Promoting effects of serotonin on hematopoiesis: ex vivo expansion of cord blood CD34+ stem/progenitor cells, proliferation of bone marrow stromal cells, and antiapoptosis.

PubMed

Yang, Mo; Li, Karen; Ng, Pak Cheung; Chuen, Carmen Ka Yee; Lau, Tze Kin; Cheng, Yuan Shan; Liu, Yuan Sheng; Li, Chi Kong; Yuen, Patrick Man Pan; James, Anthony Edward; Lee, Shuk Man; Fok, Tai Fai

2007-07-01

Serotonin is a monoamine neurotransmitter that has multiple extraneuronal functions. We previously reported that serotonin exerted mitogenic stimulation on megakaryocytopoiesis mediated by 5-hydroxytryptamine (5-HT)2 receptors. In this study, we investigated effects of serotonin on ex vivo expansion of human cord blood CD34+ cells, bone marrow (BM) stromal cell colony-forming unit-fibroblast (CFU-F) formation, and antiapoptosis of megakaryoblastic M-07e cells. Our results showed that serotonin at 200 nM significantly enhanced the expansion of CD34+ cells to early stem/progenitors (CD34+ cells, colony-forming unit-mixed [CFU-GEMM]) and multilineage committed progenitors (burst-forming unit/colony-forming unit-erythroid [BFU/CFU-E], colony-forming unit-granulocyte macrophage, colony-forming unit-megakaryocyte, CD61+ CD41+ cells). Serotonin also increased nonobese diabetic/severe combined immunodeficient repopulating cells in the expansion culture in terms of human CD45+, CD33+, CD14+ cells, BFU/CFU-E, and CFU-GEMM engraftment in BM of animals 6 weeks post-transplantation. Serotonin alone or in addition to fibroblast growth factor, platelet-derived growth factor, or vascular endothelial growth factor stimulated BM CFU-F formation. In M-07e cells, serotonin exerted antiapoptotic effects (annexin V, caspase-3, and propidium iodide staining) and reduced mitochondria membrane potential damage. The addition of ketanserin, a competitive antagonist of 5-HT2 receptor, nullified the antiapoptotic effects of serotonin. Our data suggest the involvement of serotonin in promoting hematopoietic stem cells and the BM microenvironment. Serotonin could be developed for clinical ex vivo expansion of hematopoietic stem cells for transplantation. Disclosure of potential conflicts of interest is found at the end of this article.

[Multiplication of Brucella abortus and production of nitric oxide in two macrophage cell lines of different origin].

PubMed

Serafino, J; Conde, S; Zabal, O; Samartino, L

2007-01-01

Brucella abortus is a bacterium which causes abortions and infertility in cattle and undulant fever in humans. It multiplies intracellularly, evading the mechanisms of cellular death. Nitric oxide (NO) is important in the regulation of the immune response. In the present work, we studied the ability of three B. abortus strains to survive intracellularly in two macrophage cell lines. The bacterial multiplication in both cell lines was determined at two different times in UFC/ ml units. Moreover the inoculated cells were also observed under light-field and fluorescence microscopy stained with Giemsa and acridine orange, respectively. The stain of both cellular lines showed similar results with respect to the UFC/ml determination. The presence of B. abortus was confirmed by electronic microscopy. In both macrophage cell lines inoculated with the rough strain RB51, the multiplication diminished and the level of NO was higher, compared with cells inoculated with smooth strains (S19 and 2308). These results suggest that the absence of O-chain of LPS probably affects the intracellular growth of B. abortus.

Salt-mediated multicell formation in Deinococcus radiodurans.

PubMed Central

Chou, F I; Tan, S T

1991-01-01

The highly radiation-resistant tetracoccal bacterium Deinococcus radiodurans exhibited a reversible multi-cell-form transition which depended on the NaCl concentration in the medium. In response to 0.8% NaCl addition into the medium, the pair/tetrad (designated 2/4) cells in a young culture grew and divided but did not separate and became 8-, 16-, and 32-cell units successively. In exponential growth phase, the cells divided in a 16/32 pattern. Potassium ions were equally effective as Na+ in mediating this multicell-formation effect; Mg2+, Li+, and Ca2+ also worked but produced less multiplicity. This effect appears to be species specific. This-section micrographs revealed that in a 16/32-cell unit, eight 2/4 cells were encased in an orderly manner within a large peripheral wall, showing five cycles of septation. Our results suggest the presence of a salt-sensitive mechanism for controlling cell separation in D. radiodurans. Images PMID:2022617

Wavelength-selective mid-infrared metamaterial absorbers with multiple tungsten cross resonators.

PubMed

Li, Zhigang; Stan, Liliana; Czaplewski, David A; Yang, Xiaodong; Gao, Jie

2018-03-05

Wavelength-selective metamaterial absorbers in the mid-infrared range are demonstrated by using multiple tungsten cross resonators. By adjusting the geometrical parameters of cross resonators in single-sized unit cells, near-perfect absorption with single absorption peak tunable from 3.5 µm to 5.5 µm is realized. The combination of two, three, or four cross resonators of different sizes in one unit cell enables broadband near-perfect absorption at mid-infrared range. The obtained absorption spectra exhibit omnidirectionality and weak dependence on incident polarization. The underlying mechanism of near-perfect absorption with cross resonators is further explained by the optical mode analysis, dispersion relation and equivalent RLC circuit model. Moreover, thermal analysis is performed to study the heat generation and temperature increase in the cross resonator absorbers, while the energy conversion efficiency is calculated for the thermophotovoltaic system made of the cross resonator thermal emitters and low-bandgap semiconductors.

Mechanical behavior of regular open-cell porous biomaterials made of diamond lattice unit cells.

PubMed

Ahmadi, S M; Campoli, G; Amin Yavari, S; Sajadi, B; Wauthle, R; Schrooten, J; Weinans, H; Zadpoor, A A

2014-06-01

Cellular structures with highly controlled micro-architectures are promising materials for orthopedic applications that require bone-substituting biomaterials or implants. The availability of additive manufacturing techniques has enabled manufacturing of biomaterials made of one or multiple types of unit cells. The diamond lattice unit cell is one of the relatively new types of unit cells that are used in manufacturing of regular porous biomaterials. As opposed to many other types of unit cells, there is currently no analytical solution that could be used for prediction of the mechanical properties of cellular structures made of the diamond lattice unit cells. In this paper, we present new analytical solutions and closed-form relationships for predicting the elastic modulus, Poisson׳s ratio, critical buckling load, and yield (plateau) stress of cellular structures made of the diamond lattice unit cell. The mechanical properties predicted using the analytical solutions are compared with those obtained using finite element models. A number of solid and porous titanium (Ti6Al4V) specimens were manufactured using selective laser melting. A series of experiments were then performed to determine the mechanical properties of the matrix material and cellular structures. The experimentally measured mechanical properties were compared with those obtained using analytical solutions and finite element (FE) models. It has been shown that, for small apparent density values, the mechanical properties obtained using analytical and numerical solutions are in agreement with each other and with experimental observations. The properties estimated using an analytical solution based on the Euler-Bernoulli theory markedly deviated from experimental results for large apparent density values. The mechanical properties estimated using FE models and another analytical solution based on the Timoshenko beam theory better matched the experimental observations. Copyright © 2014 Elsevier Ltd. All rights reserved.

An isolation-enhanced quad-element antenna using suspended solid wires for LTE small-cell base stations

NASA Astrophysics Data System (ADS)

Chen, Yen-Sheng; Zhou, Huang-Cheng

2017-05-01

This paper presents a multiple-input-multiple-output (MIMO) antenna that has four-unit elements enabled by an isolation technique for long-term evolution (LTE) small-cell base stations. While earlier studies on MIMO base-station antennas cope with either a lower LTE band (698-960 MHz) or an upper LTE band (1710-2690 MHz), the proposed antenna meets the full LTE specification, yet it uses the maximum number of unit elements to increase channel capacity. The antenna configuration is optimized for good impedance matching and high radiation efficiency. In particular, as the spacing between unit elements is so small that severe mutual coupling occurs, we propose a simple structure with extremely low costs to enhance the isolation. By using suspended solid wires interconnecting the position having strong coupled current of two adjacent elements, an isolation enhancement of 37 dB is achieved. Although solid wires inherently aim at direct-current applications, this work successfully employs such a low-cost technique to microwave antenna development. Experimental results have validated the design guidelines and the proposed configuration, showing that antenna performances including impedance matching, isolation, radiation features, signal correlation, and channel capacity gain are highly desired for LTE small-cell base stations.

BioSentinel: Developing a Space Radiation Biosensor

NASA Technical Reports Server (NTRS)

Santa Maria, Sergio R.

2015-01-01

BioSentinel is an autonomous fully self-contained science mission that will conduct the first study of the biological response to space radiation outside low Earth orbit (LEO) in over 40 years. The 4-unit (4U) BioSentinel biosensor system, is housed within a 6-Unit (6U) spacecraft, and uses yeast cells in multiple independent microfluidic cards to detect and measure DNA damage that occurs in response to ambient space radiation. Cell growth and metabolic activity will be measured using a 3-color LED detection system and a metabolic indicator dye with a dedicated thermal control system per fluidic card.

Replication and meiotic transmission of yeast ribosomal RNA genes.

PubMed

Brewer, B J; Zakian, V A; Fangman, W L

1980-11-01

The yeast Saccharomyces cerevisiae has approximately 120 genes for the ribosomal RNAs (rDNA) which are organized in tandem within chromosomal DNA. These multiple-copy genes are homogeneous in sequence but can undergo changes in copy number and topology. To determine if these changes reflect unusual features of rDNA metabolism, we have examined both the replication of rDNA in the mitotic cell cycle and the inheritance of rDNA during meiosis. The results indicate that rDNA behaves identically to chromosomal DNA: each rDNA unit is replicated once during the S phase of each cell cycle and each unit is conserved through meiosis. Therefore, the flexibility in copy number and topology of rDNA does not arise from the selective replication of units in each S phase nor by the selective inheritance of units in meiosis.

Anatomical, biochemical, and photosynthetic responses to recent allopolyploidy in Glycine dolichocarpa (Fabaceae).

PubMed

Coate, Jeremy E; Luciano, Amelia K; Seralathan, Vasu; Minchew, Kevin J; Owens, Tom G; Doyle, Jeff J

2012-01-01

Previous studies have shown that polyploidy has pronounced effects on photosynthesis. Most of these studies have focused on synthetic or recently formed autopolyploids, and comparatively little is known about the integrated effects of natural allopolyploidy, which involves hybridity and genome doubling and often incorporates multiple genotypes through recurrent origins and lineage recombination. Glycine dolichocarpa (designated T2) is a natural allotetraploid with multiple origins. We quantified 21 anatomical, biochemical, and physiological phenotypes relating to photosynthesis in T2 and its diploid progenitors, G. tomentella (D3) and G. syndetika (D4). To assess how direction of cross affects these phenotypes, we included three T2 accessions having D3-like plastids (T2(D3)) and two accessions having D4-like plastids (T2(D4)). T2 accessions were transgressive (more extreme than any diploid accession) for 17 of 21 phenotypes, and species means differed significantly in T2 vs. both progenitors for four of 21 phenotypes (higher for guard cell length, electron transport capacity [J(max)] per palisade cell, and J(max) per mesophyll cell; lower for palisade cells per unit leaf area). Within T2, four of 21 parameters differed significantly between T2(D3) and T2(D4) (palisade cell volume; chloroplast number and volume per unit leaf area; and J(max) per unit leaf area). T2 is characterized by transgressive photosynthesis-related phenotypes (including an ca. 2-fold increase in J(max) per cell), as well as by significant intraspecies variation correlating with plastid type. These data indicate prominent roles for both nucleotypic effects and cytoplasmic factors in photosynthetic responses to allopolyploidy.

Method for Making a Fuel Cell from a Solid Oxide Monolithic Framework

NASA Technical Reports Server (NTRS)

Sofie, Stephen W. (Inventor); Cable, Thomas L. (Inventor)

2014-01-01

The invention is a novel solid oxide fuel cell (SOFC) stack comprising individual bi-electrode supported fuel cells in which a thin electrolyte is supported between electrodes of essentially equal thickness. Individual cell units are made from graded pore ceramic tape that has been created by the freeze cast method followed by freeze drying. Each piece of graded pore tape later becomes a graded pore electrode scaffold that subsequent to sintering, is made into either an anode or a cathode by means of appropriate solution and thermal treatment means. Each cell unit is assembled by depositing of a thin coating of ion conducting ceramic material upon the side of each of two pieces of tape surface having the smallest pore openings, and then mating the coated surfaces to create an unsintered electrode scaffold pair sandwiching an electrolyte layer. The opposing major outer exposed surfaces of each cell unit is given a thin coating of electrically conductive ceramic, and multiple cell units are stacked, or built up by stacking of individual cell layers, to create an unsintered fuel cell stack. Ceramic or glass edge seals are installed to create flow channels for fuel and air. The cell stack with edge sealants is then sintered into a ceramic monolithic framework. Said solution and thermal treatments means convert the electrode scaffolds into anodes and cathodes. The thin layers of electrically conductive ceramic become the interconnects in the assembled stack.

An Organotypic 3D Assay for Primary Human Mammary Epithelial Cells that Recapitulates Branching Morphogenesis.

PubMed

Linnemann, Jelena R; Meixner, Lisa K; Miura, Haruko; Scheel, Christina H

2017-01-01

We have developed a three-dimensional organotypic culture system for primary human mammary epithelial cells (HMECs) in which the cells are cultured in free floating collagen type I gels. In this assay, luminal cells predominantly form multicellular spheres, while basal/myoepithelial cells form complex branched structures resembling terminal ductal lobular units (TDLUs), the functional units of the human mammary gland in situ. The TDLU-like organoids can be cultured for at least 3 weeks and can then be passaged multiple times. Subsequently, collagen gels can be stained with carmine or by immunofluorescence to allow for the analysis of morphology, protein expression and polarization, and to facilitate quantification of structures. In addition, structures can be isolated for gene expression analysis. In summary, this technique is suitable for studying branching morphogenesis, regeneration, and differentiation of HMECs as well as their dependence on the physical environment.

Broadband sound blocking in phononic crystals with rotationally symmetric inclusions.

PubMed

Lee, Joong Seok; Yoo, Sungmin; Ahn, Young Kwan; Kim, Yoon Young

2015-09-01

This paper investigates the feasibility of broadband sound blocking with rotationally symmetric extensible inclusions introduced in phononic crystals. By varying the size of four equally shaped inclusions gradually, the phononic crystal experiences remarkable changes in its band-stop properties, such as shifting/widening of multiple Bragg bandgaps and evolution to resonance gaps. Necessary extensions of the inclusions to block sound effectively can be determined for given incident frequencies by evaluating power transmission characteristics. By arraying finite dissimilar unit cells, the resulting phononic crystal exhibits broadband sound blocking from combinational effects of multiple Bragg scattering and local resonances even with small-numbered cells.

Each cell counts: Hematopoiesis and immunity research in the era of single cell genomics.

PubMed

Jaitin, Diego Adhemar; Keren-Shaul, Hadas; Elefant, Naama; Amit, Ido

2015-02-01

Hematopoiesis and immunity are mediated through complex interactions between multiple cell types and states. This complexity is currently addressed following a reductionist approach of characterizing cell types by a small number of cell surface molecular features and gross functions. While the introduction of global transcriptional profiling technologies enabled a more comprehensive view, heterogeneity within sampled populations remained unaddressed, obscuring the true picture of hematopoiesis and immune system function. A critical mass of technological advances in molecular biology and genomics has enabled genome-wide measurements of single cells - the fundamental unit of immunity. These new advances are expected to boost detection of less frequent cell types and fuzzy intermediate cell states, greatly expanding the resolution of current available classifications. This new era of single-cell genomics in immunology research holds great promise for further understanding of the mechanisms and circuits regulating hematopoiesis and immunity in both health and disease. In the near future, the accuracy of single-cell genomics will ultimately enable precise diagnostics and treatment of multiple hematopoietic and immune related diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design Study Conducted of a Stirred and Perfused Specimen Chamber for Culturing Suspended Cells on the International Space Station

NASA Technical Reports Server (NTRS)

Nelson, Emily S.; Kizito, John P.

2003-01-01

A tightly knit numerical/experimental collaboration among the NASA Ames Research Center, NASA Glenn Research Center, and Payload Systems, Inc., was formed to analyze cell culturing systems for the International Space Station. The Cell Culture Unit is a facility scheduled for deployment on the space station by the Cell Culture Unit team at Ames. The facility houses multiple cell specimen chambers (CSCs), all of which have inlets and outlets to allow for replenishment of nutrients and for waste removal. For improved uniformity of nutrient and waste concentrations, each chamber has a pair of counterrotating stir bars as well. Although the CSC can be used to grow a wide variety of organic cells, the current study uses yeast as a model cell. Previous work identified groundbased protocols for perfusion and stirring to achieve yeast growth within the CSC that is comparable to that for yeast cultures grown in a shaken Ehrlenmeyer flask.

Independent and high-level dual-gene expression in adult stem-progenitor cells from a single lentiviral vector.

PubMed

Tian, J; Andreadis, S T

2009-07-01

Expression of multiple genes from the same target cell is required in several technological and therapeutic applications such as quantitative measurements of promoter activity or in vivo tracking of stem cells. In spite of such need, reaching independent and high-level dual-gene expression cannot be reliably accomplished by current gene transfer vehicles. To address this issue, we designed a lentiviral vector carrying two transcriptional units separated by polyadenylation, terminator and insulator sequences. With this design, the expression level of both genes was as high as that yielded from lentiviral vectors containing only a single transcriptional unit. Similar results were observed with several promoters and cell types including epidermal keratinocytes, bone marrow mesenchymal stem cells and hair follicle stem cells. Notably, we demonstrated quantitative dynamic monitoring of gene expression in primary cells with no need for selection protocols suggesting that this optimized lentivirus may be useful in high-throughput gene expression profiling studies.

The human urothelium consists of multiple clonal units, each maintained by a stem cell.

PubMed

Gaisa, Nadine T; Graham, Trevor A; McDonald, Stuart A C; Cañadillas-Lopez, Sagrario; Poulsom, Richard; Heidenreich, Axel; Jakse, Gerhard; Tadrous, Paul J; Knuechel, Ruth; Wright, Nicholas A

2011-10-01

Little is known about the clonal architecture of human urothelium. It is likely that urothelial stem cells reside within the basal epithelial layer, yet lineage tracing from a single stem cell as a means to show the presence of a urothelial stem cell has never been performed. Here, we identify clonally related cell areas within human bladder mucosa in order to visualize epithelial fields maintained by a single founder/stem cell. Sixteen frozen cystectomy specimens were serially sectioned. Patches of cells deficient for the mitochondrially encoded enzyme cytochrome c oxidase (CCO) were identified using dual-colour enzyme histochemistry. To show that these patches represent clonal proliferations, small CCO-proficient and -deficient areas were individually laser-capture microdissected and the entire mitochondrial genome (mtDNA) in each area was PCR amplified and sequenced to identify mtDNA mutations. Immunohistochemistry was performed for the different cell layers of the urothelium and adjacent mesenchyme. CCO-deficient patches could be observed in normal urothelium of all cystectomy specimens. The two-dimensional length of these negative patches varied from 2-3 cells (about 30 µm) to 4.7 mm. Each cell area within a CCO-deficient patch contained an identical somatic mtDNA mutation, indicating that the patch was a clonal unit. Patches contained all the mature cell differentiation stages present in the urothelium, suggesting the presence of a stem cell. Our results demonstrate that the normal mucosa of human bladder contains stem cell-derived clonal units that actively replenish the urothelium during ageing. The size of the clonal unit attributable to each stem cell was broadly distributed, suggesting replacement of one stem cell clone by another. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A 40-kW fuel cell field test summary utilities activities report

NASA Astrophysics Data System (ADS)

Racine, W. C.; Londos, T. C.

1987-07-01

Forty six 40 kW fuel cell power plants were field tested by 37 host participants at 42 sites in a variety of commercial, light industrial and multifamily residential applications. The participants obtained over 300,000 hours of operating experience with the power plants covering a diverse range of applications for power plant electricity and heat utilization in both single and multiple unit installations.

Beyond Columnar Organization: Cell Type- and Target Layer-Specific Principles of Horizontal Axon Projection Patterns in Rat Vibrissal Cortex

PubMed Central

Narayanan, Rajeevan T.; Egger, Robert; Johnson, Andrew S.; Mansvelder, Huibert D.; Sakmann, Bert; de Kock, Christiaan P.J.; Oberlaender, Marcel

2015-01-01

Vertical thalamocortical afferents give rise to the elementary functional units of sensory cortex, cortical columns. Principles that underlie communication between columns remain however unknown. Here we unravel these by reconstructing in vivo-labeled neurons from all excitatory cell types in the vibrissal part of rat primary somatosensory cortex (vS1). Integrating the morphologies into an exact 3D model of vS1 revealed that the majority of intracortical (IC) axons project far beyond the borders of the principal column. We defined the corresponding innervation volume as the IC-unit. Deconstructing this structural cortical unit into its cell type-specific components, we found asymmetric projections that innervate columns of either the same whisker row or arc, and which subdivide vS1 into 2 orthogonal [supra-]granular and infragranular strata. We show that such organization could be most effective for encoding multi whisker inputs. Communication between columns is thus organized by multiple highly specific horizontal projection patterns, rendering IC-units as the primary structural entities for processing complex sensory stimuli. PMID:25838038

Noninvasive optical monitoring multiple physiological parameters response to cytokine storm

NASA Astrophysics Data System (ADS)

Li, Zebin; Li, Ting

2018-02-01

Cancer and other disease originated by immune or genetic problems have become a main cause of death. Gene/cell therapy is a highlighted potential method for the treatment of these diseases. However, during the treatment, it always causes cytokine storm, which probably trigger acute respiratory distress syndrome and multiple organ failure. Here we developed a point-of-care device for noninvasive monitoring cytokine storm induced multiple physiological parameters simultaneously. Oxy-hemoglobin, deoxy-hemoglobin, water concentration and deep-tissue/tumor temperature variations were simultaneously measured by extended near infrared spectroscopy. Detection algorithms of symptoms such as shock, edema, deep-tissue fever and tissue fibrosis were developed and included. Based on these measurements, modeling of patient tolerance and cytokine storm intensity were carried out. This custom device was tested on patients experiencing cytokine storm in intensive care unit. The preliminary data indicated the potential of our device in popular and milestone gene/cell therapy, especially, chimeric antigen receptor T-cell immunotherapy (CAR-T).

Foam generation and sample composition optimization for the FOAM-C experiment of the ISS

NASA Astrophysics Data System (ADS)

Carpy, R.; Picker, G.; Amann, B.; Ranebo, H.; Vincent-Bonnieu, S.; Minster, O.; Winter, J.; Dettmann, J.; Castiglione, L.; Höhler, R.; Langevin, D.

2011-12-01

End of 2009 and early 2010 a sealed cell, for foam generation and observation, has been designed and manufactured at Astrium Friedrichshafen facilities. With the use of this cell, different sample compositions of "wet foams" have been optimized for mixtures of chemicals such as water, dodecanol, pluronic, aethoxisclerol, glycerol, CTAB, SDS, as well as glass beads. This development is performed in the frame of the breadboarding development activities of the Experiment Container FOAM-C for operation in the ISS Fluid Science Laboratory (ISS). The sample cell supports multiple observation methods such as: Diffusing-Wave and Diffuse Transmission Spectrometry, Time Resolved Correlation Spectroscopy [1] and microscope observation, all of these methods are applied in the cell with a relatively small experiment volume <3cm3. These units, will be on orbit replaceable sets, that will allow multiple sample compositions processing (in the range of >40).

Expression, purification, crystallization and preliminary crystallographic study of isolated modules of the mouse coactivator-associated arginine methyltransferase 1

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

Troffer-Charlier, Nathalie; Cura, Vincent; Hassenboehler, Pierre

2007-04-01

Isolated modules of mouse coactivator-associated arginine methyltransferase 1 encompassing the protein arginine N-methyltransferase catalytic domain have been overexpressed, purified and crystallized. X-ray diffraction data have been collected and have enabled determination of the structures by multiple isomorphous replacement using anomalous scattering. Coactivator-associated arginine methyltransferase 1 (CARM1) plays a crucial role in gene expression as a coactivator of several nuclear hormone receptors and also of non-nuclear receptor systems. Its recruitment by the transcriptional machinery induces protein methylation, leading to chromatin remodelling and gene activation. CARM1{sub 28–507} and two structural states of CARM1{sub 140–480} were expressed, purified and crystallized. Crystals of CARM1{submore » 28–507} belong to space group P6{sub 2}22, with unit-cell parameters a = b = 136.0, c = 125.3 Å; they diffract to beyond 2.5 Å resolution using synchrotron radiation and contain one monomer in the asymmetric unit. The structure of CARM1{sub 28–507} was solved by multiple isomorphous replacement and anomalous scattering methods. Crystals of apo CARM1{sub 140–480} belong to space group I222, with unit-cell parameters a = 74.6, b = 99.0, c = 207.4 Å; they diffract to beyond 2.7 Å resolution and contain two monomers in the asymmetric unit. Crystals of CARM1{sub 140–480} in complex with S-adenosyl-l-homocysteine belong to space P2{sub 1}2{sub 1}2, with unit-cell parameters a = 74.6, b = 98.65, c = 206.08 Å; they diffract to beyond 2.6 Å resolution and contain four monomers in the asymmetric unit. The structures of apo and holo CARM1{sub 140–480} were solved by molecular-replacement techniques from the structure of CARM1{sub 28–507}.« less

Colossal positive magnetoresistance in surface-passivated oxygen-deficient strontium titanite.

PubMed

David, Adrian; Tian, Yufeng; Yang, Ping; Gao, Xingyu; Lin, Weinan; Shah, Amish B; Zuo, Jian-Min; Prellier, Wilfrid; Wu, Tom

2015-05-15

Modulation of resistance by an external magnetic field, i.e. magnetoresistance effect, has been a long-lived theme of research due to both fundamental science and device applications. Here we report colossal positive magnetoresistance (CPMR) (>30,000% at a temperature of 2 K and a magnetic field of 9 T) discovered in degenerate semiconducting strontium titanite (SrTiO3) single crystals capped with ultrathin SrTiO3/LaAlO3 bilayers. The low-pressure high-temperature homoepitaxial growth of several unit cells of SrTiO3 introduces oxygen vacancies and high-mobility carriers in the bulk SrTiO3, and the three-unit-cell LaAlO3 capping layer passivates the surface and improves carrier mobility by suppressing surface-defect-related scattering. The coexistence of multiple types of carriers and inhomogeneous transport lead to the emergence of CPMR. This unit-cell-level surface engineering approach is promising to be generalized to others oxides, and to realize devices with high-mobility carriers and interesting magnetoelectronic properties.

A modular cell-based biosensor using engineered genetic logic circuits to detect and integrate multiple environmental signals

PubMed Central

Wang, Baojun; Barahona, Mauricio; Buck, Martin

2013-01-01

Cells perceive a wide variety of cellular and environmental signals, which are often processed combinatorially to generate particular phenotypic responses. Here, we employ both single and mixed cell type populations, pre-programmed with engineered modular cell signalling and sensing circuits, as processing units to detect and integrate multiple environmental signals. Based on an engineered modular genetic AND logic gate, we report the construction of a set of scalable synthetic microbe-based biosensors comprising exchangeable sensory, signal processing and actuation modules. These cellular biosensors were engineered using distinct signalling sensory modules to precisely identify various chemical signals, and combinations thereof, with a quantitative fluorescent output. The genetic logic gate used can function as a biological filter and an amplifier to enhance the sensing selectivity and sensitivity of cell-based biosensors. In particular, an Escherichia coli consortium-based biosensor has been constructed that can detect and integrate three environmental signals (arsenic, mercury and copper ion levels) via either its native two-component signal transduction pathways or synthetic signalling sensors derived from other bacteria in combination with a cell-cell communication module. We demonstrate how a modular cell-based biosensor can be engineered predictably using exchangeable synthetic gene circuit modules to sense and integrate multiple-input signals. This study illustrates some of the key practical design principles required for the future application of these biosensors in broad environmental and healthcare areas. PMID:22981411

Study of the model of hole superconductivity in multiple band cases and its application to transition metals

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

Hong, X.Q.

1992-01-01

The authors have studied a simple model consisting of a chain of atoms with two atoms per unit cell. This model develops two bands when the inter-cell and intra-cell hopping amplitudes are different. They have found that superconductivity predominantly occurs when the Fermi level is close to the top of the upper band where the wavefunction has antibonding feature both inside the unit cell and between unit cells. Superconductivity occurs only in a restricted parameter range when the Fermi level is close to the top of the lower band because of the repulsive interaction within the unit cell. They findmore » that pair expectation values that 'mix' carriers of both bands can exist when interband interactions other than V12 of Suhl et al are present. But the magnitude of the 'mixed pairs' order parameters is much smaller than that of the intra-band pairs. The V12 of Suhl et al is the most important interband interaction that gives rise to the main features of a two-band model: a single transition temperature and two different gaps. They have used the model of hole superconductivity to study the variation of T(sub c) among transition metal series--the Matthias rules. They have found that the observed T(sub c)'s are consistent with superconductivity of a metal with multiple bands at the Fermi level being caused by the single band with strongest antibonding character at the Fermi level. When the Fermi level is the lower part of a band, there is no T(sub c). As the band is gradually filled, T(sub c) rises, passes through a maximum, then drops to zero when the band is full. This characteristic feature is independent of any fine structure of the band. The position of the peak and the width of the peak are correlated. Quantitative agreement with the experimental results is obtained by choosing parameters of onsite Coulomb interaction U, modulated hopping term Delta-t, and nearest neighbor repulsion V to fit the magnitude of T(sub c) and the positions of experimental peaks.« less

In vivo imaging of the neurovascular unit in CNS disease

PubMed Central

Merlini, Mario; Davalos, Dimitrios; Akassoglou, Katerina

2014-01-01

The neurovascular unit—comprised of glia, pericytes, neurons and cerebrovasculature—is a dynamic interface that ensures physiological central nervous system (CNS) functioning. In disease dynamic remodeling of the neurovascular interface triggers a cascade of responses that determine the extent of CNS degeneration and repair. The dynamics of these processes can be adequately captured by imaging in vivo, which allows the study of cellular responses to environmental stimuli and cell-cell interactions in the living brain in real time. This perspective focuses on intravital imaging studies of the neurovascular unit in stroke, multiple sclerosis (MS) and Alzheimer disease (AD) models and discusses their potential for identifying novel therapeutic targets. PMID:25197615

& Source apportionment of particulate matter in the United States and associations with lung inflammatory Markers

EPA Science Inventory

Size-fractionated particulate matter (PM) samples were collected from six U.S. cities and chemically analyzed as part of the Multiple Air Pollutant Study. Particles were administered to cultured lung cells and the production of three different proinflammatory markers was measured...

Identification and Therapeutic Targeting of Paracrine Senescence Factors in the Prostate Tumor Microenvironment

DTIC Science & Technology

2011-10-01

PROJECT NUMBER James P. Dean, M.D., Ph.D. 5e. TASK NUMBER E-Mail: amoreno@fhcrc.org 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S...secretion of STC1 were defined, but multiple studies seeking to define the function of STC1 in the prostate were uniformly negative. A clinical trial...men in the United States - could be prevented with more effective treatments. Overcoming tumor cell resistance to the effects of androgen

Novel web-based real-time dashboard to optimize recycling and use of red cell units at a large multi-site transfusion service.

PubMed

Sharpe, Christopher; Quinn, Jason G; Watson, Stephanie; Doiron, Donald; Crocker, Bryan; Cheng, Calvino

2014-01-01

Effective blood inventory management reduces outdates of blood products. Multiple strategies have been employed to reduce the rate of red blood cell (RBC) unit outdate. We designed an automated real-time web-based dashboard interfaced with our laboratory information system to effectively recycle red cell units. The objective of our approach is to decrease RBC outdate rates within our transfusion service. The dashboard was deployed in August 2011 and is accessed by a shortcut that was placed on the desktops of all blood transfusion services computers in the Capital District Health Authority region. It was designed to refresh automatically every 10 min. The dashboard provides all vital information on RBC units, and implemented a color coding scheme to indicate an RBC unit's proximity to expiration. The overall RBC unit outdate rate in the 7 months period following implementation of the dashboard (September 2011-March 2012) was 1.24% (123 units outdated/9763 units received), compared to similar periods in 2010-2011 and 2009-2010: 2.03% (188/9395) and 2.81% (261/9220), respectively. The odds ratio of a RBC unit outdate postdashboard (2011-2012) compared with 2010-2011 was 0.625 (95% confidence interval: 0.497-0.786; P < 0.0001). Our dashboard system is an inexpensive and novel blood inventory management system which was associated with a significant reduction in RBC unit outdate rates at our institution over a period of 7 months. This system, or components of it, could be a useful addition to existing RBC management systems at other institutions.

