Sample records for cell volume distribution

  1. 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

  2. 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

  3. 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.

  4. Therapeutic analysis of high-dose-rate {sup 192}Ir vaginal cuff brachytherapy for endometrial cancer using a cylindrical target volume model and varied cancer cell distributions

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

    Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu; Donnelly, Eric D.; Strauss, Jonathan B.

    Purpose: To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model. Methods: A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model wasmore » used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution. Results: EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0){sup 4} to (13.4){sup 4} for the radiosensitive normal tissue depending on the cylinder size, treatment lengths, prescription depth, and dose as well. However, for a uniform cancer cell distribution, the EUDs were between 6.3 Gy × 4 and 7.1 Gy × 4, and the TRs were found to be between (1.4){sup 4} and (1.7){sup 4}. For the uniformly interspersed cancer and radio-resistant normal cells, the TRs were less than 1. The two VCBT prescription regimens were found to be equivalent in terms of EUDs and TRs. Conclusions: HDR VCBT strongly favors cylindrical target volume with the cancer cell distribution following its dosimetric trend. Assuming a half-Gaussian distribution of cancer cells, the HDR VCBT provides a considerable radiobiological advantage over the external beam radiotherapy (EBRT) in terms of sparing more normal tissues while maintaining the same level of cancer cell killing. But for the uniform cancer cell distribution and radio-resistant normal tissue, the radiobiology outcome of the HDR VCBT does not show an advantage over the EBRT. This study strongly suggests that radiation therapy design should consider the cancer cell distribution inside the target volume in addition to the shape of target.« less

  5. Monte Carlo calculated microdosimetric spread for cell nucleus-sized targets exposed to brachytherapy 125I and 192Ir sources and 60Co cell irradiation.

    PubMed

    Villegas, Fernanda; Tilly, Nina; Ahnesjö, Anders

    2013-09-07

    The stochastic nature of ionizing radiation interactions causes a microdosimetric spread in energy depositions for cell or cell nucleus-sized volumes. The magnitude of the spread may be a confounding factor in dose response analysis. The aim of this work is to give values for the microdosimetric spread for a range of doses imparted by (125)I and (192)Ir brachytherapy radionuclides, and for a (60)Co source. An upgraded version of the Monte Carlo code PENELOPE was used to obtain frequency distributions of specific energy for each of these radiation qualities and for four different cell nucleus-sized volumes. The results demonstrate that the magnitude of the microdosimetric spread increases when the target size decreases or when the energy of the radiation quality is reduced. Frequency distributions calculated according to the formalism of Kellerer and Chmelevsky using full convolution of the Monte Carlo calculated single track frequency distributions confirm that at doses exceeding 0.08 Gy for (125)I, 0.1 Gy for (192)Ir, and 0.2 Gy for (60)Co, the resulting distribution can be accurately approximated with a normal distribution. A parameterization of the width of the distribution as a function of dose and target volume of interest is presented as a convenient form for the use in response modelling or similar contexts.

  6. 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.

  7. Cell population data in neonates: differences by age group and associations with perinatal factors.

    PubMed

    Lee, J; Kim, S Y; Lee, W; Han, K; Sung, I K

    2015-10-01

    Cell population data (CPD) describe physical parameters of white blood cell subpopulations and are reported to be of some value in the diagnosis of sepsis in neonates. Before using the CPD for diagnosing sepsis, the baseline features of the CPD distribution in healthy neonates should be clarified. The aim of this study was to compare the CPD distributions of healthy neonates and other age groups and to identify perinatal factors that are associated with changes in the CPD distribution of healthy neonates. The CPD distribution of 69 samples from term neonates was compared with adolescents and adults. The CPD distribution of 163 samples from healthy neonates was analyzed in association with perinatal factors, including gestational age, chronologic age, birthweight, delivery mode, premature rupture of membranes, diabetes, and pregnancy-induced hypertension. The CPD distribution for term neonates was significantly different from those in adolescents and adults. The mean lymphocyte volume showed a negative correlation with gestational age at birth (r = -0.305; P < 0.01). The mean neutrophil volume was smaller in the cesarean section group than in the normal delivery group. The small for gestational age (SGA) group had smaller mean neutrophil volume and mean monocyte volume than the appropriate for gestational age group. The CPD distribution of healthy neonates differed from those of adolescents or adults, and the differences were associated with gestational age, delivery mode, and being SGA. © 2015 John Wiley & Sons Ltd.

  8. 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.

  9. Pore size engineering applied to starved electrochemical cells and batteries

    NASA Technical Reports Server (NTRS)

    Abbey, K. M.; Thaller, L. H.

    1982-01-01

    To maximize performance in starved, multiplate cells, the cell design should rely on techniques which widen the volume tolerance characteristics. These involve engineering capillary pressure differences between the components of an electrochemical cell and using these forces to promote redistribution of electrolyte to the desired optimum values. This can be implemented in practice by prescribing pore size distributions for porous back-up plates, reservoirs, and electrodes. In addition, electrolyte volume management can be controlled by incorporating different pore size distributions into the separator. In a nickel/hydrogen cell, the separator must contain pores similar in size to the small pores of both the nickel and hydrogen electrodes in order to maintain an optimum conductive path for the electrolyte. The pore size distributions of all components should overlap in such a way as to prevent drying of the separator and/or flooding of the hydrogen electrode.

  10. Three-phase boundary length in solid-oxide fuel cells: A mathematical model

    NASA Astrophysics Data System (ADS)

    Janardhanan, Vinod M.; Heuveline, Vincent; Deutschmann, Olaf

    A mathematical model to calculate the volume specific three-phase boundary length in the porous composite electrodes of solid-oxide fuel cell is presented. The model is exclusively based on geometrical considerations accounting for porosity, particle diameter, particle size distribution, and solids phase distribution. Results are presented for uniform particle size distribution as well as for non-uniform particle size distribution.

  11. Computational Fluid Dynamics-Population Balance Model Simulation of Effects of Cell Design and Operating Parameters on Gas-Liquid Two-Phase Flows and Bubble Distribution Characteristics in Aluminum Electrolysis Cells

    NASA Astrophysics Data System (ADS)

    Zhan, Shuiqing; Wang, Junfeng; Wang, Zhentao; Yang, Jianhong

    2018-02-01

    The effects of different cell design and operating parameters on the gas-liquid two-phase flows and bubble distribution characteristics under the anode bottom regions in aluminum electrolysis cells were analyzed using a three-dimensional computational fluid dynamics-population balance model. These parameters include inter-anode channel width, anode-cathode distance (ACD), anode width and length, current density, and electrolyte depth. The simulations results show that the inter-anode channel width has no significant effect on the gas volume fraction, electrolyte velocity, and bubble size. With increasing ACD, the above values decrease and more uniform bubbles can be obtained. Different effects of the anode width and length can be concluded in different cell regions. With increasing current density, the gas volume fraction and electrolyte velocity increase, but the bubble size keeps nearly the same. Increasing electrolyte depth decreased the gas volume fraction and bubble size in particular areas and the electrolyte velocity increased.

  12. Statistical self-similarity of hotspot seamount volumes modeled as self-similar criticality

    USGS Publications Warehouse

    Tebbens, S.F.; Burroughs, S.M.; Barton, C.C.; Naar, D.F.

    2001-01-01

    The processes responsible for hotspot seamount formation are complex, yet the cumulative frequency-volume distribution of hotspot seamounts in the Easter Island/Salas y Gomez Chain (ESC) is found to be well-described by an upper-truncated power law. We develop a model for hotspot seamount formation where uniform energy input produces events initiated on a self-similar distribution of critical cells. We call this model Self-Similar Criticality (SSC). By allowing the spatial distribution of magma migration to be self-similar, the SSC model recreates the observed ESC seamount volume distribution. The SSC model may have broad applicability to other natural systems.

  13. Identification of the Centrifuged Lipoaspirate Fractions Suitable for Postgrafting Survival.

    PubMed

    Qiu, Lihong; Su, Yingjun; Zhang, Dongliang; Song, Yajuan; Liu, Bei; Yu, Zhou; Guo, Shuzhong; Yi, Chenggang

    2016-01-01

    The Coleman centrifugation procedure generates fractions with different adipocyte and progenitor cell densities. This study aimed to identify all fractions that are feasible for implantation. Human lipoaspirates were processed by Coleman centrifugation. The centrifugates were divided arbitrarily into upper, middle, and lower layers. Adipocyte viability, morphology, numbers of stromal vascular fraction cells, and adipose-derived mesenchymal stem cells of each layer were determined. The 12-week volume retention of subcutaneously implanted 0.3-ml lipoasperate of each layer was investigated in an athymic mice model. Most damaged adipocytes were located in the upper layers, whereas the intact adipocytes were distributed in the middle and lower layers. A gradient of stromal vascular fraction cell density was formed in the centrifugates. The implant volume retentions of samples from the upper, middle, and lower layers were 33.44 ± 5.9, 55.11 ± 4.4, and 71.2 ± 5.8 percent, respectively. Furthermore, the middle and lower layers contained significantly more adipose-derived stem cells than did the upper layer. The lower layer contains more viable adipocytes and stromal vascular fraction cells leading to the highest implant volume retention, whereas the most impaired cells are distributed in the upper layer, leading to the least volume retention. Although with a lower stromal vascular fraction content, the middle layer has a substantial number of intact adipocytes that are capable of retaining partial adipose tissue volume after implantation, suggesting that the middle layer may be an alternative fat source when large volumes of fat grafts are needed for transplantation.

  14. Prediction of Packed Cell Volume after Whole Blood Transfusion in Small Ruminants and South American Camelids: 80 Cases (2006-2016).

    PubMed

    Luethy, D; Stefanovski, D; Salber, R; Sweeney, R W

    2017-11-01

    Calculation of desired whole blood transfusion volume relies on an estimate of an animal's circulating blood volume, generally accepted to be 0.08 L/kg or 8% of the animal's body weight in kilograms. To use packed cell volume before and after whole blood transfusion to evaluate the accuracy of a commonly used equation to predict packed cell volume after transfusion in small ruminants and South American camelids; to determine the nature and frequency of adverse transfusion reactions in small ruminants and camelids after whole blood transfusion. Fifty-eight small ruminants and 22 alpacas that received whole blood transfusions for anemia. Retrospective case series; medical record review for small ruminants and camelids that received whole blood transfusions during hospitalization. Mean volume of distribution of blood as a fraction of body weight in sheep (0.075 L/kg, 7.5% BW) and goats (0.076 L/kg, 7.6% BW) differed significantly (P < 0.01) from alpacas (0.103 L/kg, 10.3% BW). Mild transfusion reactions were noted in 16% of transfusions. The generally accepted value of 8% for circulating blood volume (volume of distribution of blood) is adequate for calculation of transfusion volumes; however, use of the species-specific circulating blood volume can improve calculation of transfusion volume to predict and achieve desired packed cell volume. The incidence of transfusion reactions in small ruminants and camelids is low. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  15. Specific binding of sup 125 I-rErythropoietin to Friend polycythemia virus-transformed erythroleukemia cells purified by centrifugal elutriation

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

    Correa, P.N.; Bard, V.; Axelrad, A.A.

    1990-01-01

    We have used countercurrent centrifugal elutriation (CCE) to determine the distribution of cells with respect to cell volume and buoyant density for an erythroleukemia cell line (JG6) transformed by the polycythemia strain of Friend virus (FV-P), and to determine the effect of inducing the cells to differentiate with dimethylsulfoxide (DMSO) on this distribution. CCE made it possible to obtain suspensions of modal JG6 populations virtually free of dead cells and uniform with respect to volume and buoyant density. These modal populations were assayed for specific binding of erythropoietin (Epo). Between 500 and 550 Epo receptors per cell were detected. Thesemore » belonged to a single class having a dissociation constant of 0.36 nM. DMSO induction of differentiation of the JG6 cells had no effect on the number of Epo receptors expressed.« less

  16. Respiration in heterotrophic unicellular eukaryotic organisms.

    PubMed

    Fenchel, Tom

    2014-08-01

    Surface:volume quotient, mitochondrial volume fraction, and their distribution within cells were investigated and oxygen gradients within and outside cells were modelled. Cell surface increases allometrically with cell size. Mitochondrial volume fraction is invariant with cell size and constitutes about 10% and mitochondria are predominantly found close to the outer membrane. The results predict that for small and medium sized protozoa maximum respiration rates should be proportional to cell volume (scaling exponent ≈1) and access to intracellular O2 is not limiting except at very low ambient O2-tensions. Available data do not contradict this and some evidence supports this interpretation. Cell size is ultimately limited because an increasing fraction of the mitochondria becomes exposed to near anoxic conditions with increasing cell size. The fact that mitochondria cluster close to the cell surface and the allometric change in cell shape with increasing cell size alleviates the limitation of aerobic life at low ambient O2-tension and for large cell size. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. Test functions for three-dimensional control-volume mixed finite-element methods on irregular grids

    USGS Publications Warehouse

    Naff, R.L.; Russell, T.F.; Wilson, J.D.; ,; ,; ,; ,; ,

    2000-01-01

    Numerical methods based on unstructured grids, with irregular cells, usually require discrete shape functions to approximate the distribution of quantities across cells. For control-volume mixed finite-element methods, vector shape functions are used to approximate the distribution of velocities across cells and vector test functions are used to minimize the error associated with the numerical approximation scheme. For a logically cubic mesh, the lowest-order shape functions are chosen in a natural way to conserve intercell fluxes that vary linearly in logical space. Vector test functions, while somewhat restricted by the mapping into the logical reference cube, admit a wider class of possibilities. Ideally, an error minimization procedure to select the test function from an acceptable class of candidates would be the best procedure. Lacking such a procedure, we first investigate the effect of possible test functions on the pressure distribution over the control volume; specifically, we look for test functions that allow for the elimination of intermediate pressures on cell faces. From these results, we select three forms for the test function for use in a control-volume mixed method code and subject them to an error analysis for different forms of grid irregularity; errors are reported in terms of the discrete L2 norm of the velocity error. Of these three forms, one appears to produce optimal results for most forms of grid irregularity.

  18. Distribution of dehydration rates generated by maximal Gardos-channel activation in normal and sickle red blood cells.

    PubMed

    Lew, Virgilio L; Tiffert, Teresa; Etzion, Zipora; Perdomo, Deisy; Daw, Nuala; Macdonald, Lynn; Bookchin, Robert M

    2005-01-01

    The Ca(2+)-activated K+ channels of human red blood cells (RBCs) (Gardos channels, hIK1, hSK4) can mediate rapid cell dehydration, of particular relevance to the pathophysiology of sickle cell disease. Previous investigations gave widely discrepant estimates of the number of Gardos channels per RBC, from as few as 1 to 3 to as many as 300, with large cell-to-cell differences, suggesting that RBCs could differ extensively in their susceptibility to dehydration by elevated Ca2+. Here we investigated the distribution of dehydration rates induced by maximal and uniform Ca2+ loads in normal (AA) and sickle (SS) RBCs by measuring the time-dependent changes in osmotic fragility and RBC volume distributions. We found a remarkable conservation of osmotic lysis and volume distribution profiles during Ca(2+)-induced dehydration, indicating overall uniformity of dehydration rates among AA and SS RBCs. In light of these results, alternative interpretations were suggested for the previously proposed low estimates and heterogeneity of channel numbers per cell. The results support the view that stochastic Ca2+ permeabilization rather than Gardos-channel variation is the main determinant selecting which SS cells dehydrate through Gardos channels in each sickling episode.

  19. Pore size engineering applied to the design of separators for nickel-hydrogen cells and batteries

    NASA Technical Reports Server (NTRS)

    Abbey, K. M.; Britton, D. L.

    1983-01-01

    Pore size engineering in starved alkaline multiplate cells involves adopting techniques to widen the volume tolerance of individual cells. Separators with appropriate pore size distributions and wettability characteristics (capillary pressure considerations) to have wider volume tolerances and an ability to resist dimensional changes in the electrodes were designed. The separators studied for potential use in nickel-hydrogen cells consist of polymeric membranes as well as inorganic microporous mats. In addition to standard measurements, the resistance and distribution of electrolyte as a function of total cell electrolyte content were determined. New composite separators consisting of fibers, particles and/or binders deposited on Zircar cloth were developed in order to engineer the proper capillary pressure characteristics in the separator. These asymmetric separators were prepared from a variety of fibers, particles and binders.

  20. Cell Size Regulation in Bacteria

    NASA Astrophysics Data System (ADS)

    Amir, Ariel

    2014-05-01

    Various bacteria such as the canonical gram negative Escherichia coli or the well-studied gram positive Bacillus subtilis divide symmetrically after they approximately double their volume. Their size at division is not constant, but is typically distributed over a narrow range. Here, we propose an analytically tractable model for cell size control, and calculate the cell size and interdivision time distributions, as well as the correlations between these variables. We suggest ways of extracting the model parameters from experimental data, and show that existing data for E. coli supports partial size control, and a particular explanation: a cell attempts to add a constant volume from the time of initiation of DNA replication to the next initiation event. This hypothesis accounts for the experimentally observed correlations between mother and daughter cells as well as the exponential dependence of size on growth rate.

  1. Altered peripheral profile of blood cells in Alzheimer disease

    PubMed Central

    Chen, Si-Han; Bu, Xian-Le; Jin, Wang-Sheng; Shen, Lin-Lin; Wang, Jun; Zhuang, Zheng-Qian; Zhang, Tao; Zeng, Fan; Yao, Xiu-Qing; Zhou, Hua-Dong; Wang, Yan-Jiang

    2017-01-01

    Abstract Alzheimer disease (AD) has been made a global priority for its multifactorial pathogenesis and lack of disease-modifying therapies. We sought to investigate the changes of profile of blood routine in AD and its correlation with the disease severity. In all, 92 AD patients and 84 age and sex-matched normal controls were enrolled and their profiles of blood routine were evaluated. Alzheimer disease patients had increased levels of mean corpuscular hemoglobin, mean corpuscular volume, red cell distribution width-standard deviation, mean platelet volume,and decreased levels of platelet distribution width, red blood cell, hematocrit, hemoglobin, lymphocyte, and basophil compared with normal controls. Alterations in quantity and quality of blood cells may be involved in the pathogenesis of AD and contribute to the disease progression. PMID:28538375

  2. 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.

  3. Structure-function relationships in the stem cell's mechanical world B: emergent anisotropy of the cytoskeleton correlates to volume and shape changing stress exposure.

    PubMed

    Chang, Hana; Knothe Tate, Melissa L

    2011-12-01

    In the preceding study (Part A), we showed that prescribed seeding conditions as well as seeding density can be used to subject multipotent stem cells (MSCs) to volume changing stresses and that changes in volume of the cell are associated with changes in shape, but not volume, of the cell nucleus. In the current study, we aim to control the mechanical milieu of live cells using these prescribed seeding conditions concomitant to delivery of shape changing stresses via fluid flow, while observing adaptation of the cytoskeleton, a major cellular transducer that modulates cell shape, stiffness and remodeling. We hypothesize that the spatiotemporal organization of tubulin and actin elements of the cytoskeleton changes in response to volume and shape changing stresses emulating those during development, prior to the first beating of the heart or twitching of muscle. Our approach was to quantify the change over baseline in spatiotemporal distribution of actin and tubulin in live C3H/10T1/2 model stem cells subjected to volume changing stresses induced by seeding at density as well as low magnitude, short duration, shape changing (shear) stresses induced by fluid flow (0.5 or 1.0 dyne/cm2 for 30/60/90 minutes). Upon exposure to fluid flow, both tubulin thickness (height) and concentration (fluorescence intensity) change significantly over baseline, as a function of proximity to neighboring cells (density) and the substrate (apical-basal height). Given our recently published studies showing amplification of stress gradients (flow velocity) with increasing distance to nearest neighbors and the substrate, i.e. with decreasing density and toward the apical side of the cell, tubulin adaptation appears to depend significantly on the magnitude of the stress to which the cell is exposed locally. In contrast, adaptation of actin to the changing mechanical milieu is more global, exhibiting less significant differences attributable to nearest neighbors or boundaries than differences attributable to magnitude of the stress to which the cell is exposed globally (0.5 versus 1.0 dyne/cm2). Furthermore, changes in the actin cytoskeletal distribution correlate positively with one pre-mesenchymal condensation marker (Msx2) and negatively with early markers of chondrogenesis (ColIIaI alone, indicative of pre-hypertrophic chondrogenesis) and osteogenesis (Runx2). Changes in the tubulin cytoskeletal distribution correlate positively with a marker of pericondensation (Sox9 alone), negatively with chondrogenesis (ColIIaI) and positively with adipogenesis (Ppar-gamma 2). Taken as a whole, exposure of MSCs to volume and shape changing stresses results in emergent anisotropy of cytoskeletal architecture (structure), which relate to emergent cell fate (function).

  4. Pore size engineering applied to the design of separators for nickel-hydrogen cells and batteries

    NASA Technical Reports Server (NTRS)

    Abbey, K. M.; Britton, D. L.

    1983-01-01

    Pore size engineering in starved alkaline multiplate cells involves adopting techniques to widen the volume tolerance of individual cells. Separators with appropriate pore size distributions and wettability characteristics (capillary pressure considerations) to have wider volume tolerances and an ability to resist dimensional changes in the electrodes were designed. The separators studied for potential use in nickel-hydrogen cells consist of polymeric membranes as well as inorganic microporous mats. In addition to standard measurements, the resistance and distribution of electrolyte as a function of total cell electrolyte content were determined. New composite separators consisting of fibers, particles and/or binders deposited on Zircar cloth were developed in order to engineer the proper capillary pressure characteristics in the separator. These asymmetric separators were prepared from a variety of fibers, particles and binders. Previously announced in STAR as N83-24571

  5. Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.

    PubMed

    Yang, Xiaoliang; Saito, Ryuta; Nakamura, Taigen; Zhang, Rong; Sonoda, Yukihiko; Kumabe, Toshihiro; Forsayeth, John; Bankiewicz, Krystof; Tominaga, Teiji

    2016-01-01

    In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells.

  6. 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.

  7. Optimization of gluten-free formulations for French-style breads.

    PubMed

    Mezaize, S; Chevallier, S; Le Bail, A; de Lamballerie, M

    2009-04-01

    The formulation of gluten-free bread, which will be suitable for patients with coeliac disease, was optimized to provide bread similar to French bread. The effects of the presence of hydrocolloids and the substitution of the flour basis by flour or proteins from different sources were studied. The added ingredients were (1) hydrocolloids (carboxymethylcellulose [CMC], guar gum, hydroxypropylmethylcellulose [HPMC], and xanthan gum), and (2) substitutes (buckwheat flour, whole egg powder, and whey proteins). The bread quality parameters measured were specific volume, dry matter of bread, crust color, crumb hardness, and gas cell size distribution. Specific volume was increased by guar gum and HPMC. Breads with guar gum had color characteristics similar to French bread. Hardness decreased with the addition of hydrocolloids, especially HPMC and guar. Breads with guar gum had the most heterogeneous cell size distribution, and guar gum was therefore selected for further formulations. Bread prepared with buckwheat flour had improved quality: an increased specific volume, a softer texture, color characteristics, and gas-cell size distribution similar to French bread. Bread with 1.9% guar gum (w/w, total flour basis) and 5% buckwheat flour (of all flours and substitutes) mimicked French bread quality attributes.

  8. Oxygen consumption rate and mitochondrial density in human melanoma monolayer cultures and multicellular spheroids.

    PubMed

    Hystad, M E; Rofstad, E K

    1994-05-15

    Rate of oxygen consumption per cell has been shown in previous studies to decrease with increasing depth in the viable rim of multicellular spheroids initiated from rodent cells, human colon-carcinoma cells, and human glioma cells, due to progressive accumulation of quiescent cells during spheroid growth. The purpose of our work was to determine oxygen-consumption profiles in human melanoma spheroids. Monolayer cultures of 4 lines (BEX-c, COX-c, SAX-c, and WIX-c) and spheroid cultures of 2 lines (BEX-c and WIX-c) were subjected to investigation. Spheroids were initiated from monolayer cell cultures and grown in spinner flasks. Rate of oxygen consumption was measured with a Clarke-type electrode. Mitochondrial density was determined by stereological analysis of transmission electron micrographs. Thickness of viable rim and cell packing density were assessed by light microscopy of central spheroid sections. Cell-cycle distribution was determined by analysis of DNA histograms measured by flow cytometry. Cell volume was measured by an electronic particle counter. Rate of oxygen consumption per cell differed by a factor of approximately 1.8 between the 4 cell lines and was positively correlated to total volume of mitochondria per cell. Rate of oxygen consumption per cell and total volume of mitochondria per cell were equal for monolayer cell cultures, 600-microns spheroids and 1,200-microns spheroids of the same line. Mitochondrial density and location in the cell did not differ between cells at the spheroid surface, in the middle of the viable rim and adjacent to the central necrosis. Cell-cycle distribution, cell volume, and cell-packing density in the outer and inner halves of the viable rim were not significantly different. Consequently, the rate of oxygen consumption per cell in inner regions of the viable rim was probably equal to that at the spheroid surface, suggesting that oxygen diffusion distances may be shorter in some melanomas than in many other tumor types.

  9. Stochastic modeling of cell growth with symmetric or asymmetric division

    NASA Astrophysics Data System (ADS)

    Marantan, Andrew; Amir, Ariel

    2016-07-01

    We consider a class of biologically motivated stochastic processes in which a unicellular organism divides its resources (volume or damaged proteins, in particular) symmetrically or asymmetrically between its progeny. Assuming the final amount of the resource is controlled by a growth policy and subject to additive and multiplicative noise, we derive the recursive integral equation describing the evolution of the resource distribution over subsequent generations and use it to study the properties of stable resource distributions. We find conditions under which a unique stable resource distribution exists and calculate its moments for the class of affine linear growth policies. Moreover, we apply an asymptotic analysis to elucidate the conditions under which the stable distribution (when it exists) has a power-law tail. Finally, we use the results of this asymptotic analysis along with the moment equations to draw a stability phase diagram for the system that reveals the counterintuitive result that asymmetry serves to increase stability while at the same time widening the stable distribution. We also briefly discuss how cells can divide damaged proteins asymmetrically between their progeny as a form of damage control. In the appendixes, motivated by the asymmetric division of cell volume in Saccharomyces cerevisiae, we extend our results to the case wherein mother and daughter cells follow different growth policies.

  10. Solar excitation of CdS/Cu2S photovoltaic cells

    NASA Technical Reports Server (NTRS)

    Boer, K. W.

    1976-01-01

    Solar radiation of five typical clear weather days and under a variety of conditions is used to determine the spectral distribution of the photonflux at different planes of a CdS/Cu2S solar cell. The fractions of reflected and absorbed flux are determined at each of the relevant interfaces and active volume elements of the solar cell. The density of absorbed photons is given in respect to spectral and spatial distribution. The variance of the obtained distribution, with changes in insolation and absorption spectra of the active solar cell layers, is indicated. A catalog of typical examples is given in the appendix.

  11. Sex Determination in Bees. IV. Genetic Control of Juvenile Hormone Production in MELIPONA QUADRIFASCIATA (Apidae)

    PubMed Central

    Kerr, Warwick Estevam; Akahira, Yukio; Camargo, Conceição A.

    1975-01-01

    Cell number and volume of corpora allata was determined for 8 phases of development, the first prepupal stage to adults 30 days old, in the social Apidae Melipona quadrifasciata. In the second prepupal stage a strong correlation was found between cell number and body weight ( r=0.651**), and cell number and corpora allata volume in prepupal stage (r=0.535*), which indicates that juvenile hormone has a definite role in caste determination in Melipona. The distribution of the volume of corpus allatum suggest a 3:1 segregation between bees with high volume of corpora allata against low and medium volume. This implies that genes xa and xb code for an enzyme that directly participates in juvenile hormone production. It was also concluded that the number of cells in the second prepupal stage is more important than the weight of the prepupa for caste determination. A scheme summarizing the genic control of sex and caste determination in Melipona bees in the prepupal phase is given. PMID:1213273

  12. Modulation of RBC volume distributions by oxidants (phenazine methosulfate and tert-butyl hydroperoxide): role of Gardos channel activation.

    PubMed

    Lisovskaya, Irina L; Shcherbachenko, Irina M; Volkova, Rimma I; Tikhonov, Vladimir P

    2008-06-01

    A study was made comparing the effects of two oxidants--phenazine methosulfate (50-1500 microM)+10 mM ascorbate and t-butyl hydroperoxide (1-3 mM)--on the volume-related parameters of normal human red blood cells. Incubation with either oxidative system for 20-30 min resulted in red blood cell density and osmotic resistance distribution shifts. Treatment with the phenazine methosulfate+ascorbate system in the presence of Ca(2+) led to cell shrinking, with the maximum effect being more than 20%. In contrast, under the same conditions, t-BHP caused cell swelling by up to 15%. Modification of the suspending medium (Ca(2+) removing, clotrimazole addition, or enrichment with K(+)) modulated the redistribution effects, suggesting that they were mediated to some extent by Gardos channel activation. These findings are important for understanding how oxidants modulate RBC cation channels.

  13. Fluid balance concepts in medicine: Principles and practice

    PubMed Central

    Roumelioti, Maria-Eleni; Glew, Robert H; Khitan, Zeid J; Rondon-Berrios, Helbert; Argyropoulos, Christos P; Malhotra, Deepak; Raj, Dominic S; Agaba, Emmanuel I; Rohrscheib, Mark; Murata, Glen H; Shapiro, Joseph I; Tzamaloukas, Antonios H

    2018-01-01

    The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance. PMID:29359117

  14. Probing the statistics of primordial fluctuations and their evolution

    NASA Technical Reports Server (NTRS)

    Gaztanaga, Enrique; Yokoyama, Jun'ichi

    1993-01-01

    The statistical distribution of fluctuations on various scales is analyzed in terms of the counts in cells of smoothed density fields, using volume-limited samples of galaxy redshift catalogs. It is shown that the distribution on large scales, with volume average of the two-point correlation function of the smoothed field less than about 0.05, is consistent with Gaussian. Statistics are shown to agree remarkably well with the negative binomial distribution, which has hierarchial correlations and a Gaussian behavior at large scales. If these observed properties correspond to the matter distribution, they suggest that our universe started with Gaussian fluctuations and evolved keeping hierarchial form.

  15. Regional cell density distribution and oxygen consumption rates in porcine TMJ discs: an explant study.

    PubMed

    Kuo, J; Shi, C; Cisewski, S; Zhang, L; Kern, M J; Yao, H

    2011-07-01

    To determine the regional cell density distribution and basal oxygen consumption rates (based on tissue volume and cell number) of temporomandibular joint (TMJ) discs and further examine the impact of oxygen tension on these rates. TMJ discs from pigs aged 6-8 months were divided into five regions: anterior, intermediate, posterior, lateral and medial. The cell density was determined using confocal laser scanning microscopy. The change in oxygen tension was recorded while TMJ disc explants were cultured in sealed metabolism chambers. The volume based oxygen consumption rate of explants was determined by theoretical curve-fitting of the recorded oxygen tension data with the Michaelis-Menten equation. The rate on a per-cell basis was calculated based on the cell density measurements and volume based rate measured in another group of discs. The overall cell density [mean, 95% confidence interval (CI)] was 51.3 (21.3-81.3) × 10(6) cells/mL wet tissue. Along the anteroposterior axis, the anterior band had 25.5% higher cell density than the intermediate zone (P<0.02) and 29.1% higher than the posterior band (P<0.008). Along the mediolateral axes, the medial region had 26.2% higher cell density than the intermediate zone (P<0.04) and 25.4% higher than the lateral region (P<0.045). The overall volume and cell based maximum oxygen consumption rates were 1.44 (0.44-2.44) μmol/mL wet tissue/h and 28.7 (12.2-45.2)nmol/10(6)cells/h, respectively. The central regions (intermediate, lateral, and medial) had significantly higher volume based (P<0.02) and cell based (P<0.005) oxygen consumption rates than the anterior and posterior bands. At high oxygen tension, the oxygen consumption rate remained constant, but dropped as oxygen tension fell below 5%. The TMJ disc had higher cell density and oxygen consumption rates than articular cartilage reported in the literature. These results suggest that a steeper oxygen gradient may exist in the TMJ disc and may be vulnerable to pathological events that impede nutrient supply. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  16. Regional Cell Density Distribution and Oxygen Consumption Rates in Porcine TMJ Discs: An Explant Study

    PubMed Central

    Kuo, Jonathan; Shi, Changcheng; Cisewski, Sarah; Zhang, Lixia; Kern, Michael J.; Yao, Hai

    2011-01-01

    Objective To determine the regional cell density distribution and basal oxygen consumption rates (based on tissue volume and cell number) of temporomandibular joint (TMJ) discs and further examine the impact of oxygen tension on these rates. Design TMJ discs from pigs aged 6–8 months were divided into five regions: anterior, intermediate, posterior, lateral and medial. The cell density was determined using confocal laser scanning microscopy. The change in oxygen tension was recorded while TMJ disc explants were cultured in sealed metabolism chambers. The volume based oxygen consumption rate of explants was determined by theoretical curve fitting of the recoded oxygen tension data with the Michaelis-Menten equation. The rate on a per-cell basis was calculated based on the cell density measurements and volume based rate measured in another group of discs. Results The overall cell density (mean, 95% CI) was 51.3(21.3–81.3)×106cells/mL wet tissue. Along the anteroposterior axis, the anterior band had 25.5% higher cell density than the intermediate zone (p<0.02) and 29.1% higher than the posterior band (p<0.008). Along the mediolateral axes, the medial region had 26.2% higher cell density than the intermediate zone (p<0.04) and 25.4% higher than the lateral region (p<0.045). The overall volume and cell based maximum oxygen consumption rates were 1.44(0.44–2.44) μmol/mL wet tissue/hr and 28.7(12.2–45.2) nmol/106 cells/hr, respectively. The central regions (intermediate, lateral, and medial) had significantly higher volume based (p<0.02) and cell based (p<0.005) oxygen consumption rates than the anterior and posterior bands. At high oxygen tension, the oxygen consumption rate remained constant, but dropped as oxygen tension fell below 5%. Conclusions The TMJ disc had higher cell density and oxygen consumption rates than articular cartilage reported in the literature. These results suggest that a steeper oxygen gradient may exist in the TMJ disc and may be vulnerable to pathological events that impede nutrient supply. PMID:21397032

  17. A review of recent methods for efficiently quantifying immunogold and other nanoparticles using TEM sections through cells, tissues and organs.

    PubMed

    Mayhew, Terry M; Mühlfeld, Christian; Vanhecke, Dimitri; Ochs, Matthias

    2009-04-01

    Detecting, localising and counting ultrasmall particles and nanoparticles in sub- and supra-cellular compartments are of considerable current interest in basic and applied research in biomedicine, bioscience and environmental science. For particles with sufficient contrast (e.g. colloidal gold, ferritin, heavy metal-based nanoparticles), visualization requires the high resolutions achievable by transmission electron microscopy (TEM). Moreover, if particles can be counted, their spatial distributions can be subjected to statistical evaluation. Whatever the level of structural organisation, particle distributions can be compared between different compartments within a given structure (cell, tissue and organ) or between different sets of structures (in, say, control and experimental groups). Here, a portfolio of stereology-based methods for drawing such comparisons is presented. We recognise two main scenarios: (1) section surface localisation, in which particles, exemplified by antibody-conjugated colloidal gold particles or quantum dots, are distributed at the section surface during post-embedding immunolabelling, and (2) section volume localisation (or full section penetration), in which particles are contained within the cell or tissue prior to TEM fixation and embedding procedures. Whatever the study aim or hypothesis, the methods for quantifying particles rely on the same basic principles: (i) unbiased selection of specimens by multistage random sampling, (ii) unbiased estimation of particle number and compartment size using stereological test probes (points, lines, areas and volumes), and (iii) statistical testing of an appropriate null hypothesis. To compare different groups of cells or organs, a simple and efficient approach is to compare the observed distributions of raw particle counts by a combined contingency table and chi-squared analysis. Compartmental chi-squared values making substantial contributions to total chi-squared values help identify where the main differences between distributions reside. Distributions between compartments in, say, a given cell type, can be compared using a relative labelling index (RLI) or relative deposition index (RDI) combined with a chi-squared analysis to test whether or not particles preferentially locate in certain compartments. This approach is ideally suited to analysing particles located in volume-occupying compartments (organelles or tissue spaces) or surface-occupying compartments (membranes) and expected distributions can be generated by the stereological devices of point, intersection and particle counting. Labelling efficiencies (number of gold particles per antigen molecule) in immunocytochemical studies can be determined if suitable calibration methods (e.g. biochemical assays of golds per membrane surface or per cell) are available. In addition to relative quantification for between-group and between-compartment comparisons, stereological methods also permit absolute quantification, e.g. total volumes, surfaces and numbers of structures per cell. Here, the utility, limitations and recent applications of these methods are reviewed.

  18. The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors.

    PubMed

    Tüzün, Ali; Keskin, Onur; Yakut, Mustafa; Kalkan, Cagdas; Soykan, Irfan

    2014-01-01

    Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p < 0.001) and red cell distribution width (16.11 ± 3.04 vs. 13.41 ± 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

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

    Peter, Justin R; May, Peter T; Potts, Rodney J

    Statistics of radar-retrievals of precipitation are presented. A K-means clustering algorithm is applied to an historical record of radiosonde measurements which identified three major synoptic regimes; a dry, stable regime with mainly westerly winds prevalent during winter, a moist south easterly trade wind regime and a moist northerly regime both prevalent during summer. These are referred to as westerly, trade wind and northerly regimes, respectively. Cell statistics are calculated using an objective cell identification and tracking methodology on data obtained from a nearby S-band radar. Cell statistics are investigated for the entire radar observational period and also during sub-periods correspondingmore » to the three major synoptic regimes. The statistics investigated are cell initiation location, area, rainrate, volume, height, height of the maximum reflectivity, volume greater than 40 dBZ and storm speed and direction. Cells are found predominantly along the elevated topography. The cell statistics reveal that storms which form in the dry, stable westerly regime are of comparable size to the deep cells which form in the northerly regime, larger than those in the trade regime and, furthermore, have the largest rainrate. However, they occur less frequently and have shorter lifetimes than cells in the other regimes. Diurnal statistics of precipitation area and rainrate exhibit early morning and mid afternoon peaks, although the areal coverage lags the rainrate by several hours indicative of a transition from convective to stratiform precipitation. The probability distributions of cell area, rainrate, volume, height and height of the maximum re ectivity are found to follow lognormal distributions.« less

  20. No relative expansion of the number of prefrontal neurons in primate and human evolution.

    PubMed

    Gabi, Mariana; Neves, Kleber; Masseron, Carolinne; Ribeiro, Pedro F M; Ventura-Antunes, Lissa; Torres, Laila; Mota, Bruno; Kaas, Jon H; Herculano-Houzel, Suzana

    2016-08-23

    Human evolution is widely thought to have involved a particular expansion of prefrontal cortex. This popular notion has recently been challenged, although controversies remain. Here we show that the prefrontal region of both human and nonhuman primates holds about 8% of cortical neurons, with no clear difference across humans and other primates in the distribution of cortical neurons or white matter cells along the anteroposterior axis. Further, we find that the volumes of human prefrontal gray and white matter match the expected volumes for the number of neurons in the gray matter and for the number of other cells in the white matter compared with other primate species. These results indicate that prefrontal cortical expansion in human evolution happened along the same allometric trajectory as for other primate species, without modification of the distribution of neurons across its surface or of the volume of the underlying white matter. We thus propose that the most distinctive feature of the human prefrontal cortex is its absolute number of neurons, not its relative volume.

  1. Haematological values in pregnant women in Port Harcourt, Nigeria II: Serum iron and transferrin, total and unsaturated iron binding capacity and some red cell and platelet indices.

    PubMed

    Amah-Tariah, F S; Ojeka, S O; Dapper, D V

    2011-12-20

    Previous studies on the normal values of serum iron, unsaturated iron binding capacity, total iron binding capacity, serum transferrin, percent transferrin saturation, red cell distribution width, and various platelet indices: Platelet count, mean platelet volume, platelet distribution width, plateletcrit and platelet larger cell ratio in pregnant subjects in Nigeria are relatively scanty. Present study aims to determine the values of these parameters in apparently healthy pregnant subjects residing in Port Harcourt south eastern Nigeria; and help establish normal reference ranges of these parameters for the population under reference. Cross sectional prospective study involving 220 female subjects attending for the first time, the ante-natal clinics of a tertiary health care facility in Port Harcourt. Subjects were divided into 73, 75 and 72 subjects in the first, second and third trimester of pregnancy respectively. Serum iron and unsaturated iron binding capacity, red cell distribution width, platelet count and platelet distribution width were determined by automated methods; total iron binding capacity, serum transferrin concentrations, percent transferrin saturation, mean platelet volume and plateletcrit were calculated using appropriate formulas. The values of serum iron, unsaturated iron binding capacity, total iron binding capacity and serum transferrin concentrations were found to show significant variations between the various trimesters of pregnancy. However, while serum iron showed significant decreases during pregnancy; unsaturated iron binding capacity, total iron binding capacity and serum transferrin concentrations were found to show significant increases during pregnancy amongst our subjects (p<0.05). By contrast the values of red cell distribution width, platelet count, mean platelet volume, platelet distribution width, plateletcrit and platelet larger cell ratio did not show any significant differences at the different trimesters of pregnancy in our subjects (p>0.05). The present study reports, for the first time, normative values for these parameters in apparently healthy pregnant subjects in Port Harcourt south eastern Nigeria. Apparently, increases in unsaturated and total iron binding capacity and serum transferrin values seen amongst our subjects with increasing gestation may perhaps be a mechanism to ensure a fetal adequate iron delivery on account of the decreasing serum iron concentration with gestation in our subjects. The study suggests that values of serum transferrin are perhaps a more useful screening tool for iron deficiency anemia during pregnancy amongst our subjects.

  2. The shape of the transmembrane domain is a novel endocytosis signal for single-spanning membrane proteins.

    PubMed

    González Montoro, Ayelén; Bigliani, Gonzalo; Valdez Taubas, Javier

    2017-11-15

    Endocytosis is crucial for all cells as it allows them to incorporate material from the extracellular space and control the availability of transmembrane proteins at the plasma membrane. In yeast, endocytosis followed by recycling to the plasma membrane results in a polarised distribution of membrane proteins by a kinetic mechanism. Here, we report that increasing the volume of residues that constitute the exoplasmic half of the transmembrane domain (TMD) in the yeast SNARE Sso1, a type II membrane protein, results in its polarised distribution at the plasma membrane. Expression of this chimera in strains affected in either endocytosis or recycling revealed that this polarisation is achieved by endocytic cycling. A bioinformatics search of the Saccharomyces cerevisiae proteome identified several proteins with high-volume exoplasmic hemi-TMDs. Our experiments indicate that TMDs from these proteins can confer a polarised distribution to the Sso1 cytoplasmic domain, indicating that the shape of the TMD can act as a novel endocytosis and polarity signal in yeast . Additionally, a high-volume exoplasmic hemi-TMD can act as an endocytosis signal in a mammalian cell line. © 2017. Published by The Company of Biologists Ltd.

  3. Effects of porosity distribution and porosity volume fraction on the electromechanical properties of 3-3 piezoelectric foams

    NASA Astrophysics Data System (ADS)

    Nguyen, B. V.; Challagulla, K. S.; Venkatesh, T. A.; Hadjiloizi, D. A.; Georgiades, A. V.

    2016-12-01

    Unit-cell based finite element models are developed to completely characterize the role of porosity distribution and porosity volume fraction in determining the elastic, dielectric and piezoelectric properties as well as relevant figures of merit of 3-3 type piezoelectric foam structures. Eight classes of foam structures which represent structures with different types and degrees of uniformity of porosity distribution are identified; a Base structure (Class I), two H-type foam structures (Classes II, and III), a Cross-type foam structure (Class IV) and four Line-type foam structures (Classes V, VI, VII, and VIII). Three geometric factors that influence the electromechanical properties are identified: (i) the number of pores per face, pore size and the distance between the pores; (ii) pore orientation with respect to poling direction; (iii) the overall symmetry of the pore distribution with respect to the center of the face of the unit cell. To assess the suitability of these structures for such applications as hydrophones, bone implants, medical imaging and diagnostic devices, five figures of merit are determined via the developed finite element model; the piezoelectric coupling constant (K t ), the acoustic impedance (Z), the piezoelectric charge coefficient (d h ), the hydrostatic voltage coefficient (g h ), and the hydrostatic figure of merit (d h g h ). At high material volume fractions, foams with non-uniform Line-type porosity (Classes V and VII) where the pores are preferentially distributed perpendicular to poling direction, are found to exhibit the best combination of desirable piezoelectric figures of merit. For example, at about 50% volume fraction, the d h , g h , and d h g h figures of merit are 55%, 1600% and 2500% higher, respectively, for Classes V and VII of Line-like foam structures compared with the Base structure.

  4. Fundamental structural characteristics of planar granular assemblies: Self-organization and scaling away friction and initial state.

    PubMed

    Matsushima, Takashi; Blumenfeld, Raphael

    2017-03-01

    The microstructural organization of a granular system is the most important determinant of its macroscopic behavior. Here we identify the fundamental factors that determine the statistics of such microstructures, using numerical experiments to gain a general understanding. The experiments consist of preparing and compacting isotropically two-dimensional granular assemblies of polydisperse frictional disks and analyzing the emergent statistical properties of quadrons-the basic structural elements of granular solids. The focus on quadrons is because the statistics of their volumes have been found to display intriguing universal-like features [T. Matsushima and R. Blumenfeld, Phys. Rev. Lett. 112, 098003 (2014)PRLTAO0031-900710.1103/PhysRevLett.112.098003]. The dependence of the structures and of the packing fraction on the intergranular friction and the initial state is analyzed, and a number of significant results are found. (i) An analytical formula is derived for the mean quadron volume in terms of three macroscopic quantities: the mean coordination number, the packing fraction, and the rattlers fraction. (ii) We derive a unique, initial-state-independent relation between the mean coordination number and the rattler-free packing fraction. The relation is supported numerically for a range of different systems. (iii) We collapse the quadron volume distributions from all systems onto one curve, and we verify that they all have an exponential tail. (iv) The nature of the quadron volume distribution is investigated by decomposition into conditional distributions of volumes given the cell order, and we find that each of these also collapses onto a single curve. (v) We find that the mean quadron volume decreases with increasing intergranular friction coefficients, an effect that is prominent in high-order cells. We argue that this phenomenon is due to an increased probability of stable irregularly shaped cells, and we test this using a herewith developed free cell analytical model. We conclude that, in principle, the microstructural characteristics are governed mainly by the packing procedure, while the effects of intergranular friction and initial states are details that can be scaled away. However, mechanical stability constraints suppress slightly the occurrence of small quadron volumes in cells of order ≥6, and the magnitude of this effect does depend on friction. We quantify in detail this dependence and the deviation it causes from an exact collapse for these cells. (vi) We argue that our results support strongly the view that ensemble granular statistical mechanics does not satisfy the uniform measure assumption of conventional statistical mechanics. Results (i)-(iv) have been reported in the aforementioned reference, and they are reviewed and elaborated on here.

  5. Prediction of resource volumes at untested locations using simple local prediction models

    USGS Publications Warehouse

    Attanasi, E.D.; Coburn, T.C.; Freeman, P.A.

    2006-01-01

    This paper shows how local spatial nonparametric prediction models can be applied to estimate volumes of recoverable gas resources at individual undrilled sites, at multiple sites on a regional scale, and to compute confidence bounds for regional volumes based on the distribution of those estimates. An approach that combines cross-validation, the jackknife, and bootstrap procedures is used to accomplish this task. Simulation experiments show that cross-validation can be applied beneficially to select an appropriate prediction model. The cross-validation procedure worked well for a wide range of different states of nature and levels of information. Jackknife procedures are used to compute individual prediction estimation errors at undrilled locations. The jackknife replicates also are used with a bootstrap resampling procedure to compute confidence bounds for the total volume. The method was applied to data (partitioned into a training set and target set) from the Devonian Antrim Shale continuous-type gas play in the Michigan Basin in Otsego County, Michigan. The analysis showed that the model estimate of total recoverable volumes at prediction sites is within 4 percent of the total observed volume. The model predictions also provide frequency distributions of the cell volumes at the production unit scale. Such distributions are the basis for subsequent economic analyses. ?? Springer Science+Business Media, LLC 2007.

  6. Comparative stereology of the mouse and finch left ventricle.

    PubMed

    Bossen, E H; Sommer, J R; Waugh, R A

    1978-01-01

    The volume fractions and surface per unit cell volume of some subcellular components of the left ventricles of the finch and mouse were quantitated by stereologic techniques. These species were chosen for study because they have similar heart rates but differ morphologically in some respects: fiber diameter is larger in the mouse; the mouse has transverse tubules while the finch does not; and the finch has a form of junctional sarcoplasmic reticulum (JSR), extended JSR (EJSR), located in the cell interior with no direct plasmalemmal contact, while the mouse interior JSR (IJSR) abuts on transverse tubules. Our data show that the volume fraction (Vv) and surface area per unit cell volume (Sv) of total SR, and free SR (FSR) are similar. The volume fractions of mitochondria, myofibrils, and total junctional SR were also similar. The Sv of the cell surface of the finch was similar to the Sv of the cell surface of the mouse (Sv-plasmalemma plus Sv of the transverse tubules). The principal difference was in the distribution of JSR; the mouse peripheral JSR (PJSR) represents only 9% of the total JSR, while the finch PJSR accounts for 24% of the bird's JSR. The similar volume fractions of total junctional SR (PJSR + EJSR in the finch; PJSR + IJSR in the mouse) suggest that the EJSR is not an embryologic remnant, and raises the possibility that some function of JSR is independent of plasmalemmal contact.

  7. Vertical distribution of the prokaryotic cell size in the Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    La Ferla, R.; Maimone, G.; Azzaro, M.; Conversano, F.; Brunet, C.; Cabral, A. S.; Paranhos, R.

    2012-12-01

    Distributions of prokaryotic cell size and morphology were studied in different areas of the Mediterranean Sea by using image analysis on samples collected from surface down to bathypelagic layers (max depth 4,900 m) in the Southern Tyrrhenian, Southern Adriatic and Eastern Mediterranean Seas. Distribution of cell size of prokaryotes in marine ecosystem is very often not considered, which makes our study first in the context of prokaryotic ecology. In the deep Mediterranean layers, an usually-not-considered form of carbon sequestration through prokaryotic cells has been highlighted, which is consistent with an increase in cell size with the depth of the water column. A wide range in prokaryotic cell volumes was observed (between 0.045 and 0.566 μm3). Increase in cell size with depth was opposed to cell abundance distribution. Our results from microscopic observations were confirmed by the increasing HNA/LNA ratio (HNA, cells with high nucleic acid content; LNA, cells with low nucleic acid content) along the water column. Implications of our results on the increasing cell size with depth are in the fact that the quantitative estimation of prokaryotic biomass changes along the water column and the amount of carbon sequestered in the deep biota is enhanced.

  8. A coupled diffusion-fluid pressure model to predict cell density distribution for cells encapsulated in a porous hydrogel scaffold under mechanical loading.

    PubMed

    Zhao, Feihu; Vaughan, Ted J; Mc Garrigle, Myles J; McNamara, Laoise M

    2017-10-01

    Tissue formation within tissue engineering (TE) scaffolds is preceded by growth of the cells throughout the scaffold volume and attachment of cells to the scaffold substrate. It is known that mechanical stimulation, in the form of fluid perfusion or mechanical strain, enhances cell differentiation and overall tissue formation. However, due to the complex multi-physics environment of cells within TE scaffolds, cell transport under mechanical stimulation is not fully understood. Therefore, in this study, we have developed a coupled multiphysics model to predict cell density distribution in a TE scaffold. In this model, cell transport is modelled as a thermal conduction process, which is driven by the pore fluid pressure under applied loading. As a case study, the model is investigated to predict the cell density patterns of pre-osteoblasts MC3T3-e1 cells under a range of different loading regimes, to obtain an understanding of desirable mechanical stimulation that will enhance cell density distribution within TE scaffolds. The results of this study have demonstrated that fluid perfusion can result in a higher cell density in the scaffold region closed to the outlet, while cell density distribution under mechanical compression was similar with static condition. More importantly, the study provides a novel computational approach to predict cell distribution in TE scaffolds under mechanical loading. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. 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

  10. A new estimate of the volume and distribution of gas hydrate in the northern Gulf of Mexico

    NASA Astrophysics Data System (ADS)

    Majumdar, U.; Cook, A.

    2016-12-01

    In spite of the wealth of information gained over the last several decades about gas hydrate in the northern Gulf of Mexico, there is still considerable uncertainty about the distribution and volume of gas hydrate. In our assessment we build a dataset of basin-wide gas hydrate distribution and thickness, as appraised from publicly available petroleum industry well logs within the gas hydrate stability zone (HSZ), and subsequently develop a Monte Carlo to determine the volumetric estimate of gas hydrate using the dataset. We evaluate the presence of gas hydrate from electrical resistivity well logs, and categorized possible reservoir type (either sand or clay) based on the gamma ray response and resistivity curve characteristics. Out of the 798 wells with resistivity well log data within the HSZ we analyzed, we found evidence of gas hydrate in 124 wells. In this research we present a new stochastic estimate of the gas hydrate volume in the northern Gulf of Mexico guided by our well log dataset. For our Monte Carlo simulation, we divided our assessment area of 200,000 km2 into 1 km2 grid cells. Our volume assessment model incorporates variables unique to our well log dataset such as the likelihood of gas hydrate occurrence, fraction of the HSZ occupied by gas hydrate, reservoir type, and gas hydrate saturation depending on the reservoir, in each grid cell, in addition to other basic variables such as HSZ thickness and porosity. Preliminary results from our model suggests that the total volume of gas at standard temperature and pressure in gas hydrate in the northern Gulf of Mexico is in the range of 430 trillion cubic feet (TCF) to 730 TCF, with a mean volume of 585 TCF. While the reservoir distribution from our well log dataset found gas hydrate in sand reservoirs in 30 wells out of the 124 wells with evidence of gas hydrate ( 24%), we find sand reservoirs contain over half of the total volume of gas hydrate in the Gulf of Mexico, as a result of the relatively high gas hydrate saturation in sand.

  11. Blood cell counting and classification by nonflowing laser light scattering method

    NASA Astrophysics Data System (ADS)

    Yang, Ye; Zhang, Zhenxi; Yang, Xinhui; Jiang, Dazong; Yeo, Joon Hock

    1999-11-01

    A new non-flowing laser light scattering method for counting and classifying blood cells is presented. A linear charge- coupled device with 1024 elements is used to detect the scattered light intensity distribution of the blood cells. A pinhole plate is combined with the CCD to compete the focusing of the measurement system. An isotropic sphere is used to simulate the blood cell. Mie theory is used to describe the scattering of blood cells. In order to inverse the size distribution of blood cells from their scattered light intensity distribution, Powell method combined with precision punishment method is used as a dependent model method for measurement red blood cells and blood plates. Non-negative constraint least square method combined with Powell method and precision punishment method is used as an independent model for measuring white blood cells. The size distributions of white blood cells and red blood cells, and the mean diameter of red blood cells are measured by this method. White blood cells can be divided into three classes: lymphocytes, middle-sized cells and neutrocytes according to their sizes. And the number of blood cells in unit volume can also be measured by the linear dependence of blood cells concentration on scattered light intensity.

  12. Simplified Bioreactor For Growing Mammalian Cells

    NASA Technical Reports Server (NTRS)

    Spaulding, Glenn F.

    1995-01-01

    Improved bioreactor for growing mammalian cell cultures developed. Designed to support growth of dense volumes of mammalian cells by providing ample, well-distributed flows of nutrient solution with minimal turbulence. Cells relatively delicate and, unlike bacteria, cannot withstand shear forces present in turbulent flows. Bioreactor vessel readily made in larger sizes to accommodate greater cell production quantities. Molding equipment presently used makes cylinders up to 30 centimeters long. Alternative sintered plastic techniques used to vary pore size and quantity, as necessary.

  13. 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.

  14. Homogeneity of lithium distribution in cylinder-type Li-ion batteries

    PubMed Central

    Senyshyn, A.; Mühlbauer, M. J.; Dolotko, O.; Hofmann, M.; Ehrenberg, H.

    2015-01-01

    Spatially-resolved neutron powder diffraction with a gauge volume of 2 × 2 × 20 mm3 has been applied as an in situ method to probe the lithium concentration in the graphite anode of different Li-ion cells of 18650-type in charged state. Structural studies performed in combination with electrochemical measurements and X-ray computed tomography under real cell operating conditions unambiguously revealed non-homogeneity of the lithium distribution in the graphite anode. Deviations from a homogeneous behaviour have been found in both radial and axial directions of 18650-type cells and were discussed in the frame of cell geometry and electrical connection of electrodes, which might play a crucial role in the homogeneity of the lithium distribution in the active materials within each electrode. PMID:26681110

  15. Current density and catalyst-coated membrane resistance distribution of hydro-formed metallic bipolar plate fuel cell short stack with 250 cm2 active area

    NASA Astrophysics Data System (ADS)

    Haase, S.; Moser, M.; Hirschfeld, J. A.; Jozwiak, K.

    2016-01-01

    An automotive fuel cell with an active area of 250 cm2 is investigated in a 4-cell short stack with a current and temperature distribution device next to the bipolar plate with 560 current and 140 temperature segments. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this current scan shunt module. The applied fuel cell consists of bipolar plates constructed of 75-μm-thick, welded stainless-steel foils and a graphitic coating. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this module with a 6% deviation in in-plane conductivity. The current density distribution is evaluated up to 2.4 A cm-2. The entire cell's investigated volumetric power density is 4.7 kW l-1, and its gravimetric power density is 4.3 kW kg-1 at an average cell voltage of 0.5 V. The current density distribution is determined without influencing the operating cell. In addition, the current density distribution in the catalyst-coated membrane and its effective resistivity distribution with a finite volume discretisation of Ohm's law are evaluated. The deviation between the current density distributions in the catalyst-coated membrane and the bipolar plate is determined.

  16. A new hand-held microfluidic cytometer for evaluating irradiation damage by analysis of the damaged cells distribution.

    PubMed

    Wang, Junsheng; Fan, Zhiqiang; Zhao, Yile; Song, Younan; Chu, Hui; Song, Wendong; Song, Yongxin; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

    2016-03-17

    Space radiation brings uneven damages to cells. The detection of the distribution of cell damage plays a very important role in radiation medicine and the related research. In this paper, a new hand-held microfluidic flow cytometer was developed to evaluate the degree of radiation damage of cells. The device we propose overcomes the shortcomings (e.g., large volume and high cost) of commercial flow cytometers and can evaluate the radiation damage of cells accurately and quickly with potential for onsite applications. The distribution of radiation-damaged cells is analyzed by a simultaneous detection of immunofluorescence intensity of γ-H2AX and resistance pulse sensor (RPS) signal. The γ-H2AX fluorescence intensity provides information of the degree of radiation damage in cells. The ratio of the number of cells with γ-H2AX fluorescence signals to the total numbers of cells detected by RPS indicates the percentage of the cells that are damaged by radiation. The comparison experiment between the developed hand-held microfluidic flow cytometer and a commercial confocal microscope indicates a consistent and comparable detection performance.

  17. A new hand-held microfluidic cytometer for evaluating irradiation damage by analysis of the damaged cells distribution

    NASA Astrophysics Data System (ADS)

    Wang, Junsheng; Fan, Zhiqiang; Zhao, Yile; Song, Younan; Chu, Hui; Song, Wendong; Song, Yongxin; Pan, Xinxiang; Sun, Yeqing; Li, Dongqing

    2016-03-01

    Space radiation brings uneven damages to cells. The detection of the distribution of cell damage plays a very important role in radiation medicine and the related research. In this paper, a new hand-held microfluidic flow cytometer was developed to evaluate the degree of radiation damage of cells. The device we propose overcomes the shortcomings (e.g., large volume and high cost) of commercial flow cytometers and can evaluate the radiation damage of cells accurately and quickly with potential for onsite applications. The distribution of radiation-damaged cells is analyzed by a simultaneous detection of immunofluorescence intensity of γ-H2AX and resistance pulse sensor (RPS) signal. The γ-H2AX fluorescence intensity provides information of the degree of radiation damage in cells. The ratio of the number of cells with γ-H2AX fluorescence signals to the total numbers of cells detected by RPS indicates the percentage of the cells that are damaged by radiation. The comparison experiment between the developed hand-held microfluidic flow cytometer and a commercial confocal microscope indicates a consistent and comparable detection performance.

  18. GSRP/David Marshall: Fully Automated Cartesian Grid CFD Application for MDO in High Speed Flows

    NASA Technical Reports Server (NTRS)

    2003-01-01

    With the renewed interest in Cartesian gridding methodologies for the ease and speed of gridding complex geometries in addition to the simplicity of the control volumes used in the computations, it has become important to investigate ways of extending the existing Cartesian grid solver functionalities. This includes developing methods of modeling the viscous effects in order to utilize Cartesian grids solvers for accurate drag predictions and addressing the issues related to the distributed memory parallelization of Cartesian solvers. This research presents advances in two areas of interest in Cartesian grid solvers, viscous effects modeling and MPI parallelization. The development of viscous effects modeling using solely Cartesian grids has been hampered by the widely varying control volume sizes associated with the mesh refinement and the cut cells associated with the solid surface. This problem is being addressed by using physically based modeling techniques to update the state vectors of the cut cells and removing them from the finite volume integration scheme. This work is performed on a new Cartesian grid solver, NASCART-GT, with modifications to its cut cell functionality. The development of MPI parallelization addresses issues associated with utilizing Cartesian solvers on distributed memory parallel environments. This work is performed on an existing Cartesian grid solver, CART3D, with modifications to its parallelization methodology.

  19. Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development.

    PubMed

    Popken, Jens; Schmid, Volker J; Strauss, Axel; Guengoer, Tuna; Wolf, Eckhard; Zakhartchenko, Valeri

    2016-04-22

    Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling of the nuclear envelope and its underlying lamina during rabbit preimplantation development.

  20. Structure-function relationships in the stem cell's mechanical world A: seeding protocols as a means to control shape and fate of live stem cells.

    PubMed

    Zimmermann, Joshua A; Knothe Tate, Melissa L

    2011-12-01

    Shape and fate are intrinsic manifestations of form and function at the cell scale. Here we hypothesize that seeding density and protocol affect the form and function of live embryonic murine mesenchymal stem cells (MSCs) and their nuclei. First, the imperative for study of live cells was demonstrated in studies showing changes in cell nucleus shape that were attributable to fixation per se. Hence, we compared live cell and nuclear volume and shape between groups of a model MSC line (C3H10T1/2) seeded at, or proliferated from 5,000 cells/cm2 to one of three target densities to achieve targeted development contexts. Cell volume was shown to be dependent on initial seeding density whereas nucleus shape was shown to depend on developmental context but not seeding density. Both smaller cell volumes and flatter nuclei were found to correlate with increased expression of markers for mesenchymal condensation as well as chondrogenic and osteogenic differentiation but a decreased expression of pre-condensation and adipogenic markers. Considering the data presented here, both seeding density and protocol significantly alter the morphology of mesenchymal stem cells even at very early stages of cell culture. Thus, these design parameters may play a critical role in the success of tissue engineering strategies seeking to recreate condensation events. However, a better understanding of how these changes in cell volume and nucleus shape relate to the differentiation of MSCs is important for prescribing precise seeding conditions necessary for the development of the desired tissue type. In a companion study (Part B, following), we address the effect of concomitant volume and shape changing stresses on spatiotemporal distribution of the cytoskeletal proteins actin and tubulin. Taken together, these studies bring us one step closer to our ultimate goal of elucidating the dynamics of nucleus and cell shape change as tissue templates grow (cell proliferation) and specialize (cell differentiation).

  1. Plasma clots gelled by different amounts of calcium for stem cell delivery.

    PubMed

    Gessmann, Jan; Seybold, Dominik; Peter, Elvira; Schildhauer, Thomas Armin; Köller, Manfred

    2013-01-01

    Freshly prepared autologous plasma clots may serve as a carrier matrix for expanded multipotent mesenchymal stromal cells (MSCs) or bone marrow cells. By varying the calcium concentration, plasma clots with different properties can be produced. The purpose of this in vitro study was to determine the optimal calcium concentrations for the clotting process, intra-clot cell viability, and clot lysis. Different plasma clots were prepared by adding an equal volume of RPMI1640 (with or without MSCs) to citrate plasma (either containing platelets or platelet-free). Clotting was initiated by the addition of CaCl(2) (10 g/100 ml H(2)O, 10 % solution). The final concentration of CaCl(2) ranged from 1 to 10 % by volume of plasma. Viability and distribution of the MSCs were analysed by calcein-AM/propidium iodide staining. MSC-embedded plasma clots were dissolved with trypsin (0.25 %), and recovered cells were further incubated for 1 week under cell culture conditions. The viability of MSCs embedded in clots formed by the addition of 1-8 % by volume CaCl2 was not affected by incubation of up to 1 week. In contrast, clots produced by higher volumes of CaCl(2) solutions (9-10 % by volume of plasma) showed decreased numbers of viable cells. Intra-clot cell proliferation was highest in clots produced by addition of 5 % CaCl(2) by plasma volume. Osteocalcin release was not influenced in platelet-free plasma but decreased in platelet-containing plasma. Morphological analysis of stained recovered MSCs revealed that lysis of the plasma clot did not affect cell morphology or subsequent spontaneous proliferation. Clot formation and clot stability can be controlled by changing the concentration of CaCl(2) added to plasma. The addition of 5 % CaCl(2) produced a plasma clot with optimal results for stem cell delivery.

  2. Sodium chloride-induced volume changes of freshwater cyanobacterium Synechococcus sp. PCC 7942 cells can be probed by chlorophyll a fluorescence.

    PubMed

    Stamatakis, K; Ladas, N P; Alygizaki-Zorba, A; Papageorgiou, G C

    1999-10-15

    Freshwater species of the cyanobacterial genus Synechococcus import NaCl passively, and export Na(+) actively, by means of primary and secondary extrusion mechanisms. As a result of the ion and water fluxes, cell volumes are enlarged. We show in this paper that the NaCl-induced volume enlargement of Synechococcus sp. PCC 7942 cells is attended by a rapid (k = 0.39 s(-1)) increase in chlorophyll (Chl) a fluorescence. The cell turgor threshold (measured by osmotic titration of Chl a fluorescence) was lower in the absence of NaCl (0.195 Osm kg(-1)) than in the presence of 0.4 M NaCl (0.248 Osm kg(-1)) indicating NaCl uptake by the cells. Turgor thresholds of cells suspended in NaCl-containing medium were enlarged further by protonophoric uncouplers, P-type ATPase inhibitors, and light starvation, conditions that are known to interfere with the active extrusion of Na(+) ions. Cell swelling exerts probably a regulation on the distribution of phycobilisome (PBS) excitation between photosystem II (fluorescent Chl a) and photosystem I (nonfluorescent Chl a), since it affects PBS-sensitized Chl a fluorescence, but not directly excited Chl a fluorescence. The dependence of the Chl a fluorescence of cyanobacteria on cell volumes allows probing of bioenergetic phenomena that are related to dynamic osmotic volume changes, transmembrane solute and water fluxes, plasma membrane permeabilities, and internal osmotic conditions of cyanobacterial cells. Thus, cyanobacteria may serve as quite convenient models of aquatic microorganisms in experimental studies directed toward the elucidation of perception mechanisms and defense mechanisms of water and solute stresses. Copyright 1999 Academic Press.

  3. Statistical Properties of Cell Topology and Geometry in a Tissue-Growth Model

    NASA Astrophysics Data System (ADS)

    Sahlin, Patrik; Hamant, Olivier; Jönsson, Henrik

    Statistical properties of cell topologies in two-dimensional tissues have recently been suggested to be a consequence of cell divisions. Different rules for the positioning of new walls in plants have been proposed, where e.g. Errara’s rule state that new walls are added with the shortest possible path dividing the mother cell’s volume into two equal parts. Here, we show that for an isotropically growing tissue Errara’s rule results in the correct distributions of number of cell neighbors as well as cellular geometries, in contrast to a random division rule. Further we show that wall mechanics constrain the isotropic growth such that the resulting cell shape distributions more closely agree with experimental data extracted from the shoot apex of Arabidopsis thaliana.

  4. Use of Different Furnaces to Study Repeatability and Reproducibility of Three Pd-C Cells

    NASA Astrophysics Data System (ADS)

    Battuello, M.; Florio, M.; Girard, F.

    2010-09-01

    Three different Pd-C eutectic fixed-point cells were prepared and investigated at INRIM. Several tens of phase transition runs were carried out and recorded with both a Si-based radiation thermometer at 950 nm and a precision InGaAs-based thermometer at 1.6 μm. Two of the cells were of the same design with an inner volume of 12 cm3. The third one was smaller with a useful inner volume of 3.6 cm3. The three cells were filled with palladium powder 4N5 or 4N8 pure and graphite powder 6N pure. The repeatability and stability of the inflection point were investigated over a period of 1 year. The noticeably different external dimensions of the two cells, namely, 110 mm and 40 mm in length, allowed the influence of the longitudinal temperature distribution to be investigated. For this purpose, two different furnaces, a single-zone with SiC heaters and a three-zone with MoSi2 heaters, were used. Different operative conditions, namely, temperature steps, melting rate, longitudinal temperature distributions, and position of cells within the furnace, were tested to investigate the reproducibility of the cells. Effects on the duration and shape of the plateaux were also studied. This article gives details of the measurement setup and analyses of the melting plateaux obtained with the different conditions.

  5. Monitoring cell morphology during necrosis and apoptosis by quantitative phase imaging

    NASA Astrophysics Data System (ADS)

    Mugnano, Martina; Calabuig, Alejandro; Grilli, Simonetta; Miccio, Lisa; Ferraro, Pietro

    2015-05-01

    Cellular morphology changes and volume alterations play significant roles in many biological processes and they are mirrors of cell functions. In this paper, we propose the Digital Holographic microscope (DH) as a non-invasive imaging technique for a rapid and accurate extraction of morphological information related to cell death. In particular, we investigate the morphological variations that occur during necrosis and apoptosis. The study of necrosis is extremely important because it is often associated with unwarranted loss of cells in human pathologies such as ischemia, trauma, and some forms of neurodegeneration; therefore, a better elucidation in terms of cell morphological changes could pave the way for new treatments. Also, apoptosis is extremely important because it's involved in cancer, both in its formation and in medical treatments. Because the inability to initiate apoptosis enhances tumour formation, current cancer treatments target this pathway. Within this framework, we have developed a transmission off-axis DH apparatus integrated with a micro incubator for investigation of living cells in a temperature and CO2 controlled environment. We employ DH to analyse the necrosis cell death induced by laser light (wavelength 473 nm, light power 4 mW). We have chosen as cellular model NIH 3T3 mouse embryonic fibroblasts because their adhesive features such as morphological changes, and the time needed to adhere and spread have been well characterized in the literature. We have monitored cell volume changes and morphological alterations in real time in order to study the necrosis process accurately and quantitatively. Cell volume changes were evaluated from the measured phase changes of light transmitted through cells. Our digital holographic experiments showed that after exposure of cells to laser light for 90-120 min., they swell and then take on a balloon-like shape until the plasma membrane ruptures and finally the cell volume decreases. Furthermore, we present a preliminary study on the variation of morphological parameters in case of cell apoptosis induced by exposure to 10 μM cadmium chloride. We employ the same cell line, monitoring the process for 18 hours. In the vast group of environmental pollutants, the toxic heavy metal cadmium is considered a likely candidate as a causative agent of several types of cancers. Widely distributed and used in industry, and with a broad range of target organs and a long half-life (10-30 years) in the human body, this element has been long known for its multiple adverse effects on human health, through occupational or environmental exposure. In apoptosis, we measure cell volume decrease and cell shrinking. Both data of apoptosis and necrosis were analysed by means of a Sigmoidal Statistical Distribution function, which allows several quantitative data to be established, such as swelling and cell death time, flux of intracellular material from inside to outside the cell, initial and final volume versus time. In addition, we can quantitatively study the cytoplasmatic granularity that occurs during necrosis. As a future application, DH could be employed as a non-invasive and label-free method to distinguish between apoptosis and necrosis in terms of morphological parameters.

