAR generation (SVG), power line conditioning, series compensation, phase shifting and voltage balancing and fuel cell and photovoltaic utility interface systems. The M-level inverter consists of at least one phase wherein each phase has a plurality of full bridge inverters equipped with an independent DC source. This inverter develops a near sinusoidal approximation voltage waveform with only one switching per cycle as the number of levels, M, is increased. The inverter may have either single-phase or multi-phase embodiments connected in either wye or delta configurations.

Multilevel cascade voltage source inverter with seperate DC sources

DOEpatents

Peng, Fang Zheng; Lai, Jih-Sheng

2001-04-03

A multilevel cascade voltage source inverter having separate DC sources is described herein. This inverter is applicable to high voltage, high power applications such as flexible AC transmission systems (FACTS) including static VAR generation (SVG), power line conditioning, series compensation, phase shifting and voltage balancing and fuel cell and photovoltaic utility interface systems. The M-level inverter consists of at least one phase wherein each phase has a plurality of full bridge inverters equipped with an independent DC source. This inverter develops a near sinusoidal approximation voltage waveform with only one switching per cycle as the number of levels, M, is increased. The inverter may have either single-phase or multi-phase embodiments connected in either wye or delta configurations.

Multilevel cascade voltage source inverter with separate DC sources

DOEpatents

Peng, F.Z.; Lai, J.S.

1997-06-24

A multilevel cascade voltage source inverter having separate DC sources is described herein. This inverter is applicable to high voltage, high power applications such as flexible AC transmission systems (FACTS) including static VAR generation (SVG), power line conditioning, series compensation, phase shifting and voltage balancing and fuel cell and photovoltaic utility interface systems. The M-level inverter consists of at least one phase wherein each phase has a plurality of full bridge inverters equipped with an independent DC source. This inverter develops a near sinusoidal approximation voltage waveform with only one switching per cycle as the number of levels, M, is increased. The inverter may have either single-phase or multi-phase embodiments connected in either wye or delta configurations. 15 figs.

Removal of Stationary Sinusoidal Noise from Random Vibration Signals.

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

Johnson, Brian; Cap, Jerome S.

In random vibration environments, sinusoidal line noise may appear in the vibration signal and can affect analysis of the resulting data. We studied two methods which remove stationary sine tones from random noise: a matrix inversion algorithm and a chirp-z transform algorithm. In addition, we developed new methods to determine the frequency of the tonal noise. The results show that both of the removal methods can eliminate sine tones in prefabricated random vibration data when the sine-to-random ratio is at least 0.25. For smaller ratios down to 0.02 only the matrix inversion technique can remove the tones, but the metricsmore » to evaluate its effectiveness also degrade. We also found that using fast Fourier transforms best identified the tonal noise, and determined that band-pass-filtering the signals prior to the process improved sine removal. When applied to actual vibration test data, the methods were not as effective at removing harmonic tones, which we believe to be a result of mixed-phase sinusoidal noise.« less

Sinusoidal synthesis based adaptive tracking for rotating machinery fault detection

NASA Astrophysics Data System (ADS)

Li, Gang; McDonald, Geoff L.; Zhao, Qing

2017-01-01

This paper presents a novel Sinusoidal Synthesis Based Adaptive Tracking (SSBAT) technique for vibration-based rotating machinery fault detection. The proposed SSBAT algorithm is an adaptive time series technique that makes use of both frequency and time domain information of vibration signals. Such information is incorporated in a time varying dynamic model. Signal tracking is then realized by applying adaptive sinusoidal synthesis to the vibration signal. A modified Least-Squares (LS) method is adopted to estimate the model parameters. In addition to tracking, the proposed vibration synthesis model is mainly used as a linear time-varying predictor. The health condition of the rotating machine is monitored by checking the residual between the predicted and measured signal. The SSBAT method takes advantage of the sinusoidal nature of vibration signals and transfers the nonlinear problem into a linear adaptive problem in the time domain based on a state-space realization. It has low computation burden and does not need a priori knowledge of the machine under the no-fault condition which makes the algorithm ideal for on-line fault detection. The method is validated using both numerical simulation and practical application data. Meanwhile, the fault detection results are compared with the commonly adopted autoregressive (AR) and autoregressive Minimum Entropy Deconvolution (ARMED) method to verify the feasibility and performance of the SSBAT method.

Rho GTPases and their downstream effectors in megakaryocyte biology.

PubMed

Pleines, Irina; Cherpokova, Deya; Bender, Markus

2018-06-18

Megakaryocytes differentiate from hematopoietic stem cells in the bone marrow. The transition of megakaryocytes to platelets is a complex process. Thereby, megakaryocytes extend proplatelets into sinusoidal blood vessels, where the proplatelets undergo fission to release platelets. Defects in platelet production can lead to a low platelet count (thrombocytopenia) with increased bleeding risk. Rho GTPases comprise a family of small signaling G proteins that have been shown to be master regulators of the cytoskeleton controlling many aspects of intracellular processes. The generation of Pf4-Cre transgenic mice was a major breakthrough that enabled studies in megakaryocyte-/platelet-specific knockout mouse lines and provided new insights into the central regulatory role of Rho GTPases in megakaryocyte maturation and platelet production. In this review, we will summarize major findings on the role of Rho GTPases in megakaryocyte biology with a focus on mouse lines in which knockout strategies have been applied to study the function of the best-characterized members Rac1, Cdc42 and RhoA and their downstream effector proteins.

Cytoprotective and pro-angiogenic functions of thrombomodulin are preserved in the C loop of the fifth epidermal growth factor-like domain.

PubMed

Wang, Xiangmin; Pan, Bin; Honda, Goichi; Wang, Xintao; Hashimoto, Yuko; Ohkawara, Hiroshi; Xu, Kailin; Zeng, Lingyu; Ikezoe, Takayuki

2018-06-14

We previously found that the fifth epidermal growth factor-like domain of thrombomodulin (TME5) exerts cytoprotective and pro-angiogenic functions via G-protein coupled receptor 15 (GPR15). TME5 is comprised of three S-S bonds that divide it into three loops: A (TME5A), B (TME5B), and C (TME5C). Here, we identified the minimum structure of TME5 that produces favorable effects in vascular endothelial cells (ECs). We found that TME5C, composed of 19 amino acids, but not TME5A or TME5B, stimulated the proliferation of human umbilical vein endothelial cells (HUVECs) and human hepatic sinusoidal endothelial cells (HHSECs). Matrigel plug assays showed that TME5C stimulates in vivo angiogenesis. In addition, TME5C counteracted calcineurin inhibitor-induced apoptosis and vascular permeability in HUVECs and HHSECs. Western blot analysis indicated that exposure of either HUVECs or HHSECs to TME5C increased the levels of anti-apoptotic myeloid cell leukemia-1 protein in association with the activation of signal transduction pathways, including extracellular signal-regulated kinase, AKT, and mitogen-activated protein kinase p38. Importantly, TME5C did not affect the coagulation pathway in vitro. The cytoprotective function of TME5C was mediated by cell surface-expressed GPR15, as TME5C was not able to protect vascular ECs isolated from GPR15 knock-out mice. Strikingly, TME5C successfully ameliorated sinusoidal obstruction syndrome in a murine model by counteracting the reduction of sinusoidal ECs numbers. Taken together, the cytoprotective and pro-angiogenetic functions of TM are preserved in TME5C. Use of TME5C may be a promising treatment strategy to prevent or treat lethal complications such as sinusoidal obstruction syndrome whose pathogenesis is based on endothelial insults. Copyright © 2018, Ferrata Storti Foundation.

The functional interrelationship between gap junctions and fenestrae in endothelial cells of the liver organoid.

PubMed

Saito, Masaya; Matsuura, Tomokazu; Nagatsuma, Keisuke; Tanaka, Ken; Maehashi, Haruka; Shimizu, Keiko; Hataba, Yoshiaki; Kato, Fumitaka; Kashimori, Isao; Tajiri, Hisao; Braet, Filip

2007-06-01

Functional intact liver organoid can be reconstructed in a radial-flow bioreactor when human hepatocellular carcinoma (FLC-5), mouse immortalized sinusoidal endothelial M1 (SEC) and A7 (HSC) hepatic stellate cell lines are cocultured. The structural and functional characteristics of the reconstructed organoid closely resemble the in vivo liver situation. Previous liver organoid studies indicated that cell-to-cell communications might be an important factor for the functional and structural integrity of the reconstructed organoid, including the expression of fenestrae. Therefore, we examined the possible relationship between functional intact gap junctional intercellular communication (GJIC) and fenestrae dynamics in M1-SEC cells. The fine morphology of liver organoid was studied in the presence of (1) irsogladine maleate (IM), (2) oleamide and (3) oleamide followed by IM treatment. Fine ultrastructural changes were studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and compared with control liver organoid data. TEM revealed that oleamide affected the integrity of cell-to-cell contacts predominantly in FLC-5 hepatocytes. SEM observation showed the presence of fenestrae on M1-SEC cells; however, oleamide inhibited fenestrae expression on the surface of endothelial cells. Interestingly, fenestrae reappeared when IM was added after initial oleamide exposure. GJIC mediates the number of fenestrae in endothelial cells of the liver organoid.

High Power, Pulsed, RF Generation from Nonlinear Lumped Element Transmission Lines (NLETLs)

DTIC Science & Technology

2011-02-05

specific to solitons. including both overtaking and head on collision interactions and the Fermi- Pasta -Ulam recurrence phenomenon [50]. Contributions by...simulation has indicated the initiation of this curious effect. The Fernii- Pasta -Ulain recurrence phenomena, whereby a sinusoidal excitation applied to a

Perisinusoidal cell hypertrophy in a patient with acquired immunodeficiency syndrome.

PubMed

Kossaifi, T; Dupon, M; Le Bail, B; Lacut, Y; Balabaud, C; Bioulac-Sage, P

1990-08-01

A 33-year-old heterosexual white man underwent a liver biopsy for determination of mild elevation of aminotransferase levels (aspartate aminotransferase, two times; alanine aminotransferase, three times). The patient had acquired immunodeficiency syndrome (stage IVC2) with tuberculosis of the lymph nodes. Antibody to hepatitis B surface antigen and antibody to hepatitis B core antigen were positive. Syphillis tests were positive. Liver architecture was normal; sinusoids were dilated with perisinusoidal, centrilobular, and portal fibrosis. On a 1-micron-thick section and under electron microscopy, perisinusoidal cells appeared to be massively loaded with lipids, while endothelial cells contained numerous dense bodies. Some hepatocytes presented evidence of cell damage. Sinusoids were infiltrated by an increased number of lymphocytes and macrophages. This patient who had recently been treated for tuberculosis was not taking extra vitamin A. He had no disease so far reported as being associated with perisinusoidal cell hypertrophy. This case and others are evidence that acquired immunodeficiency syndrome represents another cause of perisinusoidal cell hypertrophy in which there is no documented hypervitaminosis A.

Sinusoidal voltage protocols for rapid characterisation of ion channel kinetics.

PubMed

Beattie, Kylie A; Hill, Adam P; Bardenet, Rémi; Cui, Yi; Vandenberg, Jamie I; Gavaghan, David J; de Boer, Teun P; Mirams, Gary R

2018-03-24

Ion current kinetics are commonly represented by current-voltage relationships, time constant-voltage relationships and subsequently mathematical models fitted to these. These experiments take substantial time, which means they are rarely performed in the same cell. Rather than traditional square-wave voltage clamps, we fitted a model to the current evoked by a novel sum-of-sinusoids voltage clamp that was only 8 s long. Short protocols that can be performed multiple times within a single cell will offer many new opportunities to measure how ion current kinetics are affected by changing conditions. The new model predicts the current under traditional square-wave protocols well, with better predictions of underlying currents than literature models. The current under a novel physiologically relevant series of action potential clamps is predicted extremely well. The short sinusoidal protocols allow a model to be fully fitted to individual cells, allowing us to examine cell-cell variability in current kinetics for the first time. Understanding the roles of ion currents is crucial to predict the action of pharmaceuticals and mutations in different scenarios, and thereby to guide clinical interventions in the heart, brain and other electrophysiological systems. Our ability to predict how ion currents contribute to cellular electrophysiology is in turn critically dependent on our characterisation of ion channel kinetics - the voltage-dependent rates of transition between open, closed and inactivated channel states. We present a new method for rapidly exploring and characterising ion channel kinetics, applying it to the hERG potassium channel as an example, with the aim of generating a quantitatively predictive representation of the ion current. We fitted a mathematical model to currents evoked by a novel 8 second sinusoidal voltage clamp in CHO cells overexpressing hERG1a. The model was then used to predict over 5 minutes of recordings in the same cell in response to further protocols: a series of traditional square step voltage clamps, and also a novel voltage clamp comprising a collection of physiologically relevant action potentials. We demonstrate that we can make predictive cell-specific models that outperform the use of averaged data from a number of different cells, and thereby examine which changes in gating are responsible for cell-cell variability in current kinetics. Our technique allows rapid collection of consistent and high quality data, from single cells, and produces more predictive mathematical ion channel models than traditional approaches. © 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

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

Agostoni, Marco; Lucker, Ben F.; Smith, Matthew A. Y.

Phycobilisomes (PBSs) are pigment-rich super-complexes required for efficient harvest and transfer of light energy to photosynthetic reaction centers of cyanobacteria. The model cyanobacterium Fremyella diplosiphon is able to adjust PBS pigmentation and size in response to the prevailing light spectrum through a process called complementary chromatic acclimation to optimize spectral light absorption, concomitantly optimizing photosynthesis and growth. We explored the fitness costs versus advantages of modulating antennae size and composition under sinusoidal continuous and fluctuating light conditions in F. diplosiphon by comparing growth of wild-type (WT) cells with a mutant strain deficient in PBSs in both monoculture and polyculture conditions.more » Comparative analyses of WT and the PBS-deficient FdCh1 strain under continuous vs. fluctuating sinusoidal light suggest a potential fitness advantage for maintaining PBSs in WT cells during continuous light and a fitness cost during transitions to and acclimation under fluctuating light. Here, we explored the physiological changes correlated with the observed differential growth to understand the dynamics and biochemical bases of comparative fitness of distinct strains under defined growth conditions. Wild-type F. diplosiphon appears to accumulate longer PBS rods and exhibits higher oxidative stress under fluctuating light conditions than continuous sinusoidal light, which may impact responses and the fitness of cells that do not adapt to rapid changes in external light.« less

The sinusoidal probe: a new approach to improve electrode longevity

PubMed Central

Sohal, Harbaljit S.; Jackson, Andrew; Jackson, Richard; Clowry, Gavin J.; Vassilevski, Konstantin; O’Neill, Anthony; Baker, Stuart N.

2014-01-01

Micromotion between the brain and implanted electrodes is a major contributor to the failure of invasive brain–machine interfaces. Movements of the electrode tip cause recording instabilities while spike amplitudes decline over the weeks/months post-implantation due to glial cell activation caused by sustained mechanical trauma. We have designed a sinusoidal probe in order to reduce movement of the recording tip relative to the surrounding neural tissue. The probe was microfabricated from flexible materials and incorporated a sinusoidal shaft to minimize tethering forces and a 3D spheroid tip to anchor the recording site within the brain. Compared to standard microwire electrodes, the signal-to-noise ratio and local field potential power of sinusoidal probe recordings from rabbits was more stable across recording periods up to 678 days. Histological quantification of microglia and astrocytes showed reduced neuronal tissue damage especially for the tip region between 6 and 24 months post-implantation. We suggest that the micromotion-reducing measures incorporated into our design, at least partially, decreased the magnitude of gliosis, resulting in enhanced longevity of recording. PMID:24808859

Experimental model for ELF-EMF exposure: Concern for human health

PubMed Central

D’Angelo, C.; Costantini, E.; Kamal, M.A.; Reale, M.

2014-01-01

Low frequency (LF) electromagnetic fields (EMFs) are abundantly present in modern society and in the last 20 years the interest about the possible effect of extremely low frequency (ELF) EMFs on human health has increased progressively. Epidemiological studies, designed to verify whether EMF exposure may be a potential risk factor for health, have led to controversial results. The possible association between EMFs and an increased incidence of childhood leukemia, brain tumors or neurodegenerative diseases was not fully elucidated. On the other hand, EMFs are widely used, in neurology, psychiatry, rheumatology, orthopedics and dermatology, both in diagnosis and in therapy. In vitro studies may help to evaluate the mechanism by which LF-EMFs affect biological systems. Invitro model of wound healing used keratinocytes (HaCaT), neuroblastoma cell line (SH-SY5Y) as a model for analysis of differentiation, metabolism and functions related to neurodegenerative processes, and monocytic cell line (THP-1) was used as a model for inflammation and cytokines production, while leukemic cell line (K562) was used as a model for hematopoietic differentiation. MCP-1, a chemokine that regulates the migration and infiltration of memory T cells, natural killer (NK), monocytes and epithelial cells, has been demonstrated to be induced and involved in various diseases. Since, varying the parameters of EMFs different effects may be observed, we have studied MCP-1 expression in HaCaT, SH-SY5Y, THP-1 and K562 exposed to a sinusoidal EMF at 50 Hz frequency with a flux density of 1 mT (rms). Our preliminary results showed that EMF-exposure differently modifies the expression of MCP-1 in different cell types. Thus, the MCP-1 expression needs to be better determined, with additional studies, with different parameters and times of exposure to ELF-EMF. PMID:25561888

A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD

PubMed Central

Ashworth, William B.; Bogle, I. David L.

2016-01-01

In non-alcoholic fatty liver disease (NAFLD), lipid build-up and the resulting damage is known to occur more severely in pericentral cells. Due to the complexity of studying individual regions of the sinusoid, the causes of this zone specificity and its implications on treatment are largely ignored. In this study, a computational model of liver glucose and lipid metabolism is presented which treats the sinusoid as the repeating unit of the liver rather than the single hepatocyte. This allows for inclusion of zonated enzyme expression by splitting the sinusoid into periportal to pericentral compartments. By simulating insulin resistance (IR) and high intake diets leading to the development of steatosis in the model, we identify key differences between periportal and pericentral cells accounting for higher susceptibility to pericentral steatosis. Secondly, variation between individuals is seen in both susceptibility to steatosis and in its development across the sinusoid. Around 25% of obese individuals do not show excess liver fat, whilst 16% of lean individuals develop NAFLD. Furthermore, whilst pericentral cells tend to show higher lipid levels, variation is seen in the predominant location of steatosis from pericentral to pan-sinusoidal or azonal. Sensitivity analysis was used to identify the processes which have the largest effect on both total hepatic triglyceride levels and on the sinusoidal location of steatosis. As is seen in vivo, steatosis occurs when simulating IR in the model, predominantly due to increased uptake, along with an increase in de novo lipogenesis. Additionally, concentrations of glucose intermediates including glycerol-3-phosphate increased when simulating IR due to inhibited glycogen synthesis. Several differences between zones contributed to a higher susceptibility to steatosis in pericentral cells in the model simulations. Firstly, the periportal zonation of both glycogen synthase and the oxidative phosphorylation enzymes meant that the build-up of glucose intermediates was less severe in the periportal hepatocyte compartments. Secondly, the periportal zonation of the enzymes mediating β-oxidation and oxidative phosphorylation resulted in excess fats being metabolised more rapidly in the periportal hepatocyte compartments. Finally, the pericentral expression of de novo lipogenesis contributed to pericentral steatosis when additionally simulating the increase in sterol-regulatory element binding protein 1c (SREBP-1c) seen in NAFLD patients in vivo. The hepatic triglyceride concentration was predicted to be most sensitive to inter-individual variation in the activity of enzymes which, either directly or indirectly, determine the rate of free fatty acid (FFA) oxidation. The concentration was most strongly dependent on the rate constants for β-oxidation and oxidative phosphorylation. It also showed moderate sensitivity to the rate constants for processes which alter the allosteric inhibition of β-oxidation by acetyl-CoA. The predominant sinusoidal location of steatosis meanwhile was most sensitive variations in the zonation of proteins mediating FFA uptake or triglyceride release as very low density lipoproteins (VLDL). Neither the total hepatic concentration nor the location of steatosis showed strong sensitivity to variations in the lipogenic rate constants. PMID:27632189

EFFECT OF AMBIENT LEVELS OF POWER-LINE-FREQUENCY ELECTRIC FIELDS ON A DEVELOPING VERTEBRATE (JOURNAL VERSION)

EPA Science Inventory

Fertilized eggs of Gallus domesticus were exposed continuously during their 21-day incubation period to either 50-Hz or 60-Hz sinusoidal electric fields at an average intensity of 10 Vrms/m. Within 1.5 days after hatching, the chickens were removed from the apparatus and tested. ...

Diffusion of chaotic field lines in tokamaks

NASA Astrophysics Data System (ADS)

Ali, Halima; Punjabi, Alkesh

2006-10-01

An important instability for the destruction of magnetic surfaces in tokamaks due to island overlapping is the tearing modes. Magnetic fields perturbed by tearing modes are given by the sinusoidal form Br=-1rR∑m,nbm^n ( mθ-n ) . The sinusoidal nature of perturbation creates islands structure near resonant surfaces. In this work, we consider two modes, ( m1,n1 )and ( m2,n2 )that interact with each other, leading to two chains of islands, called primary islands. We use a previously derived Hamiltonian map, the ψ-θ map, with and without higher order control terms to study the diffusion of chaotic field lines. We will present and discuss the results of this work, and discuss its implications with regard to magnetic transport barriers for a fixed q-profile and increasing strength of magnetic perturbations. This work is done under the DOE grant number DE-FG02-01ER54624. 1.A. Punjabi et al, Phys. Rev. lett., 69, 3322 (1992). 2. H. Ali, A. Punjabi, and A. Boozer, Int. J. Comp. Num. Ana. Applications 6, 17 (2005).

[Morphological pathology of classic Kaposi's sarcoma. Ultrastructural studies and reflections on histogenesis].

PubMed

Holzhausen, H J; Stiller, D; Sachs, M

1988-01-01

Histological and electron-microscopic studies were conducted into biopsy material from cases of what is called the classical type of idiopathic Kaposi's sarcoma without acquired immunodeficiency syndrome. Ultrastructural analysis was conducted, with the view to characterizing a possible progenitor cell from which the angioblastic and fibroblastic elements were likely to originate. The biopsy material had been obtained from two males, aged 86 or 83 years, who had been afflicted with the disease for 18 or 8 years. The nodular lesions were typical of Kaposi's sarcoma and were, histologically, made up of variable mixtures of vascular and spindle cell elements. The angiomatous structures were a capillary meshwork or sinusoidal patterns lined by atypical endothelial cells. The spindle cell areas contained large numbers of slit-like spaces which were without endothelial lining but were stuffed with erythrocytes. Flattened endothelioid cells were recordable from semi-thin-sections of some clefts. Haemosiderin was, typically, deposited in places. Electron microscopically, the endothelial cells of vascular channels exhibited varying amounts of characteristic organelles, such as Weibel-Palade bodies, microfilaments and pinocytotic vesicles as well as basal membranes. Cells with typical endothelial markers, too, were detectable in solid sprouts or in capillary-like differentiations with narrow or small lumina. The spindle cell tumour areas consisted of fibroblastic cells with plenty of rough endoplasmic reticulum and surrounded by material of basal membrane nature. Also visible were solid, sprout-type multilayer cell complexes surrounded by basal membranes which exhibited undifferentiated or primitive cellular forms, endothelioid and pericytic. Transitional forms from these complexes to the above vascular tumours or the spindle-cell formations were detectable. These ultrastructural findings might be interpreted to the effect that an angioblastically determined mesenchymal cell, a so-called endothelioblast, was thinkable and was discussed as the precursor cell of atypical vascular and spindle cell proliferation in Kaposi's sarcoma.

Center/surround organization of retinal bipolar cells: High correlation of fundamental responses of center and surround to sinusoidal contrasts

PubMed Central

Burkhardt, Dwight A.; Bartoletti, Theodore M.; Thoreson, Wallace B.

2012-01-01

Receptive field organization of cone-driven bipolar cells was investigated by intracellular recording in the intact light-adapted retina of the tiger salamander (Ambystoma tigrinum). Centered spots and concentric annuli of optimum dimensions were used to selectively stimulate the receptive field center and surround with sinusoidal modulations of contrast at 3 Hz. At low contrasts, responses of both the center and surround of both ON and OFF bipolar cells were linear, showing high gain and thus contrast enhancement relative to cones. The contrast/response curves for the fundamental response, measured by a Fast Fourier Transform, reached half maximum amplitude quickly at 13% contrast followed by saturation at high contrasts. The variation of the normalized amplitude of the center and surround responses was remarkably similar, showing linear regression over the entire response range with very high correlations, r2 = 0.97 for both ON and OFF cells. The contrast/response curves of both center and surround for both ON and OFF cells were well fit (r2 = 0.98) by an equation for single-site binding. In about half the cells studied, the nonlinear waveforms of center and surround could be brought into coincidence by scaling and shifting the surround response in time. This implies that a nonlinearity, common to both center and surround, occurs after polarity inversion at the cone feedback synapse. Evidence from paired whole-cell recordings between single cones and OFF bipolar cells suggests that substantial nonlinearity is not due to transmission at the cone synapse but instead arises from intrinsic bipolar cell and network mechanisms. When sinusoidal contrast modulations were applied to the center and surround simultaneously, clear additivity was observed for small responses in both ON and OFF cells, whereas the interaction was strikingly nonadditive for large responses. The contribution of the surround was then greatly reduced, suggesting attenuation at the cone feedback synapse. PMID:21439110

Frequency-Modulation Correlation Spectrometer

NASA Technical Reports Server (NTRS)

Margolis, J. S.; Martonchik, J. V.

1985-01-01

New type of correlation spectrometer eliminates need to shift between two cells, one empty and one containing reference gas. Electrooptical phase modulator sinusoidally shift frequencies of sample transmission spectrum.

Removal of cellular debris formed in the Disse space in patients with cholestasis.

PubMed

Dubuisson, L; Bioulac-Sage, P; Boussarie, L; Quinton, A; Saric, J; de Mascarel, A; Balabaud, C

1987-01-01

Using electron microscopy, we investigated how cellular debris, formed in the Disse space during cholestasis, was cleared. Ten patients with cholestasis of varied origin and severity were studied and compared with 10 controls without liver disease. In cholestatic patients, sinusoidal cells contained variable amounts of amylase PAS-positive material. In clean perfusion-fixed sinusoids the endothelial cells often appeared swollen and active, with few fenestrations. Hepatocyte blebs and cellular debris were sometimes seen in the Disse space. Two mechanisms were apparently involved in the clearing process: phagocytosis by macrophages either infiltrated into the Disse space, or forming the barrier; and the passage of debris from the Disse space into the sinusoidal lumen through the endothelial wall. Debris was either forced through enlarged pores or through the wall, with a progressive invagination followed by an outpouching in the lumen. The force, possibly provided by endothelial massage, may not be sufficient to push out cellular debris from the Disse space; morphological data seemed to indicate that endothelial damage may be a necessary factor. Debris present in the lumen was phagocytized by numerous active macrophages. Cellular debris was not observed in the Disse space of control patients.

Decrease of PECAM-1-gene-expression induced by proinflammatory cytokines IFN-γ and IFN-α is reversed by TGF-β in sinusoidal endothelial cells and hepatic mononuclear phagocytes

PubMed Central

Neubauer, Katrin; Lindhorst, Alexander; Tron, Kyrylo; Ramadori, Giuliano; Saile, Bernhard

2008-01-01

Background and aim The mechanisms of transmigration of inflammatory cells through the sinusoids are still poorly understood. This study aims to identify in vitro conditions (cytokine treatment) which may allow a better understanding of the changes in PECAM (platelet endothelial cell adhesion molecule)-1-gene-expression observed in vivo. Methods and results In this study we show by immunohistochemistry, that there is an accumulation of ICAM-1 (intercellular cell adhesion molecule-1) and ED1 positive cells in necrotic areas of livers of CCl4-treated rats, whereas there are few PECAM-1 positive cells observable. After the administration of CCl4, we could detect an early rise of levels of IFN-γ followed by an enhanced TGF-β protein level. As shown by Northern blot analysis and surface protein expression analysed by flow cytometry, IFN-γ-treatment decreased PECAM-1-gene-expression in isolated SECs (sinusoidal endothelial cells) and mononuclear phagocytes (MNPs) in parallel with an increase in ICAM-1-gene-expression in a dose and time dependent manner. In contrast, TGF-β-treatment increased PECAM-1-expression. Additional administration of IFN-γ to CCl4-treated rats and observations in IFN-γ-/- mice confirmed the effect of IFN-γ on PECAM-1 and ICAM-1-expression observed in vitro and increased the number of ED1-expressing cells 12 h after administration of the toxin. Conclusion The early decrease of PECAM-1-expression and the parallel increase of ICAM-1-expression following CCl4-treatment is induced by elevated levels of IFN-γ in livers and may facilitate adhesion and transmigration of inflammatory cells. The up-regulation of PECAM-1-expression in SECs and MNPs after TGF-β-treatment suggests the involvement of PECAM-1 during the recovery after liver damage. PMID:18466611

External synchronization of oscillating pulse edge on a transmission line with regularly spaced tunnel diodes.

PubMed

Narahara, Koichi; Misono, Masatoshi; Miyakawa, Kenji

2013-01-01

We investigate the external synchronization of the oscillating pulse edges developed in a transmission line periodically loaded with tunnel diodes (TDs), termed a TD line. It is observed that the pulse edge oscillates on a TD line when supplied by an appropriate voltage at the end of the line. We discuss how the pulse edge oscillates on a TD line and the properties of the external synchronization of the edge oscillation driven by a sinusoidal perturbation. By applying a phase-reduction scheme to the transmission equation of a TD line, we obtain the phase sensitivity, which satisfactory explains the measured spatial dependence of the locking range on the frequency. Moreover, we successfully detect the spatiotemporal behaviors of the edge oscillation by establishing synchronization with the sampling trigger of an oscilloscope.

Calcium channel dynamics limit synaptic release in response to prosthetic stimulation with sinusoidal waveforms

PubMed Central

Freeman, Daniel K.; Jeng, Jed S.; Kelly, Shawn K.; Hartveit, Espen; Fried, Shelley I.

2011-01-01

Extracellular electric stimulation with sinusoidal waveforms has been shown to allow preferential activation of individual types of retinal neurons by varying stimulus frequency. It is important to understand the mechanisms underlying this frequency dependence as a step towards improving methods of preferential activation. In order to elucidate these mechanisms, we implemented a morphologically realistic model of a retinal bipolar cell and measured the response to extracellular stimulation with sinusoidal waveforms. We compared the frequency response of a passive membrane model to the kinetics of voltage-gated calcium channels that mediate synaptic release. The passive electrical properties of the membrane exhibited lowpass filtering with a relatively high cutoff frequency (nominal value = 717 Hz). This cutoff frequency was dependent on intra-axonal resistance, with shorter and wider axons yielding higher cutoff frequencies. However, we found that the cutoff frequency of bipolar cell synaptic release was primarily limited by the relatively slow opening kinetics of Land T-type calcium channels. The cutoff frequency of calcium currents depended nonlinearly on stimulus amplitude, but remained lower than the cutoff frequency of the passive membrane model for a large range of membrane potential fluctuations. These results suggest that while it may be possible to modulate the membrane potential of bipolar cells over a wide range of stimulus frequencies, synaptic release will only be initiated at the lower end of this range. PMID:21628768

Competition-based phenotyping reveals a fitness cost for maintaining phycobilisomes under fluctuating light in the cyanobacterium Fremyella diplosiphon

DOE PAGES

Agostoni, Marco; Lucker, Ben F.; Smith, Matthew A. Y.; ...

2016-02-21

Phycobilisomes (PBSs) are pigment-rich super-complexes required for efficient harvest and transfer of light energy to photosynthetic reaction centers of cyanobacteria. The model cyanobacterium Fremyella diplosiphon is able to adjust PBS pigmentation and size in response to the prevailing light spectrum through a process called complementary chromatic acclimation to optimize spectral light absorption, concomitantly optimizing photosynthesis and growth. We explored the fitness costs versus advantages of modulating antennae size and composition under sinusoidal continuous and fluctuating light conditions in F. diplosiphon by comparing growth of wild-type (WT) cells with a mutant strain deficient in PBSs in both monoculture and polyculture conditions.more » Comparative analyses of WT and the PBS-deficient FdCh1 strain under continuous vs. fluctuating sinusoidal light suggest a potential fitness advantage for maintaining PBSs in WT cells during continuous light and a fitness cost during transitions to and acclimation under fluctuating light. Here, we explored the physiological changes correlated with the observed differential growth to understand the dynamics and biochemical bases of comparative fitness of distinct strains under defined growth conditions. Wild-type F. diplosiphon appears to accumulate longer PBS rods and exhibits higher oxidative stress under fluctuating light conditions than continuous sinusoidal light, which may impact responses and the fitness of cells that do not adapt to rapid changes in external light.« less

Ultrastructural sinusoidal changes in extrahepatic cholestasis. Light and electron microscopic immunohistochemical localization of collagen type III and type IV.

PubMed

Gulubova, M V

1996-07-01

Extrahepatic cholestasis causes excessive extracellular matrix formation perisinusoidally. Ito cells, transitional and endothelial cells are considered to be a source of extracellular matrix proteins in experimental cholestasis. The localization of collagens type III and type IV in human liver in extrahepatic cholestasis was investigated immunohistochemically in the present study. Immersion fixation was used after modification to be applied to surgical biopsies with commercially available kits. Sinusoidal changes were observed that indicated excessive collagen and matrix formation. Light microscopically, increased immunostaining with the two collagen antibodies was found perisinusoidally and portally. Ultrastructurally, collagen type III positive fibres were found beneath basement membranes of vessels, in collagen bundles and as a fibrillar network in the space of Disse. Collagen type IV immunostaining was located in portal tracts and near hepatocyte microvilli. Intracellular staining with collagen type IV was detected in the rough endoplasmic reticulum of some transitional cells. Immunostaining was located around transitional cells, Ito cells or endothelial cells mainly. Our study indicates that Ito cells, transitional and endothelial cells are the main source of collagens type III and IV in the space of Disse in extrahepatic cholestasis in humans.

Electrical stimulation of gut motility guided by an in silico model

NASA Astrophysics Data System (ADS)

Barth, Bradley B.; Henriquez, Craig S.; Grill, Warren M.; Shen, Xiling

2017-12-01

Objective. Neuromodulation of the central and peripheral nervous systems is becoming increasingly important for treating a diverse set of diseases—ranging from Parkinson’s Disease and epilepsy to chronic pain. However, neuromodulation of the gastrointestinal (GI) tract has achieved relatively limited success in treating functional GI disorders, which affect a significant population, because the effects of stimulation on the enteric nervous system (ENS) and gut motility are not well understood. Here we develop an integrated neuromechanical model of the ENS and assess neurostimulation strategies for enhancing gut motility, validated by in vivo experiments. Approach. The computational model included a network of enteric neurons, smooth muscle fibers, and interstitial cells of Cajal, which regulated propulsion of a virtual pellet in a model of gut motility. Main results. Simulated extracellular stimulation of ENS-mediated motility revealed that sinusoidal current at 0.5 Hz was more effective at increasing intrinsic peristalsis and reducing colon transit time than conventional higher frequency rectangular current pulses, as commonly used for neuromodulation therapy. Further analysis of the model revealed that the 0.5 Hz sinusoidal currents were more effective at modulating the pacemaker frequency of interstitial cells of Cajal. To test the predictions of the model, we conducted in vivo electrical stimulation of the distal colon while measuring bead propulsion in awake rats. Experimental results confirmed that 0.5 Hz sinusoidal currents were more effective than higher frequency pulses at enhancing gut motility. Significance. This work demonstrates an in silico GI neuromuscular model to enable GI neuromodulation parameter optimization and suggests that low frequency sinusoidal currents may improve the efficacy of GI pacing.

Transmission characteristics of a TEM waveguide for transient signals by the use of a damped sinusoidal

NASA Astrophysics Data System (ADS)

Briest, N.; Garbe, H.; Potthast, S.

2015-11-01

This article broaches the issue of the propagation of transient signals in gigahertz transverse electromagnetic (GTEM) cells. As a representative for transient signals a damped sinusoidal (DS) is used with three different mid-band frequencies. The signal transmission of the DS in the GTEM1250 is qualified and discussed on the basis of the Pearson correlation coefficient (Pcc). The Pcc gives an overview of the signal transmission quality for all measuring points within the testvolume and signal distortions can be identified. A 100 MHz DS is weakly distorted in several measuring points. The Pcc at those points decreases and a signal shape variance can be assumed. Furthermore inhomogeneities of the GTEM1250 caused by the cell door can be identified.

Sickle cell hepatopathy.

PubMed

Bandyopadhyay, Ranjana; Bandyopadhyay, Sanjay K; Dutta, Anita

2008-01-01

Sickle cell hepatopathy is a well-documented entity that ranges from the self-limiting hepatic right upper quadrant syndrome to the potentially lethal intrahepatic cholestasis and acute hepatic sequestration syndromes. We describe a 26-year-male with homozygous sickle cell disease who had this unique hepatic presentation and was documented to have characteristic findings of cholestasis, portal inflammation and sinusoidal dilatation on histopathology.

Rapid Fluctuations of Water Maser Emission in VY Canis Majoris

NASA Astrophysics Data System (ADS)

Zheng, Xing Wu; Scalise, Eugenio, Jr.; Han, Fu

1998-11-01

We report the observational results of short timescale monitoring of the 22 GHz water maser emission in VY CMa. A quasi-sinusoidal fluctuation has been detected with the relative flux intensity change of 20%-25% and a period of 10.3 day for two dominant features. This detected variability appears to be superimposed on the normal maser lines. We cannot easily explain the rapid fluctuation with the variation of the radiative input or the strong interstellar scintillation along the line of sight. The variation may be caused by the periodic shock.

Identification of CD22 Ligands on Bone Marrow Sinusoidal Endothelium Implicated in CD22-dependent Homing of Recirculating B Cells

PubMed Central

Nitschke, Lars; Floyd, Helen; Ferguson, David J.P.; Crocker, Paul R.

1999-01-01

CD22 is a B cell–specific transmembrane protein known to function as a negative regulator of B cell signaling. It has also been implicated in cell adhesion through recognition of α2,6-linked sialic acids on glycans of target cells. Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow despite normal B cell development. Using a soluble recombinant form of the receptor (CD22-Fc), we demonstrate here that sialylated ligands for CD22 are expressed on sinusoidal endothelial cells of murine bone marrow but not on endothelial cells in other tissues examined. Injection of CD22-Fc revealed that the CD22 ligands in the bone marrow were accessible to the circulation. Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibody led to an ∼50% reduction in mature recirculating B cells in the bone marrow without affecting numbers in the spleen. Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobulin M–secreting plasma cells in the bone marrow. PMID:10224292

Emperipolesis of erythroblasts within Kupffer cells during hepatic hemopoiesis in human fetus.

PubMed

Lee, W B; Erm, S K; Kim, K Y; Becker, R P

1999-10-01

The state in which cells can inhabit other cells without damage is known as emperipolesis. Emperipolesis has been found in various physiological and pathological conditions. We performed a study of emperipolesis of erythroblasts within Kupffer cells in the human fetal liver. We found that Kupffer cells, identified by CD68 immunolabeling, contained 4-8 erythroblasts in a hypertrophic cytoplasm on light microscopy. Emperipoletic erythroblasts were present in various maturation stages from proerythroblast to reticulocyte. By electron microscopy, we found that erythroblasts occupied membrane-bound vacuoles that were separated from each other by thin partitions of Kupffer cell cytoplasm. Neither emperipoletic erythroblasts nor their Kupffer cell hosts showed evidence of damage. Emperipoletic cells in mitosis were found, which suggests the capacity for the proliferation of erythroblasts within Kupffer cells. Some Kupffer cells were seen to contain both emperipoletic cells and phagosomes, without evidence of interaction. Erythroblasts and other hemopoietic cells were also found to be closely associated with the sinusoidal surface of Kupffer cells. However, intercellular junctions, if present, were inconspicuous. On occasion, Kupffer cells engorged with erythroblasts nearly occluded the sinusoidal lumen. Our results demonstrate that emperipolesis of erythroblasts within Kupffer cells occurs in human fetal hepatic hemopoiesis. We suggest that emperipolesis may be one of the mechanisms that support the maturation of erythroblasts in the fetal liver. Copyright 1999 Wiley-Liss, Inc.

Electron Microscopic Observations of the Carotid Body of the Cat

PubMed Central

Ross, Leonard L.

1959-01-01

Carotid bodies were removed from cats, fixed in buffered 1 per cent osmic acid, embedded in deaerated, nitrogenated methacrylate, and cut into thin sections for electron microscopic study. The carotid body is seen to be composed of islands of chemoreceptor and sustentacular cells surrounded by wide irregular sinusoids. These cells are separated from the sinusoids by relatively broad interstitial spaces which are filled with collagen, fibroblasts, and many unmyelinated nerve fibers with their Schwann cell sheaths. The chemoreceptor cells are surrounded by the flattened, multiprocessed sustentacular cells which serve to convey the axons from an interstitial to a pericellular location. These sustentacular cells are assumed to be lemmoblastic in origin. Relatively few axons are seen to abut on the chemoreceptor cells. The cytoplasm of the chemoreceptor cell is characterized by numerous small mitochondria, units of granular endoplasmic reticulum, a small Golgi complex, and a variety of vesicles. There are many small vesicles diffusely scattered throughout the cytoplasm. In addition, there is a small number of dark-cored vesicles of the type which has been previously described in the adrenal medulla. These are usually associated with the Golgi complex. These findings are discussed in relation to the concepts of the origin of the chemoreceptor cell and the nature of the synapse. PMID:14439171

High-frequency ac power distribution in Space Station

NASA Technical Reports Server (NTRS)

Tsai, Fu-Sheng; Lee, Fred C. Y.

1990-01-01

A utility-type 20-kHz ac power distribution system for the Space Station, employing resonant power-conversion techniques, is presented. The system converts raw dc voltage from photovoltaic cells or three-phase LF ac voltage from a solar dynamic generator into a regulated 20-kHz ac voltage for distribution among various loads. The results of EASY5 computer simulations of the local and global performance show that the system has fast response and good transient behavior. The ac bus voltage is effectively regulated using the phase-control scheme, which is demonstrated with both line and load variations. The feasibility of paralleling the driver-module outputs is illustrated with the driver modules synchronized and sharing a common feedback loop. An HF sinusoidal ac voltage is generated in the three-phase ac input case, when the driver modules are phased 120 deg away from one another and their outputs are connected in series.

Spectropolarimetry of magnetic stars. IV. The crossover effect.

NASA Astrophysics Data System (ADS)

Mathys, G.

1995-01-01

This paper is devoted to the study of the crossover effect in magnetic Ap stars. It is shown that this effect can be measured by the second order moment about their centre of the profiles of spectral lines recorded in the Stokes parameter V. The interpretation of these measurements in terms of magnetic field is developed. It is shown that one can derive from them a quantity called the mean asymmetry of the longitudinal magnetic field, which is the first moment of the component of the magnetic field along the line of sight, about the plane defined by the line of sight and the stellar rotation axis. The consistency of the determination of this quantity with that of the mean longitudinal magnetic field from measurements of wavelength shifts of lines between right and left circular polarization is demonstrated. This technique of analysis is applied to observations of a sample of 29 stars, among which 10 have a detectable crossover effect. For 8 of them, the available observational data allow the study of the variations of the asymmetry of the longitudinal field with rotation phase. In most cases, this variation is sinusoidal and essentially symmetric about 0, and it occurs in quadrature with the variation of the mean longitudinal field. A more complex behaviour is definitely observed in HD 147010 and HD 175362, where the variation of the asymmetry of the longitudinal field is better represented by the superposition of two sinusoids, one with the rotation frequency of the star, and the other with twice that frequency.

Arachidonic acid metabolites and endothelial dysfunction of portal hypertension.

PubMed

Sacerdoti, David; Pesce, Paola; Di Pascoli, Marco; Brocco, Silvia; Cecchetto, Lara; Bolognesi, Massimo

2015-07-01

Increased resistance to portal flow and increased portal inflow due to mesenteric vasodilatation represent the main factors causing portal hypertension in cirrhosis. Endothelial cell dysfunction, defined as an imbalance between the synthesis, release, and effect of endothelial mediators of vascular tone, inflammation, thrombosis, and angiogenesis, plays a major role in the increase of resistance in portal circulation, in the decrease in the mesenteric one, in the development of collateral circulation. Reduced response to vasodilators in liver sinusoids and increased response in the mesenteric arterioles, and, viceversa, increased response to vasoconstrictors in the portal-sinusoidal circulation and decreased response in the mesenteric arterioles are also relevant to the pathophysiology of portal hypertension. Arachidonic acid (AA) metabolites through the three pathways, cyclooxygenase (COX), lipoxygenase, and cytochrome P450 monooxygenase and epoxygenase, are involved in endothelial dysfunction of portal hypertension. Increased thromboxane-A2 production by liver sinusoidal endothelial cells (LSECs) via increased COX-1 activity/expression, increased leukotriens, increased epoxyeicosatrienoic acids (EETs) (dilators of the peripheral arterial circulation, but vasoconstrictors of the portal-sinusoidal circulation), represent a major component in the increased portal resistance, in the decreased portal response to vasodilators and in the hyper-response to vasoconstrictors. Increased prostacyclin (PGI2) via COX-1 and COX-2 overexpression, and increased EETs/heme-oxygenase-1/K channels/gap junctions (endothelial derived hyperpolarizing factor system) play a major role in mesenteric vasodilatation, hyporeactivity to vasoconstrictors, and hyper-response to vasodilators. EETs, mediators of liver regeneration after hepatectomy and of angiogenesis, may play a role in the development of regenerative nodules and collateral circulation, through stimulation of vascular endothelial growth factor (VEGF) inside the liver and in the portal circulation. Pharmacological manipulation of AA metabolites may be beneficial for cirrhotic portal hypertension. Copyright © 2015 Elsevier Inc. All rights reserved.

Spectral images of HD 199178

NASA Technical Reports Server (NTRS)

Neff, J. E.; Vilhu, O.; Walter, F. M.

1988-01-01

High-resolution IUE spectra of the Mg II k line of HD 199178 were analyzed, applying spectral imaging techniques to derive an image of the chromospheric structure and to study the transient behavior of the chromosphere. All spectra in the IUE archives were uniformly reduced and analyzed. Results are compared with ground-based observations of the photosphere. Four ultraviolet flares on HD 199178 are observed; 3 of these occurred at roughly the same rotational phase. There is no clear phase-dependence of the SWP line fluxes, but there is for the Mg II k flux. The emission centroid of the Mg II k line varies in a quasi-sinusoidal fashion, presumably due to the rotation of a nonuniform chromosphere.

Design optimization of sinusoidal glass honeycomb for flat plate solar collectors

NASA Technical Reports Server (NTRS)

Mcmurrin, J. C.; Buchberg, H.

1980-01-01

The design of honeycomb made of sinusoidally corrugated glass strips was optimized for use in water-cooled, single-glazed flat plate solar collectors with non-selective black absorbers. Cell diameter (d), cell height (L), and pitch/diameter ratio (P/d) maximizing solar collector performance and cost effectiveness for given cell wall thickness (t sub w) and optical properties of glass were determined from radiative and convective honeycomb characteristics and collector performance all calculated with experimentally validated algorithms. Relative lifetime values were estimated from present materials costs and postulated production methods for corrugated glass honeycomb cover assemblies. A honeycomb with P/d = 1.05, d = 17.4 mm, L = 146 mm and t sub w = 0.15 mm would provide near-optimal performance over the range delta T sub C greater than or equal to 0 C and less than or equal to 80 C and be superior in performance and cost effectiveness to a non-honeycomb collector with a 0.92/0.12 selective black absorber.

Optimal placement of a brachioplasty scar: a survey evaluation.

PubMed

Samra, Salem; Samra, Fares; Liu, Yuen-Jong; Sawh-Martinez, Rajendra; Persing, John

2013-10-01

Brachioplasty has become a popular procedure to rejuvenate the upper arm, with its frequency increasing proportionately to the popularity of surgical weight loss procedures. The major complication of the procedure is undesirable, visible scarring. An ongoing, unresolved debate in the brachioplasty literature is the optimal placement of the brachioplasty scar. Some authors advocate a medially based incision along the bicipital groove, whereas others prefer to leave the scar posteriorly in the brachial sulcus. In addition, some advocate a sinusoidal scar over a straight-line closure. This study attempts to resolve the question of where and how to place the scar based on population surveys. Photographs were taken of a model with her arm progressively abducted at the shoulder to a level of 90 degrees, with the elbow progressively flexed to 90 degrees and the arm externally rotated. Anterior and posterior views were included. Using Photoshop, a brachioplasty scar was digitally created and placed on the arm first medially in the bicipital groove, then posteriorly in the brachial sulcus. Straight-line scars and sinusoidal scars were also compared in each position. Before creating a computer-generated image of the scars, the scar lines were marked with a marking pen to ensure they could be followed with movement of the model's arm. An online survey was then created and distributed and included multiple variables: position of the scar, length of scar vs residual deformity, and acceptability based on phase of scar in time (early vs late result). The scale was numerical from 1 to 5, with 1 being a very objectionable scar and 5 being a very acceptable scar. The survey was disseminated among the general public, plastic surgeons, and patients in the Yale Cosmetic Surgery Resident Clinic who were either seen in consultation for brachioplasty or who underwent the procedure. Electronic surveys were distributed to and completed by the general public (n = 117), local plastic surgery residents and attendings (n = 10), and patients who had undergone or were seen in consultation for brachioplasty (n = 9). Among all participants, in the chronic phase, a medial straight scar received an average rating of 4.00, a posterior straight scar received an average rating of 3.14, a posterior sinusoidal scar received an average rating of 2.61, and a medial sinusoidal scar received an average rating of 2.03. Across age groups, gender, plastic surgeons, and patients, the medially based straight brachioplasty scar is more acceptable than the posteriorly based straight scar (4.00 vs 3.14, P < 0.001). If the scar shape is made sinusoidal, a posteriorly based scar is favored over a medial one (2.61 vs 2.03, P < 0.001), yet this is still not as aesthetically pleasing as a medial straight scar (4.00 vs 2.61, P < 0.001). Furthermore, survey participants accepted a longer scar over a residual deformity (58.8% vs 41.2%). Based on the preferences of the populations surveyed, we conclude that the medially based straight scar is the most aesthetically acceptable option when performing a brachioplasty.

Line scanning time-of-flight laser sensor for intelligent transport systems, combining wide field-of-view optics of 30 deg, high scanning speed of 0.9 ms/line, and simple sensor configuration

NASA Astrophysics Data System (ADS)

Imaki, Masaharu; Kameyama, Shumpei; Ishimura, Eitaro; Nakaji, Masaharu; Yoshinaga, Hideo; Hirano, Yoshihito

2017-03-01

We developed a line scanning time-of-flight (TOF) laser sensor for an intelligent transport system (ITS), which combines wide field-of-view (FOV) receiving optics of 30 deg and a high-speed microelectro mechanical system scanner of 0.9 ms/line with a simple sensor configuration. The newly developed high-aspect ratio photodiode realizes the scanless and wide FOV receiver. The sinusoidal wave intensity modulation method is used for the TOF measurement. This enables the noise reduction of the trans-impedance amplifier by applying the LC-resonant method. The vehicle detection and axle counting, which are the important functions in ITS, are also demonstrated.

Bone morphogenetic protein-binding endothelial regulator of liver sinusoidal endothelial cells induces iron overload in a fatty liver mouse model.

PubMed

Hasebe, Takumu; Tanaka, Hiroki; Sawada, Koji; Nakajima, Shunsuke; Ohtake, Takaaki; Fujiya, Mikihiro; Kohgo, Yutaka

2017-03-01

Non-alcoholic fatty liver disease (NAFLD) is frequently accompanied by iron overload. However, because of the complex hepcidin-regulating molecules, the molecular mechanism underlying iron overload remains unknown. To identify the key molecule involved in NAFLD-associated iron dysregulation, we performed whole-RNA sequencing on the livers of obese mice. Male C57BL/6 mice were fed a regular or high-fat diet for 16 or 48 weeks. Internal iron was evaluated by plasma iron, ferritin or hepatic iron content. Whole-RNA sequencing was performed by transcriptome analysis using semiconductor high-throughput sequencer. Mouse liver tissues or isolated hepatocytes and sinusoidal endothelial cells were used to assess the expression of iron-regulating molecules. Mice fed a high-fat diet for 16 weeks showed excess iron accumulation. Longer exposure to a high-fat diet increased hepatic fibrosis and intrahepatic iron accumulation. A pathway analysis of the sequencing data showed that several inflammatory pathways, including bone morphogenetic protein (BMP)-SMAD signaling, were significantly affected. Sequencing analysis showed 2314 altered genes, including decreased mRNA expression of the hepcidin-coding gene Hamp. Hepcidin protein expression and SMAD phosphorylation, which induces Hamp, were found to be reduced. The expression of BMP-binding endothelial regulator (BMPER), which inhibits BMP-SMAD signaling by binding BMP extracellularly, was up-regulated in fatty livers. In addition, immunohistochemical and cell isolation analyses showed that BMPER was primarily expressed in the liver sinusoidal endothelial cells (LSECs) rather than hepatocytes. BMPER secretion by LSECs inhibits BMP-SMAD signaling in hepatocytes and further reduces hepcidin protein expression. These intrahepatic molecular interactions suggest a novel molecular basis of iron overload in NAFLD.

Effects of broad frequency vibration on cultured osteoblasts

NASA Technical Reports Server (NTRS)

Tanaka, Shigeo M.; Li, Jiliang; Duncan, Randall L.; Yokota, Hiroki; Burr, David B.; Turner, Charles H.

2003-01-01

Bone is subjected in vivo to both high amplitude, low frequency strain, incurred by locomotion, and to low amplitude, broad frequency strain. The biological effects of low amplitude, broad frequency strain are poorly understood. To evaluate the effects of low amplitude strains ranging in frequency from 0 to 50 Hz on osteoblastic function, we seeded MC3T3-E1 cells into collagen gels and applied the following loading protocols for 3 min per day for either 3 or 7 days: (1) sinusoidal strain at 3 Hz, with 0-3000 microstrain peak-to-peak followed by 0.33 s resting time, (2) "broad frequency vibration" of low amplitude strain (standard deviation of 300 microstrain) including frequency components from 0 to 50 Hz, and (3) sinusoidal strain combined with broad frequency vibration (S + V). The cells were harvested on day 4 or 8. We found that the S + V stimulation significantly repressed cell proliferation by day 8. Osteocalcin mRNA was up-regulated 2.6-fold after 7 days of S + V stimulation, and MMP-9 mRNA was elevated 1.3-fold after 3 days of vibration alone. Sinusoidal stimulation alone did not affect the cell responses. No differences due to loading were observed in alkaline phosphatase activity and in mRNA levels of type I collagen, osteopontin, connexin 43, MMPs-1A, -3, -13. These results suggest that osteoblasts are more sensitive to low amplitude, broad frequency strain, and this kind of strain could sensitize osteoblasts to high amplitude, low frequency strain. This suggestion implies a potential contribution of stochastic resonance to the mechanical sensitivity of osteoblasts. Copyright 2002 Elsevier Science Ltd.

Sled Control and Safety System

NASA Technical Reports Server (NTRS)

Forrest, L. J.

1982-01-01

Computerized system for controlling motion of linear-track accelerator applied to other automated equipment, such as numerically-controlled machine tools and robot manipulators on assembly lines. System controls motions of sled with sine-wave signal created digitally by microprocessor. Dynamic parameters of sled motion are monitored so sled may be stopped safely if malfunction occurs. Sled is capable of sinusoidal accelerations up to 0.5 g with 125-kg load.

Morphology and force probing of primary murine liver sinusoidal endothelial cells.

PubMed

Zapotoczny, B; Owczarczyk, K; Szafranska, K; Kus, E; Chlopicki, S; Szymonski, M

2017-07-01

Liver sinusoidal endothelial cells (LSECs) represent unique type of endothelial cells featured by their characteristic morphology, ie, lack of a basement membrane and presence of fenestrations-transmembrane pores acting as a dynamic filter between the vascular space and the liver parenchyma. Delicate structure of LSECs membrane combined with a submicron size of fenestrations hinders their visualization in live cells. In this work, we apply atomic force microscopy contact mode to characterize fenestrations in LSECs. We reveal the structure of fenestrations in live LSECs. Moreover, we show that the high-resolution imaging of fenestrations is possible for the glutaraldehyde-fixed LSECs. Finally, thorough information about the morphology of LSECs including great contrast in visualization of sieve plates and fenestrations is provided using Force Modulation mode. We show also the ability to precisely localize the cell nuclei in fixed LSECs. It can be helpful for more precise description of nanomechanical properties of cell nuclei using atomic force microscopy. Presented methodology combining high-quality imaging of fixed cells with an additional nanomechanical information of both live and fixed LSECs provides a unique approach to study LSECs morphology and nanomechanics that could foster understanding of the role of LSECs in maintaining liver homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

Scavenger receptor B1, the HDL receptor, is expressed abundantly in liver sinusoidal endothelial cells

PubMed Central

Ganesan, Latha P.; Mates, Jessica M.; Cheplowitz, Alana M.; Avila, Christina L.; Zimmerer, Jason M.; Yao, Zhili; Maiseyeu, Andrei; Rajaram, Murugesan V. S.; Robinson, John M.; Anderson, Clark L.

2016-01-01

Cholesterol from peripheral tissue, carried by HDL, is metabolized in the liver after uptake by the HDL receptor, SR-B1. Hepatocytes have long been considered the only liver cells expressing SR-B1; however, in this study we describe two disparate immunofluorescence (IF) experiments that suggest otherwise. Using high-resolution confocal microscopy employing ultrathin (120 nm) sections of mouse liver, improving z-axis resolution, we identified the liver sinusoidal endothelial cells (LSEC), marked by FcγRIIb, as the cell within the liver expressing abundant SR-B1. In contrast, the hepatocyte, identified with β-catenin, expressed considerably weaker levels, although optical resolution of SR-B1 was inadequate. Thus, we moved to a different IF strategy, first separating dissociated liver cells by gradient centrifugation into two portions, hepatocytes (parenchymal cells) and LSEC (non-parenchymal cells). Characterizing both portions for the cellular expression of SR-B1 by flow cytometry, we found that LSEC expressed considerable amounts of SR-B1 while in hepatocytes SR-B1 expression was barely perceptible. Assessing mRNA of SR-B1 by real time PCR we found messenger expression in LSEC to be about 5 times higher than in hepatocytes. PMID:26865459

Sinusoidal Obstruction Syndrome During Chemotherapy of Pediatric Cancers and its Successful Management With Defibrotide.

PubMed

Kizilocak, Hande; Dikme, Gürcan; Özdemir, Nihal; Kuruğoğlu, Sebuh; Adaletli, İbrahim; Erkan, Tülay; Celkan, Tiraje

2017-10-01

Sinusoidal obstruction syndrome (SOS) is a life-threatening complication generally occurring after hematopoietic stem cell transplantation. SOS after standard dose chemotherapy in malignancies is rare. Between the year 1995 and 2016, 414 patients were diagnosed with acute lymphoblastic leukemia and 113 patients were diagnosed with Wilms tumor in our institution. Among these patients, 4 patients with acute lymphoblastic leukemia (0.96%) and 2 patients with Wilms tumor (1.7%) developed SOS during treatment. SOS behaves like a local disseminated intravascular coagulation. Defibrotide has proved to be effective in SOS. In this article, we report our experience with defibrotide in SOS.

Ultra-precise tracking control of piezoelectric actuators via a fuzzy hysteresis model.

PubMed

Li, Pengzhi; Yan, Feng; Ge, Chuan; Zhang, Mingchao

2012-08-01

In this paper, a novel Takagi-Sugeno (T-S) fuzzy system based model is proposed for hysteresis in piezoelectric actuators. The antecedent and consequent structures of the fuzzy hysteresis model (FHM) can be, respectively, identified on-line through uniform partition approach and recursive least squares (RLS) algorithm. With respect to controller design, the inverse of FHM is used to develop a feedforward controller to cancel out the hysteresis effect. Then a hybrid controller is designed for high-performance tracking. It combines the feedforward controller with a proportional integral differential (PID) controller favourable for stabilization and disturbance compensation. To achieve nanometer-scale tracking precision, the enhanced adaptive hybrid controller is further developed. It uses real-time input and output data to update FHM, thus changing the feedforward controller to suit the on-site hysteresis character of the piezoelectric actuator. Finally, as to 3 cases of 50 Hz sinusoidal, multiple frequency sinusoidal and 50 Hz triangular trajectories tracking, experimental results demonstrate the efficiency of the proposed controllers. Especially, being only 0.35% of the maximum desired displacement, the maximum error of 50 Hz sinusoidal tracking is greatly reduced to 5.8 nm, which clearly shows the ultra-precise nanometer-scale tracking performance of the developed adaptive hybrid controller.