A theory of cerebellar cortex and adaptive motor control based on two types of universal function approximation capability.

PubMed

Fujita, Masahiko

2016-03-01

Lesions of the cerebellum result in large errors in movements. The cerebellum adaptively controls the strength and timing of motor command signals depending on the internal and external environments of movements. The present theory describes how the cerebellar cortex can control signals for accurate and timed movements. A model network of the cerebellar Golgi and granule cells is shown to be equivalent to a multiple-input (from mossy fibers) hierarchical neural network with a single hidden layer of threshold units (granule cells) that receive a common recurrent inhibition (from a Golgi cell). The weighted sum of the hidden unit signals (Purkinje cell output) is theoretically analyzed regarding the capability of the network to perform two types of universal function approximation. The hidden units begin firing as the excitatory inputs exceed the recurrent inhibition. This simple threshold feature leads to the first approximation theory, and the network final output can be any continuous function of the multiple inputs. When the input is constant, this output becomes stationary. However, when the recurrent unit activity is triggered to decrease or the recurrent inhibition is triggered to increase through a certain mechanism (metabotropic modulation or extrasynaptic spillover), the network can generate any continuous signals for a prolonged period of change in the activity of recurrent signals, as the second approximation theory shows. By incorporating the cerebellar capability of two such types of approximations to a motor system, in which learning proceeds through repeated movement trials with accompanying corrections, accurate and timed responses for reaching the target can be adaptively acquired. Simple models of motor control can solve the motor error vs. sensory error problem, as well as the structural aspects of credit (or error) assignment problem. Two physiological experiments are proposed for examining the delay and trace conditioning of eyelid responses, as well as saccade adaptation, to investigate this novel idea of cerebellar processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

New architecture for utility scale electricity from concentrator photovoltaics

NASA Astrophysics Data System (ADS)

Angel, Roger; Connors, Thomas; Davison, Warren; Olbert, Blain; Sivanandam, Suresh

2010-08-01

The paper describes a new system architecture optimized for utility-scale generation with concentrating photovoltaic cells (CPV) at fossil fuel price. We report on-sun tests of the architecture and development at the University of Arizona of the manufacturing processes adapted for high volume production. The new system takes advantage of triple-junction cells to convert concentrated sunlight into electricity. These commercially available cells have twice the conversion efficiency of silicon panels (40%) and one-tenth the cost per watt, when used at 1000x concentration. Telescope technology is adapted to deliver concentrated light to the cells at minimum cost. The architecture combines three novel elements: large (3.1 m x 3.1 m square) dish reflectors made as back-silvered glass monoliths; 2.5 kW receivers at each dish focus, each one incorporating a spherical field lens to deliver uniform illumination to multiple cells; and a lightweight steel spaceframe structure to hold multiple dish/receiver units in coalignment and oriented to the sun. Development of the process for replicating single-piece reflector dishes is well advanced at the Steward Observatory Mirror Lab. End-to-end system tests have been completed with single cells. A lightweight steel spaceframe to hold and track eight dish/receiver units to generate 20 kW has been completed. A single 2.5 kW receiver is presently under construction, and is expected to be operated in an end-to-end on-sun test with a monolithic dish before the end of 2010. The University of Arizona has granted an exclusive license to REhnu, LLC to commercialize this technology.

Flat bands in fractal-like geometry

NASA Astrophysics Data System (ADS)

Pal, Biplab; Saha, Kush

2018-05-01

We report the presence of multiple flat bands in a class of two-dimensional lattices formed by Sierpinski gasket (SPG) fractal geometries as the basic unit cells. Solving the tight-binding Hamiltonian for such lattices with different generations of a SPG network, we find multiple degenerate and nondegenerate completely flat bands, depending on the configuration of parameters of the Hamiltonian. Moreover, we establish a generic formula to determine the number of such bands as a function of the generation index ℓ of the fractal geometry. We show that the flat bands and their neighboring dispersive bands have remarkable features, the most interesting one being the spin-1 conical-type spectrum at the band center without any staggered magnetic flux, in contrast to the kagome lattice. We furthermore investigate the effect of magnetic flux in these lattice settings and show that different combinations of fluxes through such fractal unit cells lead to a richer spectrum with a single isolated flat band or gapless electron- or holelike flat bands. Finally, we discuss a possible experimental setup to engineer such a fractal flat-band network using single-mode laser-induced photonic waveguides.

Accurate phase measurements for thick spherical objects using optical quadrature microscopy

NASA Astrophysics Data System (ADS)

Warger, William C., II; DiMarzio, Charles A.

2009-02-01

In vitro fertilization (IVF) procedures have resulted in the birth of over three million babies since 1978. Yet the live birth rate in the United States was only 34% in 2005, with 32% of the successful pregnancies resulting in multiple births. These multiple pregnancies were directly attributed to the transfer of multiple embryos to increase the probability that a single, healthy embryo was included. Current viability markers used for IVF, such as the cell number, symmetry, size, and fragmentation, are analyzed qualitatively with differential interference contrast (DIC) microscopy. However, this method is not ideal for quantitative measures beyond the 8-cell stage of development because the cells overlap and obstruct the view within and below the cluster of cells. We have developed the phase-subtraction cell-counting method that uses the combination of DIC and optical quadrature microscopy (OQM) to count the number of cells accurately in live mouse embryos beyond the 8-cell stage. We have also created a preliminary analysis to measure the cell symmetry, size, and fragmentation quantitatively by analyzing the relative dry mass from the OQM image in conjunction with the phase-subtraction count. In this paper, we will discuss the characterization of OQM with respect to measuring the phase accurately for spherical samples that are much larger than the depth of field. Once fully characterized and verified with human embryos, this methodology could provide the means for a more accurate method to score embryo viability.

Design and optimization of membrane-type acoustic metamaterials

NASA Astrophysics Data System (ADS)

Blevins, Matthew Grant

One of the most common problems in noise control is the attenuation of low frequency noise. Typical solutions require barriers with high density and/or thickness. Membrane-type acoustic metamaterials are a novel type of engineered material capable of high low-frequency transmission loss despite their small thickness and light weight. These materials are ideally suited to applications with strict size and weight limitations such as aircraft, automobiles, and buildings. The transmission loss profile can be manipulated by changing the micro-level substructure, stacking multiple unit cells, or by creating multi-celled arrays. To date, analysis has focused primarily on experimental studies in plane-wave tubes and numerical modeling using finite element methods. These methods are inefficient when used for applications that require iterative changes to the structure of the material. To facilitate design and optimization of membrane-type acoustic metamaterials, computationally efficient dynamic models based on the impedance-mobility approach are proposed. Models of a single unit cell in a waveguide and in a baffle, a double layer of unit cells in a waveguide, and an array of unit cells in a baffle are studied. The accuracy of the models and the validity of assumptions used are verified using a finite element method. The remarkable computational efficiency of the impedance-mobility models compared to finite element methods enables implementation in design tools based on a graphical user interface and in optimization schemes. Genetic algorithms are used to optimize the unit cell design for a variety of noise reduction goals, including maximizing transmission loss for broadband, narrow-band, and tonal noise sources. The tools for design and optimization created in this work will enable rapid implementation of membrane-type acoustic metamaterials to solve real-world noise control problems.

Printed droplet microfluidics for on demand dispensing of picoliter droplets and cells

PubMed Central

Cole, Russell H.; Tang, Shi-Yang; Siltanen, Christian A.; Shahi, Payam; Zhang, Jesse Q.; Poust, Sean; Gartner, Zev J.; Abate, Adam R.

2017-01-01

Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay. PMID:28760972

Printed droplet microfluidics for on demand dispensing of picoliter droplets and cells.

PubMed

Cole, Russell H; Tang, Shi-Yang; Siltanen, Christian A; Shahi, Payam; Zhang, Jesse Q; Poust, Sean; Gartner, Zev J; Abate, Adam R

2017-08-15

Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay.

Printed droplet microfluidics for on demand dispensing of picoliter droplets and cells

NASA Astrophysics Data System (ADS)

Cole, Russell H.; Tang, Shi-Yang; Siltanen, Christian A.; Shahi, Payam; Zhang, Jesse Q.; Poust, Sean; Gartner, Zev J.; Abate, Adam R.

2017-08-01

Although the elementary unit of biology is the cell, high-throughput methods for the microscale manipulation of cells and reagents are limited. The existing options either are slow, lack single-cell specificity, or use fluid volumes out of scale with those of cells. Here we present printed droplet microfluidics, a technology to dispense picoliter droplets and cells with deterministic control. The core technology is a fluorescence-activated droplet sorter coupled to a specialized substrate that together act as a picoliter droplet and single-cell printer, enabling high-throughput generation of intricate arrays of droplets, cells, and microparticles. Printed droplet microfluidics provides a programmable and robust technology to construct arrays of defined cell and reagent combinations and to integrate multiple measurement modalities together in a single assay.

The analysis of tensegrity structures for the design of a morphing wing

NASA Astrophysics Data System (ADS)

Moored, Keith W., III; Bart-Smith, Hilary

2005-05-01

Tensegrity structures have become of engineering interest in recent years, but very few have found practical use. This lack of integration is attributed to the lack of a well formulated design procedure. In this paper, a preliminary procedure is presented for developing morphing tensegrity structures that include actuating elements. To do this, the virtual work method has been modified to allow for individual actuation of struts and cables. A generalized connectivity matrix for a cantilever beam constructed from either a single 4-strut cell or multiple 4-strut cells has been developed. Global deflections resulting from actuation of specific elements have been calculated. Furthermore, the force density method is expanded to include a necessary upper bound condition such that a physically feasible structure can be designed. Finally, the importance of relative force density values on the overall shape of a structure comprising of multiple unit cells is discussed.

Large-scale progenitor cell expansion for multiple donors in a monitored hollow fibre bioreactor.

PubMed

Lambrechts, Toon; Papantoniou, Ioannis; Rice, Brent; Schrooten, Jan; Luyten, Frank P; Aerts, Jean-Marie

2016-09-01

With the increasing scale in stem cell production, a robust and controlled cell expansion process becomes essential for the clinical application of cell-based therapies. The objective of this work was the assessment of a hollow fiber bioreactor (Quantum Cell Expansion System from Terumo BCT) as a cell production unit for the clinical-scale production of human periosteum derived stem cells (hPDCs). We aimed to demonstrate comparability of bioreactor production to standard culture flask production based on a product characterization in line with the International Society of Cell Therapy in vitro benchmarks and supplemented with a compelling quantitative in vivo bone-forming potency assay. Multiple process read-outs were implemented to track process performance and deal with donor-to-donor-related variation in nutrient needs and harvest timing. The data show that the hollow fiber bioreactor is capable of robustly expanding autologous hPDCs on a clinical scale (yield between 316 million and 444 million cells starting from 20 million after ± 8 days of culture) while maintaining their in vitro quality attributes compared with the standard flask-based culture. The in vivo bone-forming assay on average resulted in 10.3 ± 3.7% and 11.0 ± 3.8% newly formed bone for the bioreactor and standard culture flask respectively. The analysis showed that the Quantum system provides a reproducible cell expansion process in terms of yields and culture conditions for multiple donors. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Raman and infrared spectroscopic study of the anhydrous carbonate minerals shortite and barytocalcite.

PubMed

Frost, Ray L; Dickfos, Marilla J

2008-11-01

The Raman spectra of shortite and barytocalcite complimented with infrared spectra have been used to characterise the structure of these carbonate minerals. The Raman spectrum of barytocalcite shows a single band at 1086 cm(-1) attributed to the (CO3)(2-) symmetric stretching mode, in contrast to shortite where two bands are observed. The observation of two bands for shortite confirms the concept of more than one crystallographically distinct carbonate unit in the unit cell. Multiple bands are observed for the antisymmetric stretching and bending region for these minerals proving that the carbonate unit is distorted in the structure of both shortite and barytocalcite.

Research Institute for Autonomous Precision Guided Systems

DTIC Science & Technology

2008-11-30

diameter) Re per unit length ( nT1 ) 5 1.6 114,000 107,406 10 3.4 238,000 220,952 15 5.2 364,000 336,760 20 6.8 490,000 454,592 25 8.8 616,000...effects, with multiple membrane cells and rounded leading-edges were tested at Re=45,000. Surface and flow visualization confirmed leading-edge...formulation is employed, using both Cartesian and contravariant velocity components (Tannehill et al, 1997). The latter can evaluate the flux at the cell

Micro-Masonry: Construction of 3D Structures by Mesoscale Self-Assembly

PubMed Central

Fernandez, Javier G.; Khademhosseini, Ali

2010-01-01

A general method for construction of three dimensional structures by directed assembly of microscale polymeric sub-units is presented. Shape-controlled microgels are directed to assemble into different shapes by limiting their movement onto a molded substrate. The capillary forces, resulting from the presence of a liquid polymer, assemble the microgels in close contact with the rest of the units and with the free surface, the latter imposing the final geometry of the resulting construct. The result is a freestanding structure composed of one or multiple layers of sub-units assembled in a tightly packed conformation. The applicability of the technique for the construction of scaffolds with cell-laden sub-units is demonstrated. In addition, scaffolds formed by the sequential aggregation of sub-units are produced. PMID:20440697

Molecular dynamics simulations of polarizable DNA in crystal environment

NASA Astrophysics Data System (ADS)

Babin, Volodymyr; Baucom, Jason; Darden, Thomas A.; Sagui, Celeste

We have investigated the role of the electrostatic description and cell environment in molecular dynamics (MD) simulations of DNA. Multiple unrestrained MD simulations of the DNA duplex d(CCAACGTTGG)2 have been carried out using two different force fields: a traditional description based on atomic point charges and a polarizable force field. For the time scales probed, and given the ?right? distribution of divalent ions, the latter performs better than the nonpolarizable force field. In particular, by imposing the experimental unit cell environment, an initial configuration with ideal B-DNA duplexes in the unit cell acquires sequence-dependent features that very closely resemble the crystallographic ones. Simultaneously, the all-atom root-mean-square coordinates deviation (RMSD) with respect to the crystallographic structure is seen to decay. At later times, the polarizable force field is able to maintain this lower RMSD, while the nonpolarizable force field starts to drift away.

Human embryonic stem cell research: an intercultural perspective.

PubMed

Walters, LeRoy

2004-03-01

In 1998, researchers discovered that embryonic stem cells could be derived from early human embryos. This discovery has raised a series of ethical and public-policy questions that are now being confronted by multiple international organizations, nations, cultures, and religious traditions. This essay surveys policies for human embryonic stem cell research in four regions of the world, reports on the recent debate at the United Nations about one type of such research, and reviews the positions that various religious traditions have adopted regarding this novel type of research. In several instances the religious traditions seem to have influenced the public-policy debates.

Unit cell-based computer-aided manufacturing system for tissue engineering.

PubMed

Kang, Hyun-Wook; Park, Jeong Hun; Kang, Tae-Yun; Seol, Young-Joon; Cho, Dong-Woo

2012-03-01

Scaffolds play an important role in the regeneration of artificial tissues or organs. A scaffold is a porous structure with a micro-scale inner architecture in the range of several to several hundreds of micrometers. Therefore, computer-aided construction of scaffolds should provide sophisticated functionality for porous structure design and a tool path generation strategy that can achieve micro-scale architecture. In this study, a new unit cell-based computer-aided manufacturing (CAM) system was developed for the automated design and fabrication of a porous structure with micro-scale inner architecture that can be applied to composite tissue regeneration. The CAM system was developed by first defining a data structure for the computing process of a unit cell representing a single pore structure. Next, an algorithm and software were developed and applied to construct porous structures with a single or multiple pore design using solid freeform fabrication technology and a 3D tooth/spine computer-aided design model. We showed that this system is quite feasible for the design and fabrication of a scaffold for tissue engineering.

Highly parallel reconfigurable computer architecture for robotic computation having plural processor cells each having right and left ensembles of plural processors

NASA Technical Reports Server (NTRS)

Fijany, Amir (Inventor); Bejczy, Antal K. (Inventor)

1994-01-01

In a computer having a large number of single-instruction multiple data (SIMD) processors, each of the SIMD processors has two sets of three individual processor elements controlled by a master control unit and interconnected among a plurality of register file units where data is stored. The register files input and output data in synchronism with a minor cycle clock under control of two slave control units controlling the register file units connected to respective ones of the two sets of processor elements. Depending upon which ones of the register file units are enabled to store or transmit data during a particular minor clock cycle, the processor elements within an SIMD processor are connected in rings or in pipeline arrays, and may exchange data with the internal bus or with neighboring SIMD processors through interface units controlled by respective ones of the two slave control units.

How we manage autologous stem cell transplantation for patients with multiple myeloma

PubMed Central

Dingli, David

2014-01-01

An estimated 22 350 patients had multiple myeloma diagnosed in 2013, representing 1.3% of all new cancers; 10 710 deaths are projected, representing 1.8% of cancer deaths. Approximately 0.7% of US men and women will have a myeloma diagnosis in their lifetime, and with advances in therapy, 77 600 US patients are living with myeloma. The 5-year survival rate was 25.6% in 1989 and was 44.9% in 2005. The median age at diagnosis is 69 years, with 62.4% of patients aged 65 or older at diagnosis. Median age at death is 75 years. The rate of new myeloma cases has been rising 0.7% per year during the past decade. The most common indication for autologous stem cell transplantation in the United States is multiple myeloma, and this article is designed to provide the specifics of organizing a transplant program for multiple myeloma. We review the data justifying use of stem cell transplantation as initial management in myeloma patients. We provide selection criteria that minimize the risks of transplantation. Specific guidelines on mobilization and supportive care through the transplant course, as done at Mayo Clinic, are given. A review of the data on tandem vs sequential autologous transplants is provided. PMID:24973360

Lattice Entertain You: Paper Modeling of the 14 Bravais Lattices on Youtube

ERIC Educational Resources Information Center

Sein, Lawrence T., Jr.; Sein, Sarajane E.

2015-01-01

A system for the construction of double-sided paper models of the 14 Bravais lattices, and important crystal structures derived from them, is described. The system allows the combination of multiple unit cells, so as to better represent the overall three-dimensional structure. Students and instructors can view the models in use on the popular…

For assessment of changes in intraoperative red blood cell transfusion practices over time, the pooled incidence of transfusion correlates highly with total units transfused.

PubMed

Dexter, Franklin; Epstein, Richard H

2017-06-01

Multiple studies nationwide and at single hospitals have examined changes over time in the incidence of perioperative red blood cell (RBC) transfusion. However, the cost of RBC transfusions is related to the number of RBC units transfused, not to the incidence. We evaluate whether the readily available incidence of RBC transfusion can be used as a valid surrogate measure. Observational retrospective study. One tertiary, academic hospital. 394,789 cases of 1885 procedures over N=42 quarters of the year. None. Incidence and number of RBC units transfused intraoperatively. The number of RBC units transfused per case did not follow a Poisson distribution, confirming that the number of units and incidence of transfusion are not interchangeable for analyzing decisions by case. However, with all cases of each quarter combined, the Spearman correlation was 0.98±0.01 between each quarter's incidence of RBC transfusion and mean RBC units transfused per case (P<0.0001). For assessment of changes in intraoperative RBC transfusion practices over years, it is sufficient to analyze the pooled incidence of transfusion, rather than to calculate the number of units transfused. Copyright © 2017 Elsevier Inc. All rights reserved.

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

PubMed

Baselski, V S; Medina, R A; Parker, C D

1978-11-01

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12.

Survival and multiplication of Vibrio cholerae in the upper bowel of infant mice.

PubMed Central

Baselski, V S; Medina, R A; Parker, C D

1978-01-01

The survival and multiplication of Vibrio cholerae strains of varying virulence in the upper bowel of orally challenged infant mice early in infection has been examined. Analysis of changes in the apparent specific activity (counts per minute per colony-forming unit) of the cell population after 4 h compared with the inoculum indicated that strain CA401 established a viable, multiplying cell population, whereas strains VB12 (a rough variant) and 569B were subject to host bactericidal and bacteriolytic mechanisms. An analysis of parameters which may affect the specific activity is included. We have defined the infective potential of the strains in terms of the changes in specific activity. The relative infective potentials are CA401 greater than 569B greater than VB12. PMID:730364

Hemorrhage and Subsequent Allogenic Red Blood Cell Transfusion are Associated With Characteristic Monocyte Messenger RNA Expression Patterns in Patients After Multiple Injury—A Genome Wide View

PubMed Central

Bogner, Viktoria; Baker, Henry V.; Kanz, Karl-Georg; Moldawer, L. L.; Mutschler, Wolf; Biberthaler, Peter

2014-01-01

Introduction As outcome to severe trauma is frequently affected by massive blood loss and consecutive hemorrhagic shock, replacement of red blood cell (RBC) units remains indispensable. Administration of RBC units is an independent risk factor for adverse outcome in patients with trauma. The impact of massive blood transfusion or uncrossmatched blood transfusion on the patients’ immune response in the early posttraumatic period remains unclear. Material Thirteen patients presenting with blunt multiple injuries (Injury Severity Score >16) were studied. Monocytes were obtained on admission and at 6, 12, 24, 48, and 72 hours after trauma. Biotinylated complementary RNA targets were hybridized to Affymetrix HG U 133A microarrays. The data were analyzed by a supervised analysis based on whether the patients received massive blood transfusions, and then subsequently, by hierarchical clustering, and by Ingenuity pathway analysis. Results Supervised analysis identified 224 probe sets to be differentially expressed (p < 0.001) in patients who received massive blood transfusion, when compared with those who did not. In addition, 331 probe sets were found differentially expressed (p < 0.001) in patients who received uncrossmatched RBC units in comparison with those who exclusively gained crossmatched ones. Functional pathway analysis of the respectively identified gene expression profiles suggests a contributory role by the AKT/PI3Kinase pathway, the mitogen-activated protein-kinase pathway, the Ubiquitin pathway, and the diverse inflammatory networks. Conclusion We exhibited for the first time a serial, sequential screening analysis of monocyte messenger RNA expression patterns in patients with multiple trauma indicating a strongly significant association between the patients’ genomic response in blood monocytes and massive or uncross-matched RBC substitution. PMID:19820587

PA-GFP: a window into the subcellular adventures of the individual mitochondrion.

PubMed

Haigh, Sarah E; Twig, Gilad; Molina, Anthony A J; Wikstrom, Jakob D; Deutsch, Motti; Shirihai, Orian S

2007-01-01

Mitochondrial connectivity is characterized by matrix lumen continuity and by dynamic rewiring through fusion and fission events. While these mechanisms homogenize the mitochondrial population, a number of studies looking at mitochondrial membrane potential have demonstrated that mitochondria exist as a heterogeneous population within individual cells. To address the relationship between mitochondrial dynamics and heterogeneity, we tagged and tracked individual mitochondria over time while monitoring their mitochondrial membrane potential (deltapsi(m)). By utilizing photoactivatible-GFP (PA-GFP), targeted to the mitochondrial matrix, we determined the boundaries of the individual mitochondrion. A single mitochondrion is defined by the continuity of its matrix lumen. The boundaries set by luminal continuity matched those set by electrical coupling, indicating that the individual mitochondrion is equipotential throughout the entire organelle. Similar results were obtained with PA-GFP targeted to the inner membrane indicating that matrix continuity parallels inner membrane continuity. Sequential photoconversion of matrix PA-GFP in multiple locations within the mitochondrial web reveals that each ramified mitochondrial structure is composed of juxtaposed but discontinuous units. Moreover, as many as half of the events in which mitochondria come into contact, do not result in fusion. While all fission events generated two electrically uncoupled discontinuous matrices, the two daughter mitochondria frequently remained juxtaposed, keeping the tubular appearance unchanged. These morphologically invisible fission events illustrate the difference between mitochondrial fission and fragmentation; the latter representing the movement and separation of disconnected units. Simultaneous monitoring of deltapsi(m) of up to four individual mitochondria within the same cell revealed that subcellular heterogeneity in deltapsi(m) does not represent multiple unstable mitochondria that appear 'heterogeneous' at any given point, but rather multiple stable, but heterogeneous units.

Dynamic electrical reconfiguration for improved capacitor charging in microbial fuel cell stacks

NASA Astrophysics Data System (ADS)

Papaharalabos, George; Greenman, John; Stinchcombe, Andrew; Horsfield, Ian; Melhuish, Chris; Ieropoulos, Ioannis

2014-12-01

A microbial fuel cell (MFC) is a bioelectrochemical device that uses anaerobic bacteria to convert chemical energy locked in biomass into small amounts of electricity. One viable way of increasing energy extraction is by stacking multiple MFC units and exploiting the available electrical configurations for increasing the current or stepping up the voltage. The present study illustrates how a real-time electrical reconfiguration of MFCs in a stack, halves the time required to charge a capacitor (load) and achieves 35% higher current generation compared to a fixed electrical configuration. This is accomplished by progressively switching in-parallel elements to in-series units in the stack, thus maintaining an optimum potential difference between the stack and the capacitor, which in turn allows for a higher energy transfer.

Association of Myosin Va and Schwann cells-derived RNA in mammal myelinated axons, analyzed by immunocytochemistry and confocal FRET microscopy.

PubMed

Canclini, Lucía; Wallrabe, Horst; Di Paolo, Andrés; Kun, Alejandra; Calliari, Aldo; Sotelo-Silveira, José Roberto; Sotelo, José Roberto

2014-03-15

Evidence from multiple sources supports the hypothesis that Schwann cells in the peripheral nervous system transfer messenger RNA and ribosomes to the axons they ensheath. Several technical and methodological difficulties exist for investigators to unravel this process in myelinated axons - a complex two-cell unit. We present an experimental design to demonstrate that newly synthesized RNA is transferred from Schwann cells to axons in association with Myosin Va. The use of quantitative confocal FRET microscopy to track newly-synthesized RNA and determine the molecular association with Myosin Va, is described in detail. Copyright © 2013 Elsevier Inc. All rights reserved.

A combined optical, SEM and STM study of growth spirals on the polytypic cadmium iodide crystals

NASA Astrophysics Data System (ADS)

Singh, Rajendra; Samanta, S. B.; Narlikar, A. V.; Trigunayat, G. C.

2000-05-01

Some novel results of a combined sequential study of growth spirals on the basal surface of the richly polytypic CdI 2 crystals by optical microscopy, scanning electron microscopy (SEM) and scanning tunneling microscopy (STM) are presented and discussed. Under the high resolution and magnification achieved in the scanning electron microscope, the growth steps of large heights seen in the optical micrographs are found to have a large number of additional steps of smaller heights existing between any two adjacent large height growth steps. When further seen by a scanning tunneling microscope, which provides still higher resolution, sequences of unit substeps, each of height equal to the unit cell height of the underlying polytype, are revealed to exist on the surface. Several large steps also lie between the unit steps, with heights equal to an integral multiple of either the unit cell height of the underlying polytype or the thickness of a molecular sheet I-Cd-I. It is suggested that initially a giant screw dislocation may form by brittle fracture of the crystal platelet, which may gradually decompose into numerous unit dislocations during subsequent crystal growth.

What utility companies should known about fuel cells

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

Hirschenhofer, J.H.; Weinstein, R.E.

1996-11-01

Fuel cells are warming up. A world that ten years ago was unaware of the concept now can witness approximately 200 fuel cell units operating in 15 countries. An increasing number of utility company planners and decision makers have begun to ask whether fuel cells might fit into their future. While the fuel cell concept is simple, determining which type of fuel cell to consider may prove taxing. The multiplicity of fuel cells and their development programs, coupled with the amount of subject material and claims-versus-reality, may seem complex. Also to be reckoned with is the changing utility environment thatmore » might portend well for distributed generation with technologies such as fuel cells. This paper provides a road map of major fuel cell development in the US. It offers some views about the impact of the changing utility environment on fuel cells.« less

Electron Microscopy of the Infection and Subsequent Development of Soybean Nodule Cells

PubMed Central

Goodchild, D. J.; Bergersen, F. J.

1966-01-01

Goodchild, D. J. (Commonwealth Scientific and Industrial Research Organization, Canberra, Australia), and F. J. Bergersen. Electron microscopy of the infection and subsequent development of soybean nodule cells. J. Bacteriol. 92:204–213. 1966—Electron microscopy of thin sections of the developing central tissue cells of young soybean root nodules has shown that infection is initiated by a few infection threads which penetrate cells of the young central tissue. Extension growth of the threads may be a result of pressure developed from the growth of the bacteria within the threads. Release of bacteria from a thread is preceded by the development on an infection thread of a bulge with a cellulose-free membrane-bounded extension; bacteria move from this into the host cells by an endocytotic process and remain enclosed in an infection vacuole which is bounded by a membrane of host-cell origin. Multiplication of the intracellular bacteria takes place within these vacuoles. Until the host cell becomes filled with bacteria, the vacuoles separate into discrete units at each division. Later, division of the bacteria occurs within each vacuole, thus leading to the mature structure of the central tissue cells in which several bacteria are enclosed within each membrane-bounded unit. Images PMID:5949564

Blastocyst transfer in human in vitro fertilization. A solution to the multiple pregnancy epidemic.

PubMed

Vidaeff, A C; Racowsky, C; Rayburn, W F

2000-07-01

Since the 1950s, the incidence of twin gestation has doubled and the incidence of triplets has increased approximately sevenfold in the United States. Of extreme concern is the fact that many of these multiple pregnancies are iatrogenic: 35% of twin gestations and 77% of higher-order pregnancies are the result of some form of infertility therapy. Anything that can be done to reduce the number of these multiple pregnancies would benefit our patients and society. Great hope is placed on emerging blastocyst technology, which has the potential of achieving higher pregnancy rates per embryo transfer while reducing the risk of multiple pregnancy. We present the evolution of the blastocyst transfer concept and the technical aspects involved. The article also outlines the experience with blastocyst culture and transfer at Brigham and Women's Hospital, Boston, and describes identifiers for application of blastocyst transfer. The number of eight-cell embryos on day 3 is an independent marker for the selection of patients who would benefit from transfer on day 5. With no eight-cell embryos on day 3, 0% and 33% pregnancies resulted from day 5 vs. day 3 transfers, suggesting that these cases would not benefit from day 5 transfer. When at least one eight-cell embryo is available, there is no difference in ongoing pregnancy rates between day 5 and day 3 transfers, but there is a significant decrease in multiple gestations with day 5 transfers.

Left-handed compact MIMO antenna array based on wire spiral resonator for 5-GHz wireless applications

NASA Astrophysics Data System (ADS)

Alqadami, Abdulrahman Shueai Mohsen; Jamlos, Mohd Faizal; Soh, Ping Jack; Rahim, Sharul Kamal Abdul; Narbudowicz, Adam

2017-01-01

A compact coplanar waveguide-fed multiple-input multiple-output antenna array based on the left-handed wire loaded spiral resonators (SR) is presented. The proposed antenna consists of a 2 × 2 wire SR with two symmetrical microstrip feed lines, each line exciting a 1 × 2 wire SR. Left-handed metamaterial unit cells are placed on its reverse side and arranged in a 2 × 3 array. A reflection coefficient of less than -16 dB and mutual coupling of less than -28 dB are achieved at 5.15 GHz WLAN band.

Large area silicon sheet by EFG

NASA Technical Reports Server (NTRS)

Kalejs, J. P.