  6. Mechanistic simulation of normal-tissue damage in radiotherapy—implications for dose-volume analyses

    NASA Astrophysics Data System (ADS)

    Rutkowska, Eva; Baker, Colin; Nahum, Alan

    2010-04-01

    A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V20 correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies.

  7. Static harmonization of dynamically harmonized Fourier transform ion cyclotron resonance cell.

    PubMed

    Zhdanova, Ekaterina; Kostyukevich, Yury; Nikolaev, Eugene

    2017-08-01

    Static harmonization in the Fourier transform ion cyclotron resonance cell improves the resolving power of the cell and prevents dephasing of the ion cloud in the case of any trajectory of the charged particle, not necessarily axisymmetric cyclotron (as opposed to dynamic harmonization). We reveal that the Fourier transform ion cyclotron resonance cell with dynamic harmonization (paracell) is proved to be statically harmonized. The volume of the statically harmonized potential distribution increases with an increase in the number of trap segments.

  8. Distributed mean curvature on a discrete manifold for Regge calculus

    NASA Astrophysics Data System (ADS)

    Conboye, Rory; Miller, Warner A.; Ray, Shannon

    2015-09-01

    The integrated mean curvature of a simplicial manifold is well understood in both Regge Calculus and Discrete Differential Geometry. However, a well motivated pointwise definition of curvature requires a careful choice of the volume over which to uniformly distribute the local integrated curvature. We show that hybrid cells formed using both the simplicial lattice and its circumcentric dual emerge as a remarkably natural structure for the distribution of this local integrated curvature. These hybrid cells form a complete tessellation of the simplicial manifold, contain a geometric orthonormal basis, and are also shown to give a pointwise mean curvature with a natural interpretation as the fractional rate of change of the normal vector.

  9. Independent Orbiter Assessment (IOA): Analysis of the Electrical Power Distribution and Control Subsystem, Volume 2

    NASA Technical Reports Server (NTRS)

    Schmeckpeper, K. R.

    1987-01-01

    The results of the Independent Orbiter Assessment (IOA) of the Failure Modes and Effects Analysis (FMEA) and Critical Items List (CIL) are presented. The IOA approach features a top-down analysis of the hardware to determine failure modes, criticality, and potential critical items. To preserve independence, this analysis was accomplished without reliance upon the results contained within the NASA FMEA/CIL documentation. This report documents the independent analysis results corresponding to the Orbiter Electrical Power Distribution and Control (EPD and C) hardware. The EPD and C hardware performs the functions of distributing, sensing, and controlling 28 volt DC power and of inverting, distributing, sensing, and controlling 117 volt 400 Hz AC power to all Orbiter subsystems from the three fuel cells in the Electrical Power Generation (EPG) subsystem. Volume 2 continues the presentation of IOA analysis worksheets and contains the potential critical items list.

  10. Bioimaging of Fluorescence-Labeled Mitochondria in Subcutaneously Grafted Murine Melanoma Cells by the “In Vivo Cryotechnique”

    PubMed Central

    Lei, Ting; Huang, Zheng; Ohno, Nobuhiko; Wu, Bao; Sakoh, Takashi; Saitoh, Yurika; Saiki, Ikuo

    2014-01-01

    The microenvironments of organs with blood flow affect the metabolic profiles of cancer cells, which are influenced by mitochondrial functions. However, histopathological analyses of these aspects have been hampered by technical artifacts of conventional fixation and dehydration, including ischemia/anoxia. The purpose of this study was to combine the in vivo cryotechnique (IVCT) with fluorescent protein expression, and examine fluorescently labeled mitochondria in grafted melanoma tumors. The intensity of fluorescent proteins was maintained well in cultured B16-BL6 cells after cryotechniques followed by freeze-substitution (FS). In the subcutaneous tumors of mitochondria-targeted DsRed2 (mitoDsRed)-expressing cells, a higher number of cancer cells were found surrounding the widely opened blood vessels that contained numerous erythrocytes. Such blood vessels were immunostained positively for immunoglobulin M and ensheathed by basement membranes. MitoDsRed fluorescence was detected in scattering melanoma cells using the IVCT-FS method, and the total mitoDsRed volume in individual cancer cells was significantly decreased with the expression of markers of hypoxia. MitoDsRed was frequently distributed throughout the cytoplasm and in processes extending along basement membranes. IVCT combined with fluorescent protein expression is a useful tool to examine the behavior of fluorescently labeled cells and organelles. We propose that the mitochondrial volume is dynamically regulated in the hypoxic microenvironment and that mitochondrial distribution is modulated by cancer cell interactions with basement membranes. PMID:24394469

  11. Oxidation-induced calcium-dependent dehydration of normal human red blood cells.

    PubMed

    Shcherbachenko, Irina M; Lisovskaya, Irina L; Tikhonov, Vladimir P

    2007-05-01

    Phenazine-methosulphate (PMS) is a strong oxidant that induces reactive oxygen species (ROS) formation in cells. Though it has been shown that PMS increases the red blood cell (RBC) membrane permeability to K(+), the hypotheses on the mechanism of PMS-induced effects are contradictory and there are no data on volume changes induced by this oxidant. Therefore, the influence of the PMS + ascorbate oxidative system on the volume of normal human RBCs was studied. In a Ca(2 + )-containing medium, PMS + ascorbate caused dehydration (shrinking) of RBCs judged by: (1) changes in the density and osmotic resistance distributions of RBCs, and (2) a decrease in their low-angle scattering assessed by FACS analysis. The dehydration resulted from activation of the Gardos channels, was PMS and ascorbate concentration-dependent, was associated with broadening of the density and osmotic resistance distributions of the RBCs, and decreased in the presence of the taxifolin and rutin antioxidants. These findings contribute to a better understanding of the physiology and pathology of oxidatively-modified RBCs and may be of practical significance in estimating the antioxidant activity of various substances.

  12. Comparison of whole body and tissue blood volumes in rainbow trout (Salmo gairdneri) with 125I bovine serum albumin and 51Cr-erythrocyte tracers

    USGS Publications Warehouse

    Gingerich, W.H.; Pityer, R.A.

    1989-01-01

    Total, packed cell and, plasma volume estimates were made for the whole body and selected tissues of rainbow trout by the simultaneous injection of radiolabelled trout erythrocyte (51Cr-RBC) and radioiodinated bovine serum albumin (125I-BSA) tracers. Blood volumes were estimated with both markers separately by the tracer-hematocrit method and as the combination of the 51Cr-RBC packed cell and 125I-BSA plasma volumes. Mean whole body blood volume was significantly less when calculated from the 51Cr-RBC tracer data (3.52±0.78 ml/100 g; ±SD) than when calculated with the 125I-BSA tracer (5.06±0.86 ml/100 g) or as the sum of the two volumes combined (4.49±0.60 ml/100 g). The whole body hematocrit (28±5%), estimated as the quotient of the 51Cr-RBC volume divided by the sum of the 125I-BSA and the 51Cr-RBC volumes, also was significantly less than the dorsal aortic microhematocrit (36±4%). Estimates of total blood volumes in most tissues were significantly smaller when calculated from the51Cr-RBC data than when calculated by the other two methods. Tissue blood volumes were greatest in highly vascularized and well perfused tissues and least in poorly vascularized tissues. The relative degree of vascularization among tissues generally remained the same regardless of whether the red cell or the plasma tracer was used to calculated blood volume. It is not clear whether the expanded plasma volume is the result of the distribution of erythrocyte-poor blood into the secondary circulation or the result of extravascular exchange of plasma proteins.

  13. Effect of an electric field on the orientation of a liquid crystal in a cell with a nonuniform director distribution

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

    Aksenova, E. V., E-mail: e.aksenova@spbu.ru; Karetnikov, A. A.; Karetnikov, N. A.

    2016-05-15

    The electric field-induced reorientation of a nematic liquid crystal in cells with a planar helicoidal or a homeoplanar structure of a director field is studied theoretically and experimentally. The dependences of the capacitances of these systems on the voltage in an applied electric field below and above the Fréedericksz threshold are experimentally obtained and numerically calculated. The calculations use the director distribution in volume that is obtained by direct minimization of free energy at various voltages. The inhomogeneity of the electric field inside a cell is taken into account. The calculation results are shown to agree with the experimental data.

  14. 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.

  15. 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.

  16. Red cell distribution width does not predict stroke severity or functional outcome.

    PubMed

    Ntaios, George; Gurer, Ozgur; Faouzi, Mohamed; Aubert, Carole; Michel, Patrik

    2012-01-01

    Red cell distribution width was recently identified as a predictor of cardiovascular and all-cause mortality in patients with previous stroke. Red cell distribution width is also higher in patients with stroke compared with those without. However, there are no data on the association of red cell distribution width, assessed during the acute phase of ischemic stroke, with stroke severity and functional outcome. In the present study, we sought to investigate this relationship and ascertain the main determinants of red cell distribution width in this population. We used data from the Acute Stroke Registry and Analysis of Lausanne for patients between January 2003 and December 2008. Red cell distribution width was generated at admission by the Sysmex XE-2100 automated cell counter from ethylene diamine tetraacetic acid blood samples stored at room temperature until measurement. An χ(2) -test was performed to compare frequencies of categorical variables between different red cell distribution width quartiles, and one-way analysis of variance for continuous variables. The effect of red cell distribution width on severity and functional outcome was investigated in univariate and multivariate robust regression analysis. Level of significance was set at 95%. There were 1504 patients (72±15·76 years, 43·9% females) included in the analysis. Red cell distribution width was significantly associated to NIHSS (β-value=0·24, P=0·01) and functional outcome (odds ratio=10·73 for poor outcome, P<0·001) at univariate analysis but not multivariate. Prehospital Rankin score (β=0·19, P<0·001), serum creatinine (β=0·008, P<0·001), hemoglobin (β=-0·009, P<0·001), mean platelet volume (β=0·09, P<0·05), age (β=0·02, P<0·001), low ejection fraction (β=0·66, P<0·001) and antihypertensive treatment (β=0·32, P<0·001) were independent determinants of red cell distribution width. Red cell distribution width, assessed during the early phase of acute ischemic stroke, does not predict severity or functional outcome. © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.

  17. Introducing stochastics into the simulation of convective precipitation events

    NASA Astrophysics Data System (ADS)

    Pistotnik, Georg

    2010-05-01

    In a joint project, the Central Institute for Meteorology and Geodynamics (ZAMG) and the Vienna University of Technology aimed to characterize strong precipitation events and their impact in the Bucklige Welt region in Eastern Austria. Both the region's hydrological and meteorological characteristics, namely its composition of virtually countless small catchments with short response times and a high frequency of summertime convective storms, cause the occurrence of flooding to be strictly tied to convective rainfall events, which is why this study has been focused on this type of precipitation. The meteorological database consists of the ZAMG's high-resolution analysis and nowcasting system INCA ("Integrated Nowcasting through Comprehensive Analysis"), which provides a set of precipitation analyses generated by a statistically optimized combination of rain gauge measurements and radar data with a temporal resolution of 15 minutes and a spatial resolution of 1 kilometre. An intensity threshold of 3.8mm/15min has been used to classify any observed precipitation as a convective one, thus extracting 245 convection days with a total number of almost 1600 individual storm events over the project region out of the 5-year data set from 2003 to 2007. Consecutive analyses were used to compute the motion of these storms, a complex process that could not be completely automatized; due to the repeated occurrence of storm splits or coalescences, a manual control of the automatically provided "suggestion" of movement had to be performed in order to merge two or more precipitation maxima to a single storm if necessary, thus yielding the smoothest and most plausible storm tracks and ensuring a high quality of the database. In the first part of the project, distributions for all characteristic parameters have been derived, including the number of storms per day, their place and time of initiation, their motion, lifetime, maximum intensity and maximum "cell volume" (i.e. overall precipitation per time step). Both components of the mean motion as well as of its deviations could be approximated by normal distributions, whereas the number of storms per day, their lifetime, maximum intensity and maximum cell volume roughly followed exponential distributions. The shapes of the convective cells were approximated by Gaussian bells with the peak intensity and the cell volume as boundary conditions. The temporal courses of the peak intensities and cell volumes were assumed to follow parabolas which are symmetric with respect to the half of the lifetime. In the second part of the project, these distributions were used to drive a random generator that allows simulating an arbitrary number of convection days in order to obtain pseudo time series of convective precipitation for each grid point. An algorithm to create correlated samples of random numbers enabled to also account for the observed correlation between some of the parameters, i.e. lifetime and maximum intensity or maximum cell volume. The spatial structures of the return periods of simulated convective precipitation events may provide valuable additional information when being assimilated to the time series measured by the (unfortunately rather sparse) rain gauges in this region. Thus, further studies have to investigate to what extent the "convection simulator" is able to reproduce these time series. Some iterative fine-tuning of the parameters' distributions as well as an extension of the database to a longer time span may further improve the results and enable to simulate realistic spatio-temporal convection scenarios ("design storms") that have the potential to feed hydrological models and, together with vegetation and soil characteristics, hopefully enable to better assess and regionalize the torrent hazard over the project region.

  18. Gold Nanoparticle Quantitation by Whole Cell Tomography.

    PubMed

    Sanders, Aric W; Jeerage, Kavita M; Schwartz, Cindi L; Curtin, Alexandra E; Chiaramonti, Ann N

    2015-12-22

    Many proposed biomedical applications for engineered gold nanoparticles require their incorporation by mammalian cells in specific numbers and locations. Here, the number of gold nanoparticles inside of individual mammalian stem cells was characterized using fast focused ion beam-scanning electron microscopy based tomography. Enhanced optical microscopy was used to provide a multiscale map of the in vitro sample, which allows cells of interest to be identified within their local environment. Cells were then serially sectioned using a gallium ion beam and imaged using a scanning electron beam. To confirm the accuracy of single cross sections, nanoparticles in similar cross sections were imaged using transmission electron microscopy and scanning helium ion microscopy. Complete tomographic series were then used to count the nanoparticles inside of each cell and measure their spatial distribution. We investigated the influence of slice thickness on counting single particles and clusters as well as nanoparticle packing within clusters. For 60 nm citrate stabilized particles, the nanoparticle cluster packing volume is 2.15 ± 0.20 times the volume of the bare gold nanoparticles.

  19. Exact solutions to model surface and volume charge distributions

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, S.; Majumdar, N.; Bhattacharya, P.; Jash, A.; Bhattacharya, D. S.

    2016-10-01

    Many important problems in several branches of science and technology deal with charges distributed along a line, over a surface and within a volume. Recently, we have made use of new exact analytic solutions of surface charge distributions to develop the nearly exact Boundary Element Method (neBEM) toolkit. This 3D solver has been successful in removing some of the major drawbacks of the otherwise elegant Green's function approach and has been found to be very accurate throughout the computational domain, including near- and far-field regions. Use of truly distributed singularities (in contrast to nodally concentrated ones) on rectangular and right-triangular elements used for discretizing any three-dimensional geometry has essentially removed many of the numerical and physical singularities associated with the conventional BEM. In this work, we will present this toolkit and the development of several numerical models of space charge based on exact closed-form expressions. In one of the models, Particles on Surface (ParSur), the space charge inside a small elemental volume of any arbitrary shape is represented as being smeared on several surfaces representing the volume. From the studies, it can be concluded that the ParSur model is successful in getting the estimates close to those obtained using the first-principles, especially close to and within the cell. In the paper, we will show initial applications of ParSur and other models in problems related to high energy physics.

  20. Evaluation of in silico pharmacokinetic properties and in vitro cytotoxic activity of selected newly synthesized N-succinimide derivatives.

    PubMed

    Milosevic, Natasa P; Kojic, Vesna; Curcic, Jelena; Jakimov, Dimitar; Milic, Natasa; Banjac, Nebojsa; Uscumlic, Gordana; Kaliszan, Roman

    2017-04-15

    Design of a new drug entity is usually preceded by analysis of quantitative structure activity (properties) relationships, QSA(P)R. Six newly synthesized succinimide derivatives have been determined for (i) in silico physico-chemical descriptors, pharmacokinetic and toxicity predictors, (ii) in vitro biological activity on four different carcinoma cell lines and on normal fetal lung cells and (iii) lipophilicity on liquid chromatography. All compounds observed were predicted for good permeability and solubility, good oral absorption rate and moderate volume of distribution as well as for modest blood brain permeation, followed by acceptable observed toxicity. In silico determined lipophilicity, permeability through jejunum and aqueous solubility were correlated with experimentally obtained lipophilic constants (by use of high pressure liquid chromatography) and linear correlations were obtained. Absorption rate and volume of distribution were predicted by chromatographic lipophilicity measurements while permeation through blood bran barrier was predicted dominantly by molecular size defined with molecular weight. Five compounds have demonstrated antiproliferative activity toward cervix carcinoma HeLa cell lines; three were cytotoxic against breast carcinoma MCF-7 cells, while one inhibited proliferation of colon carcinoma HT-29 cell lines. Only one compound was cytotoxic toward normal cell lines, while other compounds were proven as safe. Antiproliferative potential against HeLa cells was described as exponential function of lipophilicity. Based on obtained results, lead compounds were selected. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. In Operando Quantification of Three-Dimensional Water Distribution in Nanoporous Carbon-Based Layers in Polymer Electrolyte Membrane Fuel Cells.

    PubMed

    Alrwashdeh, Saad S; Manke, Ingo; Markötter, Henning; Klages, Merle; Göbel, Martin; Haußmann, Jan; Scholta, Joachim; Banhart, John

    2017-06-27

    Understanding the function of nanoporous materials employed in polymer electrolyte membrane fuel cells (PEMFCs) is crucial to improve their performance, durability, and cost efficiency. Up to now, the water distribution in the nm-sized pore structures was hardly accessible during operation of the cells. Here we demonstrate that phase contrast synchrotron X-ray tomography allows for an in operando quantification of the three-dimensional water distribution within the nm-sized pores of carbon-based microporous layers (MPLs). For this purpose, a fuel cell design optimized for tomographic phase contrast measurements was realized. Water in the pores of the entire MPL was detected and quantified. We found an inhomogeneous distribution of the local water saturation and a sharp boundary between mostly filled MPL and almost empty areas. We attribute the latter observation to the two-phase boundary created because condensation takes place predominantly on one side of the boundary. Furthermore, high water saturation in large areas hints at gas diffusion or transport along preferred three-dimensional paths through the material, therefore bypassing most of the MPL volume. Our approach may contribute significantly to future investigations of nanoporous fuel cell materials under realistic operating conditions.

  2. How Cells Can Control Their Size by Pumping Ions.

    PubMed

    Kay, Alan R

    2017-01-01

    The ability of all cells to set and regulate their size is a fundamental aspect of cellular physiology. It has been known for sometime but not widely so, that size stability in animal cells is dependent upon the operation of the sodium pump, through the so-called pump-leak mechanism (Tosteson and Hoffman, 1960). Impermeant molecules in cells establish an unstable osmotic condition, the Donnan effect, which is counteracted by the operation of the sodium pump, creating an asymmetry in the distribution of Na + and K + staving off water inundation. In this paper, which is in part a tutorial, I show how to model quantitatively the ion and water fluxes in a cell that determine the cell volume and membrane potential. The movement of water and ions is constrained by both osmotic and charge balance, and is driven by ion and voltage gradients and active ion transport. Transforming these constraints and forces into a set of coupled differential equations allows us to model how the ion distributions, volume and voltage change with time. I introduce an analytical solution to these equations that clarifies the influence of ion conductances, pump rates and water permeability in this multidimensional system. I show that the number of impermeant ions ( x ) and their average charge have a powerful influence on the distribution of ions and voltage in a cell. Moreover, I demonstrate that in a cell where the operation of active ion transport eliminates an osmotic gradient, the size of the cell is directly proportional to x . In addition, I use graphics to reveal how the physico-chemical constraints and chemical forces interact with one another in apportioning ions inside the cell. The form of model used here is applicable to all membrane systems, including mitochondria and bacteria, and I show how pumps other than the sodium pump can be used to stabilize cells. Cell biologists may think of electrophysiology as the exclusive domain of neuroscience, however the electrical effects of ion fluxes need to become an intimate part of cell biology if we are to understand a fundamental process like cell size regulation.

  3. Adult murine CNS stem cells express aquaporin channels.

    PubMed

    La Porta, Caterina A M; Gena, Patrizia; Gritti, Angela; Fascio, Umberto; Svelto, Maria; Calamita, Giuseppe

    2006-02-01

    Fluid homoeostasis is of critical importance in many functions of the CNS (central nervous system) as indicated by the fact that dysregulation of cell volume underlies clinical conditions such as brain oedema and hypoxia. Water balance is also important during neurogenesis as neural stem cells move considerable amounts of water into or out of the cell to rapidly change their volume during differentiation. Consistent with the relevance of water transport in CNS, multiple AQP (aquaporin) water channels have been recognized and partially characterized in brain cell function. However, the presence and distribution of AQPs in CNS stem cells has not yet been assessed. In the present study, we investigate the expression and subcellular localization of AQPs in murine ANSCs (adult neural stem cells). Considerable AQP8 mRNAs were found in ANSCs where, as expected, the transcript of two additional AQPs, AQP4 and AQP9, was also detected. Immunoblotting with subcellular membrane fractions of ANSCs showed predominant expression of AQP8 in the mitochondria-enriched fraction. This result was consistent with the spotted immunoreactivity profile encountered within the ANSCs by confocal immunofluorescence. AQP8 may have a role in mitochondrial volume regulation during ANSC differentiation. Recognition of AQPs in ANSCs is a step forward in our knowledge of water homoeostasis in the CNS and provides useful information for the purposes of stem cell technology.

  4. Treatment of internal sources in the finite-volume ELLAM

    USGS Publications Warehouse

    Healy, R.W.; ,; ,; ,; ,; ,

    2000-01-01

    The finite-volume Eulerian-Lagrangian localized adjoint method (FVELLAM) is a mass-conservative approach for solving the advection-dispersion equation. The method has been shown to be accurate and efficient for solving advection-dominated problems of solute transport in ground water in 1, 2, and 3 dimensions. Previous implementations of FVELLAM have had difficulty in representing internal sources because the standard assumption of lowest order Raviart-Thomas velocity field does not hold for source cells. Therefore, tracking of particles within source cells is problematic. A new approach has been developed to account for internal sources in FVELLAM. It is assumed that the source is uniformly distributed across a grid cell and that instantaneous mixing takes place within the cell, such that concentration is uniform across the cell at any time. Sub-time steps are used in the time-integration scheme to track mass outflow from the edges of the source cell. This avoids the need for tracking within the source cell. We describe the new method and compare results for a test problem with a wide range of cell Peclet numbers.

  5. Foam structure :from soap froth to solid foams.

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

    Kraynik, Andrew Michael

    2003-01-01

    The properties of solid foams depend on their structure, which usually evolves in the fluid state as gas bubbles expand to form polyhedral cells. The characteristic feature of foam structure-randomly packed cells of different sizes and shapes-is examined in this article by considering soap froth. This material can be modeled as a network of minimal surfaces that divide space into polyhedral cells. The cell-level geometry of random soap froth is calculated with Brakke's Surface Evolver software. The distribution of cell volumes ranges from monodisperse to highly polydisperse. Topological and geometric properties, such as surface area and edge length, of themore » entire foam and individual cells, are discussed. The shape of struts in solid foams is related to Plateau borders in liquid foams and calculated for different volume fractions of material. The models of soap froth are used as templates to produce finite element models of open-cell foams. Three-dimensional images of open-cell foams obtained with x-ray microtomography allow virtual reconstruction of skeletal structures that compare well with the Surface Evolver simulations of soap-froth geometry.« less

  6. Self-digitization chip for single-cell genotyping of cancer-related mutations

    PubMed Central

    Monroe, Luke D.; Kreutz, Jason E.; Schneider, Thomas; Fujimoto, Bryant S.; Chiu, Daniel T.; Radich, Jerald P.; Paguirigan, Amy L.

    2018-01-01

    Cancer is a heterogeneous disease, and patient-level genetic assessments can guide therapy choice and impact prognosis. However, little is known about the impact of genetic variability within a tumor, intratumoral heterogeneity (ITH), on disease progression or outcome. Current approaches using bulk tumor specimens can suggest the presence of ITH, but only single-cell genetic methods have the resolution to describe the underlying clonal structures themselves. Current techniques tend to be labor and resource intensive and challenging to characterize with respect to sources of biological and technical variability. We have developed a platform using a microfluidic self-digitization chip to partition cells in stationary volumes for cell imaging and allele-specific PCR. Genotyping data from only confirmed single-cell volumes is obtained and subject to a variety of relevant quality control assessments such as allele dropout, false positive, and false negative rates. We demonstrate single-cell genotyping of the NPM1 type A mutation, an important prognostic indicator in acute myeloid leukemia, on single cells of the cell line OCI-AML3, describing a more complex zygosity distribution than would be predicted via bulk analysis. PMID:29718986

  7. Self-digitization chip for single-cell genotyping of cancer-related mutations.

    PubMed

    Thompson, Alison M; Smith, Jordan L; Monroe, Luke D; Kreutz, Jason E; Schneider, Thomas; Fujimoto, Bryant S; Chiu, Daniel T; Radich, Jerald P; Paguirigan, Amy L

    2018-01-01

    Cancer is a heterogeneous disease, and patient-level genetic assessments can guide therapy choice and impact prognosis. However, little is known about the impact of genetic variability within a tumor, intratumoral heterogeneity (ITH), on disease progression or outcome. Current approaches using bulk tumor specimens can suggest the presence of ITH, but only single-cell genetic methods have the resolution to describe the underlying clonal structures themselves. Current techniques tend to be labor and resource intensive and challenging to characterize with respect to sources of biological and technical variability. We have developed a platform using a microfluidic self-digitization chip to partition cells in stationary volumes for cell imaging and allele-specific PCR. Genotyping data from only confirmed single-cell volumes is obtained and subject to a variety of relevant quality control assessments such as allele dropout, false positive, and false negative rates. We demonstrate single-cell genotyping of the NPM1 type A mutation, an important prognostic indicator in acute myeloid leukemia, on single cells of the cell line OCI-AML3, describing a more complex zygosity distribution than would be predicted via bulk analysis.

  8. 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

  9. Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

    PubMed

    Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberta; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

    2015-06-25

    Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites. © 2015 by The American Society of Hematology.

  10. Satellite Power Systems (SPS) Concept Definition Study. Volume 3: SPS Concept Evolution

    NASA Technical Reports Server (NTRS)

    Hanley, G.

    1978-01-01

    A solar photovoltaic satellite based upon the utilization of a GaAlAs solar cell is defined. Topics covered include silicon-based photovoltaics, solar thermal power conversion, microwave energy transmission, power distribution, structures, attitude control and stationkeeping, thermal, and information management and control.

  11. Impact of cholesterol on voids in phospholipid membranes

    NASA Astrophysics Data System (ADS)

    Falck, Emma; Patra, Michael; Karttunen, Mikko; Hyvönen, Marja T.; Vattulainen, Ilpo

    2004-12-01

    Free volume pockets or voids are important to many biological processes in cell membranes. Free volume fluctuations are a prerequisite for diffusion of lipids and other macromolecules in lipid bilayers. Permeation of small solutes across a membrane, as well as diffusion of solutes in the membrane interior are further examples of phenomena where voids and their properties play a central role. Cholesterol has been suggested to change the structure and function of membranes by altering their free volume properties. We study the effect of cholesterol on the properties of voids in dipalmitoylphosphatidylcholine (DPPC) bilayers by means of atomistic molecular dynamics simulations. We find that an increasing cholesterol concentration reduces the total amount of free volume in a bilayer. The effect of cholesterol on individual voids is most prominent in the region where the steroid ring structures of cholesterol molecules are located. Here a growing cholesterol content reduces the number of voids, completely removing voids of the size of a cholesterol molecule. The voids also become more elongated. The broad orientational distribution of voids observed in pure DPPC is, with a 30% molar concentration of cholesterol, replaced by a distribution where orientation along the bilayer normal is favored. Our results suggest that instead of being uniformly distributed to the whole bilayer, these effects are localized to the close vicinity of cholesterol molecules.

  12. Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

    PubMed Central

    Polli, Roberson S.; Malheiros, Jackeline M.; dos Santos, Renan; Hamani, Clement; Longo, Beatriz M.; Tannús, Alberto; Mello, Luiz E.; Covolan, Luciene

    2014-01-01

    Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human temporal lobe epilepsy (TLE) but the distribution and severity of structural lesions between these two models may differ. Magnetic resonance imaging (MRI) studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation time and volume, but simultaneous comparative results have not been reported yet. The aim of this study was to compare the MRI T2HP and volume with histological data and frequency of seizures in both models. KA- and PILO-treated rats were imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS) frequency over the 9 months following status epilepticus (SE). Compared to controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3 months post SE. In contrast, hippocampal volume was unchanged in PILO-treated animals despite detectable increased T2HP and cell loss in granule cell layer, CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3 cells was smaller than age-matched CTL group. In contrast, PILO group had MRI volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells. In this group, T2HP signal was unaltered at 6 or 9 months after status. Reductions in the number of cells were not progressive in both models. Notably, the SRS frequency was higher in PILO than in the KA model. The volumetry data correlated well with tissue damage in the epileptic brain, suggesting that MRI may be useful for tracking longitudinal hippocampal changes, allowing the assessment of individual variability and disease progression. Our results indicate that the temporal changes in hippocampal morphology are distinct for both models of TLE and that these are not significantly correlated to the frequency of SRS. PMID:25071699

  13. Lung cancers diagnosed at annual CT screening: volume doubling times.

    PubMed

    Henschke, Claudia I; Yankelevitz, David F; Yip, Rowena; Reeves, Anthony P; Farooqi, Ali; Xu, Dongming; Smith, James P; Libby, Daniel M; Pasmantier, Mark W; Miettinen, Olli S

    2012-05-01

    To empirically address the distribution of the volume doubling time (VDT) of lung cancers diagnosed in repeat annual rounds of computed tomographic (CT) screening in the International Early Lung Cancer Action Program (I-ELCAP), first and foremost with respect to rates of tumor growth but also in terms of cell types. All CT screenings in I-ELCAP from 1993 to 2009 were performed according to HIPAA-compliant protocols approved by the institutional review boards of the collaborating institutions. All instances of first diagnosis of primary lung cancer after a negative screening result 7-18 months earlier were identified, with symptom-prompted diagnoses included. Lesion diameter was calculated by using the measured length and width of each cancer at the time when the nodule was first identified for further work-up and at the time of the most recent prior screening, 7-18 months earlier. The length and width were measured a second time for each cancer, and the geometric mean of the two calculated diameters was used to calculate the VDT. The χ(2) statistic was used to compare the VDT distributions. The median VDT for 111 cancers was 98 days (interquartile range, 108). For 56 (50%) cancers it was less than 100 days, and for three (3%) cancers it was more than 400 days. Adenocarcinoma was the most frequent cell type (50%), followed by squamous cell carcinoma (19%), small cell carcinoma (19%), and others (12%). Lung cancers manifesting as subsolid nodules had significantly longer VDTs than those manifesting as solid nodules (P < .0001). Lung cancers diagnosed in annual repeat rounds of CT screening, as manifest by the VDT and cell-type distributions, are similar to those diagnosed in the absence of screening.

  14. Cell Kinetic and Histomorphometric Analysis of Microgravitational Osteopenia: PARE.03B

    NASA Technical Reports Server (NTRS)

    Roberts, W. Eugene; Garetto, Lawrence P.

    1998-01-01

    Previous methods of identifying cells undergoing DNA synthesis (S-phase) utilized H-3 thymidine (3HT) autoradiography. 5-Bromo-2'-deoxyuridine (BrdU) immunohistochemistry is a nonradioactive alternative method. This experiment compared the two methods using the nuclear volume model for osteoblast histogenesis in two different embedding media. Twenty Sprague-Dawley rats were used, with half receiving 3HT (1 micro Ci/g) and the other half BrdU (50 microgram/g). Condyies were embedded (one side in paraffin, the other in plastic) and S-phase nuclei were identified using either autoradiography or immunohistochemistry. The fractional distribution of preosteoblast cell types and the percentage of labeled cells (within each cell fraction and label index) were calculated and expressed as mean q standard error. Chi-Square analysis showed only a minor difference in the fractional distribution of cell types. However, there were significant differences (p less than 0.05) by ANOVA, in the nuclear labeling of specific cell types. With the exception of the less-differentiated A+A'cells, more BrdU label was consistently detected in paraffin than in plastic-embedded sections. In general, more nuclei were labeled with 3H-thymidine than with BrdU in both types of embedding media. Labeling index data (labeled cells/total cells sampled x 100) indicated that BrdU in paraffin, but not plastic gave the same results as 3HT in either embedding method. Thus, we conclude that the two labeling methods do not yield the same results for the nuclear volume model and that embedding media is an important factor whenusing BrdU. As a result of this work, 3HT was chosen for used in the PARE.03 flight experiments.

  15. 4D imaging of polymer electrolyte membrane fuel cell catalyst layers by soft X-ray spectro-tomography

    NASA Astrophysics Data System (ADS)

    Wu, Juan; Melo, Lis G. A.; Zhu, Xiaohui; West, Marcia M.; Berejnov, Viatcheslav; Susac, Darija; Stumper, Juergen; Hitchcock, Adam P.

    2018-03-01

    4D imaging - the three-dimensional distributions of chemical species determined using multi-energy X-ray tomography - of cathode catalyst layers of polymer electrolyte membrane fuel cells (PEM-FC) has been measured by scanning transmission x-ray microscopy (STXM) spectro-tomography at the C 1s and F 1s edges. In order to monitor the effects of radiation damage on the composition and 3D structure of the perfluorosulfonic acid (PFSA) ionomer, the same volume was measured 3 times sequentially, with spectral characterization of that same volume at several time points during the measurements. The changes in the average F 1s spectrum of the ionomer in the cathode as the measurements progressed gave insights into the degree of chemical modification, fluorine mass loss, and changes in the 3D distributions of ionomer that accompanied the spectro-tomographic measurement. The PFSA ionomer-in-cathode is modified both chemically and physically by radiation damage. The 3D volume decreases anisotropically. By reducing the incident flux, partial defocusing (50 nm spot size), limiting the number of tilt angles to 14, and using compressed sensing reconstruction, we show it is possible to reproducibly measure the 3D structure of ionomer in PEM-FC cathodes at ambient temperature while causing minimal radiation damage.

  16. The Effect of Fiber Strength Stochastics and Local Fiber Volume Fraction on Multiscale Progressive Failure of Composites

    NASA Technical Reports Server (NTRS)

    Ricks, Trenton M.; Lacy, Jr., Thomas E.; Bednarcyk, Brett A.; Arnold, Steven M.

    2013-01-01

    Continuous fiber unidirectional polymer matrix composites (PMCs) can exhibit significant local variations in fiber volume fraction as a result of processing conditions that can lead to further local differences in material properties and failure behavior. In this work, the coupled effects of both local variations in fiber volume fraction and the empirically-based statistical distribution of fiber strengths on the predicted longitudinal modulus and local tensile strength of a unidirectional AS4 carbon fiber/ Hercules 3502 epoxy composite were investigated using the special purpose NASA Micromechanics Analysis Code with Generalized Method of Cells (MAC/GMC); local effective composite properties were obtained by homogenizing the material behavior over repeating units cells (RUCs). The predicted effective longitudinal modulus was relatively insensitive to small (8%) variations in local fiber volume fraction. The composite tensile strength, however, was highly dependent on the local distribution in fiber strengths. The RUC-averaged constitutive response can be used to characterize lower length scale material behavior within a multiscale analysis framework that couples the NASA code FEAMAC and the ABAQUS finite element solver. Such an approach can be effectively used to analyze the progressive failure of PMC structures whose failure initiates at the RUC level. Consideration of the effect of local variations in constituent properties and morphologies on progressive failure of PMCs is a central aspect of the application of Integrated Computational Materials Engineering (ICME) principles for composite materials.

  17. Cathode architectures for alkali metal / oxygen batteries

    DOEpatents

    Visco, Steven J; Nimon, Vitaliy; De Jonghe, Lutgard C; Volfkovich, Yury; Bograchev, Daniil

    2015-01-13

    Electrochemical energy storage devices, such as alkali metal-oxygen battery cells (e.g., non-aqueous lithium-air cells), have a cathode architecture with a porous structure and pore composition that is tailored to improve cell performance, especially as it pertains to one or more of the discharge/charge rate, cycle life, and delivered ampere-hour capacity. A porous cathode architecture having a pore volume that is derived from pores of varying radii wherein the pore size distribution is tailored as a function of the architecture thickness is one way to achieve one or more of the aforementioned cell performance improvements.

  18. 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.

  19. Carbon dioxide and water vapor high temperature electrolysis

    NASA Technical Reports Server (NTRS)

    Isenberg, Arnold O.; Verostko, Charles E.

    1989-01-01

    The design, fabrication, breadboard testing, and the data base obtained for solid oxide electrolysis systems that have applications for planetary manned missions and habitats are reviewed. The breadboard tested contains sixteen tubular cells in a closely packed bundle for the electrolysis of carbon dioxide and water vapor. The discussion covers energy requirements, volume, weight, and operational characteristics related to the measurement of the reactant and product gas compositions, temperature distribution along the electrolyzer tubular cells and through the bundle, and thermal energy losses. The reliability of individual cell performance in the bundle configuration is assessed.

  20. Ceramic Hollow Fibre Constructs for Continuous Perfusion and Cell Harvest from 3D Hematopoietic Organoids

    PubMed Central

    Tahlawi, Asma; Li, Kang

    2018-01-01

    Tissue vasculature efficiently distributes nutrients, removes metabolites, and possesses selective cellular permeability for tissue growth and function. Engineered tissue models have been limited by small volumes, low cell densities, and invasive cell extraction due to ineffective nutrient diffusion and cell-biomaterial attachment. Herein, we describe the fabrication and testing of ceramic hollow fibre membranes (HFs) able to separate red blood cells (RBCs) and mononuclear cells (MNCs) and be incorporated into 3D tissue models to improve nutrient and metabolite exchange. These HFs filtered RBCs from human umbilical cord blood (CB) suspensions of 20% RBCs to produce 90% RBC filtrate suspensions. When incorporated within 5 mL of 3D collagen-coated polyurethane porous scaffold, medium-perfused HFs maintained nontoxic glucose, lactate, pH levels, and higher cell densities over 21 days of culture in comparison to nonperfused 0.125 mL scaffolds. This hollow fibre bioreactor (HFBR) required a smaller per-cell medium requirement and operated at cell densities > 10-fold higher than current 2D methods whilst allowing for continuous cell harvest through HFs. Herein, we propose HFs to improve 3D cell culture nutrient and metabolite diffusion, increase culture volume and cell density, and continuously harvest products for translational cell therapy biomanufacturing protocols. PMID:29760729

  1. Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres

    PubMed Central

    Alp, Murat; Cucinotta, Francis A.

    2017-01-01

    Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (>100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. PMID:28554507

  2. Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres

    NASA Astrophysics Data System (ADS)

    Alp, Murat; Cucinotta, Francis A.

    2017-05-01

    Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100 μm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3He and 12C particles at energies corresponding to a distance of 1 cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch.

  3. Track structure model of microscopic energy deposition by protons and heavy ions in segments of neuronal cell dendrites represented by cylinders or spheres.

    PubMed

    Alp, Murat; Cucinotta, Francis A

    2017-05-01

    Changes to cognition, including memory, following radiation exposure are a concern for cosmic ray exposures to astronauts and in Hadron therapy with proton and heavy ion beams. The purpose of the present work is to develop computational methods to evaluate microscopic energy deposition (ED) in volumes representative of neuron cell structures, including segments of dendrites and spines, using a stochastic track structure model. A challenge for biophysical models of neuronal damage is the large sizes (> 100µm) and variability in volumes of possible dendritic segments and pre-synaptic elements (spines and filopodia). We consider cylindrical and spherical microscopic volumes of varying geometric parameters and aspect ratios from 0.5 to 5 irradiated by protons, and 3 He and 12 C particles at energies corresponding to a distance of 1cm to the Bragg peak, which represent particles of interest in Hadron therapy as well as space radiation exposure. We investigate the optimal axis length of dendritic segments to evaluate microscopic ED and hit probabilities along the dendritic branches at a given macroscopic dose. Because of large computation times to analyze ED in volumes of varying sizes, we developed an analytical method to find the mean primary dose in spheres that can guide numerical methods to find the primary dose distribution for cylinders. Considering cylindrical segments of varying aspect ratio at constant volume, we assess the chord length distribution, mean number of hits and ED profiles by primary particles and secondary electrons (δ-rays). For biophysical modeling applications, segments on dendritic branches are proposed to have equal diameters and axes lengths along the varying diameter of a dendritic branch. Copyright © 2017. Published by Elsevier Ltd.

  4. High-resolution synchrotron X-ray analysis of bioglass-enriched hydrogels.

    PubMed

    Gorodzha, Svetlana; Douglas, Timothy E L; Samal, Sangram K; Detsch, Rainer; Cholewa-Kowalska, Katarzyna; Braeckmans, Kevin; Boccaccini, Aldo R; Skirtach, Andre G; Weinhardt, Venera; Baumbach, Tilo; Surmeneva, Maria A; Surmenev, Roman A

    2016-05-01

    Enrichment of hydrogels with inorganic particles improves their suitability for bone regeneration by enhancing their mechanical properties, mineralizability, and bioactivity as well as adhesion, proliferation, and differentiation of bone-forming cells, while maintaining injectability. Low aggregation and homogeneous distribution maximize particle surface area, promoting mineralization, cell-particle interactions, and homogenous tissue regeneration. Hence, determination of the size and distribution of particles/particle agglomerates in the hydrogel is desirable. Commonly used techniques have drawbacks. High-resolution techniques (e.g., SEM) require drying. Distribution in the dry state is not representative of the wet state. Techniques in the wet state (histology, µCT) are of lower resolution. Here, self-gelling, injectable composites of Gellan Gum (GG) hydrogel and two different types of sol-gel-derived bioactive glass (bioglass) particles were analyzed in the wet state using Synchrotron X-ray radiation, enabling high-resolution determination of particle size and spatial distribution. The lower detection limit volume was 9 × 10(-5) mm(3) . Bioglass particle suspensions were also studied using zeta potential measurements and Coulter analysis. Aggregation of bioglass particles in the GG hydrogels occurred and aggregate distribution was inhomogeneous. Bioglass promoted attachment of rat mesenchymal stem cells (rMSC) and mineralization. © 2016 Wiley Periodicals, Inc.

  5. A Designers’ Guide to Reliable Distributed Systems: Design and Analysis Methods. An Example Design. Volume 1

    DTIC Science & Technology

    1988-08-01

    exchanged between the cells, thus requiring existence of fast , high capacity, high availability communication channels. The same arguments indicate...mininet - loss of a cell - intermittent communications failure in the maxinet - partitioning of the maxinet or the mininet o Query decomposition. 3.3...take place. A new sequencer is selected by the timeout mechanism described above. This process Pj must set its priority to 0 in order to ensure fast

  6. Biofilm structures (EPS and bacterial communities) in drinking water distribution systems are conditioned by hydraulics and influence discolouration.

    PubMed

    Fish, K; Osborn, A M; Boxall, J B

    2017-09-01

    High-quality drinking water from treatment works is degraded during transport to customer taps through the Drinking Water Distribution System (DWDS). Interactions occurring at the pipe wall-water interface are central to this degradation and are often dominated by complex microbial biofilms that are not well understood. This study uses novel application of confocal microscopy techniques to quantify the composition of extracellular polymeric substances (EPS) and cells of DWDS biofilms together with concurrent evaluation of the bacterial community. An internationally unique, full-scale, experimental DWDS facility was used to investigate the impact of three different hydraulic patterns upon biofilms and subsequently assess their response to increases in shear stress, linking biofilms to water quality impacts such as discolouration. Greater flow variation during growth was associated with increased cell quantity but was inversely related to EPS-to-cell volume ratios and bacterial diversity. Discolouration was caused and EPS was mobilised during flushing of all conditions. Ultimately, biofilms developed under low-varied flow conditions had lowest amounts of biomass, the greatest EPS volumes per cell and the lowest discolouration response. This research shows that the interactions between hydraulics and biofilm physical and community structures are complex but critical to managing biofilms within ageing DWDS infrastructure to limit water quality degradation and protect public health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Comparison of volume estimation methods for pancreatic islet cells

    NASA Astrophysics Data System (ADS)

    Dvořák, JiřÃ.­; Å vihlík, Jan; Habart, David; Kybic, Jan

    2016-03-01

    In this contribution we study different methods of automatic volume estimation for pancreatic islets which can be used in the quality control step prior to the islet transplantation. The total islet volume is an important criterion in the quality control. Also, the individual islet volume distribution is interesting -- it has been indicated that smaller islets can be more effective. A 2D image of a microscopy slice containing the islets is acquired. The input of the volume estimation methods are segmented images of individual islets. The segmentation step is not discussed here. We consider simple methods of volume estimation assuming that the islets have spherical or ellipsoidal shape. We also consider a local stereological method, namely the nucleator. The nucleator does not rely on any shape assumptions and provides unbiased estimates if isotropic sections through the islets are observed. We present a simulation study comparing the performance of the volume estimation methods in different scenarios and an experimental study comparing the methods on a real dataset.

  8. Verification of Dose Distribution in Carbon Ion Radiation Therapy for Stage I Lung Cancer

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

    Irie, Daisuke; Saitoh, Jun-ichi, E-mail: junsaito@gunma-u.ac.jp; Shirai, Katsuyuki

    Purpose: To evaluate robustness of dose distribution of carbon-ion radiation therapy (C-ion RT) in non-small cell lung cancer (NSCLC) and to identify factors affecting the dose distribution by simulated dose distribution. Methods and Materials: Eighty irradiation fields for delivery of C-ion RT were analyzed in 20 patients with stage I NSCLC. Computed tomography images were obtained twice before treatment initiation. Simulated dose distribution was reconstructed on computed tomography for confirmation under the same settings as actual treatment with respiratory gating and bony structure matching. Dose-volume histogram parameters, such as %D95 (percentage of D95 relative to the prescribed dose), were calculated.more » Patients with any field for which the %D95 of gross tumor volume (GTV) was below 90% were classified as unacceptable for treatment, and the optimal target margin for such cases was examined. Results: Five patients with a total of 8 fields (10% of total number of fields analyzed) were classified as unacceptable according to %D95 of GTV, although most patients showed no remarkable change in the dose-volume histogram parameters. Receiver operating characteristic curve analysis showed that tumor displacement and change in water-equivalent pathlength were significant predictive factors of unacceptable cases (P<.001 and P=.002, respectively). The main cause of degradation of the dose distribution was tumor displacement in 7 of the 8 unacceptable fields. A 6-mm planning target volume margin ensured a GTV %D95 of >90%, except in 1 extremely unacceptable field. Conclusions: According to this simulation analysis of C-ion RT for stage I NSCLC, a few fields were reported as unacceptable and required resetting of body position and reconfirmation. In addition, tumor displacement and change in water-equivalent pathlength (bone shift and/or chest wall thickness) were identified as factors influencing the robustness of dose distribution. Such uncertainties should be regarded in planning.« less

  9. Assessing the robustness of passive scattering proton therapy with regard to local recurrence in stage III non-small cell lung cancer: a secondary analysis of a phase II trial.

    PubMed

    Zhu, Zhengfei; Liu, Wei; Gillin, Michael; Gomez, Daniel R; Komaki, Ritsuko; Cox, James D; Mohan, Radhe; Chang, Joe Y

    2014-05-06

    We assessed the robustness of passive scattering proton therapy (PSPT) plans for patients in a phase II trial of PSPT for stage III non-small cell lung cancer (NSCLC) by using the worst-case scenario method, and compared the worst-case dose distributions with the appearance of locally recurrent lesions. Worst-case dose distributions were generated for each of 9 patients who experienced recurrence after concurrent chemotherapy and PSPT to 74 Gy(RBE) for stage III NSCLC by simulating and incorporating uncertainties associated with set-up, respiration-induced organ motion, and proton range in the planning process. The worst-case CT scans were then fused with the positron emission tomography (PET) scans to locate the recurrence. Although the volumes enclosed by the prescription isodose lines in the worst-case dose distributions were consistently smaller than enclosed volumes in the nominal plans, the target dose coverage was not significantly affected: only one patient had a recurrence outside the prescription isodose lines in the worst-case plan. PSPT is a relatively robust technique. Local recurrence was not associated with target underdosage resulting from estimated uncertainties in 8 of 9 cases.

  10. An in vitro investigation to assess procedure parameters for injecting therapeutic hydrogels into the myocardium.

    PubMed

    Curley, Clive J; Dolan, Eimear B; Cavanagh, Brenton; O'Sullivan, Janice; Duffy, Garry P; Murphy, Bruce P

    2017-11-01

    Localized delivery of stem cells is potentially a promising therapeutic strategy for regenerating damaged myocardium. Many studies focus on limiting the biologic component of cell loss, but few address the contribution of mechanical factors. This study investigates optimal parameters for retaining the largest volume of cell loaded hydrogels post intramyocardial injection, without compromising cell viability. In vitro, hydrogel was injected into porcine hearts using various needle designs. Hydrogel retention and distribution pattern was then determined. The two most promising needles were then investigated to understand the effect of needle geometry on stem cell viability. The needle to best impact cell viability was then used to investigate the effect of differing hydrogels on retention and distribution. Three-dimensional experimental modeling revealed needles with smaller diameter's to have greater poloxamer 407 hydrogel retention. No difference in retention existed among various needle designs of similar gauge, despite differences in bolus geometries. When hMSC's, embedded in fibrin hydrogel, were injected through helical and 26G bevel needles no difference in the percent of live cells was seen at 48 h. However, the helical group had almost half the metabolic activity of the 26G bevel group at both time points, and had a significant decline in the percent of live cells from 24 to 48 h. Varying gel type resulted in significantly more alginate being retained in the tissue in comparison to fibrin or poloxamer hydrogels. In conclusion, mechanical properties of injected hydrogels, and the diameter of the needle used, highly influences the volume of hydrogel retained. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2618-2629, 2017. © 2016 Wiley Periodicals, Inc.

  11. Random-access scanning microscopy for 3D imaging in awake behaving animals

    PubMed Central

    Nadella, K. M. Naga Srinivas; Roš, Hana; Baragli, Chiara; Griffiths, Victoria A.; Konstantinou, George; Koimtzis, Theo; Evans, Geoffrey J.; Kirkby, Paul A.; Silver, R. Angus

    2018-01-01

    Understanding how neural circuits process information requires rapid measurements from identified neurons distributed in 3D space. Here we describe an acousto-optic lens two-photon microscope that performs high-speed focussing and line-scanning within a volume spanning hundreds of micrometres. We demonstrate its random access functionality by selectively imaging cerebellar interneurons sparsely distributed in 3D and by simultaneously recording from the soma, proximal and distal dendrites of neocortical pyramidal cells in behaving mice. PMID:27749836

  12. Molecular dynamics study on glycolic acid in the physiological salt solution

    NASA Astrophysics Data System (ADS)

    Matsunaga, S.

    2018-05-01

    Molecular dynamics (MD) study on glycolic acid in the physiological salt solution has been performed, which is a model of a biofuel cell. The structure and charge distribution of glycolic acid in aqueous solution used in MD is beforehand optimized by Gaussian09 utilizing the density functional theory. MD is performed in the NTV constant condition, i.e. the number of particles, temperature, and volume of MD cell are definite. The structure difference of the glycolic acid and oxalic acid is detected by the water distribution around the molecules using the pair distribution functions, gij(r), and the frequency dependent diffusion coefficients, Di(ν). The anomalous dielectric constant of the solution, i.e. about 12 times larger than that of water, has been obtained, which may be attributed to the ion pair formation in the solution.

  13. Study of vesicle size distribution dependence on pH value based on nanopore resistive pulse method

    NASA Astrophysics Data System (ADS)

    Lin, Yuqing; Rudzevich, Yauheni; Wearne, Adam; Lumpkin, Daniel; Morales, Joselyn; Nemec, Kathleen; Tatulian, Suren; Lupan, Oleg; Chow, Lee

    2013-03-01

    Vesicles are low-micron to sub-micron spheres formed by a lipid bilayer shell and serve as potential vehicles for drug delivery. The size of vesicle is proposed to be one of the instrumental variables affecting delivery efficiency since the size is correlated to factors like circulation and residence time in blood, the rate for cell endocytosis, and efficiency in cell targeting. In this work, we demonstrate accessible and reliable detection and size distribution measurement employing a glass nanopore device based on the resistive pulse method. This novel method enables us to investigate the size distribution dependence of pH difference across the membrane of vesicles with very small sample volume and rapid speed. This provides useful information for optimizing the efficiency of drug delivery in a pH sensitive environment.

  14. Accuracy of the Generalized Self-Consistent Method in Modelling the Elastic Behaviour of Periodic Composites

    NASA Technical Reports Server (NTRS)

    Walker, Kevin P.; Freed, Alan D.; Jordan, Eric H.

    1993-01-01

    Local stress and strain fields in the unit cell of an infinite, two-dimensional, periodic fibrous lattice have been determined by an integral equation approach. The effect of the fibres is assimilated to an infinite two-dimensional array of fictitious body forces in the matrix constituent phase of the unit cell. By subtracting a volume averaged strain polarization term from the integral equation we effectively embed a finite number of unit cells in a homogenized medium in which the overall stress and strain correspond to the volume averaged stress and strain of the constrained unit cell. This paper demonstrates that the zeroth term in the governing integral equation expansion, which embeds one unit cell in the homogenized medium, corresponds to the generalized self-consistent approximation. By comparing the zeroth term approximation with higher order approximations to the integral equation summation, both the accuracy of the generalized self-consistent composite model and the rate of convergence of the integral summation can be assessed. Two example composites are studied. For a tungsten/copper elastic fibrous composite the generalized self-consistent model is shown to provide accurate, effective, elastic moduli and local field representations. The local elastic transverse stress field within the representative volume element of the generalized self-consistent method is shown to be in error by much larger amounts for a composite with periodically distributed voids, but homogenization leads to a cancelling of errors, and the effective transverse Young's modulus of the voided composite is shown to be in error by only 23% at a void volume fraction of 75%.

  15. Experimental and numerical studies of micro PEM fuel cell

    NASA Astrophysics Data System (ADS)

    Peng, Rong-Gui; Chung, Chen-Chung; Chen, Chiun-Hsun

    2011-10-01

    A single micro proton exchange membrane fuel cell (PEMFC) has been produced using Micro-electromechanical systems (MEMS) technology with the active area of 2.5 cm2 and channel depth of about 500 µm. A theoretical analysis is performed in this study for a novel MEMS-based design of amicro PEMFC. Themodel consists of the conservation equations of mass, momentum, species and electric current in a fully integrated finite-volume solver using the CFD-ACE+ commercial code. The polarization curves of simulation are well correlated with experimental data. Three-dimensional simulations are carried out to treat prediction and analysis of micro PEMFC temperature, current density and water distributions in two different fuel flow rates (15 cm3/min and 40 cm3/min). Simulation results show that temperature distribution within the micro PEMFC is affected by water distribution in the membrane and indicate that low and uniform temperature distribution in the membrane at low fuel flow rates leads to increased membrane water distribution and obtains superior micro PEMFC current density distribution under 0.4V operating voltage. Model predictions are well within those known for experimental mechanism phenomena.

  16. Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

    PubMed Central

    Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

    2018-01-01

    Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

  17. Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model.

    PubMed

    Singleton, W G; Collins, A M; Bienemann, A S; Killick-Cole, C L; Haynes, H R; Asby, D J; Butts, C P; Wyatt, M J; Barua, N U; Gill, S S

    2017-01-01

    The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P <0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic.

  18. 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.

  19. The changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men.

    PubMed

    Huang, Rui; Zhu, Wei-Jie; Li, Jing; Gu, Yi-Qun

    2014-12-01

    To evaluate the changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men. Point counting method was used to analyze the stereological parameters of Leydig cells. The stage number of seminiferous epithelium cycle was calculated in the same testicular tissue samples which were used for Leydig cell stereological analysis. The aging group had shown more severe pathological changes as well as higher pathologic scores than the young group. Compared with the control group, the volume density (VV) and surface density (NA) of Leydig cells in the aging group were increased significantly. The stage number of seminiferous epithelium cycle in the aging group was decreased coincidently compared to the young group. Leydig cell Vv in the young group has a positive relationship with stages I, II, III, V and VI of seminiferous epithelium cycle, and Leydig cell NA and numerical density (NV) were positively related to stage IV. However, only the correlation between NV and stage II was found in the aging group. The stage number of seminiferous epithelium cycle was decreased in aging testes. Changes in the stage distribution in aging testes were related to the Leydig cell stereological parameters which presented as a sign of morphological changes. Copyright © 2014 Elsevier GmbH. All rights reserved.

  20. Splitting a droplet for femtoliter liquid patterns and single cell isolation.

    PubMed

    Li, Huizeng; Yang, Qiang; Li, Guannan; Li, Mingzhu; Wang, Shutao; Song, Yanlin

    2015-05-06

    Well-defined microdroplet generation has attracted great interest, which is important for the high-resolution patterning and matrix distribution for chemical reactions and biological assays. By sliding a droplet on a patterned superhydrophilic/superhydrophobic substrate, tiny microdroplet arrays low to femtoliter were achieved with uniform volume and composition. Using this method, cells were successfully isolated, resulting in a single cell array. The droplet-splitting method is facile, sample-effective, and low-cost, which will be of great potential for the development of microdroplet arrays for biological analysis as well as patterning system and devices.

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

    Sugano, Yasutaka; Mizuta, Masahiro; Takao, Seishin

    Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of themore » tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.« less

  2. Characterization and reproducibility of HepG2 hanging drop spheroids toxicology in vitro.

    PubMed

    Hurrell, Tracey; Ellero, Andrea Antonio; Masso, Zelie Flavienne; Cromarty, Allan Duncan

    2018-02-21

    Hepatotoxicity remains a major challenge in drug development despite preclinical toxicity screening using hepatocytes of human origin. To overcome some limitations of reproducing the hepatic phenotype, more structurally and functionally authentic cultures in vitro can be introduced by growing cells in 3D spheroid cultures. Characterisation and reproducibility of HepG2 spheroid cultures using a high-throughput hanging drop technique was performed and features contributing to potential phenotypic variation highlighted. Cultured HepG2 cells were seeded into Perfecta 3D® 96-well hanging drop plates and assessed over time for morphology, viability, cell cycle distribution, protein content and protein-mass profiles. Divergent aspects which were assessed included cell stocks, seeding density, volume of culture medium and use of extracellular matrix additives. Hanging drops are advantageous due to no complex culture matrix being present, enabling background free extractions for downstream experimentation. Varying characteristics were observed across cell stocks and batches, seeding density, culture medium volume and extracellular matrix when using immortalized HepG2 cells. These factors contribute to wide-ranging cellular responses and highlights concerns with respect to generating a reproducible phenotype in HepG2 hanging drop spheroids. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Gigantism in a bacterium, Epulopiscium fishelsoni, correlates with complex patterns in arrangement, quantity, and segregation of DNA.

    PubMed

    Bresler, V; Montgomery, W L; Fishelson, L; Pollak, P E

    1998-11-01

    Epulopiscium fishelsoni, gut symbiont of the brown surgeonfish (Acanthurus nigrofuscus) in the Red Sea, attains a larger size than any other eubacterium, varies 10- to 20-fold in length (and >2, 000-fold in volume), and undergoes a complex daily life cycle. In early morning, nucleoids contain highly condensed DNA in elongate, chromosome-like structures which are physically separated from the general cytoplasm. Cell division involves production of two (rarely three) nucleoids within a cell, deposition of cell walls around expanded nucleoids, and emergence of daughter cells from the parent cell. Fluorescence measurements of DNA, RNA, and other cell components indicate the following. DNA quantity is proportional to cell volume over cell lengths of approximately 30 micrometers to >500 micrometers. For cells of a given size, nucleoids of cells with two nucleoids (binucleoid) contain approximately equal amounts of DNA. And each nucleoid of a binucleoid cell contains one-half the DNA of the single nucleoid in a uninucleoid cell of the same size. The life cycle involves approximately equal subdivision of DNA among daughter cells, formation of apical caps of condensed DNA from previously decondensed and diffusely distributed DNA, and "pinching" of DNA near the middle of the cell in the absence of new wall formation. Mechanisms underlying these patterns remain unclear, but formation of daughter nucleoids and cells occurs both during diurnal periods of host feeding and bacterial cell growth and during nocturnal periods of host inactivity when mean bacterial cell size declines.

  4. Urtica Dioica Distillate Regenerates Pancreatic Beta Cells in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Gohari, Ali; Noorafshan, Ali; Akmali, Masoumeh; Zamani-Garmsiri, Fahimeh; Seghatoleslam, Atefeh

    2018-03-01

    Urtica dioica is known as an anti-hyperglycemic plant. Urtica dioica distillate (UD) is a traditional Iranian drink, locally known as "aragh gazaneh". In spite of its widespread consumption in Iran, according to traditional Iranian medicine, there is no scientific report on the usefulness of UD for diabetic patients. This survey was designed to evaluate its protective effects for the recovery from diabetes by determining the serum insulin, blood glucose, volume of pancreatic islets, and the number and volume of β-cells in diabetic rats. A total of 48 Sprague-Dawley male rats (200-250 g) were randomly distributed into 6 groups (n=8), including non-diabetic plus distilled water (DW), non-diabetic plus UD, diabetic plus DW, diabetic plus UD, diabetic plus insulin, and diabetic plus glibenclamide. DW, UD, and glibenclamide were administered via intragastric gavage and insulin was injected subcutaneously. After four weeks of experiments, blood samples were collected for serum insulin and blood glucose assay. Pancreas was also evaluated using stereological method. The SPSS software was used for statistical analysis. Kruskal-Wallis, repeated measurements, and Mann-Whitney U test were applied for comparisons between the groups. The treatment of diabetic rats with UD reduced the blood glucose dramatically (P<0.001) and increased serum insulin levels significantly (P=0.03) in comparison to the diabetic plus DW rats. Treatment with UD did not affect the mean β-cell volumes in the diabetic rats when compared to the diabetic plus DW rats, but the islet volumes and β-cell numbers were significantly recovered. UD treatment in diabetic rats improves hyperglycemia by partially restoring plasma insulin levels. The data suggest that UD prevents islet atrophy and/or regenerate pancreatic β-cells.

  5. Urtica Dioica Distillate Regenerates Pancreatic Beta Cells in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Gohari, Ali; Noorafshan, Ali; Akmali, Masoumeh; Zamani-Garmsiri, Fahimeh; Seghatoleslam, Atefeh

    2018-01-01

    Background Urtica dioica is known as an anti-hyperglycemic plant. Urtica dioica distillate (UD) is a traditional Iranian drink, locally known as “aragh gazaneh”. In spite of its widespread consumption in Iran, according to traditional Iranian medicine, there is no scientific report on the usefulness of UD for diabetic patients. This survey was designed to evaluate its protective effects for the recovery from diabetes by determining the serum insulin, blood glucose, volume of pancreatic islets, and the number and volume of β-cells in diabetic rats. Methods A total of 48 Sprague-Dawley male rats (200-250 g) were randomly distributed into 6 groups (n=8), including non-diabetic plus distilled water (DW), non-diabetic plus UD, diabetic plus DW, diabetic plus UD, diabetic plus insulin, and diabetic plus glibenclamide. DW, UD, and glibenclamide were administered via intragastric gavage and insulin was injected subcutaneously. After four weeks of experiments, blood samples were collected for serum insulin and blood glucose assay. Pancreas was also evaluated using stereological method. The SPSS software was used for statistical analysis. Kruskal-Wallis, repeated measurements, and Mann-Whitney U test were applied for comparisons between the groups. Results The treatment of diabetic rats with UD reduced the blood glucose dramatically (P<0.001) and increased serum insulin levels significantly (P=0.03) in comparison to the diabetic plus DW rats. Treatment with UD did not affect the mean β-cell volumes in the diabetic rats when compared to the diabetic plus DW rats, but the islet volumes and β-cell numbers were significantly recovered. Conclusion UD treatment in diabetic rats improves hyperglycemia by partially restoring plasma insulin levels. The data suggest that UD prevents islet atrophy and/or regenerate pancreatic β-cells. PMID:29749986

  6. High-pressure crystal structure of elastically isotropic CaTiO3 perovskite under hydrostatic and non-hydrostatic conditions.

    PubMed

    Zhao, Jing; Ross, Nancy L; Wang, Di; Angel, Ross J

    2011-11-16

    The structural evolution of orthorhombic CaTiO3 perovskite has been studied using high-pressure single-crystal x-ray diffraction under hydrostatic conditions up to 8.1 GPa and under a non-hydrostatic stress field formed in a diamond anvil cell (DAC) up to 4.7 GPa. Under hydrostatic conditions, the TiO6 octahedra become more tilted and distorted with increasing pressure, similar to other 2:4 perovskites. Under non-hydrostatic conditions, the experiments do not show any apparent difference in the internal structural variation from hydrostatic conditions and no additional tilts and distortions in the TiO6 octahedra are observed, even though the lattice itself becomes distorted due to the non-hydrostatic stress. The similarity between the hydrostatic and non-hydrostatic cases can be ascribed to the fact that CaTiO3 perovskite is nearly elastically isotropic and, as a consequence, its deviatoric unit-cell volume strain produced by the non-hydrostatic stress is very small; in other words, the additional octahedral tilts relevant to the extra unit-cell volume associated with the deviatoric unit-cell volume strain may be totally neglected. This study further addresses the role that three factors--the elastic properties, the crystal orientation and the pressure medium--have on the structural evolution of an orthorhombic perovskite loaded in a DAC under non-hydrostatic conditions. The influence of these factors can be clearly visualized by plotting the three-dimensional distribution of the deviatoric unit-cell volume strain in relation to the cylindrical axis of the DAC and indicates that, if the elasticity of a perovskite is nearly isotropic as it is for CaTiO3, the other two factors become relatively insignificant.

  7. Trace element distribution in the rat cerebellum

    NASA Astrophysics Data System (ADS)

    Kwiatek, W. M.; Long, G. J.; Pounds, J. G.; Reuhl, K. R.; Hanson, A. L.; Jones, K. W.

    1990-04-01

    Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic and structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with X-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and nondestructive irradiation. Trace elements were measured in thin rat brain sections of 20 μm thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppm wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semiquantitative mapping of the TE distribution in a section were used. All analyzed elements were observed in each structure of the cerebellum except mercury which was not observed in granule cell layer or fiber tract. This approach permits an exacting correlation of the TE distribution in complex structure with the diet, toxic elements, and functional status of the animal.

  8. Quantitative 3D imaging of yeast by hard X-ray tomography.

    PubMed

    Zheng, Ting; Li, Wenjie; Guan, Yong; Song, Xiangxia; Xiong, Ying; Liu, Gang; Tian, Yangchao

    2012-05-01

    Full-field hard X-ray tomography could be used to obtain three-dimensional (3D) nanoscale structures of biological samples. The image of the fission yeast, Schizosaccharomyces pombe, was clearly visualized based on Zernike phase contrast imaging technique and heavy metal staining method at a spatial resolution better than 50 nm at the energy of 8 keV. The distributions and shapes of the organelles during the cell cycle were clearly visualized and two types of organelle were distinguished. The results for cells during various phases were compared and the ratios of organelle volume to cell volume can be analyzed quantitatively. It showed that the ratios remained constant between growth and division phase and increased strongly in stationary phase, following the shape and size of two types of organelles changes. Our results demonstrated that hard X-ray microscopy was a complementary method for imaging and revealing structural information for biological samples. Copyright © 2011 Wiley Periodicals, Inc.

  9. Convection-enhanced delivery of SN-38-loaded polymeric micelles (NK012) enables consistent distribution of SN-38 and is effective against rodent intracranial brain tumor models.

    PubMed

    Zhang, Rong; Saito, Ryuta; Mano, Yui; Sumiyoshi, Akira; Kanamori, Masayuki; Sonoda, Yukihiko; Kawashima, Ryuta; Tominaga, Teiji

    2016-10-01

    Convection-enhanced delivery (CED) of therapeutic agents is a promising local delivery technique that has been extensively studied as a treatment for CNS diseases over the last two decades. One continuing challenge of CED is accurate and consistent delivery of the agents to the target. The present study focused on a new type of therapeutic agent, NK012, a novel SN-38-loaded polymeric micelle. Local delivery profiles of NK012 and SN-38 were studied using rodent brain and intracranial rodent brain tumor models. First, the cytotoxicity of NK012 against glioma cell lines was determined in vitro. Proliferations of glioma cells were significantly reduced after exposure to NK012. Then, the distribution and local toxicity after CED delivery of NK012 and SN-38 were evaluated in vivo. Volume of distribution of NK012 after CED was much larger than that of SN-38. Histological examination revealed minimum brain tissue damage in rat brains after delivery of 40 µg NK012 but severe damage with SN-38 at the same dose. Subsequently, the efficacy of NK012 delivered via CED was tested in 9L and U87MG rodent orthotopic brain tumor models. CED of NK012 displayed excellent efficacy in the 9L and U87MG orthotopic brain tumor models. Furthermore, NK012 and gadolinium diamide were co-delivered via CED to monitor the NK012 distribution using MRI. Volume of NK012 distribution evaluated by histology and MRI showed excellent agreement. CED of NK012 represents an effective treatment option for malignant gliomas. MRI-guided CED of NK012 has potential for clinical application.

  10. Stochastic properties of radiation-induced DSB: DSB distributions in large scale chromatin loops, the HPRT gene and within the visible volumes of DNA repair foci.

    PubMed

    Ponomarev, Artem L; Costes, Sylvain V; Cucinotta, Francis A

    2008-11-01

    We computed probabilities to have multiple double-strand breaks (DSB), which are produced in DNA on a regional scale, and not in close vicinity, in volumes matching the size of DNA damage foci, of a large chromatin loop, and in the physical volume of DNA containing the HPRT (human hypoxanthine phosphoribosyltransferase) locus. The model is based on a Monte Carlo description of DSB formation by heavy ions in the spatial context of the entire human genome contained within the cell nucleus, as well as at the gene sequence level. We showed that a finite physical volume corresponding to a visible DNA repair focus, believed to be associated with one DSB, can contain multiple DSB due to heavy ion track structure and the DNA supercoiled topography. A corrective distribution was introduced, which was a conditional probability to have excess DSB in a focus volume, given that there was already one present. The corrective distribution was calculated for 19.5 MeV/amu N ions, 3.77 MeV/amu alpha-particles, 1000 MeV/amu Fe ions, and X-rays. The corrected initial DSB yield from the experimental data on DNA repair foci was calculated. The DSB yield based on the corrective function converts the focus yield into the DSB yield, which is comparable with the DSB yield based on the earlier PFGE experiments. The distribution of DSB within the physical limits of the HPRT gene was analyzed by a similar method as well. This corrective procedure shows the applicability of the model and empowers the researcher with a tool to better analyze focus statistics. The model enables researchers to analyze the DSB yield based on focus statistics in real experimental situations that lack one-to-one focus-to-DSB correspondance.

  11. 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.