An efficient quantum algorithm for spectral estimation

NASA Astrophysics Data System (ADS)

Steffens, Adrian; Rebentrost, Patrick; Marvian, Iman; Eisert, Jens; Lloyd, Seth

2017-03-01

We develop an efficient quantum implementation of an important signal processing algorithm for line spectral estimation: the matrix pencil method, which determines the frequencies and damping factors of signals consisting of finite sums of exponentially damped sinusoids. Our algorithm provides a quantum speedup in a natural regime where the sampling rate is much higher than the number of sinusoid components. Along the way, we develop techniques that are expected to be useful for other quantum algorithms as well—consecutive phase estimations to efficiently make products of asymmetric low rank matrices classically accessible and an alternative method to efficiently exponentiate non-Hermitian matrices. Our algorithm features an efficient quantum-classical division of labor: the time-critical steps are implemented in quantum superposition, while an interjacent step, requiring much fewer parameters, can operate classically. We show that frequencies and damping factors can be obtained in time logarithmic in the number of sampling points, exponentially faster than known classical algorithms.

Visual Multipoles And The Assessment Of Visual Sensitivity To Displayed Images

NASA Astrophysics Data System (ADS)

Klein, Stanley A.

1989-08-01

The contrast sensitivity function (CSF) is widely used to specify the sensitivity of the visual system. Each point of the CSF specifies the amount of contrast needed to detect a sinusoidal grating of a given spatial frequency. This paper describes a set of five mathematically related visual patterns, called "multipoles," that should replace the CSF for measuring visual performance. The five patterns (ramp, edge, line, dipole and quadrupole) are localized in space rather than being spread out as sinusoidal gratings. The multipole sensitivity of the visual system provides an alternative characterization that complements the CSF in addition to offering several advantages. This paper provides an overview of the properties and uses of the multipole stimuli. This paper is largely a summary of several unpublished manuscripts with excerpts from them. Derivations and full references are omitted here. Please write me if you would like the full manuscripts.

A novel miniature in-line load-cell to measure in-situ tensile forces in the tibialis anterior tendon of rats

PubMed Central

Unger, Ewald; Bijak, Manfred; Stoiber, Martin; Lanmüller, Hermann; Jarvis, Jonathan Charles

2017-01-01

Direct measurements of muscular forces usually require a substantial rearrangement of the biomechanical system. To circumvent this problem, various indirect techniques have been used in the past. We introduce a novel direct method, using a lightweight (~0.5 g) miniature (3 x 3 x 7 mm) in-line load-cell to measure tension in the tibialis anterior tendon of rats. A linear motor was used to produce force-profiles to assess linearity, step-response, hysteresis and frequency behavior under controlled conditions. Sensor responses to a series of rectangular force-pulses correlated linearly (R2 = 0.999) within the range of 0–20 N. The maximal relative error at full scale (20 N) was 0.07% of the average measured signal. The standard deviation of the mean response to repeated 20 N force pulses was ± 0.04% of the mean response. The step-response of the load-cell showed the behavior of a PD2T2-element in control-engineering terminology. The maximal hysteretic error was 5.4% of the full-scale signal. Sinusoidal signals were attenuated maximally (-4 dB) at 200 Hz, within a measured range of 0.01–200 Hz. When measuring muscular forces this should be of minor concern as the fusion-frequency of muscles is generally much lower. The newly developed load-cell measured tensile forces of up to 20 N, without inelastic deformation of the sensor. It qualifies for various applications in which it is of interest directly to measure forces within a particular tendon causing only minimal disturbance to the biomechanical system. PMID:28934327

A novel miniature in-line load-cell to measure in-situ tensile forces in the tibialis anterior tendon of rats.

PubMed

Schmoll, Martin; Unger, Ewald; Bijak, Manfred; Stoiber, Martin; Lanmüller, Hermann; Jarvis, Jonathan Charles

2017-01-01

Direct measurements of muscular forces usually require a substantial rearrangement of the biomechanical system. To circumvent this problem, various indirect techniques have been used in the past. We introduce a novel direct method, using a lightweight (~0.5 g) miniature (3 x 3 x 7 mm) in-line load-cell to measure tension in the tibialis anterior tendon of rats. A linear motor was used to produce force-profiles to assess linearity, step-response, hysteresis and frequency behavior under controlled conditions. Sensor responses to a series of rectangular force-pulses correlated linearly (R2 = 0.999) within the range of 0-20 N. The maximal relative error at full scale (20 N) was 0.07% of the average measured signal. The standard deviation of the mean response to repeated 20 N force pulses was ± 0.04% of the mean response. The step-response of the load-cell showed the behavior of a PD2T2-element in control-engineering terminology. The maximal hysteretic error was 5.4% of the full-scale signal. Sinusoidal signals were attenuated maximally (-4 dB) at 200 Hz, within a measured range of 0.01-200 Hz. When measuring muscular forces this should be of minor concern as the fusion-frequency of muscles is generally much lower. The newly developed load-cell measured tensile forces of up to 20 N, without inelastic deformation of the sensor. It qualifies for various applications in which it is of interest directly to measure forces within a particular tendon causing only minimal disturbance to the biomechanical system.

Hepatic Sinusoidal Obstruction Syndrome During Chemotherapy for Childhood Medulloblastoma: Report of a Case and Review of the Literature

PubMed Central

Buckland, Amy; Phillips, Marianne B.; Cole, Catherine H.; Gottardo, Nicholas G.

2014-01-01

Hepatic sinusoidal obstruction syndrome (HSOS), also known as veno-occlusive disease, is a well-recognized toxic complication after autologous and allogeneic hematopoietic stem cell transplant, during treatment of Wilms tumor and rhabdomyosarcoma associated with actinomycin-D, and during acute lymphoblastic leukemia therapy due to oral 6-thioguanine. However, its occurrence in the context of chemotherapy regimens for other childhood malignancies is rare. We report a 5-year-old girl with high-risk anaplastic medulloblastoma, who developed severe HSOS during her second cycle of maintenance chemotherapy, consisting of vincristine, cisplatin, and cyclophosphamide. She was treated with defibrotide with complete resolution of the HSOS. These findings and a review of the literature, highlight the occurrence of HSOS in children outside the established settings of hematopoietic stem cell transplantation, Wilms tumor, rhabdomyosarcoma, and acute lymphoblastic leukemia. PMID:24276042

Sinusoidal visuomotor tracking: intermittent servo-control or coupled oscillations?

PubMed

Russell, D M; Sternad, D

2001-12-01

In visuomotor tasks that involve accuracy demands, small directional changes in the trajectories have been taken as evidence of feedback-based error corrections. In the present study variability, or intermittency, in visuomanual tracking of sinusoidal targets was investigated. Two lines of analyses were pursued: First, the hypothesis that humans fundamentally act as intermittent servo-controllers was re-examined, probing the question of whether discontinuities in the movement trajectory directly imply intermittent control. Second, an alternative hypothesis was evaluated: that rhythmic tracking movements are generated by entrainment between the oscillations of the target and the actor, such that intermittency expresses the degree of stability. In 2 experiments, participants (N = 6 in each experiment) swung 1 of 2 different hand-held pendulums, tracking a rhythmic target that oscillated at different frequencies with a constant amplitude. In 1 line of analyses, the authors tested the intermittency hypothesis by using the typical kinematic error measures and spectral analysis. In a 2nd line, they examined relative phase and its variability, following analyses of rhythmic interlimb coordination. The results showed that visually guided corrective processes play a role, especially for slow movements. Intermittency, assessed as frequency and power components of the movement trajectory, was found to change as a function of both target frequency and the manipulandum's inertia. Support for entrainment was found in conditions in which task frequency was identical to or higher than the effector's eigenfrequency. The results suggest that it is the symmetry between task and effector that determines which behavioral regime is dominant.

[A histological study and three-dimensional reconstruction of F4/80-positive reticular cells and macrophages at the onset of murine bone marrow hematopoiesis].

PubMed

Notsu, Eiji; Sonoda, Yuji; Sasaki, Kazunobu

2007-06-01

Adult bone marrow consists of two different compartments, a vascular compartment of sinusoid and a hematopoietic compartment consisting of stromal cells and hematopoietic cells. In the hematopoietic compartment, stromal cells play an important role in the formation of the microenvironment for hematopoiesis. To clarify the relationship between hematopoietic cells and stromal cells, particularly reticular cells and macrophages, we examined the femur bone marrow of ICR mouse fetuses and neonates using F4/80 immunostaining and three-dimensional reconstruction under light and electron microscopy. In the fetal femurs, the marrow cavity formed early from 15 days of gestation, and it showed a marked increase in volume thereafter. On the basis of the appearance of hematopoietic cells, marrow development could be classified into two stages, a pre-hematopoietic stage from 15 days of gestation to two days of age, and a beginning stage of hematopoiesis thereafter. The pre-hematopoietic bone marrow contains not only stromal reticular cells but also macrophages, and both types of stromal cells were strongly positive to F4/80 monoclonal antibody. These F4/80-positive reticular cells had a triangular cell profile with long and slender cytoplasmic processes. Reticular cells often contained large lysosomes of not only dying neutrophils but also erythroblast nuclei. A few erythroblasts accumulated around the processes, and the number of erythroblasts around reticular cells increased with bone marrow development. On the other hand, macrophages were located either close to sinusoids or in sinusoid lumen, and a close relationship to hematopoietic cells was hardly noticeable. At the beginning stage of hematopoiesis, F4/80-positive reticular cells extended their long and slender cytoplasmic processes, and the number and length of the processes appeared markedly increased. The three-dimensional cell surface of the F4/80-positive reticular cells became very complex. Numerous erythroblasts accumulated around the processes, and erythroblastic islands could gradually be recognized after four days of age. In the erythroblastic islands, central reticular cells were F4/80-positive and contained numerous large phagosomes originating from the expelled nuclei of erythroblasts. Although macrophages contained large phagosomes, the relationship between macrophages and hematopoietic cells could not clearly be elucidated even at the beginning stage of hematopoiesis. At the onset of bone marrow hematopoiesis, the hematopoietic compartment contained two kinds of F4/80-positive phagocytes, i.e., reticular cells and macrophages. In marrow erythroblastic islands, not macrophages but F4/80-positive reticular cells were located at the center of each island.

Specific gene delivery to liver sinusoidal and artery endothelial cells.

PubMed

Abel, Tobias; El Filali, Ebtisam; Waern, Johan; Schneider, Irene C; Yuan, Qinggong; Münch, Robert C; Hick, Meike; Warnecke, Gregor; Madrahimov, Nodir; Kontermann, Roland E; Schüttrumpf, Jörg; Müller, Ulrike C; Seppen, Jurgen; Ott, Michael; Buchholz, Christian J

2013-09-19

Different types of endothelial cells (EC) fulfill distinct tasks depending on their microenvironment. ECs are therefore difficult to genetically manipulate ex vivo for functional studies or gene therapy. We assessed lentiviral vectors (LVs) targeted to the EC surface marker CD105 for in vivo gene delivery. The mouse CD105-specific vector, mCD105-LV, transduced only CD105-positive cells in primary liver cell cultures. Upon systemic injection, strong reporter gene expression was detected in liver where mCD105-LV specifically transduced liver sinusoidal ECs (LSECs) but not Kupffer cells, which were mainly transduced by nontargeted LVs. Tumor ECs were specifically targeted upon intratumoral vector injection. Delivery of the erythropoietin gene with mCD105-LV resulted in substantially increased erythropoietin and hematocrit levels. The human CD105-specific vector (huCD105-LV) transduced exclusively human LSECs in mice transplanted with human liver ECs. Interestingly, when applied at higher dose and in absence of target cells in the liver, huCD105-LV transduced ECs of a human artery transplanted into the descending mouse aorta. The data demonstrate for the first time targeted gene delivery to specialized ECs upon systemic vector administration. This strategy offers novel options to better understand the physiological functions of ECs and to treat genetic diseases such as those affecting blood factors.

Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis.

PubMed

Mueller, Sebastian

2016-12-28

Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a major health problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis (SPH), which identifies an elevated sinusoidal pressure (SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts (SPH part I: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmHg and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures (SPH part II: perpetuation). It also defines the "point of no return" where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies.

Indications of stellar prominence oscillations on fast rotating stars: the cases of HK Aqr and PZ Tel

NASA Astrophysics Data System (ADS)

Leitzinger, M.; Odert, P.; Zaqarashvili, T. V.; Greimel, R.; Hanslmeier, A.; Lammer, H.

2016-11-01

We present the analysis of six nights of spectroscopic monitoring of two young and fast rotating late-type stars, namely the dMe star HK Aqr and the dG/dK star PZ Tel. On both stars, we detect absorption features reminiscent of signatures of corotating cool clouds or prominences visible in Hα. Several prominences on HK Aqr show periodic variability in the prominence tracks which follow a sinusoidal motion (indication of prominence oscillations). On PZ Tel, we could not find any periodic variability in the prominence tracks. By fitting sinusoidal functions to the prominence tracks, we derive amplitudes and periods which are similar to those of large-amplitude oscillations seen in solar prominences. In one specific event, we also derive a periodic variation of the prominence track in the Hβ spectral line which shows an anti-phase variation with the one derived for the Hα spectral line. Using these parameters and estimated mass density of a prominence on HK Aqr, we derive a minimum magnetic field strength of ˜2 G. The relatively low strength of the magnetic field is explained by the large height of this stellar prominence (≥ 0.67 stellar radii above the surface).

Formation of Fenestrae in Murine Liver Sinusoids Depends on Plasmalemma Vesicle-Associated Protein and Is Required for Lipoprotein Passage

PubMed Central

Herrnberger, Leonie; Hennig, Robert; Kremer, Werner; Hellerbrand, Claus; Goepferich, Achim; Kalbitzer, Hans Robert; Tamm, Ernst R.

2014-01-01

Liver sinusoidal endothelial cells (LSEC) are characterized by the presence of fenestrations that are not bridged by a diaphragm. The molecular mechanisms that control the formation of the fenestrations are largely unclear. Here we report that mice, which are deficient in plasmalemma vesicle-associated protein (PLVAP), develop a distinct phenotype that is caused by the lack of sinusoidal fenestrations. Fenestrations with a diaphragm were not observed in mouse LSEC at three weeks of age, but were present during embryonic life starting from embryonic day 12.5. PLVAP was expressed in LSEC of wild-type mice, but not in that of Plvap-deficient littermates. Plvap-/- LSEC showed a pronounced and highly significant reduction in the number of fenestrations, a finding, which was seen both by transmission and scanning electron microscopy. The lack of fenestrations was associated with an impaired passage of macromolecules such as FITC-dextran and quantum dot nanoparticles from the sinusoidal lumen into Disse's space. Plvap-deficient mice suffered from a pronounced hyperlipoproteinemia as evidenced by milky plasma and the presence of lipid granules that occluded kidney and liver capillaries. By NMR spectroscopy of plasma, the nature of hyperlipoproteinemia was identified as massive accumulation of chylomicron remnants. Plasma levels of low density lipoproteins (LDL) were also significantly increased as were those of cholesterol and triglycerides. In contrast, plasma levels of high density lipoproteins (HDL), albumin and total protein were reduced. At around three weeks of life, Plvap-deficient livers developed extensive multivesicular steatosis, steatohepatitis, and fibrosis. PLVAP is critically required for the formation of fenestrations in LSEC. Lack of fenestrations caused by PLVAP deficiency substantially impairs the passage of chylomicron remnants between liver sinusoids and hepatocytes, and finally leads to liver damage. PMID:25541982

Wnt9a secreted from the walls of hepatic sinusoids is essential for morphogenesis, proliferation, and glycogen accumulation of chick hepatic epithelium.

PubMed

Matsumoto, Ken; Miki, Rika; Nakayama, Mizuho; Tatsumi, Norifumi; Yokouchi, Yuji

2008-07-15

Hepatic epithelial morphogenesis, including hepatoblast migration and proliferation in the septum transversum, requires the interaction of hepatic epithelium with the embryonic sinusoidal wall. No factors that mediate this interaction have yet been identified. As the beta-catenin pathway is active in hepatoblast proliferation, then Wnt ligands might activate the canonical Wnt pathway during liver development. Here, we investigated the role of Wnts in mediating epithelial vessel interactions in the developing chick liver. We found that Wnt9a was specifically expressed in both endothelial and stellate cells of the embryonic sinusoidal wall. Induced overexpression of Wnt9a resulted in hepatomegaly with hyperplasia of the hepatocellular cords, and in hyperproliferation of hepatocytes. Knockdown of Wnt9a caused a reduction in liver size, with hypoplasia of hepatocellular cord branching, and hypoproliferation of hepatoblasts, and also inhibited glycogen accumulation at later developmental stages. Wnt9a promoted in vivo stabilization of beta-catenin through binding with Frizzled 4, 7, and 9, and activated TOPflash reporter expression in vitro via Frizzled 7 and 9. Our results demonstrate that Wnt9a from the embryonic sinusoidal wall is required for the proper morphogenesis of chick hepatocellular cords, proliferation of hepatoblasts/hepatocytes, and glycogen accumulation in hepatocytes. Wnt9a signaling appears to be mediated by an Fzd7/9-beta-catenin pathway.

Microcirculation in the murine liver: a computational fluid dynamic model based on 3D reconstruction from in vivo microscopy.

PubMed

Piergiovanni, Monica; Bianchi, Elena; Capitani, Giada; Li Piani, Irene; Ganzer, Lucia; Guidotti, Luca G; Iannacone, Matteo; Dubini, Gabriele

2017-10-03

The liver is organized in hexagonal functional units - termed lobules - characterized by a rather peculiar blood microcirculation, due to the presence of a tangled network of capillaries - termed sinusoids. A better understanding of the hemodynamics that governs liver microcirculation is relevant to clinical and biological studies aimed at improving our management of liver diseases and transplantation. Herein, we built a CFD model of a 3D sinusoidal network, based on in vivo images of a physiological mouse liver obtained with a 2-photon microscope. The CFD model was developed with Fluent 16.0 (ANSYS Inc., Canonsburg, PA), particular care was taken in imposing the correct boundary conditions representing a physiological state. To account for the remaining branches of the sinusoids, a lumped parameter model was used to prescribe the correct pressure at each outlet. The effect of an adhered cell on local hemodynamics is also investigated for different occlusion degrees. The model here proposed accurately reproduces the fluid dynamics in a portion of the sinusoidal network in mouse liver. Mean velocities and mass flow rates are in agreement with literature values from in vivo measurements. Our approach provides details on local phenomena, hardly described by other computational studies, either focused on the macroscopic hepatic vasculature or based on homogeneous porous medium model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide.

PubMed

Denda, Ayumi; Kitayama, Wakashi; Murata, Akiko; Kishida, Hideki; Sasaki, Yasutaka; Kusuoka, Osamu; Tsujiuchi, Toshifumi; Tsutsumi, Masahiro; Nakae, Dai; Takagi, Hidetoshi; Konishi, Yoichi

2002-02-01

Expression of cyclooxygenase (COX)-2 protein during rat hepatocarcinogenesis associated with fatty change, fibrosis, cirrhosis and oxidative DNA damage, caused by a choline-deficient, L-amino acid-defined (CDAA) diet were investigated in F344 male rats, along with the chemopreventive efficacy of the specific COX-2 inhibitor, nimesulide (NIM). Nimesulide, which was administered in the diet at concentrations of 200, 400, 600 and 800 p.p.m. for 12 weeks, decreased the number and size of preneoplastic enzyme-altered liver foci, levels of oxidative DNA damage, and the grade and incidence of fibrosis in a dose-dependent manner. A preliminary long-term study of 65 weeks also revealed that 800 p.p.m. NIM decreased the multiplicity of neoplastic nodules and hepatocellular carcinomas and prevented the development of cirrhosis. Western blot analysis revealed that COX-2 protein was barely expressed in control livers and increased approximately 2.9-fold in the livers of rats fed on a CDAA diet for 12 weeks and approximately 4.5-5.4-fold in tumors, with a diameter larger than 5 mm, at 80 weeks. Immunohistochemically, COX-2 protein was positive in sinusoidal and stromal cells in fibrotic septa, which were identified by immunoelectron microscopy as Kupffer cells, macrophages, either activated Ito cells or fibroblasts, after exposure to the CDAA diet for 12 weeks, whereas it was only occasionally weakly positive in sinusoidal, probably Kupffer, cells in control livers. In neoplastic nodules in rats fed on a CDAA diet for 30 and 80 weeks, sinusoidal cells and cells with relatively large round nuclei and scanty cytoplasm were strongly positive for COX-2 protein, with the neoplastic hepatocytes in the minority of the nodules, but not the cancer cells, being moderately positive. These results clearly indicate that rat hepatocarcinogenesis, along with fatty change, fibrosis and cirrhosis, is associated with increased expression of COX-2 protein, and point to the chemopreventive efficacy of a selective COX-2 inhibitor against, at least, the early stages of hepatocarcinogenesis.

FcRn Rescues Recombinant Factor VIII Fc Fusion Protein from a VWF Independent FVIII Clearance Pathway in Mouse Hepatocytes

PubMed Central

van der Flier, Arjan; Liu, Zhan; Tan, Siyuan; Chen, Kai; Drager, Douglas; Liu, Tongyao; Patarroyo-White, Susannah; Jiang, Haiyan; Light, David R.

2015-01-01

We recently developed a longer lasting recombinant factor VIII-Fc fusion protein, rFVIIIFc, to extend the half-life of replacement FVIII for the treatment of people with hemophilia A. In order to elucidate the biological mechanism for the elongated half-life of rFVIIIFc at a cellular level we delineated the roles of VWF and the tissue-specific expression of the neonatal Fc receptor (FcRn) in the biodistribution, clearance and cycling of rFVIIIFc. We find the tissue biodistribution is similar for rFVIIIFc and rFVIII and that liver is the major clearance organ for both molecules. VWF reduces the clearance and the initial liver uptake of rFVIIIFc. Pharmacokinetic studies in FcRn chimeric mice show that FcRn expressed in somatic cells (hepatocytes or liver sinusoidal endothelial cells) mediates the decreased clearance of rFVIIIFc, but FcRn in hematopoietic cells (Kupffer cells) does not affect clearance. Immunohistochemical studies show that when rFVIII or rFVIIIFc is in dynamic equilibrium binding with VWF, they mostly co localize with VWF in Kupffer cells and macrophages, confirming a major role for liver macrophages in the internalization and clearance of the VWF-FVIII complex. In the absence of VWF a clear difference in cellular localization of VWF-free rFVIII and rFVIIIFc is observed and neither molecule is detected in Kupffer cells. Instead, rFVIII is observed in hepatocytes, indicating that free rFVIII is cleared by hepatocytes, while rFVIIIFc is observed as a diffuse liver sinusoidal staining, suggesting recycling of free-rFVIIIFc out of hepatocytes. These studies reveal two parallel linked clearance pathways, with a dominant pathway in which both rFVIIIFc and rFVIII complexed with VWF are cleared mainly by Kupffer cells without FcRn cycling. In contrast, the free fraction of rFVIII or rFVIIIFc unbound by VWF enters hepatocytes, where FcRn reduces the degradation and clearance of rFVIIIFc relative to rFVIII by cycling rFVIIIFc back to the liver sinusoid and into circulation, enabling the elongated half-life of rFVIIIFc. PMID:25905473

"Pre-emptive strike"-the case for early treatment of hepatic sinusoidal obstruction syndrome with defibrotide.

PubMed

Rajagopal, Revathi; Phillips, Marianne B; Gottardo, Nicholas G

2018-07-01

The initial signs of hepatic sinusoidal obstruction syndrome (HSOS) can be challenging to recognize in children, especially outside the hematopoietic stem cell transplantation setting. To assist clinicians to promptly identify HSOS, the European Society for Blood and Marrow Transplantation has proposed pediatric HSOS diagnostic criteria which emphasize unexplained consumptive and transfusion-refractory thrombocytopenia. To highlight the importance of these "bellwether" early signs of HSOS and the efficacy of pre-emptive treatment with defibrotide, we describe the case of a child with a right 11th rib primitive neuroectodermal tumor who developed HSOS following focal radiotherapy and actinomycin-D treatment. © 2018 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide.

PubMed

Choi, Aery; Kang, Young Kyung; Lim, Sewon; Kim, Dong Ho; Lim, Jung Sub; Lee, Jun Ah

2016-10-01

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.

Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2 mediated regeneration of sinusoidal endothelial cells

PubMed Central

Hooper, Andrea T.; Butler, Jason M.; Nolan, Daniel J; Kranz, Andrea; Iida, Kaoruko; Kobayashi, Mariko; Kopp, Hans-Georg; Shido, Koji; Petit, Isabelle; Yanger, Kilangsungla; James, Daylon; Witte, Larry; Zhu, Zhenping; Wu, Yan; Pytowski, Bronislaw; Rosenwaks, Zev; Mittal, Vivek; Sato, Thomas N.; Rafii, Shahin

2011-01-01

SUMMARY The phenotypic attributes and molecular determinants for the regeneration of bone marrow (BM) sinusoidal endothelial cells (SECs) and their contribution to hematopoiesis are unknown. We show that after myelosuppression VEGFR2 activation promotes reassembly of regressed SECs, reconstituting hematopoietic stem and progenitor cells (HSPCs). VEGFR2 and VEGFR3 expression are restricted to BM vasculature, demarcating a continuous network of VEGFR2+VEGFR3+Sca1− SECs and VEGFR2+VEGFR3−Sca1+ arterioles. While chemotherapy (5FU) and sublethal irradiation (650 rad) induce minor SEC regression, lethal irradiation (950 rad) induces severe regression of SECs requiring BM transplantation (BMT) for regeneration. Conditional deletion of VEGFR2 in adult mice blocks regeneration of SECs in sublethally irradiated animals, preventing hematopoietic reconstitution. Inhibition of VEGFR2 signaling in lethally irradiated wild type mice rescued with BMT severely impairs SEC reconstruction, preventing engraftment and reconstitution of HSPCs. Therefore, activation of VEGFR2 is critical for regeneration of VEGFR3+Sca1− SECs that are essential for engraftment and restoration of HSPCs and hematopoiesis. PMID:19265665

Voltages induced by lightning strokes and ground-faults on a coaxial telecom circuit enclosed inside a composite earthwire. Part II: lightning induced voltages ant composite earthwire tehnical design

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

Anzanel, P.; Kouteynikoff, P.

1985-02-01

This Part II presents theorical and experimental work about interference generated by lightning strokes in a telecommunication coaxial circuit enclosed inside a composite earthwire for overhead transmission lines. Sinusoidal steady state and surge measurements of the composite earthwire susceptibility to interference (transfer impedance) have been carried out. Induced voltages have been calculated using an original double sampling FFT method whose validity has been checked by measurements on a test line. Finally, it is shown how the cable design can be improved and maximum induced voltage values are given.

What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance

PubMed Central

Mir, Enrique; Rovira, Montse; Escolar, Ginés; Carreras, Enric; Diaz-Ricart, Maribel

2016-01-01

Defibrotide (DF) has received European Medicines Agency authorization to treat sinusoidal obstruction syndrome, an early complication after hematopoietic cell transplantation. DF has a recognized role as an endothelial protective agent, although its precise mechanism of action remains to be elucidated. The aim of the present study was to investigate the interaction of DF with endothelial cells (ECs). A human hepatic EC line was exposed to different DF concentrations, previously labeled. Using inhibitory assays and flow cytometry techniques along with confocal microscopy, we explored: DF-EC interaction, endocytic pathways, and internalization kinetics. Moreover, we evaluated the potential role of adenosine receptors in DF-EC interaction and if DF effects on endothelium were dependent of its internalization. Confocal microscopy showed interaction of DF with EC membranes followed by internalization, though DF did not reach the cell nucleus even after 24 hours. Flow cytometry revealed concentration, temperature, and time dependent uptake of DF in 2 EC models but not in other cell types. Moreover, inhibitory assays indicated that entrance of DF into ECs occurs primarily through macropinocytosis. Our experimental approach did not show any evidence of the involvement of adenosine receptors in DF-EC interaction. The antiinflammatory and antioxidant properties of DF seem to be caused by the interaction of the drug with the cell membrane. Our findings contribute to a better understanding of the precise mechanisms of action of DF as a therapeutic and potential preventive agent on the endothelial damage underlying different pathologic situations. PMID:26755708

A fatal case of hemoperitoneum after ultrasound-guided liver biopsy in a patient with intravascular large B-cell lymphoma.

PubMed

Aoki, Yasuhiro; Takamiya, Masataka; Satoh, Takashi; Fujita, Sachiko; Kato, Hideaki; Maeno, Yoshitaka

2011-07-01

An autopsy case of fatal complication of percutaneous liver biopsy targeting a rare type of large B-cell lymphoma is presented. A 79 year-old man was referred to the hematology unit of a hospital because of anemia with thrombocytopenia and hepatosplenomegaly. Results of inguinal lymph node biopsy were inconclusive. To investigate a mass lesion in the liver visualized by ultrasonography, image-guided liver biopsy was performed following platelet infusion. The patient became unresponsive 6h post procedure because of hypotension due to intraperitoneal hemorrhage of undetermined origin. Autopsy revealed hemoperitoneum but failed to identify any macroscopic intra- or extrahepatic vascular injuries. Histopathological investigation disclosed infiltration of atypical lymphocytes into the systemic organs including the lymph nodes, spleen, liver, and lungs. Prominent hemophagocytosis was also noted. The lymphoma cells were exclusively accumulated within vascular and sinusoidal structures, and diagnosed with immunohistochemistry as Asian variant of intravascular large B-cell lymphoma. Massive blood extravasation was presumed to originate directly from the markedly dilated liver sinusoids filled with erythrocytes, macrophages and tumor cells, under the condition of impaired hemostasis. Although the biopsy was thought to have been correctly performed, this case would be instructive for evaluation of the indications and risks associated with liver biopsy. 2011 Elsevier Ireland Ltd. All rights reserved.

All-In-One: Advanced preparation of Human Parenchymal and Non-Parenchymal Liver Cells.

PubMed

Werner, Melanie; Driftmann, Sabrina; Kleinehr, Kathrin; Kaiser, Gernot M; Mathé, Zotlan; Treckmann, Juergen-Walter; Paul, Andreas; Skibbe, Kathrin; Timm, Joerg; Canbay, Ali; Gerken, Guido; Schlaak, Joerg F; Broering, Ruth

2015-01-01

Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen. Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity. Cell preparation yielded the following cell counts per gram of liver tissue: 2.0 ± 0.4 × 10(7) hepatocytes, 1.8 ± 0.5 × 10(6 )Kupffer cells, 4.3 ± 1.9 × 10(5) liver sinusoidal endothelial cells, and 3.2 ± 0.5 × 10(5) stellate cells. Hepatocytes were identified by albumin (95.5 ± 1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5 ± 1.2%) and exhibited phagocytic activity, as determined with 1 μm latex beads. Endothelial cells were CD146(+) (97.8 ± 1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1 ± 1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence. Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease.

Graphic design of pinhole cameras

NASA Technical Reports Server (NTRS)

Edwards, H. B.; Chu, W. P.

1979-01-01

The paper describes a graphic technique for the analysis and optimization of pinhole size and focal length. The technique is based on the use of the transfer function of optical elements described by Scott (1959) to construct the transfer function of a circular pinhole camera. This transfer function is the response of a component or system to a pattern of lines having a sinusoidally varying radiance at varying spatial frequencies. Some specific examples of graphic design are presented.

Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations

PubMed Central

Schwen, Lars Ole; Schenk, Arne; Kreutz, Clemens; Timmer, Jens; Bartolomé Rodríguez, María Matilde; Kuepfer, Lars; Preusser, Tobias

2015-01-01

The mammalian liver plays a key role for metabolism and detoxification of xenobiotics in the body. The corresponding biochemical processes are typically subject to spatial variations at different length scales. Zonal enzyme expression along sinusoids leads to zonated metabolization already in the healthy state. Pathological states of the liver may involve liver cells affected in a zonated manner or heterogeneously across the whole organ. This spatial heterogeneity, however, cannot be described by most computational models which usually consider the liver as a homogeneous, well-stirred organ. The goal of this article is to present a methodology to extend whole-body pharmacokinetics models by a detailed liver model, combining different modeling approaches from the literature. This approach results in an integrated four-scale model, from single cells via sinusoids and the organ to the whole organism, capable of mechanistically representing metabolization inhomogeneity in livers at different spatial scales. Moreover, the model shows circulatory mixing effects due to a delayed recirculation through the surrounding organism. To show that this approach is generally applicable for different physiological processes, we show three applications as proofs of concept, covering a range of species, compounds, and diseased states: clearance of midazolam in steatotic human livers, clearance of caffeine in mouse livers regenerating from necrosis, and a parameter study on the impact of different cell entities on insulin uptake in mouse livers. The examples illustrate how variations only discernible at the local scale influence substance distribution in the plasma at the whole-body level. In particular, our results show that simultaneously considering variations at all relevant spatial scales may be necessary to understand their impact on observations at the organism scale. PMID:26222615

Long live the liver: immunohistochemical and stereological study of hepatocytes, liver sinusoidal endothelial cells, Kupffer cells and hepatic stellate cells of male and female rats throughout ageing.

PubMed

Marcos, Ricardo; Correia-Gomes, Carla

2016-12-01

Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.

Abnormal Labyrinthine Zone in the Hectd1-null Placenta

PubMed Central

Sarkar, Anjali A.; Sabatino, Julia A.; Sugrue, Kelsey F.; Zohn, Irene E.

2016-01-01

Introduction The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta. Methods The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization. Results Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs). Discussion Together these defects indicate that Hectd1 is required for development of the labyrinthine zone or the mouse placenta. PMID:26907377

Expression of human immunodeficiency virus (HIV)-binding lectin DC-SIGNR: Consequences for HIV infection and immunity.

PubMed

Soilleux, Elizabeth J; Morris, Lesley S; Rushbrook, Simon; Lee, Benhur; Coleman, Nicholas

2002-06-01

DC-SIGNR is a human immunodeficiency virus (HIV)-binding C-type lectin that is expressed on endothelium in the hepatic sinusoids, lymph node sinuses and placenta. Like closely related DC-SIGN, DC-SIGNR can bind both ICAM-3 and HIV and can potentiate HIV infection of T lymphocytes in trans. In the present study we have investigated reasons underlying the restricted distribution of DC-SIGNR and have examined DC-SIGNR expression in relation to HIV entry receptors. We show that DC-SIGNR expression does not depend on endothelial cell specialization or on activation state. DC-SIGNR-positive endothelium continues to express DC-SIGNR in conditions of hyperplasia, whereas the molecule is lost after neoplastic transformation, most likely as a result of changes in the microenvironment of the endothelial cells. We have further shown that CCR5, but not CD4, is coexpressed with DC-SIGNR on hepatic sinusoidal and placental capillary endothelial cells. However, CD4-positive CCR5-positive cells, such as hepatic Kupffer cells, placental Hofbauer cells, and CD4-positive T lymphocytes in lymph nodes, can be found adjacent to DC-SIGNR-positive endothelium. Therefore, DC-SIGNR may be able to mediate HIV infection of these cells in trans. Finally, we demonstrate that DC-SIGN and DC-SIGNR can be coexpressed on lymph node sinus endothelial cells, which may lead to modulation of the function of both molecules. Copyright 2002, Elsevier Science (USA). All rights reserved.

Abnormal labyrinthine zone in the Hectd1-null placenta.

PubMed

Sarkar, Anjali A; Sabatino, Julia A; Sugrue, Kelsey F; Zohn, Irene E

2016-02-01

The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta. The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization. Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs). Together these defects indicate that Hectd1 is required for development of the labyrinthine zonethe mouse placenta. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biology of portal hypertension.

PubMed

McConnell, Matthew; Iwakiri, Yasuko

2018-02-01

Portal hypertension develops as a result of increased intrahepatic vascular resistance often caused by chronic liver disease that leads to structural distortion by fibrosis, microvascular thrombosis, dysfunction of liver sinusoidal endothelial cells (LSECs), and hepatic stellate cell (HSC) activation. While the basic mechanisms of LSEC and HSC dysregulation have been extensively studied, the role of microvascular thrombosis and platelet function in the pathogenesis of portal hypertension remains to be clearly characterized. As a secondary event, portal hypertension results in splanchnic and systemic arterial vasodilation, leading to the development of a hyperdynamic circulatory syndrome and subsequently to clinically devastating complications including gastroesophageal varices and variceal hemorrhage, hepatic encephalopathy from the formation of portosystemic shunts, ascites, and renal failure due to the hepatorenal syndrome. This review article discusses: (1) mechanisms of sinusoidal portal hypertension, focusing on HSC and LSEC biology, pathological angiogenesis, and the role of microvascular thrombosis and platelets, (2) the mesenteric vasculature in portal hypertension, and (3) future directions for vascular biology research in portal hypertension.

Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets

PubMed Central

Mukhitov, Nikita; Roper, Michael G.; Bertram, Richard

2016-01-01

Pancreatic islets manage elevations in blood glucose level by secreting insulin into the bloodstream in a pulsatile manner. Pulsatile insulin secretion is governed by islet oscillations such as bursting electrical activity and periodic Ca2+ entry in β-cells. In this report, we demonstrate that although islet oscillations are lost by fixing a glucose stimulus at a high concentration, they may be recovered by subsequently converting the glucose stimulus to a sinusoidal wave. We predict with mathematical modeling that the sinusoidal glucose signal’s ability to recover islet oscillations depends on its amplitude and period, and we confirm our predictions by conducting experiments with islets using a microfluidics platform. Our results suggest a mechanism whereby oscillatory blood glucose levels recruit non-oscillating islets to enhance pulsatile insulin output from the pancreas. Our results also provide support for the main hypothesis of the Dual Oscillator Model, that a glycolytic oscillator endogenous to islet β-cells drives pulsatile insulin secretion. PMID:27788129

Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis

PubMed Central

Mueller, Sebastian

2016-01-01

Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a major health problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis (SPH), which identifies an elevated sinusoidal pressure (SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts (SPH part I: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmHg and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures (SPH part II: perpetuation). It also defines the “point of no return” where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies. PMID:28082801

Study of the Polarization Strategy for Electron Cyclotron Heating Systems on HL-2M

NASA Astrophysics Data System (ADS)

Zhang, F.; Huang, M.; Xia, D. H.; Song, S. D.; Wang, J. Q.; Huang, B.; Wang, H.

2016-06-01

As important components integrated in transmission lines of electron cyclotron heating systems, polarizers are mainly used to obtain the desired polarization for highly efficient coupling between electron cyclotron waves and plasma. The polarization strategy for 105-GHz electron cyclotron heating systems of HL-2M tokamak is studied in this paper. Considering the polarizers need high efficiency, stability, and low loss to realize any polarization states, two sinusoidal-grooved polarizers, which include a linear polarizer and an elliptical polarizer, are designed with the coordinate transformation method. The parameters, the period p and the depth d, of two sinusoidal-grooved polarizers are optimized by a phase difference analysis method to achieve an almost arbitrary polarization. Finally, the optimized polarizers are manufactured and their polarization characteristics are tested with a low-power test platform. The experimental results agree well with the numerical calculations, indicating that the designed polarizers can meet the polarization requirements of the electron cyclotron heating systems of HL-2M tokamak.

Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide

PubMed Central

Choi, Aery; Kang, Young Kyung; Lim, Sewon; Kim, Dong Ho; Lim, Jung Sub; Lee, Jun Ah

2016-01-01

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver. PMID:27034141

Liver transplantation in man: morphometric analysis of the parenchymal alterations following cold ischaemia and warm ischaemia/reperfusion

PubMed Central

VIZZOTTO, LAURA; VERTEMATI, MAURIZIO; DEGNA, CARLO TOMMASINI; ASENI, PAOLO

2001-01-01

Ischaemia and reperfusion phases represent critical events during liver transplantation. The purpose of this study was to describe morphological alterations of both vascular and parenchymal compartments after ischaemia and reperfusion and to evaluate the possible relationship between morphometric parameters and biochemical/clinical data. Three needle biopsies were drawn from 20 patients who underwent orthotopic liver transplantation. The first biopsy was taken before flushing with preservation solution, and the second and the third to evaluate respectively the effects of cold ischaemia and of warm ischaemia/reperfusion. Biopsies were examined by an image analyser and morphometric parameters related to the liver parenchyma were evaluated. At the second biopsy we observed a decrease of the endothelium volume fraction while the same parameter referred to the sinusoidal lumen achieved a peak value. The hepatocytes showed a lower surface parenchymal/vascular sides ratio. This parameter was reversed at the end of the reperfusion phase; furthermore the third biopsy revealed endothelial swelling and a decreased volume fraction of the sinusoidal lumen. The results quantify the damage to the sinusoidal bed which, as already known, is one of the main targets of cold ischaemia; warm ischaemia and reperfusion accentuate endothelial damage. The end of transplantation is characterised by damage chiefly to parenchymal cells. Hepatocytes show a rearrangement of their surface sides, probably related to the alterations of the sinusoidal bed. In addition, the fluctuations of morphometric parameters during ischaemia/reperfusion correlate positively with biochemical data and clinical course of the patients. PMID:11430699

Comparative transduction mechanisms of hair cells in the bullfrog utriculus. II. Sensitivity and response dynamics to hair bundle displacement

NASA Technical Reports Server (NTRS)

Baird, R. A.

1994-01-01

1. Hair cells in whole-mount in vitro preparations of the utricular macula of the bullfrog (Rana catesbeiana) were selected according to their macular location and hair bundle morphology. The sensitivity and response dynamics of selected hair cells to natural stimulation were examined by recording their voltage responses to step and sinusoidal hair bundle displacements applied to their longest stereocilia. 2. The voltage responses of 31 hair cells to sinusoidal hair bundle displacements were characterized by their gains and phases, taken with respect to peak hair bundle displacement. The gains of Type B and Type C cells at both 0.5 and 5.0 Hz were markedly lower than those of Type F and Type E cells. Phases, with the exception of Type C cells, lagged hair bundle displacement at 0.5 Hz. Type C cells had phase leads of 25-40 degrees. At 5.0 Hz, response phases in all cells were phase lagged with respect to those at 0.5 Hz. Type C cells had larger gains and smaller phase leads at 5.0 Hz than at 0.5 Hz, suggesting the presence of low-frequency adaptation. 3. Displacement-response curves, derived from the voltage responses to 5.0-Hz sinusoids, were sigmoidal in shape and asymmetrical, with the depolarizing response having a greater magnitude and saturating less abruptly than the hyperpolarizing response. When normalized to their largest displacement the linear ranges of these curves varied from < 0.5 to 1.25 microns and were largest in Type B and smallest in Type F and Type E cells. Sensitivity, defined as the slope of the normalized displacement-response curve, was inversely correlated with linear range. 4. The contribution of geometric factors associated with the hair bundle to linear range and sensitivity were predicted from realistic models of utricular hair bundles created using morphological data obtained from light and electron microscopy. Three factors, including 1) the inverse ratio of the lengths of the kinocilium and longest stereocilia, representing the lever arm between kinociliary and stereociliary displacement; 2) tip link extension/linear displacement, largely a function of stereociliary height and separation; and 3) stereociliary number, an estimate of the number of transduction channels, were considered in this analysis. The first of these factors was quantitatively more important than the latter two factors and their total contribution was largest in Type B and Type C cells. Theoretical models were also used to calculate the relation between rotary and linear displacement.(ABSTRACT TRUNCATED AT 400 WORDS).

Alternating current electric fields of varying frequencies: effects on proliferation and differentiation of porcine neural progenitor cells.

PubMed

Lim, Ji-Hey; McCullen, Seth D; Piedrahita, Jorge A; Loboa, Elizabeth G; Olby, Natasha J

2013-10-01

Application of sinusoidal electric fields (EFs) has been observed to affect cellular processes, including alignment, proliferation, and differentiation. In the present study, we applied low-frequency alternating current (AC) EFs to porcine neural progenitor cells (pNPCs) and investigated the effects on cell patterning, proliferation, and differentiation. pNPCs were grown directly on interdigitated electrodes (IDEs) localizing the EFs to a region accessible visually for fluorescence-based assays. Cultures of pNPCs were exposed to EFs (1 V/cm) of 1 Hz, 10 Hz, and 50 Hz for 3, 7, and 14 days and compared to control cultures. Immunocytochemistry was performed to evaluate the expression of neural markers. pNPCs grew uniformly with no evidence of alignment to the EFs and no change in cell numbers when compared with controls. Nestin expression was shown in all groups at 3 and 7 days, but not at 14 days. NG2 expression was low in all groups. Co-expression of glial fibrillary acidic protein (GFAP) and TUJ1 was significantly higher in the cultures exposed to 10- and 50-Hz EFs than the controls. In summary, sinusoidal AC EFs via IDEs did not alter the alignment and proliferation of pNPCs, but higher frequency stimulation appeared to delay differentiation into mature astrocytes.

Contradictory intrahepatic immune responses activated in high-load hepatitis C virus livers compared with low-load livers.

PubMed

Ishibashi, Mariko; Yamaguchi, Hiromi; Hirotani, Yukari; Sakurada, Akihisa; Endo, Toshihide; Sugitani, Masahiko; Takayama, Tadatoshi; Makishima, Makoto; Esumi, Mariko

2018-04-01

We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area. Parenchymal hepatocytes were negative for HLA-DQA1. HLA-DQA1-positive cells in the liver sinusoid were positive for CD68 (macrophages or Kupffer cells); those in the lymphocytic infiltrates were positive for CD20 (B cells) or CD3 (T cells). mRNA levels of antigen-presenting cell (APC) markers such as CD68 and CD11c were significantly upregulated in the HCV-high group and were correlated with HLA-DQA mRNA levels. CD8B mRNA (CD8 + T cells) was upregulated in both HCV-positive livers compared with HCV-negative livers, whereas CD154 mRNA (CD4 + T helper cell) was upregulated in the HCV-high group compared with the HCV-low group. The immune regulatory molecules FOXP3 mRNA (regulatory T cell, T reg) and programmed cell death ligand-1 (PD-L1) mRNA were significantly increased in the HCV-high group. HCV-high livers had two molecular immune responses: increased APC numbers and adaptive immunity and the induction of immune tolerance. The local hepatic imbalance of contradictory immune responses might be responsible for high HCV loads.

In vivo imaging of malaria parasites in the murine liver.

PubMed

Thiberge, Sabine; Blazquez, Samantha; Baldacci, Patricia; Renaud, Olivier; Shorte, Spencer; Ménard, Robert; Amino, Rogerio

2007-01-01

The form of the malaria parasite inoculated by the mosquito, called the sporozoite, transforms inside the host liver into thousands of a new form of the parasite, called the merozoite, which infects erythrocytes. We present here a protocol to visualize in vivo the behavior of Plasmodium berghei parasites in the hepatic tissue of the murine host. The use of GFP-expressing parasites and a high-speed spinning disk confocal microscope allows for the acquisition of four-dimensional images, which provide a time lapse view of parasite displacement and development in tissue volumes. These data can be analyzed to give information on the early events of sporozoite penetration of the hepatic tissue, that is, sporozoite gliding in the liver sinusoids, crossing the sinusoidal barrier, gliding in the parenchyma and traversal of hepatocytes, and invasion of a final hepatocyte, as well as the terminal events of merosome and merozoite release from infected hepatocytes. Combined with the use of mice expressing fluorescent cell types or cell markers, the system will provide useful information not only on the primary infection process, but also on parasite interactions with the host immune cells in the liver.

Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome.

PubMed

Richardson, Paul G; Triplett, Brandon M; Ho, Vincent T; Chao, Nelson; Dignan, Fiona L; Maglio, Michelle; Mohty, Mohamad

2018-02-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable condition associated with endothelial-cell damage due to conditioning for hematopoietic stem-cell transplantation (HSCT) or chemotherapy without HSCT. Mortality in patients with VOD/SOS and multi-organ dysfunction (MOD) may be >80%. Areas covered: Defibrotide is the only approved drug for the treatment of severe hepatic VOD/SOS after HSCT in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction in the United States. Its efficacy in patients with VOD/SOS with MOD post-HSCT was demonstrated in a clinical-trial program that included a historically controlled treatment study, a phase 2 trial, and a large T-IND expanded-access program that also included patients without MOD and who received chemotherapy without HSCT. Expert commentary: Defibrotide appears to protect endothelial cells and restore the thrombolytic-fibrinolytic balance. It addresses a significant clinical need and has demonstrated favorable Day +100 survival and overall adverse-event rates that seem similar to control groups receiving supportive care alone. Currently, defibrotide is under investigation for the prevention of VOD/SOS in high-risk pediatric and adult patients.

New ways of looking at very small holes - using optical nanoscopy to visualize liver sinusoidal endothelial cell fenestrations

NASA Astrophysics Data System (ADS)

Øie, Cristina I.; Mönkemöller, Viola; Hübner, Wolfgang; Schüttpelz, Mark; Mao, Hong; Ahluwalia, Balpreet S.; Huser, Thomas R.; McCourt, Peter

2018-02-01

Super-resolution fluorescence microscopy, also known as nanoscopy, has provided us with a glimpse of future impacts on cell biology. Far-field optical nanoscopy allows, for the first time, the study of sub-cellular nanoscale biological structures in living cells, which in the past was limited to electron microscopy (EM) (in fixed/dehydrated) cells or tissues. Nanoscopy has particular utility in the study of "fenestrations" - phospholipid transmembrane nanopores of 50-150 nm in diameter through liver sinusoidal endothelial cells (LSECs) that facilitate the passage of plasma, but (usually) not blood cells, to and from the surrounding hepatocytes. Previously, these fenestrations were only discernible with EM, but now they can be visualized in fixed and living cells using structured illumination microscopy (SIM) and in fixed cells using single molecule localization microscopy (SMLM) techniques such as direct stochastic optical reconstruction microscopy. Importantly, both methods use wet samples, avoiding dehydration artifacts. The use of nanoscopy can be extended to the in vitro study of fenestration dynamics, to address questions such as the following: are they actually dynamic structures, and how do they respond to endogenous and exogenous agents? A logical further extension of these methodologies to liver research (including the liver endothelium) will be their application to liver tissue sections from animal models with different pathological manifestations and ultimately to patient biopsies. This review will cover the current state of the art of the use of nanoscopy in the study of liver endothelium and the liver in general. Potential future applications in cell biology and the clinical implications will be discussed.

Contact angle hysteresis on doubly periodic smooth rough surfaces in Wenzel's regime: The role of the contact line depinning mechanism

NASA Astrophysics Data System (ADS)

Iliev, Stanimir; Pesheva, Nina; Iliev, Pavel

2018-04-01

We report here on the contact angle hysteresis, appearing when a liquid meniscus is in contact with doubly sinusoidal wavelike patterned surfaces in Wenzel's wetting regime. Using the full capillary model we obtain numerically the contact angle hysteresis as a function of the surface roughness factor and the equilibrium contact angle for a block case and a kink case contact line depinning mechanism. We find that the dependencies of the contact angle hysteresis on the surface roughness factor are different for the different contact line depinning mechanisms. These dependencies are different also for the two types of rough surfaces we studied. The relations between advancing, receding, and equilibrium contact angles are investigated. A comparison with the existing asymptotical, numerical, and experimental results is carried out.

Contact angle hysteresis on doubly periodic smooth rough surfaces in Wenzel's regime: The role of the contact line depinning mechanism.

PubMed

Iliev, Stanimir; Pesheva, Nina; Iliev, Pavel

2018-04-01

We report here on the contact angle hysteresis, appearing when a liquid meniscus is in contact with doubly sinusoidal wavelike patterned surfaces in Wenzel's wetting regime. Using the full capillary model we obtain numerically the contact angle hysteresis as a function of the surface roughness factor and the equilibrium contact angle for a block case and a kink case contact line depinning mechanism. We find that the dependencies of the contact angle hysteresis on the surface roughness factor are different for the different contact line depinning mechanisms. These dependencies are different also for the two types of rough surfaces we studied. The relations between advancing, receding, and equilibrium contact angles are investigated. A comparison with the existing asymptotical, numerical, and experimental results is carried out.

Sinusoidal modulation analysis for optical system MTF measurements.

PubMed

Boone, J M; Yu, T; Seibert, J A

1996-12-01

The modulation transfer function (MTF) is a commonly used metric for defining the spatial resolution characteristics of imaging systems. While the MTF is defined in terms of how an imaging system demodulates the amplitude of a sinusoidal input, this approach has not been in general use to measure MTFs in the medical imaging community because producing sinusoidal x-ray patterns is technically difficult. However, for optical systems such as charge coupled devices (CCD), which are rapidly becoming a part of many medical digital imaging systems, the direct measurement of modulation at discrete spatial frequencies using a sinusoidal test pattern is practical. A commercially available optical test pattern containing spatial frequencies ranging from 0.375 cycles/mm to 80 cycles/mm was sued to determine the MRF of a CCD-based optical system. These results were compared with the angulated slit method of Fujita [H. Fujita, D. Tsia, T. Itoh, K. Doi, J. Morishita, K. Ueda, and A. Ohtsuka, "A simple method for determining the modulation transfer function in digital radiography," IEEE Trans. Medical Imaging 11, 34-39 (1992)]. The use of a semiautomated profiled iterated reconstruction technique (PIRT) is introduced, where the shift factor between successive pixel rows (due to angulation) is optimized iteratively by least-squares error analysis rather than by hand measurement of the slit angle. PIRT was used to find the slit angle for the Fujita technique and to find the sine-pattern angle for the sine-pattern technique. Computer simulation of PIRT for the case of the slit image (a line spread function) demonstrated that it produced a more accurate angle determination than "hand" measurement, and there is a significant difference between the errors in the two techniques (Wilcoxon Signed Rank Test, p < 0.001). The sine-pattern method and the Fujita slit method produced comparable MTF curves for the CCD camera evaluated.

Tumor cytotoxicity by endothelial cells. Impairment of the mitochondrial system for glutathione uptake in mouse B16 melanoma cells that survive after in vitro interaction with the hepatic sinusoidal endothelium.

PubMed

Ortega, Angel L; Carretero, Julian; Obrador, Elena; Gambini, Juan; Asensi, Miguel; Rodilla, Vicente; Estrela, José M

2003-04-18

High GSH content associates with high metastatic activity in B16-F10 melanoma cells cultured to low density (LD B16M). GSH homeostasis was investigated in LD B16M cells that survive after adhesion to the hepatic sinusoidal endothelium (HSE). Invasive B16M (iB16M) cells were isolated using anti-Met-72 monoclonal antibodies and flow cytometry-coupled cell sorting. HSE-derived NO and H(2)O(2) caused GSH depletion and a decrease in gamma-glutamylcysteine synthetase activity in iB16M cells. Overexpression of gamma-glutamylcysteine synthetase heavy and light subunits led to a rapid recovery of cytosolic GSH, whereas mitochondrial GSH (mtGSH) further decreased during the first 18 h of culture. NO and H(2)O(2) damaged the mitochondrial system for GSH uptake (rates in iB16M were approximately 75% lower than in LD B16M cells). iB16M cells also showed a decreased activity of mitochondrial complexes II, III, and IV, less O(2) consumption, lower ATP levels, higher O(2) and H(2)O(2) production, and lower mitochondrial membrane potential. In vitro growing iB16M cells maintained high viability (>98%) and repaired HSE-induced mitochondrial damages within 48 h. However, iB16M cells with low mtGSH levels were highly susceptible to TNF-alpha-induced oxidative stress and death. Therefore depletion of mtGSH levels may represent a critical target to challenge survival of invasive cancer cells.

Changes of vessel-cells complex in zones of adaptive remodeling of the bone tissue under microgravity conditions

NASA Astrophysics Data System (ADS)

Rodionova, N.; Oganov, V.; Nosova, L.

The development and differentiation of osteogenic cells in organism happen in closely topographical and functional connection with blood capillaries. We formerly proofed, that small-differentiated cells, which are in the population of perivascular cells are osteogenic cells -precursors . At the present time it is actually to clear up, how these biostructures react on conditions of less of biomechanical load on skeleton bones. We researched peculiarities of blood-bed structure and perivascular cells in metaphises of thighbones and tibial bones in rats, which were onboard the American space station SLS-2 and in experiments of modeling hypokinesia. There were used methods of cytochemistry, histology and electron microscopy. We established, that under the support and functional load decreasing in zones of bones adaptive remodeling, comparatively to control, on histosections the own volume of sinusoid capillaries reduces. The small vessels prevail here. The spaces of sinusoid capillaries are limited by 1 2 cells of the endothelia. Endotheliocytes in- general have the typical ultrastructure. Basal membranes are expressed not-distinctly. Perivascular cells don't create the unbroken layer. The population of these cells is not-homogeneous. It includes enclosed to endothelia small-differentiated forms and separating cells with sings of fibroblastic differentiation (the own volume of rough endoplasmic reticulum in cytoplasm induces). The part of these cells reacts on the alkaline phosphatase (the marker of the osteogenic differentiation). Under the conditions of support load decreasing (especially under the microgravity) there is a tendency to reducing of separating osteogenic cells number. We noted the priority of differentiating fibroblasts. It leads to further development in zones of bone remodeling of hearths of fibrous tissue, that doesn't mineralize. The obtained data are seen as one of mechanisms of osteoporosis and osteopenia development under the deficite of support load.

IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules.

PubMed

Knolle, P A; Uhrig, A; Hegenbarth, S; Löser, E; Schmitt, E; Gerken, G; Lohse, A W

1998-12-01

Our study demonstrates that antigen-presenting liver sinusoidal endothelial cells (LSEC) induce production of interferon-gamma (IFN-gamma) from cloned Th1 CD4+ T cells. We show that LSEC used the mannose receptor for antigen uptake, which further strengthened the role of LSEC as antigen-presenting cell (APC) population in the liver. The ability of LSEC to activate cloned CD4+ T cells antigen-specifically was down-regulated by exogenous prostaglandin E2 (PGE2) and by IL-10. We identify two separate mechanisms by which IL-10 down-regulated T cell activation through LSEC. IL-10 decreased the constitutive surface expression of MHC class II as well as of the accessory molecules CD80 and CD86 on LSEC. Furthermore, IL-10 diminished mannose receptor activity in LSEC. Decreased antigen uptake via the mannose receptor and decreased expression of accessory molecules may explain the down-regulation of T cell activation through IL-10. Importantly, the expression of low numbers of antigen on MHC II in the absence of accessory signals on LSEC may lead to induction of anergy in T cells. Because PGE2 and IL-10 are released from LSEC or Kupffer cells (KC) in response to those concentrations of endotoxin found physiologically in portal venous blood, it is possible that the continuous presence of these mediators and their negative effect on the local APC may explain the inability of the liver to induce T cell activation and to clear chronic infections. Our results support the notion that antigen presentation by LSEC in the hepatic microenvironment contributes to the observed inability to mount an effective cell-mediated immune response in the liver.

Langmuir Probe Distortions and Probe Compensation in an Inductively Coupled Plasma

NASA Technical Reports Server (NTRS)

Ji, J. S.; Cappelli, M. A.; Kim, J. S.; Rao, M. V. V. S.; Sharma, S. P.

1999-01-01

In many RF discharges, Langmuir probe measurements are usually made against a background of sinusoidal (and not so sinusoidal) fluctuations in the plasma parameters such as the plasma potential (Vp), the electron number density (ne), and the electron temperature (Te). The compensation of sinusoidal fluctuations in Vp has been extensively studied and is relatively well understood. Less attention has been paid to the possible distortions introduced by small fluctuations in plasma density and/or plasma temperature, which may arise in the sheath and pre-sheath regions of RF discharges. Here, we present the results of a model simulation of probe characteristics subject to fluctuations in both Vp and ne. The modeling of probe distortion due to possible fluctuations in Te is less straightforward. A comparison is presented of calculations with experimental measurements using a compensated and uncompensated Langmuir probe in an inductively coupled GEC reference cell plasma, operating on Ar and Ar/CF4 mixtures. The plasma parameters determined from the compensated probe characteristics are compared to previous measurements of others made in similar discharges, and to our own measurements of the average electron density derived from electrical impedance measurements.

Taurine transport across hepatocyte plasma membranes: analysis in isolated rat liver sinusoidal plasma membrane vesicles.

PubMed

Inoue, M; Arias, I M

1988-07-01

To elucidate the mechanism of taurine transport across the hepatic plasma membranes, rat liver sinusoidal plasma membrane vesicles were isolated and the transport process was analyzed. In the presence of a sodium gradient across the membranes (vesicle inside less than vesicle outside), an overshooting uptake of taurine occurred. In the presence of other ion gradients (K+, Li+, and choline+), taurine uptake was very small and no such overshoot was observed. Sodium-dependent uptake of taurine occurred into an osmotically active intravesicular space. Taurine uptake was stimulated by preloading vesicles with unlabeled taurine (transstimulation) in the presence of NaCl, but not in the presence of KCl. Sodium-dependent transport followed saturation kinetics with respect to taurine concentration; double-reciprocal plots of uptake versus taurine concentration gave a straight line from which an apparent Km value of 0.38 mM and Vmax of 0.27 nmol/20 s x mg of protein were obtained. Valinomycin-induced K+-diffusion potential failed to enhance the rate of taurine uptake, suggesting that taurine transport does not depend on membrane potential. Taurine transport was inhibited by structurally related omega-amino acids, such as beta-alanine and gamma-aminobutyric acid, but not by glycine, epsilon-aminocaproic acid, or other alpha-amino acids, such as L-alanine. These results suggest that Na+-dependent uptake of taurine might occur across the hepatic sinusoidal plasma membranes via a transport system that is specific for omega-amino acids having 2-3 carbon chain length.

What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance.

