Glatiramer Acetate administration does not reduce damage after cerebral ischemia in mice.

PubMed

Poittevin, Marine; Deroide, Nicolas; Azibani, Feriel; Delcayre, Claude; Giannesini, Claire; Levy, Bernard I; Pocard, Marc; Kubis, Nathalie

2013-01-15

Inflammation plays a key role in ischemic stroke pathophysiology: microglial/macrophage cells and type-1 helper cells (Th1) seem deleterious, while type-2 helper cells (Th2) and regulatory T cells (Treg) seem protective. CD4 Th0 differentiation is modulated by microglial cytokine secretion. Glatiramer Acetate (GA) is an immunomodulatory drug that has been approved for the treatment of human multiple sclerosis by means of a number of mechanisms: reduced microglial activation and pro-inflammatory cytokine production, Th0 differentiation shifting from Th2 to Th2 and Treg with anti-inflammatory cytokine production and increased neurogenesis. We induced permanent (pMCAo) or transient middle cerebral artery occlusion (tMCAo) and GA (2 mg) or vehicle was injected subcutaneously immediately after cerebral ischemia. Mice were sacrificed at D3 to measure neurological deficit, infarct volume, microglial cell density and qPCR of TNFα and IL-1β (pro-inflammatory microglial cytokines), IFNγ (Th2 cytokine), IL-4 (Th2 cytokine), TGFβ and IL-10 (Treg cytokines), and at D7 to evaluate neurological deficit, infarct volume and neurogenesis assessment. We showed that in GA-treated pMCAo mice, infarct volume, microglial cell density and cytokine secretion were not significantly modified at D3, while neurogenesis was enhanced at D7 without significant infarct volume reduction. In GA-treated tMCAo mice, microglial pro-inflammatory cytokines IL-1β and TNFα were significantly decreased without modification of microglial/macrophage cell density, cytokine secretion, neurological deficit or infarct volume at D3, or modification of neurological deficit, neurogenesis or infarct volume at D7. In conclusion, Glatiramer Acetate administered after cerebral ischemia does not reduce infarct volume or improve neurological deficit in mice despite a significant increase in neurogenesis in pMCAo and a microglial pro-inflammatory cytokine reduction in tMCAo. Copyright © 2012 Elsevier B.V. All rights reserved.

A Novel High-Efficiency Rear-Contact Solar Cell with Bifacial Sensitivity

NASA Astrophysics Data System (ADS)

Hezel, R.

At present, wafer-based silicon solar cells have a share of more than 90% of the photovoltaic market. Despite rapid growth in the manufacturing volume, accompanied by a significant drop in the module selling price, the high costs currently associated with photovoltaic power generation are one of the most important obstacles to widespread global use of solar electricity. Up to a certain level, a higher production volume is a key driver in cost reduction. However, apart from a drastic reduction of the silicon wafer thickness in conjunction with improved light-trapping schemes, innovative processing sequences combining very high solar cell efficiencies with simple and cost-effective fabrication techniques are needed to become competitive with conventional energy sources and thus to move solar energy from niche to mainstream.

Red blood cell and iron metabolism during space flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.

2002-01-01

Space flight anemia is a widely recognized phenomenon in astronauts. Reduction in circulating red blood cells and plasma volume results in a 10% to 15% decrement in circulatory volume. This effect appears to be a normal physiologic adaptation to weightlessness and results from the removal of newly released blood cells from the circulation. Iron availability increases, and (in the few subjects studied) iron stores increase during long-duration space flight. The consequences of these changes are not fully understood.

Microglial disruption in young mice with early chronic lead exposure☆

PubMed Central

Sobin, Christina; Montoya, Mayra Gisel Flores; Parisi, Natali; Schaub, Tanner; Cervantes, Miguel; Armijos, Rodrigo X.

2013-01-01

The mechanisms by which early chronic lead (Pb) exposure alter brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) ranged from 2.66 to 20.31 μg/dL. Only interleukin-6 (IL6) differed between groups and reductions were dose-dependent. Microglia cell body number also differed between groups and reductions were dose-dependent. As compared with controls, microglia cell body volume was greater but highly variable in only low-dose animals; dentate gyri volumes in low- and high-dose animals were reduced. The results did not support a model of increased neuroinflammation. Instead, early chronic exposure to Pb disrupted microglia via damage to, loss of, or lack of proliferation of microglia in the developing brains of Pb-exposed animals. PMID:23598043

Passive potassium transport in low potassium sheep red cells: dependence upon cell volume and chloride.

PubMed Central

Dunham, P B; Ellory, J C

1981-01-01

The major pathway of passive K influx (ouabain-insensitive) was characterized in low-K type (LK) red cells of sheep. 1. Passive K transport in these cells was highly sensitive to variations in cell volume; it increased threefold or more in cells swollen osmotically by 10%, and decreased up to twofold in cells shrunken 5-10%. Active K influx was insensitive to changes in cell volume. Three different methods for varying cell volume osmotically all gave similar results. 2. The volume-sensitive pathway was specific for K in that Na influx did not vary with changes in cell volume. 3. The volume-sensitive K influx was a saturable function of external K concentration. It was slightly inhibited by Na, whereas K influx in shrunken cells was unaffected by Na. 4. Passive K influx was dependent on the major anion in the medium in that replacement of Cl with any of six other anions resulted in a reduction of K influx by 50-80% (replacement of Cl by Br caused an increase in K influx). The activation of K influx by Cl followed sigmoid kinetics. 5. Passive K influx is inhibited by anti-L antibody. The antibody affected only that portion of influx which was Cl-dependent and volume-sensitve. Of the subfractions of the antibody, it is anti-L1 which inhibits passive K transport. 6. Pretreatment of cells with iodoacetamide reduced the sensitivity of K influx to cell volume in that the influx was reduced in swollen IAA-treated cells and increased in shrunken IAA-cells. 7. Intracellular Ca has no role in altering passive K transport in LK sheep cells. Therefore, the major pathway of passive K transport in LK sheep red cells is sensitive to changes in cell volume, specific for K, dependent on Cl, and inhibited by anti-L1 antibody, The minor pathway, observed in shrunken cells, has none of these properties. PMID:6798197

Thin-Film Solid Oxide Fuel Cells

NASA Technical Reports Server (NTRS)

Chen, Xin; Wu, Nai-Juan; Ignatiev, Alex

2009-01-01

The development of thin-film solid oxide fuel cells (TFSOFCs) and a method of fabricating them have progressed to the prototype stage. This can result in the reduction of mass, volume, and the cost of materials for a given power level.

Lung cancer following bronchoscopic lung volume reduction for severe emphysema: a case and its management.

PubMed

Tummino, Celine; Maldonado, Fabien; Laroumagne, Sophie; Astoul, Philippe; Dutau, Hervé

2012-01-01

Bronchoscopic lung volume reduction using endobronchial valves has been suggested as a potentially safer alternative to surgery in selected cases. Complications of this technique include pneumothoraces, pneumonia, COPD exacerbations, hemoptysis, and valve migrations. We report the case of a male patient who developed a parenchymal mass in the treated lobe after valve insertion. Due to severe emphysema, transthoracic needle aspiration was not feasible. Removal of the valves was mandatory to perform transbronchialbiopsies which revealed a non-small cell primary lung cancer. This first description illustrates the potential risk of lung cancer development following bronchoscopic lung volume reduction and highlights the different approach to diagnosis and management of indeterminate peripheral lung lesions needed in this context. Copyright © 2011 S. Karger AG, Basel.

The effects of erythrocyte deformability upon hematocrit assessed by the conductance method.

PubMed

Hayashi, Yoshihito; Katsumoto, Yoichi; Oshige, Ikuya; Omori, Shinji; Yasuda, Akio; Asami, Koji

2009-04-21

A comparative study of centrifugation and conductance methods for the estimation of cell volume fraction (phi) was performed to examine whether the strong forces exerted upon erythrocytes during centrifugation affect their volume, and the results are discussed in terms of erythrocyte deformability. Rabbit erythrocytes of four shapes (spherocytes, echinocytes, stomatocyte-like enlarged erythrocytes and discocytes) were prepared by controlling the pH of the suspending media. The packed cell volumes of the suspensions were measured by standard hematocrit determination methods using centrifugation in capillary tubes. Simultaneously, the same suspensions and their supernatants were used in dielectric spectroscopy measurements, and the low-frequency limits of their conductivities were used for the numerical estimation of phi. The hematocrit values of spherocytes and echinocytes were markedly less than the volume fractions obtained by the conductance method. Namely, the centrifugation reduced the cell volume. For enlarged erythrocytes and discocytes, however, the reduction of cell volume was not observed. These findings showed that phi obtained by the centrifugation method can be greatly affected by the deformability of the cells, but the level of the effect depends on the cell types. Consequently, phi obtained by the centrifugation method should be carefully interpreted.

[Morphological studies of rat adrenal glands after space flight on "Kosmos-1667"].

PubMed

Prodan, N G; Bara'nska, V

1989-01-01

Histological and histomorphometric examinations of rat adrenals after a 7-day flight revealed the following changes: blood congestion in the cortex and medulla, progressive delipoidization of the cortex, slight enlargement of the nuclear volume of glomerular and fascicular zones, vacuolization of the cytoplasm of medulla cells, reduction of the area of noradrenocyte islets and cell nuclei of the medulla; the adrenal weight remained however unchanged. It is concluded that an early period of adaptation to microgravity was accompanied by a weak stress-reaction. Upon return to Earth the rats developed an acute gravitational stress. From the morphological point of view the stress manifested as: increased volume of nuclei in fascicular cells, decreased content of lipids in them, and greater vacuolization of the cytoplasm of medulla cells. The lack of medulla hypertrophy, reduction of the area of noradrenocyte islets and nuclei of medulla cells suggest that 7-day exposure to microgravity did not exert of stimulating effect on the sympathetic system of rats.

Hematology and immunology studies - The second manned Skylab mission

NASA Technical Reports Server (NTRS)

Kimzey, S. L.; Johnson, P. C.; Ritzman, S. E.; Mengel, C. E.

1976-01-01

The hematologic and immunologic functions of the Skylab 3 astronauts were monitored during the preflight, inflight, and postflight phases of the mission. Plasma protein profiles showed high consistency in all phases. A transient suppression of lymphocyte responsiveness was observed postflight. A reduction in the circulating blood volume due to drops in both the plasma volume and red cell mass was found. The loss of red cell mass is most likely a suppressed erythrypoiesis. The functional integrity of the circulating red cells did not appear to be compromised in the course of flight.

Chronic corticosterone affects brain weight, and mitochondrial, but not glial volume fraction in hippocampal area CA3.

PubMed

Coburn-Litvak, P S; Tata, D A; Gorby, H E; McCloskey, D P; Richardson, G; Anderson, B J

2004-01-01

Corticosterone (CORT), the predominant glucocorticoid in rodents, is known to damage hippocampal area CA3. Here we investigate how that damage is represented at the cellular and ultrastructural level of analyses. Rats were injected with CORT (26.8 mg/kg, s.c.) or vehicle for 56 days. Cell counts were estimated with the physical disector method. Glial and mitochondrial volume fractions were obtained from electron micrographs. The effectiveness of the CORT dose used was demonstrated in two ways. First, CORT significantly inhibited body weight gain relative to vehicles. Second, CORT significantly reduced adrenal gland, heart and gastrocnemius muscle weight. Both the adrenal and gastrocnemius muscle weight to body weight ratios were also significantly reduced. Although absolute brain weight was reduced, the brain to body weight ratio was higher in the CORT group relative to vehicles, suggesting that the brain is more resistant to the effects of CORT than many peripheral organs and muscles. Consistent with that interpretation, CORT did not alter CA3 cell density, cell layer volume, or apical dendritic neuropil volume. Likewise, CORT did not significantly alter glial volume fraction, but did reduce mitochondrial volume fraction. These findings highlight the need for ultrastructural analyses in addition to cellular level analyses before conclusions can be drawn about the damaging effects of prolonged CORT elevations. The relative reduction in mitochondria may indicate a reduction in bioenergetic capacity that, in turn, could render CA3 vulnerable to metabolic challenges.

Magnetic separation of encapsulated islet cells labeled with superparamagnetic iron oxide nano particles.

PubMed

Mettler, Esther; Trenkler, Anja; Feilen, Peter J; Wiegand, Frederik; Fottner, Christian; Ehrhart, Friederike; Zimmermann, Heiko; Hwang, Yong Hwa; Lee, Dong Yun; Fischer, Stefan; Schreiber, Laura M; Weber, Matthias M

2013-01-01

Islet cell transplantation is a promising option for the restoration of normal glucose homeostasis in patients with type 1 diabetes. Because graft volume is a crucial issue in islet transplantations for patients with diabetes, we evaluated a new method for increasing functional tissue yield in xenogeneic grafts of encapsulated islets. Islets were labeled with three different superparamagnetic iron oxide nano particles (SPIONs; dextran-coated SPION, siloxane-coated SPION, and heparin-coated SPION). Magnetic separation was performed to separate encapsulated islets from the empty capsules, and cell viability and function were tested. Islets labeled with 1000 μg Fe/ml dextran-coated SPIONs experienced a 69.9% reduction in graft volume, with a 33.2% loss of islet-containing capsules. Islets labeled with 100 μg Fe/ml heparin-coated SPIONs showed a 46.4% reduction in graft volume, with a 4.5% loss of capsules containing islets. No purification could be achieved using siloxane-coated SPIONs due to its toxicity to the primary islets. SPION labeling of islets is useful for transplant purification during islet separation as well as in vivo imaging after transplantation. Furthermore, purification of encapsulated islets can also reduce the volume of the encapsulated islets without impairing their function by removing empty capsules. © 2013 John Wiley & Sons A/S.

The effect of chronic erythrocytic polycythemia and high altitude upon plasma and blood volumes.

NASA Technical Reports Server (NTRS)

Burton, R. R.; Smith, A. H.

1972-01-01

Comparison of two kinds of physiological chronic erythrocytic polycythemias in order to differentiate the specific effect of erythrocytic polycythemia from the general effects of high altitude upon the plasma volume. The two kinds were produced hormonally in female chickens, at sea level, or by protracted high-altitude exposures. It appears that the vascular system of the body may account for an increase in red blood cell mass either by reduction in plasma volume, or by no change in plasma volume, resulting in differential changes in total blood volumes.

Superficial Collagen Fibril Modulus and Pericellular Fixed Charge Density Modulate Chondrocyte Volumetric Behaviour in Early Osteoarthritis

PubMed Central

Turunen, Siru M.; Han, Sang Kuy; Herzog, Walter; Korhonen, Rami K.

2013-01-01

The aim of this study was to investigate if the experimentally detected altered chondrocyte volumetric behavior in early osteoarthritis can be explained by changes in the extracellular and pericellular matrix properties of cartilage. Based on our own experimental tests and the literature, the structural and mechanical parameters for normal and osteoarthritic cartilage were implemented into a multiscale fibril-reinforced poroelastic swelling model. Model simulations were compared with experimentally observed cell volume changes in mechanically loaded cartilage, obtained from anterior cruciate ligament transected rabbit knees. We found that the cell volume increased by 7% in the osteoarthritic cartilage model following mechanical loading of the tissue. In contrast, the cell volume decreased by 4% in normal cartilage model. These findings were consistent with the experimental results. Increased local transversal tissue strain due to the reduced collagen fibril stiffness accompanied with the reduced fixed charge density of the pericellular matrix could increase the cell volume up to 12%. These findings suggest that the increase in the cell volume in mechanically loaded osteoarthritic cartilage is primarily explained by the reduction in the pericellular fixed charge density, while the superficial collagen fibril stiffness is suggested to contribute secondarily to the cell volume behavior. PMID:23634175

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

Eshraghi, Ray

In September 2008, the U.S. Department of Energy and Martin County Economic Development Corporation entered into an agreement to further the advancement of a microtubular PEM fuel cell developed by Microcell Corporation. The overall focus of this project was on research and development related to high volume manufacturing of fuel cells and cost reduction in the fuel cell manufacturing process. The extrusion process used for the microfiber fuel cells in this project is inherently a low cost, high volume, high speed manufacturing process. In order to take advantage of the capabilities that the extrusion process provides, all subsequent manufacturing processesmore » must be enhanced to meet the extrusion line’s speed and output. Significant research and development was completed on these subsequent processes to ensure that power output and performance were not negatively impacted by the higher speeds, design changes and process improvements developed in this project. All tasks were successfully completed resulting in cost reductions, performance improvements and process enhancements in the areas of speed and quality. These results support the Department of Energy’s goal of fuel cell commercialization.« less

[Octanol preconditioning alleviates mouse cardiomyocyte swelling induced by simulated ischemia/reperfusion challenge in vitro].

PubMed

Luo, Yukun; Fang, Jun; Fan, Lin; Lin, Chaogui; Chen, Zhaoyang; Chen, Lianglong

2012-10-01

To investigate the role of connexin 43-formed hemichannels in cell volume regulation induced by simulated ischemia/reperfusion (SI/R). Mouse cardiomyocytes isolated on a Langendorff apparatus with enzyme solution were aliquoted into control, SI/R and SI/R +octanol groups. Calcein-AM was used to stain the cells and the cell volume was measured with confocal microscope by stack scanning. Trypan blue was used to measure the cell viability after the treatments. Calcein-AM staining and cofocal microscopy yielded stable and reproducible results for cell volume measurement. Mouse cardiomyocytes subjected to simulated SI/R showed obvious cell swelling as compared with the control cells [(126∓6)% vs 100%, P<0.05], and octanol preconditioning significantly attenuated the cell swelling [(113∓6)%, P<0.05]. SI/R caused a significant reduction of the cell viability compared to the control cells [(19∓2)% vs (45∓3)%, P<0.01], and octanol preconditioning obviously reduced the viability of the cells with SI/R challenge [(31∓2)%, P<0.01]. Connexin 43-formed hemichannels are involved in the regulation of cardiomyocyte volumes induced by SI/R challenge, and octanol can alleviate the cell swelling to enhance the viability of the cardiomyocytes following SI/R.

Changes in blood product utilization in a seven-hospital system after the implementation of a patient blood management program: A 9-year follow-up.

PubMed

Verdecchia, Nicole M; Wisniewski, Mary Kay; Waters, Jonathan H; Triulzi, Darrell J; Alarcon, Louis H; Yazer, Mark H

2016-09-01

To analyze changes in red blood cell (RBC), platelet (PLT), and plasma transfusion volumes 9 years after the implementation of a multifaceted patient blood management (PBM) program across multiple hospitals. Between fiscal years 2007 and 2015, the annual transfusion volumes for seven hospitals in a regional healthcare system were analyzed by hospital, and between 2014 and 2015, by four service lines including emergency department, intensive care unit (ICU), medical/surgical ward, and operating room at each hospital. The number of units of RBCs administered to transfused recipients on the wards and in ICUs was also enumerated. For these seven hospitals combined, there was a 29.9% reduction in the number of RBCs transfused between 2007 and 2015, a 24.8% reduction in plasma units, and a 25.7% reduction in PLT units. The two largest hospitals saw some of the largest reductions in RBC transfusions (40.1, 25.1%), and plasma transfusions (26.1, 33.8%), and one of those hospitals had a 49.5% reduction in PLT transfusions. Smaller-sized hospitals also had reductions in transfusion volumes, while some volumes increased at hospitals when new or expanded clinical services were introduced. The number of RBC units per transfused recipient was generally between 1.5 and 2 units on the wards and slightly higher in the ICUs. Although the overall volume of transfusions has generally decreased at each hospital site over time, the appropriateness of the administered transfusions cannot be evaluated by these data. The system-wide implementation of a PBM program has reduced transfusion volumes.

Patients with sickle cell disease taking hydroxyurea in the Hemocentro Regional de Montes Claros

PubMed Central

Santos, Fernanda Kelle de Souza; Maia, Caroline Nogueira

2011-01-01

Background The development of therapies for sickle cell disease has received special attention, particularly those that reduce the polymerization of hemoglobin S. Hydroxyurea is a commonly used medication because it has the ability to raise levels of fetal hemoglobin, decrease the frequency of vaso-occlusive episodes and thus improve the clinical course of sickle cell disease patients. Objective To study hematological data and the clinical profile of sickle cell disease patients taking hydroxyurea in a regional blood center. Methods From the charts of 20 patients with sickle cell anemia, the clinical outcomes and a number of hematological variables were analyzed before and during treatment with hydroxyurea. Results The patients' ages ranged from 6 to 41 years old, most were dark skinned and there was a predominance of women. The main symptom that defined whether patients were prescribed hydroxyurea was painful crises followed by hospitalizations. During treatment with hydroxyurea there were significant increases in hemoglobin, fetal hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin. The reticulocyte and white blood cell counts dropped significantly with treatment. A positive correlation was found between fetal hemoglobin and mean corpuscular volume before and during treatment. Additionally, a correlation was found between the white blood cell and reticulocyte counts before treatment with hydroxyurea. Conclusion Most patients showed improvements with treatment as demonstrated by increases in hemoglobin, fetal hemoglobin and mean corpuscular volume, as well as by reductions in the reticulocyte and white blood cell counts. Clinically, more than 50% of patients had a significant reduction of events. PMID:23284256

Lead hampers gill cell volume regulation in marine crabs: stronger effect in a weak osmoregulator than in an osmoconformer.

PubMed

Amado, Enelise M; Freire, Carolina A; Grassi, Marco T; Souza, Marta M

2012-01-15

Hepatus pudibundus is a strictly marine osmoconformer crab, while Callinectes ornatus inhabits estuarine areas, behaving as a weak hyper-osmoregulator in diluted seawater. Osmoconformers are expected to have higher capacity for cell volume regulation, but gill cells of a regulator are expected to display ion transporters to a higher degree. The influence of lead nitrate (10 μM) on the ability of isolated gill cells from both species to volume regulate under isosmotic and hyposmotic conditions were here evaluated. Without lead, under a 25% hyposmotic shock, the gill cells of both species were quite capable of cell volume maintenance. Cells of C. ornatus, however, had a little swelling (5%) during the hyposmotic shock of greater intensity (50%), while cells of H. pudibundus were still capable of volume regulation. In the presence of lead, even under isosmoticity, the gill cells of both species showed about 10% volume reduction, indicating that lead promotes the loss of water by the cells. When lead was associated with 25% and 50% hyposmotic shock, C. ornatus cells lost more volume (15%), when compared to isosmotic conditions, while H. pudibundus cells showed volume regulation. We then analyzed the possible ways of action of lead on the mechanisms of cell volume regulation in the two species. Verapamil (100 μM) was used to inhibit Ca²⁺ channels, ouabain (100 μM) to inhibit Na⁺/K⁺-ATPase, and HgCl₂ (100 μM) to inhibit aquaporins. Our results suggest that: (1) Ca²⁺ channels are candidates for lead entry into gill cells of H. pudibundus and C. ornatus, being the target of lead action in these cells; (2) aquaporins are much more relevant for water flux in H. pudibundus; and (3) the Na⁺/K⁺-ATPase is much more relevant for volume regulation in C. ornatus. Osmoregulators may be more susceptible to metal contamination than osmoconformers, especially in situations of reduced salinity, for two basic reasons: (1) lower capacity of volume regulation and (2) putative higher uptake of Pb²⁺ through ionic pathways that operate in salt absorption, such as, for example, the Na⁺/K⁺-ATPase. Copyright © 2011 Elsevier B.V. All rights reserved.

Experimental evaluation of boron neutron capture therapy of human breast carcinoma implanted on nude mice

NASA Astrophysics Data System (ADS)

Bose, Satya Ranjan

2000-06-01

An in-pool small animal irradiation neutron tube (SAINT) facility was designed, constructed and installed at the University of Virginia Nuclear Research Reactor (UVAR). Thermal neutron flux profiles were measured by foil activation analysis (gold) and verified with DORT and MCNP computer code models. The gamma-ray absorbed dose in the neutron-gamma mixed field was determined from TLD measurements. The SAINT thermal neutron flux was used to investigate the well characterized human breast cancer cell line MCF-7B on both in-vitro samples and in- vivo animal subjects. Boronophenylalanine (BPA enriched in 95% 10B) was used as a neutron capturing agent. The in-vitro response of MCF-7B human breast carcinoma cells to BPA in a mixed field of neutron-gamma radiation or pure 60Co gamma radiation was investigated. The best result (lowest surviving fraction) was observed in cell cultures pre-incubated with BPA and given the neutron irradiation. The least effective treatment consisted of 60Co irradiation only. Immunologically deficient nude mice were inoculated subcutaneously with human breast cancer MCF-7B cells and estradiol pellets (to support tumor growth). The tumor volume in the mouse control group increased over time, as expected. The group of mice exposed only to neutron treatment exhibited initial tumor volume reduction lasting until 35 days following the treatment, followed by renewed tumor growth. Both groups given BPA plus neutron treatment showed continuous reduction in tumor volume over the 55-day observation period. The group given the higher BPA concentration showed the best tumor reduction response. The results on both in-vitro and in-vivo studies showed increased cell killing with BPA, substantiating the incorporation of BPA into the tumor or cell line. Therefore, BNCT may be a possible choice for the treatment of human breast carcinoma. However, prior to the initiation of any clinical studies, it is necessary to determine the therapeutic efficacy in a large animal model.

Volume regulation and shape bifurcation in the cell nucleus

PubMed Central

Kim, Dong-Hwee; Li, Bo; Si, Fangwei; Phillip, Jude M.; Wirtz, Denis; Sun, Sean X.

2015-01-01

ABSTRACT Alterations in nuclear morphology are closely associated with essential cell functions, such as cell motility and polarization, and correlate with a wide range of human diseases, including cancer, muscular dystrophy, dilated cardiomyopathy and progeria. However, the mechanics and forces that shape the nucleus are not well understood. Here, we demonstrate that when an adherent cell is detached from its substratum, the nucleus undergoes a large volumetric reduction accompanied by a morphological transition from an almost smooth to a heavily folded surface. We develop a mathematical model that systematically analyzes the evolution of nuclear shape and volume. The analysis suggests that the pressure difference across the nuclear envelope, which is influenced by changes in cell volume and regulated by microtubules and actin filaments, is a major factor determining nuclear morphology. Our results show that physical and chemical properties of the extracellular microenvironment directly influence nuclear morphology and suggest that there is a direct link between the environment and gene regulation. PMID:26243474

Volume regulation and shape bifurcation in the cell nucleus.

PubMed

Kim, Dong-Hwee; Li, Bo; Si, Fangwei; Phillip, Jude M; Wirtz, Denis; Sun, Sean X

2015-09-15

Alterations in nuclear morphology are closely associated with essential cell functions, such as cell motility and polarization, and correlate with a wide range of human diseases, including cancer, muscular dystrophy, dilated cardiomyopathy and progeria. However, the mechanics and forces that shape the nucleus are not well understood. Here, we demonstrate that when an adherent cell is detached from its substratum, the nucleus undergoes a large volumetric reduction accompanied by a morphological transition from an almost smooth to a heavily folded surface. We develop a mathematical model that systematically analyzes the evolution of nuclear shape and volume. The analysis suggests that the pressure difference across the nuclear envelope, which is influenced by changes in cell volume and regulated by microtubules and actin filaments, is a major factor determining nuclear morphology. Our results show that physical and chemical properties of the extracellular microenvironment directly influence nuclear morphology and suggest that there is a direct link between the environment and gene regulation. © 2015. Published by The Company of Biologists Ltd.

Independence of nutrient limitation and carbon dioxide impacts on the Southern Ocean coccolithophore Emiliania huxleyi.

PubMed

Müller, Marius N; Trull, Thomas W; Hallegraeff, Gustaaf M

2017-08-01

Future oceanic conditions induced by anthropogenic greenhouse gas emissions include warming, acidification and reduced nutrient supply due to increased stratification. Some parts of the Southern Ocean are expected to show rapid changes, especially for carbonate mineral saturation. Here we compare the physiological response of the model coccolithophore Emiliania huxleyi (strain EHSO 5.14, originating from 50 o S, 149 o E) with pH/CO 2 gradients (mimicking ocean acidification ranging from 1 to 4 × current pCO 2 levels) under nutrient-limited (nitrogen and phosphorus) and -replete conditions. Both nutrient limitations decreased per cell photosynthesis (particulate organic carbon (POC) production) and calcification (particulate inorganic carbon (PIC) production) rates for all pCO 2 levels, with more than 50% reductions under nitrogen limitation. These impacts, however, became indistinguishable from nutrient-replete conditions when normalized to cell volume. Calcification decreased three-fold and linearly with increasing pCO 2 under all nutrient conditions, and was accompanied by a smaller ~30% nonlinear reduction in POC production, manifested mainly above 3 × current pCO 2 . Our results suggest that normalization to cell volume allows the major impacts of nutrient limitation (changed cell sizes and reduced PIC and POC production rates) to be treated independently of the major impacts of increasing pCO 2 and, additionally, stresses the importance of including cell volume measurements to the toolbox of standard physiological analysis of coccolithophores in field and laboratory studies.

Independence of nutrient limitation and carbon dioxide impacts on the Southern Ocean coccolithophore Emiliania huxleyi

PubMed Central

Müller, Marius N; Trull, Thomas W; Hallegraeff, Gustaaf M

2017-01-01

Future oceanic conditions induced by anthropogenic greenhouse gas emissions include warming, acidification and reduced nutrient supply due to increased stratification. Some parts of the Southern Ocean are expected to show rapid changes, especially for carbonate mineral saturation. Here we compare the physiological response of the model coccolithophore Emiliania huxleyi (strain EHSO 5.14, originating from 50oS, 149oE) with pH/CO2 gradients (mimicking ocean acidification ranging from 1 to 4 × current pCO2 levels) under nutrient-limited (nitrogen and phosphorus) and -replete conditions. Both nutrient limitations decreased per cell photosynthesis (particulate organic carbon (POC) production) and calcification (particulate inorganic carbon (PIC) production) rates for all pCO2 levels, with more than 50% reductions under nitrogen limitation. These impacts, however, became indistinguishable from nutrient-replete conditions when normalized to cell volume. Calcification decreased three-fold and linearly with increasing pCO2 under all nutrient conditions, and was accompanied by a smaller ~30% nonlinear reduction in POC production, manifested mainly above 3 × current pCO2. Our results suggest that normalization to cell volume allows the major impacts of nutrient limitation (changed cell sizes and reduced PIC and POC production rates) to be treated independently of the major impacts of increasing pCO2 and, additionally, stresses the importance of including cell volume measurements to the toolbox of standard physiological analysis of coccolithophores in field and laboratory studies. PMID:28430186

The Effect of Antitumor Glycosides on Glioma Cells and Tissues as Studied by Proton HR-MAS NMR Spectroscopy

PubMed Central

García-Álvarez, Isabel; Garrido, Leoncio; Romero-Ramírez, Lorenzo; Nieto-Sampedro, Manuel; Fernández-Mayoralas, Alfonso; Campos-Olivas, Ramón

2013-01-01

The effect of the treatment with glycolipid derivatives on the metabolic profile of intact glioma cells and tumor tissues, investigated using proton high resolution magic angle spinning (1H HR-MAS) nuclear magnetic resonance (NMR) spectroscopy, is reported here. Two compounds were used, a glycoside and its thioglycoside analogue, both showing anti-proliferative activity on glioma C6 cell cultures; however, only the thioglycoside exhibited antitumor activity in vivo. At the drug concentrations showing anti-proliferative activity in cell culture (20 and 40 µM), significant increases in choline containing metabolites were observed in the 1H NMR spectra of the same intact cells. In vivo experiments in nude mice bearing tumors derived from implanted C6 glioma cells, showed that reduction of tumor volume was associated with significant changes in the metabolic profile of the same intact tumor tissues; and were similar to those observed in cell culture. Specifically, the activity of the compounds is mainly associated with an increase in choline and phosphocholine, in both the cell cultures and tumoral tissues. Taurine, a metabolite that has been considered a biomarker of apoptosis, correlated with the reduction of tumor volume. Thus, the results indicate that the mode of action of the glycoside involves, at least in part, alteration of phospholipid metabolism, resulting in cell death. PMID:24194925

Regulated phosphorylation of the K-Cl cotransporter KCC3 is a molecular switch of intracellular potassium content and cell volume homeostasis.

PubMed

Adragna, Norma C; Ravilla, Nagendra B; Lauf, Peter K; Begum, Gulnaz; Khanna, Arjun R; Sun, Dandan; Kahle, Kristopher T

2015-01-01

The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K(+) and Cl(-) efflux via activation of K(+) channels, volume-regulated anion channels (VRACs), and the K(+)-Cl(-) cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the related bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter isoform 1 (NKCC1). This results in a rapid (<10 min) and significant (>90%) reduction in intracellular K(+) content (Ki) via both Cl-dependent (KCC3a + NKCC1) and Cl-independent [DCPIB (VRAC inhibitor)-sensitive] pathways, which collectively renders cells less prone to acute swelling in hypotonic osmotic stress. Together, these data demonstrate the phosphorylation state of Thr991/Thr1048 in KCC3a encodes a potent switch of transporter activity, Ki homeostasis, and cell volume regulation, and reveal novel observations into the functional interaction among ion transport molecules involved in RVD.

Regulated phosphorylation of the K-Cl cotransporter KCC3 is a molecular switch of intracellular potassium content and cell volume homeostasis

PubMed Central

Adragna, Norma C.; Ravilla, Nagendra B.; Lauf, Peter K.; Begum, Gulnaz; Khanna, Arjun R.; Sun, Dandan; Kahle, Kristopher T.

2015-01-01

The defense of cell volume against excessive shrinkage or swelling is a requirement for cell function and organismal survival. Cell swelling triggers a coordinated homeostatic response termed regulatory volume decrease (RVD), resulting in K+ and Cl− efflux via activation of K+ channels, volume-regulated anion channels (VRACs), and the K+-Cl− cotransporters, including KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991 and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory phosphorylation at these sites, not only significantly up-regulates KCC3a activity up to 25-fold in normally inhibitory isotonic conditions, but is also accompanied by reversal of activity of the related bumetanide-sensitive Na+-K+-2Cl− cotransporter isoform 1 (NKCC1). This results in a rapid (<10 min) and significant (>90%) reduction in intracellular K+ content (Ki) via both Cl-dependent (KCC3a + NKCC1) and Cl-independent [DCPIB (VRAC inhibitor)-sensitive] pathways, which collectively renders cells less prone to acute swelling in hypotonic osmotic stress. Together, these data demonstrate the phosphorylation state of Thr991/Thr1048 in KCC3a encodes a potent switch of transporter activity, Ki homeostasis, and cell volume regulation, and reveal novel observations into the functional interaction among ion transport molecules involved in RVD. PMID:26217182

The evolution of bacterial cell size: the internal diffusion-constraint hypothesis.

PubMed

Gallet, Romain; Violle, Cyrille; Fromin, Nathalie; Jabbour-Zahab, Roula; Enquist, Brian J; Lenormand, Thomas

2017-07-01

Size is one of the most important biological traits influencing organismal ecology and evolution. However, we know little about the drivers of body size evolution in unicellulars. A long-term evolution experiment (Lenski's LTEE) in which Escherichia coli adapts to a simple glucose medium has shown that not only the growth rate and the fitness of the bacterium increase over time but also its cell size. This increase in size contradicts prominent 'external diffusion' theory (EDC) predicting that cell size should have evolved toward smaller cells. Among several scenarios, we propose and test an alternative 'internal diffusion-constraint' (IDC) hypothesis for cell size evolution. A change in cell volume affects metabolite concentrations in the cytoplasm. The IDC states that a higher metabolism can be achieved by a reduction in the molecular traffic time inside of the cell, by increasing its volume. To test this hypothesis, we studied a population from the LTEE. We show that bigger cells with greater growth and CO 2 production rates and lower mass-to-volume ratio were selected over time in the LTEE. These results are consistent with the IDC hypothesis. This novel hypothesis offers a promising approach for understanding the evolutionary constraints on cell size.

Hemoglobin consumption by P. falciparum in individual erythrocytes imaged via quantitative phase spectroscopy

NASA Astrophysics Data System (ADS)

Rinehart, Matthew T.; Park, Han Sang; Walzer, Katelyn A.; Chi, Jen-Tsan Ashley; Wax, Adam

2016-04-01

Plasmodium falciparum infection causes structural and biochemical changes in red blood cells (RBCs). To quantify these changes, we apply a novel optical technique, quantitative phase spectroscopy (QPS) to characterize individual red blood cells (RBCs) during the intraerythrocytic life cycle of P. falciparum. QPS captures hyperspectral holograms of individual RBCs to measure spectroscopic changes across the visible wavelength range (475-700 nm), providing complex information, i.e. amplitude and phase, about the light field which has interacted with the cell. The complex field provides complimentary information on hemoglobin content and cell mass, which are both found to dramatically change upon infection by P. falciparum. Hb content progressively decreases with parasite life cycle, with an average 72.2% reduction observed for RBCs infected by schizont-stage P. falciparum compared to uninfected cells. Infection also resulted in a 33.1% reduction in RBC’s optical volume, a measure of the cells’ non-aqueous components. Notably, optical volume is only partially correlated with hemoglobin content, suggesting that changes in other dry mass components such as parasite mass may also be assessed using this technique. The unique ability of QPS to discriminate individual healthy and infected cells using spectroscopic changes indicates that the approach can be used to detect disease.

Osmotic Shock Induced Protein Destabilization in Living Cells and Its Reversal by Glycine Betaine.

PubMed

Stadmiller, Samantha S; Gorensek-Benitez, Annelise H; Guseman, Alex J; Pielak, Gary J

2017-04-21

Many organisms can adapt to changes in the solute content of their surroundings (i.e., the osmolarity). Hyperosmotic shock causes water efflux and a concomitant reduction in cell volume, which is countered by the accumulation of osmolytes. This volume reduction increases the crowded nature of the cytoplasm, which is expected to affect protein stability. In contrast to traditional theory, which predicts that more crowded conditions can only increase protein stability, recent work shows that crowding can destabilize proteins through transient attractive interactions. Here, we quantify protein stability in living Escherichia coli cells before and after hyperosmotic shock in the presence and absence of the osmolyte, glycine betaine. The 7-kDa N-terminal src-homology 3 domain of Drosophila signal transduction protein drk is used as the test protein. We find that hyperosmotic shock decreases SH3 stability in cells, consistent with the idea that transient attractive interactions are important under physiologically relevant crowded conditions. The subsequent uptake of glycine betaine returns SH3 to the stability observed without osmotic shock. These results highlight the effect of transient attractive interactions on protein stability in cells and provide a new explanation for why stressed cells accumulate osmolytes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adaptive changes in pancreas post Roux-en-Y gastric bypass induced weight loss.

PubMed

Lautenbach, A; Wernecke, M; Riedel, N; Veigel, J; Yamamura, J; Keller, S; Jung, R; Busch, P; Mann, O; Knop, F K; Holst, J J; Meier, J J; Aberle, J

2018-05-16

Obesity has been shown to trigger adaptive increases in pancreas parenchymal and fat volume. Consecutively, pancreatic steatosis may lead to beta-cell dysfunction. However, it is not known, whether the pancreatic tissue components decrease with weight loss and pancreatic steatosis is reversible following RYGB. Therefore, the objective of the study was to investigate the effects of RYGB-induced weight loss on pancreatic volume and glucose homeostasis. 11 patients were recruited in the Obesity Centre of the University Medical Centre Hamburg-Eppendorf. Before and 6 months after RYGB, total GLP-1 levels were measured during OGTT. To assess changes in visceral adipose tissue and pancreatic volume, MRI was performed. Measures of glucose homeostasis and insulin indices were assessed. Fractional beta-cell area was estimated by correlation with the C-peptide-to-glucose ratio, beta-cell mass was calculated by the product of beta-cell area and pancreas parenchymal weight. Pancreas volume decreased from 83.8 (75.7-92.0) to 70.5 (58.8-82.3) cm 3 [mean (95% CI), p=0.001]. The decrease in total volume was associated with a significant decrease in fat volume. Fasting insulin and C-peptide were lower post RYGB. HOMA-IR levels decreased, whereas insulin sensitivity increased (p=0.03). This was consistent with a reduction in the estimated beta-cell area and mass. Following RYGB, pancreatic volume and steatosis adaptively decreased to "normal" levels with accompanying improvement in glucose homeostasis. Moreover, obesity-driven beta-cell expansion seems to be reversible, however future studies must define a method to more accurately estimate functional beta-cell mass to increase our understanding of glucose homeostasis after RYGB. This article is protected by copyright. All rights reserved.

Experiences of the Dresdner Cord Blood Bank, supported by the Deutsche Knochenmarkspenderdatei.

PubMed

Ordemann, R; Petzold, K; Hölig, K; Schaffer, B; Mauersberger, S; Ehninger, G; Ehminger, G

1999-01-01

Allogeneic bone marrow and peripheral blood stem cell transplantation is the treatment of choice for some malignant hematologic diseases, marrow failure syndromes, and severe congenital immunodeficiency states. Since Gluckman et al reported in 1988 the first successful human leukocyte antigen (HLA)-matched sibling umbilical cord blood stem cell transplantation, it has been known that cord blood is a valuable source of hematopoietic stem cells. The Cord Blood Bank at the University Hospital of Dresden was founded in 1997 and started collecting, processing, and cryoconserving umbilical cord blood in August 1997. The cord blood bank is supported by the largest German donor registry: Deutsche Knochenmarkspenderdatei (DKMS) in Tubingen, Germany. With the informed consent of the mothers, the collection is performed in collaboration with six hospitals in Dresden, Berlin, and Bautzen. We routinely perform a volume reduction by centrifuging the blood bag and expressing the leukocyte-rich supernatant. Routinely, sterility, total nucleated cells (TNC), CD34+ cell count, HLA class I and II, ABO/Rh blood group, and colony-forming units are evaluated. The maternal blood is screened for anti-immunodeficiency virus (anti-HIV), anti-hepatitis C virus (anti-HCV), anti-hepatitis B surface antigen (HBsAg), anti-hepatitis B surface (anti-HBs), anti-hepatitis B core (anti-HBc), anticytomegalovirus (anti-CMV), and toxoplasmosis and with Treponema pallidum hemagglutination assay (TPHA). More than 1,000 cord blood units could be collected. Because of the required volume and cell count and because of sterility, 50% of the collected units had to be discharged. Our results are comparable with data of other cord blood banks: mean volume 79 mL; cell count after volume reduction-TNC, 7.16 x 10(8); mononucleated cells (MNC), 3.75 x 10(8); CD34+ cells, 1.95 x 10(6); colony-forming units (CFU), 67.1 x 10(4). To increase the pool of potential umbilical cord blood units and in order to evaluate the possibility for unrelated transplants, cryopreservation and banking of large numbers of cord bloods are necessary.

Changes in peak oxygen uptake and plasma volume in fit and unfit subjects following exposure to a simulation of microgravity

NASA Technical Reports Server (NTRS)

Convertino, V. A.

1998-01-01

To test the hypothesis that the magnitude of reduction in plasma volume and work capacity following exposure to simulated microgravity is dependent on the initial level of aerobic fitness, peak oxygen uptake (VO2peak) was measured in a group of physically fit subjects and compared with VO2peak in a group of relatively unfit subjects before and after 10 days of continuous 6 degrees head-down tilt (HDT). Ten fit subjects (40 +/- 2 year) with mean +/- SE VO2peak = 48.9 +/- 1.7 mL kg-1 min-1 were matched for age, height, and lean body weight with 10 unfit subjects (VO2peak = 37.7 +/- 1.6 mL kg-1 min-1). Before and after HDT, plasma, blood, and red cell volumes and body composition were measured and all subjects underwent a graded supine cycle ergometer test to determine VO2peak period needed. Reduced VO2peak in fit subjects (-16.2%) was greater than that of unfit subjects (-6.1%). Similarly, reductions in plasma (-18.3%) and blood volumes (-16.0%) in fit subjects were larger than those of unfit subjects (blood volume = -5.6%; plasma volume = -6.6%). Reduced plasma volume was associated with greater negative body fluid balance during the initial 24 h of HDT in the fit group (912 +/- 154 mL) compared with unfit subjects (453 +/- 200 mL). The percentage change for VO2peak correlated with percentage change in plasma volume (r = +0.79). Following exposure to simulated microgravity, fit subjects demonstrated larger reductions in VO2peak than unfit subjects which was associated with larger reductions in plasma and blood volume. These data suggest that the magnitude of physical deconditioning induced by exposure to microgravity without intervention of countermeasures was influenced by the initial fitness of the subjects.

Microfluidic devices for cell culture and handling in organ-on-a-chip applications

NASA Astrophysics Data System (ADS)

Becker, Holger; Schulz, Ingo; Mosig, Alexander; Jahn, Tobias; Gärtner, Claudia

2014-03-01

For many problems in system biology or pharmacology, in-vivo-like models of cell-cell interactions or organ functions are highly sought after. Conventional stationary cell culture in 2D plates quickly reaches its limitations with respect to an in-vivo like expression and function of individual cell types. Microfabrication technologies and microfluidics offer an attractive solution to these problems. The ability to generate flow as well as geometrical conditions for cell culture and manipulation close to the in-vivo situation allows for an improved design of experiments and the modeling of organ-like functionalities. Furthermore, reduced internal volumes lead to a reduction in reagent volumes necessary as well as an increased assay sensitivity. In this paper we present a range of microfluidic devices designed for the co-culturing of a variety of cells. The influence of substrate materials and surface chemistry on the cell morphology and viability for long-term cell culture has been investigated as well as strategies and medium supply for on-chip cell cultivation.

Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage—a modelling study

NASA Astrophysics Data System (ADS)

Røthe Arnesen, Marius; Paulsen Hellebust, Taran; Malinen, Eirik

2017-03-01

Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

Reduction of Powerplex(®) Y23 reaction volume for genotyping buccal cell samples on FTA(TM) cards.

PubMed

Raziel, Aliza; Dell'Ariccia-Carmon, Aviva; Zamir, Ashira

2015-01-01

PowerPlex(®) Y23 is a novel kit for Y-STR typing that includes new highly discriminating loci. The Israel DNA Database laboratory has recently adopted it for routine Y-STR analysis. This study examined PCR amplification from 1.2-mm FTA punch in reduced volumes of 5 and 10 μL. Direct amplification and washing of the FTA punches were examined in different PCR cycle numbers. One short robotically performed wash was found to improve the quality and the percent of profiles obtained. The optimal PCR cycle number was determined for 5 and 10 μL reaction volumes. The percent of obtained profiles, color balance, and reproducibility were examined. High-quality profiles were achieved in 90% and 88% of the samples amplified in 5 and 10 μL, respectively, in the first attempt. Volume reduction to 5 μL has a vast economic impact especially for DNA database laboratories. © 2014 American Academy of Forensic Sciences.

IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke

PubMed Central

Bodhankar, Sheetal; Chen, Yingxin; Vandenbark, Arthur A.; Murphy, Stephanie J.; Offner, Halina

2013-01-01

Clinical stroke induces inflammatory processes leading to cerebral injury. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that absence of B-cells led to larger infarct volumes and increased numbers of activated T-cells, monocytes and microglial cells in the brain, thus implicating a regulatory role of B-cell subpopulations in limiting CNS damage from stroke. The aim of this study was to determine whether the IL-10-producing regulatory B-cell subset can limit CNS inflammation and reduce infarct volume following ischemic stroke in B-cell deficient (µMT−/−) mice. Five million IL-10-producing B-cells were obtained from IL-10-GFP reporter mice and transferred i.v. to µMT−/− mice. After 24 h following this transfer, recipients were subjected to 60 min of middle cerebral artery occlusion (MCAO) followed by 48 hours of reperfusion. Compared to vehicle-treated controls, the IL-10+ B-cell-replenished µMT−/− mice had reduced infarct volume and fewer infiltrating activated T-cells and monocytes in the affected brain hemisphere. These effects in CNS were accompanied by significant increases in regulatory T-cells and expression of the co-inhibitory receptor, PD-1, with a significant reduction in the proinflammatory milieu in the periphery. These novel observations provide the first proof of both immunoregulatory and protective functions of IL-10-secreting B-cells in MCAO that potentially could impart significant benefit for stroke patients in the clinic. PMID:23640015

A review of nickel hydrogen battery technology

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Odonnell, Patricia M.

1995-01-01

This paper on nickel hydrogen batteries is an overview of the various nickel hydrogen battery design options, technical accomplishments, validation test results and trends. There is more than one nickel hydrogen battery design, each having its advantage for specific applications. The major battery designs are individual pressure vessel (IPV), common pressure vessel (CPV), bipolar and low pressure metal hydride. State-of-the-art (SOA) nickel hydrogen batteries are replacing nickel cadmium batteries in almost all geosynchronous orbit (GEO) applications requiring power above 1 kW. However, for the more severe low earth orbit (LEO) applications (greater than 30,000 cycles), the current cycle life of 4000 to 10,000 cycles at 60 percent DOD should be improved. A NASA Lewis Research Center innovative advanced design IPV nickel hydrogen cell led to a breakthrough in cycle life enabling LEO applications at deep depths of discharge (DOD). A trend for some future satellites is to increase the power level to greater than 6 kW. Another trend is to decrease the power to less than 1 kW for small low cost satellites. Hence, the challenge is to reduce battery mass, volume and cost. A key is to develop a light weight nickel electrode and alternate battery designs. A common pressure vessel (CPV) nickel hydrogen battery is emerging as a viable alternative to the IPV design. It has the advantage of reduced mass, volume and manufacturing costs. A 10 Ah CPV battery has successfully provided power on the relatively short lived Clementine Spacecraft. A bipolar nickel hydrogen battery design has been demonstrated (15,000 LEO cycles, 40 percent DOD). The advantage is also a significant reduction in volume, a modest reduction in mass, and like most bipolar designs, features a high pulse power capability. A low pressure aerospace nickel metal hydride battery cell has been developed and is on the market. It is a prismatic design which has the advantage of a significant reduction in volume and a reduction in manufacturing cost.

Nickel-Hydrogen Batteries - An Overview

NASA Technical Reports Server (NTRS)

Smithrick, John J.; ODonnell, Patricia M.

1996-01-01

This article on nickel-hydrogen batteries is an overview of the various nickel-hydrogen battery design options, technical accomplishments, validation test results, and trends. There is more than one nickel-hydrogen battery design, each having its advantage for specific applications. The major battery designs are Individual Pressure Vessel (IPV), Common Pressure Vessel (CPV), bipolar, and low-pressure metal hydride. State-of-the-art nickel-hydrogen batteries are replacing nickel-cadmium batteries in almost all geosynchronous Earth orbit applications requiring power above 1 kW. However, for the more severe Low-Earth Orbit (LEO) applications (greater than 30,000 cycles), the current cycle life of 4000-10,000 cycles at 60 - 80 % DOD should be improved. A NASA Lewis Research Center innovative advanced design IPV nickel-hydrogen cell led to a breakthrough in cycle life enabling LEO applications at deep Depths of Discharge (DOD). A trend for some future satellites is to increase the power level to greater than 6 kW. Another trend is to decrease the power to less than 1 kW for small low-cost satellites. Hence, the challenge is to reduce battery mass, volume, and cost. A key is to develop a lightweight nickel electrode and alternate battery designs. A CPV nickel-hydrogen battery is emerging as a viable alternative to the IPV design. It has the advantage of reduced mass, volume, and manufacturing costs. A 10-A-h CPV battery has successfully provided power on the relatively short-lived Clementine spacecraft. A bipolar nickel -hydrogen battery design has been demonstrated (15,000 LEO cycles, 40 % DOD). The advantage is also a significant reduction in volume, a modest reduction in mass, and like most bipolar designs, features a high-pulse power capability. A low-pressure aerospace nickel-metal-hydride battery cell has been developed and is on the market. It is a prismatic design that has the advantage of a significant reduction in volume and a reduction in manufacturing cost.

Nickel hydrogen batteries: An overview

NASA Technical Reports Server (NTRS)

Smithrick, John J.; Odonnell, Patricia M.

1994-01-01

This paper on nickel hydrogen batteries is an overview of the various nickel hydrogen battery design options, technical accomplishments, validation test results and trends. There is more than one nickel hydrogen battery design, each having its advantage for specific applications. The major battery designs are individual pressure vessel (IPV), common pressure vessel (CPV), bipolar and low pressure metal hydride. State-of-the-art (SOA) nickel hydrogen batteries are replacing nickel cadmium batteries in almost all geosynchronous orbit (GEO) applications requiring power above 1 kW. However, for the more severe low earth orbit (LEO) applications (greater than 30,000 cycles), the current cycle life of 4000 to 10,000 cycles at 60 percent DOD should be improved. A LeRC innovative advanced design IPV nickel hydrogen cell led to a breakthrough in cycle life enabling LEO applications at deep depths of discharge (DOD). A trend for some future satellites is to increase the power level to greater than 6 kW. Another trend is to decrease the power to less than 1 kW for small low cost satellites. Hence, the challenge is to reduce battery mass,volume, and cost. A key is to develop a light weight nickel electrode and alternate battery designs. A common pressure vessel (CPV) nickel hydrogen battery is emerging as a viable alternative to the IPV design. It has the advantage of reduced mass, volume and manufacturing costs. A 10 Ah CPV battery has successfully provided power on the relatively short lived Clementine Spacecraft. A bipolar nickel hydrogen battery design has been demonstrated (15,000 LEO cycles, 40 percent DOD). The advantage is also a significant reduction in volume, a modest reduction in mass, and like most bipolar designs, features a high pulse power capability. A low pressure aerospace nickel metal hydride battery cell has been developed and is on the market. It is a prismatic design which has the advantage of a significant reduction in volume and a reduction in manufacturing cost.

Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia

PubMed Central

Hutchinson, Mark R.; Northcutt, Alexis L.; Chao, Lindsey W.; Kearney, Jeffrey J.; Zhang, Yingning; Berkelhammer, Debra L.; Loram, Lisa C.; Rozeske, Robert R.; Bland, Sondra T.; Maier, Steven F.; Gleeson, Todd T.; Watkins, Linda R.

2008-01-01

Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation. PMID:18706994

PATHOLOGIC SIGNIFICANCE OF BLOOD VOLUME CHANGES IN UNTREATED POLYCYTHEMIA VERA AND AFTER P$sup 32$ THERAPY (in Hungarian)

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

Burger, T.; Keszthelyi, B.; Peer, J.

1962-02-25

Ten patients suffering from polycythemia vera were divided into three groups for evaluation purposes. The first group (2 patients) consisted of the mildest cases in which the hematocrit values were 55% or less. The second group (2 patients) had a hematocrit values of 55% or higher, and the red cell and plasma voiumes were higher than normal. The third group consisted of the severest cases with hematocrit values of 70 to 80%, red cell counts of 6 to 8 million/ mm/sup 3, and red cell and plasma volumes two to four times normai. Blood volumes were determined with /sup 32/Pmore » or /sup 51/Cr. The patients showed clinical improvement after the first treatment with /sup 32/P and hematologic examination indicated that the red cell count dropped, while hemogiobin value, white cell count, thrombocyte count, and hematocrit decreased. After the second / sup 32/P treatment the blood volume did not decrease appreciably, but plasma volume increased, leading to improvement of the patient's condition. Venesection may still be used as a therapeutic means when an immediate reduction of the blood volume is desired. This can be achieved by /sup 32/P therapy only after severai treatments. The /sup 32/P dose varied with the severity of the illness from one treatment of five mC /sup 32/P in the patients with hematocrits of 55% to two doses of 4.2 mC in those with values of 58%, and three mC /sup 32/P in another patient with a hematocrit of 82%. (BBB)« less

Biotin Decorated Gold Nanoparticles for Targeted Delivery of a Smart-Linked Anticancer Active Copper Complex: In Vitro and In Vivo Studies.

PubMed

Pramanik, Anup K; Siddikuzzaman; Palanimuthu, Duraippandi; Somasundaram, Kumaravel; Samuelson, Ashoka G

2016-12-21

The synthesis and anticancer activity of a copper(II) diacetyl-bis(N4-methylthiosemicarbazone) complex and its nanoconjugates are reported. The copper(II) complex is connected to a carboxylic acid group through a cleavable disulfide link to enable smart delivery. The copper complex is tethered to highly water-soluble 20 nm gold nanoparticles (AuNPs), stabilized by amine terminated lipoic acid-polyethylene glycol (PEG). The gold nanoparticle carrier was further decorated with biotin to achieve targeted action. The copper complex and the conjugates with and without biotin, were tested against HeLa and HaCaT cells. They show very good anticancer activity against HeLa cells, a cell line derived from cervical cancer and are less active against HaCaT cells. Slow and sustained release of the complex from conjugates is demonstrated through cleavage of disulfide linker in the presence of glutathione (GSH), a reducing agent intrinsically present in high concentrations within cancer cells. Biotin appended conjugates do not show greater activity than conjugates without biotin against HeLa cells. This is consistent with drug uptake studies, which suggests similar uptake profiles for both conjugates in vitro. However, in vivo studies using a HeLa cell xenograft tumor model shows 3.8-fold reduction in tumor volume for the biotin conjugated nanoparticle compared to the control whereas the conjugate without biotin shows only 2.3-fold reduction in the tumor volume suggesting significant targeting.

Combination therapy of cancer with cancer vaccine and immune checkpoint inhibitors: A mathematical model

PubMed Central

Friedman, Avner

2017-01-01

In this paper we consider a combination therapy of cancer. One drug is a vaccine which activates dendritic cells so that they induce more T cells to infiltrate the tumor. The other drug is a checkpoint inhibitor, which enables the T cells to remain active against the cancer cells. The two drugs are positively correlated in the sense that an increase in the amount of each drug results in a reduction in the tumor volume. We consider the question whether a treatment with combination of the two drugs at certain levels is preferable to a treatment by one of the drugs alone at ‘roughly’ twice the dosage level; if that is the case, then we say that there is a positive ‘synergy’ for this combination of dosages. To address this question, we develop a mathematical model using a system of partial differential equations. The variables include dendritic and cancer cells, CD4+ and CD8+ T cells, IL-12 and IL-2, GM-CSF produced by the vaccine, and a T cell checkpoint inhibitor associated with PD-1. We use the model to explore the efficacy of the two drugs, separately and in combination, and compare the simulations with data from mouse experiments. We next introduce the concept of synergy between the drugs and develop a synergy map which suggests in what proportion to administer the drugs in order to achieve the maximum reduction of tumor volume under the constraint of maximum tolerated dose. PMID:28542574

Vertical nanopillars for highly localized fluorescence imaging

PubMed Central

Xie, Chong; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

2011-01-01

Observing individual molecules in a complex environment by fluorescence microscopy is becoming increasingly important in biological and medical research, for which critical reduction of observation volume is required. Here, we demonstrate the use of vertically aligned silicon dioxide nanopillars to achieve below-the-diffraction-limit observation volume in vitro and inside live cells. With a diameter much smaller than the wavelength of visible light, a transparent silicon dioxide nanopillar embedded in a nontransparent substrate restricts the propagation of light and affords evanescence wave excitation along its vertical surface. This effect creates highly confined illumination volume that selectively excites fluorescence molecules in the vicinity of the nanopillar. We show that this nanopillar illumination can be used for in vitro single-molecule detection at high fluorophore concentrations. In addition, we demonstrate that vertical nanopillars interface tightly with live cells and function as highly localized light sources inside the cell. Furthermore, specific chemical modification of the nanopillar surface makes it possible to locally recruit proteins of interest and simultaneously observe their behavior within the complex, crowded environment of the cell. PMID:21368157

Fabrication and Performance of Zirconia Electrolysis Cells for Carbon Dioxide Reduction for Mars In Situ Resource Utilization Applications

NASA Technical Reports Server (NTRS)

Minh, N. Q.; Chung, B. W.; Doshi, R.; Lear, G. R.; Montgomery, K.; Ong, E. T.

1999-01-01

The use of the Martian atmosphere (95% CO2) to produce oxygen (for propellant and life support) can significantly lower the required launch mass and dramatically reduce the total cost for Mars missions. Zirconia electrolysis cells are one of the technologies being considered for oxygen generation from carbon dioxide in Mars In Situ Resource Utilization (ISRU) production plants. The attractive features of the zirconia cell for this application include simple operation and lightweight, low volume system.

A microfabricated bio-sensor for erythrocytes deformability and volume distributions analysis

NASA Astrophysics Data System (ADS)

Bransky, Avishay; Korin, Natanel; Nemirovski, Yael; Dinnar, Uri

2007-12-01

The deformability of erythrocytes is of great importance for oxygen delivery in the microcirculation. Reduced RBC deformability is associated with several types of hemolytic anaemias, malaria, sepsis and diabetes. Aging of erythrocytes is also associated with loss of deformability as well as reduction in cell volume. An automated rheoscope has been developed, utilizing a microfabricated glass flow cell, high speed camera and advanced image-processing software. RBCs suspended in a high viscosity medium were filmed flowing through a microchannel. The system produces valuable data such as velocity profiles of RBCs, spatial distribution within the microchannel, cell volume and deformation index (DI) curves. The variation of DI across the channel height, due to change in shear stress, was measured for the first time. Such DI curves were obtained for normal and Thalassemia RBCs and their diagnostic potential was demonstrated. The spatial distribution and velocity of RBCs and rigid microspheres were measured. Both RBC and rigid spheres showed enhanced inward lateral migration, however the RBCs form a depletion region at the center of flow. The volume and surface area of the flowing cells have been estimated based on a fluid mechanics model and experimental results and fell within the normal range. Hence, the system developed, provides means for examining the behavior of individual RBCs in microchannels, and may serve as a microfabricated diagnostic device for deformability and volume measurements.

Controlled Landfill Project in Yolo County, California for Environmental Benefits of Waste Stabilization and Minimization of Greenhouse Gas Emissions

NASA Astrophysics Data System (ADS)

Yazdani, R.; Augenstein, D.; Kieffer, J.; Cohen, K.

2003-12-01

The Department of Public Works of Yolo County, California, USA has been testing an advanced approach to landfill bioreactors, controlled (or "enhanced") landfilling, at its Yolo County Central Landfill site near Davis, CA, since 1994. Overall objectives have been the management of waste landfilling for: (1) rapid completion of total gas generation; (2) maximum, high-efficiency gas capture; (3) waste volume reduction; and (4) maximum greenhouse gas and carbon sequestration benefits. Methane generation is controlled and enhanced through carefully managed moisture additions, and by taking advantage of landfill temperature elevation. The generated landfill methane, an important greenhouse gas, is recovered with high efficiency through extraction from a porous recovery layer beneath a surface geomembrane cover. Instrumentation included a total of 56 moisture and 15 temperature sensors in the two cells, gas flow monitoring by positive displacement gas meters, and accurate quantification of liquid inputs and outputs. Gas composition, waste volume reduction, base hydrostatic head, and a range of environmental compliance parameters has been monitored since 1995. Partitioning gas tracer tests using the injection of two gases at dilute concentrations in the landfill have also been initiated to compute the fraction of pore space occupied by water between the points of tracer injection and tracer measurement. There has been rapid waste volume reduction in the enhanced cell that corresponds to the solids' reduction to gas. Monitoring is planned for the next several years, until stabilization parameters are determined complete. Encouraging performance is indicated by: (1) sensor data; (2) gas generation results; (3) data from landfill cores; and (4) decomposition-related indicators including rapid volume reduction. When data are synthesized, project results have attractive implications for new approaches to landfill management. Over seven-years, methane recoveries have averaged over fivefold the "typical" values for comparable landfill waste. In terms of "greenhouse benefit," fractional VOC and methane energy recovery are estimated to exceed 90%, with corresponding methane and VOC emission reductions. Analyses done for the greenhouse gas mitigation program of the U.S. Department of Energy National Energy Technology Laboratory indicate favorable economics justified on landfill life extension, as well as environmental benefits. The "controlled landfill" project findings suggest potential for low-cost mitigation of waste greenhouse methane emissions, maximum landfill carbon sequestration, and maximization of beneficial energy capture from landfills. Details and results obtained since 1994 will be presented.

Adenovirus-mediated hAQP1 expression in irradiated mouse salivary glands causes recovery of saliva secretion by enhancing acinar cell volume decrease

PubMed Central

Teos, LY; Zheng, C-Y; Liu, X; Swaim, WD; Goldsmith, CM; Cotrim, AP; Baum, BJ; Ambudkar, IS

2017-01-01

Head and neck irradiation (IR) during cancer treatment causes by-stander effects on the salivary glands leading to irreversible loss of saliva secretion. The mechanism underlying loss of fluid secretion is not understood and no adequate therapy is currently available. Delivery of an adenoviral vector encoding human aquaporin-1 (hAQP1) into the salivary glands of human subjects and animal models with radiation-induced salivary hypofunction leads to significant recovery of saliva secretion and symptomatic relief in subjects. To elucidate the mechanism underlying loss of salivary secretion and the basis for AdhAQP1-dependent recovery of salivary gland function we assessed submandibular gland function in control mice and mice 2 and 8 months after treatment with a single 15-Gy dose of IR (delivered to the salivary gland region). Salivary secretion and neurotransmitter-stimulated changes in acinar cell volume, an in vitro read-out for fluid secretion, were monitored. Consistent with the sustained 60% loss of fluid secretion following IR, a carbachol (CCh)-induced decrease in acinar cell volume from the glands of mice post IR was transient and attenuated as compared with that in cells from non-IR age-matched mice. The hAQP1 expression in non-IR mice induced no significant effect on salivary fluid secretion or CCh-stimulated cell volume changes, except in acinar cells from 8-month group where the initial rate of cell shrinkage was increased. Importantly, the expression of hAQP1 in the glands of mice post IR induced recovery of salivary fluid secretion and a volume decrease in acinar cells to levels similar to those in cells from non-IR mice. The initial rates of CCh-stimulated cell volume reduction in acinar cells from hAQP1-expressing glands post IR were similar to those from control cells. Altogether, the data suggest that expression of hAQP1 increases the water permeability of acinar cells, which underlies the recovery of fluid secretion in the salivary glands functionally compromised post IR. PMID:26966862

Cholecystokinin-producing (I) cells of intestinal mucosa in dexamethasone-treated rats.

PubMed

Glišić, Radmila; Koko, Vesna; Cvijić, Gordana; Milošević, Maja Čakić; Obradović, Jasmina

2011-11-10

The aim of this study was to investigate the morphological, immunohistochemical and ultrastructural changes of cholecystokinin-producing (I) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2mg/kg dexamethasone, rats developed diabetes similar to human diabetes mellitus type 2. The mean diameter of the duodenum was significantly decreased due to significant reduction of volume fraction and profile area of lamina propria. There was a decrease in volume fraction and number of cholecystokinin (CCK)-producing cells per mm(2) of mucosa, as well as their numerical density, but without statistical significance. Also, dexamethasone induced appearance of hyperactive duodenal I-cells with small number of granules and dilated endoplasmic reticulum. In conclusion, the present study showed that morphological changes in duodenum cholecystokinin-producing (I) cells occurred in diabetic rats, in a manner which, suggests compensatory effort of CCK cells in diabetic condition. Copyright © 2011 Elsevier B.V. All rights reserved.

Erythrocyte depletion from bone marrow: performance evaluation after 50 clinical-scale depletions with Spectra Optia BMC.

PubMed

Kim-Wanner, Soo-Zin; Bug, Gesine; Steinmann, Juliane; Ajib, Salem; Sorg, Nadine; Poppe, Carolin; Bunos, Milica; Wingenfeld, Eva; Hümmer, Christiane; Luxembourg, Beate; Seifried, Erhard; Bonig, Halvard

2017-08-11

Red blood cell (RBC) depletion is a standard graft manipulation technique for ABO-incompatible bone marrow (BM) transplants. The BM processing module for Spectra Optia, "BMC", was previously introduced. We here report the largest series to date of routine quality data after performing 50 clinical-scale RBC-depletions. Fifty successive RBC-depletions from autologous (n = 5) and allogeneic (n = 45) BM transplants were performed with the Spectra Optia BMC apheresis suite. Product quality was assessed before and after processing for volume, RBC and leukocyte content; RBC-depletion and stem cell (CD34+ cells) recovery was calculated there from. Clinical engraftment data were collected from 26/45 allogeneic recipients. Median RBC removal was 98.2% (range 90.8-99.1%), median CD34+ cell recovery was 93.6%, minimum recovery being 72%, total product volume was reduced to 7.5% (range 4.7-23.0%). Products engrafted with expected probability and kinetics. Performance indicators were stable over time. Spectra Optia BMC is a robust and efficient technology for RBC-depletion and volume reduction of BM, providing near-complete RBC removal and excellent CD34+ cell recovery.

Effect of induction chemotherapy on estimated risk of radiation pneumonitis in bulky non–small cell lung cancer

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

Amin, Neha P., E-mail: npamin@gmail.com; Miften, Moyed; Thornton, Dale

2013-10-01

Patients with bulky non–small cell lung cancer (NSCLC) may be at a high risk for radiation pneumonitis (RP) if treated with up-front concurrent chemoradiation. There is limited information about the effect of induction chemotherapy on the volume of normal lung subsequently irradiated. This study aims to estimate the reduction in risk of RP in patients with NSCLC after receiving induction chemotherapy. Between 2004 and 2009, 25 patients with Stage IV NSCLC were treated with chemotherapy alone (no surgery or radiation therapy [RT]) and had computed tomography (CT) scans before and after 2 cycles of chemotherapy. Simulated RT plans were createdmore » for the prechemotherapy and postchemotherapy scans so as to deliver 60 Gy to the thoracic disease in patients who had either a >20% volumetric increase or decrease in gross tumor volume (GTV) from chemotherapy. The prechemotherapy and postchemotherapy scans were analyzed to compare the percentage of lung volume receiving≥20 Gy (V20), mean lung dose (MLD), and normal tissue complication probability (NTCP). Eight patients (32%) had a GTV reduction >20%, 2 (8%) had GTV increase >20%, and 15 (60%) had stable GTV. In the 8 responders, there was an absolute median GTV decrease of 88.1 cc (7.3 to 351.6 cc) or a 48% (20% to 62%) relative reduction in tumor burden. One had >20% tumor progression during chemotherapy, yet had an improvement in dosimetric parameters postchemotherapy. Among these 9 patients, the median decrease in V20, MLD, and NTCP was 2.6% (p<0.01), 2.1 Gy (p<0.01), and 5.6% (p<0.01), respectively. Less than one-third of patients with NSCLC obtain >20% volumetric tumor reduction from chemotherapy alone. Even with that amount of volumetric reduction, the 5% reduced risk of RP was only modest and did not convert previously ineligible patients to safely receive definitive thoracic RT.« less

Volume-weighted particle-tracking method for solute-transport modeling; Implementation in MODFLOW–GWT

USGS Publications Warehouse

Winston, Richard B.; Konikow, Leonard F.; Hornberger, George Z.

2018-02-16

In the traditional method of characteristics for groundwater solute-transport models, advective transport is represented by moving particles that track concentration. This approach can lead to global mass-balance problems because in models of aquifers having complex boundary conditions and heterogeneous properties, particles can originate in cells having different pore volumes and (or) be introduced (or removed) at cells representing fluid sources (or sinks) of varying strengths. Use of volume-weighted particles means that each particle tracks solute mass. In source or sink cells, the changes in particle weights will match the volume of water added or removed through external fluxes. This enables the new method to conserve mass in source or sink cells as well as globally. This approach also leads to potential efficiencies by allowing the number of particles per cell to vary spatially—using more particles where concentration gradients are high and fewer where gradients are low. The approach also eliminates the need for the model user to have to distinguish between “weak” and “strong” fluid source (or sink) cells. The new model determines whether solute mass added by fluid sources in a cell should be represented by (1) new particles having weights representing appropriate fractions of the volume of water added by the source, or (2) distributing the solute mass added over all particles already in the source cell. The first option is more appropriate for the condition of a strong source; the latter option is more appropriate for a weak source. At sinks, decisions whether or not to remove a particle are replaced by a reduction in particle weight in proportion to the volume of water removed. A number of test cases demonstrate that the new method works well and conserves mass. The method is incorporated into a new version of the U.S. Geological Survey’s MODFLOW–GWT solute-transport model.

Bioprocess integration for human mesenchymal stem cells: From up to downstream processing scale-up to cell proteome characterization.

PubMed

Cunha, Bárbara; Aguiar, Tiago; Carvalho, Sofia B; Silva, Marta M; Gomes, Ricardo A; Carrondo, Manuel J T; Gomes-Alves, Patrícia; Peixoto, Cristina; Serra, Margarida; Alves, Paula M

2017-04-20

To deliver the required cell numbers and doses to therapy, scaling-up production and purification processes (at least to the liter-scale) while maintaining cells' characteristics is compulsory. Therefore, the aim of this work was to prove scalability of an integrated streamlined bioprocess compatible with current good manufacturing practices (cGMP) comprised by cell expansion, harvesting and volume reduction unit operations using human mesenchymal stem cells (hMSC) isolated from bone marrow (BM-MSC) and adipose tissue (AT-MSC). BM-MSC and AT-MSC expansion and harvesting steps were scaled-up from spinner flasks to 2L scale stirred tank single-use bioreactor using synthetic microcarriers and xeno-free medium, ensuring high cellular volumetric productivities (50×10 6 cellL -1 day -1 ), expansion factors (14-16 fold) and cell recovery yields (80%). For the concentration step, flat sheet cassettes (FSC) and hollow fiber cartridges (HF) were compared showing a fairly linear scale-up, with a need to slightly decrease the permeate flux (30-50 LMH, respectively) to maximize cell recovery yield. Nonetheless, FSC allowed to recover 18% more cells after a volume reduction factor of 50. Overall, at the end of the entire bioprocess more than 65% of viable (>95%) hMSC could be recovered without compromising cell's critical quality attributes (CQA) of viability, identity and differentiation potential. Alongside the standard quality assays, a proteomics workflow based on mass spectrometry tools was established to characterize the impact of processing on hMSC's CQA; These analytical tools constitute a powerful tool to be used in process design and development. Copyright © 2017 Elsevier B.V. All rights reserved.

Causes and consequences of reduced blood volume in space flight - A multi-discipline modeling study

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1983-01-01

A group of mathematical models of various physiological systems have been developed and applied to studying problems associated with adaptation to weightlessness. One biomedical issue which could be addressed by at least three of these models from varying perspectives was the reduction in blood volume that universally occurs in astronauts. Accordingly, models of fluid-electrolyte, erythropoiesis, and cardiovascular regulation were employed to study the causes and consequences of blood volume loss during space flight. This analysis confirms the notion that alterations of blood volume are central to an understanding of adaptation to prolonged space flight. More importantly, the modeling studies resulted in specific hypotheses accounting for plasma volume and red cell mass losses and testable predictions concerning the behavior of the circulatory system.

Implementation of image-guided brachytherapy (IGBT) for patients with uterine cervix cancer: a tumor volume kinetics approach.

PubMed

Carvalho, Heloisa de Andrade; Mendez, Lucas Castro; Stuart, Silvia Radwanski; Guimarães, Roger Guilherme Rodrigues; Ramos, Clarissa Cerchi Angotti; de Paula, Lucas Assad; de Sales, Camila Pessoa; Chen, André Tsin Chih; Blasbalg, Roberto; Baroni, Ronaldo Hueb

2016-08-01

To evaluate tumor shrinking kinetics in order to implement image-guided brachytherapy (IGBT) for the treatment of patients with cervix cancer. This study has prospectively evaluated tumor shrinking kinetics of thirteen patients with uterine cervix cancer treated with combined chemoradiation. Four high dose rate brachytherapy fractions were delivered during the course of pelvic external beam radiation therapy (EBRT). Magnetic resonance imaging (MRI) exams were acquired at diagnosis (D), first (B1), and third (B3) brachytherapy fractions. Target volumes (GTV and HR-CTV) were calculated by both the ellipsoid formula (VE) and MRI contouring (VC), which were defined by a consensus between at least two radiation oncologists and a pelvic expert radiologist. Most enrolled patients had squamous cell carcinoma and FIGO stage IIB disease, and initiated brachytherapy after the third week of pelvic external beam radiation. Gross tumor volume volume reduction from diagnostic MRI to B1 represented 61.9% and 75.2% of the initial volume, when measured by VE and VC, respectively. Only a modest volume reduction (15-20%) was observed from B1 to B3. The most expressive tumor shrinking occurred in the first three weeks of oncological treatment and was in accordance with gynecological examination. These findings may help in IGBT implementation.

Factors influencing the difference between forecasted and actual drug sales volumes under the price-volume agreement in South Korea.

PubMed

Park, Sun-Young; Han, Euna; Kim, Jini; Lee, Eui-Kyung

2016-08-01

This study analyzed factors contributing to increases in the actual sales volumes relative to forecasted volumes of drugs under price-volume agreement (PVA) policy in South Korea. Sales volumes of newly listed drugs on the national formulary are monitored under PVA policy. When actual sales volume exceeds the pre-agreed forecasted volume by 30% or more, the drug is subject to price-reduction. Logistic regression assessed the factors related to whether drugs were the PVA price-reduction drugs. A generalized linear model with gamma distribution and log-link assessed the factors influencing the increase in actual volumes compared to forecasted volume in the PVA price-reduction drugs. Of 186 PVA monitored drugs, 34.9% were price-reduction drugs. Drugs marketed by pharmaceutical companies with previous-occupation in the therapeutic markets were more likely to be PVA price-reduction drugs than drugs marketed by firms with no previous-occupation. Drugs of multinational pharmaceutical companies were more likely to be PVA price-reduction drugs than those of domestic companies. Having more alternative existing drugs was significantly associated with higher odds of being PVA price-reduction drugs. Among the PVA price-reduction drugs, the increasing rate of actual volume compared to forecasted volume was significantly higher in drugs with clinical usefulness. By focusing the negotiation efforts on those target drugs, PVA policy can be administered more efficiently with the improved predictability of the drug sales volumes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema

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

Binkley, Michael S.; Shrager, Joseph B.; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California

2014-09-01

Purpose: Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema. Methods and Materials: We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABRmore » and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3). Results: 27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, −0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, −3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r{sup 2}=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r{sup 2}=0.47, P<.0001). Conclusions: We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across multiple clinical parameters. These data serve to inform our ongoing prospective trial of stereotactic ablative volume reduction (SAVR) for severe emphysema in poor candidates for LVRS.« less

Diatom Cell Size, Coloniality and Motility: Trade-Offs between Temperature, Salinity and Nutrient Supply with Climate Change

PubMed Central

Svensson, Filip; Norberg, Jon; Snoeijs, Pauline

2014-01-01

Reduction in body size has been proposed as a universal response of organisms, both to warming and to decreased salinity. However, it is still controversial if size reduction is caused by temperature or salinity on their own, or if other factors interfere as well. We used natural benthic diatom communities to explore how “body size” (cells and colonies) and motility change along temperature (2–26°C) and salinity (0.5–7.8) gradients in the brackish Baltic Sea. Fourth-corner analysis confirmed that small cell and colony sizes were associated with high temperature in summer. Average community cell volume decreased linearly with 2.2% per °C. However, cells were larger with artificial warming when nutrient concentrations were high in the cold season. Average community cell volume increased by 5.2% per °C of artificial warming from 0 to 8.5°C and simultaneously there was a selection for motility, which probably helped to optimize growth rates by trade-offs between nutrient supply and irradiation. Along the Baltic Sea salinity gradient cell size decreased with decreasing salinity, apparently mediated by nutrient stoichiometry. Altogether, our results suggest that climate change in this century may polarize seasonality by creating two new niches, with elevated temperature at high nutrient concentrations in the cold season (increasing cell size) and elevated temperature at low nutrient concentrations in the warm season (decreasing cell size). Higher temperature in summer and lower salinity by increased land-runoff are expected to decrease the average cell size of primary producers, which is likely to affect the transfer of energy to higher trophic levels. PMID:25279720

Diatom cell size, coloniality and motility: trade-offs between temperature, salinity and nutrient supply with climate change.

PubMed

Svensson, Filip; Norberg, Jon; Snoeijs, Pauline

2014-01-01

Reduction in body size has been proposed as a universal response of organisms, both to warming and to decreased salinity. However, it is still controversial if size reduction is caused by temperature or salinity on their own, or if other factors interfere as well. We used natural benthic diatom communities to explore how "body size" (cells and colonies) and motility change along temperature (2-26°C) and salinity (0.5-7.8) gradients in the brackish Baltic Sea. Fourth-corner analysis confirmed that small cell and colony sizes were associated with high temperature in summer. Average community cell volume decreased linearly with 2.2% per °C. However, cells were larger with artificial warming when nutrient concentrations were high in the cold season. Average community cell volume increased by 5.2% per °C of artificial warming from 0 to 8.5°C and simultaneously there was a selection for motility, which probably helped to optimize growth rates by trade-offs between nutrient supply and irradiation. Along the Baltic Sea salinity gradient cell size decreased with decreasing salinity, apparently mediated by nutrient stoichiometry. Altogether, our results suggest that climate change in this century may polarize seasonality by creating two new niches, with elevated temperature at high nutrient concentrations in the cold season (increasing cell size) and elevated temperature at low nutrient concentrations in the warm season (decreasing cell size). Higher temperature in summer and lower salinity by increased land-runoff are expected to decrease the average cell size of primary producers, which is likely to affect the transfer of energy to higher trophic levels.

Performance of a vanadium redox flow battery with tubular cell design

NASA Astrophysics Data System (ADS)

Ressel, Simon; Laube, Armin; Fischer, Simon; Chica, Antonio; Flower, Thomas; Struckmann, Thorsten

2017-07-01

We present a vanadium redox flow battery with a tubular cell design which shall lead to a reduction of cell manufacturing costs and the realization of cell stacks with reduced shunt current losses. Charge/discharge cycling and polarization curve measurements are performed to characterize the single test cell performance. A maximum current density of 70 mAcm-2 and power density of 142 Wl-1 (per cell volume) is achieved and Ohmic overpotential is identified as the dominant portion of the total cell overpotential. Cycling displays Coulomb efficiencies of ≈95% and energy efficiencies of ≈55%. During 113 h of operation a stable Ohmic cell resistance is observed.

Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery.