  12. Development of a facility for high-precision irradiation of cells with carbon ions.

    PubMed

    van Goethem, Marc-Jan; Niemantsverdriet, Maarten; Brandenburg, Sytze; Langendijk, Johannes A; Coppes, Robert P; van Luijk, Peter

    2011-01-01

    Compared to photons, using particle radiation in radiotherapy reduces the dose and irradiated volume of normal tissues, potentially reducing side effects. The biological effect of dose deposited by particles such as carbon ions, however, differs from that of dose deposited by photons. The inaccuracy in models to estimate the biological effects of particle radiation remains the most important source of uncertainties in particle therapy. Improving this requires high-precision studies on biological effects of particle radiation. Therefore, the authors aimed to develop a facility for reproducible and high-precision carbon-ion irradiation of cells in culture. The combined dose nonuniformity in the lateral and longitudinal direction should not exceed +/-1.5%. Dose to the cells from particles than other carbon ions should not exceed 5%. A uniform lateral dose distribution was realized using a single scatter foil and quadrupole magnets. A modulator wheel was used to create a uniform longitudinal dose distribution. The choice of beam energy and the optimal design of these components was determined using GEANT4 and SRIM Monte Carlo simulations. Verification of the uniformity of the dose distribution was performed using a scintillating screen (lateral) and a water phantom (longitudinal). The reproducibility of dose delivery between experiments was assessed by repeated measurements of the spatial dose distribution. Moreover, the reproducibility of dose-response measurements was tested by measuring the survival of irradiated HEK293 cells in three independent experiments. The relative contribution of dose from nuclear reaction fragments to the sample was found to be <5% when using 90 MeV/u carbon ions. This energy still allows accurate dosimetry conforming to the IAEA Report TRS-398, facilitating comparison to dose-effect data obtained with other radiation qualities. A 1.3 mm long spread-out Bragg peak with a diameter of 30 mm was created, allowing the irradiation of cell samples with the specified accuracy. Measurements of the transverse and longitudinal dose distribution showed that the dose variation over the sample volume was +/-0.8% and +/-0.7% in the lateral and longitudinal directions, respectively. The track-averaged LET of 132 +/- 10 keV/microm and dose-averaged LET of 189 +/- 15 keV/microm at the position of the sample were obtained from a GEANT4 simulation, which was validated experimentally. Three separately measured cell-survival curves yielded nearly identical results. With the new facility, high-precision carbon-ion irradiations of biological samples can be performed with highly reproducible results.

  13. Cell volume change through water efflux impacts cell stiffness and stem cell fate

    PubMed Central

    Pegoraro, Adrian F.; Mao, Angelo; Zhou, Enhua H.; Arany, Praveen R.; Han, Yulong; Burnette, Dylan T.; Jensen, Mikkel H.; Kasza, Karen E.; Moore, Jeffrey R.; Mackintosh, Frederick C.; Fredberg, Jeffrey J.; Mooney, David J.; Lippincott-Schwartz, Jennifer; Weitz, David A.

    2017-01-01

    Cells alter their mechanical properties in response to their local microenvironment; this plays a role in determining cell function and can even influence stem cell fate. Here, we identify a robust and unified relationship between cell stiffness and cell volume. As a cell spreads on a substrate, its volume decreases, while its stiffness concomitantly increases. We find that both cortical and cytoplasmic cell stiffness scale with volume for numerous perturbations, including varying substrate stiffness, cell spread area, and external osmotic pressure. The reduction of cell volume is a result of water efflux, which leads to a corresponding increase in intracellular molecular crowding. Furthermore, we find that changes in cell volume, and hence stiffness, alter stem-cell differentiation, regardless of the method by which these are induced. These observations reveal a surprising, previously unidentified relationship between cell stiffness and cell volume that strongly influences cell biology. PMID:28973866

  14. Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (Ce3D)

    PubMed Central

    Li, Weizhe; Germain, Ronald N.

    2017-01-01

    Organ homeostasis, cellular differentiation, signal relay, and in situ function all depend on the spatial organization of cells in complex tissues. For this reason, comprehensive, high-resolution mapping of cell positioning, phenotypic identity, and functional state in the context of macroscale tissue structure is critical to a deeper understanding of diverse biological processes. Here we report an easy to use method, clearing-enhanced 3D (Ce3D), which generates excellent tissue transparency for most organs, preserves cellular morphology and protein fluorescence, and is robustly compatible with antibody-based immunolabeling. This enhanced signal quality and capacity for extensive probe multiplexing permits quantitative analysis of distinct, highly intermixed cell populations in intact Ce3D-treated tissues via 3D histo-cytometry. We use this technology to demonstrate large-volume, high-resolution microscopy of diverse cell types in lymphoid and nonlymphoid organs, as well as to perform quantitative analysis of the composition and tissue distribution of multiple cell populations in lymphoid tissues. Combined with histo-cytometry, Ce3D provides a comprehensive strategy for volumetric quantitative imaging and analysis that bridges the gap between conventional section imaging and disassociation-based techniques. PMID:28808033

  15. [An experiment with Chlamydomonas reinhardtii on the Kosmos-2044 biosatellite].

    PubMed

    Gavrilova, O V; Gabova, A V; Goriainova, L N; Filatova, E V

    1992-01-01

    Space experiment with Chlamydomonas reinhardtii demonstrated that the microgravity effects were noted in Chlamydomonas at both cellular and population levels: in space the cell size is increased, stage of active growth of the culture is extended, it contains the juvenile vegetative motile cells in greater quantities. Ultrastructural analysis indicated that in microgravity the changes in shape, structure and distribution of intracellular organelles and in volume ratio of organelles and cytoplasma are absent. Chlamydomonas data are in line with the results of the Infusoria and Chlorella experiments.

  16. Locked Nucleic Acid Flow Cytometry-fluorescence in situ Hybridization (LNA flow-FISH): A Method for Bacterial Small RNA Detection

    DTIC Science & Technology

    2012-01-10

    flow cytometry, locked nucleic acid, sRNA, Vibrio , Date Published: 1/10/2012 This is an open-access article distributed under the terms of the Creative...solubilization process to maintain a 10 mL volume. Aliquot the 60% dextran sulfate solution and store at -20 °C until use. 1. Harvest 1x108 cells of...bioluminescent Vibrio campbellii or your bacteria of interest and transfer them into a 1.5 mL microcentrifuge tube. This quantity of cells provides

  17. Numeric and volumetric changes in Leydig cells during aging of rats.

    PubMed

    Neves, Bruno Vinicius Duarte; Lorenzini, Fernando; Veronez, Djanira; Miranda, Eduardo Pereira de; Neves, Gabriela Duarte; Fraga, Rogério de

    2017-10-01

    To analyze the effects of aging in rats on the nuclear volume, cytoplasmic volume, and total volume of Leydig cells, as well as their number. Seventy-two Wistar rats were divided into six subgroups of 12 rats, which underwent right orchiectomy at 3, 6, 9, 12, 18, and 24 months of age. The weight and volume of the resected testicles were assessed. A stereological study of Leydig cells was conducted, which included measurements of cell number and nuclear, cytoplasmic, and total cell volumes. The weight and volume of the resected testicles showed reductions with age. Only the subgroup composed of 24-month old rats showed a decrease in the nuclear volume of Leydig cells. Significant reductions in the cytoplasmic volume and total volume of Leydig cells were observed in 18- and 24-month old rats. The number of Leydig cells did not vary significantly with age. Aging in rats resulted in reduction of the nuclear, cytoplasmic, and total cell volumes of Leydig cells. There was no change in the total number of these cells during aging.

  18. Erythrocyte Enrichment in Hematopoietic Progenitor Cell Cultures Based on Magnetic Susceptibility of the Hemoglobin

    PubMed Central

    Jin, Xiaoxia; Abbot, Stewart; Zhang, Xiaokui; Kang, Lin; Voskinarian-Berse, Vanessa; Zhao, Rui; Kameneva, Marina V.; Moore, Lee R.; Chalmers, Jeffrey J.; Zborowski, Maciej

    2012-01-01

    Using novel media formulations, it has been demonstrated that human placenta and umbilical cord blood-derived CD34+ cells can be expanded and differentiated into erythroid cells with high efficiency. However, obtaining mature and functional erythrocytes from the immature cell cultures with high purity and in an efficient manner remains a significant challenge. A distinguishing feature of a reticulocyte and maturing erythrocyte is the increasing concentration of hemoglobin and decreasing cell volume that results in increased cell magnetophoretic mobility (MM) when exposed to high magnetic fields and gradients, under anoxic conditions. Taking advantage of these initial observations, we studied a noninvasive (label-free) magnetic separation and analysis process to enrich and identify cultured functional erythrocytes. In addition to the magnetic cell separation and cell motion analysis in the magnetic field, the cell cultures were characterized for cell sedimentation rate, cell volume distributions using differential interference microscopy, immunophenotyping (glycophorin A), hemoglobin concentration and shear-induced deformability (elongation index, EI, by ektacytometry) to test for mature erythrocyte attributes. A commercial, packed column high-gradient magnetic separator (HGMS) was used for magnetic separation. The magnetically enriched fraction comprised 80% of the maturing cells (predominantly reticulocytes) that showed near 70% overlap of EI with the reference cord blood-derived RBC and over 50% overlap with the adult donor RBCs. The results demonstrate feasibility of label-free magnetic enrichment of erythrocyte fraction of CD34+ progenitor-derived cultures based on the presence of paramagnetic hemoglobin in the maturing erythrocytes. PMID:22952572

  19. Establishment of reference intervals for complete blood count parameters during normal pregnancy in Beijing.

    PubMed

    Li, Aiwei; Yang, Shuo; Zhang, Jie; Qiao, Rui

    2017-11-01

    To observe the changes of complete blood count (CBC) parameters during pregnancy and establish appropriate reference intervals for healthy pregnant women. Healthy pregnant women took the blood tests at all trimesters. All blood samples were processed on Sysmex XE-2100. The following CBC parameters were analyzed: red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), white blood cell count (WBC), and leukocyte differential count. Reference intervals were established using the 2.5th and 97.5th percentile of the distribution. Complete blood count parameters showed dynamic changes during trimesters. RBC, Hb, Hct declined at trimester 1, reaching their lowest point at trimester 2, and began to rise again at trimester 3. WBC, neutrophil count (Neut), monocyte count (MONO), RDW, and PDW went up from trimester 1 to trimester 3. On the contrary, MCHC, lymphocyte count (LYMPH), PLT, and MPV gradually descended during pregnancy. There were statistical significances in all CBC parameters between pregnant women and normal women, regardless of the trimesters (P<.001). The median obtained were (normal vs pregnancy) as follows: RBC 4.50 vs 3.94×10 12 /L, Hb 137 vs 120 g/L, WBC 5.71 vs 9.06×10 9 /L, LYMPH% 32.2 vs 18.0, Neut% 58.7 vs 75.0, and PLT 251 vs 202×10 9 /L. The changes of CBC parameters during pregnancy are described, and reference intervals for Beijing pregnant women are demonstrated in this study. © 2017 Wiley Periodicals, Inc.

  20. Gigantism in a Bacterium, Epulopiscium fishelsoni, Correlates with Complex Patterns in Arrangement, Quantity, and Segregation of DNA

    PubMed Central

    Bresler, V.; Montgomery, W. L.; Fishelson, L.; Pollak, P. E.

    1998-01-01

    Epulopiscium fishelsoni, gut symbiont of the brown surgeonfish (Acanthurus nigrofuscus) in the Red Sea, attains a larger size than any other eubacterium, varies 10- to 20-fold in length (and >2,000-fold in volume), and undergoes a complex daily life cycle. In early morning, nucleoids contain highly condensed DNA in elongate, chromosome-like structures which are physically separated from the general cytoplasm. Cell division involves production of two (rarely three) nucleoids within a cell, deposition of cell walls around expanded nucleoids, and emergence of daughter cells from the parent cell. Fluorescence measurements of DNA, RNA, and other cell components indicate the following. DNA quantity is proportional to cell volume over cell lengths of ∼30 μm to >500 μm. For cells of a given size, nucleoids of cells with two nucleoids (binucleoid) contain approximately equal amounts of DNA. And each nucleoid of a binucleoid cell contains one-half the DNA of the single nucleoid in a uninucleoid cell of the same size. The life cycle involves approximately equal subdivision of DNA among daughter cells, formation of apical caps of condensed DNA from previously decondensed and diffusely distributed DNA, and “pinching” of DNA near the middle of the cell in the absence of new wall formation. Mechanisms underlying these patterns remain unclear, but formation of daughter nucleoids and cells occurs both during diurnal periods of host feeding and bacterial cell growth and during nocturnal periods of host inactivity when mean bacterial cell size declines. PMID:9791108

  1. Muscarinic regulation of Kenyon cell dendritic arborizations in adult worker honey bees

    PubMed Central

    Dobrin, Scott E.; Herlihy, J. Daniel; Robinson, Gene E.; Fahrbach, Susan E.

    2011-01-01

    The experience of foraging under natural conditions increases the volume of mushroom body neuropil in worker honey bees. A comparable increase in neuropil volume results from treatment of worker honey bees with pilocarpine, an agonist for muscarinic-type cholinergic receptors. A component of the neuropil growth induced by foraging experience is growth of dendrites in the collar region of the calyces. We show here, via analysis of Golgi-impregnated collar Kenyon cells with wedge arborizations, that significant increases in standard measures of dendritic complexity were also found in worker honey bees treated with pilocarpine. This result suggests that signaling via muscarinic-type receptors promotes the increase in Kenyon cell dendritic complexity associated with foraging. Treatment of worker honey bees with scopolamine, a muscarinic inhibitor, inhibited some aspects of dendritic growth. Spine density on the Kenyon cell dendrites varied with sampling location, with the distal portion of the dendritic field having greater total spine density than either the proximal or medial section. This observation may be functionally significant because of the stratified organization of projections from visual centers to the dendritic arborizations of the collar Kenyon cells. Pilocarpine treatment had no effect on the distribution of spines on dendrites of the collar Kenyon cells. PMID:21262388

  2. 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.

  3. Microstructure representations for sound absorbing fibrous media: 3D and 2D multiscale modelling and experiments

    NASA Astrophysics Data System (ADS)

    Zieliński, Tomasz G.

    2017-11-01

    The paper proposes and investigates computationally-efficient microstructure representations for sound absorbing fibrous media. Three-dimensional volume elements involving non-trivial periodic arrangements of straight fibres are examined as well as simple two-dimensional cells. It has been found that a simple 2D quasi-representative cell can provide similar predictions as a volume element which is in general much more geometrically accurate for typical fibrous materials. The multiscale modelling allowed to determine the effective speeds and damping of acoustic waves propagating in such media, which brings up a discussion on the correlation between the speed, penetration range and attenuation of sound waves. Original experiments on manufactured copper-wire samples are presented and the microstructure-based calculations of acoustic absorption are compared with the corresponding experimental results. In fact, the comparison suggested the microstructure modifications leading to representations with non-uniformly distributed fibres.

  4. European Science Notes, Volume 40, Number 2.

    DTIC Science & Technology

    1986-02-01

    authors are primarily ONRL staff members. - Occasionally articles are prepared by or in Cooperation with staff members of the USAF European Office of...development of models; preparation , use, and improvement of ..’ biocatalysts; and animal and plant cell cultures. New Team Examines Acoustic Cavitation...Printing ’ Office, Washington, DC 20402. European Science Note. is a Class I Periodical prepared and distributed by the %, -’ ’ . .:..- Office of Naval

  5. Synchrotron X-ray computed laminography of the three-dimensional anatomy of tomato leaves.

    PubMed

    Verboven, Pieter; Herremans, Els; Helfen, Lukas; Ho, Quang T; Abera, Metadel; Baumbach, Tilo; Wevers, Martine; Nicolaï, Bart M

    2015-01-01

    Synchrotron radiation computed laminography (SR-CL) is presented as an imaging method for analyzing the three-dimensional (3D) anatomy of leaves. The SR-CL method was used to provide 3D images of 1-mm² samples of intact leaves at a pixel resolution of 750 nm. The method allowed visualization and quantitative analysis of palisade and spongy mesophyll cells, and showed local venation patterns, aspects of xylem vascular structure and stomata. The method failed to image subcellular organelles such as chloroplasts. We constructed 3D computer models of leaves that can provide a basis for calculating gas exchange, light penetration and water and solute transport. The leaf anatomy of two different tomato genotypes grown in saturating light conditions was compared by 3D analysis. Differences were found in calculated values of tissue porosity, cell number density, cell area to volume ratio and cell volume and cell shape distributions of palisade and spongy cell layers. In contrast, the exposed cell area to leaf area ratio in mesophyll, a descriptor that correlates to the maximum rate of photosynthesis in saturated light conditions, was no different between spongy and palisade cells or between genotypes. The use of 3D image processing avoids many of the limitations of anatomical analysis with two-dimensional sections. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  6. Characterization and optimization of cell seeding in scaffolds by factorial design: quality by design approach for skeletal tissue engineering.

    PubMed

    Chen, Yantian; Bloemen, Veerle; Impens, Saartje; Moesen, Maarten; Luyten, Frank P; Schrooten, Jan

    2011-12-01

    Cell seeding into scaffolds plays a crucial role in the development of efficient bone tissue engineering constructs. Hence, it becomes imperative to identify the key factors that quantitatively predict reproducible and efficient seeding protocols. In this study, the optimization of a cell seeding process was investigated using design of experiments (DOE) statistical methods. Five seeding factors (cell type, scaffold type, seeding volume, seeding density, and seeding time) were selected and investigated by means of two response parameters, critically related to the cell seeding process: cell seeding efficiency (CSE) and cell-specific viability (CSV). In addition, cell spatial distribution (CSD) was analyzed by Live/Dead staining assays. Analysis identified a number of statistically significant main factor effects and interactions. Among the five seeding factors, only seeding volume and seeding time significantly affected CSE and CSV. Also, cell and scaffold type were involved in the interactions with other seeding factors. Within the investigated ranges, optimal conditions in terms of CSV and CSD were obtained when seeding cells in a regular scaffold with an excess of medium. The results of this case study contribute to a better understanding and definition of optimal process parameters for cell seeding. A DOE strategy can identify and optimize critical process variables to reduce the variability and assists in determining which variables should be carefully controlled during good manufacturing practice production to enable a clinically relevant implant.

  7. Deviation from Power Law Behavior in Landslide Phenomenon

    NASA Astrophysics Data System (ADS)

    Li, L.; Lan, H.; Wu, Y.

    2013-12-01

    Power law distribution of magnitude is widely observed in many natural hazards (e.g., earthquake, floods, tornadoes, and forest fires). Landslide is unique as the size distribution of landslide is characterized by a power law decrease with a rollover in the small size end. Yet, the emergence of the rollover, i.e., the deviation from power law behavior for small size landslides, remains a mystery. In this contribution, we grouped the forces applied on landslide bodies into two categories: 1) the forces proportional to the volume of failure mass (gravity and friction), and 2) the forces proportional to the area of failure surface (cohesion). Failure occurs when the forces proportional to volume exceed the forces proportional to surface area. As such, given a certain mechanical configuration, the failure volume to failure surface area ratio must exceed a corresponding threshold to guarantee a failure. Assuming all landslides share a uniform shape, which means the volume to surface area ratio of landslide regularly increase with the landslide volume, a cutoff of landslide volume distribution in the small size end can be defined. However, in realistic landslide phenomena, where heterogeneities of landslide shape and mechanical configuration are existent, a simple cutoff of landslide volume distribution does not exist. The stochasticity of landslide shape introduce a probability distribution of the volume to surface area ratio with regard to landslide volume, with which the probability that the volume to surface ratio exceed the threshold can be estimated regarding values of landslide volume. An experiment based on empirical data showed that this probability can induce the power law distribution of landslide volume roll down in the small size end. We therefore proposed that the constraints on the failure volume to failure surface area ratio together with the heterogeneity of landslide geometry and mechanical configuration attribute for the deviation from power law behavior in landslide phenomenon. Figure shows that a rollover of landslide size distribution in the small size end is produced as the probability for V/S (the failure volume to failure surface ratio of landslide) exceeding the mechanical threshold applied to the power law distribution of landslide volume.

  8. Rapid increase in red blood cell density driven by K:Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes.

    PubMed

    Fabry, M E; Romero, J R; Buchanan, I D; Suzuka, S M; Stamatoyannopoulos, G; Nagel, R L; Canessa, M

    1991-07-01

    We have previously demonstrated that young normal (AA) and sickle cell anemia (SS) red blood cells are capable of a volume regulatory decrease response (VRD) driven by a K:Cl cotransporter that is activated by low pH or hypotonic conditions. We now report on the characteristics of young SS cells (SS2, discocytes) capable of rapid increase in density in response to swelling. We have isolated cells with high VRD response (H-VRD) and low VRD response (L-VRD) cells by incubation and density-gradient centrifugation under hypotonic conditions. Comparison of these cells in patients homozygous for hemoglobin (Hb)S indicated that H-VRD cells have 91% more reticulocytes (P less than 9 x 10(-9) than L-VRD cells, 25% less HbF (P less than 5.5 x 10(-5), 106% more NEM (N-methylmaleimide)-stimulated K:Cl cotransport activity (P less than 2 x 10(-4), and 86% more volume-stimulated K:Cl cotransport activity (P less than 1.8 x 10(-3). H-VRD and L-VRD cells have similar G-6-PD and Na+/H+ antiport activity. In agreement with the reduced percent HbF in H-VRD cells, F cells (red blood cells that contain fetal Hb) are depleted from the H-VRD population; however, F reticulocytes are enriched in the H-VRD population to the same extent as non-F reticulocytes, which suggests that both F and non-F reticulocytes have a similar initial distribution of volume-sensitive K:Cl cotransport activity but that it may be more rapidly inactivated in F than in S reticulocytes. We find that H-VRD cells consist of 20% reticulocytes (or 79% of all reticulocytes in SS2) and 80% more mature cells. This study demonstrates the role of K:Cl cotransport in determining red blood cell density, the heterogeneity of K:Cl cotransport activity in reticulocytes, and the capacity for rapid change in the density of reticulocytes with high K:Cl cotransport activity. We speculate that the H-VRD population may be more susceptible to generation of dense and irreversibly sickled cells.

  9. Convection enhanced delivery of panobinostat (LBH589)-loaded pluronic nano-micelles prolongs survival in the F98 rat glioma model

    PubMed Central

    Singleton, WG; Collins, AM; Bienemann, AS; Killick-Cole, CL; Haynes, HR; Asby, DJ; Butts, CP; Wyatt, MJ; Barua, NU; Gill, SS

    2017-01-01

    Background The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood–brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). Materials and methods The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay. Nano-micelle distribution in rat brain was analyzed following acute CED using rhodamine-labeled nano-micelles, and toxicity was assayed using immunofluorescent microscopy and synaptophysin enzyme-linked immunosorbent assay. We compared the survival of the bioluminescent syngenic F98/Fischer344 rat glioblastoma model treated by acute CED of panobinostat-loaded nano-micelles with that of untreated and vehicle-only-treated controls. Results Nano-micellar panobinostat is cytotoxic to rat and human glioma cells in vitro in a dose-dependent manner following short-time exposure to drug. Fluorescent rhodamine-labelled nano-micelles distribute with a volume of infusion/volume of distribution (Vi/Vd) ratio of four and five respectively after administration by CED. Administration was not associated with any toxicity when compared to controls. CED of panobinostat-loaded nano-micelles was associated with significantly improved survival when compared to controls (n=8 per group; log-rank test, P<0.001). One hundred percent of treated animals survived the 60-day experimental period and had tumour response on post-mortem histological examination. Conclusion CED of nano-micellar panobinostat represents a potential novel therapeutic option for malignant glioma and warrants translation into the clinic. PMID:28260886

  10. Shape functions for velocity interpolation in general hexahedral cells

    USGS Publications Warehouse

    Naff, R.L.; Russell, T.F.; Wilson, J.D.

    2002-01-01

    Numerical methods for grids with irregular cells require discrete shape functions to approximate the distribution of quantities across cells. For control-volume mixed finite-element (CVMFE) methods, vector shape functions approximate velocities and vector test functions enforce a discrete form of Darcy's law. In this paper, a new vector shape function is developed for use with irregular, hexahedral cells (trilinear images of cubes). It interpolates velocities and fluxes quadratically, because as shown here, the usual Piola-transformed shape functions, which interpolate linearly, cannot match uniform flow on general hexahedral cells. Truncation-error estimates for the shape function are demonstrated. CVMFE simulations of uniform and non-uniform flow with irregular meshes show first- and second-order convergence of fluxes in the L2 norm in the presence and absence of singularities, respectively.

  11. Managing evaporation for more robust microscale assays. Part 2. Characterization of convection and diffusion for cell biology.

    PubMed

    Berthier, Erwin; Warrick, Jay; Yu, Hongmeiy; Beebe, David J

    2008-06-01

    Cell based microassays allow the screening of a multitude of culture conditions in parallel, which can be used for various applications from drug screening to fundamental cell biology research. Tubeless microfluidic devices based on passive pumping are a step towards accessible high throughput microassays, however they are vulnerable to evaporation. In addition to volume loss, evaporation can lead to the generation of small flows. Here, we focus on issues of convection and diffusion for cell culture in microchannels and particularly the transport of soluble factors secreted by cells. We find that even for humidity levels as high as 95%, convection in a passive pumping channel can significantly alter distributions of these factors and that appropriate system design can prevent convection.

  12. 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.

  13. Phosphorylation and transport in the Na-K-2Cl cotransporters, NKCC1 and NKCC2A, compared in HEK-293 cells.

    PubMed

    Hannemann, Anke; Flatman, Peter W

    2011-03-25

    Na-K-2Cl cotransporters help determine cell composition and volume. NKCC1 is widely distributed whilst NKCC2 is only found in the kidney where it plays a vital role reabsorbing 20% of filtered NaCl. NKCC2 regulation is poorly understood because of its restricted distribution and difficulties with its expression in mammalian cell cultures. Here we compare phosphorylation of the N-termini of the cotransporters, measured with phospho-specific antibodies, with bumetanide-sensitive transport of K(+) ((86)Rb(+)) (activity) in HEK-293 cells stably expressing fNKCC1 or fNKCC2A which were cloned from ferret kidney. Activities of transfected transporters were distinguished from those of endogenous ones by working at 37 °C. fNKCC1 and fNKCC2A activities were highest after pre-incubation of cells in hypotonic low-[Cl(-)] media to reduce cell [Cl(-)] and volume during flux measurement. Phosphorylation of both transporters more than doubled. Pre-incubation with ouabain also strongly stimulated fNKCC1 and fNKCC2A and substantially increased phosphorylation, whereas pre-incubation in Na(+)-free media maximally stimulated fNKCC1 and doubled its phosphorylation, but inhibited fNKCC2A, with a small increase in its phosphorylation. Kinase inhibitors halved phosphorylation and activity of both transporters whereas inhibition of phosphatases with calyculin A strongly increased phosphorylation of both transporters but only slightly stimulated fNKCC1 and inhibited fNCCC2A. Thus kinase inhibition reduced phosphorylation and transport, and transport stimulation was only seen when phosphorylation increased, but transport did not always increase with phosphorylation. This suggests phosphorylation of the N-termini determines the transporters' potential capacity to move ions, but final activity also depends on other factors. Transport cannot be reliably inferred solely using phospho-specific antibodies on whole-cell lysates.

  14. Experimental characterization of intrapulse tissue conductivity changes for electroporation.

    PubMed

    Neal, Robert E; Garcia, Paulo A; Robertson, John L; Davalos, Rafael V

    2011-01-01

    Cells exposed to short electric pulses experience a change in their transmembrane potential, which can lead to increased membrane permeability of the cell. When the energy of the pulses surpasses a threshold, the cell dies in a non-thermal manner known as irreversible electroporation (IRE). IRE has shown promise in the focal ablation of pathologic tissues. Its non-thermal mechanism spares sensitive structures and facilitates rapid lesion resolution. IRE effects depend on the electric field distribution, which can be predicted with numerical modeling. When the cells become permeabilized, the bulk tissue properties change, affecting this distribution. For IRE to become a reliable and successful treatment of diseased tissues, robust predictive treatment planning methods must be developed. It is vital to understand the changes in tissue properties undergoing the electric pulses to improve numerical models and predict treatment volumes. We report on the experimental characterization of these changes for kidney tissue. Tissue samples were pulsed between plate electrodes while intrapulse voltage and current data were measured to determine the conductivity of the tissue during the pulse. Conductivity was then established as a function of the electric field to which the tissue is exposed. This conductivity curve was used in a numerical model to demonstrate the impact of accounting for these changes when modeling electric field distributions to develop treatment plans.

  15. Understanding leachate flow in municipal solid waste landfills by combining time-lapse ERT and subsurface flow modelling - Part I: Analysis of infiltration shape on two different waste deposit cells.

    PubMed

    Audebert, M; Clément, R; Moreau, S; Duquennoi, C; Loisel, S; Touze-Foltz, N

    2016-09-01

    Landfill bioreactors are based on an acceleration of in-situ waste biodegradation by performing leachate recirculation. To quantify the water content and to evaluate the leachate injection system, in-situ methods are required to obtain spatially distributed information, usually electrical resistivity tomography (ERT). In a previous study, the MICS (multiple inversions and clustering strategy) methodology was proposed to improve the hydrodynamic interpretation of ERT results by a precise delimitation of the infiltration area. In this study, MICS was applied on two ERT time-lapse data sets recorded on different waste deposit cells in order to compare the hydrodynamic behaviour of leachate flow between the two cells. This comparison is based on an analysis of: (i) the volume of wetted waste assessed by MICS and the wetting rate, (ii) the infiltration shapes and (iii) the pore volume used by the leachate flow. This paper shows that leachate hydrodynamic behaviour is comparable from one waste deposit cell to another with: (i) a high leachate infiltration speed at the beginning of the infiltration, which decreases with time, (ii) a horizontal anisotropy of the leachate infiltration shape and (iii) a very small fraction of the pore volume used by the leachate flow. This hydrodynamic information derived from MICS results can be useful for subsurface flow modelling used to predict leachate flow at the landfill scale. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Ultra Scale-Down Characterization of the Impact of Conditioning Methods for Harvested Cell Broths on Clarification by Continuous Centrifugation—Recovery of Domain Antibodies from rec E. coli

    PubMed Central

    Chatel, Alex; Kumpalume, Peter; Hoare, Mike

    2014-01-01

    The processing of harvested E. coli cell broths is examined where the expressed protein product has been released into the extracellular space. Pre-treatment methods such as freeze–thaw, flocculation, and homogenization are studied. The resultant suspensions are characterized in terms of the particle size distribution, sensitivity to shear stress, rheology and solids volume fraction, and, using ultra scale-down methods, the predicted ability to clarify the material using industrial scale continuous flow centrifugation. A key finding was the potential of flocculation methods both to aid the recovery of the particles and to cause the selective precipitation of soluble contaminants. While the flocculated material is severely affected by process shear stress, the impact on the very fine end of the size distribution is relatively minor and hence the predicted performance was only diminished to a small extent, for example, from 99.9% to 99.7% clarification compared with 95% for autolysate and 65% for homogenate at equivalent centrifugation conditions. The lumped properties as represented by ultra scale-down centrifugation results were correlated with the basic properties affecting sedimentation including particle size distribution, suspension viscosity, and solids volume fraction. Grade efficiency relationships were used to allow for the particle and flow dynamics affecting capture in the centrifuge. The size distribution below a critical diameter dependant on the broth pre-treatment type was shown to be the main determining factor affecting the clarification achieved. Biotechnol. Bioeng. 2014;111: 913–924. © 2013 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. PMID:24284936

  17. 3D Finite Element Analysis of Particle-Reinforced Aluminum

    NASA Technical Reports Server (NTRS)

    Shen, H.; Lissenden, C. J.

    2002-01-01

    Deformation in particle-reinforced aluminum has been simulated using three distinct types of finite element model: a three-dimensional repeating unit cell, a three-dimensional multi-particle model, and two-dimensional multi-particle models. The repeating unit cell model represents a fictitious periodic cubic array of particles. The 3D multi-particle (3D-MP) model represents randomly placed and oriented particles. The 2D generalized plane strain multi-particle models were obtained from planar sections through the 3D-MP model. These models were used to study the tensile macroscopic stress-strain response and the associated stress and strain distributions in an elastoplastic matrix. The results indicate that the 2D model having a particle area fraction equal to the particle representative volume fraction of the 3D models predicted the same macroscopic stress-strain response as the 3D models. However, there are fluctuations in the particle area fraction in a representative volume element. As expected, predictions from 2D models having different particle area fractions do not agree with predictions from 3D models. More importantly, it was found that the microscopic stress and strain distributions from the 2D models do not agree with those from the 3D-MP model. Specifically, the plastic strain distribution predicted by the 2D model is banded along lines inclined at 45 deg from the loading axis while the 3D model prediction is not. Additionally, the triaxial stress and maximum principal stress distributions predicted by 2D and 3D models do not agree. Thus, it appears necessary to use a multi-particle 3D model to accurately predict material responses that depend on local effects, such as strain-to-failure, fracture toughness, and fatigue life.

  18. European Science Notes Information Bulletin Reports on Current European/ Middle Eastern Science

    DTIC Science & Technology

    1991-06-01

    particularly those that involve shock wave/boundary layer cell-centered, finite-volume, explicit, Runge-Kutta interactions , still prov;de considerble...aircraft configuration attributed to using an interactive vcual grid generation was provided by A. Bocci and A. Baxendale, the Aircraft system developed...the surface pressure the complex problem of wing/body/pylon/store distributions with and without the mass flow through the interaction . Reasonable

  19. Monte-Carlo model development for evaluation of current clinical target volume definition for heterogeneous and hypoxic glioblastoma.

    PubMed

    Moghaddasi, L; Bezak, E; Harriss-Phillips, W

    2016-05-07

    Clinical target volume (CTV) determination may be complex and subjective. In this work a microscopic-scale tumour model was developed to evaluate current CTV practices in glioblastoma multiforme (GBM) external radiotherapy. Previously, a Geant4 cell-based dosimetry model was developed to calculate the dose deposited in individual GBM cells. Microscopic extension probability (MEP) models were then developed using Matlab-2012a. The results of the cell-based dosimetry model and MEP models were combined to calculate survival fractions (SF) for CTV margins of 2.0 and 2.5 cm. In the current work, oxygenation and heterogeneous radiosensitivity profiles were incorporated into the GBM model. The genetic heterogeneity was modelled using a range of α/β values (linear-quadratic model parameters) associated with different GBM cell lines. These values were distributed among the cells randomly, taken from a Gaussian-weighted sample of α/β values. Cellular oxygen pressure was distributed randomly taken from a sample weighted to profiles obtained from literature. Three types of GBM models were analysed: homogeneous-normoxic, heterogeneous-normoxic, and heterogeneous-hypoxic. The SF in different regions of the tumour model and the effect of the CTV margin extension from 2.0-2.5 cm on SFs were investigated for three MEP models. The SF within the beam was increased by up to three and two orders of magnitude following incorporation of heterogeneous radiosensitivities and hypoxia, respectively, in the GBM model. However, the total SF was shown to be overdominated by the presence of tumour cells in the penumbra region and to a lesser extent by genetic heterogeneity and hypoxia. CTV extension by 0.5 cm reduced the SF by a maximum of 78.6  ±  3.3%, 78.5  ±  3.3%, and 77.7  ±  3.1% for homogeneous and heterogeneous-normoxic, and heterogeneous hypoxic GBMs, respectively. Monte-Carlo model was developed to quantitatively evaluate SF for genetically heterogeneous and hypoxic GBM with two CTV margins and three MEP distributions. The results suggest that photon therapy may not provide cure for hypoxic and genetically heterogeneous GBM. However, the extension of the CTV margin by 0.5 cm could be beneficial to delay the recurrence time for this tumour type due to significant increase in tumour cell irradiation.

  20. Isolating specific cell and tissue compartments from 3D images for quantitative regional distribution analysis using novel computer algorithms.

    PubMed

    Fenrich, Keith K; Zhao, Ethan Y; Wei, Yuan; Garg, Anirudh; Rose, P Ken

    2014-04-15

    Isolating specific cellular and tissue compartments from 3D image stacks for quantitative distribution analysis is crucial for understanding cellular and tissue physiology under normal and pathological conditions. Current approaches are limited because they are designed to map the distributions of synapses onto the dendrites of stained neurons and/or require specific proprietary software packages for their implementation. To overcome these obstacles, we developed algorithms to Grow and Shrink Volumes of Interest (GSVI) to isolate specific cellular and tissue compartments from 3D image stacks for quantitative analysis and incorporated these algorithms into a user-friendly computer program that is open source and downloadable at no cost. The GSVI algorithm was used to isolate perivascular regions in the cortex of live animals and cell membrane regions of stained spinal motoneurons in histological sections. We tracked the real-time, intravital biodistribution of injected fluorophores with sub-cellular resolution from the vascular lumen to the perivascular and parenchymal space following a vascular microlesion, and mapped the precise distributions of membrane-associated KCC2 and gephyrin immunolabeling in dendritic and somatic regions of spinal motoneurons. Compared to existing approaches, the GSVI approach is specifically designed for isolating perivascular regions and membrane-associated regions for quantitative analysis, is user-friendly, and free. The GSVI algorithm is useful to quantify regional differences of stained biomarkers (e.g., cell membrane-associated channels) in relation to cell functions, and the effects of therapeutic strategies on the redistributions of biomolecules, drugs, and cells in diseased or injured tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Febrile Convulsion among Hospitalized Children Aged Six Months to Five Years and Its Association With Haemoglobin Electrophoretic Pattern.

    PubMed

    Adeboye, M; Ojuawo, A; Adeniyi, A; Ibraheem, R M; Amiwero, C

    2015-07-01

    Febrile convulsion and sickle cell disease are common in tropical countries and both are associated with significant morbidity and mortality. Worldwide, Nigeria has the highest prevalence of sickle cell disease. However, there is a dearth of knowledge on the haemoglobin electrophoresis in patients with febrile convulsions. This was a hospital based, descriptive, cross-sectional study of the relationship between haemoglobin genotype and febrile convulsion at the University of Ilorin Teaching Hospital over a period of 12 months. A self-designed pretested questionnaire was administered on the subjects, and necessary examinations and investigations were conducted. Of a total of 1675 children admitted into the emergency paediatric unit during the study period, children aged 6 months-5 years that presented with febrile convulsions were 167(10%). Of this, 1,212 were aged 6 months-5 years. Thus, the age specific, hospital-based prevalence was 13.8%. The M:F was 1.1:1. Their Haemoglobin genotype distribution was AA 131(78.4%), AS 23(13.8%), AC 6(3.6%), SS 6(3.6%), and 1(0.6%) SC. The mean age of the sickle cell disease patients was higher at 46.0±13.5 months compared to 29.2±15.4 months in the non-sickle cell disease patients (p=0.005). The mean packed cell volume in subjects with sickle cell anaemia was 8.8±1.5%; the only case of haemoglobin SC had packed cell volume of 20%, while the non-sickle cell disease patients had a normal PCV. Malaria was present in 80.4% of them. Febrile convulsion remains a common cause of hospitalisation. It is uncommon in haemoglobin SS where severe anaemia is always an accompanying derangement. The packed cell volume is nearly normal in children with normal haemoglobin genotype.

  2. Malignant induction probability maps for radiotherapy using X-ray and proton beams.

    PubMed

    Timlin, C; Houston, M; Jones, B

    2011-12-01

    The aim of this study was to display malignant induction probability (MIP) maps alongside dose distribution maps for radiotherapy using X-ray and charged particles such as protons. Dose distributions for X-rays and protons are used in an interactive MATLAB® program (MathWorks, Natick, MA). The MIP is calculated using a published linear quadratic model, which incorporates fractionation effects, cell killing and cancer induction as a function of dose, as well as relative biological effect. Two virtual situations are modelled: (a) a tumour placed centrally in a cubic volume of normal tissue and (b) the same tumour placed closer to the skin surface. The MIP is calculated for a variety of treatment field options. The results show that, for protons, the MIP increases with field numbers. In such cases, proton MIP can be higher than that for X-rays. Protons produce the lowest MIPs for superficial targets because of the lack of exit dose. The addition of a dose bath to all normal tissues increases the MIP by up to an order of magnitude. This exploratory study shows that it is possible to achieve three-dimensional displays of carcinogenesis risk. The importance of treatment geometry, including the length and volume of tissue traversed by each beam, can all influence MIP. Reducing the volume of tissue irradiated is advantageous, as reducing the number of cells at risk reduces the total MIP. This finding lends further support to the use of treatment gantries as well as the use of simpler field arrangements for particle therapy provided normal tissue tolerances are respected.

  3. Centripetal myosin redistribution in thrombin-stimulated platelets. Relationship to platelet Factor 4 secretion.

    PubMed

    Painter, R G; Ginsberg, M H

    1984-11-01

    We have examined the F-actin and myosin distribution in resting and thrombin-activated platelets by double label immunofluorescence microscopy. In resting, discoid platelets, F-actin and myosin staining was distributed in a diffuse pattern throughout the interior of the cell with slight accentuation at the cell periphery. In contrast, platelet factor 4 antigen (PF4) was more centrally localized in a fine punctate distribution which is consistent with its localization in alpha-granules. Within 5 sec after thrombin stimulation both F-actin and myosin staining were increased at the periphery of the now spherical platelets. Subsequently, a myosin-containing spherical structure decreased in diameter closely surrounding a phase-dense central zone. In contrast, F-actin staining continued to be accentuated at the cell periphery and was prominent in filopodia and blebs. As previously shown, PF4 staining was localized after 30 sec within large intracellular masses that corresponded to closed vacuolar structures at the ultrastructural level. Morphometric analysis of electron micrographs showed that formation of these vacuolar structures kinetically paralleled alpha-granule disappearance and preceded PF4 release. These PF4-containing structures translocated to the cell periphery after 1-3 min, where they appeared to fuse with the plasma membrane. Ultrastructural analysis of thin sections showed that the myosin-rich spherical structure spatially and temporally correlated with a band of microfilaments that closely surrounded the organelle-rich central zone of the cell. Morphometric analysis of these micrographs showed that the absolute volume of this central zone decreased with time after thrombin addition, showing a significant change after 15 sec and reaching a maximum value after 3-5 min. Changes in the volume of this compartment kinetically preceded PF4 release. On the basis of these data, we propose that an actomyosin contractile force is generated which centripetally redistributes the myosinrich structure and organelle zone. Conceivably this inward force may not only accelerate granule-granule fusion to form intracellular secretory vacuoles, but may also provide aid in their extrusion toward the platelet plasma membrane.

  4. Distribution of extravascular fluid volumes in isolated perfused lungs measured with H215O.

    PubMed Central

    Jones, T; Jones, H A; Rhodes, C G; Buckingham, P D; Hughes, J M

    1976-01-01

    The distributions per unit volume of extravascular water (EVLW), blood volume, and blood flow were measured in isolated perfused vertical dog lungs. A steady-state tracer technique was employed using oxygen-15, carbon-11, and nitrogen-13 isotopes and external scintillation counting of the 511-KeV annihilation radiation common to all three radionuclides. EVLW, and blood volume and flow increased from apex to base in all preparations, but the gradient of increasing flow exceeded that for blood and EVLW volumes. The regional distributions of EVLW and blood volume were almost identical. With increasing edema, lower-zone EVLW increased slightly relative to that in the upper zone. There was no change in the distribution of blood volume or flow until gross edema (100% wt gain) occurred when lower zone values were reduced. In four lungs the distribution of EVLW was compared with wet-to-dry ratios from lung biopsies taken immediately afterwards. Whereas the isotopically measured EVLW increased from apex to base, the wet-to-dry weight ratios remained essentially uniform. We concluded that isotopic methods measure only an "exchangeable" water pool whose volume is dependent on regional blood flow and capillary recruitment. Second, the isolated perfused lung can accommodate up to 60% wt gain without much change in the regional distribution of EVLW, volume, or flow. PMID:765354

  5. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy

    NASA Astrophysics Data System (ADS)

    Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei

    2015-12-01

    The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease.

  6. 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.

  7. Mesoscale characterization of local property distributions in heterogeneous electrodes

    NASA Astrophysics Data System (ADS)

    Hsu, Tim; Epting, William K.; Mahbub, Rubayyat; Nuhfer, Noel T.; Bhattacharya, Sudip; Lei, Yinkai; Miller, Herbert M.; Ohodnicki, Paul R.; Gerdes, Kirk R.; Abernathy, Harry W.; Hackett, Gregory A.; Rollett, Anthony D.; De Graef, Marc; Litster, Shawn; Salvador, Paul A.

    2018-05-01

    The performance of electrochemical devices depends on the three-dimensional (3D) distributions of microstructural features in their electrodes. Several mature methods exist to characterize 3D microstructures over the microscale (tens of microns), which are useful in understanding homogeneous electrodes. However, methods that capture mesoscale (hundreds of microns) volumes at appropriate resolution (tens of nm) are lacking, though they are needed to understand more common, less ideal electrodes. Using serial sectioning with a Xe plasma focused ion beam combined with scanning electron microscopy (Xe PFIB-SEM), two commercial solid oxide fuel cell (SOFC) electrodes are reconstructed over volumes of 126 × 73 × 12.5 and 124 × 110 × 8 μm3 with a resolution on the order of ≈ 503 nm3. The mesoscale distributions of microscale structural features are quantified and both microscale and mesoscale inhomogeneities are found. We analyze the origin of inhomogeneity over different length scales by comparing experimental and synthetic microstructures, generated with different particle size distributions, with such synthetic microstructures capturing well the high-frequency heterogeneity. Effective medium theory models indicate that significant mesoscale variations in local electrochemical activity are expected throughout such electrodes. These methods offer improved understanding of the performance of complex electrodes in energy conversion devices.

  8. Computational modelling of the scaffold-free chondrocyte regeneration: a two-way coupling between the cell growth and local fluid flow and nutrient concentration.

    PubMed

    Hossain, Md Shakhawath; Bergstrom, D J; Chen, X B

    2015-11-01

    The in vitro chondrocyte cell culture process in a perfusion bioreactor provides enhanced nutrient supply as well as the flow-induced shear stress that may have a positive influence on the cell growth. Mathematical and computational modelling of such a culture process, by solving the coupled flow, mass transfer and cell growth equations simultaneously, can provide important insight into the biomechanical environment of a bioreactor and the related cell growth process. To do this, a two-way coupling between the local flow field and cell growth is required. Notably, most of the computational and mathematical models to date have not taken into account the influence of the cell growth on the local flow field and nutrient concentration. The present research aimed at developing a mathematical model and performing a numerical simulation using the lattice Boltzmann method to predict the chondrocyte cell growth without a scaffold on a flat plate placed inside a perfusion bioreactor. The model considers the two-way coupling between the cell growth and local flow field, and the simulation has been performed for 174 culture days. To incorporate the cell growth into the model, a control-volume-based surface growth modelling approach has been adopted. The simulation results show the variation of local fluid velocity, shear stress and concentration distribution during the culture period due to the growth of the cell phase and also illustrate that the shear stress can increase the cell volume fraction to a certain extent.

  9. Hemoglobin and mean platelet volume predicts diffuse T1-MRI white matter volume decrease in sickle cell disease patients.

    PubMed

    Choi, Soyoung; Bush, Adam M; Borzage, Matthew T; Joshi, Anand A; Mack, William J; Coates, Thomas D; Leahy, Richard M; Wood, John C

    2017-01-01

    Sickle cell disease (SCD) is a life-threatening genetic condition. Patients suffer from chronic systemic and cerebral vascular disease that leads to early and cumulative neurological damage. Few studies have quantified the effects of this disease on brain morphometry and even fewer efforts have been devoted to older patients despite the progressive nature of the disease. This study quantifies global and regional brain volumes in adolescent and young adult patients with SCD and racially matched controls with the aim of distinguishing between age related changes associated with normal brain maturation and damage from sickle cell disease. T1 weighted images were acquired on 33 clinically asymptomatic SCD patients (age = 21.3 ± 7.8; F = 18, M = 15) and 32 racially matched control subjects (age = 24.4 ± 7.5; F = 22, M = 10). Exclusion criteria included pregnancy, previous overt stroke, acute chest, or pain crisis hospitalization within one month. All brain volume comparisons were corrected for age and sex. Globally, grey matter volume was not different but white matter volume was 8.1% lower (p = 0.0056) in the right hemisphere and 6.8% (p = 0.0068) in the left hemisphere in SCD patients compared with controls. Multivariate analysis retained hemoglobin (β = 0.33; p = 0.0036), sex (β = 0.35; p = 0.0017) and mean platelet volume (β = 0.27; p = 0.016) as significant factors in the final prediction model for white matter volume for a combined r 2 of 0.37 (p < 0.0001). Lower white matter volume was confined to phylogenetically younger brain regions in the anterior and middle cerebral artery distributions. Our findings suggest that there are diffuse white matter abnormalities in SCD patients, especially in the frontal, parietal and temporal lobes, that are associated with low hemoglobin levels and mean platelet volume. The pattern of brain loss suggests chronic microvascular insufficiency and tissue hypoxia as the causal mechanism. However, longitudinal studies of global and regional brain morphometry can help us give further insights on the pathophysiology of SCD in the brain.

  10. cgCorrect: a method to correct for confounding cell-cell variation due to cell growth in single-cell transcriptomics

    NASA Astrophysics Data System (ADS)

    Blasi, Thomas; Buettner, Florian; Strasser, Michael K.; Marr, Carsten; Theis, Fabian J.

    2017-06-01

    Accessing gene expression at a single-cell level has unraveled often large heterogeneity among seemingly homogeneous cells, which remains obscured when using traditional population-based approaches. The computational analysis of single-cell transcriptomics data, however, still imposes unresolved challenges with respect to normalization, visualization and modeling the data. One such issue is differences in cell size, which introduce additional variability into the data and for which appropriate normalization techniques are needed. Otherwise, these differences in cell size may obscure genuine heterogeneities among cell populations and lead to overdispersed steady-state distributions of mRNA transcript numbers. We present cgCorrect, a statistical framework to correct for differences in cell size that are due to cell growth in single-cell transcriptomics data. We derive the probability for the cell-growth-corrected mRNA transcript number given the measured, cell size-dependent mRNA transcript number, based on the assumption that the average number of transcripts in a cell increases proportionally to the cell’s volume during the cell cycle. cgCorrect can be used for both data normalization and to analyze the steady-state distributions used to infer the gene expression mechanism. We demonstrate its applicability on both simulated data and single-cell quantitative real-time polymerase chain reaction (PCR) data from mouse blood stem and progenitor cells (and to quantitative single-cell RNA-sequencing data obtained from mouse embryonic stem cells). We show that correcting for differences in cell size affects the interpretation of the data obtained by typically performed computational analysis.

  11. In vitro toxicity testing with microplate cell cultures: Impact of cell binding.

    PubMed

    Gülden, Michael; Schreiner, Jeannine; Seibert, Hasso

    2015-06-05

    In vitro generated data on toxic potencies are generally based on nominal concentrations. However, cellular and extracellular binding and elimination processes may reduce the available free fraction of a compound. Then, nominal effective concentrations do not represent appropriate measures of toxic exposure in vitro and underestimate toxic potencies. In this study it was investigated whether cell binding can affect the availability of chemicals in microplate based toxicity assays. To this end the cytotoxicity of compounds like mercury chloride, digitonin and alcohol ethoxylates, accumulated by cells via different modes, was investigated in 96-well microplate cultures with varying concentrations of Balb/c 3T3 cells. The median effective nominal concentrations of all but one of the tested compounds depended linearly from the cell concentration. Applying a previously developed equilibrium distribution model cell concentration-independent median effective extracellular concentrations and cell burdens, respectively, could be calculated. The compounds were accumulated by the cells with bioconcentration factors, BCF, between 480 and ≥ 25,000. Cell binding of the alcohol ethoxylates was correlated with their lipophilicity. The results show that significant cell binding can occur even at the small cell volume fractions (∼ 1 × 10(-5) to 3 × 10(-3) L/L) encountered in microplate assays. To what extent cell binding affects the bioavailability depends on the BCF and the cell volume fraction. EC50 measurements in the presence of at least two different cell concentrations allow for excluding or detecting significant cell binding and for determining more appropriate measures of toxic exposure in vitro like median effective extracellular (free) concentrations or cell burdens. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

    NASA Technical Reports Server (NTRS)

    Tempel, G. E.; Musacchia, X. J.; Jones, S. B.

    1977-01-01

    Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

  13. Full scale phosphoric acid fuel cell stack technology development

    NASA Technical Reports Server (NTRS)

    Christner, L.; Faroque, M.

    1984-01-01

    The technology development for phosphoric acid fuel cells is summarized. The preparation, heat treatment, and characterization of carbon composites used as bipolar separator plates are described. Characterization included resistivity, porosity, and electrochemical corrosion. High density glassy carbon/graphite composites performed well in long-term fuel cell endurance tests. Platinum alloy cathode catalysts and low-loaded platinum electrodes were evaluated in 25 sq cm cells. Although the alloys displayed an initial improvement, some of this improvement diminished after a few thousand hours of testing. Low platinum loading (0.12 mg/sq cm anodes and 0.3 mg/sq cm cathodes) performed nearly as well as twice this loading. A selectively wetproofed anode backing paper was tested in a 5 by 15 inch three-cell stack. This material may provide for acid volume expansion, acid storage, and acid lateral distribution.

  14. Computational studies for a multiple-frequency electron cyclotron resonance ion source (abstract)

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

    Alton, G.D.

    1996-03-01

    The number density of electrons, the energy (electron temperature), and energy distribution are three of the fundamental properties which govern the performance of electron cyclotron resonance (ECR) ion sources in terms of their capability to produce high charge state ions. The maximum electron energy is affected by several processes including the ability of the plasma to absorb power. In principle, the performances of an ECR ion source can be realized by increasing the physical size of the ECR zone in relation to the total plasma volume. The ECR zones can be increased either in the spatial or frequency domains inmore » any ECR ion source based on B-minimum plasma confinement principles. The former technique requires the design of a carefully tailored magnetic field geometry so that the central region of the plasma volume is a large, uniformly distributed plasma volume which surrounds the axis of symmetry, as proposed in Ref. . Present art forms of the ECR source utilize single frequency microwave power supplies to maintain the plasma discharge; because the magnetic field distribution continually changes in this source design, the ECR zones are relegated to thin {open_quote}{open_quote}surfaces{close_quote}{close_quote} which surround the axis of symmetry. As a consequence of the small ECR zone in relation to the total plasma volume, the probability for stochastic heating of the electrons is quite low, thereby compromising the source performance. This handicap can be overcome by use of broadband, multiple frequency microwave power as evidenced by the enhanced performances of the CAPRICE and AECR ion sources when two frequency microwave power was utilized. We have used particle-in-cell codes to simulate the magnetic field distributions in these sources and to demonstrate the advantages of using multiple, discrete frequencies over single frequencies to power conventional ECR ion sources. (Abstract Truncated)« less

  15. Arc Length Based Grid Distribution For Surface and Volume Grids

    NASA Technical Reports Server (NTRS)

    Mastin, C. Wayne

    1996-01-01

    Techniques are presented for distributing grid points on parametric surfaces and in volumes according to a specified distribution of arc length. Interpolation techniques are introduced which permit a given distribution of grid points on the edges of a three-dimensional grid block to be propagated through the surface and volume grids. Examples demonstrate how these methods can be used to improve the quality of grids generated by transfinite interpolation.

  16. Diffusion and related transport mechanisms in brain tissue

    NASA Astrophysics Data System (ADS)

    Nicholson, Charles

    2001-07-01

    Diffusion plays a crucial role in brain function. The spaces between cells can be likened to the water phase of a foam and many substances move within this complicated region. Diffusion in this interstitial space can be accurately modelled with appropriate modifications of classical equations and quantified from measurements based on novel micro-techniques. Besides delivering glucose and oxygen from the vascular system to brain cells, diffusion also moves informational substances between cells, a process known as volume transmission. Deviations from expected results reveal how local uptake, degradation or bulk flow may modify the transport of molecules. Diffusion is also essential to many therapies that deliver drugs to the brain. The diffusion-generated concentration distributions of well-chosen molecules also reveal the structure of brain tissue. This structure is represented by the volume fraction (void space) and the tortuosity (hindrance to diffusion imposed by local boundaries or local viscosity). Analysis of these parameters also reveals how the local geometry of the brain changes with time or under pathological conditions. Theoretical and experimental approaches borrow from classical diffusion theory and from porous media concepts. Earlier studies were based on radiotracers but the recent methods use a point-source paradigm coupled with micro-sensors or optical imaging of macromolecules labelled with fluorescent tags. These concepts and methods are likely to be applicable elsewhere to measure diffusion properties in very small volumes of highly structured but delicate material.

  17. Improved Determination of Subnuclear Position Enabled by Three-Dimensional Membrane Reconstruction.

    PubMed

    Zhao, Yao; Schreiner, Sarah M; Koo, Peter K; Colombi, Paolo; King, Megan C; Mochrie, Simon G J

    2016-07-12

    Many aspects of chromatin biology are influenced by the nuclear compartment in which a locus resides, from transcriptional regulation to DNA repair. Further, the dynamic and variable localization of a particular locus across cell populations and over time makes analysis of a large number of cells critical. As a consequence, robust and automatable methods to measure the position of individual loci within the nuclear volume in populations of cells are necessary to support quantitative analysis of nuclear position. Here, we describe a three-dimensional membrane reconstruction approach that uses fluorescently tagged nuclear envelope or endoplasmic reticulum membrane marker proteins to precisely map the nuclear volume. This approach is robust to a variety of nuclear shapes, providing greater biological accuracy than alternative methods that enforce nuclear circularity, while also describing nuclear position in all three dimensions. By combining this method with established approaches to reconstruct the position of diffraction-limited chromatin markers-in this case, lac Operator arrays bound by lacI-GFP-the distribution of loci positions within the nuclear volume with respect to the nuclear periphery can be quantitatively obtained. This stand-alone image analysis pipeline should be of broad practical utility for individuals interested in various aspects of chromatin biology, while also providing, to our knowledge, a new conceptual framework for investigators who study organelle shape. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. 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

  19. Assessment of laryngeal muscle and testicular cell types in Xenopus laevis (Anura Pipidae) inhabiting maize and non-maize growing areas of South Africa

    USGS Publications Warehouse

    Smith, E.E.; Du Preez, L.H.; Gentles, A.; Solomon, K.R.; Tandler, B.; Carr, J.A.; Van Der Kraak, G. L.; Kendall, R.J.; Giesy, J.P.; Gross, T.S.

    2005-01-01

    We tested the hypothesis that adult African clawed frogs (Xenopus laevis) inhabiting water bodies in maize-growing areas (MGA) of South Africa would exhibit differences in testicular structure compared to frogs from water bodies in non-maize-growing areas (NMGA) in the same locale. Adults of both sexes were collected during the autumn of 2002 in South Africa, and stereological analytical techniques were used to quantify the distribution of testicular cell types. In addition, total laryngeal mass was used as a gauge of secondary sex differences in animals from MGA and NMGA study sites. Evaluation of the total laryngeal mass revealed that there were no statistically significant differences between X. laevis of the same sex from the NMGA and MGA sites. Mean percent fractional-volume values for seminiferous tubule distribution of testicular cell types of mature X. laevis, ranged from 3-4% for spermatogonia, 26-28% for spermatocytes, 54-57% for spermatozoa, and 14-15% for other cells types. The mean percent volume for blood vessels ranged from 0.3-0.4%. These values did not differ significantly between frogs from NMGA and MGA areas. Collectively, these data demonstrated no differences in gonadal and laryngeal development in X. laevis collected in South Africa from MGA and NMGA areas and that there is little evidence for an effect of agricultural chemicals used in maize production functioning as endocrine disrupters in this species. Screening of X. laevis testes revealed a small incidence of Stage 1 testicular oocytes in adult male frogs collected from the NMGA (3%) and MGA (2%).

  20. Ozone and allergen exposure during postnatal development alters the frequency and airway distribution of CD25+ cells in infant rhesus monkeys

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

    Miller, Lisa A.; California National Primate Research Center, University of California, Davis, CA 95616; Gerriets, Joan E.

    2009-04-01

    The epidemiologic link between air pollutant exposure and asthma has been supported by experimental findings, but the mechanisms are not understood. In this study, we evaluated the impact of combined ozone and house dust mite (HDM) exposure on the immunophenotype of peripheral blood and airway lymphocytes from rhesus macaque monkeys during the postnatal period of development. Starting at 30 days of age, monkeys were exposed to 11 cycles of filtered air, ozone, HDM aerosol, or ozone + HDM aerosol. Each cycle consisted of ozone delivered at 0.5 ppm for 5 days (8 h/day), followed by 9 days of filtered air;more » animals received HDM aerosol during the last 3 days of each ozone exposure period. Between 2-3 months of age, animals co-exposed to ozone + HDM exhibited a decline in total circulating leukocyte numbers and increased total circulating lymphocyte frequency. At 3 months of age, blood CD4+/CD25+ lymphocytes were increased with ozone + HDM. At 6 months of age, CD4+/CD25+ and CD8+/CD25+ lymphocyte populations increased in both blood and lavage of ozone + HDM animals. Overall volume of CD25+ cells within airway mucosa increased with HDM exposure. Ozone did not have an additive effect on volume of mucosal CD25+ cells in HDM-exposed animals, but did alter the anatomical distribution of this cell type throughout the proximal and distal airways. We conclude that a window of postnatal development is sensitive to air pollutant and allergen exposure, resulting in immunomodulation of peripheral blood and airway lymphocyte frequency and trafficking.« less

  1. 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

  2. Correlation of pull-out strength of cement-augmented pedicle screws with CT-volumetric measurement of cement.

    PubMed

    Fölsch, Christian; Goost, Hans; Figiel, Jens; Paletta, Jürgen R J; Schultz, Wolfgang; Lakemeier, Stefan

    2012-12-01

    Cement augmentation of pedicle screws increases fixation strength in an osteoporotic spine. This study was designed to determine the cement distribution and the correlation between the pull-out strength of the augmented screw and the cement volume within polyurethane (PU) foam. Twenty-eight cannulated pedicle screws (6×45 mm) (Peter Brehm, Erlangen, Germany) with four holes at the distal end of the screw were augmented with the acrylic Stabilit ER Bone Cement Vertebral Augmentation System (DFine Inc., San Jose, CA, USA) and implanted into open-cell rigid PU foam (Pacific Research Laboratories, Vashon Island, WA, USA) with a density of 0.12 g/cm3, resembling severe osteoporosis. Volumetric measurement of the cement with consideration of the distribution around the screws was done with multislice computed tomography scan (Somatom Definition, Siemens, Erlangen, Germany). Pull-out strength was tested with a servohydraulic system (MTS System Corporation, Eden Prairie, MN, USA), and nonaugmented screws served as control. Pearson's correlation coefficient with significance level α=0.05 and one-way analysis of variance test were used. We found a high (r=0.88) and significant (p<0.01) correlation between the cement volume and the pull-out strength, which increased by more than 5-fold with a volume of 3 ml. The correlation appeared linear at least up to 4 ml cement volume and failure always occurred at the cement-bone interface. The cement distribution was symmetric and circular around the most proximal hole, with a distance of 14 mm from the tip, and nearly 90% of the cement was found 6 mm distal and cranial to it. The 95% confidence interval for the relative amount of cement was 37%-41% within 2 mm of the most proximal hole. Compared with the control, a cement volume between 2.0 and 3.0 ml increased the pull-out strength significantly and is relevant for clinical purposes, whereas a volume of 0.5 ml did not. A cement volume beyond 3.0 ml should further increase the pull-out strength because the correlation was linear at least up to 4.0 ml, but the possibility of in vivo cement leakage with increasing volume has to be considered. Pressure-controlled cement application might be a tool to avoid this complication. The cement almost completely penetrated the most proximal perforation.

  3. Cell wall microstructure, pore size distribution and absolute density of hemp shiv

    PubMed Central

    Lawrence, M.; Ansell, M. P.; Hussain, A.

    2018-01-01

    This paper, for the first time, fully characterizes the intrinsic physical parameters of hemp shiv including cell wall microstructure, pore size distribution and absolute density. Scanning electron microscopy revealed microstructural features similar to hardwoods. Confocal microscopy revealed three major layers in the cell wall: middle lamella, primary cell wall and secondary cell wall. Computed tomography improved the visualization of pore shape and pore connectivity in three dimensions. Mercury intrusion porosimetry (MIP) showed that the average accessible porosity was 76.67 ± 2.03% and pore size classes could be distinguished into micropores (3–10 nm) and macropores (0.1–1 µm and 20–80 µm). The absolute density was evaluated by helium pycnometry, MIP and Archimedes' methods. The results show that these methods can lead to misinterpretation of absolute density. The MIP method showed a realistic absolute density (1.45 g cm−3) consistent with the density of the known constituents, including lignin, cellulose and hemi-cellulose. However, helium pycnometry and Archimedes’ methods gave falsely low values owing to 10% of the volume being inaccessible pores, which require sample pretreatment in order to be filled by liquid or gas. This indicates that the determination of the cell wall density is strongly dependent on sample geometry and preparation. PMID:29765652

  4. Cell wall microstructure, pore size distribution and absolute density of hemp shiv

    NASA Astrophysics Data System (ADS)

    Jiang, Y.; Lawrence, M.; Ansell, M. P.; Hussain, A.

    2018-04-01

    This paper, for the first time, fully characterizes the intrinsic physical parameters of hemp shiv including cell wall microstructure, pore size distribution and absolute density. Scanning electron microscopy revealed microstructural features similar to hardwoods. Confocal microscopy revealed three major layers in the cell wall: middle lamella, primary cell wall and secondary cell wall. Computed tomography improved the visualization of pore shape and pore connectivity in three dimensions. Mercury intrusion porosimetry (MIP) showed that the average accessible porosity was 76.67 ± 2.03% and pore size classes could be distinguished into micropores (3-10 nm) and macropores (0.1-1 µm and 20-80 µm). The absolute density was evaluated by helium pycnometry, MIP and Archimedes' methods. The results show that these methods can lead to misinterpretation of absolute density. The MIP method showed a realistic absolute density (1.45 g cm-3) consistent with the density of the known constituents, including lignin, cellulose and hemi-cellulose. However, helium pycnometry and Archimedes' methods gave falsely low values owing to 10% of the volume being inaccessible pores, which require sample pretreatment in order to be filled by liquid or gas. This indicates that the determination of the cell wall density is strongly dependent on sample geometry and preparation.

  5. Conceptual Layout of Wing Structure Using Topology Optimization for Morphing Micro Air Vehicles in a Perching Maneuver

    DTIC Science & Technology

    2012-03-22

    the fraction of the design space to be filled with material (termed “volume fraction”), and any other desired design restrictions such as a ...topology problem is called a distributed parameter system because the design variables represent a field or continuum with infinite degrees of freedom... with the addition of a few solutions that were a combination of honeycomb and fiber cells. Unlike

  6. 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.

  7. Satellite power systems (SPS) concept definition study. Volume 2, part 1: System engineering

    NASA Technical Reports Server (NTRS)

    Hanley, G. M.

    1980-01-01

    Top level trade studies are presented, including comparison of solid state and klystron concepts, higher concentration on the solar cells, composite and aluminum structure, and several variations to the reference concept. Detailed trade studies are presented in each of the subsystem areas (solar array, power distribution, structures, thermal control, attitude control and stationkeeping, microwave transmission, and ground receiving station). A description of the selected point design is also presented.

  8. Correlation Characterization of Particles in Volume Based on Peak-to-Basement Ratio

    PubMed Central

    Vovk, Tatiana A.; Petrov, Nikolay V.

    2017-01-01

    We propose a new express method of the correlation characterization of the particles suspended in the volume of optically transparent medium. It utilizes inline digital holography technique for obtaining two images of the adjacent layers from the investigated volume with subsequent matching of the cross-correlation function peak-to-basement ratio calculated for these images. After preliminary calibration via numerical simulation, the proposed method allows one to quickly distinguish parameters of the particle distribution and evaluate their concentration. The experimental verification was carried out for the two types of physical suspensions. Our method can be applied in environmental and biological research, which includes analyzing tools in flow cytometry devices, express characterization of particles and biological cells in air and water media, and various technical tasks, e.g. the study of scattering objects or rapid determination of cutting tool conditions in mechanisms. PMID:28252020

  9. Isotropic stochastic rotation dynamics

    NASA Astrophysics Data System (ADS)

    Mühlbauer, Sebastian; Strobl, Severin; Pöschel, Thorsten

    2017-12-01

    Stochastic rotation dynamics (SRD) is a widely used method for the mesoscopic modeling of complex fluids, such as colloidal suspensions or multiphase flows. In this method, however, the underlying Cartesian grid defining the coarse-grained interaction volumes induces anisotropy. We propose an isotropic, lattice-free variant of stochastic rotation dynamics, termed iSRD. Instead of Cartesian grid cells, we employ randomly distributed spherical interaction volumes. This eliminates the requirement of a grid shift, which is essential in standard SRD to maintain Galilean invariance. We derive analytical expressions for the viscosity and the diffusion coefficient in relation to the model parameters, which show excellent agreement with the results obtained in iSRD simulations. The proposed algorithm is particularly suitable to model systems bound by walls of complex shape, where the domain cannot be meshed uniformly. The presented approach is not limited to SRD but is applicable to any other mesoscopic method, where particles interact within certain coarse-grained volumes.

  10. A National State of the Art Study of Curriculum Instructional Materials for Distributive Education. Volume 1.

    ERIC Educational Resources Information Center

    Hirshfeld, Marvin; Leventhal, Jerome I.

    Volume 1 of the two-volume annotated bibliography provides a partial listing of available materials for curriculum and instructional enrichment in distributive education. The grouping of all materials was made according to the U. S. Office of Education Classification of Instructional Programs for Distributive Education. Alphabetized by title under…

  11. A National State of the Art Study of Curriculum Instructional Materials for Distributive Education. Volume 2.

    ERIC Educational Resources Information Center

    Hirshfeld, Marvin; Leventhal, Jerome I.

    Volume 2 of the two-volume annotated bibliography provides a partial listing of available materials for curriculum and instructional enrichment in distributive education. The grouping of all materials was made according to the U. S. Office of Education Classification of Instructional Programs for Distributive Education. Alphabetized by title under…

  12. 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.

  13. The growth rate of bone sarcomas and survival after radiotherapy with tourniquet-induced hypoxia: a clinical study. [/sup 60/Co

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

    Balmukhanov, S.B.; Turdugulov, I.; Karibjanova, Z.

    1982-04-15

    The volume doubling time of primary bone sarcomas and lung metastases was determined by measurements made on serial radiographs. For the primary tumors, the volume doubling times were lognormal distributed and varied in the range of 20-200 days with a mean around 50 days. The volume doubling times of the metastases also showed a log-normal distribution in the range of 10-100 days, but with a mean twice as short as that of the primaries. Radiation therapy was given with three-four doses of 20-25 Gy to the tumors that, together with the surrounding normal tissues, had been made hypoxic by themore » application of a tourniquet. Amputations were not performed unless required eventually by some serious late radiation damage, such as grave functional deficiency, and/or painful fibrosis and ankyloses. In no case did microscopic examination of the amputated tissues reveal the persistance of any viable, neoplastic cell. The five-year survival of a total of 69 patients was 26%. Survival expectancy was found to be closely related to the volume doubling time of the tumors, as was the incidence of the metastases. The data stress the importance of volume doubling time as a predictive factor and indicate, furthermore, that treatment with a few massive radiation doses in combination with tourniquet-induced hypoxia is effective in the local control of bone sarcomas. The severe late reaction of the normal tissues to the treatment will, however, require amputations in most of the five-year survivors.« less

  14. 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.

  15. 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.

  16. Blood Volume: Its Adaptation to Endurance Training

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.