PubMed

Palomo, Marta; Mir, Enrique; Rovira, Montse; Escolar, Ginés; Carreras, Enric; Diaz-Ricart, Maribel

2016-03-31

Defibrotide (DF) has received European Medicines Agency authorization to treat sinusoidal obstruction syndrome, an early complication after hematopoietic cell transplantation. DF has a recognized role as an endothelial protective agent, although its precise mechanism of action remains to be elucidated. The aim of the present study was to investigate the interaction of DF with endothelial cells (ECs). A human hepatic EC line was exposed to different DF concentrations, previously labeled. Using inhibitory assays and flow cytometry techniques along with confocal microscopy, we explored: DF-EC interaction, endocytic pathways, and internalization kinetics. Moreover, we evaluated the potential role of adenosine receptors in DF-EC interaction and if DF effects on endothelium were dependent of its internalization. Confocal microscopy showed interaction of DF with EC membranes followed by internalization, though DF did not reach the cell nucleus even after 24 hours. Flow cytometry revealed concentration, temperature, and time dependent uptake of DF in 2 EC models but not in other cell types. Moreover, inhibitory assays indicated that entrance of DF into ECs occurs primarily through macropinocytosis. Our experimental approach did not show any evidence of the involvement of adenosine receptors in DF-EC interaction. The antiinflammatory and antioxidant properties of DF seem to be caused by the interaction of the drug with the cell membrane. Our findings contribute to a better understanding of the precise mechanisms of action of DF as a therapeutic and potential preventive agent on the endothelial damage underlying different pathologic situations. © 2016 by The American Society of Hematology.

High-speed high-accuracy three-dimensional shape measurement using digital binary defocusing method versus sinusoidal method

NASA Astrophysics Data System (ADS)

Hyun, Jae-Sang; Li, Beiwen; Zhang, Song

2017-07-01

This paper presents our research findings on high-speed high-accuracy three-dimensional shape measurement using digital light processing (DLP) technologies. In particular, we compare two different sinusoidal fringe generation techniques using the DLP projection devices: direct projection of computer-generated 8-bit sinusoidal patterns (a.k.a., the sinusoidal method), and the creation of sinusoidal patterns by defocusing binary patterns (a.k.a., the binary defocusing method). This paper mainly examines their performance on high-accuracy measurement applications under precisely controlled settings. Two different projection systems were tested in this study: a commercially available inexpensive projector and the DLP development kit. Experimental results demonstrated that the binary defocusing method always outperforms the sinusoidal method if a sufficient number of phase-shifted fringe patterns can be used.

High-speed 3D imaging using digital binary defocusing method vs sinusoidal method

NASA Astrophysics Data System (ADS)

Zhang, Song; Hyun, Jae-Sang; Li, Beiwen

2017-02-01

This paper presents our research findings on high-speed 3D imaging using digital light processing (DLP) technologies. In particular, we compare two different sinusoidal fringe generation techniques using the DLP projection devices: direct projection of 8-bit computer generated sinusoidal patterns (a.k.a, the sinusoidal method), and the creation of sinusoidal patterns by defocusing binary patterns (a.k.a., the binary defocusing method). This paper mainly examines their performance on high-accuracy measurement applications under precisely controlled settings. Two different projection systems were tested in this study: the commercially available inexpensive projector, and the DLP development kit. Experimental results demonstrated that the binary defocusing method always outperforms the sinusoidal method if a sufficient number of phase-shifted fringe patterns can be used.

Electromagnetically induced transparency in sinusoidal modulated ring resonator

NASA Astrophysics Data System (ADS)

Malik, Jagannath; Oruganti, Sai Kiran; Song, Seongkyu; Ko, Nak Young; Bien, Franklin

2018-06-01

In the present work, we demonstrate controlling the excitation of bright mode (continuum mode) resonance and dark mode (discrete mode) resonance in a planar metasurface made of sinusoidal modulation inside a closed rectangular metallic ring placed over a dielectric substrate. Unlike asymmetrical breaking of a meta-atom (often referred to as the unit cell) to achieve the dark mode response in regular metamaterials, in the present structure, the bright or dark mode resonance is achieved using even or odd half cycle modulation. The achieved dark-mode shows a sharp resonance for a particular polarization of the incident electric field, which results in an electromagnetically induced transparency like spectrum. The electromagnetic behavior of the proposed meta-atom has been investigated in the frequency domain using commercially available software and validated through experiments in the gigahertz regime.

A novel microcontroller-based digital instrument for measurement of electrical quantities under non-sinusoidal condition

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

Anaya, O.; Moreno, G.E.L.; Madrigal, M.M.

1999-11-01

In the last years, several definitions of power have been proposed for more accurate measurement of electrical quantities in presence of harmonics pollution on power lines. Nevertheless, only few instruments have been constructed considering these definitions. This paper describes a new microcontroller-based digital instrument, which include definitions based on Harley Transform. The algorithms are fully processed using Fast Hartley Transform (FHT) and 16 bit-microcontroller platform. The constructed prototype was compared with commercial harmonics analyzer instrument.

Copernicus observations of Iota Herculis velocity variations

NASA Technical Reports Server (NTRS)

Rogerson, J. B., Jr.

1984-01-01

Observations of Iota Her at 109.61-109.67 nm obtained with the U1 channel of the Copernicus spectrophotometer at resolution 5 pm during 3.6 days in May, 1979, are reported. Radial-velocity variations are detected and analyzed as the sum of two sinusoids with frequencies 0.660 and 0.618 cycles/day and amplitudes 9.18 and 8.11 km/s, respectively. Weak evidence supporting the 13.9-h periodicity seen in line-profile variations by Smith (1978) is found.

Impact Testing and Simulation of a Sinusoid Foam Sandwich Energy Absorber

NASA Technical Reports Server (NTRS)

Jackson, Karen E.; Fasanella, Edwin L; Littell, Justin D.

2015-01-01

A sinusoidal-shaped foam sandwich energy absorber was developed and evaluated at NASA Langley Research Center through multi-level testing and simulation performed under the Transport Rotorcraft Airframe Crash Testbed (TRACT) research project. The energy absorber, designated the "sinusoid," consisted of hybrid carbon- Kevlar® plain weave fabric face sheets, two layers for each face sheet oriented at +/-45deg with respect to the vertical or crush direction, and a closed-cell ELFOAM(TradeMark) P200 polyisocyanurate (2.0-lb/ft3) foam core. The design goal for the energy absorber was to achieve an average floor-level acceleration of between 25- and 40-g during the full-scale crash test of a retrofitted CH-46E helicopter airframe, designated TRACT 2. Variations in the design were assessed through quasi-static and dynamic crush testing of component specimens. Once the design was finalized, a 5-ft-long subfloor beam was fabricated and retrofitted into a barrel section of a CH-46E helicopter. A vertical drop test of the barrel section was conducted onto concrete to evaluate the performance of the energy absorber prior to retrofit into TRACT 2. Finite element models were developed of all test articles and simulations were performed using LSDYNA ®, a commercial nonlinear explicit transient dynamic finite element code. Test analysis results are presented for the sinusoid foam sandwich energy absorber as comparisons of load-displacement and acceleration-time-history responses, as well as predicted and experimental structural deformations and progressive damage for each evaluation level (component testing through barrel section drop testing).

Hepatoblastoma with pure fetal epithelial differentiation in a 10-year-old boy

PubMed Central

Zhong, Shanshan; Zhao, Yang; Fan, Chuifeng

2018-01-01

Abstract Rationale: Hepatoblastoma is a rare malignant embryonal tumor that only accounts for approximately 1% of all pediatric cancers and mostly develops in children younger than 5 years old. Moreover, the occurrence of hepatoblastoma in adults is extremely rare. Patient concerns: Herein, we present a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy.Pathological examination was performed. The tumor was 15 cm × 15 cm in size with clear margins. The cut surface was multiple nodular and grey-yellow. Histologically, the small cuboidal tumor cells were arranged in trabeculae with 2–3 cell layers. The tumor cells had eosinophilic or clear cytoplasm, formed dark and light areas, and were positive for alpha-fetoprotein, CK, CK8/18, CD10, hepatocyte, and GPC3. CD34 staining revealed that the sinusoids were lined by endothelial cells in the tumor tissues. The Ki67 index was approximately 20%. Diagnoses: Based on these findings, the case was diagnosed as hepatoblastoma with pure fetal epithelial differentiation. Interventions: The tumor was completely removed. Outcomes: No recurrence was found 3 months after the operation. Lessons: Hepatoblastoma with pure epithelial differentiation can also occur in older children. Children rarely notice and report any physical abnormality, and this may be among the primary reasons for the late diagnosis of the tumor. Annual heath checks may be beneficial in the detection of these rare tumors and improvement of patient outcomes. PMID:29480877

Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development.

PubMed

Pan, Jie; Copland, Ian; Post, Martin; Yeger, Herman; Cutz, Ernest

2006-01-01

Pulmonary neuroendocrine cells (PNEC) produce amine (serotonin, 5-HT) and peptides (e.g., bombesin, calcitonin) with growth factor-like properties and are thought to play an important role in lung development. Because physical forces are essential for lung growth and development, we investigated the effects of mechanical strain on 5-HT release in PNEC freshly isolated from rabbit fetal lung and in the PNEC-related tumor H727 cell line. Cultures exposed to sinusoidal cyclic stretch showed a significant 5-HT release inhibitable with gadolinium chloride (10 nM), a blocker of mechanosensitive channels. In contrast to hypoxia (Po2 approximately 20 mmHg), stretch-induced 5-HT release was not affected by Ca2+-free medium or nifedipine (50 microM), excluding the exocytic pathway. In H727 cells, stretch failed to release calcitonin, a peptide stored within dense core vesicles (DCV), whereas hypoxia caused massive calcitonin release. 5-HT released by mechanical stretch is derived predominantly from the cytoplasmic pool, because it is rapid ( approximately 5 min) and is releasable from early (20 days of gestation) fetal PNEC containing few DCV. Both mechanical stretch and hypoxia upregulated expression of tryptophan hydroxylase, the rate-limiting enzyme of 5-HT synthesis. We conclude that mechanical strain is an important physiological stimulus for the release of 5-HT from PNEC via mechanosensitive channels with potential effects on lung development and resorption of lung fluid at the time of birth.

All-In-One: Advanced preparation of Human Parenchymal and Non-Parenchymal Liver Cells

PubMed Central

Werner, Melanie; Driftmann, Sabrina; Kleinehr, Kathrin; Kaiser, Gernot M.; Mathé, Zotlan; Treckmann, Juergen-Walter; Paul, Andreas; Skibbe, Kathrin; Timm, Joerg; Canbay, Ali; Gerken, Guido; Schlaak, Joerg F.; Broering, Ruth

2015-01-01

Background & Aims Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen. Methods Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity. Results Cell preparation yielded the following cell counts per gram of liver tissue: 2.0±0.4×107 hepatocytes, 1.8±0.5×106 Kupffer cells, 4.3±1.9×105 liver sinusoidal endothelial cells, and 3.2±0.5×105 stellate cells. Hepatocytes were identified by albumin (95.5±1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5±1.2%) and exhibited phagocytic activity, as determined with 1μm latex beads. Endothelial cells were CD146+ (97.8±1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1±1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence. Conclusions Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease. PMID:26407160

Exploring the human mesenchymal stem cell tubule communication network through electron microscopy.

PubMed

Valente, Sabrina; Rossi, Roberta; Resta, Leonardo; Pasquinelli, Gianandrea

2015-04-01

Cells use several mechanisms to transfer information to other cells. In this study, we describe micro/nanotubular connections and exosome-like tubule fragments in multipotent mesenchymal stem cells (MSCs) from human arteries. Scanning and transmission electron microscopy allowed characterization of sinusoidal microtubular projections (700 nm average size, 200 µm average length, with bulging mitochondria and actin microfilaments); short, uniform, variously shaped nanotubular projections (100 nm, bidirectional communication); and tubule fragments (50 nm). This is the first study demonstrating that MSCs from human arteries constitutively interact through an articulate and dynamic tubule network allowing long-range cell to cell communication.

Sensorless optimal sinusoidal brushless direct current for hard disk drives

NASA Astrophysics Data System (ADS)

Soh, C. S.; Bi, C.

2009-04-01

Initiated by the availability of digital signal processors and emergence of new applications, market demands for permanent magnet synchronous motors have been surging. As its back-emf is sinusoidal, the drive current should also be sinusoidal for reducing the torque ripple. However, in applications like hard disk drives, brushless direct current (BLDC) drive is adopted instead of sinusoidal drive for simplification. The adoption, however, comes at the expense of increased harmonics, losses, torque pulsations, and acoustics. In this paper, we propose a sensorless optimal sinusoidal BLDC drive. First and foremost, the derivation for an optimal sinusoidal drive is presented, and a power angle control scheme is proposed to achieve an optimal sinusoidal BLDC. The scheme maintains linear relationship between the motor speed and drive voltage. In an attempt to execute the sensorless drive, an innovative power angle measurement scheme is devised, which takes advantage of the freewheeling diodes and measures the power angle through the detection of diode voltage drops. The objectives as laid out will be presented and discussed in this paper, supported by derivations, simulations, and experimental results. The proposed scheme is straightforward, brings about the benefits of sensorless sinusoidal drive, negates the need for current sensors by utilizing the freewheeling diodes, and does not incur additional cost.

Power spectral analysis of R-R interval variability before and during the sinusoidal heart rate pattern in fetal lambs.

PubMed

Suzuki, T; Okamura, K; Kimura, Y; Watanabe, T; Yaegashi, N; Murotsuki, J; Uehara, S; Yajima, A

2000-05-01

The appearance of the sinusoidal heart rate pattern found on fetal cardiotocograms has not been fully explained, either physiologically or clinically. In this study we performed power spectral analysis on the sinusoidal heart rate pattern obtained by administration of arginine vasopressin and atropine sulfate to investigate its frequency components in fetal lambs with long-term instrument implantation. Eleven tests were performed in 4 fetal lambs at 120 to 130 days' gestation. An artificial sinusoidal heart rate pattern was obtained by administration of atropine sulfate and arginine vasopressin in 9 tests. An autoregression model was used to compare the spectral patterns before and during the sinusoidal heart rate pattern. Marked decreases in low-frequency (0.025-0.125 cycles/beat) and high-frequency (0.2-0.5 cycles/beat) areas were observed in the presence of the sinusoidal heart rate pattern. However, there were no significant changes in the very-low-frequency area (0.01-0.025 cycles/beat), which corresponds to the frequency of the sinusoidal heart rate pattern. The sinusoidal heart rate pattern may represent a very low-frequency component inherent in fetal heart rate variability that appears when low- and high-frequency components are reduced as a result of strongly suppressed autonomic nervous activity.

Hypervitaminosis A-induced liver fibrosis: stellate cell activation and daily dose consumption.

PubMed

Nollevaux, M-C; Guiot, Y; Horsmans, Y; Leclercq, I; Rahier, J; Geubel, A P; Sempoux, C

2006-03-01

Hypervitaminosis A-related liver toxicity may be severe and may even lead to cirrhosis. In the normal liver, vitamin A is stored in hepatic stellate cells (HSC), which are prone to becoming activated and acquiring a myofibroblast-like phenotype, producing large amounts of extracellular matrix. In order to assess the relationship between vitamin A intake, HSC activation and fibrosis, we studied nine liver biopsies from patients belonging to a well-characterized series of 41 patients with vitamin A hepatotoxicity. Fibrosis was underlined by Sirius-red staining, whereas activated HSC were immunohistochemically identified using an antibody against alpha smooth muscle actin. The volume density (Vv) of sinusoidal and total fibrosis and of sinusoidal and total activated HSC was quantified by the point-counting method. Morphology ranged from HSC hypertrophy and hyperplasia as the sole features to severe architectural distortion. There was a significant positive correlation between Vv of perisinusoidal fibrosis and the daily consumption of vitamin A (P=0.004). The close correlation between the severity of perisinusoidal fibrosis and the daily dose of the retinol intake suggests the existence of a dose-effect relationship.

Safety and effects of prophylactic defibrotide for sinusoidal obstruction syndrome in hematopoietic stem cell transplantation.

PubMed

Park, Meerim; Park, Hyeon Jin; Eom, Hyeon-Seok; Kwon, Young Joo; Park, Jeong A; Lim, Yeon Jung; Yoon, Jong Hyung; Kong, Sun-Young; Ghim, Thad T; Lee, Hye Won; Yun, Tak; Park, Byung-Kiu

2013-01-28

Sinusoidal obstruction syndrome (SOS) is a serious complication of hematopoietic stem cell transplantation (HSCT), with a mortality rate of up to 90%. We report our experience on the use of defibrotide for SOS prophylaxis in HSCT. We retrospectively reviewed data of 49 patients who received defibrotide as SOS prophylaxis during the course of HSCT at the National Cancer Center, Goyang, Korea, between August 2005 and July 2008. Thirty-four patients (69.4%) were classified as a high-risk group for developing SOS. Defibrotide was well-tolerated, without any grade 3 or 4 toxicity. The median value of maximum total bilirubin within 100 days after HSCT was within the normal range. SOS was diagnosed in only 1 patient, who underwent autologous HSCT due to relapsed medulloblastoma. There was no day 100 treatment-related mortality in our study. Defibrotide appears to be a safe prophylaxis for SOS. This study suggests that it could be effective to use prophylactic defibrotide in advance to improve HSCT outcomes in patients at risk of SOS.

Optical Coatings With Graded Index Layers For High Power Laser Applications: Design

NASA Astrophysics Data System (ADS)

Zukic, Muamer; Guenther, Karl H.

1988-06-01

Graded index layers provide a greater flexibility for the design of optical coatings than "homogeneous" layers. A graded index layer can replace the whole or a part of a traditional multilayer stack of alternating thin films of high and low refractive index. This paper presents design examples for broadband antireflection coatings, narrowband high reflectors (also referred to as minus filters or rejection line filters), and non-polarizing beam splitters. Optimized refractive index profiles are derived for broadband antireflection coatings for various combinations of incident medium and substrate. The rejection line filter example uses a sinusoidal (rugate) index profile. The non-polarizing beamsplitter summarizes the topical contents of a paper presented in another conference at the same symposium.

X-ray backlighting of imploding aluminium liners on PTS facility

NASA Astrophysics Data System (ADS)

Yang, Qingguo; Liu, Dongbing; Mu, Jian; Huang, Xianbin; Dan, Jiakun; Xie, Xudong; Deng, Wu; Feng, Shuping; Wang, Meng; Ye, Yan; Peng, Qixian; Li, Zeren

2016-09-01

The x-ray backlighting systems, including a 1.865 keV (Si Heα line) spherically bent crystal imaging system and an ˜8.3 keV (Cu Heα line) point-projection imaging system, newly fielded on the Primary Test Stand facility are introduced and its preliminary experimental results in radiography of the aluminium (Al) liners with seeded sinusoidal perturbations are presented. The x-ray backlighter source is created using a 1 TW, 1 kJ Nd: glass high power laser, kilo-joule laser system, recently constructed at China Academy of Engineering Physics. The ablation melt and instability of the imploding Al liner outer edge under the driving current of ˜7.5 MA are successfully observed using these two backlighting systems, respectively.

Effect of positive pulse charge waveforms on cycle life of nickel-zinc cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1979-01-01

Five amp-hour nickel-zinc cells were life cycled to evaluate four different charge methods. Three of the four waveforms investigated were 120 Hz full wave rectified sinusoidal (FWRS), 120 Hz silicon controlled rectified (SCR), and 1 kHz square wave (SW). The fourth, a constant current method, was used as a baseline of comparison. Three sealed Ni-Zn cells connected in series were cycled. Each series string was charged at an average c/20 rate, and discharged at a c/2.5 rate to a 75% rated depth.

SYNTHETIC HYDROGEN SPECTRA OF OSCILLATING PROMINENCE SLABS IMMERSED IN THE SOLAR CORONA

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

Zapiór, M.; Heinzel, P.; Oliver, R.

We study the behavior of H α and H β spectral lines and their spectral indicators in an oscillating solar prominence slab surrounded by the solar corona, using an MHD model combined with a 1D radiative transfer code taken in the line of sight perpendicular to the slab. We calculate the time variation of the Doppler shift, half-width, and maximum intensity of the H α and H β spectral lines for different modes of oscillation. We find a non-sinusoidal time dependence of some spectral parameters with time. Because H α and H β spectral indicators have different behavior for differentmore » modes, caused by differing optical depths of formation and different plasma parameter variations in time and along the slab, they may be used for prominence seismology, especially to derive the internal velocity field in prominences.« less

On-Line Tracking Controller for Brushless DC Motor Drives Using Artificial Neural Networks

NASA Technical Reports Server (NTRS)

Rubaai, Ahmed

1996-01-01

A real-time control architecture is developed for time-varying nonlinear brushless dc motors operating in a high performance drives environment. The developed control architecture possesses the capabilities of simultaneous on-line identification and control. The dynamics of the motor are modeled on-line and controlled using an artificial neural network, as the system runs. The control architecture combines the experience and dependability of adaptive tracking systems with potential and promise of the neural computing technology. The sensitivity of real-time controller to parametric changes that occur during training is investigated. Such changes are usually manifested by rapid changes in the load of the brushless motor drives. This sudden change in the external load is simulated for the sigmoidal and sinusoidal reference tracks. The ability of the neuro-controller to maintain reasonable tracking accuracy in the presence of external noise is also verified for a number of desired reference trajectories.

Modification of response functions of cat visual cortical cells by spatially congruent perturbing stimuli.

PubMed

Kabara, J F; Bonds, A B

2001-12-01

Responses of cat striate cortical cells to a drifting sinusoidal grating were modified by the superimposition of a second, perturbing grating (PG) that did not excite the cell when presented alone. One consequence of the presence of a PG was a shift in the tuning curves. The orientation tuning of all 41 cells exposed to a PG and the spatial frequency tuning of 83% of the 23 cells exposed to a PG showed statistically significant dislocations of both the response function peak and center of mass from their single grating values. As found in earlier reports, the presence of PGs suppressed responsiveness. However, reductions measured at the single grating optimum orientation or spatial frequency were on average 1.3 times greater than the suppression found at the peak of the response function modified by the presence of the PG. Much of the loss in response seen at the single grating optimum is thus a result of a shift in the tuning function rather than outright suppression. On average orientation shifts were repulsive and proportional (approximately 0.10 deg/deg) to the angle between the perturbing stimulus and the optimum single grating orientation. Shifts in the spatial frequency response function were both attractive and repulsive, resulting in an overall average of zero. For both simple and complex cells, PGs generally broadened orientation response function bandwidths. Similarly, complex cell spatial frequency response function bandwidths broadened. Simple cell spatial frequency response functions usually did not change, and those that did broadened only 4% on average. These data support the hypothesis that additional sinusoidal components in compound stimuli retune cells' response functions for orientation and spatial frequency.

Diffraction grating-based sensing optofluidic device for measuring the refractive index of liquids.

PubMed

Calixto, Sergio; Bruce, Neil C; Rosete-Aguilar, Martha

2016-01-11

We describe a simple and versatile optical sensing device for measuring refractive index of liquids. The sensor consists of a sinusoidal relief grating in a glass cell. Device calibration is done by pouring in the cell different liquids of known refractive indices. Each time a liquid is poured first order intensity is measured. The fabrication process and testing of the prototype device is described. An application in the measurement of temperature is also presented.

Dynamic deformation inspection of a human arm by using a line-scan imaging system

NASA Astrophysics Data System (ADS)

Hu, Eryi

2009-11-01

A line-scan imaging system is used in the dynamic deformation measurement of a human arm when the muscle is contracting and relaxing. The measurement principle is based on the projection grating profilometry, and the measuring system is consisted of a line-scan CCD camera, a projector, optical lens and a personal computer. The detected human arm is put upon a reference plane, and a sinusoidal grating is projected onto the object surface and reference plane at an incidence angle, respectively. The deformed fringe pattern in the same line of the dynamic detected arm is captured by the line-scan CCD camera with free trigger model, and the deformed fringe pattern is recorded in the personal computer for processing. A fast Fourier transform combining with a filtering and spectrum shifting method is used to extract the phase information caused by the profile of the detected object. Thus, the object surface profile can be obtained following the geometric relationship between the fringe deformation and the object surface height. Furthermore, the deformation procedure can be obtained line by line. Some experimental results are presented to prove the feasibility of the inspection system.

Single Phase Passive Rectification Versus Active Rectification Applied to High Power Stirling Engines

NASA Technical Reports Server (NTRS)

Santiago, Walter; Birchenough, Arthur G.

2006-01-01

Stirling engine converters are being considered as potential candidates for high power energy conversion systems required by future NASA explorations missions. These types of engines typically contain two major moving parts, the displacer and the piston, in which a linear alternator is attached to the piston to produce a single phase sinusoidal waveform at a specific electric frequency. Since all Stirling engines perform at low electrical frequencies (less or equal to 100 Hz), space explorations missions that will employ these engines will be required to use DC power management and distribution (PMAD) system instead of an AC PMAD system to save on space and weight. Therefore, to supply such DC power an AC to DC converter is connected to the Stirling engine. There are two types of AC to DC converters that can be employed, a passive full bridge diode rectifier and an active switching full bridge rectifier. Due to the inherent line inductance of the Stirling Engine-Linear Alternator (SE-LA), their sinusoidal voltage and current will be phase shifted producing a power factor below 1. In order to keep power the factor close to unity, both AC to DC converters topologies will implement power factor correction. This paper discusses these power factor correction methods as well as their impact on overall mass for exploration applications. Simulation results on both AC to DC converters topologies with power factor correction as a function of output power and SE-LA line inductance impedance are presented and compared.

Self-sustained oscillations of a sinusoidally-deformed plate

NASA Astrophysics Data System (ADS)

Muriel, Diego F.; Cowen, Edwin A.

2015-11-01

Motivated by energy harvesting, the oscillatory motion of a deformed elastic material with aspect ratio Length/Width=2, immerse in an incompressible flow is studied experimentally. To induce the wave-like deformation a polycarbonate sheet is placed under longitudinal compression with external forcing provided by equispaced tension lines anchored in a frame. No additional constrains are placed in the material. Based on quantitative image-based edge detection, ADV, and PIV measurements, we document the existence of three natural states of motion. Bellow a critical velocity, a stable state presents a sinusoidal-like deformation with weak small perturbations. Above a critical velocity, instability appears in the form of a traveling wave with predictable dominant frequency accompanied by higher-order harmonics. As the flow velocity increases the instability converges faster to its limit cycle in the phase plane (e.g., vertical velocity and position), until the stable oscillatory mode transitions to chaos showing a broad energy spectrum and unstable limit cycle. The underlying objective is to induce the onset of the instability at lower critical velocities for higher bending rigidities, promoting possible energy extraction and increasing the range at which stable oscillations appear.

A portable intra-oral scanner based on sinusoidal pattern of fast phase-shifting

NASA Astrophysics Data System (ADS)

Jan, Chia-Ming; Lin, Ying-Chieh

2016-03-01

This paper presented our current research about the intra-oral scanner made by MIRDC. Utilizing the sinusoidal pattern for fast phase-shifting technique to deal with 3D digitalization of human dental surface profile, the development of pseudo-phase shifting digital projection can easily achieve one type of full-field scanning instead of the common technique of the laser line scanning. Based on traditional Moiré method, we adopt projecting fringes and retrieve phase reconstruction to forward phase unwrapping. The phase difference between the plane and object can be exactly calculated from the desired fringe images, and the surface profile of object was probably reconstructed by using the phase differences information directly. According to our algorithm of space mapping between projections and capturing orientation exchange of our intra-oral scanning configuration, the system we made certainly can be proved to achieve the required accuracy of +/-10μm to deal with intra-oral scanning on the basis of utilizing active triangulation method. The final purpose aimed to the scanning of object surface profile with its size about 10x10x10mm3.

Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein.

PubMed

Liu, Songling; Premont, Richard T; Rockey, Don C

2014-06-27

Nitric oxide (NO) is a critical regulator of vascular tone and plays an especially prominent role in liver by controlling portal blood flow and pressure within liver sinusoids. Synthesis of NO in sinusoidal endothelial cells by endothelial nitric-oxide synthase (eNOS) is regulated in response to activation of endothelial cells by vasoactive signals such as endothelins. The endothelin B (ETB) receptor is a G-protein-coupled receptor, but the mechanisms by which it regulates eNOS activity in sinusoidal endothelial cells are not well understood. In this study, we built on two previous strands of work, the first showing that G-protein βγ subunits mediated activation of phosphatidylinositol 3-kinase and Akt to regulate eNOS and the second showing that eNOS directly bound to the G-protein-coupled receptor kinase-interacting protein 1 (GIT1) scaffold protein, and this association stimulated NO production. Here we investigated the mechanisms by which the GIT1-eNOS complex is formed and regulated. GIT1 was phosphorylated on tyrosine by Src, and Y293F and Y554F mutations reduced GIT1 phosphorylation as well as the ability of GIT1 to bind to and activate eNOS. Akt phosphorylation activated eNOS (at Ser(1177)), and Akt also regulated the ability of Src to phosphorylate GIT1 as well as GIT1-eNOS association. These pathways were activated by endothelin-1 through the ETB receptor; inhibiting receptor-activated G-protein βγ subunits blocked activation of Akt, GIT1 tyrosine phosphorylation, and ET-1-stimulated GIT1-eNOS association but did not affect Src activation. These data suggest a model in which Src and Akt cooperate to regulate association of eNOS with the GIT1 scaffold to facilitate NO production. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner

PubMed Central

Badmann, A; Langsch, S; Keogh, A; Brunner, T; Kaufmann, T; Corazza, N

2012-01-01

Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic alterations. Although hepatocytes represent the main target of the cytotoxic effect of paracetamol overdose, perturbations within the endothelium involving morphological changes of liver sinusoidal endothelial cells (LSECs) have also been described in paracetamol-induced liver disease. Recently, we have shown that paracetamol-induced liver damage is synergistically enhanced by the TRAIL signaling pathway. As LSECs are constantly exposed to activated immune cells expressing death ligands, including TRAIL, we investigated the effect of TRAIL on paracetamol-induced LSEC death. We here demonstrate for the first time that TRAIL strongly enhances paracetamol-mediated LSEC death with typical features of apoptosis. Inhibition of caspases using specific inhibitors resulted in a strong reduction of cell death. TRAIL appears to enhance paracetamol-induced LSEC death via the activation of the pro-apoptotic BH3-only proteins Bid and Bim, which initiate the mitochondrial apoptotic pathway. Taken together this study shows that the liver endothelial layer, mainly LSECs, represent a direct target of the cytotoxic effect of paracetamol and that activation of TRAIL receptor synergistically enhances paracetamol-induced LSEC death via the mitochondrial apoptotic pathway. TRAIL-mediated acceleration of paracetamol-induced cell death may thus contribute to the pathogenesis of paracetamol-induced liver damage. PMID:23254290

Application of low-frequency alternating current electric fields via interdigitated electrodes: effects on cellular viability, cytoplasmic calcium, and osteogenic differentiation of human adipose-derived stem cells.

PubMed

McCullen, Seth D; McQuilling, John P; Grossfeld, Robert M; Lubischer, Jane L; Clarke, Laura I; Loboa, Elizabeth G

2010-12-01

Electric stimulation is known to initiate signaling pathways and provides a technique to enhance osteogenic differentiation of stem and/or progenitor cells. There are a variety of in vitro stimulation devices to apply electric fields to such cells. Herein, we describe and highlight the use of interdigitated electrodes to characterize signaling pathways and the effect of electric fields on the proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs). The advantage of the interdigitated electrode configuration is that cells can be easily imaged during short-term (acute) stimulation, and this identical configuration can be utilized for long-term (chronic) studies. Acute exposure of hASCs to alternating current (AC) sinusoidal electric fields of 1 Hz induced a dose-dependent increase in cytoplasmic calcium in response to electric field magnitude, as observed by fluorescence microscopy. hASCs that were chronically exposed to AC electric field treatment of 1 V/cm (4 h/day for 14 days, cultured in the osteogenic differentiation medium containing dexamethasone, ascorbic acid, and β-glycerol phosphate) displayed a significant increase in mineral deposition relative to unstimulated controls. This is the first study to evaluate the effects of sinusoidal AC electric fields on hASCs and to demonstrate that acute and chronic electric field exposure can significantly increase intracellular calcium signaling and the deposition of accreted calcium under osteogenic stimulation, respectively.

A pre-heating method based on sinusoidal alternating current for lithium-ion battery

NASA Astrophysics Data System (ADS)

Fan, Wentao; Sun, Fengchun; Guo, Shanshan

2018-04-01

In this paper, a method of low temperature pre-heating of sinusoidal alternating current (SAC) is proposed. Generally, the lower the frequency of the AC current, the higher the heat generation rate. Yet at low frequency, there is a risk of lithium-ion deposition during the half cycle of charging. This study develops a temperature-adaptive, deposition-free AC pre-heating method. a equivalent electric circuit(EEC) model is established to predict the heat generation rate and temperature status, whose parameters are calibrated from the EIS impedance measurements. The effects of current frequency and amplitude on the heating effect are investigated respectively. A multistep temperature-adaptive amplitude strategy is proposed and the cell can be heated from -20°C to 5°C within 509s at 100Hz frequency with this method.

Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1

PubMed Central

Jeffery, Hannah C.; van Wilgenburg, Bonnie; Kurioka, Ayako; Parekh, Krishan; Stirling, Kathryn; Roberts, Sheree; Dutton, Emma E.; Hunter, Stuart; Geh, Daniel; Braitch, Manjit K.; Rajanayagam, Jeremy; Iqbal, Tariq; Pinkney, Thomas; Brown, Rachel; Withers, David R.; Adams, David H.; Klenerman, Paul; Oo, Ye H.

2016-01-01

Background & Aims Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells characterised by the invariant TCR-chain, Vα7.2-Jα33, and are restricted by MR1, which presents bacterial vitamin B metabolites. They are important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) and their role in biliary immune surveillance remain unexplored. Methods The phenotype and intrahepatic localisation of human LI-MAIT cells was examined in diseased and normal livers. MAIT cell activation in response to E. coli-exposed macrophages, biliary epithelial cells (BEC) and liver B cells was assessed with/without anti-MR1. Results Intrahepatic MAIT cells predominantly localised to bile ducts in the portal tracts. Consistent with this distribution, they expressed biliary tropic chemokine receptors CCR6, CXCR6, and integrin αEβ7. LI-MAIT cells were also present in the hepatic sinusoids and possessed tissue-homing chemokine receptor CXCR3 and integrins LFA-1 and VLA-4, suggesting their recruitment via hepatic sinusoids. LI-MAIT cells were enriched in the parenchyma of acute liver failure livers compared to chronic diseased livers. LI-MAIT cells had an activated, effector memory phenotype, expressed α4β7 and receptors for IL-12, IL-18, and IL-23. Importantly, in response to E. coli-exposed macrophages, liver B cells and BEC, MAIT cells upregulated IFN-γ and CD40 Ligand and degranulated in an MR1-dependent, cytokine-independent manner. In addition, diseased liver MAIT cells expressed T-bet and RORγt and the cytokines IFN-γ, TNF-α, and IL-17. Conclusions Our findings provide the first evidence of an immune surveillance effector response for MAIT cells towards BEC in human liver; thus they could be manipulated for treatment of biliary disease in the future. PMID:26743076

Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1.

PubMed

Jeffery, Hannah C; van Wilgenburg, Bonnie; Kurioka, Ayako; Parekh, Krishan; Stirling, Kathryn; Roberts, Sheree; Dutton, Emma E; Hunter, Stuart; Geh, Daniel; Braitch, Manjit K; Rajanayagam, Jeremy; Iqbal, Tariq; Pinkney, Thomas; Brown, Rachel; Withers, David R; Adams, David H; Klenerman, Paul; Oo, Ye H

2016-05-01

Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells characterised by the invariant TCR-chain, Vα7.2-Jα33, and are restricted by MR1, which presents bacterial vitamin B metabolites. They are important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) and their role in biliary immune surveillance remain unexplored. The phenotype and intrahepatic localisation of human LI-MAIT cells was examined in diseased and normal livers. MAIT cell activation in response to E. coli-exposed macrophages, biliary epithelial cells (BEC) and liver B cells was assessed with/without anti-MR1. Intrahepatic MAIT cells predominantly localised to bile ducts in the portal tracts. Consistent with this distribution, they expressed biliary tropic chemokine receptors CCR6, CXCR6, and integrin αEβ7. LI-MAIT cells were also present in the hepatic sinusoids and possessed tissue-homing chemokine receptor CXCR3 and integrins LFA-1 and VLA-4, suggesting their recruitment via hepatic sinusoids. LI-MAIT cells were enriched in the parenchyma of acute liver failure livers compared to chronic diseased livers. LI-MAIT cells had an activated, effector memory phenotype, expressed α4β7 and receptors for IL-12, IL-18, and IL-23. Importantly, in response to E. coli-exposed macrophages, liver B cells and BEC, MAIT cells upregulated IFN-γ and CD40 Ligand and degranulated in an MR1-dependent, cytokine-independent manner. In addition, diseased liver MAIT cells expressed T-bet and RORγt and the cytokines IFN-γ, TNF-α, and IL-17. Our findings provide the first evidence of an immune surveillance effector response for MAIT cells towards BEC in human liver; thus they could be manipulated for treatment of biliary disease in the future. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Classical and alternative activation of rat hepatic sinusoidal endothelial cells by inflammatory stimuli.

PubMed

Liu, Yinglin; Gardner, Carol R; Laskin, Jeffrey D; Laskin, Debra L

2013-02-01

The ability of rat hepatic sinusoidal endothelial cells (HSEC) to become activated in response to diverse inflammatory stimuli was analyzed. Whereas the classical macrophage activators, IFNγ and/or LPS upregulated expression of iNOS in HSEC, the alternative macrophage activators, IL-10 or IL-4+IL-13 upregulated arginase-1 and mannose receptor. Similar upregulation of iNOS and arginase-1 was observed in classically and alternatively activated Kupffer cells, respectively. Removal of inducing stimuli from the cells had no effect on expression of these markers, demonstrating that activation is persistent. Washing and incubation of IFNγ treated cells with IL-4+IL-13 resulted in decreased iNOS and increased arginase-1 expression, while washing and incubation of IL-4+IL-13 treated cells with IFNγ resulted in decreased arginase-1 and increased iNOS, indicating that classical and alternative activation of the cells is reversible. HSEC were more sensitive to phenotypic switching than Kupffer cells, suggesting greater functional plasticity. Hepatocyte viability and expression of PCNA, β-catenin and MMP-9 increased in the presence of alternatively activated HSEC. In contrast, the viability of hepatocytes pretreated for 2 h with 5 mM acetaminophen decreased in the presence of classically activated HSEC. These data demonstrate that activated HSEC can modulate hepatocyte responses following injury. The ability of hepatocytes to activate HSEC was also investigated. Co-culture of HSEC with acetaminophen-injured hepatocytes, but not control hepatocytes, increased the sensitivity of HSEC to classical and alternative activating stimuli. The capacity of HSEC to respond to phenotypic activators may represent an important mechanism by which they participate in inflammatory responses associated with hepatotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

PubMed Central

Yang, Liu; Shen, Zhong-Yang; Wang, Rao-Rao; Yin, Ming-Li; Zheng, Wei-Ping; Wu, Bin; Liu, Tao; Song, Hong-Li

2017-01-01

AIM To investigate the effects of heme oxygenase-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation (RLT) in a rat model. METHODS BMMSCs were isolated and cultured in vitro using an adherent method, and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs. A rat acute rejection model following 50% RLT was established using a two-cuff technique. Recipients were divided into three groups based on the treatment received: normal saline (NS), BMMSCs and HO-1/BMMSCs. Liver function was examined at six time points. The levels of endothelin-1 (ET-1), endothelial nitric-oxide synthase (eNOS), inducible nitric-oxide synthase (iNOS), nitric oxide (NO), and hyaluronic acid (HA) were detected using an enzyme-linked immunosorbent assay. The portal vein pressure (PVP) was detected by Power Lab ML880. The expressions of ET-1, iNOS, eNOS, and von Willebrand factor (vWF) protein in the transplanted liver were detected using immunohistochemistry and Western blotting. ATPase in the transplanted liver was detected by chemical colorimetry, and the ultrastructural changes were observed under a transmission electron microscope. RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver, and improve the liver function of rats following 50% RLT, with statistically significant differences compared with those of the NS group and BMMSCs group (P < 0.05). In term of the microcirculation of hepatic sinusoids: The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group (P < 0.01); HO-1/BMMSCs could inhibit the expressions of ET-1 and iNOS, increase the expressions of eNOS and inhibit amounts of NO production, and maintain the equilibrium of ET-1/NO (P < 0.05); and HO-1/BMMSCs increased the expression of vWF in hepatic sinusoidal endothelial cells (SECs), and promoted the degradation of HA, compared with those of the NS group and BMMSCs group (P < 0.05). In term of the energy metabolism of the transplanted liver, HO-1/BMMSCs repaired the damaged mitochondria, and improved the activity of mitochondrial aspartate aminotransferase (ASTm) and ATPase, compared with the other two groups (P <0.05). CONCLUSION HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly, and recover the energy metabolism of damaged hepatocytes in rats following RLT, thus protecting the transplanted liver. PMID:28596681

Hepatic sinusoid is not well-stirred: estimation of the degree of axial mixing by analysis of lobular concentration gradients formed during uptake of thyroxine by the perfused rat liver

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

Weisiger, R.A.; Mendel, C.M.; Cavalieri, R.R.

1986-03-01

Two general models have been proposed for predicting the effects of metabolism, protein binding, and plasma flow on the removal of drugs by the liver. These models differ in the degree of plasma mixing assumed to exist within each hepatic sinusoid. The venous equilibrium model treats the sinusoid as a single well-stirred compartment, whereas the sinusoidal model effectively breaks up the sinusoid into a large number of sequentially perfused compartments which do not exchange their contents except through plasma flow. As a consequence, the sinusoidal model, but not the venous equilibrium model, predicts that the concentration of highly extracted drugsmore » will decline as the plasma flows through the hepatic lobule. To determine which of these alternative models best describes the hepatic uptake process, we looked for evidence that concentration gradients are formed during the uptake of (/sup 125/I)thyroxine by the perfused rat liver. Autoradiography of tissue slices after perfusion of the portal vein at physiologic flow rates with protein-free buffer containing (/sup 125/I)thyroxine demonstrated a rapid exponential fall in grain density with distance from the portal venule, declining by half for each 8% of the mean length of the sinusoid. Reversing the direction of perfusate flow reversed the direction of the autoradiographic gradients, indicating that they primarily reflect differences in the concentration of thyroxine within the hepatic sinusoids rather than differences in the uptake capacity of portal and central hepatocytes. Analysis of the data using models in which each sinusoid was represented by different numbers of sequentially perfused compartments (1-20) indicated that at least eight compartments were necessary to account for the magnitude of the gradients seen.« less

Stepper motor control that adjusts to motor loading

NASA Technical Reports Server (NTRS)

Howard, David E. (Inventor); Nola, Frank J. (Inventor)

2000-01-01

A system and method are provided for controlling a stepper motor having a rotor and a multi-phase stator. Sinusoidal command signals define a commanded position of the motor's rotor. An actual position of the rotor is sensed as a function of an electrical angle between the actual position and the commanded position. The actual position is defined by sinusoidal position signals. An adjustment signal is generated using the sinusoidal command signals and sinusoidal position signals. The adjustment signal is defined as a function of the cosine of the electrical angle. The adjustment signal is multiplied by each sinusoidal command signal to generate a corresponding set of excitation signals, each of which is applied to a corresponding phase of the multi-phase stator.

Basement Membrane Type IV Collagen and Laminin: An Overview of Their Biology and Value as Fibrosis Biomarkers of Liver Disease.

PubMed

Mak, Ki M; Mei, Rena

2017-08-01

Basement membranes provide structural support to epithelium, endothelium, muscles, fat cells, Schwann cells, and axons. Basement membranes are multifunctional: they modulate cellular behavior, regulate organogenesis, promote tissue repair, form a barrier to filtration and tumor metastasis, bind growth factors, and mediate angiogenesis. All basement membranes contain type IV collagen (Col IV), laminin, nidogen, and perlecan. Col IV and laminin self-assemble into two independent supramolecular networks that are linked to nidogen and perlecan to form a morphological discernable basement membrane/basal lamina. The triple helical region, 7S domain and NCI domain of Col IV, laminin and laminin fragment P1 have been evaluated as noninvasive fibrosis biomarkers of alcoholic liver disease, viral hepatitis, and nonalcoholic fatty liver disease. Elevated serum Col IV and laminin are related to degrees of fibrosis and severity of hepatitis, and may reflect hepatic basement membrane metabolism. But the serum assays have not been linked to disclosing the anatomical sites and lobular distribution of perisinusoidal basement membrane formation in the liver. Hepatic sinusoids normally lack a basement membrane, although Col IV is a normal matrix component of the space of Disse. In liver disease, laminin deposits in the space of Disse and codistributes with Col IV, forming a perisinusoidal basement membrane. Concomitantly, the sinusoidal endothelium loses its fenestrae and is transformed into vascular type endothelium. These changes lead to capillarization of hepatic sinusoids, a significant pathology that impairs hepatic function. Accordingly, codistribution of Col IV and laminin serves as histochemical marker of perisinusoidal basement membrane formation in liver disease. Anat Rec, 300:1371-1390, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Morphometric analysis of primary graft non-function in liver transplantation.

PubMed

Vertemati, M; Sabatella, G; Minola, E; Gambacorta, M; Goffredi, M; Vizzotto, L

2005-04-01

Primary graft non-function (PNF) is a life-threatening condition that is thought to be the consequence of microcirculation injury. The aim of the present study was to assess, with a computerized morphometric model, the morphological changes at reperfusion in liver biopsy specimens from patients who developed PNF after liver transplantation. Biopsy specimens were obtained at maximum ischaemia and at the end of reperfusion. Morphology included many stereological parameters, such as volumes of all parenchymal components, surface density, size distribution and mean diameter of hepatocytes. Other variables examined were intensive care unit stay, degree of steatosis, serum liver function tests and ischaemic time. In the postoperative period, the PNF group showed elevated serum levels of alanine transferase, decreased daily rate of bile production and prothrombin activity. Blood lactates were significantly higher in the PNF group than in a control group. When comparing groups, the volumetric parameters related to hepatocytes and sinusoids and the surface densities of the hepatic cells showed an inverse relationship. At the end of reperfusion, in PNF group the volume fraction of hepatocyte cytoplasm was decreased; in contrast, the volume fraction of sinusoidal lumen was markedly increased. The cell profiles showed the same inverse trend: the surface density of the parenchymal border of hepatocytes was decreased in PNF when compared with the control group, while the surface density of the vascular border was increased. In the PNF group, the surface density of the sinusoidal bed was directly correlated with alanine transferase, daily rate of bile production, prothrombin activity and cold ischaemic time. The alterations in hepatic architecture, as demonstrated by morphometric analysis in liver transplant recipients that developed PNF, provide additional information that may represent useful viability markers of the graft to complement conventional histological analysis.

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

PubMed Central

Fan, Cathy Q.; Crawford, James M.

2014-01-01

Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing and downstream occlusion of terminal hepatic venules. Contributing factors are SEC glutathione depletion, nitric oxide depletion, increased intrahepatic expression of matrix metalloproteinases and vascular endothelial growth factor (VEGF), and activation of clotting factors. The clinical presentation of SOS includes jaundice, development of right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain. Owing to the potentially critical condition of these patients, transjugular biopsy may be the preferred route for liver biopsy to exclude other potential causes of liver dysfunction and to establish a diagnosis of SOS. Treatment includes rigorous fluid management so as to avoid excessive fluid overload while avoiding too rapid diuresis or pericentesis, potential use of pharmaceutics such as defibrotide, coagulolytic agents, or methylprednisolone, and liver transplantation. Proposed strategies for prevention and prophylaxis include reduced-intensity conditioning radiation for HSCT, treatment with ursodeoxycholic acid, and inclusion of bevacizumab with oxaliplatin-based chemotherapeutic regimes. While significant progress has been made in understanding the pathogenesis of SOS and in mitigating against its adverse outcomes, this condition remains a serious complication of a selective group of medical treatments. PMID:25755580

Hepatitis C virus core protein induces dysfunction of liver sinusoidal endothelial cell by down-regulation of silent information regulator 1.

PubMed

Sun, Li-Jie; Yu, Jian-Wu; Shi, Yu-Guang; Zhang, Xiao-Yu; Shu, Meng-Ni; Chen, Mo-Yang

2018-05-01

Hepatic fibrosis is a frequent feature of chronic hepatitis C virus (HCV) infection. Some evidence has suggested the potential role of silent information regulator 1 (SIRT1) in organ fibrosis. The aim of this study was to investigate the effect of HCV core protein on expression of SIRT1 of liver sinusoidal endothelial cell (LSEC) and function of LSEC. LSECs were co-cultured with HepG2 cells or HepG2 cells expressing HCV core protein and LSECs cultured alone were used as controls. After co-culture, the activity and expression levels of mRNA and protein of SIRT1 in LSEC were detected by a SIRT1 fluorometric assay kit, real time-PCR (RT-PCR), Western blot, respectively. The levels of adiponectin receptor 2 (AdipoR2), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were measured by Western blot. Cluster of differentiation 31 (CD31), CD14, and von Willebrand factor (vWf) of LSECs was performed by flow cytometry. The level of reactive oxygen species (ROS) was assayed. Malondialdehyde (MDA), superoxide dismutase (SOD), adiponectin, nitric oxide (NO), and endothelin-1 (ET-1) levels in the co-culture supernatant were measured. The co-culture supernatant was then used to cultivate LX-2 cells. The levels of α-smooth muscle actin (ASMA) and transforming growth factor-β1 (TGF-β1) protein in LX-2 cells were measured by Western blot. Compared with LSEC co-cultured with HepG2 cells group, in LSEC co-cultured with HepG2-core cells group, the activity and expression level of mRNA and protein of SIRT1 reduced; the level of adiponectin reduced and the expression level of AdipoR2 protein decreased; ROS levels increased; the expression level of eNOS, VEGF protein decreased; and the expression level of CD14 decreased; the expression level of vWf and CD31 increased; NO and SOD levels decreased; whereas ET-1 and MDA levels increased; the levels of ASMA and TGF-β1 protein in LX-2 cells increased. SIRT1 activator improved the above-mentioned changes. HCV core protein may down-regulate the activity and the expression of SIRT1 of LSEC, then decreasing synthesis of adiponectin and the expression of AdipoR2, thus inducing contraction of LSEC and hepatic sinusoidal capillarization and increasing oxidative stress, ultimately cause hepatic stellate cell (HSC) activation. Treatment with SIRT1 activator restored the function of LSEC and inhibited the activation of HSC. © 2018 Wiley Periodicals, Inc.

Caloric restriction reduces age-related pseudocapillarization of the hepatic sinusoid

PubMed Central

Jamieson, Hamish A; Hilmer, Sarah N; Cogger, Victoria C; Warren, Alessandra; Cheluvappa, Rajkumar; Abernethy, Darrell R; Everitt, Arthur V; Fraser, Robin; de Cabo, Rafael; Le Couteur, David G

2007-01-01

Age-related changes in the hepatic sinusoid, called pseudocapillarization, may contribute to the pathogenesis of dyslipidaemia. Caloric restriction (CR) is a powerful model for the study of aging because it extends lifespan. We assessed the effects of CR on the hepatic sinusoid to determine whether pseudocapillarization is preventable and hence a target for the prevention of age-related dyslipidemia. Livers from young (6 months) and old (24 months) CR and ad libitum fed (AL) F344 rats were examined using electron microscopy and immunohistochemistry. In old age, there was increased thickness of the liver sinusoidal endothelium and reduced endothelial fenestration porosity. In old CR rats, endothelial thickness was less and fenestration porosity was greater than in old AL rats. Immunohistochemistry showed that CR prevented age-related decrease in caveolin-1 expression and increase in peri-sinusoidal collagen IV staining, but did not alter the age-related increase of von Willebrand’s factor. CR reduces age-related pseudocapillarization of the hepatic sinusoid and correlates with changes in caveolin-1 expression. PMID:17204388

Hepatic stellate cells in liver development, regeneration, and cancer

PubMed Central

Yin, Chunyue; Evason, Kimberley J.; Asahina, Kinji; Stainier, Didier Y.R.

2013-01-01

Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases. PMID:23635788

Trajectory control of robot manipulators with closed-kinematic chain mechanism

NASA Technical Reports Server (NTRS)

Nguyen, Charles C.; Pooran, Farhad J.; Premack, Timothy

1987-01-01

The problem of Cartesian trajectory control of a closed-kinematic chain mechanism robot manipulator, recently built at CAIR to study the assembly of NASA hardware for the future Space Station, is considered. The study is performed by both computer simulation and experimentation for tracking of three different paths: a straight line, a sinusoid, and a circle. Linearization and pole placement methods are employed to design controller gains. Results show that the controllers are robust and there are good agreements between simulation and experimentation. The results also show excellent tracking quality and small overshoots.

A novel WDM passive optical network architecture supporting two independent multicast data streams

NASA Astrophysics Data System (ADS)

Qiu, Yang; Chan, Chun-Kit

2012-01-01

We propose a novel scheme to perform optical multicast overlay of two independent multicast data streams on a wavelength-division-multiplexed (WDM) passive optical network. By controlling a sinusoidal clock signal and shifting the wavelength at the optical line terminal (OLT), the delivery of the two multicast data, being carried by the generated optical tones, can be independently and flexibly controlled. Simultaneous transmission of 10-Gb/s unicast downstream and upstream data as well as two independent 10-Gb/s multicast data was successfully demonstrated.

Some space shuttle tile/strain-isolator-pad sinusoidal vibration tests

NASA Technical Reports Server (NTRS)

Miserentino, R.; Pinson, L. D.; Leadbetter, S. A.

1980-01-01

Vibration tests were performed on the tile/strain-isolator-pad system used as thermal protection for the space shuttle orbiter. Experimental data on normal and in-plane vibration response and damping properties are presented. Three test specimens exhibited shear type motion during failures that occurred in the tile near the tile/strain-isolator-pad bond-line. A dynamic instability is described which has large in-plane motion at a frequency one-half that of the nominal driving frequency. Analysis shows that this phenomenon is a parametric response.

Designing a fibrotic microenvironment to investigate changes in human liver sinusoidal endothelial cell function.

PubMed

Ford, Andrew J; Jain, Gaurav; Rajagopalan, Padmavathy

2015-09-01

The deposition of extracellular matrix (ECM) proteins by hepatic cells during fibrosis leads to the stiffening of the organ and perturbed cellular functions. Changes in the elasticity of liver tissue are manifested by altered phenotype in hepatic cells. We have investigated changes in human liver sinusoidal endothelial cells (hLSECs) that occur as the elastic modulus of their matrix transitions from healthy (6kPa) to fibrotic (36kPa) conditions. We have also investigated the role played by Kupffer cells in the dedifferentiation of hLSECs. We report the complete loss of fenestrae and the expression of CD31 at the surface as a result of increasing elastic moduli. LSECs exhibited a greater number of actin stress fibers and vinculin focal adhesion on the stiffer substrate, as well. A novel finding is that these identical trends can be obtained on soft (6kPa) substrates by introducing an inflamed microenvironment through the addition of Kupffer cells. hLSEC monocultures on 6kPa gels exhibited fenestrae that were 140.7±52.6nm in diameter as well as a lack of surface CD31 expression. Co-culturing hLSECs with rat Kupffer cells (rKCs) on 6kPa substrates, resulted in the complete loss of fenestrae, an increase in CD31 expression and in a well-organized cytoskeleton. These results demonstrate that the increasing stiffness of liver matrices does not solely result in changes in hLSEC phenotype. Even on soft substrates, culturing hLSECs in an inflamed microenvironment can result in their dedifferentiation. Our findings demonstrate the interplay between matrix elasticity and inflammation in the progression of hepatic fibrosis. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

DISPLAY OF PIXEL LOSS AND REPLICATION IN REPROJECTING RASTER DATA FROM THE SINUSOIDAL PROJECTION

EPA Science Inventory

Recent studies show the sinusoidal projection to be a superior planar projection for representing global raster datasets. This study uses the sinusoidal projection as a basis for evaluating pixel loss and replication in eight other planar map projections. The percent of pixels ...

16 CFR 432.3 - Standard test conditions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... event the latter figure would control), RMS, using a sinusoidal wave containing less than 2 percent... sinusoidal wave at a frequency of 1,000 Hz; provided, however, that for amplifiers utilized as a component in a self-powered subwoofer system, the sinusoidal wave used as a preconditioning signal may be any...

16 CFR 432.3 - Standard test conditions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... event the latter figure would control), RMS, using a sinusoidal wave containing less than 2 percent... sinusoidal wave at a frequency of 1,000 Hz; provided, however, that for amplifiers utilized as a component in a self-powered subwoofer system, the sinusoidal wave used as a preconditioning signal may be any...

16 CFR 432.3 - Standard test conditions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... event the latter figure would control), RMS, using a sinusoidal wave containing less than 2 percent... sinusoidal wave at a frequency of 1,000 Hz; provided, however, that for amplifiers utilized as a component in a self-powered subwoofer system, the sinusoidal wave used as a preconditioning signal may be any...

16 CFR 432.3 - Standard test conditions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... event the latter figure would control), RMS, using a sinusoidal wave containing less than 2 percent... sinusoidal wave at a frequency of 1,000 Hz; provided, however, that for amplifiers utilized as a component in a self-powered subwoofer system, the sinusoidal wave used as a preconditioning signal may be any...

16 CFR 432.3 - Standard test conditions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... event the latter figure would control), RMS, using a sinusoidal wave containing less than 2 percent... sinusoidal wave at a frequency of 1,000 Hz; provided, however, that for amplifiers utilized as a component in a self-powered subwoofer system, the sinusoidal wave used as a preconditioning signal may be any...

The chording effect on core losses of three-phase induction motor under sinusoidal and PWM voltage supplies

NASA Astrophysics Data System (ADS)

Deshmukh, Ram; Moses, A. J.; Anayi, F.

The core losses and the lower-order voltage harmonics of four different chorded motors fed from sinusoidal supply and inverter voltage supply were invigilated at no-load condition. All the four motors were tested with 4, 8 and 16 kHz switching frequencies and 30, 40, 50 and 60 Hz modulation frequencies The motor with 120° coil pitch has the least core losses and the lower-order voltage harmonics under sinusoidal and pulse width modulation (PWM) voltage supplies at all switching and modulation frequencies. The drop in the core losses for this motor was 46% and 53% under sinusoidal and PWM voltage supplies, respectively. The motor with 120° coil pitch is recommended to be used under sinusoidal and PWM voltage supplies.

Walking strategies of visually impaired people on trapezoidal- and sinusoidal-section tactile groundsurface indicators.

PubMed

Ranavolo, A; Conte, C; Iavicoli, S; Serrao, M; Silvetti, A; Sandrini, G; Pierelli, F; Draicchio, F

2011-03-01

The visual system in walking serves to perceive feedback or feed-forward signals. Therefore, visually impaired persons (VIP) have biased motor control mechanisms. The use of leading indicators (LIs) and long canes helps to improve their walking efficiency. The aims of this study were to compare the walking efficiency of VIP on trapezoidal- and sinusoidal-section LIs using an optoelectronic motion analysis system. VIP displayed a significantly longer stance phase, a shorter swing phase and shorter step and stride lengths when they walked on the sinusoidal LI than when they walked on the trapezoidal LI. Compared with the trapezoidal LI, VIP walking on the sinusoidal LI displayed significantly lower joint ranges of motion. The centre of mass lateral displacement was wider for VIP walking on the sinusoidal LI than on the trapezoidal LI. Some significant differences were also found in sighted persons walking on both LIs. In conclusion, the trapezoidal shape enabled visually impaired subjects to walk more efficiently, whereas the sinusoidal shape caused dynamic balance problems. STATEMENT OF RELEVANCE: These findings suggest that VIP can walk more efficiently, with a lower risk of falls, on trapezoidal-section than on sinusoidal-section LIs. These results should be considered when choosing the most appropriate ground tactile surface indicators for widespread use.

Manifestations and management of veno-occlusive disease/sinusoidal obstruction syndrome in the era of contemporary therapies.

PubMed

Tewari, Priti; Wallis, Whitney; Kebriaei, Partow

2017-02-01

The concept of veno-occlusive disease (VOD), along with our understanding of it, has historically been and remains an evolving phenomenon. This review presents a broad view of VOD, also known as sinusoidal obstruction syndrome (SOS), including (1) traditional hematopoietic stem cell transplant-associated VOD/SOS, (2) late-onset VOD/SOS, (3) pulmonary VOD, and (4) VOD/SOS associated with chemotherapy only. Several VOD/SOS management modalities exist that include modes for both prophylaxis and treatment. An extensive review of the literature on monoclonal antibodies, both approved and pending approval by the US Food and Drug Administration, reveals that only a few have been associated with an increased risk for VOD/SOS. In fact, bevacizumab appears to have a protective effect against the development of VOD/SOS. As the landscape of cancer treatment changes, careful attention needs to be focused on how new therapies affect the incidence of VOD/SOS.

Evaluation and statistical judgement of neural responses to sinusoidal stimulation in cases with superimposed drift and noise.