PubMed

Manzanero, Silvia; Erion, Joanna R; Santro, Tomislav; Steyn, Frederik J; Chen, Chen; Arumugam, Thiruma V; Stranahan, Alexis M

2014-05-01

Intermittent fasting (IF) is neuroprotective across a range of insults, but the question of whether extending the interval between meals alters neurogenesis after ischemia remains unexplored. We therefore measured cell proliferation, cell death, and neurogenesis after transient middle cerebral artery occlusion (MCAO) or sham surgery (SHAM) in mice fed ad libitum (AL) or maintained on IF for 3 months. IF was associated with twofold reductions in circulating levels of the adipocyte cytokine leptin in intact mice, but also prevented further reductions in leptin after MCAO. IF/MCAO mice also exhibit infarct volumes that were less than half those of AL/MCAO mice. We observed a 30% increase in basal cell proliferation in the hippocampus and subventricular zone (SVZ) in IF/SHAM, relative to AL/SHAM mice. However, cell proliferation after MCAO was limited in IF mice, which showed twofold increases in cell proliferation relative to IF/SHAM, whereas AL/MCAO mice exhibit fivefold increases relative to AL/SHAM. Attenuation of stroke-induced neurogenesis was correlated with reductions in cell death, with AL/MCAO mice exhibiting twice the number of dying cells relative to IF/MCAO mice. These observations indicate that IF protects against neurological damage in ischemic stroke, with circulating leptin as one possible mediator.

Intermittent fasting attenuates increases in neurogenesis after ischemia and reperfusion and improves recovery

PubMed Central

Manzanero, Silvia; Erion, Joanna R; Santro, Tomislav; Steyn, Frederik J; Chen, Chen; Arumugam, Thiruma V; Stranahan, Alexis M

2014-01-01

Intermittent fasting (IF) is neuroprotective across a range of insults, but the question of whether extending the interval between meals alters neurogenesis after ischemia remains unexplored. We therefore measured cell proliferation, cell death, and neurogenesis after transient middle cerebral artery occlusion (MCAO) or sham surgery (SHAM) in mice fed ad libitum (AL) or maintained on IF for 3 months. IF was associated with twofold reductions in circulating levels of the adipocyte cytokine leptin in intact mice, but also prevented further reductions in leptin after MCAO. IF/MCAO mice also exhibit infarct volumes that were less than half those of AL/MCAO mice. We observed a 30% increase in basal cell proliferation in the hippocampus and subventricular zone (SVZ) in IF/SHAM, relative to AL/SHAM mice. However, cell proliferation after MCAO was limited in IF mice, which showed twofold increases in cell proliferation relative to IF/SHAM, whereas AL/MCAO mice exhibit fivefold increases relative to AL/SHAM. Attenuation of stroke-induced neurogenesis was correlated with reductions in cell death, with AL/MCAO mice exhibiting twice the number of dying cells relative to IF/MCAO mice. These observations indicate that IF protects against neurological damage in ischemic stroke, with circulating leptin as one possible mediator. PMID:24549184

Hemopoiesis in the pig-tailed monkey Macaca nemestrina during chronic altitude exposure.

NASA Technical Reports Server (NTRS)

Buderer, M. C.; Pace, N.

1972-01-01

Study of monkeys for 180 days at 3800 m altitude to examine their hemopoietic response. Plasma volume was found to be reduced while red cell volume increased steadily for four to five months. Reduction in mean corpuscular hemoglobin content was observed from day 30 to day 120 at altitude. Total plasma protein concentration was unchanged at altitude, but marked reduction in the albumin/globulin ratio occurred. Total circulating plasma protein and albumin were reduced in amount, whereas nonalbumin protein was unchanged. These results imply loss of albumin coupled with a corresponding loss of water from the blood and maintenance of normal plasma osmotic pressure. The body/venous hematocrit ratio was found to be reduced at altitude, possibly as a consequence of the expanded capillary volume of the body. The hemopoietic responses of the pig-tailed monkey at altitude require at least several months for completion, and closely resemble those seen in man; thus, the monkey can serve well for long-term studies of high-altitude acclimatization.

Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation.

PubMed

Ibrahim, Michael; Kukadia, Punam; Siedlecka, Urszula; Cartledge, James E; Navaratnarajah, Manoraj; Tokar, Sergiy; Van Doorn, Carin; Tsang, Victor T; Gorelik, Julia; Yacoub, Magdi H; Terracciano, Cesare M

2012-12-01

Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca(2+)-induced Ca(2+) release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart-lung transplantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca(2+) release synchronicity was reduced at 8 weeks moderate unloading only. Ca(2+) sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca(2+) transient, increased Ca(2+) spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Venous saturation and blood flow behavior during laser-induced photodissociation of oxyhemoglobin

NASA Astrophysics Data System (ADS)

Mamilov, S. A.; Yesman, S. S.; Asimov, M. M.; Gisbrecht, A. I.

2013-03-01

The value of relative oxyhemoglobin concentration (saturation) in arterial (SаO2) and venous blood (SvO2) plays a significant role in the oxygen exchange in tissue and is used as criterion of delivery of oxygen adequate to the needs of tissue cells. Reduction of the volume of blood flows as well as reduction of oxygen concentration in arterial blood causes hypoxia - deficit of oxygen in tissue. One of the main mechanisms of elimination of hypoxia is based on compensation of the oxygen deficit by increasing the oxygen extraction from arterial blood, which leads to reduction of oxygen in the venous blood 1. In this report two optical techniques for measurement of venous blood saturation are presented. The first one is based on the pulseoximetry with artificial mechanical modulation of the tissue volume and the second one on the spectrophotometry of human respiratory rhythm. Good correlation between the results obtained with both techniques is observed.

Research in Biological and Medical Sciences Including Biochemistry, Communicable Disease and Immunology, Internal Medicine, Physiology, Psychiatry, Surgery, and Veterinary Medicine. Volume 1

DTIC Science & Technology

1979-09-01

and R.P. MacDermott. Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. I. K-lymphocytes and monocytes are effective...malaria research. During the reporting period, research activities have included analyses of: 1) a hemagglutination inhibition test for early detection of...radioiodination or sodium borohydride reduction. Evaluate the potential roles of activity for each protein isolated. Compare the composition of isolated

Reorganization of chromosome architecture in replicative cellular senescence.

PubMed

Criscione, Steven W; De Cecco, Marco; Siranosian, Benjamin; Zhang, Yue; Kreiling, Jill A; Sedivy, John M; Neretti, Nicola

2016-02-01

Replicative cellular senescence is a fundamental biological process characterized by an irreversible arrest of proliferation. Senescent cells accumulate a variety of epigenetic changes, but the three-dimensional (3D) organization of their chromatin is not known. We applied a combination of whole-genome chromosome conformation capture (Hi-C), fluorescence in situ hybridization, and in silico modeling methods to characterize the 3D architecture of interphase chromosomes in proliferating, quiescent, and senescent cells. Although the overall organization of the chromatin into active (A) and repressive (B) compartments and topologically associated domains (TADs) is conserved between the three conditions, a subset of TADs switches between compartments. On a global level, the Hi-C interaction matrices of senescent cells are characterized by a relative loss of long-range and gain of short-range interactions within chromosomes. Direct measurements of distances between genetic loci, chromosome volumes, and chromatin accessibility suggest that the Hi-C interaction changes are caused by a significant reduction of the volumes occupied by individual chromosome arms. In contrast, centromeres oppose this overall compaction trend and increase in volume. The structural model arising from our study provides a unique high-resolution view of the complex chromosomal architecture in senescent cells.

The kinetics of ulvoespinel reduction - Synthetic study and applications to lunar rocks.

NASA Technical Reports Server (NTRS)

Mccallister, R. H.; Taylor, L. A.

1973-01-01

The kinetics of Fe2TiO4 reduction to FeTiO3 + Fe were studied using CO-CO2 gas mixtures with fO2 measured by a solid ceramic (calcia-zirconia) oxygen electrolyte cell. Isothermal rate studies at 900 C suggest that the mechanism of Fe2TiO4 reduction is one of nucleation and growth, where the growth stage may be controlled by the diffusion of the reactant through the product layer or volume diffusion. The activation energy for the growth stage of the process was determined to be 46 plus or minus 4 kcal/mole.

Changes in renal function and fluid and electrolyte regulation in space flight

NASA Technical Reports Server (NTRS)

Leach, C. S.

1992-01-01

The cephalad fluid redistribution resulting from weightlessness has a number of physiologic consequences. Plasma volume is reduced soon after weightlessness is reached, and red blood cell mass reduction follows. Plasma atrial natriuretic peptide, which inhibits aldosterone secretion, was elevated during space flight while plasma aldosterone was below preflight levels. Serum sodium was also reduced and potassium was elevated. Antidiuretic hormone (ADH) was markedly elevated at almost all measurement times in the first eight days of flight, but plasma volume did not return to preflight levels.

Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus.

PubMed

Reyes-Haro, Daniel; Labrada-Moncada, Francisco Emmanuel; Varman, Durairaj Ragu; Krüger, Janina; Morales, Teresa; Miledi, Ricardo; Martínez-Torres, Ataúlfo

2016-01-01

Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (-23%) and dentate gyrus (-48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression.

Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus

PubMed Central

Labrada-Moncada, Francisco Emmanuel; Varman, Durairaj Ragu; Krüger, Janina; Morales, Teresa; Miledi, Ricardo; Martínez-Torres, Ataúlfo

2016-01-01

Anorexia nervosa is an eating disorder observed primarily in young women. The neurobiology of the disorder is unknown but recently magnetic resonance imaging showed a volume reduction of the hippocampus in anorexic patients. Dehydration-induced anorexia (DIA) is a murine model that mimics core features of this disorder, including severe weight loss due to voluntary reduction in food intake. The energy supply to the brain is mediated by astrocytes, but whether their density is compromised by anorexia is unknown. Thus, the aim of this study was to estimate GFAP+ cell density in the main regions of the hippocampus (CA1, CA2, CA3, and dentate gyrus) in the DIA model. Our results showed that GFAP+ cell density was significantly reduced (~20%) in all regions of the hippocampus, except in CA1. Interestingly, DIA significantly reduced the GFAP+ cells/nuclei ratio in CA2 (−23%) and dentate gyrus (−48%). The reduction of GFAP+ cell density was in agreement with a lower expression of GFAP protein. Additionally, anorexia increased the expression of the intermediate filaments vimentin and nestin. Accordingly, anorexia increased the number of reactive astrocytes in CA2 and dentate gyrus more than twofold. We conclude that anorexia reduces the hippocampal GFAP+ cell density and increases vimentin and nestin expression. PMID:27579183

Brain volume reduction after whole-brain radiotherapy: quantification and prognostic relevance.

PubMed

Hoffmann, Christian; Distel, Luitpold; Knippen, Stefan; Gryc, Thomas; Schmidt, Manuel Alexander; Fietkau, Rainer; Putz, Florian

2018-01-22

Recent studies have questioned the value of adding whole-brain radiotherapy (WBRT) to stereotactic radiosurgery (SRS) for brain metastasis treatment. Neurotoxicity, including radiation-induced brain volume reduction, could be one reason why not all patients benefit from the addition of WBRT. In this study, we quantified brain volume reduction after WBRT and assessed its prognostic significance. Brain volumes of 91 patients with cerebral metastases were measured during a 150-day period after commencing WBRT and were compared with their pretreatment volumes. The average daily relative change in brain volume of each patient, referred to as the "brain volume reduction rate," was calculated. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the brain volume reduction rate, as well as of 3 treatment-related and 9 pretreatment factors. A one-way analysis of variance was used to compare the brain volume reduction rate across recursive partitioning analysis (RPA) classes. On multivariate Cox regression analysis, the brain volume reduction rate was a significant predictor of overall survival after WBRT (P < 0.001), as well as the number of brain metastases (P = 0.002) and age (P = 0.008). Patients with a relatively favorable prognosis (RPA classes 1 and 2) experienced significantly less brain volume decrease after WBRT than patients with a poor prognosis (RPA class 3) (P = 0.001). There was no significant correlation between delivered radiation dose and brain volume reduction rate (P = 0.147). In this retrospective study, a smaller decrease in brain volume after WBRT was an independent predictor of longer overall survival. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

NASA Astrophysics Data System (ADS)

Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

2015-04-01

Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time.

Implementation of image-guided brachytherapy (IGBT) for patients with uterine cervix cancer: a tumor volume kinetics approach

PubMed Central

Mendez, Lucas Castro; Stuart, Silvia Radwanski; Guimarães, Roger Guilherme Rodrigues; Ramos, Clarissa Cerchi Angotti; de Paula, Lucas Assad; de Sales, Camila Pessoa; Chen, André Tsin Chih; Blasbalg, Roberto; Baroni, Ronaldo Hueb

2016-01-01

Purpose To evaluate tumor shrinking kinetics in order to implement image-guided brachytherapy (IGBT) for the treatment of patients with cervix cancer. Material and methods This study has prospectively evaluated tumor shrinking kinetics of thirteen patients with uterine cervix cancer treated with combined chemoradiation. Four high dose rate brachytherapy fractions were delivered during the course of pelvic external beam radiation therapy (EBRT). Magnetic resonance imaging (MRI) exams were acquired at diagnosis (D), first (B1), and third (B3) brachytherapy fractions. Target volumes (GTV and HR-CTV) were calculated by both the ellipsoid formula (VE) and MRI contouring (VC), which were defined by a consensus between at least two radiation oncologists and a pelvic expert radiologist. Results Most enrolled patients had squamous cell carcinoma and FIGO stage IIB disease, and initiated brachytherapy after the third week of pelvic external beam radiation. Gross tumor volume volume reduction from diagnostic MRI to B1 represented 61.9% and 75.2% of the initial volume, when measured by VE and VC, respectively. Only a modest volume reduction (15-20%) was observed from B1 to B3. Conclusions The most expressive tumor shrinking occurred in the first three weeks of oncological treatment and was in accordance with gynecological examination. These findings may help in IGBT implementation. PMID:27648083

Treatment with adipose derived mesenchymal stem cells and their conditioned media reverse carrageenan induced paw oedema in db/db mice.

PubMed

Shree, Nitya; Venkategowda, Sunil; Venkatranganna, M V; Bhonde, Ramesh R

2017-06-01

Mesenchymal stem cells are known for anti inflammatory and immunomodulatory activities. The aim of our study was to evaluate the effect of human adipose derived mesenchymal stem cells (hADMSCs) and its conditioned media (CM) on carrageenan induced acute inflammation in db/db mice. We injected 5×10 5 ADMSCs or the CM in the inflamed paw. We assessed the paw volume, serum IL6 levels and histopathology of the paw to reveal the anti inflammatory effect. We observed a single injection of hADMSCs or CM could reverse the inflammation within 24h as evidenced by reduction in paw volume, IL6 levels and histological examination. Our result equivocally demonstrates the role of CM in normalising the inflammation better than hADMSCs. This study will pave way for an alternative to anti inflammatory drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Twelve-month prostate volume reduction after MRI-guided transurethral ultrasound ablation of the prostate.

PubMed

Bonekamp, David; Wolf, M B; Roethke, M C; Pahernik, S; Hadaschik, B A; Hatiboglu, G; Kuru, T H; Popeneciu, I V; Chin, J L; Billia, M; Relle, J; Hafron, J; Nandalur, K R; Staruch, R M; Burtnyk, M; Hohenfellner, M; Schlemmer, H-P

2018-06-25

To quantitatively assess 12-month prostate volume (PV) reduction based on T2-weighted MRI and immediate post-treatment contrast-enhanced MRI non-perfused volume (NPV), and to compare measurements with predictions of acute and delayed ablation volumes based on MR-thermometry (MR-t), in a central radiology review of the Phase I clinical trial of MRI-guided transurethral ultrasound ablation (TULSA) in patients with localized prostate cancer. Treatment day MRI and 12-month follow-up MRI and biopsy were available for central radiology review in 29 of 30 patients from the published institutional review board-approved, prospective, multi-centre, single-arm Phase I clinical trial of TULSA. Viable PV at 12 months was measured as the remaining PV on T2-weighted MRI, less 12-month NPV, scaled by the fraction of fibrosis in 12-month biopsy cores. Reduction of viable PV was compared to predictions based on the fraction of the prostate covered by the MR-t derived acute thermal ablation volume (ATAV, 55°C isotherm), delayed thermal ablation volume (DTAV, 240 cumulative equivalent minutes at 43°C thermal dose isocontour) and treatment-day NPV. We also report linear and volumetric comparisons between metrics. After TULSA, the median 12-month reduction in viable PV was 88%. DTAV predicted a reduction of 90%. Treatment day NPV predicted only 53% volume reduction, and underestimated ATAV and DTAV by 36% and 51%. Quantitative volumetry of the TULSA phase I MR and biopsy data identifies DTAV (240 CEM43 thermal dose boundary) as a useful predictor of viable prostate tissue reduction at 12 months. Immediate post-treatment NPV underestimates tissue ablation. • MRI-guided transurethral ultrasound ablation (TULSA) achieved an 88% reduction of viable prostate tissue volume at 12 months, in excellent agreement with expectation from thermal dose calculations. • Non-perfused volume on immediate post-treatment contrast-enhanced MRI represents only 64% of the acute thermal ablation volume (ATAV), and reports only 60% (53% instead of 88% achieved) of the reduction in viable prostate tissue volume at 12 months. • MR-thermometry-based predictions of 12-month prostate volume reduction based on 240 cumulative equivalent minute thermal dose volume are in excellent agreement with reduction in viable prostate tissue volume measured on pre- and 12-month post-treatment T2w-MRI.

Retrospective clinical evaluation of gauze-based negative pressure wound therapy.

PubMed

Campbell, Penny E; Smith, Gary S; Smith, Jennifer M

2008-06-01

Negative pressure wound therapy (NPWT) is an established modality in the treatment of challenging wounds. However, most existing clinical evidence is derived from the use of open-cell polyurethane foam at -125 mmHg. Alternative negative pressure systems are becoming available, which use gauze at a pressure of -80 mmHg. This study describes clinical results from a retrospective non comparative analysis of 30 patients treated with Chariker-Jeter gauze-based negative pressure systems (V1STA, Versatile-1 and EZ-Care; Smith & Nephew, Inc.) in a long-term care setting. The mean age of the patients was 72 years. The wounds consisted of chronic (n = 11), surgical dehiscence (n = 11) and surgical incision (n = 8). Wound volume and area were recorded at commencement and at the cessation of therapy. Discontinuation of therapy was instigated upon closure through secondary intention or when size and exudate were sufficiently reduced that the wounds could be managed by conventional wound dressing (median 41 days). An overall median reduction in wound volume of 88.0% (P < 0.001) and a 68.0% reduction in area (P < 0.001) compared with baseline were observed over the course of NPWT. The overall rate of volume reduction (15.1% per week) compares favourably with published data from foam-based systems.

Transfer of a three step mAb chromatography process from batch to continuous: Optimizing productivity to minimize consumable requirements.

PubMed

Gjoka, Xhorxhi; Gantier, Rene; Schofield, Mark

2017-01-20

The goal of this study was to adapt a batch mAb purification chromatography platform for continuous operation. The experiments and rationale used to convert from batch to continuous operation are described. Experimental data was used to design chromatography methods for continuous operation that would exceed the threshold for critical quality attributes and minimize the consumables required as compared to batch mode of operation. Four unit operations comprising of Protein A capture, viral inactivation, flow-through anion exchange (AEX), and mixed-mode cation exchange chromatography (MMCEX) were integrated across two Cadence BioSMB PD multi-column chromatography systems in order to process a 25L volume of harvested cell culture fluid (HCCF) in less than 12h. Transfer from batch to continuous resulted in an increase in productivity of the Protein A step from 13 to 50g/L/h and of the MMCEX step from 10 to 60g/L/h with no impact on the purification process performance in term of contaminant removal (4.5 log reduction of host cell proteins, 50% reduction in soluble product aggregates) and overall chromatography process yield of recovery (75%). The increase in productivity, combined with continuous operation, reduced the resin volume required for Protein A and MMCEX chromatography by more than 95% compared to batch. The volume of AEX membrane required for flow through operation was reduced by 74%. Moreover, the continuous process required 44% less buffer than an equivalent batch process. This significant reduction in consumables enables cost-effective, disposable, single-use manufacturing. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

A comparative study of U937 cell size changes during apoptosis initiation by flow cytometry, light scattering, water assay and electronic sizing.

PubMed

Yurinskaya, Valentina; Aksenov, Nikolay; Moshkov, Alexey; Model, Michael; Goryachaya, Tatyana; Vereninov, Alexey

2017-10-01

A decrease in flow cytometric forward light scatter (FSC) is commonly interpreted as a sign of apoptotic cell volume decrease (AVD). However, the intensity of light scattering depends not only on the cell size but also on its other characteristics, such as hydration, which may affect the scattering in the opposite way. That makes estimation of AVD by FSC problematic. Here, we aimed to clarify the relationship between light scattering, cell hydration (assayed by buoyant density) and cell size by the Coulter technique. We used human lymphoid cells U937 exposed to staurosporine, etoposide or hypertonic stress as an apoptotic model. An initial increase in FSC was found to occur in apoptotic cells treated with staurosporine and hypertonic solutions; it is accompanied by cell dehydration and is absent in apoptosis caused by etoposide that is consistent with the lack of dehydration in this case. Thus, the effect of dehydration on the scattering signal outweighs the effect of reduction in cell size. The subsequent FSC decrease, which occurred in parallel to accumulation of annexin-positive cells, was similar in apoptosis caused by all three types of inducers. We conclude that an increase, but not a decrease in light scattering, indicates the initial cell volume decrease associated with apoptotic cell dehydration.

Pharmacodynamically optimized erythropoietin treatment combined with phlebotomy reduction predicted to eliminate blood transfusions in selected preterm infants.

PubMed

Rosebraugh, Matthew R; Widness, John A; Nalbant, Demet; Cress, Gretchen; Veng-Pedersen, Peter

2014-02-01

Preterm very-low-birth-weight (VLBW) infants weighing <1.5 kg at birth develop anemia, often requiring multiple red blood cell transfusions (RBCTx). Because laboratory blood loss is a primary cause of anemia leading to RBCTx in VLBW infants, our purpose was to simulate the extent to which RBCTx can be reduced or eliminated by reducing laboratory blood loss in combination with pharmacodynamically optimized erythropoietin (Epo) treatment. Twenty-six VLBW ventilated infants receiving RBCTx were studied during the first month of life. RBCTx simulations were based on previously published RBCTx criteria and data-driven Epo pharmacodynamic optimization of literature-derived RBC life span and blood volume data corrected for phlebotomy loss. Simulated pharmacodynamic optimization of Epo administration and reduction in phlebotomy by ≥ 55% predicted a complete elimination of RBCTx in 1.0-1.5 kg infants. In infants <1.0 kg with 100% reduction in simulated phlebotomy and optimized Epo administration, a 45% reduction in RBCTx was predicted. The mean blood volume drawn from all infants was 63 ml/kg: 33% required for analysis and 67% discarded. When reduced laboratory blood loss and optimized Epo treatment are combined, marked reductions in RBCTx in ventilated VLBW infants were predicted, particularly among those with birth weights >1.0 kg.

Method of making formulated plastic separators for soluble electrode cells

NASA Technical Reports Server (NTRS)

Sheibley, D. W. (Inventor)

1982-01-01

A method making a membrane comprised of a hydrochloric acid-insoluble sheet of a mixture of a rubber and a powdered ion transport material is disclosed. The sheet can be present as a coating upon a flexible and porous substrate. These membranes can be used in oxidation-reduction electrical accumulator cells wherein the reduction of one member of a couple is accompained by the oxidation of the other member of the couple on the other side of the cell and this must be accompained by a change in chloride ion concentration in both sides. The method comprises preparing a mixture of fine rubber particles, a solvent for the rubber and a powdered ion transport material. The mixture is formed into a sheet and dried to produce a microporous sheet. The ion transport material includes particles ranging from about 0.01 to 10 microns in size and comprises from 20 to 50 volume percent of the microporous sheet.

Experiment K-6-07. Metabolic and morphologic properties of muscle fibers after spaceflight

NASA Technical Reports Server (NTRS)

Edgerton, R.; Miu, B.; Martin, Thomas P.; Roy, R.; Marini, J.; Leger, J. J.; Oganov, V.; Ilyina-Kakueva, E.

1990-01-01

The present study demonstrates that the general capability of skeletal muscle to maintain its proteins decreases rapidly in response to space flight. The present findings suggest further that the magnitude of enzymatic and cell volumes changes in response to space flight depend on several factors including the muscle and its fiber type composition. It appears that in order to associate physiological relevance to the observed enzymatic changes, cell volume should be considered also. Although it remains unclear as to the stimulus, or lack of stimulus, that triggers the rapid changes in muscle proteins in response to space flight, ground-based models of muscle atrophy suggest that the reduction in mechanical loading of muscle may be more important than the total amount of activation over a 24-hr period.

Reduction of neuromelanin-positive nigral volume in patients with MSA, PSP and CBD.

PubMed

Kashihara, Kenichi; Shinya, Takayoshi; Higaki, Fumiyo

2011-01-01

Diseases presenting extrapyramidal symptoms are accompanied by nigral cell loss. In the previous study, we demonstrated the reduction of the neuromelanin-positive volume of substantia nigra (SN) pars compacta (SNc) in patients with Parkinson's disease (PD) using 3-Tesla MRI. In the present study we investigated the neuromelanin-positive SNc volume in patients with the other parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) and compared the results with those with PD, spinocerebellar ataxia (SCA) and controls. Axial T1-weighted (T1W) images were obtained with a 3-Tesla MRI scanner. The border of the neuromelanin-positive region of the SNc was traced manually on these images with a pentablet pointing device and the SNc volume was calculated. The SNc volumes of 28 patients with MSA, 11 patients with PSP and 10 patients with CBD were compared with those of 80 patients with PD, 9 patients with SCA and 54 patients who had suffered mild acute ischemic stroke as controls. The mean volumes for the left and right SN were used for statistical analyses. The volumes of the neuromelanin-positive SNc region in patients with MSA, PSP and CBD, but not SCA were reduced to the same extent as PD patients compared with controls. Reduced volume of the neuromelanin-positive SNc region of patients with MSA, PSP and CBD was detected by neuromelanin MR imaging. Volumetric evaluation of neuromelanin MR imaging may provide a biomarker of nigral degeneration in patients with MSA, PSP and CBD as in patients with PD.

High-Frequency Jet Ventilation for Complete Target Immobilization and Reduction of Planning Target Volume in Stereotactic High Single-Dose Irradiation of Stage I Non-Small Cell Lung Cancer and Lung Metastases

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

Fritz, Peter, E-mail: p.h.fritz@t-online.d; Kraus, Hans-Joerg; Muehlnickel, Werner

2010-09-01

Purpose: To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase. Methods and Materials: A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTVmore » enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV. Results: The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of {>=}20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5. Conclusions: In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection.« less

High performance spiral wound microbial fuel cell with hydraulic characterization.

PubMed

Haeger, Alexander; Forrestal, Casey; Xu, Pei; Ren, Zhiyong Jason

2014-12-01

The understanding and development of functioning systems are crucial steps for microbial fuel cell (MFC) technology advancement. In this study, a compact spiral wound MFC (swMFC) was developed and hydraulic residence time distribution (RTD) tests were conducted to investigate the flow characteristics in the systems. Results show that two-chamber swMFCs have high surface area to volume ratios of 350-700m(2)/m(3), and by using oxygen cathode without metal-catalysts, the maximum power densities were 42W/m(3) based on total volume and 170W/m(3) based on effective volume. The hydraulic step-input tracer study identified 20-67% of anodic flow dead space, which presents new opportunities for system improvement. Electrochemical tools revealed very low ohmic resistance but high charge transfer and diffusion resistance due to catalyst-free oxygen reduction. The spiral wound configuration combined with RTD tool offers a holistic approach for MFC development and optimization. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of salt reduction on wheat-dough properties and quality characteristics of puff pastry with full and reduced fat content.

PubMed

Silow, Christoph; Zannini, Emanuele; Axel, Claudia; Lynch, Kieran M; Arendt, Elke K

2016-11-01

Puff pastry is a major contributor of fat and sodium intake in many countries. The objective of this research was to determine the impact of salt (0-8.4g/100g flour) on the structure and quality characteristics of puff pastry with full and reduced (-40%) fat content as well as the rheological properties of the resulting dough. Therefore, empirical rheological tests were carried out including dough extensibility, dough stickiness and GlutoPeak test. The quality of the puff pastry was characterized with the VolScan, Texture Analyzer and C-Cell. NaCl reduction significantly changed rheological properties of the basic dough as well as a number of major quality characteristics of the puff pastry. Significant differences due to NaCl addition were found in particular for dough resistance, dough stickiness, Peak Maximum Time and Maximum Torque (p<0.05). Peak firmness and total firmness decreased significantly (p<0.05) with increasing salt levels for puff pastry containing full fat. Likewise, maximal lift, specific volume, number of cells and slice brightness increased with increasing NaCl at both fat levels. Although a sensorial comparison of puff pastries revealed that salt reduction (30%) was perceptible, no significant differences were found for all other investigated attributes. Nevertheless, a reduction of 30% salt and 40% fat in puff pastry is achievable as neither the perception and visual impression nor attributes such as volume, firmness and flavour of the final products were significantly affected. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential regulation of Smad3 and of the type II transforming growth factor-β receptor in mitosis: implications for signaling.

PubMed

Hirschhorn, Tal; Barizilay, Lior; Smorodinsky, Nechama I; Ehrlich, Marcelo

2012-01-01

The response to transforming growth factor-β (TGF-β) depends on cellular context. This context is changed in mitosis through selective inhibition of vesicle trafficking, reduction in cell volume and the activation of mitotic kinases. We hypothesized that these alterations in cell context may induce a differential regulation of Smads and TGF-β receptors. We tested this hypothesis in mesenchymal-like ovarian cancer cells, arrested (or not) in mitosis with 2-methoxyestradiol (2ME2). In mitosis, without TGF-β stimulation, Smad3 was phosphorylated at the C-terminus and linker regions and localized to the mitotic spindle. Phosphorylated Smad3 interacted with the negative regulators of Smad signaling, Smurf2 and Ski, and failed to induce a transcriptional response. Moreover, in cells arrested in mitosis, Smad3 levels were progressively reduced. These phosphorylations and reduction in the levels of Smad3 depended on ERK activation and Mps1 kinase activity, and were abrogated by increasing the volume of cells arrested in mitosis with hypotonic medium. Furthermore, an Mps1-dependent phosphorylation of GFP-Smad3 was also observed upon its over-expression in interphase cells, suggesting a mechanism of negative regulation which counters increases in Smad3 concentration. Arrest in mitosis also induced a block in the clathrin-mediated endocytosis of the type II TGF-β receptor (TβRII). Moreover, following the stimulation of mitotic cells with TGF-β, the proteasome-mediated attenuation of TGF-β receptor activity, the degradation and clearance of TβRII from the plasma membrane, and the clearance of the TGF-β ligand from the medium were compromised, and the C-terminus phosphorylation of Smad3 was prolonged. We propose that the reduction in Smad3 levels, its linker phosphorylation, and its association with negative regulators (observed in mitosis prior to ligand stimulation) represent a signal attenuating mechanism. This mechanism is balanced by the retention of active TGF-β receptors at the plasma membrane. Together, both mechanisms allow for a regulated cellular response to TGF-β stimuli in mitosis.

Differential Regulation of Smad3 and of the Type II Transforming Growth Factor-β Receptor in Mitosis: Implications for Signaling

PubMed Central

Hirschhorn, Tal; Barizilay, Lior; Smorodinsky, Nechama I.; Ehrlich, Marcelo

2012-01-01

The response to transforming growth factor-β (TGF-β) depends on cellular context. This context is changed in mitosis through selective inhibition of vesicle trafficking, reduction in cell volume and the activation of mitotic kinases. We hypothesized that these alterations in cell context may induce a differential regulation of Smads and TGF-β receptors. We tested this hypothesis in mesenchymal-like ovarian cancer cells, arrested (or not) in mitosis with 2-methoxyestradiol (2ME2). In mitosis, without TGF-β stimulation, Smad3 was phosphorylated at the C-terminus and linker regions and localized to the mitotic spindle. Phosphorylated Smad3 interacted with the negative regulators of Smad signaling, Smurf2 and Ski, and failed to induce a transcriptional response. Moreover, in cells arrested in mitosis, Smad3 levels were progressively reduced. These phosphorylations and reduction in the levels of Smad3 depended on ERK activation and Mps1 kinase activity, and were abrogated by increasing the volume of cells arrested in mitosis with hypotonic medium. Furthermore, an Mps1-dependent phosphorylation of GFP-Smad3 was also observed upon its over-expression in interphase cells, suggesting a mechanism of negative regulation which counters increases in Smad3 concentration. Arrest in mitosis also induced a block in the clathrin-mediated endocytosis of the type II TGF-β receptor (TβRII). Moreover, following the stimulation of mitotic cells with TGF-β, the proteasome-mediated attenuation of TGF-β receptor activity, the degradation and clearance of TβRII from the plasma membrane, and the clearance of the TGF-β ligand from the medium were compromised, and the C-terminus phosphorylation of Smad3 was prolonged. We propose that the reduction in Smad3 levels, its linker phosphorylation, and its association with negative regulators (observed in mitosis prior to ligand stimulation) represent a signal attenuating mechanism. This mechanism is balanced by the retention of active TGF-β receptors at the plasma membrane. Together, both mechanisms allow for a regulated cellular response to TGF-β stimuli in mitosis. PMID:22927969

Intracellular Ca2+ release and Ca2+ influx during regulatory volume decrease in IMCD cells.

PubMed

Tinel, H; Wehner, F; Sauer, H

1994-07-01

Volume changes and cytosolic Ca2+ concentration ([Ca2+]i) of inner medullary collecting duct (IMCD) cells under hypotonic stress were monitored by means of confocal laser scanning microscopy and fura 2 fluorescence, respectively. Reduction of extracellular osmolality from 600 to 300 mosmol/kgH2O by omission of sucrose led to an increase in cell volume within 1 min to 135 +/- 3% (n = 9), followed by a partial regulatory volume decrease (RVD) to 109 +/- 2% (n = 9) within the ensuring 5 min. In parallel, [Ca2+]i rose from 145 +/- 9 to 433 +/- 16 nmol/l (n = 9) and thereafter reached a lower steady state of 259 +/- 9 nmol/l. Under low-Ca2+ conditions (10 nmol/l) RVD was not impeded and reduction of osmolality evoked only a transient increase of [Ca2+]i by 182 +/- 22 nmol/l (n = 6). Preincubation with 100 mumol/l 8-(N,N-diethylamino)octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8) or 20 mmol/l caffeine, both effective inhibitors of Ca2+ release from intracellular stores, in low Ca2+ as well as in high Ca2+, inhibited the Ca2+ response and abolished RVD. The temporal relationship between Ca2+ release from intracellular stores and Ca2+ entry was analyzed by determining fura 2 quenching, using Mn2+ as a substitute for external Ca2+. Intracellular Ca2+ release preceded Mn2+ influx by 17 +/- 3 s (n = 10). Mn2+ influx persisted during the whole period of exposure to hypotonicity, indicating that there is no time-dependent Ca2+ channel inactivation. Preincubation with TMB-8 or caffeine reduced Mn2+ influx to the control level, indicating that activation of Ca2+ channels in the plasma membrane occurs via intracellular Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line.

PubMed

Bakshi, Hamid; Sam, Smitha; Rozati, Roya; Sultan, Phalisteen; Islam, Tajamul; Rathore, Babita; Lone, Zahoor; Sharma, Manik; Triphati, Jagrati; Saxena, Ramesh Chand

2010-01-01

Apoptosis, a widely important mechanism that contributes to cell growth reduction, is reported to be induced by Crocus sativus in different cancer types. The present study was designed to elucidate apoptosis induction by crocin, a main component of Crocus sativus in a human pancreatic cancer cell line (BxPC-3). Cell viability was measured by MTT assay, Hoechest33258 staining was used to detect the chromatin condensation characteristic of apoptosis, and DNA fragmentation was assessed by gel electrophoresis and cell cycle analysis by flow cytometry. Crocin induced apoptosis and G1-phase cell cycle arrest of BxPC-3 cells, while decreasing cell viability in a dose dependent and time dependent manner. Cells treated with 10μg/L crocin exhibited apoptotic morphology (brightly blue-fluorescent condensed nuclei on Hoechst 33258 staining) and reduction of volume. DNA analysis revealed typical ladders as early as 12 hours after treatment indicative of apoptosis. Our preclinical study demonstrated a pancreatic cancer cell line to be highly sensitive to crocin-mediated growth inhibition and apoptotic cell death. Although the molecular mechanisms of crocin action are not yet clearly understood, it appears to have potential as a therapeutic agent.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Large-Volume Resonant Microwave Discharge for Plasma Cleaning of a CEBAF 5-Cell SRF Cavity

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

J. Mammosser, S. Ahmed, K. Macha, J. Upadhyay, M. Nikoli, S. Popovi, L. Vuakovi

2012-07-01

We report the preliminary results on plasma generation in a 5-cell CEBAF superconducting radio-frequency (SRF) cavity for the application of cavity interior surface cleaning. CEBAF currently has {approx}300 of these five cell cavities installed in the Jefferson Lab accelerator which are mostly limited by cavity surface contamination. The development of an in-situ cavity surface cleaning method utilizing a resonant microwave discharge could lead to significant CEBAF accelerator performance improvement. This microwave discharge is currently being used for the development of a set of plasma cleaning procedures targeted to the removal of various organic, metal and metal oxide impurities. These contaminantsmore » are responsible for the increase of surface resistance and the reduction of RF performance in installed cavities. The CEBAF five cell cavity volume is {approx} 0.5 m2, which places the discharge in the category of large-volume plasmas. CEBAF cavity has a cylindrical symmetry, but its elliptical shape and transversal power coupling makes it an unusual plasma application, which requires special consideration of microwave breakdown. Our preliminary study includes microwave breakdown and optical spectroscopy, which was used to define the operating pressure range and the rate of removal of organic impurities.« less

Drinking water biofilm cohesiveness changes under chlorination or hydrodynamic stress.

PubMed

Mathieu, L; Bertrand, I; Abe, Y; Angel, E; Block, J C; Skali-Lami, S; Francius, G

2014-05-15

Attempts at removal of drinking water biofilms rely on various preventive and curative strategies such as nutrient reduction in drinking water, disinfection or water flushing, which have demonstrated limited efficiency. The main reason for these failures is the cohesiveness of the biofilm driven by the physico-chemical properties of its exopolymeric matrix (EPS). Effective cleaning procedures should break up the matrix and/or change the elastic properties of bacterial biofilms. The aim of this study was to evaluate the change in the cohesive strength of two-month-old drinking water biofilms under increasing hydrodynamic shear stress τw (from ∼0.2 to ∼10 Pa) and shock chlorination (applied concentration at T0: 10 mg Cl2/L; 60 min contact time). Biofilm erosion (cell loss per unit surface area) and cohesiveness (changes in the detachment shear stress and cluster volumes measured by atomic force microscopy (AFM)) were studied. When rapidly increasing the hydrodynamic constraint, biofilm removal was found to be dependent on a dual process of erosion and coalescence of the biofilm clusters. Indeed, 56% of the biofilm cells were removed with, concomitantly, a decrease in the number of the 50-300 μm(3) clusters and an increase in the number of the smaller (i.e., <50 μm(3)) and larger (i.e., >600 μm(3)) ones. Moreover, AFM evidenced the strengthening of the biofilm structure along with the doubling of the number of contact points, NC, per cluster volume unit following the hydrodynamic disturbance. This suggests that the compactness of the biofilm exopolymers increases with hydrodynamic stress. Shock chlorination removed cells (-75%) from the biofilm while reducing the volume of biofilm clusters. Oxidation stress resulted in a decrease in the cohesive strength profile of the remaining drinking water biofilms linked to a reduction in the number of contact points within the biofilm network structure in particular for the largest biofilm cluster volumes (>200 μm(3)). Changes in the cohesive strength of drinking water biofilms subsequent to cleaning/disinfection operations call into question the effectiveness of cleaning-in-place procedures. The combined alternating use of oxidation and shear stress sequences needs to be investigated as it could be an important adjunct to improving biofilm removal/reduction procedures. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigation of the Performance of Commercial Batteries; Part II.

ERIC Educational Resources Information Center

Davies, Arthur; And Others

1996-01-01

Describes a project that involves determining, by coulometry, the energy output of different types and makes of 1.5-volt AA cells as a function of EMF and time. Involves measuring the volume of hydrogen gas collected at the cathode from the reduction of hydrogen ions in aqueous sulfuric acid by a current produced by the discharge of an AA battery.…

Quantitative ultrasound backscatter for pulsed cavitational ultrasound therapy- histotripsy.

PubMed

Wang, Tzu-yin; Xu, Zhen; Winterroth, Frank; Hall, Timothy L; Fowlkes, J Brian; Rothman, Edward D; Roberts, William W; Cain, Charles A

2009-05-01

Histotripsy is a well-controlled ultrasonic tissue ablation technology that mechanically and progressively fractionates tissue structures using cavitation. The fractionated tissue volume can be monitored with ultrasound imaging because a significant ultrasound backscatter reduction occurs.This paper correlates the ultrasound backscatter reduction with the degree of tissue fractionation characterized by the percentage of remaining normal-appearing cell nuclei on histology.Different degrees of tissue fractionation were generated in vitro in freshly excised porcine kidneys by varying the number of therapeutic ultrasound pulses from 100 to 2000 pulses per treatment location. All ultrasound pulses were 15 cycles at 1 MHz delivered at 100 Hz pulse repetition frequency and 19 MPa peak negative pressure. The results showed that the normalized backscatter intensity decreased exponentially with increasing number of pulses. Correspondingly, the percentage of normal appearing nuclei in the treated area decreased exponentially as well. A linear correlation existed between the normalized backscatter intensity and the percentage of normal appearing cell nuclei in the treated region. This suggests that the normalized backscatter intensity may be a potential quantitative real-time feedback parameter for histotripsy-induced tissue fractionation. This quantitative feedback may allow the prediction of local clinical outcomes, i.e., when a tissue volume has been sufficiently treated.

Mucoactive effects of naringin in lipopolysaccharide-induced acute lung injury mice and beagle dogs.

PubMed

Chen, Yan; Wu, Hao; Nie, Yi-chu; Li, Pei-bo; Shen, Jian-gang; Su, Wei-wei

2014-07-01

Our previous study has demonstrated that naringin attenuates EGF-induced MUC5AC hypersecretion in A549 cells by suppressing the cooperative activities of MAPKs/AP-1 and IKKs/IκB/NF-κB signaling pathways. However, the volume of airway mucus is determined by two factors including the number of mucous cells and capacity of mucus secretion. The aim of the present study is to explore the mucoactive effects of naringin in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and beagle dogs. The results demonstrated that naringin of 12.4 mg/kg treatment significantly decreased LPS-induced enhancement of sputum volume and pulmonary inflammation, remarkably increased the subglottic sputum volume and solids content in sputum of lower trachea, while partially, but not fully, significantly increased the elasticity and viscosity of sputum in lower trachea of beagle dogs. Moreover, the MUC5AC content in BALF and goblet-cells in large airways of LPS-induced ALI mice were significantly attenuated by dexamethasone (5 mg/kg), ambroxol (25 mg/kg), and naringin (15, 60 mg/kg). However, the goblet-cells hyperplasia in small airways induced by LPS was only significantly inhibited by dexamethasone and naringin (60 mg/kg). In conclusion, naringin exhibits mucoactive effects through multiple targets which including reduction of goblet cells hyperplasia and mucus hypersecretion, as well as promotion of sputum excretion. Copyright © 2014 Elsevier B.V. All rights reserved.

National Emphysema Treatment Trial redux: accentuating the positive.

PubMed

Sanchez, Pablo Gerardo; Kucharczuk, John Charles; Su, Stacey; Kaiser, Larry Robert; Cooper, Joel David

2010-09-01

Under the Freedom of Information Act, we obtained the follow-up data of the National Emphysema Treatment Trial (NETT) to determine the long-term outcome for "a heterogeneous distribution of emphysema with upper lobe predominance," postulated by the NETT hypothesis to be optimal candidates for lung volume reduction surgery. Using the NETT database, we identified patients with heterogeneous distribution of emphysema with upper lobe predominance and analyzed for the first time follow-up data for those receiving lung volume reduction surgery and those receiving medical management. Furthermore, we compared the results of the NETT reduction surgery group with a previously reported consecutive case series of 250 patients undergoing bilateral lung volume reduction surgery using similar selection criteria. Of the 1218 patients enrolled, 511 (42%) conformed to the NETT hypothesis selection criteria and received the randomly assigned surgical or medical treatment (surgical = 261; medical = 250). Lung volume reduction surgery resulted in a 5-year survival benefit (70% vs 60%; P = .02). Results at 3 years compared with baseline data favored surgical reduction in terms of residual volume reduction (25% vs 2%; P < .001), University of California San Diego dyspnea score (16 vs 0 points; P < .001), and improved St George Respiratory Questionnaire quality of life score (12 points vs 0 points; P < .001). For the 513 patients with a homogeneous pattern of emphysema randomized to surgical or medical treatment, lung volume reduction surgery produced no survival advantage and very limited functional benefit. Patients most likely to benefit from lung volume reduction surgery have heterogeneously distributed emphysema involving the upper lung zones predominantly. Such patients in the NETT trial had results nearly identical to those previously reported in a nonrandomized series of similar patients undergoing lung volume reduction surgery. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Dependence of toxicity of silver nanoparticles on Pseudomonas putida biofilm structure.

PubMed

Thuptimdang, Pumis; Limpiyakorn, Tawan; Khan, Eakalak

2017-12-01

Susceptibility of biofilms with different physical structures to silver nanoparticles (AgNPs) was studied. Biofilms of Pseudomonas putida KT2440 were formed in batch conditions under different carbon sources (glucose, glutamic acid, and citrate), glucose concentrations (5 and 50 mM), and incubation temperatures (25 and 30 °C). The biofilms were observed using confocal laser scanning microscopy for their physical characteristics (biomass amount, thickness, biomass volume, surface to volume ratio, and roughness coefficient). The biofilms forming under different growth conditions exhibited different physical structures. The biofilm thickness and the roughness coefficient were found negatively and positively correlated with the biofilm susceptibility to AgNPs, respectively. The effect of AgNPs on biofilms was low (1-log reduction of cell number) when the biofilms had high biomass amount, high thickness, high biomass volume, low surface to volume ratio, and low roughness coefficient. Furthermore, the extracellular polymeric substance (EPS) stripping process was applied to confirm the dependence of susceptibility to AgNPs on the structure of biofilm. After the EPS stripping process, the biofilms forming under different conditions showed reduction in thickness and biomass volume, and increases in surface to volume ratio and roughness coefficient, which led to more biofilm susceptibility to AgNPs. The results of this study suggest that controlling the growth conditions to alter the biofilm physical structure is a possible approach to reduce the impact of AgNPs on biofilms in engineered and natural systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diversifying biological fuel cell designs by use of nanoporous filters.

PubMed

Biffinger, Justin C; Ray, Ricky; Little, Brenda; Ringeisen, Bradley R

2007-02-15

The use of proton exchange membranes (PEMs) in biological fuel cells limits the diversity of novel designs for increasing output power or enabling autonomous function in unique environments. Here we show that selected nanoporous polymer filters (nylon, cellulose, or polycarbonate) can be used effectively in place of PEMs in a miniature microbial fuel cell (mini-MFC, device cross-section 2 cm2), generating a power density of 16 W/m3 with an uncoated graphite felt oxygen reduction reaction (ORR) cathode. The incorporation of polycarbonate or nylon membranes into biological fuel cell designs produced comparable power and durability to Nafion-117 membranes. Also, high power densities for novel larger (5 cm3 anode volume, 0.6 W/m3) and smaller (0.025 cm3 projected geometric volume, average power density 10 W/m3) chamberless and pumpless microbial fuel cells were observed. As an additional benefit, the nanoporous membranes isolated the anode from invading natural bacteria, increasing the potential applications for MFCs beyond aquatic sediment environments. This work is a practical solution for decreasing the cost of biological fuel cells while incorporating new features for powering long-term autonomous devices.

Cellular and Hormonal Disruption of Fetal Testis Development in Sheep Reared on Pasture Treated with Sewage Sludge

PubMed Central

Paul, Catriona; Rhind, Stewart M.; Kyle, Carol E.; Scott, Hayley; McKinnell, Chris; Sharpe, Richard M.

2005-01-01

The purpose of this study was to evaluate whether experimental exposure of pregnant sheep to a mixture of environmental chemicals added to pasture as sewage sludge (n = 9 treated animals) exerted effects on fetal testis development or function; application of sewage sludge was undertaken so as to maximize exposure of the ewes to its contents. Control ewes (n = 9) were reared on pasture treated with an equivalent amount of inorganic nitrogenous fertilizer. Treatment had no effect on body weight of ewes, but it reduced body weight by 12–15% in male (n = 12) and female (n = 8) fetuses on gestation day 110. In treated male fetuses (n = 11), testis weight was significantly reduced (32%), as were the numbers of Sertoli cells (34% reduction), Leydig cells (37% reduction), and gonocytes (44% reduction), compared with control fetuses (n = 8). Fetal blood levels of testosterone and inhibin A were also reduced (36% and 38%, respectively) in treated compared with control fetuses, whereas blood levels of luteinizing hormone and follicle-stimulating hormone were unchanged. Based on immunoexpression of anti-Müllerian hormone, cytochrome P450 side chain cleavage enzyme, and Leydig cell cytoplasmic volume, we conclude that the hormone changes in treated male fetuses probably result from the reduction in somatic cell numbers. This reduction could result from fetal growth restriction in male fetuses and/or from the lowered testosterone action; reduced immunoexpression of α-smooth muscle actin in peritubular cells and of androgen receptor in testes of treated animals supports the latter possibility. These findings indicate that exposure of the developing male sheep fetus to real-world mixtures of environmental chemicals can result in major attenuation of testicular development and hormonal function, which may have consequences in adulthood. PMID:16263515

76 FR 58543 - Draft Policy Statement on Volume Reduction and Low-Level Radioactive Waste Management

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-21

...-Level Radioactive Waste Management AGENCY: Nuclear Regulatory Commission. ACTION: Reopening of comment... for public comment a draft Policy Statement on Volume Reduction and Low-Level Radioactive Waste Management that updates the 1981 Policy Statement on Low-Level Waste Volume Reduction. The revised Policy...

Compression of Martian atmosphere for production of oxygen

NASA Technical Reports Server (NTRS)

Lynch, D. C.; Cutler, A. H.; Nolan, P. E.

1991-01-01

The compression of CO2 from the Martian atmosphere for production of O2 via an electrochemical cell is addressed. Design specifications call for an oxygen production rate of 10 kg per day and for compression of 50 times that mass of CO2. Those specifications require a compression rate of over 770 cfm at standard Martian temperature and pressure (SMTP). Much of the CO2 being compressed represents waste, unless it can be recycled. Recycling can reduce the volume of gas that must be compressed to 40 cfm at SMTP. That volume reduction represents significant mass savings in the compressor, heating equipment, filters, and energy source. Successful recycle of the gas requires separation of CO (produced in the electrochemical cell) from CO2, N2, and Ar found in the Martian atmosphere. That aspect was the focus of this work.

Effect of hydration on interstitial distribution of charged albumin in rat dermis in vitro

PubMed Central

Wiig, Helge; Tenstad, Olav; Bert, Joel L

2005-01-01

At physiological pH, negatively charged glycosaminoglycans in the extracellular matrix may influence distribution volume of macromolecular probes, a phenomenon of importance for hydration of the interstitium and therefore for body fluid balance. We hypothesized that such charge effect was dependent on hydration. Human serum albumin (HSA) (the pH value for the isoelectric point (pI) = 4.9) was made neutral by cationization (cHSA) (pI = 7.6). Rat dermis was studied in vitro in a specially designed equilibration cell allowing control of hydration. Using a buffer containing labelled native HSA and cHSA, the distribution volumes were calculated relative to that of 51Cr-EDTA, an extracellular tracer. During changes in hydration (H), defined as (wet weight – dry weight) (dry weight)−1), the slope of the equation describing the relationship between extracellular fluid volume (Vx) (in g H2O (g dry weight)−1) and H (Vx = 0.925 H + 0.105) differed significantly from that for available volumes of cHSA (Va,cHSA = 0.624 H – 0.538) and HSA (Va,HSA = 0.518 H – 0.518). A gradual reduction in H led to a reduction in difference between available volumes for the two albumin species. Screening the fixed charges by 1 m NaCl resulted in similar available and excluded volumes of native HSA and neutral cHSA. We conclude that during gradual dehydration, there is a reduced effect of fixed negative charges on interstitial exclusion of charged macromolecules. This effect may be explained by a reduced hydration domain surrounding tissue and probe macromolecules in conditions of increased electrostatic interactions. Furthermore, screening of negative charges suggested that hyaluronan associated with collagen may influence intrafibrillar volume of collagen and thereby available and excluded volume fraction. PMID:16210353

A prospective study analyzing the application of radiofrequency energy and high-voltage, ultrashort pulse duration electrical fields on the quantitative reduction of adipose tissue

PubMed Central

Duncan, Diane Irvine; Kim, Theresa H. M.; Temaat, Robbin

2016-01-01

Noninvasive fat reduction is claimed by many device manufacturers, but proof of efficacy has been difficult to establish. This prospective study was designed to measure the reduction of fat thickness and actual volume reduction in 20 female patients treated with an external radiofrequency (RF) device. This device combines RF heat, suction coupled vacuum, and oscillating electrical pulses that induce adipocyte death over time. Patients underwent pre- and post-treatment and intercurrent measurements of weight, body mass index, ultrasonic transcutaneous fat thickness, and 2D and 3D Vectra photography with independent calculation of circumferential and volumetric change. Mean transcutaneous ultrasound thickness at reproducible points was 2.78 cm; at 1-month post-treatment, the mean fat thickness was 1.71 cm. At 3-month post-treatment, the mean fat thickness reduction was 39.6%. Vectra circumference measurements were taken at 10-mm intervals, with postural and breathing cycle control. Independent analysis of serial measurements from + 60 to − 70 mm showed mean abdominal circumference measurement of 2.3 cm. Mean abdominal volume loss was 202.4 and 428.5 cc at 1- and 3-month post-treatment, respectively. Scanning electron microscopy confirmed that permanent cell destruction was caused by irreversible electroporation. Pyroptosis appears to be the mechanism of action. PMID:26962636

A prospective study analyzing the application of radiofrequency energy and high-voltage, ultrashort pulse duration electrical fields on the quantitative reduction of adipose tissue.

PubMed

Duncan, Diane Irvine; Kim, Theresa H M; Temaat, Robbin

2016-10-01

Noninvasive fat reduction is claimed by many device manufacturers, but proof of efficacy has been difficult to establish. This prospective study was designed to measure the reduction of fat thickness and actual volume reduction in 20 female patients treated with an external radiofrequency (RF) device. This device combines RF heat, suction coupled vacuum, and oscillating electrical pulses that induce adipocyte death over time. Patients underwent pre- and post-treatment and intercurrent measurements of weight, body mass index, ultrasonic transcutaneous fat thickness, and 2D and 3D Vectra photography with independent calculation of circumferential and volumetric change. Mean transcutaneous ultrasound thickness at reproducible points was 2.78 cm; at 1-month post-treatment, the mean fat thickness was 1.71 cm. At 3-month post-treatment, the mean fat thickness reduction was 39.6%. Vectra circumference measurements were taken at 10-mm intervals, with postural and breathing cycle control. Independent analysis of serial measurements from + 60 to - 70 mm showed mean abdominal circumference measurement of 2.3 cm. Mean abdominal volume loss was 202.4 and 428.5 cc at 1- and 3-month post-treatment, respectively. Scanning electron microscopy confirmed that permanent cell destruction was caused by irreversible electroporation. Pyroptosis appears to be the mechanism of action.

Assessment of volume reduction effect after lung lobectomy for cancer.

PubMed

Ueda, Kazuhiro; Murakami, Junichi; Sano, Fumiho; Hayashi, Masataro; Kobayashi, Taiga; Kunihiro, Yoshie; Hamano, Kimikazu

2015-07-01

Lung lobectomy results in an unexpected improvement of the remaining lung function in some patients with moderate-to-severe emphysema. Because the lung function is the main limiting factor for therapeutic decision making in patients with lung cancer, it may be advantageous to identify patients who may benefit from the volume reduction effect, particularly those with a poor functional reserve. We measured the regional distribution of the emphysematous lung and normal lung using quantitative computed tomography in 84 patients undergoing lung lobectomy for cancer between January 2010 and December 2012. The volume reduction effect was diagnosed using a combination of radiologic and spirometric parameters. Eight patients (10%) were favorably affected by the volume reduction effect. The forced expiratory volume in one second increased postoperatively in these eight patients, whereas the forced vital capacity was unchanged, thus resulting in an improvement of the airflow obstruction postoperatively. This improvement was not due to a compensatory expansion of the remaining lung but was associated with a relative decrease in the forced end-expiratory lung volume. According to a multivariate analysis, airflow obstruction and the forced end-expiratory lung volume were independent predictors of the volume reduction effect. A combined assessment using spirometry and quantitative computed tomography helped to characterize the respiratory dynamics underlying the volume reduction effect, thus leading to the identification of novel predictors of a volume reduction effect after lobectomy for cancer. Verification of our results by a large-scale prospective study may help to extend the indications for lobectomy in patients with oncologically resectable lung cancer who have a marginal pulmonary function. Copyright © 2015 Elsevier Inc. All rights reserved.

An update on methods for cryopreservation and thawing of hemopoietic stem cells.

PubMed

Lecchi, Lucilla; Giovanelli, Silvia; Gagliardi, Barbara; Pezzali, Ilaria; Ratti, Ilaria; Marconi, Maurizio

2016-06-01

The aim of this article is to review a number of variables that may affect the cryopreservation of minimally manipulated products containing allogeneic or autologous hemopoietic progenitor cells (HPC) used for transplantation, with particular reference to processing, type and addition of cryoprotectant, cell concentration, volume, freezing procedure, cooling rate, storage, thawing, and quality management. After defining final product's requirements in compliance with norms, laws and regulations, it is crucial to define the critical control points of the process. New approaches of processing were developed in the last few years such as automatic devices for volume reduction and high cell concentration in the frozen product. DMSO at 10% final concentration is still the most used cryoprotectant for HPC cryopreservation. Although controlled rate freezing is the recommended method for HPC cryopreservation, alternative methods may be used. Last generation vapor storage vessels ensure temperature stability better than older tanks. Their use may reduce risks of cross-contamination. Finally we review advantages and disadvantages of thawing procedures that may be carried out in the laboratory or at the patient's bedside. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Wei, Max; Smith, Sarah J.; Sohn, Michael D.

Fuel cells are both a longstanding and emerging technology for stationary and transportation applications, and their future use will likely be critical for the deep decarbonization of global energy systems. As we look into future applications, a key challenge for policy-makers and technology market forecasters who seek to track and/or accelerate their market adoption is the ability to forecast market costs of the fuel cells as technology innovations are incorporated into market products. Specifically, there is a need to estimate technology learning rates, which are rates of cost reduction versus production volume. Unfortunately, no literature exists for forecasting future learningmore » rates for fuel cells. In this paper, we look retrospectively to estimate learning rates for two fuel cell deployment programs: (1) the micro-combined heat and power (CHP) program in Japan, and (2) the Self-Generation Incentive Program (SGIP) in California. These two examples have a relatively broad set of historical market data and thus provide an informative and international comparison of distinct fuel cell technologies and government deployment programs. We develop a generalized procedure for disaggregating experience-curve cost-reductions in order to disaggregate the Japanese fuel cell micro-CHP market into its constituent components, and we derive and present a range of learning rates that may explain observed market trends. Finally, we explore the differences in the technology development ecosystem and market conditions that may have contributed to the observed differences in cost reduction and draw policy observations for the market adoption of future fuel cell technologies. The scientific and policy contributions of this paper are the first comparative experience curve analysis of past fuel cell technologies in two distinct markets, and the first quantitative comparison of a detailed cost model of fuel cell systems with actual market data. The resulting approach is applicable to analyzing other fuel cell markets and other energy-related technologies, and highlights the data needed for cost modeling and quantitative assessment of key cost reduction components.« less

The dynamic volume changes of polymerising polymethyl methacrylate bone cement.

PubMed

Muller, Scott D; Green, Sarah M; McCaskie, Andrew W

2002-12-01

The Swedish hip register found an increased risk of early revision of vacuum-mixed cemented total hip replacements. The influence of cement mixing technique on the dynamic volume change in polymerising PMMA is not well understood and may be relevant to this observation. Applying Archimedes' principle, we have investigated the dynamic volume changes in polymerising cement and determined the influence of mixing technique. All specimens showed an overall volume reduction: hand-mixed 3.4% and vacuum-mixed 6.0%. Regression analysis of sectional porosity and volume reduction showed a highly significant relationship. Hand-mixed porous cement showed a transient volume increase before solidification. However, vacuum-mixed cement showed a progressive volume reduction throughout polymerisation. Transient expansion of porous cement occurs at the critical time of micro-interlock formation, possibly improving fixation. Conversely, progressive volume reduction of vacuum-mixed cement throughout the formation of interlock may damage fixation. Stable fixation of vacuum-mixed cement may depend on additional techniques to offset the altered volumetric behaviour of vacuum-mixed cement.

Administration of goserelin acetate after uterine artery embolization does not change the reduction rate and volume of uterine myomas.

PubMed

Vilos, George A; Vilos, Angelos G; Abu-Rafea, Basim; Pron, Gaylene; Kozak, Roman; Garvin, Greg

2006-05-01

To determine if goserelin immediately after uterine artery embolization (UAE) affected myoma reduction. Randomized pilot study (level 1). Teaching hospital. Twenty-six women. All patients underwent UAE, and then 12 patients received 10.8 mg of goserelin 24 hours later. The treatment group was 5 years older: 43 versus 37.7 years. Uterine and myoma volumes were measured by ultrasound 2 weeks before UAE and at 3, 6, and 12 months. Uterine and fibroid volumes. Pretreatment uterine volume was 477 versus 556 cm3, and dominant fibroid volume was 257 versus 225 cm3 in the control versus goserelin groups. Analysis of variance measurements indicated that the change over time did not significantly differ between the two groups. By 12 months, the control group had a mean uterine volume reduction of 58%, while the goserelin group had a reduction of 45%. Dominant fibroid changes over time did not differ between the two groups. At 12 months, the mean fibroid volume had decreased by 86% and 58% in the control and goserelin groups, respectively. The addition of goserelin therapy to UAE did not alter the reduction rate or volume of uterine myomas.

[Clinical target volume delineation for radiotherapy of the esophagus].

PubMed

Lazarescu, I; Thureau, S; Nkhali, L; Pradier, O; Dubray, B

2013-10-01

The dense lymphatic network of the esophagus facilitates tumour spreading along the cephalo-caudal axis and to locoregional lymph nodes. A better understanding of microscopic invasion by tumour cells, based on histological analysis of surgical specimens and analysis of recurrence sites, has justified a reduction in radiotherapy target volumes. The delineation of the clinical target volume (CTV) depends on tumour characteristics (site, histology) and on its spread as assessed on endoscopic ultrasonography and ((18)F)-fluorodeoxyglucose positron-emission tomography (FDG-PET). We propose that positive and negative predictive values for FDG-PET should be used to adapt the CTV according to the risk of nodal involvement. Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

A planning study investigating dual-gated volumetric arc stereotactic treatment of primary renal cell carcinoma

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

Devereux, Thomas, E-mail: thomas.devereux@petermac.org; Pham, Daniel; Kron, Tomas

2015-04-01

This is a planning study investigating the dosimetric advantages of gated volumetric-modulated arc therapy (VMAT) to the end-exhale and end-inhale breathing phases for patients undergoing stereotactic treatment of primary renal cell carcinoma. VMAT plans were developed from the end-inhale (VMATinh) and the end-exhale (VMATexh) phases of the breathing cycle as well as a VMAT plan and 3-dimensional conformal radiation therapy plan based on an internal target volume (ITV) (VMATitv). An additional VMAT plan was created by giving the respective gated VMAT plan a 50% weighting and summing the inhale and exhale plans together to create a summed gated plan. Dosemore » to organs at risk (OARs) as well as comparison of intermediate and low-dose conformity was evaluated. There was no difference in the volume of healthy tissue receiving the prescribed dose for the planned target volume (PTV) (CI100%) for all the VMAT plans; however, the mean volume of healthy tissue receiving 50% of the prescribed dose for the PTV (CI50%) values were 4.7 (± 0.2), 4.6 (± 0.2), and 4.7 (± 0.6) for the VMATitv, VMATinh, and VMATexh plans, respectively. The VMAT plans based on the exhale and inhale breathing phases showed a 4.8% and 2.4% reduction in dose to 30 cm{sup 3} of the small bowel, respectively, compared with that of the ITV-based VMAT plan. The summed gated VMAT plans showed a 6.2% reduction in dose to 30 cm{sup 3} of the small bowel compared with that of the VMAT plans based on the ITV. Additionally, when compared with the inhale and the exhale VMAT plans, a 4% and 1.5%, respectively, reduction was observed. Gating VMAT was able to reduce the amount of prescribed, intermediate, and integral dose to healthy tissue when compared with VMAT plans based on an ITV. When summing the inhale and exhale plans together, dose to healthy tissue and OARs was optimized. However, gating VMAT plans would take longer to treat and is a factor that needs to be considered.« less

Iodine retention during evaporative volume reduction

DOEpatents

Godbee, H.W.; Cathers, G.I.; Blanco, R.E.

1975-11-18

An improved method for retaining radioactive iodine in aqueous waste solutions during volume reduction is disclosed. The method applies to evaporative volume reduction processes whereby the decontaminated (evaporated) water can be returned safely to the environment. The method generally comprises isotopically diluting the waste solution with a nonradioactive iodide and maintaining the solution at a high pH during evaporation.

A temperature-controlled photoelectrochemical cell for quantitative product analysis.

PubMed

Corson, Elizabeth R; Creel, Erin B; Kim, Youngsang; Urban, Jeffrey J; Kostecki, Robert; McCloskey, Bryan D

2018-05-01

In this study, we describe the design and operation of a temperature-controlled photoelectrochemical cell for analysis of gaseous and liquid products formed at an illuminated working electrode. This cell is specifically designed to quantitatively analyze photoelectrochemical processes that yield multiple gas and liquid products at low current densities and exhibit limiting reactant concentrations that prevent these processes from being studied in traditional single chamber electrolytic cells. The geometry of the cell presented in this paper enables front-illumination of the photoelectrode and maximizes the electrode surface area to electrolyte volume ratio to increase liquid product concentration and hence enhances ex situ spectroscopic sensitivity toward them. Gas is bubbled through the electrolyte in the working electrode chamber during operation to maintain a saturated reactant concentration and to continuously mix the electrolyte. Gaseous products are detected by an in-line gas chromatograph, and liquid products are analyzed ex situ by nuclear magnetic resonance. Cell performance was validated by examining carbon dioxide reduction on a silver foil electrode, showing comparable results both to those reported in the literature and identical experiments performed in a standard parallel-electrode electrochemical cell. To demonstrate a photoelectrochemical application of the cell, CO 2 reduction experiments were carried out on a plasmonic nanostructured silver photocathode and showed different product distributions under dark and illuminated conditions.

A temperature-controlled photoelectrochemical cell for quantitative product analysis

NASA Astrophysics Data System (ADS)

Corson, Elizabeth R.; Creel, Erin B.; Kim, Youngsang; Urban, Jeffrey J.; Kostecki, Robert; McCloskey, Bryan D.

2018-05-01

In this study, we describe the design and operation of a temperature-controlled photoelectrochemical cell for analysis of gaseous and liquid products formed at an illuminated working electrode. This cell is specifically designed to quantitatively analyze photoelectrochemical processes that yield multiple gas and liquid products at low current densities and exhibit limiting reactant concentrations that prevent these processes from being studied in traditional single chamber electrolytic cells. The geometry of the cell presented in this paper enables front-illumination of the photoelectrode and maximizes the electrode surface area to electrolyte volume ratio to increase liquid product concentration and hence enhances ex situ spectroscopic sensitivity toward them. Gas is bubbled through the electrolyte in the working electrode chamber during operation to maintain a saturated reactant concentration and to continuously mix the electrolyte. Gaseous products are detected by an in-line gas chromatograph, and liquid products are analyzed ex situ by nuclear magnetic resonance. Cell performance was validated by examining carbon dioxide reduction on a silver foil electrode, showing comparable results both to those reported in the literature and identical experiments performed in a standard parallel-electrode electrochemical cell. To demonstrate a photoelectrochemical application of the cell, CO2 reduction experiments were carried out on a plasmonic nanostructured silver photocathode and showed different product distributions under dark and illuminated conditions.

Comparison of ultrasonic energy expenditures and corneal endothelial cell density reductions during modulated and non-modulated phacoemulsification.

PubMed

Davison, James A

2007-01-01

To compare the Legacy 20000 Advantec continuous and Infiniti hyperpulse modes (Alcon Laboratories, Fort Worth, TX) with respect to average power, machine-measured phacoemulsification time, total stopwatch real time spent within the phacoemulsification process, balanced salt solution (BSS) volume, and corneal endothelial cell density losses. A background study was done of consecutive patients operated on with the Legacy (n = 60) and Infiniti (n = 40) machines programmed with identical parameters and using the continuous mode only. A primary study of another set of consecutive cases was operated on using the Legacy (n = 87) and Infiniti (n = 94) with the same parameters, but using the hyperpulse mode during quadrant removal with the Infiniti. Measurements for each set included average power and phacoemulsification time with corneal endothelial cell densities, BSS volume, and time spent in the phacoemulsification process. Similarities were found in the background study for average power percent and average minutes of phacoemulsification time. In the primary study, similarities were found for total minutes in the phacoemulsification process, BSS usage, and ECD losses, and differences were found for average power percent (P< .001) and machine-measured phacoemulsification minutes (P< .001). The Legacy and Infiniti performed similarly in continuous mode. With the Infiniti hyperpulse mode, a total ultrasonic energy reduction of 66% was noted. The machines required the same amount of total stopwatch measured time to accomplish phacoemulsification and produced the same 5% corneal endothelial cell loss. Therefore, clinically, these two machines behave in a comparable manner relative to safety and effectiveness.

1,3,4-Thiadiazole derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones cause death in Trypanosoma cruzi through oxidative stress.

PubMed

Martins, Solange C; Lazarin-Bidóia, Danielle; Desoti, Vânia C; Falzirolli, Hugo; da Silva, Cleuza C; Ueda-Nakamura, Tania; Silva, Sueli de O; Nakamura, Celso V

2016-12-01

This work evaluated the in vitro and in vivo activity of TDZ 2 on Trypanosoma cruzi amastigotes and determined the possible mechanism of action of this compound on T. cruzi death. TDZ 2 inhibited T. cruzi proliferation in vitro and had low haemolytic potential. It also induced morphological and ultrastructural alterations. We observed a reduction of cell volume, the depolarization of the mitochondrial membrane, an increase in ROS production, lipoperoxidation of the cell membrane, lipid bodies formation and production of nitric oxide, a decrease in reduced thiols levels and, presence of autophagic vacuoles. The in vivo study found a reduction of parasitemia in animals treated with TDZ 2 alone or combined with benznidazole. Altogether, the alterations induced by TDZ 2 point to an oxidative stress condition that lead to T. cruzi cell death. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Role of founder cell deficit and delayed neuronogenesis in microencephaly of the trisomy 16 mouse

NASA Technical Reports Server (NTRS)

Haydar, T. F.; Nowakowski, R. S.; Yarowsky, P. J.; Krueger, B. K.

2000-01-01

Development of the neocortex of the trisomy 16 (Ts16) mouse, an animal model of Down syndrome (DS), is characterized by a transient delay in the radial expansion of the cortical wall and a persistent reduction in cortical volume. Here we show that at each cell cycle during neuronogenesis, a smaller proportion of Ts16 progenitors exit the cell cycle than do control, euploid progenitors. In addition, the cell cycle duration was found to be longer in Ts16 than in euploid progenitors, the Ts16 growth fraction was reduced, and an increase in apoptosis was observed in both proliferative and postmitotic zones of the developing Ts16 neocortical wall. Incorporation of these changes into a model of neuronogenesis indicates that they are sufficient to account for the observed delay in radial expansion. In addition, the number of neocortical founder cells, i.e., precursors present just before neuronogenesis begins, is reduced by 26% in Ts16 mice, leading to a reduction in overall cortical size at the end of Ts16 neuronogenesis. Thus, altered proliferative characteristics during Ts16 neuronogenesis result in a delay in the generation of neocortical neurons, whereas the founder cell deficit leads to a proportional reduction in the overall number of neurons. Such prenatal perturbations in either the timing of neuron generation or the final number of neurons produced may lead to significant neocortical abnormalities such as those found in DS.

Tumor Volume Reduction Rate After Preoperative Chemoradiotherapy as a Prognostic Factor in Locally Advanced Rectal Cancer

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

Yeo, Seung-Gu; Department of Radiation Oncology, Soonchunhyang University College of Medicine, Cheonan; Kim, Dae Yong, E-mail: radiopiakim@hanmail.net

2012-02-01

Purpose: To investigate the prognostic significance of tumor volume reduction rate (TVRR) after preoperative chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and Materials: In total, 430 primary LARC (cT3-4) patients who were treated with preoperative CRT and curative radical surgery between May 2002 and March 2008 were analyzed retrospectively. Pre- and post-CRT tumor volumes were measured using three-dimensional region-of-interest MR volumetry. Tumor volume reduction rate was determined using the equation TVRR (%) = (pre-CRT tumor volume - post-CRT tumor volume) Multiplication-Sign 100/pre-CRT tumor volume. The median follow-up period was 64 months (range, 27-99 months) for survivors. Endpoints weremore » disease-free survival (DFS) and overall survival (OS). Results: The median TVRR was 70.2% (mean, 64.7% {+-} 22.6%; range, 0-100%). Downstaging (ypT0-2N0M0) occurred in 183 patients (42.6%). The 5-year DFS and OS rates were 77.7% and 86.3%, respectively. In the analysis that included pre-CRT and post-CRT tumor volumes and TVRR as continuous variables, only TVRR was an independent prognostic factor. Tumor volume reduction rate was categorized according to a cutoff value of 45% and included with clinicopathologic factors in the multivariate analysis; ypN status, circumferential resection margin, and TVRR were significant prognostic factors for both DFS and OS. Conclusions: Tumor volume reduction rate was a significant prognostic factor in LARC patients receiving preoperative CRT. Tumor volume reduction rate data may be useful for tailoring surgery and postoperative adjuvant therapy after preoperative CRT.« less

Estimating the impact of somatic cell count on the value of milk utilising parameters obtained from the published literature.

PubMed

Geary, Una; Lopez-Villalobos, Nicolas; O'Brien, Bernadette; Garrick, Dorian J; Shalloo, Laurence

2014-05-01

The impact of mastitis on milk value per litre independent of the effect of mastitis on milk volume, was quantified for Ireland using a meta-analysis and a processing sector model. Changes in raw milk composition, cheese processing and composition associated with increased bulk milk somatic cell count (BMSCC) were incorporated into the model. Processing costs and market values were representative of current industry values. It was assumed that as BMSCC increased (i) milk fat and milk protein increased and milk lactose decreased, (ii) fat and protein recoveries decreased, (iii) cheese protein decreased and cheese moisture increased. Five BMSCC categories were examined from ⩽100 000 to >400 000 cells/ml. The analysis showed that as BMSCC increased the production quantities reduced. An increase in BMSCC from 100 000 to >400 000 cells/ml saw a reduction in net revenue of 3·2% per annum (€51·3 million) which corresponded to a reduction in the value of raw milk of €0·0096 cents/l.

Pseudo tumors of the lung after lung volume reduction surgery.

PubMed

Oey, Inger F; Jeyapalan, Kanagaratnam; Entwisle, James J; Waller, David A

2004-03-01

We describe 2 patients who underwent lung volume reduction surgery, who postoperatively had computed tomographic scans that showed symptomatic mass lesions suggestive of malignancy and an inhaled foreign body. Investigations excluded these conditions with the remaining likely diagnosis of pseudotumor secondary to buttressing material. These potential sequelae of lung volume reduction surgery should be recognized in follow-up investigations.

Platinum nanoparticles on carbon-nanotube support prepared by room-temperature reduction with H2 in ethylene glycol/water mixed solvent as catalysts for polymer electrolyte membrane fuel cells

NASA Astrophysics Data System (ADS)

Zheng, Yuying; Dou, Zhengjie; Fang, Yanxiong; Li, Muwu; Wu, Xin; Zeng, Jianhuang; Hou, Zhaohui; Liao, Shijun

2016-02-01

Polyol approach is commonly used in synthesizing Pt nanoparticles in polymer electrolyte membrane fuel cells. However, the application of this process consumes a great deal of time and energy, as the reduction of precursors requires elevated temperatures and several hours. Moreover, the ethylene glycol and its oxidizing products bound to Pt are difficult to remove. In this work, we utilize the advantages of ethylene glycol and prepare Pt nanoparticles through a room-temperature hydrogen gas reduction in an ethylene glycol/water mixed solvent, which is followed by subsequent harvesting by carbon nanotubes as electrocatalysts. This method is simple, facile, and time-efficient, as the entire room-temperature reduction process is completed in a few minutes. As the solvent changes from water to an ethylene glycol/water mix, the size of Pt nanoparticles varies from 10 to 3 nm and their shape transitions from polyhedral to spherical. Pt nanoparticles prepared in a 1:1 volume ratio mixture of ethylene glycol/water are uniformly dispersed with an average size of ∼3 nm. The optimized carbon nanotube-supported Pt electrocatalyst exhibits excellent methanol oxidation and oxygen reduction activities. This work demonstrates the potential use of mixed solvents as an approach in materials synthesis.

Abuse Response of 18650 Li-Ion Cells with Different Cathodes Using EC:EMC/LiPF6 and EC:PC:DMC/LiPF6 Electrolytes

DOE PAGES

Roth, Emmanuel Peter

2008-01-01

We report Lithium-Ion batteries are being considered as a high-energy density replacement for Nickel Metal Hydride (NiMH) batteries in Hybrid Electric Vehicles (HEVs) and in the new Plug-In Hybrids (PHEVs). Although these cells can result in significant reduction in weight and volume, they have several safety related issues that still need to be addressed. We report here on the thermal response of Li-ion cells specifically assembled in our laboratory to test new materials, electrolytes and additives. Finally, improvements in the thermal abuse tolerance of cells are reported and discussed in terms of the need for overall battery system safety.

Cryo-imaging of fluorescently labeled single cells in a mouse

NASA Astrophysics Data System (ADS)

Steyer, Grant J.; Roy, Debashish; Salvado, Olivier; Stone, Meredith E.; Wilson, David L.

2009-02-01

We developed a cryo-imaging system to provide single-cell detection of fluorescently labeled cells in mouse, with particular applicability to stem cells and metastatic cancer. The Case cryoimaging system consists of a fluorescence microscope, robotic imaging positioner, customized cryostat, PC-based control system, and visualization/analysis software. The system alternates between sectioning (10-40 μm) and imaging, collecting color brightfield and fluorescent blockface image volumes >60GB. In mouse experiments, we imaged quantum-dot labeled stem cells, GFP-labeled cancer and stem cells, and cell-size fluorescent microspheres. To remove subsurface fluorescence, we used a simplified model of light-tissue interaction whereby the next image was scaled, blurred, and subtracted from the current image. We estimated scaling and blurring parameters by minimizing entropy of subtracted images. Tissue specific attenuation parameters were found [uT : heart (267 +/- 47.6 μm), liver (218 +/- 27.1 μm), brain (161 +/- 27.4 μm)] to be within the range of estimates in the literature. "Next image" processing removed subsurface fluorescence equally well across multiple tissues (brain, kidney, liver, adipose tissue, etc.), and analysis of 200 microsphere images in the brain gave 97+/-2% reduction of subsurface fluorescence. Fluorescent signals were determined to arise from single cells based upon geometric and integrated intensity measurements. Next image processing greatly improved axial resolution, enabled high quality 3D volume renderings, and improved enumeration of single cells with connected component analysis by up to 24%. Analysis of image volumes identified metastatic cancer sites, found homing of stem cells to injury sites, and showed microsphere distribution correlated with blood flow patterns. We developed and evaluated cryo-imaging to provide single-cell detection of fluorescently labeled cells in mouse. Our cryo-imaging system provides extreme (>60GB), micron-scale, fluorescence, and bright field image data. Here we describe our image preprocessing, analysis, and visualization techniques. Processing improves axial resolution, reduces subsurface fluorescence by 97%, and enables single cell detection and counting. High quality 3D volume renderings enable us to evaluate cell distribution patterns. Applications include the myriad of biomedical experiments using fluorescent reporter gene and exogenous fluorophore labeling of cells in applications such as stem cell regenerative medicine, cancer, tissue engineering, etc.

Comparison of human umbilical cord blood processing with or without hydroxyethyl starch.

PubMed

Souri, Milad; Nikougoftar Zarif, Mahin; Rasouli, Mahboobeh; Golzadeh, Khadijeh; Nakhlestani Hagh, Mozhdeh; Ezzati, Nasim; Atarodi, Kamran

2017-11-01

Umbilical cord blood (UCB) processing with hydroxyethyl starch (HES) is the most common protocol in the cord blood banks. The quality of UCB volume reduction was guaranteed by minimum manipulation of cord blood samples in the closed system. This study aimed to analyze and compare cell recovery and viability of UCB processed using the Sepax automated system in the presence and absence of HES. Thirty UCB bags with a total nucleated cell (TNC) count of more than 2.5 × 10 9 were divided in two bags with equal volume. HES solution was added to one bag and another was intact. Both bags were processed with the Sepax. To determine cell recovery, viability, and potential of colony-forming cells (CFCs), preprocessing, postprocessing, and thawing samples were analyzed. The mean TNC recovery after processing and after thaw was significantly better with the HES method (p < 0.01 for the postprocessing step and p < 0.05 for the postthaw step). There were no significant differences to mononucleated cells (MNCs) and CD34+ cell recovery between the two methods after processing and after thaw. TNC and MNC viability was significantly higher without HES after processing and after thaw (p < 0.01). The results of the CFC assay were similar for both methods after processing and after thaw. These results showed that processing of UCB using the Sepax system with the without-HES protocol due to the lower manipulation of samples could be used as an eligible protocol to reduce the volume of UCB. © 2017 AABB.