1982-01-01

Work carried out on the JPL Flat Plate Solar Array Project, for the purpose of developing a method for silicon ribbon production by Edge-defined Film-fed Growth (EEG) for use as low-cost substrate material in terrestrial solar cell manufacture, is described. A multiple ribbon furnace unit that is designed to operate on a continuous basis for periods of at least one week, with melt replenishment and automatic ribbon width control, and to produce silicon sheet at a rate of one square meter per hour, was constructed. Program milestones set for single ribbon furnace operation to demonstrate basic EEG system capabilities with respect to growth speed, thickness and cell performance were achieved for 10 cm wide ribbon: steady-state growth at 4 cm/min and 200 micron thickness over periods of an hour and longer was made routine, and a small area cell efficiency of 13+% demonstrated. Large area cells of average efficiency of 10 to 11%, with peak values of 11 to 12% were also achieved. The integration of these individual performance levels into multiple ribbon furnace operation was not accomplished.

Single-cell technologies to study the immune system.

PubMed

Proserpio, Valentina; Mahata, Bidesh

2016-02-01

The immune system is composed of a variety of cells that act in a coordinated fashion to protect the organism against a multitude of different pathogens. The great variability of existing pathogens corresponds to a similar high heterogeneity of the immune cells. The study of individual immune cells, the fundamental unit of immunity, has recently transformed from a qualitative microscopic imaging to a nearly complete quantitative transcriptomic analysis. This shift has been driven by the rapid development of multiple single-cell technologies. These new advances are expected to boost the detection of less frequent cell types and transient or intermediate cell states. They will highlight the individuality of each single cell and greatly expand the resolution of current available classifications and differentiation trajectories. In this review we discuss the recent advancement and application of single-cell technologies, their limitations and future applications to study the immune system. © 2015 The Authors. Immunology Published by John Wiley & Sons Ltd.

Short, multiple-stranded β-hairpin peptides have antimicrobial potency with high selectivity and salt resistance.

PubMed

Chou, Shuli; Shao, Changxuan; Wang, Jiajun; Shan, Anshan; Xu, Lin; Dong, Na; Li, Zhongyu

2016-01-01

The β-hairpin structure has been proposed to exhibit potent antimicrobial properties with low cytotoxicity, thus, multiple β-hairpin structures have been proved to be highly stable in structures containing tightly packed hydrophobic cores. The aim of this study was to develop peptide-based synthetic strategies for generating short, but effective AMPs as inexpensive antimicrobial agents. Multiple-stranded β-hairpin peptides with the same β-hairpin unit, (WRXxRW)n where n=1, 2, 3, or 4 and Xx represent the turn sequence, were synthesized, and their potential as antimicrobial agents was evaluated. Owning to the tightly packed hydrophobic core and paired Trp of this multiple-stranded β-hairpin structure, all the 12-residues peptides exhibited high cell selectivity towards bacterial cells over human red blood cells (hRBCs), and the peptide W2 exhibited stronger antimicrobial activities with the MIC values of 2-8μM against various tested bacteria. Not only that, but W2 also showed obvious synergy with streptomycin and chloramphenicol against Escherichia coli, and displayed synergy with ciprofloxacin against Staphylococcus aureus with the FICI values ⩽0.5. Fluorescence spectroscopy and electron microscopy analyses indicated that W2 kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Collectively, based on the multiple β-hairpin peptides, the ability to develop libraries of short and effective peptides will be a powerful approach to the discovery of novel antimicrobial agents. We successfully screened a peptide W2 ((WRPGRW)2) from a series of multiple-stranded β-hairpin antimicrobial peptides based on the "S-shaped" motif that induced the formation of a globular structure, and Trp zipper was used to replace the disulfide bonds to reduce the cost of production. This novel structure applied to AMPs improved cell selectivity and salt stability. The findings of this study will promote the development of peptide-based antimicrobial biomaterials. Further exploration of these AMPs will allow for diverse biotechnological and clinical applications such as biomedical coating, food storaging, and animal feeding. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Suppression of Red Blood Cell Autofluorescence for Immunocytochemistry on Fixed Embryonic Mouse Tissue.

PubMed

Whittington, Niteace C; Wray, Susan

2017-10-23

Autofluorescence is a problem that interferes with immunofluorescent staining and complicates data analysis. Throughout the mouse embryo, red blood cells naturally fluoresce across multiple wavelengths, spanning the emission and excitation spectra of many commonly used fluorescent reporters, including antibodies, dyes, stains, probes, and transgenic proteins, making it difficult to distinguish assay fluorescence from endogenous fluorescence. Several tissue treatment methods have been developed to bypass this issue with varying degrees of success. Sudan Black B dye has been commonly used to quench autofluorescence, but can also introduce background fluorescence. Here we present a protocol for an alternative called TrueBlack Lipofuscin Autofluorescence Quencher. The protocol described in this unit demonstrates how TrueBlack efficiently quenches red blood cell autofluorescence across red and green wavelengths in fixed embryonic tissue without interfering with immunofluorescent signal intensity or introducing background staining. We also identify optimal incubation, concentration, and multiple usage conditions for routine immunofluorescence microscopy. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

PubMed

Lublin, Fred D; Bowen, James D; Huddlestone, John; Kremenchutzky, Marcelo; Carpenter, Adam; Corboy, John R; Freedman, Mark S; Krupp, Lauren; Paulo, Corri; Hariri, Robert J; Fischkoff, Steven A

2014-11-01

Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis. This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score>0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included headache, fatigue, infusion site reactions, and urinary tract infection. PDA-001 infusions were safe and well tolerated in relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis patients. No paradoxical worsening of lesion counts was noted with either dose. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Droplet Array-Based 3D Coculture System for High-Throughput Tumor Angiogenesis Assay.

PubMed

Du, Xiaohui; Li, Wanming; Du, Guansheng; Cho, Hansang; Yu, Min; Fang, Qun; Lee, Luke P; Fang, Jin

2018-03-06

Angiogenesis is critical for tumor progression and metastasis, and it progresses through orchestral multicellular interactions. Thus, there is urgent demand for high-throughput tumor angiogenesis assays for concurrent examination of multiple factors. For investigating tumor angiogenesis, we developed a microfluidic droplet array-based cell-coculture system comprising a two-layer polydimethylsiloxane chip featuring 6 × 9 paired-well arrays and an automated droplet-manipulation device. In each droplet-pair unit, tumor cells were cultured in 3D in one droplet by mixing cell suspensions with Matrigel, and in the other droplet, human umbilical vein endothelial cells (HUVECs) were cultured in 2D. Droplets were fused by a newly developed fusion method, and tumor angiogenesis was assayed by coculturing tumor cells and HUVECs in the fused droplet units. The 3D-cultured tumor cells formed aggregates harboring a hypoxic center-as observed in vivo-and secreted more vascular endothelial growth factor (VEGF) and more strongly induced HUVEC tubule formation than did 2D-cultured tumor cells. Our single array supported 54 assays in parallel. The angiogenic potentials of distinct tumor cells and their differential responses to antiangiogenesis agent, Fingolimod, could be investigated without mutual interference in a single array. Our droplet-based assay is convenient to evaluate multicellular interaction in high throughput in the context of tumor sprouting angiogenesis, and we envision that the assay can be extensively implementable for studying other cell-cell interactions.

An efficient analytical model for baffled, multi-celled membrane-type acoustic metamaterial panels

NASA Astrophysics Data System (ADS)

Langfeldt, F.; Gleine, W.; von Estorff, O.

2018-03-01

A new analytical model for the oblique incidence sound transmission loss prediction of baffled panels with multiple subwavelength sized membrane-type acoustic metamaterial (MAM) unit cells is proposed. The model employs a novel approach via the concept of the effective surface mass density and approximates the unit cell vibrations in the form of piston-like displacements. This yields a coupled system of linear equations that can be solved efficiently using well-known solution procedures. A comparison with results from finite element model simulations for both normal and diffuse field incidence shows that the analytical model delivers accurate results as long as the edge length of the MAM unit cells is smaller than half the acoustic wavelength. The computation times for the analytical calculations are 100 times smaller than for the numerical simulations. In addition to that, the effect of flexible MAM unit cell edges compared to the fixed edges assumed in the analytical model is studied numerically. It is shown that the compliance of the edges has only a small impact on the transmission loss of the panel, except at very low frequencies in the stiffness-controlled regime. The proposed analytical model is applied to investigate the effect of variations of the membrane prestress, added mass, and mass eccentricity on the diffuse transmission loss of a MAM panel with 120 unit cells. Unlike most previous investigations of MAMs, these results provide a better understanding of the acoustic performance of MAMs under more realistic conditions. For example, it is shown that by varying these parameters deliberately in a checkerboard pattern, a new anti-resonance with large transmission loss values can be introduced. A random variation of these parameters, on the other hand, is shown to have only little influence on the diffuse transmission loss, as long as the standard deviation is not too large. For very large random variations, it is shown that the peak transmission loss value can be greatly diminished.

Hyperkalemia after irradiation of packed red blood cells: Possible effects with intravascular fetal transfusion

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

Thorp, J.A.; Plapp, F.V.; Cohen, G.R.

1990-08-01

Plasma potassium, calcium, and albumin concentrations in irradiated blood, and in fetal blood before and after transfusion, were measured. Dangerously high plasma potassium levels were observed in some units of irradiated packed red blood cells (range, 13.9 to 66.5 mEq/L; mean, 44.7 mEq/L) and could be one possible explanation for the high incidence of fetal arrhythmia associated with fetal intravascular transfusion. There are many factors operative in the preparation of irradiated packed red blood cells that may predispose to high potassium levels: the age of the red blood cells, the number of procedures used to concentrate the blood, the durationmore » of time elapsed from concentration, the duration of time elapsed from irradiation, and the hematocrit. Use of fresh blood, avoidance of multiple packing procedures, limiting the hematocrit in the donor unit to less than or equal to 80%, and minimizing the time between concentration, irradiation and transfusion may minimize the potassium levels, and therefore making an additional washing procedure unnecessary.« less

Caged Molecular Glues as Photoactivatable Tags for Nuclear Translocation of Guests in Living Cells.

PubMed

Arisaka, Akio; Mogaki, Rina; Okuro, Kou; Aida, Takuzo

2018-02-21

We developed dendritic caged molecular glues ( Caged Glue-R) as tags for nucleus-targeted drug delivery, whose multiple guanidinium ion (Gu + ) pendants are protected by an anionic photocleavable unit (butyrate-substituted nitroveratryloxycarbonyl; BA NVOC). Negatively charged Caged Glue-R hardly binds to anionic biomolecules because of their electrostatic repulsion. However, upon exposure of Caged Glue-R to UV light or near-infrared (NIR) light, the BA NVOC groups of Caged Glue-R are rapidly detached to yield an uncaged molecular glue ( Uncaged Glue-R) that carries multiple Gu + pendants. Because Gu + forms a salt bridge with PO 4 - , Uncaged Glue-R tightly adheres to anionic biomolecules such as DNA and phospholipids in cell membranes by a multivalent salt-bridge formation. When tagged with Caged Glue-R, guests can be taken up into living cells via endocytosis and hide in endosomes. However, when the Caged Glue-R tag is photochemically uncaged to form Uncaged Glue-R, the guests escape from the endosome and migrate into the cytoplasm followed by the cell nucleus. We demonstrated that quantum dots (QDs) tagged with Caged Glue-R can be delivered efficiently to cell nuclei eventually by irradiation with light.

Multiple myeloma: a clinical overview.

PubMed

Anderson, Kenneth C

2011-11-15

Multiple myeloma (MM) is the second most common hematologic malignancy in the United States, affecting slightly more men than women and twice as many African Americans as Caucasians. Older age is the primary risk factor for MM, but obesity also increases risk. MM is incurable, but treatment advances in the past decade have more than doubled the duration of survival. MM is a progressive plasma cell tumor in which an initially stable clone becomes malignant via a multistep process. Causative factors implicated in this process include radiation, environmental toxins, chronic antigen stimulation, and genetics. The malignant plasma cells interact with other hematopoietic and stromal cells within the bone marrow microenvironment to disrupt homeostasis among cells and within the extracellular matrix. These tumor-host interactions lead to MM cell proliferation and migration, angiogenesis, osteolysis, immunodeficiency, and anemia. As a result, patients often present with osteolytic bone lesions, recurrent infections, renal insufficiency, and fatigue. The Durie-Salmon and International Staging Systems are used to stage MM, with the latter providing prognostic information based on readily available laboratory data. However, a number of cytogenetic markers are emerging as prognostic indicators, introducing the possibility of more refined disease staging systems and tailored treatment strategies based on genetic profiles.

A Multi-Functional Microelectrode Array Featuring 59760 Electrodes, 2048 Electrophysiology Channels, Stimulation, Impedance Measurement and Neurotransmitter Detection Channels.

PubMed

Dragas, Jelena; Viswam, Vijay; Shadmani, Amir; Chen, Yihui; Bounik, Raziyeh; Stettler, Alexander; Radivojevic, Milos; Geissler, Sydney; Obien, Marie; Müller, Jan; Hierlemann, Andreas

2017-06-01

Biological cells are characterized by highly complex phenomena and processes that are, to a great extent, interdependent. To gain detailed insights, devices designed to study cellular phenomena need to enable tracking and manipulation of multiple cell parameters in parallel; they have to provide high signal quality and high spatiotemporal resolution. To this end, we have developed a CMOS-based microelectrode array system that integrates six measurement and stimulation functions, the largest number to date. Moreover, the system features the largest active electrode array area to date (4.48×2.43 mm 2 ) to accommodate 59,760 electrodes, while its power consumption, noise characteristics, and spatial resolution (13.5 μm electrode pitch) are comparable to the best state-of-the-art devices. The system includes: 2,048 action-potential (AP, bandwidth: 300 Hz to 10 kHz) recording units, 32 local-field-potential (LFP, bandwidth: 1 Hz to 300 Hz) recording units, 32 current recording units, 32 impedance measurement units, and 28 neurotransmitter detection units, in addition to the 16 dual-mode voltage-only or current/voltage-controlled stimulation units. The electrode array architecture is based on a switch matrix, which allows for connecting any measurement/stimulation unit to any electrode in the array and for performing different measurement/stimulation functions in parallel.

Adaptation of Rhodopseudomonas acidophila strain 7050 to growth at different light intensities: what are the benefits to changing the type of LH2?

PubMed

Gardiner, A T; Niedzwiedzki, D M; Cogdell, R J

2018-04-01

Typical purple bacterial photosynthetic units consist of light harvesting one/reaction centre 'core' complexes surrounded by light harvesting two complexes. Factors such as the number and size of photosynthetic units per cell, as well as the type of light harvesting two complex that is produced, are controlled by environmental factors. In this paper, the change in the type of LH2 present in the Rhodopsuedomonas acidophila strain 7050 is described when cells are grown at a range of different light intensities. This species contains multiple pucBA genes that encode the apoproteins that form light-harvesting complex two, and a more complex mixture of spectroscopic forms of this complex has been found than was previously thought to be the case. Femto-second time resolved absorption has been used to investigate how the energy transfer properties in the membranes of high-light and low-light adapted cells change as the composition of the LH2 complexes varies.

Palisade cell shape affects the light-induced chloroplast movements and leaf photosynthesis.

PubMed

Gotoh, Eiji; Suetsugu, Noriyuki; Higa, Takeshi; Matsushita, Tomonao; Tsukaya, Hirokazu; Wada, Masamitsu

2018-01-24

Leaf photosynthesis is regulated by multiple factors that help the plant to adapt to fluctuating light conditions. Leaves of sun-light-grown plants are thicker and contain more columnar palisade cells than those of shade-grown plants. Light-induced chloroplast movements are also essential for efficient leaf photosynthesis and facilitate efficient light utilization in leaf cells. Previous studies have demonstrated that leaves of most of the sun-grown plants exhibited no or very weak chloroplast movements and could accomplish efficient photosynthesis under strong light. To examine the relationship between palisade cell shape, chloroplast movement and distribution, and leaf photosynthesis, we used an Arabidopsis thaliana mutant, angustifolia (an), which has thick leaves that contain columnar palisade cells similar to those in the sun-grown plants. In the highly columnar cells of an mutant leaves, chloroplast movements were restricted. Nevertheless, under white light condition (at 120 µmol m -2 s -1 ), the an mutant plants showed higher chlorophyll content per unit leaf area and, thus, higher light absorption by the leaves than the wild type, which resulted in enhanced photosynthesis per unit leaf area. Our findings indicate that coordinated regulation of leaf cell shape and chloroplast movement according to the light conditions is pivotal for efficient leaf photosynthesis.

cellPACK: A Virtual Mesoscope to Model and Visualize Structural Systems Biology

PubMed Central

Johnson, Graham T.; Autin, Ludovic; Al-Alusi, Mostafa; Goodsell, David S.; Sanner, Michel F.; Olson, Arthur J.

2014-01-01

cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10−7–10−8m) between molecular and cellular biology. cellPACK’s modular architecture unites existing and novel packing algorithms to generate, visualize and analyze comprehensive 3D models of complex biological environments that integrate data from multiple experimental systems biology and structural biology sources. cellPACK is currently available as open source code, with tools for validation of models and with recipes and models for five biological systems: blood plasma, cytoplasm, synaptic vesicles, HIV and a mycoplasma cell. We have applied cellPACK to model distributions of HIV envelope protein to test several hypotheses for consistency with experimental observations. Biologists, educators, and outreach specialists can interact with cellPACK models, develop new recipes and perform packing experiments through scripting and graphical user interfaces at http://cellPACK.org. PMID:25437435

Nontesticular cancers in relatives of testicular germ cell tumor (TGCT) patients from multiple-case TGCT families

PubMed Central

McMaster, Mary L; Heimdal, Ketil R; Loud, Jennifer T; Bracci, Janet S; Rosenberg, Philip S; Greene, Mark H

2015-01-01

Testicular germ cell tumors (TGCT) exhibit striking familial aggregation that remains incompletely explained. To improve the phenotypic definition of familial TGCT (FTGCT), we studied an international cohort of multiple-case TGCT families to determine whether first-degree relatives of FTGCT cases are at increased risk of other types of cancer. We identified 1041 first-degree relatives of TGCT cases in 66 multiple-case TGCT families from Norway and 64 from the United States (combined follow-up of 31,556 person-years). We collected data on all cancers (except nonmelanoma skin cancers) reported by the family informant in these relatives, and we attempted to verify all reported cancer diagnoses through medical or cancer registry records. We calculated observed-to-expected (O/E) standardized incidence ratios, together with 95% confidence intervals (CI), for invasive cancers other than TGCT. We found no increase in risk of cancer overall (Norway O/E = 0.8; 95% CI: 0.6–1.1 and United States O/E = 0.9; 95% CI: 0.7–1.3). Site-specific analyses pooled across the two countries revealed a leukemia excess (O/E = 6.5; 95% CI: 3.0–12.3), deficit of female breast cancer (O/E = 0.0; 95% CI: 0.0–0.6) and increased risk of soft tissue sarcoma (O/E = 7.2; 95% CI: 2.0–18.4); in all instances, these results were based on small case numbers and statistically significant only in Norway. While limited by sample size and potential issues relating to completeness of cancer reporting, this study in multiple-case TGCT families does not support the hypothesis that cancers other than testis cancer contribute to the FTGCT phenotype. PMID:25882629

Programmed cell death of tobacco BY-2 cells induced by still culture conditions is affected by the age of the culture under agitation.

PubMed

Hiraga, Asahi; Kaneta, Tsuyoshi; Sato, Yasushi; Sato, Seiichi

2010-01-25

Evans Blue staining indicated that actively growing tobacco BY-2 cells in the exponential phase died more rapidly than quiescent cells in the stationary phase when the cells cultured under agitation were placed under still conditions. Fifty percent cell death was induced at about 18, 26, 80 and 140 h for early, mid, late exponential- and stationary-phase cells, respectively. Actively growing cells became TUNEL (transferase-mediated dUTP nick end labelling)-positive more rapidly than quiescent cells, suggesting that the cell death evaluated by Evans Blue is accompanied by DNA cleavages. Electrophoresis of genomic DNA showed a typical 'DNA laddering' pattern formed by multiples of about 200 bp internucleosomal units. Chromatin condensation was first detected at least within 24 h by light microscopy, and then cell shrinkage followed. These findings suggest that the death of BY-2 cells induced by still conditions is PCD (programmed cell death).

Quality and safety of red blood cells stored in two additive solutions subjected to multiple room temperature exposures.

PubMed

de Grandmont, M J; Ducas, E; Girard, M; Méthot, M; Brien, M; Thibault, L

2014-10-01

Many international standards state that red blood cell (RBC) products should be discarded if left out of controlled temperature storage for longer than 30 min to reduce the risk of bacterial growth and RBC loss of viability. This study aimed to verify whether repeated short-time exposures to room temperature (RT) influence RBCs quality and bacterial proliferation. Saline-adenine-glucose-mannitol (SAGM) and AS-3 RBC units were split and exposed to RT for 30 or 60 min on day 2, 7, 14, 21, and 42 of storage while reference units remained stored at 1-6°C. Red blood cell in vitro quality parameters were evaluated after each exposure. In a second experiment, SAGM and AS-3 RBC units were split and inoculated with Staphylococcus epidermidis (5 CFU/ml), Serratia marcescens (1 CFU/ml), and Serratia liquefaciens (1 CFU/ml). Reference units remained in storage while test units were exposed as described previously. Bacterial concentrations were investigated after each exposure. No differences were noticed between reference and test units in any of the in vitro parameters investigated. S. epidermidis did not grow in either reference or exposed RBCs. While S. marcescens did not grow in AS-3, bacterial growth was observed in RT-exposed SAGM RBCs on day 42. Similar growth was obtained for S. liquefaciens in the two additive solutions for both reference and test units. Short-time exposures to RT do not affect RBC quality and do not significantly influence bacterial growth. An expansion of the '30-minute' rule to 60 min should be considered by regulatory agencies. © 2014 International Society of Blood Transfusion.

PS3 CELL Development for Scientific Computation and Research

NASA Astrophysics Data System (ADS)

Christiansen, M.; Sevre, E.; Wang, S. M.; Yuen, D. A.; Liu, S.; Lyness, M. D.; Broten, M.

2007-12-01

The Cell processor is one of the most powerful processors on the market, and researchers in the earth sciences may find its parallel architecture to be very useful. A cell processor, with 7 cores, can easily be obtained for experimentation by purchasing a PlayStation 3 (PS3) and installing linux and the IBM SDK. Each core of the PS3 is capable of 25 GFLOPS giving a potential limit of 150 GFLOPS when using all 6 SPUs (synergistic processing units) by using vectorized algorithms. We have used the Cell's computational power to create a program which takes simulated tsunami datasets, parses them, and returns a colorized height field image using ray casting techniques. As expected, the time required to create an image is inversely proportional to the number of SPUs used. We believe that this trend will continue when multiple PS3s are chained using OpenMP functionality and are in the process of researching this. By using the Cell to visualize tsunami data, we have found that its greatest feature is its power. This fact entwines well with the needs of the scientific community where the limiting factor is time. Any algorithm, such as the heat equation, that can be subdivided into multiple parts can take advantage of the PS3 Cell's ability to split the computations across the 6 SPUs reducing required run time by one sixth. Further vectorization of the code can allow for 4 simultanious floating point operations by using the SIMD (single instruction multiple data) capabilities of the SPU increasing efficiency 24 times.

Effects of cortisone on regenerating rat liver.

PubMed

EINHORN, S L; HIRSCHBERG, E; GELLHORN, A

1954-03-01

The effects of continuous administration of cortisone on the metabolism of regenerating rat liver have been studied. Whereas the restoration of the weight of the liver after partial hepatectomy was not markedly affected by cortisone, the multiplication of cells was reduced to a significant degree after the first 2 days of regeneration. Liver restoration in terms of nucleic acids was similarly inhibited by cortisone. The results are consistent with the interpretation that the inhibition of cell multiplication in this system is dependent on and keeps pace with the inhibition of nucleic acid synthesis by this drug. At almost any time after hepatectomy, the nucleic acid content of the liver cells was the same in treated and in untreated animals. In ancillary studies, it was shown that cortisone caused the cells of regenerating liver to be increased in size and weight through the increased infiltration of lipids. Changes in water, protein, and carbohydrate content of the liver cells did not contribute to this increase in the weight of the cells. Since all animals were treated with cortisone for 5 days before hepatectomy, data were also obtained on the effect of this agent on the resting liver. This course of treatment brought about a significant decrease in the number of cells per unit wet weight and in the water content of the livers. The nucleic acid content of the cells at hepatectomy, on the other hand, was unchanged.

Neurovascular abnormalities in brain disorders: highlights with angiogenesis and magnetic resonance imaging studies.

PubMed

Chen, Chiao-Chi V; Chen, Yu-Chen; Hsiao, Han-Yun; Chang, Chen; Chern, Yijuang

2013-07-05

The coupling between neuronal activity and vascular responses is controlled by the neurovascular unit (NVU), which comprises multiple cell types. Many different types of dysfunction in these cells may impair the proper control of vascular responses by the NVU. Magnetic resonance imaging, which is the most powerful tool available to investigate neurovascular structures or functions, will be discussed in the present article in relation to its applications and discoveries. Because aberrant angiogenesis and vascular remodeling have been increasingly reported as being implicated in brain pathogenesis, this review article will refer to this hallmark event when suitable.

Reduced cellularity of bone marrow in multiple sclerosis with decreased MSC expansion potential and premature ageing in vitro.

PubMed

Redondo, Juliana; Sarkar, Pamela; Kemp, Kevin; Virgo, Paul F; Pawade, Joya; Norton, Aimie; Emery, David C; Guttridge, Martin G; Marks, David I; Wilkins, Alastair; Scolding, Neil J; Rice, Claire M

2017-05-01

Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken. In MS marrow, there was an interstitial infiltrate of inflammatory cells with lymphoid (predominantly T-cell) nodules although total cellularity was reduced. Controlling for age, MSCs isolated from patients with MS had reduced in vitro expansion potential as determined by population doubling time, colony-forming unit assay, and expression of β-galactosidase. MS MSCs expressed reduced levels of Stro-1 and displayed accelerated shortening of telomere terminal restriction fragments (TRF) in vitro. Our results are consistent with reduced proliferative capacity and ex vivo premature ageing of bone-marrow-derived cells, particularly MSCs, in MS. They have significant implication for MSC-based therapies for MS and suggest that accelerated cellular ageing and senescence may contribute to the pathophysiology of progressive MS. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for this study was provided by the Medical Research Council, UK (grant no. MR/K004166/1). The ACTiMuS study is sup-ported by the Silverman Family Foundation, Multiple Sclerosis Trust, Rosetree’s Trust, Catholic Bishops of England and Wales and Friends of Frenchay and SIAMMS-II by the Sir Halley Stewart Trust. C.M.R., P.S., and K.K. received support from the Burden Neurological Institute.

Three-dimensional finite element modeling of pericellular matrix and cell mechanics in the nucleus pulposus of the intervertebral disk based on in situ morphology.

PubMed

Cao, Li; Guilak, Farshid; Setton, Lori A

2011-02-01

Nucleus pulposus (NP) cells of the intervertebral disk (IVD) have unique morphological characteristics and biologic responses to mechanical stimuli that may regulate maintenance and health of the IVD. NP cells reside as single cell, paired or multiple cells in a contiguous pericellular matrix (PCM), whose structure and properties may significantly influence cell and extracellular matrix mechanics. In this study, a computational model was developed to predict the stress-strain, fluid pressure and flow fields for cells and their surrounding PCM in the NP using three-dimensional (3D) finite element models based on the in situ morphology of cell-PCM regions of the mature rat NP, measured using confocal microscopy. Three-dimensional geometries of the extracellular matrix and representative cell-matrix units were used to construct 3D finite element models of the structures as isotropic and biphasic materials. In response to compressive strain of the extracellular matrix, NP cells and PCM regions were predicted to experience volumetric strains that were 1.9-3.7 and 1.4-2.1 times greater than the extracellular matrix, respectively. Volumetric and deviatoric strain concentrations were generally found at the cell/PCM interface, while von Mises stress concentrations were associated with the PCM/extracellular matrix interface. Cell-matrix units containing greater cell numbers were associated with higher peak cell strains and lower rates of fluid pressurization upon loading. These studies provide new model predictions for micromechanics of NP cells that can contribute to an understanding of mechanotransduction in the IVD and its changes with aging and degeneration.

A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs)

ClinicalTrials.gov

2018-05-15

Hematologic Malignancies; Inherited Disorders of Metabolism; Inherited Abnormalities of Platelets; Histiocytic Disorders; Acute Myelogenous Leukemia (AML or ANLL); Acute Lymphoblastic Leukemia (ALL); Other Acute Leukemia; Chronic Myelogenous Leukemia (CML); Myelodysplastic (MDS) / Myeloproliferative (MPN) Diseases; Other Leukemia; Hodgkin Lymphoma; Non-hodgkin Lymphoma; Multiple Myeloma/ Plasma Cell Disorder (PCD); Inherited Abnormalities of Erythrocyte Differentiation or Function; Disorders of the Immune System; Automimmune Diseases; Severe Aplastic Anemia

Integrating fine-scale soil data into species distribution models: preparing Soil Survey Geographic (SSURGO) data from multiple counties

Treesearch

Matthew P. Peters; Louis R. Iverson; Anantha M. Prasad; Steve N. Matthews

2013-01-01

Fine-scale soil (SSURGO) data were processed at the county level for 37 states within the eastern United States, initially for use as predictor variables in a species distribution model called DISTRIB II. Values from county polygon files converted into a continuous 30-m raster grid were aggregated to 4-km cells and integrated with other environmental and site condition...

Keep it on the edge: The post-mitotic midbody as a polarity signal unit

PubMed Central

Lujan, Pablo; Rubio, Teresa; Varsano, Giulia; Köhn, Maja

2017-01-01

ABSTRACT The maintenance of the epithelial architecture during tissue proliferation is achieved by apical positioning of the midbody after cell division. Consequently, midbody mislocalization contributes to epithelial architecture disruption, a fundamental event during epithelial tumorigenesis. Studies in 3D polarized epithelial MDCK or Caco2 cell models, where midbody misplacement leads to multiple ectopic but fully polarized lumen-containing cysts, revealed that this phenotype can be caused by 2 different scenarios: the loss of mitotic spindle orientation or the loss of asymmetric abscission. In addition, we have recently proposed a third cellular mechanism where the midbody mislocalization is achieved through cytokinesis acceleration driven by the cancer-promoting phosphatase of regenerating liver (PRL)-3. Here we critically review these findings, and we furthermore present new data indicating that midbodies themselves might act as signal unit for polarization since they can infer apical characteristics to a basal membrane. PMID:28919938

Design and development of an electrically-controlled beam steering mirror for microwave tomography

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

Tayebi, A., E-mail: tayebiam@msu.edu; Tang, J.; Paladhi, P. Roy

2015-03-31

Microwave tomography has gained significant attention due to its reliability and unhazardous nature in the fields of NDE and medical industry. A new microwave tomography system is presented in this paper, which significantly reduces the design and operational complexities of traditional microwave imaging systems. The major component of the proposed system is a reconfigurable reflectarray antenna which is used for beam steering in order to generate projections from multiple angles. The design, modeling and fabrication of the building block of the antenna, a tunable unit cell, are discussed in this paper. The unit cell is capable of dynamically altering themore » phase of the reflected field which results in beam steering ability of the reflectarray antenna. A tomographically reconstructed image of a dielectric sample using this new microwave tomography system is presented in this work.« less

Subnanometre-resolution structure of the doublet microtubule reveals new classes of microtubule-associated proteins

PubMed Central

Ichikawa, Muneyoshi; Liu, Dinan; Kastritis, Panagiotis L.; Basu, Kaustuv; Hsu, Tzu Chin; Yang, Shunkai; Bui, Khanh Huy

2017-01-01

Cilia are ubiquitous, hair-like appendages found in eukaryotic cells that carry out functions of cell motility and sensory reception. Cilia contain an intriguing cytoskeletal structure, termed the axoneme that consists of nine doublet microtubules radially interlinked and longitudinally organized in multiple specific repeat units. Little is known, however, about how the axoneme allows cilia to be both actively bendable and sturdy or how it is assembled. To answer these questions, we used cryo-electron microscopy to structurally analyse several of the repeating units of the doublet at sub-nanometre resolution. This structural detail enables us to unambiguously assign α- and β-tubulins in the doublet microtubule lattice. Our study demonstrates the existence of an inner sheath composed of different kinds of microtubule inner proteins inside the doublet that likely stabilizes the structure and facilitates the specific building of the B-tubule. PMID:28462916

Nonsymmorphic symmetry-protected topological modes in plasmonic nanoribbon lattices

NASA Astrophysics Data System (ADS)

Zhang, Yong-Liang; Wu, Raymond P. H.; Kumar, Anshuman; Si, Tieyan; Fung, Kin Hung

2018-04-01

Using a dynamic eigenresponse theory, we study the topological edge plasmon modes in dispersive plasmonic lattices constructed by unit cells of multiple nanoribbons. In dipole approximation, the bulk-edge correspondence in the lattices made of dimerized unit cell and one of its square-root daughter with nonsymmorphic symmetry are demonstrated. Calculations with consideration of dynamic long-range effects and retardation are compared to those given by nearest-neighbor approximations. It is shown that nonsymmorphic symmetry opens up two symmetric gaps where versatile topological edge plasmon modes are found. Unprecedented spectral shifts of the edge states with respect to the zero modes due to long-range coupling are found. The proposed ribbon structure is favorable to electrical gating and thus could serve as an on-chip platform for electrically controllable subwavelength edge states at optical wavelengths. Our eigenresponse approach provides a powerful tool for the radiative topological mode analysis in strongly coupled plasmonic lattices.