PubMed

Jastreboff, P W

1979-06-01

Time histograms of neural responses evoked by sinuosidal stimulation often contain a slow drifting and an irregular noise which disturb Fourier analysis of these responses. Section 2 of this paper evaluates the extent to which a linear drift influences the Fourier analysis, and develops a combined Fourier and linear regression analysis for detecting and correcting for such a linear drift. Usefulness of this correcting method is demonstrated for the time histograms of actual eye movements and Purkinje cell discharges evoked by sinusoidal rotation of rabbits in the horizontal plane. In Sect. 3, the analysis of variance is adopted for estimating the probability of the random occurrence of the response curve extracted by Fourier analysis from noise. This method proved to be useful for avoiding false judgements as to whether the response curve was meaningful, particularly when the response was small relative to the contaminating noise.

Hepatoblastoma with pure fetal epithelial differentiation in a 10-year-old boy: A rare case report and review of the literature.

PubMed

Zhong, Shanshan; Zhao, Yang; Fan, Chuifeng

2018-01-01

Hepatoblastoma is a rare malignant embryonal tumor that only accounts for approximately 1% of all pediatric cancers and mostly develops in children younger than 5 years old. Moreover, the occurrence of hepatoblastoma in adults is extremely rare. Herein, we present a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy.Pathological examination was performed. The tumor was 15 cm × 15 cm in size with clear margins. The cut surface was multiple nodular and grey-yellow. Histologically, the small cuboidal tumor cells were arranged in trabeculae with 2-3 cell layers. The tumor cells had eosinophilic or clear cytoplasm, formed dark and light areas, and were positive for alpha-fetoprotein, CK, CK8/18, CD10, hepatocyte, and GPC3. CD34 staining revealed that the sinusoids were lined by endothelial cells in the tumor tissues. The Ki67 index was approximately 20%. Based on these findings, the case was diagnosed as hepatoblastoma with pure fetal epithelial differentiation. The tumor was completely removed. No recurrence was found 3 months after the operation. Hepatoblastoma with pure epithelial differentiation can also occur in older children. Children rarely notice and report any physical abnormality, and this may be among the primary reasons for the late diagnosis of the tumor. Annual heath checks may be beneficial in the detection of these rare tumors and improvement of patient outcomes. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Early stellate cell activation and veno-occlusive-disease (VOD)-like hepatotoxicity in dogs treated with AR-H047108, an imidazopyridine proton pump inhibitor.

PubMed

Berg, Anna-Lena; Böttcher, Gerhard; Andersson, Kjell; Carlsson, Enar; Lindström, Anna-Karin; Huby, Russell; Håkansson, Helen; Skånberg-Wilhelmsson, Inger; Hellmold, Heike

2008-07-01

Dogs treated with AR-H047108, an imidazopyridine potassium competitive acid blocker (P-CAB), developed clinical signs of hepatic dysfunction as well as morphologically manifest hepatotoxicity in repeat-dose toxicity studies. An investigative one-month study was performed, with interim euthanasia after one and two weeks. A detailed histopathological and immunohistochemical characterization of the liver lesions was conducted, including markers for fibrosis, Kupffer cell activation, apoptosis, and endothelial injury. In addition, hepatic retinoid and procollagen 1alpha2 mRNA levels in livers of dogs treated with AR-H047108 were analyzed. The results showed an early inflammatory process in central veins and centrilobular areas, present after one week of treatment. This inflammatory reaction was paralleled by activation of stellate/Ito cells to myofibroblasts and was associated with sinusoidal and centrivenular fibrosis. The early activation of stellate cells coincided with a significant decrease in retinyl ester levels, and a significant increase in procollagen 1alpha2 mRNA levels, in the liver. At later time points (three and six months), there was marked sinusoidal fibrosis in centrilobular areas, as well as occlusion of central veins resulting from a combination of fibrosis and increased thickness of smooth muscle bundles in the vessel wall. The pattern of lesions suggests a veno-occlusive-disease (VOD)-like scenario, possibly linked to the imidazopyridine chemical structure of the compound facilitated by specific morphological features of the dog liver.

Successful treatment with defibrotide for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.

PubMed

Yakushijin, Kimikazu; Matsui, Toshimitsu; Okamura, Atsuo; Yamamoto, Katsuya; Ito, Mitsuhiro; Chihara, Kazuo

2005-01-01

Sinusoidal obstruction syndrome (SOS) (formerly known as hepatic veno-occlusive disease (VOD)) is a life-threatening complication subsequent to hematopoietic stem cell transplantation. However, no completely satisfactory strategies for the treatment of SOS have been established yet. Defibrotide is a single-stranded polydeoxyribonucleotide with anti-thrombotic, anti-ischemic, anti-inflammatory and thrombolytic properties, but without systemic anticoagulant effects, and some encouraging results have been reported in western countries. We treated four patients with defibrotide for SOS, since there seemed to be no possibility to cure the patients with conventionally available treatments in Japan. All patients showed evidence of multiple organ failure at the start of the treatment. Defibrotide was administered intravenously in normal saline in four divided doses for 14 to 27 days. Three patients (75%) responded to the therapy, while one died of SOS and cytomegalovirus infection despite intensive therapy. None of the patients suffered from significant adverse effects such as severe hemorrhage. This is the first report dealing with the treatment with defibrotide of Japanese patients with SOS. Because defibrotide is considered to be promising for the treatment of SOS, it is important to start a phase II study as soon as possible.

Endothelial dysfunction in the regulation of portal hypertension

PubMed Central

Iwakiri, Yasuko

2013-01-01

Portal hypertension is caused by an increased intrahepatic resistance, a major consequence of cirrhosis. Endothelial dysfunction in liver sinusoidal endothelial cells (LSECs) decreases the production of vasodilators, such as nitric oxide (NO) and favors vasoconstriction. This contributes to an increased vascular resistance in the intrahepatic/sinusoidal microcirculation. Portal hypertension, once developed, causes endothelial cell (EC) dysfunction in the extrahepatic, i.e. splanchnic and systemic, circulation. Unlike LSEC dysfunction, EC dysfunction in the splanchnic and systemic circulation overproduces vasodilator molecules, leading to arterial vasodilatation. In addition, portal hypertension leads to the formation of portosystemic collateral vessels. Both arterial vasodilatation and portosystemic collateral vessel formation exacerbate portal hypertension by increasing the blood flow through the portal vein. Pathologic consequences, such as esophageal varices and ascites, result. While the sequence of pathological vascular events in cirrhosis and portal hypertension have been elucidated, the underlying cellular and molecular mechanisms causing EC dysfunctions are not yet fully understood. This review article summarizes the current cellular and molecular studies on EC dysfunctions found during the development of cirrhosis and portal hypertension with a focus on intra- and extrahepatic circulation. The article ends by discussing future directions of study for EC dysfunctions. PMID:21745318

STED microscopy: A simplified method for liver sinusoidal endothelial fenestrae analysis.

PubMed

Martino, Julie Di; Mascalchi, Patrice; Legros, Philippe; Lacomme, Sabrina; Gontier, Etienne; Bioulac-Sage, Paulette; Balabaud, Charles; Moreau, Violaine; Saltel, Frédéric

2018-05-29

Liver sinusoidal endothelial cells (LSECs) possess fenestrae, open transcellular pores with an average diameter of 100nm. These fenestrae allow for the exchange between blood and hepatocytes. Alterations in their number or diameter in liver diseases have important implications for hepatic microcirculation and function. Although decades of studies, fenestrae are still observed into fixed cells and we have poor knowledge of their dynamics. Using stimulated emission depletion (STED) super-resolution microscopy, we have established a faster and simplest method to observe and quantify fenestrae. Indeed, using cytochalasin D, an actin depolymerizing agent known to promote fenestrae formation we measure the increase of fenestrae number. We adapted this methodology to develop an automated method to study fenestrae dynamics. Moreover, with two colors STED analysis we shown that this approach could be useful to study LSECs fenestrae molecular composition. Our approach demonstrate that STED microscopy is suitable for LSEC fenestrae study. This new way of analyzing LSEC fenestrae will allow for expedited investigation of their dynamics, molecular composition and functions to better understand their function in liver pathophysiology. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nonlinear optical microscopy: use of second harmonic generation and two-photon microscopy for automated quantitative liver fibrosis studies.

PubMed

Sun, Wanxin; Chang, Shi; Tai, Dean C S; Tan, Nancy; Xiao, Guangfa; Tang, Huihuan; Yu, Hanry

2008-01-01

Liver fibrosis is associated with an abnormal increase in an extracellular matrix in chronic liver diseases. Quantitative characterization of fibrillar collagen in intact tissue is essential for both fibrosis studies and clinical applications. Commonly used methods, histological staining followed by either semiquantitative or computerized image analysis, have limited sensitivity, accuracy, and operator-dependent variations. The fibrillar collagen in sinusoids of normal livers could be observed through second-harmonic generation (SHG) microscopy. The two-photon excited fluorescence (TPEF) images, recorded simultaneously with SHG, clearly revealed the hepatocyte morphology. We have systematically optimized the parameters for the quantitative SHG/TPEF imaging of liver tissue and developed fully automated image analysis algorithms to extract the information of collagen changes and cell necrosis. Subtle changes in the distribution and amount of collagen and cell morphology are quantitatively characterized in SHG/TPEF images. By comparing to traditional staining, such as Masson's trichrome and Sirius red, SHG/TPEF is a sensitive quantitative tool for automated collagen characterization in liver tissue. Our system allows for enhanced detection and quantification of sinusoidal collagen fibers in fibrosis research and clinical diagnostics.

Real-Time Fourier Synthesis of Ensembles with Timbral Interpolation

NASA Astrophysics Data System (ADS)

Haken, Lippold

1990-01-01

In Fourier synthesis, natural musical sounds are produced by summing time-varying sinusoids. Sounds are analyzed to find the amplitude and frequency characteristics for their sinusoids; interpolation between the characteristics of several sounds is used to produce intermediate timbres. An ensemble can be synthesized by summing all the sinusoids for several sounds, but in practice it is difficult to perform such computations in real time. To solve this problem on inexpensive hardware, it is useful to take advantage of the masking effects of the auditory system. By avoiding the computations for perceptually unimportant sinusoids, and by employing other computation reduction techniques, a large ensemble may be synthesized in real time on the Platypus signal processor. Unlike existing computation reduction techniques, the techniques described in this thesis do not sacrifice independent fine control over the amplitude and frequency characteristics of each sinusoid.

Sinusoidal Analysis-Synthesis of Audio Using Perceptual Criteria

NASA Astrophysics Data System (ADS)

Painter, Ted; Spanias, Andreas

2003-12-01

This paper presents a new method for the selection of sinusoidal components for use in compact representations of narrowband audio. The method consists of ranking and selecting the most perceptually relevant sinusoids. The idea behind the method is to maximize the matching between the auditory excitation pattern associated with the original signal and the corresponding auditory excitation pattern associated with the modeled signal that is being represented by a small set of sinusoidal parameters. The proposed component-selection methodology is shown to outperform the maximum signal-to-mask ratio selection strategy in terms of subjective quality.

Compact cryocooling system for HTS sampler

NASA Astrophysics Data System (ADS)

Suzuki, H.; Maruyama, M.; Hato, T.; Wakana, H.; Tanabe, K.; Konno, T.; Uekusa, K.; Sato, N.; Kawabata, M.

2007-10-01

This paper describes a compact cooling system using a single-stage stirling-type cryocooler for a practical HTS sampler. The system was designed to cool down an HTS sampler module below 50 K, enabling a bandwidth of the chip more than 100 GHz. The system measures 150 mm in width, 140 mm in height and 310 mm in depth, and weighs 5 kg. Semi-rigid coaxial cables made of brass with a silver coated inner conductor were adopted for a signal to be measured and a trigger pulse. The loss for the signal line was less than 1.5 dB at 50 GHz with relatively small thermal inflow. Thermal inflows from low frequency lines, IF signal lines for control/output of the sampler and dc bias lines, were minimized by choosing proper wires. A new sampler module with reduced weight was placed on the cold stage, which was surrounded by double magnetic shields. The module was successfully cooled down to less than 50 K with cooling time of 1 h in the system. We have also succeeded in observing sinusoidal waveforms with the HTS sampler cooled by the compact cooling system.

In vitro recapitulation of the urea cycle using murine embryonic stem cell-derived in vitro liver model.

PubMed

Tamai, Miho; Aoki, Mami; Nishimura, Akihito; Morishita, Koji; Tagawa, Yoh-ichi

2013-12-01

Ammonia, a toxic metabolite, is converted to urea in hepatocytes via the urea cycle, a process necessary for cell/organismal survival. In liver, hepatocytes, polygonal and multipolar structures, have a few sides which face hepatic sinusoids and adjacent hepatocytes to form intercellular bile canaliculi connecting to the ductules. The critical nature of this three-dimensional environment should be related to the maintenance of hepatocyte function such as urea synthesis. Recently, we established an in vitro liver model derived from murine embryonic stem cells, IVL(mES), which included the hepatocyte layer and a surrounding sinusoid vascular-like network. The IVL(mES) culture, where the hepatocyte is polarized in a similar fashion to its in vivo counterpart, could successfully recapitulate in vivo results. L-Ornithine is an intermediate of the urea cycle, but supplemental L-ornithine does not activate the urea cycle in the apolar primary hepatocyte of monolayer culture. In the IVL(mES), supplemental L-ornithine could activate the urea cycle, and also protect against ammonium/alcohol-induced hepatocyte death. While the IVL(mES) displays architectural and functional properties similar to the liver, primary hepatocyte of monolayer culture fail to model critical functional aspects of liver physiology. We propose that the IVL(mES) will represent a useful, humane alternative to animal studies for drug toxicity and mechanistic studies of liver injury.

An integrated and highly sensitive ultrafast acoustoelectric imaging system for biomedical applications

NASA Astrophysics Data System (ADS)

Berthon, Beatrice; Dansette, Pierre-Marc; Tanter, Mickaël; Pernot, Mathieu; Provost, Jean

2017-07-01

Direct imaging of the electrical activation of the heart is crucial to better understand and diagnose diseases linked to arrhythmias. This work presents an ultrafast acoustoelectric imaging (UAI) system for direct and non-invasive ultrafast mapping of propagating current densities using the acoustoelectric effect. Acoustoelectric imaging is based on the acoustoelectric effect, the modulation of the medium’s electrical impedance by a propagating ultrasonic wave. UAI triggers this effect with plane wave emissions to image current densities. An ultrasound research platform was fitted with electrodes connected to high common-mode rejection ratio amplifiers and sampled by up to 128 independent channels. The sequences developed allow for both real-time display of acoustoelectric maps and long ultrafast acquisition with fast off-line processing. The system was evaluated by injecting controlled currents into a saline pool via copper wire electrodes. Sensitivity to low current and low acoustic pressure were measured independently. Contrast and spatial resolution were measured for varying numbers of plane waves and compared to line per line acoustoelectric imaging with focused beams at equivalent peak pressure. Temporal resolution was assessed by measuring time-varying current densities associated with sinusoidal currents. Complex intensity distributions were also imaged in 3D. Electrical current densities were detected for injected currents as low as 0.56 mA. UAI outperformed conventional focused acoustoelectric imaging in terms of contrast and spatial resolution when using 3 and 13 plane waves or more, respectively. Neighboring sinusoidal currents with opposed phases were accurately imaged and separated. Time-varying currents were mapped and their frequency accurately measured for imaging frame rates up to 500 Hz. Finally, a 3D image of a complex intensity distribution was obtained. The results demonstrated the high sensitivity of the UAI system proposed. The plane wave based approach provides a highly flexible trade-off between frame rate, resolution and contrast. In conclusion, the UAI system shows promise for non-invasive, direct and accurate real-time imaging of electrical activation in vivo.

Nothing more than a pair of curvatures: A common mechanism for the detection of both radial and non-radial frequency patterns.

PubMed

Schmidtmann, Gunnar; Kingdom, Frederick A A

2017-05-01

Radial frequency (RF) patterns, which are sinusoidal modulations of a radius in polar coordinates, are commonly used to study shape perception. Previous studies have argued that the detection of RF patterns is either achieved globally by a specialized global shape mechanism, or locally using as cue the maximum tangent orientation difference between the RF pattern and the circle. Here we challenge both ideas and suggest instead a model that accounts not only for the detection of RF patterns but also for line frequency patterns (LF), i.e. contours sinusoidally modulated around a straight line. The model has two features. The first is that the detection of both RF and LF patterns is based on curvature differences along the contour. The second is that this curvature metric is subject to what we term the Curve Frequency Sensitivity Function, or CFSF, which is characterized by a flat followed by declining response to curvature as a function of modulation frequency, analogous to the modulation transfer function of the eye. The evidence that curvature forms the basis for detection is that at very low modulation frequencies (1-3 cycles for the RF pattern) there is a dramatic difference in thresholds between the RF and LF patterns, a difference however that disappears at medium and high modulation frequencies. The CFSF feature on the other hand explains why thresholds, rather than continuously declining with modulation frequency, asymptote at medium and high modulation frequencies. In summary, our analysis suggests that the detection of shape modulations is processed by a common curvature-sensitive mechanism that is subject to a shape-frequency-dependent transfer function. This mechanism is independent of whether the modulation is applied to a circle or a straight line. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamic performance of maximum power point tracking circuits using sinusoidal extremum seeking control for photovoltaic generation

NASA Astrophysics Data System (ADS)

Leyva, R.; Artillan, P.; Cabal, C.; Estibals, B.; Alonso, C.

2011-04-01

The article studies the dynamic performance of a family of maximum power point tracking circuits used for photovoltaic generation. It revisits the sinusoidal extremum seeking control (ESC) technique which can be considered as a particular subgroup of the Perturb and Observe algorithms. The sinusoidal ESC technique consists of adding a small sinusoidal disturbance to the input and processing the perturbed output to drive the operating point at its maximum. The output processing involves a synchronous multiplication and a filtering stage. The filter instance determines the dynamic performance of the MPPT based on sinusoidal ESC principle. The approach uses the well-known root-locus method to give insight about damping degree and settlement time of maximum-seeking waveforms. This article shows the transient waveforms in three different filter instances to illustrate the approach. Finally, an experimental prototype corroborates the dynamic analysis.

Hydrogen Balmer alpha intensity distributions and line profiles from multiple scattering theory using realistic geocoronal models

NASA Technical Reports Server (NTRS)

Anderson, D. E., Jr.; Meier, R. R.; Hodges, R. R., Jr.; Tinsley, B. A.

1987-01-01

The H Balmer alpha nightglow is investigated by using Monte Carlo models of asymmetric geocoronal atomic hydrogen distributions as input to a radiative transfer model of solar Lyman-beta radiation in the thermosphere and atmosphere. It is shown that it is essential to include multiple scattering of Lyman-beta radiation in the interpretation of Balmer alpha airglow data. Observations of diurnal variation in the Balmer alpha airglow showing slightly greater intensities in the morning relative to evening are consistent with theory. No evidence is found for anything other than a single sinusoidal diurnal variation of exobase density. Dramatic changes in effective temperature derived from the observed Balmer alpha line profiles are expected on the basis of changing illumination conditions in the thermosphere and exosphere as different regions of the sky are scanned.

IIR digital filter design for powerline noise cancellation of ECG signal using arduino platform

NASA Astrophysics Data System (ADS)

Rahmatillah, Akif; Ataulkarim

2017-05-01

Powerline noise has been one of significant noises of Electrocardiogram (ECG) signal measurement. This noise is characterized by a sinusoidal signal which has 50 Hz of noise and 0.3 mV of maximum amplitude. This paper describes the design of IIR Notch filter design to reject a 50 Hz power line noise. IIR filter coefficients were calculated using pole placement method with three variations of band stop cut off frequencies of (49-51)Hz, (48 - 52)Hz, and (47 - 53)Hz. The algorithm and coefficients of filter were embedded to Arduino DUE (ARM 32 bit microcontroller). IIR notch filter designed has been able to reject power line noise with average square of error value of 0.225 on (49-51) Hz filter design and 0.2831 on (48 - 52)Hz filter design.

Free cholesterol accumulation in liver sinusoidal endothelial cells exacerbates acetaminophen hepatotoxicity via TLR9 signaling.

PubMed

Teratani, Toshiaki; Tomita, Kengo; Suzuki, Takahiro; Furuhashi, Hirotaka; Irie, Rie; Hida, Shigeaki; Okada, Yoshikiyo; Kurihara, Chie; Ebinuma, Hirotoshi; Nakamoto, Nobuhiro; Saito, Hidetsugu; Hibi, Toshifumi; Miura, Soichiro; Hokari, Ryota; Kanai, Takanori

2017-10-01

Although obesity is a risk factor for acute liver failure, the pathogenic mechanisms are not yet fully understood. High cholesterol (HC) intake, which often underlies obesity, is suggested to play a role in the mechanism. We aimed to elucidate the effect of a HC diet on acetaminophen-induced acute liver injury, the most frequent cause of acute liver failure in the USA. C57BL/6 Toll-like receptor 9 (TLR9) knockout (Tlr9 -/- ) mice and their Tlr9 +/+ littermates were fed an HC diet for fourweeks and then treated with acetaminophen. Liver sinusoidal endothelial cells (LSECs) were isolated from the mice for in vivo and in vitro analyses. The HC diet exacerbated acetaminophen-induced acute liver injury in a TLR9/inflammasome pathway-dependent manner. LSECs played a major role in the cholesterol loading-induced exacerbation. The accumulation of free cholesterol in the endolysosomes in LSECs enhanced TLR9-mediated signaling, thereby exacerbating the pathology of acetaminophen-induced liver injury through the activation of the TLR9/inflammasome pathway. The accumulation of free cholesterol in LSEC endolysosomes induced a dysfunction of the Rab7 membrane trafficking recycling mechanism, thus disrupting the transport of TLR9 from late endosomes to the lysosomes. Consequently, the level of active TLR9 in the late endosomes increased, thereby enhancing TLR9 signaling in LSECs. HC intake exaggerated acetaminophen-induced acute liver injury via free cholesterol accumulation in LSECs, demonstrating a novel role of free cholesterol as a metabolic factor in TLR9 signal regulation and pathologies of acetaminophen-induced liver injury. Therapeutic approaches may target this pathway. Lay summary: High cholesterol intake exacerbated acetaminophen-induced acute liver injury via the accumulation of free cholesterol in the endolysosomes of liver sinusoidal endothelial cells. This accumulation enhanced Toll-like receptor 9 signaling via impairment of its membrane trafficking mechanism. Thus, free cholesterol accumulation, as an underlying metabolic factor, exacerbated the pathology of acetaminophen-induced liver injury through activation of the TLR9/inflammasome pathway. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Static inverter with synchronous output waveform synthesized by time-optimal-response feedback

NASA Technical Reports Server (NTRS)

Kernick, A.; Stechschulte, D. L.; Shireman, D. W.

1976-01-01

Time-optimal-response 'bang-bang' or 'bang-hang' technique, using four feedback control loops, synthesizes static-inverter sinusoidal output waveform by self-oscillatory but yet synchronous pulse-frequency-modulation (SPFM). A single modular power stage per phase of ac output entails the minimum of circuit complexity while providing by feedback synthesis individual phase voltage regulation, phase position control and inherent compensation simultaneously for line and load disturbances. Clipped sinewave performance is described under off-limit load or input voltage conditions. Also, approaches to high power levels, 3-phase arraying and parallel modular connection are given.

Early Deposition of Ceroid in Kupffer Cells of Mice Fed Hepatic Necrogenic Diets

PubMed Central

Porta, Eduardo A.; Hartroft, W. Stanley

1963-01-01

Experiments were undertaken to study the prenecrotic morphologic changes in liver of mice that were fed diets deficient in vitamin E and selenium. When these diets were fed to male albino mice the accumulation of ceroid pigment in Kupffer cells was observed within seven days of commencing the diets, long before any evidence of necrosis was observed. In later stages of the experiment the ceroid pigment deposited in Kupffer cells was so abundant that it appeared possible that interference with hepatic sinusoidal blood flow and impairment of physiologic activity of the reticuloendothelial system had resulted. ImagesFig. 1Fig. 2 PMID:20327568

The influence of a magnetic field on the heat transfer of a magnetic nanofluid in a sinusoidal channel

NASA Astrophysics Data System (ADS)

Valiallah Mousavi, S.; Barzegar Gerdroodbary, M.; Sheikholeslami, Mohsen; Ganji, D. D.

2016-09-01

In this study, two dimensional numerical simulations are performed to investigate the influence of the magnetic field on the nanofluid flow inside a sinusoidal channel. This work reveals the influence of variable magnetic field in the heat transfer of heat exchanger while the mixture is in a single phase. In this heat exchanger, the inner tube is sinusoidal and the outer tube is considered smooth. The magnetic field is applied orthogonal to the axis of the sinusoidal tube. In our study, the ferrofluid (water with 4 vol% nanoparticles (Fe3O4)) flows in a channel with sinusoidal bottom. The finite volume method with the SIMPLEC algorithm is used for handling the pressure-velocity coupling. The numerical results present validated data with experimentally measured data and show good agreement with measurement. The influence of different parameters, like the intensity of magnetic field and Reynolds number, on the heat transfer is investigated. According to the obtained results, the sinusoidal formation of the internal tube significantly increases the Nusselt number inside the channel. Our findings show that the magnetic field increases the probability of eddy formation inside the cavities and consequently enhances the heat transfer (more than 200%) in the vicinity of the magnetic field at low Reynolds number ( Re=50). In addition, the variation of the skin friction shows that the magnetic field increases the skin friction (more than 600%) inside the sinusoidal channel.

PD-1 inhibits antiviral immunity at the effector phase in the liver.

PubMed

Iwai, Yoshiko; Terawaki, Seigo; Ikegawa, Masaya; Okazaki, Taku; Honjo, Tasuku

2003-07-07

Unlike naive T cells, effector T cells can be activated by either T cell receptor signal or costimulatory signal alone and therefore the absence of costimulatory molecules on tissue cells cannot explain the tolerance mechanism at the effector phase. Here we report that PD-L1, the ligand for the immunoinhibitory receptor PD-1, was expressed on vascular endothelium in peripheral tissues. Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1. The absence of PD-1 induced proliferation of effector T cells in the adenovirus-infected liver and resulted in rapid clearance of the virus. These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity.

Bottomside sinusoidal irregularities in the equatorial F region

NASA Technical Reports Server (NTRS)

Valladares, C. E.; Hanson, W. B.; Mcclure, J. P.; Cragin, B. L.

1983-01-01

By using the Ogo 6 satellite, McClure and Hanson (1973) have discovered sinusoidal irregularities in the equatorial F region ion number density. In the present investigation, a description is provided of the properties of a distinct category of sinusoidal irregularities found in equatorial data from the AE-C and AE-E satellites. The observed scale sizes vary from about 300 m to 3 km in the direction perpendicular to B, overlapping with and extending the range observed by using Ogo 6. Attention is given to low and high resolution data, a comparison with Huancayo ionograms, the confinement of 'bottomside sinusoidal' (BSS) irregularities essentially to the bottomside of the F layer, spectral characteristics, and BSS, scintillation, and ionosonde observations.

Stiffness and force in activated frog skeletal muscle fibers.

PubMed Central

Cecchi, G.; Griffiths, P. J.; Taylor, S.

1986-01-01

Single fibers, isolated intact from frog skeletal muscles, were held firmly very near to each end by stiff metal clasps fastened to the tendons. The fibers were then placed horizontally between two steel hooks inserted in eyelets of the tendon clasps. One hook was attached to a capacitance gauge force transducer (resonance frequency up to approximately 50 kHz) and the other was attached to a moving-coil length changer. This allowed us to impose small, rapid releases (complete in less than 0.15 ms) and high frequency oscillations (up to 13 kHz) to one end of a resting or contracting fiber and measure the consequences at the other end with fast time resolution at 4 to 6 degrees C. The stiffness of short fibers (1.8-2.6 mm) was determined directly from the ratio of force to length variations produced by the length changer. The resonance frequency of short fibers was so high (approximately 40 kHz) that intrinsic oscillations were not detectably excited. The stiffness of long fibers, on the other hand, was calculated from measurement of the mechanical resonance frequency of a fiber. Using both short and long fibers, we measured the sinusoids of force at one end of a contracting fiber that were produced by relatively small sinusoidal length changes at the other end. The amplitudes of the sinusoidal length changes were small compared with the size of step changes that produce nonlinear force-extension relations. The sinusoids of force from long fibers changed amplitude and shifted phase with changes in oscillation frequency in a manner expected of a transmission line composed of mass, compliance, and viscosity, similar to that modelled by (Ford, L. E., A. F. Huxley, and R. M. Simmons, 1981, J. Physiol. (Lond.), 311:219-249). A rapid release during the plateau of tetanic tension in short fibers caused a fall in force and stiffness, a relative change in stiffness that putatively was much smaller than that of force. Our results are, for the most part, consistent with the cross-bridge model of force generation proposed by Huxley, A. F., and R. M. Simmons (1971, Nature (Lond.), 213:533-538). However, stiffness in short fibers developed markedly faster than force during the tetanus rise. Thus our findings show the presence of one or more noteworthy cross-bridge states at the onset and during the rise of active tension towards a plateau in that attachment apparently is followed by a relatively long delay before force generation occurs. A set of equations is given in the Appendix that describes the frequency dependence of the applied sinusoid and its response. This model predicts that frequency dependent changes can be used as a measure of a change in stiffness. PMID:3955178

Climbing fibers mediate vestibular modulation of both "complex" and "simple spikes" in Purkinje cells.

PubMed

Barmack, N H; Yakhnitsa, V

2015-10-01

Climbing and mossy fibers comprise two distinct afferent paths to the cerebellum. Climbing fibers directly evoke a large multispiked action potential in Purkinje cells termed a "complex spike" (CS). By logical exclusion, the other class of Purkinje cell action potential, termed "simple spike" (SS), has often been attributed to activity conveyed by mossy fibers and relayed to Purkinje cells through granule cells. Here, we investigate the relative importance of climbing and mossy fiber pathways in modulating neuronal activity by recording extracellularly from Purkinje cells, as well as from mossy fiber terminals and interneurons in folia 8-10. Sinusoidal roll-tilt vestibular stimulation vigorously modulates the discharge of climbing and mossy fiber afferents, Purkinje cells, and interneurons in folia 9-10 in anesthetized mice. Roll-tilt onto the side ipsilateral to the recording site increases the discharge of both climbing fibers (CSs) and mossy fibers. However, the discharges of SSs decrease during ipsilateral roll-tilt. Unilateral microlesions of the beta nucleus (β-nucleus) of the inferior olive blocks vestibular modulation of both CSs and SSs in contralateral Purkinje cells. The blockage of SSs occurs even though primary and secondary vestibular mossy fibers remain intact. When mossy fiber afferents are damaged by a unilateral labyrinthectomy (UL), vestibular modulation of SSs in Purkinje cells ipsilateral to the UL remains intact. Two inhibitory interneurons, Golgi and stellate cells, could potentially contribute to climbing fiber-induced modulation of SSs. However, during sinusoidal roll-tilt, only stellate cells discharge appropriately out of phase with the discharge of SSs. Golgi cells discharge in phase with SSs. When the vestibularly modulated discharge is blocked by a microlesion of the inferior olive, the modulated discharge of CSs and SSs is also blocked. When the vestibular mossy fiber pathway is destroyed, vestibular modulation of ipsilateral CSs and SSs persists. We conclude that climbing fibers are primarily responsible for the vestibularly modulated discharge of both CSs and SSs. Modulation of the discharge of SSs is likely caused by climbing fiber-evoked stellate cell inhibition.

An investigation of the open-loop amplification of a Reynolds number dependent process by wave distortion

NASA Technical Reports Server (NTRS)

Ventrice, M. B.; Purdy, K. R.

1974-01-01

The response of a constant-temperature hot-wire anemometer to sinusoidal and distorted sinusoidal acoustic oscillations is examined. The output of the anemometer is dependent upon the Reynolds number of the flow over the wire. The response is a measure of the interaction between the anemometer output and the acoustic pressure in the neighborhood of the wire. It is an open-loop prediction of the characteristics of actual closed-loop operation of a system. If the open-loop response is large enough, unstable closed-loop operation is predicted. The study was motivated by a need to investigate the stability limits of liquid-propellant rockets when perturbed by pressure oscillations. The sinusoidal and distorted sinusoidal acoustic oscillations used for this study are the same as those characteristic of unstable rocket combustion. Qualitatively, the results are similar--the response of the system to pure sinusoidal acoustic vibration of the fluid surrounding the wire is small, even when the magnitude of the acoustic pressure is quite large; but the response can be increased by as much as an order of magnitude with respect to the sinusoidal case by the addition of distortion. The amplitude and phase of the distortion component, relative to the fundamental component, are the dominant factors in the increase in the response.

On Zwicker tones and musical pitch in the likely absence of phase locking corresponding to the pitch a)

PubMed Central

Gockel, Hedwig E.; Carlyon, Robert P.

2017-01-01

It was assessed whether Zwicker tones (ZTs) (an auditory afterimage produced by a band-stop noise) have a musical pitch. First (stage I), musically trained subjects adjusted the frequency, level, and decay time of an exponentially decaying diotic sinusoid to sound similar to the ZT they perceived following the presentation of diotic broadband noise, for various band-stop positions. Next (stage II), subjects adjusted a sinusoid in frequency and level so that its pitch was a specified musical interval below that of either a preceding ZT or a preceding sinusoid, and so that it was equally loud. For each subject the reference sinusoid corresponded to their adjusted sinusoid from stage I. Subjects selected appropriate frequency ratios for ZTs, although the standard deviations of the adjustments were larger for the ZTs than for the equally salient sinusoids by a factor of 1.0–2.2. Experiments with monaural stimuli led to similar results, although the pitch of the ZTs could differ for monaural and diotic presentation of the ZT-exciting noise. The results suggest that a weak musical pitch may exist in the absence of phase locking in the auditory nerve to the frequency corresponding to the pitch (or harmonics thereof) at the time of the percept. PMID:27794303

Frequency stabilization for multilocation optical FDM networks

NASA Astrophysics Data System (ADS)

Jiang, Quan; Kavehrad, Mohsen

1993-04-01

In a multi-location optical FDM network, the frequency of each user's transmitter can be offset-locked, through a Fabry-Perot, to an absolute frequency standard which is distributed to the users. To lock the local Fabry-Perot to the frequency standard, the standard has to be frequency-dithered by a sinusoidal signal and the sinusoidal reference has to be transmitted to the user location since the lock-in amplifier in the stabilization system requires the reference for synchronous detection. We proposed two solutions to avoid transmitting the reference. One uses an extraction circuit to obtain the sinusoidal signal from the incoming signal. A nonlinear circuit following the photodiode produces a strong second-order harmonic of the sinusoidal signal and a phase-locked loop is locked to it. The sinusoidal reference is obtained by a divide- by-2 circuit. The phase ambiguity (0 degree(s) or 180 degree(s)) is resolved by using a selection- circuit and an initial scan. The other method uses a pseudo-random sequence instead of a sinusoidal signal to dither the frequency standard and a surface-acoustic-wave (SAW) matched-filter instead of a lock-in amplifier to obtain the frequency error. The matched-filter serves as a correlator and does not require the dither reference.

Fabrication of surfactant-free quercetin-loaded PLGA nanoparticles: evaluation of hepatoprotective efficacy by nuclear scintigraphy

NASA Astrophysics Data System (ADS)

Ganguly, Soumya; Gaonkar, Raghuvir H.; Sinha, Samarendu; Gupta, Amit; Chattopadhyay, Dipankar; Chattopadhyay, Sankha; Sachdeva, Satbir S.; Ganguly, Shantanu; Debnath, Mita C.

2016-07-01

The purpose of this study was to develop surfactant-free quercetin-loaded PLGA nanoparticles (Qr-NPs) and investigate the hepatoprotective efficacy of the product non-invasively by nuclear scintigraphy. The nanoparticles were prepared using PLGA by dialysis method and ranged in size between 50 and 250 nm with a narrow range of distribution. They were found to arrive at the fenestra of liver sinusoidal epithelium for accumulation. The sizes of nanoparticles (batch S1) were optimal to reach the target and offer enough protection of the hepatocytes degenerated by CCl4 intoxication as determined by various biochemical and histopathological tests. In vitro studies exhibited the cytotoxic effect of the formulation against HepG2 cell line. The hepatoprotective efficacy of Qr-NPs evaluated non-invasively by nuclear scintigraphic technique using 99mTc-labelled sulphur colloid revealed abnormality in liver at the area of decreased uptake in rats of CCl4-treated group, which disappeared in Qr-NP-treated group. In dynamic studies with 99mTc-mebrofenin, excretion was severely impaired in CCl4-treated group but was moderate in drug-treated group, proving the recovery of animals from damage.

Electromagnetic response of the protective pellicle of Euglenoids: influence of the surface profile

NASA Astrophysics Data System (ADS)

Inchaussandague, Marina E.; Gigli, Miriam L.; Skigin, Diana C.; Tolivia, Analía.; Conforti, Visitación

2015-03-01

In a recent paper we have investigated, from an electromagnetic point of view, the role played by the pellicle of Euglenoids -unicellular aquatic organisms- in the protection of the cell against UV radiation.14 By modelling the pellicle as a diffraction grating, we computed the electromagnetic response of different species that exhibit different behaviors against UV radiation. In this previous study, the pellicle profile was approximated by a sinusoidal grating. However, it has been observed in the transversal cut images that the profiles are not exactly sinusoidal, and also vary from sample to sample. Since the electromagnetic response depends on the geometry of the grating, reflectance calculations that take into account a more accurate representation of the actual profile could provide more insight into this problem. In this paper we investigate the electromagnetic response of the pellicle of Euglenoids for different grating profiles. The diffraction problem is solved by using the Chandezon method, which has demonstrated a successful performance for deep gratings of arbitrary profiles. We analyze the influence of the shape, depth and period of the grating on the UV reflectance. We show that the pellicle characteristics are critical parameters to increase the reflectance, thus reducing the penetration of the UV radiation within the cell and therefore, minimizing the damage and increasing the survival of these organisms.

Veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic stem cell transplantation: Middle East/North Africa regional consensus on prevention, diagnosis and management.

PubMed

Al Jefri, A H; Abujazar, H; Al-Ahmari, A; Al Rawas, A; Al Zahrani, Z; Alhejazi, A; Bekadja, M A; Ibrahim, A; Lahoucine, M; Ousia, S; Bazarbachi, A

2017-04-01

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) of the liver is a serious, early complication of haematopoietic stem cell transplantation (HSCT), severe and very severe forms of which are associated with a high mortality rate. A wide variety of patient, disease and treatment-related risk factors for VOD/SOS have been identified. Several bodies have published recommendations for the diagnosis, prevention and management of VOD/SOS following HSCT. A group of regional experts have developed a consensus statement on the diagnosis, prevention and management of VOD/SOS in the Middle East and North Africa region to help in the management of HSCT patients in the region. Risk factors of particular relevance in the region include iron overload in thalassaemia patients, some hereditary metabolic disorders due to consanguinity and infection with hepatitis virus B or C. Recommendations include diagnosis of VOD/SOS based on established clinical criteria, prophylaxis with defibrotide and/or ursodeoxycholic acid in patients at increased risk of VOD/SOS, and treatment with defibrotide for patients with severe/very severe VOD/SOS (and, if clinically indicated, in those with moderate or rapidly progressing VOD/SOS, as per the new European Society for Blood and Marrow Transplantation classification).

Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload.

PubMed

Hankins, Jane S; Smeltzer, Matthew P; McCarville, M Beth; Aygun, Banu; Hillenbrand, Claudia M; Ware, Russell E; Onciu, Mihaela

2010-07-01

The rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non-chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation.

Sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: Incidence, risk factors and outcomes.

PubMed

Yakushijin, K; Atsuta, Y; Doki, N; Yokota, A; Kanamori, H; Miyamoto, T; Ohwada, C; Miyamura, K; Nawa, Y; Kurokawa, M; Mizuno, I; Mori, T; Onizuka, M; Taguchi, J; Ichinohe, T; Yabe, H; Morishima, Y; Kato, K; Suzuki, R; Fukuda, T

2016-03-01

This retrospective study was conducted in Japan to determine the incidence, risk factors and outcomes of sinusoidal obstruction syndrome (SOS) after allogeneic hematopoietic stem cell transplantation (HSCT). Among 4290 patients undergoing allogeneic HSCT between 1999 and 2010, 462 were diagnosed with SOS according to the Seattle criteria (cumulative incidence, 10.8%). The cumulative incidence of SOS diagnosed by the modified Seattle criteria was 9.3%. Of 462 patients, 107 met the Baltimore criteria and 168 had severe SOS with renal and/or respiratory failure. The median onset for SOS was 12 days after HSCT (range, -2-30). Overall survival at day 100 was 32% for SOS and 15% for severe SOS. Multivariate analyses showed that significant independent risk factors for SOS were the number of HSCTs, age, performance status, hepatitis C virus-seropositivity, advanced disease status and myeloablative regimen. SOS was highly associated with overall mortality (hazard ratio, 2.09; P<0.001). Our retrospective survey showed that the cumulative incidence of SOS in Japan was 10.8%, similar to that previously reported in Western countries, and that the overall survival of patients who developed SOS was low. Furthermore, several risk factors were identified. Preventive and therapeutic strategies for high-risk SOS patients must be established to improve overall survival.

Risk of sinusoidal obstruction syndrome in allogeneic stem cell transplantation after prior gemtuzumab ozogamicin treatment: a retrospective study from the Acute Leukemia Working Party of the EBMT.

PubMed

Battipaglia, G; Labopin, M; Candoni, A; Fanin, R; El Cheikh, J; Blaise, D; Michallet, M; Ruggeri, A; Contentin, N; Ribera, J M; Stadler, M; Sierra, J; von dem Borne, P A; Bloor, A; Socié, G; Nagler, A; Mohty, M

2017-04-01

Gemtuzumab ozogamicin (GO) may increase the risk of sinusoidal obstruction syndrome (SOS) when used prior to allogeneic stem cell transplantation (HSCT). We assessed SOS incidence and outcomes after HSCT of 146 adults, with a median age of 50 years, previously receiving GO. SOS prophylaxis was used in 69 patients (heparin n=57, ursodeoxycholic acid n=8, defibrotide n=4). Cumulative incidence (CI) of SOS was 8% (n=11), with death in 3 patients. Median interval between last GO dose and HSCT was 130 days. Overall survival (OS) and SOS incidence did not differ for patients receiving GO ⩽3.5 months before HSCT and the others. CI of acute and chronic GVHD was 31% and 25%, respectively. Probability of OS and leukemia-free survival (LFS) at 5 years was 40% and 37%, respectively. Relapse incidence and non-relapse mortality were 42% and 21%, respectively. In multivariate analysis, active disease at HSCT was associated with relapse and worse LFS and OS (P<0.03). Liver abnormalities before HSCT correlated with worse OS (P<0.03). Use of low-dose GO prior to HSCT is associated with an acceptable SOS incidence. Prospective studies investigating the role and the utility of SOS prophylaxis are warranted.

Tolvaptan as an alternative treatment for refractory fluid retention associated with sinusoidal obstruction syndrome after allogeneic stem cell transplantation.

PubMed

Yakushijin, Kimikazu; Yamamoto, Katsuya; Kurata, Keiji; Miyata, Yoshiharu; Kakiuchi, Seiji; Tomioka, Hideo; Kawamori-Iwamoto, Yuriko; Inui, Yumiko; Sanada, Yukinari; Okamura, Atsuo; Murayama, Tohru; Matsuoka, Hiroshi; Minami, Hironobu

2013-02-01

Tolvaptan is an oral vasopressin V2-receptor antagonist recognized as effective for fluid retention associated with congestive heart failure and liver cirrhosis. However, there have been no reports concerning clinical experience with tolvaptan for sinusoidal obstruction syndrome (SOS). A 42-year-old male with primarily refractory T-lymphoblastic lymphoma underwent allogeneic peripheral blood stem cell transplantation from an HLA-matched sibling donor. The myeloablative conditioning regimen consisted of busulfan and cyclophosphamide. On day 20, the total bilirubin level was elevated to 2.0 mg/dL, and body weight increased from 76 to 85 kg, allowing a diagnosis of SOS to be made. Treatments with thrombomodulin, furosemide, carperitide, and low-dose dopamine were ineffective. By day 27, the patient's body weight had increased to 90 kg, and he subsequently developed cardiopulmonary failure. Therefore, we administered low-dose tolvaptan for 2 days (3.75 mg on day 27 and 7.5 mg on day 28). Consequently, his ascites and edema were significantly reduced, and body weight returned to 77 kg by day 34. However, he died of lymphoma progression on day 55. Tolvaptan may be an alternative and promising treatment for refractory fluid retention associated with SOS, although it is unclear whether tolvaptan administration leads to improvement in clinical outcome.

Age-related changes in human vestibulo-ocular reflexes: Sinusoidal rotation and caloric tests

NASA Technical Reports Server (NTRS)

Peterka, R. J.; Black, F. O.; Schoenhoff, M. B.

1989-01-01

The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR dynamics, and to identify the distributions of parameters which describe VOR responses to caloric and to sinusoidal rotational stimuli in a putatively normal population. Caloric test parameters showed no consistent trend with age. Rotation test parameters showed declining response amplitude and slightly less compensatory response phase with increasing age. The magnitudes of these changes were not large relative to the variability within the population. The age-related trends in VOR were not consistent with the anatomic changes in the periphery reported by others which showed an increasing rate of peripheral hair cell and nerve fiber loss in subjects over 55 years. The poor correlation between physiological and anatomical data suggest that adaptive mechanisms in the central nervous system are important in maintaining the VOR.

Methods for Isolation and Purification of Murine Liver Sinusoidal Endothelial Cells: A Systematic Review.

PubMed

Meyer, Jeremy; Gonelle-Gispert, Carmen; Morel, Philippe; Bühler, Léo

2016-01-01

To study the biological functions of liver sinusoidal endothelial cells (LSEC) and to identify their interplay with blood or liver cells, techniques allowing for the isolation and purification of LSEC have been developed over the last decades. The objective of the present review is to summarize and to compare the efficiency of existing methods for isolating murine LSEC. Toward this end, the MEDLINE database was searched for all original articles describing LSEC isolation from rat and mouse livers. Out of the 489 publications identified, 23 reported the main steps and outcomes of the procedure and were included in our review. Here, we report and analyse the technical details of the essential steps of the techniques used for LSEC isolation. The correlations between the prevalence of some steps and the efficiency of LSEC isolation were also identified. We found that centrifugal elutriation, selective adherence and, more recently, magnetic-activated cell sorting were used for LSEC purification. Centrifugal elutriation procured high yields of pure LSEC (for rats 30-141.9 million cells for 85-98% purities; for mice 9-9.25 million cells for >95% purities), but the use of this method remained limited due to its high technical requirements. Selective adherence showed inconsistent results in terms of cell yields and purities in rats (5-100 million cells for 73.7-95% purities). In contrast, magnetic-activated cell sorting allowed for the isolation of highly pure LSEC, but overall lower cell yields were reported (for rats 10.7 million cells with 97.6% purity; for mice 0.5-9 million cells with 90-98% purities). Notably, the controversies regarding the accuracy of several phenotypic markers for LSEC should be considered and their use for both magnetic sorting and characterization remain doubtful. It appears that more effort is needed to refine and standardize the procedure for LSEC isolation, with a focus on the identification of specific antigens. Such a procedure is required to identify the molecular mechanisms regulating the function of LSEC and to improve our understanding of their role in complex cellular processes in the liver.

Methods for Isolation and Purification of Murine Liver Sinusoidal Endothelial Cells: A Systematic Review

PubMed Central

Meyer, Jeremy; Gonelle-Gispert, Carmen; Morel, Philippe; Bühler, Léo

2016-01-01

To study the biological functions of liver sinusoidal endothelial cells (LSEC) and to identify their interplay with blood or liver cells, techniques allowing for the isolation and purification of LSEC have been developed over the last decades. The objective of the present review is to summarize and to compare the efficiency of existing methods for isolating murine LSEC. Toward this end, the MEDLINE database was searched for all original articles describing LSEC isolation from rat and mouse livers. Out of the 489 publications identified, 23 reported the main steps and outcomes of the procedure and were included in our review. Here, we report and analyse the technical details of the essential steps of the techniques used for LSEC isolation. The correlations between the prevalence of some steps and the efficiency of LSEC isolation were also identified. We found that centrifugal elutriation, selective adherence and, more recently, magnetic-activated cell sorting were used for LSEC purification. Centrifugal elutriation procured high yields of pure LSEC (for rats 30–141.9 million cells for 85–98% purities; for mice 9–9.25 million cells for >95% purities), but the use of this method remained limited due to its high technical requirements. Selective adherence showed inconsistent results in terms of cell yields and purities in rats (5–100 million cells for 73.7–95% purities). In contrast, magnetic-activated cell sorting allowed for the isolation of highly pure LSEC, but overall lower cell yields were reported (for rats 10.7 million cells with 97.6% purity; for mice 0.5–9 million cells with 90–98% purities). Notably, the controversies regarding the accuracy of several phenotypic markers for LSEC should be considered and their use for both magnetic sorting and characterization remain doubtful. It appears that more effort is needed to refine and standardize the procedure for LSEC isolation, with a focus on the identification of specific antigens. Such a procedure is required to identify the molecular mechanisms regulating the function of LSEC and to improve our understanding of their role in complex cellular processes in the liver. PMID:26992171

Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation.

PubMed

Richardson, Paul G; Smith, Angela R; Triplett, Brandon M; Kernan, Nancy A; Grupp, Stephan A; Antin, Joseph H; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L; Nejadnik, Bijan; Soiffer, Robert J

2017-07-01

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P < 0·001). These results suggest that initiation of defibrotide should not be delayed after diagnosis of VOD/SOS. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Treatment of sinusoidal obstruction syndrome with defibrotide: a single-center experience.

PubMed

Sucak, G T; Aki, Z S; Yagcí, M; Yegin, Z A; Ozkurt, Z N; Haznedar, R

2007-06-01

Sinusoidal obstruction syndrome (SOS) is a frequent, troubling, and potentially fatal complication of hematopoietic stem cell transplantation. Despite promising results with defibrotide (DF), no treatment has been established as standard. DF is a single-stranded polydeoxyribonucleotide, obtained from controlled depolymerization of porcine intestinal mucosal cells. It has antithrombotic, antiischemic, antiinflammatory, and thrombolytic properties without significant side effects. We retrospectively evaluated the charts of 80 consecutive patients, with 89 hematopoietic stem cell transplants for hematologic malignancies. The results of early initiation of DF treatment in 14 patients with SOS are presented in this study. Fourteen patients, 8 males and 6 females % median age 40.5 years (range, 16-46 years) were diagnosed to have SOS. Disease severity was classified as severe in 6 (42.85%), moderate in 4 (28.57%), and mild in 4 (28.57%) patients. We treated 14 patients with DF for a median of 21.5 days (range, 4-39 days). All 14 patients received DF after the diagnosis of SOS. Three patients with severe and all of the patients with mild to moderate SOS responded to treatment with complete resolution of SOS-related signs and symptoms. All patients responding to DF were alive at 100 days posttransplantation. There was no significant drug-related side effect among patients treated with DF. With an overall response rate of 78.56% and a 50% complete response rate in severe SOS cases and minimal side effects, we suggest that DF is the best available agent to treat SOS.

Modelling the spatio-temporal modulation response of ganglion cells with difference-of-Gaussians receptive fields: relation to photoreceptor response kinetics.

PubMed

Donner, K; Hemilä, S

1996-01-01

Difference-of-Gaussians (DOG) models for the receptive fields of retinal ganglion cells accurately predict linear responses to both periodic stimuli (typically moving sinusoidal gratings) and aperiodic stimuli (typically circular fields presented as square-wave pulses). While the relation of spatial organization to retinal anatomy has received considerable attention, temporal characteristics have been only loosely connected to retinal physiology. Here we integrate realistic photoreceptor response waveforms into the DOG model to clarify how far a single set of physiological parameters predict temporal aspects of linear responses to both periodic and aperiodic stimuli. Traditional filter-cascade models provide a useful first-order approximation of the single-photon response in photoreceptors. The absolute time scale of these, plus a time for retinal transmission, here construed as a fixed delay, are obtained from flash/step data. Using these values, we find that the DOG model predicts the main features of both the amplitude and phase response of linear cat ganglion cells to sinusoidal flicker. Where the simplest model formulation fails, it serves to reveal additional mechanisms. Unforeseen facts are the attenuation of low temporal frequencies even in pure center-type responses, and the phase advance of the response relative to the stimulus at low frequencies. Neither can be explained by any experimentally documented cone response waveform, but both would be explained by signal differentiation, e.g. in the retinal transmission pathway, as demonstrated at least in turtle retina.

Features of Hepatitis in Hepatitis-associated Aplastic Anemia: Clinical and Histopathologic Study.

PubMed

Patel, Kalyani R; Bertuch, Alison; Sasa, Ghadir S; Himes, Ryan W; Wu, Hao

2017-01-01

Hepatitis-associated aplastic anemia (HAA) is a rare variant of aplastic anemia in which patients present with severe pancytopenia after an episode of acute hepatitis. The marrow failure is often rapid, severe, and usually fatal if untreated. The preceding hepatitis is largely under-studied. Retrospective study of the clinical and histopathologic features of hepatitis in pediatric patients who subsequently developed aplastic anemia and comparison with consecutive cases of acute liver failure and random cases of autoimmune hepatitis during the same time frame. All 7 patients of HAA had significant elevations in aminotransferases and conjugated hyperbilirubinemia at initial presentation. Echoing liver function indices, cholestatic hepatitis with sinusoidal obstruction-type endothelial injury was seen histomorphologically. Autoimmune hepatitis serology such as anti-F-actin, anti-liver/kidney microsome, and hypergammaglobulinemia was negative in all patients. Five of 7 patients (71.4%) had, however, elevated antinuclear antibody, all with a speckled pattern. Hepatitis virus serology was negative in all patients. By immunohistochemical staining, the lobular CD8/CD4 lymphocyte ratio was markedly elevated in all of the initial samples with significant reduction in this ratio (P = 0.03) in 3 patients post treatment (ursodiol, antibiotics, and/or immunosuppressive therapy). Hepatitis preceding HAA is characterized by marked elevation of aminotransferases, conjugated hyperbilirubinemia, elevated antinuclear antibody with a speckled pattern, cholestatic hepatitis with sinusoidal obstruction morphology, and CD8 dominant lobular infiltrates. The present study suggests HAA may result from cytotoxic T-cell-mediated sinusoidal endothelial and hepatocytic injury.

Core losses of a permanent magnet synchronous motor with an amorphous stator core under inverter and sinusoidal excitations

NASA Astrophysics Data System (ADS)

Yao, Atsushi; Sugimoto, Takaya; Odawara, Shunya; Fujisaki, Keisuke

2018-05-01

We report core loss properties of permanent magnet synchronous motors (PMSM) with amorphous magnetic materials (AMM) core under inverter and sinusoidal excitations. To discuss the core loss properties of AMM core, a comparison with non-oriented (NO) core is also performed. In addition, based on both experiments and numerical simulations, we estimate higher (time and space) harmonic components of the core losses under inverter and sinusoidal excitations. The core losses of PMSM are reduced by about 59% using AMM stator core instead of NO core under sinusoidal excitation. We show that the average decrease obtained by using AMM instead of NO in the stator core is about 94% in time harmonic components.

Infection as a Trigger for Portal Hypertension.

PubMed

Steib, Christian J; Schewe, Julia; Gerbes, Alexander L

2015-01-01

Microbial infections are a relevant problem for patients with liver cirrhosis. Different types of bacteria are responsible for different kinds of infections: Escherichia coli and Klebsiella pneumoniae are frequently observed in spontaneous bacterial peritonitis or urinary tract infections, and Streptococcus pneumoniae and Mycoplasma pneumoniae in pulmonary infections. Mortality is up to 4-fold higher in infected patients with liver cirrhosis than in patients without infections. Key Messages: Infections in patients with liver cirrhosis are due to three major reasons: bacterial translocation, immune deficiency and an increased incidence of systemic infections. Nonparenchymal liver cells like Kupffer cells, sinusoidal endothelial cells and hepatic stellate cells are the first liver cells to come into contact with microbial products when systemic infection or bacterial translocation occurs. Kupffer cell (KC) activation by Toll-like receptor (TLR) agonists and endothelial sinusoidal dysfunction have been shown to be important mechanisms increasing portal pressure following intraperitoneal lipopolysaccharide pretreatment in cirrhotic rat livers. Reduced intrahepatic vasodilation and increased intrahepatic vasoconstriction are the relevant pathophysiological pathways. Thromboxane A2 and leukotriene (LT) C4/D4 have been identified as important vasoconstrictors. Accordingly, treatment with montelukast to inhibit the cysteinyl-LT1 receptor reduced portal pressure in cirrhotic rat livers. Clinical studies have demonstrated that activation of KCs, estimated by the amount of soluble CD163 in the blood, correlates with the risk for variceal bleeding. Additionally, intestinal decontamination with rifaximin in patients with alcohol-associated liver cirrhosis reduced the portal pressure and the risk for variceal bleeding. TLR activation of nonparenchymal liver cells by pathogens results in portal hypertension. This might explain the pathophysiologic correlation between microbial infections and portal hypertension in patients with liver cirrhosis. These findings are the basis for both better risk stratifying and new treatment options, such as specific inhibition of TLR for patients with liver cirrhosis and portal hypertension. © 2015 S. Karger AG, Basel.

Stimulation of hair cells with ultraviolet light

NASA Astrophysics Data System (ADS)

Azimzadeh, Julien B.; Fabella, Brian A.; Hudspeth, A. J.

2018-05-01

Hair bundles are specialized organelles that transduce mechanical inputs into electrical outputs. To activate hair cells, physiologists have resorted to mechanical methods of hair-bundle stimulation. Here we describe a new method of hair-bundle stimulation, irradiation with ultraviolet light. A hair bundle illuminated by ultraviolet light rapidly moves towards its tall edge, a motion typically associated with excitatory stimulation. The motion disappears upon tip-link rupture and is associated with the opening of mechanotransduction channels. Hair bundles can be induced to move sinusoidally with oscillatory modulation of the stimulation power. We discuss the implications of ultraviolet stimulation as a novel hair-bundle stimulus.

Effect of renal nerve stimulation on responsiveness of the rat renal vasculature.

PubMed

DiBona, Gerald F; Sawin, Linda L

2002-11-01

When the renal nerves are stimulated with sinusoidal stimuli over the frequency range 0.04-0.8 Hz, low (< or =0.4 Hz)- but not high (> or =0.4 Hz)-frequency oscillations appear in renal blood flow (RBF) and are proposed to increase responsiveness of the renal vasculature to stimuli. This hypothesis was tested in anesthetized rats in which RBF responses to intrarenal injection of norepinephrine and angiotensin and to reductions in renal arterial pressure (RAP) were determined during conventional rectangular pulse and sinusoidal renal nerve stimulation. Conventional rectangular pulse renal nerve stimulation decreased RBF at 2 Hz but not at 0.2 or 1.0 Hz. Sinusoidal renal nerve stimulation elicited low-frequency oscillations (< or =0.4 Hz) in RBF only when the basal carrier signal frequency produced renal vasoconstriction, i.e., at 5 Hz but not at 1 Hz. Regardless of whether renal vasoconstriction occurred, neither conventional rectangular pulse nor sinusoidal renal nerve stimulation altered renal vasoconstrictor responses to norepinephrine and angiotensin. The RBF response to reduction in RAP was altered by both conventional rectangular pulse and sinusoidal renal nerve stimulation only when renal vasoconstriction occurred: the decrease in RBF during reduced RAP was greater. Sinusoidal renal nerve stimulation with a renal vasoconstrictor carrier frequency results in a decrease in RBF with superimposed low-frequency oscillations. However, these low-frequency RBF oscillations do not alter renal vascular responsiveness to vasoconstrictor stimuli.

[Effects of 100 Hz sinusoidal vibration on H reflex and M wave in rat soleus muscle following immobilization].

PubMed

Zhao, Xue-hong; Fan, Xiao-li; Song, Xin-ai; Shi, Lei

2011-09-01

To investigate the effects of 100 Hz sinusoidal vibration on H reflex and M wave in rat soleus muscle following immobilization. The immobilization of rat soleus muscle was induced as a disuse muscle model, and 100 Hz sinusoidal vibration was generated by a vibrator and applied to the immobilized soleus muscle, then the changes of H reflex and M wave in muscle were observed after 14 d. Compared to control, after 14 d of immobilization M(max) in soleus muscle decreased (P<0.01), stimulus threshold and S(max) increased (P<0.01); Hmax and H(max)/M(max) decreased (P<0.05, S(max) increased (P<0.05). Compared to immobilized soleus muscle, after 14 d of immobilization with 100 Hz sinusoidal vibration, the M(max) increased(P<0.01), stimulus threshold and S(Mmax) decreased (P<0.05), H(max) (P<0.01) increased and H(max)/M(max) increased (P<0.05). 100 Hz sinusoidal vibration plays a significant antagonist role against the changes in H reflex and M wave in rat soleus muscle following immobilization.

Deep-etched sinusoidal polarizing beam splitter grating.