    1991-01-01

    Expansion of blood volume (hypervolemia) has been well documented in both cross-sectional and longitudinal studies as a consequence of endurance exercise training. Plasma volume expansion can account for nearly all of the exercise-induced hypervolemia up to 2-4 wk; after this time expansion may be distributed equally between plasma and red cell volumes. The exercise stimulus for hypervolemia has both thermal and nonthermal components that increase total circulating plasma levels of electrolytes and proteins. Although protein and fluid shifts from the extravascular to intravascular space may provide a mechanism for rapid hypervolemia immediately after exercise, evidence supports the notion that chronic hypervolemia associated with exercise training represents a net expansion of total body water and solutes. This net increase of body fluids with exercise training is associated with increased water intake and decreased urine volume output. The mechanism of reduced urine output appears to be increased renal tubular reabsorption of sodium through a more sensitive aldosterone action in man. Exercise training-induced hypervolemia appears to be universal among most animal species, although the mechanisms may be quite different. The hypervolemia may provide advantages of greater body fluid for heat dissipation and thermoregulatory stability as well as larger vascular volume and filling pressure for greater cardiac stroke volume and lower heart rates during exercise.

  17. 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.

  18. Thermal stress analysis of a planar SOFC stack

    NASA Astrophysics Data System (ADS)

    Lin, Chih-Kuang; Chen, Tsung-Ting; Chyou, Yau-Pin; Chiang, Lieh-Kwang

    The aim of this study is, by using finite element analysis (FEA), to characterize the thermal stress distribution in a planar solid oxide fuel cell (SOFC) stack during various stages. The temperature profiles generated by an integrated thermo-electrochemical model were applied to calculate the thermal stress distributions in a multiple-cell SOFC stack by using a three-dimensional (3D) FEA model. The constructed 3D FEA model consists of the complete components used in a practical SOFC stack, including positive electrode-electrolyte-negative electrode (PEN) assembly, interconnect, nickel mesh, and gas-tight glass-ceramic seals. Incorporation of the glass-ceramic sealant, which was never considered in previous studies, into the 3D FEA model would produce more realistic results in thermal stress analysis and enhance the reliability of predicting potential failure locations in an SOFC stack. The effects of stack support condition, viscous behavior of the glass-ceramic sealant, temperature gradient, and thermal expansion mismatch between components were characterized. Modeling results indicated that a change in the support condition at the bottom frame of the SOFC stack would not cause significant changes in thermal stress distribution. Thermal stress distribution did not differ significantly in each unit cell of the multiple-cell stack due to a comparable in-plane temperature profile. By considering the viscous characteristics of the glass-ceramic sealant at temperatures above the glass-transition temperature, relaxation of thermal stresses in the PEN was predicted. The thermal expansion behavior of the metallic interconnect/frame had a greater influence on the thermal stress distribution in the PEN than did that of the glass-ceramic sealant due to the domination of interconnect/frame in the volume of a planar SOFC assembly.

  19. Thermodynamics of Macromolecular Association in Heterogeneous Crowding Environments: Theoretical and Simulation Studies with a Simplified Model.

    PubMed

    Ando, Tadashi; Yu, Isseki; Feig, Michael; Sugita, Yuji

    2016-11-23

    The cytoplasm of a cell is crowded with many different kinds of macromolecules. The macromolecular crowding affects the thermodynamics and kinetics of biological reactions in a living cell, such as protein folding, association, and diffusion. Theoretical and simulation studies using simplified models focus on the essential features of the crowding effects and provide a basis for analyzing experimental data. In most of the previous studies on the crowding effects, a uniform crowder size is assumed, which is in contrast to the inhomogeneous size distribution of macromolecules in a living cell. Here, we evaluate the free energy changes upon macromolecular association in a cell-like inhomogeneous crowding system via a theory of hard-sphere fluids and free energy calculations using Brownian dynamics trajectories. The inhomogeneous crowding model based on 41 different types of macromolecules represented by spheres with different radii mimics the physiological concentrations of macromolecules in the cytoplasm of Mycoplasma genitalium. The free energy changes of macromolecular association evaluated by the theory and simulations were in good agreement with each other. The crowder size distribution affects both specific and nonspecific molecular associations, suggesting that not only the volume fraction but also the size distribution of macromolecules are important factors for evaluating in vivo crowding effects. This study relates in vitro experiments on macromolecular crowding to in vivo crowding effects by using the theory of hard-sphere fluids with crowder-size heterogeneity.

  20. Impact of dose size in single fraction spatially fractionated (grid) radiotherapy for melanoma

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

    Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu, E-mail: hualinzhang@yahoo.com; Zhong, Hualiang; Barth, Rolf F.

    2014-02-15

    Purpose: To evaluate the impact of dose size in single fraction, spatially fractionated (grid) radiotherapy for selectively killing infiltrated melanoma cancer cells of different tumor sizes, using different radiobiological models. Methods: A Monte Carlo technique was employed to calculate the 3D dose distribution of a commercially available megavoltage grid collimator in a 6 MV beam. The linear-quadratic (LQ) and modified linear quadratic (MLQ) models were used separately to evaluate the therapeutic outcome of a series of single fraction regimens that employed grid therapy to treat both acute and late responding melanomas of varying sizes. The dose prescription point was atmore » the center of the tumor volume. Dose sizes ranging from 1 to 30 Gy at 100% dose line were modeled. Tumors were either touching the skin surface or having their centers at a depth of 3 cm. The equivalent uniform dose (EUD) to the melanoma cells and the therapeutic ratio (TR) were defined by comparing grid therapy with the traditional open debulking field. The clinical outcomes from recent reports were used to verify the authors’ model. Results: Dose profiles at different depths and 3D dose distributions in a series of 3D melanomas treated with grid therapy were obtained. The EUDs and TRs for all sizes of 3D tumors involved at different doses were derived through the LQ and MLQ models, and a practical equation was derived. The EUD was only one fifth of the prescribed dose. The TR was dependent on the prescribed dose and on the LQ parameters of both the interspersed cancer and normal tissue cells. The results from the LQ model were consistent with those of the MLQ model. At 20 Gy, the EUD and TR by the LQ model were 2.8% higher and 1% lower than by the MLQ, while at 10 Gy, the EUD and TR as defined by the LQ model were only 1.4% higher and 0.8% lower, respectively. The dose volume histograms of grid therapy for a 10 cm tumor showed different dosimetric characteristics from those of conventional radiotherapy. A significant portion of the tumor volume received a very large dose in grid therapy, which ensures significant tumor cell killing in these regions. Conversely, some areas received a relatively small dose, thereby sparing interspersed normal cells and increasing radiation tolerance. The radiobiology modeling results indicated that grid therapy could be useful for treating acutely responding melanomas infiltrating radiosensitive normal tissues. The theoretical model predictions were supported by the clinical outcomes. Conclusions: Grid therapy functions by selectively killing infiltrating tumor cells and concomitantly sparing interspersed normal cells. The TR depends on the radiosensitivity of the cell population, dose, tumor size, and location. Because the volumes of very high dose regions are small, the LQ model can be used safely to predict the clinical outcomes of grid therapy. When treating melanomas with a dose of 15 Gy or higher, single fraction grid therapy is clearly advantageous for sparing interspersed normal cells. The existence of a threshold fraction dose, which was found in the authors’ theoretical simulations, was confirmed by clinical observations.« less

  1. Role of peripheral pooling in porcine Escherichia coli sepsis

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

    Teule, G.J.; von Lingen, A.; Verwey von Vught, M.A.

    In anesthesized pigs the effects of E. coli (2 X 10(8)/kg) on hemodynamics and red cell distribution were studied. After injection of 99m-Tc red cells (15 mCi), regional radioactivity was followed during 3 hours. Gated bloodpool studies were performed to measure end-diastolic volumes (EDV). Escherichia coli E. coli was infused in 14 pigs, while 7 animals served as controls. E. coli resulted in an early increase in pulmonary arterial pressure. Systemic arterial pressure decreased gradually, while cardiac output did not change significantly. The gated studies revealed that especially left ventricular end-diastolic volume (LVEDV) declined, to 50% of the basal value.more » Regional radioactivity did not change over lungs, liver and abdomen. Splenic activity declined markedly. Over the hindlimb a significant increase (29 +/- 8%) was observed. It is concluded that E. coli infusion in pigs induces a hemodynamic pattern similar to human sepsis. The decrease in LVEDV is probably related to peripheral pooling and a change in right ventricle (RV) performance.« less

  2. An incompressible two-dimensional multiphase particle-in-cell model for dense particle flows

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

    Snider, D.M.; O`Rourke, P.J.; Andrews, M.J.

    1997-06-01

    A two-dimensional, incompressible, multiphase particle-in-cell (MP-PIC) method is presented for dense particle flows. The numerical technique solves the governing equations of the fluid phase using a continuum model and those of the particle phase using a Lagrangian model. Difficulties associated with calculating interparticle interactions for dense particle flows with volume fractions above 5% have been eliminated by mapping particle properties to a Eulerian grid and then mapping back computed stress tensors to particle positions. This approach utilizes the best of Eulerian/Eulerian continuum models and Eulerian/Lagrangian discrete models. The solution scheme allows for distributions of types, sizes, and density of particles,more » with no numerical diffusion from the Lagrangian particle calculations. The computational method is implicit with respect to pressure, velocity, and volume fraction in the continuum solution thus avoiding courant limits on computational time advancement. MP-PIC simulations are compared with one-dimensional problems that have analytical solutions and with two-dimensional problems for which there are experimental data.« less

  3. A neuronal morphologic type unique to humans and great apes

    PubMed Central

    Nimchinsky, Esther A.; Gilissen, Emmanuel; Allman, John M.; Perl, Daniel P.; Erwin, Joseph M.; Hof, Patrick R.

    1999-01-01

    We report the existence and distribution of an unusual type of projection neuron, a large, spindle-shaped cell, in layer Vb of the anterior cingulate cortex of pongids and hominids. These spindle cells were not observed in any other primate species or any other mammalian taxa, and their volume was correlated with brain volume residuals, a measure of encephalization in higher primates. These observations are of particular interest when considering primate neocortical evolution, as they reveal possible adaptive changes and functional modifications over the last 15–20 million years in the anterior cingulate cortex, a region that plays a major role in the regulation of many aspects of autonomic function and of certain cognitive processes. That in humans these unique neurons have been shown previously to be severely affected in the degenerative process of Alzheimer’s disease suggests that some of the differential neuronal susceptibility that occurs in the human brain in the course of age-related dementing illnesses may have appeared only recently during primate evolution. PMID:10220455

  4. SU-F-T-685: Evaluation of Tumor Hypoxic Fraction Using Serial Volumetric Imaging During Radiation Therapy

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

    Chvetsov, A

    Purpose: To develop a tumor response model which could be uses to compute tumor hypoxic fraction using serial volumetric tumor imaging. This algorithm may be used for treatment response assessment and also for guidance of more expensive PET imaging of hypoxia. Methods: Previously developed two-level cell population tumor response model was modified to include a third cell level describing hypoxic and necrotic cells. This third level was considered constant value during radiotherapy treatment; therefore, inclusion additional parameter did not compromise stability of model fitting to imaging data. Fitting the model to serial volumetric imaging data was performed using a leastmore » squares objective function and simulated annealing algorithm. The problem of reconstruction of radiobiological parameters from serial imaging data was considered as inverse ill-posed problem described by the Fredholm integral equation of the first kind. Variational regularization was used to stabilize solutions. Results: To evaluate performance of the algorithm, we used a set of serial CT imaging data on tumor-volume for 14 head and neck cancer patients. The hypoxic fractions were reconstructed for each patient and the distribution of hypoxic fractions was compared to the distribution of initial hypoxic fractions previously measured using histograph. The measured and reconstructed from imaging data distributions of hypoxic fractions are in good agreement. The reconstructed distribution of cell surviving fraction was also in better agreement with in vitro data than previously obtained using the two-level cell population model. Conclusion: Our results indicate that it is possible to evaluate the initial hypoxic tumor fraction using serial volumetric imaging and a tumor response model. This algorithm can be used for treatment response assessment and guidance of more expensive PET imaging.« less

  5. 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.

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

    Crawford, Andrew M.; Kurecka, Patrick; Yim, Tsz Kwan

    An X-ray fluorescence flow cytometer that can determine the total metal content of single cells has been developed. Capillary action or pressure was used to load cells into hydrophilic or hydrophobic capillaries, respectively. Once loaded, the cells were transported at a fixed vertical velocity past a focused X-ray beam. X-ray fluorescence was then used to determine the mass of metal in each cell. By making single-cell measurements, the population heterogeneity for metals in the µ M to m M concentration range on fL sample volumes can be directly measured, a measurement that is difficult using most analytical methods. This approachmore » has been used to determine the metal composition of 936 individual bovine red blood cells (bRBC), 31 individual 3T3 mouse fibroblasts (NIH3T3) and 18 Saccharomyces cerevisiae (yeast) cells with an average measurement frequency of ~4 cells min –1. These data show evidence for surprisingly broad metal distributions. Lastly, details of the device design, data analysis and opportunities for further sensitivity improvement are described.« less

  7. Impact of Hybrid and Complex N-Glycans on Cell Surface Targeting of the Endogenous Chloride Cotransporter Slc12a2

    PubMed Central

    Singh, Richa; Pacheco-Andrade, Romario; Almiahuob, Mohamed Y. Mahmoud

    2015-01-01

    The Na+K+2Cl− cotransporter-1 (Slc12a2, NKCC1) is widely distributed and involved in cell volume/ion regulation. Functional NKCC1 locates in the plasma membrane of all cells studied, particularly in the basolateral membrane of most polarized cells. Although the mechanisms involved in plasma membrane sorting of NKCC1 are poorly understood, it is assumed that N-glycosylation is necessary. Here, we characterize expression, N-glycosylation, and distribution of NKCC1 in COS7 cells. We show that ~25% of NKCC1 is complex N-glycosylated whereas the rest of it corresponds to core/high-mannose and hybrid-type N-glycosylated forms. Further, ~10% of NKCC1 reaches the plasma membrane, mostly as core/high-mannose type, whereas ~90% of NKCC1 is distributed in defined intracellular compartments. In addition, inhibition of the first step of N-glycan biosynthesis with tunicamycin decreases total and plasma membrane located NKCC1 resulting in almost undetectable cotransport function. Moreover, inhibition of N-glycan maturation with swainsonine or kifunensine increased core/hybrid-type NKCC1 expression but eliminated plasma membrane complex N-glycosylated NKCC1 and transport function. Together, these results suggest that (i) NKCC1 is delivered to the plasma membrane of COS7 cells independently of its N-glycan nature, (ii) most of NKCC1 in the plasma membrane is core/hybrid-type N-glycosylated, and (iii) the minimal proportion of complex N-glycosylated NKCC1 is functionally active. PMID:26351455

  8. Cell Kinetic and Histomorphometric Analysis of Microgravitational Osteopenia: PARE.03B

    NASA Technical Reports Server (NTRS)

    Roberts, W. Eugene; Garetto, Lawrence P.

    1998-01-01

    Previous methods of identifying cells undergoing DNA synthesis (S-phase) utilized 3H-thymidine (3HT) autoradiography. 5-Bromo-2'-deoxyuridine (BrdU) immunohistochemistry is a nonradioactive alternative method. This experiment compared the two methods using the nuclear volume model for osteoblast histogenesis in two different embedding media. Twenty Sprague-Dawley rats were used, with half receiving 3HT (1 micro-Ci/g) and the other half BrdU (50 micro-g/g). Condyles were embedded (one side in paraffin, the other in plastic) and S-phase nuclei were identified using either autoradiography or immunohistochemistry. The fractional distribution of preosteoblast cell types and the percentage of labeled cells (within each cell fraction and label index) were calculated and expressed as mean +/- standard error. Chi-Square analysis showed only a minor difference in the fractional distribution of cell types. However, there were,significant differences (p less than 0.05) by ANOVA, in the nuclear labeling of specific cell types. With the exception of the less-differentiated A+A' cells, more BrdU label was consistently detected in paraffin than in plastic-embedded sections. In general, more nuclei were labeled with 3H-thymidine than with BrdU in both types of embedding media (Fig 2.). Labeling index data (labeled cells/total cells sampled x 100) indicated that BrdU in paraffin, but not plastic gave the same results as 3HT in either embedding method. Thus, we conclude that the two labeling methods do not yield the same results.

  9. MAC/GMC 4.0 User's Manual: Example Problem Manual. Volume 3

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Arnold, Steven M.

    2002-01-01

    This document is the third volume in the three volume set of User's Manuals for the Micromechanics Analysis Code with Generalized Method of Cells Version 4.0 (MAC/GMC 4.0). Volume 1 is the Theory Manual, Volume 2 is the Keywords Manual, and this document is the Example Problems Manual. MAC/GMC 4.0 is a composite material and laminate analysis software program developed at the NASA Glenn Research Center. It is based on the generalized method of cells (GMC) micromechanics theory, which provides access to the local stress and strain fields in the composite material. This access grants GMC the ability to accommodate arbitrary local models for inelastic material behavior and various types of damage and failure analysis. MAC/GMC 4.0 has been built around GMC to provide the theory with a user-friendly framework, along with a library of local inelastic, damage, and failure models. Further, application of simulated thermo-mechanical loading, generation of output results, and selection of architectures to represent the composite material, have been automated in MAC/GMC 4.0. Finally, classical lamination theory has been implemented within MAC/GMC 4.0 wherein GMC is used to model the composite material response of each ply. Consequently, the full range of GMC composite material capabilities is available for analysis of arbitrary laminate configurations as well. This volume provides in-depth descriptions of 43 example problems, which were specially designed to highlight many of the most important capabilities of the code. The actual input files associated with each example problem are distributed with the MAC/GMC 4.0 software; thus providing the user with a convenient starting point for their own specialized problems of interest.

  10. Korean red ginseng extract enhances paclitaxel distribution to mammary tumors and its oral bioavailability by P-glycoprotein inhibition.

    PubMed

    Bae, Jin Kyung; Kim, You-Jin; Chae, Hee-Sung; Kim, Do Yeun; Choi, Han Seok; Chin, Young-Won; Choi, Young Hee

    2017-05-01

    1. Drug efflux by P-glycoprotein (P-gp) is a common resistance mechanism of breast cancer cells to paclitaxel, the primary chemotherapy in breast cancer. As a means of overcoming the drug resistance-mediated failure of paclitaxel chemotherapy, the potential of Korean red ginseng extract (KRG) as an adjuvant chemotherapy has been reported only in in vitro. Therefore, we assessed whether KRG alters P-gp mediated paclitaxel efflux, and therefore paclitaxel efficacy in in vitro and vivo models. 2. KRG inhibited P-gp protein expression and transcellular efflux of paclitaxel in MDCK-mdr1 cells, but KRG was not a substrate of P-gp ATPase. In female rats with mammary tumor, the combination of paclitaxel with KRG showed the greater reduction of tumor volumes, lower P-gp protein expression and higher paclitaxel distribution in tumors, and greater oral bioavailability of paclitaxel than paclitaxel alone. 3. From these results, KRG increased systemic circulation of oral paclitaxel and its distribution to tumors via P-gp inhibition in rats and under the current study conditions.

  11. Comparison of 3D ion velocity distribution measurements and models in the vicinity of an absorbing boundary oriented obliquely to a magnetic field

    NASA Astrophysics Data System (ADS)

    Henriquez, Miguel F.; Thompson, Derek S.; Kenily, Shane; Khaziev, Rinat; Good, Timothy N.; McIlvain, Julianne; Siddiqui, M. Umair; Curreli, Davide; Scime, Earl E.

    2016-10-01

    Understanding particle distributions in plasma boundary regions is critical to predicting plasma-surface interactions. Ions in the presheath exhibit complex behavior because of collisions and due to the presence of boundary-localized electric fields. Complete understanding of particle dynamics is necessary for understanding the critical problems of tokamak wall loading and Hall thruster channel wall erosion. We report measurements of 3D argon ion velocity distribution functions (IVDFs) in the vicinity of an absorbing boundary oriented obliquely to a background magnetic field. Measurements were obtained via argon ion laser induced fluorescence throughout a spatial volume upstream of the boundary. These distribution functions reveal kinetic details that provide a point-to-point check on particle-in-cell and 1D3V Boltzmann simulations. We present the results of this comparison and discuss some implications for plasma boundary interaction physics.

  12. ON Cone Bipolar Cell Axonal Synapses in the OFF Inner Plexiform Layer of the Rabbit Retina

    PubMed Central

    Lauritzen, J. Scott; Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Mohammed, Shoeb; Hoang, John V.; Marc, Robert E.

    2012-01-01

    Analysis of the rabbit retinal connectome RC1 reveals that the division between the ON and OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make non-canonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscope (ATEM) imaging, molecular tagging, tracing, and rendering of ≈ 400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include GABA-positive amacrine cells (γACs), glycine-positive amacrine cells (GACs) and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON-OFF amacrine cells. Many of these ON-OFF GACs target ON cone bipolar cell axons, ON γACs and/or ON-OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC-mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON-OFF ganglion cells in the OFF layer and provide ON drive to polarity-appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. PMID:23042441

  13. Reading Out Single-Molecule Digital RNA and DNA Isothermal Amplification in Nanoliter Volumes with Unmodified Camera Phones

    PubMed Central

    2016-01-01

    Digital single-molecule technologies are expanding diagnostic capabilities, enabling the ultrasensitive quantification of targets, such as viral load in HIV and hepatitis C infections, by directly counting single molecules. Replacing fluorescent readout with a robust visual readout that can be captured by any unmodified cell phone camera will facilitate the global distribution of diagnostic tests, including in limited-resource settings where the need is greatest. This paper describes a methodology for developing a visual readout system for digital single-molecule amplification of RNA and DNA by (i) selecting colorimetric amplification-indicator dyes that are compatible with the spectral sensitivity of standard mobile phones, and (ii) identifying an optimal ratiometric image-process for a selected dye to achieve a readout that is robust to lighting conditions and camera hardware and provides unambiguous quantitative results, even for colorblind users. We also include an analysis of the limitations of this methodology, and provide a microfluidic approach that can be applied to expand dynamic range and improve reaction performance, allowing ultrasensitive, quantitative measurements at volumes as low as 5 nL. We validate this methodology using SlipChip-based digital single-molecule isothermal amplification with λDNA as a model and hepatitis C viral RNA as a clinically relevant target. The innovative combination of isothermal amplification chemistry in the presence of a judiciously chosen indicator dye and ratiometric image processing with SlipChip technology allowed the sequence-specific visual readout of single nucleic acid molecules in nanoliter volumes with an unmodified cell phone camera. When paired with devices that integrate sample preparation and nucleic acid amplification, this hardware-agnostic approach will increase the affordability and the distribution of quantitative diagnostic and environmental tests. PMID:26900709

  14. Experimental taphonomy of giant sulphur bacteria: implications for the interpretation of the embryo-like Ediacaran Doushantuo fossils.

    PubMed

    Cunningham, J A; Thomas, C-W; Bengtson, S; Marone, F; Stampanoni, M; Turner, F R; Bailey, J V; Raff, R A; Raff, E C; Donoghue, P C J

    2012-05-07

    The Ediacaran Doushantuo biota has yielded fossils interpreted as eukaryotic organisms, either animal embryos or eukaryotes basal or distantly related to Metazoa. However, the fossils have been interpreted alternatively as giant sulphur bacteria similar to the extant Thiomargarita. To test this hypothesis, living and decayed Thiomargarita were compared with Doushantuo fossils and experimental taphonomic pathways were compared with modern embryos. In the fossils, as in eukaryotic cells, subcellular structures are distributed throughout cell volume; in Thiomargarita, a central vacuole encompasses approximately 98 per cent cell volume. Key features of the fossils, including putative lipid vesicles and nuclei, complex envelope ornament, and ornate outer vesicles are incompatible with living and decay morphologies observed in Thiomargarita. Microbial taphonomy of Thiomargarita also differed from that of embryos. Embryo tissues can be consumed and replaced by bacteria, forming a replica composed of a three-dimensional biofilm, a stable fabric for potential fossilization. Vacuolated Thiomargarita cells collapse easily and do not provide an internal substrate for bacteria. The findings do not support the hypothesis that giant sulphur bacteria are an appropriate interpretative model for the embryo-like Doushantuo fossils. However, sulphur bacteria may have mediated fossil mineralization and may provide a potential bacterial analogue for other macroscopic Precambrian remains.

  15. Experimental taphonomy of giant sulphur bacteria: implications for the interpretation of the embryo-like Ediacaran Doushantuo fossils

    PubMed Central

    Cunningham, J. A.; Thomas, C.-W.; Bengtson, S.; Marone, F.; Stampanoni, M.; Turner, F. R.; Bailey, J. V.; Raff, R. A.; Raff, E. C.; Donoghue, P. C. J.

    2012-01-01

    The Ediacaran Doushantuo biota has yielded fossils interpreted as eukaryotic organisms, either animal embryos or eukaryotes basal or distantly related to Metazoa. However, the fossils have been interpreted alternatively as giant sulphur bacteria similar to the extant Thiomargarita. To test this hypothesis, living and decayed Thiomargarita were compared with Doushantuo fossils and experimental taphonomic pathways were compared with modern embryos. In the fossils, as in eukaryotic cells, subcellular structures are distributed throughout cell volume; in Thiomargarita, a central vacuole encompasses approximately 98 per cent cell volume. Key features of the fossils, including putative lipid vesicles and nuclei, complex envelope ornament, and ornate outer vesicles are incompatible with living and decay morphologies observed in Thiomargarita. Microbial taphonomy of Thiomargarita also differed from that of embryos. Embryo tissues can be consumed and replaced by bacteria, forming a replica composed of a three-dimensional biofilm, a stable fabric for potential fossilization. Vacuolated Thiomargarita cells collapse easily and do not provide an internal substrate for bacteria. The findings do not support the hypothesis that giant sulphur bacteria are an appropriate interpretative model for the embryo-like Doushantuo fossils. However, sulphur bacteria may have mediated fossil mineralization and may provide a potential bacterial analogue for other macroscopic Precambrian remains. PMID:22158954

  16. A numerical approximation to the elastic properties of sphere-reinforced composites

    NASA Astrophysics Data System (ADS)

    Segurado, J.; Llorca, J.

    2002-10-01

    Three-dimensional cubic unit cells containing 30 non-overlapping identical spheres randomly distributed were generated using a new, modified random sequential adsortion algorithm suitable for particle volume fractions of up to 50%. The elastic constants of the ensemble of spheres embedded in a continuous and isotropic elastic matrix were computed through the finite element analysis of the three-dimensional periodic unit cells, whose size was chosen as a compromise between the minimum size required to obtain accurate results in the statistical sense and the maximum one imposed by the computational cost. Three types of materials were studied: rigid spheres and spherical voids in an elastic matrix and a typical composite made up of glass spheres in an epoxy resin. The moduli obtained for different unit cells showed very little scatter, and the average values obtained from the analysis of four unit cells could be considered very close to the "exact" solution to the problem, in agreement with the results of Drugan and Willis (J. Mech. Phys. Solids 44 (1996) 497) referring to the size of the representative volume element for elastic composites. They were used to assess the accuracy of three classical analytical models: the Mori-Tanaka mean-field analysis, the generalized self-consistent method, and Torquato's third-order approximation.

  17. Nelfinavir induces radiation sensitization in pituitary adenoma cells

    PubMed Central

    Zeng, Jing; See, Alfred P.; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P.; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K.; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T.; Lim, Michael

    2017-01-01

    Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir’s effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 d, 17 d with nelfinavir treatment, 27 d with radiation 6 Gy, and 41 d with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on protein gel blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies. PMID:21811091

  18. Nelfinavir induces radiation sensitization in pituitary adenoma cells.

    PubMed

    Zeng, Jing; See, Alfred P; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T; Lim, Michael

    2011-10-01

    Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution, and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir's effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 days, 17 days with nelfinavir treatment, 27 days with radiation 6 Gy, and 41 days with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on Western blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies.

  19. High energy density redox flow device

    DOEpatents

    Chiang, Yet -Ming; Carter, W. Craig; Duduta, Mihai; Limthongkul, Pimpa

    2015-10-06

    Redox flow devices are described including a positive electrode current collector, a negative electrode current collector, and an ion-permeable membrane separating said positive and negative current collectors, positioned and arranged to define a positive electroactive zone and a negative electroactive zone; wherein at least one of said positive and negative electroactive zone comprises a flowable semi-solid composition comprising ion storage compound particles capable of taking up or releasing said ions during operation of the cell, and wherein the ion storage compound particles have a polydisperse size distribution in which the finest particles present in at least 5 vol % of the total volume, is at least a factor of 5 smaller than the largest particles present in at least 5 vol % of the total volume.

  20. High energy density redox flow device

    DOEpatents

    Chiang, Yet-Ming; Carter, William Craig; Duduta, Mihai; Limthongkul, Pimpa

    2014-05-13

    Redox flow devices are described including a positive electrode current collector, a negative electrode current collector, and an ion-permeable membrane separating said positive and negative current collectors, positioned and arranged to define a positive electroactive zone and a negative electroactive zone; wherein at least one of said positive and negative electroactive zone comprises a flowable semi-solid composition comprising ion storage compound particles capable of taking up or releasing said ions during operation of the cell, and wherein the ion storage compound particles have a polydisperse size distribution in which the finest particles present in at least 5 vol % of the total volume, is at least a factor of 5 smaller than the largest particles present in at least 5 vol % of the total volume.

  1. Incorporation of lysosomal sequestration in the mechanistic model for prediction of tissue distribution of basic drugs.

    PubMed

    Assmus, Frauke; Houston, J Brian; Galetin, Aleksandra

    2017-11-15

    The prediction of tissue-to-plasma water partition coefficients (Kpu) from in vitro and in silico data using the tissue-composition based model (Rodgers & Rowland, J Pharm Sci. 2005, 94(6):1237-48.) is well established. However, distribution of basic drugs, in particular into lysosome-rich lung tissue, tends to be under-predicted by this approach. The aim of this study was to develop an extended mechanistic model for the prediction of Kpu which accounts for lysosomal sequestration and the contribution of different cell types in the tissue of interest. The extended model is based on compound-specific physicochemical properties and tissue composition data to describe drug ionization, distribution into tissue water and drug binding to neutral lipids, neutral phospholipids and acidic phospholipids in tissues, including lysosomes. Physiological data on the types of cells contributing to lung, kidney and liver, their lysosomal content and lysosomal pH were collated from the literature. The predictive power of the extended mechanistic model was evaluated using a dataset of 28 basic drugs (pK a ≥7.8, 17 β-blockers, 11 structurally diverse drugs) for which experimentally determined Kpu data in rat tissue have been reported. Accounting for the lysosomal sequestration in the extended mechanistic model improved the accuracy of Kpu predictions in lung compared to the original Rodgers model (56% drugs within 2-fold or 88% within 3-fold of observed values). Reduction in the extent of Kpu under-prediction was also evident in liver and kidney. However, consideration of lysosomal sequestration increased the occurrence of over-predictions, yielding overall comparable model performances for kidney and liver, with 68% and 54% of Kpu values within 2-fold error, respectively. High lysosomal concentration ratios relative to cytosol (>1000-fold) were predicted for the drugs investigated; the extent differed depending on the lysosomal pH and concentration of acidic phospholipids among cell types. Despite this extensive lysosomal sequestration in the individual cells types, the maximal change in the overall predicted tissue Kpu was <3-fold for lysosome-rich tissues investigated here. Accounting for the variability in cellular physiological model input parameters, in particular lysosomal pH and fraction of the cellular volume occupied by the lysosomes, only partially explained discrepancies between observed and predicted Kpu data in the lung. Improved understanding of the system properties, e.g., cell/organelle composition is required to support further development of mechanistic equations for the prediction of drug tissue distribution. Application of this revised mechanistic model is recommended for prediction of Kpu in lysosome-rich tissue to facilitate the advancement of physiologically-based prediction of volume of distribution and drug exposure in the tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Haematological and biochemical measurements in healthy, adult, free-ranging golden jackals (Canis aureus syriacus) held in captivity.

    PubMed

    Aroch, I; Shpigel, N Y; Avidar, Y; Yakobson, B; King, R; Shamir, M

    2005-09-10

    Blood from 31 healthy, free-ranging golden jackals held in captivity for seven days was collected while they were anaesthetised. Haematological and serum biochemical measurements were analysed and the 95 per cent confidence interval for each variable was compared with the reference value for domestic dogs. The measurements of their red blood cells were within the reference interval for dogs, but the jackals had higher white blood cell counts and eosinophil counts than dogs. The male jackals had a higher haematocrit, red blood cell count, mean corpuscular volume and mean corpuscular haemoglobin concentration, and a lower red blood cell distribution width than the female jackals. High activities of muscle enzymes were detected in many of the jackals, in several of which the activity of creatine kinase exceeded 5000 U/l; these were considered abnormal.

  3. Synchrotron-based X-ray fluorescence microscopy enables multiscale spatial visualization of ions involved in fungal lignocellulose deconstruction

    NASA Astrophysics Data System (ADS)

    Kirker, Grant; Zelinka, Sam; Gleber, Sophie-Charlotte; Vine, David; Finney, Lydia; Chen, Si; Hong, Young Pyo; Uyarte, Omar; Vogt, Stefan; Jellison, Jody; Goodell, Barry; Jakes, Joseph E.

    2017-01-01

    The role of ions in the fungal decay process of lignocellulose biomaterials, and more broadly fungal metabolism, has implications for diverse research disciplines ranging from plant pathology and forest ecology, to carbon sequestration. Despite the importance of ions in fungal decay mechanisms, the spatial distribution and quantification of ions in lignocellulosic cell walls and fungal hyphae during decay is not known. Here we employ synchrotron-based X-ray fluorescence microscopy (XFM) to map and quantify physiologically relevant ions, such as K, Ca, Mn, Fe, and Zn, in wood being decayed by the model brown rot fungus Serpula lacrymans. Two-dimensional XFM maps were obtained to study the ion spatial distributions from mm to submicron length scales in wood, fungal hyphae with the dried extracellular matrix (ECM) from the fungus, and Ca oxalate crystals. Three-dimensional ion volume reconstructions were also acquired of wood cell walls and hyphae with ECM. Results show that the fungus actively transports some ions, such as Fe, into the wood and controls the distribution of ions at both the bulk wood and cell wall length scales. These measurements provide new insights into the movement of ions during decay and illustrate how synchrotron-based XFM is uniquely suited study these ions.

  4. Developing and Testing Simulated Occupational Experiences for Distributive Education Students in Rural Communities: Volume III: Training Plans: Final Report.

    ERIC Educational Resources Information Center

    Virginia Polytechnic Inst. and State Univ., Blacksburg.

    Volume 3 of a three volume final report presents prototype job training plans developed as part of a research project which pilot tested a distributive education program for rural schools utilizing a retail store simulation plan. The plans are for 15 entry-level and 15 career-level jobs in seven categories of distributive business (department…

  5. Preliminary model of fluid and solute distribution and transport during hemorrhage.

    PubMed

    Gyenge, C C; Bowen, B D; Reed, R K; Bert, J L

    2003-01-01

    The distribution and transport of fluid, ions, and other solutes (plasma proteins and glucose) are described in a mathematical model of unresuscitated hemorrhage. The model is based on balances of each material in both the circulation and its red blood cells, as well as in a whole-body tissue compartment along with its cells. Exchange between these four compartments occurs by a number of different mechanisms. The hemorrhage model has as its basis a validated model, due to Gyenge et al., of fluid and solute exchange in the whole body of a standard human. Hypothetical but physiologically based features such as glucose and small ion releases along with cell membrane changes are incorporated into the hemorrhage model to describe the system behavior, particularly during larger hemorrhages. Moderate (10%-30% blood volume loss) and large (> 30% blood loss) hemorrhage dynamics are simulated and compared with available data. The model predictions compare well with the available information for both types of hemorrhages and provide a reasonable description of the progression of a large hemorrhage from the compensatory phase through vascular collapse.

  6. The directional response of chemotactic cells depends on a balance between cytoskeletal architecture and the external gradient.

    PubMed

    Wang, Ming-Jie; Artemenko, Yulia; Cai, Wen-Jie; Iglesias, Pablo A; Devreotes, Peter N

    2014-11-06

    Polarized migrating cells display signal transduction events, such as activation of phosphatidylinositol 3-kinase (PI3K) and Scar/Wave, and respond more readily to chemotactic stimuli at the leading edge. We sought to determine the basis of this polarized sensitivity. Inhibiting actin polymerization leads to uniform sensitivity. However, when human neutrophils were "stalled" by simultaneously blocking actin and myosin dynamics, they maintained the gradient of responsiveness to chemoattractant and also displayed noise-driven PIP3 flashes on the basal membrane, localized toward the front. Thus, polarized sensitivity does not require migration or cytoskeletal dynamics. The threshold for response is correlated with the static F-actin distribution, but not cell shape or volume changes, membrane fluidity, or the preexisting distribution of PI3K. The kinetics of responses to temporal and spatial stimuli were consistent with the local excitation global inhibition model, but the overall direction of the response was biased by the internal axis of polarity. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Lipid droplets fusion in adipocyte differentiated 3T3-L1 cells: A Monte Carlo simulation

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

    Boschi, Federico, E-mail: federico.boschi@univr.it; Department of Computer Science, University of Verona, Strada Le Grazie 15, 37134 Verona; Rizzatti, Vanni

    Several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis, atherosclerosis and other metabolic pathologies are related to the excessive accumulation of lipids in cells. Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes. It has been suggested that LDs can grow in size due to a fusion process by which a larger LD is obtained with spherical shape and volume equal to the sum of the progenitors’ ones. In this study, the size distribution of two populations of LDs was analyzed in immature and maturemore » (5-days differentiated) 3T3-L1 adipocytes (first and second populations, respectively) after Oil Red O staining. A Monte Carlo simulation of interaction between LDs has been developed in order to quantify the size distribution and the number of fusion events needed to obtain the distribution of the second population size starting from the first one. Four models are presented here based on different kinds of interaction: a surface weighted interaction (R2 Model), a volume weighted interaction (R3 Model), a random interaction (Random model) and an interaction related to the place where the LDs are born (Nearest Model). The last two models mimic quite well the behavior found in the experimental data. This work represents a first step in developing numerical simulations of the LDs growth process. Due to the complex phenomena involving LDs (absorption, growth through additional neutral lipid deposition in existing droplets, de novo formation and catabolism) the study focuses on the fusion process. The results suggest that, to obtain the observed size distribution, a number of fusion events comparable with the number of LDs themselves is needed. Moreover the MC approach results a powerful tool for investigating the LDs growth process. Highlights: • We evaluated the role of the fusion process in the synthesis of the lipid droplets. • We compared the size distribution of the lipid droplets in immature and mature cells. • We used the Monte Carlo simulation approach, simulating 10 thousand of fusion events. • Four different interaction models between the lipid droplets were tested. • The best model which mimics the experimental measures was selected.« less

  8. Automatic Stem Cell Detection in Microscopic Whole Mouse Cryo-imaging

    PubMed Central

    Wuttisarnwattana, Patiwet; Gargesha, Madhusudhana; Hof, Wouter van’t; Cooke, Kenneth R.

    2016-01-01

    With its single cell sensitivity over volumes as large as or larger than a mouse, cryo-imaging enables imaging of stem cell biodistribution, homing, engraftment, and molecular mechanisms. We developed and evaluated a highly automated software tool to detect fluorescently labeled stem cells within very large (~200GB) cryo-imaging datasets. Cell detection steps are: preprocess, remove immaterial regions, spatially filter to create features, identify candidate pixels, classify pixels using bagging decision trees, segment cell patches, and perform 3D labeling. There are options for analysis and visualization. To train the classifier, we created synthetic images by placing realistic digital cell models onto cryo-images of control mice devoid of cells. Very good cell detection results were (precision=98.49%, recall=99.97%) for synthetic cryo-images, (precision=97.81%, recall=97.71%) for manually evaluated, actual cryo-images, and <1% false positives in control mice. An α-multiplier applied to features allows one to correct for experimental variations in cell brightness due to labeling. On dim cells (37% of standard brightness), with correction, we improved recall (49.26%→99.36%) without a significant drop in precision (99.99%→99.75%). With tail vein injection, multipotent adult progenitor cells in a graft-versus-host-disease model in the first days post injection were predominantly found in lung, liver, spleen, and bone marrow. Distribution was not simply related to blood flow. The lung contained clusters of cells while other tissues contained single cells. Our methods provided stem cell distribution anywhere in mouse with single cell sensitivity. Methods should provide a rational means of evaluating dosing, delivery methods, cell enhancements, and mechanisms for therapeutic cells. PMID:26552080

  9. Theory to predict particle migration and margination in the pressure-driven channel flow of blood

    NASA Astrophysics Data System (ADS)

    Qi, Qin M.; Shaqfeh, Eric S. G.

    2017-09-01

    The inhomogeneous concentration distribution of erythrocytes and platelets in microchannel flows particularly in directions normal to the mean flow plays a significant role in hemostasis, drug delivery, and microfluidic applications. In this paper, we develop a coarse-grained theory to predict these distributions in pressure-driven channel flow at zero Reynolds number and compare them to experiments and simulations. We demonstrate that the balance between the deformability-induced lift force and the shear-induced diffusion created by hydrodynamic interactions in the suspension results in both a peak concentration of red blood cells at the channel center and a cell-free or Fahraeus-Lindqvist layer near the walls. On the other hand, the absence of a lift force and the strong red blood cell-platelet interactions result in an excess concentration of platelets in the cell-free layer. We demonstrate a strong role of hematocrit (i.e., erythrocyte volume fraction) in determining the cell-free layer thickness and the degree of platelet margination. We also demonstrate that the capillary number of the erythrocytes, based on the membrane shear modulus, plays a relatively insignificant role in the regimes that we have studied. Our theory serves as a good and simple alternative to large-scale computer simulations of the cross-stream transport processes in these mixtures.

  10. Cell counting in whole mount tissue volumes using expansion OCT (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Liu, Yehe; Gu, Shi; Watanabe, Michiko; Rollins, Andrew M.; Jenkins, Michael W.

    2017-02-01

    Abnormal cell proliferation and migration during heart development can lead to severe congenital heart defects (CHDs). Studying the spatial distribution of cells during embryonic development helps our understanding of how the heart develops and the etiology of certain CHDs. However, imaging large groups of single cells in intact tissue volumes is challenging. No current technique can accomplish this task in both a time-efficient and cost-effective manner. OCT has potential with its large field of view and micron-scale resolution, but even the highest resolution OCT systems have poor contrast for counting cells and have a small field of view compared to conventional OCT. We propose using a conventional OCT system and processing the sample to enhance cellular contrast. Inspired by the recently developed Expansion Microscopy, we permeated whole-mount embryonic tissue with a superabsorbent monomer solution and polymerized into a hydrogel. When hydrated in DI water, the tissue-hydrogel complex was uniformly enlarged ( 5X in all dimensions) without distorting the microscopic structure. This had a twofold effect: it increased the resolution by a factor of 5 and decreased scattering, which allowed us to resolve cellular level features deep in the tissue with high contrast using conventional OCT. We noted that cell nuclei caused significantly more backscattering than the other subcellular structures after expansion. Based on this property, we were able to distinguish individual cell nuclei, and thus count cells, in expanded OCT images with simple intensity thresholding. We demonstrate the technique with embryonic quail hearts at various developmental stages.

  11. 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.

  12. Image-guided convection-enhanced delivery of muscimol to the primate brain

    PubMed Central

    Heiss, John D.; Walbridge, Stuart; Asthagiri, Ashok R.; Lonser, Russell R.

    2009-01-01

    Object Muscimol is a potent γ-aminobutyric acid-A receptor agonist (GABAA) that temporarily and selectively suppresses neurons. Targeted muscimol-suppression of neuronal structures could provide insight into the pathophysiology and treatment of a variety of neurologic disorders. To determine if muscimol delivered to the brain by convection-enhanced delivery (CED) could be monitored using a co-infused surrogate magnetic resonance (MR)-imaging tracer, we perfused the striata of primates with tritiated muscimol and gadolinium-DTPA. Methods Three primates underwent convective co-infusion of 3H-muscimol (0.8 μM) and gadolinium-DTPA (−5 mM) into the bilateral striata. Primates underwent serial MR-imaging during infusion and animals were sacrificed immediately after infusion. Post-mortem quantitative autoradiography and histological analysis was performed. Results MR-imaging revealed that infusate (tritiated muscimol and gadolinium-DTPA) distribution was clearly discernible from the non-infused parenchyma. Real-time MR-imaging of the infusion revealed the precise region of anatomic perfusion in each animal. Imaging analysis during infusion revealed that the distribution volume of infusate linearly increased (R=0.92) with volume of infusion. Overall, the mean (±S.D.) volume of distribution to volume of infusion ratio was 8.2±1.3. Autoradiographic analysis revealed that MR-imaging of gadolinium-DTPA closely correlated with the distribution of 3H-muscimol and precisely estimated its volume of distribution (mean difference in volume of distribution, 7.4%). Quantitative autoradiograms revealed that muscimol was homogeneously distributed over the perfused region in a square-shaped concentration profile. Conclusions Muscimol can be effectively delivered to clinically relevant volumes of the primate brain. Moreover, the distribution of muscimol can be tracked by co-infusion of gadolinium-DTPA using MR-imaging. The ability to accurately monitor and control the anatomic extent of muscimol distribution during its convection-enhanced delivery will enhance safety, permit correlations of muscimol distribution with clinical effect, and should lead to an improved understanding of the pathophysiologic processes underlying a variety of neurologic disorders. PMID:19715424

  13. 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

  14. Monte Carlo dose distribution calculation at nuclear level for Auger-emitting radionuclide energies.

    PubMed

    Di Maria, S; Belchior, A; Romanets, Y; Paulo, A; Vaz, P

    2018-05-01

    The distribution of radiopharmaceuticals in tumor cells represents a fundamental aspect for a successful molecular targeted radiotherapy. It was largely demonstrated at microscopic level that only a fraction of cells in tumoral tissues incorporate the radiolabel. In addition, the distribution of the radionuclides at sub-cellular level, namely inside each nucleus, should also be investigated for accurate dosimetry estimation. The most used method to perform cellular dosimetry is the MIRD one, where S-values are able to estimate cellular absorbed doses for several electron energies, nucleus diameters, and considering homogeneous source distributions. However the radionuclide distribution inside nuclei can be also highly non-homogeneous. The aim of this study is to show in what extent a non-accurate cellular dosimetry could lead to misinterpretations of surviving cell fraction vs dose relationship; in this context, a dosimetric case study with 99m Tc is also presented. The state-of-art MCNP6 Monte Carlo simulation was used in order to model cell structures both in MIRD geometry (MG) and MIRD modified geometries (MMG), where also entire mitotic chromosome volumes were considered (each structure was modeled as liquid water material). In order to simulate a wide energy range of Auger emitting radionuclides, four mono energetic electron emissions were considered, namely 213eV, 6keV, 11keV and 20keV. A dosimetric calculation for 99m Tc undergoing inhomogeneous nuclear internalization was also performed. After a successful validation step between MIRD and our computed S-values for three Auger-emitting radionuclides ( 99m Tc, 125 I and 64 Cu), absorbed dose results showed that the standard MG could differ from the MMG from one to three orders of magnitude. These results were also confirmed by considering the 99m Tc spectrum emission (Auger and internal conversion electrons). Moreover, considering an inhomogeneous radionuclide distribution, the average electron energy that maximizes the absorbed dose was found to be different for MG and MMG. The modeling of realistic radionuclide localization inside cells, including a inhomogeneous nuclear distribution, revealed that i) a strong bias in surviving cell fraction vs dose relationships (taking to different radiobiological models) can arise; ii) the alternative models might contribute to a more accurate prediction of the radiobiological effects inherent to more specific molecular targeted radiotherapy strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Distributed shared memory for roaming large volumes.

    PubMed

    Castanié, Laurent; Mion, Christophe; Cavin, Xavier; Lévy, Bruno

    2006-01-01

    We present a cluster-based volume rendering system for roaming very large volumes. This system allows to move a gigabyte-sized probe inside a total volume of several tens or hundreds of gigabytes in real-time. While the size of the probe is limited by the total amount of texture memory on the cluster, the size of the total data set has no theoretical limit. The cluster is used as a distributed graphics processing unit that both aggregates graphics power and graphics memory. A hardware-accelerated volume renderer runs in parallel on the cluster nodes and the final image compositing is implemented using a pipelined sort-last rendering algorithm. Meanwhile, volume bricking and volume paging allow efficient data caching. On each rendering node, a distributed hierarchical cache system implements a global software-based distributed shared memory on the cluster. In case of a cache miss, this system first checks page residency on the other cluster nodes instead of directly accessing local disks. Using two Gigabit Ethernet network interfaces per node, we accelerate data fetching by a factor of 4 compared to directly accessing local disks. The system also implements asynchronous disk access and texture loading, which makes it possible to overlap data loading, volume slicing and rendering for optimal volume roaming.

  16. 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.

  17. 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

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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

  4. 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.

  5. SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

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

    Park, J; Molecular Imaging Program at Stanford, Stanford, CA; Bio-X Program, Stanford, CA

    2015-06-15

    Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/minmore » was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.« less

  6. 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

  7. 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.

  8. 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.

  9. Cellular Analysis of Boltzmann Most Probable Ideal Gas Statistics

    NASA Astrophysics Data System (ADS)

    Cahill, Michael E.

    2018-04-01

    Exact treatment of Boltzmann's Most Probable Statistics for an Ideal Gas of Identical Mass Particles having Translational Kinetic Energy gives a Distribution Law for Velocity Phase Space Cell j which relates the Particle Energy and the Particle Population according toB e(j) = A - Ψ(n(j) + 1)where A & B are the Lagrange Multipliers and Ψ is the Digamma Function defined byΨ(x + 1) = d/dx ln(x!)A useful sufficiently accurate approximation for Ψ is given byΨ(x +1) ≈ ln(e-γ + x)where γ is the Euler constant (≈.5772156649) & so the above distribution equation is approximatelyB e(j) = A - ln(e-γ + n(j))which can be inverted to solve for n(j) givingn(j) = (eB (eH - e(j)) - 1) e-γwhere B eH = A + γ& where B eH is a unitless particle energy which replaces the parameter A. The 2 approximate distribution equations imply that eH is the highest particle energy and the highest particle population isnH = (eB eH - 1) e-γwhich is due to the facts that population becomes negative if e(j) > eH and kinetic energy becomes negative if n(j) > nH.An explicit construction of Cells in Velocity Space which are equal in volume and homogeneous for almost all cells is shown to be useful in the analysis.Plots for sample distribution properties using e(j) as the independent variable are presented.

  10. An improved protocol for optical projection tomography imaging reveals lobular heterogeneities in pancreatic islet and β-cell mass distribution

    PubMed Central

    2011-01-01

    Optical projection tomography (OPT) imaging is a powerful tool for three-dimensional imaging of gene and protein distribution patterns in biomedical specimens. We have previously demonstrated the possibility, by this technique, to extract information of the spatial and quantitative distribution of the islets of Langerhans in the intact mouse pancreas. In order to further increase the sensitivity of OPT imaging for this type of assessment, we have developed a protocol implementing a computational statistical approach: contrast limited adaptive histogram equalization (CLAHE). We demonstrate that this protocol significantly increases the sensitivity of OPT imaging for islet detection, helps preserve islet morphology and diminish subjectivity in thresholding for tomographic reconstruction. When applied to studies of the pancreas from healthy C57BL/6 mice, our data reveal that, at least in this strain, the pancreas harbors substantially more islets than has previously been reported. Further, we provide evidence that the gastric, duodenal and splenic lobes of the pancreas display dramatic differences in total and relative islet and β-cell mass distribution. This includes a 75% higher islet density in the gastric lobe as compared to the splenic lobe and a higher relative volume of insulin producing cells in the duodenal lobe as compared to the other lobes. Altogether, our data show that CLAHE substantially improves OPT based assessments of the islets of Langerhans and that lobular origin must be taken into careful consideration in quantitative and spatial assessments of the pancreas. PMID:21633198

  11. Interaction of Poly(l-lysine)/Polysaccharide Complex Nanoparticles with Human Vascular Endothelial Cells.

    PubMed

    Weber, Dominik; Torger, Bernhard; Richter, Karsten; Nessling, Michelle; Momburg, Frank; Woltmann, Beatrice; Müller, Martin; Schwartz-Albiez, Reinhard

    2018-05-23

    Angiogenesis plays an important role in both soft and hard tissue regeneration, which can be modulated by therapeutic drugs. If nanoparticles (NP) are used as vectors for drug delivery, they have to encounter endothelial cells (EC) lining the vascular lumen, if applied intravenously. Herein the interaction of unloaded polyelectrolyte complex nanoparticles (PECNP) composed of cationic poly(l-lysine) (PLL) and various anionic polysaccharides with human vascular endothelial cells (HUVEC) was analyzed. In particular PECNP were tested for their cell adhesive properties, their cellular uptake and intracellular localization considering composition and net charge. PECNP may form a platform for both cell coating and drug delivery. PECNP, composed of PLL in combination with the polysaccharides dextran sulfate (DS), cellulose sulfate (CS) or heparin (HEP), either unlabeled or labeled with fluorescein isothiocyanate (FITC) and either with positive or negative net charge were prepared. PECNP were applied to human umbilical cord vein endothelial cells (HUVEC) in both, the volume phase and immobilized phase at model substrates like tissue culture dishes. The attachment of PECNP to the cell surface, their intracellular uptake, and effects on cell proliferation and growth behavior were determined. Immobilized PECNP reduced attachment of HUVEC, most prominently the systems PLL/HEP and PLL/DS. A small percentage of immobilized PECNP was taken up by cells during adhesion. PECNP in the volume phase showed no effect of the net charge sign and only minor effects of the composition on the binding and uptake of PECNP at HUVEC. PECNP were stored in endosomal vesicles in a cumulative manner without apparent further processing. During mitosis, internalized PECNP were almost equally distributed among the dividing cells. Both, in the volume phase and immobilized at the surface, PECNP composed of PLL/HEP and PLL/DS clearly reduced cell proliferation of HUVEC, however without an apparent cytotoxic effect, while PLL/CS composition showed minor impairment. PECNP have an anti-adhesive effect on HUVEC and are taken up by endothelial cells which may negatively influence the proliferation rate of HUVEC. The negative effects were less obvious with the composition PLL/CS. Since uptake and binding for PLL/HEP was more efficient than for PLL/DS, PECNP of PLL/HEP may be used to deliver growth factors to endothelial cells during vascularization of bone reconstitution material, whereas those of PLL/CS may have an advantage for substituting biomimetic bone scaffold material.

  12. 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.

  13. On the emergence of a generalised Gamma distribution. Application to traded volume in financial markets

    NASA Astrophysics Data System (ADS)

    Duarte Queirós, S. M.

    2005-08-01

    This letter reports on a stochastic dynamical scenario whose associated stationary probability density function is exactly a generalised form, with a power law instead of exponencial decay, of the ubiquitous Gamma distribution. This generalisation, also known as F-distribution, was empirically proposed for the first time to adjust for high-frequency stock traded volume distributions in financial markets and verified in experiments with granular material. The dynamical assumption presented herein is based on local temporal fluctuations of the average value of the observable under study. This proposal is related to superstatistics and thus to the current nonextensive statistical mechanics framework. For the specific case of stock traded volume, we connect the local fluctuations in the mean stock traded volume with the typical herding behaviour presented by financial traders. Last of all, NASDAQ 1 and 2 minute stock traded volume sequences and probability density functions are numerically reproduced.

  14. 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

  15. Studies of Tissue Perfusion Failure at LAC+USCMC and the Incorporation of the Results into a National Trauma Database

    DTIC Science & Technology

    2005-04-01

    Context Link] 29. Gibson JG, Seligman AM, Peacock WC, et al: The circulating red cell and plasma volume and the distribution of blood in large and...BS; Gandhi, Ashutosh BS; Chien, Li-Chien MD; Lu, Kevin MD; Martin, Matthew J. MD; Chan, Linda S. PhD; Demetriades, Demetrios MD, PhD; Ahmadpour...Physicians Outcome Prediction of Emergency Patients by Noninvasive Hemodynamic Monitoring* William C. Shoemaker, MD; Charles C. J. Wo, BS; Linda

  16. Quantitative Analysis of Cell Nucleus Organisation

    PubMed Central

    Shiels, Carol; Adams, Niall M; Islam, Suhail A; Stephens, David A; Freemont, Paul S

    2007-01-01

    There are almost 1,300 entries for higher eukaryotes in the Nuclear Protein Database. The proteins' subcellular distribution patterns within interphase nuclei can be complex, ranging from diffuse to punctate or microspeckled, yet they all work together in a coordinated and controlled manner within the three-dimensional confines of the nuclear volume. In this review we describe recent advances in the use of quantitative methods to understand nuclear spatial organisation and discuss some of the practical applications resulting from this work. PMID:17676980

  17. 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.

  18. The role of gluten in a pound cake system: A model approach based on gluten-starch blends.

    PubMed

    Wilderjans, Edith; Pareyt, Bram; Goesaert, Hans; Brijs, Kristof; Delcour, Jan A

    2008-10-15

    In order to evaluate the role of gluten in cake-making, gluten-starch (GS) blends with different ratios of gluten to starch were tested in a research pound cake formula. The viscosities of batters made from commercial GS blends in the otherwise standardised formula increased with their gluten content. High viscosities during heating provide the batters with the capacity to retain expanding air nuclei, and thereby led to desired product volumes. In line with the above, increasing gluten levels in the cake recipes led to a more extended oven spring period. Cakes with a starch content exceeding 92.5% in the GS blend suffered from substantial collapse during cooling. They had a coarse crumb with a solid gummy layer at the bottom. Image analysis showed statistical differences in numbers of cells per cm(2), cell to total area ratio and mean cell area (p<0.05). Both density and mean cell area were related to gluten level. Moreover, mean cell area and cell to total area ratio were the highest for cakes with the lowest density and highest gluten levels. Relative sodium dodecyl sulfate (SDS, 2.0%) buffer (pH 6.8) extractabilities of protein from cakes baked with the different GS blends decreased with gluten content and were strongly correlated with the intensity of collapse. Taken together, the results teach that protein gives the cakes resistance to collapse, resulting in desirable volumes and an optimal grain structure with uniform cell distribution. Copyright © 2008 Elsevier Ltd. All rights reserved.

  19. Determination of saturation pressure and enthalpy of vaporization of semi-volatile aerosols: the integrated volume mentod

    EPA Science Inventory

    This study presents the integrated volume method for estimating saturation pressure and enthalpy of vaporization of a whole aerosol distribution. We measure the change of total volume of an aerosol distribution between a reference state and several heated states, with the heating...

  20. RWPV bioreactor mass transport: earth-based and in microgravity

    NASA Technical Reports Server (NTRS)

    Begley, Cynthia M.; Kleis, Stanley J.

    2002-01-01

    Mass transport and mixing of perfused scalar quantities in the NASA Rotating Wall Perfused Vessel bioreactor are studied using numerical models of the flow field and scalar concentration field. Operating conditions typical of both microgravity and ground-based cell cultures are studied to determine the expected vessel performance for both flight and ground-based control experiments. Results are presented for the transport of oxygen with cell densities and consumption rates typical of colon cancer cells cultured in the RWPV. The transport and mixing characteristics are first investigated with a step change in the perfusion inlet concentration by computing the time histories of the time to exceed 10% inlet concentration. The effects of a uniform cell utilization rate are then investigated with time histories of the outlet concentration, volume average concentration, and volume fraction starved. It is found that the operating conditions used in microgravity produce results that are quite different then those for ground-based conditions. Mixing times for microgravity conditions are significantly shorter than those for ground-based operation. Increasing the differential rotation rates (microgravity) increases the mixing and transport, while increasing the mean rotation rate (ground-based) suppresses both. Increasing perfusion rates enhances mass transport for both microgravity and ground-based cases, however, for the present range of operating conditions, above 5-10 cc/min there are diminishing returns as much of the inlet fluid is transported directly to the perfusion exit. The results show that exit concentration is not a good indicator of the concentration distributions in the vessel. In microgravity conditions, the NASA RWPV bioreactor with the viscous pump has been shown to provide an environment that is well mixed. Even when operated near the theoretical minimum perfusion rates, only a small fraction of the volume provides less than the required oxygen levels. 2002 Wiley Periodicals, Inc.

  1. RWPV bioreactor mass transport: earth-based and in microgravity.

    PubMed

    Begley, Cynthia M; Kleis, Stanley J

    2002-11-20

    Mass transport and mixing of perfused scalar quantities in the NASA Rotating Wall Perfused Vessel bioreactor are studied using numerical models of the flow field and scalar concentration field. Operating conditions typical of both microgravity and ground-based cell cultures are studied to determine the expected vessel performance for both flight and ground-based control experiments. Results are presented for the transport of oxygen with cell densities and consumption rates typical of colon cancer cells cultured in the RWPV. The transport and mixing characteristics are first investigated with a step change in the perfusion inlet concentration by computing the time histories of the time to exceed 10% inlet concentration. The effects of a uniform cell utilization rate are then investigated with time histories of the outlet concentration, volume average concentration, and volume fraction starved. It is found that the operating conditions used in microgravity produce results that are quite different then those for ground-based conditions. Mixing times for microgravity conditions are significantly shorter than those for ground-based operation. Increasing the differential rotation rates (microgravity) increases the mixing and transport, while increasing the mean rotation rate (ground-based) suppresses both. Increasing perfusion rates enhances mass transport for both microgravity and ground-based cases, however, for the present range of operating conditions, above 5-10 cc/min there are diminishing returns as much of the inlet fluid is transported directly to the perfusion exit. The results show that exit concentration is not a good indicator of the concentration distributions in the vessel. In microgravity conditions, the NASA RWPV bioreactor with the viscous pump has been shown to provide an environment that is well mixed. Even when operated near the theoretical minimum perfusion rates, only a small fraction of the volume provides less than the required oxygen levels. 2002 Wiley Periodicals, Inc.

  2. Cancer-associated lysosomal changes: friends or foes?

    PubMed

    Kallunki, T; Olsen, O D; Jäättelä, M

    2013-04-18

    Rapidly dividing and invasive cancer cells are strongly dependent on effective lysosomal function. Accordingly, transformation and cancer progression are characterized by dramatic changes in lysosomal volume, composition and cellular distribution. Depending on one's point of view, the cancer-associated changes in the lysosomal compartment can be regarded as friends or foes. Most of them are clearly transforming as they promote invasive growth, angiogenesis and drug resistance. The same changes can, however, strongly sensitize cells to lysosomal membrane permeabilization and thereby to lysosome-targeting anti-cancer drugs. In this review we compile our current knowledge on cancer-associated changes in lysosomal composition and discuss the consequences of these alterations to cancer progression and the possibilities they can bring to cancer therapy.

  3. Voxelized Computational Model for Convection-Enhanced Delivery in the Rat Ventral Hippocampus: Comparison with In Vivo MR Experimental Studies

    PubMed Central

    Kim, Jung Hwan; Astary, Garrett W.; Kantorovich, Svetlana; Mareci, Thomas H.; Carney, Paul R.; Sarntinoranont, Malisa

    2012-01-01

    Convection-enhanced delivery (CED) is a promising local delivery technique for overcoming the blood–brain barrier (BBB) and treating diseases of the central nervous system (CNS). For CED, therapeutics are infused directly into brain tissue and the drug agent is spread through the extracellular space, considered to be highly tortuous porous media. In this study, 3D computational models developed using magnetic resonance (MR) diffusion tensor imaging data sets were used to predict CED transport in the rat ventral hippocampus using a voxelized modeling previously developed by our group. Predicted albumin tracer distributions were compared with MR-measured distributions from in vivo CED in the ventral hippocampus up to 10 μL of Gd-DTPA albumin tracer infusion. Predicted and measured tissue distribution volumes and distribution patterns after 5 and 10 μL infusions were found to be comparable. Tracers were found to occupy the underlying landmark structures with preferential transport found in regions with less fluid resistance such as the molecular layer of the dentate gyrus. Also, tracer spread was bounded by high fluid resistance layers such as the granular cell layer and pyramidal cell layer of dentate gyrus. Leakage of tracers into adjacent CSF spaces was observed towards the end of infusions. PMID:22532321

  4. The local matrix distribution and the functional development of tissue engineered cartilage, a finite element study.

    PubMed

    Sengers, B G; Van Donkelaar, C C; Oomens, C W J; Baaijens, F P T

    2004-12-01

    Assessment of the functionality of tissue engineered cartilage constructs is hampered by the lack of correlation between global measurements of extra cellular matrix constituents and the global mechanical properties. Based on patterns of matrix deposition around individual cells, it has been hypothesized previously, that mechanical functionality arises when contact occurs between zones of matrix associated with individual cells. The objective of this study is to determine whether the local distribution of newly synthesized extracellular matrix components contributes to the evolution of the mechanical properties of tissue engineered cartilage constructs. A computational homogenization approach was adopted, based on the concept of a periodic representative volume element. Local transport and immobilization of newly synthesized matrix components were described. Mechanical properties were taken dependent on the local matrix concentration and subsequently the global aggregate modulus and hydraulic permeability were derived. The transport parameters were varied to assess the effect of the evolving matrix distribution during culture. The results indicate that the overall stiffness and permeability are to a large extent insensitive to differences in local matrix distribution. This emphasizes the need for caution in the visual interpretation of tissue functionality from histology and underlines the importance of complementary measurements of the matrix's intrinsic molecular organization.

  5. Voltage-Gated Ion Channels in Cancer Cell Proliferation

    PubMed Central

    Rao, Vidhya R.; Perez-Neut, Mathew; Kaja, Simon; Gentile, Saverio

    2015-01-01

    Changes of the electrical charges across the surface cell membrane are absolutely necessary to maintain cellular homeostasis in physiological as well as in pathological conditions. The opening of ion channels alter the charge distribution across the surface membrane as they allow the diffusion of ions such as K+, Ca++, Cl−, Na+. Traditionally, voltage-gated ion channels (VGIC) are known to play fundamental roles in controlling rapid bioelectrical signaling including action potential and/or contraction. However, several investigations have revealed that these classes of proteins can also contribute significantly to cell mitotic biochemical signaling, cell cycle progression, as well as cell volume regulation. All these functions are critically important for cancer cell proliferation. Interestingly, a variety of distinct VGICs are expressed in different cancer cell types, including metastasis but not in the tissues from which these tumors were generated. Given the increasing evidence suggesting that VGIC play a major role in cancer cell biology, in this review we discuss the role of distinct VGIC in cancer cell proliferation and possible therapeutic potential of VIGC pharmacological manipulation. PMID:26010603

  6. Development of a single-cell X-ray fluorescence flow cytometer

    DOE PAGES

    Crawford, Andrew M.; Kurecka, Patrick; Yim, Tsz Kwan; ...

    2016-06-17

    An X-ray fluorescence flow cytometer that can determine the total metal content of single cells has been developed. Capillary action or pressure was used to load cells into hydrophilic or hydrophobic capillaries, respectively. Once loaded, the cells were transported at a fixed vertical velocity past a focused X-ray beam. X-ray fluorescence was then used to determine the mass of metal in each cell. By making single-cell measurements, the population heterogeneity for metals in the µ M to m M concentration range on fL sample volumes can be directly measured, a measurement that is difficult using most analytical methods. This approachmore » has been used to determine the metal composition of 936 individual bovine red blood cells (bRBC), 31 individual 3T3 mouse fibroblasts (NIH3T3) and 18 Saccharomyces cerevisiae (yeast) cells with an average measurement frequency of ~4 cells min –1. These data show evidence for surprisingly broad metal distributions. Lastly, details of the device design, data analysis and opportunities for further sensitivity improvement are described.« less

  7. 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.

  8. 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.

  9. Volume labeling with Alexa Fluor dyes and surface functionalization of highly sensitive fluorescent silica (SiO2) nanoparticles

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Nallathamby, Prakash D.; Foster, Carmen M.; Morrell-Falvey, Jennifer L.; Mortensen, Ninell P.; Doktycz, Mitchel J.; Gu, Baohua; Retterer, Scott T.

    2013-10-01

    A new synthesis approach is described that allows the direct incorporation of fluorescent labels into the volume or body of SiO2 nanoparticles. In this process, fluorescent Alexa Fluor dyes with different emission wavelengths were covalently incorporated into the SiO2 nanoparticles during their formation by the hydrolysis of tetraethoxysilane. The dye molecules were homogeneously distributed throughout the SiO2 nanoparticles. The quantum yields of the Alexa Fluor volume-labeled SiO2 nanoparticles were much higher than nanoparticles labeled using conventional organic dyes. The size of the resulting nanoparticles was controlled using microemulsion reaction media with sizes in the range of 20-100 nm and a polydispersity of <15%. In comparison with conventional surface tagged particles created by post-synthesis modification, this process maintains the physical and surface chemical properties that have the most pronounced effect on colloidal stability and interactions with their surroundings. These volume-labeled nanoparticles have proven to be extremely robust, showing excellent signal strength, negligible photobleaching, and minimal loss of functional organic components. The native or ``free'' surface of the volume-labeled particles can be altered to achieve a specific surface functionality without altering fluorescence. Their utility was demonstrated for visualizing the association of surface-modified fluorescent particles with cultured macrophages. Differences in particle agglomeration and cell association were clearly associated with differences in observed nanoparticle toxicity. The capacity to maintain particle fluorescence while making significant changes to surface chemistry makes these particles extremely versatile and useful for studies of particle agglomeration, uptake, and transport in environmental and biological systems.A new synthesis approach is described that allows the direct incorporation of fluorescent labels into the volume or body of SiO2 nanoparticles. In this process, fluorescent Alexa Fluor dyes with different emission wavelengths were covalently incorporated into the SiO2 nanoparticles during their formation by the hydrolysis of tetraethoxysilane. The dye molecules were homogeneously distributed throughout the SiO2 nanoparticles. The quantum yields of the Alexa Fluor volume-labeled SiO2 nanoparticles were much higher than nanoparticles labeled using conventional organic dyes. The size of the resulting nanoparticles was controlled using microemulsion reaction media with sizes in the range of 20-100 nm and a polydispersity of <15%. In comparison with conventional surface tagged particles created by post-synthesis modification, this process maintains the physical and surface chemical properties that have the most pronounced effect on colloidal stability and interactions with their surroundings. These volume-labeled nanoparticles have proven to be extremely robust, showing excellent signal strength, negligible photobleaching, and minimal loss of functional organic components. The native or ``free'' surface of the volume-labeled particles can be altered to achieve a specific surface functionality without altering fluorescence. Their utility was demonstrated for visualizing the association of surface-modified fluorescent particles with cultured macrophages. Differences in particle agglomeration and cell association were clearly associated with differences in observed nanoparticle toxicity. The capacity to maintain particle fluorescence while making significant changes to surface chemistry makes these particles extremely versatile and useful for studies of particle agglomeration, uptake, and transport in environmental and biological systems. Electronic supplementary information (ESI) available: Cell culture preparation for dose/response imaging experiments. See DOI: 10.1039/c3nr02639f

  10. Analysis of Noise Mechanisms in Cell-Size Control.

    PubMed

    Modi, Saurabh; Vargas-Garcia, Cesar Augusto; Ghusinga, Khem Raj; Singh, Abhyudai

    2017-06-06

    At the single-cell level, noise arises from multiple sources, such as inherent stochasticity of biomolecular processes, random partitioning of resources at division, and fluctuations in cellular growth rates. How these diverse noise mechanisms combine to drive variations in cell size within an isoclonal population is not well understood. Here, we investigate the contributions of different noise sources in well-known paradigms of cell-size control, such as adder (division occurs after adding a fixed size from birth), sizer (division occurs after reaching a size threshold), and timer (division occurs after a fixed time from birth). Analysis reveals that variation in cell size is most sensitive to errors in partitioning of volume among daughter cells, and not surprisingly, this process is well regulated among microbes. Moreover, depending on the dominant noise mechanism, different size-control strategies (or a combination of them) provide efficient buffering of size variations. We further explore mixer models of size control, where a timer phase precedes/follows an adder, as has been proposed in Caulobacter crescentus. Although mixing a timer and an adder can sometimes attenuate size variations, it invariably leads to higher-order moments growing unboundedly over time. This results in a power-law distribution for the cell size, with an exponent that depends inversely on the noise in the timer phase. Consistent with theory, we find evidence of power-law statistics in the tail of C. crescentus cell-size distribution, although there is a discrepancy between the observed power-law exponent and that predicted from the noise parameters. The discrepancy, however, is removed after data reveal that the size added by individual newborns in the adder phase itself exhibits power-law statistics. Taken together, this study provides key insights into the role of noise mechanisms in size homeostasis, and suggests an inextricable link between timer-based models of size control and heavy-tailed cell-size distributions. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. High energy density redox flow device

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

    Carter, W. Craig; Chiang, Yet-Ming; Duduta, Mihai

    2017-04-04

    Redox flow devices are described including a positive electrode current collector, a negative electrode current collector, and an ion-permeable membrane separating said positive and negative current collectors, positioned and arranged to define a positive electroactive zone and a negative electroactive zone; wherein at least one of said positive and negative electroactive zone comprises a flowable semi-solid composition comprising ion storage compound particles capable of taking up or releasing said ions during operation of the cell, and wherein the ion storage compound particles have a polydisperse size distribution in which the finest particles present in at least 5 vol % ofmore » the total volume, is at least a factor of 5 smaller than the largest particles present in at least 5 vol % of the total volume.« less

  12. Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro.