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia.

PubMed

Cortés-Puch, Irene; Wang, Dong; Sun, Junfeng; Solomon, Steven B; Remy, Kenneth E; Fernandez, Melinda; Feng, Jing; Kanias, Tamir; Bellavia, Landon; Sinchar, Derek; Perlegas, Andreas; Solomon, Michael A; Kelley, Walter E; Popovsky, Mark A; Gladwin, Mark T; Kim-Shapiro, Daniel B; Klein, Harvey G; Natanson, Charles

2014-02-27

In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

PubMed Central

Wang, Dong; Sun, Junfeng; Solomon, Steven B.; Remy, Kenneth E.; Fernandez, Melinda; Feng, Jing; Kanias, Tamir; Bellavia, Landon; Sinchar, Derek; Perlegas, Andreas; Solomon, Michael A.; Kelley, Walter E.; Popovsky, Mark A.; Gladwin, Mark T.; Kim-Shapiro, Daniel B.; Klein, Harvey G.; Natanson, Charles

2014-01-01

In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes. PMID:24366359

Effects of red-cell storage duration on patients undergoing cardiac surgery.

PubMed

Steiner, Marie E; Ness, Paul M; Assmann, Susan F; Triulzi, Darrell J; Sloan, Steven R; Delaney, Meghan; Granger, Suzanne; Bennett-Guerrero, Elliott; Blajchman, Morris A; Scavo, Vincent; Carson, Jeffrey L; Levy, Jerrold H; Whitman, Glenn; D'Andrea, Pamela; Pulkrabek, Shelley; Ortel, Thomas L; Bornikova, Larissa; Raife, Thomas; Puca, Kathleen E; Kaufman, Richard M; Nuttall, Gregory A; Young, Pampee P; Youssef, Samuel; Engelman, Richard; Greilich, Philip E; Miles, Ronald; Josephson, Cassandra D; Bracey, Arthur; Cooke, Rhonda; McCullough, Jeffrey; Hunsaker, Robert; Uhl, Lynne; McFarland, Janice G; Park, Yara; Cushing, Melissa M; Klodell, Charles T; Karanam, Ravindra; Roberts, Pamela R; Dyke, Cornelius; Hod, Eldad A; Stowell, Christopher P

2015-04-09

Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

Improved energy output levels from small-scale Microbial Fuel Cells.

PubMed

Ieropoulos, I; Greenman, J; Melhuish, C

2010-04-01

This study reports on the findings from the investigation into small-scale (6.25 mL) MFCs, connected together as a network of multiple units. The MFCs contained unmodified (no catalyst) carbon fibre electrodes and for initial and later experiments, a standard ion-exchange membrane for the proton transfer from the anode to the cathode. The anode microbial culture was of the type commonly found in domestic wastewater fed with 5 mM acetate as the carbon-energy (C/E) source. The cultures were mature and acclimatised in the MFC environment for approximately 2 months before being re-inoculated in the experimental MFC units. The cathode was of the O(2) diffusion open-to-air type, but for the purposes of the polarization experiments, the cathodic electrodes were moistened with ferricyanide. The main aim of this study was to investigate the effects of connecting multiples of MFC units together as a method of scale up by using stacks and comparison of the effects of different PEM and MFC structural materials on the performance. Impedance matching (maximum-power-transfer) was achieved through calculation of total internal impedance. Three different PEM materials were compared in otherwise identical MFCs in sets of three. For individual isolated MFCs, Hyflon E87-03 was shown to produce twice, whilst E87-10 produced approximately 1.5 times the power output of the control (standard) PEM. However, when MFCs containing the E87-03 and E87-10 membranes were connected in a stack, the system suffered from severe instability and cell reversal. To study the effects of the various polymeric MFC structural materials, four small-scale units were manufactured from three different types of RP material; acrylo-butadiene-styrene coated (ABS), ABS coated (ABS-MEK) and polycarbonate (polyC). The stack of four (4) units prototyped out of polyC produced the highest power density values in polarisation experiments (80 mW/m(2)). 2009 Elsevier B.V. All rights reserved.

Molecular characterization of organic electronic films.

PubMed

DeLongchamp, Dean M; Kline, R Joseph; Fischer, Daniel A; Richter, Lee J; Toney, Michael F

2011-01-18

Organic electronics have emerged as a viable competitor to amorphous silicon for the active layer in low-cost electronics. The critical performance of organic electronic materials is closely related to their morphology and molecular packing. Unlike their inorganic counterparts, polymers combine complex repeat unit structure and crystalline disorder. This combination prevents any single technique from being able to uniquely solve the packing arrangement of the molecules. Here, a general methodology for combining multiple, complementary techniques that provide accurate unit cell dimensions and molecular orientation is described. The combination of measurements results in a nearly complete picture of the organic film morphology. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

γδ T Cells and dendritic cells in refractory Lyme arthritis

PubMed Central

Divan, Ali; Budd, Ralph C.; Tobin, Richard P.; Newell-Rogers, M. Karen

2015-01-01

Lyme disease is a multisystem infection transmitted by tick vectors with an incidence of up to 300,000 individuals/yr in the United States. The primary treatments are oral or i.v. antibiotics. Despite treatment, some individuals do not recover and have prolonged symptoms affecting multiple organs, including the nervous system and connective tissues. Inflammatory arthritis is a common symptom associated with Lyme pathology. In the past decades, γδ T cells have emerged as candidates that contribute to the transition from innate to adaptive responses. These cells are also differentially regulated within the synovia of patients affected by RLA. Here, we review and discuss potential cellular mechanisms involving γδ T cells and DCs in RLA. TLR signaling and antigen processing and presentation will be the key concepts that we review in aid of understanding the impact of γδ T cells in RLA. PMID:25605869

Ultrathin lightweight plate-type acoustic metamaterials with positive lumped coupling resonant

NASA Astrophysics Data System (ADS)

Ma, Fuyin; Huang, Meng; Wu, Jiu Hui

2017-01-01

The experimental realization and theoretical understanding of a two-dimensional multiple cells lumped ultrathin lightweight plate-type acoustic metamaterials structures have been presented, wherein broadband excellent sound attenuation ability at low frequencies is realized by employing a lumped element coupling resonant effect. The basic unit cell of the metamaterials consists of an ultrathin stiff nylon plate clamped by two elastic ethylene-vinyl acetate copolymer or acrylonitrile butadiene styrene frames. The strong sound attenuation (up to nearly 99%) at low frequencies is experimentally revealed by the precisely designed metamaterials, for which the physical mechanism of the sound attenuation could be explicitly understood using the finite element simulations. As to the designed samples, the lumped effect from the frame compliance leads to a coupling flexural resonance at designable low frequencies. As a result, the whole composite structure become strongly anti-resonant with the incident sound waves, followed by a higher sound attenuation, i.e., the lumped resonant effect has been effectively reversed to be positive from negative for sound attenuation, and the acoustic metamaterial design could be extended to the lumped element containing multiple cells, rather than confined to a single cell.

Using multiple logistic regression and GIS technology to predict landslide hazard in northeast Kansas, USA

USGS Publications Warehouse

Ohlmacher, G.C.; Davis, J.C.

2003-01-01

Landslides in the hilly terrain along the Kansas and Missouri rivers in northeastern Kansas have caused millions of dollars in property damage during the last decade. To address this problem, a statistical method called multiple logistic regression has been used to create a landslide-hazard map for Atchison, Kansas, and surrounding areas. Data included digitized geology, slopes, and landslides, manipulated using ArcView GIS. Logistic regression relates predictor variables to the occurrence or nonoccurrence of landslides within geographic cells and uses the relationship to produce a map showing the probability of future landslides, given local slopes and geologic units. Results indicated that slope is the most important variable for estimating landslide hazard in the study area. Geologic units consisting mostly of shale, siltstone, and sandstone were most susceptible to landslides. Soil type and aspect ratio were considered but excluded from the final analysis because these variables did not significantly add to the predictive power of the logistic regression. Soil types were highly correlated with the geologic units, and no significant relationships existed between landslides and slope aspect. ?? 2003 Elsevier Science B.V. All rights reserved.

Wide-band/angle Blazed Surfaces using Multiple Coupled Blazing Resonances

PubMed Central

Memarian, Mohammad; Li, Xiaoqiang; Morimoto, Yasuo; Itoh, Tatsuo

2017-01-01

Blazed gratings can reflect an oblique incident wave back in the path of incidence, unlike mirrors and metal plates that only reflect specular waves. Perfect blazing (and zero specular scattering) is a type of Wood’s anomaly that has been observed when a resonance condition occurs in the unit-cell of the blazed grating. Such elusive anomalies have been studied thus far as individual perfect blazing points. In this work, we present reflective blazed surfaces that, by design, have multiple coupled blazing resonances per cell. This enables an unprecedented way of tailoring the blazing operation, for widening and/or controlling of blazing bandwidth and incident angle range of operation. The surface can thus achieve blazing at multiple wavelengths, each corresponding to different incident wavenumbers. The multiple blazing resonances are combined similar to the case of coupled resonator filters, forming a blazing passband between the incident wave and the first grating order. Blazed gratings with single and multi-pole blazing passbands are fabricated and measured showing increase in the bandwidth of blazing/specular-reflection-rejection, demonstrated here at X-band for convenience. If translated to appropriate frequencies, such technique can impact various applications such as Littrow cavities and lasers, spectroscopy, radar, and frequency scanned antenna reflectors. PMID:28211506

Final report on the United States phase I clinical trial of the hypoxic cell radiosensitizer, misonidazole (Ro-07-0582; NSC No. 261037

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

Phillips, T.L.; Wasserman, T.H.; Johnson, R.J.

1981-10-15

The hypoxic cell sensitizer misonidazole began phase I evaluation in the United States in July 1977. One hundred two patients received 104 individual courses of drug. Drug was administered from once to five times per week over time spans from one to six weeks. The individual doses ranged 1 to 5 g/m. The major toxicity noted was neurologic; 49% of evaluable courses showed peripheral neuropathy, and 9% of evaluable courses showed central nervous system effects and/or ototoxicity. In addition, 48 of 102 patients exhibited some degree of nausea and vomiting. The concomitant administration of dexamethasone and phenytoin sodium appeared tomore » lower the incidence of neuropathy. Observations of efficacy were made comparatively in five patients who had multiple lesions treated with and without misonidazole. All five showed increased response in the lesions treated with misonidazole. It is concluded that misonidazole is a reasonably safe and potentially effective hypoxic cell sensitizer whose dose-limiting toxicity is neurologic.« less

Development of High Efficiency, Stacked Multiple Bandgap Solar Cells.

DTIC Science & Technology

1982-09-01

1982 CL APPROVED FOR PUBLIC RELEASE; DISTRIBUION UNLIMITED LAJ DTIC A12o 201sION UCIA0.TORT ELECTE A=R 7ORM VUGM AZUOUUICM LMMORRIS iv IIGRH-PATTSON...connection with a definitely related Government procurement operation, the United States Government thereby incurs no responsibility nor any obligation... Public Affairs (ASD/PA) and is releasable to the National Technical Information Service (NTIS). At NTIS, it will be available to the general public

Dose-Dependent Thresholds of 10-ns Electric Pulse Induced Plasma Membrane Disruption and Cytotoxicity in Multiple Cell Lines

DTIC Science & Technology

2010-01-01

Bioelectrics, Old Dominion University, Norfolk, VA 8. PERFORMING ORGANIZATION REPORT NUMBER 3 General Dynamics Inf. Tech Brooks City-Base, San... 16 . SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON a. REPORT U b. ABSTRACT...Sta tes of America, 2 Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, Virginia, United States of America, 3 General

Local structure of Rb{sub 2}Li{sub 4}(SeO{sub 4}){sub 3}{center_dot}2H{sub 2}O by the modeling of X-ray diffuse scattering - from average-structure to microdomain model

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

Komornicka, Dorota; Wolcyrz, Marek, E-mail: m.wolcyrz@int.pan.wroc.pl; Pietraszko, Adam

2012-08-15

Local structure of dirubidium tetralithium tris(selenate(VI)) dihydrate - Rb{sub 2}Li{sub 4}(SeO{sub 4}){sub 3}{center_dot} 2H{sub 2}O has been determined basing on the modeling of X-ray diffuse scattering. The origin of observed structured diffuse streaks is SeO{sub 4} tetrahedra switching between two alternative positions in two quasi-planar layers existing in each unit cell and formation of domains with specific SeO{sub 4} tetrahedra configuration locally fulfilling condition for C-centering in the 2a Multiplication-Sign 2b Multiplication-Sign c superstructure cell. The local structure solution is characterized by a uniform distribution of rather large domains (ca. thousand of unit cells) in two layers, but also monodomainsmore » can be taken into account. Inside a single domain SeO{sub 4} tetrahedra are ordered along ab-diagonal forming two-string ribbons. Inside the ribbons SeO{sub 4} and LiO{sub 4} tetrahedra share the oxygen corners, whereas ribbons are bound to each other by a net of hydrogen bonds and fastened by corner sharing SeO{sub 4} tetrahedra of the neighboring layers. - Graphical abstract: Experimental sections of the reciprocal space showing diffraction effects observed for RLSO. Bragg spots are visible on sections with integer indices (1 kl section - on the left), streaks - on sections with fractional ones (1.5 kl section - on the right). At the center: resulting local structure of the A package modeled as a microdomain: two-string ribbons of ordered oxygen-corners-sharing SeO{sub 4} and LiO{sub 4} terahedra extended along ab-diagonal are seen; ribbons are bound by hydrogen bonds (shown in pink); the multiplied 2a Multiplication-Sign 2b unit cell is shown. Highlights: Black-Right-Pointing-Pointer X-ray diffuse scattering in RLSO was registered and modeled. Black-Right-Pointing-Pointer The origin of diffuse streaks is SeO{sub 4} tetrahedra switching in two structure layers. Black-Right-Pointing-Pointer The local structure is characterized by a uniform distribution of microdomains. Black-Right-Pointing-Pointer Inside a single domain SeO{sub 4} tetrahedra are ordered along ab-diagonal forming ribbons. Black-Right-Pointing-Pointer The ribbons are bound to each other by a net of hydrogen bonds.« less

Calculating with light using a chip-scale all-optical abacus.

PubMed

Feldmann, J; Stegmaier, M; Gruhler, N; Ríos, C; Bhaskaran, H; Wright, C D; Pernice, W H P

2017-11-02

Machines that simultaneously process and store multistate data at one and the same location can provide a new class of fast, powerful and efficient general-purpose computers. We demonstrate the central element of an all-optical calculator, a photonic abacus, which provides multistate compute-and-store operation by integrating functional phase-change materials with nanophotonic chips. With picosecond optical pulses we perform the fundamental arithmetic operations of addition, subtraction, multiplication, and division, including a carryover into multiple cells. This basic processing unit is embedded into a scalable phase-change photonic network and addressed optically through a two-pulse random access scheme. Our framework provides first steps towards light-based non-von Neumann arithmetic.

Multilayer network modeling of integrated biological systems. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

NASA Astrophysics Data System (ADS)

De Domenico, Manlio

2018-03-01

Biological systems, from a cell to the human brain, are inherently complex. A powerful representation of such systems, described by an intricate web of relationships across multiple scales, is provided by complex networks. Recently, several studies are highlighting how simple networks - obtained by aggregating or neglecting temporal or categorical description of biological data - are not able to account for the richness of information characterizing biological systems. More complex models, namely multilayer networks, are needed to account for interdependencies, often varying across time, of biological interacting units within a cell, a tissue or parts of an organism.

Quantum efficiencies exceeding unity in amorphous silicon solar cells

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

Vanmaekelbergh, D.; Lagemaat, J. van de; Schropp, R.E.I.

1994-12-31

The experimental observation of internal quantum efficiencies above unity in crystalline silicon solar cells has brought up the question whether the generation of multiple electron/hole pairs has to be taken into consideration also in solar cells based on direct gap amorphous semiconductors. To study photogenerated carrier dynamics, the authors have applied Intensity Modulated Photocurrent Spectroscopy (IMPS) to hydrogenated amorphous silicon p-i-n solar cells. In the reverse voltage bias region at low illumination intensities it has been observed that the low frequency limit of the AC quantum yield Y increases significantly above unit with decreasing light intensity, indicating that more thanmore » one electron per photon is detected in the external circuit. This phenomenon can be explained by considering trapping and thermal emission of photogenerated carriers at intragap atmospheric dangling bond defect centers.« less

Platform technology for scalable assembly of instantaneously functional mosaic tissues

PubMed Central

Zhang, Boyang; Montgomery, Miles; Davenport-Huyer, Locke; Korolj, Anastasia; Radisic, Milica

2015-01-01

Engineering mature tissues requires a guided assembly of cells into organized three-dimensional (3D) structures with multiple cell types. Guidance is usually achieved by microtopographical scaffold cues or by cell-gel compaction. The assembly of individual units into functional 3D tissues is often time-consuming, relying on cell ingrowth and matrix remodeling, whereas disassembly requires an invasive method that includes either matrix dissolution or mechanical cutting. We invented Tissue-Velcro, a bio-scaffold with a microfabricated hook and loop system. The assembly of Tissue-Velcro preserved the guided cell alignment realized by the topographical features in the 2D scaffold mesh and allowed for the instant establishment of coculture conditions by spatially defined stacking of cardiac cell layers or through endothelial cell coating. The assembled cardiac 3D tissue constructs were immediately functional as measured by their ability to contract in response to electrical field stimulation. Facile, on-demand tissue disassembly was demonstrated while preserving the structure, physical integrity, and beating function of individual layers. PMID:26601234

Designed cell consortia as fragrance-programmable analog-to-digital converters.

PubMed

Müller, Marius; Ausländer, Simon; Spinnler, Andrea; Ausländer, David; Sikorski, Julian; Folcher, Marc; Fussenegger, Martin

2017-03-01

Synthetic biology advances the rational engineering of mammalian cells to achieve cell-based therapy goals. Synthetic gene networks have nearly reached the complexity of digital electronic circuits and enable single cells to perform programmable arithmetic calculations or to provide dynamic remote control of transgenes through electromagnetic waves. We designed a synthetic multilayered gaseous-fragrance-programmable analog-to-digital converter (ADC) allowing for remote control of digital gene expression with 2-bit AND-, OR- and NOR-gate logic in synchronized cell consortia. The ADC consists of multiple sampling-and-quantization modules sensing analog gaseous fragrance inputs; a gas-to-liquid transducer converting fragrance intensity into diffusible cell-to-cell signaling compounds; a digitization unit with a genetic amplifier circuit to improve the signal-to-noise ratio; and recombinase-based digital expression switches enabling 2-bit processing of logic gates. Synthetic ADCs that can remotely control cellular activities with digital precision may enable the development of novel biosensors and may provide bioelectronic interfaces synchronizing analog metabolic pathways with digital electronics.

Cryptosporidium as a testbed for single cell genome characterization of unicellular eukaryotes.

PubMed

Troell, Karin; Hallström, Björn; Divne, Anna-Maria; Alsmark, Cecilia; Arrighi, Romanico; Huss, Mikael; Beser, Jessica; Bertilsson, Stefan

2016-06-23

Infectious disease involving multiple genetically distinct populations of pathogens is frequently concurrent, but difficult to detect or describe with current routine methodology. Cryptosporidium sp. is a widespread gastrointestinal protozoan of global significance in both animals and humans. It cannot be easily maintained in culture and infections of multiple strains have been reported. To explore the potential use of single cell genomics methodology for revealing genome-level variation in clinical samples from Cryptosporidium-infected hosts, we sorted individual oocysts for subsequent genome amplification and full-genome sequencing. Cells were identified with fluorescent antibodies with an 80 % success rate for the entire single cell genomics workflow, demonstrating that the methodology can be applied directly to purified fecal samples. Ten amplified genomes from sorted single cells were selected for genome sequencing and compared both to the original population and a reference genome in order to evaluate the accuracy and performance of the method. Single cell genome coverage was on average 81 % even with a moderate sequencing effort and by combining the 10 single cell genomes, the full genome was accounted for. By a comparison to the original sample, biological variation could be distinguished and separated from noise introduced in the amplification. As a proof of principle, we have demonstrated the power of applying single cell genomics to dissect infectious disease caused by closely related parasite species or subtypes. The workflow can easily be expanded and adapted to target other protozoans, and potential applications include mapping genome-encoded traits, virulence, pathogenicity, host specificity and resistance at the level of cells as truly meaningful biological units.

Tunable two-dimensional acoustic meta-structure composed of funnel-shaped unit cells with multi-band negative acoustic property

NASA Astrophysics Data System (ADS)

Cho, Sungjin; Kim, Boseung; Min, Dongki; Park, Junhong

2015-10-01

This paper presents a two-dimensional heat-exhaust and sound-proof acoustic meta-structure exhibiting tunable multi-band negative effective mass density. The meta-structure was composed of periodic funnel-shaped units in a square lattice. Each unit cell operates simultaneously as a Helmholtz resonator (HR) and an extended pipe chamber resonator (EPCR), leading to a negative effective mass density creating bandgaps for incident sound energy dissipation without transmission. This structure allowed large heat-flow through the cross-sectional area of the extended pipe since the resonance was generated by acoustic elements without using solid membranes. The pipes were horizontally directed to a flow source to enable small flow resistance for cooling. Measurements of the sound transmission were performed using a two-load, four-microphone method for a unit cell and small reverberation chamber for two-dimensional panel to characterize the acoustic performance. The effective mass density showed significant frequency dependent variation exhibiting negative values at the specific bandgaps, while the effective bulk modulus was not affected by the resonator. Theoretical models incorporating local resonances in the multiple resonator units were proposed to analyze the noise reduction mechanism. The acoustic meta-structure parameters to create broader frequency bandgaps were investigated using the theoretical model. The negative effective mass density was calculated to investigate the creation of the bandgaps. The effects of design parameters such as length, cross-sectional area, and volume of the HR; length and cross-sectional area of the EPCR were analyzed. To maximize the frequency band gap, the suggested acoustic meta-structure panel, small neck length, and cross-sectional area of the HR, large EPCR length was advantageous. The bandgaps became broader when the two resonant frequencies were similar.

Skin rash in the intensive care unit: Stevens-Johnson syndrome, toxic epidermal necrolysis, or a rare manifestation of a hidden cutaneous malignancy: A case report.

PubMed

Al-Saffar, Farah; Ibrahim, Saif; Patel, Pujan; Jacob, Rafik; Palacio, Carlos; Cury, James

2016-03-01

Skin rashes are infrequently encountered in the intensive care units, either as a result or as a cause of admission. The entities of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of desquamating skin diseases that have multiple etiologies, the most common being drug-related reactions; very rarely, the cause may be cutaneous malignancies. We herein present a unique case of a 54-year-old male patient with psoriasis treated with methotrexate, who presented with a cellulitis-like clinical picture, then developed a severe progressive systemic inflammatory response syndrome, and progressed clinically to SJS, then TEN even after discontinuing the antibiotics and methotrexate. A skin biopsy demonstrated an aggressive and rapidly-progressing T-cell lymphoma. The present case highlights the necessity of skin biopsy when encountering SJS and TEN in the ICU in order to identify potentially treatable/controllable causes. Although it appeared reasonable to correlate TEN solely to medications, the skin biopsies clearly demonstrated an aggressive T-cell skin lymphoma. In a patient with a better general condition it may have been helpful to treat this malignancy. TEN is a life-threatening condition and skin biopsy is the cornerstone of diagnosis, despite the presence of multiple risk factors and the typical physical findings of a drug-induced reaction.

Progress in myeloma stem cells

PubMed Central

Cruz, Richard Dela; Tricot, Guido; Zangari, Maurizio; Zhan, Fenghuang

2011-01-01

Multiple myeloma (MM) is the second most common hematologic malignancy in the United States and affects about 4 in 100,000 Americans. Even though much progress has been made in MM therapy, MM remains an incurable disease for the vast majority of patients. The existence of MM stem cell is considered one of the major causes of MM drug-resistance, leading to relapse. This highlights the importance and urgency of developing approaches to target MM stem cells. However, very little is known about the molecular characteristics of the MM stem cells, which makes it difficult to target MM stem cells therapeutically. Evidence of the existence of a myeloma stem cell has been provided by Matsui et al. showing that the CD138- and CD20+ fraction, which is a minor population of the MM cells, has a greater clonogenic potential and has the phenotype of a memory B-cell (CD19+, CD27+). In this review, we report recent progress of cell surface markers in cancer stem cells, especially in myeloma and the molecular mechanisms related to drug resistance and myeloma disease progression. PMID:22432075

Method for traceable measurement of LTE signals

NASA Astrophysics Data System (ADS)

Sunder Dash, Soumya; Pythoud, Frederic; Leuchtmann, Pascal; Leuthold, Juerg

2018-04-01

This contribution presents a reference setup to measure the power of the cell-specific resource elements present in downlink long term evolution (LTE) signals in a way that the measurements are traceable to the international system of units. This setup can be used to calibrate the LTE code-selective field probes that are used to measure the radiation of base stations for mobile telephony. It can also be used to calibrate LTE signal generators and receivers. The method is based on traceable scope measurements performed directly at the output of a measuring antenna. It implements offline digital signal processing demodulation algorithms that consider the digital down-conversion, timing synchronization, frequency synchronization, phase synchronization and robust LTE cell identification to produce the downlink time-frequency LTE grid. Experimental results on conducted test scenarios, both single-input-single-output and multiple-input-multiple-output antenna configuration, show promising results confirming measurement uncertainties of the order of 0.05 dB with a coverage factor of 2.

Anti-M Antibody Induced Prolonged Anemia Following Hemolytic Disease of the Newborn Due to Erythropoietic Suppression in 2 Siblings.

PubMed

Ishida, Atsushi; Ohto, Hitoshi; Yasuda, Hiroyasu; Negishi, Yutaka; Tsuiki, Hideki; Arakawa, Takeshi; Yagi, Yoshihito; Uchimura, Daisuke; Miyazaki, Toru; Ohashi, Wataru; Takamoto, Shigeru

2015-08-01

Hemolytic disease of the newborn (HDN) arising from MNSs incompatibility is rare, with few reports of prolonged anemia and reticulocytopenia following HDN. We report the younger of 2 male siblings, both of whom had anti-M-induced HDN and anemia persisting for over a month. Peripheral reticulocytes remained inappropriately low for the degree of anemia, and they needed multiple red cell transfusions. Viral infections were ruled out. Corticosteroids were given for suspected pure red cell aplasia. Anemia and reticulocytopenia subsequently improved. Colony-forming unit erythroid assay revealed erythropoietic suppression of M antigen-positive erythroid precursor cells cultured with maternal or infant sera containing anti-M. In conclusion, maternal anti-M caused HDN and prolonged anemia by erythropoietic suppression in 2 siblings.

Atomic Force Microscopy of Photosystem II and Its Unit Cell Clustering Quantitatively Delineate the Mesoscale Variability in Arabidopsis Thylakoids

PubMed Central

Onoa, Bibiana; Schneider, Anna R.; Brooks, Matthew D.; Grob, Patricia; Nogales, Eva; Geissler, Phillip L.; Niyogi, Krishna K.; Bustamante, Carlos

2014-01-01

Photoautotrophic organisms efficiently regulate absorption of light energy to sustain photochemistry while promoting photoprotection. Photoprotection is achieved in part by triggering a series of dissipative processes termed non-photochemical quenching (NPQ), which depend on the re-organization of photosystem (PS) II supercomplexes in thylakoid membranes. Using atomic force microscopy, we characterized the structural attributes of grana thylakoids from Arabidopsis thaliana to correlate differences in PSII organization with the role of SOQ1, a recently discovered thylakoid protein that prevents formation of a slowly reversible NPQ state. We developed a statistical image analysis suite to discriminate disordered from crystalline particles and classify crystalline arrays according to their unit cell properties. Through detailed analysis of the local organization of PSII supercomplexes in ordered and disordered phases, we found evidence that interactions among light-harvesting antenna complexes are weakened in the absence of SOQ1, inducing protein rearrangements that favor larger separations between PSII complexes in the majority (disordered) phase and reshaping the PSII crystallization landscape. The features we observe are distinct from known protein rearrangements associated with NPQ, providing further support for a role of SOQ1 in a novel NPQ pathway. The particle clustering and unit cell methodology developed here is generalizable to multiple types of microscopy and will enable unbiased analysis and comparison of large data sets. PMID:25007326

Atomic Force Microscopy of Photosystem II and Its Unit Cell Clustering Quantitatively Delineate the Mesoscale Variability in Arabidopsis Thylakoids

DOE PAGES

Onoa, Bibiana; Schneider, Anna R.; Brooks, Matthew D.; ...

2014-07-09

Photoautotrophic organisms efficiently regulate absorption of light energy to sustain photochemistry while promoting photoprotection. Photoprotection is achieved in part by triggering a series of dissipative processes termed non-photochemical quenching (NPQ), which depend on the re-organization of photosystem (PS) II supercomplexes in thylakoid membranes. Using atomic force microscopy, we characterized the structural attributes of grana thylakoids from Arabidopsis thaliana to correlate differences in PSII organization with the role of SOQ1, a recently discovered thylakoid protein that prevents formation of a slowly reversible NPQ state. We developed a statistical image analysis suite to discriminate disordered from crystalline particles and classify crystalline arraysmore » according to their unit cell properties. Through detailed analysis of the local organization of PSII supercomplexes in ordered and disordered phases, we found evidence that interactions among light-harvesting antenna complexes are weakened in the absence of SOQ1, inducing protein rearrangements that favor larger separations between PSII complexes in the majority (disordered) phase and reshaping the PSII crystallization landscape. The features we observe are distinct from known protein rearrangements associated with NPQ, providing further support for a role of SOQ1 in a novel NPQ pathway. The particle clustering and unit cell methodology developed here is generalizable to multiple types of microscopy and will enable unbiased analysis and comparison of large data sets.« less

Recent advances in multiple myeloma.

PubMed

Sjak-Shie, N N; Vescio, R A; Berenson, J R

2000-07-01

Multiple myeloma is the second most common hematologic malignancy, with approximately 15,000 new cases each year in the United States. Our understanding of the pathophysiology underlying myeloma continues to expand, but the cause of this plasma cell dyscrasia remains unclear. Though controversy remains regarding a possible viral cause of myeloma, evidence suggesting a role for the human herpesvirus-8 is mounting. The roles of cytogenetic abnormalities as well as aberrant angiogenesis and cytokine expression in the etiology of myeloma continue to be explored and may lead to future therapeutic strategies. Transplantation in myeloma is rarely curative but offers clinical benefit not only for young but possibly for older myeloma patients as well. Newer bisphosphonates may offer greater ease of administration, improved efficacy, and possibly even enhanced antitumor effect. Finally, thalidomide offers significant clinical benefit to patients with myeloma previously refractory to multiple agents, and its role in early stages of the disease is under investigation.

Oxidative stress in severe pulmonary trauma in critical ill patients. Antioxidant therapy in patients with multiple trauma--a review.