PubMed

Feng, Jijun; Zhou, Changhe; Cao, Hongchao; Lv, Peng

2010-04-01

A sinusoidal-shaped fused-silica grating as a highly efficient polarizing beam splitter (PBS) is investigated based on the simplified modal method. The grating structure depends mainly on the ratio of groove depth to grating period and the ratio of incident wavelength to grating period. These ratios can be used as a guideline for the grating design at different wavelengths. A sinusoidal-groove PBS grating is designed at a wavelength of 1310 nm under Littrow mounting, and the transmitted TM and TE polarized waves are mainly diffracted into the zeroth order and the -1st order, respectively. The grating profile is optimized by using rigorous coupled-wave analysis. The designed PBS grating is highly efficient (>95.98%) over the O-band wavelength range (1260-1360 nm) for both TE and TM polarizations. The sinusoidal grating can exhibit higher diffraction efficiency, larger extinction ratio, and less reflection loss than the rectangular-groove PBS grating. By applying wet etching technology on the rectangular grating, which was manufactured by holographic recording and inductively coupled plasma etching technology, the sinusoidal grating can be approximately fabricated. Experimental results are in agreement with theoretical values.

Liquid sinusoidal pressure measurement by laser interferometry based on the refractive index of water.

PubMed

Yang, Jun; Fan, Shangchun; Li, Cheng; Guo, Zhanshe; Li, Bo; Shi, Bo

2016-12-01

A new method with laser interferometry is used to enhance the traceability for sinusoidal pressure calibration in water. The laser vibrometer measures the dynamic pressure based on the acousto-optic effect. The relation of the refractive index of water and the optical path length with the pressure's change is built based on the Lorentz-Lorenz equation, and the conversion coefficients are tested by static calibration in situ. A device with a piezoelectric transducer and resonant pressure pipe with water is set up to generate sinusoidal pressure up to 20 kHz. With the conversion coefficients, the reference sinusoidal pressure is measured by the laser interferometer for pressure sensors' dynamic calibration. The experiment results show that under 10 kHz, the measurement results between the laser vibrometer and a piezoelectric sensor are in basic agreement and indicate that this new method and its measurement system are feasible in sinusoidal pressure calibration. Some disturbing components including small amplitude, temperature change, pressure maldistribution, and glass windows' vibration are also analyzed, especially for the dynamic calibrations above 10 kHz.

High-level magnetic activity nature of the eclipsing binary KIC 12418816

NASA Astrophysics Data System (ADS)

Dal, H. A.; Özdarcan, O.

2018-02-01

We present comprehensive spectroscopic and photometric analysis of the detached eclipsing binary KIC 12418816, which is composed of two very similar and young main-sequence stars of spectral type K0 on a circular orbit. Combining spectroscopic and photometric modelling, we find masses and radii of the components of 0.88 ± 0.06 M⊙ and 0.85 ± 0.02 R⊙ for the primary and 0.84 ± 0.05 M⊙ and 0.84 ± 0.02 R⊙ for the secondary. Both components exhibit narrow emission features superposed on the cores of the Ca II H and K lines, while H α and H β photospheric absoprtion is more completely infilled by broader emission. Very high precision Kepler photometry reveals remarkable sinusoidal light variation at out-of-eclipse phases, indicating strong spot activity, presumably on the surface of the secondary component. Spots on the secondary component appear to migrate towards decreasing orbital phase with a migration period of 0.72 ± 0.05 yr. Besides the sinusoidal variation, we detect 81 flares and find that both components possess flare activity. Our analysis shows that 25 flares out of 81 exhibit very high energies together with lower frequency, while the rest of them are very frequent but with lower energies.

Atomic spectroscopy and holography: A combined laboratory experiment at the intermediate undergraduate level

NASA Astrophysics Data System (ADS)

Bates, Harry E.

1984-05-01

Holography is a new and exciting field that has found many applications in physics and engineering. Atomic spectroscopy has been the experimental cornerstone of modern physics and chemistry. This paper reports on an intermediate undergraduate laboratory experiment that combines fundamental ideas and techniques of both fields. The student utilizes holographic techniques to make a small sinusoidal diffraction grating and then uses this grating to analyze the spectrum of hydrogen. The Rydberg constant can be determined from the wavelength, the angle between the laser beams used to make the grating, and the observed diffractions angles of lines of the Balmer series.

An Electromagnetically-Controlled Precision Orbital Tracking Vehicle (POTV)

DTIC Science & Technology

1992-12-01

assume that C > B > A. Then 0 1(t) is purely sinusoidal. tk2 (t) is also sinusoidal because the forcing function z(t) is sinusoidal. 03 (t) is more...an unpredictable -manner. The problem arises from the rank deficiency of the G input matrix as shown below. Remember we have shown already that its...rank can never exceed five because rows two, four, and six are linearly dependent. The rank deficiency arises from the "translational part" of the input

OSCILLATING FILAMENTS. I. OSCILLATION AND GEOMETRICAL FRAGMENTATION

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

Gritschneder, Matthias; Heigl, Stefan; Burkert, Andreas, E-mail: gritschm@usm.uni-muenchen.de

2017-01-10

We study the stability of filaments in equilibrium between gravity and internal as well as external pressure using the grid-based AMR code RAMSES. A homogeneous, straight cylinder below a critical line mass is marginally stable. However, if the cylinder is bent, such as with a slight sinusoidal perturbation, an otherwise stable configuration starts to oscillate, is triggered into fragmentation, and collapses. This previously unstudied behavior allows a filament to fragment at any given scale, as long as it has slight bends. We call this process “geometrical fragmentation.” In our realization, the spacing between the cores matches the wavelength of the sinusoidalmore » perturbation, whereas up to now, filaments were thought to be only fragmenting on the characteristic scale set by the mass-to-line ratio. Using first principles, we derive the oscillation period as well as the collapse timescale analytically. To enable a direct comparison with observations, we study the line-of-sight velocity for different inclinations. We show that the overall oscillation pattern can hide the infall signature of cores.« less

Hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro.

PubMed

Ng, Shengyong; March, Sandra; Galstian, Ani; Hanson, Kirsten; Carvalho, Tânia; Mota, Maria M; Bhatia, Sangeeta N

2014-02-01

Homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. In vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. Existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possibly due to missing microenvironmental support signals. One cue that could influence the infection capacity of cultured human hepatocytes is the dissolved oxygen concentration. We developed a microscale human liver platform comprised of precisely patterned primary human hepatocytes and nonparenchymal cells to model liver-stage malaria, but the oxygen concentrations are typically higher in the in vitro liver platform than anywhere along the hepatic sinusoid. Indeed, we observed that liver-stage Plasmodium parasite development in vivo correlates with hepatic sinusoidal oxygen gradients. Therefore, we hypothesized that in vitro liver-stage malaria infection efficiencies might improve under hypoxia. Using the infection of micropatterned co-cultures with Plasmodium berghei, Plasmodium yoelii or Plasmodium falciparum as a model, we observed that ambient hypoxia resulted in increased survival of exo-erythrocytic forms (EEFs) in hepatocytes and improved parasite development in a subset of surviving EEFs, based on EEF size. Further, the effective cell surface oxygen tensions (pO2) experienced by the hepatocytes, as predicted by a mathematical model, were systematically perturbed by varying culture parameters such as hepatocyte density and height of the medium, uncovering an optimal cell surface pO2 to maximize the number of mature EEFs. Initial mechanistic experiments revealed that treatment of primary human hepatocytes with the hypoxia mimetic, cobalt(II) chloride, as well as a HIF-1α activator, dimethyloxalylglycine, also enhance P. berghei infection, suggesting that the effect of hypoxia on infection is mediated in part by host-dependent HIF-1α mechanisms.

Order restricted inference for oscillatory systems for detecting rhythmic signals

PubMed Central

Larriba, Yolanda; Rueda, Cristina; Fernández, Miguel A.; Peddada, Shyamal D.

2016-01-01

Motivation: Many biological processes, such as cell cycle, circadian clock, menstrual cycles, are governed by oscillatory systems consisting of numerous components that exhibit rhythmic patterns over time. It is not always easy to identify such rhythmic components. For example, it is a challenging problem to identify circadian genes in a given tissue using time-course gene expression data. There is a great potential for misclassifying non-rhythmic as rhythmic genes and vice versa. This has been a problem of considerable interest in recent years. In this article we develop a constrained inference based methodology called Order Restricted Inference for Oscillatory Systems (ORIOS) to detect rhythmic signals. Instead of using mathematical functions (e.g. sinusoidal) to describe shape of rhythmic signals, ORIOS uses mathematical inequalities. Consequently, it is robust and not limited by the biologist's choice of the mathematical model. We studied the performance of ORIOS using simulated as well as real data obtained from mouse liver, pituitary gland and data from NIH3T3, U2OS cell lines. Our results suggest that, for a broad collection of patterns of gene expression, ORIOS has substantially higher power to detect true rhythmic genes in comparison to some popular methods, while also declaring substantially fewer non-rhythmic genes as rhythmic. Availability and Implementation: A user friendly code implemented in R language can be downloaded from http://www.niehs.nih.gov/research/atniehs/labs/bb/staff/peddada/index.cfm. Contact: peddada@niehs.nih.gov PMID:27596593

Losses analysis of soft magnetic ring core under sinusoidal pulse width modulation (SPWM) and space vector pulse width modulation (SVPWM) excitations

NASA Astrophysics Data System (ADS)

Gao, Hezhe; Li, Yongjian; Wang, Shanming; Zhu, Jianguo; Yang, Qingxin; Zhang, Changgeng; Li, Jingsong

2018-05-01

Practical core losses in electrical machines differ significantly from those experimental results using the standardized measurement method, i.e. Epstein Frame method. In order to obtain a better approximation of the losses in an electrical machine, a simulation method considering sinusoidal pulse width modulation (SPWM) and space vector pulse width modulation (SVPWM) waveforms is proposed. The influence of the pulse width modulation (PWM) parameters on the harmonic components in SPWM and SVPWM is discussed by fast Fourier transform (FFT). Three-level SPWM and SVPWM are analyzed and compared both by simulation and experiment. The core losses of several ring samples magnetized by SPWM, SVPWM and sinusoidal alternating current (AC) are obtained. In addition, the temperature rise of the samples under SPWM, sinusoidal excitation are analyzed and compared.

Annual variation in the atmospheric radon concentration in Japan.

PubMed

Kobayashi, Yuka; Yasuoka, Yumi; Omori, Yasutaka; Nagahama, Hiroyuki; Sanada, Tetsuya; Muto, Jun; Suzuki, Toshiyuki; Homma, Yoshimi; Ihara, Hayato; Kubota, Kazuhito; Mukai, Takahiro

2015-08-01

Anomalous atmospheric variations in radon related to earthquakes have been observed in hourly exhaust-monitoring data from radioisotope institutes in Japan. The extraction of seismic anomalous radon variations would be greatly aided by understanding the normal pattern of variation in radon concentrations. Using atmospheric daily minimum radon concentration data from five sampling sites, we show that a sinusoidal regression curve can be fitted to the data. In addition, we identify areas where the atmospheric radon variation is significantly affected by the variation in atmospheric turbulence and the onshore-offshore pattern of Asian monsoons. Furthermore, by comparing the sinusoidal regression curve for the normal annual (seasonal) variations at the five sites to the sinusoidal regression curve for a previously published dataset of radon values at the five Japanese prefectures, we can estimate the normal annual variation pattern. By fitting sinusoidal regression curves to the previously published dataset containing sites in all Japanese prefectures, we find that 72% of the Japanese prefectures satisfy the requirements of the sinusoidal regression curve pattern. Using the normal annual variation pattern of atmospheric daily minimum radon concentration data, these prefectures are suitable areas for obtaining anomalous radon variations related to earthquakes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Estimating Aquifer Properties Using Sinusoidal Pumping Tests

NASA Astrophysics Data System (ADS)

Rasmussen, T. C.; Haborak, K. G.; Young, M. H.

2001-12-01

We develop the theoretical and applied framework for using sinusoidal pumping tests to estimate aquifer properties for confined, leaky, and partially penetrating conditions. The framework 1) derives analytical solutions for three boundary conditions suitable for many practical applications, 2) validates the analytical solutions against a finite element model, 3) establishes a protocol for conducting sinusoidal pumping tests, and 4) estimates aquifer hydraulic parameters based on the analytical solutions. The analytical solutions to sinusoidal stimuli in radial coordinates are derived for boundary value problems that are analogous to the Theis (1935) confined aquifer solution, the Hantush and Jacob (1955) leaky aquifer solution, and the Hantush (1964) partially penetrated confined aquifer solution. The analytical solutions compare favorably to a finite-element solution of a simulated flow domain, except in the region immediately adjacent to the pumping well where the implicit assumption of zero borehole radius is violated. The procedure is demonstrated in one unconfined and two confined aquifer units near the General Separations Area at the Savannah River Site, a federal nuclear facility located in South Carolina. Aquifer hydraulic parameters estimated using this framework provide independent confirmation of parameters obtained from conventional aquifer tests. The sinusoidal approach also resulted in the elimination of investigation-derived wastes.

INVASIVE AND NON-INVASIVE TECHNIQUES FOR DETECTING PORTAL HYPERTENSION AND PREDICTING VARICEAL BLEEDING IN CIRRHOSIS: A REVIEW

PubMed Central

Zardi, Enrico Maria; Di Matteo, Francesco Maria; Pacella, Claudio Maurizio; Sanyal, Arun J

2016-01-01

Portal hypertension is a severe syndrome that may derive from pre-sinusoidal, sinusoidal and post-sinusoidal causes. As a consequence, several complications (i.e., ascites, oesophageal varices) may develop. In sinusoidal portal hypertension, hepatic venous pressure gradient (HVPG) is a reliable method for defining the grade of portal pressure, establishing the effectiveness of the treatment and predicting the occurrence of complications; however, some questions exist regarding its ability to discriminate bleeding from nonbleeding varices in cirrhotic patients. Other imaging techniques (transient elastography, endoscopy, endosonography and duplex Doppler sonography) for assessing causes and complications of portal hypertensive syndrome are available and may be valuable for the management of these patients. In this review, we evaluate invasive and non-invasive techniques currently employed to obtain a clinical prediction of deadly complications, such as variceal bleeding in patients affected by sinusoidal portal hypertension, in order to create a diagnostic algorithm to manage them. Again, HVPG appears to be the reference standard to evaluate portal hypertension and monitor the response to treatment, but its ability to predict several complications and support management decisions might be further improved through the diagnostic combination with other imaging techniques. PMID:24328372

Comparison between the water activation effects by pulsed and sinusoidal helium plasma jets

NASA Astrophysics Data System (ADS)

Xu, Han; Liu, Dingxin; Xia, Wenjie; Chen, Chen; Wang, Weitao; Liu, Zhijie; Wang, Xiaohua; Kong, Michael G.

2018-01-01

Comparisons between pulsed and sinusoidal plasma jets have been extensively reported for the discharge characteristics and gaseous reactive species, but rarely for the aqueous reactive species in water solutions treated by the two types of plasma jets. This motivates us to compare the concentrations of aqueous reactive species induced by a pulsed and a sinusoidal plasma jet, since it is widely reported that these aqueous reactive species play a crucial role in various plasma biomedical applications. Experimental results show that the aqueous H2O2, OH/O2-, and O2-/ONOO- induced by the pulsed plasma jet have higher concentrations, and the proportional difference increases with the discharge power. However, the emission intensities of OH(A) and O(3p5P) are higher for the sinusoidal plasma jet, which may be attributed to its higher gas temperature since more water vapor could participate in the plasma. In addition, the efficiency of bacterial inactivation induced by the pulsed plasma jet is higher than that for the sinusoidal plasma jet, in accordance with the concentration relation of aqueous reactive species for the two types of plasma jets.

Invasive and non-invasive techniques for detecting portal hypertension and predicting variceal bleeding in cirrhosis: a review.

PubMed

Zardi, Enrico Maria; Di Matteo, Francesco Maria; Pacella, Claudio Maurizio; Sanyal, Arun J

2014-02-01

Portal hypertension is a severe syndrome that may derive from pre-sinusoidal, sinusoidal, and post-sinusoidal causes. As a consequence, several complications (i.e. ascites, oesophageal varices) may develop. In sinusoidal portal hypertension, hepatic venous pressure gradient (HVPG) is a reliable method for defining the grade of portal pressure, establishing the effectiveness of the treatment, and predicting the occurrence of complications; however, some questions exist regarding its ability to discriminate bleeding from non-bleeding varices in cirrhotic patients. Other imaging techniques (transient elastography, endoscopy, endosonography, and duplex Doppler sonography) for assessing causes and complications of portal hypertensive syndrome are available and may be valuable for the management of these patients. In this review, we evaluate invasive and non-invasive techniques currently employed to obtain a clinical prediction of deadly complications, such as variceal bleeding in patients affected by sinusoidal portal hypertension, in order to create a diagnostic algorithm to manage them. Again, HVPG appears to be the reference standard to evaluate portal hypertension and monitor the response to treatment, but its ability to predict several complications and support management decisions might be further improved through the diagnostic combination with other imaging techniques.

Harmonic generation by yeast cells in response to low-frequency electric fields

NASA Astrophysics Data System (ADS)

Nawarathna, D.; Claycomb, J. R.; Cardenas, G.; Gardner, J.; Warmflash, D.; Miller, J. H., Jr.; Widger, W. R.

2006-05-01

We report on harmonic generation by budding yeast cells (Saccharomyces cerevisiae, 108cells/ml ) in response to sinusoidal electric fields with amplitudes ranging from zero to 5V/cm in the frequency range 10-300Hz . The cell-generated harmonics are found to exhibit strong amplitude and frequency dependence. Sodium metavanadate, an inhibitor of the proton pump known as H+ -ATPase, and glucose, a substrate of H+ -ATPase, are found to increase harmonic production at low amplitudes while reducing it at large amplitudes. This P-type proton pump can be driven by an oscillatory transmembrane potential, and its nonlinear response is believed to be largely responsible for harmonic production at low frequencies in yeast cells. We find that the observed harmonics show dramatic changes with time and in their field and frequency dependence after perturbing the system by adding an inhibitor, substrate, or membrane depolarizer to the cell suspension.

Micro-CT measurements of tumoral vessels supplied by portal circulation in hepatic colorectal metastasis mouse model.

PubMed

Jun, Hong Young; Lee, Young Hwan; Juhng, Seon Kwan; Lee, Myeung Su; Oh, Jaemin; Yoon, Kwon-Ha

2014-06-01

The purpose of this study was to elucidate the micro CT findings of tumoral vessels supplied by portal circulation during establishment of hepatic metastasis of colorectal cancer in a mouse model. Hepatic metastases were induced in 15 BALB/c mice through the injection of murine colonic adenocarcinoma tumor cells into the mesenteric vein. Micro-CT imaging of the tumoral vessels was obtained to clarify the microvascular architecture. We evaluated the sinusoidal structure, diameter of the tumoral vessels (DTV) and blood vessel density (BVD) according to tumor sizes ranging from 201 to 3,000 µm in diameter. A total of 116 tumors were observed on day 15 after cell injection. The mean diameter of a normal hepatic sinusoid was 11.7 ± 2.0 µm on micro CT. The DTV supplied by the portal vein of tumors measuring 1,001-1,500 µm in diameter was greater than that of tumors 200-1,000 µm in diameter. The mean BVD from the portal vein gradually decrease according to size of tumor from 201 to 3,000 µm in diameter (r(2)  = -0.584, P < 0.01). The characteristics of tumoral vessels supplied by portal circulation during establishment of hepatic colorectal metastases were well visualized with micro-CT imaging. © 2014 Wiley Periodicals, Inc.

Imaging of hepatic toxicity of systemic therapy in a tertiary cancer centre: chemotherapy, haematopoietic stem cell transplantation, molecular targeted therapies, and immune checkpoint inhibitors.

PubMed

Alessandrino, F; Tirumani, S H; Krajewski, K M; Shinagare, A B; Jagannathan, J P; Ramaiya, N H; Di Salvo, D N

2017-07-01

The purpose of this review is to familiarise radiologists with the spectrum of hepatic toxicity seen in the oncology setting, in view of the different systemic therapies used in cancer patients. Drug-induced liver injury can manifest in various forms, and anti-neoplastic agents are associated with different types of hepatotoxicity. Although chemotherapy-induced liver injury can present as hepatitis, steatosis, sinusoidal obstruction syndrome, and chronic parenchymal damages, molecular targeted therapy-associated liver toxicity ranges from mild liver function test elevation to fulminant life-threatening acute liver failure. The recent arrival of immune checkpoint inhibitors in oncology has introduced a new range of immune-related adverse events, with differing mechanisms of liver toxicity and varied imaging presentation of liver injury. High-dose chemotherapy regimens for haematopoietic stem cell transplantation are associated with sinusoidal obstruction syndrome. Management of hepatic toxicity depends on the clinical scenario, the drug in use, and the severity of the findings. In this article, we will (1) present the most common types of oncological drugs associated with hepatic toxicity and associated liver injuries; (2) illustrate imaging findings of hepatic toxicities and the possible differential diagnosis; and (3) provide a guide for management of these conditions. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Ultrastructural study of the human neurohypophysis. III. Vascular and perivascular structures.

PubMed

Seyama, S; Pearl, G S; Takei, Y

1980-01-01

The vascular and perivascular regions of the human neurohypophysis were studied electron microscopically. The abluminal basement membrane, perivascular space, luminal basement membrane and endothelium are interposed between the neural parenchyma and the blood stream. The capillaries are fenestrated, with pores measuring 30 to 50 nm in diameter. The perivascular and intercellular spaces form prominent networks that penetrate between rows of neurohypophysial parenchymal cells. The perivascular space contains pericytes, histiocytes, fibroblasts and mast cells, with ultrastructural features typical of each cell type. No transitional forms between histiocytes and pericytes were observed. A schema for the extracellular flow of neurohypophysial hormones through the sinusoidal and perivascular spaces is proposed, suggesting an important role for the pituicytes and their intercellular junctions in the control of hormone release.

Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.

PubMed

Heinz, Stefan; Braspenning, Joris

2015-01-01

An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro. Hepatocyte cultures indeed provide a valuable tool to study blood coagulation factors. In addition, the generation and expansion of hepatocytes or hepatocyte-like cells may be used in future for cell-based therapies of liver diseases, including blood coagulation factor deficiencies.

Influence of Waveform on Cell Viability during Ultrasound Exposure

NASA Astrophysics Data System (ADS)

Saliev, Timur; Feril, Loreto B.; McLean, Donald A.; Tachibana, Katsuro; Campbell, Paul A.

2011-09-01

We examined the role of ultrasound standing waves, and their travelling wave counterparts, on cell viability in an in-vitro insonation apparatus. Furthermore, the effect of distinct waveforms (sine and top-hat) was also explored, together with the role of microbubble presence. Measurements of cell viability in standing wave scenarios demonstrated a relatively higher rate of lysis (63.13±10.89% remaining viable) compared with the travelling wave data, where 96.22±4.0% remained viable. Significant differences were also seen as a function of waveform, where insonations employing top-hat wave shapes resulted in an average end stage viability of 30.31±5.71% compared with 61.94±14.28% in the sinusoidal counterparts.

Histochemical study of the distribution of a few enzymes in the digestive system of Indian parrot.

PubMed

Mohan, K; Agrawal, V P; Goel, K A

1977-01-01

Acid-and alkaline phosphatase, 5-nucleotidase and lipase have been localized histochemically in the gizzard, intestine liver and pancreas of Indian parrot, Psittacula krameri. In the gizzard and intestine, the mucosal epithelial cells are the main sites for the enzyme production. The tubular glands of the gizzard show intense reaction for all the enzymes tested. The hepatic sinusoid cells of the liver and the acinii of pancreas give positive reaction. Like pancreas, the intestine has also been found responsible for the production and secretion of lipase. Functional significance of phosphatases in the tissues tested has been discussed.

A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

PubMed

Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

2017-11-01

Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P < 0.05). The decrease of EndMT in cirrhotic livers correlated with a significant decrease in liver fibrosis ( P < 0.05) and an improvement in the vascular disorganization rate ( P < 0.05). We demonstrated the acquisition of the EndMT phenotype by a subpopulation of endothelial cells from cirrhotic livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American Physiological Society.

Magnetic properties of Fe-Si steel depending on compressive and tensile stresses under sinusoidal and distorted excitations

NASA Astrophysics Data System (ADS)

Permiakov, V.; Pulnikov, A.; Dupré, L.; De Wulf, M.; Melkebeek, J.

2003-05-01

In this article, the magnetic properties of nonoriented electrical steel under sinusoidal and distorted excitations are investigated for the whole range of unidirectional mechanical stresses. The distorted flux obtained from the tooth tip of 3 kW induction machine at no-load test was put into the measurement system. The total losses increase for compressive stress both under sinusoidal and distorted excitations. For tensile elastic stresses, the total losses first decrease and then increase in a very similar way for both excitations. In contrast, the difference between total losses under sinusoidal and distorted magnetic fluxes becomes smaller with increase of the plastic strain. This work is a serious step toward complete characterization of the magnetic properties of electrical steel in the teeth area of induction machines. A deeper insight of that problem can improve the design of induction machines and other electromagnetic devices.

Epstein-Barr virus-associated peripheral T-Cell lymphoma involving spleen in a renal transplant patient.

PubMed Central

Lee, Hye Kyung; Kim, Hee Jung; Lee, Eun Hee; Kim, Suk Young; Park, Tae In; Kang, Chang Suk; Yang, Woo Ick

2003-01-01

The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity. PMID:12692428

Dynamic Characteristics of Ventilatory and Gas Exchange during Sinusoidal Walking in Humans.

PubMed

Fukuoka, Yoshiyuki; Iihoshi, Masaaki; Nazunin, Juhelee Tuba; Abe, Daijiro; Fukuba, Yoshiyuki

2017-01-01

Our present study investigated whether the ventilatory and gas exchange responses show different dynamics in response to sinusoidal change in cycle work rate or walking speed even if the metabolic demand was equivalent in both types of exercise. Locomotive parameters (stride length and step frequency), breath-by-breath ventilation (V̇E) and gas exchange (CO2 output (V̇CO2) and O2 uptake (V̇O2)) responses were measured in 10 healthy young participants. The speed of the treadmill was sinusoidally changed between 3 km·h-1 and 6 km·h-1 with various periods (from 10 to 1 min). The amplitude of locomotive parameters against sinusoidal variation showed a constant gain with a small phase shift, being independent of the oscillation periods. In marked contrast, when the periods of the speed oscillations were shortened, the amplitude of V̇E decreased sharply whereas the phase shift of V̇E increased. In comparing walking and cycling at the equivalent metabolic demand, the amplitude of V̇E during sinusoidal walking (SW) was significantly greater than that during sinusoidal cycling (SC), and the phase shift became smaller. The steeper slope of linear regression for the V̇E amplitude ratio to V̇CO2 amplitude ratio was observed during SW than SC. These findings suggested that the greater amplitude and smaller phase shift of ventilatory dynamics were not equivalent between SW and SC even if the metabolic demand was equivalent between both exercises. Such phenomenon would be derived from central command in proportion to locomotor muscle recruitment (feedforward) and muscle afferent feedback.

Comparison of the efficiency of rat papillary muscles during afterloaded isotonic contractions and contractions with sinusoidal length changes.

PubMed

Mellors, L J; Gibbs, C L; Barclay, C J

2001-05-01

The results of previous studies suggest that the maximum mechanical efficiency of rat papillary muscles is lower during a contraction protocol involving sinusoidal length changes than during one involving afterloaded isotonic contractions. The aim of this study was to compare directly the efficiency of isolated rat papillary muscle preparations in isotonic and sinusoidal contraction protocols. Experiments were performed in vitro (27 degrees C) using left ventricular papillary muscles from adult rats. Each preparation performed three contraction protocols: (i) low-frequency afterloaded isotonic contractions (10 twitches at 0.2 Hz), (ii) sinusoidal length change contractions with phasic stimulation (40 twitches at 2 Hz) and (iii) high-frequency afterloaded isotonic contractions (40 twitches at 2 Hz). The first two protocols resembled those used in previous studies and the third combined the characteristics of the first two. The parameters for each protocol were adjusted to those that gave maximum efficiency. For the afterloaded isotonic protocols, the afterload was set to 0.3 of the maximum developed force. The sinusoidal length change protocol incorporated a cycle amplitude of +/-5% resting length and a stimulus phase of -10 degrees. Measurements of force output, muscle length change and muscle temperature change were used to calculate the work and heat produced during and after each protocol. Net mechanical efficiency was defined as the proportion of the energy (enthalpy) liberated by the muscle that appeared as work. The efficiency in the low-frequency, isotonic contraction protocol was 21.1+/-1.4% (mean +/- s.e.m., N=6) and that in the sinusoidal protocol was 13.2+/-0.7%, consistent with previous results. This difference was not due to the higher frequency or greater number of twitches because efficiency in the high-frequency, isotonic protocol was 21.5+/-1.0%. Although these results apparently confirm that efficiency is protocol-dependent, additional experiments designed to measure work output unambiguously indicated that the method used to calculate work output in isotonic contractions overestimated actual work output. When net work output, which excludes work done by parallel elastic elements, rather than total work output was used to determine efficiency in afterloaded isotonic contractions, efficiency was similar to that for sinusoidal contractions. The maximum net mechanical efficiency of rat papillary muscles performing afterloaded isotonic or sinusoidal length change contractions was between 10 and 15%.

A user's guide for V174, a program using a finite difference method to analyze transonic flow over oscillating wings

NASA Technical Reports Server (NTRS)

Butler, T. D.; Weatherill, W. H.; Sebastian, J. D.; Ehlers, F. E.

1977-01-01

The design and usage of a pilot program using a finite difference method for calculating the pressure distributions over harmonically oscillating wings in transonic flow are discussed. The procedure used is based on separating the velocity potential into steady and unsteady parts and linearizing the resulting unsteady differential equation for small disturbances. The steady velocity potential which must be obtained from some other program, is required for input. The unsteady differential equation is linear, complex in form with spatially varying coefficients. Because sinusoidal motion is assumed, time is not a variable. The numerical solution is obtained through a finite difference formulation and a line relaxation solution method.

Hepatic lipidosis associated with cobalt deficiency in Omani goats.

PubMed

Johnson, E H; Muirhead, D E; Annamalai, K; King, G J; Al-Busaidy, R; Hameed, M S

1999-06-01

Livers from 36 of 684 (5.3%) apparently healthy goats examined at an abattoir in the greater Muscat area of Oman exhibited gross pathological findings characterized by extremely pale, friable, fatty livers encompassing the entire organ. Histopathologically, diffuse hepatic lipidosis and occasional bile duct proliferation were observed. Periodic acid Schiff-positive, diastase-resistant pigment was observed in the macrophages lining the sinusoids. These histopathological lesions were consistent with those characteristic of ovine white liver disease. Cobalt analysis revealed that normal livers had six times more cobalt and a 3-fold less fat content than those measured in the fatty livers. This is the first report of an association between cobalt deficiency and hepatic lipidosis in Omani goats.

A users guide for A344: A program using a finite difference method to analyze transonic flow over oscillating airfoils

NASA Technical Reports Server (NTRS)

Weatherill, W. H.; Ehlers, F. E.

1979-01-01

The design and usage of a pilot program for calculating the pressure distributions over harmonically oscillating airfoils in transonic flow are described. The procedure used is based on separating the velocity potential into steady and unsteady parts and linearizing the resulting unsteady differential equations for small disturbances. The steady velocity potential which must be obtained from some other program, was required for input. The unsteady equation, as solved, is linear with spatially varying coefficients. Since sinusoidal motion was assumed, time was not a variable. The numerical solution was obtained through a finite difference formulation and either a line relaxation or an out of core direct solution method.

A D'-type symbiotic binary in the planetary nebula SMP LMC 88

NASA Astrophysics Data System (ADS)

Iłkiewicz, Krystian; Mikołajewska, Joanna; Miszalski, Brent; Kozłowski, Szymon; Udalski, Andrzej

2018-05-01

SMP LMC 88 is one of the planetary nebulae (PNe) in the Large Magellanic Cloud. We identify in its spectrum Raman scattered O VI lines at 6825 and 7083 Å. This unambiguously classifies the central object of the nebula as a symbiotic star (SySt). We identified the cold component to be a K-type giant, making this the first D'-type (yellow) SySt discovered outside the Galaxy. The photometric variability in SMP LMC 88 resembles the orbital variability of Galactic D'-type SySt with its low amplitude and sinusoidal light-curve shape. The SySt classification is also supported by the He I diagnostic diagram.

Identification of Cell Surface Molecules Involved in Dystroglycan-Independent Lassa Virus Cell Entry

PubMed Central

Ströher, Ute; Ebihara, Hideki; Feldmann, Heinz

2012-01-01

Although O-mannosylated dystroglycan is a receptor for Lassa virus, a causative agent of Lassa fever, recent findings suggest the existence of an alternative receptor(s). Here we identified four molecules as receptors for Lassa virus: Axl and Tyro3, from the TAM family, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver and lymph node sinusoidal endothelial calcium-dependent lectin (LSECtin), from the C-type lectin family. These molecules enhanced the binding of Lassa virus to cells and mediated infection independently of dystroglycan. Axl- or Tyro3-mediated infection required intracellular signaling via the tyrosine kinase activity of Axl or Tyro3, whereas DC-SIGN- or LSECtin-mediated infection and binding were dependent on a specific carbohydrate and on ions. The identification of these four molecules as Lassa virus receptors advances our understanding of Lassa virus cell entry. PMID:22156524

Distinct bone marrow blood vessels differentially regulate haematopoiesis.

PubMed

Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

2016-04-21

Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

Hepatic perivascular epithelioid cell tumor (PEComa): a case report with a review of literatures

PubMed Central

Son, Hyun-Jin; Kang, Dong Wook; Kim, Joo Heon; Han, Hyun Young; Lee, Min Koo

2017-01-01

Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA). PMID:28288506

Hepatic perivascular epithelioid cell tumor (PEComa): a case report with a review of literatures.

PubMed

Son, Hyun-Jin; Kang, Dong Wook; Kim, Joo Heon; Han, Hyun Young; Lee, Min Koo

2017-03-01

Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA).

Measurement of minority-carrier drift mobility in solar cells using a modulated electron beam

NASA Technical Reports Server (NTRS)

Othmer, S.; Hopkins, M. A.

1980-01-01

A determination of diffusivity on solar cells is here reported which utilizes a one dimensional treatment of diffusion under sinusoidal excitation. An intensity-modulated beam of a scanning electron microscope was used as a source of excitation. The beam was injected into the rear of the cell, and the modulated component of the induced terminal current was recovered phase sensitively. A Faraday cup to measure the modulated component of beam current was mounted next to the sample, and connected to the same electronics. A step up transformer and preamplifier were mounted on the sample holder. Beam currents on the order of 400-pA were used in order to minimize effects of high injection. The beam voltage was 34-kV, and the cell bias was kept at 0-V.

Dual interface gratings design for absorption enhancement in thin crystalline silicon solar cells

NASA Astrophysics Data System (ADS)

Zhang, Jinqiannan; Yu, Zhongyuan; Liu, Yumin; Chai, Hongyu; Hao, Jing; Ye, Han

2017-09-01

We numerically study and analyze the light absorption enhancement in thin crystalline silicon solar cell with dual interface gratings. The structure combines the front dielectric nanowalls and the sinusoidal plasmonic grating at back reflector. We show that having specific interfaces with well-chosen period, fill factor and height can allow more efficient dielectric and plasmonic modes coupling into active layer and can improve the solar cell performance. For 1 μm active layer case, the optimal result for the proposed structure achieves short-circuit current of 23.6 mA/cm2, which performs over 50% better than flat solar cell structure, the short-circuit current of which is 15.5 mA/cm2. In addition, the active layer thickness and angular analysis show that the proposed structure maintains its advantage over flat structure.

Retrospective study of the effect of remifentanil use during labor on fetal heart rate patterns.

PubMed

Boterenbrood, Danne; Wassen, Martine M; Visser, Gerard H A; Nijhuis, Jan G

2018-01-01

To investigate possible associations between remifentanil and the appearance of sinusoidal heart rate patterns in fetuses, and neonatal outcomes. The present retrospective cohort study included data from patients at over 37 weeks of singleton or multiple pregnancies attending Zuyderland Medical Center, Sittard, the Netherlands, in labor between June 1, and August 31, 2015. Patient data were stratified by whether remifentanil was administered during delivery (remifentanil group) or not (control group), and fetal heart rate tracings were reviewed to identify sinusoidal heart rate patterns. The neonatal outcomes compared were 5-minute Apgar scores and umbilical artery pH. There were 119 patients included in the study; 60 in the remifentanil group and 59 in the control group. Tracings from 20 (33%) patients in the remifentanil group exhibited a sinusoidal heart rate pattern after remifentanil administration, compared with 5 (8%) patients in the control group (P=0.001). The median time before the onset of sinusoidal patterns after remifentanil administration was 12 minutes. No adverse neonatal outcomes were recorded in either group. Remifentanil use during labor was associated with the occurrence of sinusoidal heart rate patterns in the fetus; this was not associated with adverse neonatal outcomes. © 2017 International Federation of Gynecology and Obstetrics.

Age-Related Pseudocapillarization of the Liver Sinusoidal Endothelium Impairs the Hepatic Clearance of Acetaminophen in Rats

PubMed Central

Huizer-Pajkos, Aniko; Cogger, Victoria C.; McLachlan, Andrew J.; Le Couteur, David G.; Jones, Brett; de Cabo, Rafael; Hilmer, Sarah N.

2011-01-01

We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer 14C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pass through the liver was significantly increased in old rats (0.64 ± 0.04, old; 0.59 ± 0.05, young; p < .05). In old age, there was significant reduction of the intercompartmental rate constant k1 (0.34 ± 0.10s-1, old; 0.61 ± 0.38s-1, young; p < .05) and the permeability-surface area product for the transfer of acetaminophen across the sinusoidal endothelium (0.034 ± 0.006 mL/s/g, old; 0.048 ± 0.014 mL/s/g, young; p < .005). There was no difference in k3, the measure of sequestration of acetaminophen that reflects enzyme activity. Age-related pseudocapillarization of the liver sinusoid resulted in increased acetaminophen recovery and decreased transfer of acetaminophen into the liver. PMID:21300741

Liver-primed memory T cells generated under noninflammatory conditions provide anti-infectious immunity.

PubMed

Böttcher, Jan P; Schanz, Oliver; Wohlleber, Dirk; Abdullah, Zeinab; Debey-Pascher, Svenja; Staratschek-Jox, Andrea; Höchst, Bastian; Hegenbarth, Silke; Grell, Jessica; Limmer, Andreas; Atreya, Imke; Neurath, Markus F; Busch, Dirk H; Schmitt, Edgar; van Endert, Peter; Kolanus, Waldemar; Kurts, Christian; Schultze, Joachim L; Diehl, Linda; Knolle, Percy A

2013-03-28

Development of CD8(+) T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling through the TCR, CD28, and IL-12R and controlled bacterial and viral infections. Gene expression profiling identified liver-primed T cells as a distinct Neuropilin-1(+) memory population. Generation of liver-primed memory T cells may prevent pathogens that avoid DC maturation by innate immune escape from also escaping adaptive immunity through attrition of the T cell repertoire. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Electron density in surface barrier discharge emerging at argon/water interface: quantification for streamers and leaders

NASA Astrophysics Data System (ADS)

Cvetanović, Nikola; Galmiz, Oleksandr; Synek, Petr; Zemánek, Miroslav; Brablec, Antonín; Hoder, Tomáš

2018-02-01

Optical emission spectroscopy, fast intensified CCD imaging and electrical measurements were applied to investigate the basic plasma parameters of surface barrier discharge emerging from a conductive water electrode. The discharge was generated at the triple-line interface of atmospheric pressure argon gas and conductive water solution at the fused silica dielectrics using a sinusoidal high-voltage waveform. The spectroscopic methods of atomic line broadening and molecular spectroscopy were used to determine the electron densities and the gas temperature in the active plasma. These parameters were obtained for both applied voltage polarities and resolved spatially. Two different spectral signatures were identified in the spatially resolved spectra resulting in electron densities differing by two orders of magnitude. It is shown that two discharge mechanisms take a place: the streamer and the leader one, with electron densities of 1014 and 1016 cm-3, respectively. This spectroscopic evidence is supported by the combined diagnostics of electrical current measurements and phase-resolved intensified CCD camera imaging.

Novel high-frequency, high-power, pulsed oscillator based on a transmission line transformer.

PubMed

Burdt, R; Curry, R D

2007-07-01

Recent analysis and experiments have demonstrated the potential for transmission line transformers to be employed as compact, high-frequency, high-power, pulsed oscillators with variable rise time, high output impedance, and high operating efficiency. A prototype system was fabricated and tested that generates a damped sinusoidal wave form at a center frequency of 4 MHz into a 200 Omega load, with operating efficiency above 90% and peak power on the order of 10 MW. The initial rise time of the pulse is variable and two experiments were conducted to demonstrate initial rise times of 12 and 3 ns, corresponding to a spectral content from 4-30 and from 4-100 MHz, respectively. A SPICE model has been developed to accurately predict the circuit behavior and scaling laws have been identified to allow for circuit design at higher frequencies and higher peak power. The applications, circuit analysis, test stand, experimental results, circuit modeling, and design of future systems are all discussed.

Radiative Amplification of Acoustic Waves in Hot Stars

NASA Technical Reports Server (NTRS)

Wolf, B. E.

1985-01-01

The discovery of broad P Cygni profiles in early type stars and the detection of X-rays emitted from the envelopes of these stars made it clear, that a considerable amount of mechanical energy has to be present in massive stars. An attack on the problem, which has proven successful when applied to late type stars is proposed. It is possible that acoustic waves form out of random fluctuations, amplify by absorbing momentum from stellar radiation field, steepen into shock waves and dissipate. A stellar atmosphere was constructed, and sinusoidal small amplitude perturbations of specified Mach number and period at the inner boundary was introduced. The partial differential equations of hydrodynamics and the equations of radiation transfer for grey matter were solved numerically. The equation of motion was augmented by a term which describes the absorption of momentum from the radiation field in the continuum and in lines, including the Doppler effect and allows for the treatment of a large number of lines in the radiative acceleration term.

Waveshaping electronic circuit

NASA Technical Reports Server (NTRS)

Harper, T. P.

1971-01-01

Circuit provides output signal with sinusoidal function in response to bipolar transition of input signal. Instantaneous transition shapes into linear rate of change and linear rate of change shapes into sinusoidal rate of change. Circuit contains only active components; therefore, compatibility with integrated circuit techniques is assured.

High-density CMOS Microelectrode Array System for Impedance Spectroscopy and Imaging of Biological Cells.

PubMed

Vijay, Viswam; Raziyeh, Bounik; Amir, Shadmani; Jelena, Dragas; Alicia, Boos Julia; Axel, Birchler; Jan, Müller; Yihui, Chen; Andreas, Hierlemann

2017-01-26

A monolithic measurement platform was implemented to enable label-free in-vitro electrical impedance spectroscopy measurements of cells on multi-functional CMOS microelectrode array. The array includes 59,760 platinum microelectrodes, densely packed within a 4.5 mm × 2.5 mm sensing region at a pitch of 13.5 μm. The 32 on-chip lock-in amplifiers can be used to measure the impedance of any arbitrarily chosen electrodes on the array by applying a sinusoidal voltage, generated by an on-chip waveform generator with a frequency range from 1 Hz to 1 MHz, and measuring the respective current. Proof-of-concept measurements of impedance sensing and imaging are shown in this paper. Correlations between cell detection through optical microscopy and electrochemical impedance scanning were established.

TNF-induced target cell killing by CTL activated through cross-presentation.

PubMed

Wohlleber, Dirk; Kashkar, Hamid; Gärtner, Katja; Frings, Marianne K; Odenthal, Margarete; Hegenbarth, Silke; Börner, Carolin; Arnold, Bernd; Hämmerling, Günter; Nieswandt, Bernd; van Rooijen, Nico; Limmer, Andreas; Cederbrant, Karin; Heikenwalder, Mathias; Pasparakis, Manolis; Protzer, Ulrike; Dienes, Hans-Peter; Kurts, Christian; Krönke, Martin; Knolle, Percy A

2012-09-27

Viruses can escape cytotoxic T cell (CTL) immunity by avoiding presentation of viral components via endogenous MHC class I antigen presentation in infected cells. Cross-priming of viral antigens circumvents such immune escape by allowing noninfected dendritic cells to activate virus-specific CTLs, but they remain ineffective against infected cells in which immune escape is functional. Here, we show that cross-presentation of antigen released from adenovirus-infected hepatocytes by liver sinusoidal endothelial cells stimulated cross-primed effector CTLs to release tumor necrosis factor (TNF), which killed virus-infected hepatocytes through caspase activation. TNF receptor signaling specifically eliminated infected hepatocytes that showed impaired anti-apoptotic defense. Thus, CTL immune surveillance against infection relies on two similarly important but distinct effector functions that are both MHC restricted, requiring either direct antigen recognition on target cells and canonical CTL effector function or cross-presentation and a noncanonical effector function mediated by TNF. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

A perisinusoidal niche for extramedullary haematopoiesis in the spleen.

PubMed

Inra, Christopher N; Zhou, Bo O; Acar, Melih; Murphy, Malea M; Richardson, James; Zhao, Zhiyu; Morrison, Sean J

2015-11-26

Haematopoietic stresses mobilize haematopoietic stem cells (HSCs) from the bone marrow to the spleen and induce extramedullary haematopoiesis (EMH). However, the cellular nature of the EMH niche is unknown. Here we assessed the sources of the key niche factors, SCF (also known as KITL) and CXCL12, in the mouse spleen after EMH induction by myeloablation, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21(+) stromal cells, primarily around sinusoids in the red pulp, while Cxcl12 was expressed by a subset of Tcf21(+) stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21(+) stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells, or of Scf or Cxcl12 from Tcf21+ stromal cells, severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow haematopoiesis. Endothelial cells and Tcf21(+) stromal cells thus create a perisinusoidal EMH niche in the spleen, which is necessary for the physiological response to diverse haematopoietic stresses.

Plasma characteristics in non-sinusoidally excited CCP discharges

NASA Astrophysics Data System (ADS)

Lafleur, Trevor; Booth, Jean-Paul

2012-10-01

Using particle-in-cell (PIC) simulations we perform a characterization of the plasma response to positive pulse-type voltage excitations (with a repetition frequency of 13.56 MHz) in a geometrically symmetric CCP reactor (with a gap length of 2 cm) operated with argon (for pressures between 20-500 mTorr). Use of these non-sinusoidal waveforms generates an electrical asymmetry effect in the system, which necessitates the formation of a DC bias. This DC bias, together with the shape of the voltage waveforms used, produces a number of new phenomena that are not present in typical sinusoidal discharges: (1) the plasma density and ion flux can be increased as the pulse width is reduced, (2) a significant asymmetry in the ion fluxes to the powered and grounded electrodes develops as the pressure increases, (3) the average ion energy striking the grounded electrode remains low and approximately constant as the pulse width decreases, and (4) the sheath at the grounded electrode never fully collapses; electrons are no longer lost in sharp pulses, but escape essentially throughout the rf cycle. Effects (1) and (3) above offer the possibility for a new form of control in these types of discharges, where the ion flux can be increased while the ion energy on the grounded electrode can be kept small and essentially constant. This effect has recently been exploited to control the crystallinity of silicon thin films [1], where the low ion bombarding energy was found to improve the quality of films grown. [4pt] [1] Johnson E V, Pouliquen S, Delattre P A, and Booth J P, J. Non-Cryst. Solids 2012, in press.

Development of Multi-Functional Voltage Restore System

NASA Astrophysics Data System (ADS)

Suzuki, Satoshi; Ueda, Yoshinobu; Koganezawa, Takehisa; Ogihara, Yoshinori; Mori, Kenjiro; Fukazu, Naoaki

Recently, with the dawn of the electric deregulation, the installation of distributed generation with power electronics device has grown. This current causes a greater concern of power quality, primarily voltage disturbance for power companies, and their interest in power quality is peaking. Utilities are also interested in keeping their customers satisfied, as well as keeping them on-line and creating more revenue for the utility. As a countermeasure against the above surroundings, a variety type of devices based on power electronics has been developed to protect customers' load from power line voltage disturbance. One of them is the series type voltage restore. The series device is an active device, designed to provide a pure sinusoidal load voltage at all times, correcting voltage disturbance. Series type device compensates for voltage anomalies by inserting the ‘missing’ voltage onto the line through insertion transformer and inverter. This paper shows the setting guideline of target level to compensate voltage disturbance, that is, voltage dip, voltage harmonics, voltage imbalance and voltage flicker, and the design approach of the prototype of series voltage restores to accomplish the required compensation level. The prototype system gives satisfactory compensation performance through evaluation tests, which confirm the validity and effectiveness of the system.

No X-Ray Excess from the HESS J1741-302 Region, except for a New Intermediate Polar Candidate

NASA Astrophysics Data System (ADS)

Uchiyama, Hideki; Koyama, Katsuji; Matsumoto, Hironori; Tibolla, Omar; Kaufmann, Sarah; Wagner, Stefan

2011-11-01

With the Suzaku satellite, we observed an unidentified TeV gamma-ray source, HESS J1741-302, and its surroundings. No diffuse or point-like X-ray sources have been detected from the bright southern emission peak of HESS J1741-302. From its neighborhood, we found a new intermediate polar candidate at the position of (α, δ)J2000.0 = (17h40m35.s6, -30°14m16s), which is designated as Suzaku J174035.6-301416. The spectrum of Suzaku J174035.6-301416 exhibits emission lines at energy of 6.4, 6.7, and 7.0 keV, which can be assigned as the Kα lines from neutral, He-like, and H-like iron, respectively. A coherent pulsation is found at a period of 432.1±0.1s. The pulse profile is quasi-sinusoidal in the hard X-ray band (4-8 keV), but is more complicated in the soft X-ray band (1-3 keV). The moderate period of pulsation, the energy flux, and the presence of the iron Kα lines indicate that Suzaku J174035.6-302 and PSR B1737-30.

Gram-Schmidt orthonormalization for retrieval of amplitude images under sinusoidal patterns of illumination

USDA-ARS?s Scientific Manuscript database

Structured illumination using sinusoidal patterns has been utilized for optical imaging of biological tissues in biomedical research and, of horticultural products. Implementation of structured-illumination imaging relies on retrieval of amplitude images, which is conventionally achieved by a phase-...

Partially coherent surface plasmon modes

NASA Astrophysics Data System (ADS)

Niconoff, G. M.; Vara, P. M.; Munoz-Lopez, J.; Juárez-Morales, J. C.; Carbajal-Dominguez, A.

2011-04-01

Elementary long-range plasmon modes are described assuming an exponential dependence of the refractive index in the neighbourhood of the interface dielectric-metal thin film. The study is performed using coupling mode theory. The interference between two long-range plasmon modes generated that way allows the synthesis of surface sinusoidal plasmon modes, which can be considered as completely coherent generalized plasmon modes. These sinusoidal plasmon modes are used for the synthesis of new partially coherent surface plasmon modes, which are obtained by means of an incoherent superposition of sinusoidal plasmon modes where the period of each one is considered as a random variable. The kinds of surface modes generated have an easily tuneable profile controlled by means of the probability density function associated to the period. We show that partially coherent plasmon modes have the remarkable property to control the length of propagation which is a notable feature respect to the completely coherent surface plasmon mode. The numerical simulation for sinusoidal, Bessel, Gaussian and Dark Hollow plasmon modes are presented.

An experimental study on flow friction and heat transfer of water in sinusoidal wavy silicon microchannels

NASA Astrophysics Data System (ADS)

Huang, Houxue; Wu, Huiying; Zhang, Chi

2018-05-01

Sinusoidal wavy microchannels have been known as a more heat transfer efficient heat sink for the cooling of electronics than normal straight microchannels. However, the existing experimental study on wavy silicon microchannels with different phase differences are few. As a result of this, in this paper an experimental study has been conducted to investigate the single phase flow friction and heat transfer of de-ionized water in eight different sinusoidal wavy silicon microchannels (SWSMCs) and one straight silicon microchannel (SMC). The SWSMCs feature different phase differences (α  =  0 to π) and different relative wavy amplitudes (β  =  A/l  =  0.05 to 0.4), but the same average hydraulic diameters (D h  =  160 µm). It is found that both flow friction constant fRe and the Nusselt number depend on the phase difference and relative wavy amplitude. For sinusoidal wavy microchannels with a relative wavy amplitude (β  =  0.05), the Nusselt number increased noticeably with the phase difference for Re  >  250, but the effect was insignificant for Re  <  250 however, both pressure drop and apparent flow friction constant fRe increased with the increase in phase difference. For sinusoidal wavy microchannels with 0 phase difference, the increase in relative wavy amplitude obtained by reducing the wavy wave length induced higher pressure drop and apparent friction constant fRe, while the Nusselt number increased with relative wavy amplitude for Re  >  300. The results indicate that the thermal resistances of sinusoidal wavy silicon microchannels were generally lower than that of straight silicon microchannels, and the thermal resistance decreased with the increase in relative wavy amplitude. The enhancement of thermal performance is attributed to the flow re-circulation occurring in the corrugation troughs and the secondary flows or Dean vortices introduced by curved channels. It is concluded that silicon sinusoidal wavy microchannels provide higher heat transfer rate albeit with a higher flow friction, making it a better choice for the cooling of high heat flux electronics.

Noise in any frequency range can enhance information transmission in a sensory neuron

NASA Astrophysics Data System (ADS)

Levin, Jacob E.

1997-05-01

The effect of noise on the neural encoding of broadband signals was investigated in the cricket cercal system, a mechanosensory system sensitive to small near-field air particle disturbances. Known air current stimuli were presented to the cricket through audio speakers in a controlled environment in a variety of background noise conditions. Spike trains from the second layer of neuronal processing, the primary sensory interneurons, were recorded with intracellular Electrodes and the performance of these neurons characterized with the tools of information theory. SNR, mutual information rates, and other measures of encoding accuracy were calculated for single frequency, narrowband, and broadband signals over the entire amplitude sensitivity range of the cells, in the presence of uncorrelated noise background also spanning the cells' frequency and amplitude sensitivity range. Significant enhancements of transmitted information through the addition of external noise were observed regardless of the frequency range of either the signal or noise waveforms, provided both were within the operating range of the cell. Considerable improvements in signal encoding were observed for almost an entire order of magnitude of near-threshold signal amplitudes. This included sinusoidal signals embedded in broadband white noise, broadband signals in broadband noise, and even broadband signals presented with narrowband noise in a completely non-overlapping frequency range. The noise related increases in mutual information rate for broadband signals were as high as 150%, and up to 600% increases in SNR were observed for sinusoidal signals. Additionally, it was shown that the amount of information about the signal carried, on average, by each spike was INCREASED for small signals when presented with noise—implying that added input noise can, in certain situations, actually improve the accuracy of the encoding process itself.

Defibrotide for the management of sinusoidal obstruction syndrome in patients who undergo haemopoietic stem cell transplantation.

PubMed

Coutsouvelis, John; Avery, Sharon; Dooley, Michael; Kirkpatrick, Carl; Spencer, Andrew

2016-11-01

Sinusoidal obstruction syndrome, previously known as veno-occlusive disease (VOD/SOS), is a complication in patients undergoing haemopoietic stem cell transplantation (HSCT). Severe VOD/SOS, including progression to multi-organ failure, has resulted in a mortality of greater than 80%. Defibrotide's varying pharmacological actions, particularly on endothelial cells, make it is a useful agent to consider for prophylaxis and treatment of VOD/SOS. Barriers to its routine use include the high acquisition cost and the fact that neither the oral or parenteral formulations are licensed products in many countries at this time. This review summarises available literature on the use of defibrotide in the management of VOD/SOS. Publications consist predominantly of single centre cohort studies and case series. Available evidence indicates that defibrotide is effective in the management of VOD/SOS. Using defibrotide prophylaxis should also be considered, especially in the paediatric setting, where there are available results from a large, open label, randomized controlled trial. Patient outcome data from the larger studies and compassionate programs can inform consensus recommendations on dosing regimen and criteria for the treatment of VOD/SOS with defibrotide in the adult population. The reviewed literature indicates an effective and safe dose for treatment is 25mg/kg/day, continued for at least 14days or until complete response is achieved. Further studies are required to determine the optimal dose and duration of treatment in both paediatric patients and adults. Recent recommendations and a phase 3 trial using historical controls indicate that defibrotide should be included as a pharmacotherapy option in protocols guiding management of VOD/SOS. Copyright © 2016 Elsevier Ltd. All rights reserved.

The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.

PubMed

Schwabl, Philipp; Hambruch, Eva; Seeland, Berit A; Hayden, Hubert; Wagner, Michael; Garnys, Lukas; Strobel, Bastian; Schubert, Tim-Lukas; Riedl, Florian; Mitteregger, Dieter; Burnet, Michael; Starlinger, Patrick; Oberhuber, Georg; Deuschle, Ulrich; Rohr-Udilova, Nataliya; Podesser, Bruno K; Peck-Radosavljevic, Markus; Reiberger, Thomas; Kremoser, Claus; Trauner, Michael

2017-04-01

Steroidal farnesoid X receptor (FXR) agonists demonstrated potent anti-fibrotic activities and lowered portal hypertension in experimental models. The impact of the novel non-steroidal and selective FXR agonist PX20606 on portal hypertension and fibrosis was explored in this study. In experimental models of non-cirrhotic (partial portal vein ligation, PPVL, 7days) and cirrhotic (carbon tetrachloride, CCl 4 , 14weeks) portal hypertension, PX20606 (PX,10mg/kg) or the steroidal FXR agonist obeticholic acid (OCA,10mg/kg) were gavaged. We then measured portal pressure, intrahepatic vascular resistance, liver fibrosis and bacterial translocation. PX decreased portal pressure in non-cirrhotic PPVL (12.6±1.7 vs. 10.4±1.1mmHg; p=0.020) and cirrhotic CCl 4 (15.2±0.5 vs. 11.8±0.4mmHg; p=0.001) rats. In PPVL animals, we observed less bacterial translocation (-36%; p=0.041), a decrease in lipopolysaccharide binding protein (-30%; p=0.024) and splanchnic tumour necrosis factor α levels (-39%; p=0.044) after PX treatment. In CCl 4 rats, PX decreased fibrotic Sirius Red area (-43%; p=0.005), hepatic hydroxyproline (-66%; p<0.001), and expression of profibrogenic proteins (Col1a1, α smooth muscle actin, transforming growth factor β). CCl 4 -PX rats had significantly lower transaminase levels and reduced hepatic macrophage infiltration. Moreover, PX induced sinusoidal vasodilation (upregulation of cystathionase, dimethylaminohydrolase (DDAH)1, endothelial nitric oxide synthase (eNOS), GTP-cyclohydrolase1) and reduced intrahepatic vasoconstriction (downregulation of endothelin-1, p-Moesin). In cirrhosis, PX improved endothelial dysfunction (decreased von-Willebrand factor) and normalized overexpression of vascular endothelial growth factor, platelet-derived growth factor and angiopoietins. While short-term 3-day PX treatment reduced portal pressure (-14%; p=0.041) by restoring endothelial function, 14week PX therapy additionally inhibited sinusoidal remodelling and decreased portal pressure to a greater extent (-22%; p=0.001). In human liver sinusoidal endothelial cells, PX increased eNOS and DDAH expression. The non-steroidal FXR agonist PX20606 ameliorates portal hypertension by reducing liver fibrosis, vascular remodelling and sinusoidal dysfunction. The novel drug PX20606 activates the bile acid receptor FXR and shows beneficial effects in experimental liver cirrhosis: In the liver, it reduces scarring and inflammation, and also widens blood vessels. Thus, PX20606 leads to an improved blood flow through the liver and decreases hypertension of the portal vein. Additionally, PX20606 improves the altered intestinal barrier and decreases bacterial migration from the gut. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Nitric oxide-mediated inhibition of taurocholate uptake involves S-nitrosylation of NTCP.

PubMed

Schonhoff, Christopher M; Ramasamy, Umadevi; Anwer, M Sawkat

2011-02-01

The sodium-taurocholate (TC) cotransporting polypeptide (NTCP) facilitates bile formation by mediating sinusoidal Na(+)-TC cotransport. During sepsis-induced cholestasis, there is a decrease in NTCP-dependent uptake of bile acids and an increase in nitric oxide (NO) levels in hepatocytes. In rat hepatocytes NO inhibits Na(+)-dependent uptake of taurocholate. The aim of this study was to extend these findings to human NTCP and to further investigate the mechanism by which NO inhibits TC uptake. Using a human hepatoma cell line stably expressing NTCP (HuH-NTCP), we performed experiments with the NO donors sodium nitroprusside and S-nitrosocysteine and demonstrated that NO inhibits TC uptake in these cells. Kinetic analyses revealed that NO significantly decreased the V(max) but not the K(m) of TC uptake by NTCP, indicating noncompetitive inhibition. NO decreased the amount of NTCP in the plasma membrane, providing a molecular mechanism for the noncompetitive inhibition of TC uptake. One way that NO can modify protein function is through a posttranslational modification known as S-nitrosylation: the binding of NO to cysteine thiols. Using a biotin switch technique we observed that NTCP is S-nitrosylated under conditions in which NO inhibits TC uptake. Moreover, dithiothreitol reversed NO-mediated inhibition of TC uptake and S-nitrosylation of NTCP, indicating that NO inhibits TC uptake via modification of cysteine thiols. In addition, NO treatment led to a decrease in Ntcp phosphorylation. Taken together these results indicate that the inhibition of TC uptake by NO involves S-nitrosylation of NTCP.