Quantitative Ultrasound Backscatter for Pulsed Cavitational Ultrasound Therapy—Histotripsy

PubMed Central

Wang, Tzu-Yin; Xu, Zhen; Winterroth, Frank; Hall, Timothy L.; Fowlkes, J. Brian; Rothman, Edward D.; Roberts, William W.; Cain, Charles A.

2011-01-01

Histotripsy is a well-controlled ultrasonic tissue ablation technology that mechanically and progressively fractionates tissue structures using cavitation. The fractionated tissue volume can be monitored with ultrasound imaging because a significant ultrasound backscatter reduction occurs. This paper correlates the ultrasound backscatter reduction with the degree of tissue fractionation characterized by the percentage of remaining normal-appearing cell nuclei on histology. Different degrees of tissue fractionation were generated in vitro in freshly excised porcine kidneys by varying the number of therapeutic ultrasound pulses from 100 to 2000 pulses per treatment location. All ultrasound pulses were 15 cycles at 1 MHz delivered at 100 Hz pulse repetition frequency and 19 MPa peak negative pressure. The results showed that the normalized backscatter intensity decreased exponentially with increasing number of pulses. Correspondingly, the percentage of normal appearing nuclei in the treated area decreased exponentially as well. A linear correlation existed between the normalized backscatter intensity and the percentage of normal appearing cell nuclei in the treated region. This suggests that the normalized backscatter intensity may be a potential quantitative real-time feedback parameter for histotripsy-induced tissue fractionation. This quantitative feedback may allow the prediction of local clinical outcomes, i.e., when a tissue volume has been sufficiently treated. PMID:19750596

High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

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

Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay

Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis ofmore » tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.« less

Practical high temperature (80 °C) storage study of industrially manufactured Li-ion batteries with varying electrolytes

NASA Astrophysics Data System (ADS)

Genieser, R.; Loveridge, M.; Bhagat, R.

2018-05-01

A previous study is focused on high temperature cycling of industrially manufactured Li-ion pouch cells (NMC-111/Graphite) with different electrolytes at 80 °C [JPS 373 (2018) 172-183]. Within this article the same test set-up is used, with cells stored for 30 days at different open circuit potentials and various electrolytes instead of electrochemical cycling. The most pronounced cell degradation (capacity fade and resistance increase) happens at high potentials. However appropriate electrolyte formulations are able to suppress ageing conditions by forming passivating surface films on both electrodes. Compared with electrochemical cycling at 80 °C, cells with enhanced electrolytes only show a slight resistance increase during storage and the capacity fade is much lower. Additionally it is shown for the first time, that the resistance is decreasing and capacity is regained once these cells are cycled again at room temperature. This is not the case for electrolytes without additives or just vinylene carbonate (VC) as an additive. It is further shown that the resistance increase of cells with the other electrolytes is accompanied by a reduction of the cell volume during further cycling. This behaviour is likely related to the reduction of CO2 at the anode to form additional SEI layer components.

Cell-populated collagen lattice contraction model for the investigation of fibroblast collagen interactions.

PubMed

Ehrlich, H Paul; Moyer, Kurtis E

2013-01-01

The fibroblast-populated collagen lattice (FPCL) was intended to act as the dermal component for "skin-equivalent" or artificial skin developed for skin grafting burn patients. The "skin-equivalent" was clinically unsuccessful as a skin graft, but today it is successfully used as a dressing for the management of chronic wounds. The FPCL has, however, become an instrument for investigating cell-connective tissue interactions within a three-dimensional matrix. Through the capacity of cell compaction of collagen fibrils, the FPCL undergoes a reduction in volume referred to as lattice contraction. Lattice contraction proceeds by cell-generated forces that reduce the water mass between collagen fibers, generating a closer relationship between collagen fibers. The compaction of collagen fibers is responsible for the reduction in the FPCL volume. Cell-generated forces through the linkage of collagen fibers with fibroblast's cytoskeletal actin-rich microfilament structures are responsible for the completion of the collagen matrix compaction. The type of culture dish used to cast FPCL as well as the cell number will dictate the mechanism for compacting collagen matrices. Fibroblasts, at moderate density, cast as an FPCL within a petri dish and released from the surface of the dish soon after casting compact collagen fibers through cell tractional forces. Fibroblasts at moderate density cast as an FPCL within a tissue culture dish and not released for 4 days upon release show rapid lattice contraction through a mechanism of cell contraction forces. Fibroblasts at high density cast in an FPCL within a petri dish, released from the surface of the dish soon after casting, compact a collagen lattice very rapidly through forces related to cell elongation. The advantage of the FPCL contraction model is the study of cells in the three-dimensional environment, which is similar to the environment from which these cells were isolated. In this chapter methods are described for manufacturing collagen lattices, which assess the three forces involved in compacting and/or organizing collagen fibrils into thicker collagen fibers. The clinical relevance of the FPCL contraction model is related to advancing our understanding of wound contraction and scar contracture.

Neuroimaging abnormalities in adults with sickle cell anemia

PubMed Central

Insel, Philip; Truran, Diana; Vichinsky, Elliot P.; Neumayr, Lynne D.; Armstrong, F.D.; Gold, Jeffrey I.; Kesler, Karen; Brewer, Joseph; Weiner, Michael W.

2014-01-01

Objective: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA). Methods: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). Results: After adjusting for age, sex, education level, and intracranial volume, participants with SCA exhibited thinner frontal lobe cortex (t = −2.99, p = 0.003) and reduced basal ganglia and thalamus volumes compared with HCs (t = −3.95, p < 0.001). Reduced volume of the basal ganglia and thalamus was significantly associated with lower Performance IQ (model estimate = 3.75, p = 0.004) as well as lower Perceptual Organization (model estimate = 1.44, p = 0.007) and Working Memory scores (model estimate = 1.37, p = 0.015). Frontal lobe cortex thickness was not significantly associated with any cognitive measures. Conclusions: Our findings suggest that basal ganglia and thalamus abnormalities may represent a particularly salient contributor to cognitive dysfunction in adults with SCA. PMID:24523480

Computed Tomography Number Changes Observed During Computed Tomography–Guided Radiation Therapy for Head and Neck Cancer

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

Feng, Mei; Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu; Yang, Cungeng

2015-04-01

Purpose: To investigate CT number (CTN) changes in gross tumor volume (GTV) and organ at risk (OAR) according to daily diagnostic-quality CT acquired during CT-guided intensity modulated radiation therapy for head and neck cancer (HNC) patients. Methods and Materials: Computed tomography scans acquired using a CT-on-rails during daily CT-guided intensity modulated radiation therapy for 15 patients with stage II to IVa squamous cell carcinoma of the head and neck were analyzed. The GTV, parotid glands, spinal cord, and nonspecified tissue were generated on each selected daily CT. The changes in CTN distributions and the mean and mode values were collected.more » Pearson analysis was used to assess the correlation between the CTN change, organ volume reduction, and delivered radiation dose. Results: Volume and CTN changes for GTV and parotid glands can be observed during radiation therapy delivery for HNC. The mean (±SD) CTNs in GTV and ipsi- and contralateral parotid glands were reduced by 6 ± 10, 8 ± 7, and 11 ± 10 Hounsfield units, respectively, for all patients studied. The mean CTN changes in both spinal cord and nonspecified tissue were almost invisible (<2 Hounsfield units). For 2 patients studied, the absolute mean CTN changes in GTV and parotid glands were strongly correlated with the dose delivered (P<.001 and P<.05, respectively). For the correlation between CTN reductions and delivered isodose bins for parotid glands, the Pearson coefficient varied from −0.98 (P<.001) in regions with low-dose bins to 0.96 (P<.001) in high-dose bins and were patient specific. Conclusions: The CTN can be reduced in tumor and parotid glands during the course of radiation therapy for HNC. There was a fair correlation between CTN reduction and radiation doses for a subset of patients, whereas the correlation between CTN reductions and volume reductions in GTV and parotid glands were weak. More studies are needed to understand the mechanism for the radiation-induced CTN changes.« less

MDCK cells are capable of water secretion and reabsorption in response to changes in the ionic environment.

PubMed

Capra, Janne P; Eskelinen, Sinikka M

2017-01-01

A prerequisite for tissue electrolyte homeostasis is highly regulated ion and water transport through kidney or intestinal epithelia. In the present work, we monitored changes in the cell and luminal volumes of type II Madin-Darby canine kidney (MDCK) cells grown in a 3D environment in response to drugs, or to changes in the composition of the basal extracellular fluid. Using fluorescent markers and high-resolution spinning disc confocal microscopy, we could show that lack of sodium and potassium ions in the basal fluid (tetramethylammonium chloride (TMACl) buffer) induces a rapid increase in the cell and luminal volumes. This transepithelial water flow could be regulated by inhibitors and agonists of chloride channels. Hence, the driving force for the transepithelial water flow is chloride secretion, stimulated by hyperpolarization. Chloride ion depletion of the basal fluid (using sodium gluconate buffer) induces a strong reduction in the lumen size, indicating reabsorption of water from the lumen to the basal side. Lumen size also decreased following depolarization of the cell interior by rendering the membrane permeable to potassium. Hence, MDCK cells are capable of both absorption and secretion of chloride ions and water; negative potential within the lumen supports secretion, while depolarizing conditions promote reabsorption.

Solar cells utilizing pulsed-energy crystallized microcrystalline/polycrystalline silicon

DOEpatents

Kaschmitter, J.L.; Sigmon, T.W.

1995-10-10

A process for producing multi-terminal devices such as solar cells wherein a pulsed high energy source is used to melt and crystallize amorphous silicon deposited on a substrate which is intolerant to high processing temperatures, whereby the amorphous silicon is converted into a microcrystalline/polycrystalline phase. Dopant and hydrogenation can be added during the fabrication process which provides for fabrication of extremely planar, ultra shallow contacts which results in reduction of non-current collecting contact volume. The use of the pulsed energy beams results in the ability to fabricate high efficiency microcrystalline/polycrystalline solar cells on the so-called low-temperature, inexpensive plastic substrates which are intolerant to high processing temperatures.

Solar cells utilizing pulsed-energy crystallized microcrystalline/polycrystalline silicon

DOEpatents

Kaschmitter, James L.; Sigmon, Thomas W.

1995-01-01

A process for producing multi-terminal devices such as solar cells wherein a pulsed high energy source is used to melt and crystallize amorphous silicon deposited on a substrate which is intolerant to high processing temperatures, whereby to amorphous silicon is converted into a microcrystalline/polycrystalline phase. Dopant and hydrogenization can be added during the fabrication process which provides for fabrication of extremely planar, ultra shallow contacts which results in reduction of non-current collecting contact volume. The use of the pulsed energy beams results in the ability to fabricate high efficiency microcrystalline/polycrystalline solar cells on the so-called low-temperature, inexpensive plastic substrates which are intolerant to high processing temperatures.

Hyaluronan Deficiency Due to Has3 Knock-Out Causes Altered Neuronal Activity and Seizures via Reduction in Brain Extracellular Space

PubMed Central

Arranz, Amaia M.; Perkins, Katherine L.; Irie, Fumitoshi; Lewis, David P.; Hrabe, Jan; Xiao, Fanrong; Itano, Naoki; Kimata, Koji

2014-01-01

Hyaluronan (HA), a large anionic polysaccharide (glycosaminoglycan), is a major constituent of the extracellular matrix of the adult brain. To address its function, we examined the neurophysiology of knock-out mice deficient in hyaluronan synthase (Has) genes. Here we report that these Has mutant mice are prone to epileptic seizures, and that in Has3−/− mice, this phenotype is likely derived from a reduction in the size of the brain extracellular space (ECS). Among the three Has knock-out models, namely Has3−/−, Has1−/−, and Has2CKO, the seizures were most prevalent in Has3−/− mice, which also showed the greatest HA reduction in the hippocampus. Electrophysiology in Has3−/− brain slices demonstrated spontaneous epileptiform activity in CA1 pyramidal neurons, while histological analysis revealed an increase in cell packing in the CA1 stratum pyramidale. Imaging of the diffusion of a fluorescent marker revealed that the transit of molecules through the ECS of this layer was reduced. Quantitative analysis of ECS by the real-time iontophoretic method demonstrated that ECS volume was selectively reduced in the stratum pyramidale by ∼40% in Has3−/− mice. Finally, osmotic manipulation experiments in brain slices from Has3−/− and wild-type mice provided evidence for a causal link between ECS volume and epileptiform activity. Our results provide the first direct evidence for the physiological role of HA in the regulation of ECS volume, and suggest that HA-based preservation of ECS volume may offer a novel avenue for development of antiepileptogenic treatments. PMID:24790187

Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment.

PubMed

Emsley, R; Asmal, L; du Plessis, S; Chiliza, B; Phahladira, L; Kilian, S

2017-09-01

Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported. We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain). Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis. Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.

The Ontario Uterine Fibroid Embolization Trial. Part 2. Uterine fibroid reduction and symptom relief after uterine artery embolization for fibroids.

PubMed

Pron, Gaylene; Bennett, John; Common, Andrew; Wall, Jane; Asch, Murray; Sniderman, Kenneth

2003-01-01

To evaluate fibroid uterine volume reduction, symptom relief, and patient satisfaction with uterine artery embolization (UAE) for symptomatic fibroids. Multicenter, prospective, single-arm clinical treatment trial. Eight Ontario university and community hospitals. Five hundred thirty-eight patients undergoing bilateral UAE. Bilateral UAE performed with polyvinyl alcohol particles sized 355-500 microm. Three-month follow-up evaluations including fibroid uterine volume reductions, patient reported symptom improvement (7-point scale), symptom life-impact (10-point scale) reduction, and treatment satisfaction (6-point scale). Median uterine and dominant fibroid volume reductions were 35% and 42%, respectively. Significant improvements were reported for menorrhagia (83%), dysmenorrhea (77%), and urinary frequency/urgency (86%). Mean menstrual duration was significantly reduced after UAE (7.6 to 5.4 days). Improvements in menorrhagia were unrelated to pre-UAE uterine size or post-UAE uterine volume reduction. Amenorrhea occurring after the procedure was highly age dependent, ranging from 3% (1%-7%) in women under age 40 to 41% (26%-58%) in women age 50 or older. Median fibroid life-impact scores were significantly reduced after UAE (8.0 to 3.0). The majority (91%) expressed satisfaction with UAE treatment. UAE reduced fibroid uterine volume and provided significant relief of menorrhagia that was unrelated to initial fibroid uterine size or volume reduction. Patient satisfaction with short-term UAE treatment outcomes was high.

Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.

PubMed

Mondoñedo, Jarred R; Suki, Béla

2017-02-01

Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction.

Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema

PubMed Central

Mondoñedo, Jarred R.

2017-01-01

Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction. PMID:28182686

Does the pancreatic volume reduction rate using serial computed tomographic volumetry predict new onset diabetes after pancreaticoduodenectomy?

PubMed Central

Yun, Sung Pil; Seo, Hyung-Il; Kim, Suk; Kim, Dong Uk; Baek, Dong Hoon

2017-01-01

Abstract Volume reduction of the pancreatic tissues following a pancreatectomy can lead to the deterioration of glucose homeostasis. This is defined as pancreatogenic diabetes mellitus (DM). The objective of this study was to investigate the occurrence of new-onset DM (NODM) and evaluate the risk factors, including the pancreas volume reduction rate in patients undergoing pancreaticoduodenectomy (PD). Sixty-six patients without preoperative DM underwent PD for periampullary tumors between August 2007 and December 2012 and were included in this analysis. These patients underwent follow-up tests and abdominal computed tomography (CT) scan 7 days, 6 months, 12 months, 24 months, and 36 months after the operation. The pancreas volume reduction rate was calculated by CT volumetry. The patients were divided into 2 groups according to the postoperative development of DM. After PD, newly diagnosed DM occurred in 16 patients (24.2%). The incidence of DM was highest among patients with carcinomas with an advanced T stage. The pancreatic volume reduction rate after 6 and 12 months in the NODM group was significantly higher than the normal glucose group in the univariate analysis. In the multivariate analysis, the pancreatic volume reduction rate 6 months after PD was the only significant predictive factor for the development of NODM (P = 0.002). This study suggests that the pancreatic volume reduction rate 6 months after PD was the only significant predictive factor for the development of NODM. CT volumetry of the pancreas may be useful as a predictor of NODM after PD. PMID:28353594

Experimental investigation of shock-cell noise reduction for single-stream nozzles in simulated flight, comprehensive data report. Volume 3: Shadowgraph photos and facility description

NASA Technical Reports Server (NTRS)

Yamamoto, K.; Brausch, J. F.; Janardan, B. A.; Hoerst, D. J.; Price, A. O.; Knott, P. R.

1984-01-01

A total of 142 shadowgraph photographs were taken on 43 different plumes that were distributed over the six nozzle configurations using the 9.5 inch diameter collimated light beam of the shadowgraph setup. Aerodynamic flow conditions of the shadowgraph test points, the location and identification of each of the photographs, and copies of the pictures are presented.

Volume reduction of the corpus callosum and its relationship with deficits in interhemispheric transfer of information in recent-onset psychosis.

PubMed

Chaim, Tiffany M; Schaufelberger, Maristela S; Ferreira, Luiz K; Duran, Fábio L S; Ayres, Adriana M; Scazufca, Marcia; Menezes, Paulo R; Amaro, Edson; Leite, Claudia C; Murray, Robin M; McGuire, Philip K; Rushe, Teresa M; Busatto, Geraldo F

2010-10-30

The present study aimed to investigate the presence of corpus callosum (CC) volume deficits in a population-based recent-onset psychosis (ROP) sample, and whether CC volume relates to interhemispheric communication deficits. For this purpose, we used voxel-based morphometry comparisons of magnetic resonance imaging data between ROP (n =122) and healthy control (n = 94) subjects. Subgroups (38 ROP and 39 controls) were investigated for correlations between CC volumes and performance on the Crossed Finger Localization Test (CFLT). Significant CC volume reductions in ROP subjects versus controls emerged after excluding substance misuse and non-right-handedness. CC reductions retained significance in the schizophrenia subgroup but not in affective psychoses subjects. There were significant positive correlations between CC volumes and CFLT scores in ROP subjects, specifically in subtasks involving interhemispheric communication. From these results, we can conclude that CC volume reductions are present in association with ROP. The relationship between such deficits and CFLT performance suggests that interhemispheric communication impairments are directly linked to CC abnormalities in ROP. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

EPA RREL'S MOBILE VOLUME REDUCTION UNIT -- APPLICATIONS ANALYSIS REPORT

EPA Science Inventory

The volume reduction unit (VRU) is a pilot-scale, mobile soil washing system designed to remove organic contaminants from the soil through particle size separation and solubilization. The VRU removes contaminants by suspending them in a wash solution and by reducing the volume of...

Insular Volume Reduction in Patients with Social Anxiety Disorder

PubMed Central

Kawaguchi, Akiko; Nemoto, Kiyotaka; Nakaaki, Shutaro; Kawaguchi, Takatsune; Kan, Hirohito; Arai, Nobuyuki; Shiraishi, Nao; Hashimoto, Nobuhiko; Akechi, Tatsuo

2016-01-01

Despite the fact that social anxiety disorder (SAD) is highly prevalent, there have been only a few structural imaging studies. Moreover, most of them reported about a volume reduction in amygdale, which plays a key role in the neural function of SAD. Insula is another region of interest. Its hyperactivity in regard to processing negative emotional information or interoceptive awareness has been detected in patients with SAD. Referring to these studies, we hypothesized that insular volumes might reduce in patients with SAD and made a comparison of insular volumes between 13 patients with SAD and 18 healthy controls with matched age and gender using voxel-based morphometry. As a result, we found a significant volume reduction in insula in the SAD group. Our results suggest that the patients with SAD might have an insular volume reduction apart from amygdala. Since insula plays a critical role in the pathology of SAD, more attention should be paid not only to functional study but also morphometrical study of insula. PMID:26834652

Anti-neoplastic activities of sepia officinalis ink and coelatura aegyptiaca extracts against Ehrlich ascites carcinoma in Swiss albino mice

PubMed Central

Soliman, Amel M; Fahmy, Sohair R; El-Abied, Salma A

2015-01-01

Objectives: With the development of sophisticated instruments for the isolation and elucidation of natural products structures from marine and freshwater organisms, major advances have been made in the discovery of aquatic derived therapeutics. Present investigations were carried out to evaluate cuttlefish (Sepia officinalis) ink extract (IE) and freshwater clam (Coelatura aegyptiaca) extract (CE) for their anticancer and antioxidant activities as compared to 5-flurouracil (5-Fu), in Ehrlich ascites carcinoma (EAC). Methods: Sixty female Swiss albino mice were divided into five groups (n = 12). All groups except group I received EAC cells (5 × 106 cells/mouse i.p.) and this was taken as the 0th day. Group I served as saline control (5 ml/kg 0.9% NaCl w/v p.o). Group II served as EAC control. Rats of groups III, IV and V received IE, CE (200 mg/kg body weight i.p.), and reference drug (5-Fu, 20 mg/kg body weight i.p.), respectively. Results: The reduction in tumor volume, packed cell volume, tumor cell counts and increase in median survival time and percentage increase in life span in treated animals were observed. There was a significant increase in RBC count; Hb content in treated animals and reduction in total WBC count. There was a significant decrease in AST, ALT, ALP and liver MDA levels and increase in GSH, SOD and NO levels were observed in all treated animals. Conclusion: Both IE and CE were effective in inhibiting the tumor growth in ascitic tumor models. The biochemical, antioxidants and histopathological studies were also supported their antitumor properties. PMID:26097537

Preclinical Pharmacological Evaluation of Letrozole as a Novel Treatment for Gliomas

PubMed Central

Dave, Nimita; Chow, Lionel M.L.; Gudelsky, Gary A.; LaSance, Kathleen; Qi, Xiaoyang; Desai, Pankaj B.

2015-01-01

We present data that letrozole, an extensively used aromatase inhibitor in the treatment of estrogen receptor-positive breast tumors in postmenopausal women, may be potentially used in the treatment of glioblastomas. First, we measured the in vitro cytotoxicity of letrozole and aromatase (CYP19A1) expression and activity in human LN229, T98G, U373MG, U251MG, and U87MG, and rat C6 glioma cell lines. Estrogen receptor (ER)positive MCF-7 and ER-negative MDA-MB-231 cells served as controls. Cytotoxicity was determined employing the MTT assay, and aromatase activity using an immunoassay that measures the conversion of testosterone to estrogen. Second, in vivo activity of letrozole was assessed in Sprague-Dawley rats orthotopically implanted with C6 gliomas. The changes in tumor volume with letrozole treatment (4 mg/kg/day) were assessed employing μPET/CT imaging, employing [18F]-fluorodeoxyglucose (F18-FDG) as the radiotracer. Brain tissues were collected for histologic evaluations. All glioma cell lines included here expressed CYP19A1 and letrozole exerted considerable cytotoxicity and decrease in aromatase activity against these cells (IC50, 0.1–3.5 μmol/L). Imaging analysis employing F18-FDG μPET/CT demonstrated a marked reduction of active tumor volume (>75%) after 8 days of letrozole treatment. Immunohistochemical analysis revealed marked reduction in aromatase expression in tumoral regions of the brain after letrozole treatment. Thus, employing multifaceted tools, we demonstrate that aromatase may be a novel target for the treatment of gliomas and that letrozole, an FDA-approved drug with an outstanding record of safety may be repurposed for the treatment of such primary brain tumors, which currently have few therapeutic options. PMID:25695958

Preclinical pharmacological evaluation of letrozole as a novel treatment for gliomas.

PubMed

Dave, Nimita; Chow, Lionel M L; Gudelsky, Gary A; LaSance, Kathleen; Qi, Xiaoyang; Desai, Pankaj B

2015-04-01

We present data that letrozole, an extensively used aromatase inhibitor in the treatment of estrogen receptor-positive breast tumors in postmenopausal women, may be potentially used in the treatment of glioblastomas. First, we measured the in vitro cytotoxicity of letrozole and aromatase (CYP19A1) expression and activity in human LN229, T98G, U373MG, U251MG, and U87MG, and rat C6 glioma cell lines. Estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cells served as controls. Cytotoxicity was determined employing the MTT assay, and aromatase activity using an immunoassay that measures the conversion of testosterone to estrogen. Second, in vivo activity of letrozole was assessed in Sprague-Dawley rats orthotopically implanted with C6 gliomas. The changes in tumor volume with letrozole treatment (4 mg/kg/day) were assessed employing μPET/CT imaging, employing [(18)F]-fluorodeoxyglucose (F18-FDG) as the radiotracer. Brain tissues were collected for histologic evaluations. All glioma cell lines included here expressed CYP19A1 and letrozole exerted considerable cytotoxicity and decrease in aromatase activity against these cells (IC50, 0.1-3.5 μmol/L). Imaging analysis employing F18-FDG μPET/CT demonstrated a marked reduction of active tumor volume (>75%) after 8 days of letrozole treatment. Immunohistochemical analysis revealed marked reduction in aromatase expression in tumoral regions of the brain after letrozole treatment. Thus, employing multifaceted tools, we demonstrate that aromatase may be a novel target for the treatment of gliomas and that letrozole, an FDA-approved drug with an outstanding record of safety may be repurposed for the treatment of such primary brain tumors, which currently have few therapeutic options. ©2015 American Association for Cancer Research.

In Situ NAPL Modification for Contaminant Source-Zone Passivation, Mass Flux Reduction, and Remediation

NASA Astrophysics Data System (ADS)

Mateas, D. J.; Tick, G.; Carroll, K. C.

2016-12-01

A remediation method was developed to reduce the aqueous solubility and mass-flux of target NAPL contaminants through the in-situ creation of a NAPL mixture source-zone. This method was tested in the laboratory using equilibrium batch tests and two-dimensional flow-cell experiments. The creation of two different NAPL mixture source zones were tested in which 1) volumes of relatively insoluble n-hexadecane (HEX) or vegetable oil (VO) were injected into a trichloroethene (TCE) contaminant source-zone; and 2) pre-determined HEX-TCE and VO-TCE mixture ratio source zones were emplaced into the flow cell prior to water flushing. NAPL-aqueous phase batch tests were conducted prior to the flow-cell experiments to evaluate the effects of various NAPL mixture ratios on equilibrium aqueous-phase concentrations of TCE and toluene (TOL) and to design optimal NAPL (HEX or VO) injection volumes for the flow-cell experiments. Uniform NAPL mixture source-zones were able to quickly decrease contaminant mass-flux, as demonstrated by the emplaced source-zone experiments. The success of the HEX and VO injections to also decrease mass flux was dependent on the ability of these injectants to homogeneously mix with TCE source-zone. Upon injection, both HEX and VO migrated away from the source-zone, to some extent. However, the lack of a steady-state dissolution phase and the inefficient mass-flux-reduction/mass-removal behavior produced after VO injection suggest that VO was more effective than HEX for mixing and partitioning within the source-zone region to form a more homogeneous NAPL mixture with TCE. VO appears to be a promising source-zone injectant-NAPL due to its negligible long-term toxicity and lower mobilization potential.

Effects of cell volume changes on membrane ionic permeabilities and sodium transport in frog skin (Rana ridibunda).

PubMed

Costa, P M; Fernandes, P L; Ferreira, H G; Ferreira, K T; Giraldez, F

1987-12-01

1. Membrane potential and conductances and short-circuit current were continuously measured with microelectrodes and conventional electrophysiological techniques in a stripped preparation of frog skin epithelium. The effects of the removal of chloride or sodium ions and the concentration or dilution of the serosal (inner) bathing solution were studied. 2. Chloride- or sodium-free solutions produced a cell depolarization of about 30 mV in parallel with a fall in the short-circuit current. Mucosal and serosal membrane conductances both decreased and the sodium permeability of the mucosal barrier was calculated to fall to about one-half its value in standard Ringer solution. The observed decrease in the short-circuit current is probably related to the combined effect of the decrease in sodium permeability and the decrease in the driving force across the mucosal membrane. 3. The removal of chloride or sodium ions reduced the depolarization caused by serosal perfusion with high-potassium solutions (50 mM-KCl). The ratio of the change in cell membrane potential under short-circuit conditions to the change in the potassium equilibrium potential (delta Ec(s.c.)/delta EK), was 0.59 in standard Ringer solution and 0.26 and 0.24 after the removal of chloride or sodium respectively. The depolarizing effect of barium-containing solutions (2 mM-BaCl2) was also markedly reduced in chloride- or sodium-free solutions, suggesting a decrease of the potassium selectivity of the serosal membrane in these conditions. 4. Increasing the osmolality of the serosal bathing solution produced similar effects, i.e. cell depolarization, fall in the short-circuit current and membrane conductances and reduction of the depolarizing effect of high-potassium and barium solutions. On the contrary, dilution of the serosal bath produced the opposite effects, consistent with an increase in the serosal permeability to potassium. 5. The effects of chloride- or sodium-free solutions were reversed by the dilution of the serosal bath. Cells repolarized when exposed to low-osmolality solutions after being in the absence of serosal chloride or sodium. The repolarization ran in parallel with the restoration of the short-circuit current and the potassium selectivity of the serosal membrane. 6. The results show that the effects produced by the removal of sodium or chloride ions from the serosal bathing solution are most probably mediated by a reduction in cell volume. Cell volume changes would lead to changes in the serosal membrane selectivity to potassium and thus to changes in cell membrane potential and sodium transport.(ABSTRACT TRUNCATED AT 400 WORDS)

Targeted disruption of BMP signaling through type IA receptor (BMPR1A) in osteocyte suppresses SOST and RANKL, leading to dramatic increase in bone mass, bone mineral density and mechanical strength.

PubMed

Kamiya, Nobuhiro; Shuxian, Lin; Yamaguchi, Ryosuke; Phipps, Matthew; Aruwajoye, Olumide; Adapala, Naga Suresh; Yuan, Hui; Kim, Harry K W; Feng, Jian Q

2016-10-01

Recent studies suggest a critical role of osteocytes in controlling skeletal development and bone remodeling although the molecular mechanism is largely unknown. This study investigated BMP signaling in osteocytes by disrupting Bmpr1a under the Dmp1-promoter. The conditional knockout (cKO) mice displayed a striking osteosclerotic phenotype with increased trabecular bone volume, thickness, number, and mineral density as assessed by X-ray and micro-CT. The bone histomorphometry, H&E, and TRAP staining revealed a dramatic increase in trabecular and cortical bone masses but a sharp reduction in osteoclast number. Moreover, there was an increase in BrdU positive osteocytes (2-5-fold) and osteoid volume (~4-fold) but a decrease in the bone formation rate (~85%) in the cKO bones, indicating a defective mineralization. The SEM analysis revealed poorly formed osteocytes: a sharp increase in cell numbers, a great reduction in cell dendrites, and a remarkable change in the cell distribution pattern. Molecular studies demonstrated a significant decrease in the Sost mRNA levels in bone (>95%), and the SOST protein levels in serum (~85%) and bone matrices. There was a significant increase in the β-catenin (>3-fold) mRNA levels as well as its target genes Tcf1 (>6-fold) and Tcf3 (~2-fold) in the cKO bones. We also showed a significant decrease in the RANKL levels of serum proteins (~65%) and bone mRNA (~57%), and a significant increase in the Opg mRNA levels (>20-fold) together with a significant reduction in the Rankl/Opg ratio (>95%), which are responsible for a sharp reduction in the cKO osteoclasts. The values of mechanical strength were higher in cKO femora (i.e. max force, displacement, and work failure). These results suggest that loss of BMP signaling specifically in osteocytes dramatically increases bone mass presumably through simultaneous inhibition of RANKL and SOST, leading to osteoclast inhibition and Wnt activation together. Finally, a working hypothesis is proposed to explain how BMPR1A controls bone remodeling by inhibiting cell proliferation and stimulating differentiation. It is reported that RANKL and SOST are abundantly expressed by osteocytes. Thus, BMP signaling through BMPR1A plays important roles in osteocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of dimethylsulfoxide on the water transport response of rat hepatocytes during freezing.

PubMed

Smith, D J; Schulte, M; Bischof, J C

1998-10-01

Successful improvement of cryopreservation protocols for cells in suspension requires knowledge of how such cells respond to the biophysical stresses of freezing (intracellular ice formation, water transport) while in the presence of a cryoprotective agent (CPA). This work investigates the biophysical water transport response in a clinically important cell type--isolated hepatocytes--during freezing in the presence of dimethylsulfoxide (DMSO). Sprague-Dawley rat liver hepatocytes were frozen in Williams E media supplemented with 0, 1, and 2 M DMSO, at rates of 5, 10, and 50 degrees C/min. The water transport was measured by cell volumetric changes as assessed by cryomicroscopy and image analysis. Assuming that water is the only species transported under these conditions, a water transport model of the form dV/dT = f(Lpg([CPA]), ELp([CPA]), T(t)) was curve-fit to the experimental data to obtain the biophysical parameters of water transport--the reference hydraulic permeability (Lpg) and activation energy of water transport (ELp)--for each DMSO concentration. These parameters were estimated two ways: (1) by curve-fitting the model to the average volume of the pooled cell data, and (2) by curve-fitting individual cell volume data and averaging the resulting parameters. The experimental data showed that less dehydration occurs during freezing at a given rate in the presence of DMSO at temperatures between 0 and -10 degrees C. However, dehydration was able to continue at lower temperatures (< -10 degrees C) in the presence of DMSO. The values of Lpg and ELp obtained using the individual cell volume data both decreased from their non-CPA values--4.33 x 10(-13) m3/N-s (2.69 microns/min-atm) and 317 kJ/mol (75.9 kcal/mol), respectively--to 0.873 x 10(-13) m3/N-s (0.542 micron/min-atm) and 137 kJ/mol (32.8 kcal/mol), respectively, in 1 M DMSO and 0.715 x 10(-13) m3/N-s (0.444 micron/min-atm) and 107 kJ/mol (25.7 kcal/mol), respectively, in 2 M DMSO. The trends in the pooled volume values for Lpg and ELp were very similar, but the overall fit was considered worse than for the individual volume parameters. A unique way of presenting the curve-fitting results supports a clear trend of reduction of both biophysical parameters in the presence of DMSO, and no clear trend in cooling rate dependence of the biophysical parameters. In addition, these results suggest that close proximity of the experimental cell volume data to the equilibrium volume curve may significantly reduce the efficiency of the curve-fitting process.

A Novel Quantitative Computed Tomographic Analysis Suggests How Sirolimus Stabilizes Progressive Air Trapping in Lymphangioleiomyomatosis

PubMed Central

Kokosi, Maria; Lo, Pechin; Kim, Hyun J.; Ravenel, James G.; Meyer, Cristopher; Goldin, Jonathan; Lee, Hye-Seung; Strange, Charlie; McCormack, Francis X.

2016-01-01

Rationale: The Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial demonstrated that sirolimus stabilized lung function and improved measures of functional performance and quality of life in patients with lymphangioleiomyomatosis. The physiologic mechanisms of these beneficial actions of sirolimus are incompletely understood. Objectives: To prospectively determine the longitudinal computed tomographic lung imaging correlates of lung function change in MILES patients treated with placebo or sirolimus. Methods: We determined the baseline to 12-month change in computed tomographic image–derived lung volumes and the volume of the lung occupied by cysts in the 31 MILES participants (17 in sirolimus group, 14 in placebo group) with baseline and 12-month scans. Measurements and Main Results: There was a trend toward an increase in median expiratory cyst volume percentage in the placebo group and a reduction in the sirolimus group (+2.68% vs. +0.97%, respectively; P = 0.10). The computed tomographic image–derived residual volume and the ratio of residual volume to total lung capacity increased more in the placebo group than in the sirolimus group (+214.4 ml vs. +2.9 ml [P = 0.054] and +0.05 ml vs. −0.01 ml [P = 0.0498], respectively). A Markov transition chain analysis of respiratory cycle cyst volume changes revealed greater dynamic variation in the sirolimus group than in the placebo group at the 12-month time point. Conclusions: Collectively, these data suggest that sirolimus attenuates progressive gas trapping in lymphangioleiomyomatosis, consistent with a beneficial effect of the drug on airflow obstruction. We speculate that a reduction in lymphangioleiomyomatosis cell burden around small airways and cyst walls alleviates progressive airflow limitation and facilitates cyst emptying. PMID:26799509

A Novel Quantitative Computed Tomographic Analysis Suggests How Sirolimus Stabilizes Progressive Air Trapping in Lymphangioleiomyomatosis.

PubMed

Argula, Rahul G; Kokosi, Maria; Lo, Pechin; Kim, Hyun J; Ravenel, James G; Meyer, Cristopher; Goldin, Jonathan; Lee, Hye-Seung; Strange, Charlie; McCormack, Francis X

2016-03-01

The Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial demonstrated that sirolimus stabilized lung function and improved measures of functional performance and quality of life in patients with lymphangioleiomyomatosis. The physiologic mechanisms of these beneficial actions of sirolimus are incompletely understood. To prospectively determine the longitudinal computed tomographic lung imaging correlates of lung function change in MILES patients treated with placebo or sirolimus. We determined the baseline to 12-month change in computed tomographic image-derived lung volumes and the volume of the lung occupied by cysts in the 31 MILES participants (17 in sirolimus group, 14 in placebo group) with baseline and 12-month scans. There was a trend toward an increase in median expiratory cyst volume percentage in the placebo group and a reduction in the sirolimus group (+2.68% vs. +0.97%, respectively; P = 0.10). The computed tomographic image-derived residual volume and the ratio of residual volume to total lung capacity increased more in the placebo group than in the sirolimus group (+214.4 ml vs. +2.9 ml [P = 0.054] and +0.05 ml vs. -0.01 ml [P = 0.0498], respectively). A Markov transition chain analysis of respiratory cycle cyst volume changes revealed greater dynamic variation in the sirolimus group than in the placebo group at the 12-month time point. Collectively, these data suggest that sirolimus attenuates progressive gas trapping in lymphangioleiomyomatosis, consistent with a beneficial effect of the drug on airflow obstruction. We speculate that a reduction in lymphangioleiomyomatosis cell burden around small airways and cyst walls alleviates progressive airflow limitation and facilitates cyst emptying.

A general gridding, discretization, and coarsening methodology for modeling flow in porous formations with discrete geological features

NASA Astrophysics Data System (ADS)

Karimi-Fard, M.; Durlofsky, L. J.

2016-10-01

A comprehensive framework for modeling flow in porous media containing thin, discrete features, which could be high-permeability fractures or low-permeability deformation bands, is presented. The key steps of the methodology are mesh generation, fine-grid discretization, upscaling, and coarse-grid discretization. Our specialized gridding technique combines a set of intersecting triangulated surfaces by constructing approximate intersections using existing edges. This procedure creates a conforming mesh of all surfaces, which defines the internal boundaries for the volumetric mesh. The flow equations are discretized on this conforming fine mesh using an optimized two-point flux finite-volume approximation. The resulting discrete model is represented by a list of control-volumes with associated positions and pore-volumes, and a list of cell-to-cell connections with associated transmissibilities. Coarse models are then constructed by the aggregation of fine-grid cells, and the transmissibilities between adjacent coarse cells are obtained using flow-based upscaling procedures. Through appropriate computation of fracture-matrix transmissibilities, a dual-continuum representation is obtained on the coarse scale in regions with connected fracture networks. The fine and coarse discrete models generated within the framework are compatible with any connectivity-based simulator. The applicability of the methodology is illustrated for several two- and three-dimensional examples. In particular, we consider gas production from naturally fractured low-permeability formations, and transport through complex fracture networks. In all cases, highly accurate solutions are obtained with significant model reduction.

Mechanism of reduction of mitral regurgitation with vasodilator therapy.

PubMed

Yoran, C; Yellin, E L; Becker, R M; Gabbay, S; Frater, R W; Sonnenblick, E H

1979-04-01

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlin's hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance of left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

The differentiation directions of the bone marrow stromal cells under modeling microgravity

NASA Astrophysics Data System (ADS)

Nesterenko, Olga; Rodionova, Natalia; Katkova, Olena

Within experiments on rats simulating microgravity by base load remove from back limbs (duration of the experiment 1,5 months) on marrow stromal cells cultures (ex vivo, in vitro) comprising osteogenic cells-predecessors, extracted from femurs, studied their peculiarities of the colony formation ablity, the cell structure, some cytological and ultra-structural characteristics and differentiation direction. It was found that that under microgravity conditions there is a decline of the stromal cells colony formation intensity, decrease of the colonies size and cells mitotic activity that indicates decrease of their growth potential. Both in control and in experiment the colonies were presented by population of low-differentiated cells, differentiated cells and mature cells. The comparative cytological and morphometric analysis have shown that the studied stromal cells in colonies have the smaller sizes, more elongated shape, and higher nucleocytoplasmic ratio. Cells composition in the experiment colonies is reliably different by the ratio of the low-differentiating to being differentiated cells; a ratio of low-differentiated to already differentiated cells; ratio of differentiated cells to total number of all cells. In comparison with control group, amount of the cells passed trough a differentiation stage and mature cells in colonies is decreased by 3 to 4 times. Among the differentiated stromal cells in colonies increasing amount of adipocytes was revealed. The analysis of electron microscope microphotographs showed that in osteogenic cells differentiated under microgravity conditions, there is a reduction of the specific volume of a granular endoplasmic reticulum, Golgi's complex and quantity of nuclei reduction that indicates depression of the specific biosyntheses process intensity in cells. The increase of lysosomes and myelinic structures quantity is linked to organelles partial reduction. Consolidation of mitochondrias is an evidence of the cells’ energy metabolism disorder. In differentiated cells, disorganization and a cytoskeleton destruction was observed. Results showed that under microgravity conditions proliferative and differentiation (including osteogenic) potentialities of low-differentiated marrow stromal cells decreased, induction of their adipocytic differentiation was observes as well. Obtained results make a new contribution into gravitation sensitivity mechanisms understanding for stromal cells of the bone marrow which contain osteogenic cells- predecessors, features of the osteoporosis development.

Reproducibility of lung tumor position and reduction of lung mass within the planning target volume using active breathing control (ABC).

PubMed

Cheung, Patrick C F; Sixel, Katharina E; Tirona, Romeo; Ung, Yee C

2003-12-01

The active breathing control (ABC) device allows for temporary immobilization of respiratory motion by implementing a breath hold at a predefined relative lung volume and air flow direction. The purpose of this study was to quantitatively evaluate the ability of the ABC device to immobilize peripheral lung tumors at a reproducible position, increase total lung volume, and thereby reduce lung mass within the planning target volume (PTV). Ten patients with peripheral non-small-cell lung cancer tumors undergoing radiotherapy had CT scans of their thorax with and without ABC inspiration breath hold during the first 5 days of treatment. Total lung volumes were determined from the CT data sets. Each peripheral lung tumor was contoured by one physician on all CT scans to generate gross tumor volumes (GTVs). The lung density and mass contained within a 1.5-cm PTV margin around each peripheral tumor was calculated using CT numbers. Using the center of the GTV from the Day 1 ABC scan as the reference, the displacement of subsequent GTV centers on Days 2 to 5 for each patient with ABC applied was calculated in three dimensions. With the use of ABC inspiration breath hold, total lung volumes increased by an average of 42%. This resulted in an average decrease in lung mass of 18% within a standard 1.5-cm PTV margin around the GTV. The average (+/- standard deviation) displacement of GTV centers with ABC breath hold applied was 0.3 mm (+/- 1.8 mm), 1.2 mm (+/- 2.3 mm), and 1.1 mm (+/- 3.5 mm) in the lateral direction, anterior-posterior direction, and superior-inferior direction, respectively. Results from this study indicate that there remains some inter-breath hold variability in peripheral lung tumor position with the use of ABC inspiration breath hold, which prevents significant PTV margin reduction. However, lung volumes can significantly increase, thereby decreasing the mass of lung within a standard PTV.

Structural assessment of the impact of environmental constraints on Arabidopsis thaliana leaf growth: a 3D approach.

PubMed

Wuyts, Nathalie; Massonnet, Catherine; Dauzat, Myriam; Granier, Christine

2012-09-01

Light and soil water content affect leaf surface area expansion through modifications in epidermal cell numbers and area, while effects on leaf thickness and mesophyll cell volumes are far less documented. Here, three-dimensional imaging was applied in a study of Arabidopsis thaliana leaf growth to determine leaf thickness and the cellular organization of mesophyll tissues under moderate soil water deficit and two cumulative light conditions. In contrast to surface area, thickness was highly conserved in response to water deficit under both low and high cumulative light regimes. Unlike epidermal and palisade mesophyll tissues, no reductions in cell number were observed in the spongy mesophyll; cells had rather changed in volume and shape. Furthermore, leaf features of a selection of genotypes affected in leaf functioning were analysed. The low-starch mutant pgm had very thick leaves because of unusually large palisade mesophyll cells, together with high levels of photosynthesis and stomatal conductance. By means of an open stomata mutant and a 9-cis-epoxycarotenoid dioxygenase overexpressor, it was shown that stomatal conductance does not necessarily have a major impact on leaf dimensions and cellular organization, pointing to additional mechanisms for the control of CO(2) diffusion under high and low stomatal conductance, respectively. © 2012 Blackwell Publishing Ltd.

Scale-up of Carbon/Carbon Bipolar Plates

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

David P. Haack

2009-04-08

This project was focused upon developing a unique material technology for use in PEM fuel cell bipolar plates. The carbon/carbon composite material developed in this program is uniquely suited for use in fuel cell systems, as it is lightweight, highly conductive and corrosion resistant. The project further focused upon developing the manufacturing methodology to cost-effectively produce this material for use in commercial fuel cell systems. United Technology Fuel Cells Corp., a leading fuel cell developer was a subcontractor to the project was interested in the performance and low-cost potential of the material. The accomplishments of the program included the developmentmore » and testing of a low-cost, fully molded, net-shape carbon-carbon bipolar plate. The process to cost-effectively manufacture these carbon-carbon bipolar plates was focused on extensively in this program. Key areas for cost-reduction that received attention in this program was net-shape molding of the detailed flow structures according to end-user design. Correlations between feature detail and process parameters were formed so that mold tooling could be accurately designed to meet a variety of flow field dimensions. A cost model was developed that predicted the cost of manufacture for the product in near-term volumes and long-term volumes (10+ million units per year). Because the roduct uses lowcost raw materials in quantities that are less than competitive tech, it was found that the cost of the product in high volume can be less than with other plate echnologies, and can meet the DOE goal of $4/kW for transportation applications. The excellent performance of the all-carbon plate in net shape was verified in fuel cell testing. Performance equivalent to much higher cost, fully machined graphite plates was found.« less

Influences of red blood cell and platelet counts on the distribution and elimination of crystalloid fluid.

PubMed

Hahn, Robert G

2017-01-01

A high number of blood cells increases the viscosity of the blood. The present study explored whether variations in blood cell counts are relevant to the distribution and elimination of infused crystalloid fluid. On three different occasions, 10 healthy male volunteers received an intravenous infusion of 25mL/kg of Ringer's acetate, Ringer's lactate, and isotonic saline over 30min. Blood hemoglobin and urinary excretion were monitored for 4h and used as input in a two-volume kinetic model, using nonlinear mixed effects software. The covariates used in the kinetic model were red blood cell and platelet counts, the total leukocyte count, the use of isotonic saline, and the arterial pressure. Red blood cell and platelet counts in the upper end of the normal range were associated with a decreased rate of distribution and redistribution of crystalloid fluid. Simulations showed that high counts were correlated with volume expansion of the peripheral (interstitial) fluid space, while the plasma volume was less affected. In contrast, the total leukocyte count had no influence on the distribution, redistribution, or elimination. The use of isotonic saline caused a transient reduction in the systolic arterial pressure (P<0.05) and doubled the half-life of infused fluid in the body when compared to the two Ringer solutions. Isotonic saline did not decrease the serum potassium concentration, despite the fact that saline is potassium-free. High red blood cell and platelet counts are associated with peripheral accumulation of infused crystalloid fluid. Copyright © 2017 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Sp. z o.o. All rights reserved.

Pharmacokinetic evidence for improved ophthalmic drug delivery by reduction of instilled volume.

PubMed

Patton, T F

1977-07-01

The bioavailability of topically applied pilocarpine nitrate was studied as a function of instilled volume. As the instilled volume decreased, the fraction of dose absorbed increased. The relationship between fraction absorbed and instilled volume was not direct, but appropriate adjustment of instilled volume and concentration should permit substantial dosage reductions without sacrifice of drug concentration in the eye. The implications of these findings from both a therapeutic and toxicity standpoint are discussed.

TREATABILITY STUDY BULLETIN: MOBILE VOLUME REDUCTION UNIT AT THE SAND CREEK SUPERFUND SITE

EPA Science Inventory

The Risk Reduction Engineering Laboratory (RREL) Releases Control Branch (RCB) has developed a pilot-scale Mobile Volume Reduction Unit (VRU) to determine the feasibility of soil washing for the remediation of contaminated soils. This mobile unit, mounted on two trailers, can pro...

Abscopal effect of boron neutron capture therapy (BNCT): proof of principle in an experimental model of colon cancer.

PubMed

Trivillin, Verónica A; Pozzi, Emiliano C C; Colombo, Lucas L; Thorp, Silvia I; Garabalino, Marcela A; Monti Hughes, Andrea; González, Sara J; Farías, Rubén O; Curotto, Paula; Santa Cruz, Gustavo A; Carando, Daniel G; Schwint, Amanda E

2017-11-01

The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10 6 DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue. The remaining group of 14 tumor-bearing rats were left untreated and used as control. Two weeks post-BNCT, 1 × 10 6 DHD/K12/TRb cells were injected subcutaneously in the contralateral left hind flank of each of the 26 BDIX rats. Tumor volume in both legs was measured weekly for 7 weeks to determine response to BNCT in the right leg and to assess a potential influence of BNCT in the right leg on tumor development in the left leg. Within the BNCT group, a statistically significant reduction was observed in contralateral left tumor volume in animals whose right leg tumor responded to BNCT (post-treatment/pre-treatment tumor volume <1) versus animals who failed to respond (post/pre ≥1), i.e., 13 ± 15 vs 271 ± 128 mm 3 . In addition, a statistically significant reduction in contralateral left leg tumor volume was observed in BNCT-responsive animals (post/pre <1) vs untreated animals, i.e., 13 ± 15 vs 254 ± 251 mm 3 . The present study performed in a simple animal model provides proof of principle that the positive response of a tumor to BNCT is capable of inducing an abscopal effect.

Allium sativum (garlic) treatment for murine transitional cell carcinoma.

PubMed

Riggs, D R; DeHaven, J I; Lamm, D L

1997-05-15

Currently, immunotherapy with Bacillus Calmette-Guerin (BCG) is the most effective treatment for superficial bladder carcinoma, but treatment-related toxicity may limit its use in some patients. Alternative treatments are needed for patients who fail to respond to BCG immunotherapy. Allium sativum (AS), or garlic, is known to have a broad range of biologic activities, including immune stimulation and reported antitumor activity. For these reasons, the authors conducted a series of experiments designed to explore the possible therapeutic effects of AS in the MBT2 murine bladder carcinoma model. C3H/HeN mice were randomized prior to initiation of each experimental protocol. Mice received 1 x 10(3) MBT2 cells in 0.1 mL RPMI-1640, administered subcutaneously into the right thigh, on Day 0 of the experiment. AS was injected at the site of tumor transplantation on Day 1 and at 2- to 7-day intervals up to Day 28. To evaluate the effects of oral AS in this model, treatment was initiated 30 days prior to tumor inoculation and continued for 30 days after tumor inoculation. Animals in all experiments were followed for tumor incidence, tumor growth, and survival. In the initial experiments, subcutaneous AS significantly reduced tumor volume compared with the saline control (P < 0.05). Unfortunately, treatment-related death was also observed, requiring reduction in the total dose of AS. Animals that received 5 weekly immunizations of AS (5 mg, 5 mg, 1 mg, 1 mg, and 1 mg; cumulative dose = 13 mg) had significantly reduced tumor incidence, tumor growth, and increased survival when compared with animals that received the saline control. No treatment-related deaths were observed with this treatment schedule. To determine whether systemic AS administration might be effective, orally administered AS was tested at doses of 5 mg, 50 mg, and 500 mg per 100 mL of drinking water. Mice that received 50 mg oral AS had significant reductions in tumor volume (P < 0.05) when compared with animals that received the saline control, and mice that received 500 mg oral AS had significant reductions in both tumor volume and mortality (P < 0.05). The significant antitumor efficacy of subcutaneous and oral AS warrants further investigation and suggests that AS may provide a new and effective form of therapy for transitional cell carcinoma of the bladder.

Can prostatic arterial embolisation (PAE) reduce the volume of the peripheral zone? MRI evaluation of zonal anatomy and infarction after PAE.

PubMed

Lin, Yen-Ting; Amouyal, Grégory; Correas, Jean-Michel; Pereira, Héléna; Pellerin, Olivier; Del Giudice, Costantino; Déan, Carole; Thiounn, Nicolas; Sapoval, Marc

2016-10-01

To assess the impact of prostatic arterial embolisation (PAE) on various prostate gland anatomical zones. We retrospectively reviewed paired MRI scans obtained before and after PAE for 25 patients and evaluated changes in volumes of the median lobe (ML), central gland (CG), peripheral zone (PZ) and whole prostate gland (WPV) following PAE. We used manual segmentation to calculate volume on axial view T2-weighted images for ML, CG and WPV. We calculated PZ volume by subtracting CG volume from WPV. Enhanced phase on dynamic contrasted-enhanced MRI was used to evaluate the infarction areas after PAE. Clinical results of International Prostate Symptom Score and International Index of Erectile Function questionnaires and the urodynamic study were evaluated before and after PAE. Significant reductions in volume were observed after PAE for ML (26.2 % decrease), CG (18.8 %), PZ (16.4 %) and WPV (19.1 %; p < 0.001 for all these volumes). Patients with clinical failure had smaller volume reductions for WPV, ML and CG (all p < 0.05). Patients with significant CG infarction after PAE displayed larger WPV, ML and CG volume reductions (all p < 0.01). PAE can significantly decrease WPV, ML, CG and PZ volumes, and poor clinical outcomes are associated with smaller volume reductions. • The MRI segmentation method provides detailed comparisons of prostate volume change. • Prostatic arterial embolisation (PAE) decreased central gland and peripheral zone volumes. • Prostates with infarction after PAE showed larger decreases in volume. • A larger decrease in prostate volume is associated with clinical success.

Reduction of variance in spectral estimates for correction of ultrasonic aberration.

PubMed

Astheimer, Jeffrey P; Pilkington, Wayne C; Waag, Robert C

2006-01-01

A variance reduction factor is defined to describe the rate of convergence and accuracy of spectra estimated from overlapping ultrasonic scattering volumes when the scattering is from a spatially uncorrelated medium. Assuming that the individual volumes are localized by a spherically symmetric Gaussian window and that centers of the volumes are located on orbits of an icosahedral rotation group, the factor is minimized by adjusting the weight and radius of each orbit. Conditions necessary for the application of the variance reduction method, particularly for statistical estimation of aberration, are examined. The smallest possible value of the factor is found by allowing an unlimited number of centers constrained only to be within a ball rather than on icosahedral orbits. Computations using orbits formed by icosahedral vertices, face centers, and edge midpoints with a constraint radius limited to a small multiple of the Gaussian width show that a significant reduction of variance can be achieved from a small number of centers in the confined volume and that this reduction is nearly the maximum obtainable from an unlimited number of centers in the same volume.

Dual membrane hollow fiber fuel cell and method of operating same

NASA Technical Reports Server (NTRS)

Ingham, J. D.; Lawson, D. D. (Inventor)

1978-01-01

A gaseous fuel cell is described which includes a pair of electrodes formed by open-ended, ion-exchange hollow fibers, each having a layer of metal catalyst deposited on the inner surface and large surface area current collectors such as braided metal mesh in contact with the metal catalyst layer. A fuel cell results when the electrodes are immersed in electrolytes and electrically connected. As hydrogen and oxygen flow through the bore of the fibers, oxidation and reduction reactions develop an electrical potential. Since the hollow fiber configuration provides large electrode area per unit volume and intimate contact between fuel and oxidizer at the interface, and due to the low internal resistance of the electrolyte, high power densities can be obtained.

Concurrent extraction and reaction for the production of biodiesel from wet microalgae.

PubMed

Im, Hanjin; Lee, HanSol; Park, Min S; Yang, Ji-Won; Lee, Jae W

2014-01-01

This work addresses a reliable in situ transesterification process which integrates lipid extraction from wet microalgae, and its conversion to biodiesel, with a yield higher than 90 wt.%. This process enables single-step production of biodiesel from microalgae by mixing wet microalgal cells with solvent, methanol, and acid catalyst; and then heating them in one pot. The effects of reaction parameters such as reaction temperature, wet cell weight, reaction time, and catalyst volume on the conversion yield are investigated. This simultaneous extraction and transesterification of wet microalgae may enable a significant reduction in energy consumption by eliminating the drying process of algal cells and realize the economic production of biodiesel using wet microalgae. Copyright © 2013 Elsevier Ltd. All rights reserved.

A new approach to kinetics study of the anhydrite crystallization at 373 K using a diamond anvil cell with Raman spectroscopy

NASA Astrophysics Data System (ADS)

Liu, C. J.; Zheng, H. F.

2013-04-01

A new approach to the kinetics study of anhydrite (CaSO4) crystallization has been performed in situ using a hydrothermal diamond anvil cell with Raman spectroscopy in the pressure range 896-1322 MPa and a constant temperature of 373 K. Transformed volume fraction X(t) was determined from Raman peak intensity of the sulfate ion in aqueous solution. The transformation-time plots display a sigmoidal shape with time, which indicates that the reaction rate is different at each stage of anhydrite crystallization. At 373 K, the rate constant k increases from 1.14 × 10-4 s-1 to 1.86 × 10-3 s-1, demonstrating a positive effect of pressure on the overall rate at isothermal condition. We first achieved the molar volume change (ΔVm) equal to -1.82 × 10-5 m3/mol in the course of anhydrite crystallization through Avrami kinetic theory, showing a process of reduction in volume at high pressure and high temperature. According to the exponent n derived from our experiments, a grain-boundary nucleation and diffusion-controlled growth kinetically dominates the crystallization of anhydrite.

Quantification of idiopathic pulmonary fibrosis using computed tomography and histology.

PubMed

Coxson, H O; Hogg, J C; Mayo, J R; Behzad, H; Whittall, K P; Schwartz, D A; Hartley, P G; Galvin, J R; Wilson, J S; Hunninghake, G W

1997-05-01

We used computed tomography (CT) and histologic analysis to quantify lung structure in idiopathic pulmonary fibrosis (IPF). CT scans were obtained from IPF and control patients and lung volumes were estimated from measurements of voxel size, and X-ray attenuation values of each voxel. Quantitative estimates of lung structure were obtained from biopsies obtained from diseased and normal CT regions using stereologic methods. CT density was used to calculate the proportion of tissue and air, and this value was used to correct the biopsy specimens to the level of inflation during the CT scan. The data show that IPF is associated with a reduction in airspace volume with no change in tissue volume or weight compared with control lungs. Lung surface area decreased two-thirds (p < 0.001) and mean parenchymal thickness increased tenfold (p < 0.001). An exudate of fluid and cells was present in the airspace of the diseased lung regions and the number of inflammatory cells, collagen, and proteoglycans was increased per 100 g of tissue in IPF. We conclude that IPF reorganized lung tissue content causing a loss of airspace and surface area without increasing the total lung tissue.

Production of Concentrated Pickering Emulsions with Narrow Size Distributions Using Stirred Cell Membrane Emulsification.

PubMed

Manga, Mohamed S; York, David W

2017-09-12

Stirred cell membrane emulsification (SCME) has been employed to prepare concentrated Pickering oil in water emulsions solely stabilized by fumed silica nanoparticles. The optimal conditions under which highly stable and low-polydispersity concentrated emulsions using the SCME approach are highlighted. Optimization of the oil flux rates and the paddle stirrer speeds are critical to achieving control over the droplet size and size distribution. Investigating the influence of oil volume fraction highlights the criticality of the initial particle loading in the continuous phase on the final droplet size and polydispersity. At a particle loading of 4 wt %, both the droplet size and polydispersity increase with increasing of the oil volume fraction above 50%. As more interfacial area is produced, the number of particles available in the continuous phase diminishes, and coincidently a reduction in the kinetics of particle adsorption to the interface resulting in larger polydisperse droplets occurs. Increasing the particle loading to 10 wt % leads to significant improvements in both size and polydispersity with oil volume fractions as high as 70% produced with coefficient of variation values as low as ∼30% compared to ∼75% using conventional homogenization techniques.

Comparison of Blood Loss in Laser Lipolysis vs Traditional Liposuction.

PubMed

Abdelaal, Mohammed Mahmoud; Aboelatta, Yasser Abdallah

2014-08-01

Laser-assisted liposuction has been associated with reduced blood loss. However, this clinical finding has not been evaluated objectively. In this study, the authors objectively estimated the blood loss volume associated with laser lipolysis vs traditional liposuction in various anatomic regions. In this prospective study, 56 patients underwent equal amounts of traditional and laser-assisted liposuction at 2 contralateral anatomic sites. Blood loss volumes were calculated from the lipoaspirates by measuring hemoglobin and red blood cell content. The data were analyzed statistically with repeated-measures analysis of variance and the Mann-Whitney U test. Laser lipolysis can reduce blood loss by more than 50% compared with traditional liposuction. Laser lipolysis resulted in significant reductions in mean blood loss volumes in the abdomen, flanks, back, and breast. The authors provide objective evidence that laser lipolysis significantly reduces blood loss compared with traditional liposuction. 3. © 2014 The American Society for Aesthetic Plastic Surgery, Inc.

Hippocampal volume in healthy controls given 3-day stress doses of hydrocortisone.

PubMed

Brown, E Sherwood; Jeon-Slaughter, Haekyung; Lu, Hanzhang; Jamadar, Rhoda; Issac, Sruthy; Shad, Mujeeb; Denniston, Daren; Tamminga, Carol; Nakamura, Alyson; Thomas, Binu P

2015-03-13

In animal models, corticosterone elevations are associated with hippocampal changes that can be prevented with phenytoin. In humans, Cushing's syndrome and long-term prescription corticosteroid use are associated with a reduction in the hippocampal volume. However, little is known about the effects of short-term corticosteroid administration on the hippocampus. The current report examines changes in the hippocampal volume during a brief hydrocortisone exposure and whether volumetric changes can be blocked by phenytoin. A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in healthy adults (n=17). Participants received hydrocortisone (160 mg/day)/placebo, phenytoin/placebo, both medications together, or placebo/placebo, with 21-day washouts between the conditions. Structural MRI scans and cortisol levels were obtained following each medication condition. No significant difference in the total brain volume was observed with hydrocortisone. However, hydrocortisone was associated with a significant 1.69% reduction in the total hippocampal volume compared with placebo. Phenytoin blocked the volume reduction associated with hydrocortisone. Reduction in hippocampal volume correlated with the change in cortisol levels (r=-0.58, P=0.03). To our knowledge, this is the first report of structural hippocampal changes with brief corticosteroid exposure. The correlation between the change in hippocampal volume and cortisol level suggests that the volume changes are related to cortisol elevation. Although the findings from this pilot study need replication, they suggest that the reductions in hippocampal volume occur even during brief exposure to corticosteroids, and that hippocampal changes can, as in animal models, be blocked by phenytoin. The results may have implications both for understanding the response of the hippocampus to stress as well as for patients receiving prescription corticosteroids.

Hippocampal Volume in Healthy Controls Given 3-Day Stress Doses of Hydrocortisone

PubMed Central

Brown, E Sherwood; Jeon-Slaughter, Haekyung; Lu, Hanzhang; Jamadar, Rhoda; Issac, Sruthy; Shad, Mujeeb; Denniston, Daren; Tamminga, Carol; Nakamura, Alyson; Thomas, Binu P

2015-01-01

In animal models, corticosterone elevations are associated with hippocampal changes that can be prevented with phenytoin. In humans, Cushing's syndrome and long-term prescription corticosteroid use are associated with a reduction in the hippocampal volume. However, little is known about the effects of short-term corticosteroid administration on the hippocampus. The current report examines changes in the hippocampal volume during a brief hydrocortisone exposure and whether volumetric changes can be blocked by phenytoin. A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in healthy adults (n=17). Participants received hydrocortisone (160 mg/day)/placebo, phenytoin/placebo, both medications together, or placebo/placebo, with 21-day washouts between the conditions. Structural MRI scans and cortisol levels were obtained following each medication condition. No significant difference in the total brain volume was observed with hydrocortisone. However, hydrocortisone was associated with a significant 1.69% reduction in the total hippocampal volume compared with placebo. Phenytoin blocked the volume reduction associated with hydrocortisone. Reduction in hippocampal volume correlated with the change in cortisol levels (r=−0.58, P=0.03). To our knowledge, this is the first report of structural hippocampal changes with brief corticosteroid exposure. The correlation between the change in hippocampal volume and cortisol level suggests that the volume changes are related to cortisol elevation. Although the findings from this pilot study need replication, they suggest that the reductions in hippocampal volume occur even during brief exposure to corticosteroids, and that hippocampal changes can, as in animal models, be blocked by phenytoin. The results may have implications both for understanding the response of the hippocampus to stress as well as for patients receiving prescription corticosteroids. PMID:25409592

Ultrasound-guided microwave ablation in the treatment of benign thyroid nodules in 435 patients

PubMed Central

Qian, Lin-Xue; Liu, Dong; Zhao, Jun-Feng

2017-01-01

The objective of the present study was to investigate the effectiveness and safety of ultrasound-guided microwave ablation in the treatment of benign thyroid nodules. A total of 474 benign thyroid nodules in 435 patients who underwent ultrasound-guided microwave ablation from September 2012 to August 2015 were included. Nodule volume and thyroid function were measured before treatment and at 1, 3, 6, and 12 months and subsequently after every 6 months. The nodule volume reduction rate and changes of thyroid function were evaluated. The volume of all thyroid nodules significantly decreased after ultrasound-guided microwave ablation. The average volume was 13.07 ± 0.95 ml before treatment, and 1.14 ± 0.26 ml at 12-months follow-up. The mean volume reduction rate was 90% and the final volume reduction rate was 94%. The volume reduction rate of mainly cystic nodules was significantly higher than that of simple solid and mainly solid nodules (all P < 0.05). The pretreatment volume of nodules was positively correlated with the final volume reduction rate at final follow-up (P = 0.004). No serious complications were observed after treatment. In conclusion, ultrasound-guided microwave ablation is an effective and safe technique for treatment of benign thyroid nodules, and has the potential for clinical applications. Impact statement Ultrasound-guided MWA is an effective and safe technique for the treatment of benign thyroid nodules. It can significantly reduce the nodule volume, improve the patients’ clinical symptoms, has less complication, guarantees quick recovery, meets patients' aesthetic needs, and shows less interference on the physiological and psychological aspects of the body. MWA should be a good complement to traditional open surgery and has potentials in clinical applications. PMID:28847173

Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity, Cognition and Antipsychotic Medication

PubMed Central

Veijola, Juha; Guo, Joyce Y.; Moilanen, Jani S.; Jääskeläinen, Erika; Miettunen, Jouko; Kyllönen, Merja; Haapea, Marianne; Huhtaniska, Sanna; Alaräisänen, Antti; Mäki, Pirjo; Kiviniemi, Vesa; Nikkinen, Juha; Starck, Tuomo; Remes, Jukka J.; Tanskanen, Päivikki; Tervonen, Osmo; Wink, Alle-Meije; Kehagia, Angie; Suckling, John; Kobayashi, Hiroyuki; Barnett, Jennifer H.; Barnes, Anna; Koponen, Hannu J.; Jones, Peter B.; Isohanni, Matti; Murray, Graham K.

2014-01-01

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions. PMID:25036617

Ultrasound-guided microwave ablation in the treatment of benign thyroid nodules in 435 patients.

PubMed

Liu, Yu-Jiang; Qian, Lin-Xue; Liu, Dong; Zhao, Jun-Feng

2017-09-01

The objective of the present study was to investigate the effectiveness and safety of ultrasound-guided microwave ablation in the treatment of benign thyroid nodules. A total of 474 benign thyroid nodules in 435 patients who underwent ultrasound-guided microwave ablation from September 2012 to August 2015 were included. Nodule volume and thyroid function were measured before treatment and at 1, 3, 6, and 12 months and subsequently after every 6 months. The nodule volume reduction rate and changes of thyroid function were evaluated. The volume of all thyroid nodules significantly decreased after ultrasound-guided microwave ablation. The average volume was 13.07 ± 0.95 ml before treatment, and 1.14 ± 0.26 ml at 12-months follow-up. The mean volume reduction rate was 90% and the final volume reduction rate was 94%. The volume reduction rate of mainly cystic nodules was significantly higher than that of simple solid and mainly solid nodules (all P < 0.05). The pretreatment volume of nodules was positively correlated with the final volume reduction rate at final follow-up ( P = 0.004). No serious complications were observed after treatment. In conclusion, ultrasound-guided microwave ablation is an effective and safe technique for treatment of benign thyroid nodules, and has the potential for clinical applications. Impact statement Ultrasound-guided MWA is an effective and safe technique for the treatment of benign thyroid nodules. It can significantly reduce the nodule volume, improve the patients' clinical symptoms, has less complication, guarantees quick recovery, meets patients' aesthetic needs, and shows less interference on the physiological and psychological aspects of the body. MWA should be a good complement to traditional open surgery and has potentials in clinical applications.

Neuronal cell reconstruction with umbilical cord blood cells in the brain hypoxia-ischemia.

PubMed

Ghaffaripour, Hossein Ali; Jalali, Mehdi; Nikravesh, Mohammad Reza; Seghatoleslam, Masoumeh; Sanchooli, Javad

2015-01-01

Brain hypoxia-ischemia is a human neonatal injury that is considered a candidate for stem cell therapy. The possible therapeutic potential of human umbilical cord blood (HUCB) stem cells was evaluated in 14-day-old rats subjected to the right common carotid occlusion, a model of neonatal brain hypoxia-ischemia. Seven days after hypoxia-ischemia, rats received either saline solution or 4 × 105 HUCB cells i.v. Rats in control group did not receive any injection. After two weeks, rats were assessed using two motor tests. Subsequently, rats were scarified for histological and immunohistochemical analyses. Our immunohistochemical findings demonstrated selective migration of the injected HUCB cells to the ischemic area as well as reduction in infarct volume. Seven days after surgery, we found significant recovery in the behavioral performance in the test group (12.7 +/- 0.3) compared to the sham group (10.0 +/-0.05), a trend which continued to day 14 (15.3 ± 0.3 vs. 11.9 ± 0.5, P<0.05). Postural and motor asymmetries at days 7 and 14 in the test group showed a significant decrease in the percentage of right turns in comparison to the sham group (75% and 59% vs. 97% and 96%, P<0.05). The results show the potential of HUCB stem cells in reduction of neurologic deficits associated with neonatal hypoxia-ischemia.

Solar silicon via the Dow Corning process

NASA Technical Reports Server (NTRS)

Hunt, L. P.; Dosaj, V. D.

1979-01-01

Technical feasibility for high volume production of solar cell-grade silicon is investigated. The process consists of producing silicon from pure raw materials via the carbothermic reduction of quartz. This silicon was then purified to solar grade by impurity segregation during Czochralski crystal growth. Commercially available raw materials were used to produce 100 kg quantities of silicon during 60 hour periods in a direct arc reactor. This silicon produced single crystalline ingot, during a second Czochralski pull, that was fabricated into solar cells having efficiencies ranging from 8.2 percent to greater than 14 percent. An energy analysis of the entire process indicated a 5 month payback time.

Gas-phase mercury reduction to measure total mercury in the flue gas of a coal-fired boiler.

PubMed

Meischen, Sandra J; Van Pelt, Vincent J; Zarate, Eugene A; Stephens, Edward A

2004-01-01

Gaseous elemental and total (elemental + oxidized) mercury (Hg) in the flue gas from a coal-fired boiler was measured by a modified ultraviolet (UV) spectrometer. Challenges to Hg measurement were the spectral interferences from other flue gas components and that UV measures only elemental Hg. To eliminate interference from flue gas components, a cartridge filled with gold-coated sand removed elemental Hg from a flue gas sample. The Hg-free flue gas was the reference gas, eliminating the spectral interferences. To measure total Hg by UV, oxidized Hg underwent a gas-phase, thermal-reduction in a quartz cell heated to 750 degrees C. Simultaneously, hydrogen was added to flash react with the oxygen present forming water vapor and preventing Hg re-oxidation as it exits the cell. Hg concentration results are in parts per billion by volume Hg at the flue gas oxygen concentration. The modified Hg analyzer and the Ontario Hydro method concurrently measured Hg at a field test site. Measurements were made at a 700-MW steam turbine plant with scrubber units and selective catalytic reduction. The flue gas sampled downstream of the selective catalytic reduction contained 2100 ppm SO2 and 75 ppm NOx. Total Hg measured by the Hg analyzer was within 20% of the Ontario Hydro results.

A highly efficient electrocatalyst for oxygen reduction reaction: phosphorus and nitrogen co-doped hierarchically ordered porous carbon derived from an iron-functionalized polymer

NASA Astrophysics Data System (ADS)

Deng, Chengwei; Zhong, Hexiang; Li, Xianfeng; Yao, Lan; Zhang, Huamin

2016-01-01

Heteroatom-doped carbon materials have shown respectable activity for the oxygen reduction reaction (ORR) in alkaline media. However, the performances of these materials are not satisfactory for energy conversion devices, such as fuel cells. Here, we demonstrate a new type of phosphorus and nitrogen co-doped hierarchically ordered porous carbon (PNHOPC) derived from an iron-functionalized mesoporous polymer through an evaporation-induced self-assembly process that simultaneously combines the carbonization and nitrogen doping processes. The soft template and the nitrogen doping process facilitate the formation of the hierarchically ordered structure for the PNHOPC. The catalyst possesses a large surface area (1118 cm2 g-1) and a pore volume of 1.14 cm3 g-1. Notably, it exhibits excellent ORR catalytic performance, superior stability and methanol tolerance in acidic electrolytes, thus making the catalyst promising for fuel cells. The correlations between the unique pore structure and the nitrogen and phosphorus configuration of the catalysts with high catalytic activity are thoroughly investigated.Heteroatom-doped carbon materials have shown respectable activity for the oxygen reduction reaction (ORR) in alkaline media. However, the performances of these materials are not satisfactory for energy conversion devices, such as fuel cells. Here, we demonstrate a new type of phosphorus and nitrogen co-doped hierarchically ordered porous carbon (PNHOPC) derived from an iron-functionalized mesoporous polymer through an evaporation-induced self-assembly process that simultaneously combines the carbonization and nitrogen doping processes. The soft template and the nitrogen doping process facilitate the formation of the hierarchically ordered structure for the PNHOPC. The catalyst possesses a large surface area (1118 cm2 g-1) and a pore volume of 1.14 cm3 g-1. Notably, it exhibits excellent ORR catalytic performance, superior stability and methanol tolerance in acidic electrolytes, thus making the catalyst promising for fuel cells. The correlations between the unique pore structure and the nitrogen and phosphorus configuration of the catalysts with high catalytic activity are thoroughly investigated. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06749a

Reduction of high-energy shock-wave-induced renal tubular injury by selenium.

PubMed

Strohmaier, W L; Lahme, S; Weidenbach, P M; Bichler, K H

1999-10-01

In shock-wave-induced renal injury cavitation-generated free radicals play an important role. Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we investigated the influence of selenium, a free radical scavenger, in shock-wave-induced tubular cell injury. Suspensions of MDCK cells (33 x 10(6) cells/ml) were placed in small containers (volume 1.1 ml) for shock wave exposure. Two groups of 12 containers each were examined: (1) control (no medication), (2) selenium (0.4 microg/ml nutrient medium). Six containers in each group were exposed to shock waves (impulse rate 256, frequency 60 Hz, generator voltage 18 kV), while the other six containers in each group served as a control. After shock wave exposure, the concentration of cellular enzymes such as lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), glutamate oxaloacetate transaminase (GOT) and glutamate lactate dehydrogenase (GLDH) in the nutrient medium was examined. Following shock wave exposure there was a significant rise in LDH, NAG, GOT and GLDH concentrations. Selenium reduced this enzyme leakage significantly. Thus we conclude that selenium protects renal tubular cells against shock-wave-induced injury. Since selenium is an essential part of glutathione peroxidase, this effect seems to be mediated by a reduction in reactive oxygen species.

Reducing the Viscosity of Blood by Pulsed Magnetic Field

NASA Astrophysics Data System (ADS)

Tao, R.; Huang, K.

2010-03-01

Blood viscosity is a major player in heart disease. When blood is viscous, in addition to a high blood pressure required for the blood circulation, blood vessel walls are also easy to be damaged. While this issue is very important, currently the only method to reduce the blood viscosity is to take medicine, such as aspirin. Here we report our new finding that the blood viscosity can be reduced by pulsed magnetic field. Blood is a suspension of red blood cells (erythrocytes), white blood cells (leukocytes) and platelets in plasma, a complex solution of gases, salts, proteins, carbohydrates, and lipids. The base liquid, plasma, has low viscosity. The effective viscosity of whole blood increases mainly due to the red blood cells, which have a volume fraction about 40% or above. Red blood cells contain iron and are sensitive to magnetic field. Therefore, when we apply a strong magnetic field, the red cells make their diameters align in the field direction to form short chains. This change in rheology reduces the effective viscosity as high as 20-30%. While this reduction is not permanent, it lasts for several hours and repeatable. The reduction rate can be controlled by selecting suitable magnetic field and duration of field application to make blood viscosity within the normal range.

Influence of ozonation and biodegradation on toxicity of industrial textile wastewater.

PubMed

Paździor, Katarzyna; Wrębiak, Julita; Klepacz-Smółka, Anna; Gmurek, Marta; Bilińska, Lucyna; Kos, Lech; Sójka-Ledakowicz, Jadwiga; Ledakowicz, Stanisław

2017-06-15

The textile industry demands huge volumes of high quality water which converts into wastewater contaminated by wide spectrum of chemicals. Estimation of textile wastewater influence on the aquatic systems is a very important issue. Therefore, closing of the water cycle within the factories is a promising method of decreasing its environmental impact as well as operational costs. Taking both reasons into account, the aim of this work was to establish the acute toxicity of the textile wastewater before and after separate chemical, biological as well as combined chemical-biological treatment. For the first time the effects of three different combinations of chemical and biological methods were investigated. The acute toxicity analysis were evaluated using the Microtox ® toxicity test. Ozonation in two reactors of working volume 1 dm 3 (stirred cell) and 20 dm 3 (bubble column) were tested as chemical process, while biodegradation was conducted in two, different systems - Sequence Batch Reactors (SBR; working volume 1.5 dm 3 ) and Horizontal Continuous Flow Bioreactor (HCFB; working volume 12 dm 3 ). The untreated wastewater had the highest toxicity (EC50 value in range: 3-6%). Ozonation caused lower reduction of the toxicity than biodegradation. In the system with SBR the best results were obtained for the biodegradation followed by the ozonation and additional biodegradation - 96% of the toxicity removal. In the second system (with HCFB) two-stage treatment (biodegradation followed by the ozonation) led to the highest toxicity reduction (98%). Copyright © 2016 Elsevier Ltd. All rights reserved.

Postnatal day 7 ethanol treatment causes persistent reductions in adult mouse brain volume and cortical neurons with sex specific effects on neurogenesis

PubMed Central

Coleman, Leon G.; Oguz, Ipek; Lee, Joohwi; Styner, Martin; Crews, Fulton T.

2013-01-01

Ethanol treatment on postnatal day seven (P7) causes robust brain cell death and is a model of late gestational alcohol exposure (Ikonomidou et al., 2000). To investigate the long-term effects of P7 ethanol treatment on adult brain, mice received either two doses of saline or ethanol on P7 (2.5g/kg, s.c., 2 hours apart) and were assessed as adults (P82) for brain volume (using postmortem MRI) and cellular architecture (using immunohistochemistry). Adult mice that received P7 ethanol had reduced MRI total brain volume (4%) with multiple brain regions being reduced in both males and females. Immunohistochemistry indicated reduced frontal cortical parvalbumin immunoreactive (PV+IR) interneurons (18-33%) and reduced Cux1+IR layer II pyramidal neurons (15%) in both sexes. Interestingly, markers of adult hippocampal neurogenesis differed between sexes, with only ethanol treated males showing increased doublecortin and Ki67 expression (52 and 57% respectively) in the dentate gyrus, consistent with increased neurogenesis compared to controls. These findings suggest that P7 ethanol treatment causes persistent reductions in adult brain volume and frontal cortical neurons in both males and females. Increased adult neurogenesis in males, but not females, is consistent with differential adaptive responses to P7 ethanol toxicity between the sexes. One day of ethanol exposure, e.g. P7, causes persistent adult brain dysmorphology. PMID:22572057

Potential means of cost reduction in grade crossing automatic gate systems. volume II : improved gate arm concepts for railroad/highway grade crossings gate systems

DOT National Transportation Integrated Search

1977-02-28

This report, Volume II of a two-volume study, examines the potential for reduction of the cost of installing and maintaining automatic gates at railroad-highway grade crossings. It includes a review of current practices, equipment, and standards; con...

Potential means of cost reduction in grade crossing automatic gate systems. volume I : overview and low cost railroad/highway grade crossing gate systems

DOT National Transportation Integrated Search

1977-02-28

This report, Volume I of a two-volume study, examines the potential for reduction of the cost of installing and maintaining automatic gates at railroad-highway grade crossings. It comprises a general overview; a review of current practices, equipment...

A simple method to determine evaporation and compensate for liquid losses in small-scale cell culture systems.

PubMed

Wiegmann, Vincent; Martinez, Cristina Bernal; Baganz, Frank

2018-04-24

Establish a method to indirectly measure evaporation in microwell-based cell culture systems and show that the proposed method allows compensating for liquid losses in fed-batch processes. A correlation between evaporation and the concentration of Na + was found (R 2  = 0.95) when using the 24-well-based miniature bioreactor system (micro-Matrix) for a batch culture with GS-CHO. Based on these results, a method was developed to counteract evaporation with periodic water additions based on measurements of the Na + concentration. Implementation of this method resulted in a reduction of the relative liquid loss after 15 days of a fed-batch cultivation from 36.7 ± 6.7% without volume corrections to 6.9 ± 6.5% with volume corrections. A procedure was established to indirectly measure evaporation through a correlation with the level of Na + ions in solution and deriving a simple formula to account for liquid losses.