PubMed

Bedreag, Ovidiu Horea; Rogobete, Alexandru Florin; Sarandan, Mirela; Cradigati, Alina Carmen; Papurica, Marius; Dumbuleu, Maria Corina; Chira, Alexandru Mihai; Rosu, Oana Maria; Sandesc, Dorel

2015-01-01

Multiple trauma patients require extremely good management and thus, the trauma team needs to be prepared and to be up to date with the new standards of intensive therapy. Oxidative stress and free radicals represent an extremely aggressive factor to cells, having a direct consequence upon the severity of lung inflammation. Pulmonary tissue is damaged by oxidative stress, leading to biosynthesis of mediators that exacerbate inflammation modulators. The subsequent inflammation spreads throughout the body, leading most of the time to multiple organ dysfunction and death. In this paper, we briefly present an update of biochemical effects of oxidative stress and free radical damage to the pulmonary tissue in patients in critical condition in the intensive care unit. Also, we would like to present a series of active substances that substantially reduce the aggressiveness of free radicals, increasing the chances of survival.

Extraordinary electromagnetic transmission by antenna arrays and frequency selective surfaces having compound unit cells with dissimilar elements

DOEpatents

Loui, Hung; Strassner, II, Bernd H.

2018-03-20

The various embodiments presented herein relate to extraordinary electromagnetic transmission (EEMT) to enable multiple inefficient (un-matched) but coupled radiators and/or apertures to radiate and/or pass electromagnetic waves efficiently. EEMT can be utilized such that signal transmission from a plurality of antennas and/or apertures occurs at a transmission frequency different to transmission frequencies of the individual antennas and/or aperture elements. The plurality of antennas/apertures can comprise first antenna/aperture having a first radiating area and material(s) and second antenna/aperture having a second radiating area and material(s), whereby the first radiating/aperture area and second radiating/aperture area can be co-located in a periodic compound unit cell. Owing to mutual coupling between the respective antennas/apertures in their arrayed configuration, the transmission frequency of the array can be shifted from the transmission frequencies of the individual elements. EEMT can be utilized for an array of evanescent of inefficient radiators connected to a transmission line(s).

Delivery of adipose-derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration.

PubMed

Allbright, Kassandra O; Bliley, Jacqueline M; Havis, Emmanuelle; Kim, Deok-Yeol; Dibernardo, Gabriella A; Grybowski, Damian; Waldner, Matthias; James, Isaac B; Sivak, Wesley N; Rubin, J Peter; Marra, Kacey G

2018-02-06

Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

Pluggable microbial fuel cell stacks for septic wastewater treatment and electricity production.

PubMed

Yazdi, Hadi; Alzate-Gaviria, Liliana; Ren, Zhiyong Jason

2015-03-01

Septic tanks and other decentralized wastewater treatment systems play an important role in protecting public health and water resource for remote or developing communities. Current septic systems do not have energy production capability, yet such feature can be very valuable for areas lack access to electricity. Here we present an easy-to-operate microbial fuel cell (MFC) stack that consists a common base and multiple pluggable units, which can be connected in either series or parallel for electricity generation during waste treatment in septic tanks. Lab studies showed such easy configuration obtained a power density of 142±6.71mWm(-2) when 3 units are connected in parallel, and preliminary calculation indicates that a system that costs approximately US $25 can power a 6-watt LED light for 4h per day with great improvement potential. Detailed electrochemical characterizations provide insights on system internal loss and technology advancement needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Utility of Thin-Film Solar Cells on Flexible Substrates for Space Power

NASA Technical Reports Server (NTRS)

Dickman, J. E.; Hepp, A. F.; Morel, D. L.; Ferekides, C. S.; Tuttle, J. R.; Hoffman, D. J.; Dhere, N. G.

2004-01-01

The thin-film solar cell program at NASA GRC is developing solar cell technologies for space applications which address two critical metrics: specific power (power per unit mass) and launch stowed volume. To be competitive for many space applications, an array using thin film solar cells must significantly increase specific power while reducing stowed volume when compared to the present baseline technology utilizing crystalline solar cells. The NASA GRC program is developing two approaches. Since the vast majority of the mass of a thin film solar cell is in the substrate, a thin film solar cell on a very lightweight flexible substrate (polymer or metal films) is being developed as the first approach. The second approach is the development of multijunction thin film solar cells. Total cell efficiency can be increased by stacking multiple cells having bandgaps tuned to convert the spectrum passing through the upper cells to the lower cells. Once developed, the two approaches will be merged to yield a multijunction, thin film solar cell on a very lightweight, flexible substrate. The ultimate utility of such solar cells in space require the development of monolithic interconnections, lightweight array structures, and ultra-lightweight support and deployment techniques.

Structural convergence properties of amorphous InGaZnO4 from simulated liquid-quench methods.

PubMed

Buchanan, Jacob C; Fast, Dylan B; Hanken, Benjamin E; Mustard, Thomas J L; Laurita, Geneva; Chiang, Tsung-Han; Keszler, Douglas A; Subramanian, Mas A; Wager, John F; Dolgos, Michelle R; Rustad, James R; Cheong, Paul Ha-Yeon

2017-11-14

The study of structural properties of amorphous structures is complicated by the lack of long-range order and necessitates the use of both cutting-edge computer modeling and experimental techniques. With regards to the computer modeling, many questions on convergence arise when trying to assess the accuracy of a simulated system. What cell size maximizes the accuracy while remaining computationally efficient? More importantly, does averaging multiple smaller cells adequately describe features found in bulk amorphous materials? How small is too small? The aims of this work are: (1) to report a newly developed set of pair potentials for InGaZnO 4 and (2) to explore the effects of structural parameters such as simulation cell size and numbers on the structural convergence of amorphous InGaZnO 4 . The total number of formula units considered over all runs is found to be the critical factor in convergence as long as the cell considered contains a minimum of circa fifteen formula units. There is qualitative agreement between these simulations and X-ray total scattering data - peak trends and locations are consistently reproduced while intensities are weaker. These new IGZO pair potentials are a valuable starting point for future structural refinement efforts.

Models of utricular bouton afferents: role of afferent-hair cell connectivity in determining spike train regularity.

PubMed

Holmes, William R; Huwe, Janice A; Williams, Barbara; Rowe, Michael H; Peterson, Ellengene H

2017-05-01

Vestibular bouton afferent terminals in turtle utricle can be categorized into four types depending on their location and terminal arbor structure: lateral extrastriolar (LES), striolar, juxtastriolar, and medial extrastriolar (MES). The terminal arbors of these afferents differ in surface area, total length, collecting area, number of boutons, number of bouton contacts per hair cell, and axon diameter (Huwe JA, Logan CJ, Williams B, Rowe MH, Peterson EH. J Neurophysiol 113: 2420-2433, 2015). To understand how differences in terminal morphology and the resulting hair cell inputs might affect afferent response properties, we modeled representative afferents from each region, using reconstructed bouton afferents. Collecting area and hair cell density were used to estimate hair cell-to-afferent convergence. Nonmorphological features were held constant to isolate effects of afferent structure and connectivity. The models suggest that all four bouton afferent types are electrotonically compact and that excitatory postsynaptic potentials are two to four times larger in MES afferents than in other afferents, making MES afferents more responsive to low input levels. The models also predict that MES and LES terminal structures permit higher spontaneous firing rates than those in striola and juxtastriola. We found that differences in spike train regularity are not a consequence of differences in peripheral terminal structure, per se, but that a higher proportion of multiple contacts between afferents and individual hair cells increases afferent firing irregularity. The prediction that afferents having primarily one bouton contact per hair cell will fire more regularly than afferents making multiple bouton contacts per hair cell has implications for spike train regularity in dimorphic and calyx afferents. NEW & NOTEWORTHY Bouton afferents in different regions of turtle utricle have very different morphologies and afferent-hair cell connectivities. Highly detailed computational modeling provides insights into how morphology impacts excitability and also reveals a new explanation for spike train irregularity based on relative numbers of multiple bouton contacts per hair cell. This mechanism is independent of other proposed mechanisms for spike train irregularity based on ionic conductances and can explain irregularity in dimorphic units and calyx endings. Copyright © 2017 the American Physiological Society.

Hetero-cellular prototyping by synchronized multi-material bioprinting for rotary cell culture system.

PubMed

Snyder, Jessica; Son, Ae Rin; Hamid, Qudus; Wu, Honglu; Sun, Wei

2016-01-13

Bottom-up tissue engineering requires methodological progress of biofabrication to capture key design facets of anatomical arrangements across micro, meso and macro-scales. The diffusive mass transfer properties necessary to elicit stability and functionality require hetero-typic contact, cell-to-cell signaling and uniform nutrient diffusion. Bioprinting techniques successfully build mathematically defined porous architecture to diminish resistance to mass transfer. Current limitations of bioprinted cell assemblies include poor micro-scale formability of cell-laden soft gels and asymmetrical macro-scale diffusion through 3D volumes. The objective of this work is to engineer a synchronized multi-material bioprinter (SMMB) system which improves the resolution and expands the capability of existing bioprinting systems by packaging multiple cell types in heterotypic arrays prior to deposition. This unit cell approach to arranging multiple cell-laden solutions is integrated with a motion system to print heterogeneous filaments as tissue engineered scaffolds and nanoliter droplets. The set of SMMB process parameters control the geometric arrangement of the combined flow's internal features and constituent material's volume fractions. SMMB printed hepatocyte-endothelial laden 200 nl droplets are cultured in a rotary cell culture system (RCCS) to study the effect of microgravity on an in vitro model of the human hepatic lobule. RCCS conditioning for 48 h increased hepatocyte cytoplasm diameter 2 μm, increased metabolic rate, and decreased drug half-life. SMMB hetero-cellular models present a 10-fold increase in metabolic rate, compared to SMMB mono-culture models. Improved bioprinting resolution due to process control of cell-laden matrix packaging as well as nanoliter droplet printing capability identify SMMB as a viable technique to improve in vitro model efficacy.

An emerging treatment option for glaucoma: Rho kinase inhibitors

PubMed Central

Wang, Sean K; Chang, Robert T

2014-01-01

Rho kinase (ROCK) inhibitors are a novel potential class of glaucoma therapeutics with multiple compounds currently in Phase II and III US Food and Drug Administration trials in the United States. These selective agents work by relaxing the trabecular meshwork through inhibition of the actin cytoskeleton contractile tone of smooth muscle. This results in increased aqueous outflow directly through the trabecular meshwork, achieving lower intraocular pressures in a range similar to prostaglandins. There are also animal studies indicating that ROCK inhibitors may improve blood flow to the optic nerve, increase ganglion cell survival, and reduce bleb scarring in glaucoma surgery. Given the multiple beneficial effects for glaucoma patients, ROCK inhibitors are certainly a highly anticipated emerging treatment option for glaucoma. PMID:24872673

Threshold units: A correct metric for reaction time?

PubMed Central

Zele, Andrew J.; Cao, Dingcai; Pokorny, Joel

2007-01-01

Purpose To compare reaction time (RT) to rod incremental and decremental stimuli expressed in physical contrast units or psychophysical threshold units. Methods Rod contrast detection thresholds and suprathreshold RTs were measured for Rapid-On and Rapid-Off ramp stimuli. Results Threshold sensitivity to Rapid-Off stimuli was higher than to Rapid-On stimuli. Suprathreshold RTs specified in Weber contrast for Rapid-Off stimuli were shorter than for Rapid-On stimuli. Reaction time data expressed in multiples of threshold reversed the outcomes: Reaction times for Rapid-On stimuli were shorter than those for Rapid-Off stimuli. The use of alternative contrast metrics also failed to equate RTs. Conclusions A case is made that the interpretation of RT data may be confounded when expressed in threshold units. Stimulus energy or contrast is the only metric common to the response characteristics of the cells underlying speeded responses. The use of threshold metrics for RT can confuse the interpretation of an underlying physiological process. PMID:17240416

Accumulation of Human-Adapting Mutations during Circulation of A(H1N1)pdm09 Influenza Virus in Humans in the United Kingdom

PubMed Central

Elderfield, Ruth A.; Watson, Simon J.; Godlee, Alexandra; Adamson, Walt E.; Thompson, Catherine I.; Dunning, Jake; Fernandez-Alonso, Mirian; Blumenkrantz, Deena; Hussell, Tracy; Zambon, Maria; Openshaw, Peter; Kellam, Paul

2014-01-01

ABSTRACT The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to α-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves. IMPORTANCE Although most people infected with the 2009 pandemic influenza virus had mild or unapparent symptoms, some suffered severe and devastating disease. The reasons for this variability were unknown, but the numbers of severe cases increased during successive waves of human infection in the United Kingdom. To determine the causes of this variation, we studied genetic changes in virus isolates from individual hospitalized patients. There were no consistent differences between these viruses and those circulating in the community, but we found multiple evolutionary changes that in combination over time increased the virus's ability to infect human cells. These adaptations may explain the remarkable ability of A(H1N1)pdm09 virus to continue to circulate despite widespread immunity and the apparent increase in severity of influenza over successive waves of infection. PMID:25210166

Accumulation of human-adapting mutations during circulation of A(H1N1)pdm09 influenza virus in humans in the United Kingdom.

PubMed

Elderfield, Ruth A; Watson, Simon J; Godlee, Alexandra; Adamson, Walt E; Thompson, Catherine I; Dunning, Jake; Fernandez-Alonso, Mirian; Blumenkrantz, Deena; Hussell, Tracy; Zambon, Maria; Openshaw, Peter; Kellam, Paul; Barclay, Wendy S

2014-11-01

The influenza pandemic that emerged in 2009 provided an unprecedented opportunity to study adaptation of a virus recently acquired from an animal source during human transmission. In the United Kingdom, the novel virus spread in three temporally distinct waves between 2009 and 2011. Phylogenetic analysis of complete viral genomes showed that mutations accumulated over time. Second- and third-wave viruses replicated more rapidly in human airway epithelial (HAE) cells than did the first-wave virus. In infected mice, weight loss varied between viral isolates from the same wave but showed no distinct pattern with wave and did not correlate with viral load in the mouse lungs or severity of disease in the human donor. However, second- and third-wave viruses induced less alpha interferon in the infected mouse lungs. NS1 protein, an interferon antagonist, had accumulated several mutations in second- and third-wave viruses. Recombinant viruses with the third-wave NS gene induced less interferon in human cells, but this alone did not account for increased virus fitness in HAE cells. Mutations in HA and NA genes in third-wave viruses caused increased binding to α-2,6-sialic acid and enhanced infectivity in human mucus. A recombinant virus with these two segments replicated more efficiently in HAE cells. A mutation in PA (N321K) enhanced polymerase activity of third-wave viruses and also provided a replicative advantage in HAE cells. Therefore, multiple mutations allowed incremental changes in viral fitness, which together may have contributed to the apparent increase in severity of A(H1N1)pdm09 influenza virus during successive waves. Although most people infected with the 2009 pandemic influenza virus had mild or unapparent symptoms, some suffered severe and devastating disease. The reasons for this variability were unknown, but the numbers of severe cases increased during successive waves of human infection in the United Kingdom. To determine the causes of this variation, we studied genetic changes in virus isolates from individual hospitalized patients. There were no consistent differences between these viruses and those circulating in the community, but we found multiple evolutionary changes that in combination over time increased the virus's ability to infect human cells. These adaptations may explain the remarkable ability of A(H1N1)pdm09 virus to continue to circulate despite widespread immunity and the apparent increase in severity of influenza over successive waves of infection. Copyright © 2014 Elderfield et al.

Comparative analysis of quantitative methodologies for Vibrionaceae biofilms.

PubMed

Chavez-Dozal, Alba A; Nourabadi, Neda; Erken, Martina; McDougald, Diane; Nishiguchi, Michele K

2016-11-01

Multiple symbiotic and free-living Vibrio spp. grow as a form of microbial community known as a biofilm. In the laboratory, methods to quantify Vibrio biofilm mass include crystal violet staining, direct colony-forming unit (CFU) counting, dry biofilm cell mass measurement, and observation of development of wrinkled colonies. Another approach for bacterial biofilms also involves the use of tetrazolium (XTT) assays (used widely in studies of fungi) that are an appropriate measure of metabolic activity and vitality of cells within the biofilm matrix. This study systematically tested five techniques, among which the XTT assay and wrinkled colony measurement provided the most reproducible, accurate, and efficient methods for the quantitative estimation of Vibrionaceae biofilms.

Passive dendrites enable single neurons to compute linearly non-separable functions.

PubMed

Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

2013-01-01

Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non-separable functions.

Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions

PubMed Central

Cazé, Romain Daniel; Humphries, Mark; Gutkin, Boris

2013-01-01

Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites, the so-called dendritic spikes, results in independent spiking dendritic sub-units, which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions, such as the exclusive OR. Other neuron classes, such as interneurons, may possess only a few independent dendritic sub-units, or only passive dendrites where input summation is purely sub-linear, and where dendritic sub-units are only saturating. To determine if such neurons can also compute linearly non-separable functions, we enumerate, for a given parameter range, the Boolean functions implementable by a binary neuron model with a linear sub-unit and either a single spiking or a saturating dendritic sub-unit. We then analytically generalize these numerical results to an arbitrary number of non-linear sub-units. First, we show that a single non-linear dendritic sub-unit, in addition to the somatic non-linearity, is sufficient to compute linearly non-separable functions. Second, we analytically prove that, with a sufficient number of saturating dendritic sub-units, a neuron can compute all functions computable with purely excitatory inputs. Third, we show that these linearly non-separable functions can be implemented with at least two strategies: one where a dendritic sub-unit is sufficient to trigger a somatic spike; another where somatic spiking requires the cooperation of multiple dendritic sub-units. We formally prove that implementing the latter architecture is possible with both types of dendritic sub-units whereas the former is only possible with spiking dendrites. Finally, we show how linearly non-separable functions can be computed by a generic two-compartment biophysical model and a realistic neuron model of the cerebellar stellate cell interneuron. Taken together our results demonstrate that passive dendrites are sufficient to enable neurons to compute linearly non-separable functions. PMID:23468600

Acute adaptation of the vestibuloocular reflex: signal processing by floccular and ventral parafloccular Purkinje cells.

PubMed

Hirata, Y; Highstein, S M

2001-05-01

The gain of the vertical vestibuloocular reflex (VVOR), defined as eye velocity/head velocity was adapted in squirrel monkeys by employing visual-vestibular mismatch stimuli. VVOR gain, measured in the dark, could be trained to values between 0.4 and 1.5. Single-unit activity of vertical zone Purkinje cells was recorded from the flocculus and ventral paraflocculus in alert squirrel monkeys before and during the gain change training. Our goal was to evaluate the site(s) of learning of the gain change. To aid in the evaluation, a model of the vertical optokinetic reflex (VOKR) and VVOR was constructed consisting of floccular and nonfloccular systems divided into subsystems based on the known anatomy and input and output parameters. Three kinds of input to floccular Purkinje cells via mossy fibers were explicitly described, namely vestibular, visual (retinal slip), and efference copy of eye movement. The characteristics of each subsystem (gain and phase) were identified at different VOR gains by reconstructing single-unit activity of Purkinje cells during VOKR and VVOR with multiple linear regression models consisting of sensory input and motor output signals. Model adequacy was checked by evaluating the residual following the regressions and by predicting Purkinje cells' activity during visual-vestibular mismatch paradigms. As a result, parallel changes in identified characteristics with VVOR adaptation were found in the prefloccular/floccular subsystem that conveys vestibular signals and in the nonfloccular subsystem that conveys vestibular signals, while no change was found in other subsystems, namely prefloccular/floccular subsystems conveying efference copy or visual signals, nonfloccular subsystem conveying visual signals, and postfloccular subsystem transforming Purkinje cell activity to eye movements. The result suggests multiple sites for VVOR motor learning including both flocculus and nonflocculus pathways. The gain change in the nonfloccular vestibular subsystem was in the correct direction to cause VOR gain adaptation while the change in the prefloccular/floccular vestibular subsystem was incorrect (anti-compensatory). This apparent incorrect directional change might serve to prevent instability of the VOR caused by positive feedback via the efference copy pathway.

Multiple chiral topological states in liquid crystals from unstructured light beams

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

Loussert, Charles; Brasselet, Etienne, E-mail: e.brasselet@loma.u-bordeaux1.fr

2014-02-03

It is shown experimentally that unstructured light beams can generate a wealth of distinct metastable defect structures in thin films of chiral liquid crystals. Various kinds of individual chiral topological states are obtained as well as dimers and trimers, which correspond to the entanglement of several topological unit cells. Self-assembled nested assemblies of several metastable particle-like topological states can also be formed. Finally, we propose and experimentally demonstrate an opto-electrical approach to generate tailor-made architectures.

Elicitors and defense gene induction in plants with altered lignin compositions.

PubMed

Gallego-Giraldo, Lina; Posé, Sara; Pattathil, Sivakumar; Peralta, Angelo Gabriel; Hahn, Michael G; Ayre, Brian G; Sunuwar, Janak; Hernandez, Jonathan; Patel, Monika; Shah, Jyoti; Rao, Xiaolan; Knox, J Paul; Dixon, Richard A

2018-06-27

A reduction in the lignin content in transgenic plants induces the ectopic expression of defense genes, but the importance of altered lignin composition in such phenomena remains unclear. Two Arabidopsis lines with similar lignin contents, but strikingly different lignin compositions, exhibited different quantitative and qualitative transcriptional responses. Plants with lignin composed primarily of guaiacyl units overexpressed genes responsive to oomycete and bacterial pathogen attack, whereas plants with lignin composed primarily of syringyl units expressed a far greater number of defense genes, including some associated with cis-jasmone-mediated responses to aphids; these plants exhibited altered responsiveness to bacterial and aphid inoculation. Several of the defense genes were differentially induced by water-soluble extracts from cell walls of plants of the two lines. Glycome profiling, fractionation and enzymatic digestion studies indicated that the different lignin compositions led to differential extractability of a range of heterogeneous oligosaccharide epitopes, with elicitor activity originating from different cell wall polymers. Alteration of lignin composition affects interactions with plant cell wall matrix polysaccharides to alter the sequestration of multiple latent defense signal molecules with an impact on biotic stress responses. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

In vivo imaging of the dynamics of different variants of EGFR in glioblastomas.

PubMed

Shah, Khalid

2011-01-01

A number of altered pathways in cancer cells depend on growth factor receptors. The amplification/alteration of the epidermal growth factor receptor (EGFR) has been shown to play a significant role in enhancing tumor burden in a number of tumors, including malignant glioblastomas (GBM). To dissect the role of EGFR expression in tumor progression in mouse models of cancer and ultimately evaluate targeted therapies, it is necessary to visualize the dynamics of EGFR in real time in vivo. Non-invasive imaging based on quantitative and qualitative changes in light emission by fluorescent and bioluminescent markers offers a huge potential to facilitate drug development. Multiple approaches could be used to follow a molecular target or pathway with the fusion of a bioluminescent-fluorescent marker. This unit describes a protocol for simultaneously imaging EGFR activity and progression of GBM in a mouse model. Human glioma cells transduced with lentiviral vectors bearing different combinations of fluorescent and bioluminescent proteins either fused to EGFR or expressed alone can be grown as monolayers and maintained over several passages. The unit begins with a method for transducing glioma cells with lentiviral vectors for stable expression of these fluorescent and bioluminescent markers in vitro, followed by transplantation of engineered glioma cells in mice, and, finally, sequential bioluminescent imaging of EGFR expression and GBM progression in mice. The protocol details characterization of engineered glioma cells in culture, surgical preparation, craniotomy, cell implantation, animal recovery, and imaging procedures to study kinetics of EGFR expression and GBM progression.

JPIC-Rad-Hard JPEG2000 Image Compression ASIC

NASA Astrophysics Data System (ADS)

Zervas, Nikos; Ginosar, Ran; Broyde, Amitai; Alon, Dov

2010-08-01

JPIC is a rad-hard high-performance image compression ASIC for the aerospace market. JPIC implements tier 1 of the ISO/IEC 15444-1 JPEG2000 (a.k.a. J2K) image compression standard [1] as well as the post compression rate-distortion algorithm, which is part of tier 2 coding. A modular architecture enables employing a single JPIC or multiple coordinated JPIC units. JPIC is designed to support wide data sources of imager in optical, panchromatic and multi-spectral space and airborne sensors. JPIC has been developed as a collaboration of Alma Technologies S.A. (Greece), MBT/IAI Ltd (Israel) and Ramon Chips Ltd (Israel). MBT IAI defined the system architecture requirements and interfaces, The JPEG2K-E IP core from Alma implements the compression algorithm [2]. Ramon Chips adds SERDES interfaces and host interfaces and integrates the ASIC. MBT has demonstrated the full chip on an FPGA board and created system boards employing multiple JPIC units. The ASIC implementation, based on Ramon Chips' 180nm CMOS RadSafe[TM] RH cell library enables superior radiation hardness.

Developing Novel Oncolytic Adenoviruses through Bioselection

PubMed Central

Yan, Wen; Kitzes, Galila; Dormishian, Farid; Hawkins, Lynda; Sampson-Johannes, Adam; Watanabe, Josh; Holt, Jenny; Lee, Vivian; Dubensky, Thomas; Fattaey, Ali; Hermiston, Terry; Balmain, Allan; Shen, Yuqiao

2003-01-01

Mutants of human adenovirus 5 (Ad5) with enhanced oncolytic activity were isolated by using a procedure termed bioselection. Two mutants, ONYX-201 and ONYX-203, were plaque purified from a pool of randomly mutagenized Ad5 that was repeatedly passaged in the human colorectal cancer cell line HT29, and they were subsequently characterized. ONYX-201 and ONYX-203 replicated more rapidly in HT29 cells than wild-type Ad5, and they lysed HT29 cells up to 1,000-fold more efficiently. The difference was most profound when cells were infected at a relatively low multiplicity of infection, presumably due to the compounding effects of multiple rounds of infection. This enhanced cytolytic activity was observed not only in HT29 cells but also in many other human cancer cell lines tested. In contrast, the cytotoxicity of the bioselected mutants in a number of normal primary human cells was similar to that of wild-type Ad5, thus enhancing the therapeutic index (cytotoxicity in tumor cells versus that in normal cells) of these oncolytic agents. Both ONYX-201 and -203 contain seven single-base-pair mutations when compared with Ad5, four of which were common between ONYX-201 and -203. The mutation at nucleotide 8350, shared by both mutant viruses, was shown to be essential for the observed phenotypes. This mutation was mapped to the i-leader region of the major late transcription unit, resulting in the truncation of 21 amino acids from the C terminus of the i-leader protein. This work demonstrates that bioselection is a powerful tool for developing novel tumor-selective oncolytic viruses. Other potential applications of this technology are discussed. PMID:12552003

One-Carbon Metabolism in Health and Disease

PubMed Central

Ducker, Gregory S.; Rabinowitz, Joshua D.

2017-01-01

One-carbon (1C) metabolism, mediated by the folate cofactor, supports multiple physiological processes. These include biosynthesis (purines and thymidine), amino acid homeostasis (glycine, serine, and methionine), epigenetic maintenance, and redox defense. Both within eukaryotic cells and across organs, 1C metabolic reactions are compartmentalized. Here we review the fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states. Emphasis is given to recent discoveries enabled by modern genetics, analytical chemistry, and isotope tracing. An emerging theme is the biological importance of mitochondrial 1C reactions, both for producing 1C units that are exported to the cytosol and for making additional products, including glycine and NADPH. Increased clarity regarding differential folate pathway usage in cancer, stem cells, development, and adult physiology is reviewed and highlights new opportunities for selective therapeutic intervention. PMID:27641100

Methods for the Detection of Autophagy in Mammalian Cells

PubMed Central

Zhang, Ziyan; Singh, Rajat; Aschner, Michael

2016-01-01

Macroautophagy (hereafter referred to as autophagy) is a degradation pathway that delivers cytoplasmic materials to lysosomes via double-membraned vesicles designated autophagosomes. Cytoplasmic constituents are sequestered into autophagosomes, which subsequently fuse with lysosomes, where the cargo is degraded. Autophagy is a crucial mechanism involved in many aspects of cell function, including cellular metabolism and energy balance; and alterations in autophagy have been linked to various human pathological processes. Thus, methods that accurately measure autophagic activity are necessary. In this unit, we introduce several approaches to analyze autophagy in mammalian cells, including immunoblotting analysis of LC3 and p62, detection of autophagosome formation by fluorescence microscopy, and monitoring autophagosome maturation by tandem mRFP-GFP fluorescence microscopy. Overall, we recommend a combined use of multiple methods to accurately assess the autophagic activity in any given biological setting. PMID:27479363

An Analysis of Blood Utilization for Stem Cell Transplant Patients in a Tertiary Care Hospital.

PubMed

Ali, Natasha

2017-05-30

Haematopoietic stem cell transplant is a potentially curative treatment option in various benign and malignant haematological diseases. Patients undergoing stem cell transplant procedure require blood transfusion on a daily basis. Currently, there is paucity of data from developing countries on transfusion practices. This audit was undertaken to determine the consumption of packed red blood cells (PRBCs) transfusion in the bone marrow transplant unit of the Aga Khan University Hospital. A retrospective audit was conducted for packed red cell transfusion ordering practice over a period from June 2014∼June 2015. All consecutive patients, admitted for stem cell transplant procedure for various underlying diseases were included. Outcome measures used in this study were (i) cross match to transfusion (C: T) ratio and (ii) transfusion trigger. During the study period, n=25 patients underwent haematopoietic stem cell transplant. There were n=19 males and n=6 females. One patient was less than 15 years of age while rests were adults. Median age±SD was 26.5±14.5 years (12∼54 years). The underlying diagnosis included Aplastic anemia (n=8), Thalassemia major (n=3), Multiple Myeloma (n=4), Acute leukemia (n=5), Hodgkin's lymphoma (n=4), PRCA (n=1). Grand total consumption of PRBCs during the study period was 204 while 258 products were crossmatch. The C:T ratio was 1.26. The transfusion trigger was Hb level of less than 8 gms/dl. The results of our BMT unit indicate that the C:T ratio and transfusion trigger is comparable to the international benchmark.

IMMUNOLOGIC MEMORY CELLS OF BONE MARROW ORIGIN

PubMed Central

Miller, Harold C.; Cudkowicz, Gustavo

1972-01-01

Individual immunocompetent precursor cells of (C57BL/10 x C3H)F1 mouse marrow generate, on transplantation, three to five times more antibody-forming cells localized in recipient spleens during secondary than during primary immune responses. The increased burst size is immunologically specific since antigens of horse and chicken erythrocytes and of Salmonella typhimurium do not cause this effect in marrow cells responsive to sheep red blood cells. Both sensitized and nonsensitized precursors require the helper function of thymus-derived cells and antigen for the final steps of differentiation and maturation. The burst size of primed precursor cells is the same after cooperative interactions with virgin or educated helper cells of thymic origin. The greater potential of these marrow precursors may be attributable to self-replication and migration before differentiation into antibody-forming descendants. In fact, the progeny cells of primed precursor units are distributed among a multiplicity of foci, whereas those of nonimmune precursors are clustered into one focus. The described properties of specifically primed marrow precursors are those underlying immunologic memory. It remains to be established whether memory cells are induced or selected by antigens and whether the thymus plays a role in this process. PMID:4553850

Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis.

PubMed

Planchon, Sarah M; Lingas, Karen T; Reese Koç, Jane; Hooper, Brittney M; Maitra, Basabi; Fox, Robert M; Imrey, Peter B; Drake, Kylie M; Aldred, Micheala A; Lazarus, Hillard M; Cohen, Jeffrey A

2018-01-01

Multiple sclerosis is an inflammatory, neurodegenerative disease of the central nervous system for which therapeutic mesenchymal stem cell transplantation is under study. Published experience of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical trials is limited. To determine the feasibility of culture-expanding multiple sclerosis patients' mesenchymal stem cells for clinical use. In a phase I trial, autologous, bone marrow-derived mesenchymal stem cells were isolated from 25 trial participants with multiple sclerosis and eight matched controls, and culture-expanded to a target single dose of 1-2 × 10 6 cells/kg. Viability, cell product identity and sterility were assessed prior to infusion. Cytogenetic stability was assessed by single nucleotide polymorphism analysis of mesenchymal stem cells from 18 multiple sclerosis patients and five controls. One patient failed screening. Mesenchymal stem cell culture expansion was successful for 24 of 25 multiple sclerosis patients and six of eight controls. The target dose was achieved in 16-62 days, requiring two to three cell passages. Growth rate and culture success did not correlate with demographic or multiple sclerosis disease characteristics. Cytogenetic studies identified changes on one chromosome of one control (4.3%) after extended time in culture. Culture expansion of mesenchymal stem cells from multiple sclerosis patients as donors is feasible. However, culture time should be minimized for cell products designated for therapeutic administration.