The influence of modulated sinusoidal current on the state of chromatin from neurons of the cerebral cortex of rats in hypokinesia

NASA Technical Reports Server (NTRS)

Sokolova, Z. A.

1980-01-01

The biochemical changes under the influence of modulated sinusoidal current in the central nervous system were investigated. The methodology used is discussed, the results are reported in a table, and conclusions are presented.

EFFECTS OF CONTINUOUS-WAVE, PULSED, AND SINUSOIDAL-AMPLITUDE-MODULATED MICROWAVES ON BRAIN ENERGY METABOLISM

EPA Science Inventory

A comparison of the effects of continuous wave, sinusoidal-amplitude modulated, and pulsed square-wave-modulated 591-MHz microwave exposures on brain energy metabolism was made in male Sprague Dawley rats (175-225g). Brain NADH fluorescence, adensine triphosphate (ATP) concentrat...

Biodistribution of small interfering RNA at the organ and cellular levels after lipid nanoparticle-mediated delivery.

PubMed

Shi, Bin; Keough, Ed; Matter, Andrea; Leander, Karen; Young, Stephanie; Carlini, Ed; Sachs, Alan B; Tao, Weikang; Abrams, Marc; Howell, Bonnie; Sepp-Lorenzino, Laura

2011-08-01

Chemically stabilized small interfering RNA (siRNA) can be delivered systemically by intravenous injection of lipid nanoparticles (LNPs) in rodents and primates. The biodistribution and kinetics of LNP-siRNA delivery in mice at organ and cellular resolution have been studied using immunofluorescence (IF) staining and quantitative polymerase chain reaction (qPCR). At 0.5 and 2 hr post tail vein injection of Cy5-labeled siRNA encapsulated in LNP, the organ rank-order of siRNA levels is liver > spleen > kidney, with only negligible accumulation in duodenum, lung, heart, and brain. Similar conclusions were drawn by using qPCR to measure tissue siRNA levels as a secondary end point. siRNA levels in these tissues decreased by more than 10-fold after 24 hr. Within the liver, LNPs delivered siRNA to hepatocytes, Kupffer cells, and sinusoids in a time-dependent manner, as revealed by IF staining and signal quantitation methods established using OPERA/Columbus software. siRNA first accumulated in liver sinusoids and trafficked to hepatocytes by 2 hr post dose, corresponding to the onset of target mRNA silencing. Fluorescence in situ hybridization methods were used to detect both strands of siRNA in fixed tissues. Collectively, the authors have implemented a platform to evaluate biodistribution of siRNA across cell types and across tissues in vivo, with the objective of elucidating the pharmacokinetic and pharmacodynamic relationship to guide optimization of delivery vehicles. © The Author(s) 2011

Biodistribution of Small Interfering RNA at the Organ and Cellular Levels after Lipid Nanoparticle-mediated Delivery

PubMed Central

Shi, Bin; Keough, Ed; Matter, Andrea; Leander, Karen; Young, Stephanie; Carlini, Ed; Sachs, Alan B.; Tao, Weikang; Abrams, Marc; Howell, Bonnie; Sepp-Lorenzino, Laura

2011-01-01

Chemically stabilized small interfering RNA (siRNA) can be delivered systemically by intravenous injection of lipid nanoparticles (LNPs) in rodents and primates. The biodistribution and kinetics of LNP–siRNA delivery in mice at organ and cellular resolution have been studied using immunofluorescence (IF) staining and quantitative polymerase chain reaction (qPCR). At 0.5 and 2 hr post tail vein injection of Cy5-labeled siRNA encapsulated in LNP, the organ rank-order of siRNA levels is liver > spleen > kidney, with only negligible accumulation in duodenum, lung, heart, and brain. Similar conclusions were drawn by using qPCR to measure tissue siRNA levels as a secondary end point. siRNA levels in these tissues decreased by more than 10-fold after 24 hr. Within the liver, LNPs delivered siRNA to hepatocytes, Kupffer cells, and sinusoids in a time-dependent manner, as revealed by IF staining and signal quantitation methods established using OPERA/Columbus software. siRNA first accumulated in liver sinusoids and trafficked to hepatocytes by 2 hr post dose, corresponding to the onset of target mRNA silencing. Fluorescence in situ hybridization methods were used to detect both strands of siRNA in fixed tissues. Collectively, the authors have implemented a platform to evaluate biodistribution of siRNA across cell types and across tissues in vivo, with the objective of elucidating the pharmacokinetic and pharmacodynamic relationship to guide optimization of delivery vehicles. PMID:21804077

Gemtuzumab ozogamicin-induced sinusoidal obstructive syndrome treated with defibrotide: a case report.

PubMed

Lannoy, D; Decaudin, B; Grozieux de Laguérenne, A; Barrier, F; Pignon, J M; Wetterwald, M; Odou, P

2006-08-01

New treatments for relapse of acute myeloid leukaemia (AML), include gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody. We describe a second case of GO-induced sinusoidal obstructive syndrome (SOS) effectively treated with defibrotide (DF). No stem-cell transplantation was involved. On day 23 after the first GO dose, a patient presented with ascites, weight gain, liver enlargement and pain in the right upper quadrant. Sudden hepatic cytolysis (transaminases at six times the normal range: grade 3) and cholestasis [alkaline phosphatase ALP and gamma-glutamyltransferase (GGT) respectively at four and eight times the normal range: grade 2] were observed but there was no evidence of increase serum bilirubin. Treatment with DF (Prociclide), Crinos; 10 mg/kg/day, or 200 mg, q.i.d.) improved the hepatic abnormality within a few days (serum transaminases decreased from 312 to 103 IU/L for aspartate aminotransferase (AST) and from 141 to 80 IU/L for alanine aminotransferase (ALT) within 3 days ALP increased from 253 to 383 IU/L and gamma-GT from 238 to 417 IU/L 4 days after administration of DF. The clinical and biological features of our case suggest a direct involvement of GO in causing SOS, even when used as monotherapy, without allogenic stem-cell transplantation. Low dose DF (10 mg/kg/day) given early during the development of SOS associated with GO was effective. Unfortunately, in our case the patient eventually died of multi-organ failure probably because of failure of GO.

The reliability of nonlinear least-squares algorithm for data analysis of neural response activity during sinusoidal rotational stimulation in semicircular canal neurons.

PubMed

Ren, Pengyu; Li, Bowen; Dong, Shiyao; Chen, Lin; Zhang, Yuelin

2018-01-01

Although many mathematical methods were used to analyze the neural activity under sinusoidal stimulation within linear response range in vestibular system, the reliabilities of these methods are still not reported, especially in nonlinear response range. Here we chose nonlinear least-squares algorithm (NLSA) with sinusoidal model to analyze the neural response of semicircular canal neurons (SCNs) during sinusoidal rotational stimulation (SRS) over a nonlinear response range. Our aim was to acquire a reliable mathematical method for data analysis under SRS in vestibular system. Our data indicated that the reliability of this method in an entire SCNs population was quite satisfactory. However, the reliability was strongly negatively depended on the neural discharge regularity. In addition, stimulation parameters were the vital impact factors influencing the reliability. The frequency had a significant negative effect but the amplitude had a conspicuous positive effect on the reliability. Thus, NLSA with sinusoidal model resulted a reliable mathematical tool for data analysis of neural response activity under SRS in vestibular system and more suitable for those under the stimulation with low frequency but high amplitude, suggesting that this method can be used in nonlinear response range. This method broke out of the restriction of neural activity analysis under nonlinear response range and provided a solid foundation for future study in nonlinear response range in vestibular system.

The reliability of nonlinear least-squares algorithm for data analysis of neural response activity during sinusoidal rotational stimulation in semicircular canal neurons

PubMed Central

Li, Bowen; Dong, Shiyao; Chen, Lin; Zhang, Yuelin

2018-01-01

Although many mathematical methods were used to analyze the neural activity under sinusoidal stimulation within linear response range in vestibular system, the reliabilities of these methods are still not reported, especially in nonlinear response range. Here we chose nonlinear least-squares algorithm (NLSA) with sinusoidal model to analyze the neural response of semicircular canal neurons (SCNs) during sinusoidal rotational stimulation (SRS) over a nonlinear response range. Our aim was to acquire a reliable mathematical method for data analysis under SRS in vestibular system. Our data indicated that the reliability of this method in an entire SCNs population was quite satisfactory. However, the reliability was strongly negatively depended on the neural discharge regularity. In addition, stimulation parameters were the vital impact factors influencing the reliability. The frequency had a significant negative effect but the amplitude had a conspicuous positive effect on the reliability. Thus, NLSA with sinusoidal model resulted a reliable mathematical tool for data analysis of neural response activity under SRS in vestibular system and more suitable for those under the stimulation with low frequency but high amplitude, suggesting that this method can be used in nonlinear response range. This method broke out of the restriction of neural activity analysis under nonlinear response range and provided a solid foundation for future study in nonlinear response range in vestibular system. PMID:29304173

Multi-speed multi-phase resolver converter

NASA Technical Reports Server (NTRS)

Alhorn, Dean (Inventor); Howard, David (Inventor)

1994-01-01

A multiphase converter circuit generates a plurality of sinusoidal outputs of displaced phase and given speed value from the output of an angular resolver system attachable to a motor excited by these multi-phase outputs, the resolver system having a lower speed value than that of the motor. The angular resolver system provides in parallel format sequential digital numbers indicative of the amount of rotation of the shaft of an angular position sensor associated with the angular resolver system. These numbers are used to excite simultaneously identical addresses of a plurality of addressable memory systems, each memory system having stored therein at sequential addresses sequential values of a sinusoidal wavetrain of a given number of sinusoids. The stored wavetrain values represent sinusoids displaced from each other in phase according to the number of output phases desired. A digital-to-analog converter associated with each memory system converts each accessed word to a corresponding analog value to generate attendant to rotation of the angular resolver a sinusoidal wave of proper phase at each of the plurality of outputs. By properly orienting the angular resolver system with respect to the rotor of the motor, essentially ripple-free torque is supplied to the rotor. The angular resolver system may employ an analog resolver feeding an integrated circuit resolver-to-digital converter to produce the requisite digital values serving as addresses. Alternative versions employing incremental or absolute encoders are also described.

Multi-speed multi-phase resolver converter

NASA Technical Reports Server (NTRS)

Alhorn, Dean C. (Inventor); Howard, David E. (Inventor)

1995-01-01

A multiphase converter circuit generates a plurality of sinusoidal outputs of displaced phase and given speed value from the output of an angular resolver system attachable to a motor excited by these multi-phase outputs, the resolver system having a lower speed value than that of the motor. The angular resolver system provides in parallel format sequential digital numbers indicative of the amount of rotation of the shaft of an angular position sensor associated with the angular resolver system. These numbers are used to excite simultaneously identical addresses of a plurality of addressable memory systems, each memory system having stored therein at sequential addresses sequential values of a sinusoidal wavetrain of a given number of sinusoids. The stored wavetrain values represent sinusoids displaced from each other in phase according to the number of output phases desired. A digital-to-analog converter associated with each memory system converts each accessed word to a corresponding analog value to generate attendant to rotation of the angular resolver a sinusoidal wave of proper phase at each of the plurality of outputs. By properly orienting the angular resolver system with respect to the rotor of the motor, essentially ripple-free torque is supplied to the rotor. The angular resolver system may employ an analog resolver feeding an integrated circuit resolver-to-digital converter to produce the requisite digital values serving as addresses. Alternative versions employing incremental or absolute encoders are also described.

Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis

PubMed Central

Bleau, Christian; Filliol, Aveline; Samson, Michel

2016-01-01

ABSTRACT Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. IMPORTANCE Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis. PMID:27489277

Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during Acute Hepatitis.

PubMed

Bleau, Christian; Filliol, Aveline; Samson, Michel; Lamontagne, Lucie

2016-10-15

Under physiological conditions, the liver sinusoidal endothelial cells (LSECs) mediate hepatic immune tolerance toward self or foreign antigens through constitutive expression of anti-inflammatory mediators. However, upon viral infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve proinflammatory functions, but their role in hepatic inflammation during acute viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type 3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC infection on their proinflammatory profiles and the aggravation of acute hepatitis process. In vivo infection with virulent MHV3, in comparison to attenuated strains, resulted in fulminant hepatitis associated with higher hepatic viral load, tissue necrosis, and levels of inflammatory mediators and earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders correlated with disturbed production of interleukin-10 (IL-10) and vascular factors by LSECs. We next showed in vitro that infection of LSECs by the virulent MHV3 strain altered their production of anti-inflammatory cytokines and promoted higher release of proinflammatory and procoagulant factors and earlier cell damage than infection by attenuated strains. This higher replication and proinflammatory activation in LSECs by the virulent MHV3 strain was associated with a specific activation of TLR2 signaling by the virus. We provide evidence that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic inflammation and correlates with the severity of hepatitis. Taken together, these results indicate that preservation of the immunotolerant properties of LSECs during acute viral hepatitis is imperative in order to limit hepatic inflammation and damage. Viral hepatitis B and C infections are serious health problems affecting over 350 million and 170 million people worldwide, respectively. It has been suggested that a balance between protection and liver damage mediated by the host's immune response during the acute phase of infection would be determinant in hepatitis outcome. Thus, it appears crucial to identify the factors that predispose in exacerbating liver inflammation to limit hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both anti- and proinflammatory functions, but their role in acute viral hepatitis has never been investigated. Using mouse hepatitis virus (MHV) infections as animal models of viral hepatitis, we report for the first time that in vitro and in vivo infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to as disorders in vascular factors, correlating with the severity of hepatitis. These results highlight a new virus-promoted mechanism of exacerbation of liver inflammatory response during acute hepatitis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Effect of positive pulse charge waveforms on the energy efficiency of lead-acid traction cells

NASA Technical Reports Server (NTRS)

Smithrick, J. J.

1981-01-01

The effects of four different charge methods on the energy conversion efficiency of 300 ampere hour lead acid traction cells were investigated. Three of the methods were positive pulse charge waveforms; the fourth, a constant current method, was used as a baseline of comparison. The positive pulse charge waveforms were: 120 Hz full wave rectified sinusoidal; 120 Hz silicon controlled rectified; and 1 kHz square wave. The constant current charger was set at the time average pulse current of each pulse waveform, which was 150 amps. The energy efficiency does not include charger losses. The lead acid traction cells were charged to 70 percent of rated ampere hour capacity in each case. The results of charging the cells using the three different pulse charge waveforms indicate there was no significant difference in energy conversion efficiency when compared to constant current charging at the time average pulse current value.

Using composite sinusoidal patterns in structured-illumination reflectance imaging (SIRI) for enhanced detection of defects in food

USDA-ARS?s Scientific Manuscript database

Structured-illumination reflectance imaging (SIRI) provides a new means for enhanced detection of defects in horticultural products. Implementing the technique relies on retrieving amplitude images by illuminating the object with sinusoidal patterns of single spatial frequencies, which, however, are...

Using Antenna Arrays to Motivate the Study of Sinusoids

ERIC Educational Resources Information Center

Becker, J. P.

2010-01-01

Educational activities involving antenna arrays to motivate the study of sinusoids are described. Specifically, using fundamental concepts related to phase and simple geometric arguments, students are asked to predict the location of interference nulls in the radiation pattern of two-element phased array antennas. The location of the radiation…

Cutting Edge: Eosinophils Undergo Caspase-1-Mediated Pyroptosis in Response to Necrotic Liver Cells.

PubMed

Palacios-Macapagal, Daphne; Connor, Jane; Mustelin, Tomas; Ramalingam, Thirumalai R; Wynn, Thomas A; Davidson, Todd S

2017-08-01

Many chronic liver disorders are characterized by dysregulated immune responses and hepatocyte death. We used an in vivo model to study the immune response to necrotic liver injury and found that necrotic liver cells induced eosinophil recruitment. Necrotic liver induced eosinophil IL-1β and IL-18 secretion, degranulation, and cell death. Caspase-1 inhibitors blocked all of these responses. Caspase-1-mediated cell death with accompanying cytokine release is the hallmark of a novel form of cell death termed pyroptosis. To confirm this response in a disease model, we isolated eosinophils from the livers of Schistosoma mansoni -infected mice. S. mansoni eggs lodge in the hepatic sinusoids of infected mice, resulting in hepatocyte death, inflammation, and progressive liver fibrosis. This response is typified by massive eosinophilia, and we were able to confirm pyroptosis in the infiltrating eosinophils. This demonstrated that pyroptosis is a cellular pathway used by eosinophils in response to large-scale hepatic cell death. Copyright © 2017 by The American Association of Immunologists, Inc.

Mechanism of hard-nanomaterial clearance by the liver.

PubMed

Tsoi, Kim M; MacParland, Sonya A; Ma, Xue-Zhong; Spetzler, Vinzent N; Echeverri, Juan; Ouyang, Ben; Fadel, Saleh M; Sykes, Edward A; Goldaracena, Nicolas; Kaths, Johann M; Conneely, John B; Alman, Benjamin A; Selzner, Markus; Ostrowski, Mario A; Adeyi, Oyedele A; Zilman, Anton; McGilvray, Ian D; Chan, Warren C W

2016-11-01

The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture and cellular phenotype. We found that nanomaterial velocity reduces 1,000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8 ± 6.4%), hepatic B cells (81.5 ± 9.3%) and liver sinusoidal endothelial cells (64.6 ± 13.7%) interacted with administered PEGylated quantum dots, but splenic macrophages took up less material (25.4 ± 10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating the cellular phenotype to alter hepatic cell interactions.

Root-sum-square structural strength verification approach

NASA Technical Reports Server (NTRS)

Lee, Henry M.

1994-01-01

Utilizing a proposed fixture design or some variation thereof, this report presents a verification approach to strength test space flight payload components, electronics boxes, mechanisms, lines, fittings, etc., which traditionally do not lend themselves to classical static loading. The fixture, through use of ordered Euler rotation angles derived herein, can be mounted on existing vibration shakers and can provide an innovative method of applying single axis flight load vectors. The versatile fixture effectively loads protoflight or prototype components in all three axes simultaneously by use of a sinusoidal burst of desired magnitude at less than one-third the first resonant frequency. Cost savings along with improved hardware confidence are shown. The end product is an efficient way to verify experiment hardware for both random vibration and strength.

Outflow from the outer Lagrangian point - Observations and models of 4U 2127 + 12 in M15

NASA Technical Reports Server (NTRS)

Bailyn, Charles D.; Garcia, Michael R.; Grindlay, Jonathan

1989-01-01

MMT observations of AC 211, the optical counterpart of the high-luminosity X-ray source in globular cluster M15, are presented. The observation of Naylor et al. (1988) that the He I absorption is blueshifted by more than 100 km/s with respect to the mean velocity of the cluster is confirmed. It is shown that if the absorption occurs in a stream of gas outflowing from the L2 point of a binary system, as might be expected for a common envelope binary, both the blueshift and the unexpectedly low velocity variations of the He I lines can be understood. The model predicts that the He I velocity curve is not sinusoidal.

A New Human 3D-Liver Model Unravels the Role of Galectins in Liver Infection by the Parasite Entamoeba histolytica

PubMed Central

Petropolis, Debora B.; Faust, Daniela M.; Deep Jhingan, Gagan; Guillen, Nancy

2014-01-01

Investigations of human parasitic diseases depend on the availability of appropriate in vivo animal models and ex vivo experimental systems, and are particularly difficult for pathogens whose exclusive natural hosts are humans, such as Entamoeba histolytica, the protozoan parasite responsible for amoebiasis. This common infectious human disease affects the intestine and liver. In the liver sinusoids E. histolytica crosses the endothelium and penetrates into the parenchyma, with the concomitant initiation of inflammatory foci and subsequent abscess formation. Studying factors responsible for human liver infection is hampered by the complexity of the hepatic environment and by the restrictions inherent to the use of human samples. Therefore, we built a human 3D-liver in vitro model composed of cultured liver sinusoidal endothelial cells and hepatocytes in a 3D collagen-I matrix sandwich. We determined the presence of important hepatic markers and demonstrated that the cell layers function as a biological barrier. E. histolytica invasion was assessed using wild-type strains and amoebae with altered virulence or different adhesive properties. We showed for the first time the dependence of endothelium crossing upon amoebic Gal/GalNAc lectin. The 3D-liver model enabled the molecular analysis of human cell responses, suggesting for the first time a crucial role of human galectins in parasite adhesion to the endothelial cells, which was confirmed by siRNA knockdown of galectin-1. Levels of several pro-inflammatory cytokines, including galectin-1 and -3, were highly increased upon contact of E. histolytica with the 3D-liver model. The presence of galectin-1 and -3 in the extracellular medium stimulated pro-inflammatory cytokine release, suggesting a further role for human galectins in the onset of the hepatic inflammatory response. These new findings are relevant for a better understanding of human liver infection by E. histolytica. PMID:25211477

Veno occlusive disease: Update on clinical management

PubMed Central

Senzolo, M; Germani, G; Cholongitas, E; Burra, P; Burroughs, AK

2007-01-01

Hepatic veno-occlusive disease is a clinical syndrome characterized by hepatomegaly, ascites, weight gain and jaundice, due to sinusoidal congestion which can be caused by alkaloid ingestion, but the most frequent cause is haematopoietic stem cell transplantation (STC) and is also seen after solid organ transplantation. The incidence of veno occlusive disease (VOD) after STC ranges from 0 to 70%, but is decreasing. Survival is good when VOD is a mild form, but when it is severe and associated with an increase of hepatic venous pressure gradient > 20 mmHg, and mortality is about 90%. Prevention remains the best therapeutic strategy, by using non-myeloablative conditioning regimens before STC. Prophylactic administration of ursodeoxycholic acid, being an antioxidant and antiapoptotic agent, can have some benefit in reducing overall mortality. Defibrotide, which has pro-fibrinolytic and antithrombotic properties, is the most effective therapy; decompression of the sinusoids by a transjugular intrahepatic portosystemic shunt (TIPS) can be tried, especially to treat VOD after liver transplantation and when multiorgan failure (MOF) is not present. Liver transplantation can be the last option, but can not be considered a standard rescue therapy, because usually the concomitant presence of multiorgan failure contraindicates this procedure. PMID:17663504

Seeing blur: 'motion sharpening' without motion.

PubMed Central

Georgeson, Mark A; Hammett, Stephen T

2002-01-01

It is widely supposed that things tend to look blurred when they are moving fast. Previous work has shown that this is true for sharp edges but, paradoxically, blurred edges look sharper when they are moving than when stationary. This is 'motion sharpening'. We show that blurred edges also look up to 50% sharper when they are presented briefly (8-24 ms) than at longer durations (100-500 ms) without motion. This argues strongly against high-level models of sharpening based specifically on compensation for motion blur. It also argues against a recent, low-level, linear filter model that requires motion to produce sharpening. No linear filter model can explain our finding that sharpening was similar for sinusoidal and non-sinusoidal gratings, since linear filters can never distort sine waves. We also conclude that the idea of a 'default' assumption of sharpness is not supported by experimental evidence. A possible source of sharpening is a nonlinearity in the contrast response of early visual mechanisms to fast or transient temporal changes, perhaps based on the magnocellular (M-cell) pathway. Our finding that sharpening is not diminished at low contrast sets strong constraints on the nature of the nonlinearity. PMID:12137571

Focal nodular hyperplasia with major sinusoidal dilatation: a misleading entity

PubMed Central

Laumonier, Hervé; Frulio, Nora; Laurent, Christophe; Balabaud, Charles; Zucman-Rossi, Jessica; Bioulac-Sage, Paulette

2010-01-01

Focal nodular hyperplasia (FNH) is a benign liver lesion thought to be a non-specific response to locally increased blood flow. Although the diagnosis of FNH and hepatocellular adenoma (HCA) has made great progress over the last few years using modern imaging techniques, there are still in daily practice some difficulties concerning some atypical nodules. Here, the authors report the case of a 47-year-old woman with a single liver lesion thought to be, by imaging, an inflammatory HCA with major sinusoidal congestion. This nodule was revealed to be, at the microscopical level and after specific immunostaining and molecular analysis, an FNH with sinusoidal dilatation (so-called telangiectatic focal nodular hyperplasia). PMID:22798311

Inertial frictional ratchets and their load bearing efficiencies

NASA Astrophysics Data System (ADS)

Kharkongor, D.; Reenbohn, W. L.; Mahato, Mangal C.

2018-03-01

We investigate the performance of an inertial frictional ratchet in a sinusoidal potential driven by a sinusoidal external field. The dependence of the performance on the parameters of the sinusoidally varying friction, such as the mean friction coefficient and its phase difference with the potential, is studied in detail. Interestingly, under certain circumstances, the thermodynamic efficiency of the ratchet against an applied load shows a non-monotonic behaviour as a function of the mean friction coefficient. Also, in the large friction ranges, the efficiency is shown to increase with increasing applied load even though the corresponding ratchet current decreases as the applied load increases. These counterintuitive numerical results are explained in the text.

Temperature characteristics of fusion splicing Hollow Core Photonic Crystal Fiber by sinusoidal modulation CO2 laser

NASA Astrophysics Data System (ADS)

Fu, Guangwei; Li, Kuixing; Fu, Xinghu; Bi, Weihong

2013-07-01

During the fusion splicing Hollow Core Photonic Crystal Fiber (HC-PCF), the air-holes collapse easily due to the improper fusion duration time and optical power. To analyze the temperature characteristics of fusion splicing HC-PCF, a heating method by sinusoidal modulation CO2 laser has been proposed. In the sinusoidal modulation, the variation relationships among laser power, temperature difference and angular frequency are analyzed. The results show that the theoretical simulation is basically in accordance with the experimental data. Therefore, a low-loss fusion splicing can be achieved by modulating the CO2 laser frequency to avoid the air-holes collapse of HC-PCF. Further, the errors are also given.

Perception of the dynamic visual vertical during sinusoidal linear motion.

PubMed

Pomante, A; Selen, L P J; Medendorp, W P

2017-10-01

The vestibular system provides information for spatial orientation. However, this information is ambiguous: because the otoliths sense the gravitoinertial force, they cannot distinguish gravitational and inertial components. As a consequence, prolonged linear acceleration of the head can be interpreted as tilt, referred to as the somatogravic effect. Previous modeling work suggests that the brain disambiguates the otolith signal according to the rules of Bayesian inference, combining noisy canal cues with the a priori assumption that prolonged linear accelerations are unlikely. Within this modeling framework the noise of the vestibular signals affects the dynamic characteristics of the tilt percept during linear whole-body motion. To test this prediction, we devised a novel paradigm to psychometrically characterize the dynamic visual vertical-as a proxy for the tilt percept-during passive sinusoidal linear motion along the interaural axis (0.33 Hz motion frequency, 1.75 m/s 2 peak acceleration, 80 cm displacement). While subjects ( n =10) kept fixation on a central body-fixed light, a line was briefly flashed (5 ms) at different phases of the motion, the orientation of which had to be judged relative to gravity. Consistent with the model's prediction, subjects showed a phase-dependent modulation of the dynamic visual vertical, with a subject-specific phase shift with respect to the imposed acceleration signal. The magnitude of this modulation was smaller than predicted, suggesting a contribution of nonvestibular signals to the dynamic visual vertical. Despite their dampening effect, our findings may point to a link between the noise components in the vestibular system and the characteristics of dynamic visual vertical. NEW & NOTEWORTHY A fundamental question in neuroscience is how the brain processes vestibular signals to infer the orientation of the body and objects in space. We show that, under sinusoidal linear motion, systematic error patterns appear in the disambiguation of linear acceleration and spatial orientation. We discuss the dynamics of these illusory percepts in terms of a dynamic Bayesian model that combines uncertainty in the vestibular signals with priors based on the natural statistics of head motion. Copyright © 2017 the American Physiological Society.

Using composite sinusoidal patterns in structured-illumination reflectance imaging (SIRI) for enhanced detection of defects in food

USDA-ARS?s Scientific Manuscript database

This study presented a first exploration of using composite sinusoidal patterns that integrated two and three spatial frequencies of interest, in structured-illumination reflectance imaging (SIRI) for enhanced detection of defects in food (e.g., bruises in apples). Three methods based on Fourier tra...

Design of Helical Capacitance Sensor for Holdup Measurement in Two-Phase Stratified Flow: A Sinusoidal Function Approach

PubMed Central

Lim, Lam Ghai; Pao, William K. S.; Hamid, Nor Hisham; Tang, Tong Boon

2016-01-01

A 360° twisted helical capacitance sensor was developed for holdup measurement in horizontal two-phase stratified flow. Instead of suppressing nonlinear response, the sensor was optimized in such a way that a ‘sine-like’ function was displayed on top of the linear function. This concept of design had been implemented and verified in both software and hardware. A good agreement was achieved between the finite element model of proposed design and the approximation model (pure sinusoidal function), with a maximum difference of ±1.2%. In addition, the design parameters of the sensor were analysed and investigated. It was found that the error in symmetry of the sinusoidal function could be minimized by adjusting the pitch of helix. The experiments of air-water and oil-water stratified flows were carried out and validated the sinusoidal relationship with a maximum difference of ±1.2% and ±1.3% for the range of water holdup from 0.15 to 0.85. The proposed design concept therefore may pose a promising alternative for the optimization of capacitance sensor design. PMID:27384567

Force sensor characterization under sinusoidal excitations.

PubMed

Medina, Nieves; de Vicente, Jesús

2014-10-06

The aim in the current work is the development of a method to characterize force sensors under sinusoidal excitations using a primary standard as the source of traceability. During this work the influence factors have been studied and a method to minimise their contributions, as well as the corrections to be performed under dynamic conditions have been established. These results will allow the realization of an adequate characterization of force sensors under sinusoidal excitations, which will be essential for its further proper use under dynamic conditions. The traceability of the sensor characterization is based in the direct definition of force as mass multiplied by acceleration. To do so, the sensor is loaded with different calibrated loads and is maintained under different sinusoidal accelerations by means of a vibration shaker system that is able to generate accelerations up to 100 m/s2 with frequencies from 5 Hz up to 2400 Hz. The acceleration is measured by means of a laser vibrometer with traceability to the units of time and length. A multiple channel data acquisition system is also required to simultaneously acquire the electrical output signals of the involved instrument in real time.

Enhanced ν-optical time domain reflectometry using gigahertz sinusoidally gated InGaAs/InP single-photon avalanche detector

NASA Astrophysics Data System (ADS)

Zhang, Xuping; Shi, Yuanlei; Shan, Yuanyuan; Sun, Zhenhong; Qiao, Weiyan; Zhang, Yixin

2016-09-01

Optical time domain reflectometry (OTDR) is one of the most successful diagnostic tools for nondestructive attenuation measurement of a fiber link. To achieve better sensitivity, spatial resolution, and avoid dead-zone in conversional OTDR, a single-photon detector has been introduced to form the photon-counting OTDR (ν-OTDR). We have proposed a ν-OTDR system using a gigahertz sinusoidally gated InGaAs/InP single-photon avalanche detector (SPAD). Benefiting from the superior performance of a sinusoidal gated SPAD on dark count probability, gating frequency, and gate duration, our ν-OTDR system has achieved a dynamic range (DR) of 33.4 dB with 1 μs probe pulse width after an equivalent measurement time of 51 s. This obtainable DR corresponds to a sensing length over 150 km. Our system has also obtained a spatial resolution of 5 cm at the end of a 5-km standard single-mode fiber. By employing a sinusoidal gating technique, we have improved the ν-OTDR spatial resolution and significantly reduced the measurement time.

Research on a new magnetic-field-modulated brushless double-rotor machine with sinusoidal-permeance modulating ring

NASA Astrophysics Data System (ADS)

Zheng, Ping; Liu, Jiaqi; Bai, Jingang; Song, Zhiyi; Liu, Yong

2017-05-01

The magnetic-field-modulated brushless double-rotor machine (MFM-BDRM), composed of a stator, a modulating ring rotor, and a PM rotor, is a kind of power-split device for hybrid electric vehicles (HEVs). In this paper, a new MFM-BDRM with sinusoidal-permeance modulating ring named Sinusoidal-Permeance-Modulating-Ring Brushless Double-Rotor Machine (SPMR-BDRM) is proposed to solve the problem of poor mechanical strength and large iron loss. The structure and the operating principle of the MFM-BDRM are introduced. The design principle of the sinusoidal-permeance modulating ring is analyzed and derived. The main idea of that is to minimize the harmonic permeance of air gap, thereby the harmonic magnetic fields can be restrained. There are comparisons between a MFM-BDRM with sinusoidal-permeance modulating ring and a same size MFM-BDRM with traditional modulating ring, including magnetic field distributions and electromagnetic performances. Most importantly, the iron losses are compared under six different conditions. The result indicates that the harmonic magnetic fields in the air gap are restrained; the electromagnetic torque and power factor are almost the same with same armature current; the torque ripples of the modulating ring rotor and the PM rotor are reduced; the stator loss is reduced by 13% at least and the PM loss is reduced by 20% at least compared with the same size traditional MFM-BDRM under the same operating conditions.

Decreased collagen types I and IV, laminin, CK-19 and α-SMA expression after bone marrow cell transplantation in rats with liver fibrosis.

PubMed

Carvalho, S N; Lira, D C; Oliveira, G P; Thole, A A; Stumbo, A C; Caetano, C E; Marques, R G; Carvalho, L

2010-11-01

Bone marrow cells have frequently been tested in animal models of liver fibrosis to assess their role in hepatic regeneration. The mononuclear fraction of bone marrow cells is of particular interest, as many studies show that these cells may be beneficial to treat hepatic fibrosis. In this study, we used the bile duct ligation model to induce hepatic fibrosis in an irreversible manner, and rats were treated with bone marrow mononuclear (BMMN) cells after fibrosis was established. Analysis of collagen types I and IV, laminin and α-SMA showed a decreased expression of these proteins in fibrotic livers after 7 days of BMMN cell injection. Moreover, cytokeratin-19 analysis showed a reduction in bile ducts in the BMMN cell-treated group. These results were accompanied by ameliorated levels of hepatic enzymes GPT (Glutamic-pyruvic transaminase), GOT (glutamic-oxaloacetic transaminase) and alkaline phosphatase (AP). Therefore, we showed that BMMN cells decrease hepatic fibrosis by significantly reducing myofibroblast numbers and through reduction of the collagen and laminin-rich extracellular matrix of fibrotic septa and hepatic sinusoids.

Age differences between the controlled force exertion measured by a computer-generated sinusoidal and a bar chart display.

PubMed

Nagasawa, Yoshinori; Demura, Shinichi; Takahashi, Kenji

2013-01-01

It is important to develop an accurate method of measuring controlled force exertion. This study examined the age differences between the controlled force exertion measured by a sinusoidal waveform and a bar chart display. The participants comprised 175 right-handed male adults aged 20-86 years. The participants were divided into three age groups: young (n=53), middle-aged (n=71), and elderly (n=51). They matched the submaximal grip strength exerted by their dominant hand to changing demand values displayed as either a sinusoidal waveform or a bar chart appearing on a personal computer screen. The participants performed the controlled force exertion test three times with a 1-min inter-trial interval using their dominant hand. The dependent variable was the total sum of the percentage values of the differences between the demand value and grip exertion value for more than 25s. The coefficient of variance had almost the same range in all age groups in both displays (CVSW=28.0-36.9, CVBC=29.1-32.6), but the elderly group showed a somewhat higher value with the sinusoidal waveform. Significant correlations were found between the scores with sinusoidal waveform and bar chart displays in the young, middle-aged, and elderly groups (r=0.47-0.68), but the correlations did not differ significantly between the age groups. Scores over 1500% in sinusoidal and bar chart display were found in one and two participants, respectively, in the middle-aged group and in 12% and 16% of the participants, respectively, in the elderly group. Furthermore, among all participants, only 8% of participants in the elderly group scored over 1500% in both displays. Scores over 1500% in both displays are considered to be considerably worse in controlled force exertion than lower scores. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Propulsion by sinusoidal locomotion: A motion inspired by Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Ulrich, Xialing

Sinusoidal locomotion is commonly seen in snakes, fish, nematodes, or even the wings of some birds and insects. This doctoral thesis presents the study of sinusoidal locomotion of the nematode C. elegans in experiments and the application of the state-space airloads theory to the theoretical forces of sinusoidal motion. An original MATLAB program has been developed to analyze the video records of C. elegans' movement in different fluids, including Newtonian and non-Newtonian fluids. The experimental and numerical studies of swimming C. elegans has revealed three conclusions. First, though the amplitude and wavelength are varying with time, the motion of swimming C. elegans can still be viewed as sinusoidal locomotion with slips. The average normalized wavelength is a conserved character of the locomotion for both Newtonian and non-Newtonian fluids. Second, fluid viscosity affects the frequency but not the moving speed of C. elegans, while fluid elasticity affects the moving speed but not the frequency. Third, by the resistive force theory, for more elastic fluids the ratio of resistive coefficients becomes smaller. Inspired by the motion of C. elegans and other animals performing sinusoidal motion, we investigated the sinusoidal motion of a thin flexible wing in theory. Given the equation of the motion, we have derived the closed forms of propulsive force, lift and other generalized forces applying on the wing. We also calculated the power required to perform the motion, the power lost due to the shed vortices and the propulsive efficiency. These forces and powers are given as functions of reduced frequency k, dimensionless wavelength z, dimensionless amplitude A/b, and time. Our results show that a positive, time-averaged propulsive force is produced for all k>k0=pi/ z. At k=k0, which implies the moment when the moving speed of the wing is the same as the wave speed of its undulation, the motion reaches a steady state with all forces being zero. If there were no shed vorticity effects, the propulsive force would be zero at z = 0.569 and z = 1.3 for all k, and for a fixed k the wing would gain the optimal propulsive force when z = 0.82. With the effects of shed vorticity, the propulsive efficiency decreases from 1.0 to 0.5 as k goes to infinity, and the propulsive efficiency increases almost in a linear relationship with k0.

Satellite Attitude Control Utilizing the Earth's Magnetic Field

NASA Technical Reports Server (NTRS)

White, John S.; Shigemoto, Fred H.; Bourquin, Kent

1961-01-01

A study was conducted to determine the feasibility of a satellite attitude fine-control system using the interaction of the earth's magnetic field with current-carrying coils to produce torque. The approximate intensity of the earth's magnetic field was determined as a function of the satellite coordinates. Components of the magnetic field were found to vary essentially sinusoidally at approximately twice orbital frequency. Amplitude and distortion of the sinusoidal components were a function of satellite orbit. Two systems for two-axis attitude control evolved from this study, one using three coils and the other using two coils. The torques developed by the two systems differ only when the component of magnetic field along the tracking line is zero. For this case the two-coil system develops no torque whereas the three-coil system develops some effective torque which allows partial control. The equations which describe the three-coil system are complex in comparison to those of the two-coil system and require the measurement of all three components of the magnetic field as compared with only one for the two-coil case. Intermittent three-axis torquing can also be achieved. This torquing can be used for coarse attitude control, or for dumping the stored momentum of inertia reaction wheels. Such a system has the advantage of requiring no fuel aboard the satellite. For any of these magnetic torquing schemes the power required to produce the magnetic moment and the weight of the coil seem reasonable.

Defibrotide in the treatment of hepatic veno-occlusive disease

PubMed Central

Fulgenzi, Alessandro; Ferrero, Maria Elena

2016-01-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), represents the most frequent complication in patients in early phase following hematopoietic stem-cell transplantation (HSCT). In its severe form, VOD/SOS can be associated with multiorgan failure and with a mortality rate >80% by day +100. Defibrotide (DF) (a mixture of 90% single-stranded phosphodiester oligonucleotides and 10% double-stranded phosphodiester oligonucleotides derived from controlled depolarization of porcine intestinal mucosal DNA) has been proposed for the treatment of SOS due to its ability to restore thrombo-fibrinolytic balance and protect endothelial cells. The present review highlights why the mechanisms of action of DF allow its successful use in the prevention and treatment of SOS following HSCT. PMID:27843363

Defibrotide in the treatment of hepatic veno-occlusive disease.

PubMed

Fulgenzi, Alessandro; Ferrero, Maria Elena

2016-01-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), represents the most frequent complication in patients in early phase following hematopoietic stem-cell transplantation (HSCT). In its severe form, VOD/SOS can be associated with multiorgan failure and with a mortality rate >80% by day +100. Defibrotide (DF) (a mixture of 90% single-stranded phosphodiester oligonucleotides and 10% double-stranded phosphodiester oligonucleotides derived from controlled depolarization of porcine intestinal mucosal DNA) has been proposed for the treatment of SOS due to its ability to restore thrombo-fibrinolytic balance and protect endothelial cells. The present review highlights why the mechanisms of action of DF allow its successful use in the prevention and treatment of SOS following HSCT.

Effect of spaceflight on rat hepatocytes - A morphometric study

NASA Technical Reports Server (NTRS)

Racine, Richard N.; Cormier, Susan M.

1992-01-01

Hepatic tissue from flight, synchronous, vivarium, and tail-suspended rats was examined by light microscopy and computer-assisted image analysis. Glycogen levels in flight rats were found to be significantly elevated over those in controls. Lipid was also higher but not significantly different. Hepatocytes appeared larger in flight animals because of area attributed to increased glycogen. Sinusoids were less prominent in flight animals than in controls. The total Kupffer cell population appeared to be reduced in flight animals and may represent changes in defensive capacity of the liver. Alterations in the storage of glycogen and number of Kupffer cells suggest an important effect of spacefligtht on the function of the liver that may have important implications for long-term spaceflight.

Three-Space Interaction in Doubly Sinusoidal Periodic Media

NASA Astrophysics Data System (ADS)

Tian-Lin, Dong; Ping, Chen

2006-06-01

Three-space-harmonic (3SH) interaction in doubly sinusoidal periodic (DSP) medium is investigated. Associated physical effects such as additional gap, defect state, and indirect gaps, are theoretically and numerically revealed. This simple DSP model can facilitate the understanding and utilizing of a series of effects in rather complicated periodic structures with additional defect or modulation.

The Relativistic Transformation for an Electromagnetic Plane Wave with General Time Dependence

ERIC Educational Resources Information Center

Smith, Glenn S.

2012-01-01

In special relativity, the transformation between inertial frames for an electromagnetic plane wave is usually derived for the time-harmonic case (the field is a sinusoid of infinite duration), even though all practical waves are of finite duration and may not even contain a dominant sinusoid. This paper presents an alternative derivation in which…

Diagnosis of sinusoidal obstruction syndrome by positron emission tomography/computed tomography: report of two cases treated by defibrotide.

PubMed

Gauthé, Mathieu; Bozec, Laurence; Bedossa, Pierre

2014-11-01

Sinusoidal obstruction syndrome (SOS) is a potentially fatal liver injury that mainly occurs after myeloablative chemotherapy. We report two cases of SOS investigated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and treated with defibrotide. © 2014 by the American Association for the Study of Liver Diseases.

Riding the Ferris Wheel: A Sinusoidal Model

ERIC Educational Resources Information Center

Mittag, Kathleen Cage; Taylor, Sharon E.

2011-01-01

When thinking of models for sinusoidal waves, examples such as tides of the ocean, daily temperatures for one year in your town, light and sound waves, and certain types of motion are used. Many textbooks [1, p. 222] also present a "Ferris wheel description problem" for students to work. This activity takes the Ferris wheel problem out of the…

Multiple polarization states of vector soliton in fiber laser

NASA Astrophysics Data System (ADS)

Chen, Weicheng; Xu, Wencheng; Cao, Hui; Han, Dingan

2007-11-01

Vector soliton is obtained in erbium-doped fiber laser via nonlinear polarization rotation techniques. In experiment, we observe the every 4- and 7-pulse sinusoidal peak modulation. Temporal pulse sinusoidal peak modulation owes to evolution behavior of vector solitons in multiple polarization states. The polarizer in the laser modulates the mode-locked pulses with different polarization states into periodical pulse train intensities modulation. Moreover, the increasing pumping power lead to the appearance of the harmonic pulses and change the equivalent beat length to accelerate the polarization rotation. When the laser cavity length is the n-th multiple ratios to the beat length to maintain the mode-locking, the mode-locked vector soliton is in n-th multiple polarization states, exhibiting every n-pulse sinusoidal peak modulation.

Sinusoidal portal hypertension in hepatic amyloidosis.

PubMed Central

Bion, E; Brenard, R; Pariente, E A; Lebrec, D; Degott, C; Maitre, F; Benhamou, J P

1991-01-01

Hepatic venous catheterisation and transvenous liver biopsy were performed in five patients with hepatic amyloidosis. In three patients, hepatic venous pressures were normal and histological examination of the liver biopsy specimen showed discrete and sparse perisinusoidal amyloid deposits. In the other two, however, the gradient between wedged and free hepatic venous pressures was increased (12 and 16 mmHg; normal 1-4 mmHg) and amyloid deposits were abundant and diffuse in the Disse's space. This study shows that portal hypertension in patients with hepatic amyloidosis is of the sinusoidal type and is related to the reduction of vascular space of hepatic sinusoids by massive perisinusoidal amyloid deposits. Furthermore, portal hypertension is associated with a poor prognosis in patients with hepatic amyloidosis. Images Figure 1 Figure 2 PMID:1864548

An OKQPSK modem incorporating numerically controlled carrier synthesis

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

Oetken, R.E.

1988-04-04

The feasibility of incorporating numerically controlled oscillators (NCO) in communication related applications is evaluated. NCO generation of sinusoids may prove useful in systems requiring precise frequency control, tuning linearity, and orthogonality versus frequency. An OKQPSK modem operating at a data rate of 200 kb/s was fabricated. The modem operates in a back to back hardwired channel and thus does not incorporate carrier or symbol timing recovery. Spectra of the NCO generated sinusoids are presented along with waveforms from the modulation and demodulation process. Generation of sinusoids in the digital domain is a viable alternative to analog oscillators. Implementation of anmore » NCO should be considered when frequency allocation, tuning bandwidth, or frequency hopped transmission requires precise frequency synthesis. 24 figs.« less

CLO: The cell line ontology

PubMed Central

2014-01-01

Background Cell lines have been widely used in biomedical research. The community-based Cell Line Ontology (CLO) is a member of the OBO Foundry library that covers the domain of cell lines. Since its publication two years ago, significant updates have been made, including new groups joining the CLO consortium, new cell line cells, upper level alignment with the Cell Ontology (CL) and the Ontology for Biomedical Investigation, and logical extensions. Construction and content Collaboration among the CLO, CL, and OBI has established consensus definitions of cell line-specific terms such as ‘cell line’, ‘cell line cell’, ‘cell line culturing’, and ‘mortal’ vs. ‘immortal cell line cell’. A cell line is a genetically stable cultured cell population that contains individual cell line cells. The hierarchical structure of the CLO is built based on the hierarchy of the in vivo cell types defined in CL and tissue types (from which cell line cells are derived) defined in the UBERON cross-species anatomy ontology. The new hierarchical structure makes it easier to browse, query, and perform automated classification. We have recently added classes representing more than 2,000 cell line cells from the RIKEN BRC Cell Bank to CLO. Overall, the CLO now contains ~38,000 classes of specific cell line cells derived from over 200 in vivo cell types from various organisms. Utility and discussion The CLO has been applied to different biomedical research studies. Example case studies include annotation and analysis of EBI ArrayExpress data, bioassays, and host-vaccine/pathogen interaction. CLO’s utility goes beyond a catalogue of cell line types. The alignment of the CLO with related ontologies combined with the use of ontological reasoners will support sophisticated inferencing to advance translational informatics development. PMID:25852852

Arrays of High-Aspect Ratio Microchannels for High-Throughput Isolation of Circulating Tumor Cells (CTCs).

PubMed

Hupert, Mateusz L; Jackson, Joshua M; Wang, Hong; Witek, Małgorzata A; Kamande, Joyce; Milowsky, Matthew I; Whang, Young E; Soper, Steven A

2014-10-01

Microsystem-based technologies are providing new opportunities in the area of in vitro diagnostics due to their ability to provide process automation enabling point-of-care operation. As an example, microsystems used for the isolation and analysis of circulating tumor cells (CTCs) from complex, heterogeneous samples in an automated fashion with improved recoveries and selectivity are providing new opportunities for this important biomarker. Unfortunately, many of the existing microfluidic systems lack the throughput capabilities and/or are too expensive to manufacture to warrant their widespread use in clinical testing scenarios. Here, we describe a disposable, all-polymer, microfluidic system for the high-throughput (HT) isolation of CTCs directly from whole blood inputs. The device employs an array of high aspect ratio (HAR), parallel, sinusoidal microchannels (25 µm × 150 µm; W × D; AR = 6.0) with walls covalently decorated with anti-EpCAM antibodies to provide affinity-based isolation of CTCs. Channel width, which is similar to an average CTC diameter (12-25 µm), plays a critical role in maximizing the probability of cell/wall interactions and allows for achieving high CTC recovery. The extended channel depth allows for increased throughput at the optimized flow velocity (2 mm/s in a microchannel); maximizes cell recovery, and prevents clogging of the microfluidic channels during blood processing. Fluidic addressing of the microchannel array with a minimal device footprint is provided by large cross-sectional area feed and exit channels poised orthogonal to the network of the sinusoidal capillary channels (so-called Z-geometry). Computational modeling was used to confirm uniform addressing of the channels in the isolation bed. Devices with various numbers of parallel microchannels ranging from 50 to 320 have been successfully constructed. Cyclic olefin copolymer (COC) was chosen as the substrate material due to its superior properties during UV-activation of the HAR microchannels surfaces prior to antibody attachment. Operation of the HT-CTC device has been validated by isolation of CTCs directly from blood secured from patients with metastatic prostate cancer. High CTC sample purities (low number of contaminating white blood cells, WBCs) allowed for direct lysis and molecular profiling of isolated CTCs.

Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy.

PubMed

Jemail, Leila; Miyao, Masashi; Kotani, Hirokazu; Kawai, Chihiro; Minami, Hirozo; Abiru, Hitoshi; Tamaki, Keiji

2018-04-23

Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.

Thyroid cell lines in research on goitrogenesis.

PubMed

Gerber, H; Peter, H J; Asmis, L; Studer, H

1991-12-01

Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes.

In vivo mouse inferior olive neurons exhibit heterogeneous subthreshold oscillations and spiking patterns

PubMed Central

Khosrovani, S.; Van Der Giessen, R. S.; De Zeeuw, C. I.; De Jeu, M. T. G.

2007-01-01

In vitro whole-cell recordings of the inferior olive have demonstrated that its neurons are electrotonically coupled and have a tendency to oscillate. However, it remains to be shown to what extent subthreshold oscillations do indeed occur in the inferior olive in vivo and whether its spatiotemporal firing pattern may be dynamically generated by including or excluding different types of oscillatory neurons. Here, we did whole-cell recordings of olivary neurons in vivo to investigate the relation between their subthreshold activities and their spiking behavior in an intact brain. The vast majority of neurons (85%) showed subthreshold oscillatory activities. The frequencies of these subthreshold oscillations were used to distinguish four main olivary subtypes by statistical means. Type I showed both sinusoidal subthreshold oscillations (SSTOs) and low-threshold Ca2+ oscillations (LTOs) (16%); type II showed only sinusoidal subthreshold oscillations (13%); type III showed only low-threshold Ca2+ oscillations (56%); and type IV did not reveal any subthreshold oscillations (15%). These subthreshold oscillation frequencies were strongly correlated with the frequencies of preferred spiking. The frequency characteristics of the subthreshold oscillations and spiking behavior of virtually all olivary neurons were stable throughout the recordings. However, the occurrence of spontaneous or evoked action potentials modified the subthreshold oscillation by resetting the phase of its peak toward 90°. Together, these findings indicate that the inferior olive in intact mammals offers a rich repertoire of different neurons with relatively stable frequency settings, which can be used to generate and reset temporal firing patterns in a dynamically coupled ensemble. PMID:17895389

Defibrotide for the treatment of sinusoidal obstruction syndrome: evaluation of response to therapy and patient outcomes.

PubMed

Coutsouvelis, John; Avery, Sharon; Dooley, Michael; Kirkpatrick, Carl; Spencer, Andrew

2018-03-01

Defibrotide is an agent used to treat sinusoidal obstruction syndrome (SOS/VOD) in patients undergoing haemopoietic stem cell transplantation. The aim of this study was to evaluate the effectiveness of defibrotide used within institutional guidelines for the treatment of SOS/VOD in patients undergoing haemopoietic stem cell transplantation (HSCT). Data for 23 patients was retrospectively reviewed to evaluate the effectiveness of defibrotide and the utility of response criteria to direct therapy as specified within institution guidelines. Patients met institutional criteria for a diagnosis of SOS/VOD based on predominantly Baltimore criteria and received defibrotide. Stabilisation or improvement in symptoms and biochemical markers was required for continuation of therapy with defibrotide. Overall, 14 patients responded to therapy. Survival at day 100 post HSCT was 70%. Median serum (total) bilirubin concentrations in all evaluable patients had decreased at days 5 and 10 (p < 0.001). There was a proportional reduction in median weight of 4% by day 5 and 6.6% by day 10 (p < 0.001). On cessation of defibrotide, there was a decrease in the proportion of patients exhibiting hepatomegaly (p = 0.02), ascites (p < 0.01) and requiring oxygen supplementation (p < 0.01), with 70% survival at day 100 post HSCT. Defibrotide to treat SOS/VOD and continued based on attainment of early response was effective management of this condition. Defibrotide should be considered in any consensus protocol providing guidance on the management of SOS/VOD, with future studies considered to assess appropriate time points for response to therapy during treatment.

Analysis of renal cancer cell lines from two major resources enables genomics-guided cell line selection

NASA Astrophysics Data System (ADS)

Sinha, Rileen; Winer, Andrew G.; Chevinsky, Michael; Jakubowski, Christopher; Chen, Ying-Bei; Dong, Yiyu; Tickoo, Satish K.; Reuter, Victor E.; Russo, Paul; Coleman, Jonathan A.; Sander, Chris; Hsieh, James J.; Hakimi, A. Ari

2017-05-01

The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines.

Evaluating cell lines as tumour models by comparison of genomic profiles

PubMed Central

Domcke, Silvia; Sinha, Rileen; Levine, Douglas A.; Sander, Chris; Schultz, Nikolaus

2013-01-01

Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types. PMID:23839242

Stress singularities in a model of a wood disk under sinusoidal pressure

Treesearch

Jay A. Johnson; John C. Hermanson; Steven M. Cramer; Charles Amundson

2005-01-01

A thin, solid, circular wood disk, cut from the transverse plane of a tree stem, can be modeled as a cylindrically orthotropic elastic material. It is known that a stress singularity can occur at the center of a cylindrically orthotropic disk subjected to uniform pressure. If a solid cylindrically orthotropic disk is subjected to sinusoidal pressure distributions, then...

The dynamics of certain indicators of nuclein metabolism during hypokinesia in rats of different ages under the influence of sinusoidal modulated currents and measured physical load

NASA Technical Reports Server (NTRS)

Sokolova, Z. A.

1980-01-01

The influence of sinusoidal modulated currents was studied and physical loads on the nucleic acid content and the nucleotide composition of the total RNA in muscles of rats of various ages under conditions of hypodynamia were measured. Methodology utilized is described and conclusions are presented.

Sensor-less pseudo-sinusoidal drive for a permanent-magnet brushless ac motor

NASA Astrophysics Data System (ADS)

Liu, Li-Hsiang; Chern, Tzuen-Lih; Pan, Ping-Lung; Huang, Tsung-Mou; Tsay, Der-Min; Kuang, Jao-Hwa

2012-04-01

The precise rotor-position information is required for a permanent-magnet brushless ac motor (BLACM) drive. In the conventional sinusoidal drive method, either an encoder or a resolver is usually employed. For position sensor-less vector control schemes, the rotor flux estimation and torque components are obtained by complicated coordinate transformations. These computational intensive methods are susceptible to current distortions and parameter variations. To simplify the method complexity, this work presents a sensor-less pseudo-sinusoidal drive scheme with speed control for a three-phase BLACM. Based on the sinusoidal drive scheme, a floating period of each phase current is inserted for back electromotive force detection. The zero-crossing point is determined directly by the proposed scheme, and the rotor magnetic position and rotor speed can be estimated simultaneously. Several experiments for various active angle periods are undertaken. Furthermore, a current feedback control is included to minimize and compensate the torque fluctuation. The experimental results show that the proposed method has a competitive performance compared with the conventional drive manners for BLACM. The proposed scheme is straightforward, bringing the benefits of sensor-less drive and negating the need for coordinate transformations in the operating process.

Ultra-Wideband Chaos Life-Detection Radar with Sinusoidal Wave Modulation

NASA Astrophysics Data System (ADS)

Xu, Hang; Li, Ying; Zhang, Jianguo; Han, Hong; Zhang, Bing; Wang, Longsheng; Wang, Yuncai; Wang, Anbang

2017-12-01

We propose and experimentally demonstrate an ultra-wideband (UWB) chaos life-detection radar. The proposed radar transmits a wideband chaotic-pulse-position modulation (CPPM) signal modulated by a single-tone sinusoidal wave. A narrow-band split ring sensor is used to collect the reflected sinusoidal wave, and a lock-in amplifier is utilized to identify frequencies of respiration and heartbeat by detecting the phase change of the sinusoidal echo signal. Meanwhile, human location is realized by correlating the CPPM echo signal with its delayed duplicate and combining the synthetic aperture technology. Experimental results demonstrate that the human target can be located accurately and his vital signs can be detected in a large dynamic range through a 20-cm-thick wall using our radar system. The down-range resolution is 15cm, benefiting from the 1-GHz bandwidth of the CPPM signal. The dynamic range for human location is 50dB, and the dynamic ranges for heartbeat and respiration detection respectively are 20dB and 60dB in our radar system. In addition, the bandwidth of the CPPM signal can be adjusted from 620MHz to 1.56GHz to adapt to different requirements.

Force Sensor Characterization Under Sinusoidal Excitations

PubMed Central

Medina, Nieves; de Vicente, Jesús

2014-01-01

The aim in the current work is the development of a method to characterize force sensors under sinusoidal excitations using a primary standard as the source of traceability. During this work the influence factors have been studied and a method to minimise their contributions, as well as the corrections to be performed under dynamic conditions have been established. These results will allow the realization of an adequate characterization of force sensors under sinusoidal excitations, which will be essential for its further proper use under dynamic conditions. The traceability of the sensor characterization is based in the direct definition of force as mass multiplied by acceleration. To do so, the sensor is loaded with different calibrated loads and is maintained under different sinusoidal accelerations by means of a vibration shaker system that is able to generate accelerations up to 100 m/s2 with frequencies from 5 Hz up to 2400 Hz. The acceleration is measured by means of a laser vibrometer with traceability to the units of time and length. A multiple channel data acquisition system is also required to simultaneously acquire the electrical output signals of the involved instrument in real time. PMID:25290287

Dynamics of a railway vehicle on a laterally disturbed track

NASA Astrophysics Data System (ADS)

Christiansen, Lasse Engbo; True, Hans

2018-02-01

In this article a theoretical investigation of the dynamics of a railway bogie running on a tangent track with a periodic disturbance of the lateral track geometry is presented. The dynamics is computed for two values of the speed of the vehicle in combination with different values of the wavelength and amplitude of the disturbance. Depending on the combinations of the speed, the wavelength and the amplitude, straight line forward motion, different modes of symmetric or asymmetric periodic oscillations or aperiodic motions, which are presumably chaotic, are found. Statistical methods are applied for the investigation. In the case of sinusoidal oscillations they provide information about the phase shift between the different variables and the amplitudes of the oscillations. In the case of an aperiodic motion the statistical measures indicate some non-smooth transitions.

Extracting tissue deformation using Gabor filter banks

NASA Astrophysics Data System (ADS)

Montillo, Albert; Metaxas, Dimitris; Axel, Leon

2004-04-01

This paper presents a new approach for accurate extraction of tissue deformation imaged with tagged MR. Our method, based on banks of Gabor filters, adjusts (1) the aspect and (2) orientation of the filter"s envelope and adjusts (3) the radial frequency and (4) angle of the filter"s sinusoidal grating to extract information about the deformation of tissue. The method accurately extracts tag line spacing, orientation, displacement and effective contrast. Existing, non-adaptive methods often fail to recover useful displacement information in the proximity of tissue boundaries while our method works in the proximity of the boundaries. We also present an interpolation method to recover all tag information at a finer resolution than the filter bank parameters. Results are shown on simulated images of translating and contracting tissue.

Investigations of the Rayleigh-Taylor and Richtmyer-Meshkov Instabilities

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

Riccardo Bonazza; Mark Anderson; Jason Oakley

2008-03-14

The present program is centered on the experimental study of shock-induced interfacial fluid instabilities. Both 2-D (near-sinusoids) and 3-D (spheres) initial conditions are studied in a large, vertical square shock tube facility. The evolution of the interface shape, its distortion, the modal growth rates and the mixing of the fluids at the interface are all objectives of the investigation. In parallel to the experiments, calculations are performed using the Raptor code, on platforms made available by LLNL. These flows are of great relevance to both ICF and stockpile stewardship. The involvement of four graduate students is in line with themore » national laboratories' interest in the education of scientists and engineers in disciplines and technologies consistent with the labs' missions and activities.« less

Investigation of the Richtmyer-Meshkov instability

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

Riccardo Bonazza; Mark Anderson; Jason Oakley

2008-12-22

The present program is centered on the experimental study of shock-induced interfacial fluid instabilities. Both 2-D (near-sinusoids) and 3-D (spheres) initial conditions are studied in a large, vertical square shock tube facility. The evolution of the interface shape, its distortion, the modal growth rates and the mixing of the fluids at the interface are all objectives of the investigation. In parallel to the experiments, calculations are performed using the Raptor code, on platforms made available by LLNL. These flows are of great relevance to both ICF and stockpile stewardship. The involvement of three graduate students is in line with themore » national laboratories' interest in the education of scientists and engineers in disciplines and technologies consistent with the labs' missions and activities.« less

Continuous hematopoietic cell lines as model systems for leukemia-lymphoma research.