Documentation of normal and leukemic myelopoietic progenitor cells with high-resolution phase-contrast time-lapse cinematography.

PubMed

Boll, I T

2001-08-01

The high-resolution phase-contrast, time-lapse cinematography using oil immersion lenses and 16-mm film demonstrates the kinetic cell events as maturation, locomotion, mitosis, and apoptosis of cells cultivated at 37 degrees C for up to 10 days. 0.5 v/v frozen-thawed sera with presumably high cytokine concentrations were added to the plasma or agar clot. Vital progenitor cells from human bone marrow and blood have a large, bright, unstructured nucleus with a large nucleolus and a narrow rim of cytoplasm (nuclear/cytoplasmic volume ratio = 0.7). Their nuclei are 6-14 micrometer in diameter and double their volume within 8 h. Many (70%) move at a mean speed of 2 micrometer/min, and many (30%) multiply with alpha-2alpha mitoses, generating progenitor cell families. Various disturbances during the course of mitosis lead to the formation of polyploid cells, thereby yielding the megakaryocytic cell line. Some of the progenitor cells undergo asymmetric alpha-alphan mitoses: One of the two initially identical daughter cells remains a progenitor cell in the morphological sense, whereas the other daughter cell - depending on the size of its mother cell - matures in the same culture medium to form a granulocytopoietic, monocytopoietic or erythrocytopoietic cell line. - In acute myeloid leukemias (AML), the blasts and their nuclei are slightly larger than the corresponding progenitor cells and move faster (5 micrometer/min). Symmetric alpha-2alpha mitoses permit unlimited multiplication of the leukemic blasts if contact with cytotoxic lymphocytes does not render them apoptotic. This results in more stromal cells than normal. Granulocytopenia, monocytopenia, and anemia occur due to the genetic impairment of signaling control for asymmetric alpha-alphan mitoses, and thrombocytopenia occurs due to the reduction in polyploidization. Copyright 2001 S. Karger GmbH, Freiburg

Neuroprotectin D1 Attenuates Laser-induced Choroidal Neovascularization in Mouse

PubMed Central

Sheets, Kristopher G.; Zhou, Yongdong; Ertel, Monica K.; Knott, Eric J.; Regan, Cornelius E.; Elison, Jasmine R.; Gordon, William C.; Gjorstrup, Per

2010-01-01

Purpose To examine the effects of neuroprotectin D1 (NPD1), a stereospecific derivative of docosahexaenoic acid, on choroidal neovascularization (CNV) in a laser-induced mouse model. Specifically, this was assessed by clinically grading laser-induced lesions, measuring leakage area, and volumetrically quantifying vascular endothelial cell proliferation. Methods C57Bl/6 mice were treated with vehicle control or NPD1, and choroidal neovascularization was induced by laser rupture of Bruch's membrane; treatment was administered throughout the first week of recovery. One and two weeks after CNV induction, fundus fluorescein angiography was performed. Angiograms were clinically graded to assess leakage severity, while leakage area was measured by image analysis of angiograms. Proliferation of vascular endothelial cells was evaluated volumetrically by three-dimensional laser confocal immunofluorescent microscopy of cytoskeletal, nuclear, and endothelial cell markers. Results At seven days after CNV induction, NPD1-treated mice had 60% fewer clinically relevant lesions than controls, dropping to 80% fewer by 14 days. NPD1 mice exhibited 25% smaller leakage area than controls at 7 days and 44% smaller area at 14 days. Volumetric immunofluorescence revealed 46% less vascular endothelial cell volume in 7-day NPD1-treated mice than in 7-day controls, and by 14 days NPD1 treatment was 68% lower than controls. Furthermore, comparison of 7- and 14-day volumes of NPD1-treated mice revealed a 50% reduction at 14 days. Conclusions NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-κB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be effective after treatment is concluded, suggesting sustained protection and highlighting the potential applicability of this lipid mediator in preventing or ameliorating endothelial cell growth in pathoangiogenesis. PMID:20216940

In situ transmission electron microscopic observations of redox cycling of a Ni-ScSZ cermet fuel cell anode.

PubMed

Matsuda, Junko; Kawasaki, Tatsuya; Futamura, Shotaro; Kawabata, Tsutomu; Taniguchi, Shunsuke; Sasaki, Kazunari

2018-05-19

In situ transmission electron microscopy (TEM) observations of a Ni(O)-Sc2O3-stabilized ZrO2 (ScSZ; 10 mol% Sc2O3, 1 mol% CeO2, 89 mol% ZrO2) anode in a solid oxide fuel cell (SOFC) have been performed at high temperatures under a hydrogen/oxygen gas atmosphere using an environmental transmission electron microscope (ETEM); the specimens were removed from cross-sections of the real SOFC by focused ion beam milling and lifting. When heating the NiO-ScSZ anode under a hydrogen atmosphere of 3 mbar in ETEM, nano-pores were formed at the grain boundaries and on the surface of NiO particles at around 400°C due to the volume shrinkage accompanying the reduction of NiO to Ni. Moreover, densification of Ni occurred when increasing the temperature from 600 to 700°C. High-magnification TEM images obtained in the early stages of NiO reduction revealed that the (111) planes of Ni grew almost parallel to the (111) planes of NiO. In the case of heating Ni-ScSZ under an oxygen atmosphere of 3 mbar in ETEM, oxidation of Ni starting from the surface of the particles occurred above 300°C. All Ni particles became polycrystalline NiO after the temperature was increased to 800°C. Volume expansion/contraction by mass transfer to the outside/inside of the Ni particles in the anode during repeated oxidation/reduction seems to result in the agglomeration of Ni catalysts during long-term SOFC operation. We emphasize that our in situ TEM observations will be applied to observe electrochemical reactions in SOFCs under applied electric fields.

Natural Arctium lappa fruit extract improves the clinical signs of aging skin.

PubMed

Knott, Anja; Reuschlein, Katja; Mielke, Heiko; Wensorra, Ursula; Mummert, Christopher; Koop, Urte; Kausch, Martina; Kolbe, Ludger; Peters, Nils; Stäb, Franz; Wenck, Horst; Gallinat, Stefan

2008-12-01

Subclinical, chronic tissue inflammation involving the generation of cytokines (e.g., interleukin-6 and tumor necrosis factor-alpha) might contribute to the cutaneous aging process. This study aims to screen for an active ingredient with anti-inflammatory (i.e., reduction of interleukin-6 and tumor necrosis factor-alpha) and matrix-stimulating efficacy which improves the clinical signs of skin aging in vivo. In vitro studies with pure Arctiin were performed investigating the inhibition of cytokine induction and stimulation of collagen neo-synthesis. In vivo home-in-use studies using an Arctium lappa fruit extract-containing formulation were carried out to determine procollagen and hyaluronan synthesis, hyaluronan synthase-2 gene expression, and reduction of wrinkle volume after treatment. In vitro studies on human dermal fibroblasts and monocyte-derived dendritic cells supplemented with pure Arctiin showed relative to untreated control cells a stimulation of collagen synthesis and a decrease in interleukin-6 and tumor necrosis factor-alpha concentration, respectively. In addition, topical in vivo application of an A. lappa fruit extract-containing formulation for 12 weeks significantly stimulated procollagen synthesis and increased hyaluronan synthase-2 expression as well as hyaluronan levels compared to vehicle-treated control areas. Similarly, after a 4-week treatment with an A. lappa fruit extract-containing formulation, wrinkle volume in the crow's feet area was significantly reduced as compared to treatment with the vehicle. Our data show that topical treatment with a natural A. lappa fruit extract significantly improves the metabolism of the dermal extracellular matrix and leads to a visible wrinkle reduction in vivo. In conclusion, A. lappa fruit extract represents a targeted means to regenerate dermal structures and, thus, offers an effective treatment option for mature skin.

Telomere maintenance in laser capture microdissection-purified Barrett's adenocarcinoma cells and effect of telomerase inhibition in vivo.

PubMed

Shammas, Masood A; Qazi, Aamer; Batchu, Ramesh B; Bertheau, Robert C; Wong, Jason Y Y; Rao, Manjula Y; Prasad, Madhu; Chanda, Diptiman; Ponnazhagan, Selvarangan; Anderson, Kenneth C; Steffes, Christopher P; Munshi, Nikhil C; De Vivo, Immaculata; Beer, David G; Gryaznov, Sergei; Weaver, Donald W; Goyal, Raj K

2008-08-01

The aims of this study were to investigate telomere function in normal and Barrett's esophageal adenocarcinoma (BEAC) cells purified by laser capture microdissection and to evaluate the effect of telomerase inhibition in cancer cells in vitro and in vivo. Epithelial cells were purified from surgically resected esophagi. Telomerase activity was measured by modified telomeric repeat amplification protocol and telomere length was determined by real-time PCR assay. To evaluate the effect of telomerase inhibition, adenocarcinoma cell lines were continuously treated with a specific telomerase inhibitor (GRN163L) and live cell number was determined weekly. Apoptosis was evaluated by Annexin labeling and senescence by beta-galactosidase staining. For in vivo studies, severe combined immunodeficient mice were s.c. inoculated with adenocarcinoma cells and following appearance of palpable tumors, injected i.p. with saline or GRN163L. Telomerase activity was significantly elevated whereas telomeres were shorter in BEAC cells relative to normal esophageal epithelial cells. The treatment of adenocarcinoma cells with telomerase inhibitor, GRN163L, led to loss of telomerase activity, reduction in telomere length, and growth arrest through induction of both the senescence and apoptosis. GRN163L-induced cell death could also be expedited by addition of the chemotherapeutic agents doxorubicin and ritonavir. Finally, the treatment with GRN163L led to a significant reduction in tumor volume in a subcutaneous tumor model. We show that telomerase activity is significantly elevated whereas telomeres are shorter in BEAC and suppression of telomerase inhibits proliferation of adenocarcinoma cells both in vitro and in vivo.

The use of a computerized algorithm to determine single cardiac cell volumes.

PubMed

Marino, T A; Cook, L; Cook, P N; Dwyer, S J

1981-04-01

Single cardiac muscles cell volume data have been difficult to obtain, especially because the shape of a cell is quite complex. With the aid of a surface reconstruction method, a cell volume estimation algorithm has been developed that can be used on serial of cells. The cell surface is reconstructed by means of triangular tiles so that the cell is represented as a polyhedron. When this algorithm was tested on computer generated surfaces of a known volume, the difference was less than 1.6%. Serial sections of two phantoms of a known volume were also reconstructed and a comparison of the mathematically derived volumes and the computed volume estimations gave a per cent difference of between 2.8% and 4.1%. Finally cell volumes derived using conventional methods and volumes calculated using the algorithm were compared. The mean atrial muscle cell volume derived using conventional methods was 7752.7 +/- 644.7 micrometers3, while the mean computerized algorithm estimated atrial muscle cell volume was 7110.6 +/- 625.5 micrometers3. For AV bundle cells the mean cell volume obtained by conventional methods was 484.4 +/- 88.8 micrometers3 and the volume derived from the computer algorithm was 506.0 +/- 78.5 micrometers3. The differences between the volumes calculated using conventional methods and the algorithm were not significantly different.

Prostaglandin E2 stimulates a Ca2+-dependent K+ channel in human erythrocytes and alters cell volume and filterability.

PubMed

Li, Q; Jungmann, V; Kiyatkin, A; Low, P S

1996-08-02

To understand the mechanism by which human red blood cells (RBCs) contribute to hemostasis and thrombosis, we have examined the effects of metabolites released by activated platelets on intact RBCs. Prostaglandin E2 (PGE2), a signal molecule produced by activated platelets, was observed to lower the filterability of human erythrocytes by approximately 30% at 10(-10) M. PGE2 also caused a reduction in mean cell volume of approximately 10%. The shrinkage of red cells after PGE2 treatment was confirmed by documenting a decrease in osmotic fragility and an increase in cell density following exposure to the hormone. Careful analysis, however, revealed that only approximately 15% of the erythrocytes responded to stimulation with PGE2. Examination of the cause of cell shrinkage showed that induction of a PGE2-stimulated K+ efflux pathway leading to rapid loss of cellular K+ was responsible. The PGE2-stimulated K+ loss was also observed to be Ca2+-dependent, suggesting the possible involvement of the Gardos channel. Gardos channel participation was supported by the observation that two Gardos channel inhibitors, charybdotoxin and clotrimazole, independently blocked the PGE2-stimulated K+ efflux. Further evidence for Gardos channel activation came from experiments aimed at characterizing the efflux pathway followed by the obligatory counterion. Thus, K+ efflux was readily stimulated even when NO3- was substituted for Cl-, suggesting that neither KCl cotransport nor Na/K/2Cl cotransport plays a prominent role in the PGE2-induced cell shrinkage. Further, the anion transporter band 3 was implicated as the counterion efflux route, since DIDS inhibited the PGE2-stimulated cell volume change without blocking the change in membrane potential. Taken together, we propose that release of PGE2 by activated platelets constitutes part of a mechanism by which activated platelets may recruit adjacent erythrocytes to assist in clot formation.

Cardiovascular consequences of bed rest: effect on maximal oxygen uptake

NASA Technical Reports Server (NTRS)

Convertino, V. A.

1997-01-01

Maximal oxygen uptake (VO2max) is reduced in healthy individuals confined to bed rest, suggesting it is independent of any disease state. The magnitude of reduction in VO2max is dependent on duration of bed rest and the initial level of aerobic fitness (VO2max), but it appears to be independent of age or gender. Bed rest induces an elevated maximal heart rate which, in turn, is associated with decreased cardiac vagal tone, increased sympathetic catecholamine secretion, and greater cardiac beta-receptor sensitivity. Despite the elevation in heart rate, VO2max is reduced primarily from decreased maximal stroke volume and cardiac output. An elevated ejection fraction during exercise following bed rest suggests that the lower stroke volume is not caused by ventricular dysfunction but is primarily the result of decreased venous return associated with lower circulating blood volume, reduced central venous pressure, and higher venous compliance in the lower extremities. VO2max, stroke volume, and cardiac output are further compromised by exercise in the upright posture. The contribution of hypovolemia to reduced cardiac output during exercise following bed rest is supported by the close relationship between the relative magnitude (% delta) and time course of change in blood volume and VO2max during bed rest, and also by the fact that retention of plasma volume is associated with maintenance of VO2max after bed rest. Arteriovenous oxygen difference during maximal exercise is not altered by bed rest, suggesting that peripheral mechanisms may not contribute significantly to the decreased VO2max. However reduction in baseline and maximal muscle blood flow, red blood cell volume, and capillarization in working muscles represent peripheral mechanisms that may contribute to limited oxygen delivery and, subsequently, lowered VO2max. Thus, alterations in cardiac and vascular functions induced by prolonged confinement to bed rest contribute to diminution of maximal oxygen uptake and reserve capacity to perform physical work.

Cortical grey matter volume reduction in people with schizophrenia is associated with neuro-inflammation

PubMed Central

Zhang, Y; Catts, V S; Sheedy, D; McCrossin, T; Kril, J J; Shannon Weickert, C

2016-01-01

Cortical grey matter volume deficits and neuro-inflammation exist in patients with schizophrenia, although it is not clear whether elevated cytokines contribute to the cortical volume reduction. We quantified cortical and regional brain volumes in fixed postmortem brains from people with schizophrenia and matched controls using stereology. Interleukin (IL)-6, IL-1β, IL-8 and SERPINA3 messenger RNAs (mRNAs) were quantified in the contralateral fresh frozen orbitofrontal cortex. We found a small, but significant reduction in cortical grey matter (1.3% F(1,85)=4.478, P=0.037) and superior frontal gyrus (6.5% F(1,80)=5.700, P=0.019) volumes in individuals with schizophrenia compared with controls. Significantly reduced cortical grey matter (9.2% F(1,24)=8.272, P=0.008) and superior frontal gyrus (13.9% F(1,20)=5.374, P=0.031) volumes were found in cases with schizophrenia and ‘high inflammation' status relative to schizophrenia cases with ‘low inflammation' status in the prefrontal cortex. The expression of inflammatory mRNAs in the orbitofrontal cortex was significantly correlated with those in dorsolateral prefrontal cortex (all r>0.417, all P<0.022), except for IL-8. Moreover, average daily and lifetime antipsychotic intake negatively correlated with cortical grey matter and superior frontal gyrus volumes (all r<−0.362, all P<0.05). The results suggest that the reduction in cortical grey matter volume in people with schizophrenia is exaggerated in those who have high expression of inflammatory cytokines. Further, antipsychotic medication intake does not appear to ameliorate the reduction in brain volume. PMID:27959331

Physiologic Basis for Improved Pulmonary Function after Lung Volume Reduction

PubMed Central

Fessler, Henry E.; Scharf, Steven M.; Ingenito, Edward P.; McKenna, Robert J.; Sharafkhaneh, Amir

2008-01-01

It is not readily apparent how pulmonary function could be improved by resecting portions of the lung in patients with emphysema. In emphysema, elevation in residual volume relative to total lung capacity reduces forced expiratory volumes, increases inspiratory effort, and impairs inspiratory muscle mechanics. Lung volume reduction surgery (LVRS) better matches the size of the lungs to the size of the thorax containing them. This restores forced expiratory volumes and the mechanical advantage of the inspiratory muscles. In patients with heterogeneous emphysema, LVRS may also allow space occupied by cysts to be reclaimed by more normal lung. Newer, bronchoscopic methods for lung volume reduction seek to achieve similar ends by causing localized atelectasis, but may be hindered by the low collateral resistance of emphysematous lung. Understanding of the mechanisms of improved function after LVRS can help select patients more likely to benefit from this approach. PMID:18453348

Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment.

PubMed

Gornicka-Pawlak, El Bieta; Janowski, Miroslaw; Habich, Aleksandra; Jablonska, Anna; Drela, Katarzyna; Kozlowska, Hanna; Lukomska, Barbara; Sypecka, Joanna; Domanska-Janik, Krystyna

2011-01-01

The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 10(7) of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30(th) day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.

Body composition changes in men and women after 2-3 weeks of bed rest

NASA Technical Reports Server (NTRS)

Pace, N.; Kodama, A. M.; Grunbaum, B. W.; Rahlmann, D. F.; Price, D. C.; Newsom, B. D.

1976-01-01

Several parameters of body composition were measured in eight men before and after 14 days of continuous recumbency, and in eight women before and after 17 days of recumbency. The parameters measured included body weight, body water, body potassium, plasma volume, and plasma protein concentrations. From these, values were derived for body fat content, lean body mass, body mass, and circulating plasma proteins. In general, the men and women responded similarly to continuous recumbency. Characteristically, there was significant reduction of plasma volume and body potassium in both groups. The women showed a significant reduction in circulating plasma protein, entirely in the albumin fraction; a similar change was observed in the men. The women, but not the men, showed a significant increase in circulating fibrinogen. Both men and women lost body cell mass, while body fat content remained the same or tended to increase slightly. It is expected that similar changes would occur in weightlessness. It is further concluded that women should tolerate the weightlessness of space flight physiologically as well as men.

Mitoprotective antioxidant EUK-134 stimulates fatty acid oxidation and prevents hypertrophy in H9C2 cells.

PubMed

Purushothaman, Sreeja; Nair, R Renuka

2016-09-01

Oxidative stress is an important contributory factor for the development of cardiovascular diseases like hypertension-induced hypertrophy. Mitochondrion is the major source of reactive oxygen species. Hence, protecting mitochondria from oxidative damage can be an effective therapeutic strategy for the prevention of hypertensive heart disease. Conventional antioxidants are not likely to be cardioprotective, as they cannot protect mitochondria from oxidative damage. EUK-134 is a salen-manganese complex with superoxide dismutase and catalase activity. The possible role of EUK-134, a mitoprotective antioxidant, in the prevention of hypertrophy of H9C2 cells was examined. The cells were stimulated with phenylephrine (50 μM), and hypertrophy was assessed based on cell volume and expression of brain natriuretic peptide and calcineurin. Enhanced myocardial lipid peroxidation and protein carbonyl content, accompanied by nuclear factor-kappa B gene expression, confirmed the presence of oxidative stress in hypertrophic cells. Metabolic shift was evident from reduction in the expression of medium-chain acyl-CoA dehydrogenase. Mitochondrial oxidative stress was confirmed by the reduced expression of mitochondria-specific antioxidant peroxiredoxin-3 and enhanced mitochondrial superoxide production. Compromised mitochondrial function was apparent from reduced mitochondrial membrane potential. Pretreatment with EUK-134 (10 μM) was effective in the prevention of hypertrophic changes in H9C2 cells, reduction of oxidative stress, and prevention of metabolic shift. EUK-134 treatment improved the oxidative status of mitochondria and reversed hypertrophy-induced reduction of mitochondrial membrane potential. Supplementation with EUK-134 is therefore identified as a novel approach to attenuate cardiac hypertrophy and lends scope for the development of EUK-134 as a therapeutic agent in the management of human cardiovascular disease.

Reduction in Tumor Volume by Cone Beam Computed Tomography Predicts Overall Survival in Non-Small Cell Lung Cancer Treated With Chemoradiation Therapy

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

Jabbour, Salma K., E-mail: jabbousk@cinj.rutgers.edu; Kim, Sinae; Department of Biostatistics, School of Public Health, Rutgers University, New Brunswick, New Jersey

2015-07-01

Purpose: We sought to evaluate whether tumor response using cone beam computed tomography (CBCT) performed as part of the routine care during chemoradiation therapy (CRT) could forecast the outcome of unresectable, locally advanced, non-small cell lung cancer (NSCLC). Methods and Materials: We manually delineated primary tumor volumes (TV) of patients with NSCLC who were treated with radical CRT on days 1, 8, 15, 22, 29, 36, and 43 on CBCTs obtained as part of the standard radiation treatment course. Percentage reductions in TV were calculated and then correlated to survival and pattern of recurrence using Cox proportional hazard models. Clinicalmore » information including histologic subtype was also considered in the study of such associations. Results: We evaluated 38 patients with a median follow-up time of 23.4 months. The median TV reduction was 39.3% (range, 7.3%-69.3%) from day 1 (D1) to day 43 (D43) CBCTs. Overall survival was associated with TV reduction from D1 to D43 (hazard ratio [HR] 0.557, 95% CI 0.39-0.79, P=.0009). For every 10% decrease in TV from D1 to D43, the risk of death decreased by 44.3%. For patients whose TV decreased ≥39.3 or <39.3%, log-rank test demonstrated a separation in survival (P=.02), with median survivals of 31 months versus 10 months, respectively. Neither local recurrence (HR 0.791, 95% CI 0.51-1.23, P=.29), nor distant recurrence (HR 0.78, 95% CI 0.57-1.08, P=.137) correlated with TV decrease from D1 to D43. Histologic subtype showed no impact on our findings. Conclusions: TV reduction as determined by CBCT during CRT as part of routine care predicts post-CRT survival. Such knowledge may justify intensification of RT or application of additional therapies. Assessment of genomic characteristics of these tumors may permit a better understanding of behavior or prediction of therapeutic outcomes.« less

Effects of Dracontomelon duperreanum defoliation extract on Microcystis aeruginosa: physiological and morphological aspects.

PubMed

Wang, Xiaoxiong; Jiang, Chenchun; Szeto, Yim-Tong; Li, Ho-Kin; Yam, Kwei-Lam; Wang, Xiaojun

2016-05-01

Harmful cyanobacteria bloom contributes to economic loss as well as the threat to human health. Agricultural waste products, particularly straw, have been used to control bloom while arbor plant is the potential candidate for limiting antialgal activity. This study investigated the use of Dracontomelon duperreanum defoliation extract (DDDE) to inhibit the activity of Microcystis aeruginosa. The primary goal of the research was to explore the solution to control cyanobacterial bloom. The photosynthetic activity, cell morphology, membrane integrity, and esterase activity of M. aeruginosa were determined using phytoplankton analyzer pulse amplitude modulation (Phyto-PAM) and flow cytometry before and after exposure to DDDE. The inhibitory rate of M. aeruginosa was about 99.6 % on day 15 when exposed to 2.0 g L(-1). A reduction of chlorophyll a (Chl-a) activity and changes in cell membrane suggested the algistatic property of DDDE. Inhibition of photosynthetic activity was reflected by changing mean Chl-a fluorescence intensity (MFI) which was about 52.5 % on day 15 when exposed to 2.0 g L(-1) DDDE as well as relative electron transport rates (rETRs) of algal cell. These changes might contribute to the suppression of M. aeruginosa. Algal cell exposed to DDDE may lead to cell volume reduction or slow growth. This resulted in a decreased proportion of normal or swollen granular cells after DDDE treatment.

Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer

PubMed Central

Sato, Kazuhide; Hanaoka, Hirofumi; Watanabe, Rira; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka

2014-01-01

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated peritoneal ovarian cancer. In vitro and in vivo experiments were conducted with a HER2-expressing, luciferase expressing, ovarian cancer cell line (SKOV-luc). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized (tra-IR700) and cells or tumors were exposed to near infrared (NIR) light. In vitro PIT cytotoxicity was assessed with dead staining and luciferase activity in freely growing cells and in a 3D spheroid model. In vivo NIR-PIT was performed in mice with tumors implanted in the peritoneum and in the flank and these assessed by tumor volume and/or bioluminescence. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. Repeated light exposures induced complete tumor cell killing in the 3D spheroid model. In vivo the anti-tumor effects of NIR-PIT were confirmed by significant reductions in both tumor volume and luciferase activity in the flank model (NIR-PIT vs control in tumor volume changes at day 10; p=0.0001, NIR-PIT vs control in luciferase activity at day 4; p=0.0237), and the peritoneal model (NIR-PIT vs control in luciferase activity at day 7; p=0.0037). NIR-PIT provided effective cell killing in this HER2 positive model of disseminated peritoneal ovarian cancer. Thus, NIR-PIT is a promising new therapy for the treatment of disseminated peritoneal tumors. PMID:25416790

Study on the influences of reduction temperature on nickel-yttria-stabilized zirconia solid oxide fuel cell anode using nickel oxide-film electrode

NASA Astrophysics Data System (ADS)

Jiao, Zhenjun; Ueno, Ai; Suzuki, Yuji; Shikazono, Naoki

2016-10-01

In this study, the reduction processes of nickel oxide at different temperatures were investigated using nickel-film anode to study the influences of reduction temperature on the initial performances and stability of nickel-yttria-stabilized zirconia anode. Compared to conventional nickel-yttria-stabilized zirconia composite cermet anode, nickel-film anode has the advantage of direct observation at nickel-yttria-stabilized zirconia interface. The microstructural changes were characterized by scanning electron microscopy. The reduction process of nickel oxide is considered to be determined by the competition between the mechanisms of volume reduction in nickel oxide-nickel reaction and nickel sintering. Electrochemical impedance spectroscopy was applied to analyze the time variation of the nickel-film anode electrochemical characteristics. The anode performances and microstructural changes before and after 100 hours discharging and open circuit operations were analyzed. The degradation of nickel-film anode is considered to be determined by the co-effect between the nickel sintering and the change of nickel-yttria-stabilized zirconia interface bonding condition.

Root restriction: A tool for improving volume utilization efficiency in bioregenerative life-support systems

NASA Astrophysics Data System (ADS)

Graham, Thomas; Wheeler, Raymond

2016-06-01

The objective of this study was to evaluate root restriction as a tool to increase volume utilization efficiency in spaceflight crop production systems. Bell pepper plants (Capsicum annuum cv. California Wonder) were grown under restricted rooting volume conditions in controlled environment chambers. The rooting volume was restricted to 500 ml and 60 ml in a preliminary trial, and 1500 ml (large), 500 ml (medium), and 250 ml (small) for a full fruiting trial. To reduce the possible confounding effects of water and nutrient restrictions, care was taken to ensure an even and consistent soil moisture throughout the study, with plants being watered/fertilized several times daily with a low concentration soluble fertilizer solution. Root restriction resulted in a general reduction in biomass production, height, leaf area, and transpiration rate; however, the fruit production was not significantly reduced in the root restricted plants under the employed environmental and horticultural conditions. There was a 21% reduction in total height and a 23% reduction in overall crown diameter between the large and small pot size in the fruiting study. Data from the fruiting trial were used to estimate potential volume utilization efficiency improvements for edible biomass in a fixed production volume. For fixed lighting and rooting hardware situations, the majority of improvement from root restriction was in the reduction of canopy area per plant, while height reductions could also improve volume utilization efficiency in high stacked or vertical agricultural systems.

Root restriction: A tool for improving volume utilization efficiency in bioregenerative life-support systems.

PubMed

Graham, Thomas; Wheeler, Raymond

2016-06-01

The objective of this study was to evaluate root restriction as a tool to increase volume utilization efficiency in spaceflight crop production systems. Bell pepper plants (Capsicum annuum cv. California Wonder) were grown under restricted rooting volume conditions in controlled environment chambers. The rooting volume was restricted to 500ml and 60ml in a preliminary trial, and 1500ml (large), 500ml (medium), and 250ml (small) for a full fruiting trial. To reduce the possible confounding effects of water and nutrient restrictions, care was taken to ensure an even and consistent soil moisture throughout the study, with plants being watered/fertilized several times daily with a low concentration soluble fertilizer solution. Root restriction resulted in a general reduction in biomass production, height, leaf area, and transpiration rate; however, the fruit production was not significantly reduced in the root restricted plants under the employed environmental and horticultural conditions. There was a 21% reduction in total height and a 23% reduction in overall crown diameter between the large and small pot size in the fruiting study. Data from the fruiting trial were used to estimate potential volume utilization efficiency improvements for edible biomass in a fixed production volume. For fixed lighting and rooting hardware situations, the majority of improvement from root restriction was in the reduction of canopy area per plant, while height reductions could also improve volume utilization efficiency in high stacked or vertical agricultural systems. Copyright © 2016 The Committee on Space Research (COSPAR). All rights reserved.

Decreased cerebral perfusion in Duchenne muscular dystrophy patients.

PubMed

Doorenweerd, Nathalie; Dumas, Eve M; Ghariq, Eidrees; Schmid, Sophie; Straathof, Chiara S M; Roest, Arno A W; Wokke, Beatrijs H; van Zwet, Erik W; Webb, Andrew G; Hendriksen, Jos G M; van Buchem, Mark A; Verschuuren, Jan J G M; Asllani, Iris; Niks, Erik H; van Osch, Matthias J P; Kan, Hermien E

2017-01-01

Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. We have previously shown that these patients have a smaller total brain and grey matter volume, and altered white matter microstructure compared to healthy controls. Patients with more distal gene mutations, predicted to affect dystrophin isoforms Dp140 and Dp427, showed greater grey matter reduction. Now, we studied if cerebral blood flow in Duchenne muscular dystrophy patients is altered, since cerebral expression of dystrophin also occurs in vascular endothelial cells and astrocytes associated with cerebral vasculature. T1-weighted anatomical and pseudo-continuous arterial spin labeling cerebral blood flow images were obtained from 26 patients and 19 age-matched controls (ages 8-18 years) on a 3 tesla MRI scanner. Group comparisons of cerebral blood flow were made with and without correcting for grey matter volume using partial volume correction. Results showed that patients had a lower cerebral blood flow than controls (40.0 ± 6.4 and 47.8 ± 6.3 mL/100 g/min respectively, p = 0.0002). This reduction was independent of grey matter volume, suggesting that they are two different aspects of the pathophysiology. Cerebral blood flow was lowest in patients lacking Dp140. There was no difference in CBF between ambulant and non-ambulant patients. Only three patients showed a reduced left ventricular ejection fraction. No correlation between cerebral blood flow and age was found. Our results indicate that cerebral perfusion is reduced in Duchenne muscular dystrophy patients independent of the reduced grey matter volume. Copyright © 2016 Elsevier B.V. All rights reserved.

Internal Kinematics of the Tongue Following Volume Reduction

PubMed Central

SHCHERBATYY, VOLODYMYR; PERKINS, JONATHAN A.; LIU, ZI-JUN

2008-01-01

This study was undertaken to determine the functional consequences following tongue volume reduction on tongue internal kinematics during mastication and neuromuscular stimulation in a pig model. Six ultrasonic-crystals were implanted into the tongue body in a wedge-shaped configuration which allows recording distance changes in the bilateral length (LENG) and posterior thickness (THICK), as well as anterior (AW), posterior dorsal (PDW), and ventral (PVW) widths in 12 Yucatan-minipigs. Six animals received a uniform mid-sagittal tongue volume reduction surgery (reduction), and the other six had identical incisions without tissue removal (sham). The initial-distances among each crystal-pairs were recorded before, and immediately after surgery to calculate the dimensional losses. Referring to the initial-distance there were 3−66% and 1−4% tongue dimensional losses by the reduction and sham surgeries, respectively. The largest deformation in sham animals during mastication was in AW, significantly larger than LENG, PDW, PVW, and THICK (P < 0.01−0.001). In reduction animals, however, these deformational changes significantly diminished and enhanced in the anterior and posterior tongue, respectively (P < 0.05−0.001). In both groups, neuromuscular stimulation produced deformational ranges that were 2−4 times smaller than those occurred during chewing. Furthermore, reduction animals showed significantly decreased ranges of deformation in PVW, LENG, and THICK (P < 0.05−0.01). These results indicate that tongue volume reduction alters the tongue internal kinematics, and the dimensional losses in the anterior tongue caused by volume reduction can be compensated by increased deformations in the posterior tongue during mastication. This compensatory effect, however, diminishes during stimulation of the hypoglossal nerve and individual tongue muscles. PMID:18484603

Static high-pressure structural studies on Dy to 119 GPa

NASA Astrophysics Data System (ADS)

Patterson, Reed; Saw, Cheng K.; Akella, Jagannadham

2004-05-01

Structural phase transitions in the rare-earth metal dysprosium have been studied in a diamond anvil cell to 119 GPa by x-ray diffraction. Four transformations following the sequence hcp→Sm-type→dhcp→hR24 (hexagonal)→bcm (monoclinic) are observed at 6, 15, 43, and 73 GPa, respectively. The hexagonal to monoclinic transformation is accompanied by a 6% reduction in volume, which is attributed to delocalization of the 4f electrons, similar to that seen in Ce, Pr, and Gd.

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

Larkin, Robert M.; Stefano, Giovanni; Ruckle, Michael E.

Eukaryotic cells require mechanisms to establish the proportion of cellular volume devoted to particular organelles. These mechanisms are poorly understood. From a screen for plastid-to-nucleus signaling mutants in Arabidopsis thaliana, we cloned a mutant allele of a gene that encodes a protein of unknown function that is homologous to two other Arabidopsis genes of unknown function and Arabidopsis. In contrast to FRIENDLY, these three homologs of FRIENDLY are found only in photosynthetic organisms. Based on these data, we proposed that FRIENDLY expanded into a small gene family to help regulate the energy metabolism of cells that contain both mitochondria andmore » chloroplasts. Indeed, we found that knocking out these genes caused a number of chloroplast phenotypes, including a reduction in the proportion of cellular volume devoted to chloroplasts to 50% of wild type. Thus, we refer to these genes as REDUCED CHLOROPLAST COVERAGE (REC). The size of the chloroplast compartment was reduced most in rec1 mutants. The REC1 protein accumulated in the cytosol and the nucleus. REC1 was excluded from the nucleus when plants were treated with amitrole, which inhibits cell expansion and chloroplast function. Finally, we conclude that REC1 is an extraplastidic protein that helps to establish the size of the chloroplast compartment, and that signals derived from cell expansion or chloroplasts may regulate REC1.« less

Clathrin-Independent Endocytosis Suppresses Cancer Cell Blebbing and Invasion.

PubMed

Holst, Mikkel Roland; Vidal-Quadras, Maite; Larsson, Elin; Song, Jie; Hubert, Madlen; Blomberg, Jeanette; Lundborg, Magnus; Landström, Maréne; Lundmark, Richard

2017-08-22

Cellular blebbing, caused by local alterations in cell-surface tension, has been shown to increase the invasiveness of cancer cells. However, the regulatory mechanisms balancing cell-surface dynamics and bleb formation remain elusive. Here, we show that an acute reduction in cell volume activates clathrin-independent endocytosis. Hence, a decrease in surface tension is buffered by the internalization of the plasma membrane (PM) lipid bilayer. Membrane invagination and endocytosis are driven by the tension-mediated recruitment of the membrane sculpting and GTPase-activating protein GRAF1 (GTPase regulator associated with focal adhesion kinase-1) to the PM. Disruption of this regulation by depleting cells of GRAF1 or mutating key phosphatidylinositol-interacting amino acids in the protein results in increased cellular blebbing and promotes the 3D motility of cancer cells. Our data support a role for clathrin-independent endocytic machinery in balancing membrane tension, which clarifies the previously reported role of GRAF1 as a tumor suppressor. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Therapeutic effects of autologous lymphocytes activated with trastuzumab for xenograft mouse models of human breast cancer.

PubMed

Nakagawa, Shinichiro; Matsuoka, Yusuke; Ichihara, Hideaki; Yoshida, Hitoji; Yoshida, Kenshi; Ueoka, Ryuichi

2013-01-01

Trastuzumab (TTZ) is molecular targeted drug used for metastatic breast cancer patients overexpressing human epidermal growth factor receptor 2 (HER2). Therapeutic effects of lymphocytes activated with TTZ (TTZ-LAK) using xenograft mouse models of human breast cancer (MDA-MB-453) cells were examined in vivo. Remarkable reduction of tumor volume in a xenograft mouse models intravenously treated with TTZ-LAK cells after the subcutaneously inoculated of MDA-MB-453 cells was verified in vivo. The migration of TTZ-LAK cells in tumor of mouse models subcutaneously inoculated MDA-MB-453 cells was observed on the basis of histological analysis using immunostaining with CD-3. Induction of apoptosis in tumor of xenograft mice treated with TTZ-LAK cells was observed in micrographs using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method. It was noteworthy that the therapeutic effects of TTZ-LAK cells along with apoptosis were obtained for xenograft mouse models of human breast tumor in vivo.

Inhibitory effects of CP on the growth of human gastric adenocarcinoma BGC-823 tumours in nude mice.

PubMed

Wang, Hai-Jun; Liu, Yu; Zhou, Bao-Jun; Zhang, Zhan-Xue; Li, Ai-Ying; An, Ran; Yue, Bin; Fan, Li-Qiao; Li, Yong

2018-05-01

Objective To investigate the potential antitumour effects of [2-(6-amino-purine-9-yl)-1-hydroxy-phosphine acyl ethyl] phosphonic acid (CP) against gastric adenocarcinoma. Methods Human BGC-823 xenotransplants were established in nude mice. Animals were randomly divided into control and CP groups, which were administered NaHCO 3 vehicle alone or CP dissolved in NaHCO 3 (200 µg/kg body weight) daily, respectively. Tumour volume was measured weekly for 6 weeks. Resected tumours were assayed for proliferative activity with anti-Ki-67 or anti-proliferating cell nuclear antigen (PCNA) antibodies. Cell apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays and with caspase-3 immunostaining. Proteins were measured by Western blotting. Results There was a significant reduction in tumour volume and a reduced percentage of Ki-67-positive or PCNA-positive cells in the CP group compared with the control group. The percentage of TUNEL-positive or caspase 3-positive cells significantly increased following CP treatment compared with the control group. Tumours from the CP group had higher levels of phosphorylated-extracellular signal-regulated kinase (p-ERK) and phosphorylated-AKT (p-AKT) compared with control tumours. Conclusion CP treatment inhibited tumour growth and induced tumour cell apoptosis in a nude mouse model of BGC-823 gastric adenocarcinoma. Activation of the AKT and ERK signalling pathways may mediate this antitumour activity.

Influence of Pre-Storage Irradiation on the Oxidative Stress Markers, Membrane Integrity, Size and Shape of the Cold Stored Red Blood Cells

PubMed Central

Antosik, Adam; Czubak, Kamila; Gajek, Arkadiusz; Marczak, Agnieszka; Glowacki, Rafal; Borowczyk, Kamila; Zbikowska, Halina Malgorzata

2015-01-01

Background To investigate the extent of oxidative damage and changes in morphology of manually isolated red blood cells (RBCs) from whole blood, cold stored (up to 20 days) in polystyrene tubes and subjected to pre-storage irradiation (50 Gy) and to compare the properties of SAGM-preserved RBCs stored under experimental conditions (polystyrene tubes) with RBCs from standard blood bag storage. Methods The percentage of hemolysis as well as the extracellular activity of LDH, thiobarbituric acid-reactive substances, reduced glutathione (GSH), and total antioxidant capacity (TAC) were measured. Changes in the topology of RBC membrane, shape, and size were evaluated by flow cytometry and judged against microscopy images. Results Irradiation caused significant LDH release as well as increased hemolysis and lipid peroxidation, GSH depletion, and reduction of TAC. Prolonged storage of irradiated RBCs resulted in phosphatidylserine exposure on the cell surface. By day 20, approximately 60% of RBCs displayed non-discoid shape. We did not notice significant differences in percentage of altered cells and cell volume between RBCs exposed to irradiation and those not exposed. Conclusion Irradiation of RBC transfusion units with a dose of 50 Gy should be avoided. For research purposes such as studying the role of antioxidants, storage of small volumes of RBCs derived from the same donor would be more useful, cheaper, and blood-saving. PMID:26195927

Influence of Pre-Storage Irradiation on the Oxidative Stress Markers, Membrane Integrity, Size and Shape of the Cold Stored Red Blood Cells.

PubMed

Antosik, Adam; Czubak, Kamila; Gajek, Arkadiusz; Marczak, Agnieszka; Glowacki, Rafal; Borowczyk, Kamila; Zbikowska, Halina Malgorzata

2015-05-01

To investigate the extent of oxidative damage and changes in morphology of manually isolated red blood cells (RBCs) from whole blood, cold stored (up to 20 days) in polystyrene tubes and subjected to pre-storage irradiation (50 Gy) and to compare the properties of SAGM-preserved RBCs stored under experimental conditions (polystyrene tubes) with RBCs from standard blood bag storage. The percentage of hemolysis as well as the extracellular activity of LDH, thiobarbituric acid-reactive substances, reduced glutathione (GSH), and total antioxidant capacity (TAC) were measured. Changes in the topology of RBC membrane, shape, and size were evaluated by flow cytometry and judged against microscopy images. Irradiation caused significant LDH release as well as increased hemolysis and lipid peroxidation, GSH depletion, and reduction of TAC. Prolonged storage of irradiated RBCs resulted in phosphatidylserine exposure on the cell surface. By day 20, approximately 60% of RBCs displayed non-discoid shape. We did not notice significant differences in percentage of altered cells and cell volume between RBCs exposed to irradiation and those not exposed. Irradiation of RBC transfusion units with a dose of 50 Gy should be avoided. For research purposes such as studying the role of antioxidants, storage of small volumes of RBCs derived from the same donor would be more useful, cheaper, and blood-saving.

Region-specific reduction in brain volume in young adults with perinatal hypoxic-ischaemic encephalopathy.

PubMed

Bregant, Tina; Rados, Milan; Vasung, Lana; Derganc, Metka; Evans, Alan C; Neubauer, David; Kostovic, Ivica

2013-11-01

A severe form of perinatal hypoxic-ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequelae while in mild HIE only discrete cognitive disorders may occur. To compare total brain volumes and region-specific cortical measurements between young adults with mild-moderate perinatal HIE and a healthy control group of the same age. MR imaging was performed in a cohort of 14 young adults (9 males, 5 females) with a history of mild or moderate perinatal HIE. The control group consisted of healthy participants, matched with HIE group by age and gender. Volumetric analysis was done after the processing of MR images using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of grey and white matter, and of cerebrospinal fluid. We also measured volume, thickness and area of the cerebral cortex in the parietal, occipital, frontal, and temporal lobe, and of the isthmus cinguli, parahippocampal and cingulated gyrus, and insula. The HIE patient group showed smaller absolute volumetric data. Statistically significant (p < 0.05) reductions of gyrification index in the right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. Our analysis of total brain volumes and region-specific corticometric parameters suggests that mild-moderate forms of perinatal HIE lead to reductions in whole brain volumes. In the study reductions were most pronounced in temporal lobe and parahippocampal gyrus. Copyright © 2013 European Paediatric Neurology Society. All rights reserved.

Human trabecular meshwork cell volume decrease by NO-independent soluble guanylate cyclase activators YC-1 and BAY-58-2667 involves the BKCa ion channel.

PubMed

Dismuke, William M; Sharif, Najam A; Ellis, Dorette Z

2009-07-01

There is a correlation between cell volume changes and changes in the rate of aqueous humor outflow; agents that decrease trabecular meshwork (TM) cell volume increase the rate of aqueous humor outflow. This study investigated the effects of the nitric oxide (NO)-independent activators of soluble guanylate cyclase (sGC), YC-1, and BAY-58-2667 on TM cell volume and the signal transduction pathways and ion channel involved. Cell volume was measured with the use of calcein AM fluorescent dye, detected by confocal microscopy. Inhibitors and activators of sGC, 3',5'-cyclic guanosine monophosphate (cGMP), protein kinase G (PKG), and the BK(Ca) channel were used to characterize their involvement in the YC-1- and BAY-58-2667-induced regulation of TM cell volume. cGMP was assayed by an enzyme immunoassay. YC-1 (10 nM-200 microM) and BAY-58-2667 (10 nM-100 microM) each elicited a biphasic effect on TM cell volume. YC-1 (1 microM) increased TM cell volume, but higher concentrations decreased TM cell volume. Similarly, BAY-58-2667 (100 nM) increased TM cell volume, but higher concentrations decreased cell volume. The YC-1-induced cell volume decrease was mimicked by 8-Br-cGMP and abolished by the sGC inhibitor ODQ, the PKG inhibitor (RP)-8-Br-PET-cGMP-S, and the BK(Ca) channel inhibitor IBTX. The BAY-58-2667-induced cell volume decrease was mimicked by 8-Br-cGMP and was abolished by the PKG inhibitor and the BK(Ca) channel inhibitor. Unlike the YC-1 response, ODQ potentiated the BAY-58-2667-induced decreases in cell volume. These data suggest that the NO-independent decrease in TM cell volume is mediated by the sGC/cGMP/PKG pathway and involves K(+) efflux.

Radiotherapy planning: PET/CT scanner performances in the definition of gross tumour volume and clinical target volume.

PubMed

Brianzoni, Ernesto; Rossi, Gloria; Ancidei, Sergio; Berbellini, Alfonso; Capoccetti, Francesca; Cidda, Carla; D'Avenia, Paola; Fattori, Sara; Montini, Gian Carlo; Valentini, Gianluca; Proietti, Alfredo; Algranati, Carlo

2005-12-01

Positron emission tomography is the most advanced scintigraphic imaging technology and can be employed in the planning of radiation therapy (RT). The aim of this study was to evaluate the possible role of fused images (anatomical CT and functional FDG-PET), acquired with a dedicated PET/CT scanner, in delineating gross tumour volume (GTV) and clinical target volume (CTV) in selected patients and thus in facilitating RT planning. Twenty-eight patients were examined, 24 with lung cancer (17 non-small cell and seven small cell) and four with non-Hodgkin's lymphoma in the head and neck region. All patients underwent a whole-body PET scan after a CT scan. The CT images provided morphological volumetric information, and in a second step, the corresponding PET images were overlaid to define the effective target volume. The images were exported off-line via an internal network to an RT simulator. Three patient were excluded from the study owing to change in the disease stage subsequent to the PET/CT study. Among the remaining 25 patients, PET significantly altered the GTV or CTV in 11 (44%) . In five of these 11 cases there was a reduction in GTV or CTV, while in six there was an increase in GTV or CTV. FDG-PET is a highly sensitive imaging modality that offers better visualisation of local and locoregional tumour extension. This study confirmed that co-registration of CT data and FDG-PET images may lead to significant modifications of RT planning and patient management.

The role of PET in target localization for radiotherapy treatment planning.

PubMed

Rembielak, Agata; Price, Pat

2008-02-01

Positron emission tomography (PET) is currently accepted as an important tool in oncology, mostly for diagnosis, staging and restaging purposes. It provides a new type of information in radiotherapy, functional rather than anatomical. PET imaging can also be used for target volume definition in radiotherapy treatment planning. The need for very precise target volume delineation has arisen with the increasing use of sophisticated three-dimensional conformal radiotherapy techniques and intensity modulated radiation therapy. It is expected that better delineation of the target volume may lead to a significant reduction in the irradiated volume, thus lowering the risk of treatment complications (smaller safety margins). Better tumour visualisation also allows a higher dose of radiation to be applied to the tumour, which may lead to better tumour control. The aim of this article is to review the possible use of PET imaging in the radiotherapy of various cancers. We focus mainly on non-small cell lung cancer, lymphoma and oesophageal cancer, but also include current opinion on the use of PET-based planning in other tumours including brain, uterine cervix, rectum and prostate.

Three-dimensional histology: tools and application to quantitative assessment of cell-type distribution in rabbit heart

PubMed Central

Burton, Rebecca A.B.; Lee, Peter; Casero, Ramón; Garny, Alan; Siedlecka, Urszula; Schneider, Jürgen E.; Kohl, Peter; Grau, Vicente

2014-01-01

Aims Cardiac histo-anatomical organization is a major determinant of function. Changes in tissue structure are a relevant factor in normal and disease development, and form targets of therapeutic interventions. The purpose of this study was to test tools aimed to allow quantitative assessment of cell-type distribution from large histology and magnetic resonance imaging- (MRI) based datasets. Methods and results Rabbit heart fixation during cardioplegic arrest and MRI were followed by serial sectioning of the whole heart and light-microscopic imaging of trichrome-stained tissue. Segmentation techniques developed specifically for this project were applied to segment myocardial tissue in the MRI and histology datasets. In addition, histology slices were segmented into myocytes, connective tissue, and undefined. A bounding surface, containing the whole heart, was established for both MRI and histology. Volumes contained in the bounding surface (called ‘anatomical volume’), as well as that identified as containing any of the above tissue categories (called ‘morphological volume’), were calculated. The anatomical volume was 7.8 cm3 in MRI, and this reduced to 4.9 cm3 after histological processing, representing an ‘anatomical’ shrinkage by 37.2%. The morphological volume decreased by 48% between MRI and histology, highlighting the presence of additional tissue-level shrinkage (e.g. an increase in interstitial cleft space). The ratio of pixels classified as containing myocytes to pixels identified as non-myocytes was roughly 6:1 (61.6 vs. 9.8%; the remaining fraction of 28.6% was ‘undefined’). Conclusion Qualitative and quantitative differentiation between myocytes and connective tissue, using state-of-the-art high-resolution serial histology techniques, allows identification of cell-type distribution in whole-heart datasets. Comparison with MRI illustrates a pronounced reduction in anatomical and morphological volumes during histology processing. PMID:25362175

Pollutant-specific and general lysosomal responses in digestive cells of mussels exposed to model organic chemicals.

PubMed

Marigómez, Ionan; Baybay-Villacorta, Lurraine

2003-08-20

The present study was carried out to elucidate whether lysosomal size reduction in digestive cells of mussels Mytilus galloprovincialis constitutes a selective response against a particular group of organic chemical compounds, in contrast to the lysosomal enlargement characteristic of general stress response. Mussels were treated with di(2-ethylhexyl) phthalate (DEHP), benzo(a)pyrene (B[a]P), and the water accommodated fraction (WAF) of a lubricant oil, which were daily applied by either injection through the adductor muscle for 7 days or water-exposure for 21 days. Control mussels were either kept untreated in clean sea water, or treated with acetone (injection and water-exposure), vehicle used for DEHP and B[a]P. A third set of controls consisted of mussels with pierced shell kept in clean seawater. Digestive glands were excised at various treatment days and beta-glucuronidase activity was demonstrated in 8-microm cryotome sections. Lysosomal volume, surface and numerical densities, and surface-to-volume ratio were quantified by image analysis. Other sections were stained with oil red 0 to demonstrate neutral lipids and changes in lipid levels were quantified by image analysis. Neutral lipid accumulation in digestive cells was used as a complementary indication of exposure to organic chemicals. It resulted to be a very prompt and all-or-nothing response, which reached a plateau before 1 day of treatment with WAF, DEHP and B[a]P after both injection and water-exposure. DEHP-treatment induced a general stress response characterised by lysosomal enlargement in digestive cells, which was already induced after 1 day. Treatment with either WAF or B[a]P elicited a comparable biphasic response. A transient lysosomal enlargement, shorter with WAF than with B[a]P treatment, was evidenced after both injection and water-exposure. Further, under water-exposure conditions, WAF reduced the endo-lysosomal system in size more markedly than B[a]P. Such lysosomal size reduction constitutes a transient response after exposure to diverse organic xenobiotics (acetone, WAF and B[a]P). In addition, this lysosomal size reduction might be followed by a further lysosomal enlargement, which later might yet again give rise to an apparent lysosomal size reduction under chronic exposure conditions. As a whole, the lysosomal response is intricate and cannot be simply interpreted in environmental pollution monitoring programmes. Nevertheless, it still constitutes a powerful and sensitive biomarker extremely useful as early-warning signal.

An integrated approach to place Green Infrastructure strategies in marginalized communities and evaluate stormwater mitigation

NASA Astrophysics Data System (ADS)

Garcia-Cuerva, Laura; Berglund, Emily Zechman; Rivers, Louie

2018-04-01

Increasing urbanization augments impervious surface area, which results in increased run off volumes and peak flows. Green Infrastructure (GI) approaches are a decentralized alternative for sustainable urban stormwater and provide an array of ecosystem services and foster community building by enhancing neighborhood aesthetics, increasing property value, and providing shared green spaces. While projects involving sustainability concepts and environmental design are favored in privileged communities, marginalized communities have historically been located in areas that suffer from environmental degradation. Underprivileged communities typically do not receive as many social and environmental services as advantaged communities. This research explores GI-based management strategies that are evaluated at the watershed scale to improve hydrological performance by mitigating storm water run off volumes and peak flows. GI deployment strategies are developed to address environmental justice issues by prioritizing placement in communities that are underprivileged and locations with high outreach potential. A hydrologic/hydraulic stormwater model is developed using the Storm Water Management Model (SWMM 5.1) to simulate the impacts of alternative management strategies. Management scenarios include the implementation of rain water harvesting in private households, the decentralized implementation of bioretention cells in private households, the centralized implementation of bioretention cells in municipally owned vacant land, and combinations of those strategies. Realities of implementing GI on private and public lands are taken into account to simulate various levels of coverage and routing for bioretention cell scenarios. The effects of these strategies are measured by the volumetric reduction of run off and reduction in peak flow; social benefits are not evaluated. This approach is applied in an underprivileged community within the Walnut Creek Watershed in Raleigh, North Carolina.

Water uptake by growing cells: an assessment of the controlling roles of wall relaxation, solute uptake, and hydraulic conductance

NASA Technical Reports Server (NTRS)

Cosgrove, D. J.

1993-01-01

Growing plant cells increase in volume principally by water uptake into the vacuole. There are only three general mechanisms by which a cell can modulate the process of water uptake: (a) by relaxing wall stress to reduce cell turgor pressure (thereby reducing cell water potential), (b) by modifying the solute content of the cell or its surroundings (likewise affecting water potential), and (c) by changing the hydraulic conductance of the water uptake pathway (this works only for cells remote from water potential equilibrium). Recent studies supporting each of these potential mechanisms are reviewed and critically assessed. The importance of solute uptake and hydraulic conductance is advocated by some recent studies, but the evidence is indirect and conclusions remain controversial. For most growing plant cells with substantial turgor pressure, it appears that reduction in cell turgor pressure, as a consequence of wall relaxation, serves as the major initiator and control point for plant cell enlargement. Two views of wall relaxation as a viscoelastic or a chemorheological process are compared and distinguished.

On the mechanism of injury to slowly frozen erythrocytes.

PubMed Central

Pegg, D E; Diaper, M P

1988-01-01

When cells are frozen slowly in aqueous suspensions, the solutes in the suspending solution concentrate as the amount of ice increases; the cells undergo osmotic dehydration and are sequestered in ever-narrowing liquid-filled channels. Cryoprotective solutes, such as glycerol, reduce the amount of ice that forms at any specified subzero temperature, thereby controlling the buildup in concentration of those other solutes present, as well as increasing the volume of the channels that remain to accommodate the cells. It has generally been thought that freezing injury is mediated by the increase in electrolyte concentration in the milieu surrounding the cells, rather than reduction of temperature or any direct action of ice. In this study we have frozen human erythrocytes in isotonic solutions of sodium chloride and glycerol and have demonstrated a correlation between the extent of damage at specific subzero temperatures, and that caused by the action at 0 degrees C of solutions having the same composition as those produced by freezing. The cell lysis observed increased directly with glycerol concentration, both in the freezing experiments and when the cells were exposed to corresponding solutions at 0 degrees C, showing that the concentration of sodium chloride alone is not sufficient to account quantitatively for the damage observed. We then studied the effect of freezing in anisotonic solutions to break the fixed relationship between solute concentration and the volume of the unfrozen fraction, as described by Mazur, P., W. F. Rall, and N. Rigopoulos (1981. Biophys. J. 653-675). We confirmed their experimental findings, but we explain them differently. We ascribe the apparently dominant effect of the unfrozen fraction to the fact that the cells were frozen in, and returned to, anisotonic solutions in which their volume was either less than, or greater than, their physiological volume. When similar cell suspensions were subjected to a similar cycle of increase and then decrease in solution strength, but in the absence of ice (at 20 degrees C), a similar pattern of hemolysis was observed. We conclude that freezing injury to human erythrocytes is due solely to changes that occur in the composition of their surrounding milieu, and is most probably mediated by a temporary leak in the plasma membrane that occurs during the thawing (reexpansion) phase. PMID:3207835

Timing, predictors, and progress of third space fluid accumulation during preliminary phase fluid resuscitation in adult patients with dengue.

PubMed

Premaratna, R; Ragupathy, A; Miththinda, J K N D; de Silva, H J

2013-07-01

Fluid leakage remains the hallmark of dengue hemorrhagic fever (DHF). The applicability of currently recommended predictors of DHF for adults with dengue is questionable as these are based on studies conducted in children. One hundred and two adults with dengue were prospectively followed up to investigate whether home-based or hospital-based early phase fluid resuscitation has an impact on clinical and hematological parameters used for the diagnosis of early or critical phase fluid leakage. In the majority of subjects, third space fluid accumulation (TSFA) was detected on the fifth and sixth days of infection. The quantity and quality of fluids administered played no role in TSFA. A reduction in systolic blood pressure appeared to be more helpful than a reduction in pulse pressure in predicting fluid leakage. TSFA occurred with lower percentage rises in packed cell volume (PCV) than stated in the current recommendations. A rapid reduction in platelets, progressive reduction in white blood cells, percentage rises in Haemoglobin (Hb), and PCV, and rises in aspartate aminotransferase and alanine aminotransferase were observed in patients with TSFA and therefore with the development of severe illness. Clinicians should be aware of the limitations of currently recommended predictors of DHF in adult patients who are receiving fluid resuscitation. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Accelerated Loss of TCR Repertoire Diversity in Common Variable Immunodeficiency

PubMed Central

Wong, Gabriel K.; Millar, David; Penny, Sarah; Heather, James M.; Mistry, Punam; Buettner, Nico; Bryon, Jane; Huissoon, Aarnoud P.

2016-01-01

Although common variable immunodeficiency (CVID) has long been considered as a group of primary Ab deficiencies, growing experimental data now suggest a global disruption of the entire adaptive immune response in a segment of patients. Oligoclonality of the TCR repertoire was previously demonstrated; however, the manner in which it relates to other B cell and T cell findings reported in CVID remains unclear. Using a combination approach of high-throughput TCRβ sequencing and multiparametric flow cytometry, we compared the TCR repertoire diversity between various subgroups of CVID patients according to their B cell immunophenotypes. Our data suggest that the reduction in repertoire diversity is predominantly restricted to those patients with severely reduced class-switched memory B cells and an elevated level of CD21lo B cells (Freiburg 1a), and may be driven by a reduced number of naive T cells unmasking underlying memory clonality. Moreover, our data indicate that this loss in repertoire diversity progresses with advancing age far exceeding the expected physiological rate. Radiological evidence supports the loss in thymic volume, correlating with the decrease in repertoire diversity. Evidence now suggests that primary thymic failure along with other well-described B cell abnormalities play an important role in the pathophysiology in Freiburg group 1a patients. Clinically, our findings emphasize the integration of combined B and T cell testing to identify those patients at the greatest risk for infection. Future work should focus on investigating the link between thymic failure and the severe reduction in class-switched memory B cells, while gathering longitudinal laboratory data to examine the progressive nature of the disease. PMID:27481850

Alternative Hand Contamination Technique To Compare the Activities of Antimicrobial and Nonantimicrobial Soaps under Different Test Conditions▿

PubMed Central

Fuls, Janice L.; Rodgers, Nancy D.; Fischler, George E.; Howard, Jeanne M.; Patel, Monica; Weidner, Patrick L.; Duran, Melani H.

2008-01-01

Antimicrobial hand soaps provide a greater bacterial reduction than nonantimicrobial soaps. However, the link between greater bacterial reduction and a reduction of disease has not been definitively demonstrated. Confounding factors, such as compliance, soap volume, and wash time, may all influence the outcomes of studies. The aim of this work was to examine the effects of wash time and soap volume on the relative activities and the subsequent transfer of bacteria to inanimate objects for antimicrobial and nonantimicrobial soaps. Increasing the wash time from 15 to 30 seconds increased reduction of Shigella flexneri from 2.90 to 3.33 log10 counts (P = 0.086) for the antimicrobial soap, while nonantimicrobial soap achieved reductions of 1.72 and 1.67 log10 counts (P > 0.6). Increasing soap volume increased bacterial reductions for both the antimicrobial and the nonantimicrobial soaps. When the soap volume was normalized based on weight (∼3 g), nonantimicrobial soap reduced Serratia marcescens by 1.08 log10 counts, compared to the 3.83-log10 reduction caused by the antimicrobial soap (P < 0.001). The transfer of Escherichia coli to plastic balls following a 15-second hand wash with antimicrobial soap resulted in a bacterial recovery of 2.49 log10 counts, compared to the 4.22-log10 (P < 0.001) bacterial recovery on balls handled by hands washed with nonantimicrobial soap. This indicates that nonantimicrobial soap was less active and that the effectiveness of antimicrobial soaps can be improved with longer wash time and greater soap volume. The transfer of bacteria to objects was significantly reduced due to greater reduction in bacteria following the use of antimicrobial soap. PMID:18441107

Alternative hand contamination technique to compare the activities of antimicrobial and nonantimicrobial soaps under different test conditions.

PubMed

Fuls, Janice L; Rodgers, Nancy D; Fischler, George E; Howard, Jeanne M; Patel, Monica; Weidner, Patrick L; Duran, Melani H

2008-06-01

Antimicrobial hand soaps provide a greater bacterial reduction than nonantimicrobial soaps. However, the link between greater bacterial reduction and a reduction of disease has not been definitively demonstrated. Confounding factors, such as compliance, soap volume, and wash time, may all influence the outcomes of studies. The aim of this work was to examine the effects of wash time and soap volume on the relative activities and the subsequent transfer of bacteria to inanimate objects for antimicrobial and nonantimicrobial soaps. Increasing the wash time from 15 to 30 seconds increased reduction of Shigella flexneri from 2.90 to 3.33 log(10) counts (P = 0.086) for the antimicrobial soap, while nonantimicrobial soap achieved reductions of 1.72 and 1.67 log(10) counts (P > 0.6). Increasing soap volume increased bacterial reductions for both the antimicrobial and the nonantimicrobial soaps. When the soap volume was normalized based on weight (approximately 3 g), nonantimicrobial soap reduced Serratia marcescens by 1.08 log(10) counts, compared to the 3.83-log(10) reduction caused by the antimicrobial soap (P < 0.001). The transfer of Escherichia coli to plastic balls following a 15-second hand wash with antimicrobial soap resulted in a bacterial recovery of 2.49 log(10) counts, compared to the 4.22-log(10) (P < 0.001) bacterial recovery on balls handled by hands washed with nonantimicrobial soap. This indicates that nonantimicrobial soap was less active and that the effectiveness of antimicrobial soaps can be improved with longer wash time and greater soap volume. The transfer of bacteria to objects was significantly reduced due to greater reduction in bacteria following the use of antimicrobial soap.

CAD/CAM-designed 3D-printed electroanalytical cell for the evaluation of nanostructured gas-diffusion electrodes

NASA Astrophysics Data System (ADS)

Chervin, Christopher N.; Parker, Joseph F.; Nelson, Eric S.; Rolison, Debra R.; Long, Jeffrey W.

2016-04-01

The ability to effectively screen and validate gas-diffusion electrodes is critical to the development of next-generation metal-air batteries and regenerative fuel cells. The limiting electrode in a classic two-terminal device such as a battery or fuel cell is difficult to discern without an internal reference electrode, but the flooded electrolyte characteristic of three-electrode electroanalytical cells negates the prime function of an air electrode—a void volume freely accessible to gases. The nanostructured catalysts that drive the energy-conversion reactions (e.g., oxygen reduction and evolution in the air electrode of metal-air batteries) are best evaluated in the electrode structure as-used in the practical device. We have designed, 3D-printed, and characterized an air-breathing, thermodynamically referenced electroanalytical cell that allows us to mimic the Janus arrangement of the gas-diffusion electrode in a metal-air cell: one face freely exposed to gases, the other wetted by electrolyte.

CAD/CAM-designed 3D-printed electroanalytical cell for the evaluation of nanostructured gas-diffusion electrodes.

PubMed

Chervin, Christopher N; Parker, Joseph F; Nelson, Eric S; Rolison, Debra R; Long, Jeffrey W

2016-04-29

The ability to effectively screen and validate gas-diffusion electrodes is critical to the development of next-generation metal-air batteries and regenerative fuel cells. The limiting electrode in a classic two-terminal device such as a battery or fuel cell is difficult to discern without an internal reference electrode, but the flooded electrolyte characteristic of three-electrode electroanalytical cells negates the prime function of an air electrode-a void volume freely accessible to gases. The nanostructured catalysts that drive the energy-conversion reactions (e.g., oxygen reduction and evolution in the air electrode of metal-air batteries) are best evaluated in the electrode structure as-used in the practical device. We have designed, 3D-printed, and characterized an air-breathing, thermodynamically referenced electroanalytical cell that allows us to mimic the Janus arrangement of the gas-diffusion electrode in a metal-air cell: one face freely exposed to gases, the other wetted by electrolyte.

Flat-plate solar array project. Volume 4: High-efficiency solar cells

NASA Technical Reports Server (NTRS)

Leipold, M.; Cheng, L.; Daud, T.; Mokashi, A.; Burger, D.; Christensen, E. (Editor); Murry, J. (Editor); Bengelsdorf, I. (Editor)

1986-01-01

The High Efficiency Solar Cell Task was assigned the objective of understanding and developing high efficiency solar cell devices that would meet the cost and performance goals of the Flat Plate Solar Array (FSA) Project. The need for research dealing with high efficiency devices was considered important because of the role efficiency plays in reducing price per watt of generated energy. The R&D efforts conducted during the 1982 to 1986 period are summarized to provide understanding and control of energy conversion losses associated with crystalline silicon solar cells. New levels of conversion efficiency were demonstrated. Major contributions were made both to the understanding and reduction of bulk and surface losses in solar cells. For example, oxides, nitrides, and polysilicon were all shown to be potentially useful surface passivants. Improvements in measurement techniques were made and Auger coefficients and spectral absorption data were obtained for unique types of silicon sheets. New modelling software was developed including a program to optimize a device design based on input characteristics of a cell.

Ferrokinetic and hematologic studies in cystic fibrosis patients

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

Wagener, J.S.; McNeill, G.C.; Taussig, L.M.

We investigated 28 cystic fibrosis (CF) patients to determine why hypoxia from their obstructive pulmonary disease does not produce polycythemia. Oxygen saturation was lower and erythropoietin levels were higher in CF patients than in 25 age-comparable reference subjects (90.8% and 47 mimu vs. 94.7% and 29 mimu, p less than 0.01). Hematocrit and red blood cell (RBC) indices were not different between groups. Serum vitamin and iron levels, ferrokinetics, RBC volume, and RBC survival were studied in 10 of the 28 CF patients. Total iron-binding capacity and vitamin E levels were low, and serum iron, ferritin, vitamin B12, and folatemore » levels were normal in these patients. Red blood cell survival was minimally decreased in six patients although there was no other evidence for hemolysis. Ferrokinetics (/sup 59/Fe) indicated a reduction in total erythropoiesis in only two patients. Plasma volume was high-normal in five and above normal in four CF patients; RBC mass was increased appropriately for each patient's degree of hypoxia, when compared to healthy individuals living at different altitudes. These results suggest that CF patients are able to compensate for hypoxia by increasing RBC mass; however, an expanded plasma volume prevents a detectable rise in hematocrit.« less

Characterization of fluid physics effects on cardiovascular response to microgravity (G-572)

NASA Technical Reports Server (NTRS)

Pantalos, George M.; Bennett, Thomas E.; Sharp, M. Keith; Woodruff, Stewart; Oleary, Sean; Gillars, Kevin; Lemon, Mark; Sojka, Jan

1995-01-01

The investigation of cardiovascular adaptation to space flight has seen substantial advancement in the last several years. In-flight echocardiographic measurements of astronaut cardiac function on the Space Shuttle have documented an initial increase, followed by a progressive reduction in both left ventricular volume index and stroke volume with a compensatory increase in heart rate to maintain cardiac output. To date, the reduced cardiac size and stroke volume have been presumed to be the consequence of the reduction in circulating fluid volume within a few days after orbital insertion. However, no specific mechanism for the reduced stroke volume has been identified. The following investigation proposes the use of a hydraulic model of the cardiovascular system to examine the possibility that the observed reduction in stroke volume may, in part, be related to fluid physics effects on heart function. The automated model is being prepared to fly as a Get Away Special (GAS) payload within the next year.

In situ stabilization of NAPL contaminant source-zones as a remediation technique to reduce mass discharge and flux to groundwater.

PubMed

Mateas, Douglas J; Tick, Geoffrey R; Carroll, Kenneth C

2017-09-01

Widely used flushing and in-situ destruction based remediation techniques (i.e. pump-and treat, enhanced-solubilization, and chemical oxidation/reduction) for sites contaminated by nonaqueous phase liquid (NAPL) contaminant sources have been shown to be ineffective at complete mass removal and reducing aqueous-phase contaminant of concern (COC) concentrations to levels suitable for site closure. A remediation method was developed to reduce the aqueous solubility and mass-flux of COCs within NAPL through the in-situ creation of a NAPL mixture source-zone. In contrast to remediation techniques that rely on the rapid removal of contaminant mass, this technique relies on the stabilization of difficult-to-access NAPL sources to reduce COC mass flux to groundwater. A specific amount (volume) of relatively insoluble n-hexadecane (HEXDEC) or vegetable oil (VO) was injected into a trichloroethene (TCE) contaminant source-zone through a bench-scale flow cell port (i.e. well) to form a NAPL mixture of targeted mole fraction (TCE:HEXDEC or TCE:VO). NAPL-aqueous phase batch tests were conducted prior to the flow-cell experiments to evaluate the effects of various NAPL mixture ratios on equilibrium aqueous-phase concentrations of TCE to design optimal NAPL (HEXDEC or VO) injection volumes for the flow-cell experiments. The NAPL-stabilization flow-cell experiments initiated and sustained significant reductions in COC concentration and mass flux due to a combination of both reduced relative permeability (increased NAPL-saturation) and via modification of NAPL composition (decreased TCE mole fraction). Variations in remediation performance (i.e. impacts on TCE concentration and mass flux reduction) between the different HEXDEC injection volumes were relatively minor, and therefore inconsistent with Raoult's Law predictions. This phenomenon likely resulted from non-uniform mixing of the injected HEXDEC with TCE in the source-zone. VO injection caused TCE concentrations and mass-flux to decrease more rapidly than with HEXDEC injections. This phenomenon occurred because the injected VO was observed to mix more uniformly with TCE in the source-zone due to a lower mobilization potential. The relative lower density differences (buoyancy effects) between VO and the flushing solution (water) was the primary factor contributing to the lower mobilization potential for VO. Overall, this study indicated that the delivery of HEXDEC or VO into the toxic TCE source-zone was effective in significantly reducing contaminant aqueous-phase concentration and mass-flux. However, the effectiveness of this in-situ NAPL stabilization technique depends on source delivery, uniform mixing of amendment, and that the amendment remains immobilized within and around the NAPL contaminant source. Copyright © 2017 Elsevier B.V. All rights reserved.

Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells.

PubMed

Hoffmann, Else Kay

2011-01-01

This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation, and programmed cell death. Copyright © 2011 S. Karger AG, Basel.

A clinical investigation of the mechanism of loxoprofen, a non-steroidal anti-inflammatory drug, for patients with nocturia.

PubMed

Araki, Tohru; Yokoyama, Teruhiko; Araki, Motoo; Furuya, Seiji

2008-12-01

We previously reported the effectiveness of loxoprofen sodium (loxoprofen), a non-steroidal anti-inflammatory drug, for patients with lower urinary tract symptoms (LUTS) complaining of nocturia. In this study, we explored the mechanism of loxoprofen in the treatment of nocturia. Fifty-six patients complaining of nocturia were enrolled. They took a single 60-mg tablet of loxoprofen at bedtime for 14 days. The effects of this treatment were assessed by bladder diaries. Nocturia improved (nocturia decreased >or=1 void/night) in 40 patients (71.4%). Nocturnal urine volume was reduced in 31 of 40 (77.5%) without nocturnal single-void volume increase. Nocturnal single-void volume increased in 4 of 40 (10.0%) without nocturnal urine volume reduction. Two of 40 (5.0%) demonstrated both nocturnal urine volume reduction and nocturnal single-void volume increase. Three (7.5%) were exceptions to the above. In conclusion, the main mechanism of loxoprofen is the reduction of nocturnal urine volume for the treatment of nocturia and the second mechanism is the increased bladder capacity.

Utility Of Nitric Oxide And Hydrogen Sulfide-Releasing Chimeras As Anticancer Agents.

PubMed

Kashfi, Khosrow

2015-08-01

Aspirin is chemopreventive but has significant side effects. We developed NOSH-aspirin a safer, nitric oxide and hydrogen sulfide releasing hybrid. Here we report on NOSH-aspirin as an anti-inflammatory and its effects on human cancer cell kinetics and various cancer xenografts. Anti-inflammatory: Carageenan rat paw edema model. Cancer cell lines: Colon, HT-29, HCT 15, SW 480; breast, MCF-7, MDA-MB-231; pancreas, MIA PaCa2, BxPC3. Normal cell lines: human mammary, HMEpC; pancreatic epithelial, ACBRI 515. Xenografts: nude mice implanted with HT-29, MDA-MB-231, MIA PaCa2 cells, were treated with NOSH-aspirin (100mg/kg/d) or vehicle. After 3 weeks, mice were sacrificed, tumors excised, weighed, and fixed for IHC studies. NOSH-aspirin significantly reduced paw edema as function of time. NOSH-aspirin's IC 50 in nM at 24h for cell growth inhibition ranged from 50±2 to 250±10 in the cancer cell lines and about 400-fold higher in the normal cell lines. The cell growth inhibitory effects were due to a dose-dependent induction of apoptosis and cell cycle arrest (G0/G1), leading to reductions in cell proliferation. In xenografts, NOSH-aspirin had no effect on the weight of the mice. Tumor volume was reduced as a function of treatment time. At sacrifice, tumor mass reductions were colon: 89%, P=0.005; breast: 91%, P=0.006; pancreas: 75%, P=0.0031. Growth inhibition was due to reduced proliferation (decreased PCNA expression), and induction of apoptosis (increased TUNEL positive cells). NOSH-aspirin is a potent anti-inflammatory, preferentially affecting cancer cells and targets parameters important in determining cellular mass. Copyright © 2015. Published by Elsevier B.V.

Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice.

PubMed

García-Martínez, J M; Wullschleger, S; Preston, G; Guichard, S; Fleming, S; Alessi, D R; Duce, S L

2011-03-29

The PI3K-mTOR (phosphoinositide 3-kinase-mammalian target of rapamycin kinase) pathway is activated in the majority of tumours, and there is interest in assessing whether inhibitors of PI3K or mTOR kinase have efficacy in treating cancer. Here, we define the effectiveness of specific mTOR (AZD8055) and PI3K (GDC-0941) inhibitors, currently in clinical trials, in treating spontaneous B-cell follicular lymphoma that develops in PTEN(+/-)LKB1(+/hypo) mice. The PTEN(+/-)LKB1(+/hypo) mice were administered AZD8055 or GDC-0941, and the volumes of B-cell follicular lymphoma were measured by MRI. Tumour samples were analysed by immunohistochemistry, immunoblot and flow cytometry. The AZD8055 or GDC-0941 induced ∼40% reduction in tumour volume within 2 weeks, accompanied by ablation of phosphorylation of AKT, S6K and SGK (serum and glucocorticoid protein kinase) protein kinases. The drugs reduced tumour cell proliferation, promoted apoptosis and suppressed centroblast population. The AZD8055 or GDC-0941 treatment beyond 3 weeks caused a moderate additional decrease in tumour volume, reaching ∼50% of the initial volume after 6 weeks of treatment. Tumours grew back at an increased rate and displayed similar high grade and diffuse morphology as the control untreated tumours upon cessation of drug treatment. These results define the effects that newly designed and specific mTOR and PI3K inhibitors have on a spontaneous tumour model, which may be more representative than xenograft models frequently employed to assess effectiveness of kinase inhibitors. Our data suggest that mTOR and PI3K inhibitors would benefit treatment of cancers in which the PI3K pathway is inappropriately activated; however, when administered alone, may not cause complete regression of such tumours.

Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice

PubMed Central

García-Martínez, J M; Wullschleger, S; Preston, G; Guichard, S; Fleming, S; Alessi, D R; Duce, S L

2011-01-01

Background: The PI3K–mTOR (phosphoinositide 3-kinase–mammalian target of rapamycin kinase) pathway is activated in the majority of tumours, and there is interest in assessing whether inhibitors of PI3K or mTOR kinase have efficacy in treating cancer. Here, we define the effectiveness of specific mTOR (AZD8055) and PI3K (GDC-0941) inhibitors, currently in clinical trials, in treating spontaneous B-cell follicular lymphoma that develops in PTEN+/−LKB1+/hypo mice. Methods: The PTEN+/−LKB1+/hypo mice were administered AZD8055 or GDC-0941, and the volumes of B-cell follicular lymphoma were measured by MRI. Tumour samples were analysed by immunohistochemistry, immunoblot and flow cytometry. Results: The AZD8055 or GDC-0941 induced ∼40% reduction in tumour volume within 2 weeks, accompanied by ablation of phosphorylation of AKT, S6K and SGK (serum and glucocorticoid protein kinase) protein kinases. The drugs reduced tumour cell proliferation, promoted apoptosis and suppressed centroblast population. The AZD8055 or GDC-0941 treatment beyond 3 weeks caused a moderate additional decrease in tumour volume, reaching ∼50% of the initial volume after 6 weeks of treatment. Tumours grew back at an increased rate and displayed similar high grade and diffuse morphology as the control untreated tumours upon cessation of drug treatment. Conclusion: These results define the effects that newly designed and specific mTOR and PI3K inhibitors have on a spontaneous tumour model, which may be more representative than xenograft models frequently employed to assess effectiveness of kinase inhibitors. Our data suggest that mTOR and PI3K inhibitors would benefit treatment of cancers in which the PI3K pathway is inappropriately activated; however, when administered alone, may not cause complete regression of such tumours. PMID:21407213

Evaluation of percutaneous ethanol injections in benign thyroid nodules.

PubMed

Perez, Camila Luhm Silva; Fighera, Tayane Muniz; Miasaki, Fabiola; Mesa Junior, Cleo Otaviano; Paz Filho, Gilberto Jorge da; Graf, Hans; Carvalho, Gisah Amaral de

2014-12-01

The objective of this study was to evaluate the efficacy and safety of percutaneous ethanol injection (PEI) in the treatment of benign thyroid nodules. We evaluated 120 patients with benign thyroid nodules. Patients underwent evaluation of serum TSH and free T4, cervical ultrasound, and thyroid scintigraphy (in those with suppressed TSH levels). The application of sterile ethanol 99% was guided by ultrasound, with the injected volume amounting to one-third of the nodule volume. Response was considered complete (reduction of 90%); partial (reduction between 50 and 90%); or none (reduction of < 50%). Autonomous nodules were evaluated for normalization of TSH levels. Among the nodules studied, 30.8% were solid, 56.7% were mixed, 12.5% were cystic, and 21.6% were hyperfunctioning. The initial volume of the treated nodules ranged from 0.9 to 74.8 mL (mean 13.1 ± 12.4 mL). We performed 1-8 sessions of PEI, applying an average of 6.2 mL of ethanol for patient. After 2 years of follow-up, 17% of patients achieved a complete response (94% reduction); 53%, a partial response (70% reduction); and 30%, no response. A reduction in the volume of autonomous nodules was noted in 70% of cases, and 54% had a normalized value of TSH. The main side effect is local pain, lasting less than 24 hours in most cases. This study showed that PEI is a safe and effective procedure for treatment of benign, solid or mixed thyroid nodules. Most cases resulted in significant reduction in nodule volume, with normalization of thyroid function.

Seasoning degrade in kiln drying ponderosa pine in south central Oregon.

Treesearch

A.C. Knauss

1957-01-01

This report presents the results of a study to determine the loss in volume and value of lumber when kiln drying and surfacing the production from ponderosa pine logs. The study measured (1) the reduction in volume due to trimming and culling dry lumber after surfacing, (2) the reduction in grade due to seasoning defects, (3) the reduction in grade due to failure of...

Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: digital morphometric analyses.

PubMed

Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E; Freedman, Stephen; Schenk, Dale; Young, Warren G; Morrison, John H; Bloom, Floyd E

2004-05-04

Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, beta-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs.

Selective vulnerability of dentate granule cells prior to amyloid deposition in PDAPP mice: Digital morphometric analyses

PubMed Central

Wu, Chi-Cheng; Chawla, Faisal; Games, Dora; Rydel, Russell E.; Freedman, Stephen; Schenk, Dale; Young, Warren G.; Morrison, John H.; Bloom, Floyd E.