Co-immobilization of adhesive peptides and VEGF within a dextran-based coating for vascular applications.

PubMed

Noel, Samantha; Fortier, Charles; Murschel, Frederic; Belzil, Antoine; Gaudet, Guillaume; Jolicoeur, Mario; De Crescenzo, Gregory

2016-06-01

Multifunctional constructs providing a proper environment for adhesion and growth of selected cell types are needed for most tissue engineering and regenerative medicine applications. In this context, vinylsulfone (VS)-modified dextran was proposed as a matrix featuring low-fouling properties as well as multiple versatile moieties. The displayed VS groups could indeed react with thiol, amine or hydroxyl groups, be it for surface grafting, crosslinking or subsequent tethering of biomolecules. In the present study, a library of dextran-VS was produced, grafted to aminated substrates and characterized in terms of degree of VS modification (%VS), cell-repelling properties and potential for the oriented grafting of cysteine-tagged peptides. As a bioactive coating of vascular implants, ECM peptides (e.g. RGD) as well as vascular endothelial growth factor (VEGF) were co-immobilized on one of the most suitable dextran-VS coating (%VS=ca. 50% of saccharides units). Both RGD and VEGF were efficiently tethered at high densities (ca. 1nmol/cm(2) and 50fmol/cm(2), respectively), and were able to promote endothelial cell adhesion as well as proliferation. The latter was enhanced to the same extent as with soluble VEGF and proved selective to endothelial cells over smooth muscle cells. Altogether, multiple biomolecules could be efficiently incorporated into a dextran-VS construct, while maintaining their respective biological activity. This work addresses the need for multifunctional coatings and selective cell response inherent to many tissue engineering and regenerative medicine applications, for instance, vascular graft. More specifically, a library of dextrans was first generated through vinylsulfone (VS) modification. Thoroughly selected dextran-VS provided an ideal platform for unbiased study of cell response to covalently grafted biomolecules. Considering that processes such as healing and angiogenesis require multiple factors acting synergistically, vascular endothelial growth factor (VEGF) was then co-immobilized with the cell adhesive RGD peptide within our dextran coating through a relevant strategy featuring orientation and specificity. Altogether, both adhesive and proliferative cues could be incorporated into our construct with additive, if not synergetic, effects. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A general multiscale framework for the emergent effective elastodynamics of metamaterials

NASA Astrophysics Data System (ADS)

Sridhar, A.; Kouznetsova, V. G.; Geers, M. G. D.

2018-02-01

This paper presents a general multiscale framework towards the computation of the emergent effective elastodynamics of heterogeneous materials, to be applied for the analysis of acoustic metamaterials and phononic crystals. The generality of the framework is exemplified by two key characteristics. First, the underlying formalism relies on the Floquet-Bloch theorem to derive a robust definition of scales and scale separation. Second, unlike most homogenization approaches that rely on a classical volume average, a generalized homogenization operator is defined with respect to a family of particular projection functions. This yields a generalized macro-scale continuum, instead of the classical Cauchy continuum. This enables (in a micromorphic sense) to homogenize the rich dispersive behavior resulting from both Bragg scattering and local resonance. For an arbitrary unit cell, the homogenization projection functions are constructed using the Floquet-Bloch eigenvectors obtained in the desired frequency regime at select high symmetry points, which effectively resolves the emergent phenomena dominating that regime. Furthermore, a generalized Hill-Mandel condition is proposed that ensures power consistency between the homogenized and full-scale model. A high-order spatio-temporal gradient expansion is used to localize the multiscale problem leading to a series of recursive unit cell problems giving the appropriate micro-mechanical corrections. The developed multiscale method is validated against standard numerical Bloch analysis of the dispersion spectra of example unit cells encompassing multiple high-order branches generated by local resonance and/or Bragg scattering.

Space Station Biological Research Project (SSBRP) Cell Culture Unit (CCU) and incubator for International Space Station (ISS) cell culture experiments

NASA Technical Reports Server (NTRS)

Vandendriesche, Donald; Parrish, Joseph; Kirven-Brooks, Melissa; Fahlen, Thomas; Larenas, Patricia; Havens, Cindy; Nakamura, Gail; Sun, Liping; Krebs, Chris; de Luis, Javier;

Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model.

PubMed

Swift, Brenna E; Williams, Brent A; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A; Viswanathan, Sowmya; Martinez-Lopez, Joaquin; Keating, Armand

2012-07-01

Novel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. The cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. Three multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2- to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89-99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. This study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma tumor burden in a xenograft mouse model was reduced by intravenous NK-92 cell therapy. Since multiple myeloma colony frequency correlates with survival, our observations have important clinical implications and suggest that clinical studies of NK cell lines to treat MM are warranted.

Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

PubMed Central

Li, Xia; Rao, Shaoqi; Jiang, Wei; Li, Chuanxing; Xiao, Yun; Guo, Zheng; Zhang, Qingpu; Wang, Lihong; Du, Lei; Li, Jing; Li, Li; Zhang, Tianwen; Wang, Qing K

2006-01-01

Background It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. Results In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network) to address the underlying regulations of genes that can span any unit(s) of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. Conclusion We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex gene regulations related to the development, aging and progressive pathogenesis of a complex disease where potential dependences between different experiment units might occurs. PMID:16420705

Heterogeneity and Developmental Connections between Cell Types Inhabiting Teeth

PubMed Central

Krivanek, Jan; Adameyko, Igor; Fried, Kaj

2017-01-01

Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix–producing populations: ameloblasts generating enamel and odontoblasts producing dentin. However, the real picture is far from this quite simplified view. Diverse pulp cells, the immune system, the vascular system, the innervation and cells organizing the dental follicle all interact, and jointly participate in transforming lifeless matrix into a functional organ that can sense and protect itself. Here we outline the heterogeneity of cell types that inhabit the tooth, and also provide a life history of the major populations. The mouse model system has been indispensable not only for the studies of cell lineages and heterogeneity, but also for the investigation of dental stem cells and tooth patterning during development. Finally, we briefly discuss the evolutionary aspects of cell type diversity and dental tissue integration. PMID:28638345

Preparation of chitosan-based multifunctional nanocarriers overcoming multiple barriers for oral delivery of insulin.

PubMed

Li, Lei; Jiang, Guohua; Yu, Weijiang; Liu, Depeng; Chen, Hua; Liu, Yongkun; Tong, Zaizai; Kong, Xiangdong; Yao, Juming

2017-01-01

To overcome multiple barriers for oral delivery of insulin, the chitosan-based multifunctional nanocarriers modified by L-valine (LV, used as a target ligand to facilitate the absorption of the small intestine) and phenylboronic acid (PBA, used as a glucose-responsive unit) have been designed and evaluated in this study. The resultant nanocarriers exhibited low cytotoxicity against HT-29 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. The chemical stability of loaded insulin against digestive enzyme were established in presence of simulated gastric fluid (SGF) containing pepsin and simulated intestinal fluid (SIF) containing pancreatin, respectively. The uptake behavior of HT-29 cells was evaluated by confocal laser scanning microscope. After oral administration to the diabetic rats, an effective hypoglycemic effect was obtained compared with subcutaneous injection of insulin. This work suggests that L-valine modified chitosan-based multifunctional nanocarriers may be a promising drug delivery carrier for oral administration of insulin. Copyright © 2016 Elsevier B.V. All rights reserved.

Four crystal forms of a Bence-Jones protein

PubMed Central

Makino, Debora L.; Henschen-Edman, Agnes H.; McPherson, Alexander

2005-01-01

Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40 years ago. Closely related tetragonal and orthorhombic forms belonging to space groups P43212 and P212121, with unit-cell parameters a = b = 68.7, c = 182.1 and a = 67.7, b = 69.4, c = 87.3 Å, diffract to 1.5 and 1.9 Å, respectively. Two closely related trigonal forms, both belonging to space group P3121 with unit-cell parameters a = b = 154.3 Å but differing by a doubling of the c axis, one 46.9 Å and the other 94.0 Å, diffract to 2.9 and 2.6 Å resolution, respectively. The trigonal crystal of short c-axis length shows a positive indication of twinning. The trigonal crystal of longer c axis, which appeared only after eight months of incubation at room temperature, is likely to be composed of proteolytically degraded molecules and unlike the other crystal forms contains two entire Bence-Jones dimers in the asymmetric unit. This latter crystal form may shed some light on the formation of fibrils common to certain storage diseases. PMID:16508097

Distributed parallel messaging for multiprocessor systems

DOEpatents

Chen, Dong; Heidelberger, Philip; Salapura, Valentina; Senger, Robert M; Steinmacher-Burrow, Burhard; Sugawara, Yutaka

2013-06-04

A method and apparatus for distributed parallel messaging in a parallel computing system. The apparatus includes, at each node of a multiprocessor network, multiple injection messaging engine units and reception messaging engine units, each implementing a DMA engine and each supporting both multiple packet injection into and multiple reception from a network, in parallel. The reception side of the messaging unit (MU) includes a switch interface enabling writing of data of a packet received from the network to the memory system. The transmission side of the messaging unit, includes switch interface for reading from the memory system when injecting packets into the network.

Plasmonic Nanobubbles as Tunable Cellular Probes for Cancer Theranostics

PubMed Central

Lapotko, Dmitri

2011-01-01

This review is focused on a novel cellular probe, the plasmonic nanobubble (PNB), which has the dynamically tunable and multiple functions of imaging, diagnosis, delivery, therapy and, ultimately, theranostics. The concept of theranostics was recently introduced in order to unite the clinically important stages of treatment, namely diagnosis, therapy and therapy guidance, into one single, rapid and highly accurate procedure. Cell level theranostics will have far-reaching implications for the treatment of cancer and other diseases at their earliest stages. PNBs were developed to support cell level theranostics as a new generation of on-demand tunable cellular probes. A PNB is a transient vapor nanobubble that is generated within nanoseconds around an overheated plasmonic nanoparticle with a short laser pulse. In the short term, we expect that PNB technology will be rapidly adaptable to clinical medicine, where the single cell resolution it provides will be critical for diagnosing incipient or residual disease and eliminating cancer cells, while leaving healthy cells intact. This review discusses mechanisms of plasmonic nanobubbles and their biomedical applications with the focus on cancer cell theranostics. PMID:21442036

δ-Generalized Labeled Multi-Bernoulli Filter Using Amplitude Information of Neighboring Cells

PubMed Central

Liu, Chao; Lei, Peng; Qi, Yaolong

2018-01-01

The amplitude information (AI) of echoed signals plays an important role in radar target detection and tracking. A lot of research shows that the introduction of AI enables the tracking algorithm to distinguish targets from clutter better and then improves the performance of data association. The current AI-aided tracking algorithms only consider the signal amplitude in the range-azimuth cell where measurement exists. However, since radar echoes always contain backscattered signals from multiple cells, the useful information of neighboring cells would be lost if directly applying those existing methods. In order to solve this issue, a new δ-generalized labeled multi-Bernoulli (δ-GLMB) filter is proposed. It exploits the AI of radar echoes from neighboring cells to construct a united amplitude likelihood ratio, and then plugs it into the update process and the measurement-track assignment cost matrix of the δ-GLMB filter. Simulation results show that the proposed approach has better performance in target’s state and number estimation than that of the δ-GLMB only using single-cell AI in low signal-to-clutter-ratio (SCR) environment. PMID:29642595

Concise review: stem cell-based approaches to red blood cell production for transfusion.

PubMed

Shah, Siddharth; Huang, Xiaosong; Cheng, Linzhao

2014-03-01

Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply. Even in developed countries where the supply is currently adequate, projected demographics predict an insufficient supply as early as 2050. The blood supply is also strained during occasional widespread disasters and crises. Transfusion of blood components such as red blood cells (RBCs), platelets, or neutrophils is increasingly used from the same blood unit for multiple purposes and to reduce alloimmune responses. Even for RBCs and platelets lacking nuclei and many antigenic cell-surface molecules, alloimmunity could occur, especially in patients with chronic transfusion requirements. Once alloimmunization occurs, such patients require RBCs from donors with a different blood group antigen combination, making it a challenge to find donors after every successive episode of alloimmunization. Alternative blood substitutes such as synthetic oxygen carriers have so far proven unsuccessful. In this review, we focus on current research and technologies that permit RBC production ex vivo from hematopoietic stem cells, pluripotent stem cells, and immortalized erythroid precursors.

Ultra Wideband Polarization-Selective Conversions of Electromagnetic Waves by Metasurface under Large-Range Incident Angles.

PubMed

Yin, Jia Yuan; Wan, Xiang; Zhang, Qian; Cui, Tie Jun

2015-07-23

We propose an ultra-wideband polarization-conversion metasurface with polarization selective and incident-angle insensitive characteristics using anchor-shaped units through multiple resonances. The broadband characteristic is optimized by the genetic optimization algorithm, from which the anchor-shaped unit cell generates five resonances, resulting in expansion of the operating frequency range. Owing to the structural feature of the proposed metasurface, only x- and y-polarized incident waves can reach high-efficiency polarization conversions, realizing the polarization-selective property. The proposed metasurface is also insensitive to the angle of incident waves, which indicates a promising future in modern communication systems. We fabricate and measure the proposed metasurface, and both the simulated and measured results show ultra-wide bandwidth for the x- and y-polarized incident waves.

Ultra Wideband Polarization-Selective Conversions of Electromagnetic Waves by Metasurface under Large-Range Incident Angles

PubMed Central

Yin, Jia Yuan; Wan, Xiang; Zhang, Qian; Cui, Tie Jun

2015-01-01

We propose an ultra-wideband polarization-conversion metasurface with polarization selective and incident-angle insensitive characteristics using anchor-shaped units through multiple resonances. The broadband characteristic is optimized by the genetic optimization algorithm, from which the anchor-shaped unit cell generates five resonances, resulting in expansion of the operating frequency range. Owing to the structural feature of the proposed metasurface, only x- and y-polarized incident waves can reach high-efficiency polarization conversions, realizing the polarization-selective property. The proposed metasurface is also insensitive to the angle of incident waves, which indicates a promising future in modern communication systems. We fabricate and measure the proposed metasurface, and both the simulated and measured results show ultra-wide bandwidth for the x- and y-polarized incident waves. PMID:26202495

Preclinical studies in support of defibrotide for the treatment of multiple myeloma and other neoplasias.

PubMed

Mitsiades, Constantine S; Rouleau, Cecile; Echart, Cinara; Menon, Krishna; Teicher, Beverly; Distaso, Maria; Palumbo, Antonio; Boccadoro, Mario; Anderson, Kenneth C; Iacobelli, Massimo; Richardson, Paul G

2009-02-15

Defibrotide, an orally bioavailable polydisperse oligonucleotide, has promising activity in hepatic veno-occlusive disease, a stem cell transplantation-related toxicity characterized by microangiopathy. The antithrombotic properties of defibrotide and its minimal hemorrhagic risk could serve for treatment of cancer-associated thrombotic complications. Given its cytoprotective effect on endothelium, we investigated whether defibrotide protects tumor cells from cytotoxic antitumor agents. Further, given its antiadhesive properties, we evaluated whether defibrotide modulates the protection conferred to multiple myeloma cells by bone marrow stromal cells. Defibrotide lacks significant single-agent in vitro cytotoxicity on multiple myeloma or solid tumor cells and does not attenuate their in vitro response to dexamethasone, bortezomib, immunomodulatory thalidomide derivatives, and conventional chemotherapeutics, including melphalan and cyclophosphamide. Importantly, defibrotide enhances in vivo chemosensitivity of multiple myeloma and mammary carcinoma xenografts in animal models. In cocultures of multiple myeloma cells with bone marrow stromal cells in vitro, defibrotide enhances the multiple myeloma cell sensitivity to melphalan and dexamethasone, and decreases multiple myeloma-bone marrow stromal cell adhesion and its sequelae, including nuclear factor-kappaB activation in multiple myeloma and bone marrow stromal cells, and associated cytokine production. Moreover, defibrotide inhibits expression and/or function of key mediators of multiple myeloma interaction with bone marrow stromal cell and endothelium, including heparanase, angiogenic cytokines, and adhesion molecules. Defibrotide's in vivo chemosensitizing properties and lack of direct in vitro activity against tumor cells suggest that it favorably modulates antitumor interactions between bone marrow stromal cells and endothelia in the tumor microenvironment. These data support clinical studies of defibrotide in combination with conventional and novel therapies to potentially improve patient outcome in multiple myeloma and other malignancies.

The self-organization of grid cells in 3D

PubMed Central

Stella, Federico; Treves, Alessandro

2015-01-01

Do we expect periodic grid cells to emerge in bats, or perhaps dolphins, exploring a three-dimensional environment? How long will it take? Our self-organizing model, based on ring-rate adaptation, points at a complex answer. The mathematical analysis leads to asymptotic states resembling face centered cubic (FCC) and hexagonal close packed (HCP) crystal structures, which are calculated to be very close to each other in terms of cost function. The simulation of the full model, however, shows that the approach to such asymptotic states involves several sub-processes over distinct time scales. The smoothing of the initially irregular multiple fields of individual units and their arrangement into hexagonal grids over certain best planes are observed to occur relatively quickly, even in large 3D volumes. The correct mutual orientation of the planes, though, and the coordinated arrangement of different units, take a longer time, with the network showing no sign of convergence towards either a pure FCC or HCP ordering. DOI: http://dx.doi.org/10.7554/eLife.05913.001 PMID:25821989

Nucleated red blood cells in growth-restricted fetuses: associations with short-term neonatal outcome.

PubMed

Minior, V K; Bernstein, P S; Divon, M Y

2000-01-01

To determine the utility of the neonatal nucleated red blood cell (NRBC) count as an independent predictor of short-term perinatal outcome in growth-restricted fetuses. Hospital charts of neonates with a discharge diagnosis indicating a birth weight <10th percentile were reviewed for perinatal outcome. We studied all eligible neonates who had a complete blood count on the first day of life. After multiple gestations, anomalous fetuses and diabetic pregnancies were excluded; 73 neonates comprised the study group. Statistical analysis included ANOVA, simple and stepwise regression. Elevated NRBC counts were significantly associated with cesarean section for non-reassuring fetal status, neonatal intensive care unit admission and duration of neonatal intensive care unit stay, respiratory distress and intubation, thrombocytopenia, hyperbilirubinemia, intraventricular hemorrhage and neonatal death. Stepwise regression analysis including gestational age at birth, birth weight and NRBC count demonstrated that in growth-restricted fetuses, NRBC count was the strongest predictor of neonatal intraventricular hemorrhage, neonatal respiratory distress and neonatal death. An elevated NRBC count independently predicts adverse perinatal outcome in growth-restricted fetuses. Copyright 2000 S. Karger AG, Basel.

New edge-centered photonic square lattices with flat bands

NASA Astrophysics Data System (ADS)

Zhang, Da; Zhang, Yiqi; Zhong, Hua; Li, Changbiao; Zhang, Zhaoyang; Zhang, Yanpeng; Belić, Milivoj R.

2017-07-01

We report a new class of edge-centered photonic square lattices with multiple flat bands, and consider in detail two examples: the Lieb-5 and Lieb-7 lattices. In these lattices, there are 5 and 7 sites in the unit cell and in general, the number is restricted to odd integers. The number of flat bands m in the new Lieb lattices is related to the number of sites N in the unit cell by a simple formula m =(N - 1) / 2. The flat bands reported here are independent of the pseudomagnetic field. The properties of lattices with even and odd number of flat bands are different. We consider the localization of light in such Lieb lattices. If the input beam excites the flat-band mode, it will not diffract during propagation, owing to the strong mode localization. In the Lieb-7 lattice, the beam will also oscillate during propagation and still not diffract. The period of oscillation is determined by the energy difference between the two flat bands. This study provides a new platform for investigating light trapping, photonic topological insulators, and pseudospin-mediated vortex generation.

Cytoskeleton-centric protein transportation by exosomes transforms tumor-favorable macrophages.

PubMed

Chen, Zhipeng; Yang, Lijuan; Cui, Yizhi; Zhou, Yanlong; Yin, Xingfeng; Guo, Jiahui; Zhang, Gong; Wang, Tong; He, Qing-Yu

2016-10-11

The exosome is a key initiator of pre-metastatic niche in numerous cancers, where macrophages serve as primary inducers of tumor microenvironment. However, the proteome that can be exosomally transported from cancer cells to macrophages has not been sufficiently characterized so far. Here, we used colorectal cancer (CRC) exosomes to educate tumor-favorable macrophages. With a SILAC-based mass spectrometry strategy, we successfully traced the proteome transported from CRC exosomes to macrophages. Such a proteome primarily focused on promoting cytoskeleton rearrangement, which was biologically validated with multiple cell lines. We reproduced the exosomal transportation of functional vimentin as a proof-of-concept example. In addition, we found that some CRC exosomes could be recognized by macrophages via Fc receptors. Therefore, we revealed the active and necessary role of exosomes secreted from CRC cells to transform cancer-favorable macrophages, with the cytoskeleton-centric proteins serving as the top functional unit.

Design of the frame structure for a multiservice interactive system using ATM-PON

NASA Astrophysics Data System (ADS)

Nam, Jae-Hyun; Jang, Jongwook; Lee, Jung-Tae

1998-10-01

The MAC (Medium Access Control) protocol controls B-NT1s' (Optical Network Unit) access to the shared capacity on the PON, this protocol is very important if TDMA (Time Division Multiple Access) multiplexing is used on the upstream. To control the upstream traffic some kind of access protocol has to be implemented. There are roughly two different approaches to use request cells: in a collision free way or such that collisions in a request slot are allowed. It is the objective of this paper to describe a MAC-protocol structure that supports both approaches and hybrids of it. In our paper we grantee the QoS (Quality of Service) of each B-NT1 through LOC, LOV, LOA field that are the length field of the transmitted cell at each B-NT1. Each B-NT1 transmits its status of request on request cell.

Plasmonic and SERS performances of compound nanohole arrays fabricated by shadow sphere lithography

NASA Astrophysics Data System (ADS)

Skehan, Connor; Ai, Bin; Larson, Steven R.; Stone, Keenan M.; Dennis, William M.; Zhao, Yiping

2018-03-01

Several plasmonic compound nanohole arrays (CNAs), such as triangular nanoholes and fan-like nanoholes with multiple nanotips and nanogaps, are designed by a simple and efficient shadow sphere lithography technique by tuning the sphere mask size, the deposition and azimuthal angles, substrate temperature T S , and the number of deposition steps N. Compared with conventional circular nanohole arrays, the CNAs show more hot spots and exhibit new transmission speaks. Systematic finite-difference time-domain calculations indicate that different resonance modes excited by the various shaped and sized nanoholes are responsible for the enhanced plasmonic performances of CNAs. Compared to the CNA samples with only one circular hole in the unit cell, the Raman scattering intensity of the CNA with multiple triangular nanoholes, nanogaps, and nanotips can be enhanced up to 5-fold. These CNAs, due to the strong resonance due to the multiple structural features, are promising applications as optical filters, plasmonic sensors, and surface-enhanced spectroscopies.

Single-unit muscle sympathetic nervous activity and its relation to cardiac noradrenaline spillover

PubMed Central

Lambert, Elisabeth A; Schlaich, Markus P; Dawood, Tye; Sari, Carolina; Chopra, Reena; Barton, David A; Kaye, David M; Elam, Mikael; Esler, Murray D; Lambert, Gavin W

2011-01-01

Abstract Recent work using single-unit sympathetic nerve recording techniques has demonstrated aberrations in the firing pattern of sympathetic nerves in a variety of patient groups. We sought to examine whether nerve firing pattern is associated with increased noradrenaline release. Using single-unit muscle sympathetic nerve recording techniques coupled with direct cardiac catheterisation and noradrenaline isotope dilution methodology we examined the relationship between single-unit firing patterns and cardiac and whole body noradrenaline spillover to plasma. Participants comprised patients with hypertension (n = 6), depression (n = 7) and panic disorder (n = 9) who were drawn from our ongoing studies. The patient groups examined did not differ in their single-unit muscle sympathetic nerve firing characteristics nor in the rate of spillover of noradrenaline to plasma from the heart. The median incidence of multiple spikes per beat was 9%. Patients were stratified according to the firing pattern: low level of incidence (less than 9% incidence of multiple spikes per beat) and high level of incidence (greater than 9% incidence of multiple spikes per beat). High incidence of multiple spikes within a cardiac cycle was associated with higher firing rates (P < 0.0001) and increased probability of firing (P < 0.0001). Whole body noradrenaline spillover to plasma and (multi-unit) muscle sympathetic nerve activity in subjects with low incidence of multiple spikes was not different to that of those with high incidence of multiple spikes. In those with high incidence of multiple spikes there occurred a parallel activation of the sympathetic outflow to the heart, with cardiac noradrenaline spillover to plasma being two times that of subjects with low nerve firing rates (11.0 ± 1.5 vs. 22.0 ± 4.5 ng min−1, P < 0.05). This study indicates that multiple within-burst firing and increased single-unit firing rates of the sympathetic outflow to the skeletal muscle vasculature is associated with high cardiac noradrenaline spillover. PMID:21486790

Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model

PubMed Central

Swift, Brenna E.; Williams, Brent A.; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A.; Viswanathan, Sowmya; Martinez-Lopez, Joaquin; Keating, Armand

2012-01-01

Background Novel therapies capable of targeting drug resistant clonogenic MM cells are required for more effective treatment of multiple myeloma. This study investigates the cytotoxicity of natural killer cell lines against bulk and clonogenic multiple myeloma and evaluates the tumor burden after NK cell therapy in a bioluminescent xenograft mouse model. Design and Methods The cytotoxicity of natural killer cell lines was evaluated against bulk multiple myeloma cell lines using chromium release and flow cytometry cytotoxicity assays. Selected activating receptors on natural killer cells were blocked to determine their role in multiple myeloma recognition. Growth inhibition of clonogenic multiple myeloma cells was assessed in a methylcellulose clonogenic assay in combination with secondary replating to evaluate the self-renewal of residual progenitors after natural killer cell treatment. A bioluminescent mouse model was developed using the human U266 cell line transduced to express green fluorescent protein and luciferase (U266eGFPluc) to monitor disease progression in vivo and assess bone marrow engraftment after intravenous NK-92 cell therapy. Results Three multiple myeloma cell lines were sensitive to NK-92 and KHYG-1 cytotoxicity mediated by NKp30, NKp46, NKG2D and DNAM-1 activating receptors. NK-92 and KHYG-1 demonstrated 2- to 3-fold greater inhibition of clonogenic multiple myeloma growth, compared with killing of the bulk tumor population. In addition, the residual colonies after treatment formed significantly fewer colonies compared to the control in a secondary replating for a cumulative clonogenic inhibition of 89–99% at the 20:1 effector to target ratio. Multiple myeloma tumor burden was reduced by NK-92 in a xenograft mouse model as measured by bioluminescence imaging and reduction in bone marrow engraftment of U266eGFPluc cells by flow cytometry. Conclusions This study demonstrates that NK-92 and KHYG-1 are capable of killing clonogenic and bulk multiple myeloma cells. In addition, multiple myeloma tumor burden in a xenograft mouse model was reduced by intravenous NK-92 cell therapy. Since multiple myeloma colony frequency correlates with survival, our observations have important clinical implications and suggest that clinical studies of NK cell lines to treat MM are warranted. PMID:22271890

Production of high-titer human influenza A virus with adherent and suspension MDCK cells cultured in a single-use hollow fiber bioreactor.

PubMed

Tapia, Felipe; Vogel, Thomas; Genzel, Yvonne; Behrendt, Ilona; Hirschel, Mark; Gangemi, J David; Reichl, Udo

2014-02-12

Hollow fiber bioreactors (HFBRs) have been widely described as capable of supporting the production of highly concentrated monoclonal antibodies and recombinant proteins. Only recently HFBRs have been proposed as new single-use platforms for production of high-titer influenza A virus. These bioreactors contain multiple hollow fiber capillary tubes that separate the bioreactor in an intra- and an extra-capillary space. Cells are usually cultured in the extra-capillary space and can grow to a very high cell concentration. This work describes the evaluation of the single-use hollow fiber bioreactor PRIMER HF (Biovest International Inc., USA) for production of influenza A virus. The process was setup, characterized and optimized by running a total of 15 cultivations. The HFBRs were seeded with either adherent or suspension MDCK cells, and infected with influenza virus A/PR/8/34 (H1N1), and the pandemic strain A/Mexico/4108/2009 (H1N1). High HA titers and TCID₅₀ of up to 3.87 log₁₀(HA units/100 μL) and 1.8 × 10(10)virions/mL, respectively, were obtained for A/PR/8/34 influenza strain. Influenza virus was collected by performing multiple harvests of the extra-capillary space during a virus production time of up to 12 days. Cell-specific virus yields between 2,000 and 8,000 virions/cell were estimated for adherent MDCK cells, and between 11,000 and 19,000 virions/cell for suspension MDCK.SUS2 cells. These results do not only coincide with the cell-specific virus yields obtained with cultivations in stirred tank bioreactors and other high cell density systems, but also demonstrate that HFBRs are promising and competitive single-use platforms that can be considered for commercial production of influenza virus. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multiple myeloma

MedlinePlus

Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... Multiple myeloma most commonly causes: Low red blood cell count ( anemia ), which can lead to fatigue and ...

Motor control differs for increasing and releasing force

PubMed Central

Park, Seoung Hoon; Kwon, MinHyuk; Solis, Danielle; Lodha, Neha

2016-01-01

Control of the motor output depends on our ability to precisely increase and release force. However, the influence of aging on force increase and release remains unknown. The purpose of this study, therefore, was to determine whether force control differs while increasing and releasing force in young and older adults. Sixteen young adults (22.5 ± 4 yr, 8 females) and 16 older adults (75.7 ± 6.4 yr, 8 females) increased and released force at a constant rate (10% maximum voluntary contraction force/s) during an ankle dorsiflexion isometric task. We recorded the force output and multiple motor unit activity from the tibialis anterior (TA) muscle and quantified the following outcomes: 1) variability of force using the SD of force; 2) mean discharge rate and variability of discharge rate of multiple motor units; and 3) power spectrum of the multiple motor units from 0–4, 4–10, 10–35, and 35–60 Hz. Participants exhibited greater force variability while releasing force, independent of age (P < 0.001). Increased force variability during force release was associated with decreased modulation of multiple motor units from 35 to 60 Hz (R2 = 0.38). Modulation of multiple motor units from 35 to 60 Hz was further correlated to the change in mean discharge rate of multiple motor units (r = 0.66) and modulation from 0 to 4 Hz (r = −0.64). In conclusion, these findings suggest that force control is altered while releasing due to an altered modulation of the motor units. PMID:26961104

47 CFR 76.800 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... CABLE TELEVISION SERVICE Cable Inside Wiring § 76.800 Definitions. (a) MDU. A multiple dwelling unit... owns or controls the common areas of a multiple dwelling unit building. (c) MVPD. A multichannel video...

47 CFR 76.800 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... CABLE TELEVISION SERVICE Cable Inside Wiring § 76.800 Definitions. (a) MDU. A multiple dwelling unit... owns or controls the common areas of a multiple dwelling unit building. (c) MVPD. A multichannel video...

47 CFR 76.800 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... CABLE TELEVISION SERVICE Cable Inside Wiring § 76.800 Definitions. (a) MDU. A multiple dwelling unit... owns or controls the common areas of a multiple dwelling unit building. (c) MVPD. A multichannel video...

Mineral shock signatures in rocks from Dhala (Mohar) impact structure, Shivpuri district, Madhya Pradesh, India

NASA Astrophysics Data System (ADS)

Roy, Madhuparna; Pandey, Pradeep; Kumar, Shailendra; Parihar, P. S.