    PubMed

    Germain, M A; Hatton, A; Williams, S; Matthews, J B; Stone, M H; Fisher, J; Ingham, E

    2003-02-01

    Concern over polyethylene wear particle induced aseptic loosening of metal-on-polyethylene hip prostheses has led to renewed interest in alternative materials such as metal-on-metal and alumina ceramic-on-alumina ceramic for total hip replacement. This study compared the effects of clinically relevant cobalt-chromium and alumina ceramic wear particles on the viability of U937 histiocytes and L929 fibroblasts in vitro. Clinically relevant cobalt-chromium wear particles were generated using a flat pin-on-plate tribometer. The mean size of the clinically relevant metal particles was 29.5+/-6.3 nm (range 5-200 nm). Clinically relevant alumina ceramic particles were generated in the Leeds MkII anatomical hip simulator from a Mittelmieier prosthesis using micro-separation motion. This produced particles with a bimodal size distribution. The majority (98%) of the clinically relevant alumina ceramic wear debris was 5-20 nm in size. The cytotoxicity of the clinically relevant wear particles was compared to commercially available cobalt-chromium (9.87 microm+/-5.67) and alumina ceramic (0.503+/-0.19 microm) particles. The effects of the particles on the cells over a 5 day period at different particle volume (microm(3)) to cell number ratios were tested and viability determined using ATP-Lite(TM). Clinically relevant cobalt-chromium particles 50 and 5 microm(3) per cell reduced the viability of U937 cells by 97% and 42% and reduced the viability of L929 cells by 95% and 73%, respectively. At 50 microm(3) per cell, the clinically relevant ceramic particles reduced U937 cell viability by 18%. None of the other concentrations of the clinically relevant particles were toxic. The commercial cobalt-chromium and alumina particles did not affect the viability of either the U937 histiocytes or the L929 fibroblasts.Thus at equivalent particle volumes the clinically relevant cobalt-chromium particles were more toxic then the alumina ceramic particles. This study has emphasised the fact that the nature, size and volume of particles are important in assessing biological effects of wear debris on cells in vitro.

  13. 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.

  14. 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

  15. Stereological estimation of the surface area and oxygen diffusing capacity of the respiratory stomach of the air-breathing armored catfish Pterygoplichthys anisitsi (Teleostei: Loricariidae).

    PubMed

    da Cruz, André Luis; Pedretti, Ana Carolina Elias; Fernandes, Marisa Narciso

    2009-05-01

    The stomach of Pterygoplichthys anisitsi has a thin, translucent wall and a simple squamous epithelium with an underlying dense capillary network. In the cardiac and pyloric regions, most cells have short microvilli distributed throughout the cell surface and their edges are characterized by short, densely packed microvilli. The mucosal layer of the stomach has two types of pavement epithelial cells that are similar to those in the aerial respiratory organs. Type 1 pavement epithelial cells, resembling the Type I pneumocyte in mammal lungs, are flat, with a large nucleus, and extend a thin sheet of cytoplasm on the underlying capillary. Type 2 cells, resembling the Type II pneumocyte, possess numerous mitochondria, a well-developed Golgi complex, rough endoplasmic reticulum, and numerous lamellar bodies in different stages of maturation. The gastric glands, distributed throughout the mucosal layer, also have several cells with many lamellar bodies. The total volume (air + tissue), tissue, and air capacity of the stomach when inflated, increase along with body mass. The surface-to-tissue-volume ratio of stomach varies from 108 cm(-1) in the smallest fish (0.084 kg) to 59 cm(-1) in the largest fish (0.60 kg). The total stomach surface area shows a low correlation to body mass. Nevertheless, the body-mass-specific surface area varied from 281.40 cm(2) kg(-1) in the smallest fish to 68.08 cm(2) kg(-1) in the largest fish, indicating a negative correlation to body mass (b = -0.76). The arithmetic mean barrier thickness between air and blood was 1.52 +/- 0.07 microm, whereas the harmonic mean thickness (tau(h)) of the diffusion barrier ranged from 0.40 to 0.74 microm. The anatomical diffusion factor (ADF = cm(2) microm(-1) kg(-1)) and the morphological O(2) diffusion capacity (D(morphol)O(2) = cm(3) min(-1) mmHg(-1) kg(-1)) are higher in the smallest specimen and lower in the largest one. In conclusion, the structure and morphometric data of P. anisitsi stomach indicate that this organ is adapted for oxygen uptake from air. (c) 2008 Wiley-Liss, Inc.

  16. Population Pharmacokinetics of Vancomycin in Patients Undergoing Allogeneic Hematopoietic Stem-Cell Transplantation.

    PubMed

    Okada, Akira; Kariya, Misato; Irie, Kei; Okada, Yutaka; Hiramoto, Nobuhiro; Hashimoto, Hisako; Kajioka, Ryosuke; Maruyama, Chika; Kasai, Hidefumi; Hamori, Mami; Nishimura, Asako; Shibata, Nobuhito; Fukushima, Keizo; Sugioka, Nobuyuki

    2018-05-15

    Vancomycin is a commonly used antimicrobial agent for patients undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). Vancomycin has large inter- and intraindividual pharmacokinetic variability, which is mainly described by renal function; various studies have indicated that vancomycin pharmacokinetics are altered in special populations. However, little is known regarding vancomycin pharmacokinetics in patients undergoing allo-HSCT. Therefore, we aimed to develop a population pharmacokinetic (PopPK) model of vancomycin in patients undergoing allo-HSCT for effective and safe antimicrobial therapy and to develop a vancomycin dosing nomogram for a vancomycin optimal-dosing strategy. In total, 285 observations from 95 patients undergoing allo-HSCT were available. The final PopPK parameter estimates were central volume of distribution (V1, L), 39.2; clearance (L/h), 4.25; peripheral volume of distribution (V2, L), 56.1; and intercompartmental clearance (L/h), 1.95. The developed vancomycin model revealed an increase in V1 and V2 compared with those in the general population that consisted of patients with methicillin-resistant Staphylococcus aureus. Moreover, serum creatinine was reduced because of an increase in the plasma fraction because of destruction of hematopoietic stem cells accompanying allo-HSCT pretreatment, suggesting that the Cockcroft-Gault equation-based creatinine clearance value was overestimated. To our knowledge, this is the first PopPK study to develop a dosing nomogram for vancomycin in patients undergoing allo-HSCT and was proven to be useful in optimizing the dosage and dosing interval of vancomycin in these patients. This strategy will provide more useful information for vancomycin therapy with an evidence-based dose adjustment. © 2018, The American College of Clinical Pharmacology.

  17. Myocardial serotonin exchange: negligible uptake by capillary endothelium

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

    Moffett, T.C.; Chan, I.S.; Bassingthwaighte, J.B.

    1988-03-01

    The extraction of serotonin from the blood during transorgan passage through the heart was studied using Langendorff-perfused rabbit hearts. Outflow dilution curves of /sup 131/I- or /sup 125/I-labeled albumin, (/sup 14/C)sucrose, and (3H)serotonin injected simultaneously into the inflow were fitted with an axially distributed blood-tissue exchange model to examine the extraction process. The model fits of the albumin and sucrose outflow dilution curves were used to define flow heterogeneity, intravascular dispersion, capillary permeability, and the volume of the interstitial space, which reduced the degrees of freedom in fitting the model to the serotonin curves. Serotonin extractions, measured against albumin, duringmore » single transcapillary passage, ranged from 24 to 64%. The ratio of the capillary permeability-surface area products for serotonin and sucrose, based on the maximum instantaneous extraction, was 1.37 +/- 0.2 (n = 18), very close to the predicted value of 1.39, the ratio of free diffusion coefficients calculated from the molecular weights. This result shows that the observed uptake of serotonin can be accounted for solely on the basis of diffusion between endothelial cells into the interstitial space. Thus it appears that the permeability of the luminal surface of the endothelial cell is negligible in comparison to diffusion through the clefts between endothelial cells. In 18 sets of dilution curves, with and without receptor and transport blockers or competitors (ketanserin, desipramine, imipramine, serotonin), the extractions and estimates of the capillary permeability-surface area product were not reduced, nor were the volumes of distribution. The apparent absence of transporters and receptors in rabbit myocardial capillary endothelium contrasts with their known abundance in the pulmonary vasculature.« less

  18. 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

  19. [Clinical evaluation of heavy-particle radiotherapy using dose volume histogram (DVH)].

    PubMed

    Terahara, A; Nakano, T; Tsujii, H

    1998-01-01

    Radiotherapy with heavy particles such as proton and heavy-charged particles is a promising modality for treatment of localized malignant tumors because of the good dose distribution. A dose calculation and radiotherapy planning system which is essential for this kind of treatment has been developed in recent years. It has the capability to compute the dose volume histogram (DVH) which contains dose-volume information for the target volume and other interesting volumes. Recently, DVH is commonly used to evaluate and compare dose distributions in radiotherapy with both photon and heavy particles, and it shows that a superior dose distribution is obtained in heavy particle radiotherapy. DVH is also utilized for the evaluation of dose distribution related to clinical outcomes. Besides models such as normal tissue complication probability (NTCP) and tumor control probability (TCP), which can be calculated from DVH are proposed by several authors, they are applied to evaluate dose distributions themselves and to evaluate them in relation to clinical results. DVH is now a useful and important tool, but further studies are needed to use DVH and these models practically for clinical evaluation of heavy-particle radiotherapy.

  20. Parallel Measurements of Light Scattering and Characterization of Marine Particles in Water: An Evaluation of Methodology

    DTIC Science & Technology

    2008-01-01

    A second objective is to characterize variability in the volume scattering function and particle size distribution for various optical water types...volume scattering function (VSF) and the particle size distribution (PSD) • Analysis of in situ optical measurements and particle size distributions ...SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION /AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY

  1. The Effect of Stochastically Varying Creep Parameters on Residual Stresses in Ceramic Matrix Composites

    NASA Technical Reports Server (NTRS)

    Pineda, Evan J.; Mital, Subodh K.; Bednarcyk, Brett A.; Arnold, Steven M.

    2015-01-01

    Constituent properties, along with volume fraction, have a first order effect on the microscale fields within a composite material and influence the macroscopic response. Therefore, there is a need to assess the significance of stochastic variation in the constituent properties of composites at the higher scales. The effect of variability in the parameters controlling the time-dependent behavior, in a unidirectional SCS-6 SiC fiber-reinforced RBSN matrix composite lamina, on the residual stresses induced during processing is investigated numerically. The generalized method of cells micromechanics theory is utilized to model the ceramic matrix composite lamina using a repeating unit cell. The primary creep phases of the constituents are approximated using a Norton-Bailey, steady state, power law creep model. The effect of residual stresses on the proportional limit stress and strain to failure of the composite is demonstrated. Monte Carlo simulations were conducted using a normal distribution for the power law parameters and the resulting residual stress distributions were predicted.

  2. Extraction of thermalized projectile fragments from a large volume gas cell

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

    Cooper, K.; Sumithrarachchi, C. S.; Morrissey, D. J.

    2014-11-01

    Experiments to determine the stopping and extraction efficiency of energetic (90 MeV/u) 76Ga fragments in a 1.2 m long gas cell filled with helium at 123 mbar are reported. The thermalized ions were transported by DC and RF fields as well as gas flow, then jetted through a supersonic nozzle into a RF quadrupole ion-guide and accelerated into an electrostatic beam line. The ions were collected in either a Faraday cup or a silicon beta-detector immediately after acceleration or after magnetic analysis. The range distributions of the ions and extraction efficiency of the system were measured for different implantation ratesmore » and compared with the theoretically calculated values. The singly charged 76Ga ions were observed as [ 76Ga(H 2O) n] + molecular ions with n=0, 1, and 2. The stopping efficiency and the extraction efficiency were obtained from the measured distributions and compared to previous results from other devices.« less

  3. A multiphase mixture model for substrate concentration distribution characteristics and photo-hydrogen production performance of the entrapped-cell photobioreactor.

    PubMed

    Guo, Cheng-Long; Cao, Hong-Xia; Pei, Hong-Shan; Guo, Fei-Qiang; Liu, Da-Meng

    2015-04-01

    A multiphase mixture model was developed for revealing the interaction mechanism between biochemical reactions and transfer processes in the entrapped-cell photobioreactor packed with gel granules containing Rhodopseudomonas palustris CQK 01. The effects of difference operation parameters, including operation temperature, influent medium pH value and porosity of packed bed, on substrate concentration distribution characteristics and photo-hydrogen production performance were investigated. The results showed that the model predictions were in good agreement with the experimental data reported. Moreover, the operation temperature of 30 °C and the influent medium pH value of 7 were the most suitable conditions for photo-hydrogen production by biodegrading substrate. In addition, the lower porosity of packed bed was beneficial to enhance photo-hydrogen production performance owing to the improvement on the amount of substrate transferred into gel granules caused by the increased specific area for substrate transfer in the elemental volume. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Energy Transitions | Integrated Energy Solutions | NREL

    Science.gov Websites

    clean energy access to remote populations across West Africa. NREL Supports Effort to Take Distributed develops and implements pilot projects to accelerate the development of distributed photovoltaics Renewable Energy into India's Electric Grid Volume 1 Volume 2 Designing Distributed Generation in Mexico

  5. Higher organization and histone modification of the plant nucleus and chromosome.

    PubMed

    Wako, T; Fukui, K

    2010-07-01

    Plants have a wide range of genome sizes. The length of each DNA molecule is usually much longer than the diameter of the cell and the length of each metaphase chromosome is effectively shortened to progress through mitosis. Thus some questions arise, such as: How is genomic DNA folded and shortened into chromosomes? What kind of proteins and/or their modifications contribute to chromosome structure? Are there any upper limits for the ratio of DNA volume to nuclear volume? This review attempts to answer these questions based on recent advances in chromosome research. Genomic DNA is first folded into nucleosomal fibers and then superfolded into metaphase chromosomes to sufficiently shorten its length to less than the upper limit for normal progression of cell division. Nucleosomes play structural roles, not only for DNA folding, but also for determination of euchromatin, heterochromatin, and centromeres, together with post-translational modifications and replacement of core histones with histone variants, and for the regulation of their structure and transcriptional status. More than 200 proteins of human metaphase chromosomes have been identified, including 5 types of nucleosome histones. They are categorized into 4 groups, and a 4-layer model of the human metaphase chromosome has been developed. There are upper limits for DNA volume. In all plants examined to date the DNA volume does not exceed 3% of the nuclear volume. Histone modification also has an impact on the spatial distribution of chromosomes within a nucleus, which seems to be related to the plant genome size. These points are discussed as well, as they are essential to maintain proper nuclear functions. Copyright 2010 S. Karger AG, Basel.

  6. Dynamic Contrast-Enhanced MRI of Gd-albumin Delivery to the Rat Hippocampus In Vivo by Convection-Enhanced Delivery

    PubMed Central

    Kim, Jung Hwan; Astary, Garrett W.; Nobrega, Tatiana L.; Kantorovich, Svetlana; Carney, Paul R.; Mareci, Thomas H.; Sarntinoranont, Malisa

    2013-01-01

    Convection enhanced delivery (CED) shows promise in treating neurological diseases due to its ability to circumvent the blood-brain barrier (BBB) and deliver therapeutics directly to the parenchyma of the central nervous system (CNS). Such a drug delivery method may be useful in treating CNS disorders involving the hippocampus such temporal lobe epilepsy and gliomas; however, the influence of anatomical structures on infusate distribution is not fully understood. As a surrogate for therapeutic agents, we used gadolinium-labeled-albumin (Gd-albumin) tagged with Evans blue dye to observe the time dependence of CED infusate distributions into the rat dorsal and ventral hippocampus in vivo with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). For finer anatomical detail, final distribution volumes (Vd) of the infusate were observed with high-resolution T1-weighted MR imaging and light microscopy of fixed brain sections. Dynamic images demonstrated that Gd-albumin preferentially distributed within the hippocampus along neuroanatomical structures with less fluid resistance and less penetration was observed in dense cell layers. Furthermore, significant leakage into adjacent cerebrospinal fluid (CSF) spaces such as the hippocampal fissure, velum interpositum and midbrain cistern occurred toward the end of infusion. Vd increased linearly with infusion volume (Vi) at a mean Vd/Vi ratio of 5.51 ± 0.55 for the dorsal hippocampus infusion and 5.30 ± 0.83 for the ventral hippocampus infusion. This study demonstrated the significant effects of tissue structure and CSF space boundaries on infusate distribution during CED. PMID:22687936

  7. Evaluation of anemia diagnosis based on elastic light scattering (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tong, Lieshu; Wang, Xinrui; Xie, Dengling; Chen, Xiaoya; Chu, Kaiqin; Dou, Hu; Smith, Zachary J.

    2017-03-01

    Currently, one-third of humanity is still suffering from anemia. In China the most common forms of anemia are iron deficiency and Thalassemia minor. Differentiating these two is the key to effective treatment. Iron deficiency is caused by malnutrition and can be cured by iron supplementation. Thalassemia is a hereditary disease in which the hemoglobin β chain is lowered or absent. Iron therapy is not effective, and there is evidence that iron therapy may be harmful to patients with Thalassemia. Both anemias can be diagnosed using red blood cell morphology: Iron deficiency presents a smaller mean cell volume compared to normal cells, but with a wide distribution; Thalassemia, meanwhile, presents a very small cell size and tight particle size distribution. Several researchers have proposed diagnostic indices based on red cell morphology to differentiate these two diseases. However, these indices lack sensitivity and specificity and are constructed without statistical rigor. Using multivariate methods we demonstrate a new classification method based on red cell morphology that diagnoses anemia in a Chinese population with enough accuracy for its use as a screening method. We further demonstrate a low cost instrument that precisely measures red cell morphology using elastic light scattering. This instrument is combined with an automated analysis program that processes scattering data to report red cell morphology without the need for user intervention. Despite using consumer-grade components, when comparing our experimental results with gold-standard measurements, the device can still achieve the high precision required for sensing clinically significant changes in red cell morphology.

  8. Internal magnesium, 2,3-diphosphoglycerate, and the regulation of the steady-state volume of human red blood cells by the Na/K/2Cl cotransport system

    PubMed Central

    1992-01-01

    This study is concerned with the relationship between the Na/K/Cl cotransport system and the steady-state volume (MCV) of red blood cells. Cotransport rate was determined in unfractionated and density- separated red cells of different MCV from different donors to see whether cotransport differences contribute to the difference in the distribution of MCVs. Cotransport, studied in cells at their original MCVs, was determined as the bumetanide (10 microM)-sensitive 22Na efflux in the presence of ouabain (50 microM) after adjusting cellular Na (Nai) and Ki to achieve near maximal transport rates. This condition was chosen to rule out MCV-related differences in Nai and Ki that might contribute to differences in the net chemical driving force for cotransport. We found that in both unfractionated and density-separated red cells the cotransport rate was inversely correlated with MCV. MCV was correlated directly with red cell 2,3-diphosphoglycerate (DPG), whereas total red cell Mg was only slightly elevated in cells with high MCV. Thus intracellular free Mg (Mgifree) is evidently lower in red cells with high 2,3-DPG (i.e., high MCV) and vice versa. Results from flux measurements at their original MCVs, after altering Mgifree with the ionophore A23187, indicated a high Mgi sensitivity of cotransport: depletion of Mgifree inhibited and an elevation of Mgifree increased the cotransport rate. The apparent K0.5 for Mgifree was approximately 0.4 mM. Maximizing Mgifree at optimum Nai and Ki minimized the differences in cotransport rates among the different donors. It is concluded that the relative cotransport rate is regulated for cells in the steady state at their original cell volume, not by the number of copies of the cotransporter but by differences in Mgifree. The interindividual differences in Mgifree, determined primarily by differences in the 2,3-DPG content, are responsible for the differences in the relative cotransport activity that results in an inverse relationship with in vivo differences in MCV. Indirect evidence indicates that the relative cotransport rate, as indexed by Mgifree, is determined by the phosphorylated level of the cotransport system. PMID:1607852

  9. Biasing and High-Order Statistics from the Southern-Sky Redshift Survey

    NASA Astrophysics Data System (ADS)

    Benoist, C.; Cappi, A.; da Costa, L. N.; Maurogordato, S.; Bouchet, F. R.; Schaeffer, R.

    1999-04-01

    We analyze different volume-limited samples extracted from the Southern-Sky Redshift Survey (SSRS2), using counts-in-cells to compute the count probability distribution function (CPDF). From the CPDF we derive volume-averaged correlation functions to fourth order and the normalized skewness and kurtosis S3=ξ3¯/ξ¯22 and S4=ξ4¯/ξ¯32. We find that the data satisfies the hierarchical relations in the range 0.3<~ξ2¯<~10. In this range we find S3 to be scale independent, with a value of ~1.8, in good agreement with the values measured from other optical redshift surveys probing different volumes, but significantly smaller than that inferred from the Automatic Plate Measuring Facility (APM) angular catalog. In addition, the measured values of S3 do not show a significant dependence on the luminosity of the galaxies considered. This result is supported by several tests of systematic errors that could affect our measures and estimates of the cosmic variance determined from mock catalogs extracted from N-body simulations. This result is in marked contrast to what would be expected from the strong dependence of the two-point correlation function on luminosity in the framework of a linear biasing model. We discuss the implications of our results and compare them to some recent models of the galaxy distribution that address the problem of bias.

  10. 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.

  11. 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.

  12. A mathematical model relating response durations to amount of subclinical resistant disease.

    PubMed

    Gregory, W M; Richards, M A; Slevin, M L; Souhami, R L

    1991-02-15

    A mathematical model is presented which seeks to determine, from examination of the response durations of a group of patients with malignant disease, the mean and distribution of the resistant tumor volume. The mean tumor-doubling time and distribution of doubling times are also estimated. The model assumes that in a group of patients there is a log-normal distribution both of resistant disease and of tumor-doubling times and implies that the shapes of certain parts of an actuarial response-duration curve are related to these two factors. The model has been applied to data from two reported acute leukemia trials: (a) a recent acute myelogenous leukemia trial was examined. Close fits were obtained for both the first and second remission-duration curves. The model results suggested that patients with long first remissions had less resistant disease and had tumors with slower growth rates following second line treatment; (b) an historical study of maintenance therapy for acute lymphoblastic leukemia was used to estimate the mean cell-kill (approximately 10(4) cells) achieved with single agent, 6-mercaptopurine. Application of the model may have clinical relevance, for example, in identifying groups of patients likely to benefit from further intensification of treatment.

  13. Intracranial cerebrospinal fluid spaces imaging using a pulse-triggered three-dimensional turbo spin echo MR sequence with variable flip-angle distribution.

    PubMed

    Hodel, Jérôme; Silvera, Jonathan; Bekaert, Olivier; Rahmouni, Alain; Bastuji-Garin, Sylvie; Vignaud, Alexandre; Petit, Eric; Durning, Bruno; Decq, Philippe

    2011-02-01

    To assess the three-dimensional turbo spin echo with variable flip-angle distribution magnetic resonance sequence (SPACE: Sampling Perfection with Application optimised Contrast using different flip-angle Evolution) for the imaging of intracranial cerebrospinal fluid (CSF) spaces. We prospectively investigated 18 healthy volunteers and 25 patients, 20 with communicating hydrocephalus (CH), five with non-communicating hydrocephalus (NCH), using the SPACE sequence at 1.5T. Volume rendering views of both intracranial and ventricular CSF were obtained for all patients and volunteers. The subarachnoid CSF distribution was qualitatively evaluated on volume rendering views using a four-point scale. The CSF volumes within total, ventricular and subarachnoid spaces were calculated as well as the ratio between ventricular and subarachnoid CSF volumes. Three different patterns of subarachnoid CSF distribution were observed. In healthy volunteers we found narrowed CSF spaces within the occipital aera. A diffuse narrowing of the subarachnoid CSF spaces was observed in patients with NCH whereas patients with CH exhibited narrowed CSF spaces within the high midline convexity. The ratios between ventricular and subarachnoid CSF volumes were significantly different among the volunteers, patients with CH and patients with NCH. The assessment of CSF spaces volume and distribution may help to characterise hydrocephalus.

  14. Dosimetric and Clinical Analysis of Spatial Distribution of the Radiation Dose in Gamma Knife Radiosurgery for Vestibular Schwannoma

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

    Massager, Nicolas, E-mail: nmassage@ulb.ac.be; Neurosurgery-Department, Hospital Erasme, Brussels; Lonneville, Sarah

    2011-11-15

    Objectives: We investigated variations in the distribution of radiation dose inside (dose inhomogeneity) and outside (dose falloff) the target volume during Gamma Knife (GK) irradiation of vestibular schwannoma (VS). We analyzed the relationship between some parameters of dose distribution and the clinical and radiological outcome of patients. Methods and Materials: Data from dose plans of 203 patients treated for a vestibular schwannoma by GK C using same prescription dose (12 Gy at the 50% isodose) were collected. Four different dosimetric indexes were defined and calculated retrospectively in all plannings on the basis of dose-volume histograms: Paddick conformity index (PI), gradientmore » index (GI), homogeneity index (HI), and unit isocenter (UI). The different measures related to distribution of the radiation dose were compared with hearing and tumor outcome of 203 patients with clinical and radiological follow-up of minimum 2 years. Results: Mean, median, SD, and ranges of the four indexes of dose distribution analyzed were calculated; large variations were found between dose plans. We found a high correlation between the target volume and PI, GI, and UI. No significant association was found between the indexes of dose distribution calculated in this study and tumor control, tumor volume shrinkage, hearing worsening, loss of functional hearing, or complete hearing loss at last follow-up. Conclusions: Parameters of distribution of the radiation dose during GK radiosurgery for VS can be highly variable between dose plans. The tumor and hearing outcome of patients treated is not significantly related to these global indexes of dose distribution inside and around target volume. In GK radiosurgery for VS, the outcome seems more to be influenced by local radiation dose delivered to specific structures or volumes than by global dose gradients.« less

  15. Clinical outcomes using carbon-ion radiotherapy and dose-volume histogram comparison between carbon-ion radiotherapy and photon therapy for T2b-4N0M0 non-small cell lung cancer-A pilot study.

    PubMed

    Shirai, Katsuyuki; Kawashima, Motohiro; Saitoh, Jun-Ichi; Abe, Takanori; Fukata, Kyohei; Shigeta, Yuka; Irie, Daisuke; Shiba, Shintaro; Okano, Naoko; Ohno, Tatsuya; Nakano, Takashi

    2017-01-01

    The safety and efficacy of carbon-ion radiotherapy for advanced non-small cell lung cancer have not been established. We evaluated the clinical outcomes and dose-volume histogram parameters of carbon-ion radiotherapy compared with photon therapy in T2b-4N0M0 non-small cell lung cancer. Twenty-three patients were treated with carbon-ion radiotherapy between May 2011 and December 2015. Seven, 14, and 2 patients had T2b, T3, and T4, respectively. The median age was 78 (range, 53-91) years, with 22 male patients. There were 12 adenocarcinomas, 8 squamous cell carcinomas, 1 non-small cell lung carcinoma, and 2 clinically diagnosed lung cancers. Eleven patients were operable, and 12 patients were inoperable. Most patients (91%) were treated with carbon-ion radiotherapy of 60.0 Gy relative biological effectiveness (RBE) in 4 fractions or 64.0 Gy (RBE) in 16 fractions. Local control and overall survival rates were calculated. Dose-volume histogram parameters of normal lung and tumor coverages were compared between carbon-ion radiotherapy and photon therapies, including three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). The median follow-up of surviving patients was 25 months. Three patients experienced local recurrence, and the 2-year local control rate was 81%. During follow-up, 5 patients died of lung cancer, and 1 died of intercurrent disease. The 2-year overall survival rate was 70%. Operable patients had a better overall survival rate compared with inoperable patients (100% vs. 43%; P = 0.04). There was no grade ≥2 radiation pneumonitis. In dose-volume histogram analysis, carbon-ion radiotherapy had a significantly lower dose to normal lung and greater tumor coverage compared with photon therapies. Carbon-ion radiotherapy was effectively and safely performed for T2b-4N0M0 non-small cell lung cancer, and the dose distribution was superior compared with those for photon therapies. A Japanese multi-institutional study is ongoing to prospectively evaluate these patients and establish the use of carbon-ion radiotherapy.

  16. Multilayer cell-seeded polymer nanofiber constructs for soft-tissue reconstruction.

    PubMed

    Barker, Daniel A; Bowers, Daniel T; Hughley, Brian; Chance, Elizabeth W; Klembczyk, Kevin J; Brayman, Kenneth L; Park, Stephen S; Botchwey, Edward A

    2013-09-01

    Cell seeding throughout the thickness of a nanofiber construct allows for patient-specific implant alternatives with long-lasting effects, earlier integration, and reduced inflammation when compared with traditional implants. Cell seeding may improve implant integration with host tissue; however, the effect of cell seeding on thick nanofiber constructs has not been studied. To use a novel cell-preseeded nanofiber tissue engineering technique to create a 3-dimensional biocompatible implant alternative to decellularized extracellular matrix. Animal study with mammalian cell culture to study tissue engineered scaffolds. Academic research laboratory. Thirty-six Sprague-Dawley rats. The rats each received 4 implant types. The grafts included rat primary (enhanced green fluorescent protein-positive [eGFP+]) fibroblast-seeded polycaprolactone (PCL)/collagen nanofiber scaffold, PCL/collagen cell-free nanofiber scaffold, acellular human cadaveric dermis (AlloDerm), and acellular porcine dermis (ENDURAGen). Rats were monitored postoperatively and received enrofloxacin in the drinking water for 4 days prophylactically and buprenorphine (0.2-0.5 mg/kg administered subcutaneously twice a day postoperatively for pain for 48 hours). The viability of NIH/3T3 fibroblasts cultured on PCL electrospun nanofibers was evaluated using fluorescence microscopy. Soft-tissue remodeling was examined histologically and with novel ex vivo volume determinations of implants using micro-computed tomography of cell-seeded implants relative to nanofibers without cells and commonly used dermal grafts of porcine and human origin (ENDURAGen and AlloDerm, respectively). The fate and distribution of eGFP+ seeded donor fibroblasts were assessed using immunohistochemistry. Fibroblasts migrated across nanofiber layers within 12 hours and remained viable on a single layer for up to 14 days. Scanning electron microscopy confirmed a nanoscale structure with a mean (SD) diameter of 158 (72) nm. Low extrusion rates demonstrated the excellent biocompatibility in vivo. Histological examination of the scaffolds demonstrated minimal inflammation. Cell seeding encouraged rapid vascularization of the nanofiber implants. Cells of donor origin (eGFP+) declined with the duration of implantation. Implant volume was not significantly affected for up to 8 weeks by the preseeding of cells (P > .05). Polymer nanofiber-based scaffolds mimic natural extracellular matrix. Preseeding the nanofiber construct with cells improved vascularization without notable effects on volume. An effect of cell preseeding on scaffold vascularization was evident beyond the presence of preseeded cells. This 3-dimensional, multilayer method of cell seeding throughout a 1-mm-thick construct is simple and feasible for clinical application. Further development of this technique may affect the clinical practice of facial plastic and reconstructive surgeons.

  17. 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

  18. Porosimetry and packing morphology of vertically-aligned carbon nanotube arrays via impedance spectroscopy.

    PubMed

    Mutha, Heena K; Lu, Yuan; Stein, Itai; Cho, H Jeremy; Suss, Matthew; Laoui, Tahar; Thompson, Carl; Wardle, Brian; Wang, Evelyn

    2016-12-13

    Vertically aligned one-dimensional nanostructure arrays are promising in many applications such as electrochemical systems, solar cells, and electronics, taking advantage of high surface area per unit volume, nanometer length scale packing, and alignment leading to high conductivity. However, many devices need to optimize arrays for device performance by selecting an appropriate morphology. Developing a simple, non-invasive tool for understanding the role of pore volume distribution and interspacing would aid in the optimization of nanostructure morphologies in electrodes. In this work, we combined electrochemical impedance spectroscopy (EIS) with capacitance measurements and porous electrode theory to conduct in situ porosimetry of vertically-aligned carbon nanotubes (VA-CNTs) non-destructively. We utilized the EIS measurements with a pore size distribution model to quantify the average and dispersion of inter-CNT spacing (Γ), stochastically, in carpets that were mechanically densified from 1.7 × 1010 tubes/cm2 to 4.5 × 1011 tubes/cm2. Our analysis predicts that the inter-CNT spacing ranges from over 100 ± 50 nm in sparse carpets to sub 10 ± 5 nm in packed carpets. Our results suggest that waviness of CNTs leads to variations in the inter-CNT spacing, which can be significant in sparse carpets. This methodology can be used to predict the performance of many nanostructured devices, including supercapacitors, batteries, solar cells, and semiconductor electronics. Copyright 2016 IOP Publishing Ltd.

  19. Simulation of the Formation of DNA Double Strand Breaks and Chromosome Aberrations in Irradiated Cells

    NASA Technical Reports Server (NTRS)

    Plante, Ianik; Ponomarev, Artem L.; Wu, Honglu; Blattnig, Steve; George, Kerry

    2014-01-01

    The formation of DNA double-strand breaks (DSBs) and chromosome aberrations is an important consequence of ionizing radiation. To simulate DNA double-strand breaks and the formation of chromosome aberrations, we have recently merged the codes RITRACKS (Relativistic Ion Tracks) and NASARTI (NASA Radiation Track Image). The program RITRACKS is a stochastic code developed to simulate detailed event-by-event radiation track structure: [1] This code is used to calculate the dose in voxels of 20 nm, in a volume containing simulated chromosomes, [2] The number of tracks in the volume is calculated for each simulation by sampling a Poisson distribution, with the distribution parameter obtained from the irradiation dose, ion type and energy. The program NASARTI generates the chromosomes present in a cell nucleus by random walks of 20 nm, corresponding to the size of the dose voxels, [3] The generated chromosomes are located within domains which may intertwine, and [4] Each segment of the random walks corresponds to approx. 2,000 DNA base pairs. NASARTI uses pre-calculated dose at each voxel to calculate the probability of DNA damage at each random walk segment. Using the location of double-strand breaks, possible rejoining between damaged segments is evaluated. This yields various types of chromosomes aberrations, including deletions, inversions, exchanges, etc. By performing the calculations using various types of radiations, it will be possible to obtain relative biological effectiveness (RBE) values for several types of chromosome aberrations.

  20. [Towards a structuring fibrillar ontology].

    PubMed

    Guimberteau, J-C

    2012-10-01

    Over previous decades and centuries, the difficulty encountered in the manner in which the tissue of our bodies is organised, and structured, is clearly explained by the impossibility of exploring it in detail. Since the creation of the microscope, the perception of the basic unity, which is the cell, has been essential in understanding the functioning of reproduction and of transmission, but has not been able to explain the notion of form; since the cells are not everywhere and are not distributed in an apparently balanced manner. The problems that remain are those of form and volume and also of connection. The concept of multifibrillar architecture, shaping the interfibrillar microvolumes in space, represents a solution to all these questions. The architectural structures revealed, made up of fibres, fibrils and microfibrils, from the mesoscopic to the microscopic level, provide the concept of a living form with structural rationalism that permits the association of psychochemical molecular biodynamics and quantum physics: the form can thus be described and interpreted, and a true structural ontology is elaborated from a basic functional unity, which is the microvacuole, the intra and interfibrillar volume of the fractal organisation, and the chaotic distribution. Naturally, new, less linear, less conclusive, and less specific concepts will be implied by this ontology, leading one to believe that the emergence of life takes place under submission to forces that the original form will have imposed and oriented the adaptive finality. Copyright © 2012. Published by Elsevier SAS.

  1. Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo.

    PubMed

    Astary, Garrett W; Kantorovich, Svetlana; Carney, Paul R; Mareci, Thomas H; Sarntinoranont, Malisa

    2010-03-15

    Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate distribution is unclear. We have utilized this approach to study extracellular transport and distribution of a contrast agent in the hippocampus, a complex structure susceptible to CNS disorders. The magnetic resonance (MR) contrast agent diethylene triamene penta-acetic acid chelated gadolinium-labeled albumin (Gd-albumin), tagged with Evans blue dye, was directly infused (V(i)=5 microl) into the dorsal and ventral hippocampus of seven male Sprague-Dawley rats. The final distribution profile of the contrast agent, a product of CED and limited diffusion, was observed in vivo using high-resolution T1-weighted MR imaging at 11.1T. Dense cell layers, such as the granule cell layer of the dentate gyrus and the pyramidal cell layer of CA1, appeared to be barriers to transport of the tracer. Three-dimensional distribution shape and volume (V(d)) differences, between the dorsal and ventral hippocampus infusions, were determined from the MR images using a semi-automatic segmentation routine (dorsal V(d)=23.4+/-1.8 microl, ventral V(d)=36.4+/-5.1 microl). Finer structural detail of the hippocampus was obtained using a combination of histological analysis and fluorescence imaging. This study demonstrates that CED has the potential to target all regions of the hippocampus and that tracer distribution is influenced by infusion site, underlying structure and circuitry, and extent of backflow. Therefore, CED, combined with high-resolution MR imaging, may be a useful strategy for delivering therapeutics for the treatment of CNS disorders affecting the hippocampus. Published by Elsevier B.V.

  2. Potential implications of the bystander effect on TCP and EUD when considering target volume dose heterogeneity.

    PubMed

    Balderson, Michael J; Kirkby, Charles

    2015-01-01

    In light of in vitro evidence suggesting that radiation-induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumor control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: One incorporating bystander effects derived from previously published in vitro bystander data ( McMahon et al. 2012 , 2013a); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced. The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced. In terms of EUD and TCP, the bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV varies. The results suggest, at least in a limiting sense, the potential for allowing some degree of dose heterogeneity within a CTV, although further investigation of the assumptions of the bystander model are warranted.

  3. Effect of fatigue/ageing on the lithium distribution in cylinder-type Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Mühlbauer, M. J.; Dolotko, O.; Hofmann, M.; Ehrenberg, H.; Senyshyn, A.

    2017-04-01

    The lithium concentration in the graphite anode of fatigued (cycled 1000 times at 25 °C) Li-ion cell of 18650-type has been probed non-destructively by spatially resolved neutron diffraction. The amount x of Li in LixC6 has been determined in a central plane of a cylinder-type Li-ion cell. A radial mesh with a gauge volume of 2 × 2 × 20 mm3 was used. Besides the evidently lower lithiation grade, caused by a lack of free movable lithium and a loss of electrolyte, a development of fatigue-driven spatial lithium inhomogeneities has been observed in radial direction. Observed changes have been discussed in light of their correlations to an increase of the internal cell resistance and to a change of the electrolyte concentration.

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

    Daily, Michael D.; Olsen, Brett N.; Schlesinger, Paul H.

    In mammalian cells cholesterol is essential for membrane function, but in excess can be cytototoxic. The cellular response to acute cholesterol loading involves biophysical-based mechanisms that regulate cholesterol levels, through modulation of the “activity” or accessibility of cholesterol to extra-membrane acceptors. Experiments and united atom (UA) simulations show that at high concentrations of cholesterol, lipid bilayers thin significantly and cholesterol availability to external acceptors increases substantially. Such cholesterol activation is critical to its trafficking within cells. Here we aim to reduce the computational cost to enable simulation of large and complex systems involved in cholesterol regulation, such as those includingmore » oxysterols and cholesterol-sensing proteins. To accomplish this, we have modified the published MARTINI coarse-grained force field to improve its predictions of cholesterol-induced changes in both macroscopic and microscopic properties of membranes. Most notably, MARTINI fails to capture both the (macroscopic) area condensation and membrane thickening seen at less than 30% cholesterol and the thinning seen above 40% cholesterol. The thinning at high concentration is critical to cholesterol activation. Microscopic properties of interest include cholesterol-cholesterol radial distribution functions (RDFs), tilt angle, and accessible surface area. First, we develop an “angle-corrected” model wherein we modify the coarse-grained bond angle potentials based on atomistic simulations. This modification significantly improves prediction of macroscopic properties, most notably the thickening/thinning behavior, and also slightly improves microscopic property prediction relative to MARTINI. Second, we add to the angle correction a “volume correction” by also adjusting phospholipid bond lengths to achieve a more accurate volume per molecule. The angle + volume correction substantially further improves the quantitative agreement of the macroscopic properties (area per molecule and thickness) with united atom simulations. However, this improvement also reduces the accuracy of microscopic predictions like radial distribution functions and cholesterol tilt below that of either MARTINI or the angle-corrected model. Thus, while both of our forcefield corrections improve MARTINI, the combined angle and volume correction should be used for problems involving sterol effects on the overall structure of the membrane, while our angle-corrected model should be used in cases where the properties of individual lipid and sterol models are critically important.« less

  5. Recurrence interval analysis of trading volumes

    NASA Astrophysics Data System (ADS)

    Ren, Fei; Zhou, Wei-Xing

    2010-06-01

    We study the statistical properties of the recurrence intervals τ between successive trading volumes exceeding a certain threshold q . The recurrence interval analysis is carried out for the 20 liquid Chinese stocks covering a period from January 2000 to May 2009, and two Chinese indices from January 2003 to April 2009. Similar to the recurrence interval distribution of the price returns, the tail of the recurrence interval distribution of the trading volumes follows a power-law scaling, and the results are verified by the goodness-of-fit tests using the Kolmogorov-Smirnov (KS) statistic, the weighted KS statistic and the Cramér-von Mises criterion. The measurements of the conditional probability distribution and the detrended fluctuation function show that both short-term and long-term memory effects exist in the recurrence intervals between trading volumes. We further study the relationship between trading volumes and price returns based on the recurrence interval analysis method. It is found that large trading volumes are more likely to occur following large price returns, and the comovement between trading volumes and price returns is more pronounced for large trading volumes.

  6. Recurrence interval analysis of trading volumes.

    PubMed

    Ren, Fei; Zhou, Wei-Xing

    2010-06-01

    We study the statistical properties of the recurrence intervals τ between successive trading volumes exceeding a certain threshold q. The recurrence interval analysis is carried out for the 20 liquid Chinese stocks covering a period from January 2000 to May 2009, and two Chinese indices from January 2003 to April 2009. Similar to the recurrence interval distribution of the price returns, the tail of the recurrence interval distribution of the trading volumes follows a power-law scaling, and the results are verified by the goodness-of-fit tests using the Kolmogorov-Smirnov (KS) statistic, the weighted KS statistic and the Cramér-von Mises criterion. The measurements of the conditional probability distribution and the detrended fluctuation function show that both short-term and long-term memory effects exist in the recurrence intervals between trading volumes. We further study the relationship between trading volumes and price returns based on the recurrence interval analysis method. It is found that large trading volumes are more likely to occur following large price returns, and the comovement between trading volumes and price returns is more pronounced for large trading volumes.

  7. Mechanisms of Aquaporin-Facilitated Cancer Invasion and Metastasis

    NASA Astrophysics Data System (ADS)

    De Ieso, Michael L.; Yool, Andrea J.

    2018-04-01

    Cancer is a leading cause of death worldwide, and its incidence is rising with numbers expected to increase 70% in the next two decades. The fact that current mainline treatments for cancer patients are accompanied by debilitating side effects prompts a growing demand for new therapies that not only inhibit growth and proliferation of cancer cells, but also control invasion and metastasis. One class of targets gaining international attention is the aquaporins, a family of membrane-spanning water channels with diverse physiological functions and extensive tissue-specific distributions in humans. Aquaporins -1, -2, -3, -4, -5, -8, and -9 have been linked to roles in cancer proliferation, invasion and metastasis, but their mechanisms of action remain to be fully defined. Aquaporins are implicated in the metastatic cascade in processes of angiogenesis, cellular dissociation, migration and invasion. Cancer invasion and metastasis are proposed to be potentiated by aquaporins in boosting tumor angiogenesis, enhancing cell volume regulation, regulating cell-cell and cell-matrix adhesions, interacting with actin cytoskeleton, regulating proteases and extracellular-matrix degrading molecules, contributing to the regulation of epithelial-mesenchymal transitions, and interacting with signaling pathways enabling motility and invasion. Pharmacological modulators of aquaporin channels are being identified and tested for therapeutic potential, including compounds derived from loop diuretics, metal-containing organic compounds, plant natural products, and other small molecules. Further studies on aquaporin-dependent functions in cancer metastasis are needed to define the differential contributions of different classes of aquaporin channels to regulation of fluid balance, cell volume, small solute transport, signal transduction, their possible relevance as rate limiting steps, and potential values as therapeutic targets for proliferation and invasion.

  8. The cranial cartilages of teleosts and their classification.

    PubMed

    Benjamin, M

    1990-04-01

    The structure and distribution of cartilages has been studied in 45 species from 24 families. The resulting data have been used as a basis for establishing a new classification. A cartilage is regarded as 'cell-rich' if its cells or their lacunae occupy more than half of the tissue volume. Five classes of cell-rich cartilage are recognised (a) hyaline-cell cartilage (common in the lips of bottom-dwelling cyprinids) and its subtypes fibro/hyaline-cell cartilage, elastic/hyaline-cell cartilage and lipo/hyaline-cell cartilage, (b) Schaffer's Zellknorpel, typified by the cartilage in the gill filaments of most teleosts examined, (c) elastic/cell-rich cartilage, such as that which supports the barbels and oral valves of catfish, e.g. Corydoras metae, (d) fibro/cell-rich cartilage, as in the submaxillary meniscus of Sphaerichthys osphromenoides, (e) cell-rich hyaline and (f) matrix-rich hyaline cartilage--both of which are common in the neurocranium and gill arches of most teleosts. The range of cartilages seen, and the predominant cartilage type, is recorded for each species and a list is provided of the tissues that most typify different organs or regions of the head. As a preliminary pointer to developmental relationships between the cartilages, note was taken of gradual transitions between one cartilage and another. It is suggested that hyaline-cell cartilage occupies a key position in teleosts as the most labile of the supporting tissues and is highly characteristic of Cypriniformes. The cartilage that best resembles mammalian hyaline cartilage (matrix-rich hyaline cartilage) has a very conservative distribution in different skeletal elements and the least number of associations with other tissues. It is well represented in Siluriformes.

  9. A molecular signaling model of platelet phosphoinositide and calcium regulation during homeostasis and P2Y1 activation.

    PubMed

    Purvis, Jeremy E; Chatterjee, Manash S; Brass, Lawrence F; Diamond, Scott L

    2008-11-15

    To quantify how various molecular mechanisms are integrated to maintain platelet homeostasis and allow responsiveness to adenosine diphosphate (ADP), we developed a computational model of the human platelet. Existing kinetic information for 77 reactions, 132 fixed kinetic rate constants, and 70 species was combined with electrochemical calculations, measurements of platelet ultrastructure, novel experimental results, and published single-cell data. The model accurately predicted: (1) steady-state resting concentrations for intracellular calcium, inositol 1,4,5-trisphosphate, diacylglycerol, phosphatidic acid, phosphatidylinositol, phosphatidylinositol phosphate, and phosphatidylinositol 4,5-bisphosphate; (2) transient increases in intracellular calcium, inositol 1,4,5-trisphosphate, and G(q)-GTP in response to ADP; and (3) the volume of the platelet dense tubular system. A more stringent test of the model involved stochastic simulation of individual platelets, which display an asynchronous calcium spiking behavior in response to ADP. Simulations accurately reproduced the broad frequency distribution of measured spiking events and demonstrated that asynchronous spiking was a consequence of stochastic fluctuations resulting from the small volume of the platelet. The model also provided insights into possible mechanisms of negative-feedback signaling, the relative potency of platelet agonists, and cell-to-cell variation across platelet populations. This integrative approach to platelet biology offers a novel and complementary strategy to traditional reductionist methods.

  10. The role of neural precursor cells and self assembling peptides in nerve regeneration

    PubMed Central

    2013-01-01

    Objective Cranial nerve injury involves loss of central neural cells in the brain stem and surrounding support matrix, leading to severe functional impairment. Therapeutically targeting cellular replacement and enhancing structural support may promote neural regeneration. We examined the combinatorial effect of neural precursor cells (NPC) and self assembling peptide (SAP) administration on nerve regeneration. Methods Nerve injury was induced by clip compression of the rodent spinal cord. SAPs were injected immediately into the injured cord and NPCs at 2 weeks post-injury. Behavioral analysis was done weekly and rats were sacrificed at 11 weeks post injury. LFB-H&E staining was done on cord tissue to assess cavitation volume. Motor evoked potentials (MEP) were measured at week 11 to assess nerve conduction and Kaplan meier curves were created to compare survival estimates. Results NPCs and SAPs were distributed both caudal and rostral to the injury site. Behavioral analysis showed that SAP + NPC transplantation significantly improved locomotor score p <0.03) and enhanced survival (log rank test, p = 0.008) compared to control. SAP + NPC treatment also improved nerve conduction velocity (p = 0.008) but did not affect cavitation volume (p = 0.73). Conclusion Combinatorial NPC and SAP injection into injured nerve tissue may enhance neural repair and regeneration. PMID:24351041

  11. The role of neural precursor cells and self assembling peptides in nerve regeneration.

    PubMed

    Zhao, Xiao; Yao, Gordon S; Liu, Yang; Wang, Jian; Satkunendrarajah, Kajana; Fehlings, Michael

    2013-12-19

    Cranial nerve injury involves loss of central neural cells in the brain stem and surrounding support matrix, leading to severe functional impairment. Therapeutically targeting cellular replacement and enhancing structural support may promote neural regeneration. We examined the combinatorial effect of neural precursor cells (NPC) and self assembling peptide (SAP) administration on nerve regeneration. Nerve injury was induced by clip compression of the rodent spinal cord. SAPs were injected immediately into the injured cord and NPCs at 2 weeks post-injury. Behavioral analysis was done weekly and rats were sacrificed at 11 weeks post injury. LFB-H&E staining was done on cord tissue to assess cavitation volume. Motor evoked potentials (MEP) were measured at week 11 to assess nerve conduction and Kaplan Meier curves were created to compare survival estimates. NPCs and SAPs were distributed both caudal and rostral to the injury site. Behavioral analysis showed that SAP + NPC transplantation significantly improved locomotor score p <0.03) and enhanced survival (log rank test, p = 0.008) compared to control. SAP + NPC treatment also improved nerve conduction velocity (p = 0.008) but did not affect cavitation volume (p = 0.73). Combinatorial NPC and SAP injection into injured nerve tissue may enhance neural repair and regeneration.

  12. A robust, efficient equidistribution 2D grid generation method

    NASA Astrophysics Data System (ADS)

    Chacon, Luis; Delzanno, Gian Luca; Finn, John; Chung, Jeojin; Lapenta, Giovanni

    2007-11-01

    We present a new cell-area equidistribution method for two- dimensional grid adaptation [1]. The method is able to satisfy the equidistribution constraint to arbitrary precision while optimizing desired grid properties (such as isotropy and smoothness). The method is based on the minimization of the grid smoothness integral, constrained to producing a given positive-definite cell volume distribution. The procedure gives rise to a single, non-linear scalar equation with no free-parameters. We solve this equation numerically with the Newton-Krylov technique. The ellipticity property of the linearized scalar equation allows multigrid preconditioning techniques to be effectively used. We demonstrate a solution exists and is unique. Therefore, once the solution is found, the adapted grid cannot be folded due to the positivity of the constraint on the cell volumes. We present several challenging tests to show that our new method produces optimal grids in which the constraint is satisfied numerically to arbitrary precision. We also compare the new method to the deformation method [2] and show that our new method produces better quality grids. [1] G.L. Delzanno, L. Chac'on, J.M. Finn, Y. Chung, G. Lapenta, A new, robust equidistribution method for two-dimensional grid generation, in preparation. [2] G. Liao and D. Anderson, A new approach to grid generation, Appl. Anal. 44, 285--297 (1992).

  13. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation.

    PubMed

    Unkelbach, Jan; Menze, Bjoern H; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A

    2014-02-07

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most crucial model input. We conclude that the tumor growth model provides a method to account for anisotropic growth patterns of glioma, and may therefore provide a tool to make target delineation more objective and automated.

  14. Radiotherapy planning for glioblastoma based on a tumor growth model: improving target volume delineation

    NASA Astrophysics Data System (ADS)

    Unkelbach, Jan; Menze, Bjoern H.; Konukoglu, Ender; Dittmann, Florian; Le, Matthieu; Ayache, Nicholas; Shih, Helen A.

    2014-02-01

    Glioblastoma differ from many other tumors in the sense that they grow infiltratively into the brain tissue instead of forming a solid tumor mass with a defined boundary. Only the part of the tumor with high tumor cell density can be localized through imaging directly. In contrast, brain tissue infiltrated by tumor cells at low density appears normal on current imaging modalities. In current clinical practice, a uniform margin, typically two centimeters, is applied to account for microscopic spread of disease that is not directly assessable through imaging. The current treatment planning procedure can potentially be improved by accounting for the anisotropy of tumor growth, which arises from different factors: anatomical barriers such as the falx cerebri represent boundaries for migrating tumor cells. In addition, tumor cells primarily spread in white matter and infiltrate gray matter at lower rate. We investigate the use of a phenomenological tumor growth model for treatment planning. The model is based on the Fisher-Kolmogorov equation, which formalizes these growth characteristics and estimates the spatial distribution of tumor cells in normal appearing regions of the brain. The target volume for radiotherapy planning can be defined as an isoline of the simulated tumor cell density. This paper analyzes the model with respect to implications for target volume definition and identifies its most critical components. A retrospective study involving ten glioblastoma patients treated at our institution has been performed. To illustrate the main findings of the study, a detailed case study is presented for a glioblastoma located close to the falx. In this situation, the falx represents a boundary for migrating tumor cells, whereas the corpus callosum provides a route for the tumor to spread to the contralateral hemisphere. We further discuss the sensitivity of the model with respect to the input parameters. Correct segmentation of the brain appears to be the most crucial model input. We conclude that the tumor growth model provides a method to account for anisotropic growth patterns of glioma, and may therefore provide a tool to make target delineation more objective and automated.

  15. Dual Functions of α-Ketoglutarate Dehydrogenase E2 in the Krebs Cycle and Mitochondrial DNA Inheritance in Trypanosoma brucei

    PubMed Central

    Sykes, Steven E.

    2013-01-01

    The dihydrolipoyl succinyltransferase (E2) of the multisubunit α-ketoglutarate dehydrogenase complex (α-KD) is an essential Krebs cycle enzyme commonly found in the matrices of mitochondria. African trypanosomes developmentally regulate mitochondrial carbohydrate metabolism and lack a functional Krebs cycle in the bloodstream of mammals. We found that despite the absence of a functional α-KD, bloodstream form (BF) trypanosomes express α-KDE2, which localized to the mitochondrial matrix and inner membrane. Furthermore, α-KDE2 fractionated with the mitochondrial genome, the kinetoplast DNA (kDNA), in a complex with the flagellum. A role for α-KDE2 in kDNA maintenance was revealed in α-KDE2 RNA interference (RNAi) knockdowns. Following RNAi induction, bloodstream trypanosomes showed pronounced growth reduction and often failed to equally distribute kDNA to daughter cells, resulting in accumulation of cells devoid of kDNA (dyskinetoplastic) or containing two kinetoplasts. Dyskinetoplastic trypanosomes lacked mitochondrial membrane potential and contained mitochondria of substantially reduced volume. These results indicate that α-KDE2 is bifunctional, both as a metabolic enzyme and as a mitochondrial inheritance factor necessary for the distribution of kDNA networks to daughter cells at cytokinesis. PMID:23125353

  16. Dual functions of α-ketoglutarate dehydrogenase E2 in the Krebs cycle and mitochondrial DNA inheritance in Trypanosoma brucei.

    PubMed

    Sykes, Steven E; Hajduk, Stephen L

    2013-01-01

    The dihydrolipoyl succinyltransferase (E2) of the multisubunit α-ketoglutarate dehydrogenase complex (α-KD) is an essential Krebs cycle enzyme commonly found in the matrices of mitochondria. African trypanosomes developmentally regulate mitochondrial carbohydrate metabolism and lack a functional Krebs cycle in the bloodstream of mammals. We found that despite the absence of a functional α-KD, bloodstream form (BF) trypanosomes express α-KDE2, which localized to the mitochondrial matrix and inner membrane. Furthermore, α-KDE2 fractionated with the mitochondrial genome, the kinetoplast DNA (kDNA), in a complex with the flagellum. A role for α-KDE2 in kDNA maintenance was revealed in α-KDE2 RNA interference (RNAi) knockdowns. Following RNAi induction, bloodstream trypanosomes showed pronounced growth reduction and often failed to equally distribute kDNA to daughter cells, resulting in accumulation of cells devoid of kDNA (dyskinetoplastic) or containing two kinetoplasts. Dyskinetoplastic trypanosomes lacked mitochondrial membrane potential and contained mitochondria of substantially reduced volume. These results indicate that α-KDE2 is bifunctional, both as a metabolic enzyme and as a mitochondrial inheritance factor necessary for the distribution of kDNA networks to daughter cells at cytokinesis.

  17. Apparent Anomalous Diffusion in the Cytoplasm of Human Cells: The Effect of Probes' Polydispersity.

    PubMed

    Kalwarczyk, Tomasz; Kwapiszewska, Karina; Szczepanski, Krzysztof; Sozanski, Krzysztof; Szymanski, Jedrzej; Michalska, Bernadeta; Patalas-Krawczyk, Paulina; Duszynski, Jerzy; Holyst, Robert

    2017-10-26

    This work, based on in vivo and in vitro measurements, as well as in silico simulations, provides a consistent analysis of diffusion of polydisperse nanoparticles in the cytoplasm of living cells. Using the example of fluorescence correlation spectroscopy (FCS), we show the effect of polydispersity of probes on the experimental results. Although individual probes undergo normal diffusion, in the ensemble of probes, an effective broadening of the distribution of diffusion times occurs-similar to anomalous diffusion. We introduced fluorescently labeled dextrans into the cytoplasm of HeLa cells and found that cytoplasmic hydrodynamic drag, exponentially dependent on probe size, extraordinarily broadens the distribution of diffusion times across the focal volume. As a result, the in vivo FCS data were effectively fitted with the anomalous subdiffusion model while for a monodisperse probe the normal diffusion model was most suitable. Diffusion time obtained from the anomalous diffusion model corresponds to a probe whose size is determined by the weight-average molecular weight of the polymer. The apparent anomaly exponent decreases with increasing polydispersity of the probes. Our results and methodology can be applied in intracellular studies of the mobility of nanoparticles, polymers, or oligomerizing proteins.

  18. 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.

  19. 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.

  20. 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

  1. Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

    PubMed Central

    Romero, María del Mar; Fernández-López, José Antonio; Remesar, Xavier; Alemany, Marià

    2012-01-01

    It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding. PMID:22479617

  2. Evaluating visibility of age spot and freckle based on simulated spectral reflectance distribution and facial color image

    NASA Astrophysics Data System (ADS)

    Hirose, Misa; Toyota, Saori; Tsumura, Norimichi

    2018-02-01

    In this research, we evaluate the visibility of age spot and freckle with changing the blood volume based on simulated spectral reflectance distribution and the actual facial color images, and compare these results. First, we generate three types of spatial distribution of age spot and freckle in patch-like images based on the simulated spectral reflectance. The spectral reflectance is simulated using Monte Carlo simulation of light transport in multi-layered tissue. Next, we reconstruct the facial color image with changing the blood volume. We acquire the concentration distribution of melanin, hemoglobin and shading components by applying the independent component analysis on a facial color image. We reproduce images using the obtained melanin and shading concentration and the changed hemoglobin concentration. Finally, we evaluate the visibility of pigmentations using simulated spectral reflectance distribution and facial color images. In the result of simulated spectral reflectance distribution, we found that the visibility became lower as the blood volume increases. However, we can see that a specific blood volume reduces the visibility of the actual pigmentations from the result of the facial color images.

  3. A serine residue in ClC-3 links phosphorylation-dephosphorylation to chloride channel regulation by cell volume.

    PubMed

    Duan, D; Cowley, S; Horowitz, B; Hume, J R

    1999-01-01

    In many mammalian cells, ClC-3 volume-regulated chloride channels maintain a variety of normal cellular functions during osmotic perturbation. The molecular mechanisms of channel regulation by cell volume, however, are unknown. Since a number of recent studies point to the involvement of protein phosphorylation/dephosphorylation in the control of volume-regulated ionic transport systems, we studied the relationship between channel phosphorylation and volume regulation of ClC-3 channels using site-directed mutagenesis and patch-clamp techniques. In native cardiac cells and when overexpressed in NIH/3T3 cells, ClC-3 channels were opened by cell swelling or inhibition of endogenous PKC, but closed by PKC activation, phosphatase inhibition, or elevation of intracellular Ca2+. Site-specific mutational studies indicate that a serine residue (serine51) within a consensus PKC-phosphorylation site in the intracellular amino terminus of the ClC-3 channel protein represents an important volume sensor of the channel. These results provide direct molecular and pharmacological evidence indicating that channel phosphorylation/dephosphorylation plays a crucial role in the regulation of volume sensitivity of recombinant ClC-3 channels and their native counterpart, ICl.vol.

  4. Counter-current chromatography: simple process and confusing terminology.

    PubMed

    Conway, Walter D

    2011-09-09

    The origin of counter-current chromatography is briefly stated, followed by a description of the mechanism of elution of solutes, which illustrates the elegance and simplicity of the technique. The CCC retention equation can be mentally derived from three facts; that a substance with a distribution coefficient of 0 elutes at the mobile phase solvent front (one mobile phase volume); and one with a distribution coefficient of 1 elutes at the column volume of mobile phase; and solutes with higher distribution coefficients elute at additional multiples of the stationary phase volume. The pattern corresponds to the classical solute retention equation for chromatography, V(R)=V(M)+K(C)V(S), K(C) not being limited to integer values. This allows the entire pattern of solute retention to be visualized on the chromatogram. The high volume fraction of stationary phase in CCC greatly enhances resolution. A survey of the names, symbols and definitions of several widely used chromatography and liquid-liquid distribution parameters in the IUPAC Gold Book and in a recent summary in LC-GC by Majors and Carr revealed numerous conflicts in both names and definitions. These will retard accurate dissemination of CCC research unless the discordance is resolved. It is proposed that the chromatography retention parameter, K(C), be called the distribution coefficient and that a new biphasic distribution parameter, K(Δ(A)), be defined for CCC and be called the species partition ratio. The definition of V(M) should be clarified. V(H) is suggested to represent the holdup volume and V(X) is suggested for the extra-column volume. H(V) and H(L) are suggested to represent the volume and length of a theoretical plate in CCC. Definitions of the phase ratio, β, conflict and should be clarified. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Preferred numbers and the distributions of trade sizes and trading volumes in the Chinese stock market

    NASA Astrophysics Data System (ADS)

    Mu, G.-H.; Chen, W.; Kertész, J.; Zhou, W.-X.

    2009-03-01

    The distributions of trade sizes and trading volumes are investigated based on the limit order book data of 22 liquid Chinese stocks listed on the Shenzhen Stock Exchange in the whole year 2003. We observe that the size distribution of trades for individualstocks exhibits jumps, which is caused by the number preference of traders when placing orders. We analyze the applicability of the “q-Gamma” function for fitting the distribution by the Cramér-von Mises criterion. The empirical PDFs of tradingvolumes at different timescales Δt ranging from 1 min to 240 min can be well modeled. The applicability of the q-Gamma functions for multiple trades is restricted to the transaction numbers Δn≤ 8. We find that all the PDFs have power-law tails for large volumes. Using careful estimation of the average tail exponents α of the distributions of trade sizes and trading volumes, we get α> 2, well outside the Lévy regime.

  6. Size distribution and growth rate of crystal nuclei near critical undercooling in small volumes

    NASA Astrophysics Data System (ADS)

    Kožíšek, Z.; Demo, P.

    2017-11-01

    Kinetic equations are numerically solved within standard nucleation model to determine the size distribution of nuclei in small volumes near critical undercooling. Critical undercooling, when first nuclei are detected within the system, depends on the droplet volume. The size distribution of nuclei reaches the stationary value after some time delay and decreases with nucleus size. Only a certain maximum size of nuclei is reached in small volumes near critical undercooling. As a model system, we selected recently studied nucleation in Ni droplet [J. Bokeloh et al., Phys. Rev. Let. 107 (2011) 145701] due to available experimental and simulation data. However, using these data for sample masses from 23 μg up to 63 mg (corresponding to experiments) leads to the size distribution of nuclei, when no critical nuclei in Ni droplet are formed (the number of critical nuclei < 1). If one takes into account the size dependence of the interfacial energy, the size distribution of nuclei increases to reasonable values. In lower volumes (V ≤ 10-9 m3) nucleus size reaches some maximum extreme size, which quickly increases with undercooling. Supercritical clusters continue their growth only if the number of critical nuclei is sufficiently high.

  7. IMPACT OF OBESITY SEVERITY AND DURATION ON PANCREATIC β-AND α-CELLS DYNAMICS IN NORMOGLYCEMIC NON-HUMAN PRIMATES

    PubMed Central

    Guardado-Mendoza, Rodolfo; Jimenez-Ceja, Lilia; Majluf-Cruz, Abraham; Kamath, Subhash; Fiorentino, Teresa Vanessa; Casiraghi, Francesca; Velazquez, Alberto Omar Chavez; DeFronzo, Ralph Anthony; Dick, Edward; Davalli, Alberto; Folli, Franco

    2012-01-01

    Objective Obesity is associated to high insulin and glucagon plasma levels. Enhanced β–cell function and β–cell expansion are responsible for insulin hypersecretion. It is unknown whether hyperglucagonemia is due to α-cell hypersecretion or to an increase in α-cell mass. In this study, we investigated the dynamics of the β-cell and α-cell function and mass in pancreas of obese normoglycemic baboons. Methods Pancreatic β- and α-cell volumes were measured in 51 normoglycemic baboons divided into 6 groups according to overweight severity or duration. Islets morphometric parameters were correlated to overweight and to diverse metabolic and laboratory parameters. Results Relative α-cell volume (RαV) and relative islet α-cell volume (RIαV) increased significantly with both overweight duration and severity. Conversely, in spite of the induction of insulin resistance, overweight produced only modest effects on relative β-cell volume (RβV) and relative islet β-cell volume (RIβV). Of note, RIβV did not increase neither with overweight duration nor with overweight severity, supposedly because of the concomitant, greater, increase in RIαV. Baboons' body weights correlated with serum levels of Interleukin-6 and Tumour Necrosis Factor-α soluble Receptors (IL-6sR and sTNF-R1), demonstrating that overweight induces abnormal activation of the signaling of two cytokines known to impact differently β- and α-cell viability and replication. Conclusion In conclusion, overweight and insulin resistance induce in baboons a significant increase in α-cell volumes (RαV, RIαV) while have minimal effects on the β-cells. This study suggests that an increase in the α-cell mass may precede the loss of β-cells and the transition to overt hyperglycemia and diabetes. PMID:23229736

  8. Organization of P, S, and Fe Inclusions in a Freshwater Magnetococcus

    NASA Technical Reports Server (NTRS)

    Cox, Lea; Popa Radu; Douglas, Susanne; Belz, Andrea; Nealson, Kenneth H.

    2001-01-01

    Magnetotactic bacteria are a heterogeneous group of motile, mainly aquatic procaryotes that align and swim along geomagnetic field lines. They are of interest to astrobiologists because of the magnetite crystals found in the Mars meteorite ALH84001 which share many characteristics with the magnetite produced intracellularly by magnetotactic bacteria. These bacteria are diverse morphologically, physiologically and phylogenetically, sharing a few key characteristics: 1) the presence of intracellular membrane-bound magnetic crystals (magnetosomes), usually but not always arranged in chains; 2) motility by means of flagella; and 3) microaerophillic or anaerobic physiology. The bilophotrichous (having two flagella bundles) magnetotactic cocci (MC) are ubiquitous in aquatic habitats but have proven extremely difficult to cultivate. Because only several marine strains have been isolated and grown in axenic culture, little is known about the physiology and the biogeochemical roles of the MC. We studied the composition and distribution of intracellular structures in an uncultured MC, designated ARB-1. To do this, a combination of light microscopy, environmental scanning electron microscopy (ESEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS) were used. Cells of ARB-1 were separated from sediments collected from Baldwin Lake (Los Angeles Arboretum, Arcadia, CA). They are large spherical to oblate spheroidal Gram-negative cells, ranging from 1 to 4 micrometers along the maximum dimension, which is perpendicular to the direction of swimming. Cells have two large phosphorus-containing inclusions that comprise a large percentage of the cell volume. Many smaller sulfur inclusions are located at the convex end of the cell. Most of the cellular Fe is present in the magnetosomes. These may be arranged as a clump at the concave end of the cell, near the two flagella bundles, or as chains, or as both a clump and chains. The magnetosomes were identified as magnetite (Fe3O4) by selected area electron diffraction (SAED) and high resolution TEM. We saw a trend between cell size and organization of the magnetosomes. Smaller, more spherical cells were more likely to have chains than were larger, more oblate cells. This may indicate different populations of cells, or it may be attributed to variations in cell growth cycle. The size distribution (length) of magnetosomes in chains was similar to that of magnetosomes in clusters, except that there was a larger size range for clustered magnetosomes. Magnetosomes from ARB-1 cells average 82 nm in length. If plotted on a graph of length as a function of aspect ratio, they fall within the single domain region of the plot. If compared with the size distributions of magnetite from ALH84001 and magnetosomes from the cultured magnetotactic vibrio MV-1, the magnetites produced by ARB-1 cells are, on average, larger and have a wider range of aspect ratio. ARB-1 cells have a specific organization of the P, S, and Fe inclusions. The P inclusions always occupy the majority of the cell volume and separate the S inclusions from the disorganized clumps of magnetosomes and the flagella bundles. The P inclusions may contain polyphosphate, which could play several roles in motility, adaptation to stress, growth and division, buoyancy, and energy. The S inclusions might be a way to store S, a potential energy source, when the cells move from sulfide to oxygen zones. The consistency of P, S, and Fe organization in ARB-1 cells suggests that these inclusions have some specific and interactive functions.