2004-01-01

Increasing evidence from mouse models of Alzheimer's disease shows that overexpression of a mutant form of the amyloid precursor protein (APP) and its product, β-amyloid peptide, initiate pathological changes before amyloid deposition. To evaluate the cytological basis for one of these early changes, namely reduced volume of the dentate gyrus (DG), we have used high-throughput diOlistic cell loading and 3D neuronal reconstruction to investigate potential dendritic pathology of granule cells (GCs) in 90-day-old PDAPP mice. Labeled GCs from fixed hippocampal slices were selected randomly and imaged digitally by using confocal laser-scanning microscopy. The dendritic complexity of GCs was quantified according to subordinate morphological parameters, including soma position within the granule cell layer (superficial versus deep) and topographic location within the DG (dorsal versus ventral blade) along the anterior-posterior hippocampal axis. Initial analysis, which included all sampled GC types, revealed a 12% reduction of total dendritic length in PDAPP mice compared with littermate controls. Further analysis, performed with refined subgroups, found that superficially located GCs in the dorsal blade were profoundly altered, exhibiting a 23% loss in total dendritic length, whereas neurons in the ventral blade were unaffected. Superficial GCs were particularly vulnerable (a 32% reduction) in the posterior region of the DG. Furthermore, the dendritic reductions of this select group were uniformly localized within middle-to-outer portions of the dentate molecular layer. We conclude that substantial dendritic pathology is evident in 90-day-old PDAPP mice for a spatially defined subset of GCs well before amyloid accumulation occurs. PMID:15118092

Gross morphology and morphometric sequelae in the hippocampus, fornix, and corpus callosum of patients with severe non-missile traumatic brain injury without macroscopically detectable lesions: a T1 weighted MRI study

PubMed Central

Tomaiuolo, F; Carlesimo, G; Di, P; Petrides, M; Fera, F; Bonanni, R; Formisano, R; Pasqualetti, P; Caltagirone, C

2004-01-01

Objective: The gross morphology and morphometry of the hippocampus, fornix, and corpus callosum in patients with severe non-missile traumatic brain injury (nmTBI) without obvious neuroradiological lesions was examined and the volumes of these structures were correlated with performance on memory tests. In addition, the predictability of the length of coma from the selected anatomical volumes was examined. Method: High spatial resolution T1 weighted MRI scans of the brain (1 mm3) and neuropsychological evaluations with standardised tests were performed at least 3 months after trauma in 19 patients. Results: In comparison with control subjects matched in terms of gender and age, volume reduction in the hippocampus, fornix, and corpus callosum of the nmTBI patients was quantitatively significant. The length of coma correlated with the volume reduction in the corpus callosum. Immediate free recall of word lists correlated with the volume of the fornix and the corpus callosum. Delayed recall of word lists and immediate recall of the Rey figure both correlated with the volume of the fornix. Delayed recall of the Rey figure correlated with the volume of the fornix and the right hippocampus. Conclusion: These findings demonstrate that in severe nmTBI without obvious neuroradiological lesions there is a clear hippocampal, fornix, and callosal volume reduction. The length of coma predicts the callosal volume reduction, which could be considered a marker of the severity of axonal loss. A few memory test scores correlated with the volumes of the selected anatomical structures. This relationship with memory performance may reflect the diffuse nature of the damage, leading to the disruption of neural circuits at multiple levels and the progressive neural degeneration occurring in TBI. PMID:15314123

Impact of Radiofrequency Ablation of Atrial Fibrillation on Pulmonary Vein Cross Sectional Area: Implications for the Diagnosis of Pulmonary Vein Stenosis.

PubMed

Jazayeri, Mohammad-Ali; Vanga, Subba Reddy; Vuddanda, Venkat; Turagam, Mohit; Parikh, Valay; Lavu, Madhav; Bommana, Sudharani; Atkins, Donita; Nath, Jayant; Rosamond, Thomas; Vacek, James; Madhu Reddy, Y; Lakkireddy, Dhanunjaya

2017-01-01

Restoration of normal sinus rhythm by radiofrequency ablation (RFA) in atrial fibrillation (AF) patients can result in a reduction of left atrial (LA) volume and pulmonary vein (PV) dimensions. It is not clear if this PV size reduction represents a secondary effect of overall LA volume reduction or true PV stenosis. We assessed the relationship between LA volume reduction and PV orifice area pre- and post-RFA. A retrospective cohort study was conducted at a tertiary care academic hospital. Pre- and post-RFA cardiac computed tomography (CT) studies of 100 consecutive AF patients were reviewed. Studies identifying obvious segmental PV narrowing were excluded. Left atrial volumes and PV orifice cross-sectional areas (PVOCA) were measured using proprietary software from the CT scanner vendor (GE Healthcare, Waukesha, WI). The cohort had a mean age of 60 ± 8 years, 73% were male, and 90% were Caucasian. Non-paroxysmal AF was present in 76% of patients with a mean duration from diagnosis to RFA of 55 ± 54 months. Mean procedural time was 244 ± 70 min. AF recurred in 27% at 3 month follow-up. Pre-RFA LA volumes were 132 ± 60 ml and mean PVOCA was 2.89 ± 2.32 cm 2 . In patients with successful ablation, mean LA volume decreased by 10% and PVOCA decreased by 21%. PVOCA was significantly reduced in patients with successful RFA compared to those who had recurrence (2.18 ± 1.12 vs. 2.8 ± 1.9 cm 2 , p = 0.04) but reduction in LA volume between groups was not significant (118 ± 42 vs. 133 ± 54 ml, p=0.15). The study demonstrates that both PV orifice dimensions and LA volume are reduced after successful AF ablation. These data warrant a reassessment of criteria for diagnosing PV stenosis based on changes in PV caliber alone, ideally incorporating LA volume changes.

Logistics Reduction Technologies for Exploration Missions

NASA Technical Reports Server (NTRS)

Broyan, James L., Jr.; Ewert, Michael K.; Fink, Patrick W.

2014-01-01

Human exploration missions under study are limited by the launch mass capacity of existing and planned launch vehicles. The logistical mass of crew items is typically considered separate from the vehicle structure, habitat outfitting, and life support systems. Although mass is typically the focus of exploration missions, due to its strong impact on launch vehicle and habitable volume for the crew, logistics volume also needs to be considered. NASA's Advanced Exploration Systems (AES) Logistics Reduction and Repurposing (LRR) Project is developing six logistics technologies guided by a systems engineering cradle-to-grave approach to enable after-use crew items to augment vehicle systems. Specifically, AES LRR is investigating the direct reduction of clothing mass, the repurposing of logistical packaging, the use of autonomous logistics management technologies, the processing of spent crew items to benefit radiation shielding and water recovery, and the conversion of trash to propulsion gases. Reduction of mass has a corresponding and significant impact to logistical volume. The reduction of logistical volume can reduce the overall pressurized vehicle mass directly, or indirectly benefit the mission by allowing for an increase in habitable volume during the mission. The systematic implementation of these types of technologies will increase launch mass efficiency by enabling items to be used for secondary purposes and improve the habitability of the vehicle as mission durations increase. Early studies have shown that the use of advanced logistics technologies can save approximately 20 m(sup 3) of volume during transit alone for a six-person Mars conjunction class mission.

Incorporating Storm Sewer Exfiltration into SWMM: Proof of Concept

EPA Science Inventory

This study evaluates the peak flow and volume reduction achieved by exfiltration from a perforated storm sewer in an urban catchment. There are three related objectives: [1] quantify peak flow and volume reduction; [2] demonstrate adaptability to climate change; and [3] evaluate ...

Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: a divided treatment response?

PubMed

Kelsen, Jesper; Kjaer, Katrine; Chen, Gang; Pedersen, Michael; Røhl, Lisbeth; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Rønn, Lars Christian B

2006-12-06

Anti-inflammatory treatment affects ischemic damage and neurogenesis in rodent models of cerebral ischemia. We investigated the potential benefit of COX-2 inhibition with parecoxib in spontaneously hypertensive rats (SHRs) subjected to transient middle cerebral artery occlusion (tMCAo). Sixty-four male SHRs were randomized to 90 min of intraluminal tMCAo or sham surgery. Parecoxib (10 mg/kg) or isotonic saline was administered intraperitoneally (IP) during the procedure, and twice daily thereafter. Nineteen animals were euthanized after 24 hours, and each hemisphere was examined for mRNA expression of pro-inflammatory cytokines and COX enzymes by quantitative RT-PCR. Twenty-three tMCAo animals were studied with diffusion and T2 weighted MRI within the first 24 hours, and ten of the SHRs underwent follow-up MRI six days later. Thirty-three SHRs were given 5-bromo-2'-deoxy-uridine (BrdU) twice daily on Day 4 to 7 after tMCAo. Animals were euthanized on Day 8 and the brains were studied with free-floating immunohistochemistry for activated microglia (ED-1), hippocampal granule cell BrdU incorporation, and neuronal nuclei (NeuN). Infarct volume estimation was done using the 2D nucleator and Cavalieri principle on NeuN-stained coronal brain sections. The total number of BrdU+ cells in the dentate gyrus (DG) of the hippocampus was estimated using the optical fractionator. We found a significant reduction in infarct volume in parecoxib treated animals one week after tMCAo (p < 0.03). Cortical ADC values in the parecoxib group were markedly less increased on Day 8 (p < 0.01). Interestingly, the parecoxib treated rats were segregated into two subgroups, suggesting a responder vs. non-responder phenomenon. We found indications of mRNA up-regulation of IL-1beta, IL-6, TNF-alpha and COX-2, whereas COX-1 remained unaffected. Hippocampal granule cell BrdU incorporation was not affected by parecoxib treatment. Presence of ED-1+ activated microglia in the hippocampus was related to an increase in BrdU uptake in the DG. IP parecoxib administration during tMCAo was neuroprotective, as evidenced by a large reduction in mean infarct volume and a lower cortical ADC increment. Increased pro-inflammatory cytokine mRNA levels and hippocampal granule cell BrdU incorporation remained unaffected.

SU-F-R-54: CT-Texture Based Early Tumor Treatment Response Assessment During Radiation Therapy Delivery: Small Cell Versus Non-Small Cell Lung Cancers

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

Paul, J; Gore, E; Li, X

Purpose: Tumor treatment response may potentially be assessed during radiation therapy (RT) by analyzing changes in CT-textures. We investigated the different early RT-responses between small cell (SCLC) and non-small cell lung cancer (NSCLC) as assessed by CT-texture. Methods: Daily diagnostic-quality CT acquired during routine CT-guided RT using a CT-on-Rails for 13-NSCLC and 5-SCLC patients were analyzed. These patient had ages ranging from 45–78 and 38–63 years, respectively, for NSCLC and SCLC groups, and tumor-stages ranging from T2-T4, and were treated with either RT or chemotherapy and RT with 45–66Gy/ 20–34 fractions. Gross-tumor volume (GTV) contour was generated on each dailymore » CT by populating GTV contour from simulation to daily CTs with manual editing if necessary. CT-texture parameters, such as Hounsfield Unit (HU) histogram, mean HU, skewness, kurtosis, entropy, and short-run high-gray level emphasis (SRHGLE), were calculated in GTV from each daily CT-set using an in house software tool. Difference in changes of these texture parameters during RT between NSCLC and SCLC was analyzed and compared with GTV volume changes. Results: Radiation-induced changes in CT-texture were different between SCLC and NSCLC. Average changes from first to the last fractions for NSCLC and SCLC in GTV were 28±10(12–44) and 30±15(11–47) HU (mean HU reduction), 12.7% and 18.3% (entropy), 50% and 55% (SRHGLE), 19% and 22% (kurtosis), and 5.2% and 22% (skewness), respectively. Good correlation in kurtosis changes and GTV was seen (R{sup 2}=0.8923) for SCLC, but not for NSCLC (R{sup 2}=0.4748). SCLC had better correlations between GTV volume reduction and entropy (SCLC R{sup 2}=0.847; NSCLC R{sup 2}=0.6485), skewness (SCLC R{sup 2}=0.935; NSCLC R{sup 2}=0.7666), or SRHGLE (SCLC R{sup 2}=0.9619; NSCLC R{sup 2}=0.787). Conclusion: NSCLC and SCLC exhibited different early RT-responses as assessed by CT-texture changes during RT-delivery. The observed larger changes in various CT-texture parameters for SCLC indicate that SCLC may respond to RT more rapid than NSCLC.« less

High intensity focused ultrasound in the treatment of breast fibroadenomata: results of the HIFU-F trial.

PubMed

Peek, M C L; Ahmed, M; Scudder, J; Baker, R; Pinder, S E; Douek, M

2016-12-01

Breast fibroadenomata (FAD) are the most common breast lumps in women. High intensity focused ultrasound (HIFU) is a non-invasive ablative technique that can be used to treat FAD but is associated with prolonged treatment times. In the HIFU-F trial, we evaluated the change in volume over time with circumferential HIFU treatment of FAD and compared this to no treatment. Patients ≥18 years, diagnosed with symptomatic, palpable FAD, visible on ultrasound (US) were recruited. Twenty patients were treated using US-guided HIFU under local anaesthesia. Another 20 participants underwent an US 6 months after diagnosis. Outcome measures included: reduction in treatment time compared to whole lesion ablation; feasibility to achieve a 50% reduction in volume after 6 months; decrease in volume compared to a control group and reduction in symptoms. Circumferential ablation reduced the mean treatment time by 37.5% (SD 20.1%) compared to whole lesion ablation. US demonstrated a significant mean reduction in FAD volume of 43.5% (SD 38.8%; p = 0.016, paired t-test) in the HIFU group compared to 4.6% (SD 46.0%; p = 0.530) in the control group after 6 months. This mean reduction in FAD volume between the two groups was significant in favour of the HIFU group (p = 0.002, grouped t-test). Pre-treatment pain completely resolved in 6 out of 8 patients 6 months post-treatment. Circumferential HIFU ablation of FAD is feasible, with a significant reduction in pain and volume compared to control participants. It provides a simple, non-invasive, outpatient-based alternative to surgical excision for FAD.

Modelling the impact of retention-detention units on sewer surcharge and peak and annual runoff reduction.

PubMed

Locatelli, Luca; Gabriel, Søren; Mark, Ole; Mikkelsen, Peter Steen; Arnbjerg-Nielsen, Karsten; Taylor, Heidi; Bockhorn, Britta; Larsen, Hauge; Kjølby, Morten Just; Blicher, Anne Steensen; Binning, Philip John

2015-01-01

Stormwater management using water sensitive urban design is expected to be part of future drainage systems. This paper aims to model the combination of local retention units, such as soakaways, with subsurface detention units. Soakaways are employed to reduce (by storage and infiltration) peak and volume stormwater runoff; however, large retention volumes are required for a significant peak reduction. Peak runoff can therefore be handled by combining detention units with soakaways. This paper models the impact of retrofitting retention-detention units for an existing urbanized catchment in Denmark. The impact of retrofitting a retention-detention unit of 3.3 m³/100 m² (volume/impervious area) was simulated for a small catchment in Copenhagen using MIKE URBAN. The retention-detention unit was shown to prevent flooding from the sewer for a 10-year rainfall event. Statistical analysis of continuous simulations covering 22 years showed that annual stormwater runoff was reduced by 68-87%, and that the retention volume was on average 53% full at the beginning of rain events. The effect of different retention-detention volume combinations was simulated, and results showed that allocating 20-40% of a soakaway volume to detention would significantly increase peak runoff reduction with a small reduction in the annual runoff.

On the fluid dynamics of a laboratory scale single-use stirred bioreactor

PubMed Central

Odeleye, A.O.O.; Marsh, D.T.J.; Osborne, M.D.; Lye, G.J.; Micheletti, M.

2014-01-01

The commercial success of mammalian cell-derived recombinant proteins has fostered an increase in demand for novel single-use bioreactor (SUB) systems that facilitate greater productivity, increased flexibility and reduced costs (Zhang et al., 2010). These systems exhibit fluid flow regimes unlike those encountered in traditional glass/stainless steel bioreactors because of the way in which they are designed. With such disparate hydrodynamic environments between SUBs currently on the market, traditional scale-up approaches applied to stirred tanks should be revised. One such SUB is the Mobius® 3 L CellReady, which consists of an upward-pumping marine scoping impeller. This work represents the first experimental study of the flow within the CellReady using a Particle Image Velocimetry (PIV) approach, combined with a biological study into the impact of these fluid dynamic characteristics on cell culture performance. The PIV study was conducted within the actual vessel, rather than using a purpose-built mimic. PIV measurements conveyed a degree of fluid compartmentalisation resulting from the up-pumping impeller. Both impeller tip speed and fluid working volume had an impact upon the fluid velocities and spatial distribution of turbulence within the vessel. Cell cultures were conducted using the GS-CHO cell-line (Lonza) producing an IgG4 antibody. Disparity in cellular growth and viability throughout the range of operating conditions used (80–350 rpm and 1–2.4 L working volume) was not substantial, although a significant reduction in recombinant protein productivity was found at 350 rpm and 1 L working volume (corresponding to the highest Reynolds number tested in this work). The study shows promise in the use of PIV to improve understanding of the hydrodynamic environment within individual SUBs and allows identification of the critical hydrodynamic parameters under the different flow regimes for compatibility and scalability across the range of bioreactor platforms. PMID:24864128

On the fluid dynamics of a laboratory scale single-use stirred bioreactor.

PubMed

Odeleye, A O O; Marsh, D T J; Osborne, M D; Lye, G J; Micheletti, M

2014-05-24

The commercial success of mammalian cell-derived recombinant proteins has fostered an increase in demand for novel single-use bioreactor (SUB) systems that facilitate greater productivity, increased flexibility and reduced costs (Zhang et al., 2010). These systems exhibit fluid flow regimes unlike those encountered in traditional glass/stainless steel bioreactors because of the way in which they are designed. With such disparate hydrodynamic environments between SUBs currently on the market, traditional scale-up approaches applied to stirred tanks should be revised. One such SUB is the Mobius ® 3 L CellReady, which consists of an upward-pumping marine scoping impeller. This work represents the first experimental study of the flow within the CellReady using a Particle Image Velocimetry (PIV) approach, combined with a biological study into the impact of these fluid dynamic characteristics on cell culture performance. The PIV study was conducted within the actual vessel, rather than using a purpose-built mimic. PIV measurements conveyed a degree of fluid compartmentalisation resulting from the up-pumping impeller. Both impeller tip speed and fluid working volume had an impact upon the fluid velocities and spatial distribution of turbulence within the vessel. Cell cultures were conducted using the GS-CHO cell-line (Lonza) producing an IgG 4 antibody. Disparity in cellular growth and viability throughout the range of operating conditions used (80-350 rpm and 1-2.4 L working volume) was not substantial, although a significant reduction in recombinant protein productivity was found at 350 rpm and 1 L working volume (corresponding to the highest Reynolds number tested in this work). The study shows promise in the use of PIV to improve understanding of the hydrodynamic environment within individual SUBs and allows identification of the critical hydrodynamic parameters under the different flow regimes for compatibility and scalability across the range of bioreactor platforms.

Inorganic mercury accumulation in brain following waterborne exposure elicits a deficit on the number of brain cells and impairs swimming behavior in fish (white seabream-Diplodus sargus).

PubMed

Pereira, Patrícia; Puga, Sónia; Cardoso, Vera; Pinto-Ribeiro, Filipa; Raimundo, Joana; Barata, Marisa; Pousão-Ferreira, Pedro; Pacheco, Mário; Almeida, Armando

2016-01-01

The current study contributes to fill the knowledge gap on the neurotoxicity of inorganic mercury (iHg) in fish through the implementation of a combined evaluation of brain morphometric alterations (volume and total number of neurons plus glial cells in specific regions of the brain) and swimming behavior (endpoints related with the motor activity and mood/anxiety-like status). White seabream (Diplodus sargus) was exposed to realistic levels of iHg in water (2μgL(-1)) during 7 (E7) and 14 days (E14). After that, fish were allowed to recover for 28 days (PE28) in order to evaluate brain regeneration and reversibility of behavioral syndromes. A significant reduction in the number of cells in hypothalamus, optic tectum and cerebellum was found at E7, accompanied by relevant changes on swimming behavior. Moreover, the decrease in the number of neurons and glia in the molecular layer of the cerebellum was followed by a contraction of its volume. This is the first time that a deficit on the number of cells is reported in fish brain after iHg exposure. Interestingly, a recovery of hypothalamus and cerebellum occurred at E14, as evidenced by the identical number of cells found in exposed and control fish, and volume of cerebellum, which might be associated with an adaptive phenomenon. After 28 days post-exposure, the optic tectum continued to show a decrease in the number of cells, pointing out a higher vulnerability of this region. These morphometric alterations coincided with numerous changes on swimming behavior, related both with fish motor function and mood/anxiety-like status. Overall, current data pointed out the iHg potential to induce brain morphometric alterations, emphasizing a long-lasting neurobehavioral hazard. Copyright © 2015 Elsevier B.V. All rights reserved.

Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo.

PubMed

Srivastava, Sanjay K; Xiao, Dong; Lew, Karen L; Hershberger, Pamela; Kokkinakis, Demetrius M; Johnson, Candace S; Trump, Donald L; Singh, Shivendra V

2003-10-01

We have shown previously that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits survival of PC-3 and LNCaP human prostate cancer cells in culture, whereas proliferation of a normal prostate epithelial cell line is minimally affected by AITC even at concentrations that are highly cytotoxic to the prostate cancer cells. The present studies were designed to test the hypothesis that AITC administration may retard growth of human prostate cancer xenografts in vivo. Bolus i.p. injection of 10 micromol AITC, three times per week (Monday, Wednesday and Friday) beginning the day of tumor cell implantation, significantly inhibited the growth of PC-3 xenograft (P < 0.05 by two-way ANOVA). For example, 26 days after tumor cell implantation, the average tumor volume in control mice (1025 +/- 205 mm3) was approximately 1.7-fold higher compared with AITC-treated mice. Histological analysis of tumors excised at the termination of the experiment revealed a statistically significant increase in number of apoptotic bodies with a concomitant decrease in cells undergoing mitosis in the tumors of AITC-treated mice compared with that of control mice. Western blot analysis indicated an approximately 70% reduction in the levels of anti-apoptotic protein Bcl-2 in the tumor lysate of AITC-treated mice compared with that of control mice. Moreover, the tumors from AITC-treated mice, but not control mice, exhibited cleavage of BID, which is known to promote apoptosis. Statistically significant reduction in the expression of several proteins that regulate G2/M progression, including cyclin B1, cell division cycle (Cdc)25B and Cdc25C (44, 45 and 90% reduction, respectively, compared with control), was also observed in the tumors of AITC-treated mice relative to control tumors. In conclusion, the results of the present study indicate that AITC administration inhibits growth of PC-3 xenografts in vivo by inducing apoptosis and reducing mitotic activity.

Acute Exposure to High Dose γ-Radiation Results in Transient Activation of Bone Lining Cells

PubMed Central

Turner, Russell T.; Iwaniec, Urszula T.; Wong, Carmen P.; Lindenmaier, Laurence B.; Wagner, Lindsay A.; Branscum, Adam J.; Menn, Scott A.; Taylor, James; Zhang, Ye; Wu, Honglu; Sibonga, Jean D.

2014-01-01

The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced fractional cancellous bone volume, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14 days following γ-irradiation with 6 Gy. To establish the cellular mechanism for the architectural changes, vertebrae were analyzed by histomorphometry 1, 3, and 14 days following irradiation. Marrow cell density decreased within 1 day (67% reduction, p<0.0001), reached a minimum value after 3 days (86% reduction, p<0.0001), and partially rebounded by 14 days (30% reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone perimeter was increased by 290% (1 day, p=0.04), 1230% (3 days, p<0.0001), and 530% (14 days, p=0.003), respectively. There was a strong association between radiation-induced marrow cell death and activation of bone lining cells to express the osteoblast phenotype (Pearson correlation −0.85, p<0.0001). An increase (p=0.004) in osteoclast-lined bone perimeter was also detected with irradiation. A priming dose of γ-radiation (0.5 mGy), previously shown to reduce mortality, had minimal effect on the cellular responses to radiation and did not prevent detrimental changes in bone architecture. Bone marrow transplantation normalized marrow cell density, bone turnover, and most indices of bone architecture following irradiation. In summary, radiation-induced death of marrow cells is associated with 1) a transient increase in bone formation due, at least in part, to activation of bone lining cells, and 2) an increase in bone resorption due to increased osteoclast perimeter. Bone marrow transplantation is effective in mitigating the detrimental effects of acute exposure to high dose whole body γ-radiation on bone turnover. PMID:23954507

Human Dental Pulp Stem Cells Are More Effective Than Human Bone Marrow-Derived Mesenchymal Stem Cells in Cerebral Ischemic Injury.

PubMed

Song, Miyeoun; Lee, Jae-Hyung; Bae, Jinhyun; Bu, Youngmin; Kim, Eun-Cheol

2017-06-09

We compared the therapeutic effects and mechanism of transplanted human dental pulp stem cells (hDPSCs) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in a rat stroke model and an in vitro model of ischemia. Rats were intravenously injected with hDPSCs or hBM-MSCs 24 h after middle cerebral artery occlusion (MCAo), and both groups showed improved functional recovery and reduced infarct volume versus control rats, but the hDPSC group showed greater reduction in infarct volume than the hBM-MSC group. The positive area for the endothelial cell marker was greater in the lesion boundary areas in the hDPSC group than in the hBM-MSC group. Administration of hDPSCs to rats with stroke significantly decreased reactive gliosis, as evidenced by the attenuation of MCAo-induced GFAP+/nestin+ and GFAP+/Musashi-1+ cells, compared with hBM-MSCs. In vivo findings were confirmed by in vitro data illustrating that hDPSCs showed superior neuroprotective, migratory, and in vitro angiogenic effects in oxygen-glucose deprivation (OGD)-injured human astrocytes (hAs) versus hBM-MSCs. Comprehensive comparative bioinformatics analyses from hDPSC- and hBM-MSC-treated in vitro OGD-injured hAs were examined by RNA sequencing technology. In gene ontology and KEGG pathway analyses, significant pathways in the hDPSC-treated group were the MAPK and TGF-β signaling pathways. Thus, hDPSCs may be a better cell therapy source for ischemic stroke than hBM-MSCs.

Fluid/electrolyte and endocrine changes in space flight

NASA Technical Reports Server (NTRS)

Huntoon, Carolyn Leach

1989-01-01

The primary effects of space flight that influence the endocrine system and fluid and electrolyte regulation are the reduction of hydrostatic gradients, reduction in use and gravitational loading of bone and muscle, and stress. Each of these sets into motion a series of responses that culminates in alteration of some homeostatic set points for the environment of space. Set point alterations are believed to include decreases in venous pressure; red blood cell mass; total body water; plasma volume; and serum sodium, chloride, potassium, and osmolality. Serum calcium and phosphate increase. Hormones such as erythropoietin, atrial natriuretic peptide, aldosterone, cortisol, antidiuretic hormone, and growth hormone are involved in the dynamic processes that bring about the new set points. The inappropriateness of microgravity set points for 1-G conditions contributes to astronaut postflight responses.

Hot-isostatically pressed wasteforms for Magnox sludge immobilisation

NASA Astrophysics Data System (ADS)

Heath, Paul G.; Stewart, Martin W. A.; Moricca, Sam; Hyatt, Neil C.

2018-02-01

Thermal treatment technologies offer many potential benefits for the treatment of radioactive wastes including the passivation of reactive species and significant waste volume reductions. This paper presents a study investigating the production of wasteforms using Hot-isostatic pressing technology for the immobilisation of Magnox sludges from the UK's Sellafield Site. Simulants considered physically representative of these sludges were used to determine possible processing parameters and to determine the phase assemblages and morphologies produced during processing. The study showed hot-isostatic pressing is capable of processing Magnox sludges at up to 60 wt% (oxide basis) into dense, mixed ceramic wasteforms. The wasteforms produced are a glass-bonded ceramic of mixed magnesium titanates, encapsulating localised grains of periclase. The ability to co-process Magnox sludges with SIXEP sand/clinoptilolite slurries has also been demonstrated. The importance of these results is presented through a comparison of volume reduction data, which shows HIPing may provide a 20-fold volume reduction over the current cementitious baseline and double the volume reduction attainable for vitrification technologies.

SU-E-T-625: Potential for Reduced Radiation Induced Toxicity for the Treatment of Inoperable Non-Small-Cell Lung Cancer Using RapidArc Planning

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

Pokhrel, D; Sood, S; Badkul, R

2015-06-15

Purpose: To investigate the feasibility of using RapidArc (RA) treatment planning to reduce irradiation volume of normal lung and other organs at risk (OARs) in the treatment of inoperable non-small-cell lung cancer (NSCLC) patients. Methods: A retrospective treatment planning and delivery study was performed to compare target coverage and the volumes of the normal lung, spinal cord, heart and esophagus on 4D-CT scan above their dose tolerances delivered by RA vs. IMRT for ten inoperable NSCLC patients (Stage I-IIIB). RA plans consisted of either one-full or two-partial co-planar arcs used to treat 95% of the planning target volume (PTV) withmore » 6MV beam to a prescription of 66Gy in 33 fractions. IMRT plans were generated using 5–7 co-planar fields with 6MV beam. PTV coverage, dose-volume histograms, homogeneity/conformity indices (CI), total number of monitor units(MUs), beam-on time and delivery accuracy were compared between the two treatment plans. Results: Similar target coverage was obtained between the two techniques. RA (CI=1.02) provided more conformal plans without loss of homogeneity compared to IMRT plans (CI=1.12). Compared to IMRT, RA achieved a significant median dose reduction in V10 (3%), V20 (8%), and mean lung dose (3%) on average, respectively. On average, V5 was comparable between the two treatment plans. RA reduced mean esophagus (6%), mean heart (18%), and maximum spinal cord dose (7%), on average, respectively. Total number of MUs and beam-on time were each reduced almost by a factor of 2 when compared to IMRT-patient comfort, reduced intra-fraction-motion and leakage dose. The average IMRT and RA QA pass rate was about 98% for both types of plans for 3%/3mm criterion. Conclusion: Compared to IMRT plans, RA provided not only comparable target coverage, but also improved conformity, treatment time, and significant reduction in irradiation of OARs. This may potentially allow for target dose escalation without increase in normal tissue toxicity.« less

Dissociable contributions of MRI volume reductions of superior temporal and fusiform gyri to symptoms and neuropsychology in schizophrenia.

PubMed

Nestor, Paul G; Onitsuka, Toshiaki; Gurrera, Ronald J; Niznikiewicz, Margaret; Frumin, Melissa; Shenton, Martha E; McCarley, Robert W

2007-03-01

We sought to identify the functional correlates of reduced magnetic resonance imaging (MRI) volumes of the superior temporal gyrus (STG) and the fusiform gyrus (FG) in patients with chronic schizophrenia. MRI volumes, positive/negative symptoms, and neuropsychological tests of facial memory and executive functioning were examined within the same subjects. The results indicated two distinct, dissociable brain structure-function relationships: (1) reduced left STG volume-positive symptoms-executive deficits; (2) reduced left FG-negative symptoms-facial memory deficits. STG and FG volume reductions may each make distinct contributions to symptoms and cognitive deficits of schizophrenia.

Familial and environmental influences on brain volumes in twins with schizophrenia.

PubMed

Picchioni, Marco M; Rijsdijk, Fruhling; Toulopoulou, Timothea; Chaddock, Christopher; Cole, James H; Ettinger, Ulrich; Oses, Ana; Metcalfe, Hugo; Murray, Robin M; McGuire, Philip

2017-03-01

Reductions in whole brain and grey matter volumes are robust features of schizophrenia, yet their etiological influences are unclear. We investigated the association between the genetic and environmental risk for schizophrenia and brain volumes. Whole brain, grey matter and white matter volumes were established from structural MRIs from twins varying in their zygosity and concordance for schizophrenia. Hippocampal volumes were measured manually. We conducted between-group testing and full genetic modelling. We included 168 twins in our study. Whole brain, grey matter, white matter and right hippocampal volumes were smaller in twins with schizophrenia. Twin correlations were larger for whole brain, grey matter and white matter volumes in monozygotic than dizygotic twins and were significantly heritable, whereas hippocampal volume was the most environmentally sensitive. There was a significant phenotypic correlation between schizophrenia and reductions in all the brain volumes except for that of the left hippocampus. For whole brain, grey matter and the right hippocampus the etiological links with schizophrenia were principally associated with the shared familial environment. Lower birth weight and perinatal hypoxia were both associated with lower whole brain volume and with lower white matter and grey matter volumes, respectively. Scan data were collected across 2 sites, and some groups were modest in size. Whole brain, grey matter and right hippocampal volume reductions are linked to schizophrenia through correlated familial risk (i.e., the shared familial environment). The degree of influence of etiological factors varies between brain structures, leading to the possibility of a neuroanatomically specific etiological imprint.

Flat-plate solar array project. Volume 3: Silicon sheet: Wafers and ribbons

NASA Technical Reports Server (NTRS)

Briglio, A.; Dumas, K.; Leipold, M.; Morrison, A.

1986-01-01

The primary objective of the Silicon Sheet Task of the Flat-Plate Solar Array (FSA) Project was the development of one or more low cost technologies for producing silicon sheet suitable for processing into cost-competitive solar cells. Silicon sheet refers to high purity crystalline silicon of size and thickness for fabrication into solar cells. Areas covered in the project were ingot growth and casting, wafering, ribbon growth, and other sheet technologies. The task made and fostered significant improvements in silicon sheet including processing of both ingot and ribbon technologies. An additional important outcome was the vastly improved understanding of the characteristics associated with high quality sheet, and the control of the parameters required for higher efficiency solar cells. Although significant sheet cost reductions were made, the technology advancements required to meet the task cost goals were not achieved.

Cellular pressure and volume regulation and implications for cell mechanics

NASA Astrophysics Data System (ADS)

Jiang, Hongyuan; Sun, Sean

2013-03-01

In eukaryotic cells, small changes in cell volume can serve as important signals for cell proliferation, death and migration. Volume and shape regulation also directly impacts the mechanics of the cell and multi-cellular tissues. Recent experiments found that during mitosis, eukaryotic cells establish a preferred steady volume and pressure, and the steady volume and pressure can robustly adapt to large osmotic shocks. Here we develop a mathematical model of cellular pressure and volume regulation, incorporating essential elements such as water permeation, mechano-sensitive channels, active ion pumps and active stresses in the actomyosin cortex. The model can fully explain the available experimental data, and predicts the cellular volume and pressure for several models of cell cortical mechanics. Furthermore, we show that when cells are subjected to an externally applied load, such as in an AFM indentation experiment, active regulation of volume and pressure leads to complex cellular response. We found the cell stiffness highly depends on the loading rate, which indicates the transport of water and ions might contribute to the observed viscoelasticity of cells.

A Two-Year Longitudinal MRI Study of the Corpus Callosum in Autism

PubMed Central

Frazier, Thomas W.; Keshavan, Matcheri S.; Minshew, Nancy J.; Hardan, Antonio Y.

2015-01-01

A growing body of literature has identified size reductions of the corpus callosum (CC) in autism. However, to our knowledge, no published studies have reported on the growth of CC volumes in youth with autism. Volumes of the total CC and its sub-divisions were obtained from 23 male children with autism and 23 age-matched male controls at baseline and 2-year follow-up. Persistent reductions in total CC volume were observed in participants with autism relative to controls. Only the rostral body sub-division showed a normalization of size over time. Persistent reductions are consistent with the diagnostic stability and life-long impairment observed in many individuals with autism. Multimodal imaging studies are needed to identify specific fiber tracks contributing to CC reductions. PMID:22350341

A review on optical actuators for microfluidic systems

NASA Astrophysics Data System (ADS)

Yang, Tie; Chen, Yue; Minzioni, Paolo

2017-12-01

During the last few decades microfluidic systems have become more and more popular and their relevance in different fields is continually growing. In fact, the use of microchannels allows a significant reduction of the required sample-volume and opens the way to a completely new set of possible investigations, including the study of the properties of cells, the development of new cells’ separation techniques and the analysis of single-cell proteins. One of the main differences between microscopic and macroscopic systems is obviously dictated by the need for suitable actuation mechanisms, which should allow precise control of microscopic fluid volumes and of micro-samples inside the fluid. Even if both syringe-pump and pneumatic-pump technologies significantly evolved and they currently enable sub-μL samples control, completely new approaches were recently developed for the manipulation of samples inside the microchannel. This review is dedicated to describing different kinds of optical actuators that can be applied in microfluidic systems for sample manipulation as well as for pumping. The basic principles underlying the optical actuation mechanisms will be described first, and then several experimental demonstrations will be reviewed and compared.

BDNF is Associated With Age-Related Decline in Hippocampal Volume

PubMed Central

Erickson, Kirk I.; Prakash, Ruchika Shaurya; Voss, Michelle W.; Chaddock, Laura; Heo, Susie; McLaren, Molly; Pence, Brandt D.; Martin, Stephen A.; Vieira, Victoria J.; Woods, Jeffrey A.; Kramer, Arthur F.

2010-01-01

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood. PMID:20392958

Antibody-Dependent Cell-Mediated Cytotoxicity Effector-Enhanced EphA2 Agonist Monoclonal Antibody Demonstrates Potent Activity against Human Tumors1

PubMed Central

Bruckheimer, Elizabeth M; Fazenbaker, Christine A; Gallagher, Sandra; Mulgrew, Kathy; Fuhrmann, Stacy; Coffman, Karen T; Walsh, William; Ready, Shannon; Cook, Kim; Damschroder, Melissa; Kinch, Michael; Kiener, Peter A; Woods, Rob; Gao, Changshou; Dall'Acqua, William; Wu, Herren; Coats, Steven

2009-01-01

EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vitro and in vivo antibody-dependent cell-mediated cytotoxicity (ADCC) activity of EphA2 effector-enhanced agonist monoclonal antibodies was evaluated. With tumor cell lines and healthy human peripheral blood monocytes, the EphA2 antibodies demonstrated ∼80% tumor cell killing. In a dose-dependent manner, natural killer (NK) cells were required for the in vitro ADCC activity and became activated as demonstrated by the induction of cell surface expression of CD107a. To assess the role of NK cells on antitumor efficacy in vivo, the EphA2 antibodies were evaluated in xenograft models in severe compromised immunodeficient (SCID) mice (which have functional NK cells and monocytes) and SCID nonobese diabetic (NOD) mice (which largely lack functional NK cells and monocytes). Dosing of EphA2 antibody in the SCID murine tumor model resulted in a 6.2-fold reduction in tumor volume, whereas the SCID/nonobese diabetic model showed a 1.6-fold reduction over the isotype controls. Together, these results demonstrate that the anti-EphA2 monoclonal antibodies may function through at least two mechanisms of action: EphA2 receptor activation and ADCC-mediated activity. These novel EphA2 monoclonal antibodies provide additional means by which host effector mechanisms can be activated for selective destruction of EphA2-expressing tumor cells. PMID:19484140

Involvement of reactive oxygen species/c-Jun NH{sub 2}-terminal kinase pathway in kotomolide A induces apoptosis in human breast cancer cells

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

Kuo, P.-L.; Chen, C.-Y.; Tzeng, T.-F.

2008-06-01

The anticancer effects of kotomolide A (KTA), a new butanolide constituent isolated from the leaves of Cinnamomum kotoense (Lauraceae), on the two human breast cancer cell lines MCF-7 and MDA-MB-231, were first investigated in our study. KTA exhibited selectively antiproliferative effects in cancer cell lines without showing any toxicity in normal mammary epithelial cells. Treatment of cancer cells with KTA to trigger G2/M phase arrest was associated with increased p21/WAF1 levels and reduced amounts of cyclin A, cyclin B1, cdc2 and cdc25C. KTA induced cancer cell death treatment by triggering mitochondrial and death receptor 5 (DR5) apoptotic pathways, but didmore » not act on the Fas receptor. Exposure of MCF-7 and MDA-MB-231 cells to KTA resulted in cellular glutathione reduction and ROS generation, accompanied by JNK activation and apoptosis. Both antioxidants, NAC and catalase, significantly decreased apoptosis by inhibiting the phosphorylation of JNK and subsequently triggering DR5 cell death pathways. The reduction of JNK expression by siRNA decreased KTA-mediated Bim cleavage, DR5 upregulation and apoptosis. Furthermore, daily KTA i.p. injections in nude mice with MDA-MB-231 s.c. tumors resulted in a 50% decrease of mean tumor volume, compared with vehicle-treated controls. Taken together, the data show that cell death of breast cancer cells in response to KTA is dependent upon ROS generation and JNK activation, triggering intrinsic and extrinsic apoptotic pathways. The ROS/JNK pathway could be a useful target for novel approaches in breast cancer chemotherapy.« less

The cerebral embolism evoked by intra-arterial delivery of allogeneic bone marrow mesenchymal stem cells in rats is related to cell dose and infusion velocity.

PubMed

Cui, Li-li; Kerkelä, Erja; Bakreen, Abdulhameed; Nitzsche, Franziska; Andrzejewska, Anna; Nowakowski, Adam; Janowski, Miroslaw; Walczak, Piotr; Boltze, Johannes; Lukomska, Barbara; Jolkkonen, Jukka

2015-01-27

Intra-arterial cell infusion is an efficient delivery route with which to target organs such as the ischemic brain. However, adverse events including microembolisms and decreased cerebral blood flow were recently reported after intra-arterial cell delivery in rodent models, raising safety concerns. We tested the hypothesis that cell dose, infusion volume, and velocity would be related to the severity of complications after intra-arterial cell delivery. In this study, 38 rats were subjected to a sham middle cerebral artery occlusion (sham-MCAO) procedure before being infused with allogeneic bone-marrow mesenchymal stem cells at different cell doses (0 to 1.0 × 10(6)), infusion volumes (0.5 to 1.0 ml), and infusion times (3 to 6 minutes). An additional group (n = 4) was infused with 1.0 × 10(6) cells labeled with iron oxide for in vivo tracking of cells. Cells were infused through the external carotid artery under laser Doppler flowmetry monitoring 48 hours after sham-MCAO. Magnetic resonance imaging (MRI) was performed 24 hours after cell infusion to reveal cerebral embolisms or hemorrhage. Limb placing, cylinder, and open field tests were conducted to assess sensorimotor functions before the rats were perfused for histology. A cell dose-related reduction in cerebral blood flow was noted, as well as an increase in embolic events and concomitant lesion size, and sensorimotor impairment. In addition, a low infusion velocity (0.5 ml/6 minutes) was associated with high rate of complications. Lesions on MRI were confirmed with histology and corresponded to necrotic cell loss and blood-brain barrier leakage. Particularly cell dose but also infusion velocity contribute to complications encountered after intra-arterial cell transplantation. This should be considered before planning efficacy studies in rats and, potentially, in patients with stroke.

Near infrared photoimmunotherapy for lung metastases

PubMed Central

Sato, Kazuhide; Nagaya, Tadanobu; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka

2015-01-01

Lung metastases are a leading cause of cancer related deaths; nonetheless current treatments are limited. Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies that target tumors with the toxicity induced by photosensitizers activated by NIR-light. Herein, we demonstrate the efficacy of NIR-PIT in a mouse model of lung metastases. Experiments were conducted with a HER2, luciferase and GFP expressing cell line (3T3/HER2-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. With 3D culture, repeated NIR-PIT could eradicate entire spheroids. In vivo anti-tumor effects of NIR-PIT included significant reductions in both tumor volume (p = 0.0141 vs. APC) and bioluminescence image (BLI) (p = 0.0086 vs. APC) in the flank model, and prolonged survival (p < 0.0001). BLI demonstrated a significant reduction in lung metastases volume (p = 0.0117 vs. APC). Multiple NIR-PIT doses significantly prolonged survival in the lung metastases model (p < 0.0001). These results suggested that NIR-PIT is a potential new therapy for the local control of lung metastases. PMID:26021765

Experimental investigation of shock-cell noise reduction for single-stream nozzles in simulated flight, comprehensive data report. Volume 2: Laser velocimeter data

NASA Technical Reports Server (NTRS)

Yamamoto, K.; Brausch, J. F.; Janardan, B. A.; Hoerst, D. J.; Price, A. O.; Knott, P. R.

1984-01-01

Mean velocity (axial component) and turbulent velocity (axial component) measurements for thirty one selected flow conditions of six models were performed employing the Laser Doppler Velocimeter Aerodynamic conditions which define the test points are given. Tabulations which explain the scope of mean velocity traverses and turbulence histogram measurements are also presented. The actual LV position, the type of traverse, and measured mean and turbulent velocities along copies of the LV mean velocity traces are contained.

Experimental Evidence of Negative Linear Compressibility in the MIL-53 Metal-organic Framework Family

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

Serra-Crespo, Pablo; Dikhtiarenko, Alla; Stavitski, Eli

Here we report a series of powder X-ray diffraction experiments performed on the soft porous crystals MIL-53(Al) and NH 2-MIL-53(Al) in a diamond anvil cell under different pressurization media. Systematic refinements of the obtained powder patterns demonstrate that these materials expand along a specific direction while undergoing total volume reduction under an increasing hydrostatic pressure. Our results confirm for the first time the negative linear compressibility behaviour of this family of materials, recently predicted from quantum chemical calculations.

Experimental evidence of negative linear compressibility in the MIL-53 metal–organic framework family

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

Serra-Crespo, Pablo; Dikhtiarenko, Alla; Stavitski, Eli

Here we report a series of powder X-ray diffraction experiments performed on the soft porous crystals MIL-53(Al) and NH 2-MIL-53(Al) in a diamond anvil cell under different pressurization media. Systematic refinements of the obtained powder patterns demonstrate that these materials expand along a specific direction while undergoing total volume reduction under an increasing hydrostatic pressure. The results confirm for the first time the negative linear compressibility behaviour of this family of materials, recently predicted from quantum chemical calculations.

Experimental Evidence of Negative Linear Compressibility in the MIL-53 Metal-Organic Framework Family

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

Serra-Crespo, Pablo; Dikhtiarenko, Alla; Stavitski, Eli

Here, we report a series of powder X-ray diffraction experiments performed on the soft porous crystals MIL-53(Al) and NH 2-MIL-53(Al) in a diamond anvil cell under different pressurization media. Systematic refinements of the obtained powder patterns demonstrate that these materials expand along a specific direction while undergoing total volume reduction under an increasing hydrostatic pressure. Our results confirm for the first time the negative linear compressibility behaviour of this family of materials, recently predicted from quantum chemical calculations.

Experimental evidence of negative linear compressibility in the MIL-53 metal–organic framework family

DOE PAGES

Serra-Crespo, Pablo; Dikhtiarenko, Alla; Stavitski, Eli; ...

2014-03-24

Here we report a series of powder X-ray diffraction experiments performed on the soft porous crystals MIL-53(Al) and NH 2-MIL-53(Al) in a diamond anvil cell under different pressurization media. Systematic refinements of the obtained powder patterns demonstrate that these materials expand along a specific direction while undergoing total volume reduction under an increasing hydrostatic pressure. The results confirm for the first time the negative linear compressibility behaviour of this family of materials, recently predicted from quantum chemical calculations.

Electrochemical carbon dioxide concentrator advanced technology tasks

NASA Technical Reports Server (NTRS)

Schneider, J. J.; Schubert, F. H.; Hallick, T. M.; Woods, R. R.

1975-01-01

Technology advancement studies are reported on the basic electrochemical CO2 removal process to provide a basis for the design of the next generation cell, module and subsystem hardware. An Advanced Electrochemical Depolarized Concentrator Module (AEDCM) is developed that has the characteristics of low weight, low volume, high CO2, removal, good electrical performance and low process air pressure drop. Component weight and noise reduction for the hardware of a six man capacity CO2 collection subsystem was developed for the air revitalization group of the Space Station Prototype (SSP).

Static High Pressure Structural studies on Dy to 119 GPa

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

Patterson, J R; Saw, C K; Akella, J

2003-11-12

Structural phase transitions in the rare-earth metal Dysprosium have been studied in a Diamond Anvil Cell (DAC) to 119 GPa by x-ray diffraction. Four transformations following the sequence hcp {yields} Sm-type {yields} dhcp {yields} hR24 (hexagonal) {yields} bcm (monoclinic) are observed at 6, 15, 43, and 73 GPa respectively. The hexagonal to monoclinic transformation is accompanied by a 6% reduction in volume, which is attributed to delocalization of the 4f electrons, similar to that seen in Ce, Pr, and Gd.

Bromelain inhibits COX-2 expression by blocking the activation of MAPK regulated NF-kappa B against skin tumor-initiation triggering mitochondrial death pathway.

PubMed

Bhui, Kulpreet; Prasad, Sahdeo; George, Jasmine; Shukla, Yogeshwer

2009-09-18

Chemoprevention impels the pursuit for either single targeted or cocktail of multi-targeted agents. Bromelain, potential agent in this regard, is a pharmacologically active compound, present in stems and fruits of pineapple (Ananas cosmosus), endowed with anti-inflammatory, anti-invasive and anti-metastatic properties. Herein, we report the anti tumor-initiating effects of bromelain in 2-stage mouse skin tumorigenesis model. Pre-treatment of bromelain resulted in reduction in cumulative number of tumors (CNT) and average number of tumors per mouse. Preventive effect was also comprehended in terms of reduction in tumor volume up to a tune of approximately 65%. Components of the cell signaling pathways, connecting proteins involved in cell death were targeted. Bromelain treatment resulted in upregulation of p53 and Bax and subsequent activation of caspase 3 and caspase 9 with concomitant decrease in Bcl-2. A marked inhibition in cyclooxygenase-2 (Cox-2) expression and inactivation of nuclear factor-kappa B (NF-kappaB) was recorded, as phosphorylation and consequent degradation of I kappa B alpha was blocked by bromelain. Also, bromelain treatment curtailed extracellular signal regulated protein kinase (ERK1/2), p38 mitogen-activated protein kinase (MAPK) and Akt activity. The basis of anti tumor-initiating activity of bromelain was revealed by its time dependent reduction in DNA nick formation and increase in percentage prevention. Thus, modulation of inappropriate cell signaling cascades driven by bromelain is a coherent approach in achieving chemoprevention.

Childhood maltreatment and corpus callosum volume in recently diagnosed patients with bipolar I disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

PubMed

Bücker, J; Muralidharan, K; Torres, I J; Su, W; Kozicky, J; Silveira, L E; Bond, D J; Honer, W G; Kauer-Sant'anna, M; Lam, R W; Yatham, L N

2014-01-01

Childhood trauma (CT) has been associated with abnormalities in the corpus callosum (CC). Decreased CC volumes have been reported in children and adolescents with trauma as well as adults with CT compared to healthy controls. CC morphology is potentially susceptible to the effects of Bipolar Disorder (BD) itself. Therefore, we evaluated the relationship between CT and CC morphology in BD. We using magnetic resonance imaging in 53 adults with BD recently recovered from their first manic episode, with (n = 23) and without (n = 30) CT, defined using the Childhood Trauma Questionnaire (CTQ) and 16 healthy controls without trauma. ANCOVA was performed with age, gender and intracranial volume as covariates in order to evaluate group differences in CC volume. The total CC volume was found to be smaller in BD patients with trauma compared to BD patients without trauma (p < .05). The differences were more pronounced in the anterior region of the CC. There was a significant negative correlation between CTQ scores and total CC volume in BD patients with trauma (p = .01). We did not find significant differences in the CC volume of patients with/without trauma compared to the healthy subjects. Our sample consists of patients recovered from a first episode of mania and are early in the course of illness and reductions in CC volume may occur late in the course of BD. It might mean there may be two sources of CC volume reduction in these patients: the reduction due to trauma, and the further reduction due to the illness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clinical evidence to demonstrate that simultaneous growth of epithelial and fibroblast cells is essential for deep wound healing.

PubMed

Shrivastava, Ravi

2011-04-01

The aim of this study was to evaluate the chronic wound healing properties of tannin rich plant extracts. The cell growth stimulating potential of 128 procyanidin rich plant extracts was evaluated in in vitro cell culture models. For clinical trial, a 3% solution of two plant extracts having synergistic effect on cell growth was prepared in glycerol and honey. Placebo test product contained only glycerol and honey. 93 adult patients with one or more lower extremity deep wounds were divided at randomly in two groups. 41 patients in the placebo (AS-22) and 52 in the active treatment (AS-21) groups having respectively 49 and 69 wounds of a mean surface area of 56.70 and 52.03 cm(2), and volume of 57.22 and 52.15 cm(3), were treated by applying the test products topically for a period of 6-weeks. A statistically significant difference was observed between the placebo and the AS-21 treated groups with respect to reduction in the wound surface area (33.37 vs 97.87%) and wound volume (29.45 vs 94.17%) after 6-weeks of treatment. Mean wound humidity and pain scores were also reduced. Tannin rich plant extracts are highly interesting for the treatment of chronic wounds. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

REDUCED CHLOROPLAST COVERAGE genes from Arabidopsis thaliana help to establish the size of the chloroplast compartment

DOE PAGES

Larkin, Robert M.; Stefano, Giovanni; Ruckle, Michael E.; ...

2016-02-09

Eukaryotic cells require mechanisms to establish the proportion of cellular volume devoted to particular organelles. These mechanisms are poorly understood. From a screen for plastid-to-nucleus signaling mutants in Arabidopsis thaliana, we cloned a mutant allele of a gene that encodes a protein of unknown function that is homologous to two other Arabidopsis genes of unknown function and Arabidopsis. In contrast to FRIENDLY, these three homologs of FRIENDLY are found only in photosynthetic organisms. Based on these data, we proposed that FRIENDLY expanded into a small gene family to help regulate the energy metabolism of cells that contain both mitochondria andmore » chloroplasts. Indeed, we found that knocking out these genes caused a number of chloroplast phenotypes, including a reduction in the proportion of cellular volume devoted to chloroplasts to 50% of wild type. Thus, we refer to these genes as REDUCED CHLOROPLAST COVERAGE (REC). The size of the chloroplast compartment was reduced most in rec1 mutants. The REC1 protein accumulated in the cytosol and the nucleus. REC1 was excluded from the nucleus when plants were treated with amitrole, which inhibits cell expansion and chloroplast function. Finally, we conclude that REC1 is an extraplastidic protein that helps to establish the size of the chloroplast compartment, and that signals derived from cell expansion or chloroplasts may regulate REC1.« less

Topical application of benzalkonium chloride to the stomach serosa increases gastric emptying time, acid secretion, serum gastrin and size of the mucosa.

PubMed

Zucoloto, S; Romanello, L M F; Garcia, S B; Sobreira, L F R; Barbosa, A J A; Troncon, L E A

2002-11-01

In the present study we evaluated the effects of gastric myenteric denervation using benzalkonium chloride (BAC) on the time for gastric emptying, as well as gastric secretion, and mucosal epithelial cell size and population in rats. Wistar rats were treated with topical serosal application of BAC to the stomach. Control animals received saline. Ninety days after surgery, gastric emptying time, gastric acid secretion and serum gastrin levels were studied. Next, the animals were sacrificed and the stomachs were removed, fixed in formalin and histologically processed for histomorphometry of the height, area and volume of the glandular portion, and volume and population of mucous, chief, parietal, G- and labelled cells. BAC animals showed a significant delay in gastric emptying and an increase in gastric acid secretion and serum gastrin levels. These animals also presented a significant reduction of myenteric neuron number, hypertrophy of parietal and chief cells, hyperplasia of G cells and an increase in the gastric mucosa area. The absence of the myenteric plexus seems to protect the stomach from the hyperplastic effects of hypergastrinemia. Gastric food stasis may act as a factor triggering morphological and functional alterations of the gastric epithelium. Although gastric food stasis is a common finding in medical practice, its physiopathological consequences are poorly understood and have not been frequently discussed in the literature.

Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo

PubMed Central

Hashemzaei, Mahmoud; Far, Amin Delarami; Yari, Arezoo; Heravi, Reza Entezari; Tabrizian, Kaveh; Taghdisi, Seyed Mohammad; Sadegh, Sarvenaz Ekhtiari; Tsarouhas, Konstantinos; Kouretas, Dimitrios; Tzanakakis, George; Nikitovic, Dragana; Anisimov, Nikita Yurevich; Spandidos, Demetrios A.; Tsatsakis, Aristides M.; Rezaee, Ramin

2017-01-01

The present study focused on the elucidation of the putative anticancer potential of quercetin. The anticancer activity of quercetin at 10, 20, 40, 80 and 120 µM was assessed in vitro by MMT assay in 9 tumor cell lines (colon carcinoma CT-26 cells, prostate adenocarcinoma LNCaP cells, human prostate PC3 cells, pheocromocytoma PC12 cells, estrogen receptor-positive breast cancer MCF-7 cells, acute lymphoblastic leukemia MOLT-4 T-cells, human myeloma U266B1 cells, human lymphoid Raji cells and ovarian cancer CHO cells). Quercetin was found to induce the apoptosis of all the tested cancer cell lines at the utilized concentrations. Moreover, quercetin significantly induced the apoptosis of the CT-26, LNCaP, MOLT-4 and Raji cell lines, as compared to control group (P<0.001), as demonstrated by Annexin V/PI staining. In in vivo experiments, mice bearing MCF-7 and CT-26 tumors exhibited a significant reduction in tumor volume in the quercetin-treated group as compared to the control group (P<0.001). Taken together, quercetin, a naturally occurring compound, exhibits anticancer properties both in vivo and in vitro. PMID:28677813

Measurement of breast volume is a useful supplement to select candidates for surgical breast reduction.

PubMed

Ikander, Peder; Drejøe, Jennifer Berg; Lumholt, Pavia; Sjøstrand, Helle; Matzen, Steen; Quirinia, Anne; Siersen, Hans Erik; Ringberg, Anita; Lambaa, Susanne; Hölmich, Lisbet Rosenkrantz

2014-01-01

The indication for breast reduction in a public welfare or an insurance paid setting depends on the severity of the subjective symptoms and the clinical evaluation. The purpose of this study was to evaluate the use of breast volume as an objective criterion to establish the indication for breast reduction surgery, thus establishing a standard decision basis that can be shared by surgeons and departments to secure patients fair and equal treatment opportunities. A total of 427 patients who were referred to three Danish public hospitals with breast hypertrophy in the period from January 2007 to March 2011 were included prospectively in the study. The patients' subjective complaints, height, weight and standard breast measurements were registered as well as the decision for or against surgery. Breast volume was measured using transparent plastic cups. Cut-off values for breast volume were calculated based on whether or not the patients were offered reduction surgery. Most patients (93%) with a breast volume below 800 cc were not offered surgery, while most with a volume exceeding 900 cc were offered surgery (94%). In the grey zone between 800 and 900 cc, the indication seemed to be less clear-cut, and additional parameters need to be included. Breast volume can be used as an objective criterion in addition to the presently used criteria. Breast volume can easily be measured and has become appreciated by plastic surgeons dealing with patients with breast hypertrophy as a tool which facilitates their decision-making and patients' acceptance of the decisions made. not relevant. not relevant.

Research on the effect of rainfall flood regulation and control of wetland park based on SWMM model—a case study of wetland park in Yuanjia village, Qishan county, Shaanxi province

NASA Astrophysics Data System (ADS)

Xu, Da; Liu, Yijie

2018-02-01

Taking the wetland park of Yuan Village in Qishan County of Shaanxi Province as the research object, this paper makes a reasonable generalization of the study area, and establishes two models of low impact development (LID) and traditional development in the park. Meantime, rainwater in the surrounding built up area is introduced to into the park for digestion. SWMM model is used to simulate the variation of the total runoff, peak flow and peak time of two development models in Wetland Park under one-hour rainfall at different recurrence periods.The runoff control effect in each single LID facility in the one-hour rainfall once during five years in the built-up area is simulated. The simulation results show that the SWMM model can not only quantify the runoff reduction effect of different LID facilities, but also provide theoretical basis and data support for the urban rainfall flood problem. LID facilities have effects on runoff reduction and peak delay. However, the combined LID facility has obvious advantages for the peak time delay and peak flow control. A single LID facility is more efficient in a single runoff volume control. The order of runoff reduction by various LID facilities is as follows: Rain garden>combined LID facility> vegetative swale> bio-retention cell > permeable pavement. The order of peak time delay effect by the LID facilities is as follows: combined LID facility> Rain garden> vegetative swale> bio-retention cell > permeable pavement. The order of peak flow reduction efficiency by various LID facilities is: combined LID facility> Rain garden> bio-retention cell > vegetative swale> permeable pavement.

The Whitfield Solar CPV Collector

NASA Astrophysics Data System (ADS)

Bentley, Roger; Anstey, Ben; Callear, Jason; Chonavel, Sylvain; Clark, Ian; Collins, Ian; Ramallo, Alfonso; Scanlon, Hamilton; Weatherby, Clive

2010-10-01

Whitfield Solar is now in production with a point-focus Fresnel lens 70x PV concentrator that uses LGBC silicon cells. The design builds on initial research carried out under a number of EU-funded R&D projects. Each collector has twenty-four V-troughs 1.2 m long by 110 mm wide by 110 mm deep, and each trough carries 12 cells. Tracking is closed-loop, in a 2-axis tilt & roll system. Initial prototypes were installed in Spain in 2006, and subsequent production-version collectors have been on-sun since September 2008. In-field normalised d.c. system efficiency is 13.5%. Volume-manufactured sales price—including support frame and mark-up—is €2.40/Wp,dc, with scope for further significant cost reduction identified.

Defect Detection in Fuel Cell Gas Diffusion Electrodes Using Infrared Thermography

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

Ulsh, Michael; Porter, Jason M.; Bittinat, Daniel C.

2016-04-01

Polymer electrolyte membrane fuel cells are energy conversion devices that offer high power densities and high efficiencies for mobile and other applications. Successful introduction into the marketplace requires addressing cost barriers such as production volumes and platinum loading. For cost reduction, it is vital to minimize waste and maximize quality during the manufacturing of platinum-containing electrodes, including gas diffusion electrodes (GDEs). In this work, we report on developing a quality control diagnostic for GDEs, involving creating an ex situ exothermic reaction on the electrode surface and using infrared thermography to measure the resulting temperature profile. Experiments with a moving GDEmore » containing created defects were conducted to demonstrate the applicability of the diagnostic for real-time web-line inspection.« less

Frictional Torque Reduction in Taylor-Couette Flows with Riblet-Textured Rotors

NASA Astrophysics Data System (ADS)

Raayai, Shabnam; McKinley, Gareth

2017-11-01

Inspired by the riblets on the denticles of fast swimming shark species, periodic surface microtextures of different shapes have been studied under laminar and turbulent flow conditions to understand their drag reduction mechanism and to offer guides for designing optimized low-friction bio-inspired surfaces. Various reports over the past four decades have suggested that riblet surfaces can reduce the frictional drag force in high Reynolds number laminar and turbulent flow regimes. Here, we investigate the effect of streamwise riblets on torque reduction in steady flow between concentric cylinders, known as Taylor-Couette Flow. Using 3D printed riblet-textured rotors and a custom-built Taylor-Couette cell which can be mounted on a rheometer we measure the torque on the inner rotor as a function of three different dimensionless parameters; the Reynolds number of the flow, the sharpness of the riblets, and the size of the riblets with respect to the scale of the Taylor-Couette cell. Our experimental results in the laminar viscous flow regime show a reduction in torque up to 10% over a wide range of Reynolds numbers, that is a non-monotonic function of the aspect ratio and independent of Re. However, after transition to the Taylor vortex regime, the modification in torque becomes a function of the Reynolds number, while remaining a non-monotonic function of the aspect ratio. Using finite volume modelling of the geometry we discuss the changes in the Taylor-Couette flow in presence of the riblets compared to the case of smooth rotors and the resulting torque reduction as a function of the parameter space defined above.

In vitro culture of individual mouse preimplantation embryos: the role of embryo density, microwells, oxygen, timing and conditioned media.

PubMed

Kelley, Rebecca L; Gardner, David K

2017-05-01

Single embryo culture is suboptimal compared with group culture, but necessary for embryo monitoring, and culture systems should be improved for single embryos. Pronucleate mouse embryos were used to assess the effect of culture conditions on single embryo development. Single culture either before or after compaction reduced cell numbers (112.2 ± 3.1; 110.2 ± 3.5) compared with group culture throughout (127.0 ± 3.4; P < 0.05). Reduction of media volume from 20 µl to 2 µl increased blastocyst cell numbers in single embryos cultured in 5% oxygen (84.4 ± 3.2 versus 97.8 ± 2.8; P < 0.05), but not in 20% oxygen (55.2 ± 2.9 versus 57.1 ± 2.8). Culture in microwell plates for the EmbryoScope and Primo Vision time-lapse systems changed cleavage timings and increased inner cell mass cell number (24.1 ± 1.0; 23.4 ± 1.2) compared with a 2 µl microdrop (18.4 ± 1.0; P < 0.05). Addition of embryo-conditioned media to single embryos increased hatching rate and blastocyst cell number (91.5 ± 4.7 versus 113.1 ± 4.4; P < 0.01). Single culture before or after compaction is therefore detrimental; oxygen, media volume and microwells influence single embryo development; and embryo-conditioned media may substitute for group culture. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Neuroanatomical profiles of alexithymia dimensions and subtypes.

PubMed

Goerlich-Dobre, Katharina Sophia; Votinov, Mikhail; Habel, Ute; Pripfl, Juergen; Lamm, Claus

2015-10-01

Alexithymia, a major risk factor for a range of psychiatric and neurological disorders, has been recognized to comprise two dimensions, a cognitive dimension (difficulties identifying, analyzing, and verbalizing feelings) and an affective one (difficulties emotionalizing and fantasizing). Based on these dimensions, the existence of four distinct alexithymia subtypes has been proposed, but never empirically tested. In this study, 125 participants were assigned to four groups corresponding to the proposed alexithymia subtypes: Type I (impairment on both dimensions), Type II (impairment on the cognitive, but not the affective dimension), Type III (impairment on the affective, but not the cognitive dimension), and Lexithymics (no impairment on either dimension). By means of voxel-based morphometry, associations of the alexithymia dimensions and subtypes with gray and white matter volumes were analyzed. Type I and Type II alexithymia were characterized by gray matter volume reductions in the left amygdala and the thalamus. The cognitive dimension was further linked to volume reductions in the right amygdala, left posterior insula, precuneus, caudate, hippocampus, and parahippocampus. Type III alexithymia was marked by volume reduction in the MCC only, and the affective dimension was further characterized by larger sgACC volume. Moreover, individuals with the intermediate alexithymia Types II and III showed gray matter volume reductions in distinct regions, and had larger corpus callosum volumes compared to Lexithymics. These results substantiate the notion of a differential impact of the cognitive and affective alexithymia dimensions on brain morphology and provide evidence for separable neuroanatomical representations of the different alexithymia subtypes. © 2015 Wiley Periodicals, Inc.

A novel approach to restore atrial function after the maze procedure in patients with an enlarged left atrium.

PubMed

Marui, Akira; Tambara, Keiichi; Tadamura, Eiji; Saji, Yoshiaki; Sasahashi, Nozomu; Ikeda, Tadashi; Nishina, Takeshi; Komeda, Masashi

2007-08-01

Left atrial (LA) volume reduction surgery concomitant with the maze procedure has been reported to facilitate sinus rhythm recovery even in patients with refractory atrial fibrillation (AF) with an enlarged LA. However, it is unknown whether the procedures can also restore effective atrial function of the enlarged LA with over-stretched myocardium. The maze procedures in association with mitral valve surgery were performed to 57 AF patients with an enlarged LA (LA diameter >or=60mm). Among them, 32 patients had concomitant LA volume reduction surgery (VR group). Another 25 patients did not have the volume reduction (control group). Three months postoperatively LA end-diastolic volume (LAEDV, ml) assessed by magnetic resonance (MR) imaging was larger in the VR group than that in the control group (291+/-117 vs 223+/-81 ml, p<0.05). Postoperatively, sinus rhythm recovery rate was better (84 vs 68%, p<0.05) and LAEDV was drastically smaller (118+/-48 vs 203+/-76 ml, p<0.001) in the VR group than those in the control group. Among the patients with sinus rhythm recovery in both groups, LA contraction ejection fraction (%) improved in the VR group but not in the control group (22.3+/-7.8 vs 10.3+/-4.7%, p<0.001). The LA volume reduction surgery concomitant with the maze procedure restored contraction of the enlarged LA; however, the maze procedure alone did not restore LA contraction in spite of successful sinus rhythm recovery. LA volume reduction surgery may be desirable to the patients with refractory AF with over-stretched LA.

TREATABILITY STUDY BULLETIN: MOBILE VOLUME REDUCTION UNIT AT THE ESCAMBIA SUPERFUND SITE

EPA Science Inventory

The RREL has developed a pilot-scale Mobile Volume Reduction Unit (VRU) to determine the feasibility of soil washing for the remediation of contaminated soils. This mobile unit, mounted on two trailers, can process 100 lb/hr of soil feed. Soil washing is a cost effective technolo...

DEMONSTRATION BULLETIN: MOBILE VOLUME REDUCTION UNIT - U.S. ENVIRONMENTAL PROTECTION AGENCY

EPA Science Inventory

The Volume Reduction Unit (VRU), which was developed by EPA, is a mobile, pilot-scale soil washing system for stand-alone field use in cleaning soil contaminated with hazardous substances. Removal efficiencies depend on the contaminant as well as the type of soil. Soil washing...

SU-E-J-269: Tracking of Tumor Regression for Stage III Lung Cancer Using CBCT

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

Kang, K; Biswas, T; Podder, T

2015-06-15

Purpose: This study is to evaluate the tumor regression over the course of EBRT treatment and to determine the difference of tumor reduction for stage III lung squamous cell cancer (SCC) and adenocarcinoma using CBCT. Methods: Twenty three stage III lung cancer patients treated in our clinic who had daily cone beam CT (CBCT) were selected for this study (16 adenocarcinoma and 7 SCC cases). Patients received prescription dose in the range of 50Gy–71.4Gy (mean =60.3Gy, median =50Gy) at 1.8Gy or 2Gy per fraction. Treatments spanned over a minimum of five weeks. Initial mean volume of the gross tumor volumemore » (GTV) was 123cc (range = 14.7cc–353.3cc). For this study, we choose six sets of CBCTs at an interval of one week, starting from the first fraction of treatment. Daily CBCTs from treatment linac computer were transferred to MIM Software version 6.0. An experienced physician contoured the primary GTV on each slices of the CBCT for these patients. Results: A consistent regression of the GTVs was observed in all patients, except in one patient (adeno case) where GTV did not change. Weekly volumetric reduction was in the range of 11.2%–16.6%. Maximum reductions were noticed in the first two weeks of the treatment cycle; mean overall (for adeno+SCC) reductions were 16.6%, 14.2% in week-1 and week-2, respectively. Mean reduction over five weeks of treatment was 49.8% (range = 0.1%–75.5%). Higher reduction was observed in SCC patients as compare to adenocarcinoma cases (54.9% vs. 47.6%); however, the difference was not statistically significant (p-value > 0.05). Conclusion: Large regression of tumors over the course of EBRT for stage III lung cancer patients was observed. Both SCC and adenocarcinoma responded well; overall reduction for SCC cases was higher. A future study is warranted for determining the co-relation between tumor volume reduction and treatment outcome.« less

Relation Between the Cell Volume and the Cell Cycle Dynamics in Mammalian cell

NASA Astrophysics Data System (ADS)

Magno, A. C. G.; Oliveira, I. L.; Hauck, J. V. S.

2016-08-01

The main goal of this work is to add and analyze an equation that represents the volume in a dynamical model of the mammalian cell cycle proposed by Gérard and Goldbeter (2011) [1]. The cell division occurs when the cyclinB/Cdkl complex is totally degraded (Tyson and Novak, 2011)[2] and it reaches a minimum value. At this point, the cell is divided into two newborn daughter cells and each one will contain the half of the cytoplasmic content of the mother cell. The equations of our base model are only valid if the cell volume, where the reactions occur, is constant. Whether the cell volume is not constant, that is, the rate of change of its volume with respect to time is explicitly taken into account in the mathematical model, then the equations of the original model are no longer valid. Therefore, every equations were modified from the mass conservation principle for considering a volume that changes with time. Through this approach, the cell volume affects all model variables. Two different dynamic simulation methods were accomplished: deterministic and stochastic. In the stochastic simulation, the volume affects every model's parameters which have molar unit, whereas in the deterministic one, it is incorporated into the differential equations. In deterministic simulation, the biochemical species may be in concentration units, while in stochastic simulation such species must be converted to number of molecules which are directly proportional to the cell volume. In an effort to understand the influence of the new equation a stability analysis was performed. This elucidates how the growth factor impacts the stability of the model's limit cycles. In conclusion, a more precise model, in comparison to the base model, was created for the cell cycle as it now takes into consideration the cell volume variation

Intensity-Modulated and 3D-Conformal Radiotherapy for Whole-Ventricular Irradiation as Compared With Conventional Whole-Brain Irradiation in the Management of Localized Central Nervous System Germ Cell Tumors

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

Chen, Michael Jenwei, E-mail: michaelchen@einstein.b; Silva Santos, Adriana da; Sakuraba, Roberto Kenji

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a 'boost' to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluatedmore » at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.« less

Impact of meriolins, a new class of cyclin-dependent kinase inhibitors, on malignant glioma proliferation and neo-angiogenesis.

PubMed

Jarry, Marie; Lecointre, Céline; Malleval, Céline; Desrues, Laurence; Schouft, Marie-Thérèse; Lejoncour, Vadim; Liger, François; Lyvinec, Gildas; Joseph, Benoît; Loaëc, Nadège; Meijer, Laurent; Honnorat, Jérôme; Gandolfo, Pierrick; Castel, Hélène

2014-11-01

Glioblastomas are the most frequent and most aggressive primary brain tumors in adults. The median overall survival is limited to a few months despite surgery, radiotherapy, and chemotherapy. It is now clearly established that hyperactivity of cyclin-dependent kinases (CDKs) is one of the processes underlying hyperproliferation and tumoral growth. The marine natural products meridianins and variolins, characterized as CDK inhibitors, display a kinase-inhibitory activity associated with cytotoxic effects. In order to improve selectivity and efficiency of these CDK inhibitors, a series of hybrid compounds called meriolins have been synthesized. The potential antitumoral activity of meriolins was investigated in vitro on glioma cell lines (SW1088 and U87), native neural cells, and a human endothelial cell line (HUV-EC-C). The impact of intraperitoneal or intratumoral administrations of meriolin 15 was evaluated in vivo on 2 different nude mice-xenografted glioma models. Meriolins 3, 5, and 15 exhibited antiproliferative properties with nanomolar IC50 and induced cell-cycle arrest and CDK inhibition associated with apoptotic events in human glioma cell lines. These meriolins blocked the proliferation rate of HUV-EC-C through cell cycle arrest and apoptosis. In vivo, meriolin 15 provoked a robust reduction in tumor volume in spite of toxicity for highest doses, associated with inhibition of cell division, activation of caspase 3, reduction of CD133 cells, and modifications of the vascular architecture. Meriolins, and meriolin 15 in particular, exhibit antiproliferative and proapoptotic activities on both glioma and intratumoral endothelial cells, constituting key promising therapeutic lead compounds for the treatment of glioblastoma. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impact of meriolins, a new class of cyclin-dependent kinase inhibitors, on malignant glioma proliferation and neo-angiogenesis

PubMed Central

Jarry, Marie; Lecointre, Céline; Malleval, Céline; Desrues, Laurence; Schouft, Marie-Thérèse; Lejoncour, Vadim; Liger, François; Lyvinec, Gildas; Joseph, Benoît; Loaëc, Nadège; Meijer, Laurent; Honnorat, Jérôme; Gandolfo, Pierrick; Castel, Hélène

2014-01-01

Background Glioblastomas are the most frequent and most aggressive primary brain tumors in adults. The median overall survival is limited to a few months despite surgery, radiotherapy, and chemotherapy. It is now clearly established that hyperactivity of cyclin-dependent kinases (CDKs) is one of the processes underlying hyperproliferation and tumoral growth. The marine natural products meridianins and variolins, characterized as CDK inhibitors, display a kinase-inhibitory activity associated with cytotoxic effects. In order to improve selectivity and efficiency of these CDK inhibitors, a series of hybrid compounds called meriolins have been synthesized. Methods The potential antitumoral activity of meriolins was investigated in vitro on glioma cell lines (SW1088 and U87), native neural cells, and a human endothelial cell line (HUV-EC-C). The impact of intraperitoneal or intratumoral administrations of meriolin 15 was evaluated in vivo on 2 different nude mice-xenografted glioma models. Results Meriolins 3, 5, and 15 exhibited antiproliferative properties with nanomolar IC50 and induced cell-cycle arrest and CDK inhibition associated with apoptotic events in human glioma cell lines. These meriolins blocked the proliferation rate of HUV-EC-C through cell cycle arrest and apoptosis. In vivo, meriolin 15 provoked a robust reduction in tumor volume in spite of toxicity for highest doses, associated with inhibition of cell division, activation of caspase 3, reduction of CD133 cells, and modifications of the vascular architecture. Conclusion Meriolins, and meriolin 15 in particular, exhibit antiproliferative and proapoptotic activities on both glioma and intratumoral endothelial cells, constituting key promising therapeutic lead compounds for the treatment of glioblastoma. PMID:24891448

Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury.

PubMed

Lee, Yee-Shuan; Funk, Lucy H; Lee, Jae K; Bunge, Mary Bartlett

2018-04-01

Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with macrophage depletion does improve histopathology of the injury site, the effect on axon growth and behavioral recovery appears no better than what can be achieved with Schwann cell transplants alone.

Vancomycin Reduces Cell Wall Stiffness and Slows Swim Speed of the Lyme Disease Bacterium.

PubMed

Harman, Michael W; Hamby, Alex E; Boltyanskiy, Ross; Belperron, Alexia A; Bockenstedt, Linda K; Kress, Holger; Dufresne, Eric R; Wolgemuth, Charles W

2017-02-28

Borrelia burgdorferi, the spirochete that causes Lyme disease, is a tick-transmitted pathogen that requires motility to invade and colonize mammalian and tick hosts. These bacteria use a unique undulating flat-wave shape to penetrate and propel themselves through host tissues. Previous mathematical modeling has suggested that the morphology and motility of these spirochetes depends crucially on the flagellar/cell wall stiffness ratio. Here, we test this prediction using the antibiotic vancomycin to weaken the cell wall. We found that low to moderate doses of vancomycin (≤2.0 μg/mL for 24 h) produced small alterations in cell shape and that as the dose was increased, cell speed decreased. Vancomycin concentrations >1.0 μg/mL also inhibited cell growth and led to bleb formation on a fraction of the cells. To quantitatively assess how vancomycin affects cell stiffness, we used optical traps to bend unflagellated mutants of B. burgdorferi. We found that in the presence of vancomycin, cell wall stiffness gradually decreased over time, with a 40% reduction in the bending stiffness after 36 h. Under the same conditions, the swimming speed of wild-type B. burgdorferi slowed by ∼15%, with only marginal changes to cell morphology. Interestingly, our biophysical model for the swimming dynamics of B. burgdorferi suggested that cell speed should increase with decreasing cell stiffness. We show that this discrepancy can be resolved if the periplasmic volume decreases as the cell wall becomes softer. These results provide a testable hypothesis for how alterations of cell wall stiffness affect periplasmic volume regulation. Furthermore, since motility is crucial to the virulence of B. burgdorferi, the results suggest that sublethal doses of antibiotics could negatively impact spirochete survival by impeding their swim speed, thereby enabling their capture and elimination by phagocytes. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

PubMed Central

Lee, Yee-Shuan; Funk, Lucy H.; Lee, Jae K.; Bunge, Mary Bartlett

2018-01-01

Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone. These changes were not associated, however, with improved Schwann cell survival, axon growth, or locomotor recovery. Although combining Schwann cell transplantation with macrophage depletion does improve histopathology of the injury site, the effect on axon growth and behavioral recovery appears no better than what can be achieved with Schwann cell transplants alone. PMID:29722321

Activated Monocytes Enhance Platelet-Driven Contraction of Blood Clots via Tissue Factor Expression.

PubMed

Peshkova, Alina D; Le Minh, Giang; Tutwiler, Valerie; Andrianova, Izabella A; Weisel, John W; Litvinov, Rustem I

2017-07-11

Platelet-driven reduction in blood clot volume (clot contraction or retraction) has been implicated to play a role in hemostasis and thrombosis. Although these processes are often linked with inflammation, the role of inflammatory cells in contraction of blood clots and thrombi has not been investigated. The aim of this work was to study the influence of activated monocytes on clot contraction. The effects of monocytes were evaluated using a quantitative optical tracking methodology to follow volume changes in a blood clot formed in vitro. When a physiologically relevant number of isolated human monocytes pre-activated with phorbol-12-myristate-13-acetate (PMA) were added back into whole blood, the extent and rate of clot contraction were increased compared to addition of non-activated cells. Inhibition of tissue factor expression or its inactivation on the surface of PMA-treated monocytes reduced the extent and rate of clot contraction back to control levels with non-activated monocytes. On the contrary, addition of tissue factor enhanced clot contraction, mimicking the effects of tissue factor expressed on the activated monocytes. These data suggest that the inflammatory cells through their expression of tissue factor can directly affect hemostasis and thrombosis by modulating the size and density of intra- and extravascular clots and thrombi.

Enhanced fluorescence detection using liquid-liquid extraction in a microfluidic droplet system.

PubMed

Chen, Yan-Yu; Chen, Zhao-Ming; Wang, Hsiang-Yu

2012-11-07

Reducing the fluorescence background in microfluidic assays is important in obtaining accurate outcomes and enhancing the quality of detections. This study demonstrates an integrated process including cell labelling, fluorescence background reduction, and biomolecule detection using liquid-liquid extraction in a microfluidic droplet system. The cellular lipids in Chlorella vulgaris and NIH/3T3 cells were labelled with a hydrophobic dye, Nile red, to investigate the performance of the proposed method. The fluorescence background of the lipid detection can be reduced by 85% and the removal efficiency increased with the volume of continuous phase surrounding a droplet. The removal rate of the fluorescence background increased as the surface area to volume ratio of a droplet increased. Before Nile red was removed from the droplet, the signal to noise ratio was as low as 1.30 and it was difficult to distinguish cells from the background. Removing Nile red increased the signal to noise ratio to 22 and 34 for Chlorella vulgaris and NIH/3T3, respectively, and these were 17 fold and 10 fold of the values before extraction. The proposed method successfully demonstrates the enhancement of fluorescence detection of cellular lipids and has great potential in improving other fluorescence-based detections in microfluidic systems.