PubMed

Drexler, H G; Matsuo, A Y; MacLeod, R A

2000-11-01

Along with other improvements, the advent of continuous human leukemia-lymphoma (LL) cell lines as a rich resource of abundant, accessible and manipulable living cells has contributed significantly to a better understanding of the pathophysiology of hematopoietic tumors. The first LL cell lines, Burkitt's lymphoma-derived lines, were established in 1963. Since then, more than 1000 cell lines have been described, although not all of them in full detail. The major advantages of continuous cell lines is the unlimited supply and worldwide availability of identical cell material, and the infinite viable storability in liquid nitrogen. LL cell lines are characterized generally by monoclonal origin and differentiation arrest, sustained proliferation in vitro under preservation of most cellular features, and specific genetic alterations. The most practical classification of LL cell lines assigns them to one of the physiologically occurring cell lineages, based on their immunophenotype, genotype and functional features. Truly malignant cell lines must be discerned from Epstein-Barr virus (EBV)-immortalized normal cells, using various distinguishing parameters. However, the picture is not quite so straightforward, as some types of LL cell lines are indeed EBV+, and some EBV+ normal cell lines carry also genetic aberrations and may mimic malignancy-associated features. Apart from EBV and human T-cell leukemia virus in some lines, the majority of wild-type LL cell lines are virus-negative. The efficiency of cell line establishment is rather low and the deliberate establishment of new LL cell lines remains by and large an unpredictable random process. Difficulties in establishing continuous cell lines may be caused by the inappropriate selection of nutrients and growth factors for these cells. Clearly, a generally suitable microenvironment for hematopoietic cells, either malignant or normal, cannot yet be created in vitro. The characterization and publication of new LL cell lines should provide important and informative core data, attesting to their scientific significance. Large percentages of LL cell lines are contaminated with mycoplasma (about 30%) or are cross-contaminated with other cell lines (about 15-20%). Solutions to these problems are sensitive detection, effective elimination and rigorous prevention of mycoplasma infection, and proper, regular authentication of cell lines. The underlying cause, however, appears to be negligent cell culture practice. The willingness of investigators to make their LL cell lines available to others is all too often limited. There is a need in the scientific community for clean and authenticated high-quality LL cell lines to which every scientist has access. These are offered by various institutionalized public cell line banks. It has been argued that LL cell lines are genetically unstable (both cytogenetically and molecular genetically). For instance, cell lines are supposed to acquire numerical and structural chromosomal alterations and various types of mutations (e.g. point mutations) in vitro. We present evidence that while nearly 100% of all LL cell lines indeed carry genetic alterations, these alterations appear to be stable rather than unstable. As an example of the practical utility of LL cell lines, the recent advances in studies of classical and molecular cytogenetics, which in large part were made possible by cell lines, are highlighted. A list of the most useful, robust and publicly available reference cell lines that may be used for a variety of experimental purposes is proposed. Clearly, by opening new avenues for investigation, studies of LL cell lines have provided seminal insights into the biology of hematopoietic neoplasia. Over a period of nearly four decades, these initially rather exotic cell cultures, known only to a few specialists, have become ubiquitous powerful research tools that are available to every investigator.

Performance analysis of cascaded h-bridge multilevel inverter using mixed switching frequency with various dc-link voltages

NASA Astrophysics Data System (ADS)

Citarsa, I. B. F.; Satiawan, I. N. W.; Wiryajati, I. K.; Supriono

2016-01-01

Multilevel inverters have been widely used in many applications since the technology is advantageous to increase the converter capability as well as to improve the output voltage quality. According to the applied switching frequency, multilevel modulations can be subdivided into three classes, i.e: fundamental switching frequency, high switching frequency and mixed switching frequency. This paper investigates the performance of cascaded H-bridge (CHB) multilevel inverter that is modulated using mixed switching frequency (MSF) PWM with various dc-link voltage ratios. The simulation results show the nearly sinusoidal load output voltages are successfully achieved. It is revealed that there is improvement in output voltages quality in terms of THD and low-order harmonics content. The CHB inverter that is modulated using MSF PWM with equal dc-link voltage ratio (½ Vdc: ½ Vdc) produces output voltage with the lowest low-order harmonics (less than 1% of fundamental) while the CHB inverter that is modulated using MSF PWM with un-equal dc-link voltage ratio (2/3 Vdc: 1/3 Vdc) produces a 7-level output voltage with the lowest THD (16.31%) compared to the other PWM methods. Improvement of the output voltage quality here is also in line with improvement of the number of available levels provided in the output voltage. Here only 2 cells H-bridge inverter (contain 8 switches) are needed to produce a 7- level output voltage, while in the conventional CHB inverter at least 3 cells of H-bridge inverter (contain 12 switches) are needed to produce a 7-level output voltage. Hence it is valuable in term of saving number of component.

Regulatory role of Megakaryocytes on Hematopoietic Stem Cells Quiescence by CXCL4/PF4 in Bone Marrow Niche.

PubMed

Norozi, Fatemeh; Shahrabi, Saeid; Hajizamani, Saeideh; Saki, Najmaldin

2016-09-01

Platelet factor-4 (CXCL4/PF-4) is a member of CXC-chemokine family produced by megakaryocytic lineage and stored in platelet α-granules. Platelet stimulation by aggregating agents such as thrombin and ADP leads to CXCL4 secretion. CXCL4 plays several roles in coagulation, angiogenesis control, immune system modulation and spread of cancer. Megakaryocytes (Mks) are associated with the vascular niche in the bone marrow (BM) and are located in vicinity of BM sinusoids. Mk-derived CXCL4 is involved in several hematopoietic processes, including inhibition of megakaryopoiesis and maintenance of hematopoietic stem cell (HSC) quiescence. The major aim of this review article was to evaluate the role of CXCL4 in hematological malignancies, promotion of HSC quiescence as well as BM niche cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ontological representation, integration, and analysis of LINCS cell line cells and their cellular responses.

PubMed

Ong, Edison; Xie, Jiangan; Ni, Zhaohui; Liu, Qingping; Sarntivijai, Sirarat; Lin, Yu; Cooper, Daniel; Terryn, Raymond; Stathias, Vasileios; Chung, Caty; Schürer, Stephan; He, Yongqun

2017-12-21

Aiming to understand cellular responses to different perturbations, the NIH Common Fund Library of Integrated Network-based Cellular Signatures (LINCS) program involves many institutes and laboratories working on over a thousand cell lines. The community-based Cell Line Ontology (CLO) is selected as the default ontology for LINCS cell line representation and integration. CLO has consistently represented all 1097 LINCS cell lines and included information extracted from the LINCS Data Portal and ChEMBL. Using MCF 10A cell line cells as an example, we demonstrated how to ontologically model LINCS cellular signatures such as their non-tumorigenic epithelial cell type, three-dimensional growth, latrunculin-A-induced actin depolymerization and apoptosis, and cell line transfection. A CLO subset view of LINCS cell lines, named LINCS-CLOview, was generated to support systematic LINCS cell line analysis and queries. In summary, LINCS cell lines are currently associated with 43 cell types, 131 tissues and organs, and 121 cancer types. The LINCS-CLO view information can be queried using SPARQL scripts. CLO was used to support ontological representation, integration, and analysis of over a thousand LINCS cell line cells and their cellular responses.

A flyer-impact technique for measuring viscosity of metal under shock compression

NASA Astrophysics Data System (ADS)

Li, Yilei; Liu, Fusheng; Ma, Xiaojuan; Li, Yinglei; Yu, Ming; Zhang, Jichun; Jing, Fuqian

2009-01-01

A flyer-impact technique, different from the explosive method of [Sakharov et al., Sov. Phys. Dokl. 9, 1091 (1965)], is developed to investigate the viscosity of shocked metals. The shock wave with a front of sinusoidal perturbation is induced by the sinusoidal profile of the impact surface of the sample by use of two-stage light-gas gun. The oscillatory damping process of the perturbation amplitude is monitored by electric pins. Two damping curves (perturbation amplitude relative to its initial value versus propagated distance relative to the wavelength of sinusoidal perturbation) of aluminum are determined at 78 and 101 GPa. The effective shear viscosity coefficients are deduced to be about 1300 and 800 Pa s based on the Miller and Ahrens analytic solution for viscous fluid.

Sinusoidal Siemens star spatial frequency response measurement errors due to misidentified target centers

DOE PAGES

Birch, Gabriel Carisle; Griffin, John Clark

2015-07-23

Numerous methods are available to measure the spatial frequency response (SFR) of an optical system. A recent change to the ISO 12233 photography resolution standard includes a sinusoidal Siemens star test target. We take the sinusoidal Siemens star proposed by the ISO 12233 standard, measure system SFR, and perform an analysis of errors induced by incorrectly identifying the center of a test target. We show a closed-form solution for the radial profile intensity measurement given an incorrectly determined center and describe how this error reduces the measured SFR of the system. As a result, using the closed-form solution, we proposemore » a two-step process by which test target centers are corrected and the measured SFR is restored to the nominal, correctly centered values.« less

Multilevel-Dc-Bus Inverter For Providing Sinusoidal And Pwm Electrical Machine Voltages

DOEpatents

Su, Gui-Jia [Knoxville, TN

2005-11-29

A circuit for controlling an ac machine comprises a full bridge network of commutation switches which are connected to supply current for a corresponding voltage phase to the stator windings, a plurality of diodes, each in parallel connection to a respective one of the commutation switches, a plurality of dc source connections providing a multi-level dc bus for the full bridge network of commutation switches to produce sinusoidal voltages or PWM signals, and a controller connected for control of said dc source connections and said full bridge network of commutation switches to output substantially sinusoidal voltages to the stator windings. With the invention, the number of semiconductor switches is reduced to m+3 for a multi-level dc bus having m levels. A method of machine control is also disclosed.

Incorrect strain information for mouse cell lines: sequential influence of misidentification on sublines.

PubMed

Uchio-Yamada, Kozue; Kasai, Fumio; Ozawa, Midori; Kohara, Arihiro

2017-03-01

Misidentification or cross-contamination of cell lines can cause serious issues. Human cell lines have been authenticated by short tandem repeat profiling; however, mouse cell lines have not been adequately assessed. In this study, mouse cell lines registered with the JCRB cell bank were examined by simple sequence length polymorphism (SSLP) analysis to identify their strains. Based on comparisons with 7 major inbred strains, our results revealed their strains in 80 of 90 cell lines. However, 12 of the 80 cell lines (15%) were found to differ from registered information. Of them, 4 cell lines originated from the same mouse, which had been generated through mating between two different inbred strains. The genotype of the mouse sample had not been examined after the backcross, leading to strain misidentification in those cell lines. Although 8 other cell lines had been established as sublines of a BALB/c cell line, their SSLP profiles are similar to a Swiss cell line. This affects differences in genotypes between inbred and outbred strains. Because the use of inbred samples and interbreeding between strains are not involved in human materials, our results suggest that the cause and influence of misidentification in mouse cell lines are different from those in human.

Establishment and characterization of three immortal bovine muscular epithelial cell lines.

PubMed

Jin, Xun; Lee, Joong-Seob; Kwak, Sungwook; Lee, Soo-Yeon; Jung, Ji-Eun; Kim, Tae-Kyung; Xu, Chenxiong; Hong, Zhongshan; Li, Zhehu; Kim, Sun-Myung; Pian, Xumin; Lee, Dong-Hee; Yoon, Jong-Taek; You, Seungkwon; Choi, Yun-Jaie; Kim, Huunggee

2006-02-28

We have established three immortal bovine muscular epithelial (BME) cell lines, one spontaneously immortalized (BMES), the second SV40LT-mediated (BMEV) and the third hTERT-mediated (BMET). The morphology of the three immortal cell lines was similar to that of early passage primary BME cells. Each of the immortal cell lines made cytokeratin, a typical epithelial marker. BMET grew faster than the other immortal lines and the BME cells, in 10% FBS-DMEM medium, whereas neither the primary cells nor the three immortal cell lines grew in 0.5% FBS-DMEM. The primary BME cells and the immortal cell lines, with the exception of BMES, made increasing amounts of p53 protein when treated with doxorubicin, a DNA damaging agent. On the other hand, almost half of the cells in populations of the three immortal cell lines may lack p16(INK4a) regulatory function, compared to primary BME cells that were growth arrested by enforced expression of p16(INK4a). In soft-agar assays, the primary cells and immortal cell lines proved to be less transformed in phenotype than HeLa cells. The three immortal epithelial-type cell lines reported here are the first cell lines established from muscle tissue of bovine or other species.

Investigation of the expression of RIF1 gene on head and neck, pancreatic and brain cancer and cancer stem cells.

PubMed

GursesCila, Hacer E; Acar, Muradiye; Barut, Furkan B; Gunduz, Mehmet; Grenman, Reidar; Gunduz, Esra

2016-12-01

Recent studies have shown that cancer stem cells are resistant to chemotherapy. The aim of this study was to compare RIF1 gene expression in head and neck, pancreatic cancer and glioma cell lines and the cancer stem cells isolated from these cell lines. UT-SCC-74 from Turku University and UT-SCC-74B primary tumor metastasis and neck cancer cell lines, YKG-1 glioma cancer cell line from RIKEN, pancreatic cancer cell lines and ASPC-1 cells from ATCC were grown in cell culture. To isolate cancer stem cells, ALDH-1 for UT-SCC-74 and UT-SCC-74B cell line, CD-133 for YKG-1 cell line and CD-24 for ASPC-1 cell line, were used as markers of cancer stem cells. RNA isolation was performed for both cancer lines and cancer stem cells. RNAs were converted to cDNA. RIF1 gene expression was performed by qRT-PCR analysis. RIF1 gene expression was compared with cancer cell lines and cancer stem cells isolated from these cell lines. The possible effect of RIF1 gene was evaluated. In the pancreatic cells, RIF1 gene expression in the stem cell-positive cell line was 256 time that seen in the stem cell-negative cell line. Considering the importance of RIF1 in NHEJ and of NHEJ in pancreatic cancer, RIF1 may be one of the genes that plays an important role in the diagnoses and therapeutic treatment of pancreatic cancer. The results of head and neck and brain cancers are inconclusive and further studies are required to elucidate the connection between RIF1 gene and these other types of cancers.

Mix-ups and mycoplasma: the enemies within.

PubMed

Drexler, Hans G; Uphoff, Cord C; Dirks, Willy G; MacLeod, Roderick A F

2002-04-01

Human leukemia-lymphoma (LL) cell lines represent important tools for experimental research. Among the various problems associated with cell lines, the two most common concern contaminations: (1) cross-contamination with unrelated cells and (2) contamination with microorganisms, in particular mycoplasma. The bad news is that about one-third of the cell lines are either cross-contaminated or mycoplasma-infected or both. The good news is that there are means to recognize and overcome these problems. In cases where, during attempts to establish new LL cell lines, primary LL cultures are cross-contaminated with continuous cell lines, intended new cell lines simply cannot be established ("early" cross-contamination). In cases of "late" cross-contamination of existing LL cell lines where the intrusive cells have a growth advantage, the original ("uncontaminated") cell lines may still be available elsewhere. DNA fingerprinting and cytogenetic analysis appear to be the most suitable approaches to detect cross-contaminations and to authenticate LL cell lines. A different but related aspect of "false" LL cell lines is the frequent misclassification of cell lines whereby the actual cell type of the cell line does not correspond to the purported model character of the cell line. Mycoplasma infection can have a multitude of effects on the eukaryotic cells which, due to the variety of infecting mycoplasma species and many other contributing parameters, cannot be predicted, rendering resulting data questionable at best. Practical procedures for the detection and elimination of mycoplasma contamination have been developed. Diagnostic and preventive strategies in order to hem the alarming increase in "false" and mycoplasma-positive LL cell lines are recommended.

The Structure of the Mammalian Area Postrema

NASA Technical Reports Server (NTRS)

Brizzee, K. R.; Klara, P. M.

1984-01-01

The area postrema in mammals other than rodents and lagomorphs is a bilateral mound of gelatinous-appearing tissue that protrudes into the caudal fourth ventricle on either side of the obex. In rodents and lagomorphs it is a single midline structure at the apex of the calamus scriptorius. The vasculature is derived mainly from the posterior inferior cerebellar arteries and consists mainly of sinusoidal capillaries. It appears to constitute a portal system, at least in the rat. Many of the capillaries are fenestrated, and many large perivascular spaces with both vascular and parenchymal basal laminae are present. The cell population is composed of flattened ependymal cells exhibiting microvilli, and of small neurons, normal astrocytes, glialoid cells, and a very few oligodendroglia. Mast cells are occasionally present. The glialoid cells appear to be the predominant cell type and exhibit great numbers of vascular podia. Axodendritic synapses are numerous and axosomatic synapses are occasionally seen in the parenchyma. Synaptic vesicles are mainly of the clear-cored type but large dense-cored vesicles are commonly observed in some axon terminals.

Feeder-cell-independent culture of the pig-embryonic-stem-cell-derived exocrine pancreatic cell line, PICM-31

USDA-ARS?s Scientific Manuscript database

The adaptation to feeder-independent growth of a pig embryonic stem cell-derived pancreatic cell line is described. The parental PICM-31 cell line, previously characterized as an exocrine pancreas cell line, was colony-cloned two times in succession resulting in the subclonal cell line, PICM-31A1. P...

Molecularly Targeted Dose-Enhancement Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model

DTIC Science & Technology

2013-10-01

cell lines, such as cervix cancer cell line (HeLa) and breast cancer cell line (MDA-MB-231), were also employed. The experiments with other cell lines...breast cancer cell line (MDA-MB- 231), and cervix cancer cell line (HeLa). Different from our hypothesis, prostate cancer cell lines did not present...Radiotherapy Using Gold and Luminescent Nanoparticles in an Orthotopic Human Prostate Cancer Rat Model PRINCIPAL INVESTIGATOR: Kwang Song

Open the gates: vascular neurocrine signaling mobilizes hematopoietic stem and progenitor cells.

PubMed

Itkin, Tomer; Gómez-Salinero, Jesús María; Rafii, Shahin

2017-12-01

Mobilization of hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) into the peripheral blood is a complex process that is enhanced dramatically under stress-induced conditions. A better understanding of how the mobilization process is regulated will likely facilitate the development of improved clinical protocols for stem cell harvesting and transplantation. In this issue of the JCI, Singh et al. (1) showed that the truncated cleaved form of neurotransmitter neuropeptide Y (NPY) actively promotes a breach of BM vascular sinusoidal portals, thereby augmenting HSPC trafficking to the circulation. The authors report a previously unrecognized axis, in which expression of the enzyme dipeptidylpeptidase-4 (DPP4)/CD26 by endothelial cells activates NPY-mediated signaling by increasing the bioavailability of the truncated form of NPY. These findings underscore the importance of and urgency to develop pharmacological therapies that target the vasculature and regulate diverse aspects of hematopoiesis, such as HSPC trafficking, in steady-state and stress-induced conditions.

Pathogenesis of liver cirrhosis.

PubMed

Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

2014-06-21

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

Pathogenesis of liver cirrhosis

PubMed Central

Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

2014-01-01

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions. PMID:24966602

[The factors involved in invasive ability of endometrial carcinoma cells].

PubMed

Mori, Y; Mizuuchi, H; Sato, K; Okamura, N; Kudo, R

1994-06-01

The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.

Current Review of Iron Overload and Related Complications in Hematopoietic Stem Cell Transplantation

PubMed Central

Atilla, Erden; Toprak, Selami K.; Demirer, Taner

2017-01-01

Iron overload is an adverse prognostic factor for patients undergoing hematopoietic stem cell transplantation (HSCT). In the HSCT setting, pretransplant and early posttransplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload was shown to be related to infections, hepatic sinusoidal obstruction syndrome, mucositis, liver dysfunction, and acute graft-versus-host disease. Hyperferritinemia causes decreased survival rates in both pre- and posttransplant settings. Serum ferritin levels, magnetic resonance imaging, and liver biopsy are diagnostic tools for iron overload. Organ dysfunction due to iron overload may cause high mortality rates and therefore sufficient iron chelation therapy is recommended in this setting. In this review the management of iron overload in adult HSCT is discussed. PMID:27956374

In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies

PubMed Central

McDermott, Martina; Eustace, Alex J.; Busschots, Steven; Breen, Laura; Crown, John; Clynes, Martin; O’Donovan, Norma; Stordal, Britta

2014-01-01

The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical drug resistance. PMID:24639951

Navy High-Strength Steel Corrosion-Fatigue Modeling Program

DTIC Science & Technology

2006-10-01

interest. In the global analysis, the axial loading and residual stress (via the temperature profile discussed in the previous section) were applied to...developed based on observa- tions from analyses of axial load components with sinusoidally varying surface geometries. These observations indicated that...profile parameters (height and wavelength in each surface direction) and the applied axial loading . Stress Varies Sinusoidally 180° Out of Phase

Comparison of arterial potassium and ventilatory dynamics during sinusoidal work rate variation in man.

PubMed Central

Casaburi, R; Stringer, W W; Singer, E

1995-01-01

1. The mechanisms underlying the exercise hyperpnoea have been difficult to define. Recently it has been suggested that exercise ventilation (VE) changes in proportion to changes in arterial potassium concentration ([K+]a). Similar VE and [K+]a time courses following work rate changes have been cited as supporting evidence. This study compared [K+]a and VE dynamics during moderate exercise in man. 2. We observed VE and gas exchange responses in five healthy men to sinusoidal work rate variation between 25 and approximately 105 W. Tests of approximately 30 min duration were performed at sinusoidal periods of 9, 6 and 3 min and in the steady state. In each test, during two or three sine periods, arterial blood was sampled (24 per test) and analysed for [K+] and blood gases. Response amplitude and phase (relative to work rate) were determined for each variable. 3. [K+]a fluctuated in response to sinusoidal work rate forcing with mean-to-peak amplitude averaging 0.15 mmol 1(-1). However, among tests, VE amplitude and phase were not highly correlated with [K+]a (r = 0.36 and 0.67, respectively). Further, average [K+]a amplitude in the 9 and 6 min sinusoidal studies tended to exceed the steady-state amplitude, while average VE amplitude fell progressively with increasing forcing frequency. The dissimilar dynamics of [K+]a and VE seem inconsistent with a major role for [K+]a as a proportional controller of ventilation during non-steady state moderate exercise in man. 4. Among tests, VE and CO2 output (VCO2) amplitude and phase were closely correlated (r = 0.87 and 0.94, respectively). Further, arterial CO2 pressure (Pa,CO2) and arterial pH(pHa) did not fluctuate significantly in ten of twenty and thirteen of twenty studies, respectively. In tests where sinusoidal fluctuation was detected, amplitude averaged 1.1 mmHg and 0.008 units, respectively. Thus VE demonstrated a close dynamic coupling to CO2 output, with consequent tight regulation of Pa,CO2 and pHa. PMID:7666376

Immortal, telomerase-negative cell lines derived from a Li-Fraumeni syndrome patient exhibit telomere length variability and chromosomal and minisatellite instabilities.

PubMed

Tsutsui, Takeki; Kumakura, Shin-Ichi; Tamura, Yukiko; Tsutsui, Takeo W; Sekiguchi, Mizuki; Higuchi, Tokihiro; Barrett, J Carl

2003-05-01

Five immortal cell lines derived from a Li-Fraumeni syndrome patient (MDAH 087) with a germline mutant p53 allele were characterized with respect to telomere length and genomic instability. The remaining wild-type p53 allele is lost in the cell lines. Telomerase activity was undetectable in all immortal cell lines. Five subclones of each cell line and five re-subclones of each of the subclones also showed undetectable telomerase activity. All five immortal cell lines exhibited variability in the mean length of terminal restriction fragments (TRFs). Subclones of each cell line, and re-subclones of the subclones also showed TRF variability, indicating that the variability is owing to clonal heterogeneity. Chromosome aberrations were observed at high frequencies in these cell lines including the subclones and re-subclones, and the principal types of aberrations were breaks, double minute chromosomes and dicentric chromosomes. In addition, minisatellite instability detected by DNA fingerprints was observed in the immortal cell lines. However, all of the cell lines were negative for microsatellite instability. As minisatellite sequences are considered recombinogenic in mammalian cells, these results suggest that recombination rates can be increased in these cell lines. Tumor-derived human cell lines, HT1080 cells and HeLa cells that also lack p53 function, exhibited little genomic instability involving chromosomal and minisatellite instabilities, indicating that chromosomal and minisatellite instabilities observed in the immortal cell lines lacking telomerase activity could not result from loss of p53 function.

Effects of varying particle size of forage on digestion and chewing behavior of dairy heifers.

PubMed

Jaster, E H; Murphy, M R

1983-04-01

Eighteen Holstein heifers were fed long and chopped coarse and fine alfalfa hay ad libitum to evaluate effects of physical form on digestion and chemical composition of feed and fecal particles and to examine the applicability of a sinusoidal model to chewing behavior. Recordings of jaw movement were divided into 1-h segments for analysis. Least square mean size of fecal particles from coarse and finely chopped diets were 290 and 297 micrometers as compared to 227 micrometers on long hay. Intakes of dry matter were greater an digestibilities lower for chopped as compared to long hay. Crude protein content of separated feed and fecal particles increased as particle size decreased. Neural and acid detergent fiber concentrations decreased in feed and feces with decreasing particle size. Lignin content of feed particles decreased as particle size decreased, whereas for fecal particles lignin as a percent of cell wall followed a "U" shaped pattern of declining then increasing as size decreased. Patterns were sinusoidal for eating and ruminating long and chopped hays and total chewing (eating and ruminating) of long hay. Our results suggest a gradual effect on chemical degradation and physical detrition of digesta particles and chewing behavior as forage particle size decreased.

Development of apoptosis-resistant dihydrofolate reductase-deficient Chinese hamster ovary cell line.

PubMed

Lee, Suk Kyoo; Lee, Gyun Min

2003-06-30

Apoptosis-resistant dihydrofolate reductase-deficient CHO cell line (dhfr(-) CHO-bcl2) was developed by introduction of the bcl-2 gene into the dhfr(-) CHO cell line (DUKX-B11, ATCC CRL-9096) and subsequent selection of clones stably overexpressing Bcl-2 in the absence of selection pressure. When the dhfr(-) CHO-bcl2 cell line was used as a host cell line for development of a recombinant CHO (rCHO) cell line expressing a humanized antibody, it displayed stable expression of the bcl-2 gene during rCHO cell line development and no detrimental effect of Bcl-2 overexpression on specific antibody productivity. Taken together, the results obtained demonstrate that the use of an apoptosis-resistant dhfr(-) CHO cell line as the host cell line saves the effort of establishing an apoptosis-resistant rCHO cell line and expedites the development process of apoptosis-resistant rCHO cells producing therapeutic proteins. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 872-876, 2003.

Experimental and CFD modeling of fluid mixing in sinusoidal microchannels with different phase shift between side walls

NASA Astrophysics Data System (ADS)

Khosravi Parsa, Mohsen; Hormozi, Faramarz

2014-06-01

In the present work, a passive model of a micromixer with sinusoidal side walls, a convergent-divergent cross section and a T-shape entrance was experimentally fabricated and modeled. The main aim of this modeling was to conduct a study on the Dean and separation vortices created inside the sinusoidal microchannels with a convergent-divergent cross section. To fabricate the microchannels, CO2 laser micromachining was utilized and the fluid mixing pattern is observed using a digital microscope imaging system. Also, computational fluid dynamics was applied with the finite element method to solve Navier-Stokes equations and the diffusion-convection mode in inlet Reynolds numbers of 0.2-75. Numerically obtained results were in reasonable agreement with experimental data. According to the previous studies, phase shift and wavelength of side walls are important parameters in designing sinusoidal microchannels. An increase of phase shift between side walls of microchannels leads the cross section being convergent-divergent. Results also show that at an inlet Reynolds number of <20 the molecular diffusion is the dominant mixing factor and the mixing index extent is nearly identical in all designs. For higher inlet Reynolds numbers (>20), secondary flow is the main factor of mixing. Noticeably, mixing index drastically depends on phase shift (ϕ) and wavelength of side walls (λ) such that the best mixing can be observed in ϕ = 3π/4 and at a wavelength to amplitude ratio of 3.3. Likewise, the maximum pressure drop is reported at ϕ = π. Therefore, the sinusoidal microchannel with phase shifts between π/2 and 3π/4 is the best microchannel for biological and chemical analysis, for which a mixing index value higher than 90% and a pressure drop less than 12 kPa is reported.

Endothelin antagonism in portal hypertensive mice: implications for endothelin receptor-specific signaling in liver disease

PubMed Central

Feng, Hong-Qiang; Weymouth, Nate D.; Rockey, Don C.

2009-01-01

Endothelin-1 (ET-1), a potent vasoactive peptide, plays an important role in the pathogenesis of liver disease and portal hypertension. Two major endothelin receptors (ET-A and ET-B) mediate biological effects, largely on the basis of their known downstream signaling pathways. We hypothesized that the different receptors are likely to mediate divergent effects in portal hypertensive mice. Liver fibrosis and cirrhosis and portal hypertension were induced in 8-wk-old male BALB/c mice by gavage with carbon tetrachloride (CCl4). Portal pressure was recorded acutely during intravenous infusion of endothelin receptor antagonists in normal or portal hypertensive mice. In vivo microscopy was used to monitor sinusoidal dynamics. Additionally, the effect of chronic exposure to endothelin antagonists was assessed in mice during induction of fibrosis and cirrhosis with CCl4 for 8 wk. Intravenous infusion of ET-A receptor antagonists into normal and cirrhotic mice reduced portal pressure whereas ET-B receptor antagonism increased portal pressure. A mixed endothelin receptor antagonist also significantly reduced portal pressure. Additionally, the ET-A receptor antagonist caused sinusoidal dilation, whereas the ET-B receptor antagonist caused sinusoidal constriction. Chronic administration of each the endothelin receptor antagonists during the induction of fibrosis and portal hypertension led to reduced fibrosis, a significant reduction in portal pressure, and altered sinusoidal dynamics relative to controls. Acute effects of endothelin receptor antagonists are likely directly on the hepatic and sinusoidal vasculature, whereas chronic endothelin receptor antagonism appears to be more complicated, likely affecting fibrogenesis and the hepatic microcirculation. The data imply a relationship between hepatic fibrogenesis or fibrosis and vasomotor responses. PMID:19299580

Pre- and post-alpha motoneuronal control of the soleus H-reflex during sinusoidal hip movements in human spinal cord injury

PubMed Central

Knikou, Maria; Chaudhuri, Debjani; Kay, Elizabeth; Schmit, Brian D.

2006-01-01

The aim of this study was to establish the contribution of hip-mediated sensory feedback to spinal interneuronal circuits during dynamic conditions in people with incomplete spinal cord injury (SCI). Specifically, we investigated the effects of synergistic and antagonistic group I afferents on the soleus H-reflex during imposed sinusoidal hip movements. The soleus H-reflex was conditioned by stimulating the common peroneal nerve (CPN) at short (2, 3, and 4 ms) and long (80, 100, and 120 ms) conditioning test (C-T) intervals to assess the reciprocal and pre-synaptic inhibition of the soleus H-reflex, respectively. The soleus H-reflex was also conditioned by medial gastrocnemius (MG) nerve stimulation at C-T intervals ranging from 4 to 7 ms to assess changes in autogenic Ib inhibition during hip movement. Sinusoidal hip movements were imposed to the right hip joint at 0.2 Hz by the Biodex system while subjects were supine. The effects of sinusoidal hip movement on five leg muscles along with hip, knee, and ankle joint torques were also established during sensorimotor conditioning of the reflex. Phase-dependent modulation of antagonistic and synergistic muscle afferents was present during hip movement, with the reciprocal, pre-synaptic, and Ib inhibition to be significantly reduced during hip extension and reinforced during hip flexion. Reflexive muscle and joint torque responses – induced by the hip movement – were entrained to specific phases of hip movement. This study provides evidence that hip-mediated input acts as a controlling signal of pre- and post-alpha motoneuronal control of the soleus H-reflex. The expression of these spinal interneuronal circuits during imposed sinusoidal hip movements is discussed with respect to motor recovery in humans after SCI. PMID:16782072

N-cadherin{sup +} HSCs in fetal liver exhibit higher long-term bone marrow reconstitution activity than N-cadherin{sup -} HSCs

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

Toyama, Hirofumi; Arai, Fumio; Hosokawa, Kentaro

Highlights: Black-Right-Pointing-Pointer High N-cad expression was detected in E12.5 mouse FL LT-HSCs (EPCR{sup +} LSK cells). Black-Right-Pointing-Pointer Immunohistochemically, N-cad{sup +} HSCs co-localized with sinusoidal ECs (Lyve-1{sup +} cells) in E12.5 FL, but these gradually detached in E15.5 and E18.5 FL. Black-Right-Pointing-Pointer N-cad{sup +} LSK cells in E12.5 FL exhibited higher LTR activity versus N-cad{sup -} LSK cells, which decreased in E15.5 and E18.5. Black-Right-Pointing-Pointer N-cad expression may confer high LTR activity to HSCs by facilitating interactions with the perisinusoidal niche in FL. -- Abstract: Adult hematopoietic stem cells (HSCs) are maintained in a microenvironment known as the stem cell niche.more » The regulation of HSCs in fetal liver (FL) and their niche, however, remains to be elucidated. In this study, we investigated the role of N-cadherin (N-cad) in the maintenance of HSCs during FL hematopoiesis. By using anti-N-cad antibodies (Abs) produced by our laboratory, we detected high N-cad expression in embryonic day 12.5 (E12.5) mouse FL HSCs, but not in E15.5 and E18.5 FL. Immunofluorescence staining revealed that N-cad{sup +}c-Kit{sup +} and N-cad{sup +} endothelial protein C receptor (EPCR){sup +} HSCs co-localized with Lyve-1{sup +} sinusoidal endothelial cells (ECs) in E12.5 FL and that some of these cells also expressed N-cad. However, N-cad{sup +} HSCs were also observed to detach from the perisinusoidal niche at E15.5 and E18.5, concomitant with a down-regulation of N-cad and an up-regulation of E-cadherin (E-cad) in hepatic cells. Moreover, EPCR{sup +} long-term (LT)-HSCs were enriched in the N-cad{sup +}Lin{sup -}Sca-1{sup +}c-Kit{sup +} (LSK) fraction in E12.5 FL, but not in E15.5 or E18.5 FL. In a long-term reconstitution (LTR) activity assay, higher engraftment associated with N-cad{sup +} LSK cells versus N-cad{sup -} LSK cells in E12.5 FL when transplanted into lethally irradiated recipient mice. However, the higher engraftment of N-cad{sup +} LSK cells decreased subsequently in E15.5 and E18.5 FL. It is possible that N-cad expression conferred higher LTR activity to HSCs by facilitating interactions with the perisinusoidal niche, especially at E12.5. The down-regulation of N-cad during FL hematopoiesis may help us better understand the regulation and mobility of HSCs before migration into BM.« less

Leukemia-lymphoma cell lines as model systems for hematopoietic research.

PubMed

Drexler, Hans G; MacLeod, Roderick A F

2003-01-01

Continuous human leukemia-lymphoma (LL) cell lines comprise a rich self-renewing resource of accessible and manipulable living cells which has illuminated the pathophysiology of hematopoietic tumors as well as basic cell biology. The major key advantages of continuous cell lines are the unlimited supply and worldwide availability of identical cell material and their cryopreservation. LL cell lines are characterized generally by monoclonal origin and differentiation arrest, sustained proliferation in vitro with preservation of most cellular features, and specific genetic alterations. The most practical classification of LL cell lines assigns them to one of the physiologically occurring cell lineages, based on their immunophenotype, genotype and functional features. Truly malignant cell lines may be distinguished from Epstein-Barr virus (EBV)-immortalized normal cells, using various operational and conceptual parameters. The characterization and publication of new LL cell lines provides important and informative core data which, by opening new avenues for investigation, have become ubiquitous powerful research tools that are available to every investigator by reference cell repositories. There is a need in the scientific community for clean and authenticated LL cell lines to which every scientist has access as offered by these institutionalized public cell line banks. A list of the most useful, robust and freely available reference cell lines is proposed in this review. Clearly, studies of LL cell lines have provided seminal insights into the biology of hematopoietic neoplasia.

Evaluation of thromboelastometry parameters as predictive markers for sinusoidal obstruction syndrome in patients undergoing allogeneic stem cell transplantation for acute leukaemia

PubMed Central

Rupa-Matysek, Joanna; Gil, Lidia; Wojtasińska, Ewelina; Kanduła, Zuzanna; Nowicki, Adam; Matuszak, Magdalena; Komarnicki, Mieczysław

2017-01-01

Hepatic sinusoidal obstruction syndrome (previously named veno-occlusive disease, SOS/VOD) is a serious complication of allogeneic stem cell transplantation (HSCT). Early identification of patients at risk of SOS/VOD may possibly improve the outcome and reduce mortality. Rotation thromboelastometry (ROTEM) is global assay allowing for the precise assessment of both bleeding and thrombotic conditions, however, its usefulness in patients undergoing HSCT for acute leukaemia has not been studied. We evaluated the thromboelastometry parameters in patients undergoing allogeneic HSCT for acute leukaemia to identify candidate biomarkers of SOS/VOD occurrence. ROTEM assays (INTEM, EXTEM, FIBTEM, APTEM) were performed on day -10, on the day of stem cell infusion (day 0) and on days +12 and +28 post-HSCT. The diagnosis of SOS/VOD was based on the Baltimore criteria. Seven patients (26%) developed SOS/VOD. On day +12, the patients with SOS/VOD had statistically significant longer INTEM-CT (clotting time, 199 ± 33.41vs166 ± 23.65s, p = 0.0033), EXTEM-CT (69.5 ± 6.39vs.52 ± 3.42s, p = 0.0139) and FIBTEM-CT (69.5 ± 22.75vs. 50.8 ± 14.31s, p = 0.0124) compared to SOS/VOD (-). ROC curve on day +12 indicated a cut-off value of 179s in INTEM-CT (AUC = 0.91), 69s in EXTEM-CT (AUC = 0.90) and 102s in FIBTEM-CT (AUC = 0.82) for the prediction of SOS/VOD. This is the first study evaluating the usefulness of ROTEM assays in the early detection of haemostasis abnormalities predictive of SOS/VOD development in patients undergoing HSCT for acute leukemia. Patients with SOS/VOD had a significant delay in the initiation of thrombin formation in the analysed ROTEM assays. The utility of ROTEM assays in the optimal management of patients undergoing HSCT should be clarified in further prospective studies. PMID:28938703

Transforming Growth Factor-β Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells.

PubMed

Koudelkova, Petra; Costina, Victor; Weber, Gerhard; Dooley, Steven; Findeisen, Peter; Winter, Peter; Agarwal, Rahul; Schlangen, Karin; Mikulits, Wolfgang

2017-10-10

The entry of malignant hepatocytes into blood vessels is a key step in the dissemination and metastasis of hepatocellular carcinoma (HCC). The identification of molecular mechanisms involved in the transmigration of malignant hepatocytes through the endothelial barrier is of high relevance for therapeutic intervention and metastasis prevention. In this study, we employed a model of hepatocellular transmigration that mimics vascular invasion using hepatic sinusoidal endothelial cells and malignant hepatocytes evincing a mesenchymal-like, invasive phenotype by transforming growth factor (TGF)-β. Labelling of respective cell populations with various stable isotopes and subsequent mass spectrometry analyses allowed the "real-time" detection of molecular changes in both transmigrating hepatocytes and endothelial cells. Interestingly, the proteome profiling revealed 36 and 559 regulated proteins in hepatocytes and endothelial cells, respectively, indicating significant changes during active transmigration that mostly depends on cell-cell interaction rather than on TGF-β alone. Importantly, matching these in vitro findings with HCC patient data revealed a panel of common molecular alterations including peroxiredoxin-3, epoxide hydrolase, transgelin-2 and collectin 12 that are clinically relevant for the patient's survival. We conclude that hepatocellular plasticity induced by TGF-β is crucially involved in blood vessel invasion of HCC cells.

Fiber Optic Sensor Embedment Study for Multi-Parameter Strain Sensing

PubMed Central

Drissi-Habti, Monssef; Raman, Venkadesh; Khadour, Aghiad; Timorian, Safiullah

2017-01-01

The fiber optic sensors (FOSs) are commonly used for large-scale structure monitoring systems for their small size, noise free and low electrical risk characteristics. Embedded fiber optic sensors (FOSs) lead to micro-damage in composite structures. This damage generation threshold is based on the coating material of the FOSs and their diameter. In addition, embedded FOSs are aligned parallel to reinforcement fibers to avoid micro-damage creation. This linear positioning of distributed FOS fails to provide all strain parameters. We suggest novel sinusoidal sensor positioning to overcome this issue. This method tends to provide multi-parameter strains in a large surface area. The effectiveness of sinusoidal FOS positioning over linear FOS positioning is studied under both numerical and experimental methods. This study proves the advantages of the sinusoidal positioning method for FOS in composite material’s bonding. PMID:28333117

Design modification of airfoil by integrating sinusoidal leading edge and dimpled surface

NASA Astrophysics Data System (ADS)

Masud, M. H.; Naim-Ul-Hasan, Arefin, Amit Md. Estiaque; Joardder, Mohammad U. H.

2017-06-01

Airfoil is widely used for aircraft wings and blades of helicopters, turbines, propellers, fans and compressors. Many researches have been conducted on focusing the leading edge, surface and trailing edge of airfoil in order to maximize airfoil lift and to reduce drag. Literature shows that using protuberances along the leading edge of NACA 2412, it is possible to attain better performance from the baseline. Besides, the inward dimpled surface of NACA 0018 produces lesser drag at a positive angle of attacks. However, there is no literature that integrates sinusoidal leading edge and dimpled to attain the benefits of the both. In this study, simulation has been done for design improvement of airfoil by integrating sinusoidal leading edge and dimpled surface. Simulations have been run using finite element method environment. Significant improvement has been observed from the simulation results.

Signal bi-amplification in networks of unidirectionally coupled MEMS

NASA Astrophysics Data System (ADS)

Tchakui, Murielle Vanessa; Woafo, Paul; Colet, Pere

2016-01-01

The purpose of this paper is to analyze the propagation and the amplification of an input signal in networks of unidirectionally coupled micro-electro-mechanical systems (MEMS). Two types of external excitations are considered: sinusoidal and stochastic signals. We show that sinusoidal signals are amplified up to a saturation level which depends on the transmission rate and despite MEMS being nonlinear the sinusoidal shape is well preserved if the number of MEMS is not too large. However, increasing the number of MEMS, there is an instability that leads to chaotic behavior and which is triggered by the amplification of the harmonics generated by the nonlinearities. We also show that for stochastic input signals, the MEMS array acts as a band-pass filter and after just a few elements the signal has a narrow power spectra.

Effects of vibration and shock on the performance of gas-bearing space-power Brayton cycle turbomachinery. 2: Sinusoidal and random vibration

NASA Technical Reports Server (NTRS)

Tessarzik, J. M.; Chiang, T.; Badgley, R. H.

1973-01-01

The vibration response of a gas-bearing rotor-support system was analyzed experimentally documented for sinusoidal and random vibration environments. The NASA Brayton Rotating Unit (BRU), 36,000 rpm; 10 KWe turbogenerator; was subjected in the laboratory to sinusoidal and random vibrations to evaluate the capability of the BRU to (1) survive the vibration levels expected to be encountered during periods of nonoperation and (2) operate satisfactorily (that is, without detrimental bearing surface contacts) at the vibration levels expected during normal BRU operation. Response power spectral density was calculated for specified input random excitation, with particular emphasis upon the dynamic motions of the thrust bearing runner and stator. A three-mass model with nonlinear representation of the engine isolator mounts was used to calculate axial rotor-bearing shock response.

Helical structures in a Rosette elephant trunk

NASA Astrophysics Data System (ADS)

Carlqvist, Per; Kristen, Helmuth; Gahm, Gosta F.

1998-04-01

We discuss small-scale, helical, interstellar filaments on the basis of optical observations of an elephant trunk in the Rosette nebula. The trunk studied is composed of a number of sinusoidal or serpentine-like dark filaments, preferentially in the outer part of the trunk, where their wavelength is 7-9 times the trunk radius. The diameters are down to the limit of resolution of 1.0 arcsec, corresponding to 1600 au, and ranging up to about 6400 au. At some positions filament crossings give rise to enhanced extinction. We suggest that the sinusoidal filaments are helices lined up by magnetic fields. We derive average extinctions of 0.5-1.0 mag in the filaments, implying molecular densities of n_H2 ~ 10(4) cm(-3) . From existing data on the Rosette HiI region, we conclude that the surrounding kinetic and dynamic pressure and the background radiation field suffice to balance even the denser filaments and to exert drag forces on the trunk as a whole, consistent with evidence of stretching of the trunk. The helical magnetic structures imply the presence of electric currents along the trunk axis. These currents should form a nearly force-free geometry and are consistent with a model consisting of 4-7 helical cables on the surface of a cylinder and which produce the observed wavelength of the helices. We suggest that the Rosette elephant trunks form an interconnected system of rope-like structures which are relics from filamentary skeletons of magnetic fields in the primordial cloud. Based on observations collected at the Nordic Optical Telescope, La Palma, Spain

[Establishment of human embryonic stem cell lines and their therapeutic application].

PubMed

Suemori, Hirofumi

2004-03-01

Embryonic stem (ES) cell lines are pluripotent stem cell lines that can be propagated indefinitely in culture, retaining their potency to differentiate into every type of cell and tissue in the body. ES cell lines were first established from mouse blastocysts, and have been used for research in developmental biology. ES cells have been proven to be very valuable in the genetic modification of the mouse, especially in producing knockout mice. Since establishment of human ES cell lines was reported, their use in cell replacement therapies has been enthusiastically expected. There have been reports of the differentiation of several useful cell types from human ES cell lines, and clinical use of functional tissues and cells from human ES cells is anticipated. In Japan, there have also been many demands for the use of human ES cells in basic and pre-clinical research. We obtained governmental permission to establish human ES cell lines in April 2002 and started research using donated frozen embryos in January 2003. We successfully established three ES cell line from three blastocysts. These cell lines will be distributed at cost to researchers who have governmental permission to use human ES cells.

Chandipura virus growth kinetics in vertebrate cell lines, insect cell lines & embryonated eggs.

PubMed

Jadi, R S; Sudeep, A B; Kumar, Satyendra; Arankalle, V A; Mishra, A C

2010-08-01

Since not much information on Chandipura virus is available, an attempt was made to study the growth kinetics of the virus in certain vertebrate, invertebrate cell lines and embryonated chicken eggs. Comparative study of Chandipura virus (CHPV) growth kinetics in three vertebrate cell lines [Vero E6, Rhabdo myosarcoma (RD), Porcine stable kidney (PS) cell lines], two insect cell lines [Aedes aegypti (AA) and Phlebotomus papatasi (PP-9) cell lines] and embryonated pathogen free chicken eggs was conducted, by tissue culture infective dose 50 per cent (TCID(50)) and indirect immunofluorescence assay (IFA). All the cell lines and embryonated egg supported the growth of CHPV and yielded high virus titre. The vertebrate cell lines showed distinct cytopathic effect (CPE) within 4-6 h post infection (PI), while no CPE was observed in insect cell lines. PP-9 cell line was the most sensitive system to CHPV as viral antigen could be detected at 1 h PI by IFA. Our results demonstrated that all the systems were susceptible to CHPV and achieved high yield of virus. However, the PP-9 cell line had an edge over the others due to its high sensitivity to the virus which might be useful for detection and isolation of the virus during epidemics.

Auditory Models for Speech Analysis

DTIC Science & Technology

1988-01-01

to encode stimulus frequency by firing in period with the clicks, up to a critical value. (Godfrey ct al., 1975). Some binaural processing appears to...masking experiments avoid sinosoiVs since a sinusoidal signal combined with a sinusoidal masker can cause " beats " due to regular fluctuations in the...such as sound localisation (Lyon, 1983). Jeffress (1956) proposed a binaural localisation model where the "mechanism receives impulses from corresponding

Conversion of Radio-Frequency Pulses to Continuous-Wave Sinusoids by Fast Switching and Narrowband Filtering

DTIC Science & Technology

2016-09-01

Switching and Narrowband Filtering by Gregory J Mazzaro, Andrew J Sherbondy, Kenneth I Ranney, and Kelly D Sherbondy...Switching and Narrowband Filtering by Gregory J Mazzaro, Andrew J Sherbondy, Kenneth I Ranney, and Kelly D Sherbondy Sensors and Electron Devices...08/2016 4. TITLE AND SUBTITLE Conversion of Radio-Frequency Pulses to Continuous-Wave Sinusoids by Fast Switching and Narrowband Filtering 5a

Instability of isolated planar shock waves

DTIC Science & Technology

2007-06-07

Note that multi-mode perturbations can be treated by the inclusion of additional terms in Eq. (4), but owing to the linear independence of the... Volterra equation Figure 4 shows five examples of the evolution of the amplitude of a linear sinusoidal perturbation on a shock front obtained by...showing the evolution of the amplitude of a linear sinusoidal perturbation on a shock front obtained by numerically solving the Volterra equation in

Computer Program for Thin Wire Antenna over a Perfectly Conducting Ground Plane. [using Galerkins method and sinusoidal bases

NASA Technical Reports Server (NTRS)

Richmond, J. H.

1974-01-01

A computer program is presented for a thin-wire antenna over a perfect ground plane. The analysis is performed in the frequency domain, and the exterior medium is free space. The antenna may have finite conductivity and lumped loads. The output data includes the current distribution, impedance, radiation efficiency, and gain. The program uses sinusoidal bases and Galerkin's method.

Synchronous meteorological satellite system description document, volume 3

NASA Technical Reports Server (NTRS)

Pipkin, F. B.

1971-01-01

The structural design, analysis, and mechanical integration of the synchronous meteorological satellite system are presented. The subjects discussed are: (1) spacecraft configuration, (2) structural design, (3) static load tests, (4) fixed base sinusoidal vibration survey, (5) flight configuration sinusoidal vibration tests, (6) spacecraft acoustic test, and (7) separation and shock test. Descriptions of the auxiliary propulsion subsystem, the apogee boost motor, communications system, and thermal control subsystem are included.

Electrical properties of AlGaN/GaN HEMTs in stretchable geometries

NASA Astrophysics Data System (ADS)

Tompkins, R. P.; Mahaboob, I.; Shahedipour-Sandvik, F.; Lazarus, N.

2017-10-01

Many biological materials are naturally soft and stretchable, far more so than crystalline semiconductors. Creating systems that can be placed directly on a surface such as human skin has required new approaches in electronic device design and materials, a field known as stretchable electronics. One common method for fabricating a highly brittle semiconductor device able to survive tens of percent strain is to incorporate stress relief structures ('waves'). Although the mechanical advantages of this approach are well known, the effects on the electrical behavior of a device such as a transistor compared to a more traditional geometry have not been studied. Here, AlGaN/GaN high electron mobility transistors (HEMTs) grown on rigid sapphire substrates were fabricated in a common wavy geometry, a sinusoid, with dimensions similar to those used in stretchable electronics. The study analyzes control parameters available to the designer including gate location along the sinusoid, angle the source-drain contacts make with the gate, as well as variation of the gate length at the peak of the sinusoid. Common electrical parameters such as saturation current density, threshold voltage, and transconductance were compared between the sinusoidal and conventional straight geometries and results found to fall to within experimental uncertainty, suggesting shifting to a stretchable geometry is possible without appreciably degrading semiconductor device performance.

Zero-crossing approach to high-resolution reconstruction in frequency-domain optical-coherence tomography.

PubMed

Krishnan, Sunder Ram; Seelamantula, Chandra Sekhar; Bouwens, Arno; Leutenegger, Marcel; Lasser, Theo

2012-10-01

We address the problem of high-resolution reconstruction in frequency-domain optical-coherence tomography (FDOCT). The traditional method employed uses the inverse discrete Fourier transform, which is limited in resolution due to the Heisenberg uncertainty principle. We propose a reconstruction technique based on zero-crossing (ZC) interval analysis. The motivation for our approach lies in the observation that, for a multilayered specimen, the backscattered signal may be expressed as a sum of sinusoids, and each sinusoid manifests as a peak in the FDOCT reconstruction. The successive ZC intervals of a sinusoid exhibit high consistency, with the intervals being inversely related to the frequency of the sinusoid. The statistics of the ZC intervals are used for detecting the frequencies present in the input signal. The noise robustness of the proposed technique is improved by using a cosine-modulated filter bank for separating the input into different frequency bands, and the ZC analysis is carried out on each band separately. The design of the filter bank requires the design of a prototype, which we accomplish using a Kaiser window approach. We show that the proposed method gives good results on synthesized and experimental data. The resolution is enhanced, and noise robustness is higher compared with the standard Fourier reconstruction.

Malignant hematopoietic cell lines: in vitro models for the study of natural killer cell leukemia-lymphoma.

PubMed

Drexler, H G; Matsuo, Y

2000-05-01

Malignancies involving natural killer (NK) cells are rare disorders. The complexity of NK cell-involving disorders has only recently been appreciated. Modern classifications discern immature (precursor) from mature NK cell leukemias-lymphomas. Continuous NK leukemia-lymphoma cell lines represent important model systems to study these neoplasms. While there are a number of putative NK cell lines which are, however, either not characterized, not immortalized, non-malignant, non-NK, or plain false cell lines, six bona fide malignant NK cell lines have been established and are sufficiently well characterized: HANK1, KHYG-1, NK-92, NKL, NK-YS and YT. Except for YT which was derived from a not further defined acute lymphoblastic lymphoma, these cell lines were established from patients with various NK cell malignancies. Five of the six cell lines are constitutively interleukin-2-dependent. Their immunoprofile is remarkably similar: CD1-, CD2+, surface CD3 (but cytoplasmic CD3epsilon+), CD4-, CD5-, CD7+, CD8-, CD16-, CD56+, CD57-, TCRalphabeta-, TCRgammadelta-, negative for B cell and myelomonocytic markers. The immunoglobulin heavy chain and T cell receptor genes are all in germline configuration. All six lines show complex chromosomal alterations, with both numerical and structural aberrations, attesting to their malignant and monoclonal nature. Functionally, these cells which contain azurophilic granules in their cytoplasm are nearly universally positive in NK activity assays. Three of five cell lines are Epstein-Barr virus-positive (type II latency). The composite data on these six cell lines allow for the operational definition of a typical malignant NK cell line profile. NK leukemia-lymphoma cell lines will prove invaluable for studies of normal and malignant NK cell biology.

Derivation and characterization of Chinese human embryonic stem cell line with high potential to differentiate into pancreatic and hepatic cells.

PubMed

Shi, Cheng; Shen, Huan; Jiang, Wei; Song, Zhi-Hua; Wang, Cheng-Yan; Wei, Li-Hui

2011-04-01

Human embryonic stem cells have prospective uses in regenerative medicine and drug screening. Every human embryonic stem cell line has its own genetic background, which determines its specific ability for differentiation as well as susceptibility to drugs. It is necessary to compile many human embryonic stem cell lines with various backgrounds for future clinical use, especially in China due to its large population. This study contributes to isolating new Chinese human embryonic stem cell lines with clarified directly differentiation ability. Donated embryos that exceeded clinical use in our in vitro fertilization-embryo transfer (IVF-ET) center were collected to establish human embryonic stem cells lines with informed consent. The classic growth factors of basic fibroblast growth factor (bFGF) and recombinant human leukaemia inhibitory factor (hLIF) for culturing embryonic stem cells were used to capture the stem cells from the plated embryos. Mechanical and enzymetic methods were used to propagate the newly established human embryonic stem cells line. The new cell line was checked for pluripotent characteristics with detecting the expression of stemness genes and observing spontaneous differentiation both in vitro and in vivo. Finally similar step-wise protocols from definitive endoderm to target specific cells were used to check the cell line's ability to directly differentiate into pancreatic and hepatic cells. We generated a new Chinese human embryonic stem cells line, CH1. This cell line showed the same characteristics as other reported Chinese human embryonic stem cells lines: normal morphology, karyotype and pluripotency in vitro and in vivo. The CH1 cells could be directly differentiated towards pancreatic and hepatic cells with equal efficiency compared to the H1 cell line. This newly established Chinese cell line, CH1, which is pluripotent and has high potential to differentiate into pancreatic and hepatic cells, will provide a useful tool for embryo development research, along with clinical treatments for diabetes and some hepatic diseases.

77 FR 5489 - Identification of Human Cell Lines Project

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-03

...-01] Identification of Human Cell Lines Project AGENCY: National Institute of Standards and Technology... cell line samples as part of the Identification of Human Cell Lines Project. All data and corresponding... cell lines accepted on the NIST Applied Genetics Group Web site at http://www.nist.gov/mml/biochemical...

Numerical study on xenon positive column discharges of mercury-free lamp

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

Ouyang, Jiting; He, Feng; Miao, Jinsong

2007-02-15

In this paper, the numerical study has been performed on the xenon positive column discharges of mercury-free fluorescent lamp. The plasma discharge characteristics are analyzed by numerical simulation based on two-dimensional fluid model. The effects of cell geometry, such as the dielectric layer, the electrode width, the electrode gap, and the cell height, and the filling gas including the pressure and the xenon percentage are investigated in terms of discharge current and discharge efficiency. The results show that a long transient positive column will form in the xenon lamp when applying ac sinusoidal power and the lamp can operate inmore » a large range of voltage and frequency. The front dielectric layer of the cell plays an important role in the xenon lamp while the back layer has little effect. The ratio of electrode gap to cell height should be large to achieve a long positive column xenon lamp and higher efficiency. Increase of pressure or xenon concentration results in an increase of discharge efficiency and voltage. The discussions will be helpful for the design of commercial xenon lamp cells.« less

Development and characterization of two new cell lines from milkfish (Chanos chanos) and grouper (Epinephelus coioides) for virus isolation.

PubMed

Parameswaran, V; Ishaq Ahmed, V P; Shukla, Ravi; Bhonde, R R; Sahul Hameed, A S

2007-01-01

Two new cell lines, SIMH and SIGE, were derived from the heart of milkfish (Chanos chanos), a euryhaline teleost, and from the eye of grouper (Epinephelus coioides), respectively. These cell lines were maintained in Leibovitz's L-15 supplemented with 20% fetal bovine serum (FBS). The SIMH cell line was subcultured more than 50 times over a period of 210 days and SIGE cell line has been subcultured 100 times over a period of 1 1/2 years. The SIMH cell line consists predominantly of fibroblastic-like cells. The SIGE cell line consists predominantly of epithelial cells. Both the cell lines were able to grow at temperatures between 25 and 32 degrees C with an optimum temperature of 28 degrees C. The growth rate of these cells increased as the proportion of FBS increased from 2% to 20% at 28 degrees C with optimum growth at the concentrations of 15% or 20% FBS. Seven marine fish viruses were tested to determine the susceptibility of these cell lines. The SIGE cell line was found to be susceptible to nodavirus, MABV NC-1 and Y6, and the infection was confirmed by cytopathic effect (CPE) and reverse transcriptase-polymerase chain reaction. When these cells were transfected with pEGFP-N1 vector DNA, significant fluorescent signals were observed, suggesting that these cell lines can be a useful tool for transgenic and genetic manipulation studies. Further, these cell lines are characterized by immunocytochemistry using confocal laser scanning microscopy (CFLSM).

Von Willebrand Factor Deposition and ADAMTS-13 Consumption in Allograft Tissue of Thrombotic Microangiopathy-like Disorder After Living Donor Liver Transplantation: A Case Report.

PubMed

Nakanuma, S; Miyashita, T; Hayashi, H; Ohbatake, Y; Takamura, H; Okazaki, M; Yamaguchi, T; Sakai, S; Makino, I; Oyama, K; Tajima, H; Ninomiya, I; Fushida, S; Ohta, T

2017-09-01

Thrombotic microangiopathy (TMA) pathogenesis after living donor liver transplantation (LDLT) is thought to be caused by release of unusually large von Willebrand factor multimers (UL-vWFMs) resulting from sinusoidal endothelial cell damage and induction of platelet adhesion and aggregation. A decrease in a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs-13 (ADAMTS-13) that cleave UL-vWFMs might cause excessive UL-vWFMs activity and result in platelet thrombus formation. However, this phenomenon has not undergone a full pathologic assessment. A 60-year-old man was diagnosed with hepatitis C-related end-stage cirrhosis. His son was the donor, and he underwent LDLT. On postoperative day 44, his laboratory findings met most TMA diagnostic criteria, and he was diagnosed with TMA-like disorder (TMALD). Localization of CD42b as a platelet marker, vWF, and ADAMTS-13 in allograft tissue of this patient were evaluated using immunohistochemistry. CD42b expression was observed as platelet aggregates attached to hepatocytes or within the hepatocyte cytoplasm, a morphology called extravasated platelet aggregation (EPA). vWF expression was observed mainly as deposited compact clusters, and ADAMTS-13 expression resembled distinct dots throughout the liver tissue. These findings suggest that EPA indicated sinusoidal endothelial cell damage followed by detachment, and vWF deposition resulted from UL-vWFM oversynthesis. ADAMTS-13 might be consumed in the allograft tissue to cleave UL-vWFMs, but ADAMTS-13 levels might be insufficient to cleave all the deposited UL-vWFMs. We present the case of an LDLT recipient diagnosed with TMALD using blood tests, which showed the presence of TMA pathogenesis in the allograft. Copyright © 2017 Elsevier Inc. All rights reserved.

Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration.

PubMed

Luo, Xiaoying; Dan Wang; Luo, Xuan; Zhu, Xintao; Wang, Guozhen; Ning, Zuowei; Li, Yang; Ma, Xiaoxin; Yang, Renqiang; Jin, Siyi; Huang, Yun; Meng, Ying; Li, Xu

2017-10-01

Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models. In vitro, fenestrae of primary LSECs gradually shrank, along with the down-regulation of the NO-dependent pathway and the augment of the AMPK-dependent autophagy; these effects were aggravated by rapamycin (an autophagy activator) or aldosterone treatment. Additionally, aldosterone increased oxidation mediated by Cav1, reduced ATP generation, and subsequently induced the AMPK-dependent autophagy, leading to the down-regulation of the NO-dependent pathway and LSECs defenestration. These effects were reversed by MR antagonist spironolactone, antioxidants or autophagy inhibitors. Besides, aldosterone enhanced the co-immunoprecipitation of Cav1 with p62 and ubiquitin, and induced Cav1 co-immunofluorescence staining with LC3, ubiquitin, and F-actin in the perinuclear area of LSECs. Furthermore, aldosterone treatment increased the membrane protein level of Cav1, whereas decrease the cytoplasmic protein level of Cav1, indicating that aldosterone induced Cav1-related selective autophagy and F-actin remodeling to promote defenestration. Consequently, Cav1-related selective autophagy initiated by aldosterone-induced oxidation promotes LSECs defenestration via activating the AMPK-ULK1 pathway and inhibiting the NO-dependent pathway. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

CD147 promotes liver fibrosis progression via VEGF-A/VEGFR2 signalling-mediated cross-talk between hepatocytes and sinusoidal endothelial cells.

PubMed

Yan, Zhaoyong; Qu, Kai; Zhang, Jing; Huang, Qichao; Qu, Ping; Xu, Xinsen; Yuan, Peng; Huang, Xiaojun; Shao, Yongping; Liu, Chang; Zhang, Hongxin; Xing, Jinliang

2015-10-01

Although previous evidence indicates close involvement of CD147 in the pathogenesis of liver fibrosis, the underlying molecular mechanisms and its therapeutic value remain largely unknown. In the present study, we investigated the biological roles of CD147 in liver fibrosis and assessed its therapeutic value as a target molecule in the CCl4-induced liver fibrosis mouse model. We found that CD147 was highly expressed in both hepatocytes and SECs (sinusoidal endothelial cells) in fibrotic liver tissues. Additionally, it was significantly associated with the fibrosis stage. TGF-β1 (transforming growth factor β1) was found to be mainly responsible for the up-regulation of CD147. Bioinformatic and experimental data suggest a functional link between CD147 expression and VEGF-A (vascular endothelial growth factor A)/VEGR-2 (VEGF receptor 2) signalling-mediated angiogenesis in fibrotic liver tissues. Furthermore, we observed that the CD147-induced activation of the PI3K (phosphoinositide 3-kinase)/Akt signalling pathway promotes the production of VEGF-A in hepatocytes and expression of VEGFR-2 in SECs, which was found to enhance the angiogenic capability of SECs. Finally, our data indicate that blocking of CD147 using an mAb (monoclonal antibody) attenuated liver fibrosis progression via inhibition of VEGF-A/VEGFR-2 signalling and subsequent amelioration of microvascular abnormality in the CCl4-induced mouse model. Our findings suggest a novel functional mechanism that CD147 may promote liver fibrosis progression via inducing the VEGF-A/VEGFR-2 signalling pathway-mediated cross-talk between hepatocytes and SECs. New strategies based on the intervention of CD147 can be expected for prevention of liver fibrosis. © 2015 Authors; published by Portland Press Limited.

A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

PubMed

Cherkaoui-Rbati, Mohammed H; Paine, Stuart W; Littlewood, Peter; Rauch, Cyril

2017-01-01

All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit), located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level). A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK) model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s) including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

Recognition and processing of randomly fluctuating electric signals by Na,K-ATPase.

PubMed Central

Xie, T. D.; Marszalek, P.; Chen, Y. D.; Tsong, T. Y.

1994-01-01

Previous work has shown that Na,K-ATPase of human erythrocytes can extract free energy from sinusoidal electric fields to pump cations up their respective concentration gradients. Because regularly oscillating waveform is not a feature of the transmembrane electric potential of cells, questions have been raised whether these observed effects are biologically relevant. Here we show that a random-telegraph fluctuating electric field (RTF) consisting of alternating square electric pulses with random lifetimes can also stimulate the Rb(+)-pumping mode of the Na,K-ATPase. The net RTF-stimulated, ouabain-sensitive Rb+ pumping was monitored with 86Rb+. The tracer-measured, Rb+ influx exhibited frequency and amplitude dependencies that peaked at the mean frequency of 1.0 kHz and amplitude of 20 V/cm. At 4 degrees C, the maximal pumping activity under these optimal conditions was 28 Rb+/RBC-hr, which is approximately 50% higher than that obtained with the sinusoidal electric field. These findings indicate that Na,K-ATPase can recognize an electric signal, either regularly oscillatory or randomly fluctuating, for energy coupling, with high fidelity. The use of RTF for activation also allowed a quantitative theoretical analysis of kinetics of a membrane transport model of any complexity according to the theory of electroconformational coupling (ECC) by the diagram methods. A four-state ECC model was shown to produce the amplitude and the frequency windows of the Rb(+)-pumping if the free energy of interaction of the transporter with the membrane potential was to include a nonlinear quadratic term. Kinetic constants for the ECC model have been derived. These results indicate that the ECC is a plausible mechanism for the recognition and processing of electric signals by proteins of the cell membrane. PMID:7811939

Authentication of M14 melanoma cell line proves misidentification of MDA‐MB‐435 breast cancer cell line

PubMed Central

Korch, Christopher; Hall, Erin M.; Dirks, Wilhelm G.; Ewing, Margaret; Faries, Mark; Varella‐Garcia, Marileila; Robinson, Steven; Storts, Douglas; Turner, Jacqueline A.; Wang, Ying; Burnett, Edward C.; Healy, Lyn; Kniss, Douglas; Neve, Richard M.; Nims, Raymond W.; Reid, Yvonne A.; Robinson, William A.

2017-01-01

A variety of analytical approaches have indicated that melanoma cell line UCLA‐SO‐M14 (M14) and breast carcinoma cell line MDA‐MB‐435 originate from a common donor. This indicates that at some point in the past, one of these cell lines became misidentified, meaning that it ceased to correspond to the reported donor and instead became falsely identified (through cross‐contamination or other means) as a cell line from a different donor. Initial studies concluded that MDA‐MB‐435 was the misidentified cell line and M14 was the authentic cell line, although contradictory evidence has been published, resulting in further confusion. To address this question, we obtained early samples of the melanoma cell line (M14), a lymphoblastoid cell line from the same donor (ML14), and donor serum preserved at the originator's institution. M14 samples were cryopreserved in December 1975, before MDA‐MB‐435 cells were established in culture. Through a series of molecular characterizations, including short tandem repeat (STR) profiling and cytogenetic analysis, we demonstrated that later samples of M14 and MDA‐MB‐435 correspond to samples of M14 frozen in 1975, to the lymphoblastoid cell line ML14, and to the melanoma donor's STR profile, sex and blood type. This work demonstrates conclusively that M14 is the authentic cell line and MDA‐MB‐435 is misidentified. With clear provenance information and authentication testing of early samples, it is possible to resolve debates regarding the origins of problematic cell lines that are widely used in cancer research. PMID:28940260

Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling.

PubMed

Povey, Jane F; O'Malley, Christopher J; Root, Tracy; Martin, Elaine B; Montague, Gary A; Feary, Marc; Trim, Carol; Lang, Dietmar A; Alldread, Richard; Racher, Andrew J; Smales, C Mark

2014-08-20

Despite many advances in the generation of high producing recombinant mammalian cell lines over the last few decades, cell line selection and development is often slowed by the inability to predict a cell line's phenotypic characteristics (e.g. growth or recombinant protein productivity) at larger scale (large volume bioreactors) using data from early cell line construction at small culture scale. Here we describe the development of an intact cell MALDI-ToF mass spectrometry fingerprinting method for mammalian cells early in the cell line construction process whereby the resulting mass spectrometry data are used to predict the phenotype of mammalian cell lines at larger culture scale using a Partial Least Squares Discriminant Analysis (PLS-DA) model. Using MALDI-ToF mass spectrometry, a library of mass spectrometry fingerprints was generated for individual cell lines at the 96 deep well plate stage of cell line development. The growth and productivity of these cell lines were evaluated in a 10L bioreactor model of Lonza's large-scale (up to 20,000L) fed-batch cell culture processes. Using the mass spectrometry information at the 96 deep well plate stage and phenotype information at the 10L bioreactor scale a PLS-DA model was developed to predict the productivity of unknown cell lines at the 10L scale based upon their MALDI-ToF fingerprint at the 96 deep well plate scale. This approach provides the basis for the very early prediction of cell lines' performance in cGMP manufacturing-scale bioreactors and the foundation for methods and models for predicting other mammalian cell phenotypes from rapid, intact-cell mass spectrometry based measurements. Copyright © 2014 Elsevier B.V. All rights reserved.

Casein gene expression in mouse mammary epithelial cell lines: Dependence upon extracellular matrix and cell type

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

Medina, D.; Oborn, C.J.; Li, M.L.

1987-09-01

The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D lines. None of the four clonal lines appearedmore » to represent myoepithelial cells. The cell lines were examined for expression of {beta}-casein mRNA in the presence or absence of prolactin. The inducibility of {beta}-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types.« less

Adventitious viruses in insect cell lines used for recombinant protein expression.

PubMed

Geisler, Christoph; Jarvis, Donald L

2018-04-01

Insect cells are widely used for recombinant protein expression, typically as hosts for recombinant baculovirus vectors, but also for plasmid-mediated transient transfection or stable genetic transformation. Insect cells are used to express proteins for research, as well as to manufacture biologicals for human and veterinary medicine. Recently, several insect cell lines used for recombinant protein expression were found to be persistently infected with adventitious viruses. This has raised questions about how these infections might affect research performed using those cell lines. Furthermore, these findings raised serious concerns about the safety of biologicals produced using those cell lines. In response, new insect cell lines lacking adventitious viruses have been isolated for use as improved research tools and safer biological manufacturing platforms. Here, we review the scientific and patent literature on adventitious viruses found in insect cell lines, affected cell lines, and new virus-free cell lines. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of curcumin on stem-like cells in human esophageal squamous carcinoma cell lines.

PubMed

Almanaa, Taghreed N; Geusz, Michael E; Jamasbi, Roudabeh J

2012-10-24

Many cancers contain cell subpopulations that display characteristics of stem cells. Because these cancer stem cells (CSCs) appear to provide resistance to chemo-radiation therapy, development of therapeutic agents that target CSCs is essential. Curcumin is a phytochemical agent that is currently used in clinical trials to test its effectiveness against cancer. However, the effect of curcumin on CSCs is not well established. The current study evaluated curcumin-induced cell death in six cancer cell lines derived from human esophageal squamous cell carcinomas. Moreover, these cell lines and the ones established from cells that survived curcumin treatments were characterized. Cell loss was assayed after TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2 cells were exposed to 20-80 μM curcumin for 30 hrs. Cell lines surviving 40 or 60 μM curcumin were established from these six original lines. The stem cell markers aldehyde dehydrogenase-1A1 (ALDH1A1) and CD44 as well as NF-κB were used to compare CSC-like subpopulations within and among the original lines as well as the curcumin-surviving lines. YES-2 was tested for tumorsphere-forming capabilities. Finally, the surviving lines were treated with 40 and 60 μM curcumin to determine whether their sensitivity was different from the original lines. The cell loss after curcumin treatment increased in a dose-dependent manner in all cell lines. The percentage of cells remaining after 60 μM curcumin treatment varied from 10.9% to 36.3% across the six lines. The cell lines were heterogeneous with respect to ALDH1A1, NF-κB and CD44 expression. KY-5 and YES-1 were the least sensitive and had the highest number of stem-like cells whereas TE-1 had the lowest. The curcumin-surviving lines showed a significant loss in the high staining ALDH1A1 and CD44 cell populations. Tumorspheres formed from YES-2 but were small and rare in the YES-2 surviving line. The curcumin-surviving lines showed a small but significant decrease in sensitivity to curcumin when compared with the original lines. Our results suggest that curcumin not only eliminates cancer cells but also targets CSCs. Therefore, curcumin may be an effective compound for treating esophageal and possibly other cancers in which CSCs can cause tumor recurrence.

Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines

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

Gestl, Erin E., E-mail: egestl@wcupa.edu; Anne Boettger, S., E-mail: aboettger@wcupa.edu

2012-06-29

Highlights: Black-Right-Pointing-Pointer Eight human colorectal cell lines were evaluated for p53 and mortalin localization. Black-Right-Pointing-Pointer Six cell lines displayed cytoplasmic sequestration of the tumor suppressor p53. Black-Right-Pointing-Pointer Direct interaction between mortalin and p53 was shown in five cell lines. Black-Right-Pointing-Pointer Cell lines positive for p53 sequestration yielded elevated p53 expression levels. Black-Right-Pointing-Pointer This study yields the first evidence of cytoplasmic sequestration p53 by mortalin. -- Abstract: While it is known that cytoplasmic retention of p53 occurs in many solid tumors, the mechanisms responsible for this retention have not been positively identified. Since heatshock proteins like mortalin have been associated withmore » p53 inactivation in other tumors, the current study sought to characterize this potential interaction in never before examined colorectal adenocarcinoma cell lines. Six cell lines, one with 3 different fractions, were examined to determine expression of p53 and mortalin and characterize their cellular localization. Most of these cell lines displayed punctate p53 and mortalin localization in the cell cytoplasm with the exception of HCT-8 and HCT116 379.2 cells, where p53 was not detected. Nuclear p53 was only observed in HCT-116 40-16, LS123, and HT-29 cell lines. Mortalin was only localized in the cytoplasm in all cell lines. Co-immunoprecipitation and immunohistochemistry revealed that p53 and mortalin were bound and co-localized in the cytoplasmic fraction of four cell lines, HCT-116 (40-16 and 386; parental and heterozygous fractions respectively of the same cell line), HT-29, LS123 and LoVo, implying that p53 nuclear function is limited in those cell lines by being restricted to the cytoplasm. Mortalin gene expression levels were higher than gene expression levels of p53 in all cell lines. Cell lines with cytoplasmic sequestration of p53, however, also displayed elevated p53 gene expression levels compared to cell lines without p53 sequestration. Our data reveal the characteristic cytoplasmic sequestration of p53 by the heat shock protein mortalin in human colorectal adenocarcinoma cell lines, as is the case for other cancers, such as glioblastomas and hepatocellular carcinomas.« less

Transforming Growth Factor-β Drives the Transendothelial Migration of Hepatocellular Carcinoma Cells

PubMed Central

Koudelkova, Petra; Costina, Victor; Weber, Gerhard; Dooley, Steven; Findeisen, Peter; Winter, Peter; Agarwal, Rahul; Schlangen, Karin

2017-01-01

The entry of malignant hepatocytes into blood vessels is a key step in the dissemination and metastasis of hepatocellular carcinoma (HCC). The identification of molecular mechanisms involved in the transmigration of malignant hepatocytes through the endothelial barrier is of high relevance for therapeutic intervention and metastasis prevention. In this study, we employed a model of hepatocellular transmigration that mimics vascular invasion using hepatic sinusoidal endothelial cells and malignant hepatocytes evincing a mesenchymal-like, invasive phenotype by transforming growth factor (TGF)-β. Labelling of respective cell populations with various stable isotopes and subsequent mass spectrometry analyses allowed the “real-time” detection of molecular changes in both transmigrating hepatocytes and endothelial cells. Interestingly, the proteome profiling revealed 36 and 559 regulated proteins in hepatocytes and endothelial cells, respectively, indicating significant changes during active transmigration that mostly depends on cell–cell interaction rather than on TGF-β alone. Importantly, matching these in vitro findings with HCC patient data revealed a panel of common molecular alterations including peroxiredoxin-3, epoxide hydrolase, transgelin-2 and collectin 12 that are clinically relevant for the patient’s survival. We conclude that hepatocellular plasticity induced by TGF-β is crucially involved in blood vessel invasion of HCC cells. PMID:28994702

Development of a new canine osteosarcoma cell line.

PubMed

Séguin, B; Zwerdling, T; McCallan, J L; DeCock, H E V; Dewe, L L; Naydan, D K; Young, A E; Bannasch, D L; Foreman, O; Kent, M S

2006-12-01

Establishing a canine osteosarcoma (OSA) cell line can be useful to develop in vivo and in vitro models of OSA. The goal of this study was to develop, characterize and authenticate a new canine OSA cell line and a clone. A cell line and a clone were developed with standard cell culture techniques from a naturally occurring OSA in a dog. The clonal cell line induced a tumour after injection in RAG 1-deficient mouse. Histology was consistent with OSA. The original tumour from the dog and the tumour induced in the mouse were both reactive with vimentin and osteonectin (ON). The parent cell line and clonal cell line were reactive with ON, osteocalcin and alkaline phosphatase. Loss of heterozygosity was found in the same three microsatellite markers in the parent and clonal cell lines, and the tumour tissue grown in the mouse.

Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines

PubMed Central

Bock, Christoph; Kiskinis, Evangelos; Verstappen, Griet; Gu, Hongcang; Boulting, Gabriella; Smith, Zachary D.; Ziller, Michael; Croft, Gist F.; Amoroso, Mackenzie W.; Oakley, Derek H.; Gnirke, Andreas; Eggan, Kevin; Meissner, Alexander

2011-01-01

SUMMARY The developmental potential of human pluripotent stem cells suggests that they can produce disease-relevant cell types for biomedical research. However, substantial variation has been reported among pluripotent cell lines, which could affect their utility and clinical safety. Such cell-line-specific differences must be better understood before one can confidently use embryonic stem (ES) or induced pluripotent stem (iPS) cells in translational research. Toward this goal we have established genome-wide reference maps of DNA methylation and gene expression for 20 previously derived human ES lines and 12 human iPS cell lines, and we have measured the in vitro differentiation propensity of these cell lines. This resource enabled us to assess the epigenetic and transcriptional similarity of ES and iPS cells and to predict the differentiation efficiency of individual cell lines. The combination of assays yields a scorecard for quick and comprehensive characterization of pluripotent cell lines. PMID:21295703

Two-stage single-phase grid-connected photovoltaic system with reduced complexity

NASA Astrophysics Data System (ADS)

da Silva, Cintia S.; Motta, Filipe R.; Tofoli, Fernando L.

2011-06-01

This article presents a grid-connected photovoltaic (PV) system using the classical DC-DC buck converter, which is responsible for stepping down the resulting voltage from several series-connected panels. Besides, the structure provides high power factor operation by injecting a quasi-sinusoidal current into the grid, with near no displacement in relation to the line voltage at the point of common coupling among the PV system and the loads. A CSI employing thyristors is cascaded with the DC-DC stage so that AC voltage results. The inverter output voltage level is adjusted by using a low-frequency transformer, which also provides galvanic isolation. The proposed system is described as mathematical approach and design guidelines are presented, providing an overview of the topology. An experimental prototype is also implemented, and relevant results to validate the proposal are discussed.

Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

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

Felthaus, O.; Department of Oral and Maxillofacial Surgery, University of Regensburg; Ettl, T.

2011-04-01

Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simplemore » method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.« less

Derivation and Osmotolerance Characterization of Three Immortalized Tilapia (Oreochromis mossambicus) Cell Lines

PubMed Central

Gardell, Alison M.; Qin, Qin; Rice, Robert H.; Li, Johnathan; Kültz, Dietmar

2014-01-01

Fish cell cultures are becoming more widely used models for investigating molecular mechanisms of physiological response to environmental challenge. In this study, we derived two immortalized Mozambique tilapia (Oreochromis mossambicus) cell lines from brain (OmB) and lip epithelium (OmL), and compared them to a previously immortalized bulbus arteriosus (TmB) cell line. The OmB and OmL cell lines were generated without or with Rho-associated kinase (ROCK) inhibitor/3T3 feeder layer supplementation. Although both approaches were successful, ROCK inhibitor/feeder layer supplementation was found to offer the advantages of selecting for epithelial-like cell type and decreasing time to immortalization. After immortalization (≥ passage 5), we characterized the proteomes of the newly derived cell lines (OmB and OmL) using LCMS and identified several unique cell markers for each line. Subsequently, osmotolerance for each of the three cell lines following acute exposure to elevated sodium chloride was evaluated. The acute maximum osmotolerance of these tilapia cell lines (>700 mOsm/kg) was markedly higher than that of any other known vertebrate cell line, but was significantly higher in the epithelial-like OmL cell line. To validate the physiological relevance of these tilapia cell lines, we quantified the effects of acute hyperosmotic challenge (450 mOsm/kg and 700 mOsm/kg) on the transcriptional regulation of two enzymes involved in biosynthesis of the compatible organic osmolyte, myo-inositol. Both enzymes were found to be robustly upregulated in all three tilapia cell lines. Therefore, the newly established tilapia cells lines represent valuable tools for studying molecular mechanisms involved in the osmotic stress response of euryhaline fish. PMID:24797371

HIV integration sites in latently infected cell lines: evidence of ongoing replication.

PubMed

Symons, Jori; Chopra, Abha; Malatinkova, Eva; De Spiegelaere, Ward; Leary, Shay; Cooper, Don; Abana, Chike O; Rhodes, Ajantha; Rezaei, Simin D; Vandekerckhove, Linos; Mallal, Simon; Lewin, Sharon R; Cameron, Paul U

2017-01-13

Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines. Latently infected cell lines infected with intact virus demonstrated multiple distinct HIV integration sites (28 different sites in U1, 110 in ACH-2 and 117 in J1.1 per 150,000 cells). In contrast, cell lines infected with replication-incompetent viruses (J-Lat cells) demonstrated single integration sites. Following in vitro passaging of the ACH-2 cell line, we observed a significant increase in the frequency of unique HIV integration sites and there were multiple mutations and large deletions in the proviral DNA. When the ACH-2 cell line was cultured with the integrase inhibitor raltegravir, there was a significant decrease in the number of unique HIV integration sites and a transient increase in the frequency of 2-LTR circles consistent with virus replication in these cells. Cell lines latently infected with intact HIV demonstrated multiple unique HIV integration sites indicating that these cell lines are not clonal and in the ACH-2 cell line there was evidence of low level virus replication. These findings have implications for the use of latently infected cell lines as models of HIV latency and for the use of these cells as standards.

Cell lines authentication and mycoplasma detection as minimun quality control of cell lines in biobanking.

PubMed

Corral-Vázquez, C; Aguilar-Quesada, R; Catalina, P; Lucena-Aguilar, G; Ligero, G; Miranda, B; Carrillo-Ávila, J A

2017-06-01

Establishment of continuous cell lines from human normal and tumor tissues is an extended and useful methodology for molecular characterization of cancer pathophysiology and drug development in research laboratories. The exchange of these cell lines between different labs is a common practice that can compromise assays reliability due to contamination with microorganism such as mycoplasma or cells from different flasks that compromise experiment reproducibility and reliability. Great proportions of cell lines are contaminated with mycoplasma and/or are replaced by cells derived for a different origin during processing or distribution process. The scientific community has underestimated this problem and thousand of research experiment has been done with cell lines that are incorrectly identified and wrong scientific conclusions have been published. Regular contamination and authentication tests are necessary in order to avoid negative consequences of widespread misidentified and contaminated cell lines. Cell banks generate, store and distribute cell lines for research, being mandatory a consistent and continuous quality program. Methods implementation for guaranteeing both, the absence of mycoplasma and authentication in the supplied cell lines, has been performed in the Andalusian Health System Biobank. Specifically, precise results were obtained using real time PCR detection for mycoplasma and 10 STRs identification by capillary electrophoresis for cell line authentication. Advantages and disadvantages of these protocols are discussed.

Age-Related Corresponding Relationships of Controlled Force Exertion Measured by a Computer-Generated Sinusoidal and Quasi-Random Display

ERIC Educational Resources Information Center

Nagasawa, Yoshinori; Demura, Shinichi

2011-01-01

This study examined age-group corresponding relationships of the controlled force exertion based on sinusoidal and quasi-random waveforms in 175 right-handed male adults aged 20 to 86 years. The subjects were divided into 3 groups based on age-level: 53 young (mean age 24.6, SD = 3.3 years), 71 middle aged (mean age 44.3, SD = 8.7 years), and 51…

Quantifying ataxia: ideal trajectory analysis--a technical note

NASA Technical Reports Server (NTRS)

McPartland, M. D.; Krebs, D. E.; Wall, C. 3rd

2000-01-01

We describe a quantitative method to assess repeated stair stepping stability. In both the mediolateral (ML) and anterioposterior (AP) directions, the trajectory of the subject's center of mass (COM) was compared to an ideal sinusoid. The two identified sinusoids were unique in each direction but coupled. Two dimensionless numbers-the mediolateral instability index (IML) and AP instability index (IAP)-were calculated using the COM trajectory and ideal sinusoids for each subject with larger index values resulting from less stable performance. The COM trajectories of nine nonimpaired controls and six patients diagnosed with unilateral or bilateral vestibular labyrinth hypofunction were analyzed. The average IML and IAP values of labyrinth disorder patients were respectively 127% and 119% greater than those of controls (p<0.014 and 0.006, respectively), indicating that the ideal trajectory analysis distinguishes persons with labyrinth disorder from those without. The COM trajectories also identify movement inefficiencies attributable to vestibulopathy.

R Dump Converter without DC Link Capacitor for an 8/6 SRM: Experimental Investigation

PubMed Central

Kavitha, Pasumalaithevan; Umamaheswari, Bhaskaran

2015-01-01

The objective of this paper is to investigate the performance of 8/6 switched reluctance motor (SRM) when excited with sinusoidal voltage. The conventional R dump converter provides DC excitation with the help of capacitor. In this paper the converter used is the modified R dump converter without DC link capacitor providing AC or sinusoidal excitation. Torque ripple and speed ripple are investigated based on hysteresis current control. Constant and sinusoidal current references are considered for comparison in both DC and AC excitation. Extensive theoretical and experimental investigations are made to bring out the merits and demerits of AC versus DC excitation. It is shown that the constructionally simple SRM can be favorably controlled with simple R dump converter with direct AC excitation without need for DC link capacitor. A 4-phase 8/6 0.5 kW SRM is used for experimentation. PMID:25642452

R dump converter without DC link capacitor for an 8/6 SRM: experimental investigation.

PubMed

Kavitha, Pasumalaithevan; Umamaheswari, Bhaskaran

2015-01-01

The objective of this paper is to investigate the performance of 8/6 switched reluctance motor (SRM) when excited with sinusoidal voltage. The conventional R dump converter provides DC excitation with the help of capacitor. In this paper the converter used is the modified R dump converter without DC link capacitor providing AC or sinusoidal excitation. Torque ripple and speed ripple are investigated based on hysteresis current control. Constant and sinusoidal current references are considered for comparison in both DC and AC excitation. Extensive theoretical and experimental investigations are made to bring out the merits and demerits of AC versus DC excitation. It is shown that the constructionally simple SRM can be favorably controlled with simple R dump converter with direct AC excitation without need for DC link capacitor. A 4-phase 8/6 0.5 kW SRM is used for experimentation.

Unified design of sinusoidal-groove fused-silica grating.

PubMed

Feng, Jijun; Zhou, Changhe; Cao, Hongchao; Lu, Peng

2010-10-20

A general design rule of deep-etched subwavelength sinusoidal-groove fused-silica grating as a highly efficient polarization-independent or polarization-selective device is studied based on the simplified modal method, which shows that the device structure depends little on the incident wavelength, but mainly on the ratio of groove depth to incident wavelength and the ratio of wavelength to grating period. These two ratios could be used as the design guidelines for wavelength-independent structure from deep ultraviolet to far infrared. The optimized grating profile with a different function as a polarizing beam splitter, a polarization-independent two-port beam splitter, or a polarization-independent grating with high efficiency of -1st order is obtained at a wavelength of 1064 nm, and verified by using the rigorous coupled-wave analysis. The performance of the sinusoidal grating is better than a conventional rectangular one, which could be useful for practical applications.

Compact broadband polarization beam splitter using a symmetric directional coupler with sinusoidal bends.

PubMed

Zhang, Fan; Yun, Han; Wang, Yun; Lu, Zeqin; Chrostowski, Lukas; Jaeger, Nicolas A F

2017-01-15

We design and demonstrate a compact broadband polarization beam splitter (PBS) using a symmetric directional coupler with sinusoidal bends on a silicon-on-insulator platform. The sinusoidal bends in our PBS suppress the power exchange between two parallel symmetric strip waveguides for the transverse-electric (TE) mode, while allowing for the maximum power transfer to the adjacent waveguide for the transverse-magnetic (TM) mode. Our PBS has a nominal coupler length of 8.55 μm, and it has an average extinction ratio (ER) of 12.0 dB for the TE mode, an average ER of 20.1 dB for the TM mode, an average polarization isolation (PI) of 20.6 dB for the through port, and an average PI of 11.5 dB for the cross port, all over a bandwidth of 100 nm.

Buckling instability in amorphous carbon films

NASA Astrophysics Data System (ADS)

Zhu, X. D.; Narumi, K.; Naramoto, H.

2007-06-01

In this paper, we report the buckling instability in amorphous carbon films on mirror-polished sapphire (0001) wafers deposited by ion beam assisted deposition at various growth temperatures. For the films deposited at 150 °C, many interesting stress relief patterns are found, which include networks, blisters, sinusoidal patterns with π-shape, and highly ordered sinusoidal waves on a large scale. Starting at irregular buckling in the centre, the latter propagate towards the outer buckling region. The maximum length of these ordered patterns reaches 396 µm with a height of ~500 nm and a wavelength of ~8.2 µm. However, the length decreases dramatically to 70 µm as the deposition temperature is increased to 550 °C. The delamination of the film appears instead of sinusoidal waves with a further increase of the deposition temperature. This experimental observation is correlated with the theoretic work of Crosby (1999 Phys. Rev. E 59 R2542).

SNDR enhancement in noisy sinusoidal signals by non-linear processing elements

NASA Astrophysics Data System (ADS)

Martorell, Ferran; McDonnell, Mark D.; Abbott, Derek; Rubio, Antonio

2007-06-01

We investigate the possibility of building linear amplifiers capable of enhancing the Signal-to-Noise and Distortion Ratio (SNDR) of sinusoidal input signals using simple non-linear elements. Other works have proven that it is possible to enhance the Signal-to-Noise Ratio (SNR) by using limiters. In this work we study a soft limiter non-linear element with and without hysteresis. We show that the SNDR of sinusoidal signals can be enhanced by 0.94 dB using a wideband soft limiter and up to 9.68 dB using a wideband soft limiter with hysteresis. These results indicate that linear amplifiers could be constructed using non-linear circuits with hysteresis. This paper presents mathematical descriptions for the non-linear elements using statistical parameters. Using these models, the input-output SNDR enhancement is obtained by optimizing the non-linear transfer function parameters to maximize the output SNDR.

Telangiectatic focal nodular hyperplasia of the liver: a case detected at birth.

PubMed Central

Kim, Han-Seong; Kim, Young A.; Kim, Chong Jai; Suh, Yeon-Lim; Jang, Ja-June; Chi, Je G.

2003-01-01

A case of telangiectatic focal nodular hyperplasia (FNH) was detected at birth and was surgically removed. Grossly, the lesion was a solitary nodule and showed vague nodularity, appearing as an adenoma-like mass with fine fibrous septa, but having no macroscopic scar. On microscopic scale, the mass typically had neither fibrous central scar nor hyperplastic nodules different from the usual FNHs. The hepatic plates were separated by sinusoidal dilatation, sometimes alternating with areas of marked ectasia. Instead of large fibrous scar, thin fibrous septa were often found, and contained abnormal tortuous large arteries. These high-pressure vessels were connected directly into the adjacent sinusoids and made marked dilation of sinusoids. Bile ductular proliferation was also noted in the thin fibrous septa. To our knowledge, this is considered to be the first reported case of telangiectatic FNH detected at birth. PMID:14555832

Sinusoidal input describing function for hysteresis followed by elementary backlash

NASA Technical Reports Server (NTRS)

Ringland, R. F.

1976-01-01

The author proposes a new sinusoidal input describing function which accounts for the serial combination of hysteresis followed by elementary backlash in a single nonlinear element. The output of the hysteresis element drives the elementary backlash element. Various analytical forms of the describing function are given, depending on the a/A ratio, where a is the half width of the hysteresis band or backlash gap, and A is the amplitude of the assumed input sinusoid, and on the value of the parameter representing the fraction of a attributed to the backlash characteristic. The negative inverse describing function is plotted on a gain-phase plot, and it is seen that a relatively small amount of backlash leads to domination of the backlash character in the describing function. The extent of the region of the gain-phase plane covered by the describing function is such as to guarantee some form of limit cycle behavior in most closed-loop systems.

Development of dynamic calibration methods for POGO pressure transducers. [for space shuttle

NASA Technical Reports Server (NTRS)

Hilten, J. S.; Lederer, P. S.; Vezzetti, C. F.; Mayo-Wells, J. F.

1976-01-01

Two dynamic pressure sources are described for the calibration of pogo pressure transducers used to measure oscillatory pressures generated in the propulsion system of the space shuttle. Rotation of a mercury-filled tube in a vertical plane at frequencies below 5 Hz generates sinusoidal pressures up to 48 kPa, peak-to-peak; vibrating the same mercury-filled tube sinusoidally in the vertical plane extends the frequency response from 5 Hz to 100 Hz at pressures up to 140 kPa, peak-to-peak. The sinusoidal pressure fluctuations can be generated by both methods in the presence of high pressures (bias) up to 55 MPa. Calibration procedures are given in detail for the use of both sources. The dynamic performance of selected transducers was evaluated using these procedures; the results of these calibrations are presented. Calibrations made with the two sources near 5 Hz agree to within 3% of each other.

Wide-field fluorescence diffuse optical tomography with epi-illumination of sinusoidal pattern

NASA Astrophysics Data System (ADS)

Li, Tongxin; Gao, Feng; Chen, Weiting; Qi, Caixia; Yan, Panpan; Zhao, Huijuan

2017-02-01

We present a wide-field fluorescence tomography with epi-illumination of sinusoidal pattern. In this scheme, a DMD projector is employed as a spatial light modulator to generate independently wide-field sinusoidal illumination patterns at varying spatial frequencies on a sample, and then the emitted photons at the sample surface were captured with a EM-CCD camera. This method results in a significantly reduced number of the optical field measurements as compared to the point-source-scanning ones and thereby achieves a fast data acquisition that is desired for a dynamic imaging application. Fluorescence yield images are reconstructed using the normalized-Born formulated inversion of the diffusion model. Experimental reconstructions are presented on a phantom embedding the fluorescent targets and compared for a combination of the multiply frequencies. The results validate the ability of the method to determine the target relative depth and quantification with an increasing accuracy.

Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis).

PubMed

Jager, Martine J; Magner, J Antonio Bermudez; Ksander, Bruce R; Dubovy, Sander R

2016-08-01

To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines.

Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis)

PubMed Central

Jager, Martine J.; Magner, J. Antonio Bermudez; Ksander, Bruce R.; Dubovy, Sander R.

2016-01-01

Purpose To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor. Methods Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived. Results Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor. Conclusions All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines. PMID:28018010

Different toxic effects of YTX in tumor K-562 and lymphoblastoid cell lines

PubMed Central

Fernández-Araujo, Andrea; Sánchez, Jon A.; Alfonso, Amparo; Vieytes, Mercedes R.; Botana, Luis M.

2015-01-01

Yessotoxin (YTX) modulates cellular phosphodiesterases (PDEs). In this regard, opposite effects had been described in the tumor model K-562 cell line and fresh human lymphocytes in terms of cell viability, cyclic adenosine 3',5'-cyclic monophosphate (cAMP) production and protein expression after YTX treatment. Studies in depth of the pathways activated by YTX in K-562 cell line, have demonstrated the activation of two different cell death types, apoptosis, and autophagy after 24 and 48 h of treatment, respectively. Furthermore, the key role of type 4A PDE (PDE4A) in both pathways activated by YTX was demonstrated. Therefore, taking into account the differences between cellular lines and fresh cells, a study of cell death pathways activated by YTX in a non-tumor cell line with mitotic activity, was performed. The cellular model used was the lymphoblastoid cell line that represents a non-tumor model with normal apoptotic and mitotic machinery. In this context, cell viability and cell proliferation, expression of proteins involved in cell death activated by YTX and mitochondrial mass, were studied after the incubation with the toxin. Opposite to the tumor model, no cell death activation was observed in lymphoblastoid cell line in the presence of YTX. In this sense, variations in apoptosis hallmarks were not detected in the lymphoblastoid cell line after YTX incubation, whereas this type I of programmed cell death was observed in K-562 cells. On the other hand, autophagy cell death was triggered in this cellular line, while other autophagic process is suggested in lymphoblastoid cells. These YTX effects are related to PDE4A in both cellular lines. In addition, while cell death is triggered in K-562 cells after YTX treatment, in lymphoblastoid cells the toxin stops cellular proliferation. These results point to YTX as a specific toxic compound of tumor cells, since in the non-tumor lymphoblastoid cell line, no cell death hallmarks are observed. PMID:26136685

Lung Cancer Cell Lines as Tools for Biomedical Discovery and Research

PubMed Central

Girard, Luc; Lockwood, William W.; Lam, Wan L.; Minna, John D.

2010-01-01

Lung cancer cell lines have made a substantial contribution to lung cancer translational research and biomedical discovery. A systematic approach to initiating and characterizing cell lines from small cell and non–small cell lung carcinomas has led to the current collection of more than 200 lung cancer cell lines, a number that exceeds those for other common epithelial cancers combined. The ready availability and widespread dissemination of the lines to investigators worldwide have resulted in more than 9000 citations, including multiple examples of important biomedical discoveries. The high (but not perfect) genomic similarities between lung cancer cell lines and the lung tumor type from which they were derived provide evidence of the relevance of their use. However, major problems including misidentification or cell line contamination remain. Ongoing studies and new approaches are expected to reveal the full potential of the lung cancer cell line panel. PMID:20679594

Cell lines derived from feline fibrosarcoma display unstable chromosomal aneuploidy and additionally centrosome number aberrations.

PubMed

von Erichsen, J; Hecht, W; Löhberg-Gruene, C; Reinacher, M

2012-07-01

The purpose of the study was to evaluate clonality and presence of numerical chromosomal and centrosomal aberrations in 5 established feline fibrosarcoma cell lines and in a fetal dermal fibroblast cell line as a control. The clonality of all cell lines was examined using limited-dilution cloning. The number of chromosomes was counted in metaphase spreads. The immunocytochemical analysis of centrosome numbers was performed by indirect immunofluorescence using a monoclonal antibody that targets γ-tubulin, a well-characterized component of centrosomes. Monoclonal cell populations could be established from all cell lines. In all feline fibrosarcoma cell lines, the number of chromosomes deviated abnormally from the normal feline chromosome number of 2n = 38, ranging from 19 to 155 chromosomes per cell. Centrosome hyperamplification was observed in all 5 feline fibrosarcoma cell lines with a proportion of cells (5.7 to 15.2%) having more than 2 centrosomes. In the control cell line, only 0.6% of the cells had more than 2 centrosomes. In conclusion, the examinations revealed that centrosome hyperamplification occurs in feline fibrosarcoma cell lines. The feline fibrosarcoma cell lines possessed 10 to 25 times as many cells with centrosome hyperamplification as the control cell line. These observations suggest an association of numerical centrosome aberrations with karyotype instability by increasing the frequency of chromosome missegregation. The results of this study may be helpful for further characterization of feline fibrosarcomas and may contribute to the knowledge of cytogenetic factors that may be important for the pathogenesis of feline fibrosarcomas.

Attempt to develop taste bud models in three-dimensional culture.

PubMed

Nishiyama, Miyako; Yuki, Saori; Fukano, Chiharu; Sako, Hideyuki; Miyamoto, Takenori; Tomooka, Yasuhiro

2011-09-01

Taste buds are the end organs of taste located in the gustatory papillae, which occur on the surface of the oral cavity. The goal of the present study was to establish a culture model mimicking the lingual taste bud of the mouse. To this end, three cell lines were employed: taste bud-derived cell lines (TBD cell lines), a lingual epithelial cell-derived cell line (20A cell line), and a mesenchymal cell-derived cell line (TMD cell line). TBD cells embedded in collagen gel formed three-dimensional clusters, which had an internal cavity equipped with a tight junction-like structure, a microvilluslike structure, and a laminin-positive layer surrounding the cluster. The cells with this epitheliumlike morphology expressed marker proteins of taste cells: gustducin and NCAM. TBD cells formed a monolayer on collagen gel when they were co-cultured with TMD cells. TBD, 20A, and TMD cell lines were maintained in a triple cell co-culture, in which TBD cells were pre-seeded as aggregates or in suspension on the collagen gel containing TMD cells, and 20A cells were laid over the TBD cells. TBD cells in the triple cell co-culture expressed NCAM. This result suggests that co-cultured TBD cells exhibited a characteristic of Type III taste cells. The culture model would be useful to study morphogenesis and functions of the gustatory organ.

Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition

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

Blattmann, Claudia, E-mail: claudia.blattmann@med.uni-heidelberg.d; Oertel, Susanne; Ehemann, Volker

2010-09-01

Purpose: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines. Methods and Materials: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RMS (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry. Results: SAHA induced anmore » inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80). Conclusion: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair, as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs.« less

Generation of genome-modified Drosophila cell lines using SwAP.

PubMed

Franz, Alexandra; Brunner, Erich; Basler, Konrad

2017-10-02

The ease of generating genetically modified animals and cell lines has been markedly increased by the recent development of the versatile CRISPR/Cas9 tool. However, while the isolation of isogenic cell populations is usually straightforward for mammalian cell lines, the generation of clonal Drosophila cell lines has remained a longstanding challenge, hampered by the difficulty of getting Drosophila cells to grow at low densities. Here, we describe a highly efficient workflow to generate clonal Cas9-engineered Drosophila cell lines using a combination of cell pools, limiting dilution in conditioned medium and PCR with allele-specific primers, enabling the efficient selection of a clonal cell line with a suitable mutation profile. We validate the protocol by documenting the isolation, selection and verification of eight independently Cas9-edited armadillo mutant Drosophila cell lines. Our method provides a powerful and simple workflow that improves the utility of Drosophila cells for genetic studies with CRISPR/Cas9.

Insights into defibrotide: an updated review.

PubMed

Morabito, F; Gentile, M; Gay, F; Bringhen, S; Mazzone, C; Vigna, E; Musto, P; Di Raimondo, F; Palumbo, A

2009-06-01

Defibrotide is a polydisperse oligonucleotide with antiatherosclerotic, anti-inflammatory, anti-ischaemic, pro-fibrinolytic and antithrombotic actions without significant systemic anticoagulant effects. It has been used in the treatment of various cardiovascular disorders, and especially in endothelial complications of allogeneic stem-cell transplantation. We reviewed the published work for the mechanism of action and clinical use of defibrotide to consolidate data and to describe new applications of this drug. We reviewed the most relevant papers on defibrotide published from November 1982 to January 2008. (selected through PubMed), and used recent meeting abstracts as sources for this review. Reports have suggested that defibrotide has clinical efficacy for treatment and prophylaxis of hepatic sinusoidal obstruction syndrome occurring after stem-cell transplantation. Animal models have clearly shown the potential antineoplastic effect of this drug. Further clinical investigations are needed to clarify this new application.

Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children

PubMed Central

Franca, Raffaella; Stocco, Gabriele; Favretto, Diego; Giurici, Nagua; Decorti, Giuliana; Rabusin, Marco

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is an established therapeutic procedure for several congenital and acquired disorders, both malignant and nonmalignant. Despite the great improvements in HSCT clinical practices over the last few decades, complications, such as graft vs. host disease (GVHD) and sinusoidal obstructive syndrome (SOS), are still largely unpredictable and remain the major causes of morbidity and mortality. Both donor and patient genetic background might influence the success of bone marrow transplantation and could at least partially explain the inter-individual variability in HSCT outcome. This review summarizes some of the recent studies on candidate gene polymorphisms in HSCT, with particular reference to pediatric cohorts. The interest is especially focused on pharmacogenetic variants affecting myeloablative and immunosuppressive drugs, although genetic traits involved in SOS susceptibility and transplant-related mortality are also reviewed. PMID:26266406

Sudden death of an Indian peafowl (Pavo cristatus) at a zoo due to non-pigmented Serratia marcescens infection

PubMed Central

LEE, Seung-Hun; PARK, Sang-Joon; KWAK, Dongmi; KIM, Kyoo-Tae

2017-01-01

A 16-year-old female Indian peafowl (Pavo cristatus) died two days after recognition of conjunctivitis in the right eye, anorexia and depression. Gross necropsy revealed a thick pseudomembrane under the eyelid and hydropericardium. Histopathological examination revealed hepatocellular necrosis, sinusoidal and vascular congestion and infiltrated inflammatory cells. Infiltration by inflammatory cells was noted in the epicardium. The lungs had mild interstitial pneumonia with the extensive congestion within the capillaries of the air sacs. Tubular interstitial congestion and necrosis was noted in the kidneys. Bacterial culture and nucleotide sequencing of the inflammatory specimens identified the causative agent as Serratia marcescens, an uncommon bacterium in birds. In summary, this study describes the sudden death of an Indian peafowl due to S. marcescens infection, which is rarely seen in animals. PMID:29081475

Fluoroorotic acid-selected Nicotiana plumbaginifolia cell lines with a stable thymine starvation phenotype have lost the thymine-regulated transcriptional program.

PubMed

Santoso, D; Thornburg, R

2000-08-01

We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and was therefore analyzed in detail. The selected cell lines showed no differences with wild-type cells with respect to uptake of orotic acid, affinity of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative detoxification mechanisms were also excluded. The elevated enzyme activity was correlated with elevated UMP synthase protein levels as well as elevated UMP synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid-selected cell lines did not respond to thymine or to other biochemicals that affect thymine levels. In addition, there was also a concomitant up-regulation of aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate dehydrogenase are not up-regulated in these cell lines.

Fluoroorotic Acid-Selected Nicotiana plumbaginifolia Cell Lines with a Stable Thymine Starvation Phenotype Have Lost the Thymine-Regulated Transcriptional Program1

PubMed Central

Santoso, Djoko; Thornburg, Robert

2000-01-01

We have selected 143 independent Nicotiana plumbaginifolia cell lines that survive in the presence of 5-fluoroorotic acid. These lines show several diverse phenotypes. The majority of these cell lines showed reduced levels of UMP synthase. However, one particular phenotype, which represents 14% of the total independent lines (20 cell lines), showed an unexpected, high level of UMP synthase and was therefore analyzed in detail. The selected cell lines showed no differences with wild-type cells with respect to uptake of orotic acid, affinity of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative detoxification mechanisms were also excluded. The elevated enzyme activity was correlated with elevated UMP synthase protein levels as well as elevated UMP synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid-selected cell lines did not respond to thymine or to other biochemicals that affect thymine levels. In addition, there was also a concomitant up-regulation of aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate dehydrogenase are not up-regulated in these cell lines. PMID:10938367

The T47D cell line is an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer.

PubMed

Yu, Sungryul; Kim, Taemook; Yoo, Kyung Hyun; Kang, Keunsoo

2017-05-06

Cell lines are often used as in vitro tools to mimic certain types of in vivo system; several cell lines, including MCF-7 and T47D, have been widely used in breast cancer studies without investigating the cell lines' characteristics. In this study, we compared the genome-wide binding profiles of ERα, PR, and P300, and the gene expression changes between MCF-7 and T47D cell lines that represent the luminal A subtype of breast cancer. Surprisingly, several thousand genes were differentially expressed under estrogenic condition. In addition, ERα, PR, and P300 binding to regulatory elements showed distinct genomic landscapes between MCF-7 and T47D cell lines in the same hormonal states. In particular, the T47D cell line was markedly susceptible to progesterone, whereas the MCF-7 cell line did not respond to progesterone in the presence of estrogen. Consistently, changes in the expression level of the PR-target gene, STAT5A, were only observed in the T47D cell line, not the MCF-7 cell line, when treated with progesterone. Overall, the results highlight the importance of selecting appropriate cell lines for breast cancer studies and suggest that T47D cell lines can be an ideal experimental model to elucidate the progesterone-specific effects of a luminal A subtype of breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research.

PubMed

Kniss, Douglas A; Summerfield, Taryn L

2014-08-01

Continuous cell lines are used frequently in reproductive biology research to study problems in early pregnancy events and parturition. It has been recognized for 50 years that many mammalian cell lines contain inter- or intraspecies contaminations with other cells. However, most investigators do not routinely test their culture systems for cross-contamination. The most frequent contributor to cross-contamination of cell lines is the HeLa cell isolated from an aggressive cervical adenocarcinoma. We report on the discovery of HeLa cell contamination of the human endometrial epithelial cell line HES isolated in our laboratory. Short tandem repeat analysis of 9 unique genetic loci demonstrated molecular identity between HES and HeLa cells. In addition, we verified that WISH cells, isolated originally from human amnion epithelium, were also contaminated with HeLa cells. Inasmuch as our laboratory did not culture HeLa cells at the time of HES cell derivations, the source of contamination was the WISH cell line. These data highlight the need for continued diligence in authenticating cell lines used in reproductive biology research. © The Author(s) 2014.

Fatty acid binding proteins (FABPs) in prostate, bladder and kidney cancer cell lines and the use of IL-FABP as survival predictor in patients with renal cell carcinoma

PubMed Central

2011-01-01

Background Fatty acid binding proteins (FABP) play an important role in carcinogenesis. Modified FABP expression patterns were described for prostate, bladder and for renal cell carcinoma. Studies on metabolic relationships and interactions in permanent cell lines allow a deeper insight into molecular processes. The aim of this study is therefore a systematic overview on mRNA and protein expressions of seven FABPs in frequently used urological cell lines. Methods Nine cell lines of renal carcinomas, seven of urinary bladder carcinomas, and five of prostate carcinomas were investigated. Quantitative RT-qPCR and western blotting were used to determine different FABPs. In addition, 46 paired cancerous and noncancerous tissue samples from nephrectomy specimen with renal cell carcinomas were investigated regarding the ileum FABP mRNA expression level and associated with survival outcome. Results General characteristics of all urological carcinoma cell lines were the expression of E-and IL-FABP on mRNA and protein level, while the expressions differed between the cell lines. The protein expression was not always congruent with the mRNA expression. Renal cell carcinoma cell lines showed expressions of L-, H- and B-FABP mRNA in addition to the general FABP expression in five out of the eight investigated cell lines. In bladder cancer cell lines, we additionally found the expression of A-FABP mRNA in six cell lines, while H-FABP was present only in three cell lines. In prostate cancer cell lines, a strong reduction of A- and E- FABP mRNA was observed. The expression of B-FABP mRNA and protein was observed only in the 22 RV-1 cells. IL-FABP mRNA was over-expressed in renal tumour tissue. The IL-FABP ratio was identified as an independent indicator of survival outcome. Conclusions Distinctly different FABP expression patterns were observed not only between the cell lines derived from the three cancer types, but also between the cell lines from the same cancer. The FABP patterns in the cell lines do not always reflect the real situation in the tumours. These facts have to be considered in functional studies concerning the different FABPs. PMID:21767383

Utility of human embryonic kidney cell line HEK-293 for rapid isolation of fixed and street rabies viruses: comparison with Neuro-2a and BHK-21 cell lines.

PubMed

Madhusudana, Shampur Narayan; Sundaramoorthy, Subha; Ullas, Padinjaremattatthil Thankappan

2010-12-01

A confirmatory rabies diagnosis can be achieved by rapid virus isolation in cell culture using brain tissue from the suspect animal. Several cell lines have been used for this purpose and the murine neuroblastoma cell line Neuro-2a has been found to be the most sensitive. The human embryonic kidney cell line HEK-293 is known to express several neuronal proteins and is believed to be of neuronal origin. We hypothesized that this cell line could be susceptible to rabies virus, which is highly neurotropic. First we tested the sensitivity of HEK-293 cells to the laboratory strain, challenge virus standard (CVS). We then tested 120 brain samples from different animals and humans suspected to have died of rabies by fluorescent antibody test (FAT). Both FAT-positive and FAT-negative brains were tested for virus isolation using Neuro-2a, BHK-21, and HEK-293 cell lines and also by mouse inoculation. There was 100% correlation between FAT, virus isolation in Neuro-2a and HEK-293 cells, and mouse inoculation. However, the rate of virus isolation in the BHK-21 cell line was only 28% when compared to the other cell lines. The sensitivity of HEK-293 to CVS strain of virus was similar to that of Neuro-2a. We conclude that the HEK-293 cell line is as sensitive as the Neuro-2a cell line for the rapid isolation of rabies virus and may serve as an alternative cell line for rabies diagnosis and future research. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Establishment and characterization of fetal fibroblast cell lines for generating human lysozyme transgenic goats by somatic cell nuclear transfer.

PubMed

Liu, Jun; Luo, Yan; Zheng, Liming; Liu, Qingqing; Yang, Zhongcai; Wang, Yongsheng; Su, Jianmin; Quan, Fusheng; Zhang, Yong

2013-10-01

This study was performed to qualify goat fetal fibroblast (GFF) cell lines for genetic modification and somatic cell nuclear transfer (SCNT) to produce human lysozyme (hLYZ) transgenic goats. Nine GFF cell lines were established from different fetuses, and the proliferative lifespan and chromosomal stability were analyzed. The results suggested that cell lines with a longer lifespan had stable chromosomes compared with those of cells lines with a shorter lifespan. According to the proliferative lifespan, we divided GFF cell lines into two groups: cell lines with a long lifespan (GFF1/2/7/8/9; group L) and cell lines with a short lifespan (GFF3/4/5/6; group S). Next, a hLYZ expression vector was introduced into these cell lines by electroporation. The efficiencies of colony formation, expansion in culture, and the quality of transgenic clonal cell lines were significant higher in group L than those in group S. The mean fusion rate and blastocyst rate in group L were higher than those in group S (80.3 ± 1.7 vs. 65.1 ± 4.2 % and 19.5 ± 0.6 vs. 15.1 ± 1.1 %, respectively, P < 0.05). After transferring cloned embryos into the oviducts of recipient goats, three live kids were born. PCR and Southern blot analyses confirmed integration of the transgene in cloned goats. In conclusion, the lifespan of GFF cell lines has a major effect on the efficiency to produce transgenic cloned goats. Therefore, the proliferative lifespan of primary cells may be used as a criterion to characterize the quality of cell lines for genetic modification and SCNT.

[Establishment of Z-HL16C cell line.].

PubMed

Chen, J P; Li, J; Zhao, S L; Tian, J Y; Ye, F

2006-09-01

To establish and study the nature and the application of Z-HL16C cell line. The cell line was continuously passed, frozen stored and recovered. Its application was expanded and the cell type was identified. The cell line had an epithelial-cell-like shape, the size appeared uniform, the cell boundary was distinct. It has been continuously passed, frozen stored and recovered for ten years. Its recovery rate was about 90%. It has been proved to be sensitive to the tested viruses which were enteroviruses (Polio, Cox, Echo), influenza viruses, parainfluenzaviruses, adenoviruses, measles virus. This cell line has been identified as a cancerization cell. The cell line Z-HL16C has been stably established, it has a broad spectrum in sensitivity for culturing viruses.

SU-E-J-74: Impact of Respiration-Correlated Image Quality On Tumor Motion Reconstruction in 4D-CBCT: A Phantom Study

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

Lee, S; Lu, B; Samant, S

2014-06-01

Purpose: To investigate the effects of scanning parameters and respiratory patterns on the image quality for 4-dimensional cone-beam computed tomography(4D-CBCT) imaging, and assess the accuracy of computed tumor trajectory for lung imaging using registration of phased 4D-CBCT imaging with treatment planning-CT. Methods: We simulated a periodic and non-sinusoidal respirations with various breathing periods and amplitudes using a respiratory phantom(Quasar, Modus Medical Devices Inc) to acquire respiration-correlated 4D-CBCT images. 4D-CBCT scans(Elekta Oncology Systems Ltd) were performed with different scanning parameters for collimation size(e.g., small and medium field-of-views) and scanning speed(e.g., slow 50°·min{sup −1}, fast 100°·min{sup −1}). Using a standard CBCT-QA phantom(Catphan500,more » The Phantom Laboratory), the image qualities of all phases in 4D-CBCT were evaluated with contrast-to-noise ratio(CNR) for lung tissue and uniformity in each module. Using a respiratory phantom, the target imaging in 4D-CBCT was compared to 3D-CBCT target image. The target trajectory from 10-respiratory phases in 4D-CBCT was extracted using an automatic image registration and subsequently assessed the accuracy by comparing with actual motion of the target. Results: Image analysis indicated that a short respiration with a small amplitude resulted in superior CNR and uniformity. Smaller variation of CNR and uniformity was present amongst different respiratory phases. The small field-of-view with a partial scan using slow scan can improve CNR, but degraded uniformity. Large amplitude of respiration can degrade image quality. RMS of voxel densities in tumor area of 4D-CBCT images between sinusoidal and non-sinusoidal motion exhibited no significant difference. The maximum displacement errors of motion trajectories were less than 1.0 mm and 13.5 mm, for sinusoidal and non-sinusoidal breathings, respectively. The accuracy of motion reconstruction showed good overall agreement with the 4D-CBCT image quality results only using sinusoidal breathings. Conclusion: This information can be used to determine the appropriate acquisition parameters of 4D-CBCT imaging for registration accuracy and target trajectory measurements in a clinical setting.« less

Development and characterization of a cell line WAF from freshwater shark Wallago attu.

PubMed

Dubey, Akhilesh; Goswami, Mukunda; Yadav, Kamalendra; Sharma, Bhagwati S

2014-02-01

A new epithelial cell line, WAF was developed from caudal fin of freshwater shark, Wallago attu. The cell line was optimally maintained at 28 °C in Leibovitz-15 (L-15) medium supplemented with 20 % fetal bovine serum. The cell line was characterized by various cytogenetic and molecular markers. The cytogenetic analysis revealed a diploid count of 86 chromosomes at different passages. The origin of the cell lines was confirmed by the amplification of 547 and 654 bp sequences of 16S rRNA and cytochrome oxidase subunit I genes of mitochondrial DNA, respectively. WAF cells were characterized for their growth characteristics at different temperature and serum concentration. Epithelial morphology of the cell line was confirmed using immunocytochemistry. Further cell plating efficiency, transfection efficiency and viability of cryopreserved WAF cells was also determined. Cytotoxicity and genotoxicity assessment of cadmium salts on WAF cells by MTT, NR and comet assay illustrated the utility of this cell line as an in vitro model for aquatic toxicological studies. The cell line will be further useful for studying oxidative stress markers against aquatic pollutants.

Characterization of a Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma Cell Line CVG-1.

PubMed

Velásquez, Celestino; Amako, Yutaka; Harold, Alexis; Toptan, Tuna; Chang, Yuan; Shuda, Masahiro

2018-01-01

Merkel cell polyomavirus (MCV) plays a causal role in ∼80% of Merkel cell carcinomas (MCC). MCV is clonally integrated into the MCC tumor genome, which results in persistent expression of large T (LT) and small T (sT) antigen oncoproteins encoded by the early locus. In MCV-positive MCC tumors, LT is truncated by premature stop codons or deletions that lead to loss of the C-terminal origin binding (OBD) and helicase domains important for replication. The N-terminal Rb binding domain remains intact. MCV-positive cell lines derived from MCC explants have been valuable tools to study the molecular mechanism of MCV-induced Merkel cell carcinogenesis. Although all cell lines have integrated MCV and express truncated LT antigens, the molecular sizes of the LT proteins differ between cell lines. The copy number of integrated viral genome also varies across cell lines, leading to significantly different levels of viral protein expression. Nevertheless, these cell lines share phenotypic similarities in cell morphology, growth characteristics, and neuroendocrine marker expression. Several low-passage MCV-positive MCC cell lines have been established since the identification of MCV. We describe a new MCV-positive MCV cell line, CVG-1, with features distinct from previously reported cell lines. CVG-1 tumor cells grow in more discohesive clusters in loose round cell suspension, and individual cells show dramatic size heterogeneity. It is the first cell line to encode an MCV sT polymorphism resulting in a unique leucine (L) to proline (P) substitution mutation at amino acid 144. CVG-1 possesses a LT truncation pattern near identical to that of MKL-1 cells differing by the last two C-terminal amino acids and also shows an LT protein expression level similar to MKL-1. Viral T antigen knockdown reveals that, like other MCV-positive MCC cell lines, CVG-1 requires T antigen expression for cell proliferation.