  9. Analytical performance evaluation of a high-volume hematology laboratory utilizing sigma metrics as standard of excellence.

    PubMed

    Shaikh, M S; Moiz, B

    2016-04-01

    Around two-thirds of important clinical decisions about the management of patients are based on laboratory test results. Clinical laboratories are required to adopt quality control (QC) measures to ensure provision of accurate and precise results. Six sigma is a statistical tool, which provides opportunity to assess performance at the highest level of excellence. The purpose of this study was to assess performance of our hematological parameters on sigma scale in order to identify gaps and hence areas of improvement in patient care. Twelve analytes included in the study were hemoglobin (Hb), hematocrit (Hct), red blood cell count (RBC), mean corpuscular volume (MCV), red cell distribution width (RDW), total leukocyte count (TLC) with percentages of neutrophils (Neutr%) and lymphocytes (Lymph %), platelet count (Plt), mean platelet volume (MPV), prothrombin time (PT), and fibrinogen (Fbg). Internal quality control data and external quality assurance survey results were utilized for the calculation of sigma metrics for each analyte. Acceptable sigma value of ≥3 was obtained for the majority of the analytes included in the analysis. MCV, Plt, and Fbg achieved value of <3 for level 1 (low abnormal) control. PT performed poorly on both level 1 and 2 controls with sigma value of <3. Despite acceptable conventional QC tools, application of sigma metrics can identify analytical deficits and hence prospects for the improvement in clinical laboratories. © 2016 John Wiley & Sons Ltd.

  10. 3D magnetospheric parallel hybrid multi-grid method applied to planet–plasma interactions

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

    Leclercq, L., E-mail: ludivine.leclercq@latmos.ipsl.fr; Modolo, R., E-mail: ronan.modolo@latmos.ipsl.fr; Leblanc, F.

    2016-03-15

    We present a new method to exploit multiple refinement levels within a 3D parallel hybrid model, developed to study planet–plasma interactions. This model is based on the hybrid formalism: ions are kinetically treated whereas electrons are considered as a inertia-less fluid. Generally, ions are represented by numerical particles whose size equals the volume of the cells. Particles that leave a coarse grid subsequently entering a refined region are split into particles whose volume corresponds to the volume of the refined cells. The number of refined particles created from a coarse particle depends on the grid refinement rate. In order tomore » conserve velocity distribution functions and to avoid calculations of average velocities, particles are not coalesced. Moreover, to ensure the constancy of particles' shape function sizes, the hybrid method is adapted to allow refined particles to move within a coarse region. Another innovation of this approach is the method developed to compute grid moments at interfaces between two refinement levels. Indeed, the hybrid method is adapted to accurately account for the special grid structure at the interfaces, avoiding any overlapping grid considerations. Some fundamental test runs were performed to validate our approach (e.g. quiet plasma flow, Alfven wave propagation). Lastly, we also show a planetary application of the model, simulating the interaction between Jupiter's moon Ganymede and the Jovian plasma.« less

  11. Planning evaluation of radiotherapy for complex lung cancer cases using helical tomotherapy

    NASA Astrophysics Data System (ADS)

    Kron, Tomas; Grigorov, Grigor; Yu, Edward; Yartsev, Slav; Chen, Jeff Z.; Wong, Eugene; Rodrigues, George; Trenka, Kris; Coad, Terry; Bauman, Glenn; Van Dyk, Jake

    2004-08-01

    Lung cancer treatment is one of the most challenging fields in radiotherapy. The aim of the present study was to investigate what role helical tomotherapy (HT), a novel approach to the delivery of highly conformal dose distributions using intensity-modulated radiation fan beams, can play in difficult cases with large target volumes typical for many of these patients. Tomotherapy plans were developed for 15 patients with stage III inoperable non-small-cell lung cancer. While not necessarily clinically indicated, elective nodal irradiation was included for all cases to create the most challenging scenarios with large target volumes. A 2 cm margin was used around the gross tumour volume (GTV) to generate primary planning target volume (PTV2) and 1 cm margin around elective nodes for secondary planning target volume (PTV1) resulting in PTV1 volumes larger than 1000 cm3 in 13 of the 15 patients. Tomotherapy plans were created using an inverse treatment planning system (TomoTherapy Inc.) based on superposition/convolution dose calculation for a fan beam thickness of 25 mm and a pitch factor between 0.3 and 0.8. For comparison, plans were created using an intensity-modulated radiation therapy (IMRT) approach planned on a commercial treatment planning system (TheraplanPlus, Nucletron). Tomotherapy delivery times for the large target volumes were estimated to be between 4 and 19 min. Using a prescribed dose of 60 Gy to PTV2 and 46 Gy to PTV1, the mean lung dose was 23.8 ± 4.6 Gy. A 'dose quality factor' was introduced to correlate the plan outcome with patient specific parameters. A good correlation was found between the quality of the HT plans and the IMRT plans with HT being slightly better in most cases. The overlap between lung and PTV was found to be a good indicator of plan quality for HT. The mean lung dose was found to increase by approximately 0.9 Gy per percent overlap volume. Helical tomotherapy planning resulted in highly conformal dose distributions. It allowed easy achievement of two different dose levels in the target simultaneously. As the overlap between PTV and lung volume is a major predictor of mean lung dose, future work will be directed to control of margins. Work is underway to investigate the possibility of breath-hold techniques for tomotherapy delivery to facilitate this aim.

  12. The "chloride theory", a unifying hypothesis for renal handling and body fluid distribution in heart failure pathophysiology.

    PubMed

    Kataoka, Hajime

    2017-07-01

    Body fluid volume regulation is a complex process involving the interaction of various afferent (sensory) and neurohumoral efferent (effector) mechanisms. Historically, most studies focused on the body fluid dynamics in heart failure (HF) status through control of the balance of sodium, potassium, and water in the body, and maintaining arterial circulatory integrity is central to a unifying hypothesis of body fluid regulation in HF pathophysiology. The pathophysiologic background of the biochemical determinants of vascular volume in HF status, however, has not been known. I recently demonstrated that changes in vascular and red blood cell volumes are independently associated with the serum chloride concentration, but not the serum sodium concentration, during worsening HF and its recovery. Based on these observations and the established central role of chloride in the renin-angiotensin-aldosterone system, I propose a unifying hypothesis of the "chloride theory" for HF pathophysiology, which states that changes in the serum chloride concentration are the primary determinant of changes in plasma volume and the renin-angiotensin-aldosterone system under worsening HF and therapeutic resolution of worsening HF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Solar power satellite system definition study. Volume 1: Executive summary

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Configuration concepts, option sizes, and systems definitions study design evolutions are reviewed. The main features of the present reference design silicon solar cell solar power satellite are described, as well as the provisions for space construction and support systems. The principal study accomplishments and conclusions are summarized according to the following tasks: (1) baseline critique; (2) construction and maintenance; (3) industrial complex needs, cost estimates, and production capacity; (4) launch complex requirements at KSC or at an offshore facility; (5) integration of the SPS/ground power network; (6) technology advancement and development; (7) costs and schedules; and (8) exploratory technology: laser annealing of solar cells degraded by proton irradiation, and a fiber-optic phase distribution link at 980 MHz.

  14. Fluid shear stress enhances the cell volume decrease of osteoblast cells by increasing the expression of the ClC-3 chloride channel

    PubMed Central

    LIU, LI; CAI, SIYI; QIU, GUIXING; LIN, JIN

    2016-01-01

    ClC-3 is a volume-sensitive chloride channel that is responsible for cell volume adjustment and regulatory cell volume decrease (RVD). In order to evaluate the effects of fluid shear stress (FSS) stimulation on the osteoblast ClC-3 chloride channel, MC3T3-E1 cells were stimulated by FSS in the experimental group. Fluorescence quantitative polymerase chain reaction was used to detect changes in ClC-3 mRNA expression, the chloride ion fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) was used to detect the chloride channel activity, and whole-cell patch clamping was used to monitor the changes in the volume-sensitive chloride current activated by a hypotonic environment following mechanical stimulation. The results show that the expression of the osteoblast chloride channel ClC-3 was significantly higher in the FSS group compared with the control group. MQAE fluorescence intensity was significantly reduced in the FSS group compared to the control group, suggesting that mechanical stimulation increased chloride channel activity and increased the efflux of intracellular chloride ions. Image analysis of osteoblast volume changes showed that osteoblast RVD was enhanced by mechanical stimulation. Whole-cell patch clamping showed that the osteoblast volume-sensitive chloride current was larger in the stimulated group compared to the control group, suggesting that elevated ClC-3 chloride channel expression results in an increased volume-sensitive chloride current. In conclusion, FSS stimulation enhances the RVD of osteoblast cell by increasing the expression of the ClC-3 and enhancing the chloride channel activity. PMID:27073622

  15. Effects of 1.9 MeV monoenergetic neutrons on Vicia faba chromosomes: microdosimetric considerations.

    PubMed

    Geard, C R

    1980-01-01

    Aerated Vicia faba root meristems were irradiated with 1.9 MeV monoenergetic neutrons. This source of neutrons optimally provides one class of particles (recoil protons) with ranges able to traverse cell nuclei at moderate to high-LET. The volumes of the Vicia faba nuclei were log-normally distributed with a mean of 1100 micrometer3. The yield of chromatid-type aberrations was linear against absorbed dose and near-constant over 5 collection periods (2-12 h), after irradiation. Energy deposition events (recoil protons) determined by microdosimetry were related to cytological changes with the finding that 19% of incident recoil protons initiate visible changes in Vicia faba chromosomes. It is probable that a substantial fraction of recoil proton track length and deposited energy is in insensitive (non-DNA containing) portions of the nuclear volume.

  16. Identification of a multifunctional protein, PhaM, that determines number, surface to volume ratio, subcellular localization and distribution to daughter cells of poly(3-hydroxybutyrate), PHB, granules in Ralstonia eutropha H16.

    PubMed

    Pfeiffer, Daniel; Wahl, Andreas; Jendrossek, Dieter

    2011-11-01

    A two-hybrid approach was applied to screen for proteins with the ability to interact with PHB synthase (PhaC1) of Ralstonia eutropha. The H16_A0141 gene (phaM) was identified in the majority of positive clones. PhaM (26.6 kDa) strongly interacted with PhaC1 and with phasin PhaP5 but not with PhaP1 or other PHB granule-associated proteins. A ΔphaM mutant accumulated only one or two large PHB granules instead of three to six medium-sized PHB granules of the wild type, and distribution of granules to daughter cells was disordered. All three phenotypes (number, size and distribution of PHB granules) were reversed by reintroduction of phaM. Purified PhaM revealed DNA-binding properties in gel mobility shift experiments. Expression of a fusion of the yellow fluorescent protein (eYfp) with PhaM resulted in formation of many small fluorescent granules that were bound to the nucleoid region. Remarkably, an eYfp-PhaP5 fusion localized at the cell poles in a PHB-negative background and overexpression of eYfp-PhaP5 in the wild type conferred binding of PHB granules to the cell poles. In conclusion, subcellular localization of PHB granules in R. eutropha depends on a concerted expression of at least three PHB granule-associated proteins, namely PhaM, PhaP5 and PHB synthase PhaC1. © 2011 Blackwell Publishing Ltd.

  17. Comparison of aerosol volume size distributions between column and surface measurements downwind of Seoul, Korea

    NASA Astrophysics Data System (ADS)

    Park, J. S.; Choi, Y.; Ghim, Y. S.

    2015-12-01

    The aerosol volume size distribution is one of the most important parameters in retrieving aerosol optical properties and studying radiative forcing. The column-integrated aerosol volume size distribution for AERONET was obtained from inversion product level 1.5 (22 bins between 0.1 and 30 μm in diameter) from the measurements of CIMEL sunphotometer (CE-318); that for SKYNET was obtained using skyrad.pack V5 (20 bins, 0.02-33 μm) from the measurements of PREDE skyradiometer (POM-02). The aerosol volume size distribution at the surface was measured using a wide range aerosol spectrometer system consisting of a scanning mobility particle scanner (Grimm, Model 5.419; 89 bins, 0.005-0.35 μm) and an optical particle counter (Grimm, Model 1.109; 31 bins, 0.27-34 μm). The measurement was conducted in Yongin, downwind of Seoul, Korea, from April 30 to June 27, 2015. The measurement site is located on the rooftop of a five-story building on the hill (37.34°N, 127.27°E, 167 m above sea level) in the global campus of Hankuk University of Foreign Studies. To investigate the discrepancy in effective diameter and fine mode volume fraction, we compared the volume size distributions when the measurement time coincided within 5 minutes because the measurement intervals were different between instruments.

  18. Effects of stiffness and volume on the transit time of an erythrocyte through a slit.

    PubMed

    Salehyar, Sara; Zhu, Qiang

    2017-06-01

    By using a fully coupled fluid-cell interaction model, we numerically simulate the dynamic process of a red blood cell passing through a slit driven by an incoming flow. The model is achieved by combining a multiscale model of the composite cell membrane with a boundary element fluid dynamics model based on the Stokes flow assumption. Our concentration is on the correlation between the transit time (the time it takes to finish the whole translocation process) and different conditions (flow speed, cell orientation, cell stiffness, cell volume, etc.) that are involved. According to the numerical prediction (with some exceptions), the transit time rises as the cell is stiffened. It is also highly sensitive to volume increase inside the cell. In general, even slightly swollen cells (i.e., the internal volume is increased while the surface area of the cell kept unchanged) travel dramatically slower through the slit. For these cells, there is also an increased chance of blockage.

  19. Application of evolutionary games to modeling carcinogenesis.

    PubMed

    Swierniak, Andrzej; Krzeslak, Michal

    2013-06-01

    We review a quite large volume of literature concerning mathematical modelling of processes related to carcinogenesis and the growth of cancer cell populations based on the theory of evolutionary games. This review, although partly idiosyncratic, covers such major areas of cancer-related phenomena as production of cytotoxins, avoidance of apoptosis, production of growth factors, motility and invasion, and intra- and extracellular signaling. We discuss the results of other authors and append to them some additional results of our own simulations dealing with the possible dynamics and/or spatial distribution of the processes discussed.

  20. Satellite Power Systems (SPS) concept definition study exhibit C. Volume 3: Experimental verification definition

    NASA Technical Reports Server (NTRS)

    1979-01-01

    An environmentally oriented microwave technology exploratory research program aimed at reducing the uncertainty associated with microwave power system critical technical issues is described. Topics discussed include: (1) Solar Power Satellite System (SPS) development plan elements; (2) critical technology issues related to the SPS preliminary reference configuration; (3) pilot plant to demonstrate commercial viability of the SPS system; and (4) research areas required to demonstrate feasibility of the SPS system. Progress in the development of advanced GaAs solar cells is reported along with a power distribution subsystem.

  1. K-Cl cotransporters, cell volume homeostasis, and neurological disease

    PubMed Central

    Kahle, Kristopher T.; Khanna, Arjun R.; Alper, Seth L.; Adragna, Norma C.; Lauf, Peter K.; Sun, Dandan; Delpire, Eric

    2016-01-01

    K+-Cl− cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. PMID:26142773

  2. K-Cl cotransporters, cell volume homeostasis, and neurological disease.

    PubMed

    Kahle, Kristopher T; Khanna, Arjun R; Alper, Seth L; Adragna, Norma C; Lauf, Peter K; Sun, Dandan; Delpire, Eric

    2015-08-01

    K(+)-Cl(-) cotransporters (KCCs) were originally characterized as regulators of red blood cell (RBC) volume. Since then, four distinct KCCs have been cloned, and their importance for volume regulation has been demonstrated in other cell types. Genetic models of certain KCCs, such as KCC3, and their inhibitory WNK-STE20/SPS1-related proline/alanine-rich kinase (SPAK) serine-threonine kinases, have demonstrated the evolutionary necessity of these molecules for nervous system cell volume regulation, structure, and function, and their involvement in neurological disease. The recent characterization of a swelling-activated dephosphorylation mechanism that potently stimulates the KCCs has pinpointed a potentially druggable switch of KCC activity. An improved understanding of WNK/SPAK-mediated KCC cell volume regulation in the nervous system might reveal novel avenues for the treatment of multiple neurological diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Physiological Role of Gap-Junctional Hemichannels

    PubMed Central

    Quist, Arjan Pieter; Rhee, Seung Keun; Lin, Hai; Lal, Ratneshwar

    2000-01-01

    Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to ≤1.6 mM) in an otherwise isosmotic condition, real-time AFM imaging revealed a significant and reversible increase in the volume of cells expressing gap-junctional proteins (connexins). Volume change did not occur in cells that were not expressing connexins. However, after the transient or stable transfection of connexin43, volume change did occur. The volume increase was accompanied by cytochalasin D-sensitive higher cell stiffness, which helped maintain cell integrity. These cellular physical changes were prevented by gap-junctional blockers, oleamide and β-glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation. PMID:10704454

  4. Femtosecond two-photon high-resolution 3D imaging, spatial-volume rendering and microspectral characterization of immunolocalized MHC-II and mLangerin/CD207 antigens in the mouse epidermis.

    PubMed

    Tirlapur, Uday K; Mulholland, William J; Bellhouse, Brian J; Kendall, Mark; Cornhill, J Fredrick; Cui, Zhanfeng

    2006-10-01

    Langerhans cells (LCs) play a sentinel role by initiating both adaptive and innate immune responses to antigens pertinent to the skin. With the discovery of various LCs markers including antibodies to major histocompatibility complex class II (MHC-II) molecules and CD1a, intracellular presence of racket-shaped "Birbeck granules," and very recently Langerin/CD207, LCs can be readily distinguished from other subsets of dendritic cells. Femtosecond two-photon laser scanning microscopy (TPLSM) in recent years has emerged as an alternative to the single photon-excitation based confocal laser scanning microscope (CLSM), particularly for minimally-invasive deep-tissue 3D and 4D vital as well as nonvital biomedical imaging. We have recently combined high resolution two-photon immunofluorescence (using anti MHC-II and Langerin/CD207 antibodies) imaging with microspectroscopy and advanced image-processing/volume-rendering modalities. In this work, we demonstrate the use of this novel state-of-the-art combinational approach to characterize the steady state 3D organization and spectral features of the mouse epidermis, particularly to identify the spatial distribution of LCs. Our findings provide unequivocal direct evidence that, in the mouse epidermis, the MHC-II and mLangerin/CD207 antigens do indeed manifest a high degree of colocalization around the nucleus of the LCs, while in the distal dendritic processes, mLangerin/CD207 antigens are rather sparsely distributed as punctuate structures. This unique possibility to simultaneously visualize high resolution 3D-resolved spatial distributions of two different immuno-reactive antigens, namely MHC-II and mLangerin/CD207, along with the nuclei of LCs and the adjacent epidermal cells can find interesting applications. These could involve aspects associated with pragmatic analysis of the kinetics of LCs migration as a function of immuno-dermatological responses during (1) human Immunodeficiency virus disease progression, (2) vaccination and targeted gene therapy, (3) skin transplantation/plastic surgery, (4) ultraviolet and other radiation exposure, (5) tissue-engineering of 3D skin constructs, as well as in (6) cosmetic industry, to unravel the influence of cosmeceuticals.

  5. Active unjamming of confluent cell layers

    NASA Astrophysics Data System (ADS)

    Marchetti, M. Cristina

    Cell motion inside dense tissues governs many biological processes, including embryonic development and cancer metastasis, and recent experiments suggest that these tissues exhibit collective glassy behavior. Motivated by these observations, we have studied a model of dense tissues that combines self-propelled particle models and vertex models of confluent cell layers. In this model, referred to as self-propelled Voronoi (SPV), cells are described as polygons in a Voronoi tessellation with directed noisy cell motility and interactions governed by a shape energy that incorporates the effects of cell volume incompressibility, contractility and cell-cell adhesion. Using this model, we have demonstrated a new density-independent solid-liquid transition in confluent tissues controlled by cell motility and a cell-shape parameter measuring the interplay of cortical tension and cell-cell adhesion. An important insight of this work is that the rigidity and dynamics of cell layers depends sensitively on cell shape. We have also used the SPV model to test a new method developed by our group to determine cellular forces and tissue stresses from experimentally accessible cell shapes and traction forces, hence providing the spatio-temporal distribution of stresses in motile dense tissues. This work was done with Dapeng Bi, Lisa Manning and Xingbo Yang. MCM was supported by NSF-DMR-1305184 and by the Simons Foundation.

  6. TRPV4 and AQP4 Channels Synergistically Regulate Cell Volume and Calcium Homeostasis in Retinal Müller Glia

    PubMed Central

    Jo, Andrew O.; Phuong, Tam T.T.; Verkman, Alan S.; Yarishkin, Oleg; MacAulay, Nanna

    2015-01-01

    Brain edema formation occurs after dysfunctional control of extracellular volume partly through impaired astrocytic ion and water transport. Here, we show that such processes might involve synergistic cooperation between the glial water channel aquaporin 4 (AQP4) and the transient receptor potential isoform 4 (TRPV4), a polymodal swelling-sensitive cation channel. In mouse retinas, TRPV4 colocalized with AQP4 in the end feet and radial processes of Müller astroglia. Genetic ablation of TRPV4 did not affect the distribution of AQP4 and vice versa. However, retinas from Trpv4−/− and Aqp4−/− mice exhibited suppressed transcription of genes encoding Trpv4, Aqp4, and the Kir4.1 subunit of inwardly rectifying potassium channels. Swelling and [Ca2+]i elevations evoked in Müller cells by hypotonic stimulation were antagonized by the selective TRPV4 antagonist HC-067047 (2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide) or Trpv4 ablation. Elimination of Aqp4 suppressed swelling-induced [Ca2+]i elevations but only modestly attenuated the amplitude of Ca2+ signals evoked by the TRPV4 agonist GSK1016790A [(N-((1S)-1-{[4-((2S)-2-{[(2,4-dichlorophenyl)sulfonyl]amino}-3-hydroxypropanoyl)-1-piperazinyl]carbonyl}-3-methylbutyl)-1-benzothiophene-2-carboxamide]. Glial cells lacking TRPV4 but not AQP4 showed deficits in hypotonic swelling and regulatory volume decrease. Functional synergy between TRPV4 and AQP4 during cell swelling was confirmed in the heterologously expressing Xenopus oocyte model. Importantly, when the swelling rate was osmotically matched for AQP4-positive and AQP4-negative oocytes, TRPV4 activation became independent of AQP4. We conclude that AQP4-mediated water fluxes promote the activation of the swelling sensor, whereas Ca2+ entry through TRPV4 channels reciprocally modulates volume regulation, swelling, and Aqp4 gene expression. Therefore, TRPV4–AQP4 interactions constitute a molecular system that fine-tunes astroglial volume regulation by integrating osmosensing, calcium signaling, and water transport and, when overactivated, triggers pathological swelling. SIGNIFICANCE STATEMENT We characterize the physiological features of interactions between the astroglial swelling sensor transient receptor potential isoform 4 (TRPV4) and the aquaporin 4 (AQP4) water channel in retinal Müller cells. Our data reveal an elegant and complex set of mechanisms involving reciprocal interactions at the level of glial gene expression, calcium homeostasis, swelling, and volume regulation. Specifically, water influx through AQP4 drives calcium influx via TRPV4 in the glial end foot, which regulates expression of Aqp4 and Kir4.1 genes and facilitates the time course and amplitude of hypotonicity-induced swelling and regulatory volume decrease. We confirm the crucial facets of the signaling mechanism in heterologously expressing oocytes. These results identify the molecular mechanism that contributes to dynamic regulation of glial volume but also provide new insights into the pathophysiology of glial reactivity and edema formation. PMID:26424896

  7. SU-E-T-429: Uncertainties of Cell Surviving Fractions Derived From Tumor-Volume Variation Curves

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

    Chvetsov, A

    2014-06-01

    Purpose: To evaluate uncertainties of cell surviving fraction reconstructed from tumor-volume variation curves during radiation therapy using sensitivity analysis based on linear perturbation theory. Methods: The time dependent tumor-volume functions V(t) have been calculated using a twolevel cell population model which is based on the separation of entire tumor cell population in two subpopulations: oxygenated viable and lethally damaged cells. The sensitivity function is defined as S(t)=[δV(t)/V(t)]/[δx/x] where δV(t)/V(t) is the time dependent relative variation of the volume V(t) and δx/x is the relative variation of the radiobiological parameter x. The sensitivity analysis was performed using direct perturbation method wheremore » the radiobiological parameter x was changed by a certain error and the tumor-volume was recalculated to evaluate the corresponding tumor-volume variation. Tumor volume variation curves and sensitivity functions have been computed for different values of cell surviving fractions from the practically important interval S{sub 2}=0.1-0.7 using the two-level cell population model. Results: The sensitivity functions of tumor-volume to cell surviving fractions achieved a relatively large value of 2.7 for S{sub 2}=0.7 and then approached zero as S{sub 2} is approaching zero Assuming a systematic error of 3-4% we obtain that the relative error in S{sub 2} is less that 20% in the range S2=0.4-0.7. This Resultis important because the large values of S{sub 2} are associated with poor treatment outcome should be measured with relatively small uncertainties. For the very small values of S2<0.3, the relative error can be larger than 20%; however, the absolute error does not increase significantly. Conclusion: Tumor-volume curves measured during radiotherapy can be used for evaluation of cell surviving fractions usually observed in radiation therapy with conventional fractionation.« less

  8. Volume and surface area size distribution, water mass and model fitting of GCE/CASE/WATOX marine aerosols

    NASA Astrophysics Data System (ADS)

    Kim, Y.; Sievering, H.; Boatman, J.

    1990-06-01

    As a part of the Global Change Expedition/Coordinated Air-Sea Experiment/Western Atlantic Ocean Experiment (GCE/CASE/WATOX), size distributions of marine aerosols were measured at two altitudes of about 2750 and 150 m above sea level (asl) over the size range 0.1 ˜ 32 μm. Lognormal fitting was applied to the corrected aerosol size spectra to determine the volume and surface area size distributions of the CASE-WATOX marine aerosols. Each aerosol size distribution was fitted with three lognormal distributions representing fine-, large-, and giant-particle modes. Water volume fraction and dry particle size of each aerosol size distribution were also calculated using empirical formulas for particle size as a function of relative humidity and particle type. Because of the increased influence from anthropogenic sources in the continental United States, higher aerosol volume concentrations were observed in the fine-particle mode near-shore off the east coast; 2.11 and 3.63 μm3 cm-3 for free troposphere (FT) and marine boundary layer (MBL), compared with the open-sea Bermuda area values; 0.13 and 0.74 μm3 cm-3 for FT and MBL. The large-particle mode exhibits the least variations in volume distributions between the east coast and open-sea Bermuda area, having a volume geometric median diameter (VGMD) between 1.4 and 1.6 μm and a geometric standard deviation between 1.57 and 1.68. For the giant-particle mode, larger VGMD and volume concentrations were observed for marine aerosols nearshore off the east coast than in the open-sea Bermuda area because of higher relative humidity and higher surface wind speed conditions. Wet VGMD and aerosol water volume concentrations at 15 m asl ship level were determined by extrapolating from those obtained by analysis of the CASE-WATOX aircraft aerosol data. Abundance of aerosol water in the MBL serves as an important pathway for heterogeneous conversion of SO2 in sea salt aerosol particles.

  9. Electrolyte volume effects on electrochemical performance and solid electrolyte interphase in Si-graphite/NMC lithium-ion pouch cells

    DOE PAGES

    An, Seong Jin; Li, Jianlin; Daniel, Claus; ...

    2017-05-15

    This study aims to explore the correlations between electrolyte volume, electrochemical performance, and properties of the solid electrolyte interphase in pouch cells with Si-graphite composite anodes. The electrolyte is 1.2 M LiPF 6 in ethylene carbonate:ethylmethyl carbonate with 10 wt.% fluoroethylene carbonate. Single layer pouch cells (100 mAh) were constructed with 15 wt.% Si-graphite/LiNi 0.5Mn 0.3CO 0.2O 2 electrodes. It is found that a minimum electrolyte volume factor of 3.1 times the total pore volume of cell components (cathode, anode, and separator) is needed for better cycling stability. Less electrolyte causes increases in ohmic and charge transfer resistances. Lithium dendritesmore » are observed when the electrolyte volume factor is low. The resistances from the anodes become significant as the cells are discharged. As a result, solid electrolyte interphase thickness grows as the electrolyte volume factor increases and is non-uniform after cycling.« less

  10. Reproducibility and relative stability in magnetic resonance imaging indices of tumor vascular physiology over a period of 24h in a rat 9L gliosarcoma model.

    PubMed

    Nagaraja, Tavarekere N; Elmghirbi, Rasha; Brown, Stephen L; Schultz, Lonni R; Lee, Ian Y; Keenan, Kelly A; Panda, Swayamprava; Cabral, Glauber; Mikkelsen, Tom; Ewing, James R

    2017-12-01

    The objective was to study temporal changes in tumor vascular physiological indices in a period of 24h in a 9L gliosarcoma rat model. Fischer-344 rats (N=14) were orthotopically implanted with 9L cells. At 2weeks post-implantation, they were imaged twice in a 24h interval using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Data-driven model-selection-based analysis was used to segment tumor regions with varying vascular permeability characteristics. The region with the maximum number of estimable parameters of vascular kinetics was chosen for comparison across the two time points. It provided estimates of three parameters for an MR contrast agent (MRCA): i) plasma volume (v p ), ii) forward volumetric transfer constant (K trans ) and interstitial volume fraction (v e , ratio of K trans to reverse transfer constant, k ep ). In addition, MRCA extracellular distribution volume (V D ) was estimated in the tumor and its borders, along with tumor blood flow (TBF) and peritumoral MRCA flux. Descriptors of parametric distributions were compared between the two times. Tumor extent was examined by hematoxylin and eosin (H&E) staining. Picrosirus red staining of secreted collagen was performed as an additional index for 9L cells. Test-retest differences between population summaries for any parameter were not significant (paired t and Wilcoxon signed rank tests). Bland-Altman plots showed no apparent trends between the differences and averages of the test-retest measures for all indices. The intraclass correlation coefficients showed moderate to almost perfect reproducibility for all of the parameters, except v p . H&E staining showed tumor infiltration in parenchyma, perivascular space and white matter tracts. Collagen staining was observed along the outer edges of main tumor mass. The data suggest the relative stability of these MR indices of tumor microenvironment over a 24h duration in this gliosarcoma model. Copyright © 2017. Published by Elsevier Inc.

  11. 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.

  12. SYNTHESIS OF NOVEL ALL-DIELECTRIC GRATING FILTERS USING GENETIC ALGORITHMS

    NASA Technical Reports Server (NTRS)

    Zuffada, Cinzia; Cwik, Tom; Ditchman, Christopher

    1997-01-01

    We are concerned with the design of inhomogeneous, all dielectric (lossless) periodic structures which act as filters. Dielectric filters made as stacks of inhomogeneous gratings and layers of materials are being used in optical technology, but are not common at microwave frequencies. The problem is then finding the periodic cell's geometric configuration and permittivity values which correspond to a specified reflectivity/transmittivity response as a function of frequency/illumination angle. This type of design can be thought of as an inverse-source problem, since it entails finding a distribution of sources which produce fields (or quantities derived from them) of given characteristics. Electromagnetic sources (electric and magnetic current densities) in a volume are related to the outside fields by a well known linear integral equation. Additionally, the sources are related to the fields inside the volume by a constitutive equation, involving the material properties. Then, the relationship linking the fields outside the source region to those inside is non-linear, in terms of material properties such as permittivity, permeability and conductivity. The solution of the non-linear inverse problem is cast here as a combination of two linear steps, by explicitly introducing the electromagnetic sources in the computational volume as a set of unknowns in addition to the material unknowns. This allows to solve for material parameters and related electric fields in the source volume which are consistent with Maxwell's equations. Solutions are obtained iteratively by decoupling the two steps. First, we invert for the permittivity only in the minimization of a cost function and second, given the materials, we find the corresponding electric fields through direct solution of the integral equation in the source volume. The sources thus computed are used to generate the far fields and the synthesized triter response. The cost function is obtained by calculating the deviation between the synthesized value of reflectivity/transmittivity and the desired one. Solution geometries for the periodic cell are sought as gratings (ensembles of columns of different heights and widths), or combinations of homogeneous layers of different dielectric materials and gratings. Hence the explicit unknowns of the inversion step are the material permittivities and the relative boundaries separating homogeneous parcels of the periodic cell.

  13. Decoding Size Distribution Patterns in Marine and Transitional Water Phytoplankton: From Community to Species Level

    PubMed Central

    Roselli, Leonilde; Basset, Alberto

    2015-01-01

    Understanding the mechanisms of phytoplankton community assembly is a fundamental issue of aquatic ecology. Here, we use field data from transitional (e.g. coastal lagoons) and coastal water environments to decode patterns of phytoplankton size distribution into organization and adaptive mechanisms. Transitional waters are characterized by higher resource availability and shallower well-mixed water column than coastal marine environments. Differences in physico-chemical regime between the two environments have been hypothesized to exert contrasting selective pressures on phytoplankton cell morphology (size and shape). We tested the hypothesis focusing on resource availability (nutrients and light) and mixed layer depth as ecological axes that define ecological niches of phytoplankton. We report fundamental differences in size distributions of marine and freshwater diatoms, with transitional water phytoplankton significantly smaller and with higher surface to volume ratio than marine species. Here, we hypothesize that mixing condition affecting size-dependent sinking may drive phytoplankton size and shape distributions. The interplay between shallow mixed layer depth and frequent and complete mixing of transitional waters may likely increase the competitive advantage of small phytoplankton limiting large cell fitness. The nutrient regime appears to explain the size distribution within both marine and transitional water environments, while it seem does not explain the pattern observed across the two environments. In addition, difference in light availability across the two environments appear do not explain the occurrence of asymmetric size distribution at each hierarchical level. We hypothesize that such competitive equilibria and adaptive strategies in resource exploitation may drive by organism’s behavior which exploring patch resources in transitional and marine phytoplankton communities. PMID:25974052

  14. A physical multifield model predicts the development of volume and structure in the human brain

    NASA Astrophysics Data System (ADS)

    Rooij, Rijk de; Kuhl, Ellen

    2018-03-01

    The prenatal development of the human brain is characterized by a rapid increase in brain volume and a development of a highly folded cortex. At the cellular level, these events are enabled by symmetric and asymmetric cell division in the ventricular regions of the brain followed by an outwards cell migration towards the peripheral regions. The role of mechanics during brain development has been suggested and acknowledged in past decades, but remains insufficiently understood. Here we propose a mechanistic model that couples cell division, cell migration, and brain volume growth to accurately model the developing brain between weeks 10 and 29 of gestation. Our model accurately predicts a 160-fold volume increase from 1.5 cm3 at week 10 to 235 cm3 at week 29 of gestation. In agreement with human brain development, the cortex begins to form around week 22 and accounts for about 30% of the total brain volume at week 29. Our results show that cell division and coupling between cell density and volume growth are essential to accurately model brain volume development, whereas cell migration and diffusion contribute mainly to the development of the cortex. We demonstrate that complex folding patterns, including sinusoidal folds and creases, emerge naturally as the cortex develops, even for low stiffness contrasts between the cortex and subcortex.

  15. Correlating Free-Volume Hole Distribution to the Glass Transition Temperature of Epoxy Polymers.

    PubMed

    Aramoon, Amin; Breitzman, Timothy D; Woodward, Christopher; El-Awady, Jaafar A

    2017-09-07

    A new algorithm is developed to quantify the free-volume hole distribution and its evolution in coarse-grained molecular dynamics simulations of polymeric networks. This is achieved by analyzing the geometry of the network rather than a voxelized image of the structure to accurately and efficiently find and quantify free-volume hole distributions within large scale simulations of polymer networks. The free-volume holes are quantified by fitting the largest ellipsoids and spheres in the free-volumes between polymer chains. The free-volume hole distributions calculated from this algorithm are shown to be in excellent agreement with those measured from positron annihilation lifetime spectroscopy (PALS) experiments at different temperature and pressures. Based on the results predicted using this algorithm, an evolution model is proposed for the thermal behavior of an individual free-volume hole. This model is calibrated such that the average radius of free-volumes holes mimics the one predicted from the simulations. The model is then employed to predict the glass-transition temperature of epoxy polymers with different degrees of cross-linking and lengths of prepolymers. Comparison between the predicted glass-transition temperatures and those measured from simulations or experiments implies that this model is capable of successfully predicting the glass-transition temperature of the material using only a PDF of the initial free-volume holes radii of each microstructure. This provides an effective approach for the optimized design of polymeric systems on the basis of the glass-transition temperature, degree of cross-linking, and average length of prepolymers.

  16. Continuous distributions of specific ventilation recovered from inert gas washout

    NASA Technical Reports Server (NTRS)

    Lewis, S. M.; Evans, J. W.; Jalowayski, A. A.

    1978-01-01

    A new technique is described for recovering continuous distributions of ventilation as a function of tidal ventilation/volume ratio from the nitrogen washout. The analysis yields a continuous distribution of ventilation as a function of tidal ventilation/volume ratio represented as fractional ventilations of 50 compartments plus dead space. The procedure was verified by recovering known distributions from data to which noise had been added. Using an apparatus to control the subject's tidal volume and FRC, mixed expired N2 data gave the following results: (a) the distributions of young, normal subjects were narrow and unimodal; (b) those of subjects over age 40 were broader with more poorly ventilated units; (c) patients with pulmonary disease of all descriptions showed enlarged dead space; (d) patients with cystic fibrosis showed multimodal distributions with the bulk of the ventilation going to overventilated units; and (e) patients with obstructive lung disease fell into several classes, three of which are illustrated.

  17. Availability and temporal heterogeneity of water supply affect the vertical distribution and mortality of a belowground herbivore and consequently plant growth.

    PubMed

    Tsunoda, Tomonori; Kachi, Naoki; Suzuki, Jun-Ichirou

    2014-01-01

    We examined how the volume and temporal heterogeneity of water supply changed the vertical distribution and mortality of a belowground herbivore, and consequently affected plant biomass. Plantago lanceolata (Plantaginaceae) seedlings were grown at one per pot under different combinations of water volume (large or small volume) and heterogeneity (homogeneous water conditions, watered every day; heterogeneous conditions, watered every 4 days) in the presence or absence of a larva of the belowground herbivorous insect, Anomala cuprea (Coleoptera: Scarabaeidae). The larva was confined in different vertical distributions to top feeding zone (top treatment), middle feeding zone (middle treatment), or bottom feeding zone (bottom treatment); alternatively no larva was introduced (control treatment) or larval movement was not confined (free treatment). Three-way interaction between water volume, heterogeneity, and the herbivore significantly affected plant biomass. With a large water volume, plant biomass was lower in free treatment than in control treatment regardless of heterogeneity. Plant biomass in free treatment was as low as in top treatment. With a small water volume and in free treatment, plant biomass was low (similar to that under top treatment) under homogeneous water conditions but high under heterogeneous ones (similar to that under middle or bottom treatment). Therefore, there was little effect of belowground herbivory on plant growth under heterogeneous water conditions. In other watering regimes, herbivores would be distributed in the shallow soil and reduced root biomass. Herbivore mortality was high with homogeneous application of a large volume or heterogeneous application of a small water volume. Under the large water volume, plant biomass was high in pots in which the herbivore had died. Thus, the combinations of water volume and heterogeneity affected plant growth via the change of a belowground herbivore.

  18. The Relationship of Mean Platelet Volume/Platelet Distribution Width and Duodenal Ulcer Perforation.

    PubMed

    Fan, Zhe; Zhuang, Chengjun

    2017-03-01

    Duodenal ulcer perforation (DUP) is a severe acute abdominal disease. Mean platelet volume (MPV) and platelet distribution width (PDW) are two platelet parameters, participating in many inflammatory processes. This study aims to investigate the relation of MPV/PDW and DUP. A total of 165 patients were studied retrospectively, including 21 females and 144 males. The study included two groups: 87 normal patients (control group) and 78 duodenal ulcer perforation patients (DUP group). Routine blood parameters were collected for analysis including white blood cell count (WBC), neutrophil ratio (NR), platelet count (PLT), MPV and PDW. Receiver operating curve (ROC) analysis was applied to evaluate the parameters' sensitivity. No significant differences were observed between the control group and DUP group in age and gender. WBC, NR and PDW were significantly increased in the DUP group ( P <0.001, respectively); PLT and MPV were significantly decreased in the DUP group ( P <0.001, respectively) compared to controls. MPV had the high sensitivity. Our results suggested a potential association between MPV/PDW and disease activity in DUP patients, and high sensitivity of MPV. © 2017 by the Association of Clinical Scientists, Inc.

  19. Building an experimental model of the human body with non-physiological parameters.

    PubMed

    Labuz, Joseph M; Moraes, Christopher; Mertz, David R; Leung, Brendan M; Takayama, Shuichi

    2017-03-01

    New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform - commonly called a 'human-on-a-chip (HOC)' - requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo -like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O 2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10 -6 ) microfluidic model of the human body.

  20. Integrated microfluidic system with simultaneous emulsion generation and concentration.

    PubMed

    Koppula, Karuna S; Fan, Rong; Veerapalli, Kartik R; Wan, Jiandi

    2016-03-15

    Because the size, size distribution, and concentration of emulsions play an important role in most of the applications, controlled emulsion generation and effective concentration are of great interest in fundamental and applied studies. While microfluidics has been demonstrated to be able to produce emulsion drops with controlled size, size distribution, and hierarchical structures, progress of controlled generation of concentrated emulsions is limited. Here, we present an effective microfluidic emulsion generation system integrated with an orifice structure to separate aqueous droplets from the continuous oil phase, resulting in concentrated emulsion drops in situ. Both experimental and simulation results show that the efficiency of separation is determined by a balance between pressure drop and droplet accumulation near the orifice. By manipulating this balance via changing flow rates and microfluidic geometry, we can achieve monodisperse droplets on chip that have a concentration as high as 80,000 drops per microliter (volume fraction of 66%). The present approach thus provides insights to the design of microfluidic device that can be used to concentrate emulsions (drops and bubbles), colloidal particles (drug delivery polymer particles), and biological particles (cells and bacteria) when volume fractions as high as 66% are necessary. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Building an experimental model of the human body with non-physiological parameters

    PubMed Central

    Labuz, Joseph M.; Moraes, Christopher; Mertz, David R.; Leung, Brendan M.; Takayama, Shuichi

    2017-01-01

    New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform — commonly called a ‘human-on-a-chip (HOC)’ — requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo-like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10−6) microfluidic model of the human body. PMID:28713851

  2. FORSPAN Model Users Guide

    USGS Publications Warehouse

    Klett, T.R.; Charpentier, Ronald R.

    2003-01-01

    The USGS FORSPAN model is designed for the assessment of continuous accumulations of crude oil, natural gas, and natural gas liquids (collectively called petroleum). Continuous (also called ?unconventional?) accumulations have large spatial dimensions and lack well defined down-dip petroleum/water contacts. Oil and natural gas therefore are not localized by buoyancy in water in these accumulations. Continuous accumulations include ?tight gas reservoirs,? coalbed gas, oil and gas in shale, oil and gas in chalk, and shallow biogenic gas. The FORSPAN model treats a continuous accumulation as a collection of petroleumcontaining cells for assessment purposes. Each cell is capable of producing oil or gas, but the cells may vary significantly from one another in their production (and thus economic) characteristics. The potential additions to reserves from continuous petroleum resources are calculated by statistically combining probability distributions of the estimated number of untested cells having the potential for additions to reserves with the estimated volume of oil and natural gas that each of the untested cells may potentially produce (total recovery). One such statistical method for combination of number of cells with total recovery, used by the USGS, is called ACCESS.

  3. Lightweight armor system

    DOEpatents

    Chu, Henry S; Langhorst, Benjamin R; Bakas, Michael P; Thinnes, Gary L

    2013-02-26

    The disclosure provides a shock absorbing layer comprised of one or more shock absorbing cells, where a shock absorbing cell is comprised of a cell interior volume containing a plurality of hydrogel particles and a free volume, and where the cell interior volume is surrounded by a containing layer. The containing layer has a permeability such that the hydrogel particles when swollen remain at least partially within the cell interior volume when subjected to a design shock pressure wave, allowing for force relaxation through hydrogel compression response. Additionally, the permeability allows for the flow of exuded free water, further dissipating wave energy. In an embodiment, a plurality of shock absorbing cells is combined with a penetration resistant material to mitigate the transmitted shock wave generated by an elastic precursor wave in the penetration resistant material.

  4. The influence of gravity on the formation of amyloplasts in columella cells of Zea mays L

    NASA Technical Reports Server (NTRS)

    Moore, R.; Fondren, W. M.; Koon, E. C.; Wang, C. L.

    1986-01-01

    Columella (i.e., putative graviperceptive) cells of Zea mays seedlings grown in the microgravity of outer space allocate significantly less volume to putative statoliths (amyloplasts) than do columella cells of Earth-grown seedlings. Amyloplasts of flight-grown seedlings are significantly smaller than those of ground controls, as is the average volume of individual starch grains. Similarly, the relative volume of starch in amyloplasts in columella cells of flight-grown seedlings is significantly less than that of Earth-grown seedlings. Microgravity does not significantly alter the volume of columella cells, the average number of amyloplasts per columella cell, or the number of starch grains per amyloplast. These results are discussed relative to the influence of gravity on cellular and organellar structure.

  5. Third-space fluid distribution of pemetrexed in non-small cell lung cancer patients.

    PubMed

    Honoré, Per Hartvig; Joensen, Sigrid Jóhansdóttir; Olsen, Michelle; Hansen, Steen Honoré; Mellemgaard, Anders

    2014-08-01

    Hydrophilic drugs particularly those with low plasma protein binding may accumulate in third-space fluid in the body. Cytotoxic drugs like methotrexate (MTX) cause damage in the tissue, and evacuation of the third-space fluid in pleura is strongly recommended before new dosing. Pemetrexed (PEM) is a multi-targeted antifolate similar to MTX approved for the treatment for malignant pleural mesothelioma and non-small cell lung cancer. Current recommendations for patients receiving treatment with PEM prescribe draining of the pleural fluid. This is based upon the recommendations for MTX and not directly to any specific findings relating to PEM. The recommendations are the same because PEM is an analogue of MTX; the molecular structures and pharmacokinetic parameters are similar. However, since draining the pleural fluid is painful and cancer patient are particularly susceptible to infection subsequently, it is relevant to examine the recommendations for PEM explicitly. Eight patients treated with a 500 mg/m(2) PEM combined with platinum salt were examined. Plasma samples were first collected in relation to the start of PEM infusion. Thereafter, plasma and pleura samples were taken at various times after drug infusion from each patient; in two patients, sampling was done twice but on different occasions. The quantitative determination of PEM was performed with reversed-phase high-performance liquid chromatography, and sample preparation was performed using protein precipitation with perchloric acid. Pharmacokinetic analysis was performed using a non-compartment method as well a two-compartment model. The results were calculated from 10 samples taken from eight patients, where data from one patient point were excluded as the patient had impaired renal function, and three samples were reported as below limit of quantification. The plasma PEM pharmacokinetics calculated showed an elimination half-life (t ½ elimination) of 3.2 h and distribution half-life (t ½-distribution) of 6 min. Clearance (CL) was 5.1 L/h, central volume of distribution (V(central)) 23.2 L and peripheral volume distribution (V(peripheral)) 10.6 L, and the area under the curve was 186 μg h/mL. Using non-compartment methods, an elimination half-life of 3.1 h and an apparent CL of 3.2 L/h were measured, whereas an apparent steady-state volume became 14.2 L. The pleura concentrations were only half of simultaneous plasma concentrations, and elimination half-life was 3.15 h. Pemetrexed is not likely to accumulate in the pleural fluid, and evacuation of fluid might not be necessary. Further investigation is needed to recommend no drainage of the fluid, i.e., in patients with renal impairment.

  6. Optical properties of porous polylactide scaffolds

    NASA Astrophysics Data System (ADS)

    Yusupov, Vladimir I.; Sviridov, Alexander P.; Zhigarkov, Vyacheslav S.; Shubnyy, Andrey G.; Vorobieva, Nataliya N.; Churbanov, Semyon N.; Minaev, Nikita V.; Timashev, Peter S.; Rochev, Yury A.; Bagratashvili, Victor N.

    2018-04-01

    Light field intensity distribution in three-dimensional polylactide scaffolds after irradiation with low-intensity light from one side of the samples has been determined in the visible and near-infrared regions of the spectrum. Two different types of scaffolds manufactured by the methods of supercritical fluid foaming and surface selective laser sintering have been investigated. The problem is solved by numerical calculation according to the Monte Carlo method involving experimentally obtained information about effective optical parameters of the scaffold material. Information about intensity distribution of the incident light in the matrix volume is needed to assess the radiation level for the scaffold cells after photobiostimulation. It has been shown that the formation of the light field in case of strongly scattering media, such as polylactide scaffolds, is determined by anisotropy g and the scattering coefficient μs.

  7. Detection of atomic scale changes in the free volume void size of three-dimensional colorectal cancer cell culture using positron annihilation lifetime spectroscopy.

    PubMed

    Axpe, Eneko; Lopez-Euba, Tamara; Castellanos-Rubio, Ainara; Merida, David; Garcia, Jose Angel; Plaza-Izurieta, Leticia; Fernandez-Jimenez, Nora; Plazaola, Fernando; Bilbao, Jose Ramon

    2014-01-01

    Positron annihilation lifetime spectroscopy (PALS) provides a direct measurement of the free volume void sizes in polymers and biological systems. This free volume is critical in explaining and understanding physical and mechanical properties of polymers. Moreover, PALS has been recently proposed as a potential tool in detecting cancer at early stages, probing the differences in the subnanometer scale free volume voids between cancerous/healthy skin samples of the same patient. Despite several investigations on free volume in complex cancerous tissues, no positron annihilation studies of living cancer cell cultures have been reported. We demonstrate that PALS can be applied to the study in human living 3D cell cultures. The technique is also capable to detect atomic scale changes in the size of the free volume voids due to the biological responses to TGF-β. PALS may be developed to characterize the effect of different culture conditions in the free volume voids of cells grown in vitro.

  8. Detection of Atomic Scale Changes in the Free Volume Void Size of Three-Dimensional Colorectal Cancer Cell Culture Using Positron Annihilation Lifetime Spectroscopy

    PubMed Central

    Castellanos-Rubio, Ainara; Merida, David; Garcia, Jose Angel; Plaza-Izurieta, Leticia; Fernandez-Jimenez, Nora; Plazaola, Fernando; Bilbao, Jose Ramon

    2014-01-01

    Positron annihilation lifetime spectroscopy (PALS) provides a direct measurement of the free volume void sizes in polymers and biological systems. This free volume is critical in explaining and understanding physical and mechanical properties of polymers. Moreover, PALS has been recently proposed as a potential tool in detecting cancer at early stages, probing the differences in the subnanometer scale free volume voids between cancerous/healthy skin samples of the same patient. Despite several investigations on free volume in complex cancerous tissues, no positron annihilation studies of living cancer cell cultures have been reported. We demonstrate that PALS can be applied to the study in human living 3D cell cultures. The technique is also capable to detect atomic scale changes in the size of the free volume voids due to the biological responses to TGF-β. PALS may be developed to characterize the effect of different culture conditions in the free volume voids of cells grown in vitro. PMID:24392097

  9. Information theory lateral density distribution for Earth inferred from global gravity field

    NASA Technical Reports Server (NTRS)

    Rubincam, D. P.

    1981-01-01

    Information Theory Inference, better known as the Maximum Entropy Method, was used to infer the lateral density distribution inside the Earth. The approach assumed that the Earth consists of indistinguishable Maxwell-Boltzmann particles populating infinitesimal volume elements, and followed the standard methods of statistical mechanics (maximizing the entropy function). The GEM 10B spherical harmonic gravity field coefficients, complete to degree and order 36, were used as constraints on the lateral density distribution. The spherically symmetric part of the density distribution was assumed to be known. The lateral density variation was assumed to be small compared to the spherically symmetric part. The resulting information theory density distribution for the cases of no crust removed, 30 km of compensated crust removed, and 30 km of uncompensated crust removed all gave broad density anomalies extending deep into the mantle, but with the density contrasts being the greatest towards the surface (typically + or 0.004 g cm 3 in the first two cases and + or - 0.04 g cm 3 in the third). None of the density distributions resemble classical organized convection cells. The information theory approach may have use in choosing Standard Earth Models, but, the inclusion of seismic data into the approach appears difficult.

  10. Compartmentalization of the outer hair cell demonstrated by slow diffusion in the extracisternal space.

    PubMed

    Gliko, Olga; Saggau, Peter; Brownell, William E

    2009-08-19

    In the outer hair cell (OHC), the extracisternal space (ECiS) is a conduit and reservoir of the molecular and ionic substrates of the lateral wall, including those necessary for electromotility. To determine the mechanisms through which molecules are transported in the ECiS of the OHC, we selectively imaged the time-dependent spatial distribution of fluorescent molecules in a <100 nm layer near the cell/glass interface of the recording chamber after their photolytic activation in a diffraction-limited volume. The effective diffusion coefficient was calculated using the analytical solution of the diffusion equation. It was found that diffusion in the ECiS is isotropic and not affected by depolarizing the OHC. Compared with free solution, the diffusion of 10 kDa dextran was slowed down in both the ECiS and the axial core by a factor of 4.6 and 1.6, respectively.

  11. In Situ Hot-Spot Assembly as a General Strategy for Probing Single Biomolecules.

    PubMed

    Liu, Huiqiao; Li, Qiang; Li, Mingmin; Ma, Sisi; Liu, Dingbin

    2017-05-02

    Single-molecule detection using surface-enhanced Raman spectroscopy (SERS) has attracted increasing attention in chemical and biomedical analysis. However, it remains a major challenge to probe single biomolecules by means of SERS hot spots owing to the small volume of hot spots and their random distribution on substrates. We here report an in situ hot-spot assembly method as a general strategy for probing single biomolecules. As a proof-of-concept, this proposed strategy was successfully used for the detection of single microRNA-21 (miRNA-21, a potential cancer biomarker) at the single-cell level, showing great capability in differentiating the expression of miRNA-21 in single cancer cells from normal cells. This approach was further extended to single-protein detection. The versatility of the strategy opens an exciting avenue for single-molecule detection of biomarkers of interest and thus holds great promise in a variety of biological and biomedical applications.

  12. Size distribution of submarine landslides along the U.S. Atlantic margin

    USGS Publications Warehouse

    Chaytor, J.D.; ten Brink, Uri S.; Solow, A.R.; Andrews, B.D.

    2009-01-01

    Assessment of the probability for destructive landslide-generated tsunamis depends on the knowledge of the number, size, and frequency of large submarine landslides. This paper investigates the size distribution of submarine landslides along the U.S. Atlantic continental slope and rise using the size of the landslide source regions (landslide failure scars). Landslide scars along the margin identified in a detailed bathymetric Digital Elevation Model (DEM) have areas that range between 0.89??km2 and 2410??km2 and volumes between 0.002??km3 and 179??km3. The area to volume relationship of these failure scars is almost linear (inverse power-law exponent close to 1), suggesting a fairly uniform failure thickness of a few 10s of meters in each event, with only rare, deep excavating landslides. The cumulative volume distribution of the failure scars is very well described by a log-normal distribution rather than by an inverse power-law, the most commonly used distribution for both subaerial and submarine landslides. A log-normal distribution centered on a volume of 0.86??km3 may indicate that landslides preferentially mobilize a moderate amount of material (on the order of 1??km3), rather than large landslides or very small ones. Alternatively, the log-normal distribution may reflect an inverse power law distribution modified by a size-dependent probability of observing landslide scars in the bathymetry data. If the latter is the case, an inverse power-law distribution with an exponent of 1.3 ?? 0.3, modified by a size-dependent conditional probability of identifying more failure scars with increasing landslide size, fits the observed size distribution. This exponent value is similar to the predicted exponent of 1.2 ?? 0.3 for subaerial landslides in unconsolidated material. Both the log-normal and modified inverse power-law distributions of the observed failure scar volumes suggest that large landslides, which have the greatest potential to generate damaging tsunamis, occur infrequently along the margin. ?? 2008 Elsevier B.V.

  13. Bayesian prediction of future ice sheet volume using local approximation Markov chain Monte Carlo methods

    NASA Astrophysics Data System (ADS)

    Davis, A. D.; Heimbach, P.; Marzouk, Y.

    2017-12-01

    We develop a Bayesian inverse modeling framework for predicting future ice sheet volume with associated formal uncertainty estimates. Marine ice sheets are drained by fast-flowing ice streams, which we simulate using a flowline model. Flowline models depend on geometric parameters (e.g., basal topography), parameterized physical processes (e.g., calving laws and basal sliding), and climate parameters (e.g., surface mass balance), most of which are unknown or uncertain. Given observations of ice surface velocity and thickness, we define a Bayesian posterior distribution over static parameters, such as basal topography. We also define a parameterized distribution over variable parameters, such as future surface mass balance, which we assume are not informed by the data. Hyperparameters are used to represent climate change scenarios, and sampling their distributions mimics internal variation. For example, a warming climate corresponds to increasing mean surface mass balance but an individual sample may have periods of increasing or decreasing surface mass balance. We characterize the predictive distribution of ice volume by evaluating the flowline model given samples from the posterior distribution and the distribution over variable parameters. Finally, we determine the effect of climate change on future ice sheet volume by investigating how changing the hyperparameters affects the predictive distribution. We use state-of-the-art Bayesian computation to address computational feasibility. Characterizing the posterior distribution (using Markov chain Monte Carlo), sampling the full range of variable parameters and evaluating the predictive model is prohibitively expensive. Furthermore, the required resolution of the inferred basal topography may be very high, which is often challenging for sampling methods. Instead, we leverage regularity in the predictive distribution to build a computationally cheaper surrogate over the low dimensional quantity of interest (future ice sheet volume). Continual surrogate refinement guarantees asymptotic sampling from the predictive distribution. Directly characterizing the predictive distribution in this way allows us to assess the ice sheet's sensitivity to climate variability and change.

  14. Effects of passive heating on central blood volume and ventricular dimensions in humans

    PubMed Central

    Crandall, C G; Wilson, T E; Marving, J; Vogelsang, T W; Kjaer, A; Hesse, B; Secher, N H

    2008-01-01

    Mixed findings regarding the effects of whole-body heat stress on central blood volume have been reported. This study evaluated the hypothesis that heat stress reduces central blood volume and alters blood volume distribution. Ten healthy experimental and seven healthy time control (i.e. non-heat stressed) subjects participated in this protocol. Changes in regional blood volume during heat stress and time control were estimated using technetium-99m labelled autologous red blood cells and gamma camera imaging. Whole-body heating increased internal temperature (≥ 1.0°C), cutaneous vascular conductance (approximately fivefold), and heart rate (52 ± 2 to 93 ± 4 beats min−1), while reducing central venous pressure (5.5 ± 07 to 0.2 ± 0.6 mmHg) accompanied by minor decreases in mean arterial pressure (all P < 0.05). The heat stress reduced the blood volume of the heart (18 ± 2%), heart plus central vasculature (17 ± 2%), thorax (14 ± 2%), inferior vena cava (23 ± 2%) and liver (23 ± 2%) (all P≤ 0.005 relative to time control subjects). Radionuclide multiple-gated acquisition assessment revealed that heat stress did not significantly change left ventricular end-diastolic volume, while ventricular end-systolic volume was reduced by 24 ± 6% of pre-heat stress levels (P < 0.001 relative to time control subjects). Thus, heat stress increased left ventricular ejection fraction from 60 ± 1% to 68 ± 2% (P= 0.02). We conclude that heat stress shifts blood volume from thoracic and splanchnic regions presumably to aid in heat dissipation, while simultaneously increasing heart rate and ejection fraction. PMID:17962331

  15. On strain and stress in living cells

    NASA Astrophysics Data System (ADS)

    Cox, Brian N.; Smith, David W.

    2014-11-01

    Recent theoretical simulations of amelogenesis and network formation and new, simple analyses of the basic multicellular unit (BMU) allow estimation of the order of magnitude of the strain energy density in populations of living cells in their natural environment. A similar simple calculation translates recent measurements of the force-displacement relation for contacting cells (cell-cell adhesion energy) into equivalent volume energy densities, which are formed by averaging the changes in contact energy caused by a cell's migration over the cell's volume. The rates of change of these mechanical energy densities (energy density rates) are then compared to the order of magnitude of the metabolic activity of a cell, expressed as a rate of production of metabolic energy per unit volume. The mechanical energy density rates are 4-5 orders of magnitude smaller than the metabolic energy density rate in amelogenesis or bone remodeling in the BMU, which involve modest cell migration velocities, and 2-3 orders of magnitude smaller for innervation of the gut or angiogenesis, where migration rates are among the highest for all cell types. For representative cell-cell adhesion gradients, the mechanical energy density rate is 6 orders of magnitude smaller than the metabolic energy density rate. The results call into question the validity of using simple constitutive laws to represent living cells. They also imply that cells need not migrate as inanimate objects of gradients in an energy field, but are better regarded as self-powered automata that may elect to be guided by such gradients or move otherwise. Thus Ġel=d/dt 1/2 >[(C11+C12)ɛ02+2μγ02]=(C11+C12)ɛ0ɛ˙0+2μγ0γ˙0 or Ġel=ηEɛ0ɛ˙0+η‧Eγ0γ˙0 with 1.4≤η≤3.4 and 0.7≤η‧≤0.8 for Poisson's ratio in the range 0.2≤ν≤0.4 and η=1.95 and η‧=0.75 for ν=0.3. The spatial distribution of shear strains arising within an individual cell as cells slide past one another during amelogenesis is not known in detail. However, estimates can be inferred from the known relative velocities of the cells' centers of mass. When averaged over a volume comparable to the cell size, representative values of the strain are, to order of magnitude, ɛ0≈0.1 and γ0≈0.1. The shape distortions of cells seen, for example, in Fig. 1c, imply peak strains in minor segments of a cell of magnitude unity, ɛ0≈1 and γ0≈1; these values represent the upper bound of plausible values and are included for discussion of the extremes of attainable strain energy rates.Given the strain magnitudes, the strain rates follow from the fact that a cell switches from one contacting neighbor in the adjacent row to the next in approximately 0.25 d, during which motion the strains might vary from zero to their maximum values and back again. Thus the most probable shear strain rate is inferred to be γ˙0=10-6 s-1 and the most probable tensile strain rate is inferred to be ɛ˙0≈10-6 s-1, with high bounds γ˙0=10-5 s-1 and ɛ˙0=10-5 s-1.

  16. Susceptibility-matched plugs for microcoil NMR probes

    NASA Astrophysics Data System (ADS)

    Kc, Ravi; Gowda, Yashas N.; Djukovic, Danijel; Henry, Ian D.; Park, Gregory H. J.; Raftery, Daniel

    2010-07-01

    For mass-limited samples, the residual sample volume outside the detection coil is an important concern, as is good base line resolution. Here, we present the construction and evaluation of magnetic susceptibility-matched plugs for microcoil NMR sample cells which address these issues. Mixed-epoxy glue and ultem tube plugs that have susceptibility values close to those of perfluorocarbon FC-43 (fluorinert) and copper were used in small volume (0.5-2 μL) and larger volume (15-20 μL) thin glass capillary sample cells. Using these plugs, the sample volume efficiency (i.e. ratio of active volume to total sample volume in the microcoil NMR cell) was improved by 6-12-fold without sensitivity and resolution trade-offs. Comparison with laser etched or heat etched microcoil sample cells is provided. The approaches described are potentially useful in metabolomics for biomarkers detection in mass limited biological samples.

  17. Susceptibility-matched plugs for microcoil NMR probes.

    PubMed

    Kc, Ravi; Gowda, Yashas N; Djukovic, Danijel; Henry, Ian D; Park, Gregory H J; Raftery, Daniel

    2010-07-01

    For mass-limited samples, the residual sample volume outside the detection coil is an important concern, as is good base line resolution. Here, we present the construction and evaluation of magnetic susceptibility-matched plugs for microcoil NMR sample cells which address these issues. Mixed-epoxy glue and ultem tube plugs that have susceptibility values close to those of perfluorocarbon FC-43 (fluorinert) and copper were used in small volume (0.5-2 microL) and larger volume (15-20 microL) thin glass capillary sample cells. Using these plugs, the sample volume efficiency (i.e. ratio of active volume to total sample volume in the microcoil NMR cell) was improved by 6-12-fold without sensitivity and resolution trade-offs. Comparison with laser etched or heat etched microcoil sample cells is provided. The approaches described are potentially useful in metabolomics for biomarkers detection in mass limited biological samples. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  18. Susceptibility-matched plugs for microcoil NMR probes

    PubMed Central

    Kc, Ravi; Gowda, Yashas N.; Djukovic, Danijel; Henry, Ian D; Park, Gregory H J; Raftery, Daniel

    2010-01-01

    For mass limited samples, the residual sample volume outside the detection coil is an important concern, as is good base line resolution. Here, we present the construction and evaluation of magnetic susceptibility-matched plugs for microcoil NMR sample cells which address these issues. Mixed-epoxy glue and ultem tube plugs that have susceptibility values close to those of perfluorocarbon FC-43 (fluorinert) and copper were used in small volume (0.5 to 2 μL) and larger volume (15 to 20 μL) thin glass capillary sample cells. Using these plugs, the sample volume efficiency (i.e. ratio of active volume to total sample volume in the microcoil NMR cell) was improved by 6 to 12 fold without sensitivity and resolution trade-offs. Comparison with laser etched or heat etched microcoil sample cells is provided. The approaches described are potentially useful in metabolomics for biomarkers detection in mass limited biological samples. PMID:20510638

  19. Cell volumes, maximal growth rates of unicellular algae and ciliates, and the role of ciliates in the marine pelagial

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

    Banse, K.

    1982-01-01

    A review of growth rates of diatoms and dinoflagellates in light-saturated, nutrient-replete cultures at 20/sup 0/C confirms weak dependence on cell volume or mass. These maximal (intrinsic) rates are not linearly related to surface area or surface-to-volume ratio of the cells. The growth of most diatoms is materially faster than that of dinoflagellates; other algae fall in between or below the dinoflagellates. Small ciliates have appreciably higher intrinsic growth rates than algae of the same cell volume. The average food consumption per ciliate in the marine pelagic realm is inferred to be very low, so that the realized specific growthmore » rates are much smaller than the intrinsic potentials. Also, a previously postulated refuge from predation, afforded by small size, is extended down to about 10-..mu..m/sup 3/ cell volume.« less

  20. Prenatal alcohol-induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine.

    PubMed

    Sogut, Ibrahim; Uysal, Onur; Oglakci, Aysegul; Yucel, Ferruh; Kartkaya, Kazim; Kanbak, Gungor

    2017-03-01

    Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy. Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei. Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments. We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.

  1. Scaling of number, size, and metabolic rate of cells with body size in mammals.

    PubMed

    Savage, Van M; Allen, Andrew P; Brown, James H; Gillooly, James F; Herman, Alexander B; Woodruff, William H; West, Geoffrey B

    2007-03-13

    The size and metabolic rate of cells affect processes from the molecular to the organismal level. We present a quantitative, theoretical framework for studying relationships among cell volume, cellular metabolic rate, body size, and whole-organism metabolic rate that helps reveal the feedback between these levels of organization. We use this framework to show that average cell volume and average cellular metabolic rate cannot both remain constant with changes in body size because of the well known body-size dependence of whole-organism metabolic rate. Based on empirical data compiled for 18 cell types in mammals, we find that many cell types, including erythrocytes, hepatocytes, fibroblasts, and epithelial cells, follow a strategy in which cellular metabolic rate is body size dependent and cell volume is body size invariant. We suggest that this scaling holds for all quickly dividing cells, and conversely, that slowly dividing cells are expected to follow a strategy in which cell volume is body size dependent and cellular metabolic rate is roughly invariant with body size. Data for slowly dividing neurons and adipocytes show that cell volume does indeed scale with body size. From these results, we argue that the particular strategy followed depends on the structural and functional properties of the cell type. We also discuss consequences of these two strategies for cell number and capillary densities. Our results and conceptual framework emphasize fundamental constraints that link the structure and function of cells to that of whole organisms.

  2. Genetic models in applied physiology: selected contribution: effects of spaceflight on immunity in the C57BL/6 mouse. II. Activation, cytokines, erythrocytes, and platelets

    NASA Technical Reports Server (NTRS)

    Gridley, Daila S.; Nelson, Gregory A.; Peters, Luanne L.; Kostenuik, Paul J.; Bateman, Ted A.; Morony, Sean; Stodieck, Louis S.; Lacey, David L.; Simske, Steven J.; Pecaut, Michael J.

    2003-01-01

    This portion of the study quantified the effects of a 12-day space shuttle mission (Space Transport System-108/UF-1) on body and lymphoid organ masses, activation marker expression, cytokine secretion, and erythrocyte and thrombocyte characteristics in C57BL/6 mice. Animals in flight (Flt group) had 10-12% lower body mass compared with ground controls housed either in animal enclosure modules or under standard vivarium conditions (P < 0.001) and the smallest thymus and spleen masses. Percentages of CD25(+) lymphocytes, CD3(+)/CD25(+) T cells, and NK1.1(+)/CD25(+) natural killer cells from Flt mice were higher compared with both controls (P < 0.05). In contrast, CD71 expression was depressed in the Flt and animal enclosure module control mice compared with vivarium control animals (P < 0.001). Secretion of interferon-gamma, IL-2, and IL-4, but not tumor necrosis factor-alpha and IL-5, by splenocytes from Flt mice was decreased relative to either one or both ground controls (P < 0.05). Flt mice also had high red blood cell and thrombocyte counts compared with both sets of controls; low red blood cell volume and distribution width, percentage of reticulocytes, and platelet volume were also noted (P < 0.05) and were consistent with dehydration. These data indicate that relatively short exposure to the spaceflight environment can induce profound changes that may become significant during long-term space missions.

  3. Biology of high single doses of IORT: RBE, 5 R's, and other biological aspects.

    PubMed

    Herskind, Carsten; Ma, Lin; Liu, Qi; Zhang, Bo; Schneider, Frank; Veldwijk, Marlon R; Wenz, Frederik

    2017-01-19

    Intraoperative radiotherapy differs from conventional, fractionated radiotherapy in several aspects that may influence its biological effect. The radiation quality influences the relative biologic effectiveness (RBE), and the role of the five R's of radiotherapy (reassortment, repair, reoxygenation, repopulation, radiosensitivity) is different. Furthermore, putative special biological effects and the small volume receiving a high single dose may be important. The present review focuses on RBE, repair, and repopulation, and gives an overview of the other factors that potentially contribute to the efficacy. The increased RBE should be taken into account for low-energy X-rays while evidence of RBE < 1 for high-energy electrons at higher doses is presented. Various evidence supports a hypothesis that saturation of the primary DNA double-strand break (DSB) repair mechanisms leads to increasing use of an error-prone backup repair system leading to genomic instability that may contribute to inactivate tumour cells at high single doses. Furthermore, the elimination of repopulation of residual tumour cells in the tumour bed implies that some patients are likely to have very few residual tumour cells which may be cured even by low doses to the tumour bed. The highly localised dose distribution of IORT has the potential to inactivate tumour cells while sparing normal tissue by minimising the volume exposed to high doses. Whether special effects of high single doses also contribute to the efficacy will require further experimental and clinical studies.

  4. Trends in white blood cell and platelet indices in a comparison of patients with papillary thyroid carcinoma and multinodular goiter do not permit differentiation between the conditions.