Patient-Specific Instrumentation Affects Perioperative Blood Loss in Total Knee Arthroplasty.

PubMed

Cucchi, Davide; Menon, Alessandra; Zanini, Beatrice; Compagnoni, Riccardo; Ferrua, Paolo; Randelli, Pietro

2018-05-23

Patient-specific instrumentation (PSI) may contribute to reduced blood loss related to total knee arthroplasty (TKA). The purpose of this study was to compare the estimated hemoglobin (Hb) and red blood cell volume (RBC) losses in two groups of patients undergoing TKA with PSI and conventional instrumentation. Pre- and postoperative blood samples were collected from 22 patients randomly assigned to receive a PSI-assisted or conventional TKA. Post- to preoperative Hb difference was calculated and RBC loss was estimated according to Sehat et al. A significant difference in Hb reduction in favor of the PSI group was registered on the last day of stay ( p  = 0.0084) and significant treatment effect ( p  = 0.027) on Hb reduction after intervention was found with a regression model for longitudinal measurements. This study demonstrated that PSI leads to a significant trend in earlier Hb regain. These promising results suggest a beneficial effect of PSI in blood loss reduction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Reduced left ventricular filling following blood volume extraction does not result in compensatory augmentation of cardiac mechanics.

PubMed

Lord, Rachel; MacLeod, David; George, Keith; Oxborough, David; Shave, Rob; Stembridge, Mike

2018-04-01

What is the central question of this study? A reduction in left ventricular (LV) filling, and concomitant increase in heart rate, augments LV mechanics to maintain stroke volume (SV); however, the impact of reduced LV filling in isolation on SV and LV mechanics is currently unknown. What is the main finding and its importance? An isolated decrease in LV filling did not provoke a compensatory increase in mechanics to maintain SV; in contrast, LV mechanics and SV were reduced. These data indicate that when LV filling is reduced without changes in heart rate, LV mechanics do not compensate to maintain SV. An acute non-invasive reduction in preload has been shown to augment cardiac mechanics to maintain stroke volume and cardiac output. Such interventions induce concomitant changes in heart rate, whereas blood volume extraction reduces preload without changes in heart rate. Therefore, the purpose of this study was to determine whether a preload reduction in isolation resulted in augmented stroke volume achieved via enhanced cardiac mechanics. Nine healthy volunteers (four female, age 29 ± 11 years) underwent echocardiography for the assessment of left ventricular (LV) volumes and mechanics in a supine position at baseline and end extraction after the controlled removal of 25% of total blood volume (1062 ± 342 ml). Arterial blood pressure was monitored continuously by a pressure transducer attached to an indwelling radial artery catheter. Heart rate and total peripheral resistance were unchanged from baseline to end extraction, but systolic blood pressure was reduced (from 148 to 127 mmHg). From baseline to end extraction there were significant reductions in left ventricular end-diastolic volume (from 89 to 71 ml) and stroke volume (from 56 to 37 ml); however, there was no change in LV twist, basal or apical rotation. In contrast, LV longitudinal strain (from -20 to -17%) and basal circumferential strain (from -22 to -19%) were significantly reduced from baseline to end extraction. In conclusion, a reduction in preload during blood volume extraction does not result in compensatory changes in stroke volume or cardiac mechanics. Our data suggest that LV strain is dependent on LV filling and consequent geometry, whereas LV twist could be mediated by heart rate. © 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.

Destruction of newly released red blood cells in space flight

NASA Technical Reports Server (NTRS)

Alfrey, C. P.; Udden, M. M.; Huntoon, C. L.; Driscoll, T.

1996-01-01

Space flight results in a rapid change in total blood volume, plasma volume, and red blood cell mass because the space to contain blood is decreased. The plasma volume and total blood volume decreases during the first hours in space and remain at a decreased level for the remainder of the flight. During the first several hours following return to earth, plasma volume and total blood volume increase to preflight levels. During the first few days in space recently produced red blood cells disappear from the blood resulting in a decrease in red blood cell mass of 10-15%. Red cells 12 d old or older survive normally and production of new cells continues at near preflight levels. After the first few days in space, the red cell mass is stable at the decreased level. Following return to earth the hemoglobin and red blood cell mass concentrations decrease reflecting the increase in plasma volume. The erythropoietin levels increase responding to "postflight anemia"; red cell production increases, and the red cell mass is restored to preflight levels after several weeks.

Serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats.

PubMed

Glisić, Radmila; Koko, Vesna; Todorović, Vera; Drndarević, Neda; Cvijić, Gordana

2006-09-11

The aim of our study was to investigate the morphological, immunohistochemical and ultrastructural changes of rat serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2 mg/kg dexamethasone, rats developed diabetes similar to human diabetes type 2. Stomach, small and large intestines were examined. Large serotonin positive EC cells appeared in the corpus mucosa epithelium of D group of rats, although these cells were not present in control (C) rats. Both volume fraction and the number of EC cells per mm(2) of mucosa were significantly increased only in the duodenum. However, the number of EC cells per circular sections of both antrum and small intestine was increased, but reduced both in the ascending and descending colon in D group. The dexamethasone treatment caused a strong reduction in number of granules in the antral EC cells, while it was gradually increased beginning from the jejunum to descending colon. The mean granular content was reduced in the antral EC cells but increased in the jejunal EC cells in D group. In conclusion, the present study showed that morphological changes in gut serotonin-producing EC cells occurred in diabetic rats.

Effect of cytoplasmic volume on developmental competence of buffalo (Bubalus bubalis) embryos produced through hand-made cloning.

PubMed

Panda, Sudeepta K; George, Aman; Saha, Ambika P; Sharma, Ruchi; Manik, Radhey S; Chauhan, Manmohan S; Palta, Prabhat; Singla, Suresh K

2011-06-01

This study examined the effects of cytoplasmic volume on the developmental competence of hand-made cloned buffalo embryos. Two different cell types, that is, buffalo fetal fibroblast (BFF) and buffalo embryonic stem (ES) cell-like cells were taken as donor cell and fused with one, two, or three demicytoplasts to generate embryos with decreased, normal (control), and increased cytoplasmic volume. Using BFF as a nuclear donor, the cleavage rate was similar in all the groups (p > 0.05), but the blastocysts rate was significantly lower (p < 0.05) for embryos generated with decreased cytoplasmic volume. Using ES cell-like cells, the cleavage and blastocyst rate with increased cytoplasmic volume was significantly higher (p < 0.05) compared that with reduced cytoplasmic volume. Blastocysts produced from embryos having increased cytoplasmic volume had significantly higher (p < 0.05) cell number than normal (control) embryos in both BFF and ES cell-like cells groups. Pregnancies were established in all the groups except for the embryos reconstructed with decreased cytoplasmic volume. The pregnancy rate was almost double for embryos reconstructed using increased cytoplasmic volume compared to that with the controls. Most of the pregnancies aborted in the first trimester and one live calf was delivered through Caesarean, which died 4 h after birth.

Correction of anaemia through the use of darbepoetin alfa improves chemotherapeutic outcome in a murine model of Lewis lung carcinoma

PubMed Central

Shannon, A M; Bouchier-Hayes, D J; Condron, C M; Toomey, D

2005-01-01

Darbepoetin alfa (Aranesp®, Amgen) is a novel erythropoiesis-stimulating protein with a serum half-life longer than recombinant human erythropoietin (Epo), used in the treatment of cancer-associated anaemia. Anaemia is known to adversely affect prognosis and response to treatment in cancer patients. Solid tumours contain regions of hypoxia due to poor vascular supply and cellular compaction. Although hypoxic stress usually results in cell death, hypoxia-resistant tumour cells are genetically unstable and often acquire a drug-resistant phenotype. Increasing tumour oxygenation and perfusion during treatment could have the doubly beneficial outcome of reducing the fraction of treatment-resistant cells, while increasing drug delivery to previously hypoxic tissue. In this study, we examined the effect of darbepoetin alfa on chemotherapy sensitivity and delivery in an in vivo model of Lewis lung carcinoma, shown here to express the Epo receptor (EpoR). We identified that weekly darbepoetin alfa treatment, commencing 10 days before chemotherapy, resulted in a significant reduction in tumour volume compared to chemotherapy alone. This was mediated by the prevention of anaemia, a reduction in tumour hypoxia and a concomitant increase in drug delivery. Darbepoetin alfa treatment alone did not modulate the growth of the EpoR-expressing tumour cells. This study identifies an important role for darbepoetin alfa in increasing the therapeutic index of chemotherapy. PMID:15999100

Isovolemic hemodilution alters the ratio of whole-body to large-vessel hematocrit (F-cell ratio). A prospective, randomized study comparing the volume effects of hydroxyethyl starch 200,000/0.62 and albumin.

PubMed

Haller, M; Brechtelsbauer, H; Akbulut, C; Fett, W; Briegel, J; Finsterer, U

1995-04-01

To evaluate potential changes in the ratio of whole-body/large-vessel hematocrit (f-cell ratio) during isovolemic hemodilution and to compare the volume effects of 2 different plasma exchange solutions (hydroxyethyl starch 200,000/0.62 6% and human albumin 5%). Prospective, randomized, controlled trial. Operating theater in a university hospital. 24 gynecological patients scheduled for elective surgery. Isovolemic hemodilution was performed using 2 different plasma exchange solutions. Plasma volume was determined using dye dilution technique before and after hemodilution. The volume of withdrawn blood was measured from the change in weight of the blood bags taking into account the specific gravity of blood. The volume of administered plasma exchange solutions exceeded the amount of withdrawn blood by 80 +/- 47 ml (p < 0.001). Plasma volume was 3,067 +/- 327 ml before and 3,517 +/- 458 ml after hemodilution. Using red cell volumes calculated from measured plasma volumes and peripheral hematocrit, a deficit of 249 +/- 133 ml (p < 0.0001) in red cells after hemodilution appeared with the measured withdrawn red cell volumes taken into account. This finding can be explained by a change in the f-cell ratio during isovolemic hemodilution. The volume effect of the exchange solutions was 1.05 for hydroxyethyl starch and 0.95 for albumin. The results demonstrate that a change in the f-cell ratio occurs during isovolemic hemodilution. The estimation of red cell volume or plasma volume changes by using either the hematocrit or plasma or red cell volume determinations together with the hematocrit may lead to erroneous results.

Protective Effect of Human Leukocyte Antigen (HLA) Allele DRB1*13:02 on Age-Related Brain Gray Matter Volume Reduction in Healthy Women.

PubMed

James, Lisa M; Christova, Peka; Lewis, Scott M; Engdahl, Brian E; Georgopoulos, Angeliki; Georgopoulos, Apostolos P

2018-03-01

Reduction of brain volume (brain atrophy) during healthy brain aging is well documented and dependent on genetic, lifestyle and environmental factors. Here we investigated the possible dependence of brain gray matter volume reduction in the absence of the Human Leukocyte Antigen (HLA) allele DRB1*13:02 which prevents brain atrophy in Gulf War Illness (James et al., 2017). Seventy-one cognitively healthy women (32-69years old) underwent a structural Magnetic Resonance Imaging (sMRI) scan to measure the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter. Participants were assigned to two groups, depending on whether they lacked the DRB1*13:02 allele (No DRB1*13:02 group, N=60) or carried the DRB1*13:02 allele (N=11). We assessed the change of brain gray matter volume with age in each group by performing a linear regression where the brain volume (adjusted for total intracranial volume) was the dependent variable and age was the independent variable. In the No DRB1*13:02 group, the volumes of total gray matter, cerebrocortical gray matter, and subcortical gray matter were reduced highly significantly. In contrast, none of these volumes showed a statistically significant reduction with age in the DRB1*13:02 group. These findings document the protective effect of DRB1*13:02 on age-dependent reduction of brain gray matter in healthy individuals. Since the role of this allele is to connect to matching epitopes of external antigens for the subsequent production of antibodies and elimination of the offending antigen, we hypothesize that its protective effect may be due to the successful elimination of such antigens to which we are exposed during the lifespan, antigens that otherwise would persist causing gradual brain atrophy. In addition, we consider a possible beneficial role of DRB1*13:02 attributed to its binding to cathepsin S, a known harmful substance in brain aging (Wendt et al., 2008). Of course, other factors covarying with the presence of DRB1*13:02 could be involved. Published by Elsevier B.V.

Morphometry of the midgut of Melipona quadrifasciata anthidioides (Lepeletier) (Hymenoptera: Apidae) during metamorphosis.

PubMed

Cruz, L C; Araújo, V A; Dolder, H; Araújo, A P A; Serrão, J E; Neves, C A

2011-01-01

In Hymenoptera, midgut changes begin in the last instar. At this stage, the larval epithelial digestive cells degenerate, leaving only the basal membrane and the regenerative cells which will develop into a new epithelium during the pupal stage and in the adult. Epithelium renewal is followed by changes in volume and shape of the midgut. Morphometric analysis of digestive cells and total midgut volume of Melipona quadrifasciata anthidioides (Lepeletier) were conducted to verify whether cell volume increase are sufficient to account for the total midgut volume increase that occurs during metamorphosis. An increase in midgut volume was verified in spite of the scarcity of cell proliferation found during metamorphosis. At the end of metamorphosis, the increase in cell volume was not sufficient to explain the increase in volume of the midgut, indicating that an increase in the number of digestive cells is apparently necessary. Nevertheless, the mechanism by which regenerative cells reconstitute the epithelium during metamorphosis remains unknown.

Effect of Slotted Anode on Gas Bubble Behaviors in Aluminum Reduction Cell

NASA Astrophysics Data System (ADS)

Sun, Meijia; Li, Baokuan; Li, Linmin; Wang, Qiang; Peng, Jianping; Wang, Yaowu; Cheung, Sherman C. P.

2017-12-01

In the aluminum reduction cells, gas bubbles are generated at the bottom of the anode which eventually reduces the effective current contact area and the system efficiency. To encourage the removal of gas bubbles, slotted anode has been proposed and increasingly adopted by some industrial aluminum reduction cells. Nonetheless, the exact gas bubble removal mechanisms are yet to be fully understood. A three-dimensional (3D) transient, multiphase flow mathematical model coupled with magnetohydrodynamics has been developed to investigate the effect of slotted anode on the gas bubble movement. The Eulerian volume of fluid approach is applied to track the electrolyte (bath)-molten aluminum (metal) interface. Meanwhile, the Lagrangian discrete particle model is employed to handle the dynamics of gas bubbles with considerations of the buoyancy force, drag force, virtual mass force, and pressure gradient force. The gas bubble coalescence process is also taken into account based on the O'Rourke's algorithm. The two-way coupling between discrete bubbles and fluids is achieved by the inter-phase momentum exchange. Numerical predictions are validated against the anode current variation in an industrial test. Comparing the results using slotted anode with the traditional one, the time-averaged gas bubble removal rate increases from 36 to 63 pct; confirming that the slotted anode provides more escaping ways and shortens the trajectories for gas bubbles. Furthermore, the slotted anode also reduces gas bubble's residence time and the probability of coalescence. Moreover, the bubble layer thickness in aluminum cell with slotted anode is reduced about 3.5 mm (17.4 pct), so the resistance can be cut down for the sake of energy saving and the metal surface fluctuation amplitude is significantly reduced for the stable operation due to the slighter perturbation with smaller bubbles.

40 CFR 60.664 - Test methods and procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (less methane and ethane) reduction efficiency shall be prior to the inlet of the control device and... methane and ethane), dry basis, ppm by volume. %O2d=Concentration of O2, dry basis, percent by volume. (4... emission reduction (R) of TOC (minus methane and ethane) shall be determined using the following equation...

76 FR 50500 - Request for Comments on the Draft Policy Statement on Volume Reduction and Low-Level Radioactive...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0183] Request for Comments on the Draft Policy Statement on Volume Reduction and Low-Level Radioactive Waste Management AGENCY: Nuclear Regulatory Commission. ACTION: Request for public comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) is revising its...

Original predictive approach to the compressibility of pharmaceutical powder mixtures based on the Kawakita equation.

PubMed

Mazel, Vincent; Busignies, Virginie; Duca, Stéphane; Leclerc, Bernard; Tchoreloff, Pierre

2011-05-30

In the pharmaceutical industry, tablets are obtained by the compaction of two or more components which have different physical properties and compaction behaviours. Therefore, it could be interesting to predict the physical properties of the mixture using the single-component results. In this paper, we have focused on the prediction of the compressibility of binary mixtures using the Kawakita model. Microcrystalline cellulose (MCC) and L-alanine were compacted alone and mixed at different weight fractions. The volume reduction, as a function of the compaction pressure, was acquired during the compaction process ("in-die") and after elastic recovery ("out-of-die"). For the pure components, the Kawakita model is well suited to the description of the volume reduction. For binary mixtures, an original approach for the prediction of the volume reduction without using the effective Kawakita parameters was proposed and tested. The good agreement between experimental and predicted data proved that this model was efficient to predict the volume reduction of MCC and L-alanine mixtures during compaction experiments. Copyright © 2011 Elsevier B.V. All rights reserved.

Near Infrared Photoimmunotherapy in the Treatment of Pleural Disseminated NSCLC: Preclinical Experience

PubMed Central

Sato, Kazuhide; Nagaya, Tadanobu; Choyke, Peter L.; Kobayashi, Hisataka

2015-01-01

Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet is difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of pleural disseminated non-small cell lung carcinoma (NSCLC). In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180). Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease. In conclusion, NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC in mice. Thus, NIR-PIT is a promising therapy for pleural disseminated tumors. PMID:25897335

Permeabilization Activated Reduction in Fluorescence (PARF): a novel method to measure kinetics of protein interactions with intracellular structures

PubMed Central

Singh, Pali P.; Hawthorne, Jenci L.; Davis, Christie A.; Quintero, Omar A.

2016-01-01

Understanding kinetic information is fundamental in understanding biological function. Advanced imaging technologies have fostered the development of kinetic analyses in cells. We have developed Permeabilization Activated Reduction in Fluorescence (PARF) analysis for determination of apparent t1/2 and immobile fraction, describing the dissociation of a protein of interest from intracellular structures. To create conditions where dissociation events are observable, cells expressing a fluorescently-tagged protein are permeabilized with digitonin, diluting the unbound protein into the extracellular media. As the media volume is much larger than the cytosolic volume, the concentration of the unbound pool decreases drastically, shifting the system out of equilibrium--favoring dissociation events. Loss of bound protein is observed as loss of fluorescence from intracellular structures and can be fit to an exponential decay. We compared PARF dissociation kinetics with previously published equilibrium kinetics as determined by FRAP. PARF dissociation rates agreed with the equilibrium-based FRAP analysis predictions of the magnitude of those rates. When used to investigate binding kinetics of a panel of cytoskeletal proteins, PARF analysis revealed that filament stabilization resulted in slower fluorescence loss. Additionally, commonly used “general” F-actin labels display differences in kinetic properties, suggesting that not all fluorescently-tagged actin labels interact with the actin network in the same way. We also observed differential dissociation kinetics for GFP-VASP depending on which cellular structure was being labeled. These results demonstrate that PARF analysis of non-equilibrium systems reveals kinetic information without the infrastructure investment required for other quantitative approaches such as FRAP, photoactivation, or in vitro reconstitution assays. PMID:27126922

Effect of preload reduction by hemodialysis on left atrial volume and echocardiographic Doppler parameters in patients with end-stage renal disease.

PubMed

Barberato, Silvio H; Mantilla, Diego E V; Misocami, M Arcio; Gonçalves, Simone M; Bignelli, Alexandre T; Riella, Miguel C; Pecoits-Filho, Roberto

2004-11-01

Left atrial (LA) volume has been proposed as a less preload-dependent parameter of diastolic function than Doppler mitral inflow. We hypothesize that in the absence of mitral regurgitation and atrial fibrilation, LA enlargement could be a more practical (and relatively preload-independent) method for the evaluation of left ventricular diastolic function. The aim of the present study was to determine the effects of preload reduction by hemodialysis on LA volume.

High-throughput imaging method for direct assessment of GM1 ganglioside levels in mammalian cells

PubMed Central

Acosta, Walter; Martin, Reid; Radin, David N.; Cramer, Carole L.

2016-01-01

GM1-gangliosidosis is an inherited autosomal recessive disorder caused by mutations in the gene GLB1, which encodes acid β-galactosidase (β-gal). The lack of activity in this lysosomal enzyme leads to accumulation of GM1 gangliosides (GM1) in cells. We have developed a high-content-imaging method to assess GM1 levels in fibroblasts that can be used to evaluate substrate reduction in treated GLB1−/− cells [1]. This assay allows fluorescent quantification in a multi-well system which generates unbiased and statistically significant data. Fluorescently labeled Cholera Toxin B subunit (CTXB), which specifically binds to GM1 gangliosides, was used to detect in situ GM1 levels in a fixed monolayer of fibroblasts. This sensitive, rapid, and inexpensive method facilitates in vitro drug screening in a format that allows a high number of replicates using low working volumes. PMID:26958633

High-throughput imaging method for direct assessment of GM1 ganglioside levels in mammalian cells.

PubMed

Acosta, Walter; Martin, Reid; Radin, David N; Cramer, Carole L

2016-03-01

GM1-gangliosidosis is an inherited autosomal recessive disorder caused by mutations in the gene GLB1, which encodes acid β-galactosidase (β-gal). The lack of activity in this lysosomal enzyme leads to accumulation of GM1 gangliosides (GM1) in cells. We have developed a high-content-imaging method to assess GM1 levels in fibroblasts that can be used to evaluate substrate reduction in treated GLB1(-/-) cells [1]. This assay allows fluorescent quantification in a multi-well system which generates unbiased and statistically significant data. Fluorescently labeled Cholera Toxin B subunit (CTXB), which specifically binds to GM1 gangliosides, was used to detect in situ GM1 levels in a fixed monolayer of fibroblasts. This sensitive, rapid, and inexpensive method facilitates in vitro drug screening in a format that allows a high number of replicates using low working volumes.

Fuel Cell Auxiliary Power Study Volume 1: RASER Task Order 5

NASA Technical Reports Server (NTRS)

Mak, Audie; Meier, John

2007-01-01

This study evaluated the feasibility of a hybrid solid oxide fuel cell (SOFC) auxiliary power unit (APU) and the impact in a 90-passenger More-Electric Regional Jet application. The study established realistic hybrid SOFC APU system weight and system efficiencies, and evaluated the impact on the aircraft total weight, fuel burn, and emissions from the main engine and the APU during cruise, landing and take-off (LTO) cycle, and at the gate. Although the SOFC APU may be heavier than the current conventional APU, its weight disadvantage can be offset by fuel savings in the higher SOFC APU system efficiencies against the main engine bleed and extraction during cruise. The higher SOFC APU system efficiency compared to the conventional APU on the ground can also provide considerable fuel saving and emissions reduction, particularly at the gate, but is limited by the fuel cell stack thermal fatigue characteristic.

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Research on the boron contamination at the p/i interface of microcrystalline silicon solar cells deposited in a single PECVD chamber

NASA Astrophysics Data System (ADS)

Zhang, Xiao-Dan; Sun, Fu-He; Wei, Chang-Chun; Sun, Jian; Zhang, De-Kun; Geng, Xin-Hua; Xiong, Shao-Zhen; Zhao, Ying

2009-10-01

This paper studies boron contamination at the interface between the p and i layers of μc-Si:H solar cells deposited in a single-chamber PECVD system. The boron depth profile in the i layer was measured by Secondary Ion Mass Spectroscopy. It is found that the mixed-phase μc-Si:H materials with 40% crystalline volume fraction is easy to be affected by the residual boron in the reactor. The experimental results showed that a 500-nm thick μc-Si:H covering layer or a 30-seconds of hydrogen plasma treatment can effectively reduce the boron contamination at the p/i interface. However, from viewpoint of cost reduction, the hydrogen plasma treatment is desirable for solar cell manufacture because the substrate is not moved during the hydrogen plasma treatment.

Autologous fibrin sealant reduces the incidence of prolonged air leak and duration of chest tube drainage after lung volume reduction surgery: a prospective randomized blinded study.

PubMed

Moser, C; Opitz, I; Zhai, W; Rousson, V; Russi, E W; Weder, W; Lardinois, D

2008-10-01

Prolonged air leak is reported in up to 50% of patients after lung volume reduction surgery. The effect of an autologous fibrin sealant on the intensity and duration of air leak and on the time to chest drain removal after lung volume reduction surgery was investigated in a randomized prospective clinical trial. Twenty-five patients underwent bilateral thoracoscopic lung volume reduction surgery. In each patient, an autologous fibrin sealant was applied along the staple lines on one side, whereas no additional measure was taken on the other side. Randomization of treatment was performed at the end of the resection on the first side. Air leak was assessed semiquantitatively by use of a severity score (0 = no leak; 4 = continuous severe leak) by two investigators blinded to the treatment. Mean value of the total severity scores for the first 48 hours postoperative was significantly lower in the treated group (4.7 +/- 7.7) than in the control group (16.0 +/- 10.1) (P < .001), independently of the length of the resection. Prolonged air leak and mean duration of drainage were also significantly reduced after application of the sealant (4.5% and 2.8 +/- 1.9 days versus 31.8% and 5.9 +/- 2.9 days) (P = .03 and P < .001). Autologous fibrin sealant for reinforcement of the staple lines after lung volume reduction surgery significantly reduces prolonged air leak and duration of chest tube drainage.

Cell volume and plasma membrane osmotic water permeability in epithelial cell layers measured by interferometry.

PubMed

Farinas, J; Verkman, A S

1996-12-01

The development of strategies to measure plasma membrane osmotic water permeability (Pf) in epithelial cells has been motivated by the identification of a family of molecular water channels. A general approach utilizing interferometry to measure cell shape and volume was developed and applied to measure Pf in cell layers. The method is based on the cell volume dependence of optical path length (OPL) for a light beam passing through the cell. The small changes in OPL were measured by interferometry. A mathematical model was developed to relate the interference signal to cell volume changes for cells of arbitrary shape and size. To validate the model, a Mach-Zehnder interference microscope was used to image OPL in an Madin Darby Canine Kidney (MDCK) cell layer and to reconstruct the three-dimensional cell shape (OPL resolution < lambda/25). As predicted by the model, a doubling of cell volume resulted in a change in OPL that was proportional to the difference in refractive indices between water and the extracellular medium. The time course of relative cell volume in response to an osmotic gradient was computed from serial interference images. To measure cell volume without microscopy and image analysis, a Mach-Zehnder interferometer was constructed in which one of two interfering laser beams passed through a flow chamber containing the cell layer. The interference signal in response to an osmotic gradient was analyzed to quantify the time course of relative cell volume. The calculated MDCK cell plasma membrane Pf of 6.1 x 10(-4) cm/s at 24 degrees C agreed with that obtained by interference microscopy and by a total internal reflection fluorescence method. Interferometry was also applied to measure the apical plasma membrane water permeability of intact toad urinary bladder; Pf increased fivefold after forskolin stimulation to 0.04 cm/s at 23 degrees C. These results establish and validate the application of interferometry to quantify cell volume and osmotic water permeability in cell layers.

Estrogen Receptor β as a Therapeutic Target in Breast Cancer Stem Cells

PubMed Central

Ma, Ran; Karthik, Govindasamy-Muralidharan; Lövrot, John; Haglund, Felix; Rosin, Gustaf; Katchy, Anne; Zhang, Xiaonan; Viberg, Lisa; Frisell, Jan; Williams, Cecilia; Linder, Stig; Fredriksson, Irma

2017-01-01

Abstract Background: Breast cancer cells with tumor-initiating capabilities (BSCs) are considered to maintain tumor growth and govern metastasis. Hence, targeting BSCs will be crucial to achieve successful treatment of breast cancer. Methods: We characterized mammospheres derived from more than 40 cancer patients and two breast cancer cell lines for the expression of estrogen receptors (ERs) and stem cell markers. Mammosphere formation and proliferation assays were performed on cells from 19 cancer patients and five healthy individuals after incubation with ER-subtype selective ligands. Transcriptional analysis was performed to identify pathways activated in ERβ-stimulated mammospheres and verified using in vitro experiments. Xenograft models (n = 4 or 5 per group) were used to study the role of ERs during tumorigenesis. Results: We identified an absence of ERα but upregulation of ERβ in BSCs associated with phenotypic stem cell markers and responsible for the proliferative role of estrogens. Knockdown of ERβ caused a reduction of mammosphere formation in cell lines and in patient-derived cancer cells (40.7%, 26.8%, and 39.1%, respectively). Gene set enrichment analysis identified glycolysis-related pathways (false discovery rate < 0.001) upregulated in ERβ-activated mammospheres. We observed that tamoxifen or fulvestrant alone was insufficient to block proliferation of patient-derived BSCs while this could be accomplished by a selective inhibitor of ERβ (PHTPP; 53.7% in luminal and 45.5% in triple-negative breast cancers). Furthermore, PHTPP reduced tumor initiation in two patient-derived xenografts (75.9% and 59.1% reduction in tumor volume, respectively) and potentiated tamoxifen-mediated inhibition of tumor growth in MCF7 xenografts. Conclusion: We identify ERβ as a mediator of estrogen action in BSCs and a novel target for endocrine therapy. PMID:28376210

Effects of moisture content and initial pH in composting process on heavy metal removal characteristics of grass clipping compost used for stormwater filtration.

PubMed

Khan, Eakalak; Khaodhir, Sutha; Ruangrote, Darin

2009-10-01

Heavy metals are common contaminants in stormwater runoff. One of the devices that can be used to effectively and economically remove heavy metals from runoff is a yard waste compost stormwater filter. The primary goal of composting is to reduce waste volume rather than to produce stormwater filter media. Moisture content (MC) and initial pH, the two important parameters in composting, were studied for their effects on yard waste volume reduction and heavy metal adsorption performances of the compost. The main objective of this investigation was to examine whether the conditions that provided high yard waste volume reduction would also result in compost with good heavy metal removal performances. Manila grass was composted at different initial pHs (5-9) and MCs (30-70%) and the composts were used to adsorb cadmium, copper, lead and zinc from water. Results indicated that MC is more critical than initial pH for both volume reduction and production of compost with high metal adsorption performances. The most optimal conditions for the two attributes were not exactly the same but lower MCs of 30-40% and pH 7 or higher tended to satisfy both high volume reduction and effective metal adsorption.

Volume reduction of benign thyroid nodules 3 months after a single treatment with high-intensity focused ultrasound (HIFU).

PubMed

Korkusuz, Huedayi; Fehre, Niklas; Sennert, Michael; Happel, Christian; Grünwald, Frank

2015-01-01

High-intensity focused ultrasound (HIFU) is a promising, non-invasive technique in treating benign thyroid nodules (TNs). The aim of this study was to evaluate the efficacy of HIFU to induce clinically meaningful shrinkage in benign predominantly solid TNs and to identify variables that influence or predict the magnitude of TN volume reduction. For each of ten subjects, HIFU treatment was conducted on a single nodule. Nodular volume was measured sonographically at baseline and at 3 months post-procedure. Nodular function and early treatment assessment was done scintigraphically. Median nodular volume reduction was 0.7 ml absolute and 48.8% relative to pre-interventional size (p < 0.05). Absolute shrinkage was negatively correlated with the average treatment depth (τ = -0.61, p < 0.05). Absolute nodular volume was positively correlated with the scintigraphic nodular uptake reduction (τ = 0.66, p < 0.05). HIFU treatment of benign predominantly solid TNs appears to be safe and effective for inducing nodular shrinkage. Despite potential for improvement, a single treatment session with HIFU is already a viable alternative to more standard methods. The feasibility of multiple HIFU treatments requires further investigation. Due to the small sample size, the findings of this analysis need conformation by larger studies.

Pulse oximeter plethysmographic waveform changes in awake, spontaneously breathing, hypovolemic volunteers.

PubMed

McGrath, Susan P; Ryan, Kathy L; Wendelken, Suzanne M; Rickards, Caroline A; Convertino, Victor A

2011-02-01

The primary objective of this study was to determine whether alterations in the pulse oximeter waveform characteristics would track progressive reductions in central blood volume. We also assessed whether changes in the pulse oximeter waveform provide an indication of blood loss in the hemorrhaging patient before changes in standard vital signs. Pulse oximeter data from finger, forehead, and ear pulse oximeter sensors were collected from 18 healthy subjects undergoing progressive reduction in central blood volume induced by lower body negative pressure (LBNP). Stroke volume measurements were simultaneously recorded using impedance cardiography. The study was conducted in a research laboratory setting where no interventions were performed. Pulse amplitude, width, and area under the curve (AUC) features were calculated from each pulse wave recording. Amalgamated correlation coefficients were calculated to determine the relationship between the changes in pulse oximeter waveform features and changes in stroke volume with LBNP. For pulse oximeter sensors on the ear and forehead, reductions in pulse amplitude, width, and area were strongly correlated with progressive reductions in stroke volume during LBNP (R(2) ≥ 0.59 for all features). Changes in pulse oximeter waveform features were observed before profound decreases in arterial blood pressure. The best correlations between pulse features and stroke volume were obtained from the forehead sensor area (R(2) = 0.97). Pulse oximeter waveform features returned to baseline levels when central blood volume was restored. These results support the use of pulse oximeter waveform analysis as a potential diagnostic tool to detect clinically significant hypovolemia before the onset of cardiovascular decompensation in spontaneously breathing patients.

Tumor Shrinkage Assessed by Volumetric MRI in Long-Term Follow-Up After Fractionated Stereotactic Radiotherapy of Nonfunctioning Pituitary Adenoma

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

Kopp, Christine, E-mail: Christine.Kopp@lrz.tu-muenchen.de; Theodorou, Marilena; Poullos, Nektarios

2012-03-01

Purpose: To evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent nonfunctioning pituitary adenomas (NFPAs). Methods and Materials: We assessed exact tumor volume shrinkage in 16 patients with NFPA after FSRT. All patients had previously undergone surgery. Gross tumor volume (GTV) was outlined on contrast-enhanced magnetic resonance imaging (MRI) before and median 63 months (range, 28-100 months) after FSRT. MRI was performed as an axial three-dimensional gradient echo T1-weighted sequence at 1.6-mm slice thickness without gap (3D MRI). Results: Mean tumor size of all 16 pituitary adenomas before treatment wasmore » 7.4 mL (3.3-18.9 mL). We found shrinkage of the treated pituitary adenoma in all patients. Within a median follow-up of 63 months (28-100 months) an absolute mean volume reduction of 3.8 mL (0.9-12.4 mL) was seen. The mean relative size reduction compared with the volume before radiotherapy was 51% (22%-95%). Shrinkage measured by 3D MRI was greater at longer time intervals after radiotherapy. A strong negative correlation between the initial tumor volume and the absolute volume reduction after FSRT was found. There was no correlation between tumor size reduction and patient age, sex, or number of previous surgeries. Conclusions: By using 3D MRI in all patients undergoing FSRT of an NFPA, tumor shrinkage is detected. Our data demonstrate that volumetric assessment based on 3D MRI adds additional information to routinely used radiological response measurements. After FSRT a mean relative size reduction of 51% can be expected within 5 years.« less

The Checkpoint Kinase 1 Inhibitor Prexasertib Induces Regression of Preclinical Models of Human Neuroblastoma.

PubMed

Lowery, Caitlin D; VanWye, Alle B; Dowless, Michele; Blosser, Wayne; Falcon, Beverly L; Stewart, Julie; Stephens, Jennifer; Beckmann, Richard P; Bence Lin, Aimee; Stancato, Louis F

2017-08-01

Purpose: Checkpoint kinase 1 (CHK1) is a key regulator of the DNA damage response and a mediator of replication stress through modulation of replication fork licensing and activation of S and G 2 -M cell-cycle checkpoints. We evaluated prexasertib (LY2606368), a small-molecule CHK1 inhibitor currently in clinical testing, in multiple preclinical models of pediatric cancer. Following an initial assessment of prexasertib activity, this study focused on the preclinical models of neuroblastoma. Experimental Design: We evaluated the antiproliferative activity of prexasertib in a panel of cancer cell lines; neuroblastoma cell lines were among the most sensitive. Subsequent Western blot and immunofluorescence analyses measured DNA damage and DNA repair protein activation. Prexasertib was investigated in several cell line-derived xenograft mouse models of neuroblastoma. Results: Within 24 hours, single-agent prexasertib promoted γH2AX-positive double-strand DNA breaks and phosphorylation of DNA damage sensors ATM and DNA-PKcs, leading to neuroblastoma cell death. Knockdown of CHK1 and/or CHK2 by siRNA verified that the double-strand DNA breaks and cell death elicited by prexasertib were due to specific CHK1 inhibition. Neuroblastoma xenografts rapidly regressed following prexasertib administration, independent of starting tumor volume. Decreased Ki67 and increased immunostaining of endothelial and pericyte markers were observed in xenografts after only 6 days of exposure to prexasertib, potentially indicating a swift reduction in tumor volume and/or a direct effect on tumor vasculature. Conclusions: Overall, these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy. Clin Cancer Res; 23(15); 4354-63. ©2017 AACR . ©2017 American Association for Cancer Research.

Nanovesicular carrier-based formulation for skin cancer targeting: evaluation of cytotoxicity, intracellular uptake, and preclinical anticancer activity.

PubMed

Jain, Subheet Kumar; Puri, Richa; Mahajan, Mohit; Yadav, Subodh; Pathak, C M; Ganesh, N

2015-04-01

Skin cancer has turned into global epidemic leading to higher incidences among cancer stricken population. The aim of the present investigation is to evaluate the anticancer potential and intracellular uptake of a novel nanovesicular formulation of 5-FU. Detailed intracellular uptake study in conjunction with estimation of intracellular reactive oxygen species was done using skin melanoma cell lines (A375) along with cytotoxicity studies. To further obtain the mechanistic insights into inhibition of tumor cell proliferation, cell-cycle arrest studies were conducted. The preclinical anticancer activity was carried out employing in vivo DMBA-croton oil-induced skin cancer model in mice. Significant reduction in the number of papillomas was observed in skin cancer-bearing mice on treatment with nanovesicular formulation (51.4 ± 3.2%) in comparison with marketed formulation (21.3 ± 2.1%) of 5-FU. Tumor volume was found to be reduced to 46.3 ± 3.5% with prepared formulation, whereas the marketed formulation-treated group showed the reduction of 18.6 ± 1.8% in comparison with the control (untreated) group. The results of present study demonstrated that nanovesicular formulation of 5-FU possessed the enhanced anticancer activity which could be attributed to better intracellular uptake, cellular retention, and sustained release of drug.

Learning and memory depend on fibroblast growth factor receptor 2 functioning in hippocampus.

PubMed

Stevens, Hanna E; Jiang, Ginger Y; Schwartz, Michael L; Vaccarino, Flora M

2012-06-15

Fibroblast growth factor (FGF) signaling controls self-renewal of neural stem cells during embryonic telencephalic development. FGF receptor 2 (FGFR2) has a significant role in the production of cortical neurons during embryogenesis, but its role in the hippocampus during development and in adulthood has not been described. Here we dissociate the role of FGFR2 in the hippocampus during development and during adulthood with the use of embryonic knockout and inducible knockout mice. Embryonic knockout of FGFR2 causes a reduction of hippocampal volume and impairment in adult spatial memory in mice. Spatial reference memory, as assessed by performance on the water maze probe trial, was correlated with reduced hippocampal parvalbumin+ cells, whereas short-term learning was correlated with reduction in immature neurons in the dentate gyrus. Furthermore, short-term learning and newly generated neurons in the dentate gyrus were deficient even when FGFR2 was lacking only in adulthood. Taken together, these findings support a dual role for FGFR2 in hippocampal short-term learning and long-term reference memory, which appear to depend on the abundance of two separate cellular components, parvalbumin interneurons and newly generated granule cells in the hippocampus. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Failure analysis of fuel cell electrodes using three-dimensional multi-length scale X-ray computed tomography

NASA Astrophysics Data System (ADS)

Pokhrel, A.; El Hannach, M.; Orfino, F. P.; Dutta, M.; Kjeang, E.

2016-10-01

X-ray computed tomography (XCT), a non-destructive technique, is proposed for three-dimensional, multi-length scale characterization of complex failure modes in fuel cell electrodes. Comparative tomography data sets are acquired for a conditioned beginning of life (BOL) and a degraded end of life (EOL) membrane electrode assembly subjected to cathode degradation by voltage cycling. Micro length scale analysis shows a five-fold increase in crack size and 57% thickness reduction in the EOL cathode catalyst layer, indicating widespread action of carbon corrosion. Complementary nano length scale analysis shows a significant reduction in porosity, increased pore size, and dramatically reduced effective diffusivity within the remaining porous structure of the catalyst layer at EOL. Collapsing of the structure is evident from the combination of thinning and reduced porosity, as uniquely determined by the multi-length scale approach. Additionally, a novel image processing based technique developed for nano scale segregation of pore, ionomer, and Pt/C dominated voxels shows an increase in ionomer volume fraction, Pt/C agglomerates, and severe carbon corrosion at the catalyst layer/membrane interface at EOL. In summary, XCT based multi-length scale analysis enables detailed information needed for comprehensive understanding of the complex failure modes observed in fuel cell electrodes.

Tumor volume changes on serial imaging with megavoltage CT for non-small-cell lung cancer during intensity-modulated radiotherapy: how reliable, consistent, and meaningful is the effect?

PubMed

Siker, Malika L; Tomé, Wolfgang A; Mehta, Minesh P

2006-09-01

Adaptive radiotherapy allows treatment plan modification based on data obtained during treatment. Assessing volume changes during treatment is now possible with intratreatment imaging capabilities on radiotherapy devices. This study assesses non-small-cell lung cancer (NSCLC) volume changes during treatment with conformal intensity-modulated radiotherapy by evaluating serial megavoltage computed tomography (MVCT) scans, with a specific emphasis on the frequency, reliability, and meaningfulness of these changes. Megavoltage CTs were retrospectively reviewed for 25 patients treated with the TomoTherapy Hi-Art system at the University of Wisconsin. Twenty-one patients received definitive radiotherapy, 4 with extracranial stereotactic radioablation (60 Gy in five fractions) and 17 on a dose-per-fraction escalation protocol (57-80.5 Gy in 25 fractions). Four patients were treated palliatively (22-30 Gy in 8 to 10 fractions). Gross tumor volumes were contoured on serial MVCTs at weekly intervals. Each patient had 4 to 25 scans, including at least one at the beginning, midway, and one at the end of treatment. At completion of treatment, no patient demonstrated a complete response. Partial response occurred in 3 (12%) and marginal response was noted in 5 (20%). The remaining 17 patients (68%) showed stable disease. The minimum "scorable threshold" for volume discrepancy between scans to account for interscan assessment variability was set at >25% volume change; 10 patients (40%) had >25% tumor regression. None of the patients treated ablatively or palliatively showed tumor regression during treatment. Although gross tumor regression during treatment may be objectively measured using MVCTs, substantial volumetric decrease occurs only in a minority. The clinical significance of this regression is questionable, because there is no way to document histologic tumor clearance, and therefore field reductions during radiotherapy cannot be recommended.

Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.

PubMed

Koohestani, Faezeh; Qiang, Wenan; MacNeill, Amy L; Druschitz, Stacy A; Serna, Vanida A; Adur, Malavika; Kurita, Takeshi; Nowak, Romana A

2016-07-01

Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. Uterine leiomyomas are the most common benign tumors of the female reproductive tract. HF can suppress the growth of human uterine leiomyoma cells in vitro. The mouse xenograft model reflects the characteristics of human leiomyomas. Primary leiomyoma smooth muscle cells from eight patients were xenografted under the renal capsule of adult, ovariectomized NOD-scid IL2Rγ(null) mice (NSG). Mice were treated with two different doses of HF or vehicle for 4 weeks with six to eight mice per group. Mouse body weight measurements and immunohistochemical analysis of body organs were carried out to assess the safety of HF treatment. Xenografted tumors were measured and analyzed for cellular and molecular changes induced by HF. Ovarian steroid hormone receptors were evaluated for possible modulation by HF. Treatment of mice carrying human UL xenografts with HF at 0.25 or 0.50 mg/kg body weight for 4 weeks resulted in a 35-40% (P < 0.05) reduction in tumor volume. The HF-induced volume reduction was accompanied by increased apoptosis and decreased cell proliferation. In contrast, there was no significant change in the collagen content either at the transcript or protein level between UL xenografts in control and HF groups. HF treatment did not change the expression level of ovarian steroid hormone receptors. No adverse pathological effects were observed in other tissues from mice undergoing treatment at these doses. While this study did test the effects of HF on human leiomyoma cells in an in vivo model, HF was administered to mice whose tolerance and metabolism of the drug may differ from that in humans. Also, the longer term effects of HF treatment are yet unclear. The results of this study showing the effectiveness of HF in reducing UL tumor growth by interfering with the main cellular processes regulating cell proliferation and apoptosis are in agreement with previous studies on the effects of HF on other fibrotic diseases. HF can be considered as a candidate for reducing the size of leiomyomas, particularly prior to surgery. This project was funded by NIH PO1HD057877 and R01 HD064402. Authors report no competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Brain volume reductions in adolescent heavy drinkers.

PubMed

Squeglia, Lindsay M; Rinker, Daniel A; Bartsch, Hauke; Castro, Norma; Chung, Yoonho; Dale, Anders M; Jernigan, Terry L; Tapert, Susan F

2014-07-01

Brain abnormalities in adolescent heavy drinkers may result from alcohol exposure, or stem from pre-existing neural features. This longitudinal morphometric study investigated 40 healthy adolescents, ages 12-17 at study entry, half of whom (n=20) initiated heavy drinking over the 3-year follow-up. Both assessments included high-resolution magnetic resonance imaging. FreeSurfer was used to segment brain volumes, which were measured longitudinally using the newly developed quantitative anatomic regional change analysis (QUARC) tool. At baseline, participants who later transitioned into heavy drinking showed smaller left cingulate, pars triangularis, and rostral anterior cingulate volume, and less right cerebellar white matter volumes (p<.05), compared to continuous non-using teens. Over time, participants who initiated heavy drinking showed significantly greater volume reduction in the left ventral diencephalon, left inferior and middle temporal gyrus, and left caudate and brain stem, compared to substance-naïve youth (p<.05). Findings suggest pre-existing volume differences in frontal brain regions in future drinkers and greater brain volume reduction in subcortical and temporal regions after alcohol use was initiated. This is consistent with literature showing pre-existing cognitive deficits on tasks recruited by frontal regions, as well as post-drinking consequences on brain regions involved in language and spatial tasks. Published by Elsevier Ltd.

Regulation of cell volume by glycosaminoglycans.

PubMed

Joerges, Jelena; Schulz, Tobias; Wegner, Jeannine; Schumacher, Udo; Prehm, Peter

2012-01-01

Cell volume is regulated by a delicate balance between ion distribution across the plasma membrane and the osmotic properties of intra- and extracellular components. Using a fluorescent calcein indicator, we analysed the effects of glycosaminoglycans on the cell volume of hyaluronan producing fibroblasts and hyaluronan deficient HEK cells over a time period of 30 h. Exogenous glycosaminoglycans induced cell blebbing after 2 min and swelling of fibroblasts to about 110% of untreated cell volume at low concentrations which decreased at higher concentrations. HEK cells did not show cell blebbing and responded by shrinking to 65% of untreated cell volume. Heparin induced swelling of both fibroblasts and HEK cells. Hyaluronidase treatment or inhibition of hyaluronan export led to cell shrinkage indicating that the hyaluronan coat maintained fibroblasts in a swollen state. These observations were explained by the combined action of the Donnan effect and molecular crowding. Copyright © 2011 Wiley Periodicals, Inc.

A glucose-starvation response regulates the diffusion of macromolecules

PubMed Central

Joyner, Ryan P; Tang, Jeffrey H; Helenius, Jonne; Dultz, Elisa; Brune, Christiane; Holt, Liam J; Huet, Sebastien; Müller, Daniel J; Weis, Karsten

2016-01-01

The organization and biophysical properties of the cytosol implicitly govern molecular interactions within cells. However, little is known about mechanisms by which cells regulate cytosolic properties and intracellular diffusion rates. Here, we demonstrate that the intracellular environment of budding yeast undertakes a startling transition upon glucose starvation in which macromolecular mobility is dramatically restricted, reducing the movement of both chromatin in the nucleus and mRNPs in the cytoplasm. This confinement cannot be explained by an ATP decrease or the physiological drop in intracellular pH. Rather, our results suggest that the regulation of diffusional mobility is induced by a reduction in cell volume and subsequent increase in molecular crowding which severely alters the biophysical properties of the intracellular environment. A similar response can be observed in fission yeast and bacteria. This reveals a novel mechanism by which cells globally alter their properties to establish a unique homeostasis during starvation. DOI: http://dx.doi.org/10.7554/eLife.09376.001 PMID:27003290

Comparison of surgical conditions in 2 different anesthesia techniques of esmolol-induced controlled hypotension in breast reduction surgery

PubMed Central

Besir, Ahmet; Cekic, Bahanur; Kutanis, Dilek; Akdogan, Ali; Livaoglu, Murat

2017-01-01

Abstract Background: Breast reduction surgery is a common cosmetic surgery with a high incidence of blood loss and transfusion. In this surgery, the reduction of blood loss related to surgical manipulation and the volume of resected tissue is a target. In the present study, we compared the effects of esmolol-induced controlled hypotension on surgical visibility, surgical bleeding, and the duration of surgery in patients anesthetized with propofol/remifentanil (PR) or sevoflurane/remifentanil (SR). Methods: Patients in the American Society of Anesthesiologists I/II risk group undergoing breast reduction surgery were prospectively randomized into PR (n = 25) and SR (n = 25) groups. Controlled hypotension was induced with esmolol in both groups. During the intraoperative period, the heart rate (HR), mean arterial pressure (MAP), operation duration, volume of intraoperative blood loss, volume of blood received through postoperative drains, volume of resected tissues, and surgical area bleeding score were recorded. Results: The duration of operation in the incisional period was shorter in group PR compared to group SR (P = 0.04). The change in HR was lower in incision and hemostasis periods in the group PR compared to the group SR (P < 0.001). Total intraoperative intraoperative bleeding volume and volume of blood received through drains on postoperative postoperative day 1, day 2, and in total were found to be significantly lower in group PR compared to group SR. Surgical visibility scoring was more effective in group PR compared to SR. Conclusion: In the breast reduction surgery performed under esmolol-induced controlled hypotension, the effect of propofol + remifentanil anesthesia on the duration of incisional surgery, surgical visibility, and volume of surgical blood loss was more reliable and effective compared to that of sevoflurane + remifentanil, which seems to be an advantage. PMID:28272228

Decreased subcortical volumes in alcohol dependent individuals: effect of polysubstance use disorder.

PubMed

Grodin, Erica N; Momenan, Reza

2017-09-01

Chronic alcohol use has widespread effects on brain morphometry. Alcohol dependent individuals are often diagnosed with comorbid substance use disorders. Alterations in brain morphometry may be different in individuals that are dependent on alcohol alone and individuals dependent on alcohol and other substances. We examined subcortical brain volumes in 37 individuals with alcohol dependence only (ADO), 37 individuals with polysubstance use disorder (PS) and 37 healthy control participants (HC). Participants underwent a structural MR scan and a model-based segmentation tool was used to measure the volume of 14 subcortical regions (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens). Compared to HC, ADO had smaller volume in the bilateral hippocampus, right nucleus accumbens and right thalamus. PS only had volume reductions in the bilateral thalamus compared to HC. PS had a larger right caudate compared to ADO. Subcortical volume was negatively associated with drinking measures only in the ADO group. This study confirms the association between alcohol dependence and reductions in subcortical brain volume. It also suggests that polysubstance use interacts with alcohol use to produce limited subcortical volume reduction and at least one region of subcortical volume increase. These findings indicate that additional substance use may mask damage through inflammation or may function in a protective manner, shielding subcortical regions from alcohol-induced damage. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Investigations on the nephrotoxicity and hepatotoxicity of trivalent and hexavalent chromium compounds.

PubMed

Dartsch, P C; Hildenbrand, S; Kimmel, R; Schmahl, F W

1998-09-01

In contrast to trivalent chromium (Cr(III)) compounds, hexavalent chromium ((Cr(VI)) compounds are oxidizing agents capable of directly inducing tissue damage and possessing carcinogenic, mutagenic and teratogenic potency. After oral or dermal absorption of Cr(VI), the kidney is the main target organ for chromium accumulation, which might result in acute tubular necrosis in humans. In contrast, an acute toxic effect of Cr(VI) on the liver has not yet been described. Therefore, we used two established epithelial cell lines from the kidney (Opossum kidney cells) and the liver (Hep G2 cells) to design an in vitro-assay which is able to examine acute toxic effects of chromium compounds. Cells of both cell lines were treated with various concentrations of Cr(III) and Cr(VI) ranging from 0.01 micromol/l to 1 mmol/l for 24 h. Thereafter, cell morphology, organization of the intracellular cytoskeleton, number of viable cells and mean cell volume were examined. The results show that Cr(VI), but not Cr(III), has an acute cytotoxic effect and causes a dose-dependent loss in cell viability. The effective dose that caused 50% of cell death was 5 micromol/l for kidney epithelial cells and 50 micromol/l for liver epithelial cells. This means that kidney epithelial cells are 10 times more sensitive towards Cr(VI) treatment than liver epithelial cells and this might explain the known nephrotoxicity in vivo. The loss in cell viability was accompanied by a rounding and detachment of the cells and a marked reduction of intracellular F-actin-containing stress fibers. Microtubules and intermediate-sized filaments were observed to be unaffected. Only in the case of kidney epithelial cells, a dose-dependent cell volume increase was observed after Cr(VI) treatment at concentrations up to 50 micromol/l. At higher concentrations, the cell volume decreased due to the high number of cells undergoing lysis and the appearance of cellular fragments. Various chloride channel blockers with different specificities, molecular structures and inhibitory potentials were tested for their ability to prevent Cr(VI)-induced cell damage. None of the channel blockers was able to inhibit cell damage, suggesting that the uptake of Cr(VI) through the general anion transport system of the cell membrane might be only one facet of cellular uptake and toxification. The data presented here not only confirm the different organ-specific effects of Cr(III) and Cr(VI), but also provide a basis for future experiments on the understanding of acute toxicity of Cr(VI) compounds. Moreover, the results demonstrate that the designed in vitro-assay might be a useful tool to prove whether non-toxic Cr(III) can be oxidized to Cr(VI) under specific industrial conditions (for example, in the leather or chrome industry).

An application specific integrated circuit based multi-anode microchannel array readout system

NASA Technical Reports Server (NTRS)

Smeins, Larry G.; Stechman, John M.; Cole, Edward H.

1991-01-01

Size reduction of two new multi-anode microchannel array (MAMA) readout systems is described. The systems are based on two analog and one digital application specific integrated circuits (ASICs). The new readout systems reduce volume over previous discrete designs by 80 percent while improving electrical performance on virtually every significant parameter. Emphasis is made on the packaging used to achieve the volume reduction. Surface mount technology (SMT) is combined with modular construction for the analog portion of the readout. SMT reliability concerns and the board area impact of MIL SPEC SMT components is addressed. Package selection for the analog ASIC is discussed. Future sytems will require even denser packaging and the volume reduction progression is shown.

Incidental lung volume reduction following fulminant pulmonary hemorrhage in a patient with severe emphysema.

PubMed

Hetzel, Juergen; Spengler, Werner; Horger, Marius; Boeckeler, Michael

2015-06-01

Endoscopic lung volume reduction is an emerging technique meant to improve lung function parameters, quality of life, and exercise tolerance in patients with severe lung emphysema. This is the first report of lung volume reduction by autologous blood in a patient with non-bullous lung emphysema. A 74-year-old woman with heterogeneous lung emphysema developed accidentally diffuse lobar bleeding immediately after valve placement. Due to persistent hemorrhage, the valves had to be removed shortly thereafter. Despite extraction of the valves, respiratory function of the patient improved rapidly indicated also by a drop in the COPD assessment test questionnaire, 3 months later. This was consistent with both improvement of lung function tests and six-minute walking test.

Impact of gray matter reductions on theory of mind abilities in patients with schizophrenia.

PubMed

Koelkebeck, Katja; Hirao, Kazuyuki; Miyata, Jun; Kawada, Ryosaku; Saze, Teruyasu; Dannlowski, Udo; Ubukata, Shiho; Ohrmann, Patricia; Bauer, Jochen; Pedersen, Anya; Fukuyama, Hidenao; Sawamoto, Nobukatsu; Takahashi, Hidehiko; Murai, Toshiya

2013-01-01

To identify the brain regions involved in the interpretation of intentional movement by patients with schizophrenia, we investigated the association between cerebral gray matter (GM) volumes and performance on a theory of mind (ToM) task using voxel-based morphometry. Eighteen patients with schizophrenia and thirty healthy controls participated in the study. Participants were given a moving shapes task that employs the interpretation of intentional movement. Verbal descriptions were rated according to intentionality. ToM performance deficits in patients were found to be positively correlated with GM volume reductions in the superior temporal sulcus and medial prefrontal cortex. Our findings confirm that divergent brain regions contribute to mentalizing abilities and that GM volume reductions impact behavioral deficits in patients with schizophrenia.

DVH- and NTCP-based dosimetric comparison of different longitudinal margins for VMAT-IMRT of esophageal cancer.

PubMed

Münch, S; Oechsner, M; Combs, S E; Habermehl, D

2017-08-15

To cover the microscopic tumor spread in squamous cell carcinoma of the esophagus (SCC), longitudinal margins of 3-4 cm are used for radiotherapy (RT) protocols. However, smaller margins of 2-3 cm might be reasonable when advanced diagnostic imaging is integrated into target volume delineation. Purpose of this study was to compare the dose distribution and deposition to the organs at risk (OAR) for different longitudinal margins using a DVH- and NTCP-based approach. Ten patients with SCC of the middle or lower third were retrospectively selected. Three planning target volumes (PTV) with longitudinal margins of 4 cm, 3 cm and 2 cm and an axial margin of 1.5 cm to the gross target volume (GTV) were defined for each patient. For each PTV two treatment plans with total doses of 41.4 Gy (neoadjuvant treatment) and 50.4 Gy (definite treatment) were calculated. Dose to the lungs, heart, myelon and liver were then evaluated and compared between different PTVs. When using a longitudinal margin of 3 cm instead of 4 cm, all dose parameters (Dmin, Dmean, Dmedian and V5-V35), except Dmax could be significantly reduced for the lungs. Regarding the heart, a significant reduction was seen for Dmean and V5, but not for Dmin, Dmax, Dmedian and V10-V35. When comparing a longitudinal margin of 4 cm to a longitudinal margin of 2 cm, a significant difference was calculated for Dmin, Dmean, Dmedian and V5-V35 of the lungs and for Dmax, Dmean and V5-V35 of the heart. Nevertheless, no difference was seen for median heart dose. An additional dose reduction for V10 of the heart was achieved for definite treatment plans when using a longitudinal margin of 3 cm. The NTCP-based risk of pneumonitis was significantly reduced by a margin reduction to 2 cm for neoadjuvant and definite treatment plans. Reduction of longitudinal margins from 4 cm to 3 cm can significantly reduce the dose to lungs and Dmean of the heart. Despite clinical benefit and oncologic outcome remain unclear, reduction of the longitudinal margins might provide the opportunity to reduce side effects of chemoradiation (CRT) for SCC in upcoming studies.

"Pulmonary valve replacement diminishes the presence of restrictive physiology and reduces atrial volumes": a prospective study in Tetralogy of Fallot patients.

PubMed

Pijuan-Domenech, Antonia; Pineda, Victor; Castro, Miguel Angel; Sureda-Barbosa, Carlos; Ribera, Aida; Cruz, Luz M; Ferreira-Gonzalez, Ignacio; Dos-Subirà, Laura; Subirana-Domènech, Teresa; Garcia-Dorado, David; Casaldàliga-Ferrer, Jaume

2014-11-15

Pulmonary valve replacement (PVR) reduces right ventricular (RV) volumes in the setting of long-term pulmonary regurgitation after Tetralogy of Fallot (ToF) repair; however, little is known of its effect on RV diastolic function. Right atrial volumes may reflect the burden of RV diastolic dysfunction. The objective of this paper is to evaluate the clinical, echocardiographic, biochemical and cardiac magnetic resonance (CMR) variables, focusing particularly on right atrial response and right ventricular diastolic function prior to and after elective PVR in adult patients with ToF. This prospective study was conducted from January 2009 to April 2013 in consecutive patients > 18 years of age who had undergone ToF repair in childhood and were accepted for elective PVR. Twenty patients (mean age: 35 years; 70% men) agreed to enter the study. PVR was performed with a bioporcine prosthesis. Concomitant RV reduction was performed in all cases when technically possible. Pulmonary end-diastolic forward flow (EDFF) decreased significantly from 5.4 ml/m(2) to 0.3 ml/m(2) (p < 0.00001), and right atrial four-chamber echocardiographic measurements and volumes by 25% (p = 0.0024): mean indexed diastolic/systolic atrial volumes prior to surgery were 43 ml/m(2) (SD+/-4.6)/63 ml/m(2) (SD+/-5.5), and dropped to 33 ml/m(2) (SD+/-3)/46 ml/m(2) (SD+/-2.55) post-surgery. All patients presented right ventricular diastolic and systolic volume reductions, with a mean volume reduction of 35% (p < 0.00001). Right ventricular diastolic dysfunction was common in a population of severely dilated RV patients long term after ToF repair. Right ventricular diastolic parameters improved as did right atrial volumes in keeping with the known reduction in RV volumes, after PVR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mechanics of Fluid-Filled Interstitial Gaps. I. Modeling Gaps in a Compact Tissue.

PubMed

Parent, Serge E; Barua, Debanjan; Winklbauer, Rudolf

2017-08-22

Fluid-filled interstitial gaps are a common feature of compact tissues held together by cell-cell adhesion. Although such gaps can in principle be the result of weak, incomplete cell attachment, adhesion is usually too strong for this to occur. Using a mechanical model of tissue cohesion, we show that, instead, a combination of local prevention of cell adhesion at three-cell junctions by fluidlike extracellular material and a reduction of cortical tension at the gap surface are sufficient to generate stable gaps. The size and shape of these interstitial gaps depends on the mechanical tensions between cells and at gap surfaces, and on the difference between intracellular and interstitial pressures that is related to the volume of the interstitial fluid. As a consequence of the dependence on tension/tension ratios, the presence of gaps does not depend on the absolute strength of cell adhesion, and similar gaps are predicted to occur in tissues of widely differing cohesion. Tissue mechanical parameters can also vary within and between cells of a given tissue, generating asymmetrical gaps. Within limits, these can be approximated by symmetrical gaps. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Search for biomarkers of asbestos exposure and asbestos-induced cancers in investigations of the immunological effects of asbestos.

PubMed

Matsuzaki, Hidenori; Kumagai-Takei, Naoko; Lee, Suni; Maeda, Megumi; Sada, Nagisa; Hatayama, Tamayo; Yamamoto, Shoko; Ikeda, Miho; Yoshitome, Kei; Min, Yu; Nishimura, Yasumitsu; Otsuki, Takemi

2017-06-09

The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells. These findings were used to explore biological markers associated with asbestos exposure and asbestos-induced cancers and suggested the usefulness of serum/plasma IL-10 and TGF-β, surface CXCR3 expression in Tresp, the secreting potential of IFN-γ in Tresp, intracellular perforin level in CTL, and surface expression NKp46 in NK cells. Although other unexplored cytokines in serum/plasma and molecules in these immunological cells, including Th17, should be investigated by experimental procedures in addition to a comprehensive analysis of screening methods, biomarkers based on immunological alterations may be helpful in clinical situations to screen the high-risk population exposed to asbestos and susceptible to asbestos-related cancers such as mesothelioma.

Three-dimensional CT might be a potential evaluation modality in correction of asymmetrical masseter muscle hypertrophy by botulinum toxin injection.

PubMed

No, Yeon A; Ahn, Byeong Heon; Kim, Beom Joon; Kim, Myeung Nam; Hong, Chang Kwon

2016-01-01

For correction of this asymmetrical hypertrophy, botulinum toxin type A (BTxA) injection is one of convenient treatment modalities. Unfortunately, physical examination of masseter muscle is not enough to estimate the exact volume of muscle hypertrophy difference. Two Koreans, male and female, of bilateral masseter hypertrophy with asymmetricity were evaluated. BTxA (NABOTA(®), Daewoong, Co. Ltd., Seoul, Korea) was injected at master muscle site with total 50 U (25 U at each side) and volume change was evaluated with three-dimensional (3D) CT image analysis. Maximum reduction of masseter hypertrophy was recognized at 2-month follow-up and reduced muscle size started to restore after 3 months. Mean reduction of masseter muscle volume was 36% compared with baseline. More hypertrophied side of masseter muscle presented 42% of volume reduction at 2-month follow-up but less hypertrophied side of masseter muscle showed 30% of volume shrinkage. In conclusion, 3D CT image analysis might be the exact evaluation tool for correction of asymmetrical masseter hypertrophy by botulinum toxin injection.

Rapid rather than gradual weight reduction impairs hemorheological parameters of Taekwondo athletes through reduction in RBC-NOS activation.

PubMed

Yang, Woo Hwi; Heine, Oliver; Pauly, Sebastian; Kim, Pilsang; Bloch, Wilhelm; Mester, Joachim; Grau, Marijke

2015-01-01

Rapid weight reduction is part of the pre-competition routine and has been shown to negatively affect psychological and physiological performance of Taekwondo (TKD) athletes. This is caused by a reduction of the body water and an electrolyte imbalance. So far, it is unknown whether weight reduction also affects hemorheological properties and hemorheology-influencing nitric oxide (NO) signaling, important for oxygen supply to the muscles and organs. For this purpose, ten male TKD athletes reduced their body weight by 5% within four days (rapid weight reduction, RWR). After a recovery phase, athletes reduced body weight by 5% within four weeks (gradual weight reduction, GWR). Each intervention was preceded by two baseline measurements and followed by a simulated competition. Basal blood parameters (red blood cell (RBC) count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean cellular hemoglobin and mean cellular hemoglobin concentration), RBC-NO synthase activation, RBC nitrite as marker for NO synthesis, RBC deformability and aggregation parameters were determined on a total of eight investigation days. Basal blood parameters were not affected by the two interventions. In contrast to GWR, RWR decreased activation of RBC-NO synthase, RBC nitrite, respective NO concentration and RBC deformability. Additionally, RWR increased RBC aggregation and disaggregation threshold. The results point out that a rapid weight reduction negatively affects hemorheological parameters and NO signaling in RBC which might limit performance capacity. Thus, GWR should be preferred to achieve the desired weight prior to a competition to avoid these negative effects.

Capacity Decay Mitigation by Asymmetric Positive/Negative Electrolyte Volumes in Vanadium Redox Flow Batteries.

PubMed

Park, Jong Ho; Park, Jung Jin; Park, O Ok; Yang, Jung Hoon

2016-11-23

Capacity decay in vanadium redox flow batteries during charge-discharge cycling has become an important issue because it lowers the practical energy density of the battery. The battery capacity tends to drop rapidly within the first tens of cycles and then drops more gradually over subsequent cycles during long-term operation. This paper analyzes and discusses the reasons for this early capacity decay. The imbalanced crossover rate of vanadium species was found to remain high until the total difference in vanadium concentration between the positive and negative electrolytes reached almost 1 mol dm -3 . To minimize the initial crossover imbalance, we introduced an asymmetric volume ratio between the positive and negative electrolytes during cell operation. Changing this ratio significantly reduced the capacity fading rate of the battery during the early cycles and improved its capacity retention at steady state. As an example, the practical energy density of the battery increased from 15.5 to 25.2 Wh L -1 simply after reduction of the positive volume by 25 %. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly deformation-tolerant carbon nanotube sponges as supercapacitor electrodes.

PubMed

Li, Peixu; Kong, Chuiyan; Shang, Yuanyuan; Shi, Enzheng; Yu, Yuntao; Qian, Weizhong; Wei, Fei; Wei, Jinquan; Wang, Kunlin; Zhu, Hongwei; Cao, Anyuan; Wu, Dehai

2013-09-21

Developing flexible and deformable supercapacitor electrodes based on porous materials is of high interest in energy related fields. Here, we show that carbon nanotube sponges, consisting of highly porous conductive networks, can serve as compressible and deformation-tolerant supercapacitor electrodes in aqueous or organic electrolytes. In aqueous electrolytes, the sponges maintain a similar specific capacitance (>90% of the original value) under a predefined compressive strain of 50% (corresponding to a volume reduction of 50%), and retain more than 70% of the original capacitance under 80% strain while the volume normalized capacitance increases by 3-fold. The sponge electrode maintains a stable performance after 1000 large strain compression cycles. A coin-shaped cell assembled with these sponges shows excellent stability over 15,000 charging cycles with negligible degradation after 500 cycles. Our results indicate that carbon nanotube sponges have the potential to fabricate deformable supercapacitor electrodes with stable performance.

Pillared graphite anodes for reversible sodiation.

PubMed

Zhang, Hanyang; Li, Zhifei; Xu, Wei; Chen, Yicong; Ji, Xiulei; Lerner, Michael M

2018-08-10

There has been a major effort recently to develop new rechargeable sodium-ion electrodes. In lithium ion batteries, LiC 6 forms from graphite and desolvated Li cations during the first charge. With sodium ions, graphite only shows a significant capacity when Na + intercalates as a solvated complex, resulting in ternary graphite intercalation compounds (GICs). Although this chemistry has been shown to be highly reversible and to support high rates in small test cells, these GICs can require >250% volume expansion and contraction during cycling. Here we demonstrate the first example of GICs that reversibly sodiate/desodiate without any significant volume change. These pillared GICs are obtained by electrochemical reduction of graphite in an ether/amine co-solvent electrolyte. The initial gallery expansion, 0.36 nm, is less than half of that in diglyme-based systems, and shows a similar capacity. Thermal analyses suggest the pillaring phenomenon arises from stronger co-intercalate interactions in the GIC galleries.

Cellular volume regulation and substrate stiffness modulate the detachment dynamics of adherent cells

NASA Astrophysics Data System (ADS)

Yang, Yuehua; Jiang, Hongyuan

2018-03-01

Quantitative characterizations of cell detachment are vital for understanding the fundamental mechanisms of cell adhesion. Experiments have found that cell detachment shows strong rate dependence, which is mostly attributed to the binding-unbinding kinetics of receptor-ligand bond. However, our recent study showed that the cellular volume regulation can significantly regulate the dynamics of adherent cell and cell detachment. How this cellular volume regulation contributes to the rate dependence of cell detachment remains elusive. Here, we systematically study the role of cellular volume regulation in the rate dependence of cell detachment by investigating the cell detachments of nonspecific adhesion and specific adhesion. We find that the cellular volume regulation and the bond kinetics dominate the rate dependence of cell detachment at different time scales. We further test the validity of the traditional Johnson-Kendall-Roberts (JKR) contact model and the detachment model developed by Wyart and Gennes et al (W-G model). When the cell volume is changeable, the JKR model is not appropriate for both the detachments of convex cells and concave cells. The W-G model is valid for the detachment of convex cells but is no longer applicable for the detachment of concave cells. Finally, we show that the rupture force of adherent cells is also highly sensitive to substrate stiffness, since an increase in substrate stiffness will lead to more associated bonds. These findings can provide insight into the critical role of cell volume in cell detachment and might have profound implications for other adhesion-related physiological processes.

Establishing a cost-per-result of laboratory-based, reflex Cryptococcal antigenaemia screening (CrAg) in HIV+ patients with CD4 counts less than 100 cells/μl using a Lateral Flow Assay (LFA) at a typical busy CD4 laboratory in South Africa.

PubMed

Cassim, Naseem; Schnippel, Kathryn; Coetzee, Lindi Marie; Glencross, Deborah Kim

2017-01-01

Cryptococcal meningitis is a major cause of mortality and morbidity in countries with high HIV prevalence, primarily affecting patients whose CD4 are < = 100 cells/μl. Routine Cryptococcal Antigen (CrAg) screening is thus recommended in the South African HIV treatment guidelines for all patients with CD4 counts < = 100 cells/μl, followed by pre-emptive anti-fungal therapy where CrAg results are positive. A laboratory-based reflexed CrAg screening approach, using a Lateral Flow Assay (LFA) on remnant EDTA CD4 blood samples, was piloted at three CD4 laboratories. This study aimed to assess the cost-per-result of laboratory-based reflexed CrAg screening at one pilot CD4 referral laboratory. CD4 test volumes from 2014 were extracted to estimate percentage of CD4 < = 100 cells/μl. Daily average volumes were derived, assuming 12 months per/year and 21.73 working days per/month. Costing analyses were undertaken using Microsoft Excel and Stata with a provider prospective. The cost-per-result was estimated using a bottom-up method, inclusive of test kits and consumables (reagents), laboratory equipment and technical effort costs. The ZAR/$ exchange of 14.696/$1 was used, where applicable. One-way sensitivity analyses on the cost-per-result were conducted for possible error rates (3%- 8%, reductions or increases in reagent costs as well as test volumes (ranging from -60% to +60%). The pilot CD4 laboratory performed 267000 CD4 tests in 2014; ~ 9.3% (27500) reported CD4< = 100 cells/μl, equivalent to 106 CrAg tests performed daily. A batch of 30-tests could be performed in 1.6 hours, including preparation and analysis time. A cost-per-result of $4.28 was reported, with reagents contributing $3.11 (72.8%), while technical effort and laboratory equipment overheads contributed $1.17 (27.2%) and $0.03 (<1%) respectively. One-way sensitivity analyses including increasing or decreasing test volumes by 60% revealed a cost-per-result range of $3.84 to $6.03. A cost-per-result of $4.28 was established in a typical CD4 service laboratory to enable local budgetary cost projections and programmatic cost-effectiveness modelling. Varying reagent costs linked to currency exchange and varying test volumes in different levels of service can lead to varying cost-per-test and technical effort to manage workload, with an inverse relationship of higher costs expected at lower volumes of tests.

Developmental and Adult GAP-43 Deficiency in Mice Dynamically Alters Hippocampal Neurogenesis and Mossy Fiber Volume

PubMed Central

Latchney, Sarah E.; Masiulis, Irene; Zaccaria, Kimberly J.; Lagace, Diane C.; Powell, Craig M.; McCasland, James S.; Eisch, Amelia J.

2014-01-01

Growth Associated Protein-43 (GAP-43) is a pre-synaptic protein that plays key roles in axonal growth and guidance and in modulating synapse formation. Previous work has demonstrated that mice lacking one allele of this gene [GAP-43(+/-) mice] exhibit hippocampal structural abnormalities and impaired spatial learning and stress-induced behavioral withdrawal and anxiety (Zaccaria et al., 2010), behaviors that are dependent on proper hippocampal circuitry and function. Given the correlation between hippocampal function, synaptic connectivity, and neurogenesis, we tested if behaviorally-naïve GAP-43(+/-) mice had alterations in either neurogenesis or synaptic connectivity in the hippocampus during early postnatal development and young adulthood, and following behavior testing in older adults. To test our hypothesis, we examined hippocampal cell proliferation (Ki67), number of immature neuroblasts (DCX), and mossy fiber volume (synaptoporin) in behaviorally-naïve postnatal (P) day 9 (P9), P26, and behaviorally-experienced 5-7 month old GAP-43(+/-) and (+/+) littermate mice. P9 GAP-43(+/-) mice had fewer Ki67+ and DCX+ cells compared to (+/+) mice, particularly in the posterior dentate gyrus, and smaller mossy fiber volume in the same region. In young adulthood, however, male GAP-43(+/-) mice had more Ki67+ and DCX+ cells and greater mossy fiber volume in the posterior dentate gyrus relative to male (+/+). These increases were not seen in females. In 5-7 month old GAP-43(+/-) mice whose behaviors were the focus of our prior publication (Zaccaria et al., 2010), there was no global change in number of proliferating or immature neurons relative to (+/+) mice. However, more detailed analysis revealed fewer proliferative DCX+ cells in the anterior dentate gyrus of male GAP-43(+/-) mice compared to male (+/+) mice. This reduction was not observed in females. These results suggest that young GAP-43(+/-) mice have decreased hippocampal neurogenesis and synaptic connectivity, but slightly older mice have greater hippocampal neurogenesis and synaptic connectivity. In conjunction with our previous study, these findings suggest GAP-43 is dynamically involved in early postnatal and adult hippocampal neurogenesis and synaptic connectivity, possibly contributing to the GAP-43(+/-) behavioral phenotype. PMID:24576816

Forced expirations and maximum expiratory flow-volume curves during sustained microgravity on SLS-1.

PubMed

Elliott, A R; Prisk, G K; Guy, H J; Kosonen, J M; West, J B

1996-07-01

Gravity is known to influence the mechanical behavior of the lung and chest wall. However, the effect of sustained microgravity (microG) on forced expirations has not previously been reported. Tests were carried out by four subjects in both the standing and supine postures during each of seven preflight and four postflight data-collection sessions and four times during the 9 days of microG exposure on Spacelab Life Sciences-1. Compared with preflight standing values, peak expiratory flow rate (PEFR) was significantly reduced by 12.5% on flight day 2 (FD2), 11.6% on FD4, and 5.0% on FD5 but returned to standing values by FD9. The supine posture caused a 9% reduction in PEFR. Forced vital capacity and forced expired volume in 1 s were slightly reduced (approximately 3-4%) on FD2 but returned to preflight standing values on FD4 and FD5, and by FD9 both values were slightly but significantly greater than standing values. Forced vital capacity and forced expiratory volume in 1 s were both reduced in the supine posture (approximately 8-10%). Forced expiratory flows at 50% and between 25 and 75% of vital capacity did not change during microG but were reduced in the supine posture. Analysis of the maximum expiratory flow-volume curve showed that microG caused no consistent change in the curve configuration when individual in-flight days were compared with preflight standing curves, although two subjects did show a slight reduction in flows at low lung volumes from FD2 to FD9. The interpretation of the lack of change in curve configuration must be made cautiously because the lung volumes varied from day to day in flight. Therefore, the flows at absolute lung volumes in microG and preflight standing are not being compared. The supine curves showed a subtle but consistent reduction in flows at low lung volumes. The mechanism responsible for the reduction in PEFR is not clear. It could be due to a lack of physical stabilization when performing the maneuver in the absence of gravity or a transient reduction in respiratory muscle strength.

Hypervolemia from Drinking Hyperhydration Solutions at Rest and Exercise

NASA Technical Reports Server (NTRS)

Greenleaf, John E.; Looft-Wilson, Robin; Jackson, Catherine G. R.; Geelen, Ghislaine; Barnes, Paul R.; Jensen, Christopher D.; Whittam, James H.

1995-01-01

The mechanism of muscular fatigue from physical work and exercise (high metabolism) is not clear, but involves disturbances of muscle surface membrane excitation-contraction coupling from changes in sarcoplasmic reticulum Ca2+ release, cell H+ and Pi responses, and carbohydrate metabolism. Fatigue in people at rest (low metabolism) involves both psychological and physiological factors, probably in different proportions. One common factor appears to be the level and distribution of water and electrolytes within muscle cells and other vascular, interstitial, body fluid compartments. The vascular fluid volume, composed of plasma and red blood cells, is a primary regulatory factor for cardiovascular function; reduction of vascular volume (hypovolemia) and total body water (hypohydration) adversely affect exercise performance. Plasma volume and plasma ionic-osmotic constituent concentrations are also regulatory factors for body thermoregulation, which is often compromised from exercise induced hypovolemia and hypohydration. Rehydration of dehydrated people on earth is relatively easy with appropriate food (osmols), fluid, and a restful environment. But ad libitum drinking under stressful conditions; e.g., heat, exercise, or prior dehydration, results in involuntary dehydration defined as the delay in full fluid replacement (euhydration) during and following loss of body fluid. Astronauts, with their reduced total body water are euhydrated while in weightlessness, but become "dehydrated" during reentry and landing. Thus, people subjected to acute or chronic stress are probably somewhat "dehydrated" as well as fatigued. Many rehydration drinks are more concentrated (hypertonic-hyperosmotic) with respect to the normal plasma osmolality of 285 mOsm/kg H2O and more of the drink osmols are contributed by carbohydrates than by ionized substances. There have been few studies on the efficacy of various drink formulations for increasing body fluid compartment volumes, especially plasma volume, in rested hydrated subjects. Recent findings from our laboratory have indicated that drinks containing greater concentrations of ionized substances (Performance 1 and AstroAde) up to 157 mEq/L Na+ induced greater levels of hypervolemia in resting, moderately dehydrated men, and were also better than water for attenuating the characteristic hypovolemia during supine, submaximal, leg ergometer exercise.

Proceedings of the American Power Conference. Volume 60-1

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

McBride, A.E.

1998-12-01

The American Power Conference, 60th annual meeting, 1998, addressed reliability and economy as related to technology for competition and globalization. The topics of the papers included needs and advances in power engineering education, global climate change, distributed generation, the critical role of the nations largest coal, nuclear and hydropower stations, advances in generation technology, financing electric power projects, successful deregulation, year 2000 outlook for equipment conflict with information and control, system planning, asset management, relay and communication, particulate and SO{sub x} control, environmental protection compliance strategies, fuel cells, gas turbines, renewable energy, steam turbines, and cost reduction strategies.

Proceedings of the American Power Conference. Volume 60-2

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

McBride, A.E.

1998-12-01

The American Power Conference, 60th annual meeting, 1998, addressed reliability and economy as related to technology for competition and globalization. The topics of the papers included needs and advances in power engineering education, global climate change, distributed generation, the critical role of the nations largest coal, nuclear and hydropower stations, advances in generation technology, financing electric power projects, successful deregulation, year 2000 outlook for equipment conflict with information and control, system planning, asset management, relay and communication, particulate and SO{sub x} control, environmental protection compliance strategies, fuel cells, gas turbines, renewable energy, steam turbines, and cost reduction strategies.

Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: selective inhibitors of Aurora B kinase with potent anti-tumor activity.

PubMed

Foote, Kevin M; Mortlock, Andrew A; Heron, Nicola M; Jung, Frédéric H; Hill, George B; Pasquet, Georges; Brady, Madeleine C; Green, Stephen; Heaton, Simon P; Kearney, Sarah; Keen, Nicholas J; Odedra, Rajesh; Wedge, Stephen R; Wilkinson, Robert W

2008-03-15

A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume.