2017-12-01

A concrete study combining optical microscopy, Raman spectroscopy and X-ray diffractometry, was carried out on subsurface samples of basement granite and melt breccia from Mohar (Dhala) impact structure, Shivpuri district, Madhya Pradesh, India. Optical microscopy reveals aberrations in the optical properties of quartz and feldspar in the form of planar deformation feature-like structures, lowered birefringence and mosaics in quartz, toasting, planar fractures and ladder texture in alkali feldspar and near-isotropism in bytownite. It also brings to light incidence of parisite, a radioactive rare mineral in shocked granite. Raman spectral pattern, peak positions, peak widths and multiplicity of peak groups of all minerals, suggest subtle structural/crystallographic deviations. XRD data further reveals minute deviations of unit cell parameters of quartz, alkali feldspar and plagioclase, with respect to standard α-quartz, high- and low albite and microcline. Reduced cell volumes in these minerals indicate compression due to pressure. The c0/a0 values indicate an inter-tetrahedral angle roughly between 120o and 144o, further pointing to a possible pressure maxima of around 12 GPa. The observed unit cell aberration of minerals may indicate an intermediate stage between crystalline and amorphous stages, thereby, signifying possible overprinting of decompression signatures over shock compression effects, from a shock recovery process.

Reducing intraoperative red blood cell unit wastage in a large academic medical center.

PubMed

Whitney, Gina M; Woods, Marcella C; France, Daniel J; Austin, Thomas M; Deegan, Robert J; Paroskie, Allison; Booth, Garrett S; Young, Pampee P; Dmochowski, Roger R; Sandberg, Warren S; Pilla, Michael A

2015-11-01

The wastage of red blood cell (RBC) units within the operative setting results in significant direct costs to health care organizations. Previous education-based efforts to reduce wastage were unsuccessful at our institution. We hypothesized that a quality and process improvement approach would result in sustained reductions in intraoperative RBC wastage in a large academic medical center. Utilizing a failure mode and effects analysis supplemented with time and temperature data, key drivers of perioperative RBC wastage were identified and targeted for process improvement. Multiple contributing factors, including improper storage and transport and lack of accurate, locally relevant RBC wastage event data were identified as significant contributors to ongoing intraoperative RBC unit wastage. Testing and implementation of improvements to the process of transport and storage of RBC units occurred in liver transplant and adult cardiac surgical areas due to their history of disproportionately high RBC wastage rates. Process interventions targeting local drivers of RBC wastage resulted in a significant reduction in RBC wastage (p < 0.0001; adjusted odds ratio, 0.24; 95% confidence interval, 0.15-0.39), despite an increase in operative case volume over the period of the study. Studied process interventions were then introduced incrementally in the remainder of the perioperative areas. These results show that a multidisciplinary team focused on the process of blood product ordering, transport, and storage was able to significantly reduce operative RBC wastage and its associated costs using quality and process improvement methods. © 2015 AABB.

Reducing intraoperative red blood cell unit wastage in a large academic medical center

PubMed Central

Whitney, Gina M.; Woods, Marcella C.; France, Daniel J.; Austin, Thomas M.; Deegan, Robert J.; Paroskie, Allison; Booth, Garrett S.; Young, Pampee P.; Dmochowski, Roger R.; Sandberg, Warren S.; Pilla, Michael A.

2015-01-01

BACKGROUND The wastage of red blood cell (RBC) units within the operative setting results in significant direct costs to health care organizations. Previous education-based efforts to reduce wastage were unsuccessful at our institution. We hypothesized that a quality and process improvement approach would result in sustained reductions in intraoperative RBC wastage in a large academic medical center. STUDY DESIGN AND METHODS Utilizing a failure mode and effects analysis supplemented with time and temperature data, key drivers of perioperative RBC wastage were identified and targeted for process improvement. RESULTS Multiple contributing factors, including improper storage and transport and lack of accurate, locally relevant RBC wastage event data were identified as significant contributors to ongoing intraoperative RBC unit wastage. Testing and implementation of improvements to the process of transport and storage of RBC units occurred in liver transplant and adult cardiac surgical areas due to their history of disproportionately high RBC wastage rates. Process interventions targeting local drivers of RBC wastage resulted in a significant reduction in RBC wastage (p <0.0001; adjusted odds ratio, 0.24; 95% confidence interval, 0.15–0.39), despite an increase in operative case volume over the period of the study. Studied process interventions were then introduced incrementally in the remainder of the perioperative areas. CONCLUSIONS These results show that a multidisciplinary team focused on the process of blood product ordering, transport, and storage was able to significantly reduce operative RBC wastage and its associated costs using quality and process improvement methods. PMID:26202213

Device for monitoring cell voltage

DOEpatents

Doepke, Matthias [Garbsen, DE; Eisermann, Henning [Edermissen, DE

2012-08-21

A device for monitoring a rechargeable battery having a number of electrically connected cells includes at least one current interruption switch for interrupting current flowing through at least one associated cell and a plurality of monitoring units for detecting cell voltage. Each monitoring unit is associated with a single cell and includes a reference voltage unit for producing a defined reference threshold voltage and a voltage comparison unit for comparing the reference threshold voltage with a partial cell voltage of the associated cell. The reference voltage unit is electrically supplied from the cell voltage of the associated cell. The voltage comparison unit is coupled to the at least one current interruption switch for interrupting the current of at least the current flowing through the associated cell, with a defined minimum difference between the reference threshold voltage and the partial cell voltage.

Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

ClinicalTrials.gov

2016-06-27

Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Waldenström Macroglobulinemia

Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

PubMed

Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

2014-07-01

The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

Hair-cell counts and afferent innervation patterns in the cristae ampullares of the squirrel monkey with a comparison to the chinchilla

NASA Technical Reports Server (NTRS)

Fernandez, C.; Lysakowski, A.; Goldberg, J. M.

1995-01-01

1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas. The three zones can be distinguished by the sizes of individual hair cells and calyx endings, by the density of hair cells, and by the relative frequency of calyx endings innervating single or multiple type I hair cells. 3. In the monkey crista, type I hair cells outnumber type II hair cells by a ratio of almost 3:1. The ratio decreases from 4-5:1 in the central and intermediate zones to under 2:1 in the peripheral zone. For the chinchilla, the ratio is near 1:1 for the entire crista and decreases only slightly between the central and peripheral zones. 4. Nerve fibers supplying the cristae in the squirrel monkey were labeled by extracellular injections of horseradish peroxidase (HRP) into the vestibular nerve. Peripheral terminations of individual fibers were reconstructed and related to the zones of the cristae they innervated and to the sizes of their parent axons. Results were similar for the horizontal, superior, and posterior cristae. 5. Axons seldom bifurcate below the neuroepithelium. Most fibers begin branching shortly after crossing the basement membrane. Their terminal arbors are compact, usually extending no more than 50-100 microns from the parent exon. A small number of long intraepithelial fibers enter the intermediate and peripheral zones of the cristae near its base, then run unbranched for long distances through the neuroepithelium to reach the central zone. 6. There are three classes of afferent fibers innervating the monkey crista. Calyx fibers terminate exclusively on type I hair cells, and bouton fibers end only on type II hair cells. Dimorphic fibers provide a mixed innervation, including calyx endings to type I hair cells and bouton endings to type II hair cells. Long intraepithelial fibers are calyx and dimorphic units, whose terminal fields are similar to those of other fibers. The central zone is innervated by calyx and dimorphic fibers; the peripheral zone, by bouton and dimorphic fibers; and the intermediate zone, by all three kinds of fibers. Internal (axon) diameters are largest for calyx fibers and smallest for bouton fibers. Of the entire sample of 286 labeled fibers, 52% were dimorphic units, 40% were calyx units, and 8% were bouton units.(ABSTRACT TRUNCATED AT 400 WORDS).

Use of Multiple GPUs to Speedup the Execution of a Three-Dimensional Computational Model of the Innate Immune System

NASA Astrophysics Data System (ADS)

Xavier, M. P.; do Nascimento, T. M.; dos Santos, R. W.; Lobosco, M.

2014-03-01

The development of computational systems that mimics the physiological response of organs or even the entire body is a complex task. One of the issues that makes this task extremely complex is the huge computational resources needed to execute the simulations. For this reason, the use of parallel computing is mandatory. In this work, we focus on the simulation of temporal and spatial behaviour of some human innate immune system cells and molecules in a small three-dimensional section of a tissue. To perform this simulation, we use multiple Graphics Processing Units (GPUs) in a shared-memory environment. Despite of high initialization and communication costs imposed by the use of GPUs, the techniques used to implement the HIS simulator have shown to be very effective to achieve this purpose.

Learning about the Unit Cell and Crystal Lattice with Computerized Simulations and Games: A Pilot Study

ERIC Educational Resources Information Center

Luealamai, Sutha; Panijpan, Bhinyo

2012-01-01

The authors have developed a computer-based learning module on the unit cell of various types of crystal. The module has two components: the virtual unit cell (VUC) part and the subsequent unit cell hunter part. The VUC is a virtual reality simulation for students to actively arrive at the unit cell from exploring, from a broad view, the crystal…

Development of a Recombinant Multifunctional Biomacromolecule for Targeted Gene Transfer to Prostate Cancer Cells.

PubMed

Hatefi, Arash; Karjoo, Zahra; Nomani, Alireza

2017-09-11

The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repeatative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide, and PC-3 cell targeting peptide was designed. To examine the functionality of each motif in the vector sequence, it was characterized in terms of size and zeta potential by Zetasizer, PC-3 cell targeting and transfection by flowcytometry, IgG induction by immunogenicity assay, and PC-3 tumor transfection by quantitative live animal imaging. Overall, the results of this study showed the possibility of using genetic engineering techniques to program various functionalities into one single chain vector and create a multifunctional nonimmunogenic biomacromolecule for targeted gene transfer to prostate cancer cells. This proof-of-concept study is a significant step forward toward creating a library of vectors for targeted gene transfer to any cancer cell type at both in vitro and in vivo levels.

The New Federalism: State Policies Regarding Embryonic Stem Cell Research.

PubMed

Acosta, Nefi D; Golub, Sidney H

2016-09-01

Stem cell policy in the United States is an amalgam of federal and state policies. The scientific development of human pluripotent embryonic stem cells (ESCs) triggered a contentious national stem cell policy debate during the administration of President George W. Bush. The Bush "compromise" that allowed federal funding to study only a very limited number of ESC derived cell lines did not satisfy either the researchers or the patient advocates who saw great medical potential being stifled. Neither more restrictive legislation nor expansion of federal funding proved politically possible and the federal impasse opened the door for a variety of state-based experiments. In 2004, California became the largest and most influential state venture into stem cell research by passing "Prop 71," a voter initiative that created a new stem cell agency and funded it with $3 billion. Several states followed suit with similar programs to protect the right of investigators to do stem cell research and in some cases to invest state funding in such projects. Other states devised legislation to restrict stem cell research and in five states, criminal penalties were included. Thus, the US stem cell policy is a patchwork of multiple, often conflicting, state and federal policies. © 2016 American Society of Law, Medicine & Ethics.

Complex neural codes in rat prelimbic cortex are stable across days on a spatial decision task

PubMed Central

Powell, Nathaniel J.; Redish, A. David

2014-01-01

The rodent prelimbic cortex has been shown to play an important role in cognitive processing, and has been implicated in encoding many different parameters relevant to solving decision-making tasks. However, it is not known how the prelimbic cortex represents all these disparate variables, and if they are simultaneously represented when the task requires it. In order to investigate this question, we trained rats to run the Multiple-T Left Right Alternate (MT-LRA) task and recorded multi-unit ensembles from their prelimbic regions. Significant populations of cells in the prelimbic cortex represented the strategy controlling reward receipt on a given lap, whether the animal chose to go right or left on a given lap, and whether the animal made a correct decision or an error on a given lap. These populations overlapped in the cells recorded, with several cells demonstrating differential firing to all three variables. The spatial and strategic firing patterns of individual prelimbic cells were highly conserved across several days of running this task, indicating that each cell encoded the same information across days. PMID:24795579

T-COMP—A suite of programs for extracting transmissivity from MODFLOW models

USGS Publications Warehouse

Halford, Keith J.

2016-02-12

Simulated transmissivities are constrained poorly by assigning permissible ranges of hydraulic conductivities from aquifer-test results to hydrogeologic units in groundwater-flow models. These wide ranges are derived from interpretations of many aquifer tests that are categorized by hydrogeologic unit. Uncertainty is added where contributing thicknesses differ between field estimates and numerical models. Wide ranges of hydraulic conductivities and discordant thicknesses result in simulated transmissivities that frequently are much greater than aquifer-test results. Multiple orders of magnitude differences frequently occur between simulated and observed transmissivities where observed transmissivities are less than 1,000 feet squared per day.Transmissivity observations from individual aquifer tests can constrain model calibration as head and flow observations do. This approach is superior to diluting aquifer-test results into generalized ranges of hydraulic conductivities. Observed and simulated transmissivities can be compared directly with T-COMP, a suite of three FORTRAN programs. Transmissivity observations require that simulated hydraulic conductivities and thicknesses in the volume investigated by an aquifer test be extracted and integrated into a simulated transmissivity. Transmissivities of MODFLOW model cells are sampled within the volume affected by an aquifer test as defined by a well-specific, radial-flow model of each aquifer test. Sampled transmissivities of model cells are averaged within a layer and summed across layers. Accuracy of the approach was tested with hypothetical, multiple-aquifer models where specified transmissivities ranged between 250 and 20,000 feet squared per day. More than 90 percent of simulated transmissivities were within a factor of 2 of specified transmissivities.

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

PubMed Central

Pessoa de Magalhães, Roberto J.; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C.; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M.; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F.; Orfao, Alberto

2013-01-01

Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance. PMID:22773604

Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes.

PubMed

Yáñez-Mó, María; Barreiro, Olga; Gordon-Alonso, Mónica; Sala-Valdés, Mónica; Sánchez-Madrid, Francisco

2009-09-01

Membrane lipids and proteins are non-randomly distributed and are unable to diffuse freely in the plane of the membrane. This is because of multiple constraints imposed both by the cortical cytoskeleton and by the preference of lipids and proteins to cluster into diverse and specialized membrane domains, including tetraspanin-enriched microdomains, glycosylphosphatidyl inositol-linked proteins nanodomains and caveolae, among others. Recent biophysical characterization of tetraspanin-enriched microdomains suggests that they might be specially suited for the regulation of avidity of adhesion receptors and the compartmentalization of enzymatic activities. Moreover, modulation by tetraspanins of the function of adhesion receptors involved in inflammation, lymphocyte activation, cancer and pathogen infection suggests potential as therapeutic targets. This review explores this emerging picture of tetraspanin microdomains and discusses the implications for cell adhesion, proteolysis and pathogenesis.

14 CFR 23.511 - Ground load; unsymmetrical loads on multiple-wheel units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... CATEGORY AIRPLANES Structure Ground Loads § 23.511 Ground load; unsymmetrical loads on multiple-wheel units... coefficient of friction of 0.8 applied to the main gear and its supporting structure. (b) Unequal tire loads... distribution, to the dual wheels and tires in each dual wheel landing gear unit. (c) Deflated tire loads. For...

Genetic variation in cell death genes and risk of non-Hodgkin lymphoma.

PubMed

Schuetz, Johanna M; Daley, Denise; Graham, Jinko; Berry, Brian R; Gallagher, Richard P; Connors, Joseph M; Gascoyne, Randy D; Spinelli, John J; Brooks-Wilson, Angela R

2012-01-01

Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5(th) highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility. We tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate. Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63-4.82]; p(F) = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing. This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma.

A Review of the Literature on the Multiple Dimensions of Chronic Pain in Adults with Sickle Cell Disease

PubMed Central

Taylor, Lou Ella V.; Stotts, Nancy A.; Humphreys, Janice; Treadwell, Marsha J.; Miaskowski, Christine

2010-01-01

Sickle cell disease (SCD) is a major healthcare and societal problem that affects millions of people worldwide. In Nigeria, 45,000 to 90,000 babies are born each year with SCD. In the United States, SCD is the most common genetic disorder, affecting more than 80,000 people, the majority of whom are African American. Sickle cell pain is the hallmark feature of SCD. Most of the research on pain from SCD has focused on children with acute pain associated with sickle cell crisis. Consequently, very little is known about the occurrence and characteristics of chronic pain, especially in adults with SCD. Individuals with SCD who experience chronic pain are often underserved and their pain is under-treated. This under-treatment may result in millions of dollars per year spent on emergency room visits, hospitalizations, and lost work productivity. The primary purpose of this literature review was to summarize the findings from studies that evaluated the characteristics of chronic pain in adults with SCD. Each of the studies included in this review was evaluated to determine if it provided data on the following multidimensional characteristics of chronic pain: occurrence, number of pain episodes, duration, pattern, quality, location, intensity, aggravating factors, relieving factors, and impact of pain on function. A secondary purpose was to identify gaps in knowledge and directions for future research on the multiple dimensions of chronic pain in adults with SCD. PMID:20656451

Trainable Gene Regulation Networks with Applications to Drosophila Pattern Formation

NASA Technical Reports Server (NTRS)

Mjolsness, Eric

2000-01-01

This chapter will very briefly introduce and review some computational experiments in using trainable gene regulation network models to simulate and understand selected episodes in the development of the fruit fly, Drosophila melanogaster. For details the reader is referred to the papers introduced below. It will then introduce a new gene regulation network model which can describe promoter-level substructure in gene regulation. As described in chapter 2, gene regulation may be thought of as a combination of cis-acting regulation by the extended promoter of a gene (including all regulatory sequences) by way of the transcription complex, and of trans-acting regulation by the transcription factor products of other genes. If we simplify the cis-action by using a phenomenological model which can be tuned to data, such as a unit or other small portion of an artificial neural network, then the full transacting interaction between multiple genes during development can be modelled as a larger network which can again be tuned or trained to data. The larger network will in general need to have recurrent (feedback) connections since at least some real gene regulation networks do. This is the basic modeling approach taken, which describes how a set of recurrent neural networks can be used as a modeling language for multiple developmental processes including gene regulation within a single cell, cell-cell communication, and cell division. Such network models have been called "gene circuits", "gene regulation networks", or "genetic regulatory networks", sometimes without distinguishing the models from the actual modeled systems.

Treatment of leprosy/Hansen's disease in the early 21st century.

PubMed

Worobec, Sophie M

2009-01-01

Leprosy, or Hansen's disease (HD), is caused by Mycobacterium leprae, a slowly dividing mycobacterium that has evolved to be an intracellular parasite, causing skin lesions and nerve damage. Less than 5% of people exposed to M. leprae develop clinical disease. Host cell-mediated resistance determines whether an individual will develop paucibacillary or multibacillary disease. Hansen's disease is a worldwide disease with about 150 new cases reported annually in the United States. Effective anti-mycobacterial treatments are available, and many patients experience severe reversal and erythema nodosum leprosum reactions that also require treatment. Leprosy has been the target of a World Health Organization multiple drug therapy campaign to eliminate it as a national public health problem in member countries, but endemic regions persist. In the United States, the National Hansen's Disease Program has primary responsibility for medical care, research, and information.

Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

Cancer.gov

Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

Multistage Magnetic Separator of Cells and Proteins

NASA Technical Reports Server (NTRS)

Barton, Ken; Ainsworth, Mark; Daily, Bruce; Dunn, Scott; Metz, Bill; Vellinger, John; Taylor, Brock; Meador, Bruce

2005-01-01

The multistage electromagnetic separator for purifying cells and magnetic particles (MAGSEP) is a laboratory apparatus for separating and/or purifying particles (especially biological cells) on the basis of their magnetic susceptibility and magnetophoretic mobility. Whereas a typical prior apparatus based on similar principles offers only a single stage of separation, the MAGSEP, as its full name indicates, offers multiple stages of separation; this makes it possible to refine a sample population of particles to a higher level of purity or to categorize multiple portions of the sample on the basis of magnetic susceptibility and/or magnetophoretic mobility. The MAGSEP includes a processing unit and an electronic unit coupled to a personal computer. The processing unit includes upper and lower plates, a plate-rotation system, an electromagnet, an electromagnet-translation system, and a capture-magnet assembly. The plates are bolted together through a roller bearing that allows the plates to rotate with respect to each other. An interface between the plates acts as a seal for separating fluids. A lower cuvette can be aligned with as many as 15 upper cuvette stations for fraction collection during processing. A two-phase stepping motor drives the rotation system, causing the upper plate to rotate for the collection of each fraction of the sample material. The electromagnet generates a magnetic field across the lower cuvette, while the translation system translates the electromagnet upward along the lower cuvette. The current supplied to the electromagnet, and thus the magnetic flux density at the pole face of the electromagnet, can be set at a programmed value between 0 and 1,400 gauss (0.14 T). The rate of translation can be programmed between 5 and 2,000 m/s so as to align all sample particles in the same position in the cuvette. The capture magnet can be a permanent magnet. It is mounted on an arm connected to a stepping motor. The stepping motor rotates the arm to position the capture magnet above the upper cuvette into which a fraction of the sample is collected. The electronic unit includes a power switch, power-supply circuitry that accepts 110-Vac input power, an RS-232 interface, and status lights. The personal computer runs the MAGSEP software and controls the operation of the MAGSEP through the RS-232 interface. The status of the power, the translating electromagnet, the capture magnet, and the rotation of the upper plate are indicated in a graphical user interface on the computer screen.

Fluctuations of pol I and fibrillarin contents of the nucleoli.

PubMed

Hornáček, M; Kováčik, L; Mazel, T; Cmarko, D; Bártová, E; Raška, I; Smirnov, E

2017-07-04

Nucleoli are formed on the basis of ribosomal DNA (rDNA) clusters called Nucleolus Organizer Regions (NORs). Each NOR contains multiple genes coding for RNAs of the ribosomal particles. The prominent components of the nucleolar ultrastructure, fibrillar centers (FC) and dense fibrillar components (DFC), together compose FC/DFC units. These units are centers of rDNA transcription by RNA polymerase I (pol I), as well as the early processing events, in which an essential role belongs to fibrillarin. Each FC/DFC unit probably corresponds to a single transcriptionally active gene. In this work, we transfected human-derived cells with GFP-RPA43 (subunit of pol I) and RFP-fibrillarin. Following changes of the fluorescent signals in individual FC/DFC units, we found two kinds of kinetics: 1) the rapid fluctuations with periods of 2-3 min, when the pol I and fibrillarin signals oscillated in anti-phase manner, and the intensities of pol I in the neighboring FC/DFC units did not correlate. 2) fluctuations with periods of 10 to 60 min, in which pol I and fibrillarin signals measured in the same unit did not correlate, but pol I signals in the units belonging to different nucleoli were synchronized. Our data indicate that a complex pulsing activity of transcription as well as early processing is common for ribosomal genes.

40 CFR 75.82 - Monitoring of Hg mass emissions and heat input at common and multiple stacks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... heat input at common and multiple stacks. 75.82 Section 75.82 Protection of Environment ENVIRONMENTAL... Provisions § 75.82 Monitoring of Hg mass emissions and heat input at common and multiple stacks. (a) Unit... systems and perform the Hg emission testing described under § 75.81(b). If reporting of the unit heat...

Cell-based therapeutic strategies for multiple sclerosis

PubMed Central

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A; Atkins, Harold; Banwell, Brenda; Bar-Or, Amit; Bebo, Bruce; Bowen, James; Burt, Richard; Calabresi, Peter; Cohen, Jeffrey; Comi, Giancarlo; Connick, Peter; Cross, Anne; Cutter, Gary; Derfuss, Tobias; Ffrench-Constant, Charles; Freedman, Mark; Galipeau, Jacques; Goldman, Myla; Goldman, Steven; Goodman, Andrew; Green, Ari; Griffith, Linda; Hartung, Hans-Peter; Hemmer, Bernhard; Hyun, Insoo; Iacobaeus, Ellen; Inglese, Matilde; Jubelt, Burk; Karussis, Dimitrios; Küry, Patrick; Landsman, Douglas; Laule, Cornelia; Liblau, Roland; Mancardi, Giovanni; Ann Marrie, Ruth; Miller, Aaron; Miller, Robert; Miller, David; Mowry, Ellen; Muraro, Paolo; Nash, Richard; Ontaneda, Daniel; Pasquini, Marcelo; Pelletier, Daniel; Peruzzotti-Jametti, Luca; Pluchino, Stefano; Racke, Michael; Reingold, Stephen; Rice, Claire; Ringdén, Olle; Rovira, Alex; Saccardi, Riccardo; Sadiq, Saud; Sarantopoulos, Stefanie; Savitz, Sean; Scolding, Neil; Soelberg Sorensen, Per; Pia Sormani, Maria; Stuve, Olaf; Tesar, Paul; Thompson, Alan; Trojano, Maria; Uccelli, Antonio; Uitdehaag, Bernard; Utz, Ursula; Vukusic, Sandra; Waubant, Emmanuelle; Wilkins, Alastair

2017-01-01

Abstract The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. PMID:29053779

Development and evaluation of a novel modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride as model drugs.

PubMed

Zeeshan, Farrukh; Bukhari, Nadeem Irfan

2010-06-01

Modified-release multiple-unit tablets of loratadine and pseudoephedrine hydrochloride with different release profiles were prepared from the immediate-release pellets comprising the above two drugs and prolonged-release pellets containing only pseudoephedrine hydrochloride. The immediate-release pellets containing pseudoephedrine hydrochloride alone or in combination with loratadine were prepared using extrusion-spheronization method. The pellets of pseudoephedrine hydrochloride were coated to prolong the drug release up to 12 h. Both immediate- and prolonged-release pellets were filled into hard gelatin capsule and also compressed into tablets using inert tabletting granules of microcrystalline cellulose Ceolus KG-801. The in vitro drug dissolution study conducted using high-performance liquid chromatography method showed that both multiple-unit capsules and multiple-unit tablets released loratadine completely within a time period of 2 h, whereas the immediate-release portion of pseudoephedrine hydrochloride was liberated completely within the first 10 min of dissolution study. On the other hand, the release of pseudoephedrine hydrochloride from the prolonged release coated pellets was prolonged up to 12 hr and followed zero-order release kinetic. The drug dissolution profiles of multiple-unit tablets and multiple-unit capsules were found to be closely similar, indicating that the integrity of pellets remained unaffected during the compression process. Moreover, the friability, hardness, and disintegration time of multiple-unit tablets were found to be within BP specifications. In conclusion, modified-release pellet-based tablet system for the delivery of loratadine and pseudoephedrine hydrochloride was successfully developed and evaluated.

Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Multiple Trauma.

PubMed

Jo, Young Goun; Choi, Hyun Jung; Kim, Jung Chul; Cho, Young Nan; Kang, Jeong Hwa; Jin, Hye Mi; Kee, Seung Jung; Park, Yong Wook

2017-05-01

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma. © 2017 The Korean Academy of Medical Sciences.

Coordination of Leaf Photosynthesis, Transpiration, and Structural Traits in Rice and Wild Relatives (Genus Oryza)1[W][OA

PubMed Central

Giuliani, Rita; Koteyeva, Nuria; Voznesenskaya, Elena; Evans, Marc A.; Cousins, Asaph B.; Edwards, Gerald E.

2013-01-01

The genus Oryza, which includes rice (Oryza sativa and Oryza glaberrima) and wild relatives, is a useful genus to study leaf properties in order to identify structural features that control CO2 access to chloroplasts, photosynthesis, water use efficiency, and drought tolerance. Traits, 26 structural and 17 functional, associated with photosynthesis and transpiration were quantified on 24 accessions (representatives of 17 species and eight genomes). Hypotheses of associations within, and between, structure, photosynthesis, and transpiration were tested. Two main clusters of positively interrelated leaf traits were identified: in the first cluster were structural features, leaf thickness (Thickleaf), mesophyll (M) cell surface area exposed to intercellular air space per unit of leaf surface area (Smes), and M cell size; a second group included functional traits, net photosynthetic rate, transpiration rate, M conductance to CO2 diffusion (gm), stomatal conductance to gas diffusion (gs), and the gm/gs ratio. While net photosynthetic rate was positively correlated with gm, neither was significantly linked with any individual structural traits. The results suggest that changes in gm depend on covariations of multiple leaf (Smes) and M cell (including cell wall thickness) structural traits. There was an inverse relationship between Thickleaf and transpiration rate and a significant positive association between Thickleaf and leaf transpiration efficiency. Interestingly, high gm together with high gm/gs and a low Smes/gm ratio (M resistance to CO2 diffusion per unit of cell surface area exposed to intercellular air space) appear to be ideal for supporting leaf photosynthesis while preserving water; in addition, thick M cell walls may be beneficial for plant drought tolerance. PMID:23669746

Coordination of Leaf Photosynthesis, Transpiration, and Structural Traits in Rice and Wild Relatives (Genus Oryza).

PubMed

Giuliani, Rita; Koteyeva, Nuria; Voznesenskaya, Elena; Evans, Marc A; Cousins, Asaph B; Edwards, Gerald E

2013-07-01

The genus Oryza, which includes rice (Oryza sativa and Oryza glaberrima) and wild relatives, is a useful genus to study leaf properties in order to identify structural features that control CO(2) access to chloroplasts, photosynthesis, water use efficiency, and drought tolerance. Traits, 26 structural and 17 functional, associated with photosynthesis and transpiration were quantified on 24 accessions (representatives of 17 species and eight genomes). Hypotheses of associations within, and between, structure, photosynthesis, and transpiration were tested. Two main clusters of positively interrelated leaf traits were identified: in the first cluster were structural features, leaf thickness (Thick(leaf)), mesophyll (M) cell surface area exposed to intercellular air space per unit of leaf surface area (S(mes)), and M cell size; a second group included functional traits, net photosynthetic rate, transpiration rate, M conductance to CO(2) diffusion (g(m)), stomatal conductance to gas diffusion (g(s)), and the g(m)/g(s) ratio.While net photosynthetic rate was positively correlated with gm, neither was significantly linked with any individual structural traits. The results suggest that changes in gm depend on covariations of multiple leaf (S(mes)) and M cell (including cell wall thickness) structural traits. There was an inverse relationship between Thick(leaf) and transpiration rate and a significant positive association between Thick(leaf) and leaf transpiration efficiency. Interestingly, high g(m) together with high g(m)/g(s) and a low S(mes)/g(m) ratio (M resistance to CO(2) diffusion per unit of cell surface area exposed to intercellular air space) appear to be ideal for supporting leaf photosynthesis while preserving water; in addition, thick M cell walls may be beneficial for plant drought tolerance.

Multi-gel casting apparatus for vertical polyacrylamide gels with in-built solution flow system and liquid level detectors.

PubMed

Maurye, Praveen; Basu, Arpita; Bandyopadhyay, Tapas Kumar; Biswas, Jayanta Kumar; Mohanty, Bimal Prasana

2017-08-01

PAGE is the most widely used technique for the separation and biochemical analysis of biomolecules. The ever growing field of proteomics and genomics necessitates the analysis of many proteins and nucleic acid samples to understand further about the structure and function of cells. Simultaneous analysis of multiple protein samples often requires casting of many PAGE gels. Several variants of multi-gel casting/electrophoresis apparatuses are frequently used in research laboratories. Requirement of supplementary gels to match the growing demand for analyzing additional protein samples sometimes become a cause of concern. Available apparatuses are not amenable to and therefore, not recommended for any modification to accommodate additional gel casting units other than what is prescribed by the manufacturer. A novel apparatus is described here for casting multiple PAGE gels comprising four detachable components that provide enhanced practicability and performance of the apparatus. This newly modified apparatus promises to be a reliable source for making multiple gels in less time without hassle. Synchronized functioning of unique components broaden the possibilities of developing inexpensive, safe, and time-saving multi-gel casting apparatus. This apparatus can be easily fabricated and modified to accommodate desired number of gel casting units. The estimated cost (∼$300) for fabrication of the main apparatus is very competitive and effortless assembly procedure can be completed within ∼30 min. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Short-Term and Long-Term Survival and Virulence of Legionella pneumophila in the Defined Freshwater Medium Fraquil.

PubMed

Mendis, Nilmini; McBride, Peter; Faucher, Sébastien P

2015-01-01

Legionella pneumophila (Lp) is the etiological agent responsible for Legionnaires' disease, a potentially fatal pulmonary infection. Lp lives and multiplies inside protozoa in a variety of natural and man-made water systems prior to human infection. Fraquil, a defined freshwater medium, was used as a highly reproducible medium to study the behaviour of Lp in water. Adopting a reductionist approach, Fraquil was used to study the impact of temperature, pH and trace metal levels on the survival and subsequent intracellular multiplication of Lp in Acanthamoeba castellanii, a freshwater protozoan and a natural host of Legionella. We show that temperature has a significant impact on the short- and long-term survival of Lp, but that the bacterium retains intracellular multiplication potential for over six months in Fraquil. Moreover, incubation in Fraquil at pH 4.0 resulted in a rapid decline in colony forming units, but was not detrimental to intracellular multiplication. In contrast, variations in trace metal concentrations had no impact on either survival or intracellular multiplication in amoeba. Our data show that Lp is a resilient bacterium in the water environment, remaining infectious to host cells after six months under the nutrient-deprived conditions of Fraquil.