    PubMed

    Machairas, Nikolaos; Kostakis, Ioannis D; Prodromidou, Anastasia; Stamopoulos, Paraskevas; Feretis, Themistoklis; Garoufalia, Zoe; Damaskos, Christos; Tsourouflis, Gerasimos; Kouraklis, Gregory

    2017-11-01

    Carcinogenesis has been related to systematic inflammatory response. Our aim was to study white blood cell and platelet indices as markers of this inflammatory response in thyroid cancer and to associate them with various clinicopathological parameters. We included 228 patients who underwent thyroidectomy within a period of 54 months, 89 with papillary thyroid carcinoma and 139 with multinodular hyperplasia. We examined potential links between white blood cell and platelet indices on the one hand and the type thyroid pathology and various clinicopathological parameters on the other. No significant differences were detected between thyroid cancer and multinodular hyperplasia and no significant associations were detected with regard to lymphovascular invasion and tumor size. However, the mean platelet volume was higher in multifocal tumors, while the platelet count, plateletcrit, and platelet-to-lymphocyte ratio were increased in cases with extrathyroidal extension and in T3 tumors. Additionally, T3 tumors had lower platelet distribution width. These associations demonstrated low accuracy in predicting these pathological features, but they were found to provide a satisfying negative predictive value, with the exception of the mean platelet volume. White blood cell and platelet indices cannot assist in distinguishing benign goiter from thyroid cancer. However, they can provide information about tumor multifocality, extrathyroidal extension, and presence of a T3 tumor, and they may be used as a means to exclude these pathological characteristics, especially the last two, in papillary thyroid carcinoma.

  5. Dual-wavelength OR-PAM with compressed sensing for cell tracking in a 3D cell culture system

    NASA Astrophysics Data System (ADS)

    Huang, Rou-Xuan; Fu, Ying; Liu, Wang; Ma, Yu-Ting; Hsieh, Bao-Yu; Chen, Shu-Ching; Sun, Mingjian; Li, Pai-Chi

    2018-02-01

    Monitoring dynamic interactions of T cells migrating toward tumor is beneficial to understand how cancer immunotherapy works. Optical-resolution photoacoustic microscope (OR-PAM) can provide not only high spatial resolution but also deeper penetration than conventional optical microscopy. With the aid of exogenous contrast agents, the dual-wavelength OR-PAM can be applied to map the distribution of CD8+ cytotoxic T lymphocytes (CTLs) with gold nanospheres (AuNS) under 523nm laser irradiation and Hepta1-6 tumor spheres with indocyanine green (ICG) under 800nm irradiation. However, at 1K laser PRF, it takes approximately 20 minutes to obtain a full sample volume of 160 × 160 × 150 μm3 . To increase the imaging rate, we propose a random non-uniform sparse sampling mechanism to achieve fast sparse photoacoustic data acquisition. The image recovery process is formulated as a low-rank matrix recovery (LRMR) based on compressed sensing (CS) theory. We show that it could be stably recovered via nuclear-norm minimization optimization problem to maintain image quality from a significantly fewer measurement. In this study, we use the dual-wavelength OR-PAM with CS to visualize T cell trafficking in a 3D culture system with higher temporal resolution. Data acquisition time is reduced by 40% in such sample volume where sampling density is 0.5. The imaging system reveals the potential to understand the dynamic cellular process for preclinical screening of anti-cancer drugs.

  6. Study of Automobile Market Dynamics : Volume 2. Analysis.

    DOT National Transportation Integrated Search

    1977-08-01

    Volume II describes the work in providing statistical inputs to a computer model by examining the effects of various options on the number of automobiles sold; the distribution of sales among small, medium and large cars; the distribution between aut...

  7. Induction of morphological changes in death-induced cancer cells monitored by holographic microscopy.

    PubMed

    El-Schich, Zahra; Mölder, Anna; Tassidis, Helena; Härkönen, Pirkko; Falck Miniotis, Maria; Gjörloff Wingren, Anette

    2015-03-01

    We are using the label-free technique of holographic microscopy to analyze cellular parameters including cell number, confluence, cellular volume and area directly in the cell culture environment. We show that death-induced cells can be distinguished from untreated counterparts by the use of holographic microscopy, and we demonstrate its capability for cell death assessment. Morphological analysis of two representative cell lines (L929 and DU145) was performed in the culture flasks without any prior cell detachment. The two cell lines were treated with the anti-tumour agent etoposide for 1-3days. Measurements by holographic microscopy showed significant differences in average cell number, confluence, volume and area when comparing etoposide-treated with untreated cells. The cell volume of the treated cell lines was initially increased at early time-points. By time, cells decreased in volume, especially when treated with high doses of etoposide. In conclusion, we have shown that holographic microscopy allows label-free and completely non-invasive morphological measurements of cell growth, viability and death. Future applications could include real-time monitoring of these holographic microscopy parameters in cells in response to clinically relevant compounds. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Experimental evidence for negative turgor pressure in small leaf cells of Robinia pseudoacacia L versus large cells of Metasequoia glyptostroboides Hu et W.C. Cheng. 2. Höfler diagrams below the volume of zero turgor and the theoretical implication for pressure-volume curves of living cells.

    PubMed

    Yang, Dongmei; Li, Junhui; Ding, Yiting; Tyree, Melvin T

    2017-03-01

    The physiological advantages of negative turgor pressure, P t , in leaf cells are water saving and homeostasis of reactants. This paper advances methods for detecting the occurrence of negative P t in leaves. Biomechanical models of pressure-volume (PV) curves predict that negative P t does not change the linearity of PV curve plots of inverse balance pressure, P B , versus relative water loss, but it does predict changes in either the y-intercept or the x-intercept of the plots depending on where cell collapse occurs in the P B domain because of negative P t . PV curve analysis of Robinia leaves revealed a shift in the x-intercept (x-axis is relative water loss) of PV curves, caused by negative P t of palisade cells. The low x-intercept of the PV curve was explained by the non-collapse of palisade cells in Robinia in the P B domain. Non-collapse means that P t smoothly falls from positive to negative values with decreasing cell volume without a dramatic change in slope. The magnitude of negative turgor in non-collapsing living cells was as low as -1.3 MPa and the relative volume of the non-collapsing cell equaled 58% of the total leaf cell volume. This study adds to the growing evidence for negative P t . © 2016 John Wiley & Sons Ltd.

  9. A systems analysis of the erythropoietic responses to weightlessness. Volume 2: Description of the model of erythropoiesis regulation. Part A: Model for regulation of erythropoiesis. Part B: Detailed description of the model for regulation of erythropoiesis

    NASA Technical Reports Server (NTRS)

    Leonard, J. I.

    1985-01-01

    A mathematical model of the erythropoiesis on total red blood cell mass is presented. The loss of red cell mass has been a consistent finding during space flight. Computer simulation of this phenomenon required a model that could account for oxygen transport, red cell production, and red cell destruction. The elements incorporated into the feedback regulation loop of the model are based on the accepted concept that erythrocyte production is governed by the balance between oxygen supply and demand in the body. The mechanisms and pathways of the control circuit include oxygenation of hemoglobin and oxygenation of tissues by blood transport and diffusional processes. Other features of the model include a variable oxygen-hemoglobin affinity, and time delays which represent time for erythropoietin (erythrocyte-stimulating hormone) distribution in plasma, and time for maturation of the erythrocytes in bone marrow.

  10. Full elastic strain and stress tensor measurements from individual dislocation cells in copper through-Si vias

    DOE PAGES

    Levine, Lyle E.; Okoro, Chukwudi A.; Xu, Ruqing

    2015-09-30

    We report non-destructive measurements of the full elastic strain and stress tensors from individual dislocation cells distributed along the full extent of a 50 mm-long polycrystalline copper via in Si is reported. Determining all of the components of these tensors from sub-micrometre regions within deformed metals presents considerable challenges. The primary issues are ensuring that different diffraction peaks originate from the same sample volume and that accurate determination is made of the peak positions from plastically deformed samples. For these measurements, three widely separated reflections were examined from selected, individual grains along the via. The lattice spacings and peak positionsmore » were measured for multiple dislocation cell interiors within each grain and the cell-interior peaks were sorted out using the measured included angles. A comprehensive uncertainty analysis using a Monte Carlo uncertainty algorithm provided uncertainties for the elastic strain tensor and stress tensor components.« less

  11. Manipulating biological agents and cells in micro-scale volumes for applications in medicine

    PubMed Central

    Tasoglu, Savas; Gurkan, Umut Atakan; Wang, ShuQi

    2013-01-01

    Recent technological advances provide new tools to manipulate cells and biological agents in micro/nano-liter volumes. With precise control over small volumes, the cell microenvironment and other biological agents can be bioengineered; interactions between cells and external stimuli can be monitored; and the fundamental mechanisms such as cancer metastasis and stem cell differentiation can be elucidated. Technological advances based on the principles of electrical, magnetic, chemical, optical, acoustic, and mechanical forces lead to novel applications in point-of-care diagnostics, regenerative medicine, in vitro drug testing, cryopreservation, and cell isolation/purification. In this review, we first focus on the underlying mechanisms of emerging examples for cell manipulation in small volumes targeting applications such as tissue engineering. Then, we illustrate how these mechanisms impact the aforementioned biomedical applications, discuss the associated challenges, and provide perspectives for further development. PMID:23575660

  12. Compact cell-centered discretization stencils at fine-coarse block structured grid interfaces

    NASA Astrophysics Data System (ADS)

    Pletzer, Alexander; Jamroz, Ben; Crockett, Robert; Sides, Scott

    2014-03-01

    Different strategies for coupling fine-coarse grid patches are explored in the context of the adaptive mesh refinement (AMR) method. We show that applying linear interpolation to fill in the fine grid ghost values can produce a finite volume stencil of comparable accuracy to quadratic interpolation provided the cell volumes are adjusted. The volume of fine cells expands whereas the volume of neighboring coarse cells contracts. The amount by which the cells contract/expand depends on whether the interface is a face, an edge, or a corner. It is shown that quadratic or better interpolation is required when the conductivity is spatially varying, anisotropic, the refinement ratio is other than two, or when the fine-coarse interface is concave.

  13. 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.

  14. Calculations for reproducible autologous skin cell-spray grafting.

    PubMed

    Esteban-Vives, Roger; Young, Matthew T; Zhu, Toby; Beiriger, Justin; Pekor, Chris; Ziembicki, Jenny; Corcos, Alain; Rubin, Peter; Gerlach, Jörg C

    2016-12-01

    Non-cultured, autologous cell-spray grafting is an alternative to mesh grafting for larger partial- and deep partial-thickness burn wounds. The treatment uses a suspension of isolated cells, from a patient's donor site skin tissue, and cell-spray deposition onto the wound that facilitates re-epithelialization. Existing protocols for therapeutic autologous skin cell isolation and cell-spray grafting have defined the donor site area to treatment area ratio of 1:80, substantially exceeding the coverage of conventional mesh grafting. However, ratios of 1:100 are possible by maximizing the wound treatment area with harvested cells from a given donor site skin tissue according to a given burn area. Although cell isolation methods are very well described in the literature, a rational approach addressing critical aspects of these techniques are of interest in planning clinical study protocols. We considered in an experimental study the cell yield as a function of the donor site skin tissue, the cell density for spray grafting, the liquid spray volume, the sprayed distribution area, and the percentage of surface coverage. The experimental data was then used for the development of constants and mathematical equations to give a rationale for the cell isolation and cell-spray grafting processes and in planning for clinical studies. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  15. Automated Cell-Cutting for Cell Cloning

    NASA Astrophysics Data System (ADS)

    Ichikawa, Akihiko; Tanikawa, Tamio; Matsukawa, Kazutsugu; Takahashi, Seiya; Ohba, Kohtaro

    We develop an automated cell-cutting technique for cell cloning. Animal cells softened by the cytochalasin treatment are injected into a microfluidic chip. The microfluidic chip contains two orthogonal channels: one microchannel is wide, used to transport cells, and generates the cutting flow; the other is thin and used for aspiration, fixing, and stretching of the cell. The injected cell is aspirated and stretched in the thin microchannel. Simultaneously, the volumes of the cell before and after aspiration are calculated; the volumes are used to calculate the fluid flow required to aspirate half the volume of the cell into the thin microchannel. Finally, we apply a high-speed flow in the orthogonal microchannel to bisect the cell. This paper reports the cutting process, the cutting system, and the results of the experiment.

  16. Estrogen receptor {alpha} gene promoter 0/B usage in the rat sexually dimorphic nucleus of the preoptic area.

    PubMed

    Hamada, Tomohiro; Sakuma, Yasuo

    2010-04-01

    The volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) is two to four times larger in male rats than in females; however, the mechanism for the establishment of sexual dimorphism and the function of this nucleus is almost unknown. Perinatal estrogen can cause sexual dimorphism via the estrogen receptor alpha (ERalpha). Recently, transgenic rats were generated that express enhanced green fluorescent protein (EGFP) under the control of the ERalpha gene promoter 0/B to tag ERalpha-positive neurons in the brain. In the present study, we examined whether this EGFP expression could be a marker for the SDN-POA in adults. EGFP-labeled cells were distributed in the core of the SDN-POA (0/B-SDN) of male and female transgenic rats, in accordance with the Nissl staining and immunoreactivity for the SDN marker, calbindin. They were also immunoreactive for ERalpha. The core was bigger in volume and contained more 0/B-SDN neurons in males than in females. The EGFP-tagged cells were packed more densely in the female core than that in males. Subcutaneous injection of 100 mug 17beta-estradiol to females on the day of birth, or orchidectomy of male neonates, reversed the sexually dimorphic phenotype of the volume of the 0/B-SDN, despite not affecting the cell number. We suggest that this EGFP expression in the SDN-POA could be a useful marker to clarify the sexual differentiation and function of the SDN-POA. Moreover, the ERalpha gene promoter 0/B plays a key role in the organization of the sexual differentiation of the SDN-POA.

  17. Laboratory-Scale Simulation and Real-Time Tracking of a Microbial Contamination Event and Subsequent Shock-Chlorination in Drinking Water

    PubMed Central

    Besmer, Michael D.; Sigrist, Jürg A.; Props, Ruben; Buysschaert, Benjamin; Mao, Guannan; Boon, Nico; Hammes, Frederik

    2017-01-01

    Rapid contamination of drinking water in distribution and storage systems can occur due to pressure drop, backflow, cross-connections, accidents, and bio-terrorism. Small volumes of a concentrated contaminant (e.g., wastewater) can contaminate large volumes of water in a very short time with potentially severe negative health impacts. The technical limitations of conventional, cultivation-based microbial detection methods neither allow for timely detection of such contaminations, nor for the real-time monitoring of subsequent emergency remediation measures (e.g., shock-chlorination). Here we applied a newly developed continuous, ultra high-frequency flow cytometry approach to track a rapid pollution event and subsequent disinfection of drinking water in an 80-min laboratory scale simulation. We quantified total (TCC) and intact (ICC) cell concentrations as well as flow cytometric fingerprints in parallel in real-time with two different staining methods. The ingress of wastewater was detectable almost immediately (i.e., after 0.6% volume change), significantly changing TCC, ICC, and the flow cytometric fingerprint. Shock chlorination was rapid and detected in real time, causing membrane damage in the vast majority of bacteria (i.e., drop of ICC from more than 380 cells μl-1 to less than 30 cells μl-1 within 4 min). Both of these effects as well as the final wash-in of fresh tap water followed calculated predictions well. Detailed and highly quantitative tracking of microbial dynamics at very short time scales and for different characteristics (e.g., concentration, membrane integrity) is feasible. This opens up multiple possibilities for targeted investigation of a myriad of bacterial short-term dynamics (e.g., disinfection, growth, detachment, operational changes) both in laboratory-scale research and full-scale system investigations in practice. PMID:29085343

  18. Preclinical pharmacokinetics of the novel PI3K inhibitor GDC-0941 and prediction of its pharmacokinetics and efficacy in human.

    PubMed

    Salphati, Laurent; Pang, Jodie; Plise, Emile G; Chou, Bilin; Halladay, Jason S; Olivero, Alan G; Rudewicz, Patrick J; Tian, Qingping; Wong, Susan; Zhang, Xiaolin

    2011-12-01

    The phosphatidylinositol 3-kinase (PI3K) pathway is a major determinant of cell cycling and proliferation. Its deregulation is associated with the development of many cancers. GDC-0941, a potent and selective inhibitor of PI3K, was characterised preclinically in in vitro and in vivo studies. Plasma protein binding was extensive, with free fraction less than 7%, and blood-to-plasma ratio ranged from 0.6 to 1.2 among the species tested. GDC-0941 human hepatic clearance was predicted to be moderate by liver microsomal incubations. GDC-0941 had high permeability in Madin-Darby canine kidney cells. The clearance of GDC-0941 was high in mouse (63.7 mL/min/kg), rat (49.3 mL/min/kg) and cynomolgus monkey (58.6 mL/min/kg), and moderate in dog (11.9 mL/min/kg). The volume of distribution ranged from 2.52 L/kg in rat to 2.94 L/kg in monkey. Oral bioavailability ranged from 18.6% in monkey to 77.9% in mouse. Predicted human clearance and volume of distribution using allometry were 6 mL/min/kg and 2.9 L/kg, respectively. The human efficacious doses were predicted based on results from preclinical pharmacokinetic studies and xenograft models. GDC-0941 preclinical characterisation and predictions of its properties in human supported its progression towards clinical development. GDC-0941 is currently in phase II clinical trials.

  19. Association of erythrocyte deformability with red blood cell distribution width in metabolic diseases and thalassemia trait.

    PubMed

    Vayá, Amparo; Alis, Rafael; Suescún, Marta; Rivera, Leonor; Murado, Julian; Romagnoli, Marco; Solá, Eva; Hernandez-Mijares, Antonio

    2015-01-01

    Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other hematological and biochemical parameters in 36 α-thalassemia, 20 β-thalassemia, 20 δβ-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients. RDW correlated inversely with erythrocyte deformability in minor β-thalassemia (r =-0.530, p <  0.05), and directly in both metabolic syndrome and morbidly obese patients (ρ= 0.270, p <  0.05 and ρ= 0.258, p <  0.05, respectively). Minor β-thalassemia is often accompanied by more marked cell-shaped perturbations than other thalassemia traits. This could be the reason for this negative association only in this setting. Higher anisocytosis seems to be associated with greater morphologic alterations (shape/volume), which reduce erythrocyte deformability. The proinflammatory profile in metabolic patients can be related to the positive association of RDW with erythrocyte deformability found in these patients. However, further research is needed to explain the mechanisms underlying this association.

  20. Quantitative characterization of the protein contents of the exocrine pancreatic acinar cell by soft x-ray microscopy and advanced digital imaging methods

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

    Loo, Jr., Billy W.

    2000-06-01

    The study of the exocrine pancreatic acinar cell has been central to the development of models of many cellular processes, especially of protein transport and secretion. Traditional methods used to examine this system have provided a wealth of qualitative information from which mechanistic models have been inferred. However they have lacked the ability to make quantitative measurements, particularly of the distribution of protein in the cell, information critical for grounding of models in terms of magnitude and relative significance. This dissertation describes the development and application of new tools that were used to measure the protein content of the majormore » intracellular compartments in the acinar cell, particularly the zymogen granule. Soft x-ray microscopy permits image formation with high resolution and contrast determined by the underlying protein content of tissue rather than staining avidity. A sample preparation method compatible with x-ray microscopy was developed and its properties evaluated. Automatic computerized methods were developed to acquire, calibrate, and analyze large volumes of x-ray microscopic images of exocrine pancreatic tissue sections. Statistics were compiled on the protein density of several organelles, and on the protein density, size, and spatial distribution of tens of thousands of zymogen granules. The results of these measurements, and how they compare to predictions of different models of protein transport, are discussed.« less

  1. Efficient volume computation for three-dimensional hexahedral cells

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

    Dukowicz, J.K.

    1988-02-01

    Currently, algorithms for computing the volume of hexahedral cells with ''ruled'' surfaces require a minimum of 122 FLOPs (floating point operations) per cell. A new algorithm is described which reduces the operation count to 57 FLOPs per cell. copyright 1988 Academic Press, Inc.

  2. An Unstructured Finite Volume Approach for Structural Dynamics in Response to Fluid Motions.

    PubMed

    Xia, Guohua; Lin, Ching-Long

    2008-04-01

    A new cell-vortex unstructured finite volume method for structural dynamics is assessed for simulations of structural dynamics in response to fluid motions. A robust implicit dual-time stepping method is employed to obtain time accurate solutions. The resulting system of algebraic equations is matrix-free and allows solid elements to include structure thickness, inertia, and structural stresses for accurate predictions of structural responses and stress distributions. The method is coupled with a fluid dynamics solver for fluid-structure interaction, providing a viable alternative to the finite element method for structural dynamics calculations. A mesh sensitivity test indicates that the finite volume method is at least of second-order accuracy. The method is validated by the problem of vortex-induced vibration of an elastic plate with different initial conditions and material properties. The results are in good agreement with existing numerical data and analytical solutions. The method is then applied to simulate a channel flow with an elastic wall. The effects of wall inertia and structural stresses on the fluid flow are investigated.

  3. Red Blood Cell Volume, Plasma Volume and Total Blood Volume in Healthy Elderly Men and Women Aged 64 to 100

    DTIC Science & Technology

    1992-05-06

    Robert Valeri, Linda E. Pivacek, Hiliary Siebens, and Mark D. Altschule ». PERFORMING ORGANIZATION NAME AND AOORESS Naval Blood Research Laboratory...Gibson JG, Peacock WC, Seligman AM, Sack T: Circulating red cell volume measured simultaneously by the radioactive iron and dye methods. J Clin

  4. Tumor-volume simulation during radiotherapy for head-and-neck cancer using a four-level cell population model.

    PubMed

    Chvetsov, Alexei V; Dong, Lei; Palta, Jantinder R; Amdur, Robert J

    2009-10-01

    To develop a fast computational radiobiologic model for quantitative analysis of tumor volume during fractionated radiotherapy. The tumor-volume model can be useful for optimizing image-guidance protocols and four-dimensional treatment simulations in proton therapy that is highly sensitive to physiologic changes. The analysis is performed using two approximations: (1) tumor volume is a linear function of total cell number and (2) tumor-cell population is separated into four subpopulations: oxygenated viable cells, oxygenated lethally damaged cells, hypoxic viable cells, and hypoxic lethally damaged cells. An exponential decay model is used for disintegration and removal of oxygenated lethally damaged cells from the tumor. We tested our model on daily volumetric imaging data available for 14 head-and-neck cancer patients treated with an integrated computed tomography/linear accelerator system. A simulation based on the averaged values of radiobiologic parameters was able to describe eight cases during the entire treatment and four cases partially (50% of treatment time) with a maximum 20% error. The largest discrepancies between the model and clinical data were obtained for small tumors, which may be explained by larger errors in the manual tumor volume delineation procedure. Our results indicate that the change in gross tumor volume for head-and-neck cancer can be adequately described by a relatively simple radiobiologic model. In future research, we propose to study the variation of model parameters by fitting to clinical data for a cohort of patients with head-and-neck cancer and other tumors. The potential impact of other processes, like concurrent chemotherapy, on tumor volume should be evaluated.

  5. Study of Parameters Affecting the Level of Ultrasound Exposure with In Vitro Set-Ups

    NASA Astrophysics Data System (ADS)

    Leskinen, Jarkko J.; Hynynen, Kullervo

    2010-03-01

    Ultrasound (US) exposures are widely used with in vitro cell systems e.g. in stem cell and tissue engineering research. However, without the knowledge of factors affecting the level of US exposure, the outcome of the biological result may vary from test to test or even be misinterpreted. Thereby, some of the factors affecting in vitro US exposures were studied. The level of US exposure was characterized in standard commercial cell culturing plates. The temperature distributions were measured inside the wells using infrared camera and fine wire thermocouples, and pressure and intensity distributions using a laser vibrometer and a schlieren system. The measurements were made at operating frequency of around 1 MHz with varying temporal parameters and powers (up to 2 W of acoustic power). Heat accumulation between the wells varied up to 40-50% depending on the location of the well on the plate. This well-to-well variation was be linked to the activity of reporter plasmid on osteoblastic cells. Similar temperature variations within the wells were also measured. Small sub-wavelength change in the exposure distance or, respectively, liquid volume inside the well was found to alter the acoustic field in both magnitude and shape due the standing waves. The gathered data reveals the complexity of the acoustic field in a typical in vitro set-up and gives new information about the environment of the in vitro cells during US exposures. This data may be especially useful when US set-ups are designed or characterized.

  6. Phenotypic Characterization of Toxic Compound Effects on Liver Spheroids Derived from iPSC Using Confocal Imaging and Three-Dimensional Image Analysis.

    PubMed

    Sirenko, Oksana; Hancock, Michael K; Hesley, Jayne; Hong, Dihui; Cohen, Avrum; Gentry, Jason; Carlson, Coby B; Mann, David A

    2016-09-01

    Cell models are becoming more complex to better mimic the in vivo environment and provide greater predictivity for compound efficacy and toxicity. There is an increasing interest in exploring the use of three-dimensional (3D) spheroids for modeling developmental and tissue biology with the goal of accelerating translational research in these areas. Accordingly, the development of high-throughput quantitative assays using 3D cultures is an active area of investigation. In this study, we have developed and optimized methods for the formation of 3D liver spheroids derived from human iPS cells and used those for toxicity assessment. We used confocal imaging and 3D image analysis to characterize cellular information from a 3D matrix to enable a multi-parametric comparison of different spheroid phenotypes. The assay enables characterization of compound toxicities by spheroid size (volume) and shape, cell number and spatial distribution, nuclear characterization, number and distribution of cells expressing viability, apoptosis, mitochondrial potential, and viability marker intensities. In addition, changes in the content of live, dead, and apoptotic cells as a consequence of compound exposure were characterized. We tested 48 compounds and compared induced pluripotent stem cell (iPSC)-derived hepatocytes and HepG2 cells in both two-dimensional (2D) and 3D cultures. We observed significant differences in the pharmacological effects of compounds across the two cell types and between the different culture conditions. Our results indicate that a phenotypic assay using 3D model systems formed with human iPSC-derived hepatocytes is suitable for high-throughput screening and can be used for hepatotoxicity assessment in vitro.

  7. The anatomical relationships between the serotonergic afferents and the neurons containing calcium-binding proteins in the rat claustrum.

    PubMed

    Wójcik, Slawomir; Dziewiatkowski, Jerzy; Klejbor, Ilona; Spodnik, Jan Henryk; Kowiański, Przemysław; Moryś, Janusz

    2006-01-01

    Claustrum is a telencephalic structure integrating information of various modalities. Proper functioning of this structure depends on the presence of a network of intrinsic connections. This includes GABA-ergic neuronal populations that also contain calcium-binding proteins (CaBPs). The goal of this study was to analyze qualitative and quantitative the 5-HT-containing fibers in the rat claustrum and to assess the relationships between these fibers and the populations of claustral neurons expressing CaBPs. We used the methods of immunocytochemistry and morphometry. The serotonergic fibers in the claustrum are heterogeneous, both with respect to their morphology and spatial distribution. Thin varicose fibers are more numerous and are homogeneously distributed within the claustrum. Remaining fibers were thicker and possessed larger varicosities. They were present mainly in the ventral part of the claustrum. Although the serotonergic fibers are found in the vicinity of claustral cells containing CaBPs, direct contacts between these fibers and cells are rare. Other mechanisms, including volume transmission, may possibly mediate serotonergic influences.

  8. Transformation around intruders in granular media

    NASA Astrophysics Data System (ADS)

    Jop, Pierre; Merceron, Aymeric; Sauret, Alban

    2017-06-01

    Sintering, glass melting and other industrially relevant processes turn batches of grains into homogeneous products. Such processes involve coupled chemical and physical transformations of the granular packing. For sake of simplicity, we study how local evolutions on grains (volume decreases for example) entail mechanical rearrangements in the overall pile. Inert bidisperse metallic disks are mixed and confined in a vertical 2D cell. At the bottom of this set-up, initial intruders (one or two) have been previously set and mechanically linked to a linear motorized jack. While we quasi-statically pull the intruder(s) downward out of the cell at constant speed and constant liberated surface, we tracked the surrounding granular packing. Events largely distributed both spatially and temporally occur around intruders. We focus on the influence of the distance between the intruders on the local dynamic of the packing. We compare the distribution of the size of the event and their frequency as function of the relative position of the intruder, as a function of their radius. We show that their influence decreases rapidly. At short distance the mechanical perturbation induced by one intruder can destabilize the packing around the other.

  9. Three-Dimensional Random Voronoi Tessellations: From Cubic Crystal Lattices to Poisson Point Processes

    NASA Astrophysics Data System (ADS)

    Lucarini, Valerio

    2009-01-01

    We perturb the simple cubic (SC), body-centered cubic (BCC), and face-centered cubic (FCC) structures with a spatial Gaussian noise whose adimensional strength is controlled by the parameter α and analyze the statistical properties of the cells of the resulting Voronoi tessellations using an ensemble approach. We concentrate on topological properties of the cells, such as the number of faces, and on metric properties of the cells, such as the area, volume and the isoperimetric quotient. The topological properties of the Voronoi tessellations of the SC and FCC crystals are unstable with respect to the introduction of noise, because the corresponding polyhedra are geometrically degenerate, whereas the tessellation of the BCC crystal is topologically stable even against noise of small but finite intensity. Whereas the average volume of the cells is the intensity parameter of the system and does not depend on the noise, the average area of the cells has a rather interesting behavior with respect to noise intensity. For weak noise, the mean area of the Voronoi tessellations corresponding to perturbed BCC and FCC perturbed increases quadratically with the noise intensity. In the case of perturbed SCC crystals, there is an optimal amount of noise that minimizes the mean area of the cells. Already for a moderate amount of noise ( α>0.5), the statistical properties of the three perturbed tessellations are indistinguishable, and for intense noise ( α>2), results converge to those of the Poisson-Voronoi tessellation. Notably, 2-parameter gamma distributions constitute an excellent model for the empirical pdf of all considered topological and metric properties. By analyzing jointly the statistical properties of the area and of the volume of the cells, we discover that also the cells shape, measured by the isoperimetric quotient, fluctuates. The Voronoi tessellations of the BCC and of the FCC structures result to be local maxima for the isoperimetric quotient among space-filling tessellations, which suggests a weaker form of the recently disproved Kelvin conjecture. Moreover, whereas the size of the isoperimetric quotient fluctuations go to zero linearly with noise in the SC and BCC case, the decrease is quadratic in the FCC case. Correspondingly, anomalous scaling relations with exponents larger than 3/2 are observed between the area and the volumes of the cells for all cases considered, and, except for the FCC structure, also for infinitesimal noise. In the Poisson-Voronoi limit, the exponent is ˜1.67. The anomaly in the scaling indicates that large cells preferentially feature large isoperimetric quotients. The FCC structure, in spite of being topologically unstable, results to be the most stable against noise when the shape—as measured by the isoperimetric quotient—of the cells is considered. These scaling relations apply only for a finite range and should be taken as descriptive of the bulk statistical properties of the cells. As the number of faces is strongly correlated with the sphericity (cells with more faces are bulkier), the anomalous scaling is heavily reduced when we perform power law fits separately on cells with a specific number of faces.

  10. Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon).

    PubMed

    Scala, Christopher; Marsot, Amélie; Limoges, Marie-Josée; Locatelli, Yann; Simon, Nicolas; Alvarez, Jean-Claude

    2015-03-01

    To assess the population pharmacokinetics of methadone in deer. Prospective non-randomized experimental trial. Twelve healthy adult sika deer (nine males and three females). Deer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg(-1) or 1 mg kg(-1) . Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM). A two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour(-1) ), metabolic clearance (34.6 L hour(-1) ), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour(-1) ), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour(-1) , 121.0 L hour (-1) , 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration. Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  11. Interspecies scaling: predicting volumes, mean residence time and elimination half-life. Some suggestions.

    PubMed

    Mahmood, I

    1998-05-01

    Extrapolation of animal data to assess pharmacokinetic parameters in man is an important tool in drug development. Clearance, volume of distribution and elimination half-life are the three most frequently extrapolated pharmacokinetic parameters. Extensive work has been done to improve the predictive performance of allometric scaling for clearance. In general there is good correlation between body weight and volume, hence volume in man can be predicted with reasonable accuracy from animal data. Besides the volume of distribution in the central compartment (Vc), two other volume terms, the volume of distribution by area (Vbeta) and the volume of distribution at steady state (VdSS), are also extrapolated from animals to man. This report compares the predictive performance of allometric scaling for Vc, Vbeta and VdSS in man from animal data. The relationship between elimination half-life (t(1/2)) and body weight across species results in poor correlation, most probably because of the hybrid nature of this parameter. To predict half-life in man from animal data, an indirect method (CL=VK, where CL=clearance, V is volume and K is elimination rate constant) has been proposed. This report proposes another indirect method which uses the mean residence time (MRT). After establishing that MRT can be predicted across species, it was used to predict half-life using the equation MRT=1.44 x t(1/2). The results of the study indicate that Vc is predicted more accurately than Vbeta and VdSS in man. It should be emphasized that for first-time dosing in man, Vc is a more important pharmacokinetic parameter than Vbeta or VdSS. Furthermore, MRT can be predicted reasonably well for man and can be used for prediction of half-life.

  12. Dose-volume histogram prediction using density estimation.

    PubMed

    Skarpman Munter, Johanna; Sjölund, Jens

    2015-09-07

    Knowledge of what dose-volume histograms can be expected for a previously unseen patient could increase consistency and quality in radiotherapy treatment planning. We propose a machine learning method that uses previous treatment plans to predict such dose-volume histograms. The key to the approach is the framing of dose-volume histograms in a probabilistic setting.The training consists of estimating, from the patients in the training set, the joint probability distribution of some predictive features and the dose. The joint distribution immediately provides an estimate of the conditional probability of the dose given the values of the predictive features. The prediction consists of estimating, from the new patient, the distribution of the predictive features and marginalizing the conditional probability from the training over this. Integrating the resulting probability distribution for the dose yields an estimate of the dose-volume histogram.To illustrate how the proposed method relates to previously proposed methods, we use the signed distance to the target boundary as a single predictive feature. As a proof-of-concept, we predicted dose-volume histograms for the brainstems of 22 acoustic schwannoma patients treated with stereotactic radiosurgery, and for the lungs of 9 lung cancer patients treated with stereotactic body radiation therapy. Comparing with two previous attempts at dose-volume histogram prediction we find that, given the same input data, the predictions are similar.In summary, we propose a method for dose-volume histogram prediction that exploits the intrinsic probabilistic properties of dose-volume histograms. We argue that the proposed method makes up for some deficiencies in previously proposed methods, thereby potentially increasing ease of use, flexibility and ability to perform well with small amounts of training data.

  13. The interstitial distribution of macromolecules in rat tumours is influenced by the negatively charged matrix components

    PubMed Central

    Wiig, Helge; Gyenge, Christina C; Tenstad, Olav

    2005-01-01

    Knowledge of macromolecular distribution volumes is essential in understanding fluid transport within normal and pathological tissues. In this study in vivo we determined the distribution volumes of several macromolecules, including one monoclonal antibody, in tumours and tested whether charges associated with the tumour extracellular matrix influence their available volumes. Steady state levels of the monoclonal antibody trastuzumab (Herceptin) (pI = 9.2), IgG (pI = 7.6) as well as native (pI = 5.0) and cationized albumin (pI = 7.6) were established in rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours by continuous infusion using osmotic minipumps. After a 5–7 day infusion period, the rats were nephrectomized and the extracellular volume was determined with 51Cr-labelled EDTA. Plasma volumes were measured with 125I-labelled human serum albumin or rat IgM in a separate series. Steady state concentrations of probes were determined in the interstitial fluid that was isolated by centrifugation from tumours or by post mortem wick implantation in the back skin. Calculations were made for interstitial fluid volume (Vi), along with the available (Va/Vi) and excluded (Ve/Vi) relative interstitial volume fractions. The Ve/Vi for the positively charged trastuzumab in tumours averaged 0.29 ± 0.03 (n = 16), a value which was significantly lower than the corresponding one for IgG of 0.36 ± 0.02 (n = 16). Native albumin was excluded from 38% of the tumour interstitial fluid, whereas cationization of albumin reduced the excluded volume by ∼50%. Our experiments suggest that the tumour interstitium acts as a negatively charged matrix and is an important factor in determining the macromolecular distribution volume. PMID:15994186

  14. The interstitial distribution of macromolecules in rat tumours is influenced by the negatively charged matrix components.

    PubMed

    Wiig, Helge; Gyenge, Christina C; Tenstad, Olav

    2005-09-01

    Knowledge of macromolecular distribution volumes is essential in understanding fluid transport within normal and pathological tissues. In this study in vivo we determined the distribution volumes of several macromolecules, including one monoclonal antibody, in tumours and tested whether charges associated with the tumour extracellular matrix influence their available volumes. Steady state levels of the monoclonal antibody trastuzumab (Herceptin) (pI = 9.2), IgG (pI = 7.6) as well as native (pI = 5.0) and cationized albumin (pI = 7.6) were established in rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours by continuous infusion using osmotic minipumps. After a 5-7 day infusion period, the rats were nephrectomized and the extracellular volume was determined with 51Cr-labelled EDTA. Plasma volumes were measured with 125I-labelled human serum albumin or rat IgM in a separate series. Steady state concentrations of probes were determined in the interstitial fluid that was isolated by centrifugation from tumours or by post mortem wick implantation in the back skin. Calculations were made for interstitial fluid volume (Vi), along with the available (Va/Vi) and excluded (Ve/Vi) relative interstitial volume fractions. The Ve/Vi for the positively charged trastuzumab in tumours averaged 0.29 +/- 0.03 (n = 16), a value which was significantly lower than the corresponding one for IgG of 0.36 +/- 0.02 (n = 16). Native albumin was excluded from 38% of the tumour interstitial fluid, whereas cationization of albumin reduced the excluded volume by approximately 50%. Our experiments suggest that the tumour interstitium acts as a negatively charged matrix and is an important factor in determining the macromolecular distribution volume.

  15. Analysis of growth of tetraploid nuclei in roots of Vicia faba.

    PubMed

    Bansal, J; Davidson, D

    1978-03-01

    Growth of nuclei of a marked population of cells was determined from G1 to prophase in roots of Vicia faba. The cells were marked by inducing them to become tetraploid by treatment with 0.002% colchicine for 1 hr. Variation in nuclear volume is large; it is established in early G1 and maintained through interphase and into prophase. One consequence of this variation is that there is considerable overlap between volumes of nuclei of different ages in the cell cycle; nuclear volume, we suggest, cannot be used as an accurate indicator of the age of the cell in its growth cycle. Nuclei exhibit considerable variation in their growth rate through the cell cycle. Of the marked population of cells, about 65% had completed a cell cycle 14--15 hr after they were formed. These tetraploid nuclei have a cell cycle duration similar to that of fast cycling diploid cells of the same roots. Since they do complete a cell cycle, at least 65% of the nuclei studied must come from rapidly proliferating cells, showing that variability in nuclear volumes must be present in growing cells and cannot be attributed solely to the presence, in our samples, of non-cycling cells.

  16. Relationship of pericardial fat with lipoprotein distribution: The Multi-Ethnic study of atherosclerosis.

    PubMed

    Ong, Kwok-Leung; Ding, Jingzhong; McClelland, Robyn L; Cheung, Bernard M Y; Criqui, Michael H; Barter, Philip J; Rye, Kerry-Anne; Allison, Matthew A

    2015-08-01

    Pericardial fat and lipoprotein abnormalities contribute to increased risk of cardiovascular disease (CVD). We investigated the relationship between pericardial fat volume and lipoprotein distribution, and whether the association of pericardial fat volume with subclinical atherosclerosis and incident CVD events differs according to lipoprotein distribution. We analyzed data from 5407 participants from the Multi-Ethnic Study of Atherosclerosis who had measurements of pericardial fat volume, lipoprotein distribution, carotid intima-media thickness (IMT), and coronary artery calcium (CAC). All participants were free of clinically apparent CVD at baseline. Incident CVD was defined as any adjudicated CVD event. After adjusting for demographic factors, traditional risk factors, and biomarkers of inflammation and hemostasis, a larger pericardial fat volume was associated with higher large VLDL particle (VLDL-P) concentration and small HDL particle (HDL-P) concentration, and smaller HDL-P size (regression coefficients = 0.585 nmol/L, 0.366 μmol/L, and -0.025 nm per SD increase in pericardial fat volume respectively, all P < 0.05). The association of pericardial fat volume with large VLDL-P concentration and HDL-P size, but not small HDL-P concentration, remained significant after further adjusting for each other as well as LDL cholesterol, HDL cholesterol, and triglycerides. The relationship of pericardial fat volume with incident CVD events, carotid IMT, and prevalence and severity of CAC did not differ by quartiles of large VLDL-P concentration, small HDL-P concentration, or HDL-P size (P for interaction>0.05). Pericardial fat is associated with atherogenic lipoprotein abnormalities. However, its relationship with subclinical atherosclerosis and incident CVD events does not differ according to lipoprotein distribution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Single-cell adhesion probed in-situ using optical tweezers: A case study with Saccharomyces cerevisiae

    NASA Astrophysics Data System (ADS)

    Castelain, Mickaël; Rouxhet, Paul G.; Pignon, Frédéric; Magnin, Albert; Piau, Jean-Michel

    2012-06-01

    A facile method of using optical trapping to measure cell adhesion forces is presented and applied to the adhesion of Saccharomyces cerevisiae on glass, in contact with solutions of different compositions. Trapping yeast cells with optical tweezers (OT) is not perturbed by cell wall deformation or cell deviation from a spherical shape. The trapping force calibration requires correction not only for the hydrodynamic effect of the neighboring wall but also for spherical aberrations affecting the focal volume and the trap stiffness. Yeast cells trapped for up to 5 h were still able to undergo budding but showed an increase of doubling time. The proportion of adhering cells showed the expected variation according to the solution composition. The detachment force varied in the same way. This observation and the fact that the detachment stress was exerted parallel to the substrate surface point to the role of interactions involving solvated macromolecules. Both the proportion of adhering cells and the removal force showed a distribution which, in our experimental conditions, must be attributed to a heterogeneity of surface properties at the cell level or at the subcellular scale. As compared with magnetic tweezers, atomic force microscopy, and more conventional ways of studying cell adhesion (shear-flow cells), OT present several advantages that are emphasized in this paper.

  18. Evaluation and treatment of iron deficiency anemia: a gastroenterological perspective.

    PubMed

    Zhu, Amy; Kaneshiro, Marc; Kaunitz, Jonathan D

    2010-03-01

    A substantial volume of the consultations requested of gastroenterologists are directed towards the evaluation of anemia. Since iron deficiency anemia often arises from bleeding gastrointestinal lesions, many of which are malignant, establishment of a firm diagnosis usually obligates an endoscopic evaluation. Although the laboratory tests used to make the diagnosis have not changed in many decades, their interpretation has, and this is possibly due to the availability of extensive testing in key populations. We provide data supporting the use of the serum ferritin as the sole useful measure of iron stores, setting the lower limit at 100 microg/l for some populations in order to increase the sensitivity of the test. Trends of the commonly obtained red cell indices, mean corpuscular volume, and the red cell distribution width can provide valuable diagnostic information. Once the diagnosis is established, upper and lower gastrointestinal endoscopy is usually indicated. Nevertheless, in many cases a gastrointestinal source is not found after routine evaluation. Additional studies, including repeat upper and lower endoscopy and often investigation of the small intestine may thus be required. Although oral iron is inexpensive and usually effective, there are many gastrointestinal conditions that warrant treatment of iron deficiency with intravenous iron.

  19. 3DGRAPE/AL User's Manual

    NASA Technical Reports Server (NTRS)

    Sorenson, Reese L.; Alter, Stephen J.

    1995-01-01

    This document is a users' manual for a new three-dimensional structured multiple-block volume g generator called 3DGRAPE/AL. It is a significantly improved version of the previously-released a widely-distributed programs 3DGRAPE and 3DMAGGS. It generates volume grids by iteratively solving the Poisson Equations in three-dimensions. The right-hand-side terms are designed so that user-specific; grid cell heights and user-specified grid cell skewness near boundary surfaces result automatically, with little user intervention. The code is written in Fortran-77, and can be installed with or without a simple graphical user interface which allows the user to watch as the grid is generated. An introduction describing the improvements over the antecedent 3DGRAPE code is presented first. Then follows a chapter on the basic grid generator program itself, and comments on installing it. The input is then described in detail. After that is a description of the Graphical User Interface. Five example cases are shown next, with plots of the results. Following that is a chapter on two input filters which allow use of input data generated elsewhere. Last is a treatment of the theory embodied in the code.

  20. Planar digital nanoliter dispensing system based on thermocapillary actuation.

    PubMed

    Darhuber, Anton A; Valentino, Joseph P; Troian, Sandra M

    2010-04-21

    We provide guidelines for the design and operation of a planar digital nanodispensing system based on thermocapillary actuation. Thin metallic microheaters embedded within a chemically patterned glass substrate are electronically activated to generate and control 2D surface temperature distributions which either arrest or trigger liquid flow and droplet formation on demand. This flow control is a consequence of the variation of a liquid's surface tension with temperature, which is used to draw liquid toward cooler regions of the supporting substrate. A liquid sample consisting of several microliters is placed on a flat rectangular supply cell defined by chemical patterning. Thermocapillary switches are then activated to extract a slender fluid filament from the cell and to divide the filament into an array of droplets whose position and volume are digitally controlled. Experimental results for the power required to extract a filament and to divide it into two or more droplets as a function of geometric and operating parameters are in excellent agreement with hydrodynamic simulations. The capability to dispense ultralow volumes onto a 2D substrate extends the functionality of microfluidic devices based on thermocapillary actuation previously shown effective in routing and mixing nanoliter liquid samples on glass or silicon substrates.

  1. Temporal processing and adaptation in the songbird auditory forebrain.

    PubMed

    Nagel, Katherine I; Doupe, Allison J

    2006-09-21

    Songbird auditory neurons must encode the dynamics of natural sounds at many volumes. We investigated how neural coding depends on the distribution of stimulus intensities. Using reverse-correlation, we modeled responses to amplitude-modulated sounds as the output of a linear filter and a nonlinear gain function, then asked how filters and nonlinearities depend on the stimulus mean and variance. Filter shape depended strongly on mean amplitude (volume): at low mean, most neurons integrated sound over many milliseconds, while at high mean, neurons responded more to local changes in amplitude. Increasing the variance (contrast) of amplitude modulations had less effect on filter shape but decreased the gain of firing in most cells. Both filter and gain changes occurred rapidly after a change in statistics, suggesting that they represent nonlinearities in processing. These changes may permit neurons to signal effectively over a wider dynamic range and are reminiscent of findings in other sensory systems.

  2. Hybrid Parallelism for Volume Rendering on Large-, Multi-, and Many-Core Systems

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

    Howison, Mark; Bethel, E. Wes; Childs, Hank

    2012-01-01

    With the computing industry trending towards multi- and many-core processors, we study how a standard visualization algorithm, ray-casting volume rendering, can benefit from a hybrid parallelism approach. Hybrid parallelism provides the best of both worlds: using distributed-memory parallelism across a large numbers of nodes increases available FLOPs and memory, while exploiting shared-memory parallelism among the cores within each node ensures that each node performs its portion of the larger calculation as efficiently as possible. We demonstrate results from weak and strong scaling studies, at levels of concurrency ranging up to 216,000, and with datasets as large as 12.2 trillion cells.more » The greatest benefit from hybrid parallelism lies in the communication portion of the algorithm, the dominant cost at higher levels of concurrency. We show that reducing the number of participants with a hybrid approach significantly improves performance.« less

  3. Computational analysis of species transport and electrochemical characteristics of a MOLB-type SOFC

    NASA Astrophysics Data System (ADS)

    Hwang, J. J.; Chen, C. K.; Lai, D. Y.

    A multi-physics model coupling electrochemical kinetics with fluid dynamics has been developed to simulate the transport phenomena in mono-block-layer built (MOLB) solid oxide fuel cells (SOFC). A typical MOLB module is composed of trapezoidal flow channels, corrugated positive electrode-electrolyte-negative electrode (PEN) plates, and planar inter-connecters. The control volume-based finite difference method is employed for calculation, which is based on the conservation of mass, momentum, energy, species, and electric charge. In the porous electrodes, the flow momentum is governed by a Darcy model with constant porosity and permeability. The diffusion of reactants follows the Bruggman model. The chemistry within the plates is described via surface reactions with a fixed surface-to-volume ratio, tortuosity and average pore size. Species transports as well as the local variations of electrochemical characteristics, such as overpotential and current density distributions in the electrodes of an MOLB SOFC, are discussed in detail.

  4. Quantitative tomographic measurements of opaque multiphase flows

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

    GEORGE,DARIN L.; TORCZYNSKI,JOHN R.; SHOLLENBERGER,KIM ANN

    2000-03-01

    An electrical-impedance tomography (EIT) system has been developed for quantitative measurements of radial phase distribution profiles in two-phase and three-phase vertical column flows. The EIT system is described along with the computer algorithm used for reconstructing phase volume fraction profiles. EIT measurements were validated by comparison with a gamma-densitometry tomography (GDT) system. The EIT system was used to accurately measure average solid volume fractions up to 0.05 in solid-liquid flows, and radial gas volume fraction profiles in gas-liquid flows with gas volume fractions up to 0.15. In both flows, average phase volume fractions and radial volume fraction profiles from GDTmore » and EIT were in good agreement. A minor modification to the formula used to relate conductivity data to phase volume fractions was found to improve agreement between the methods. GDT and EIT were then applied together to simultaneously measure the solid, liquid, and gas radial distributions within several vertical three-phase flows. For average solid volume fractions up to 0.30, the gas distribution for each gas flow rate was approximately independent of the amount of solids in the column. Measurements made with this EIT system demonstrate that EIT may be used successfully for noninvasive, quantitative measurements of dispersed multiphase flows.« less

  5. Comment on ‘Monte Carlo calculated microdosimetric spread for cell nucleus-sized targets exposed to brachytherapy 125I and 192Ir sources and 60Co cell irradiation’

    NASA Astrophysics Data System (ADS)

    Lindborg, Lennart; Lillhök, Jan; Grindborg, Jan-Erik

    2015-11-01

    The relative standard deviation, σr,D, of calculated multi-event distributions of specific energy for 60Co ϒ rays was reported by the authors F Villegas, N Tilly and A Ahnesjö (Phys. Med. Biol. 58 6149-62). The calculations were made with an upgraded version of the Monte Carlo code PENELOPE. When the results were compared to results derived from experiments with the variance method and simulated tissue equivalent volumes in the micrometre range a difference of about 50% was found. Villegas et al suggest wall-effects as the likely explanation for the difference. In this comment we review some publications on wall-effects and conclude that wall-effects are not a likely explanation.

  6. Comment on 'Monte Carlo calculated microdosimetric spread for cell nucleus-sized targets exposed to brachytherapy (125)I and (192)Ir sources and (60)Co cell irradiation'.

    PubMed

    Lindborg, Lennart; Lillhök, Jan; Grindborg, Jan-Erik

    2015-11-07

    The relative standard deviation, σr,D, of calculated multi-event distributions of specific energy for (60)Co ϒ rays was reported by the authors F Villegas, N Tilly and A Ahnesjö (Phys. Med. Biol. 58 6149-62). The calculations were made with an upgraded version of the Monte Carlo code PENELOPE. When the results were compared to results derived from experiments with the variance method and simulated tissue equivalent volumes in the micrometre range a difference of about 50% was found. Villegas et al suggest wall-effects as the likely explanation for the difference. In this comment we review some publications on wall-effects and conclude that wall-effects are not a likely explanation.

  7. Size distribution and volume fraction of T(1) phase precipitates from TEM images: Direct measurements and related correction.

    PubMed

    Dorin, Thomas; Donnadieu, Patricia; Chaix, Jean-Marc; Lefebvre, Williams; Geuser, Frédéric De; Deschamps, Alexis

    2015-11-01

    Transmission Electron Microscopy (TEM) can be used to measure the size distribution and volume fraction of fine scale precipitates in metallic systems. However, such measurements suffer from a number of artefacts that need to be accounted for, related to the finite thickness of the TEM foil and to the projected observation in two dimensions of the microstructure. We present a correction procedure to describe the 3D distribution of disc-like particles and apply this method to the plate-like T1 precipitates in an Al-Li-Cu alloy in two ageing conditions showing different particle morphologies. The precipitates were imaged in a High-Angular Annular Dark Field Microscope (HAADF-STEM). The corrected size distribution is further used to determine the precipitate volume fraction. Atom probe tomography (APT) is finally utilised as an alternative way to measure the precipitate volume fraction and test the validity of the electron microscopy results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Distribution of mast cells and macrophages and expression of interleukin-6 in periapical cysts.

    PubMed

    Bracks, Igor Vieira; Armada, Luciana; Gonçalves, Lúcio Souza; Pires, Fábio Ramôa

    2014-01-01

    Mast cells and macrophages are important components of the inflammatory infiltrate found in inflammatory periapical diseases. Several cytokines participate in the mechanisms of inflammation, tissue repair, and bone resorption associated with periapical cysts. The aim of the present study was to evaluate the distribution of mast cells and macrophages and the expression of interleukin-6 (IL-6) in periapical cysts. Thirty periapical cysts were selected for the study, and clinical, demographic, and gross information from the cases was obtained from the laboratory records. Five-micrometer sections stained with hematoxylin-eosin were reviewed for analysis of the microscopic features of the cysts, and 3-μm sections on silanized slides were used for immunohistochemical reactions with anti-tryptase, anti-CD68, and anti-IL-6. There was no statistically significant difference in the mean number of mast cells and macrophages when comparing superficial and deep regions of the fibrous capsule of the cysts. Mean number of mast cells on the superficial region of the fibrous capsule was higher in cysts showing intense superficial inflammation and exocytosis. Macrophages were more commonly found in areas showing IL-6 expression, and IL-6 was less expressed in deep regions of the fibrous capsule in cysts showing greater gross volume. The results reinforced the participation of mast cells and macrophages in the pathogenesis of periapical cysts and suggested that IL-6 is not the major bone resorption mediator in larger periapical cysts. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  9. Biomarkers for radiation pneumonitis using non-invasive molecular imaging

    PubMed Central

    Medhora, Meetha; Haworth, Steven; Liu, Yu; Narayanan, Jayashree; Gao, Feng; Zhao, Ming; Audi, Said; Jacobs, Elizabeth R.; Fish, Brian L.; Clough, Anne V.

    2016-01-01

    Rationale Our goal is to develop minimally-invasive biomarkers for predicting radiation-induced lung injury before symptoms develop. Currently there are no biomarkers that can predict radiation pneumonitis. Radiation damage to the whole lung is a serious risk in nuclear accidents or in case of radiological terrorism. Our previous studies have shown a single dose of 15 Gy X-rays to the thorax causes severe pneumonitis in rats by 6–8 weeks. We have also developed a mitigator for radiation pneumonitis and fibrosis that can be started as late as 5 weeks after radiation. Methods We used two functional single photon emission computed tomography (SPECT) probes in vivo in irradiated rat lungs. Regional pulmonary perfusion was measured by injection of technetium labeled macroaggregated albumin (99mTc-MAA). Perfused volume was determined by comparing the volume of distribution of 99mTc-MAA to the anatomical lung volume obtained by micro-CT. A second probe, technetium labeled duramycin that binds to apoptotic cells, was used to measure pulmonary cell death in the same rat model. Results Perfused volume of lung was decreased by ~25% at 1, 2 and 3 weeks after 15 Gy and 99mTc-duramycin uptake was more than doubled at 2 and 3 weeks. There was no change in body weight, breathing rate or lung histology between irradiated and non-irradiated rats at these times. Pulmonary vascular resistance and vascular permeability measured in isolated perfused lungs ex vivo increased at 2 weeks after 15 Gy. Principal conclusions Our results suggest the potential for SPECT biomarkers for predicting radiation injury to the lungs before substantial functional or histological damage is observed. Early prediction of radiation pneumonitis will benefit those receiving radiation in the context of therapy, accidents or terrorism in time to initiate mitigation. PMID:27033892

  10. Toward 2D and 3D imaging of magnetic nanoparticles using EPR measurements.

    PubMed

    Coene, A; Crevecoeur, G; Leliaert, J; Dupré, L

    2015-09-01

    Magnetic nanoparticles (MNPs) are an important asset in many biomedical applications. An effective working of these applications requires an accurate knowledge of the spatial MNP distribution. A promising, noninvasive, and sensitive technique to visualize MNP distributions in vivo is electron paramagnetic resonance (EPR). Currently only 1D MNP distributions can be reconstructed. In this paper, the authors propose extending 1D EPR toward 2D and 3D using computer simulations to allow accurate imaging of MNP distributions. To find the MNP distribution belonging to EPR measurements, an inverse problem needs to be solved. The solution of this inverse problem highly depends on the stability of the inverse problem. The authors adapt 1D EPR imaging to realize the imaging of multidimensional MNP distributions. Furthermore, the authors introduce partial volume excitation in which only parts of the volume are imaged to increase stability of the inverse solution and to speed up the measurements. The authors simulate EPR measurements of different 2D and 3D MNP distributions and solve the inverse problem. The stability is evaluated by calculating the condition measure and by comparing the actual MNP distribution to the reconstructed MNP distribution. Based on these simulations, the authors define requirements for the EPR system to cope with the added dimensions. Moreover, the authors investigate how EPR measurements should be conducted to improve the stability of the associated inverse problem and to increase reconstruction quality. The approach used in 1D EPR can only be employed for the reconstruction of small volumes in 2D and 3D EPRs due to numerical instability of the inverse solution. The authors performed EPR measurements of increasing cylindrical volumes and evaluated the condition measure. This showed that a reduction of the inherent symmetry in the EPR methodology is necessary. By reducing the symmetry of the EPR setup, quantitative images of larger volumes can be obtained. The authors found that, by selectively exciting parts of the volume, the authors could increase the reconstruction quality even further while reducing the amount of measurements. Additionally, the inverse solution of this activation method degrades slower for increasing volumes. Finally, the methodology was applied to noisy EPR measurements: using the reduced EPR setup's symmetry and the partial activation method, an increase in reconstruction quality of ≈ 80% can be seen with a speedup of the measurements with 10%. Applying the aforementioned requirements to the EPR setup and stabilizing the EPR measurements showed a tremendous increase in noise robustness, thereby making EPR a valuable method for quantitative imaging of multidimensional MNP distributions.

  11. Air Force Civil Engineer, Volume 12, Number 1, 2004

    DTIC Science & Technology

    2004-01-01

    Building the ARRK Volume 12 • No. 1 • 2004 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of...Air Force Civil Engineer, Volume 12 , Number 01, 2004) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12 . DISTRIBUTION/AVAILABILITY STATEMENT Approved for public release; distribution

  12. Revised congressional budget request, FY 1982. Conservation and renewable energy program

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

    Not Available

    1981-03-01

    Programs dealing with conservation and renewable energy are reprinted from the Revised Congressional Budget Request FY 1982. From Volume 7, Energy Conservation, information is presented on: buildings and community systems; industrial programs; transportation programs; state and local programs; inventor's program energy conversion technology; energy impact assistance; and residential/commercial retrofit. From Volume 2, Energy Supply Research and Development, information and data are presented on: solar building applications; solar industrial applications; solar power applications; solar information systems; SERI facility; solar international activities; alcohol fuels; geothermal; and hydropower. From Volume 6, Energy Production, Demonstration, and Distribution, information and data on solar energy production,more » demonstration, and distribution are presented. From Volume 3, Energy Supply and R and D Appropriation, information and data on electric energy systems and energy storage systems are included. From Volume 4, information and data are included on geothermal resources development fund. In Volume 5, Power Marketing Administrations, information and data are presented on estimates by appropriations, positions and staff years by appropriation, staffing distribution, and power marketing administrations. Recissions and deferrals for FY 1981 are given. (MCW)« less

  13. 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

  14. Dose Distribution in Bladder and Surrounding Normal Tissues in Relation to Bladder Volume in Conformal Radiotherapy for Bladder Cancer

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

    Majewski, Wojciech, E-mail: wmajewski1@poczta.onet.p; Wesolowska, Iwona; Urbanczyk, Hubert

    2009-12-01

    Purpose: To estimate bladder movements and changes in dose distribution in the bladder and surrounding tissues associated with changes in bladder filling and to estimate the internal treatment margins. Methods and Materials: A total of 16 patients with bladder cancer underwent planning computed tomography scans with 80- and 150-mL bladder volumes. The bladder displacements associated with the change in volume were measured. Each patient had treatment plans constructed for a 'partially empty' (80 mL) and a 'partially full' (150 mL) bladder. An additional plan was constructed for tumor irradiation alone. A subsequent 9 patients underwent sequential weekly computed tomography scanningmore » during radiotherapy to verify the bladder movements and estimate the internal margins. Results: Bladder movements were mainly observed cranially, and the estimated internal margins were nonuniform and largest (>2 cm) anteriorly and cranially. The dose distribution in the bladder worsened if the bladder increased in volume: 70% of patients (11 of 16) would have had bladder underdosed to <95% of the prescribed dose. The dose distribution in the rectum and intestines was better with a 'partially empty' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 23%, 20%, and 15% for the rectum and 162, 144, 123 cm{sup 3} for the intestines, respectively) than with a 'partially full' bladder (volume that received >70%, 80%, and 90% of the prescribed dose was 28%, 24%, and 18% for the rectum and 180, 158, 136 cm{sup 3} for the intestines, respectively). The change in bladder filling during RT was significant for the dose distribution in the intestines. Tumor irradiation alone was significantly better than whole bladder irradiation in terms of organ sparing. Conclusion: The displacements of the bladder due to volume changes were mainly related to the upper wall. The internal margins should be nonuniform, with the largest margins cranially and anteriorly. The changes in bladder filling during RT could influence the dose distribution in the bladder and intestines. The dose distribution in the rectum and bowel was slightly better with a 'partially empty' than with a 'full' bladder.« less

  15. The influence of hepatic transport on the distribution volumes and mean residence time of drug in the body and the accuracy of estimating these parameters by the traditional pharmacokinetic calculations.

    PubMed

    Berezhkovskiy, Leonid M

    2011-11-01

    The influence of hepatic uptake and efflux, which includes passive diffusion and transporter-mediated component, on drug distribution volumes [steady-state volume of distribution (V(ss)) and terminal volume of distribution (V(β))], mean residence time (MRT), clearance, and terminal half-life is considered using a simplified physiologically based pharmacokinetic model. To account for hepatic uptake, liver is treated as two-compartmental unit with drug transfer from extracellular water into hepatocytes. The exactly calculated distribution volumes and MRT are compared with that obtained by the traditional equations based on the assumption of central elimination. It was found that V(ss) may increase more than 10-fold and V(β) more than 100-fold due to the contribution of transporter-mediated uptake. The terminal half-life may be substantially shortened (more than 100-fold) due to transporters. It may also decrease significantly due to the increase of intrinsic hepatic clearance (CL(int)), whereas hepatic clearance has already reached saturation (and stays close to the possible maximum value). It is shown that in case of transporter-mediated uptake of compound into hepatocytes, in the absence of efflux and passive diffusion (unidirectional uptake), hepatic clearance is independent of CL(int) and is determined by hepatic blood flow and uptake rate constant. The effects of transporter-mediated uptake are mostly pronounced for hydrophilic acidic compounds and moderately lipophilic neutral compounds. For basic compounds and lipophilic neutral compounds the change of distribution volumes due to transporters is rather unlikely. It was found that the traditional equations provide very accurate values of V(ss), V(β), and MRT in the absence of transporter action even for very low rates of passive diffusion. On the other hand, the traditional equations fail to provide the correct values of these parameters when the increase of distribution volumes due to transporters takes place, and actually yield the values substantially smaller than the true ones (up to an order of magnitude for V(ss) and MRT, and three orders of magnitude for V(β)). Copyright © 2011 Wiley-Liss, Inc.

  16. Optimization-based mesh correction with volume and convexity constraints

    DOE PAGES

    D'Elia, Marta; Ridzal, Denis; Peterson, Kara J.; ...

    2016-02-24

    In this study, we consider the problem of finding a mesh such that 1) it is the closest, with respect to a suitable metric, to a given source mesh having the same connectivity, and 2) the volumes of its cells match a set of prescribed positive values that are not necessarily equal to the cell volumes in the source mesh. This volume correction problem arises in important simulation contexts, such as satisfying a discrete geometric conservation law and solving transport equations by incremental remapping or similar semi-Lagrangian transport schemes. In this paper we formulate volume correction as a constrained optimizationmore » problem in which the distance to the source mesh defines an optimization objective, while the prescribed cell volumes, mesh validity and/or cell convexity specify the constraints. We solve this problem numerically using a sequential quadratic programming (SQP) method whose performance scales with the mesh size. To achieve scalable performance we develop a specialized multigrid-based preconditioner for optimality systems that arise in the application of the SQP method to the volume correction problem. Numerical examples illustrate the importance of volume correction, and showcase the accuracy, robustness and scalability of our approach.« less

  17. An ancillary method in urine cytology: Nucleolar/nuclear volume ratio for discrimination between benign and malignant urothelial cells.

    PubMed

    Tone, Kiyoshi; Kojima, Keiko; Hoshiai, Keita; Kumagai, Naoya; Kijima, Hiroshi; Kurose, Akira

    2016-06-01

    The essential of urine cytology for the diagnosis and the follow-up of urothelial neoplasia has been widely recognized. However, there are some cases in which a definitive diagnosis cannot be made due to difficulty in discriminating between benign and malignant. This study evaluated the practicality of nucleolar/nuclear volume ratio (%) for the discrimination. Using Papanicolaou-stained slides, 253 benign urothelial cells and 282 malignant urothelial cells were selected and divided into a benign urothelial cell and an urothelial carcinoma (UC) cell groups. Three suspicious cases and four cases in which discrimination between benign and malignant was difficult were prepared for verification test. Subject cells were decolorized and stained with 4',6-diamidino-2-phenylindole for detection of the nuclei and the nucleoli. Z-stack method was performed to analyze. When the cutoff point of 1.514% discriminating benign urothelial cells and UC cells from nucleolar/nuclear volume ratio (%) was utilized, the sensitivity was 56.0%, the specificity was 88.5%, the positive predictive value was 84.5%, and the negative predictive value was 64.4%. Nuclear and nucleolar volume, number of the nucleoli, and nucleolar/nuclear volume ratio (%) were significantly higher in the UC cell group than in the benign urothelial cell group (P <0.001). In the verification test using the nucleolar/nuclear ratio (%), four of the seven cases were concordant with the final diagnosis. This study analyzed the nuclear and nucleolar volume to establish an index for discrimination of benign and malignant urothelial cells, providing possible additional information in urine cytology. Diagn. Cytopathol. 2016;44:483-491. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. [Grain Size Distribution Characteristics of Suspended Particulate Matter as Influenced by the Apparent Pollution in the Eutrophic Urban Landscape Water Body].

    PubMed

    Gong, Dan-yan; Pan, Yang; Huang, Yong; Bao, Wei; Li, Qian-qian

    2016-03-15

    Grain size distribution characteristics of suspended particulate matter (SPM) reflects the apparent polluted condition of the urban landscape water. In order to explore the internal relationship between the eutrophication of urban landscape water's apparent pollution and grain size distribution of SPM, and its influencing factors, this paper selected five representative sampling sites in Feng Jin River which is a typical eutrophication river in Suzhou City, measured the grain size distribution of SPM, sensation pollution index (SPI) and water quality index, and analyzed their correlation. The results showed that: The rich nutrient water possessed a similar characteristics in grain size distribution. The grain size distribution of SPM in water was multimodal, and the the peak position was roughly the same; the grain size distribution of SPM was composed by multiple components. It could be roughly divided into six parts with the particle size range of every group being < 1.5 µm, 1.5-8 µm, 8-35 µm, 35-186 µm, 186-516 µm, > 516 µm. The component III was superior (with an average volume fraction of 38.3%-43.2%), and its volume fraction had a significant positive relation with the SPI value and the Chl-a content. The increase of component III volume fraction was the reflection of particle size's result of increasing SPI value. The increase of component III volume fraction was mainly derived from the increasing algal content. The volume fraction of group IV + group VI + group V was significantly higher under the condition of exogenous enter. When there was no exogenous component, the volume fraction of group IV + group VI + group V had a significant negative correlation with SPI value; when there were exogenous components, the volume fraction of group IV + group VI + group V had a weak positive correlation with SPI value, but the correlation did not reach a significant level. Environmental factors (Fv/Fm and DO) and exogenous factors had an influence by functioning on the algal content which signified the polluted material, and then affected the volume fraction of particle size's components and the quality of apparent water. Hydrodynamic conditions mainly had a certain influence on the median particle size, and had no effect on the apparent polluted condition of water.

  19. Influence of grain size distribution on the mechanical behavior of light alloys in wide range of strain rates

    NASA Astrophysics Data System (ADS)

    Skripnyak, Vladimir A.; Skripnyak, Natalia V.; Skripnyak, Evgeniya G.; Skripnyak, Vladimir V.

    2017-01-01

    Inelastic deformation and damage at the mesoscale level of ultrafine grained (UFG) light alloys with distribution of grain size were investigated in wide loading conditions by experimental and computer simulation methods. The computational multiscale models of representative volume element (RVE) with the unimodal and bimodal grain size distributions were developed using the data of structure researches aluminum and magnesium UFG alloys. The critical fracture stress of UFG alloys on mesoscale level depends on relative volumes of coarse grains. Microcracks nucleation at quasi-static and dynamic loading is associated with strain localization in UFG partial volumes with bimodal grain size distribution. Microcracks arise in the vicinity of coarse and ultrafine grains boundaries. It is revealed that the occurrence of bimodal grain size distributions causes the increasing of UFG alloys ductility, but decreasing of the tensile strength.

  20. Gravitational potential wells and the cosmic bulk flow

    NASA Astrophysics Data System (ADS)

    Wang, Yuyu; Kumar, Abhinav; Feldman, Hume; Watkins, Richard

    2016-03-01

    The bulk flow is a volume average of the peculiar velocities and a useful probe of the mass distribution on large scales. The gravitational instability model views the bulk flow as a potential flow that obeys a Maxwellian Distribution. We use two N-body simulations, the LasDamas Carmen and the Horizon Run, to calculate the bulk flows of various sized volumes in the simulation boxes. Once we have the bulk flow velocities as a function of scale, we investigate the mass and gravitational potential distribution around the volume. We found that matter densities can be asymmetrical and difficult to detect in real surveys, however, the gravitational potential and its gradient may provide better tools to investigate the underlying matter distribution. This study shows that bulk flows are indeed potential flows and thus provides information on the flow sources. We also show that bulk flow magnitudes follow a Maxwellian distribution on scales > 10h-1 Mpc.