The perioperative management of patients with polycythaemia.

PubMed Central

Cundy, J.

1980-01-01

The types of polycythaemia are reviewed and evidence presented indicating the need for reduction of the packed cell volume in polycythaemic patients before operation. Such patients must also be offered a full regimen of perioperative antithrombosis therapy, the only possible exception being in cases of primary polycythaemia with a bleeding tendency. Either heparin or dextran should be given intravenously and pulsating boots or elastic stockings placed on the patient's legs. An indication is given of the evidence pointing towards mild anaemia, by British standards, being the optimum state for circulatory efficiency and ways of producing this in the polycythaemic patient are described. PMID:7436307

Antitumor activity of 7-O-succinyl macrolactin A tromethamine salt in the mouse glioma model.

PubMed

Jin, Jun; Choi, Suh Hee; Lee, Jung Eun; Joo, Jin-Deok; Han, Jung Ho; Park, Su-Young; Kim, Chae-Yong

2017-05-01

Chemoradiotherapy with temozolomide is the current standard treatment option for patients with glioblastoma. However, the majority of patients with glioblastoma survive for <2 years. Therefore, it is necessary to develop more effective therapeutic strategies for the treatment of glioblastoma. 7-O-succinyl macrolactin A tromethamine salt (SMA salt), a macrolactin compound, is known to possess an antiangiogenic activity. The present study investigated the antitumor effects of SMA salt in the treatment of glioblastoma by evaluating in vitro and in vivo antitumor effects of SMA salt in an experimental glioblastoma model. The antitumor effects of the drug on human glioblastoma U87MG, U251MG and LN229 cell lines were assessed using in vitro cell viability, migration and invasion assays. Nude mice with established U87MG glioblastoma were assigned to either the control or SMA salt treatment group. The volume of tumors and the duration of survival were also measured. SMA salt affected cell viability and caused a concentration-dependent inhibition effect on the migration and invasion of glioblastoma cell lines. Animals in the SMA salt treatment group demonstrated a significant reduction in tumor volume and an increase in survival (P<0.05). Treatment with SMA salt presented more cytotoxic effects as well as anti-migration and anti-invasion activity compared with the control group in vitro and in vivo . These results suggest that SMA salt has significant antitumor effects on glioblastoma.

ABT-510 induces tumor cell apoptosis and inhibits ovarian tumor growth in an orthotopic, syngeneic model of epithelial ovarian cancer

PubMed Central

Greenaway, James; Henkin, Jack; Lawler, Jack; Moorehead, Roger; Petrik, Jim

2012-01-01

Epithelial ovarian cancer (EOC) is the fifth most common cancer in women and is characterized by a low 5-year survival rate. One strategy that can potentially improve the overall survival rate in ovarian cancer is the use of antitumor agents such as ABT-510. ABT-510 is a small mimetic peptide of the naturally occurring antiangiogenic compound thrombospondin-1 and has been shown to significantly reduce tumor growth and burden in preclinical mouse models and in naturally occurring tumors in dogs. This is the first evaluation of ABT-510 in a preclinical model of human EOC. Tumorigenic mouse surface epithelial cells were injected into the bursa of C57BL/6 mice that were treated with either 100 mg/kg ABT-510 or an equivalent amount of PBS. ABT-510 caused a significant reduction in tumor size, ascites fluid volume, and secondary lesion dissemination when compared with PBS controls. Analysis of the vasculature of ABT-510-treated mice revealed vascular remodeling with smaller diameter vessels and lower overall area, increased number of mature vessels, and decreased tissue hypoxia. Tumors of ABT-510-treated mice had a significantly higher proportion of apoptotic tumor cells compared with the PBS-treated controls. Immunoblot analysis of cell lysates revealed a reduction in vascular endothelial growth factor, vascular endothelial growth factor receptor-2, and proliferating cell nuclear antigen protein expression as well as expression of members of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase survival pathways. In vitro, ABT-510 induced tumor cell apoptosis in mouse and human ovarian cancer cells. This study shows ABT-510 as a promising candidate for inhibiting tumor growth and ascites formation in human EOC. PMID:19139114

ABT-510 induces tumor cell apoptosis and inhibits ovarian tumor growth in an orthotopic, syngeneic model of epithelial ovarian cancer.

PubMed

Greenaway, James; Henkin, Jack; Lawler, Jack; Moorehead, Roger; Petrik, Jim

2009-01-01

Epithelial ovarian cancer (EOC) is the fifth most common cancer in women and is characterized by a low 5-year survival rate. One strategy that can potentially improve the overall survival rate in ovarian cancer is the use of antitumor agents such as ABT-510. ABT-510 is a small mimetic peptide of the naturally occurring antiangiogenic compound thrombospondin-1 and has been shown to significantly reduce tumor growth and burden in preclinical mouse models and in naturally occurring tumors in dogs. This is the first evaluation of ABT-510 in a preclinical model of human EOC. Tumorigenic mouse surface epithelial cells were injected into the bursa of C57BL/6 mice that were treated with either 100 mg/kg ABT-510 or an equivalent amount of PBS. ABT-510 caused a significant reduction in tumor size, ascites fluid volume, and secondary lesion dissemination when compared with PBS controls. Analysis of the vasculature of ABT-510-treated mice revealed vascular remodeling with smaller diameter vessels and lower overall area, increased number of mature vessels, and decreased tissue hypoxia. Tumors of ABT-510-treated mice had a significantly higher proportion of apoptotic tumor cells compared with the PBS-treated controls. Immunoblot analysis of cell lysates revealed a reduction in vascular endothelial growth factor, vascular endothelial growth factor receptor-2, and proliferating cell nuclear antigen protein expression as well as expression of members of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase survival pathways. In vitro, ABT-510 induced tumor cell apoptosis in mouse and human ovarian cancer cells. This study shows ABT-510 as a promising candidate for inhibiting tumor growth and ascites formation in human EOC.

Is copper chelation an effective anti-angiogenic strategy for cancer treatment?

PubMed

Antoniades, V; Sioga, A; Dietrich, E M; Meditskou, S; Ekonomou, L; Antoniades, K

2013-12-01

Angiogenesis and the acquisition of an angiogenic phenotype is important for cancer cell proliferation. Copper in an essential trace element that participates in many enzymatic complexes like the cytochrome c, superoxide dismutase and lysyl oxidase and it is involved in processes, like embryogenesis, growth, angiogenesis and carcinogenesis. In particular, its involvement in carcinogenesis was described for the first time in oral submucous fibrosis, where fibroblasts produce large amounts of collagen in the presence of copper. Copper's action in carcinogenesis is two-fold: (1) it participates in reactions with an increased redox potential that result in the production of oxidative products and oxidative stress. Through this mechanism, copper may cause DNA mutations in the nucleus and mitochondria or alterations to membrane phospholipids, (2) it participates in angiogenesis even in the absence of angiogenic molecules, as it was reported for the first time in rabbit cornea models with copolymer pellets charged with PGE1. Copper chelation regimens like penicillamine and tetrathiomolybdate are being described in the literature as having anti-angiogenic, anti-fibrotic and anti-inflammatory actions. Animal models of brain cancer that evaluated the anti-angiogenic properties of copper, have proven evidence of the reduction of tumor's microvascular supply, tumor volume and vascular permeability after plasma copper levels reduction. Interestingly, plasma copper levels reduction was shown to suppress micrometastases generation in mice models of breast cancer. We hypothesize that copper chelation therapy: increases oxidative stress in cancer cells to a level that does not allow survival because of the reduction of anti-oxidative enzymes production. It may also result in inhibition of angiogenesis and of the initiation of the angiogenic switch, because copper normally enhances endothelial cell migration and proliferation, improves binding of growth factors to endothelial cells and enhances the expression of angiogenic molecules. Copper chelation may also reduce extracellular matrix degradation and cancer spread, through reduction of MMP-9 production and probably of other collagenases and may inhibit propagation of micrometastases. However, copper chelation therapy may enhance angiogenesis through reduction of thrombospondin-1, that results into an increase in VEGF-VEGFR2 complexes and a high level of active MMP-9. These hypotheses help in understanding of the anti-angiogenic action of copper chelation therapies and of the complex network of interactions between copper and other molecules involved in angiogenesis. It may also stimulate further research regarding differences in copper metabolism, the effects of anti-copper regimens on organs, the development of resistance, and their possible angiogenic action through thrombospondin expression reduction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cell volume and plasma membrane osmotic water permeability in epithelial cell layers measured by interferometry.

PubMed Central

Farinas, J; Verkman, A S

1996-01-01

The development of strategies to measure plasma membrane osmotic water permeability (Pf) in epithelial cells has been motivated by the identification of a family of molecular water channels. A general approach utilizing interferometry to measure cell shape and volume was developed and applied to measure Pf in cell layers. The method is based on the cell volume dependence of optical path length (OPL) for a light beam passing through the cell. The small changes in OPL were measured by interferometry. A mathematical model was developed to relate the interference signal to cell volume changes for cells of arbitrary shape and size. To validate the model, a Mach-Zehnder interference microscope was used to image OPL in an Madin Darby Canine Kidney (MDCK) cell layer and to reconstruct the three-dimensional cell shape (OPL resolution < lambda/25). As predicted by the model, a doubling of cell volume resulted in a change in OPL that was proportional to the difference in refractive indices between water and the extracellular medium. The time course of relative cell volume in response to an osmotic gradient was computed from serial interference images. To measure cell volume without microscopy and image analysis, a Mach-Zehnder interferometer was constructed in which one of two interfering laser beams passed through a flow chamber containing the cell layer. The interference signal in response to an osmotic gradient was analyzed to quantify the time course of relative cell volume. The calculated MDCK cell plasma membrane Pf of 6.1 x 10(-4) cm/s at 24 degrees C agreed with that obtained by interference microscopy and by a total internal reflection fluorescence method. Interferometry was also applied to measure the apical plasma membrane water permeability of intact toad urinary bladder; Pf increased fivefold after forskolin stimulation to 0.04 cm/s at 23 degrees C. These results establish and validate the application of interferometry to quantify cell volume and osmotic water permeability in cell layers. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 6 PMID:8968620

Role of isothiocyanate conjugate of pterostilbene on the inhibition of MCF-7 cell proliferation and tumor growth in Ehrlich ascitic cell induced tumor bearing mice

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

Nikhil, Kumar; Sharan, Shruti; Chakraborty, Ajanta

2014-01-15

Naturally occurring pterostilbene (PTER) and isothiocyanate (ITC) attract great attention due to their wide range of biological properties, including anti-cancer, anti-leukemic, anti-bacterial and anti-inflammatory activities. A novel class of hybrid compound synthesized by introducing an ITC moiety on PTER backbone was evaluated for its anti-cancer efficacy in hormone-dependent breast cancer cell line (MCF-7) in vitro and Ehrlich ascitic tumor bearing mice model in vivo. The novel hybrid molecule showed significant in vitro anti-cancer activity (IC{sub 50}=25±0.38) when compared to reference compound PTER (IC{sub 50}=65±0.42). The conjugate molecule induced both S and G2/M phase cell cycle arrest as indicated by flowmore » cytometry analysis. In addition, the conjugate induced cell death was characterized by changes in cell morphology, DNA fragmentation, activation of caspase-9, release of cytochrome-c into cytosol and increased Bax: Bcl-2 ratio. The conjugate also suppressed the phosphorylation of Akt and ERK. The conjugate induced cell death was significantly increased in presence of A6730 (a potent Akt1/2 kinase inhibitor) and PD98059 (a specific ERK inhibitor). Moreover, the conjugated PTER inhibited tumor growth in Ehrlich ascitic cell induced tumor bearing mice as observed by reduction in tumor volume compared to untreated animals. Collectively, the pro-apoptotic effect of conjugate is mediated through the activation of caspases, and is correlated with the blockade of the Akt and ERK signaling pathways in MCF-7 cells. - Highlights: • Conjugate was prepared by appending isothiocyanate moiety on pterostilbene backbone. • Conjugate showed anticancer effects at comparatively lower dose than pterostilbene. • Conjugate caused blockage of the Akt and ERK signaling pathways in MCF-7 cells. • Conjugate significantly reduced solid tumor volume as compared to pterostilbene.« less

Embryonic stem cell therapy improves bone quality in a model of impaired fracture healing in the mouse; tracked temporally using in vivo micro-CT.

PubMed

Taiani, J T; Buie, H R; Campbell, G M; Manske, S L; Krawetz, R J; Rancourt, D E; Boyd, S K; Matyas, J R

2014-07-01

In the current study, we used an estrogen-deficient mouse model of osteoporosis to test the efficacy of a cell-generated bone tissue construct for bone augmentation of an impaired healing fracture. A reduction in new bone formation at the defect site was observed in ovariectomized fractures compared to the control group using repeated measures in vivo micro-computed tomography (μCT) imaging over 4 weeks. A significant increase in the bone mineral density (BMD), trabecular bone volume ratio, and trabecular number, thickness and connectivity were associated with fracture repair in the control group, whereas the fractured bones of the ovariectomized mice exhibited a loss in all of these parameters (p<0.001). In a separate group, ovariectomized fractures were treated with murine embryonic stem (ES) cell-derived osteoblasts loaded in a three-dimensional collagen I gel and recovery of the bone at the defect site was observed. A significant increase in the trabecular bone volume ratio (p<0.001) and trabecular number (p<0.01) was observed by 4 weeks in the fractures treated with cell-loaded collagen matrix compared to those treated with collagen I alone. The stem cell-derived osteoblasts were identified at the fracture site at 4 weeks post-implantation through in situ hybridization histochemistry. Although this cell tracking method was effective, the formation of an ectopic cellular nodule adjacent to the knee joints of two mice suggested that alternative in vivo cell tracking methods should be employed in order to definitively assess migration of the implanted cells. To our knowledge, this study is the first of its kind to examine the efficacy of stem cell therapy for fracture repair in an osteoporosis-related fracture model in vivo. The findings presented provide novel insight into the use of stem cell therapies for bone injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

Cinnamic Acid Derivatives Enhance the Efficacy of Transarterial Embolization in a Rat Model of Hepatocellular Carcinoma

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

Wilkins, Luke R., E-mail: lrw6n@virginia.edu; Brautigan, David L., E-mail: db8g@virginia.edu; Wu, Hanping, E-mail: hanpingwumd@gmail.com

IntroductionWe hypothesize that the combination of transarterial embolization (TAE) plus inhibition of lactate export will limit anaerobic metabolism and reduce tumor survival compared to TAE alone. The purpose of this study was to test this hypothesis in a rat model of hepatocellular carcinoma (HCC).MethodsRat N1-S1 hepatoma cells were assayed in vitro using the Seahorse XF analyzer to measure extracellular acidification (lactate excretion) comparing effects of the addition of caffeic acid (CA) or ferulic acid (FA) or UK-5099 with control. Monocarboxylate transporter Slc16a3 was knocked down by RNAi. N1S1 tumors were orthotopically implanted in rats and 4 groups evaluated: (1) Control,more » (2) TAE-only, (3) TAE plus CA, and (4) TAE plus FA. Tumor size was determined by ultrasound and analyzed by repeated measures statistics. Tumors harvested at 4 weeks were examined by microscopy.ResultsSeahorse assays showed that CA and FA caused a significant reduction by >90% in lactate efflux by N1S1 tumor cells (p < 0.01). Knockdown of Slc16a3 prevented inhibition by CA. In vivo tumors grew 30-fold in volume over 4 weeks in untreated controls. By comparison, TAE resulted in near cessation of growth (10% in 4-week time period). However, both TAE + CA and TAE + FA caused a significant reduction of tumor volumes (87 and 72%, respectively) compared to control and TAE (p < 0.05). Pathologic evaluation revealed residual tumor in the TAE group but no residual viable tumor cells in the TAE + CA and TAE + FA groups.ConclusionAddition of CA or FA enhances the effectiveness of TAE therapy for HCC in part by blocking lactate efflux.« less

[Lung volume reduction surgery in advanced emphysema--results of the Washington University, St. Louis].

PubMed

Cooper, J D; Gaissert, H A; Patterson, G A; Pohl, M S; Yusen, R D; Trulock, E P

1996-01-01

The aim of lung volume reduction surgery is to alleviate the symptoms of severe emphysema and to improve the life quality of the patient. The appropriate candidates (approximately 20% of all emphysematic patients examined in our clinic) had considerable dyspnea, an increased lung capacity, and a heterogenous dissemination of the emphysema with regional destruction of the parenchyma, hyperinflation and poor perfusion. After preoperative physiotherapie with a specified rehabilitation aim, a resection of 20 to 30% of the total lung volume was performed via sternotomy. From January 1993 to February 1996, 150 patients underwent bilateral lung volume reduction (age range = 36 to 77 years). The mean forced expiratory volume in 1 s (FEV1) was preoperatively 25% of the predicted value, the total lung capacity (TLC) 142% and the residual volume (RV) 283%, 94% of these patients necessitated oxygen supply at rest or during exercise. The 90-day mortality was 4%. All patients except 1 were extubated immediately after operation. The median hospital stay was 10 days in the first 100 patients and 7 days in the last 50. An increase of the FEV1 by 51% and a decrease of the RV by 28% was observed 6 months after operation. The mean PaO2 was improved by 8 mm Hg while the percentage of oxygen dependent patients went down from 50 to 16%. In addition a raise of the perseverance capacity, a clear decrease of dyspnea and an improvement of the life quality were achieved. These results persist after 1 (n = 56) and 2 (n = 20) years after operation. Lung volume reduction leads to an improvement of the lung function, symptoms and the quality of life, which is superior to that achieved by maximal clinical intervention.

On the Mechanism of Human Red Blood Cell Longevity: Roles of Calcium, the Sodium Pump, PIEZO1, and Gardos Channels.

PubMed

Lew, Virgilio L; Tiffert, Teresa

2017-01-01

In a healthy adult, the transport of O 2 and CO 2 between lungs and tissues is performed by about 2 · 10 13 red blood cells, of which around 1.7 · 10 11 are renewed every day, a turnover resulting from an average circulatory lifespan of about 120 days. Cellular lifespan is the result of an evolutionary balance between the energy costs of maintaining cells in a fit functional state versus cell renewal. In this Review we examine how the set of passive and active membrane transporters of the mature red blood cells interact to maximize their circulatory longevity thus minimizing costs on expensive cell turnover. Red blood cell deformability is critical for optimal rheology and gas exchange functionality during capillary flow, best fulfilled when the volume of each human red blood cell is kept at a fraction of about 0.55-0.60 of the maximal spherical volume allowed by its membrane area, the optimal-volume-ratio range. The extent to which red blood cell volumes can be preserved within or near these narrow optimal-volume-ratio margins determines the potential for circulatory longevity. We show that the low cation permeability of red blood cells allows volume stability to be achieved with extraordinary cost-efficiency, favouring cell longevity over cell turnover. We suggest a mechanism by which the interplay of a declining sodium pump and two passive membrane transporters, the mechanosensitive PIEZO1 channel, a candidate mediator of P sickle in sickle cells, and the Ca 2+ -sensitive, K + -selective Gardos channel, can implement red blood cell volume stability around the optimal-volume-ratio range, as required for extended circulatory longevity.

On the Mechanism of Human Red Blood Cell Longevity: Roles of Calcium, the Sodium Pump, PIEZO1, and Gardos Channels

PubMed Central

Lew, Virgilio L.; Tiffert, Teresa

2017-01-01

In a healthy adult, the transport of O2 and CO2 between lungs and tissues is performed by about 2 · 1013 red blood cells, of which around 1.7 · 1011 are renewed every day, a turnover resulting from an average circulatory lifespan of about 120 days. Cellular lifespan is the result of an evolutionary balance between the energy costs of maintaining cells in a fit functional state versus cell renewal. In this Review we examine how the set of passive and active membrane transporters of the mature red blood cells interact to maximize their circulatory longevity thus minimizing costs on expensive cell turnover. Red blood cell deformability is critical for optimal rheology and gas exchange functionality during capillary flow, best fulfilled when the volume of each human red blood cell is kept at a fraction of about 0.55–0.60 of the maximal spherical volume allowed by its membrane area, the optimal-volume-ratio range. The extent to which red blood cell volumes can be preserved within or near these narrow optimal-volume-ratio margins determines the potential for circulatory longevity. We show that the low cation permeability of red blood cells allows volume stability to be achieved with extraordinary cost-efficiency, favouring cell longevity over cell turnover. We suggest a mechanism by which the interplay of a declining sodium pump and two passive membrane transporters, the mechanosensitive PIEZO1 channel, a candidate mediator of Psickle in sickle cells, and the Ca2+-sensitive, K+-selective Gardos channel, can implement red blood cell volume stability around the optimal-volume-ratio range, as required for extended circulatory longevity. PMID:29311949

21 CFR 864.6400 - Hematocrit measuring device.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., racks, and a sealer and a holder. The device is used to measure the packed red cell volume in blood to determine whether the patient's total red cell volume is normal or abnormal. Abnormal states include anemia...). The packed red cell volume is produced by centrifuging a given volume of blood. (b) Classification...

21 CFR 864.6400 - Hematocrit measuring device.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., racks, and a sealer and a holder. The device is used to measure the packed red cell volume in blood to determine whether the patient's total red cell volume is normal or abnormal. Abnormal states include anemia...). The packed red cell volume is produced by centrifuging a given volume of blood. (b) Classification...

21 CFR 864.6400 - Hematocrit measuring device.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., racks, and a sealer and a holder. The device is used to measure the packed red cell volume in blood to determine whether the patient's total red cell volume is normal or abnormal. Abnormal states include anemia...). The packed red cell volume is produced by centrifuging a given volume of blood. (b) Classification...

21 CFR 864.6400 - Hematocrit measuring device.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., racks, and a sealer and a holder. The device is used to measure the packed red cell volume in blood to determine whether the patient's total red cell volume is normal or abnormal. Abnormal states include anemia...). The packed red cell volume is produced by centrifuging a given volume of blood. (b) Classification...

21 CFR 864.6400 - Hematocrit measuring device.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., racks, and a sealer and a holder. The device is used to measure the packed red cell volume in blood to determine whether the patient's total red cell volume is normal or abnormal. Abnormal states include anemia...). The packed red cell volume is produced by centrifuging a given volume of blood. (b) Classification...

Comparative Evaluation of Cutting Methods of Activated Concrete from Nuclear Power Plant Decommissioning - 13548

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

Kim, HakSoo; Chung, SungHwan; Maeng, SungJun

2013-07-01

The amount of radioactive wastes from decommissioning of a nuclear power plant varies greatly depending on factors such as type and size of the plant, operation history, decommissioning options, and waste treatment and volume reduction methods. There are many methods to decrease the amount of decommissioning radioactive wastes including minimization of waste generation, waste reclassification through decontamination and cutting methods to remove the contaminated areas. According to OECD/NEA, it is known that the radioactive waste treatment and disposal cost accounts for about 40 percentage of the total decommissioning cost. In Korea, it is needed to reduce amount of decommissioning radioactivemore » waste due to high disposal cost, about $7,000 (as of 2010) per a 200 liter drum for the low- and intermediate-level radioactive waste (LILW). In this paper, cutting methods to minimize the radioactive waste of activated concrete were investigated and associated decommissioning cost impact was assessed. The cutting methods considered are cylindrical and volume reductive cuttings. The study showed that the volume reductive cutting is more cost-effective than the cylindrical cutting. Therefore, the volume reductive cutting method can be effectively applied to the activated bio-shield concrete. (authors)« less

Lung volume reduction for emphysema.

PubMed

Shah, Pallav L; Herth, Felix J; van Geffen, Wouter H; Deslee, Gaetan; Slebos, Dirk-Jan

2017-02-01

Advanced emphysema is a lung disease in which alveolar capillary units are destroyed and supporting tissue is lost. The combined effect of reduced gas exchange and changes in airway dynamics impairs expiratory airflow and leads to progressive air trapping. Pharmacological therapies have limited effects. Surgical resection of the most destroyed sections of the lung can improve pulmonary function and exercise capacity but its benefit is tempered by significant morbidity. This issue stimulated a search for novel approaches to lung volume reduction. Alternative minimally invasive approaches using bronchoscopic techniques including valves, coils, vapour thermal ablation, and sclerosant agents have been at the forefront of these developments. Insertion of endobronchial valves in selected patients could have benefits that are comparable with lung volume reduction surgery. Endobronchial coils might have a role in the treatment of patients with emphysema with severe hyperinflation and less parenchymal destruction. Use of vapour thermal energy or a sclerosant might allow focal treatment but the unpredictability of the inflammatory response limits their current use. In this Review, we aim to summarise clinical trial evidence on lung volume reduction and provide guidance on patient selection for available therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heteromeric Slick/Slack K+ channels show graded sensitivity to cell volume changes

PubMed Central

Hashem, Nadia; Calloe, Kirstine; Klaerke, Dan A.

2017-01-01

Slick and Slack high-conductance K+ channels are found in the CNS, kidneys, pancreas, among other organs, where they play an important role in cell excitability as well as in ion transport processes. They are both activated by Na+ and Cl- but show a differential regulation by cell volume changes. Slick has been shown to be regulated by cell volume changes, whereas Slack is insensitive. α-subunits of these channels form homomeric as well as heteromeric channels. It is the aim of this work to explore whether the subunit composition of the Slick/Slack heteromeric channel affects the response to osmotic challenges. In order to provide with the adequate water permeability to the cell membrane of Xenopus laevis oocytes, mRNA of aquaporin 1 was co-expressed with homomeric or heteromeric Slick and Slack α-subunits. Oocytes were superfused with hypotonic or hypertonic buffers and changes in currents were measured by two-electrode voltage clamp. This work presents the first heteromeric K+ channel with a characteristic graded sensitivity to small and fast changes in cell volume. Our results show that the cell volume sensitivity of Slick/Slack heteromeric channels is dependent on the number of volume sensitive Slick α-subunits in the tetrameric channels, giving rise to graded cell volume sensitivity. Regulation of the subunit composition of a channel may constitute a novel mechanism to determine volume sensitivity of cells. PMID:28222129

Heteromeric Slick/Slack K+ channels show graded sensitivity to cell volume changes.

PubMed

Tejada, Maria A; Hashem, Nadia; Calloe, Kirstine; Klaerke, Dan A

2017-01-01

Slick and Slack high-conductance K+ channels are found in the CNS, kidneys, pancreas, among other organs, where they play an important role in cell excitability as well as in ion transport processes. They are both activated by Na+ and Cl- but show a differential regulation by cell volume changes. Slick has been shown to be regulated by cell volume changes, whereas Slack is insensitive. α-subunits of these channels form homomeric as well as heteromeric channels. It is the aim of this work to explore whether the subunit composition of the Slick/Slack heteromeric channel affects the response to osmotic challenges. In order to provide with the adequate water permeability to the cell membrane of Xenopus laevis oocytes, mRNA of aquaporin 1 was co-expressed with homomeric or heteromeric Slick and Slack α-subunits. Oocytes were superfused with hypotonic or hypertonic buffers and changes in currents were measured by two-electrode voltage clamp. This work presents the first heteromeric K+ channel with a characteristic graded sensitivity to small and fast changes in cell volume. Our results show that the cell volume sensitivity of Slick/Slack heteromeric channels is dependent on the number of volume sensitive Slick α-subunits in the tetrameric channels, giving rise to graded cell volume sensitivity. Regulation of the subunit composition of a channel may constitute a novel mechanism to determine volume sensitivity of cells.

Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

PubMed Central

Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

2017-01-01

Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and recorded, and at the end of experiments, tumor xenografts were removed for Western blot and immunohistochemical analyses. Compared to control groups (negative control, regular-dose icotinib [IcoR], high-dose icotinib [IcoH], and docetaxel [DTX]) and regular icotinib dose (60 mg/kg) with docetaxel, treatment of mice with a high-dose (1200 mg/kg) of icotinib plus sequential docetaxel for 3 weeks (IcoH-DTX) had an additive effect on suppression of tumor xenograft size and volume (P < 0.05). Icotinib-containing treatments markedly reduced phosphorylation of EGFR, mitogen activated protein kinase (MAPK), and protein kinase B (Akt), but only the high-dose icotinib-containing treatments showed an additive effect on CD34 inhibition (P < 0.05), an indication of reduced microvessel density in tumor xenografts. Moreover, high-dose icotinib plus docetaxel had a similar effect on mouse weight loss (a common way to measure adverse reactions in mice), compared to the other treatment combinations. The study indicate that the high dose of icotinib plus sequential docetaxel (IcoH-DTX) have an additive effect on suppressing the growth of wild-type EGFR NSCLC cell nude mouse xenografts, possibly through microvessel density reduction. Future clinical trials are needed to confirm the findings of this study. PMID:27852073

Pilot scale nanofiltration treatment of olive mill wastewater: a technical and economical evaluation.

PubMed

Sanches, S; Fraga, M C; Silva, N A; Nunes, P; Crespo, J G; Pereira, V J

2017-02-01

The treatment of large volumes of olive mill wastewater is presently a challenge. This study reports the technical and economical feasibility of a sequential treatment of olive mill wastewater comprising a dissolved air flotation pre-treatment and nanofiltration. Different pilot nanofiltration assays were conducted in a concentration mode up to different volume reduction factors (29, 45, 58, and 81). Data attained demonstrated that nanofiltration can be operated at considerably high volume reduction factors and still be effective towards the removal of several components. A flux decline of approximately 50% was observed at the highest volume reduction factor, mainly due to increase of the osmotic pressure. Considerably high rejections were obtained across all experiments for total suspended solids (83 to >99%), total organic carbon (64 to 99%), chemical oxygen demand (53 to 77%), and oil and grease (67 to >82%). Treated water was in compliance with European legal limits for discharge regarding total suspended solids and oil and grease. The potential recovery of phenolic compounds was evaluated and found not relevant. It was demonstrated that nanofiltration is economically feasible, involving operation costs of approximately 2.56-3.08 €/m 3 , depending on the working plan schedule and volume reduction factor, and requiring a footprint of approximately 52 m 2 to treat 1000 m 3 of olive mill wastewater.

Techno-economic analysis of three different substrate removal and reuse strategies for III-V solar cells: Techno-economic analysis for III-V solar cells

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

Ward, J. Scott; Remo, Timothy; Horowitz, Kelsey

The high cost of wafers suitable for epitaxial deposition of III-V solar cells has been a primary barrier to widespread use of these cells in low-concentration and one-sun terrestrial solar applications. A possible solution is to reuse the substrate many times, thus spreading its cost across many cells. We performed a bottom-up techno-economic analysis of three different strategies for substrate reuse in high-volume manufacturing: epitaxial lift-off, spalling, and the use of a porous germanium release layer. The analysis shows that the potential cost reduction resulting from substrate reuse is limited in all three strategies--not by the number of reuse cyclesmore » achievable, but by the costs that are incurred in each cycle to prepare the substrate for another epitaxial deposition. The dominant substrate-preparation cost component is different for each of the three strategies, and the cost-ranking of these strategies is subject to change if future developments substantially reduce the cost of epitaxial deposition.« less

Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

PubMed Central

Wang, Li-li; Miller, Dori; Wanders, Desiree; Nanayakkara, Gayani; Amin, Rajesh; Judd, Robert; Morrison, Edward E; Zhong, Ju-ming

2016-01-01

Aim: Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods: Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously administered adenoviral adiponectin at 2-, 6- and 9-weeks following fistula. The protein expression of adiponectin, adiponectin receptors (AdipoR1/R2 and T-cadherin) and AMPK activity were measured using Western blot analyses. Isolated ventricular myocytes were prepared at 12 weeks post-fistula to examine the contractile performance of myocytes and intracellular Ca2+ transient. Results: A-V fistula resulted in significant reductions in serum and myocardial adiponectin levels, myocardial adiponectin receptor (AdipoR1/R2 and T-cadherin) levels, as well as myocardial AMPK activity. Consistent with these changes, the isolated myocytes exhibited significant depression in cell shortening and intracellular Ca2+ transient. Administration of adenoviral adiponectin significantly increased serum adiponectin levels and prevented myocyte contractile dysfunction in fistula rats. Furthermore, pretreatment of isolated myocytes with recombinant adiponectin (2.5 μg/mL) significantly improved their contractile performance in fistula rats, but had no effects in control or adenoviral adiponectin-administered rats. Conclusion: These results demonstrate a positive correlation between adiponectin downregulation and volume overload-induced ventricular remodeling. Adiponectin plays a protective role in volume overload-induced heart failure. PMID:26616727

A double-blind, placebo-controlled trial of epsilon-aminocaproic acid for reducing blood loss in coronary artery bypass grafting surgery.

PubMed

Kikura, Mutsuhito; Levy, Jerrold H; Tanaka, Kenichi A; Ramsay, James G

2006-02-01

Epsilon-aminocaproic acid is a plasmin inhibitor that potentially reduces perioperative bleeding when administered prophylactically to cardiac surgery patients. To evaluate the efficacy of epsilon-aminocaproic acid, a prospective placebo-controlled trial was conducted in patients undergoing primary coronary artery bypass grafting surgery. One hundred patients were randomly assigned to receive either epsilon-aminocaproic acid (100 mg/kg before skin incision followed by 1 g/hour continuous infusion until chest closure, 10 g in cardiopulmonary bypass circuit) or placebo, and the efficacy of epsilon-aminocaproic acid was evaluated by the reduction in postoperative thoracic-drainage volume and in donor-blood transfusion up to postoperative day 12. Postoperative thoracic-drainage volume was significantly lower in the epsilon-aminocaproic acid group compared with the placebo group (epsilon-aminocaproic acid, 649 +/- 261 mL; versus placebo, 940 +/- 626 mL; p=0.003). There were no significant differences between the epsilon-aminocaproic acid and placebo groups in the percentage of patients requiring donor red blood cell transfusions (epsilon-aminocaproic acid, 24%; versus placebo, 18%; p=0.62) or in the number of units of donor red blood cells transfused (epsilon-aminocaproic acid, 2.2 +/- 0.8 U; versus placebo, 1.9 +/- 0.8 U; p=0.29). Epsilon-aminocaproic acid did not reduce the risk of donor red blood cell transfusions compared with placebo (odds ratio: 1.2, 95% confidence interval; 0.4 to 3.2, p=0.63). Prophylactic administration of epsilon-aminocaproic acid reduces postoperative thoracic-drainage volume by 30%, but it may not be potent enough to reduce the requirement and the risk for donor blood transfusion in cardiac surgery patients. This information is useful for deciding on a therapy for hemostasis in cardiac surgery.

The cooling time of fertile chicken eggs at different stages of incubation.

PubMed

Mortola, Jacopo P; Gaonac'h-Lovejoy, Vanda

2016-01-01

We asked whether or not the thermal characteristics of fertile avian eggs changed throughout incubation. The cooling and warming times, expressed by the time constant τ of the egg temperature response to a rapid change in ambient temperature, were measured in fertile chicken eggs at early (E7), intermediate (E11) and late (E20) stages of embryonic development. Same measurements were conducted on eggs emptied of their content and refilled with water by various amounts. The results indicated that (1) the τ of a freshly laid egg was ~50 min; (2) τ decreased linearly with the drop in egg water volume; (3) the dry eggshell had almost no thermal resistance but its wet inner membrane contributed about one-third to the stability of egg temperature; (4) the egg constituents (yolk, albumen and embryonic tissues) and the chorioallantoic circulation had no measurable effect on τ; (5) the presence of an air pocket equivalent in volume to the air cell of fertile eggs reduced τ by about 3 min (E7), 5 min (E11) and 11 min (E20). Hence, in response to warming the egg τ at E20 was slightly shorter than at E7. In response to cooling, the egg τ at E20 was similar to, or longer than, E7 because embryonic thermogenesis (evaluated by measurements of oxygen consumption during cold) offset the reduction in τ introduced by the air cell. In conclusion, until the onset of thermogenesis the thermal behavior of a fertile egg is closely approximated by that of a water-filled egg with an air volume equivalent to the air cell. It is possible to estimate the cooling τ of avian eggs of different species from their weight and incubation time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Measurement of In Vivo Three-Dimensional Corneal Cell Density and Size Using Two-Photon Imaging in C57BL/6 Mice.

PubMed

Zhang, Hongmin; He, Siyu; Liu, Susu; Xie, Yanting; Chen, Guoming; Zhang, Junjie; Sun, Shengtao; Liang, David; Wang, Liya

2016-04-01

To measure the cell size and cell density in five layers of the central cornea in the widely used inbred C57BL/6 mouse strain using in vivo three-dimensional (3D) two-photon (2PH) imaging. Corneas were scanned using a 2PH laser scanning fluorescence microscope after staining with plasma membrane stain and Hoechst 33342. Good quality 3D images were selected for the cell density and cell size analysis. Cell density was determined by counting the cell nuclei in a predefined cube of 3D images. Cell size measurements, including cell surface area, cell volume, nuclear surface area and nuclear volume, were automatically quantified using the Imaris software. The cell and nuclear surface-area-to-volume ratio (S:V ratio) and the cell nuclear-cytoplasmic ratio (N:C ratio) were calculated. The highest cell density was observed in the basal epithelium and the lowest in the posterior stroma. The highest cell surface area was found in the anterior stroma, and the highest cell volume was observed in the superficial epithelium. The lowest cell surface area and cell volume were both found in the basal epithelium. The highest S:V ratio was observed in the basal epithelium and the lowest in the superficial epithelium. The highest cell nuclear surface area and volume were both observed in the superficial epithelium and the lowest in the basal epithelium. The highest cell nuclear S:V ratio was observed in the basal epithelium and the lowest in the superficial epithelium. The highest N:C ratio was found in the basal epithelial cells and the lowest in the posterior keratocytes. We are the first to quantify the cell density and size parameters, including cell surface area and volume, cell nuclear surface area and volume, and the S:V ratio, in the five layers of the central cornea. These data provide important cell morphology features for the study of corneal physiology, pathology and disease in mice, particularly in C57BL/6 mice.

Cell volume changes regulate slick (Slo2.1), but not slack (Slo2.2) K+ channels.

PubMed

Tejada, Maria A; Stople, Kathleen; Hammami Bomholtz, Sofia; Meinild, Anne-Kristine; Poulsen, Asser Nyander; Klaerke, Dan A

2014-01-01

Slick (Slo2.1) and Slack (Slo2.2) channels belong to the family of high-conductance K+ channels and have been found widely distributed in the CNS. Both channels are activated by Na+ and Cl- and, in addition, Slick channels are regulated by ATP. Therefore, the roles of these channels in regulation of cell excitability as well as ion transport processes, like regulation of cell volume, have been hypothesized. It is the aim of this work to evaluate the sensitivity of Slick and Slack channels to small, fast changes in cell volume and to explore mechanisms, which may explain this type of regulation. For this purpose Slick and Slack channels were co-expressed with aquaporin 1 in Xenopus laevis oocytes and cell volume changes of around 5% were induced by exposure to hypotonic or hypertonic media. Whole-cell currents were measured by two electrode voltage clamp. Our results show that Slick channels are dramatically stimulated (196% of control) by cell swelling and inhibited (57% of control) by a decrease in cell volume. In contrast, Slack channels are totally insensitive to similar cell volume changes. The mechanism underlining the strong volume sensitivity of Slick channels needs to be further explored, however we were able to show that it does not depend on an intact actin cytoskeleton, ATP release or vesicle fusion. In conclusion, Slick channels, in contrast to the similar Slack channels, are the only high-conductance K+ channels strongly sensitive to small changes in cell volume.

Morphometric analysis of the placenta in the New World mouse Necromys lasiurus (Rodentia, Cricetidae): a comparison of placental development in cricetids and murids

PubMed Central

2013-01-01

Background Stereology is an established method to extrapolate three-dimensional quantities from two-dimensional images. It was applied to placentation in the mouse, but not yet for other rodents. Herein, we provide the first study on quantitative placental development in a sigmodontine rodent species with relatively similar gestational time. Placental structure was also compared to the mouse, in order to evaluate similarities and differences in developmental patterns at the end of gestation. Methods Fetal and placental tissues of Necromys lasiurus were collected and weighed at 3 different stages of gestation (early, mid and late gestation) for placental stereology. The total and relative volumes of placenta and of its main layers were investigated. Volume fractions of labyrinth components were quantified by the One Stop method in 31 placentae collected from different individuals, using the Mercator® software. Data generated at the end of gestation from N. lasiurus placentae were compared to those of Mus musculus domesticus obtained at the same stage. Results A significant increase in the total absolute volumes of the placenta and its main layers occurred from early to mid-gestation, followed by a reduction near term, with the labyrinth layer becoming the most prominent area. Moreover, at the end of gestation, the total volume of the mouse placenta was significantly increased compared to that of N. lasiurus although the proportions of the labyrinth layer and junctional zones were similar. Analysis of the volume fractions of the components in the labyrinth indicated a significant increase in fetal vessels and sinusoidal giant cells, a decrease in labyrinthine trophoblast whereas the proportion of maternal blood space remained stable in the course of gestation. On the other hand, in the mouse, volume fractions of fetal vessels and sinusoidal giant cells decreased whereas the volume fraction of labyrinthine trophoblast increased compared to N. lasiurus placenta. Conclusions Placental development differed between N. lasiurus and M. musculus domesticus. In particular, the low placental efficiency in N. lasiurus seemed to induce morphological optimization of fetomaternal exchanges. In conclusion, despite similar structural aspects of placentation in these species, the quantitative dynamics showed important differences. PMID:23433040

Evaluation of trichloroethene recovery processes in heterogeneous aquifer cells flushed with biodegradable surfactants

NASA Astrophysics Data System (ADS)

Suchomel, Eric J.; Ramsburg, C. Andrew; Pennell, Kurt D.

2007-12-01

The ability of two biodegradable surfactants, polyoxyethylene (20) sorbitan monooleate (Tween® 80) and sodium dihexyl sulfosuccinate (Aerosol® MA), to recover a representative dense non-aqueous-phase liquid (DNAPL), trichloroethene (TCE), from heterogeneous porous media was evaluated through a combination of batch and aquifer cell experiments. An aqueous solution containing 3.3% Aerosol MA, 8% 2-propanol and 6 g/l CaCl 2 yielded a weight solubilization ratio (WSR) of 1.21 g TCE/g surfactant, with a corresponding liquid-liquid interfacial tension (IFT) of 0.19 dyn/cm. Flushing of aquifer cells containing a TCE-DNAPL source zone with approximately two pore volumes of the AMA formulation resulted in substantial (> 30%) mobilization of TCE-DNAPL. However, a TCE mass recovery of 81% was achieved when the aqueous-phase flow rate was sufficient to displace the mobile TCE-DNAPL toward the effluent well. Aqueous solutions of Tween 80 exhibited a greater capacity to solubilize TCE (WSR = 1.74 g TCE/g surfactant) and exerted markedly less reduction in IFT (10.4 dyn/cm). These data contradict an accepted empirical correlation used to estimate IFT values from solubilization capacity, and indicate a unique capacity of T80 to form concentrated TCE emulsions. Flushing of aquifer cells with less than 2.5 pore volumes of a 4% T80 solution achieved TCE mass recoveries ranging from 66 to 85%, with only slight TCE-DNAPL mobilization (< 5%) occurring when the total trapping number exceeded 2 × 10 - 5 . These findings demonstrate the ability of Tween 80 and Aerosol MA solutions to efficiently recover TCE from a heterogeneous DNAPL source zone, and the utility of the total trapping number as a design parameter for a priori prediction of DNAPL mobilization and bank angle formation when flushing with low-IFT solutions. Given their potential to stimulate microbial reductive dechlorination at low concentrations, these surfactants are well-suited for remedial action plans that couple aggressive mass removal followed by enhanced bioremediation to treat chlorinated solvent source zones.

The coordination of ploidy and cell size differs between cell layers in leaves

PubMed Central

Katagiri, Yohei; Hasegawa, Junko; Fujikura, Ushio; Hoshino, Rina; Matsunaga, Sachihiro; Tsukaya, Hirokazu

2016-01-01

Growth and developmental processes are occasionally accompanied by multiple rounds of DNA replication, known as endoreduplication. Coordination between endoreduplication and cell size regulation often plays a crucial role in proper organogenesis and cell differentiation. Here, we report that the level of correlation between ploidy and cell volume is different in the outer and inner cell layers of leaves of Arabidopsis thaliana using a novel imaging technique. Although there is a well-known, strong correlation between ploidy and cell volume in pavement cells of the epidermis, this correlation was extremely weak in palisade mesophyll cells. Induction of epidermis cell identity based on the expression of the homeobox gene ATML1 in mesophyll cells enhanced the level of correlation between ploidy and cell volume to near that of wild-type epidermal cells. We therefore propose that the correlation between ploidy and cell volume is regulated by cell identity. PMID:26903507

SU-E-T-427: Cell Surviving Fractions Derived From Tumor-Volume Variation During Radiotherapy for Non-Small Cell Lung Cancer: Comparison with Predictive Assays

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

Chvetsov, A; Schwartz, J; Mayr, N

2014-06-01

Purpose: To show that a distribution of cell surviving fractions S{sub 2} in a heterogeneous group of patients can be derived from tumor-volume variation curves during radiotherapy for non-small cell lung cancer. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage (MV) computed tomography (CT). Statistical distributions of cell surviving fractions S{sup 2} and cell clearance half-lives of lethally damaged cells T1/2 have been reconstructed in eachmore » patient group by using a version of the two-level cell population tumor response model and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Non-small cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S{sub 2} for non-small cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sup 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Comparison of the reconstructed cell surviving fractions with patient survival data shows that the patient survival time decreases as the cell surviving fraction increases. Conclusion: The data obtained in this work suggests that the cell surviving fractions S{sub 2} can be reconstructed from the tumor volume variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.« less

Maintenance of parenteral nutrition volume reduction, without weight loss, after stopping teduglutide in a subset of patients with short bowel syndrome.

PubMed

Compher, Charlene; Gilroy, Richard; Pertkiewicz, Marek; Ziegler, Thomas R; Ratcliffe, Sarah J; Joly, Francisca; Rochling, Fedja; Messing, Bernard

2011-09-01

Teduglutide was discontinued after being tested for ≥ 24 weeks in patients with parenteral nutrition (PN) -dependent short bowel syndrome in a clinical trial for efficacy to reduce PN volume. This study was describes change in body mass index (BMI) and PN volume over 12 months in patients who stopped drug after the clinical trial. Prescribed PN volume, weight, and complications were reported. Patients with stable (NEUT, n = 15) or decreased (DEC, n = 7) PN volume by 12 months after stopping drug (NEUT/DEC, n = 22) were compared to those who had increased PN volume (INC, n = 15). With drug response defined by ≥ 20% reduction from pre-drug PN volume to end of drug therapy, 12 INC and 13 NEUT/DEC patients were drug responders. Eleven of 20 eligible sites reported data for 39 of 53 eligible study participants, with follow-up data for 37. INC patients had shorter colon and less frequently had colon in continuity than NEUT/DEC. BMI was decreased at 3, 6, and 12 months relative to the first off-drug visit in INC patients (P = .001), but not in NEUT/DEC patients. Change in BMI off-drug was predicted by colon and small bowel length, baseline BMI, and on-drug change in PN volume (adjusted R2 = 0.708). Gastrointestinal anatomy, baseline BMI, and PN volume reduction on-drug predicted change in BMI off-drug. Whether this response would be maintained for a longer time or in the context of a challenging clinical situation has not been evaluated.

[Intraarterial chemotherapy for uterine cervical adenocarcinoma: evaluation of its efficacy as neoadjuvant therapy].

PubMed

Usuki, N; Hirokawa, K; Tashiro, T; Saiwai, S; Miyamoto, T

1999-10-01

We performed preoperative intraarterial chemotherapy in twenty cases of uterine cervical adenocarcinoma (stage Ib: 2, II: 15, III: 3) and evaluated the efficacy of this therapy. The dosages used were 75-120 mg of CDDP, 10-20 mg of MMC and 30-60 mg of EPIR. These drugs were administered by intraarterial one-shot infusion twice every three weeks. In five cases, complete response (CR) of the primary lesion was confirmed by histologic examination. There were no cases of CR inpatients with well differentiated adenocarcinoma. Stage reduction was achieved in all cases except three. In all but one case, more than 50% volume reduction was recognized on MR images. These results were not significantly different from those in cases of uterine cervical squamous cell carcinoma in which we performed this therapy. Therefore, we concluded that intraarterial chemotherapy is highly effective and should be carried out as neoadjuvant therapy for advanced uterine cervical adenocarcinoma.

Polybenzimidazole (PBI) functionalized nanographene as highly stable catalyst support for polymer Electrolyte membrane fuel cells (PEMFCs)

DOE PAGES

Xin, Le; Yang, Fan; Qiu, Yang; ...

2016-08-25

Nanoscale graphenes were used as cathode catalyst supports in proton exchange membrane fuel cells (PEMFCs). Surface-initiated polymerization that covalently bonds polybenzimidazole (PBI) polymer on the surface of graphene supports enables the uniform distribution of the Pt nanoparticles, as well as allows the sealing of the unterminated carbon bonds usually present on the edge of graphene from the chemical reduction of graphene oxide. The nanographene effectively shortens the length of channels and pores for O 2 diffusion/water dissipation and significantly increases the primary pore volume. Further addition of p-phenyl sulfonic functional graphitic carbon particles as spacers, increases the specific volume ofmore » the secondary pores and greatly improves O 2 mass transport within the catalyst layers. The developed composite cathode catalyst of Pt/PBI-nanographene (50 wt%) + SO 3H-graphitic carbon black demonstrates a higher beginning of life (BOL) PEMFC performance as compared to both Pt/PBI-nanographene (50 wt%) and Pt/PBI-graphene (50 wt%) + SO 3H-graphitic carbon black (GCB). Accelerated stress tests show excellent support durability compared to that of traditional Pt/Vulcan XC72 catalysts, when subjected to 10,000 cycles from 1.0 V to 1.5 V. As a result, this study suggests the promise of using PBI-nanographene + SO 3H-GCB hybrid supports in fuel cells to achieve the 2020 DOE targets for transportation applications.« less

Photoimmunotherapy of Gastric Cancer Peritoneal Carcinomatosis in a Mouse Model

PubMed Central

Sato, Kazuhide; Choyke, Peter L.; Kobayashi, Hisataka

2014-01-01

Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. We performed PIT in a model of disseminated gastric cancer peritoneal carcinomatosis and monitored efficacy with in vivo GFP fluorescence imaging. In vitro and in vivo experiments were conducted with a HER2-expressing, GFP-expressing, gastric cancer cell line (N87-GFP). A conjugate comprised of a photosensitizer, IR-700, conjugated to trastuzumab (tra-IR700), followed by NIR light was used for PIT. In vitro PIT was evaluated by measuring cytotoxicity with dead staining and a decrease in GFP fluorescence. In vivo PIT was evaluated in a disseminated peritoneal carcinomatosis model and a flank xenograft using tumor volume measurements and GFP fluorescence intensity. In vivo anti-tumor effects of PIT were confirmed by significant reductions in tumor volume (at day 15, p<0.0001 vs. control) and GFP fluorescence intensity (flank model: at day 3, PIT treated vs. control p<0.01 and peritoneal disseminated model: at day 3 PIT treated vs. control, p<0.05). Cytotoxic effects in vitro were shown to be dependent on the light dose and caused necrotic cell rupture leading to GFP release and a decrease in fluorescence intensity in vitro. Thus, loss of GFP fluorescence served as a useful biomarker of cell necrosis after PIT. PMID:25401794

Plumbing the depths: extracellular water storage in specialized leaf structures and its functional expression in a three-domain pressure -volume relationship.

PubMed

Nguyen, Hoa T; Meir, Patrick; Wolfe, Joe; Mencuccini, Maurizio; Ball, Marilyn C

2017-07-01

A three-domain pressure-volume relationship (PV curve) was studied in relation to leaf anatomical structure during dehydration in the grey mangrove, Avicennia marina. In domain 1, relative water content (RWC) declined 13% with 0.85 MPa decrease in leaf water potential, reflecting a decrease in extracellular water stored primarily in trichomes and petiolar cisternae. In domain 2, RWC decreased by another 12% with a further reduction in leaf water potential to -5.1 MPa, the turgor loss point. Given the osmotic potential at full turgor (-4.2 MPa) and the effective modulus of elasticity (~40 MPa), domain 2 emphasized the role of cell wall elasticity in conserving cellular hydration during leaf water loss. Domain 3 was dominated by osmotic effects and characterized by plasmolysis in most tissues and cell types without cell wall collapse. Extracellular and cellular water storage could support an evaporation rate of 1 mmol m -2 s -1 for up to 54 and 50 min, respectively, before turgor loss was reached. This study emphasized the importance of leaf anatomy for the interpretation of PV curves, and identified extracellular water storage sites that enable transient water use without substantive turgor loss when other factors, such as high soil salinity, constrain rates of water transport. © 2016 John Wiley & Sons Ltd.

Mixed Neurodevelopmental and Neurodegenerative Pathology in Nhe6-Null Mouse Model of Christianson Syndrome

PubMed Central

Xu, Meiyu; Ouyang, Qing; Gong, Jingyi; Pescosolido, Matthew F.; Mishra, Sasmita; Schmidt, Michael; Jones, Richard N.; Gamsiz Uzun, Ece D.; Lizarraga, Sofia B.

2017-01-01

Abstract Christianson syndrome (CS) is an X-linked disorder resulting from loss-of-function mutations in SLC9A6, which encodes the endosomal Na+/H+ exchanger 6 (NHE6). Symptoms include early developmental delay, seizures, intellectual disability, nonverbal status, autistic features, postnatal microcephaly, and progressive ataxia. Neuronal development is impaired in CS, involving defects in neuronal arborization and synaptogenesis, likely underlying diminished brain growth postnatally. In addition to neurodevelopmental defects, some reports have supported neurodegenerative pathology in CS with age. The objective of this study was to determine the nature of progressive changes in the postnatal brain in Nhe6-null mice. We examined the trajectories of brain growth and atrophy in mutant mice from birth until very old age (2 yr). We report trajectories of volume changes in the mutant that likely reflect both brain undergrowth as well as tissue loss. Reductions in volume are first apparent at 2 mo, particularly in the cerebellum, which demonstrates progressive loss of Purkinje cells (PCs). We report PC loss in two distinct Nhe6-null mouse models. More widespread reductions in tissue volumes, namely, in the hippocampus, striatum, and cortex, become apparent after 2 mo, largely reflecting delays in growth with more limited tissue losses with aging. Also, we identify pronounced glial responses, particularly in major fiber tracts such as the corpus callosum, where the density of activated astrocytes and microglia are substantially increased. The prominence of the glial response in axonal tracts suggests a primary axonopathy. Importantly, therefore, our data support both neurodevelopmental and degenerative mechanisms in the pathobiology of CS. PMID:29349289

Multiple White Matter Volume Reductions in Patients with Panic Disorder: Relationships between Orbitofrontal Gyrus Volume and Symptom Severity and Social Dysfunction

PubMed Central

Konishi, Jun; Asami, Takeshi; Hayano, Fumi; Yoshimi, Asuka; Hayasaka, Shunsuke; Fukushima, Hiroshi; Whitford, Thomas J.; Inoue, Tomio; Hirayasu, Yoshio

2014-01-01

Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p<0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD. PMID:24663245

Long-Term Occupational Stress Is Associated with Regional Reductions in Brain Tissue Volumes

PubMed Central

Blix, Eva; Perski, Aleksander; Berglund, Hans; Savic, Ivanka

2013-01-01

There are increasing reports of cognitive and psychological declines related to occupational stress in subjects without psychiatric premorbidity or major life trauma. The underlying neurobiology is unknown, and many question the notion that the described disabilities represent a medical condition. Using PET we recently found that persons suffering from chronic occupational stress had limbic reductions in the 5-HT1A receptor binding potential. Here we examine whether chronic work-related stress is also associated with changes in brain structure. We performed MRI-based voxel-based morphometry and structural volumetry in stressed subjects and unstressed controls focusing on gray (GM) and white matter (WM) volumes, and the volumes of hippocampus, caudate, and putamen – structures known to be susceptible to neurotoxic changes. Stressed subjects exhibited significant reductions in the GM volumes of the anterior cingulate cortex and the dorsolateral prefrontal cortex. Furthermore, their caudate and putamen volumes were reduced, and the volumes correlated inversely to the degree of perceived stress. Our results add to previous data on chronic psychosocial stress, and indicate a morphological involvement of the frontostriatal circuits. The present findings of morphological changes in these regions confirm our previous conclusion that symptoms from occupational stress merit careful investigations and targeted treatment. PMID:23776438

Antisense oligonucleotides suppress cell-volume-induced activation of chloride channels.

PubMed

Gschwentner, M; Nagl, U O; Wöll, E; Schmarda, A; Ritter, M; Paulmichl, M

1995-08-01

Cell volume regulation is an essential feature of most cells. After swelling in hypotonic media, the simultaneous activation of potassium and chloride channels is believed to be the initial, time-determining step in cell volume regulation. The activation of both pathways is functionally linked and enables the cells to lose ions and water, subsequently leading to cell shrinkage and readjustment of the initial volume. NIH 3T3 fibroblasts efficiently regulate their volume after swelling and bear chloride channels that are activated by decreasing extracellular osmolarity. The chloride current elicited in these cells after swelling is reminiscent of the current found in oocytes expressing an outwardly rectifying chloride current termed ICln. Introduction of antisense oligodeoxynucleotides complementary to the first 30 nucleotides of the coding region of the ICln channel into NIH 3T3 fibroblasts suppresses the activation of the swelling-induced chloride current. The experiments directly demonstrate an unambiguous link between a volume-activated chloride current and a cloned protein involved in chloride transport.

Evidence that downregulation of hexose transport limits intracellular glucose in 3T3-L1 fibroblasts

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

Whitesell, R.R.; Regen, D.M.; Pelletier, D.

1990-10-01

Measurements of initial glucose entry rate and intracellular glucose concentration in cultured cells are difficult because of rapid transport relative to intracellular volume and a substantial extracellular space from which glucose cannot be completely removed by quick exchanges of medium. In 3T3-L1 cells, we obtained good estimates of initial entry of ({sup 14}C)methylglucose and D-({sup 14}C)glucose with (1) L-({sup 3}H)glucose as an extracellular marker together with the ({sup 14}C)glucose or ({sup 14}C)methylglucose in the substrate mixture, (2) sampling times as short as 2 s, (3) ice-cold phloretin-containing medium to stop uptake and rinse away the extracellular label, and (4) nonlinearmore » regression of time courses. Methylglucose equilibrated in two phases--the first with a half-time of 1.7 s and the second with a half-time of 23 s; it eventually equilibrated in an intracellular space of 8 microliters/mg protein. Entry of glucose remained almost linear for 10 s, making its transport kinetics easier to study (Km = 5.7 mM, Vmax = 590 nmol.s-1.ml-1 cell water). Steady-state intracellular glucose concentration was 75-90% of extracellular glucose concentration. Cells grown in a high-glucose medium (24 mM) exhibited a 67% reduction of glucose-transport activity and a 50% reduction of steady-state ratio of intracellular glucose to extracellular glucose.« less

The productivity limit of manufacturing blood cell therapy in scalable stirred bioreactors

PubMed Central

Bayley, Rachel; Ahmed, Forhad; Glen, Katie; McCall, Mark; Stacey, Adrian

2017-01-01

Abstract Manufacture of red blood cells (RBCs) from progenitors has been proposed as a method to reduce reliance on donors. Such a process would need to be extremely efficient for economic viability given a relatively low value product and high (2 × 1012) cell dose. Therefore, the aim of these studies was to define the productivity of an industry standard stirred‐tank bioreactor and determine engineering limitations of commercial red blood cells production. Cord blood derived CD34+ cells were cultured under erythroid differentiation conditions in a stirred micro‐bioreactor (Ambr™). Enucleated cells of 80% purity could be created under optimal physical conditions: pH 7.5, 50% oxygen, without gas‐sparging (which damaged cells) and with mechanical agitation (which directly increased enucleation). O2 consumption was low (~5 × 10–8 μg/cell.h) theoretically enabling erythroblast densities in excess of 5 × 108/ml in commercial bioreactors and sub‐10 l/unit production volumes. The bioreactor process achieved a 24% and 42% reduction in media volume and culture time, respectively, relative to unoptimized flask processing. However, media exchange limited productivity to 1 unit of erythroblasts per 500 l of media. Systematic replacement of media constituents, as well as screening for inhibitory levels of ammonia, lactate and key cytokines did not identify a reason for this limitation. We conclude that the properties of erythroblasts are such that the conventional constraints on cell manufacturing efficiency, such as mass transfer and metabolic demand, should not prevent high intensity production; furthermore, this could be achieved in industry standard equipment. However, identification and removal of an inhibitory mediator is required to enable these economies to be realized. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd. PMID:27696710

Scanning ion conductance microscopy: a convergent high-resolution technology for multi-parametric analysis of living cardiovascular cells

PubMed Central

Miragoli, Michele; Moshkov, Alexey; Novak, Pavel; Shevchuk, Andrew; Nikolaev, Viacheslav O.; El-Hamamsy, Ismail; Potter, Claire M. F.; Wright, Peter; Kadir, S.H. Sheikh Abdul; Lyon, Alexander R.; Mitchell, Jane A.; Chester, Adrian H.; Klenerman, David; Lab, Max J.; Korchev, Yuri E.; Harding, Sian E.; Gorelik, Julia

2011-01-01

Cardiovascular diseases are complex pathologies that include alterations of various cell functions at the levels of intact tissue, single cells and subcellular signalling compartments. Conventional techniques to study these processes are extremely divergent and rely on a combination of individual methods, which usually provide spatially and temporally limited information on single parameters of interest. This review describes scanning ion conductance microscopy (SICM) as a novel versatile technique capable of simultaneously reporting various structural and functional parameters at nanometre resolution in living cardiovascular cells at the level of the whole tissue, single cells and at the subcellular level, to investigate the mechanisms of cardiovascular disease. SICM is a multimodal imaging technology that allows concurrent and dynamic analysis of membrane morphology and various functional parameters (cell volume, membrane potentials, cellular contraction, single ion-channel currents and some parameters of intracellular signalling) in intact living cardiovascular cells and tissues with nanometre resolution at different levels of organization (tissue, cellular and subcellular levels). Using this technique, we showed that at the tissue level, cell orientation in the inner and outer aortic arch distinguishes atheroprone and atheroprotected regions. At the cellular level, heart failure leads to a pronounced loss of T-tubules in cardiac myocytes accompanied by a reduction in Z-groove ratio. We also demonstrated the capability of SICM to measure the entire cell volume as an index of cellular hypertrophy. This method can be further combined with fluorescence to simultaneously measure cardiomyocyte contraction and intracellular calcium transients or to map subcellular localization of membrane receptors coupled to cyclic adenosine monophosphate production. The SICM pipette can be used for patch-clamp recordings of membrane potential and single channel currents. In conclusion, SICM provides a highly informative multimodal imaging platform for functional analysis of the mechanisms of cardiovascular diseases, which should facilitate identification of novel therapeutic strategies. PMID:21325316

The Short-Term Effect of Weight Loss Surgery on Volumetric Breast Density and Fibroglandular Volume.

PubMed

Vohra, Nasreen A; Kachare, Swapnil D; Vos, Paul; Schroeder, Bruce F; Schuth, Olga; Suttle, Dylan; Fitzgerald, Timothy L; Wong, Jan H; Verbanac, Kathryn M

2017-04-01

Obesity and breast density are both associated with an increased risk of breast cancer and are potentially modifiable. Weight loss surgery (WLS) causes a significant reduction in the amount of body fat and a decrease in breast cancer risk. The effect of WLS on breast density and its components has not been documented. Here, we analyze the impact of WLS on volumetric breast density (VBD) and on each of its components (fibroglandular volume and breast volume) by using three-dimensional methods. Fibroglandular volume, breast volume, and their ratio, the VBD, were calculated from mammograms before and after WLS by using Volpara™ automated software. For the 80 women included, average body mass index decreased from 46.0 ± 7.22 to 33.7 ± 7.06 kg/m 2 . Mammograms were performed on average 11.6 ± 9.4 months before and 10.1 ± 7 months after WLS. There was a significant reduction in average breast volume (39.4 % decrease) and average fibroglandular volume (15.5 % decrease), and thus, the average VBD increased from 5.15 to 7.87 % (p < 1 × 10 -9 ) after WLS. When stratified by menopausal status and diabetic status, VBD increased significantly in all groups but only perimenopausal and postmenopausal women and non-diabetics experienced a significant reduction in fibroglandular volume. Breast volume and fibroglandular volume decreased, and VBD increased following WLS, with the most significant change observed in postmenopausal women and non-diabetics. Further studies are warranted to determine how physical and biological alterations in breast density components after WLS may impact breast cancer risk.

[Structure of maxillary sinus mucous membrane under normal conditions and in odontogenic perforative sinusitis].

PubMed

Baĭdik, O D; Logvinov, S V; Zubarev, S G; Sysoliatin, P G; Gurin, A A

2011-01-01

Methods of light, electron microscopy and immunohistochemistry were used to study the samples of maxillary sinus (MS) mucous membrane (MM) under normal conditions and in odontogenic sinusitis. To study the normal structure, the samples were obtained at autopsy from 26 human corpses 12-24 hours after death. Electron microscopic and immunohistochemical study was performed on biopsies of grossly morphologically unchanged MS MM, obtained during the operations for retention cysts in 6 patients. MS MM in perforative sinusitis was studied using the biopsies obtained from 43 patients. The material is broken into 4 groups depending on perforative sinusitis duration. Under normal conditions, MS MM is lined with a pseudostratified columnar ciliated epithelium. Degenerative changes of ciliated epithelial cells were already detected at short time intervals after MS perforations and become apparent due to reduction of specific volume of mitochondria and, rough endoplasmic reticulum, and increase of nuclear-cytoplasmic ratio. In the globlet cells, the reduction of nuclear-cytoplasmic ratio was associated with the disturbance of the secretory product release. At time intervals exceeding 3 months, epithelium underwent metaplasia into simple cuboidal and stratified squamous keratinized, while in MS MM lamina propria, cellular infiltration was increased. CD4+ cell content in sinus MM gradually increased, while at late periods after perforation occurrence it decreased. Low CD4+ cell count within the epithelium and the absence of muromidase on the surface of MS MM was detected. With the increase of the time interval since MS perforation, the number of CD8+ and CD20+ cells in MS MM was found to increase.

The effect of in-vivo intravenous administration of sodium meglumine diatrizoate on some haematological parameters.

PubMed

Agwu, K K; Mgbor, S; Ogbu, S O I; Okeji, M

2007-01-01

To investigate the in-vivo effects of intravenous administration of sodium meglumine diatrizoate on some haematological parameters in a Nigerian population. Blood samples were collected before and one hour after intravenous injection of sodium-meglumine diatrizoate from 50 subjects undergoing intravenous urography examinations who had no history of and laboratory confirmed diseases that may affect haematological parameters. Standard laboratory methods were used to assay the haemoglobin concentration (Hb), packed cell volume (PCV), total white blood cell (WBC) count and differentials and blood film for any morphological changes in the red blood cells (RBC). Comparisons were made between the mean values of these haematological parameters before and one hour post injection using paired t-test for any statistically significant differences. There were statistically significant reductions in the mean values of Hb concentration and the neutrophil count one hour post injection compared with their pretest values (p < 0.05). The lymphocytes were also significantly increased post injection compared to the pretest values whereas 70% of the erythrocytes were morphologically altered from their approximately 100% normocytic shape at pre-test. Intravenous administration of sodium-meglumine diatrizoate causes in-vivo reduction in Hb concentration and neutrophil count in humans as well as poikilocytosis of the erythrocytes. Some of these effects have the potential of triggering or exacerbating crisis in a sickle cell anaemia subject which is endemic in our locality. Caution should therefore be exercised in the choice and administration of radiological contrast agents to sickle cell subjects. Preparations that are iso-osmolar with plasma and have less probability in precipitating crises should be preferred instead.

Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma.

PubMed

Keunen, Olivier; Johansson, Mikael; Oudin, Anaïs; Sanzey, Morgane; Rahim, Siti A Abdul; Fack, Fred; Thorsen, Frits; Taxt, Torfinn; Bartos, Michal; Jirik, Radovan; Miletic, Hrvoje; Wang, Jian; Stieber, Daniel; Stuhr, Linda; Moen, Ingrid; Rygh, Cecilie Brekke; Bjerkvig, Rolf; Niclou, Simone P

2011-03-01

Bevacizumab, an antibody against vascular endothelial growth factor (VEGF), is a promising, yet controversial, drug in human glioblastoma treatment (GBM). Its effects on tumor burden, recurrence, and vascular physiology are unclear. We therefore determined the tumor response to bevacizumab at the phenotypic, physiological, and molecular level in a clinically relevant intracranial GBM xenograft model derived from patient tumor spheroids. Using anatomical and physiological magnetic resonance imaging (MRI), we show that bevacizumab causes a strong decrease in contrast enhancement while having only a marginal effect on tumor growth. Interestingly, dynamic contrast-enhanced MRI revealed a significant reduction of the vascular supply, as evidenced by a decrease in intratumoral blood flow and volume and, at the morphological level, by a strong reduction of large- and medium-sized blood vessels. Electron microscopy revealed fewer mitochondria in the treated tumor cells. Importantly, this was accompanied by a 68% increase in infiltrating tumor cells in the brain parenchyma. At the molecular level we observed an increase in lactate and alanine metabolites, together with an induction of hypoxia-inducible factor 1α and an activation of the phosphatidyl-inositol-3-kinase pathway. These data strongly suggest that vascular remodeling induced by anti-VEGF treatment leads to a more hypoxic tumor microenvironment. This favors a metabolic change in the tumor cells toward glycolysis, which leads to enhanced tumor cell invasion into the normal brain. The present work underlines the need to combine anti-angiogenic treatment in GBMs with drugs targeting specific signaling or metabolic pathways linked to the glycolytic phenotype.

Effects of Lugol's iodine solution and formalin on cell volume of three bloom-forming dinoflagellates

NASA Astrophysics Data System (ADS)

Yang, Yang; Sun, Xiaoxia; Zhao, Yongfang

2017-07-01

Fixatives are traditionally used in marine ecosystem research. The bias introduced by fixatives on the dimensions of plankton cells may lead to an overestimation or underestimation of the carbon biomass. To determine the impact of traditional fixatives on dinoflagellates during short- and long-term fixation, we analyzed the degree of change in three bloom-forming dinoflagellates ( Prorocentrum micans, Scrippsiella trochoidea and Noctiluca scintillans) brought about by Lugol's iodine solution (hereafter Lugol's) and formalin. The fixation effects were species-specific. P. micans cell volume showed no significant change following long-term preservation, and S. trochoidea swelled by approximately 8.06% in Lugol's and by 20.97% in formalin as a percentage of the live cell volume, respectively. N. scintillans shrank significantly in both fixatives. The volume change due to formalin in N. scintillans was not concentration-dependent, whereas the volume shrinkage of N. scintillans cells fixed with Lugol's at a concentration of 2% was nearly six-fold that in cells fixed with Lugol's at a concentration of 0.6%-0.8%. To better estimate the volume of N. scintillans fixed in formalin at a concentration of 5%, we suggest that the conversion relationship was as follows: volume of live cell=volume of intact fixed cell/0.61. Apart from size change, damage induced by fixatives on N. scintillans was obvious. Lugol's is not a suitable fixative for N. scintillans due to high frequency of broken cells. Accurate carbon biomass estimate of N. scintillans should be performed on live samples. These findings help to improve the estimate of phytoplankton cell volume and carbon biomass in marine ecosystem.

Blood volume reduction counteracts fluid shifts in water immersion

NASA Technical Reports Server (NTRS)

Simanonok, Karl E.; Bernauer, Edmund

1993-01-01

Six healthy men were bled by 15 percent of their total blood volume (TBV) before 7 h of seated water immersion, to test the hypothesis that some of the major physiological responses to an expansion of central blood volume can be counteracted by prior reduction of TBV. Subjects were their own controls under two conditions: seated dry in air and seated immersed to the suprasternal notch in water. Immersion without prior reduction of TBV Wet Control (WC) caused a statistically significant 22-percent increase in cardiac output (CO), 368-percent increase in urine production, and 200-percent increase in sodium excretion relative to dry control (DC) sessions. When TBV was reduced before immersion, CO was the same as during DC sessions; however there were significant increases above DC in urine flow (+73 percent) and sodium excretion (+120 percent), although they were significantly reduced from WC values. Potassium excretion was similar during DC and WC sessions, but was significantly increased (+75 percent) when subjects were immersed after 15-percent reduction of TBV.

Solar cell array design handbook, volume 1

NASA Technical Reports Server (NTRS)

Rauschenbach, H. S.

1976-01-01

Twelve chapters discuss the following: historical developments, the environment and its effects, solar cells, solar cell filters and covers, solar cell and other electrical interconnections, blocking and shunt diodes, substrates and deployment mechanisms, material properties, design synthesis and optimization, design analysis, procurement, production and cost aspects, evaluation and test, orbital performance, and illustrative design examples. A comprehensive index permits rapid locating of desired topics. The handbook consists of two volumes: Volume 1 is of an expository nature while Volume 2 contains detailed design data in an appendix-like fashion. Volume 2 includes solar cell performance data, applicable unit conversion factors and physical constants, and mechanical, electrical, thermal optical, magnetic, and outgassing material properties. Extensive references are provided.

Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall cell lung cancer using tumor-volume variation data

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

Chvetsov, Alexei V., E-mail: chvetsov2@gmail.com; Schwartz, Jeffrey L.; Mayr, Nina

2014-06-15

Purpose: In our previous work, the authors showed that a distribution of cell surviving fractionsS{sub 2} in a heterogeneous group of patients could be derived from tumor-volume variation curves during radiotherapy for head and neck cancer. In this research study, the authors show that this algorithm can be applied to other tumors, specifically in nonsmall cell lung cancer. This new application includes larger patient volumes and includes comparison of data sets obtained at independent institutions. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancermore » with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage computed tomography. Statistical distributions of cell surviving fractionsS{sub 2} and clearance half-lives of lethally damaged cells T{sub 1/2} have been reconstructed in each patient group by using a version of the two-level cell population model of tumor response and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Nonsmall cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractionsS{sub 2} for nonsmall cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sub 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Conclusions: The data obtained in this work, when taken together with the data obtained previously for head and neck cancer, suggests that the cell surviving fractionsS{sub 2} can be reconstructed from the tumor volume variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.« less

Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall cell lung cancer using tumor-volume variation data.

PubMed

Chvetsov, Alexei V; Yartsev, Slav; Schwartz, Jeffrey L; Mayr, Nina

2014-06-01

In our previous work, the authors showed that a distribution of cell surviving fractions S2 in a heterogeneous group of patients could be derived from tumor-volume variation curves during radiotherapy for head and neck cancer. In this research study, the authors show that this algorithm can be applied to other tumors, specifically in nonsmall cell lung cancer. This new application includes larger patient volumes and includes comparison of data sets obtained at independent institutions. Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage computed tomography. Statistical distributions of cell surviving fractions S2 and clearance half-lives of lethally damaged cells T(1/2) have been reconstructed in each patient group by using a version of the two-level cell population model of tumor response and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Nonsmall cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractions S2 for nonsmall cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S2 reconstructed from tumor volume variation agree with the PDF measured in vitro. The data obtained in this work, when taken together with the data obtained previously for head and neck cancer, suggests that the cell surviving fractions S2 can be reconstructed from the tumor volume variation curves measured during radiotherapy with conventional fractionation. The proposed method can be used for treatment evaluation and adaptation.

Impacts of age and sex on retinal layer thicknesses measured by spectral domain optical coherence tomography with Spectralis.

PubMed

Nieves-Moreno, María; Martínez-de-la-Casa, José M; Morales-Fernández, Laura; Sánchez-Jean, Rubén; Sáenz-Francés, Federico; García-Feijoó, Julián

2018-01-01

To examine differences in individual retinal layer thicknesses measured by spectral domain optical coherence tomography (SD-OCT) (Spectralis®) produced with age and according to sex. Cross-sectional, observational study. The study was conducted in 297 eyes of 297 healthy subjects aged 18 to 87 years. In one randomly selected eye of each participant the volume and mean thicknesses of the different macular layers were measured by SD-OCT using the instrument's macular segmentation software. Volume and mean thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigmentary epithelium (RPE) and photoreceptor layer (PR). Retinal thickness was reduced by 0.24 μm for every one year of age. Age adjusted linear regression analysis revealed mean GCL, IPL, ONL and PR thickness reductions and a mean OPL thickness increase with age. Women had significantly lower mean GCL, IPL, INL, ONL and PR thicknesses and volumes and a significantly greater mRNFL volume than men. The thickness of most retinal layers varies both with age and according to sex. Longitudinal studies are needed to determine the rate of layer thinning produced with age.

Plasma volume and renal function during and after ultramarathon running.

PubMed

Irving, R A; Noakes, T D; Burger, S C; Myburgh, K H; Querido, D; van Zyl Smit, R

1990-10-01

Plasma volume (PV) and renal function were studied in eight subjects for 3 d prior to and 6 d after a 56 km footrace. Immediately following the race, PV, creatinine clearance, and urine flow were unchanged from pre-race values. Over the subsequent 3 d, PV increased due initially to a 17 g influx of serum albumin and an associated increase in plasma sodium content, which persisted throughout the study period. A reduction in urine sodium secretion occurred during the race day. Creatinine clearance increased after the race and remained elevated for 48 h. Increases serum enzyme activities, C-reactive protein concentration, serum uric acid content, and plasma creatinine concentration and production suggest muscle damage. We suggested the following. First, the persistent post-exercise plasma volume expansion is initiated by an influx of albumin into the intravascular space with an associated increase in plasma sodium content. A decrease in urine sodium excretion during the race day would contribute to the latter. Second, the interpretation of post-race changes in serum constituents must take account of changes in plasma volume. Third, there is an increase in creatinine clearance, indicating an increase in glomerular filtration rate, after both standard and ultramarathon running. This may be caused by the products of muscle cell damage although the physiologic mechanism for this is unclear.

Differentiations and Functional State of Osteogenic Cells in Conditions of Microgravity

NASA Astrophysics Data System (ADS)

Onishchenko, Ganna; Rodionova, Natalia; Markevich, Ganna; Markevich, Ganna

The space flight factors (space radiation, magnetic fields etc.) affect considerably the state of bone tissue, leading to the development of osteoporosis and osteopenia in the bone skeleton. Many aspects of reactions of bone tissue cells still remain unclear until now. With the use of electron microscopy and autoradiography with 3H-thymidine we studied the samples gathered from the femoral bone epiphyses and metaphyses of rats flown on board American Spacelab -2 and in experiments with modeling of microgravity ("tail suspension" method). In our work the main attention is focused on studying the ultrastructure and metabolism of osteogenetic cells. The degree of differentiation and functional state are evaluated according to the degree of development of organelles for specific biosynthesis: rough endoplasmic reticulum (RER), Golgy complex (GC), as well as the state of mitochondria and cell nucleus. As compared with a control, the population of osteogenetic cells from zones of bone reconstruction shows a decrease in the number of functionally active forms. We can judge of this from the reduction volume of RER, GC, mitochondria in osteoblasts. RER loses architectonics typical for osteoblasts and, as against the control, is represented by short narrow canaliculi distributed throughout the cy-toplasm; some canals disintegrate. GC is slightly pronounced, mitochondria become smaller in size and acquire an optically dark matrix. These phenomena are supposed to be associated with the desorganization of microtubules and microfilaments in the cells under microgravity condi-tions. The number of degrading and apoptotic cells increases in the population of osteoblasts. The dynamics of labeled cells following various intervals after 3H-thymidine injection testifies to a delay in the rates of osteoblasts' differentiation and their transformation to osteocytes in the experiment animals. A lower 3H-glycine uptake by the osteogenic cells and bone matrix as compared with a control is indicative of a decrease of the osteoplastic process under hypokinesia and modeling microgravity. We concluded that microgravity results in low differentiations and reduction specific functions of osteogenic cells.

Recovery from impaired muscle growth arises from prolonged postnatal accretion of myonuclei in Atrx mutant mice

PubMed Central

Yan, Keqin; Price-O’Dea, Tina

2017-01-01

Reduced muscle mass due to pathological development can occur through several mechanisms, including the loss or reduced proliferation of muscle stem cells. Muscle-specific ablation of the α-thalassemia mental retardation syndrome mutant protein, Atrx, in transgenic mice results in animals with a severely reduced muscle mass at three weeks of age; yet this muscle mass reduction resolves by adult age. Here, we explore the cellular mechanism underlying this effect. Analysis of Atrx mutant mice included testing for grip strength and rotorod performance. Muscle fiber length, fiber volume and numbers of myofiber-associated nuclei were determined from individual EDL or soleus myofibers isolated at three, five, or eight weeks. Myofibers from three week old Atrx mutant mice are smaller with fewer myofiber-associated nuclei and reduced volume compared to control animals, despite similar fiber numbers. Nonetheless, the grip strength of Atrx mutant mice was comparable to control mice when adjusted for body weight. Myofiber volume remained smaller at five weeks, becoming comparable to controls by 8 weeks of age. Concomitantly, increased numbers of myofiber-associated nuclei and Ki67+ myoblasts indicated that the recovery of muscle mass likely arises from the prolonged accretion of new myonuclei. This suggests that under disease conditions the muscle satellite stem cell niche can remain in a prolonged active state, allowing for the addition of a minimum number of myonuclei required to achieve a normal muscle size. PMID:29095838

Polyphenolics from mango (Mangifera indica L.) suppress breast cancer ductal carcinoma in situ proliferation through activation of AMPK pathway and suppression of mTOR in athymic nude mice.

PubMed

Nemec, Matthew J; Kim, Hyemee; Marciante, Alexandria B; Barnes, Ryan C; Hendrick, Erik D; Bisson, William H; Talcott, Stephen T; Mertens-Talcott, Susanne U

2017-03-01

The objective of this study was to assess the underlying mechanisms of mango polyphenol decreased cell proliferation and tumor volume in ductal carcinoma in situ breast cancer. We hypothesized that mango polyphenols suppress signaling along the AKT/mTOR axis while up-regulating AMPK. To test this hypothesis, mango polyphenols (0.8 mg gallic acid equivalents per day) and pyrogallol (0.2 mg/day) were administered for 4 weeks to mice xenografted with MCF10DCIS.com cells subcutaneously (n=10 per group). Tumor volumes were significantly decreased, both mango and pyrogallol groups displayed greater than 50% decreased volume compared to control. There was a significant reduction of phosphorylated protein levels of IR, IRS1, IGF-1R, and mTOR by mango; while pyrogallol significantly reduced the phosphorylation levels of IR, IRS1, IGF-1R, p70S6K, and ERK. The protein levels of Sestrin2, which is involved in AMPK-signaling, were significantly elevated in both groups. Also, mango significantly elevated AMPK phosphorylation and pyrogallol significantly elevated LKB1 protein levels. In an in vitro model, mango and pyrogallol increased reactive oxygen species (ROS) generation and arrested cells in S phase. In silico modeling indicates that pyrogallol has the potential to bind directly to the allosteric binding site of AMPK, inducing activation. When AMPK expression was down-regulated using siRNA in vitro, pyrogallol reversed the reduced expression of AMPK. This indicates that pyrogallol not only activates AMPK, but also increases constitutive protein expression. These results suggest that mango polyphenols and their major microbial metabolite, pyrogallol, inhibit proliferation of breast cancer cells through ROS-dependent up-regulation of AMPK and down-regulation of the AKT/mTOR pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic efficacy and molecular mechanisms of snake (Walterinnesia aegyptia) venom-loaded silica nanoparticles in the treatment of breast cancer- and prostate cancer-bearing experimental mouse models.

PubMed

Badr, Gamal; Al-Sadoon, Mohamed K; Rabah, Danny M

2013-12-01

The treatment of drug-resistant cancer is a clinical challenge, and thus screening for novel anticancer drugs is critically important. We recently demonstrated a strong enhancement of the antitumor activity of snake (Walterinnesia aegyptia) venom (WEV) in vitro in breast carcinoma, prostate cancer, and multiple myeloma cell lines but not in normal cells when the venom was combined with silica nanoparticles (WEV+NP). In the present study, we investigated the in vivo therapeutic efficacy of WEV+NP in breast cancer- and prostate cancer-bearing experimental mouse models. Xenograft breast and prostate tumor mice models were randomized into 4 groups for each cancer model (10 mice per group) and were treated with vehicle (control), NP, WEV, or WEV+NP daily for 28 days post tumor inoculation. The tumor volumes were monitored throughout the experiment. On Day 28 post tumor inoculation, breast and prostate tumor cells were collected and either directly cultured for flow cytometry analysis or lysed for Western blot and ELISA analysis. Treatment with WEV+NP or WEV alone significantly reduced both breast and prostate tumor volumes compared to treatment with NP or vehicle alone. Compared to treatment with WEV alone, treatment of breast and prostate cancer cells with WEV+NP induced marked elevations in the levels of reactive oxygen species (ROS), hydroperoxides, and nitric oxide; robust reductions in the levels of the chemokines CXCL9, CXCL10, CXCL12, CXCL13, and CXCL16 and decreased surface expression of their cognate chemokine receptors CXCR3, CXCR4, CXCR5, and CXCR6; and subsequent reductions in the chemokine-dependent migration of both breast and prostate cancer cells. Furthermore, we found that WEV+NP strongly inhibited insulin-like growth factor 1 (IGF-1)- and epidermal growth factor (EGF)-mediated proliferation of breast and prostate cancer cells, respectively, and enhanced the induction of apoptosis by increasing the activity of caspase-3,-8, and -9 in both breast and prostate cancer cells. In addition, treatment of breast and prostate cancer cells with WEV+NP or WEV alone revealed that the combination of WEV with NP robustly decreased the phosphorylation of AKT, ERK, and IκBα; decreased the expression of cyclin D1, surviving, and the antiapoptotic Bcl-2 family members Bcl-2, Bcl-XL, and Mcl-1; markedly increased the expression of cyclin B1 and the proapoptotic Bcl-2 family members Bak, Bax, and Bim; altered the mitochondrial membrane potential; and subsequently sensitized tumor cells to growth arrest. Our data reveal the therapeutic potential of the nanoparticle-sustained delivery of snake venom against different cancer cell types. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

N-doped graphene coupled with Co nanoparticles as an efficient electrocatalyst for oxygen reduction in alkaline media

NASA Astrophysics Data System (ADS)

Zhang, Geng; Lu, Wangting; Cao, Feifei; Xiao, Zhidong; Zheng, Xinsheng

2016-01-01

Development of low-cost and highly efficient electrocatalysts for oxygen reduction reaction (ORR) is still a great challenge for the large-scale application of fuel cells and metal-air batteries. Herein, a noble metal-free ORR electrocatalyst in the form of N-doped graphene coupled with part of Co nanoparticles encased in N-doped graphitic shells (named as SUCo-0.03-800) is prepared by facile one-step pyrolysis of the mixture of sucrose, urea and cobalt nitrate. The novel structure is confirmed by High Resolution-TEM, XRD, XPS and Raman spectroscopy. SUCo-0.03-800 presents comparable ORR catalytic activity to commercial Pt/C catalyst with a dominating four-electron pathway under alkaline conditions, and both of its mass activity and volume activity also outperform Co-free N-doped graphene and other Co/N-C hybrids with higher Co content, which may probably be ascribed to the high specific surface area, novel structure and synergistic effect between encased Co nanoparticles and N-doped graphitic shell. Additionally, SUCo-0.03-800 also shows outstanding stability and improved selectivity towards ORR, making it a promising alternative to Pt with potential application in fuel cells and metal-air batteries.

Low light intensity and nitrogen starvation modulate the chlorophyll content of Scenedesmus dimorphus.

PubMed

Ferreira, V S; Pinto, R F; Sant'Anna, C

2016-03-01

Chlorophyll is a photosynthetic pigment found in plants and algal organisms and is a bioproduct with human health benefits and a great potential for use in the food industry. The chlorophyll content in microalgae strains varies in response to environmental factors. In this work, we assessed the effect of nitrogen depletion and low light intensity on the chlorophyll content of the Scenedesmus dimorphus microalga. The growth of S. dimorphus under low light intensity led to a reduction in cell growth and volume as well as increased cellular chlorophyll content. Nitrogen starvation led to a reduction in cell growth and the chlorophyll content, changes in the yield and productivity of chlorophylls a and b. Transmission electron microscopy was used to investigate the ultrastructural changes in the S. dimorphus exposed to nitrogen and light deficiency. In contrast to nitrogen depletion, low light availability was an effective mean for increasing the total chlorophyll content of green microalga S. dimorphus. The findings acquired in this work are of great biotechnological importance to extend knowledge of choosing the right culture condition to stimulate the effectiveness of microalgae strains for chlorophyll production purposes. © 2015 The Society for Applied Microbiology.

Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma.

PubMed

Kudou, Michihiro; Shiozaki, Atsushi; Kosuga, Toshiyuki; Ichikawa, Daisuke; Konishi, Hirotaka; Morimura, Ryo; Komatsu, Shuhei; Ikoma, Hisashi; Fujiwara, Hitoshi; Okamoto, Kazuma; Hosogi, Shigekuni; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

2016-01-01

Background : Hypotonic shock induces cytocidal effects through cell rupture, and cancer therapy based on this mechanism has been clinically administered to hepatocellular carcinoma patients. We herein investigated the effectiveness of hypotonic shock combined with the inhibition of regulatory volume decrease as cancer therapy for hepatocellular carcinoma. Methods : Morphological changes in human hepatocellular carcinoma cell lines were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes under hypotonic shock with or without chloride, potassium, or water channel blockers were observed using a high-resolution flow cytometer. In order to investigate cytocidal effects, the number of surviving cells was compared after exposure to hypotonic solution with and without each channel blocker (re-incubation experiment). Results : Video recordings showed that cells exposed to distilled water rapidly swelled and then ruptured. Cell volume measurements revealed regulatory volume decrease under mild hypotonic shock, whereas severe hypotonic shock increased the number of broken fragments as a result of cell rupture. Moreover, regulatory volume decrease was inhibited in cells treated with each channel blocker. Re-incubation experiments showed the cytocidal effects of hypotonic shock in cells exposed to hypotonic solution, and additional treatments with each channel blocker enhanced these effects. Conclusion : The inhibition of regulatory volume decrease with chloride, potassium, or water channel blockers may enhance the cytocidal effects of hypotonic shock in hepatocellular carcinoma. Hypotonic shock combined with the inhibition of regulatory volume decrease was a more effective therapy than hypotonic shock alone.

Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma

PubMed Central

Kudou, Michihiro; Shiozaki, Atsushi; Kosuga, Toshiyuki; Ichikawa, Daisuke; Konishi, Hirotaka; Morimura, Ryo; Komatsu, Shuhei; Ikoma, Hisashi; Fujiwara, Hitoshi; Okamoto, Kazuma; Hosogi, Shigekuni; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

2016-01-01

Background: Hypotonic shock induces cytocidal effects through cell rupture, and cancer therapy based on this mechanism has been clinically administered to hepatocellular carcinoma patients. We herein investigated the effectiveness of hypotonic shock combined with the inhibition of regulatory volume decrease as cancer therapy for hepatocellular carcinoma. Methods: Morphological changes in human hepatocellular carcinoma cell lines were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes under hypotonic shock with or without chloride, potassium, or water channel blockers were observed using a high-resolution flow cytometer. In order to investigate cytocidal effects, the number of surviving cells was compared after exposure to hypotonic solution with and without each channel blocker (re-incubation experiment). Results: Video recordings showed that cells exposed to distilled water rapidly swelled and then ruptured. Cell volume measurements revealed regulatory volume decrease under mild hypotonic shock, whereas severe hypotonic shock increased the number of broken fragments as a result of cell rupture. Moreover, regulatory volume decrease was inhibited in cells treated with each channel blocker. Re-incubation experiments showed the cytocidal effects of hypotonic shock in cells exposed to hypotonic solution, and additional treatments with each channel blocker enhanced these effects. Conclusion: The inhibition of regulatory volume decrease with chloride, potassium, or water channel blockers may enhance the cytocidal effects of hypotonic shock in hepatocellular carcinoma. Hypotonic shock combined with the inhibition of regulatory volume decrease was a more effective therapy than hypotonic shock alone. PMID:27471568

Optical volume and mass measurements show that mammalian cells swell during mitosis

PubMed Central

Zlotek-Zlotkiewicz, Ewa; Monnier, Sylvain; Cappello, Giovanni; Le Berre, Mael

2015-01-01

The extent, mechanism, and function of cell volume changes during specific cellular events, such as cell migration and cell division, have been poorly studied, mostly because of a lack of adequate techniques. Here we unambiguously report that a large range of mammalian cell types display a significant increase in volume during mitosis (up to 30%). We further show that this increase in volume is tightly linked to the mitotic state of the cell and not to its spread or rounded shape and is independent of the presence of an intact actomyosin cortex. Importantly, this volume increase is not accompanied by an increase in dry mass and thus corresponds to a decrease in cell density. This mitotic swelling might have important consequences for mitotic progression: it might contribute to produce strong pushing forces, allowing mitotic cells to round up; it might also, by lowering cytoplasmic density, contribute to the large change of physicochemical properties observed in mitotic cells. PMID:26598614

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

Swaminath, Anand; Knox, Jennifer J.; Brierley, James D.

Purpose: The purpose of this study was to quantify unexpected liver volume reductions in patients treated with sorafenib prior to and during liver radiation therapy (RT). Methods and Materials: Fifteen patients were treated in a phase 1 study of sorafenib for 1 week, followed by concurrent sorafenib-RT (in 6 fractions). Patients had either focal cancer (treated with stereotactic body RT [SBRT]) or diffuse disease (treated with whole-liver RT). Liver volumes were contoured and recorded at planning (day 0) from the exhale CT. After 1 week of sorafenib (day 8), RT image guidance at each fraction was performed using cone beam CT (CBCT).more » Planning liver contours were propagated and modified on the reconstructed exhale CBCT. This was repeated in 12 patients treated with SBRT alone without sorafenib. Three subsequent patients (2 sorafenib-RT and 1 non-sorafenib) were also assessed with multiphasic helical breath-hold CTs. Results: Liver volume reductions on CBCT were observed in the 15 sorafenib-RT patients (median decrease of 68 cc, P=.02) between day 0 and 8; greater in the focal (P=.025) versus diffuse (P=.52) cancer stratum. Seven patients (47%) had reductions larger than the 95% intraobserver contouring error. Liver reductions were also observed from multiphasic CTs in the 2 additional sorafenib-RT patients between days 0 and 8 (decreases of 232.5 cc and 331.7 cc, respectively) and not in the non-sorafenib patient (increase of 92 cc). There were no significant changes in liver volume between planning and first RT in 12 patients with focal cancer treated with SBRT alone (median increase, 4.8 cc, P=.86). Conclusions: Liver volume reductions were observed after 7 days of sorafenib, prior to RT, most marked in patients with focal liver tumors, suggesting an effect of sorafenib on normal liver. Careful assessment of potential liver volume changes immediately prior to SBRT may be necessary in patients in sorafenib or other targeted therapies.« less

Effects of nitroglycerin and nitroprusside on vascular capacitance of anesthetized ganglion-blocked dogs.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1991-10-01

To determine whether changes in vascular capacitance induced by nitroglycerin (NTG) and nitroprusside were due to changes in compliance or unstressed vascular volume, doses producing similar reductions in arterial pressure (Psa) were studied on separate days in six dogs anesthetized and ventilated with pentobarbital after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline blood volumes and after increases of 5 and 10 ml/kg. Central blood volumes (CBVs, pulmonary artery to aortic root) were determined from transit times, and separately measured cardiac output (CO) was estimated by thermodilution (right atrium to pulmonary artery). NTG and nitroprusside produced similar reductions in Psa and Pmcf without significantly altering right atrial pressure (Pra), pressure gradient for venous return, or CO. Total vascular compliance was not altered, but total vascular capacitance was increased on an average of 4.0 +/- 1.4 ml/kg after NTG and 3.0 +/- 1.3 ml/kg after nitroprusside by increases in unstressed volume. Both drugs caused a variable reduction in CBV, averaging 2 ml/kg. Thus, both drugs produced a large increase in peripheral venous capacitance by increasing unstressed vascular volume without altering total vascular compliance.

Stress predicts brain changes in children: a pilot longitudinal study on youth stress, posttraumatic stress disorder, and the hippocampus.

PubMed

Carrion, Victor G; Weems, Carl F; Reiss, Allan L

2007-03-01

Does stress damage the brain? Studies of adults with posttraumatic stress disorder have demonstrated smaller hippocampal volumes when compared with the volumes of adults with no posttraumatic stress disorder. Studies of children with posttraumatic stress disorder have not replicated the smaller hippocampal findings in adults, which suggests that smaller hippocampal volume may be caused by neurodevelopmental experiences with stress. Animal research has demonstrated that the glucocorticoids secreted during stress can be neurotoxic to the hippocampus, but this has not been empirically demonstrated in human samples. We hypothesized that cortisol volumes would predict hippocampal volume reduction in patients with posttraumatic symptoms. We report data from a pilot longitudinal study of children (n = 15) with history of maltreatment who underwent clinical evaluation for posttraumatic stress disorder, cortisol, and neuroimaging. Posttraumatic stress disorder symptoms and cortisol at baseline predicted hippocampal reduction over an ensuing 12- to 18-month interval. Results from this pilot study suggest that stress is associated with hippocampal reduction in children with posttraumatic stress disorder symptoms and provide preliminary human evidence that stress may indeed damage the hippocampus. Additional studies seem to be warranted.

Advantages and disadvantages of graduated and inverse graduated compression hosiery in patients with chronic venous insufficiency and healthy volunteers: A prospective, mono-centric, blinded, open randomised, controlled and cross-over trial.

PubMed

Riebe, Helene; Konschake, Wolfgang; Haase, Hermann; Jünger, Michael

2018-02-01

Background The therapeutic effectiveness of compression therapy depends on the selection of compression hosiery. Objectives To assess efficacy and tolerability of graduated elastic compression stockings (GECS) and inverse graduated elastic compression stockings (PECS). Methods Thirty-two healthy volunteers and thirty-two patients with chronic venous insufficiency were analysed; wear period: one week for each stocking type (randomised, blinded). volume reduction of 'Lower leg' (Image3D®) and 'Distal leg and foot' (water plethysmography). clinical symptoms of chronic venous insufficiency assessed by the Venous Clinical Severity Score, side effects and wear comfort in both groups. Results Volume of 'Lower leg': significant reduction in healthy volunteers (mean GECS: -37.5 mL, mean PECS: -37.2 mL) and in patients (mean GECS: -55.6 mL, mean PECS: -41.6 mL). Volume of 'Distal lower leg and foot': significant reduction in healthy volunteers (mean GECS: -27 mL, mean PECS: -16.7 mL), significant reduction in patients by GECS (mean: -43.4 mL), but non-significant reduction by PECS (mean: -22.6 mL). Clinical symptoms of chronic venous insufficiency were improved significantly better with GECS than with PECS, p < 0.001. GECS led to more painful constrictions, p = 0.047, PECS slipped down more often, p < 0.001. Conclusion GECS and PECS reduce volume of the segment 'Lower leg' in patients and healthy volunteers. Patients' volume of the 'Distal lower leg and foot', however, were diminished significantly only by GECS ( p = 0.0001). Patients' complaints were improved by both GECS and PECS, and GECS were superior to PECS.

Dehydration reduces left ventricular filling at rest and during exercise independent of twist mechanics.

PubMed

Stöhr, Eric J; González-Alonso, José; Pearson, James; Low, David A; Ali, Leena; Barker, Horace; Shave, Rob

2011-09-01

The purpose of this study was to determine whether the reduction in stroke volume (SV), previously shown to occur with dehydration and increases in internal body temperatures during prolonged exercise, is caused by a reduction in left ventricular (LV) function, as indicated by LV volumes, strain, and twist ("LV mechanics"). Eight healthy men [age: 20 ± 2, maximal oxygen uptake (VO₂max): 58 ± 7 ml·kg⁻¹·min⁻¹] completed two, 1-h bouts of cycling in the heat (35°C, 50% peak power) without fluid replacement, resulting in 2% and 3.5% dehydration, respectively. Conventional and two-dimensional speckle-tracking echocardiography was used to determine LV volumes, strain, and twist at rest and during one-legged knee-extensor exercise at baseline, both levels of dehydration, and following rehydration. Progressive dehydration caused a significant reduction in end-diastolic volume (EDV) and SV at rest and during one-legged knee-extensor exercise (rest: Δ-33 ± 14 and Δ-21 ± 14 ml, respectively; exercise: Δ-30 ± 10 and Δ-22 ± 9 ml, respectively, during 3.5% dehydration). In contrast to the marked decline in EDV and SV, systolic and diastolic LV mechanics were either maintained or even enhanced with dehydration at rest and during knee-extensor exercise. We conclude that dehydration-induced reductions in SV at rest and during exercise are the result of reduced LV filling, as reflected by the decline in EDV. The concomitant maintenance of LV mechanics suggests that the decrease in LV filling, and consequently ejection, is likely caused by the reduction in blood volume and/or diminished filling time rather than impaired LV function.

Cost effectiveness of lung-volume-reduction surgery for patients with severe emphysema.

PubMed

Ramsey, Scott D; Berry, Kristin; Etzioni, Ruth; Kaplan, Robert M; Sullivan, Sean D; Wood, Douglas E

2003-05-22

The National Emphysema Treatment Trial, a randomized clinical trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema, included a prospective economic analysis. After pulmonary rehabilitation, 1218 patients at 17 medical centers were randomly assigned to lung-volume-reduction surgery or continued medical treatment. Costs for the use of medical care, medications, transportation, and time spent receiving treatment were derived from Medicare claims and data from the trial. Cost effectiveness was calculated over the duration of the trial and was estimated for 10 years of follow-up with the use of modeling based on observed trends in survival, cost, and quality of life. Interim analyses identified a group of patients with excess mortality and little chance of improved functional status after surgery. When these patients were excluded, the cost-effectiveness ratio for lung-volume-reduction surgery as compared with medical therapy was 190,000 dollars per quality-adjusted life-year gained at 3 years and 53,000 dollars per quality-adjusted life-year gained at 10 years. Subgroup analyses identified patients with predominantly upper-lobe emphysema and low exercise capacity after pulmonary rehabilitation who had lower mortality and better functional status than patients who received medical therapy. The cost-effectiveness ratio in this subgroup was 98,000 dollars per quality-adjusted life-year gained at 3 years and 21,000 dollars at 10 years. Bootstrap analysis revealed substantial uncertainty for the subgroup and 10-year estimates. Given its cost and benefits over three years of follow-up, lung-volume-reduction surgery is costly relative to medical therapy. Although the predictions are subject to substantial uncertainty, the procedure may be cost effective if benefits can be maintained over time. Copyright 2003 Massachusetts Medical Society

Learning curve in transradial cardiac catheterization: procedure-related parameters stratified by operators' transradial volume.

PubMed

Kasasbeh, Ehab S; Parvez, Babar; Huang, Robert L; Hasselblad, Michele Marie; Glazer, Mark D; Salloum, Joseph G; Cleator, John H; Zhao, David X

2012-11-01

To determine whether radial artery access is associated with a reduction in fluoroscopy time, procedure time, and other procedural variables over a 27-month period during which the radial artery approach was incorporated in a single academic Medical Center. Although previous studies have demonstrated a relationship between increased volume and decreased procedural time, no studies have looked at the integration of radial access over time. Data were collected from consecutive patients who presented to the Vanderbilt University Medical Center cardiac catheterization laboratory from January 1, 2009 to April 1, 2011. Patients who underwent radial access diagnostic catheterization with and without percutaneous coronary intervention were included in this study. A total of 1112 diagnostic cardiac catheterizations through the radial access site were analyzed. High-volume, intermediate-volume, and low-volume operators were grouped based on the percentage of procedures performed through a radial approach. From 2009 to 2011, there was a significant decrease in fluoroscopy time in all operator groups for diagnostic catheterization (P=.035). The high-volume operator group had 1.88 and 3.66 minute reductions in fluoroscopy time compared to the intermediate- and low-volume operator groups, respectively (both P<.001). Likewise, the intermediate-volume operator group had a 1.77 minute improvement compared to the low-volume operator group, but this did not reach statistical significance (P=.102). The improvement in fluoroscopy time and other procedure-related parameters was seen after approximately 25 cases with further improvement after 75 cases. The incorporation of the radial access approach in the cardiac catheterization laboratory led to a decrease in fluoroscopy time for each operator and operator group over the last 3 years. Our data demonstrated that higher-volume radial operators have better procedure, room, and fluoroscopy times when compared to intermediate- and low-volume operators. However, lower-volume operators have a reduction in procedure-related parameters with increased radial cases. Number of procedures needed to become sufficient was demonstrated in the current study.

Tissue ablation after 120W greenlight laser vaporization and bipolar plasma vaporization of the prostate: a comparison using transrectal three-dimensional ultrasound volumetry

NASA Astrophysics Data System (ADS)

Kranzbühler, Benedikt; Gross, Oliver; Fankhauser, Christian D.; Hefermehl, Lukas J.; Poyet, Cédric; Largo, Remo; Müntener, Michael; Seifert, Hans-Helge; Zimmermann, Matthias; Sulser, Tullio; Müller, Alexander; Hermanns, Thomas

2012-02-01

Introduction and objectives: Greenlight laser vaporization (LV) of the prostate is characterized by simultaneous vaporization and coagulation of prostatic tissue resulting in tissue ablation together with excellent hemostasis during the procedure. It has been reported that bipolar plasma vaporization (BPV) of the prostate might be an alternative for LV. So far, it has not been shown that BPV is as effective as LV in terms of tissue ablation or hemostasis. We performed transrectal three-dimensional ultrasound investigations to compare the efficiency of tissue ablation between LV and BPV. Methods: Between 11.2009 and 5.2011, 50 patients underwent pure BPV in our institution. These patients were matched with regard to the pre-operative prostate volume to 50 LV patients from our existing 3D-volumetry-database. Transrectal 3D ultrasound and planimetric volumetry of the prostate were performed pre-operatively, after catheter removal, 6 weeks and 6 months. Results: Median pre-operative prostate volume was not significantly different between the two groups (45.3ml vs. 45.4ml; p=1.0). After catheter removal, median absolute volume reduction (BPV 12.4ml, LV 6.55ml) as well as relative volume reduction (27.8% vs. 16.4%) were significantly higher in the BPV group (p<0.001). After six weeks (42.9% vs. 33.3%) and six months (47.2% vs. 39.7%), relative volume reduction remained significantly higher in the BPV group (p<0.001). Absolute volume reduction was non-significantly higher in the BPV group after six weeks (18.4ml, 13.8ml; p=0.051) and six months (20.8ml, 18ml; p=0.3). Clinical outcome parameters improved significantly in both groups without relevant differences between the groups. Conclusions: Both vaporization techniques result in efficient tissue ablation with initial prostatic swelling. BPV seems to be superior due to a higher relative volume reduction. This difference had no clinical impact after a follow-up of 6M.

Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers.

PubMed

Pang, T; Su, X; Wakabayashi, S; Shigekawa, M

2001-05-18

The Na+/H+ exchangers (NHEs) comprise a family of transporters that catalyze cell functions such as regulation of the pH and volume of a cell and epithelial absorption of Na+ and bicarbonate. Ubiquitous calcineurin B homologous protein (CHP or p22) is co-localized and co-immunoprecipitated with expressed NHE1, NHE2, or NHE3 independently of its myristoylation and Ca2+ binding, and its binding site was identified as the juxtamembrane region within the carboxyl-terminal cytoplasmic domain of exchangers. CHP binding-defective mutations of NHE1-3 or CHP depletion by injection of the competitive CHP-binding region of NHE1 into Xenopus oocytes resulted in a dramatic reduction (>90%) in the Na+/H+ exchange activity. The data suggest that CHP serves as an essential cofactor, which supports the physiological activity of NHE family members.

Effect of acute heat stress on rat adrenal glands: a morphological and stereological study.

PubMed

Koko, Vesna; Djordjeviae, Jelena; Cvijiae, Gordana; Davidoviae, Vukosava

2004-11-01

The morphological and stereological structure of rat adrenal gland was analysed by light microscopy after an acute (60 min) exposure to high ambient temperature (38 degrees C). A significant increase in plasma corticotrophin (ACTH) and serum corticosterone (CORT) concentrations was observed, confirming that acute heat exposure has a strong stressful effect. Under these conditions the adrenal gland mass and volume were decreased, probably as the consequence of adrenal cortex reduction, especially that of the zona fasciculata (ZF). Histological examination revealed that many ZF cells were deprived of lipid droplets. Fibrosis was observed in all parts of the adrenal gland, both cortex and medulla, of heat stressed animals. Mitotic figures were absent in cortical cells after heat exposure, but there were no differences in ZF and zona reticularis (ZR) small blood vessels compared to nonstressed controls.

Lactobacillus johnsonii inhibits indoleamine 2,3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats.

PubMed

Valladares, Ricardo; Bojilova, Lora; Potts, Anastasia H; Cameron, Evan; Gardner, Christopher; Lorca, Graciela; Gonzalez, Claudio F

2013-04-01

In our previous work, we found that feeding Lactobacillus johnsonii to BioBreeding diabetes-prone (BBDP) rats decreased the incidence of diabetes development. The aim of this study was to investigate host pathways affected by L. johnsonii, with specific focus on the rate-limiting enzyme of tryptophan catabolism, indoleamine 2,3-dioxygenase (IDO). Suspensions of L. johnsonii or an equal volume of vehicle were orally administered to BBDP rats. Tissue IDO was investigated using quantitative RT-PCR and Western blot, whereas tryptophan, kynurenine, and 5-hydroxytryptamine (5-HT) concentrations were quantified by HPLC and ELISA. IDO activity was also investigated using L. johnsonii culture cell-free supernatant (CFS) with affinity-purified IDO and HT-29 intestinal epithelial cells. L. johnsonii feeding resulted in a 17% reduction in serum kynurenine compared with that in vehicle-fed controls, correlating with a 1.4-fold elevation in 5-HT levels. H₂O₂ produced by L. johnsonii abolished IDO activity in vitro, and L. johnsonii feeding resulted in a 3.9-fold increase in ileum lumen H₂O₂. L. johnsonii CFS significantly reduced IDO activity in HT-29 intestinal epithelial cells (47% reduction) compared with that in vehicle-treated controls, an effect abolished by catalase treatment. These data support the role of H₂O₂ in commensal bacteria-host interactions and highlight the influence of commensal bacteria-derived H₂O₂ on host physiology.

Cell volume regulation and apoptotic volume decrease in rat distal colon superficial enterocytes.

PubMed

Antico, Stefania; Lionetto, Maria Giulia; Giordano, Maria Elena; Caricato, Roberto; Schettino, Trifone

2013-01-01

The colon epithelium is physiologically exposed to osmotic stress, and the activation of cell volume regulation mechanisms is essential in colonocyte physiology. Moreover, colon is characterized by a high apoptotic rate of mature cells balancing the high division rate of stem cells. The aim of the present work was to investigate the main cell volume regulation mechanisms in rat colon surface colonocytes and their role in apoptosis. Cell volume changes were measured by light microscopy and video imaging on colon explants; apoptosis sign appearance was monitored by confocal microscopy on annexin V/propidium iodide labeled explants. Superficial colonocytes showed a dynamic regulation of their cell volume during anisosmotic conditions with a Regulatory Volume Increase (RVI) response following hypertonic shrinkage and Regulatory Volume Decrease (RVD) response following hypotonic swelling. RVI was completely inhibited by bumetanide, while RVD was completely abolished by high K(+) or iberiotoxin treatment and by extracellular Ca(2+) removal. DIDS incubation was also able to affect the RVD response. When colon explants were exposed to H2O2 as apoptotic inducer, colonocytes underwent an isotonic volume decrease ascribable to Apoptotic Volume Decrease (AVD) within about four hours of exposure. AVD was shown to precede annexin V positivity. It was also inhibited by high K(+) or iberiotoxin treatment. Interestingly, treatment with iberiotoxin significantly inhibited apoptosis progression. In rat superficial colonocytes K(+) efflux through high conductance Ca(2+)-activated K(+) channels (BK channels) was demonstrated to be the main mechanism of RVD and to plays also a crucial role in the AVD process and in the progression of apoptosis. © 2013 S. Karger AG, Basel.

The coordination of ploidy and cell size differs between cell layers in leaves.

PubMed

Katagiri, Yohei; Hasegawa, Junko; Fujikura, Ushio; Hoshino, Rina; Matsunaga, Sachihiro; Tsukaya, Hirokazu

2016-04-01

Growth and developmental processes are occasionally accompanied by multiple rounds of DNA replication, known as endoreduplication. Coordination between endoreduplication and cell size regulation often plays a crucial role in proper organogenesis and cell differentiation. Here, we report that the level of correlation between ploidy and cell volume is different in the outer and inner cell layers of leaves of Arabidopsis thaliana using a novel imaging technique. Although there is a well-known, strong correlation between ploidy and cell volume in pavement cells of the epidermis, this correlation was extremely weak in palisade mesophyll cells. Induction of epidermis cell identity based on the expression of the homeobox gene ATML1 in mesophyll cells enhanced the level of correlation between ploidy and cell volume to near that of wild-type epidermal cells. We therefore propose that the correlation between ploidy and cell volume is regulated by cell identity. © 2016. Published by The Company of Biologists Ltd.

Ablative efficiency of lithium triborate laser vaporization and conventional transurethral resection of the prostate: a comparison using transrectal three-dimensional ultrasound volumetry

NASA Astrophysics Data System (ADS)

Gross, Oliver; Sulser, Tullio; Hefermehl, Lukas J.; Strebel, Daniel D.; Largo, Remo; Mortezavi, Ashkan; Poyet, Cédric; Eberli, Daniel; Zimmermann, Matthias; Müller, Alexander; Michel, Maurice S.; Müntener, Michael; Seifert, Hans-Helge; Hermanns, Thomas

2011-03-01

Introduction and objectives: It is unknown if tissue ablation following 120W lithium triborate (LBO) laser vaporization (LV) of the prostate is comparable to that following transurethral resection of the prostate (TURP). Therefore, transrectal 3D-ultrasound volumetry of the prostate was performed to compare the efficiency of tissue ablation between LBO-LV and TURP. Methods: Between 03/2008 and 03/2010 110 patients underwent routine LBO-LV (n=61) or TURP (n=49). Transrectal 3D-ultrasound with planimetric volumetry of the prostate was performed pre-operatively, after catheter removal, 6 weeks and 6 months. Results: Median prostate volume was 52.5ml in the LV group and 46.9ml in the TURP group. After catheter removal, median absolute volume reduction (LV: 7.05ml, TURP: 15.8ml) and relative volume reduction (15.9% vs. 34.2%) were significantly lower in the LV group (p<0.001). After 6 weeks/ 6 months, the relative volume reduction but not the absolute remained significantly lower in the LV group. Conclusions: LBO-LV is an efficient procedure evidenced by an absolute tissue ablation not significantly different to that after TURP. However, TURP seems to be superior due to a higher relative tissue ablation. The differences in tissue ablation had no impact on the early clinical outcome. Delayed volume reduction indicates that prostatic swelling occurs early after LV and then decreases subsequently.

Transfusion of cell saver salvaged blood in neonates and infants undergoing open heart surgery significantly reduces RBC and coagulant product transfusions and donor exposures: results of a prospective, randomized, clinical trial.

PubMed

Cholette, Jill M; Powers, Karen S; Alfieris, George M; Angona, Ronald; Henrichs, Kelly F; Masel, Debra; Swartz, Michael F; Daugherty, L Eugene; Belmont, Kevin; Blumberg, Neil

2013-02-01

To evaluate whether transfusion of cell saver salvaged, stored at the bedside for up to 24 hrs, would decrease the number of postoperative allogeneic RBC transfusions and donor exposures, and possibly improve clinical outcomes. Prospective, randomized, controlled, clinical trial. Pediatric cardiac intensive care unit. Infants weighing less than 20 kg (n = 106) presenting for cardiac surgery with cardiopulmonary bypass. Subjects were randomized to a cell saver transfusion group where cell saver blood was available for transfusion up to 24 hrs after collection, or to a control group. Cell saver subjects received cell saver blood for volume replacement and/or RBC transfusions. Control subjects received crystalloid or albumin for volume replacement and RBCs for anemia. Blood product transfusions, donor exposures, and clinical outcomes were compared between groups. Children randomized to the cell saver group had significantly fewer RBC transfusions (cell saver: 0.19 ± 0.44 vs. control: 0.75 ± 1.2; p = 0.003) and coagulant product transfusions in the first 48 hrs post-op (cell saver: 0.09 ± 0.45 vs. control: 0.62 ± 1.4; p = 0.013), and significantly fewer donor exposures (cell saver: 0.60 ± 1.4 vs. control: 2.3 ± 4.8; p = 0.019). This difference persisted over the first week post-op, but did not reach statistical significance (cell saver: 0.64 ± 1.24 vs. control: 1.1 ± 1.4; p = 0.07). There were no significant clinical outcome differences. Cell saver blood can be safely stored at the bedside for immediate transfusion for 24 hrs after collection. Administration of cell saver blood significantly reduces the number of RBC and coagulant product transfusions and donor exposures in the immediate postoperative period. Reduction of blood product transfusions has the potential to reduce transfusion-associated complications and decrease postoperative morbidity. Larger studies are needed to determine whether this transfusion strategy will improve clinical outcomes.

DCE-MRI-Derived Volume Transfer Constant (Ktrans) and DWI Apparent Diffusion Coefficient as Predictive Markers of Short- and Long-Term Efficacy of Chemoradiotherapy in Patients With Esophageal Cancer.

PubMed

Ye, Zhi-Min; Dai, Shu-Jun; Yan, Feng-Qin; Wang, Lei; Fang, Jun; Fu, Zhen-Fu; Wang, Yue-Zhen

2018-01-01

This study aimed to evaluate both the short- and long-term efficacies of chemoradiotherapy in relation to the treatment of esophageal cancer . This was achieved through the use of dynamic contrast-enhanced magnetic resonance imaging-derived volume transfer constant and diffusion weighted imaging-derived apparent diffusion coefficient . Patients with esophageal cancer were assigned into the sensitive and resistant groups based on respective efficacies in chemoradiotherapy. Dynamic contrast-enhanced magnetic resonance imaging and diffusion weighted imaging were used to measure volume transfer constant and apparent diffusion coefficient, while computed tomography was used to calculate tumor size reduction rate. Pearson correlation analyses were conducted to analyze correlation between volume transfer constant, apparent diffusion coefficient, and the tumor size reduction rate. Receiver operating characteristic curve was constructed to analyze the short-term efficacy of volume transfer constant and apparent diffusion coefficient, while Kaplan-Meier curve was employed for survival rate analysis. Cox proportional hazard model was used for the risk factors for prognosis of patients with esophageal cancer. Our results indicated reduced levels of volume transfer constant, while increased levels were observed in ADC min , ADC mean , and ADC max following chemoradiotherapy. A negative correlation was determined between ADC min , ADC mean , and ADC max , as well as in the tumor size reduction rate prior to chemoradiotherapy, whereas a positive correlation was uncovered postchemoradiotherapy. Volume transfer constant was positively correlated with tumor size reduction rate both before and after chemoradiotherapy. The 5-year survival rate of patients with esophageal cancer having high ADC min , ADC mean , and ADC max and volume transfer constant before chemoradiotherapy was greater than those with respectively lower values. According to the Cox proportional hazard model, ADC mean , clinical stage, degree of differentiation, and tumor stage were all confirmed as being independent risk factors in regard to the prognosis of patients with EC. The findings of this study provide evidence suggesting that volume transfer constant and apparent diffusion coefficient as being tools allowing for the evaluation of both the short- and long-term efficacies of chemoradiotherapy esophageal cancer treatment.

A Multi-institutional Clinical Trial of Rectal Dose Reduction via Injected Polyethylene-Glycol Hydrogel During Intensity Modulated Radiation Therapy for Prostate Cancer: Analysis of Dosimetric Outcomes

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

Song, Danny Y., E-mail: dsong2@jhmi.edu; Herfarth, Klaus K.; Uhl, Matthias

2013-09-01

Purpose: To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. Methods and Materials: Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥25%. Multiple regression analysis was performed tomore » evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. Results: Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. Conclusions: Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.« less

Rationale for the development and the mechanism of action of endoscopic thermal vapor ablation (InterVapor) for the treatment of emphysema.

PubMed

Kesten, Steven; Anderson, Joseph C; Tuck, Stephanie A

2012-07-01

Emphysema remains a disabling disease despite current treatment. Novel approaches to the underlying physiological abnormalities responsible for symptom generation are warranted. A review of current hypotheses and preclinical and clinical data on the utility of endoscopic thermal vapor ablation (InterVapor) in the treatment of emphysema. In animal studies, thermal energy in the form of heated water vapor both in healthy and in papain-induced emphysema in dogs and sheep leads to an inflammatory response followed by healing with airway and parenchymal fibrosis. The fibrosis and associated distal atelectasis result in volume reduction. The amount of thermal energy delivered has been based on the amount of target tissue mass determined from a high-resolution computed tomogram. Early human studies indicated the feasibility of InterVapor with 5 cal/g tissue; however, the dose appeared insufficient to induce lobar volume reduction. A study using 10 cal/g to 1 upper lobe (n=44) induced a mean of 46% lobar volume reduction at 12 months along with significant improvements in the physiology and health outcomes. InterVapor induces lung volume reduction in patients with emphysema. The mechanism of action is through a thermally induced inflammatory response followed by healing with subsequent remodeling of tissue (fibrosis and distal atelectasis).

Quantitative measurement of radiofrequency volumetric tissue reduction by multidetector CT in patients with inferior turbinate hypertrophy.

PubMed

Bahadir, Osman; Kosucu, Polat

2012-12-01

To objectively assess the efficacy of radiofrequency thermal ablation of inferior turbinate hypertrophy. Thirty-five patients with nasal obstruction secondary to inferior turbinate hypertrophy were prospectively enrolled. Radiofrequency energy was delivered to four sites in each inferior turbinate. Patients were evaluated before and 8 weeks after intervention. Subjective evaluation of nasal obstruction was performed using a visual analogue scale (VAS), and objective evaluation of the turbinate volume reduction was calculated using multidetector CT. Volumetric measurements of the preoperative inferior turbinate were compared with postoperative values on both sides. The great majority of patients (91.4%) exhibited subjective postoperative improvement. Mean obstruction (VAS) improved significantly from 7.45±1.48 to 3.54±1.96. Significant turbinate volume reduction was achieved by the surgery on both right and left sides [(preoperative vs. postoperative, right: 6.55±1.62cm(3) vs. 5.10±1.47cm(3), (P<0.01); left: 6.72±1.53cm(3) vs. 5.00±1.37cm(3), (P<0.01)] respectively. Radiofrequency is a safe and effective surgical procedure in reducing turbinate volume in patients with inferior turbinate hypertrophy. Multidetector CT is an objective method of assessment in detecting radiofrequency turbinate volume reduction. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Glomerular loss after arteriovenous and arterial clamping for renal warm ischemia in a swine model.

PubMed

Bechara, Gustavo Ruschi; Damasceno-Ferreira, José Aurelino; Abreu, Leonardo Albuquerque Dos Santos; Costa, Waldemar Silva; Sampaio, Francisco José Barcellos; Pereira-Sampaio, Marco Aurélio; Souza, Diogo Benchimol De

2016-11-01

To evaluate the glomerular loss after arteriovenous or arterial warm ischemia in a swine model. Twenty four pigs were divided into Group Sham (submitted to all surgical steps except the renal ischemia), Group AV (submitted to 30 minutes of warm ischemia by arteriovenous clamping of left kidney vessels), and Group A (submitted to 30 minutes of ischemia by arterial clamping). Right kidneys were used as controls. Weigh, volume, cortical volume, glomerular volumetric density (Vv[Glom]), volume-weighted glomerular volume (VWGV), and the total number of glomeruli were measured for each organ. Group AV showed a 24.5% reduction in its left kidney Vv[Glom] and a 25.4% reduction in the VWGV, when compared to the right kidney. Reductions were also observed when compared to kidneys of sham group. There was a reduction of 19.2% in the total number of glomeruli in AV kidneys. No difference was observed in any parameters analyzed on the left kidneys from group A. Renal warm ischemia of 30 minutes by arterial clamping did not caused significant glomerular damage, but arteriovenous clamping caused significant glomerular loss in a swine model. Clamping only the renal artery should be considered to minimize renal injury after partial nephrectomies.

Maturation of sperm volume regulation in the rat epididymis

PubMed Central

Damm, Oliver S.; Cooper, Trevor G.

2010-01-01

Sperm maturation in the epididymis may involve differences between mature and immature spermatozoa in their volume regulatory osmolyte response. Spermatozoa obtained from the rat caput and cauda epididymidis were examined for their ability to regulate volume after transfer from in situ epididymal osmolality (measured to be 343 ± 13 and 365 ± 19 mmol kg−1, respectively) to that of the female tract in single- and multiple-step protocols. Cells withstood the single-step treatment better than the multistep protocol. Sperm volume estimates by flow cytometric measurements of forward scatter of cells with intact head membranes was more sensitive than those by assessing cell coiling microscopically. At osmolalites below 210 mmol kg−1 both caput and cauda cells ruptured, limiting the use of flow cytometry. Above this critical value, the use of quinine showed that both caput and cauda cells could regulate volume, but cauda cells were the more effective. Of several organic osmolytes studied, myo-inositol, glutamate and KCl caused only temporary and slight swelling of spermatozoa cells in hypotonic medium. Spermatozoa of both maturities seemed to use potassium as the preferred osmolyte for regulating volume. PMID:20531277

Lethality of chlorine, chlorine dioxide, and a commercial fruit and vegetable sanitizer to vegetative cells and spores of Bacillus cereus and spores of Bacillus thuringiensis.

PubMed

Beuchat, Larry R; Pettigrew, Charles A; Tremblay, Mario E; Roselle, Brian J; Scouten, Alan J

2004-08-01

Chlorine, ClO2, and a commercial raw fruit and vegetable sanitizer were evaluated for their effectiveness in killing vegetative cells and spores of Bacillus cereus and spores of Bacillus thuringiensis. The ultimate goal was to use one or both species as a potential surrogate(s) for Bacillus anthracis in studies that focus on determining the efficacy of sanitizers in killing the pathogen on food contact surfaces and foods. Treatment with alkaline (pH 10.5 to 11.0) ClO2 (200 microg/ml) produced by electrochemical technologies reduced populations of a five-strain mixture of vegetative cells and a five-strain mixture of spores of B. cereus by more than 5.4 and more than 6.4 log CFU/ml respectively, within 5 min. This finding compares with respective reductions of 4.5 and 1.8 log CFU/ml resulting from treatment with 200 microg/ml of chlorine. Treatment with a 1.5% acidified (pH 3.0) solution of Fit powder product was less effective, causing 2.5- and 0.4-log CFU/ml reductions in the number of B. cereus cells and spores, respectively. Treatment with alkaline ClO2 (85 microg/ml), acidified (pH 3.4) ClO2 (85 microg/ml), and a mixture of ClO2 (85 microg/ml) and Fit powder product (0.5%) (pH 3.5) caused reductions in vegetative cell/spore populations of more than 5.3/5.6, 5.3/5.7, and 5.3/6.0 log CFU/ml, respectively. Treatment of B. cereus and B. thuringiensis spores in a medium (3.4 mg/ml of organic and inorganic solids) in which cells had grown and produced spores with an equal volume of alkaline (pH 12.1) ClO2 (400 microg/ml) for 30 min reduced populations by 4.6 and 5.2 log CFU/ml, respectively, indicating high lethality in the presence of materials other than spores that would potentially react with and neutralize the sporicidal activity of ClO2.

The Effect of Microstructure and Pre-strain on the Change in Apparent Young's Modulus of a Dual-Phase Steel

NASA Astrophysics Data System (ADS)

Kupke, A.; Hodgson, P. D.; Weiss, M.

2017-07-01

The elastic recovery in dual-phase (DP) steels is not a linear process and changes with plastic deformation. The level of change in the apparent Young's modulus has been reported to depend on material composition and microstructure, but most previous experimental studies were limited to industrial DP steels and led to contradicting results. This work represents a first fundamental study that investigates the separate and combined effect of phase volume fraction and hardness on the change in apparent Young's modulus in DP steel. A common automotive DP steel (DP780) is heat treated to obtain seven different combinations of martensite and ferrite volume fraction and hardness while keeping the chemical composition as well as the shape of the martensite and ferrite phases unchanged. Loading-unloading tests were performed to analyze the chord modulus at various levels of pre-strain. The results suggest that the point of saturation of the chord modulus with pre-strain depends on the morphology of the microstructure, occurring earlier for microstructures consisting of ferrite grains surrounded by martensite laths. It is further revealed that the reduction of the apparent Young's modulus, which is the difference between the material's initial Young's modulus and the chord modulus, increases with martensite hardness if the martensite volume fraction is kept constant. A higher martensite volume fraction initially elevates the reduction of the apparent Young's modulus. After a critical volume fraction of martensite phase of 35%, a decrease in apparent Young's modulus reduction was observed. A comparison of the plastic unloading strain suggests that the mechanisms leading to a reduction in apparent Young's modulus are strongest for the microstructure consisting of 35% martensite volume fraction.

Bronchoscopic Thermal Vapor Ablation: Best Practice Recommendations from an Expert Panel on Endoscopic Lung Volume Reduction.

PubMed

Gompelmann, Daniela; Shah, Pallav L; Valipour, Arschang; Herth, Felix J F

2018-06-12

Bronchoscopic thermal vapor ablation (BTVA) represents one of the endoscopic lung volume reduction (ELVR) techniques that aims at hyperinflation reduction in patients with advanced emphysema to improve respiratory mechanics. By targeted segmental vapor ablation, an inflammatory response leads to tissue and volume reduction of the most diseased emphysematous segments. So far, BTVA has been demonstrated in several single-arm trials and 1 multinational randomized controlled trial to improve lung function, exercise capacity, and quality of life in patients with upper lobe-predominant emphysema irrespective of the collateral ventilation. In this review, we emphasize the practical aspects of this ELVR method. Patients with upper lobe-predominant emphysema, forced expiratory volume in 1 second (FEV1) between 20 and 45% of predicted, residual volume (RV) > 175% of predicted, and carbon monoxide diffusing capacity (DLCO) ≥20% of predicted can be considered for BTVA treatment. Prior to the procedure, a special software assists in identifying the target segments with the highest emphysema index, volume and the highest heterogeneity index to the untreated ipsilateral lung lobes. The procedure may be performed under deep sedation or preferably under general anesthesia. After positioning of the BTVA catheter and occlusion of the target segment by the occlusion balloon, heated water vapor is delivered in a predetermined specified time according to the vapor dose. After the procedure, patients should be strictly monitored to proactively detect symptoms of localized inflammatory reaction that may temporarily worsen the clinical status of the patient and to detect complications. As the data are still very limited, BTVA should be performed within clinical trials or comprehensive registries where the product is commercially available. © 2018 S. Karger AG, Basel.

Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Carboplatin Effects Against Ovarian Cancer.

PubMed

Yu, Jun; Ma, Yan; Drisko, Jeanne; Chen, Qi

2013-12-01

Tumor resistance to platinum-based drugs has been an obstacle to the treatment of ovarian cancer. Extract of the plant Rauwolfia vomitoria has long been used by cancer patients. However, there have not been systematic studies of its anticancer activity. In an effort to enhance the effectiveness of platinum-based drugs, we investigated the anticancer effect of a Rauwolfia vomitoria extract (Rau), both alone and in combination with carboplatin (Cp). In vitro cytotoxicity and colony formation were evaluated in several ovarian cancer cell lines. In vivo effects were evaluated in an intraperitoneal ovarian cancer mouse model. The combination of Rau and Cp was assessed using Chou-Talalay's constant ratio design and median effect analysis based on the isobologram principle to determine the combination index values. Rau decreased cell growth in all 3 tested ovarian cancer cell lines dose dependently and completely inhibited formation of colonies in soft agar. Apoptosis was induced in a time- and dose-dependent manner and was the predominant form of Rau-induced cell death. Synergy of Rau with Cp was detected, with combination index values <1 and dose reduction index values for Cp ranging from 1.7- to 7-fold. Tumor growth in mice was significantly suppressed by 36% or 66% with Rau treatment alone at a low (20 mg/kg) or a high dose (50 mg/kg), respectively, an effect comparable to that of Cp alone. The volume of ascitic fluid and the number of nonblood cells in ascites were also significantly decreased. Combining Rau with Cp remarkably enhanced the effect of Cp and reduced tumor burden by 87% to 90% and ascites volume by 89% to 97%. Rau has potent antitumor activity and in combination significantly enhances the effect of Cp against ovarian cancer.

Optimization for the blockade of epidermal growth factor receptor signaling for therapy of human pancreatic carcinoma.

PubMed

Solorzano, C C; Baker, C H; Tsan, R; Traxler, P; Cohen, P; Buchdunger, E; Killion, J J; Fidler, I J

2001-08-01

We determined the optimal administration schedule of a novel epidermal growth factor receptor (EGFR) protein tyrosine kinase inhibitor (PKI), PKI 166 (4-(R)-phenethylamino-6-(hydroxyl)phenyl-7H-pyrrolo[2.3-d]-pyrimidine), alone or in combination with gemcitabine (administered i.p.) for therapy of L3.6pl human pancreatic carcinoma growing in the pancreas of nude mice. Seven days after orthotopic implantation of L3.6pl cells, the mice received daily oral doses of PKI 166. PKI 166 therapy significantly inhibited phosphorylation of the EGFR without affecting EGFR expression. EGFR phosphorylation was restored 72 h after cessation of therapy. Seven days after orthotopic injection of L3.6pl cells, groups of mice received daily or thrice weekly oral doses of PKI 166 alone or in combination with gemcitabine. Treatment with PKI 166 (daily), PKI 166 (3 times/week), or gemcitabine alone produced a 72%, 69%, or 70% reduction in the volume of pancreatic tumors in mice, respectively. Daily oral PKI 166 or thrice weekly oral PKI 166 in combination with injected gemcitabine produced 97% and 95% decreases in volume of pancreatic cancers and significant inhibition of lymph node and liver metastasis. Daily oral PKI 166 produced a 20% decrease in body weight, whereas treatment 3 times/week did not. Decreased microvessel density, decreased proliferating cell nuclear antigen staining, and increased tumor cell and endothelial cell apoptosis correlated with therapeutic success. Collectively, our results demonstrate that three weekly oral administrations of an EGFR tyrosine kinase inhibitor in combination with gemcitabine are sufficient to significantly inhibit primary and metastatic human pancreatic carcinoma.

Absence of gender effect on amygdala volume in temporal lobe epilepsy.

PubMed

Silva, Ivaldo; Lin, Katia; Jackowski, Andrea P; Centeno, Ricardo da Silva; Pinto, Magali L; Carrete, Henrique; Yacubian, Elza M; Amado, Débora

2010-11-01

Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres. Copyright © 2010 Elsevier Inc. All rights reserved.

Theoretical study of the partial molar volume change associated with the pressure-induced structural transition of ubiquitin

PubMed Central

Imai, Takashi; Ohyama, Shusaku; Kovalenko, Andriy; Hirata, Fumio

2007-01-01

The partial molar volume (PMV) change associated with the pressure-induced structural transition of ubiquitin is analyzed by the three-dimensional reference interaction site model (3D-RISM) theory of molecular solvation. The theory predicts that the PMV decreases upon the structural transition, which is consistent with the experimental observation. The volume decomposition analysis demonstrates that the PMV reduction is primarily caused by the decrease in the volume of structural voids in the protein, which is partially canceled by the volume expansion due to the hydration effects. It is found from further analysis that the PMV reduction is ascribed substantially to the penetration of water molecules into a specific part of the protein. Based on the thermodynamic relation, this result implies that the water penetration causes the pressure-induced structural transition. It supports the water penetration model of pressure denaturation of proteins proposed earlier. PMID:17660257

Theoretical study of the partial molar volume change associated with the pressure-induced structural transition of ubiquitin.

PubMed

Imai, Takashi; Ohyama, Shusaku; Kovalenko, Andriy; Hirata, Fumio

2007-09-01

The partial molar volume (PMV) change associated with the pressure-induced structural transition of ubiquitin is analyzed by the three-dimensional reference interaction site model (3D-RISM) theory of molecular solvation. The theory predicts that the PMV decreases upon the structural transition, which is consistent with the experimental observation. The volume decomposition analysis demonstrates that the PMV reduction is primarily caused by the decrease in the volume of structural voids in the protein, which is partially canceled by the volume expansion due to the hydration effects. It is found from further analysis that the PMV reduction is ascribed substantially to the penetration of water molecules into a specific part of the protein. Based on the thermodynamic relation, this result implies that the water penetration causes the pressure-induced structural transition. It supports the water penetration model of pressure denaturation of proteins proposed earlier.

Fasciolicidal efficacy of Albizia anthelmintica and Balanites aegyptiaca compared with albendazole.

PubMed

Koko, W S; Galal, M; Khalid, H S

2000-07-01

An attempt was made to evaluate the oral doses of 9 g/kg-body weight of Albizzia anthelmintica Brong. Mimoaseae stem bark water extract and 9 g/kg body weight of B. aegyptiaca (L) Del. (Balanitaceae) fruit mesocarp water extract (traditionally used as an anthelmintic in the Sudan) compared with 20 mg/kg body weight (recommended dose) of albendazole against Fasciola gigantica adult worm (12 weeks old) in five groups each of three goats (6 month old). Group (I) uninfected control, group (II) infected untreated control, group (III, IV and V) infected and treated as mentioned above respectively. Based on the percentage reduction in fluke counts from the liver post mortum 2 weeks after treatment, the efficacy of the mentioned therapeutics was 95.5, 93.2 and 97.7%, respectively. The characteristic lesions of liver fasciolosis, egg/gm of faeces (EPG), packed cell volume (PCV), haemoglobin concentration, total red blood cells count (RBC), total white blood cells count (WBC) and oesinophil% were significantly different from control and treated groups (P<0.05).

Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

PubMed Central

Otto, Christoph; Kaemmerer, Ulrike; Illert, Bertram; Muehling, Bettina; Pfetzer, Nadja; Wittig, Rainer; Voelker, Hans Ullrich; Thiede, Arnulf; Coy, Johannes F

2008-01-01

Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis. PMID:18447912

A high gas fraction, reduced power, syngas bioprocessing method demonstrated with a Clostridium ljungdahlii OTA1 paper biocomposite

PubMed Central

Schulte, Mark J.; Wiltgen, Jeff; Ritter, John; Mooney, Charles B.; Flickinger, Michael C.

2018-01-01

We propose a novel approach to continuous bioprocessing of gases. A miniaturized coated-paper high gas fraction biocomposite absorber has been developed using slowly shaken horizontal anaerobic tubes with concentrated Clostridium ljungdahlii OTA1 absorbing syngas as a model system. These gas absorbers demonstrate elevated CO mass transfer with low power input, reduced liquid requirements, elevated substrate consumption, and increased product secretion compared to shaken suspended cells. We concentrate OTA1 in a cell paste which was coated by extrusion onto chromatography paper. Cell adhesion was by adsorption to the cellulose fibers; visualized by SEM. The C. ljungdahlii OTA1 coated paper mounted above the liquid level absorbs CO and H2 from a model syngas producing acetate with minimal ethanol. At 100 rpm shaking speed (7.7 W m−3) the optimal cell loading is 6.5 gDCW m−2 to maintain high CO absorbing reactivity without the cells coming off of the paper into the liquid phase. Reducing the medium volume from 10 mL to 4 mL (15% of tube volume) did not decrease CO reactivity. The reduced liquid volume increased secreted product concentration by 80%. The specific CO consumption by paper biocomposites was higher at all shaking frequencies <100 rpm than suspended cells under identical incubation conditions. At 25 rpm the biocomposite outperforms suspended cells for CO absorption by 2.5 fold, with a power reduction of 97% over the power input at 100 rpm. The estimated minimum apparent kLa for these biocomposite gas-absorbers is ~100 h−1, a 10 to 104 less power input than other syngas fermentation systems at similar kLa. Specific consumption rates in a biocomposite were measured as ~14 mmol gDCW−1 h−1. This work intensified CO absorption and reactivity by 14 fold to 94 mmol CO m−2 h−1 over previous C. ljungdahlii OTA1 work by our group. Specific acetate production rates were 23 mM h−1 or 46 mmol m−2 h−1. The specific rates and apparent kLa were shown to scale linearly with biocomposite coating area. These proof of concept results will be used to engineer a continuous biocomposite gas absorber bioreactor. PMID:26927418

Dioscin augments HSV-tk-mediated suicide gene therapy for melanoma by promoting connexin-based intercellular communication

PubMed Central

Li, Bin; Wu, Yingya; Liu, Xijuan; Tan, Yuhui; Du, Biaoyan

2017-01-01

Suicide gene therapy is a promising strategy against melanoma. However, the low efficiency of the gene transfer technique can limit its application. Our preliminary data showed that dioscin, a glucoside saponin, could upregulate the expression of connexins Cx26 and Cx43, major components of gap junctions, in melanoma cells. We hypothesized that dioscin may increase the bystander effect of herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) through increasing the formation of gap junctions. Further analysis showed that dioscin indeed could increase the gap junctional intercellular communication in B16 melanoma cells, resulting in more efficient GCV-induced bystander killing in B16tk cells. By contrast, overexpression of dominant negative Cx43 impaired the cell-cell communication of B16 cells and subsequently weakened the bystander effect of HSV-tk/GCV gene therapy. In vivo, combination treatment with dioscin and GCV of tumor-bearing mice with 30% positive B16tk cells and 70% wild-type B16 cells caused a significant reduction in tumor volume and weight compared to treatment with GCV or dioscin alone. Taken together, these results demonstrated that dioscin could augment the bystander effect of the HSV-tk/GCV system through increasing connexin-mediated gap junction coupling. PMID:27903977

Fuel cells for transport: can the promise be fulfilled? Technical requirements and demands from customers

NASA Astrophysics Data System (ADS)

Klaiber, Thomas

The paper discusses the technical requirements and the customer demands for vehicles that have an on-board methanol reformer and fuel cells. The research concentrates on the technical developmental risks which include minimizing volume, reducing weight and, at the same time, improving efficiency and system dynamics. Fuel cell powered vehicles with methanol reformers are not only suitable for a niche market but also these vehicles will compete with conventional vehicles. The greatest hindrance will be the price of the fuel cell. A possible progressive development of the number of fuel cell powered vehicles in conjunction with a reduction in costs will be discussed in the paper. When fuel cell vehicles come to the market it is necessary that an infrastructure for the fuel methanol or hydrogen is installed. Therefore, it will only be possible to introduce fuel cell vehicles into special markets, e.g. California. Such a process will need to be subsidized by additional incentives like tax concessions. Today there are many technical risks and unsolved problems relating to production technologies, infrastructure, and costs. Nevertheless, among the alternative power units, the fuel cell seems to be the only one that might be competitive to the conventional power unit, especially relating to emissions.

Simultaneous reduction of nitrate and selenate by cell suspensions of selenium-respiring bacteria

USGS Publications Warehouse

Oremland, R.S.; Blum, J.S.; Bindi, A.B.; Dowdle, P.R.; Herbel, M.; Stolz, J.F.

1999-01-01

Washed-cell suspensions of Sulfurospirillum barnesii reduced selenate [Se(VI)] when cells were cultured with nitrate, thiosulfate, arsenate, or fumarate as the electron acceptor. When the concentration of the electron donor was limiting, Se(VI) reduction in whole cells was approximately fourfold greater in Se(VI)-grown cells than was observed in nitrate-grown cells; correspondingly, nitrate reduction was ~11-fold higher in nitrate-grown cells than in Se(VI)-grown cells. However, a simultaneous reduction of nitrate and Se(VI) was observed in both cases. At nonlimiting electron donor concentrations, nitrate- grown cells suspended with equimolar nitrate and selenate achieved a complete reductive removal of nitrogen and selenium oxyanions, with the bulk of nitrate reduction preceding that of selenate reduction. Chloramphenicol did not inhibit these reductions. The Se(VI)-respiring haloalkaliphile Bacillus arsenicoselenatis gave similar results, but its Se(VI) reductase was not constitutive in nitrate-grown cells. No reduction of Se(VI) was noted for Bacillus selenitireducens, which respires selenite. The results of kinetic experiments with cell membrane preparations of S. barnesii suggest the presence of constitutive selenate and nitrate reduction, as well as an inducible, high- affinity nitrate reductase in nitrate-grown cells which also has a low affinity for selenate. The simultaneous reduction of micromolar Se(VI) in the presence of millimolar nitrate indicates that these organisms may have a functional use in bioremediating nitrate-rich, seleniferous agricultural wastewaters. Results with 75Se-selenate tracer show that these organisms can lower ambient Se(VI) concentrations to levels in compliance with new regulations proposed for release of selenium oxyanions into the environment.

Group differences in anterior hippocampal volume and in the retrieval of spatial and temporal context memory in healthy young versus older adults.

PubMed

Rajah, M Natasha; Kromas, Michelle; Han, Jung Eun; Pruessner, Jens C

2010-12-01

The ability to retrieve temporal and spatial context information from memory declines with healthy aging. The hippocampus (HC) has been shown to be associated with successful encoding and retrieval of spatio-temporal context, versus item recognition information (Davachi, Mitchell, & Wagner, 2003; Nadel, Samsonovich, Ryan, & Moscovitch, 2000; Ross & Slotnick, 2008). Aging has been linked to volume reduction in the HC (Bouchard, Malykhin, Martin, Hanstock, Emery, Fisher, & Camicioli, 2008; Malykhin, Bouchard, Camicioli, & Coupland, 2008; Raz et al., 2005). As such, age-associated reductions in anterior HC volume may contribute to the context memory deficits observed in older adults. In the current MRI study we investigated whether item recognition, spatial context and temporal context memory performance would be predicted by regional volumes in HC head (HH), body (HB) and tail (HT) volumes, using within group multiple regression analyses in a sample of 19 healthy young (mean age 24.3) and 20 older adults (mean age 67.7). We further examined between age-group differences in the volumes of the same HC sub-regions. Multiple regression analyses revealed that in younger adults both spatial and temporal context retrieval performance was predicted by anterior HC volume. Older age was associated with significant volume reductions in HH and HB, but not HT; and with reduced ability to retrieve spatial and temporal contextual details from episodic memory. However, HC volumes did not predict context retrieval performance in older adults. We conclude that individual differences in anterior, not posterior, HC volumes predict context memory performance in young adults. With age there may be a posterior-to-anterior shift from using HC-related processes, due to HC volume loss, to employing the prefrontal cortex to aid in the performance of cognitively demanding context memory tasks. However, due to concomitant changes in the prefrontal system with age, there are limits to compensation in the aging brain. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

The effect of laparotomy and external fixator stabilization on pelvic volume in an unstable pelvic injury.

PubMed

Ghanayem, A J; Wilber, J H; Lieberman, J M; Motta, A O

1995-03-01

Determine if laparotomy further destabilizes an unstable pelvic injury and increases pelvic volume, and if reduction and stabilization restores pelvic volume and prevents volume changes secondary to laparotomy. Cadaveric pelvic fracture model. Unilateral open-book pelvic ring injuries were created in five fresh cadaveric specimens by directly disrupting the pubic symphysis, left sacroliac joint, and sacrospinous and sacrotuberous ligaments. Pelvic volume was determined using computerized axial tomography for the intact pelvis, disrupted pelvis with both a laparotomy incision opened and closed, and disrupted pelvis stabilized and reduced using an external fixator with the laparotomy incision opened. The average volume increase in the entire pelvis (from the top of the iliac crests to the bottom of the ischial tuberosities) between a nonstabilized injury with the abdomen closed and then subsequently opened was 15 +/- 5% (423 cc). The average increase in entire pelvic volume between a stabilized and reduced pelvis and nonstabilized pelvis, both with the abdomen open, was 26 +/- 5% (692 cc). The public diastasis increased from 3.9 to 9.3 cm in a nonstabilized pelvis with the abdomen closed and then subsequently opened. Application of a single-pin anterior-frame external fixator reduced the pubic diastasis anatomically and reduced the average entire and true (from the pelvic brim to the ischeal tuberosities) pelvic volumes to within 3 +/- 4 and 8 +/- 6% of the initial volume, respectively. We believe that the abdominal wall provides stability to an unstable pelvic ring injury via a tension band effect on the iliac wings. Our results demonstrate that a laparotomy further destabilized an open-book pelvic injury and subsequently increased pelvic volume and pubic diastasis. This could potentially increase blood loss from the pelvic injury and delay the tamponade effect of reduction and stabilization. A single-pin external fixator prevents the destabilizing effect of the laparotomy and effectively reduces pelvic volume. These data support reduction and temporary stabilization of unstable pelvic injuries before or concomitantly with laparotomy.

Effect of the oncolytic ECHO-7 virus Rigvir® on the viability of cell lines of human origin in vitro.

PubMed

Tilgase, Andra; Patetko, Liene; Blāķe, Ilze; Ramata-Stunda, Anna; Borodušķis, Mārtiņš; Alberts, Pēteris

2018-01-01

Background: The role of oncolytic viruses in cancer treatment is increasingly studied. The first oncolytic virus (Rigvir®, ECHO-7) was registered in Latvia over a decade ago. In a recent retrospective study Rigvir® decreased mortality 4.39-6.57-fold in stage IB-IIC melanoma patients. The aims of the present study are to test the effect of Rigvir® on cell line viability in vitro and to visualize the cellular presence of Rigvir® by immunocytochemistry. Methods: The cytolytic effect of Rigvir® on the viability of FM-9, RD, AGS, A549, HDFa, HPAF‑II, MSC, MCF7, HaCaT, and Sk-Mel-28 cell lines was measured using live cell imaging. PBMC viability was measured using flow cytometry. The presence of ECHO-7 virus was visualized using immunocytochemistry. Statistical difference between treatment groups was calculated using two-way ANOVA. Results: Rigvir® (10%, volume/volume) reduced cell viability in FM-9, RD, AGS, A549, HDFa, HPAF‑II and MSC cell lines by 67-100%. HaCaT cell viability was partly affected while Rigvir® had no effect on MCF7, Sk-Mel-28 and PBMC viability. Detection of ECHO-7 by immunocytochemistry in FM-9, RD, AGS, A549, HDFa, HPAF-II and Sk-Mel-28 cell lines suggests that the presence of Rigvir® in the cells preceded or coincided with the time of reduction of cell viability. Rigvir® (10%) had no effect on live PBMC count. Conclusions: The results suggest that Rigvir® in vitro reduces the viability of cells of human melanoma, rhabdomyosarcoma, gastric adenocarcinoma, lung carcinoma, pancreas adenocarcinoma but not in PBMC. The presence of Rigvir® in the sensitive cells was confirmed using anti-ECHO-7 antibodies. The present results suggest that a mechanism of action for the clinical benefit of Rigvir® is its cytolytic properties. The present results suggest that the effect of Rigvir® could be tested in other cancers besides melanoma. Further studies of possible Rigvir® entry receptors are needed.

Constant volume gas cell optical phase-shifter

DOEpatents

Phillion, Donald W.

2002-01-01

A constant volume gas cell optical phase-shifter, particularly applicable for phase-shifting interferometry, contains a sealed volume of atmospheric gas at a pressure somewhat different than atmospheric. An optical window is present at each end of the cell, and as the length of the cell is changed, the optical path length of a laser beam traversing the cell changes. The cell comprises movable coaxial tubes with seals and a volume equalizing opening. Because the cell is constant volume, the pressure, temperature, and density of the contained gas do not change as the cell changes length. This produces an exactly linear relationship between the change in the length of the gas cell and the change in optical phase of the laser beam traversing it. Because the refractive index difference between the gas inside and the atmosphere outside is very much the same, a large motion must be made to change the optical phase by the small fraction of a wavelength that is required by phase-shifting interferometry for its phase step. This motion can be made to great fractional accuracy.

A Solar Volumetric Receiver: Influence of Absorbing Cells Configuration on Device Thermal Performance

NASA Astrophysics Data System (ADS)

Yilbas, B. S.; Shuja, S. Z.

2017-01-01

Thermal performance of a solar volumetric receiver incorporating the different cell geometric configurations is investigated. Triangular, hexagonal, and rectangular absorbing cells are incorporated in the analysis. The fluid volume fraction, which is the ratio of the volume of the working fluid over the total volume of solar volumetric receiver, is introduced to assess the effect of cell size on the heat transfer rates in the receiver. In this case, reducing the fluid volume fraction corresponds to increasing cell size in the receiver. SiC is considered as the cell material, and air is used as the working fluid in the receiver. The Lambert's Beer law is incorporated to account for the solar absorption in the receiver. A finite element method is used to solve the governing equation of flow and heat transfer. It is found that the fluid volume fraction has significant effect on the flow field in the solar volumetric receiver, which also modifies thermal field in the working fluid. The triangular absorbing cell gives rise to improved effectiveness of the receiver and then follows the hexagonal and rectangular cells. The second law efficiency of the receiver remains high when hexagonal cells are used. This occurs for the fluid volume fraction ratio of 0.5.

Computational Analysis of the Effect of Porosity on Shock Cell Strength at Cruise

NASA Technical Reports Server (NTRS)

Massey, Steven J.; Elmiligui, Alaa A.; Pao, S. Paul; Abdol-Hamid, Khaled S.; Hunter, Craig A.

2006-01-01

A computational flow field analysis is presented of the effect of core cowl porosity on shock cell strength for a modern separate flow nozzle at cruise conditions. The goal of this study was to identify the primary physical mechanisms by which the application of porosity can reduce shock cell strength and hence the broadband shock associated noise. The flow is simulated by solving the asymptotically steady, compressible, Reynoldsaveraged Navier-Stokes equations on a structured grid using an implicit, up-wind, flux-difference splitting finite volume scheme. The standard two-equation k - epsilon turbulence model with a linear stress representation is used with the addition of a eddy viscosity dependence on total temperature gradient normalized by local turbulence length scale. Specific issues addressed in this study were the optimal area required to weaken a shock impinging on the core cowl surface and the optimal level of porosity and placement of porous areas for reduction of the overall shock cell strength downstream. Two configurations of porosity were found to reduce downstream shock strength by approximately 50%.

Integrated microfluidic systems for sample preparation and detection of respiratory pathogen Bordetella pertussis.

PubMed

de la Rosa, Carlos; Prakash, Ranjit; Tilley, Peter A; Fox, Julie D; Kaler, Karan V i S

2007-01-01

An integrated microfluidic system for combined manipulation, pre-concentration, and lysis of samples containing Bordetella pertussis by dielectrophoresis and electroporation has been developed and implemented. The microfluidic device was able to pre-concentrate the amount of B. pertussis cells present in 200 microl of a B. pertussis suspension stock into a 20 microl volume. The device exhibited optimal sample pre-concentration of 6.7x at a stock value of 10(3) cfu/ml and at a flow rate of 250 microl/h. Electro-disruption experiments showed that on-chip-based electroporation is an effective solution for lysis of B. pertussis cells that is easily integrated with dielectrophoresis assisted pre-concentration procedures. Pulsed voltage applied, number of pulses, and presence of potassium chloride in a B. pertussis suspension showed a reduction in B. pertussis cell viability by electroporation; and transmission electron microscopy confirmed B. pertussis cell disruption by electroporation. Genetic amplification and detection of the pre-concentrated sample employing an integrated chip-based system demonstrated a complete chip approach for pathogen detection.

Preparation and in vitro function of granulocyte concentrates for transfusion to neonates using the IBM 2991 blood processor.

PubMed

Goldfinger, D; Medici, M A; Hsi, R; McPherson, J; Connelly, M

1983-01-01

Clinical studies have suggested that granulocyte transfusions may be of value in the treatment of septic neonatal patients who present with severe granulocytopenia. We have developed a protocol for the preparation of granulocyte concentrates from freshly collected units of whole blood, using an automated blood cell processor. The red cells were washed with saline. Then, the buffy coats were collected from the washed red cells and studied for their suitability as granulocyte concentrates for neonatal transfusion. The mean number of granulocytes per concentrate was 1.6 X 10(9) in a mean volume of 25 ml. Studies of granulocyte function, including viability, random mobility, chemotaxis, phagocytosis and nitro-blue tetrazolium reduction, demonstrated that the granulocytes were functionally unimpaired following preparation of the concentrates. These studies suggest that concentrates of functional granulocytes, suitable for transfusion to neonatal patients, can be prepared from fresh units of whole blood, using a cell processor. This procedure is more cost-effective than leukapheresis and allows for delivery of granulocytes for transfusion in a more timely fashion.

One-pot synthesis of transition metal ion-chelating ordered mesoporous carbon/carbon nanotube composites for active and durable fuel cell catalysts

NASA Astrophysics Data System (ADS)

Dombrovskis, Johanna K.; Palmqvist, Anders E. C.

2017-07-01

Development of non-precious metal catalysts for the oxygen reduction reaction (ORR) in proton exchange membrane (PEM) fuel cells with high activity and durability and with optimal water management properties is of outmost technological importance and highly challenging. Here we study the possibilities offered through judicious selection of small molecular precursors used for the formation of ordered mesoporous carbon-based non-precious metal ORR catalysts. By combining two complementary precursors, we present a one-pot synthesis that leads to a composite material consisting of transition metal ion-chelating ordered mesoporous carbon and multi-walled carbon nanotubes (TM-OMC/CNT). The resulting composite materials show high specific surface areas and a carbon structure that exhibits graphitic signatures. The synthesis procedure allows for tuning of the carbon structure, the surface area, the pore volume and the ratio of the two components of the composite. The TM-OMC/CNT composites were processed into membrane electrode assemblies and evaluated in single cell fuel cell measurements where they showed a combination of good ORR activity and very high durability.

Effects of nifedipine and captopril on vascular capacitance of ganglion-blocked anesthetized dogs.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1990-03-01

The hemodynamic effects of nifedipine and captopril at doses producing similar reductions in arterial pressure were studied in pentobarbital-anesthetized ventilated dogs after splenectomy during ganglion blockade with hexamethonium. Mean circulatory filling pressure (Pmcf) was determined during transient circulatory arrest induced by acetylcholine at baseline circulating blood volumes and after increases of 5 and 10 mL/kg. Central blood volumes (pulmonary artery to aortic root) were determined from transit times, and separately determined cardiac outputs (right atrium to pulmonary artery) were estimated by thermodilution. Nifedipine (n = 5) increased Pmcf at all circulating blood volumes and reduced total vascular capacitance without a change in total vascular compliance. Central blood volume, right atrial pressure, and cardiac output were increased with induced increases in circulating blood volume. In contrast, captopril (n = 5) did not alter total vascular capacitance, central blood volume, right atrial pressure, or cardiac output at baseline or with increased circulating volume. Thus, at doses producing similar reductions in arterial pressure, nifedipine but not captopril increased venous return and cardiac output in ganglion-blocked dogs.

Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: a case series and literature review.

PubMed

Heathcote, Karen L; Cockcroft, Donald W; Fladeland, Derek A; Fenton, Mark E

2011-01-01

Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

Three-dimensional confocal morphometry – a new approach for studying dynamic changes in cell morphology in brain slices

PubMed Central

Chvátal, Alexandr; Anděrová, Miroslava; Kirchhoff, Frank

2007-01-01

Pathological states in the central nervous system lead to dramatic changes in the activity of neuroactive substances in the extracellular space, to changes in ionic homeostasis and often to cell swelling. To quantify changes in cell morphology over a certain period of time, we employed a new technique, three-dimensional confocal morphometry. In our experiments, performed on enhanced green fluorescent protein/glial fibrillary acidic protein astrocytes in brain slices in situ and thus preserving the extracellular microenvironment, confocal morphometry revealed that the application of hypotonic solution evoked two types of volume change. In one population of astrocytes, hypotonic stress evoked small cell volume changes followed by a regulatory volume decrease, while in the second population volume changes were significantly larger without subsequent volume regulation. Three-dimensional cell reconstruction revealed that even though the total astrocyte volume increased during hypotonic stress, the morphological changes in various cell compartments and processes were more complex than have been previously shown, including swelling, shrinking and structural rearrangement. Our data show that astrocytes in brain slices in situ during hypotonic stress display complex behaviour. One population of astrocytes is highly capable of cell volume regulation, while the second population is characterized by prominent cell swelling, accompanied by plastic changes in morphology. It is possible to speculate that these two astrocyte populations play different roles during physiological and pathological states. PMID:17488344

Alteration of functional loads after tongue volume reduction.

PubMed

Ye, W; Duan, Y Z; Liu, Z J

2013-11-01

An earlier study revealed that the patterns of biomechanical loads on bones around the tongue altered significantly right after tongue volume reduction surgery. The current study was to examine whether these alterations persist or vanish over time post-surgery. Five sibling pairs of 12-week-old Yucatan minipigs were used. For each pair, one had surgery reducing tongue volume by about 15% (reduction) while the other had same incisions without tissue removal (sham). All animals were raised for 4 weeks after surgery. Three rosette strain gauges were placed on the bone surfaces of pre-maxilla (PM), mandibular incisor (MI), and mandibular molar (MM); two single-element gauges were placed across the pre-maxilla-maxillar suture (PMS) and mandibular symphysis (MSP), and two pressure transducers were placed on the bone surfaces of hard palate (PAL) and mandibular body (MAN). These bone strains and pressures were recorded during natural mastication. Overall amount of all loads increased significantly as compared to those in previous study in all animals. Instead of decreased loads in reduction animals as seen in that study, shear strains at PM, MI, and MM, tensile strains at PMS, and pressure at MAN were significantly higher in reduction than sham animals. Compared to the sham, strain dominance shifted at PM, MI, and MM and orientation of tensile strain altered at MI in reduction animals. A healed volume-reduced tongue may change loading regime significantly by elevating loading and altering strain-dominant pattern and orientation on its surrounding structures, and these changes are more remarkable in mandibular than maxillary sites. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fibrinogen Reduction During Selective Plasma Exchange due to Membrane Fouling.

PubMed

Ohkubo, Atsushi; Okado, Tomokazu; Miyamoto, Satoko; Hashimoto, Yurie; Komori, Shigeto; Yamamoto, Motoki; Maeda, Takuma; Itagaki, Ayako; Yamamoto, Hiroko; Seshima, Hiroshi; Kurashima, Naoki; Iimori, Soichiro; Naito, Shotaro; Sohara, Eisei; Uchida, Shinichi; Rai, Tatemitsu

2017-06-01

Fibrinogen is substantially reduced by most plasmapheresis modalities but retained in selective plasma exchange using Evacure EC-4A10 (EC-4A). Although EC-4A's fibrinogen sieving coefficient is 0, a session of selective plasma exchange reduced fibrinogen by approximately 19%. Here, we investigated sieving coefficient in five patients. When the mean processed plasma volume was 1.15 × plasma volume, the mean reduction of fibrinogen during selective plasma exchange was approximately 15%. Fibrinogen sieving coefficient was 0 when the processed plasma volume was 1.0 L, increasing to 0.07 when the processed plasma volume was 3.0 L, with a mean of 0.03 during selective plasma exchange. When fibrinogen sieving coefficient was 0, selective plasma exchange reduced fibrinogen by approximately 10%. Scanning electron microscopy images revealed internal fouling of EC-4A's hollow fiber membrane by substances such as fibrinogen fibrils. Thus, fibrinogen reduction by selective plasma exchange may be predominantly caused by membrane fouling rather than filtration. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Amplification volume reduction on DNA database samples using FTA™ Classic Cards.

PubMed

Wong, Hang Yee; Lim, Eng Seng Simon; Tan-Siew, Wai Fun

2012-03-01

The DNA forensic community always strives towards improvements in aspects such as sensitivity, robustness, and efficacy balanced with cost efficiency. Therefore our laboratory decided to study the feasibility of PCR amplification volume reduction using DNA entrapped in FTA™ Classic Card and to bring cost savings to the laboratory. There were a few concerns the laboratory needed to address. First, the kinetics of the amplification reaction could be significantly altered. Second, an increase in sensitivity might affect interpretation due to increased stochastic effects even though they were pristine samples. Third, statics might cause FTA punches to jump out of its allocated well into another thus causing sample-to-sample contamination. Fourth, the size of the punches might be too small for visual inspection. Last, there would be a limit to the extent of volume reduction due to evaporation and the possible need of re-injection of samples for capillary electrophoresis. The laboratory had successfully optimized a reduced amplification volume of 10 μL for FTA samples. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.