  1. SU-D-201-07: Exploring the Utility of 4D FDG-PET/CT Scans in Design of Radiation Therapy Planning Compared with 3D PET/CT: A Prospective Study

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

    Ma, C; Yin, Y

    2015-06-15

    Purpose: A method using four-dimensional(4D) PET/CT in design of radiation treatment planning was proposed and the target volume and radiation dose distribution changes relative to standard three-dimensional (3D) PET/CT were examined. Methods: A target deformable registration method was used by which the whole patient’s respiration process was considered and the effect of respiration motion was minimized when designing radiotherapy planning. The gross tumor volume of a non-small-cell lung cancer was contoured on the 4D FDG-PET/CT and 3D PET/CT scans by use of two different techniques: manual contouring by an experienced radiation oncologist using a predetermined protocol; another technique using amore » constant threshold of standardized uptake value (SUV) greater than 2.5. The target volume and radiotherapy dose distribution between VOL3D and VOL4D were analyzed. Results: For all phases, the average automatic and manually GTV volume was 18.61 cm3 (range, 16.39–22.03 cm3) and 31.29 cm3 (range, 30.11–35.55 cm3), respectively. The automatic and manually volume of merged IGTV were 27.82 cm3 and 49.37 cm3, respectively. For the manual contour, compared to 3D plan the mean dose for the left, right, and total lung of 4D plan have an average decrease 21.55%, 15.17% and 15.86%, respectively. The maximum dose of spinal cord has an average decrease 2.35%. For the automatic contour, the mean dose for the left, right, and total lung have an average decrease 23.48%, 16.84% and 17.44%, respectively. The maximum dose of spinal cord has an average decrease 1.68%. Conclusion: In comparison to 3D PET/CT, 4D PET/CT may better define the extent of moving tumors and reduce the contouring tumor volume thereby optimize radiation treatment planning for lung tumors.« less

  2. Dose to mass for evaluation and optimization of lung cancer radiation therapy.

    PubMed

    Tyler Watkins, William; Moore, Joseph A; Hugo, Geoffrey D; Siebers, Jeffrey V

    2017-11-01

    To evaluate potential organ at risk dose-sparing by using dose-mass-histogram (DMH) objective functions compared with dose-volume-histogram (DVH) objective functions. Treatment plans were retrospectively optimized for 10 locally advanced non-small cell lung cancer patients based on DVH and DMH objectives. DMH-objectives were the same as DVH objectives, but with mass replacing volume. Plans were normalized to dose to 95% of the PTV volume (PTV-D95v) or mass (PTV-D95m). For a given optimized dose, DVH and DMH were intercompared to ascertain dose-to-volume vs. dose-to-mass differences. Additionally, the optimized doses were intercompared using DVH and DMH metrics to ascertain differences in optimized plans. Mean dose to volume, D v ‾, mean dose to mass, D M ‾, and fluence maps were intercompared. For a given dose distribution, DVH and DMH differ by >5% in heterogeneous structures. In homogeneous structures including heart and spinal cord, DVH and DMH are nearly equivalent. At fixed PTV-D95v, DMH-optimization did not significantly reduce dose to OARs but reduced PTV-D v ‾ by 0.20±0.2Gy (p=0.02) and PTV-D M ‾ by 0.23±0.3Gy (p=0.02). Plans normalized to PTV-D95m also result in minor PTV dose reductions and esophageal dose sparing (D v ‾ reduced 0.45±0.5Gy, p=0.02 and D M ‾ reduced 0.44±0.5Gy, p=0.02) compared to DVH-optimized plans. Optimized fluence map comparisons indicate that DMH optimization reduces dose in the periphery of lung PTVs. DVH- and DMH-dose indices differ by >5% in lung and lung target volumes for fixed dose distributions, but optimizing DMH did not reduce dose to OARs. The primary difference observed in DVH- and DMH-optimized plans were variations in fluence to the periphery of lung target PTVs, where low density lung surrounds tumor. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Lhermitte Sign After Chemo-IMRT of Head-and-Neck Cancer: Incidence, Doses, and Potential Mechanisms

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

    Pak, Daniel; Vineberg, Karen; Feng, Felix

    2012-08-01

    Purpose: We have observed a higher rate of Lhermitte sign (LS) after chemo-intensity-modulated radiotherapy (IMRT) of head-and-neck cancer than the published rates after conventional radiotherapy. We hypothesized that the inhomogeneous spinal cord dose distributions produced by IMRT caused a 'bath-and-shower' effect, characterized by low doses in the vicinity of high doses, reducing spinal cord tolerance. Methods and Materials: Seventy-three patients with squamous cell carcinoma of the oropharynx participated in a prospective study of IMRT concurrent with weekly carboplatin and paclitaxel. Of these, 15 (21%) reported LS during at least 2 consecutive follow-up visits. Mean dose, maximum dose, and partial volumemore » and absolute volume (in milliliters) of spinal cord receiving specified doses ({>=}10 Gy, {>=}20 Gy, {>=}30 Gy, and {>=}40 Gy), as well as the pattern of dose distributions at the 'anatomic' spinal cord (from the base of the skull to the aortic arch) and 'plan-related' spinal cord (from the top through the bottom of the planning target volumes), were compared between LS patients and 34 non-LS patients. Results: LS patients had significantly higher spinal cord mean doses, V{sub 30}, V{sub 40}, and absolute volumes receiving 30 Gy or more and 40 Gy or more compared with the non-LS patients (p < 0.05). The strongest predictors of LS were higher V{sub 40} and higher cord volumes receiving 40 Gy or more (p {<=} 0.007). There was no evidence of larger spinal cord volumes receiving low doses in the vicinity of higher doses (bath-and-shower effect) in LS compared with non-LS patients. Conclusions: Greater mean dose, V{sub 30}, V{sub 40}, and cord volumes receiving 30 Gy or more and 40 Gy or more characterized LS compared with non-LS patients. Bath-and-shower effects could not be validated in this study as a potential contributor to LS. The higher-than-expected rates of LS may be because of the specific concurrent chemotherapy agents or more accurate identification of LS in the setting of a prospective study.« less

  4. Red cell volume with changes in plasma osmolarity during maximal exercise.

    NASA Technical Reports Server (NTRS)

    Van Beaumont, W.

    1973-01-01

    The volume of the red cell in vivo was measured during acute changes in plasma osmolarity evoked through short (6 to 8 min) maximal exercise in six male volunteer subjects. Simultaneous measurements of mean corpuscular red cell volume (MCV), hematocrit, blood hemoglobin, mean corpuscular hemoglobin concentration (MCHC), and plasma osmolarity showed that there was no change in the MCV or MCHC with a concomitant rise of nearly 6% in plasma osmolarity. Apparently, in vivo, the volume of the red cell in exercising healthy human subjects does not change measurably, in spite of significant changes in osmotic pressure of the surrounding medium. Consequently, it is not justified to correct postexercise hematocrit measurements for changes in plasma osmolarity.

  5. Vascular wall flow-induced forces in a progressively enlarged aneurysm model.

    PubMed

    Neofytou, Panagiotis; Tsangaris, Sokrates; Kyriakidis, Michalis

    2008-12-01

    The current study is focused on the numerical investigation of the flow field induced by the unsteady flow in the vicinity of an abdominal aortic aneurysm model. The computational fluid dynamics code used is based on the finite volume method, and it has already been used in various bioflow studies. For modelling the rheological behaviour of blood, the Quemada non-Newtonian model is employed, which is suitable for simulating the two-phase character of blood namely a suspension of blood cells in plasma. For examining its non-Newtonian effects a comparison with a corresponding Newtonian flow is carried out. Furthermore, the investigation is focused on the distribution of the flow-induced forces on the interior wall of the aneurysm and in order to study the development of the distribution with the gradual enlargement of the aneurysm, three different degrees of aneurysm-growth have been assumed. Finally and for examining the effect of the distribution on the aneurysm growth, a comparison is made between the pressure and wall shear-stress distributions at the wall for each growth-degree.

  6. Rapid quenching effects in glassy polymers

    NASA Technical Reports Server (NTRS)

    Mcgarry, F. J.

    1982-01-01

    Using a specially constructed microbalance for hydrostatic weighing, density changes in PVC thin film due to rapid quenching through the glass transition temperature were observed. The more severe the quench, the greater the free volume content. Isobaric volume recovery of PVC was also studied by volume dilatometry. Both show aging of relaxing molecular rearrangements taking place as a linear function of logarithmic aging time at room temperature. Distribution of retardation times and Primak's distributed activation energy spectra were applied to the volume recovery data. The concomitant changes in mechanical properties of PVC after quenching were monitored by tensile creep stress-stran to failure rates. All reflect the presence of excess free volume content due to rapid quenching.

  7. Characterisation of the physical composition and microbial community structure of biofilms within a model full-scale drinking water distribution system.

    PubMed

    Fish, Katherine E; Collins, Richard; Green, Nicola H; Sharpe, Rebecca L; Douterelo, Isabel; Osborn, A Mark; Boxall, Joby B

    2015-01-01

    Within drinking water distribution systems (DWDS), microorganisms form multi-species biofilms on internal pipe surfaces. A matrix of extracellular polymeric substances (EPS) is produced by the attached community and provides structure and stability for the biofilm. If the EPS adhesive strength deteriorates or is overcome by external shear forces, biofilm is mobilised into the water potentially leading to degradation of water quality. However, little is known about the EPS within DWDS biofilms or how this is influenced by community composition or environmental parameters, because of the complications in obtaining biofilm samples and the difficulties in analysing EPS. Additionally, although biofilms may contain various microbial groups, research commonly focuses solely upon bacteria. This research applies an EPS analysis method based upon fluorescent confocal laser scanning microscopy (CLSM) in combination with digital image analysis (DIA), to concurrently characterize cells and EPS (carbohydrates and proteins) within drinking water biofilms from a full-scale DWDS experimental pipe loop facility with representative hydraulic conditions. Application of the EPS analysis method, alongside DNA fingerprinting of bacterial, archaeal and fungal communities, was demonstrated for biofilms sampled from different positions around the pipeline, after 28 days growth within the DWDS experimental facility. The volume of EPS was 4.9 times greater than that of the cells within biofilms, with carbohydrates present as the dominant component. Additionally, the greatest proportion of EPS was located above that of the cells. Fungi and archaea were established as important components of the biofilm community, although bacteria were more diverse. Moreover, biofilms from different positions were similar with respect to community structure and the quantity, composition and three-dimensional distribution of cells and EPS, indicating that active colonisation of the pipe wall is an important driver in material accumulation within the DWDS.

  8. Characterisation of the Physical Composition and Microbial Community Structure of Biofilms within a Model Full-Scale Drinking Water Distribution System

    PubMed Central

    Fish, Katherine E.; Collins, Richard; Green, Nicola H.; Sharpe, Rebecca L.; Douterelo, Isabel; Osborn, A. Mark; Boxall, Joby B.

    2015-01-01

    Within drinking water distribution systems (DWDS), microorganisms form multi-species biofilms on internal pipe surfaces. A matrix of extracellular polymeric substances (EPS) is produced by the attached community and provides structure and stability for the biofilm. If the EPS adhesive strength deteriorates or is overcome by external shear forces, biofilm is mobilised into the water potentially leading to degradation of water quality. However, little is known about the EPS within DWDS biofilms or how this is influenced by community composition or environmental parameters, because of the complications in obtaining biofilm samples and the difficulties in analysing EPS. Additionally, although biofilms may contain various microbial groups, research commonly focuses solely upon bacteria. This research applies an EPS analysis method based upon fluorescent confocal laser scanning microscopy (CLSM) in combination with digital image analysis (DIA), to concurrently characterize cells and EPS (carbohydrates and proteins) within drinking water biofilms from a full-scale DWDS experimental pipe loop facility with representative hydraulic conditions. Application of the EPS analysis method, alongside DNA fingerprinting of bacterial, archaeal and fungal communities, was demonstrated for biofilms sampled from different positions around the pipeline, after 28 days growth within the DWDS experimental facility. The volume of EPS was 4.9 times greater than that of the cells within biofilms, with carbohydrates present as the dominant component. Additionally, the greatest proportion of EPS was located above that of the cells. Fungi and archaea were established as important components of the biofilm community, although bacteria were more diverse. Moreover, biofilms from different positions were similar with respect to community structure and the quantity, composition and three-dimensional distribution of cells and EPS, indicating that active colonisation of the pipe wall is an important driver in material accumulation within the DWDS. PMID:25706303

  9. Quantitative chemical imaging of the intracellular spatial distribution of fundamental elements and light metals in single cells.

    PubMed

    Malucelli, Emil; Iotti, Stefano; Gianoncelli, Alessandra; Fratini, Michela; Merolle, Lucia; Notargiacomo, Andrea; Marraccini, Chiara; Sargenti, Azzurra; Cappadone, Concettina; Farruggia, Giovanna; Bukreeva, Inna; Lombardo, Marco; Trombini, Claudio; Maier, Jeanette A; Lagomarsino, Stefano

    2014-05-20

    We report a method that allows a complete quantitative characterization of whole single cells, assessing the total amount of carbon, nitrogen, oxygen, sodium, and magnesium and providing submicrometer maps of element molar concentration, cell density, mass, and volume. This approach allows quantifying elements down to 10(6) atoms/μm(3). This result was obtained by applying a multimodal fusion approach that combines synchrotron radiation microscopy techniques with off-line atomic force microscopy. The method proposed permits us to find the element concentration in addition to the mass fraction and provides a deeper and more complete knowledge of cell composition. We performed measurements on LoVo human colon cancer cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin. The comparison of LoVo-S and LoVo-R revealed different patterns in the maps of Mg concentration with higher values within the nucleus in LoVo-R and in the perinuclear region in LoVo-S cells. This feature was not so evident for the other elements, suggesting that Mg compartmentalization could be a significant trait of the drug-resistant cells.

  10. Three-dimensional preservation of cellular and subcellular structures suggests 1.6 billion-year-old crown-group red algae

    PubMed Central

    Bengtson, Stefan; Sallstedt, Therese; Belivanova, Veneta; Whitehouse, Martin

    2017-01-01

    The ~1.6 Ga Tirohan Dolomite of the Lower Vindhyan in central India contains phosphatized stromatolitic microbialites. We report from there uniquely well-preserved fossils interpreted as probable crown-group rhodophytes (red algae). The filamentous form Rafatazmia chitrakootensis n. gen, n. sp. has uniserial rows of large cells and grows through diffusely distributed septation. Each cell has a centrally suspended, conspicuous rhomboidal disk interpreted as a pyrenoid. The septa between the cells have central structures that may represent pit connections and pit plugs. Another filamentous form, Denaricion mendax n. gen., n. sp., has coin-like cells reminiscent of those in large sulfur-oxidizing bacteria but much more recalcitrant than the liquid-vacuole-filled cells of the latter. There are also resemblances with oscillatoriacean cyanobacteria, although cell volumes in the latter are much smaller. The wider affinities of Denaricion are uncertain. Ramathallus lobatus n. gen., n. sp. is a lobate sessile alga with pseudoparenchymatous thallus, “cell fountains,” and apical growth, suggesting florideophycean affinity. If these inferences are correct, Rafatazmia and Ramathallus represent crown-group multicellular rhodophytes, antedating the oldest previously accepted red alga in the fossil record by about 400 million years. PMID:28291791

  11. Three-dimensional preservation of cellular and subcellular structures suggests 1.6 billion-year-old crown-group red algae.

    PubMed

    Bengtson, Stefan; Sallstedt, Therese; Belivanova, Veneta; Whitehouse, Martin

    2017-03-01

    The ~1.6 Ga Tirohan Dolomite of the Lower Vindhyan in central India contains phosphatized stromatolitic microbialites. We report from there uniquely well-preserved fossils interpreted as probable crown-group rhodophytes (red algae). The filamentous form Rafatazmia chitrakootensis n. gen, n. sp. has uniserial rows of large cells and grows through diffusely distributed septation. Each cell has a centrally suspended, conspicuous rhomboidal disk interpreted as a pyrenoid. The septa between the cells have central structures that may represent pit connections and pit plugs. Another filamentous form, Denaricion mendax n. gen., n. sp., has coin-like cells reminiscent of those in large sulfur-oxidizing bacteria but much more recalcitrant than the liquid-vacuole-filled cells of the latter. There are also resemblances with oscillatoriacean cyanobacteria, although cell volumes in the latter are much smaller. The wider affinities of Denaricion are uncertain. Ramathallus lobatus n. gen., n. sp. is a lobate sessile alga with pseudoparenchymatous thallus, "cell fountains," and apical growth, suggesting florideophycean affinity. If these inferences are correct, Rafatazmia and Ramathallus represent crown-group multicellular rhodophytes, antedating the oldest previously accepted red alga in the fossil record by about 400 million years.

  12. Value-cell bar charts for visualizing large transaction data sets.

    PubMed

    Keim, Daniel A; Hao, Ming C; Dayal, Umeshwar; Lyons, Martha

    2007-01-01

    One of the common problems businesses need to solve is how to use large volumes of sales histories, Web transactions, and other data to understand the behavior of their customers and increase their revenues. Bar charts are widely used for daily analysis, but only show highly aggregated data. Users often need to visualize detailed multidimensional information reflecting the health of their businesses. In this paper, we propose an innovative visualization solution based on the use of value cells within bar charts to represent business metrics. The value of a transaction can be discretized into one or multiple cells: high-value transactions are mapped to multiple value cells, whereas many small-value transactions are combined into one cell. With value-cell bar charts, users can 1) visualize transaction value distributions and correlations, 2) identify high-value transactions and outliers at a glance, and 3) instantly display values at the transaction record level. Value-Cell Bar Charts have been applied with success to different sales and IT service usage applications, demonstrating the benefits of the technique over traditional charting techniques. A comparison with two variants of the well-known Treemap technique and our earlier work on Pixel Bar Charts is also included.

  13. Time-dependent cell disintegration kinetics in lung tumors after irradiation

    NASA Astrophysics Data System (ADS)

    Chvetsov, Alexei V.; Palta, Jatinder J.; Nagata, Yasushi

    2008-05-01

    We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T1/2. The half-life T1/2 is determined using the least-squares fit to the clinical data on lung tumor size variation with time after stereotactic radiotherapy. We show that the tumor volume variation after stereotactic radiotherapy of solitary lung tumors can be approximated by an exponential function. A small constant component in the volume variation does not change with time; however, this component may be the residual irregular density due to radiation fibrosis and was, therefore, subtracted from the total volume variation in our computations. Using computerized fitting of the exponent function to the clinical data for selected patients, we have determined that the average half-life T1/2 of cell disintegration is 28.2 days for squamous cell carcinoma and 72.4 days for adenocarcinoma. This model is needed for simulating the tumor volume variation during radiotherapy, which may be important for time-dependent treatment planning of proton therapy that is sensitive to density variations.

  14. Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state.

    PubMed

    Mudie, Deanna M; Murray, Kathryn; Hoad, Caroline L; Pritchard, Susan E; Garnett, Martin C; Amidon, Gordon L; Gowland, Penny A; Spiller, Robin C; Amidon, Gregory E; Marciani, Luca

    2014-09-02

    The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent upon the volumes and distribution of gastric and small intestinal water. However, little is known about the time courses and distribution of water volumes in vivo in an undisturbed gut. Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds.

  15. Spatial distribution of Eucalyptus roots in a deep sandy soil in the Congo: relationships with the ability of the stand to take up water and nutrients.

    PubMed

    Laclau, J P; Arnaud, M; Bouillet, J P; Ranger, J

    2001-02-01

    Spatial statistical analyses were performed to describe root distribution and changes in soil strength in a mature clonal plantation of Eucalyptus spp. in the Congo. The objective was to analyze spatial variability in root distribution. Relationships between root distribution, soil strength and the water and nutrient uptake by the stand were also investigated. We studied three, 2.35-m-wide, vertical soil profiles perpendicular to the planting row and at various distances from a representative tree. The soil profiles were divided into 25-cm2 grid cells and the number of roots in each of three diameter classes counted in each grid cell. Two profiles were 2-m deep and the third profile was 5-m deep. There was both vertical and horizontal anisotropy in the distribution of fine roots in the three profiles, with root density decreasing sharply with depth and increasing with distance from the stump. Roots were present in areas with high soil strength values (> 6,000 kPa). There was a close relationship between soil water content and soil strength in this sandy soil. Soil strength increased during the dry season mainly because of water uptake by fine roots. There were large areas with low root density, even in the topsoil. Below a depth of 3 m, fine roots were spatially concentrated and most of the soil volume was not explored by roots. This suggests the presence of drainage channels, resulting from the severe hydrophobicity of the upper soil.

  16. Intratumor distribution and test-retest comparisons of physiological parameters quantified by dynamic contrast-enhanced MRI in rat U251 glioma.

    PubMed

    Aryal, Madhava P; Nagaraja, Tavarekere N; Brown, Stephen L; Lu, Mei; Bagher-Ebadian, Hassan; Ding, Guangliang; Panda, Swayamprava; Keenan, Kelly; Cabral, Glauber; Mikkelsen, Tom; Ewing, James R

    2014-10-01

    The distribution of dynamic contrast-enhanced MRI (DCE-MRI) parametric estimates in a rat U251 glioma model was analyzed. Using Magnevist as contrast agent (CA), 17 nude rats implanted with U251 cerebral glioma were studied by DCE-MRI twice in a 24 h interval. A data-driven analysis selected one of three models to estimate either (1) plasma volume (vp), (2) vp and forward volume transfer constant (K(trans)) or (3) vp, K(trans) and interstitial volume fraction (ve), constituting Models 1, 2 and 3, respectively. CA distribution volume (VD) was estimated in Model 3 regions by Logan plots. Regions of interest (ROIs) were selected by model. In the Model 3 ROI, descriptors of parameter distributions--mean, median, variance and skewness--were calculated and compared between the two time points for repeatability. All distributions of parametric estimates in Model 3 ROIs were positively skewed. Test-retest differences between population summaries for any parameter were not significant (p ≥ 0.10; Wilcoxon signed-rank and paired t tests). These and similar measures of parametric distribution and test-retest variance from other tumor models can be used to inform the choice of biomarkers that best summarize tumor status and treatment effects. Copyright © 2014 John Wiley & Sons, Ltd.

  17. 39 CFR 3010.23 - Calculation of percentage change in rates.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... rate cell in the class is multiplied by the planned rate for the respective cell and the resulting products are summed. Then, the same set of rate cell volumes are multiplied by the corresponding current..., 2, ..., N) Ri,n = planned rate of rate cell i Ri,c = current rate of rate cell i Vi = volume of rate...

  18. 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

  19. Flash X-Ray measurements on the shock-induced dispersal of a dense particle curtain

    DOE PAGES

    Wagner, Justin L.; Kearney, Sean P.; Beresh, Steven J.; ...

    2015-11-23

    The interaction of a Mach 1.67 shock wave with a dense particle curtain is quantified using flash radiography. These new data provide a view of particle transport inside a compressible, dense gas–solid flow of high optical opacity. The curtain, composed of 115-µm glass spheres, initially spans 87 % of the test section width and has a streamwise thickness of about 2 mm. Radiograph intensities are converted to particle volume fraction distributions using the Beer–Lambert law. The mass in the particle curtain, as determined from the X-ray data, is in reasonable agreement with that given from a simpler method using amore » load cell and particle imaging. Following shock impingement, the curtain propagates downstream and the peak volume fraction decreases from about 23 to about 4 % over a time of 340 µs. The propagation occurs asymmetrically, with the downstream side of the particle curtain experiencing a greater volume fraction gradient than the upstream side, attributable to the dependence of particle drag on volume fraction. Bulk particle transport is quantified from the time-dependent center of mass of the curtain. Furthermore, the bulk acceleration of the curtain is shown to be greater than that predicted for a single 115-µm particle in a Mach 1.67 shock-induced flow.« less

  20. Flash X-Ray measurements on the shock-induced dispersal of a dense particle curtain

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

    Wagner, Justin L.; Kearney, Sean P.; Beresh, Steven J.

    The interaction of a Mach 1.67 shock wave with a dense particle curtain is quantified using flash radiography. These new data provide a view of particle transport inside a compressible, dense gas–solid flow of high optical opacity. The curtain, composed of 115-µm glass spheres, initially spans 87 % of the test section width and has a streamwise thickness of about 2 mm. Radiograph intensities are converted to particle volume fraction distributions using the Beer–Lambert law. The mass in the particle curtain, as determined from the X-ray data, is in reasonable agreement with that given from a simpler method using amore » load cell and particle imaging. Following shock impingement, the curtain propagates downstream and the peak volume fraction decreases from about 23 to about 4 % over a time of 340 µs. The propagation occurs asymmetrically, with the downstream side of the particle curtain experiencing a greater volume fraction gradient than the upstream side, attributable to the dependence of particle drag on volume fraction. Bulk particle transport is quantified from the time-dependent center of mass of the curtain. Furthermore, the bulk acceleration of the curtain is shown to be greater than that predicted for a single 115-µm particle in a Mach 1.67 shock-induced flow.« less

  1. Flash X-ray measurements on the shock-induced dispersal of a dense particle curtain

    NASA Astrophysics Data System (ADS)

    Wagner, Justin L.; Kearney, Sean P.; Beresh, Steven J.; DeMauro, Edward P.; Pruett, Brian O.

    2015-12-01

    The interaction of a Mach 1.67 shock wave with a dense particle curtain is quantified using flash radiography. These new data provide a view of particle transport inside a compressible, dense gas-solid flow of high optical opacity. The curtain, composed of 115-µm glass spheres, initially spans 87 % of the test section width and has a streamwise thickness of about 2 mm. Radiograph intensities are converted to particle volume fraction distributions using the Beer-Lambert law. The mass in the particle curtain, as determined from the X-ray data, is in reasonable agreement with that given from a simpler method using a load cell and particle imaging. Following shock impingement, the curtain propagates downstream and the peak volume fraction decreases from about 23 to about 4 % over a time of 340 µs. The propagation occurs asymmetrically, with the downstream side of the particle curtain experiencing a greater volume fraction gradient than the upstream side, attributable to the dependence of particle drag on volume fraction. Bulk particle transport is quantified from the time-dependent center of mass of the curtain. The bulk acceleration of the curtain is shown to be greater than that predicted for a single 115-µm particle in a Mach 1.67 shock-induced flow.

  2. 31P NMR spectroscopy studies of phospholipid metabolism in human melanoma xenograft lines differing in rate of tumour cell proliferation.

    PubMed

    Lyng, H; Olsen, D R; Petersen, S B; Rofstad, E K

    1995-04-01

    The concentration of phospholipid metabolites in tumours has been hypothesized to be related to rate of cell membrane turnover and may reflect rate of cell proliferation. The purpose of the study reported here was to investigate whether 31P NMR resonance ratios involving the phosphomonoester (PME) or phosphodiester (PDE) resonance are correlated to fraction of cells in S-phase or volume-doubling time in experimental tumours. Four human melanoma xenograft lines (BEX-t, HUX-t, SAX-t, WIX-t) were included in the study. The tumours were grown subcutaneously in male BALB/c-nu/nu mice. 31P NMR spectroscopy was performed at a magnetic field strength of 4.7 T. Fraction of cells in S-phase was measured by flow cytometry. Tumour volume-doubling time was determined by Gompertzian analysis of volumetric growth data. BEX-t and SAX-t tumours differed in fraction of cells in S-phase and volume-doubling time, but showed similar 31P NMR resonance ratios. BEX-t and WIX-t tumours showed significantly different 31P NMR resonance ratios but similar fractions of cells in S-phase. The 31P NMR resonance ratios were significantly different for small and large HUX-t tumours even though fraction of cells in S-phase and volume-doubling time did not differ with tumour volume. None of the 31P NMR resonance ratios showed significant increase with increasing fraction of cells in S-phase or significant decrease with increasing tumour volume-doubling time across the four xenograft lines.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Converging stereotactic radiotherapy using kilovoltage X-rays: experimental irradiation of normal rabbit lung and dose-volume analysis with Monte Carlo simulation.

    PubMed

    Kawase, Takatsugu; Kunieda, Etsuo; Deloar, Hossain M; Tsunoo, Takanori; Seki, Satoshi; Oku, Yohei; Saitoh, Hidetoshi; Saito, Kimiaki; Ogawa, Eileen N; Ishizaka, Akitoshi; Kameyama, Kaori; Kubo, Atsushi

    2009-10-01

    To validate the feasibility of developing a radiotherapy unit with kilovoltage X-rays through actual irradiation of live rabbit lungs, and to explore the practical issues anticipated in future clinical application to humans through Monte Carlo dose simulation. A converging stereotactic irradiation unit was developed, consisting of a modified diagnostic computed tomography (CT) scanner. A tiny cylindrical volume in 13 normal rabbit lungs was individually irradiated with single fractional absorbed doses of 15, 30, 45, and 60 Gy. Observational CT scanning of the whole lung was performed every 2 weeks for 30 weeks after irradiation. After 30 weeks, histopathologic specimens of the lungs were examined. Dose distribution was simulated using the Monte Carlo method, and dose-volume histograms were calculated according to the data. A trial estimation of the effect of respiratory movement on dose distribution was made. A localized hypodense change and subsequent reticular opacity around the planning target volume (PTV) were observed in CT images of rabbit lungs. Dose-volume histograms of the PTVs and organs at risk showed a focused dose distribution to the target and sufficient dose lowering in the organs at risk. Our estimate of the dose distribution, taking respiratory movement into account, revealed dose reduction in the PTV. A converging stereotactic irradiation unit using kilovoltage X-rays was able to generate a focused radiobiologic reaction in rabbit lungs. Dose-volume histogram analysis and estimated sagittal dose distribution, considering respiratory movement, clarified the characteristics of the irradiation received from this type of unit.

  4. Spatial and temporal single-cell volume estimation by a fluorescence imaging technique with application to astrocytes in primary culture

    NASA Astrophysics Data System (ADS)

    Khatibi, Siamak; Allansson, Louise; Gustavsson, Tomas; Blomstrand, Fredrik; Hansson, Elisabeth; Olsson, Torsten

    1999-05-01

    Cell volume changes are often associated with important physiological and pathological processes in the cell. These changes may be the means by which the cell interacts with its surrounding. Astroglial cells change their volume and shape under several circumstances that affect the central nervous system. Following an incidence of brain damage, such as a stroke or a traumatic brain injury, one of the first events seen is swelling of the astroglial cells. In order to study this and other similar phenomena, it is desirable to develop technical instrumentation and analysis methods capable of detecting and characterizing dynamic cell shape changes in a quantitative and robust way. We have developed a technique to monitor and to quantify the spatial and temporal volume changes in a single cell in primary culture. The technique is based on two- and three-dimensional fluorescence imaging. The temporal information is obtained from a sequence of microscope images, which are analyzed in real time. The spatial data is collected in a sequence of images from the microscope, which is automatically focused up and down through the specimen. The analysis of spatial data is performed off-line and consists of photobleaching compensation, focus restoration, filtering, segmentation and spatial volume estimation.

  5. Can Platelet and Leukocyte Indicators Give Us an Idea about Distant Metastasis in Nasopharyngeal Cancer?

    PubMed

    Arıcıgil, Mitat; Dündar, Mehmet Akif; Yücel, Abitter; Arbağ, Hamdi; Aziz, Suhayb Kuria

    This study aimes to evaluate platelet and leucocyte indicators, such as the mean platelet volume, platelet distribution width, plateletcrit, white blood cell count, neutrophil to lymphocyte ratio in nasopharyngeal cancer patients and also to evaluate the relationship between these indicators and nasopharyngeal cancer with distant metastasis. The medical records of 118 patients diagnosed with nasopharyngeal cancer in our hospital between January 2006 and August 2015 were reviewed. The nasopharyngeal cancer group was further sub grouped according to the presence or absence of distant metastasis and TNM (tumour - T, node - N, metastasis - M) classification. A control group consisted of 120 healthy patients. The platelet and leucocyte values at the time of the initial diagnosis were recorded. Neutrophil to lymphocyte ratio and platelet distribution width values were significantly higher in the nasopharyngeal cancer group. But only platelet distribution width values were significantly higher in the nasopharyngeal cancer group with distant metastasis compared to the nasopharyngeal cancer group without distant metastasis. Neutrophil to lymphocyte ratio and platelet distribution width values may increase in nasopharyngeal cancer. But only the platelet distribution width values may give us an idea about the distant metastasis in nasopharyngeal cancer.

  6. 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.

  7. 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.

  8. Role of environmental and antibiotic stress on Staphylococcus epidermidis biofilm microstructure.

    PubMed

    Stewart, Elizabeth J; Satorius, Ashley E; Younger, John G; Solomon, Michael J

    2013-06-11

    Cellular clustering and separation of Staphylococcus epidermidis surface adherent biofilms were found to depend significantly on both antibiotic and environmental stress present during growth under steady flow. Image analysis techniques common to colloidal science were applied to image volumes acquired with high-resolution confocal laser scanning microscopy to extract spatial positions of individual bacteria in volumes of size ~30 × 30 × 15 μm(3). The local number density, cluster distribution, and radial distribution function were determined at each condition by analyzing the statistics of the bacterial spatial positions. Environmental stressors of high osmotic pressure (776 mM NaCl) and sublethal antibiotic dose (1.9 μg/mL vancomycin) decreased the average bacterial local number density 10-fold. Device-associated bacterial biofilms are frequently exposed to these environmental and antibiotic stressors while undergoing flow in the bloodstream. Characteristic density phenotypes associated with low, medium, and high local number densities were identified in unstressed S. epidermidis biofilms, while stressed biofilms contained medium- and low-density phenotypes. All biofilms exhibited clustering at length scales commensurate with cell division (~1.0 μm). However, density phenotypes differed in cellular connectivity at the scale of ~6 μm. On this scale, nearly all cells in the high- and medium-density phenotypes were connected into a single cluster with a structure characteristic of a densely packed disordered fluid. However, in the low-density phenotype, the number of clusters was greater, equal to 4% of the total number of cells, and structures were fractal in nature with d(f) =1.7 ± 0.1. The work advances the understanding of biofilm growth, informs the development of predictive models of transport and mechanical properties of biofilms, and provides a method for quantifying the kinetics of bacterial surface colonization as well as biofilm fracture and fragmentation.

  9. Determination of Normal Distribution of Distended Colon Volumes to Guide Performance of Colonic Imaging With Fluid Distention.

    PubMed

    Zheng, Karen S; Small, William C; Mittal, Pardeep K; Cai, Qingpo; Kang, Jian; Moreno, Courtney C

    2016-01-01

    The purpose was to determine the normal distribution of distended colon volumes as a guide for rectal contrast material administration protocols. All computed tomography colonography studies performed at Emory University Hospital, Atlanta, Georgia, between January 2009 and January 2015, were reviewed retrospectively. In total, 85 subjects were included in the analysis (64% [54 of 85] female and 36% [31 of 85] male). Mean patient age was 65 years (range: 42-86y). Distended colon volumes were determined from colon length and transaxial diameter measurements made using a 3-dimensional workstation. Age, sex, race, height, weight, and body mass index were recorded. The normal distributions of distended colon volumes and lengths were determined. Correlations between colonic volume and colonic length, and demographic variables were assessed. Mean colon volume was 2.1L (range: 0.7-4.4L). Nearly, 17% of patients had a distended colonic volume of >3L. Mean colon length was 197cm (range: 118-285cm). A weak negative correlation was found between age and colonic volume (r = -0.221; P = 0.04). A weak positive correlation was found between body mass index and colonic length (r = 0.368; P = 0.007). Otherwise, no significant correlations were found for distended colonic volume or length and demographic variables. In conclusion, an average of approximately 2L of contrast material may be necessary to achieve full colonic opacification. This volume is larger than previously reported volumes (0.8-1.5L) for rectal contrast material administration protocols. Copyright © 2015 Mosby, Inc. All rights reserved.

  10. Globally distributed software defined storage (proposal)

    NASA Astrophysics Data System (ADS)

    Shevel, A.; Khoruzhnikov, S.; Grudinin, V.; Sadov, O.; Kairkanov, A.

    2017-10-01

    The volume of the coming data in HEP is growing. The volume of the data to be held for a long time is growing as well. Large volume of data - big data - is distributed around the planet. The methods, approaches how to organize and manage the globally distributed data storage are required. The distributed storage has several examples for personal needs like own-cloud.org, pydio.com, seafile.com, sparkleshare.org. For enterprise-level there is a number of systems: SWIFT - distributed storage systems (part of Openstack), CEPH and the like which are mostly object storage. When several data center’s resources are integrated, the organization of data links becomes very important issue especially if several parallel data links between data centers are used. The situation in data centers and in data links may vary each hour. All that means each part of distributed data storage has to be able to rearrange usage of data links and storage servers in each data center. In addition, for each customer of distributed storage different requirements could appear. The above topics are planned to be discussed in data storage proposal.

  11. A Monte Carlo study of the impact of the choice of rectum volume definition on estimates of equivalent uniform doses and the volume parameter

    NASA Astrophysics Data System (ADS)

    Kvinnsland, Yngve; Muren, Ludvig Paul; Dahl, Olav

    2004-08-01

    Calculations of normal tissue complication probability (NTCP) values for the rectum are difficult because it is a hollow, non-rigid, organ. Finding the true cumulative dose distribution for a number of treatment fractions requires a CT scan before each treatment fraction. This is labour intensive, and several surrogate distributions have therefore been suggested, such as dose wall histograms, dose surface histograms and histograms for the solid rectum, with and without margins. In this study, a Monte Carlo method is used to investigate the relationships between the cumulative dose distributions based on all treatment fractions and the above-mentioned histograms that are based on one CT scan only, in terms of equivalent uniform dose. Furthermore, the effect of a specific choice of histogram on estimates of the volume parameter of the probit NTCP model was investigated. It was found that the solid rectum and the rectum wall histograms (without margins) gave equivalent uniform doses with an expected value close to the values calculated from the cumulative dose distributions in the rectum wall. With the number of patients available in this study the standard deviations of the estimates of the volume parameter were large, and it was not possible to decide which volume gave the best estimates of the volume parameter, but there were distinct differences in the mean values of the values obtained.

  12. [Comparison of SIB-IMRT treatment plans for upper esophageal carcinoma].

    PubMed

    Fu, Wei-hua; Wang, Lv-hua; Zhou, Zong-mei; Dai, Jian-rong; Hu, Yi-min

    2003-06-01

    To implement simultaneous integrated boost intensity-modulated radiotherapy(SIB-IMRT) plans for upper esophageal carcinoma and investigate the dose profiles of tumor and electively treated region and the dose to organs at risk (OARs). SIB-IMRT plans were designed for two patients with upper esophageal carcinoma. Two target volumes were predefined: PTV1, the target volume of the primary lesion, which was given to 67.2 Gy, and PTV2, the target volume of electively treated region, which was given to 50.4 Gy. With the same dose-volume constraints, but different beams arrangements (3, 5, 7, or 9 equispaced coplanar beams), four plans were generated. Indices, including dose distribution, dose volume histogram (DVH) and conformity index, were used for comparison of these plans. The plan with three intensity-modulated beams could produce good dose distribution for the two target volumes. The dose conformity to targets and the dose to OARs were improved as the beam number increased. The dose distributions in targets changed little when the beam number increased from 7 to 9. Five to seven intensity-modulated beams can produce desirable dose distributions for simultaneous integrated boost (SIB) treatment for upper esophageal carcinoma. The primary tumor can get higher equivalent dose by SIB treatments. It is easier and more efficient to design plans with equispaced coplanar beams. The efficacy of SIB-IMRT remains to be determined by the clinical outcome.

  13. [Mid-infrared distributed-feedback quantum cascade laser-based photoacoustic detection of trace methane gas].

    PubMed

    Tan, Song; Liu, Wan-feng; Wang, Li-jun; Zhang, Jin-chuan; Li, Lu; Liu, Jun-qi; Liu, Feng-qi; Wang, Zhan-guo

    2012-05-01

    There have been considerable interests in methane detection based on infrared absorption spectroscopy for industrial and environment monitoring. The authors report on the realization of photoacoustic detection of methane (CH4) using mid-infrared distributed-feedback quantum cascade laser (DFB-QCL). The absorption line at 1316.83 cm(-1) was selected for CH4 detection, which can be reached by the self-manufactured DFB-QCL source operating in pulsed mode near 7.6 microm at room-temperature. The CH4 gas is filled to a Helmholtz resonant photoacoustic cell, which was equipped with a commercial electret microphone. The DFB-QCL was operated at 234 Hz with an 80 mW optical peak power. A detection limit of 189 parts per billion in volume was derived when the signal-to-noise ratio equaled 1.

  14. Measurement variability error for estimates of volume change

    Treesearch

    James A. Westfall; Paul L. Patterson

    2007-01-01

    Using quality assurance data, measurement variability distributions were developed for attributes that affect tree volume prediction. Random deviations from the measurement variability distributions were applied to 19381 remeasured sample trees in Maine. The additional error due to measurement variation and measurement bias was estimated via a simulation study for...

  15. Parallel Microchannel-Based Measurements of Individual Erythrocyte Areas and Volumes

    PubMed Central

    Gifford, Sean C.; Frank, Michael G.; Derganc, Jure; Gabel, Christopher; Austin, Robert H.; Yoshida, Tatsuro; Bitensky, Mark W.

    2003-01-01

    We describe a microchannel device which utilizes a novel approach to obtain area and volume measurements on many individual red blood cells. Red cells are aspirated into the microchannels much as a single red blood cell is aspirated into a micropipette. Inasmuch as there are thousands of identical microchannels with defined geometry, data for many individual red cells can be rapidly acquired, and the fundamental heterogeneity of cell membrane biophysics can be analyzed. Fluorescent labels can be used to quantify red cell surface and cytosolic features of interest simultaneously with the measurement of area and volume for a given cell. Experiments that demonstrate and evaluate the microchannel measuring capabilities are presented and potential improvements and extensions are discussed. PMID:12524315

  16. Bistability: Requirements on Cell-Volume, Protein Diffusion, and Thermodynamics

    PubMed Central

    Endres, Robert G.

    2015-01-01

    Bistability is considered wide-spread among bacteria and eukaryotic cells, useful e.g. for enzyme induction, bet hedging, and epigenetic switching. However, this phenomenon has mostly been described with deterministic dynamic or well-mixed stochastic models. Here, we map known biological bistable systems onto the well-characterized biochemical Schlögl model, using analytical calculations and stochastic spatiotemporal simulations. In addition to network architecture and strong thermodynamic driving away from equilibrium, we show that bistability requires fine-tuning towards small cell volumes (or compartments) and fast protein diffusion (well mixing). Bistability is thus fragile and hence may be restricted to small bacteria and eukaryotic nuclei, with switching triggered by volume changes during the cell cycle. For large volumes, single cells generally loose their ability for bistable switching and instead undergo a first-order phase transition. PMID:25874711

  17. Three-dimensional radiotherapy of head and neck and esophageal carcinomas: a monoisocentric treatment technique to achieve improved dose distributions.

    PubMed

    Ahmad, M; Nath, R

    2001-02-20

    The specific aim of three-dimensional conformal radiotherapy is to deliver adequate therapeutic radiation dose to the target volume while concomitantly keeping the dose to surrounding and intervening normal tissues to a minimum. The objective of this study is to examine dose distributions produced by various radiotherapy techniques used in managing head and neck tumors when the upper part of the esophagus is also involved. Treatment planning was performed with a three-dimensional (3-D) treatment planning system. Computerized tomographic (CT) scans used by this system to generate isodose distributions and dose-volume histograms were obtained directly from the CT scanner, which is connected via ethernet cabling to the 3-D planning system. These are useful clinical tools for evaluating the dose distribution to the treatment volume, clinical target volume, gross tumor volume, and certain critical organs. Using 6 and 18 MV photon beams, different configurations of standard treatment techniques for head and neck and esophageal carcinoma were studied and the resulting dose distributions were analyzed. Film validation dosimetry in solid-water phantom was performed to assess the magnitude of dose inhomogeneity at the field junction. Real-time dose measurements on patients using diode dosimetry were made and compared with computed dose values. With regard to minimizing radiation dose to surrounding structures (i.e., lung, spinal cord, etc.), the monoisocentric technique gave the best isodose distributions in terms of dose uniformity. The mini-mantle anterior-posterior/posterior-anterior (AP/PA) technique produced grossly non-uniform dose distribution with excessive hot spots. The dose measured on the patient during the treatment agrees to within +/- 5 % with the computed dose. The protocols presented in this work for simulation, immobilization and treatment planning of patients with head and neck and esophageal tumors provide the optimum dose distributions in the target volume with reduced irradiation of surrounding non-target tissues, and can be routinely implemented in a radiation oncology department. The presence of a real-time dose-measuring system plays an important role in verifying the actual delivery of radiation dose.

  18. [Microscopic structure of the epithelium of the oviducts in cows during the estrus cycle].

    PubMed

    Uhrín, V

    1983-03-01

    The mucous membrane of a cow is covered with ciliary and secretory cells. The so-called basal cells occur at the basal membrane. The counts of ciliary cells vary during the sexual cycle: they reach the maximum (up to 68%) during oestrus. About 13% of cells lose cilia during metoestrus and at the beginning of dioestrus. Reciliation occurs during pro-oestrus. Light and dark ciliary cells can be discerned by the staining of cytoplasm and by the density of nuclei. A higher variability was found in the secretory cells. There are light and dark cells, cells with a wedge shape and rod-shaped cells. Their frequency and function are discussed. Mitoses of epithelium were found in rare cases. The relative volume of epithelium and the mucous membrane of connective tissues change during the sexual cycle. The volume of secretory cells increases during metoestrus and dioestrus and the volume of ciliary cells increases during pro-oestrus and heat. The volume of nuclei decreases in metoestrus and mainly in dioestrus. PAS positive granules occur in the cytoplasm of secretory cells, mainly during metoestrus, in the apical regions. Ptyalin-resistant polysaccharides, besides glycogen, were detected in the cells. The occurrence rate of lipids varies just slightly during the oestrous cycle.

  19. Helicobacter pylori infection in Mongolian gerbils does not initiate hematological diseases

    PubMed Central

    Xie, Chuan; Xu, Li-Yao; Li, Wei; Yang, Zhen; Lu, Nong-Hua

    2014-01-01

    AIM: To investigate whether Helicobacter pylori (H. pylori) infection contributes to idiopathic thrombocytopenic purpura (ITP) or iron-deficiency anemia (IDA) onset in gerbils. METHODS: A total of 135 Mongolian gerbils were randomly divided into two groups: an H. pylori infection group and a control group. Both groups were fed the same diet and the same amount of food. Each group was then divided into three subgroups, which were sacrificed at 6, 12, or 18 mo for analysis. At each time point, arterial blood was collected from the abdominal aorta and a complete blood cell count was analyzed in the clinical laboratory in the First Affiliated Hospital of Nanchang University. RESULTS: There were no significant differences in platelet counts (938.00 ± 270.27/L vs 962.95 ± 162.56 × 109/L), red blood cell counts (8.11 ± 1.25/L vs 8.44 ± 1.48 × 1012/L), or hemoglobin levels (136.9 ± 8.76 g/L vs 123.21 ± 18.42 g/L) between the control and the H. pylori groups, respectively, at 18 mo. With the exception of the mean corpuscular volume (MCV), all other indicators, including white blood cell counts, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cell distribution width, mean platelet volume, platelet distribution width, lymphocyte count, and lymphocyte count percentage, showed no significant differences between the control and H. pylori infection groups at each time point. The MCV in the H. pylori infection group (52.32 f/L ± 2.86 f/L) was significantly lower than the control group (55.63 ± 1.89 f/L) at 18 mo (P = 0.005), though no significant differences were observed at 6 (54.40 ± 2.44 f/L vs 53.30 ± 1.86 f/L) or 12 mo (53.73 ± 2.31 f/L vs 54.80 ± 3.34 f/L). CONCLUSION: A single H. pylori infection is insufficient to cause onset of ITP or IDA and other factors may be required for disease onset. PMID:25232266

  20. Atomic force microscopic study of the effects of ethanol on yeast cell surface morphology.

    PubMed

    Canetta, Elisabetta; Adya, Ashok K; Walker, Graeme M

    2006-02-01

    The detrimental effects of ethanol toxicity on the cell surface morphology of Saccharomyces cerevisiae (strain NCYC 1681) and Schizosaccharomyces pombe (strain DVPB 1354) were investigated using an atomic force microscope (AFM). In combination with culture viability and mean cell volume measurements AFM studies allowed us to relate the cell surface morphological changes, observed on nanometer lateral resolution, with the cellular stress physiology. Exposing yeasts to increasing stressful concentrations of ethanol led to decreased cell viabilities and mean cell volumes. Together with the roughness and bearing volume analyses of the AFM images, the results provided novel insight into the relative ethanol tolerance of S. cerevisiae and Sc. pombe.

  1. The cranial cartilages of teleosts and their classification.

    PubMed Central

    Benjamin, M

    1990-01-01

    The structure and distribution of cartilages has been studied in 45 species from 24 families. The resulting data have been used as a basis for establishing a new classification. A cartilage is regarded as 'cell-rich' if its cells or their lacunae occupy more than half of the tissue volume. Five classes of cell-rich cartilage are recognised (a) hyaline-cell cartilage (common in the lips of bottom-dwelling cyprinids) and its subtypes fibro/hyaline-cell cartilage, elastic/hyaline-cell cartilage and lipo/hyaline-cell cartilage, (b) Schaffer's Zellknorpel, typified by the cartilage in the gill filaments of most teleosts examined, (c) elastic/cell-rich cartilage, such as that which supports the barbels and oral valves of catfish, e.g. Corydoras metae, (d) fibro/cell-rich cartilage, as in the submaxillary meniscus of Sphaerichthys osphromenoides, (e) cell-rich hyaline and (f) matrix-rich hyaline cartilage--both of which are common in the neurocranium and gill arches of most teleosts. The range of cartilages seen, and the predominant cartilage type, is recorded for each species and a list is provided of the tissues that most typify different organs or regions of the head. As a preliminary pointer to developmental relationships between the cartilages, note was taken of gradual transitions between one cartilage and another. It is suggested that hyaline-cell cartilage occupies a key position in teleosts as the most labile of the supporting tissues and is highly characteristic of Cypriniformes. The cartilage that best resembles mammalian hyaline cartilage (matrix-rich hyaline cartilage) has a very conservative distribution in different skeletal elements and the least number of associations with other tissues. It is well represented in Siluriformes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 Fig. 20 Fig. 24 Fig. 25 Fig. 26 Fig. 27 PMID:2384333

  2. Water-filled balloon in the postoperative resection cavity improves dose distribution to target volumes in radiotherapy of maxillary sinus carcinoma.

    PubMed

    Zhang, Qun; Lin, Shi-Rong; He, Fang; Kang, De-Hua; Chen, Guo-Zhang; Luo, Wei

    2011-11-01

    Postoperative radiotherapy is a major treatment for patients with maxillary sinus carcinoma. However, the irregular resection cavity poses a technical difficulty for this treatment, causing uneven dose distribution to target volumes. In this study, we evaluated the dose distribution to target volumes and normal tissues in postoperative intensity-modulated radiotherapy (IMRT) after placing a water-filled balloon into the resection cavity. Three postoperative patients with advanced maxillary sinus carcinoma were selected in this trial. Water-filled balloons and supporting dental stents were fabricated according to the size of the maxillary resection cavity. Simulation CT scans were performed with or without water-filled balloons, IMRT treatment plans were established, and dose distribution to target volumes and organs at risk were evaluated. Compared to those in the treatment plan without balloons, the dose (D98) delivered to 98% of the gross tumor volume (GTV) increased by 2.1 Gy (P = 0.009), homogeneity index (HI) improved by 2.3% (P = 0.001), and target volume conformity index (TCI) of 68 Gy increased by 18.5% (P = 0.011) in the plan with balloons. Dosimetry endpoints of normal tissues around target regions in both plans were not significantly different (P > 0.05) except for the optic chiasm. In the plan without balloons, 68 Gy high-dose regions did not entirely cover target volumes in the ethmoid sinus, posteromedial wall of the maxillary sinus, or surgical margin of the hard palate. In contrast, 68 Gy high-dose regions entirely covered the GTV in the plan with balloons. These results suggest that placing a water-filled balloon in the resection cavity for postoperative IMRT of maxillary sinus carcinoma can reduce low-dose regions and markedly and simultaneously increase dose homogeneity and conformity of target volumes.

  3. Recording High Resolution 3D Lagrangian Motions In Marine Dinoflagellates using Digital Holographic Microscopic Cinematography

    NASA Astrophysics Data System (ADS)

    Sheng, J.; Malkiel, E.; Katz, J.; Place, A. R.; Belas, R.

    2006-11-01

    Detailed data on swimming behavior and locomotion for dense population of dinoflagellates constitutes a key component to understanding cell migration, cell-cell interactions and predator-prey dynamics, all of which affect algae bloom dynamics. Due to the multi-dimensional nature of flagellated cell motions, spatial-temporal Lagrangian measurements of multiple cells in high concentration are very limited. Here we present detailed data on 3D Lagrangian motions for three marine dinoflagellates: Oxyrrhis marina, Karlodinium veneficum, and Pfiesteria piscicida, using digital holographic microscopic cinematography. The measurements are performed in a 5x5x25mm cuvette with cell densities varying from 50,000 ˜ 90,000 cells/ml. Approximately 200-500 cells are tracked simultaneously for 12s at 60fps in a sample volume of 1x1x5 mm at a spatial resolution of 0.4x0.4x2 μm. We fully resolve the longitudinal flagella (˜200nm) along with the Lagrangian trajectory of each organism. Species dependent swimming behavior are identified and categorized quantitatively by velocities, radii of curvature, and rotations of pitch. Statistics on locomotion, temporal & spatial scales, and diffusion rate show substantial differences between species. The scaling between turning radius and cell dimension can be explained by a distributed stokeslet model for a self-propelled body.

  4. Determination of regional lung air volume distribution at mid-tidal breathing from computed tomography: a retrospective study of normal variability and reproducibility

    PubMed Central

    2014-01-01

    Background Determination of regional lung air volume has several clinical applications. This study investigates the use of mid-tidal breathing CT scans to provide regional lung volume data. Methods Low resolution CT scans of the thorax were obtained during tidal breathing in 11 healthy control male subjects, each on two separate occasions. A 3D map of air volume was derived, and total lung volume calculated. The regional distribution of air volume from centre to periphery of the lung was analysed using a radial transform and also using one dimensional profiles in three orthogonal directions. Results The total air volumes for the right and left lungs were 1035 +/− 280 ml and 864 +/− 315 ml, respectively (mean and SD). The corresponding fractional air volume concentrations (FAVC) were 0.680 +/− 0.044 and 0.658 +/− 0.062. All differences between the right and left lung were highly significant (p < 0.0001). The coefficients of variation of repeated measurement of right and left lung air volumes and FAVC were 6.5% and 6.9% and 2.5% and 3.6%, respectively. FAVC correlated significantly with lung space volume (r = 0.78) (p < 0.005). FAVC increased from the centre towards the periphery of the lung. Central to peripheral ratios were significantly higher for the right (0.100 +/− 0.007 SD) than the left (0.089 +/− 0.013 SD) (p < 0.0001). Conclusion A technique for measuring the distribution of air volume in the lung at mid-tidal breathing is described. Mean values and reproducibility are described for healthy male control subjects. Fractional air volume concentration is shown to increase with lung size. PMID:25063729

  5. Solution of the Average-Passage Equations for the Incompressible Flow through Multiple-Blade-Row Turbomachinery

    DTIC Science & Technology

    1994-02-01

    numerical treatment. An explicit numerical procedure based on Runqe-Kutta time stepping for cell-centered, hexahedral finite volumes is...An explicit numerical procedure based on Runge-Kutta time stepping for cell-centered, hexahedral finite volumes is outlined for the approximate...Discretization 16 3.1 Cell-Centered Finite -Volume Discretization in Space 16 3.2 Artificial Dissipation 17 3.3 Time Integration 21 3.4 Convergence

  6. Basal CD34+ Cell Count Predicts Peripheral Blood Stem Cell Mobilization in Healthy Donors after Administration of Granulocyte Colony-Stimulating Factor: A Longitudinal, Prospective, Observational, Single-Center, Cohort Study.

    PubMed

    Martino, Massimo; Gori, Mercedes; Pitino, Annalisa; Gentile, Massimo; Dattola, Antonia; Pontari, Antonella; Vigna, Ernesto; Moscato, Tiziana; Recchia, Anna Grazia; Barilla', Santina; Tripepi, Giovanni; Morabito, Fortunato

    2017-07-01

    A longitudinal, prospective, observational, single-center, cohort study on healthy donors (HDs) was designed to identify predictors of CD34 + cells on day 5 with emphasis on the predictive value of the basal CD34 + cell count. As potential predictors of mobilization, age, sex, body weight, height, blood volume as well as white blood cell count, peripheral blood (PB) mononuclear cells, platelet count, hematocrit, and hemoglobin levels were considered. Two different evaluations of CD34 + cell counts were determined for each donor: baseline (before granulocyte colony-stimulating factor [G-CSF] administration) and in PB after G-CSF administration on the morning of the fifth day (day 5). A total of 128 consecutive HDs (66 males) with a median age of 43 years were enrolled. CD34 + levels on day 5 displayed a non-normal distribution, with a median value of 75.5 cells/µL. To account for the non-normal distribution of the dependent variable, a quantile regression analysis to predict CD34 + on day 5 using the baseline value of CD34 + as the key predictor was performed. On crude analysis, a baseline value of CD34 + ranging from .5 cells/µL to 1 cells/µL predicts a median value of 50 cells/µL on day 5; a value of 2 cells/µL predicts a median value of 70.7 cells/µL; a value of 3 cells/µL to 4 cells/µL predicts a median value of 91.3 cells/µL, and a value ≥ 5 predicts a median value of 112 cells/µL. In conclusion, the baseline PB CD34 + cell count correlates with the effectiveness of allogeneic PB stem cell mobilization and could be useful to plan the collection. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Curcumin affects cell survival and cell volume regulation in human renal and intestinal cells

    PubMed Central

    Kössler, Sonja; Nofziger, Charity; Jakab, Martin; Dossena, Silvia; Paulmichl, Markus

    2012-01-01

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current IClswell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The IClswell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates IClswell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect IClswell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on IClswell can be ruled out. Furthermore, we show that curcumin exposure induces apoptosis in human kidney cells, and at a concentration of 5.0–10 μM induces the appearance of a sub-population of cells with a dramatically increased volume. In these cells the regulation of the cell volume seems to be impaired, most likely as a consequence of the IClswell blockade. Similarly, 50 μM curcumin induced apoptosis, caused cell cycle arrest in G1-phase and increased the volume of human colorectal adenocarcinoma HT-29 cells. The cell cycle arrest in G1 phase may be the mechanism underlying the volume increase observed in this cell line after exposure to curcumin. PMID:22178266

  8. Screening Smoke Performance of Commercially Available Powders. 2. Visible Screening by Titanium Dioxide

    DTIC Science & Technology

    1994-06-01

    NY 10562 (Continued on page ii) 12a. DISTRIBUTION I AVAILABILITY STATEMENT 12b. DISTRIBUTION CODE Approved for public release; distribution is...the weight F., volume (1,. and financial ()F limited figures of merit for numerous grades of commercially available titania are listed in Table 1...is usefull in volume limited applications such as grenades, rockets, artillery rounds, mortars and smoke pots. The third figure of merit gives the

  9. Best Statistical Distribution of flood variables for Johor River in Malaysia

    NASA Astrophysics Data System (ADS)

    Salarpour Goodarzi, M.; Yusop, Z.; Yusof, F.

    2012-12-01

    A complex flood event is always characterized by a few characteristics such as flood peak, flood volume, and flood duration, which might be mutually correlated. This study explored the statistical distribution of peakflow, flood duration and flood volume at Rantau Panjang gauging station on the Johor River in Malaysia. Hourly data were recorded for 45 years. The data were analysed based on water year (July - June). Five distributions namely, Log Normal, Generalize Pareto, Log Pearson, Normal and Generalize Extreme Value (GEV) were used to model the distribution of all the three variables. Anderson-Darling and Kolmogorov-Smirnov goodness-of-fit tests were used to evaluate the best fit. Goodness-of-fit tests at 5% level of significance indicate that all the models can be used to model the distribution of peakflow, flood duration and flood volume. However, Generalize Pareto distribution is found to be the most suitable model when tested with the Anderson-Darling test and the, Kolmogorov-Smirnov suggested that GEV is the best for peakflow. The result of this research can be used to improve flood frequency analysis. Comparison between Generalized Extreme Value, Generalized Pareto and Log Pearson distributions in the Cumulative Distribution Function of peakflow

  10. Molecular analysis and association with clinical and laboratory manifestations in children with sickle cell anemia

    PubMed Central

    Camilo-Araújo, Roberta Faria; Amancio, Olga Maria Silverio; Figueiredo, Maria Stella; Cabanãs-Pedro, Ana Carolina; Braga, Josefina Aparecida Pellegrini

    2014-01-01

    Objectives To analyze the frequency of βS-globin haplotypes and alpha-thalassemia, and their influence on clinical manifestations and the hematological profile of children with sickle cell anemia. Method The frequency of βS-globin haplotypes and alpha-thalassemia and any association with clinical and laboratorial manifestations were determined in 117 sickle cell anemia children aged 3–71 months. The confirmation of hemoglobin SS and determination of the haplotypes were achieved by polymerase chain reaction-restriction fragment length polymorphism, and alpha-thalassemia genotyping was by multiplex polymerase chain reaction (single-tube multiplex-polymerase chain reaction). Results The genotype distribution of haplotypes was 43 (36.7%) Central African Republic/Benin, 41 (35.0%) Central African Republic/Central African Republic, 20 (17.0%) Rare/atypical, and 13 (11.1%) Benin/Benin. The frequency of the α3.7 deletion was 1.71% as homozygous (−α3.7/−α3.7) and 11.9% as heterozygous (−α3.7/αα). The only significant association in respect to haplotypes was related to the mean corpuscular volume. The presence of alpha-thalassemia was significantly associated to decreases in mean corpuscular volume, mean corpuscular hemoglobin and reticulocyte count and to an increase in the red blood cell count. There were no significant associations of βS-globin haplotypes and alpha-thalassemia with clinical manifestations. Conclusions In the study population, the frequency of alpha-thalassemia was similar to published data in Brazil with the Central African Republic haplotype being the most common, followed by the Benin haplotype. βS-globin haplotypes and interaction between alpha-thalassemia and sickle cell anemia did not influence fetal hemoglobin concentrations or the number of clinical manifestations. PMID:25305165

  11. The Neutron Tomography Studies of the Rocks from the Kola Superdeep Borehole

    NASA Astrophysics Data System (ADS)

    Kichanov, S. E.; Kozlenko, D. P.; Ivankina, T. I.; Rutkauskas, A. V.; Lukin, E. V.; Savenko, B. N.

    The volume morphology of a gneiss sample K-8802 recovered from the deep of 8802 m of the Kola Superdeep Borehole and its surface homologue sample PL-36 have been studied by means of neutron radiography and tomography methods. The volumes and size distributions of a biotite-muscovite grains as well as grains orientation distribution have been obtained from experimental data. It was found that the average volumes of the biotite-muscovite grains in surface homologue sample is noticeably larger than the average volume of grains in the deep-seated gneiss sample K-8802. This drastically differences in grains volumes can be explained by the recrystallization processes in deep of the Kola Superdeep Borehole at high temperatures and high pressures.

  12. Quality of red cell concentrates in relation to the volume of the buffy coat removed by automated processing in a top and bottom system.

    PubMed

    Pietersz, R N; Dekker, W J; Reesink, H A

    1991-01-01

    The effect of automated removal of increasing volumes of buffy coat in a 'top and bottom' system on the composition of red cell concentrates (RCC) was investigated. The volume of the buffy coat was adjusted to group 1:50 ml (n = 31), group 2: 70 ml (n = 31) and group 3: 100 ml (n = 31), respectively. The numbers of platelets and leukocytes in the buffy coats were comparable between the groups, whereas the red cell volumes in the buffy coats showed a significant difference (17 +/- 3.6 ml group 1, versus 22 +/- 4.1 ml group 2 and 26 +/- 3.88 ml group 3; p less than 0.001). The volumes, hematocrits and cell counts of the RCC were not significantly different. The plasma volumes were inversely correlated with the volume of buffy coat removed, i.e. 268 +/- 19 ml group 1, versus 257 +/- 15 ml group 2 and 233 +/- 20 ml group 3 (p less than 0.001). We conclude that in the 'top and bottom' system an increase of the volume of the buffy coat from 50 to 100 ml did not improve the quality of the RCC regarding contamination with leukocytes and platelets.

  13. [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.

  14. Bridging stylized facts in finance and data non-stationarities

    NASA Astrophysics Data System (ADS)

    Camargo, Sabrina; Duarte Queirós, Sílvio M.; Anteneodo, Celia

    2013-04-01

    Employing a recent technique which allows the representation of nonstationary data by means of a juxtaposition of locally stationary paths of different length, we introduce a comprehensive analysis of the key observables in a financial market: the trading volume and the price fluctuations. From the segmentation procedure we are able to introduce a quantitative description of statistical features of these two quantities, which are often named stylized facts, namely the tails of the distribution of trading volume and price fluctuations and a dynamics compatible with the U-shaped profile of the volume in a trading section and the slow decay of the autocorrelation function. The segmentation of the trading volume series provides evidence of slow evolution of the fluctuating parameters of each patch, pointing to the mixing scenario. Assuming that long-term features are the outcome of a statistical mixture of simple local forms, we test and compare different probability density functions to provide the long-term distribution of the trading volume, concluding that the log-normal gives the best agreement with the empirical distribution. Moreover, the segmentation of the magnitude price fluctuations are quite different from the results for the trading volume, indicating that changes in the statistics of price fluctuations occur at a faster scale than in the case of trading volume.

  15. Studies on the erythron and the ferrokinetic responses in beagles adapted to hypergravity

    NASA Technical Reports Server (NTRS)

    Beckman, D. A.; Evans, J. W.; Oyama, J.

    1978-01-01

    Red cell survival, ferrokinetics, and hematologic parameters were investigated in beagle dogs exposed to chronic hypergravity (2.6 Gx). Ineffective erythropoiesis, red cell mass, plasma volume, and Cr-51-elution were significantly increased; maximum Fe-59 incorporation was decreased; and there was no change in the mean erythrocyte life span following autologous injection of Cr-51-labeled red cells and Fe-59-labeled transferrin. Red cell count, F(cells), total body hemoglobin (Hb), susceptability to osmotic lysis, and differential reticulocyte count were increased. White blood cell count, venous blood %Hb, mean cell volume, mean cell Hb, mean cell Hb concentration, and serum iron were decreased. No changes were observed for body mass, mg Fe per g Hb, iron binding capacity, percent saturation of iron carrying capacity, or the electrophoretic mobility of purified Hb. This study indicated that chronic exposure to hypergravity induced changes in red cell size, volume, total mass, and membrane permeability.

  16. An assessment of the effects of cell size on AGNPS modeling of watershed runoff

    USGS Publications Warehouse

    Wu, S.-S.; Usery, E.L.; Finn, M.P.; Bosch, D.D.

    2008-01-01

    This study investigates the changes in simulated watershed runoff from the Agricultural NonPoint Source (AGNPS) pollution model as a function of model input cell size resolution for eight different cell sizes (30 m, 60 m, 120 m, 210 m, 240 m, 480 m, 960 m, and 1920 m) for the Little River Watershed (Georgia, USA). Overland cell runoff (area-weighted cell runoff), total runoff volume, clustering statistics, and hot spot patterns were examined for the different cell sizes and trends identified. Total runoff volumes decreased with increasing cell size. Using data sets of 210-m cell size or smaller in conjunction with a representative watershed boundary allows one to model the runoff volumes within 0.2 percent accuracy. The runoff clustering statistics decrease with increasing cell size; a cell size of 960 m or smaller is necessary to indicate significant high-runoff clustering. Runoff hot spot areas have a decreasing trend with increasing cell size; a cell size of 240 m or smaller is required to detect important hot spots. Conclusions regarding cell size effects on runoff estimation cannot be applied to local watershed areas due to the inconsistent changes of runoff volume with cell size; but, optimal cells sizes for clustering and hot spot analyses are applicable to local watershed areas due to the consistent trends.

  17. Correlation between the extent of pneumatization of Agger agger Nasi nasi cells and the anterior-to-posterior length of the frontal recess: A a computer-assisted anatomical study.

    PubMed

    Altıntaş, Ahmet; Çelik, Mustafa; Yegin, Yakup; Canpolat, Sinan; Olgun, Burak; Tülin Kayhan, Fatma

    2017-06-30

    To explore the correlation between the volume of the aAgger nNasi (AN) cell bulge and the A-P length of the frontal recess (FR). In total, 120 patients, who underwent septoplasty, were included. All patients underwent preoperative paranasal sinus computed tomography of the paranasal sinuses (PNS CT) imaging. In total, CT data on of all 120 PNSs patients were analyzed in terms of thewith respect to the extent of pneumatization of the AN cell bulge and the A-P dimensions of the FR. Each side was analyzed separately. We included 120 patients,: 78 (65.0%) females and 42 (35.0 %) males. Their average age was 33.7 ± 11.6 years (range: 18-65 years). The mean volume of the AN cell bulge was 0.26 ± 0.4 mm3 on both the right and left sides. The A-P length of the FR was 7.7 ± 2.2 mm. No significant between-side difference in the mean volume of the AN cell bulge was apparent observed (p=0.906). This volume did not differ significantly by age or sex (p=0.844 and p=0.971, respectively). We found no correlation between the volume of the AN cell bulge and the A-P length of the FR (r = 0.098, p=0.192). In the present study, no correlation between AN cell volume and the A-P length of the FR was found. When studying the anatomical complexity of the FR, it is essential to consider the AN cell volume. We suggest that preoperative CT imaging is critical when endoscopic sinus surgery is planned. However, further studies with larger numbers of patients are needed to explore the relationship between AN cell pneumatization and the anatomy of the FR.

  18. Bidirectional light-scattering image processing method for high-concentration jet sprays

    NASA Astrophysics Data System (ADS)

    Shimizu, I.; Emori, Y.; Yang, W.-J.; Shimoda, M.; Suzuki, T.

    1985-01-01

    In order to study the distributions of droplet size and volume density in high-concentration jet sprays, a new technique is developed, which combines the forward and backward light scattering method and an image processing method. A pulsed ruby laser is used as the light source. The Mie scattering theory is applied to the results obtained from image processing on the scattering photographs. The time history is obtained for the droplet size and volume density distributions, and the method is demonstrated by diesel fuel sprays under various injecting conditions. The validity of the technique is verified by a good agreement in the injected fuel volume distributions obtained by the present method and by injection rate measurements.

  19. Estimating sales and sales market share from sales rank data for consumer appliances

    NASA Astrophysics Data System (ADS)

    Touzani, Samir; Van Buskirk, Robert

    2016-06-01

    Our motivation in this work is to find an adequate probability distribution to fit sales volumes of different appliances. This distribution allows for the translation of sales rank into sales volume. This paper shows that the log-normal distribution and specifically the truncated version are well suited for this purpose. We demonstrate that using sales proxies derived from a calibrated truncated log-normal distribution function can be used to produce realistic estimates of market average product prices, and product attributes. We show that the market averages calculated with the sales proxies derived from the calibrated, truncated log-normal distribution provide better market average estimates than sales proxies estimated with simpler distribution functions.

  20. ( sup 99m Tc)diphosphonate uptake and hemodynamics in arthritis of the immature dog knee

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

    Hansen, E.S.; Soballe, K.; Henriksen, T.B.

    1991-03-01

    The relationship between (99mTc)diphosphonate uptake and bone hemodynamics was studied in canine carrageenan-induced juvenile chronic arthritis. Blood flow was determined with microspheres, plasma and red cell volumes were measured by labeled fibrinogen and red cells, and the microvascular volume and mean transit time of blood were calculated. Normal femoral epiphyses had lower central and higher subchondral blood flow and diphosphonate uptake values. Epiphyseal vascular volume was uniform, resulting in a greater transit time of blood centrally. In arthritis, blood flow and diphosphonate uptake were increased subchondrally and unaffected centrally, while epiphyseal vascular volume was increased throughout, leading to prolonged transitmore » time centrally. The normal metaphyses had low blood flow and diphosphonate uptake values in cancellous bone and very high values in growth plates, but a large vascular volume throughout. The mean transit time therefore was low in growth plates and high in adjacent cancellous bone. Arthritis caused decreased blood flow and diphosphonate uptake in growth plates but increased vascular volume and transit time of blood. Diphosphonate uptake correlated positively with blood flow and plasma volume and negatively with red cell volume in a nonlinear fashion. Thus, changes in diphosphonate uptake and microvascular hemodynamics occur in both epiphyseal and metaphyseal bone in chronic synovitis of the immature knee. The (99mTc)diphosphonate bone scan seems to reflect blood flow, plasma volume, and red cell volume of bone.« less

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