Evaluation of the impact of banking umbilical cord blood units with high cell dose for ethnically diverse patients.

PubMed

Stritesky, Gretta; Wadsworth, Kimberly; Duffy, Merry; Buck, Kelly; Dehn, Jason

2018-02-01

Umbilical cord blood units provide an important stem cell source for transplantation, particularly for patients of ethnic diversity who may not have suitably matched available, adult-unrelated donors. However, with the cost of cord blood unit acquisition from public banks significantly higher than that for adult-unrelated donors, attention is focused on decreasing cost yet still providing cord blood units to patients in need. Historical practices of banking units with low total nucleated cell counts, including units with approximately 90 × 10 7 total nucleated cells, indicates that most banked cord blood units have much lower total nucleated cell counts than are required for transplant. The objective of this study was to determine the impact on the ability to identify suitable cord blood units for transplantation if the minimum total nucleated cell count for banking were increased from 90 × 10 7 to 124 or 149 × 10 7 . We analyzed ethnically diverse patients (median age, 3 years) who underwent transplantation of a single cord blood unit in 2005 to 2016. A cord blood unit search was evaluated to identify units with equal or greater human leukocyte antigen matching and a greater total nucleated cell count than that of the transplanted cord blood unit (the replacement cord blood unit). If the minimum total nucleated cell count for banking increased to 124 or 149 × 10 7 , then from 75 to 80% of patients would still have at least 1 replacement cord blood unit in the current (2016) cord blood unit inventory. The best replacement cord blood units were often found among cords with the same ethnic background as the patient. The current data suggest that, if the minimum total nucleated cell count were increased for banking, then it would likely lead to an inventory of more desirable cord blood units while having minimal impact on the identification of suitable cord blood units for transplantation. © 2017 AABB.

Complete structure of the cell surface polysaccharide of Streptococcus oralis C104: A 600-MHz NMR study

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

Abeygunawardana, C.; Bush, C.A.; Cisar, J.O.

1991-09-03

Specific lectin-carbohydrate interactions between certain oral streptococci and actinomyces contribute to the microbial colonization of teeth. The receptor molecules of Streptococcus oralis, 34, ATCC 10557, and Streptococcus mitis J22 for the galactose and N-acetylgalactosamine reactive fimbrial lectins of Actinomyces viscosus and Actinomyces naeslundii are antigenically distinct polysaccharides, each formed by a different phosphodiester-linked oligosaccharide repeating unit. Receptor polysaccharide was isolated form S. oralis C104 cells and was shown to contain galactose, N-acetylgalactosamine, ribitol, and phosphate with molar ratios of 4:1:1:1. The {sup 1}H NMR spectrum of the polysaccharide shows that it contains a repeating structure. The individual sugars in themore » repeating unit were identified by {sup 1}H coupling constants observed in E-COSY and DQF-COSY spectra. NMR methods included complete resonance assignments ({sup 1}H and {sup 13}C) by various homonuclear and heteronuclear correlation experiments that utilize scalar couplings. Sequence and linkage assignments were obtained from the heteronuclear multiple-bond correlation (HMBC) spectrum. This analysis shows that the receptor polysaccharide of S. oralis C104 is a ribitol teichoic acid polymer composed of a linear hexasaccharide repeating unit containing two residues each of galactopyranose and galactofuranose and a residue each of GalNAc and ribitol joined end to end by phosphodiester linkages.« less

Detection of bacteria in platelet concentrates prepared from spiked single donations using cultural and molecular genetic methods.

PubMed

Störmer, M; Cassens, U; Kleesiek, K; Dreier, J

2007-02-01

Bacteria show differences in their growth kinetics depending on the type of blood component. On to storage at 22 degrees C, platelet concentrates (PCs) seem to be more prone to bacterial multiplication than red cell concentrates. Knowledge of the potential for bacterial proliferation in blood components, which are stored at a range of temperatures, is essential before considering implementation of a detection strategy. The efficacy of bacterial detection was determined, using real-time reverse transcriptase-polymerase chain reaction (RT-PCR), following bacterial growth in blood components obtained from a deliberately contaminated whole-blood (WB) unit. Cultivation was used as the reference method. WB was spiked with 2 colony-forming units mL(-1)Staphylococcus epidermidis or Klebsiella pneumoniae, kept for 15 h at room temperature and component preparation was processed. Samples were drawn, at intervals throughout the whole separation process, from each blood component. Nucleic acids were extracted using an automated high-volume extraction method. The 15-h storage revealed an insignificant increase in bacterial titre. No bacterial growth was detected in red blood cell or plasma units. K. pneumoniae showed rapid growth in the pooled PC and could be detected immediately after preparation using RT-PCR. S. epidermidis grew slowly and was detected 24 h after separation. These experiments show that sampling is indicative at 24 h after preparation of PCs at the earliest to minimize the sampling error.

Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome

PubMed Central

Singhal, Deepak; Kutyna, Monika M.; Chhetri, Rakchha; Wee, Li Yan A.; Hague, Sophia; Nath, Lakshmi; Nath, Shriram V.; Sinha, Romi; Wickham, Nicholas; Lewis, Ian D.; Ross, David M.; Bardy, Peter G.; To, Luen Bik; Reynolds, John; Wood, Erica M.; Roxby, David J.; Hiwase, Devendra K.

2017-01-01

Up to 90% of patients with a myelodysplastic syndrome require red blood cell transfusion; nevertheless, comprehensive data on red cell alloimmunization in such patients are limited. This study evaluates the incidence and clinical impact of red cell alloimmunization in a large cohort of patients with myelodysplastic syndrome registered in the statewide South Australian-MDS registry. The median age of the 817 patients studied was 73 years, and 66% were male. The cumulative incidence of alloimmunization was 11%. Disease-modifying therapy was associated with a lower risk of alloimmunization while alloimmunization was significantly higher in patients with a revised International Prognostic Scoring System classification of Very Low, Low or Intermediate risk compared to those with a High or Very High risk (P=0.03). Alloantibodies were most commonly directed against antigens in the Rh (54%) and Kell (24%) systems. Multiple alloantibodies were present in 49% of alloimmunized patients. Although 73% of alloimmunized patients developed alloantibodies during the period in which they received their first 20 red cell units, the total number of units transfused was significantly higher in alloimmunized patients than in non-alloimmunized patients (90±100 versus 30±52; P<0.0001). In individual patients, red cell transfusion intensity increased significantly following alloimmunization (2.8±1.3 versus 4.1±2.0; P<0.0001). A significantly higher proportion of alloimmunized patients than non-alloimmunized patients had detectable autoantibodies (65% versus 18%; P<0.0001) and the majority of autoantibodies were detected within a short period of alloimmunization. In conclusion, this study characterizes alloimmunization in a large cohort of patients with myelodysplastic syndrome and demonstrates a signficant increase in red cell transfusion requirements following alloimmunization, most probably due to development of additional alloantibodies and autoantibodies, resulting in subclinical/clinical hemolysis. Strategies to mitigate alloimmunization risk are critical for optimizing red cell transfusion support. PMID:28983058

Li-ion battery thermal runaway suppression system using microchannel coolers and refrigerant injections

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

Bandhauer, Todd M.; Farmer, Joseph C.

A battery management system with thermally integrated fire suppression includes a multiplicity of individual battery cells in a housing; a multiplicity of cooling passages in the housing within or between the multiplicity of individual battery cells; a multiplicity of sensors operably connected to the individual battery cells, the sensors adapted to detect a thermal runaway event related to one or more of the multiplicity of individual battery cells; and a management system adapted to inject coolant into at least one of the multiplicity of cooling passages upon the detection of the thermal runaway event by the any one of themore » multiplicity of sensors, so that the thermal runaway event is rapidly quenched.« less

Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges

PubMed Central

Iyer, Rohin K.; Bowles, Paul A.; Kim, Howard; Dulgar-Tulloch, Aaron

2018-01-01

Cell therapy has proven to be a burgeoning field of investigation, evidenced by hundreds of clinical trials being conducted worldwide across a variety of cell types and indications. Many cell therapies have been shown to be efficacious in humans, such as modified T-cells and natural killer (NK) cells. Adoptive immunotherapy has shown the most promise in recent years, with particular emphasis on autologous cell sources. Chimeric Antigen Receptor (CAR)-based T-cell therapy targeting CD19-expressing B-cell leukemias has shown remarkable efficacy and reproducibility in numerous clinical trials. Recent marketing approval of Novartis' Kymriah™ (tisagenlecleucel) and Gilead/Kite's Yescarta™ (axicabtagene ciloleucel) by the FDA further underscores both the promise and legwork to be done if manufacturing processes are to become widely accessible. Further work is needed to standardize, automate, close, and scale production to bring down costs and democratize these and other cell therapies. Given the multiple processing steps involved, commercial-scale manufacturing of these therapies necessitates tighter control over process parameters. This focused review highlights some of the most recent advances used in the manufacturing of therapeutic immune cells, with a focus on T-cells. We summarize key unit operations and pain points around current manufacturing solutions. We also review emerging technologies, approaches and reagents used in cell isolation, activation, transduction, expansion, in-process analytics, harvest, cryopreservation and thaw, and conclude with a forward-look at future directions in the manufacture of adoptive immunotherapies.

Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges.

PubMed

Iyer, Rohin K; Bowles, Paul A; Kim, Howard; Dulgar-Tulloch, Aaron

2018-01-01

Cell therapy has proven to be a burgeoning field of investigation, evidenced by hundreds of clinical trials being conducted worldwide across a variety of cell types and indications. Many cell therapies have been shown to be efficacious in humans, such as modified T-cells and natural killer (NK) cells. Adoptive immunotherapy has shown the most promise in recent years, with particular emphasis on autologous cell sources. Chimeric Antigen Receptor (CAR)-based T-cell therapy targeting CD19-expressing B-cell leukemias has shown remarkable efficacy and reproducibility in numerous clinical trials. Recent marketing approval of Novartis' Kymriah™ (tisagenlecleucel) and Gilead/Kite's Yescarta™ (axicabtagene ciloleucel) by the FDA further underscores both the promise and legwork to be done if manufacturing processes are to become widely accessible. Further work is needed to standardize, automate, close, and scale production to bring down costs and democratize these and other cell therapies. Given the multiple processing steps involved, commercial-scale manufacturing of these therapies necessitates tighter control over process parameters. This focused review highlights some of the most recent advances used in the manufacturing of therapeutic immune cells, with a focus on T-cells. We summarize key unit operations and pain points around current manufacturing solutions. We also review emerging technologies, approaches and reagents used in cell isolation, activation, transduction, expansion, in-process analytics, harvest, cryopreservation and thaw, and conclude with a forward-look at future directions in the manufacture of adoptive immunotherapies.

Red Cell Alloantibodies in Multiple Transfused Thalassaemia Patients.

PubMed

Chaudhari, C N

2011-01-01

Thalassaemia major patients require lifelong transfusion support due to which they are prone for alloimmunization to foreign RBCs. Alloimmunization can be prevented by extended phenotype match blood transfusion. The study was conducted to know the extent of problem of alloimmunization and to find important red cell antibodies in thalassaemia patients. A cross-sectional study was conducted. A total of 32 thalassaemia patients were enrolled. The specimen was subjected to red cell alloantibody and autoantibody by column gel agglutination technique. R 1 (w) R 1 , R 2 R 2 , rr (papaine and non papain) and 11 cell panel reagent cells were used in screening and identification of alloantibodies respectively. Six (18.8 %) subjects were alloimmunized. All alloimmunized subjects were recipient of more than 20 units of transfusion. Total seven clinically significant alloantibodies were identified. Anti E and anti c were commonest antibodies in four (12.5%) patients. Red cell alloimmunization is an important risk in thalassaemia patient. 71.4% of alloantibodies were anti E and anti c type. Extended phenotype match blood transfusion for Rh-c and Rh-E antigens or level 2 antigen matching stringency needs to be explored in preventing alloimmunization in thalassaemia patients.

How to Make a Synthetic Multicellular Computer

PubMed Central

Macia, Javier; Sole, Ricard

2014-01-01

Biological systems perform computations at multiple scales and they do so in a robust way. Engineering metaphors have often been used in order to provide a rationale for modeling cellular and molecular computing networks and as the basis for their synthetic design. However, a major constraint in this mapping between electronic and wet computational circuits is the wiring problem. Although wires are identical within electronic devices, they must be different when using synthetic biology designs. Moreover, in most cases the designed molecular systems cannot be reused for other functions. A new approximation allows us to simplify the problem by using synthetic cellular consortia where the output of the computation is distributed over multiple engineered cells. By evolving circuits in silico, we can obtain the minimal sets of Boolean units required to solve the given problem at the lowest cost using cellular consortia. Our analysis reveals that the basic set of logic units is typically non-standard. Among the most common units, the so called inverted IMPLIES (N-Implies) appears to be one of the most important elements along with the NOT and AND functions. Although NOR and NAND gates are widely used in electronics, evolved circuits based on combinations of these gates are rare, thus suggesting that the strategy of combining the same basic logic gates might be inappropriate in order to easily implement synthetic computational constructs. The implications for future synthetic designs, the general view of synthetic biology as a standard engineering domain, as well as potencial drawbacks are outlined. PMID:24586222

Unusually large unit cell of lipid bicontinuous cubic phase: towards nature's length scales

NASA Astrophysics Data System (ADS)

Kim, Hojun; Leal, Cecilia

Lipid bicontinuous cubic phases are of great interest for drug delivery, protein crystallization, biosensing, and templates for directing hard material assembly. Structural modulations of lipid mesophases regarding phase identity and unit cell size are often necessary to augment loading and gain pore size control. One important example is the need for unit cells large enough to guide the crystallization of bigger proteins without distortion of the templating phase. In nature, bicontinuous cubic constructs achieve unit cell dimensions as high as 300 nm. However, the largest unit cell of lipid mesophases synthesized in the lab is an order of magnitude lower. In fact, it has been predicted theoretically that lipid bicontinuous cubic phases of unit cell dimensions exceeding 30 nm could not exist, as high membrane fluctuations would damp liquid crystalline order. Here we report non-equilibrium assembly methods of synthesizing metastable bicontinuous cubic phases with unit cell dimensions as high as 70 nm. The phases are stable for very long periods and become increasingly ordered as time goes by without changes to unit cell dimensions. We acknowledge the funding source as a NIH.

Survival of Human Multiple Myeloma Cells Is Dependent on MUC1 C-Terminal Transmembrane Subunit Oncoprotein Function

PubMed Central

Yin, Li; Ahmad, Rehan; Kosugi, Michio; Kufe, Turner; Vasir, Baldev; Avigan, David; Kharbanda, Surender

2010-01-01

The MUC1 C-terminal transmembrane subunit (MUC1-C) oncoprotein is a direct activator of the canonical nuclear factor-κB (NF-κB) RelA/p65 pathway and is aberrantly expressed in human multiple myeloma cells. However, it is not known whether multiple myeloma cells are sensitive to the disruption of MUC1-C function for survival. The present studies demonstrate that peptide inhibitors of MUC1-C oligomerization block growth of human multiple myeloma cells in vitro. Inhibition of MUC1-C function also blocked the interaction between MUC1-C and NF-κB p65 and activation of the NF-κB pathway. In addition, inhibition of MUC1-C in multiple myeloma cells was associated with activation of the intrinsic apoptotic pathway and induction of late apoptosis/necrosis. Primary multiple myeloma cells, but not normal B-cells, were also sensitive to MUC1-C inhibition. Significantly, treatment of established U266 multiple myeloma xenografts growing in nude mice with a lead candidate MUC1-C inhibitor resulted in complete tumor regression and lack of recurrence. These findings indicate that multiple myeloma cells are dependent on intact MUC1-C function for constitutive activation of the canonical NF-κB pathway and for their growth and survival. PMID:20444960

Rhombicuboctahedron unit cell based scaffolds for bone regeneration: geometry optimization with a mechanobiology - driven algorithm.

PubMed

Boccaccio, Antonio; Fiorentino, Michele; Uva, Antonio E; Laghetti, Luca N; Monno, Giuseppe

2018-02-01

In a context more and more oriented towards customized medical solutions, we propose a mechanobiology-driven algorithm to determine the optimal geometry of scaffolds for bone regeneration that is the most suited to specific boundary and loading conditions. In spite of the huge number of articles investigating different unit cells for porous biomaterials, no studies are reported in the literature that optimize the geometric parameters of such unit cells based on mechanobiological criteria. Parametric finite element models of scaffolds with rhombicuboctahedron unit cell were developed and incorporated into an optimization algorithm that combines them with a computational mechanobiological model. The algorithm perturbs iteratively the geometry of the unit cell until the best scaffold geometry is identified, i.e. the geometry that allows to maximize the formation of bone. Performances of scaffolds with rhombicuboctahedron unit cell were compared with those of other scaffolds with hexahedron unit cells. We found that scaffolds with rhombicuboctahedron unit cell are particularly suited for supporting medium-low loads, while, for higher loads, scaffolds with hexahedron unit cells are preferable. The proposed algorithm can guide the orthopaedic/surgeon in the choice of the best scaffold to be implanted in a patient-specific anatomic region. Copyright © 2017 Elsevier B.V. All rights reserved.

Structures of the N-acetyltransferase domain of Xylella fastidiosa N-acetyl-L-glutamate synthase/kinase with and without a His tag bound to N-acetyl-L-glutamate.

PubMed

Zhao, Gengxiang; Jin, Zhongmin; Allewell, Norma M; Tuchman, Mendel; Shi, Dashuang

2015-01-01

Structures of the catalytic N-acetyltransferase (NAT) domain of the bifunctional N-acetyl-L-glutamate synthase/kinase (NAGS/K) from Xylella fastidiosa bound to N-acetyl-L-glutamate (NAG) with and without an N-terminal His tag have been solved and refined at 1.7 and 1.4 Å resolution, respectively. The NAT domain with an N-terminal His tag crystallized in space group P4(1)2(1)2, with unit-cell parameters a=b=51.72, c=242.31 Å. Two subunits form a molecular dimer in the asymmetric unit, which contains ∼41% solvent. The NAT domain without an N-terminal His tag crystallized in space group P21, with unit-cell parameters a=63.48, b=122.34, c=75.88 Å, β=107.6°. Eight subunits, which form four molecular dimers, were identified in the asymmetric unit, which contains ∼38% solvent. The structures with and without the N-terminal His tag provide an opportunity to evaluate how the His tag affects structure and function. Furthermore, multiple subunits in different packing environments allow an assessment of the plasticity of the NAG binding site, which might be relevant to substrate binding and product release. The dimeric structure of the X. fastidiosa N-acetytransferase (xfNAT) domain is very similar to that of human N-acetyltransferase (hNAT), reinforcing the notion that mammalian NAGS is evolutionally derived from bifunctional bacterial NAGS/K.

Neural Representations that Support Invariant Object Recognition

PubMed Central

Goris, Robbe L. T.; Op de Beeck, Hans P.

2008-01-01

Neural mechanisms underlying invariant behaviour such as object recognition are not well understood. For brain regions critical for object recognition, such as inferior temporal cortex (ITC), there is now ample evidence indicating that single cells code for many stimulus aspects, implying that only a moderate degree of invariance is present. However, recent theoretical and empirical work seems to suggest that integrating responses of multiple non-invariant units may produce invariant representations at population level. We provide an explicit test for the hypothesis that a linear read-out mechanism of a pool of units resembling ITC neurons may achieve invariant performance in an identification task. A linear classifier was trained to decode a particular value in a 2-D stimulus space using as input the response pattern across a population of units. Only one dimension was relevant for the task, and the stimulus location on the irrelevant dimension (ID) was kept constant during training. In a series of identification tests, the stimulus location on the relevant dimension (RD) and ID was manipulated, yielding estimates for both the level of sensitivity and tolerance reached by the network. We studied the effects of several single-cell characteristics as well as population characteristics typically considered in the literature, but found little support for the hypothesis. While the classifier averages out effects of idiosyncratic tuning properties and inter-unit variability, its invariance is very much determined by the (hypothetical) ‘average’ neuron. Consequently, even at population level there exists a fundamental trade-off between selectivity and tolerance, and invariant behaviour does not emerge spontaneously. PMID:19242556

77 FR 22561 - Drawn Stainless Steel Sinks From the People's Republic of China: Correction to Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-16

... with multiple bowls that are joined through a welding operation to form one unit are covered by the... bowls that are joined through a welding operation to form one unit are covered by the scope of the... sinks with multiple drawn bowls that are joined through a welding operation to form one unit are covered...

Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells.

PubMed

Brown, Rachel C; Morris, Andrew P; O'Neil, Roger G

2007-01-26

Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions.

TIGHT JUNCTION PROTEIN EXPRESSION AND BARRIER PROPERTIES OF IMMORTALIZED MOUSE BRAIN MICROVESSEL ENDOTHELIAL CELLS

PubMed Central

Brown, Rachel C.; Morris, Andrew P.; O’Neil, Roger G.

2007-01-01

Understanding the molecular and biochemical mechanisms regulating the blood-brain barrier is aided by in vitro model systems. Many studies have used primary cultures of brain microvessel endothelial cells for this purpose. However, primary cultures limit the generation of material for molecular and biochemical assays since cells grow slowly, are prone to contamination by other neurovascular unit cells, and lose blood-brain barrier characteristics when passaged. To address these issues, immortalized cell lines have been generated. In these studies, we assessed the suitability of the immortalized mouse brain endothelial cell line, bEnd3, as a blood-brain barrier model. RT-PCR and immunofluorescence indicated expression of multiple tight junction proteins. bEnd3 cells formed barriers to radiolabeled sucrose, and responded like primary cultures to disrupting stimuli. Exposing cells to serum-free media on their basolateral side significantly decreased paracellular permeability; astrocyte-conditioned media did not enhance barrier properties. The serum-free media-induced decrease in permeability was correlated with an increase in claudin-5 and zonula occludens-1 immunofluorescence at cell-cell contracts. We conclude that bEnd3 cells are an attractive candidate as a model of the blood-brain barrier due to their rapid growth, maintenance of blood-brain barrier characteristics over repeated passages, formation of functional barriers and amenability to numerous molecular interventions. PMID:17169347

Kinetics of Cell Fusion Induced by a Syncytia-Producing Mutant of Herpes Simplex Virus Type I

PubMed Central

Person, Stanley; Knowles, Robert W.; Read, G. Sullivan; Warner, Susan C.; Bond, Vincent C.

1976-01-01

We have isolated a number of plaque-morphology mutants from a strain of herpes simplex virus type I which, unlike the wild type, cause extensive cell fusion during a productive viral infection. After the onset of fusion, there is an exponential decrease in the number of single cells as a function of time after infection. At a multiplicity of infection (MOI) of 3.8 plaque-forming units per cell, fusion begins 5.3 h after infection with the number of single cells decreasing to 10% of the original number 10.2 h after infection. As the MOI is gradually increased from 0.4 to 8, the onset of fusion occurs earlier during infection. However, when the MOI is increased from 8 to 86, the onset of fusion does not occur any earlier. The rate of fusion is independent of the MOI for an MOI greater than 1. The rate of fusion varies linearly with initial cell density up to 3.5 × 104 cells/cm2 and is independent of initial cell density at higher cell concentrations. To assay cell fusion we have developed a simple quantitative assay using a Coulter counter to measure the number of single cells as a function of time after infection. Data obtained using a Coulter counter are similar to those obtained with a microscope assay. PMID:173881

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

Zitney, S.E.

This paper highlights the use of the CAPE-OPEN (CO) standard interfaces in the Advanced Process Engineering Co-Simulator (APECS) developed at the National Energy Technology Laboratory (NETL). The APECS system uses the CO unit operation, thermodynamic, and reaction interfaces to provide its plug-and-play co-simulation capabilities, including the integration of process simulation with computational fluid dynamics (CFD) simulation. APECS also relies heavily on the use of a CO COM/CORBA bridge for running process/CFD co-simulations on multiple operating systems. For process optimization in the face of multiple and some time conflicting objectives, APECS offers stochastic modeling and multi-objective optimization capabilities developed to complymore » with the CO software standard. At NETL, system analysts are applying APECS to a wide variety of advanced power generation systems, ranging from small fuel cell systems to commercial-scale power plants including the coal-fired, gasification-based FutureGen power and hydrogen production plant.« less

Development of an Immunochromatography Assay (QuickNavi-Ebola) to Detect Multiple Species of Ebolaviruses

PubMed Central

Yoshida, Reiko; Muramatsu, Shino; Akita, Hiroshi; Saito, Yuji; Kuwahara, Miwa; Kato, Daisuke; Changula, Katendi; Miyamoto, Hiroko; Kajihara, Masahiro; Manzoor, Rashid; Furuyama, Wakako; Marzi, Andrea; Feldmann, Heinz; Mweene, Aaron; Masumu, Justin; Kapeteshi, Jimmy; Muyembe-Tamfum, Jean-Jacques; Takada, Ayato

2016-01-01

The latest outbreak of Ebola virus disease (EVD) in West Africa has highlighted the urgent need for the development of rapid and reliable diagnostic assays. We used monoclonal antibodies specific to the ebolavirus nucleoprotein to develop an immunochromatography (IC) assay (QuickNavi-Ebola) for rapid diagnosis of EVD. The IC assay was first evaluated with tissue culture supernatants of infected Vero E6 cells and found to be capable of detecting 103–104 focus-forming units/mL of ebolaviruses. Using serum samples from experimentally infected nonhuman primates, we confirmed that the assay could detect the viral antigen shortly after disease onset. It was also noted that multiple species of ebolaviruses could be detected by the IC assay. Owing to the simplicity of the assay procedure and absence of requirements for special equipment and training, QuickNavi-Ebola is expected to be a useful tool for rapid diagnosis of EVD. PMID:27462094

Human in vitro 3D co-culture model to engineer vascularized bone-mimicking tissues combining computational tools and statistical experimental approach.

PubMed

Bersini, Simone; Gilardi, Mara; Arrigoni, Chiara; Talò, Giuseppe; Zamai, Moreno; Zagra, Luigi; Caiolfa, Valeria; Moretti, Matteo

2016-01-01

The generation of functional, vascularized tissues is a key challenge for both tissue engineering applications and the development of advanced in vitro models analyzing interactions among circulating cells, endothelium and organ-specific microenvironments. Since vascularization is a complex process guided by multiple synergic factors, it is critical to analyze the specific role that different experimental parameters play in the generation of physiological tissues. Our goals were to design a novel meso-scale model bridging the gap between microfluidic and macro-scale studies, and high-throughput screen the effects of multiple variables on the vascularization of bone-mimicking tissues. We investigated the influence of endothelial cell (EC) density (3-5 Mcells/ml), cell ratio among ECs, mesenchymal stem cells (MSCs) and osteo-differentiated MSCs (1:1:0, 10:1:0, 10:1:1), culture medium (endothelial, endothelial + angiopoietin-1, 1:1 endothelial/osteo), hydrogel type (100%fibrin, 60%fibrin+40%collagen), tissue geometry (2 × 2 × 2, 2 × 2 × 5 mm(3)). We optimized the geometry and oxygen gradient inside hydrogels through computational simulations and we analyzed microvascular network features including total network length/area and vascular branch number/length. Particularly, we employed the "Design of Experiment" statistical approach to identify key differences among experimental conditions. We combined the generation of 3D functional tissue units with the fine control over the local microenvironment (e.g. oxygen gradients), and developed an effective strategy to enable the high-throughput screening of multiple experimental parameters. Our approach allowed to identify synergic correlations among critical parameters driving microvascular network development within a bone-mimicking environment and could be translated to any vascularized tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electromagnetic reprogrammable coding-metasurface holograms.

PubMed

Li, Lianlin; Jun Cui, Tie; Ji, Wei; Liu, Shuo; Ding, Jun; Wan, Xiang; Bo Li, Yun; Jiang, Menghua; Qiu, Cheng-Wei; Zhang, Shuang

2017-08-04

Metasurfaces have enabled a plethora of emerging functions within an ultrathin dimension, paving way towards flat and highly integrated photonic devices. Despite the rapid progress in this area, simultaneous realization of reconfigurability, high efficiency, and full control over the phase and amplitude of scattered light is posing a great challenge. Here, we try to tackle this challenge by introducing the concept of a reprogrammable hologram based on 1-bit coding metasurfaces. The state of each unit cell of the coding metasurface can be switched between '1' and '0' by electrically controlling the loaded diodes. Our proof-of-concept experiments show that multiple desired holographic images can be realized in real time with only a single coding metasurface. The proposed reprogrammable hologram may be a key in enabling future intelligent devices with reconfigurable and programmable functionalities that may lead to advances in a variety of applications such as microscopy, display, security, data storage, and information processing.Realizing metasurfaces with reconfigurability, high efficiency, and control over phase and amplitude is a challenge. Here, Li et al. introduce a reprogrammable hologram based on a 1-bit coding metasurface, where the state of each unit cell of the coding metasurface can be switched electrically.

On the edge of periodicity: Unconventional magnetism of Gd 117Co 56.4Sn 114.3

DOE PAGES

Liu, J.; Mudryk, Yaroslav; Ryan, D. H.; ...

2017-08-04

Magnetization measurements reveal the onset of magnetic ordering at T C = 65 K followed by three additional magnetic anomalies at T 1 = 47 K, T 2 = 28 K, and T 3 = 11 K in Gd 117Co 56.4Sn 114.3 – a compound with a giant cubic unit cell that crystallizes in the Dy 117Co 56Sn 112 structure type with space group Fm3¯m and lattice parameter a = 30.186 Å. The magnetic ordering temperature increases with applied magnetic field; however, the analysis of magnetic data indicates that antiferromagnetic interactions also play a role in the ground state. ACmore » magnetic susceptibility confirms multiple magnetic anomalies and shows minor frequency dependence. The local magnetic ordering below 60 K is supported by the Mössbauer spectroscopy. A single broad anomaly is detected at T 3 in the heat capacity; we suggest that magnetic domains form below this temperature. Furthermore, these data highlight unique features of magnetism in this and, potentially, other rare-earth intermetallics crystallizing with giant unit-cells where the exchange correlation lengths are much shorter when compared to the periodicity of the crystal lattice.« less

Microelectromechanically tunable multiband metamaterial with preserved isotropy

NASA Astrophysics Data System (ADS)

Pitchappa, Prakash; Ho, Chong Pei; Qian, You; Dhakar, Lokesh; Singh, Navab; Lee, Chengkuo

2015-06-01

We experimentally demonstrate a micromachined reconfigurable metamaterial with polarization independent characteristics for multiple resonances in terahertz spectral region. The metamaterial unit cell consists of eight out-of-plane deformable microcantilevers placed at each corner of an octagon ring. The octagon shaped unit cell geometry provides the desired rotational symmetry, while the out-of-plane movable cantilevers preserves the symmetry at different configurations of the metamaterial. The metamaterial is shown to provide polarization independent response for both electrical inductive-capacitive (eLC) resonance and dipolar resonance at all states of actuation. The proposed metamaterial has a switching range of 0.16 THz and 0.37 THz and a transmission intensity change of more than 0.2 and 0.7 for the eLC and dipolar resonances, respectively for both TE and TM modes. Further optimization of the metal layer thickness, provides an improvement of up to 80% modulation at 0.57 THz. The simultaneously tunable dual band isotropic metamaterial will enable the realization of high performance electro-optic devices that would facilitate numerous terahertz applications such as compressive terahertz imaging, miniaturized terahertz spectroscopy and next generation high speed wireless communication possible in the near future.

A programmable metasurface with dynamic polarization, scattering and focusing control

NASA Astrophysics Data System (ADS)

Yang, Huanhuan; Cao, Xiangyu; Yang, Fan; Gao, Jun; Xu, Shenheng; Li, Maokun; Chen, Xibi; Zhao, Yi; Zheng, Yuejun; Li, Sijia

2016-10-01

Diverse electromagnetic (EM) responses of a programmable metasurface with a relatively large scale have been investigated, where multiple functionalities are obtained on the same surface. The unit cell in the metasurface is integrated with one PIN diode, and thus a binary coded phase is realized for a single polarization. Exploiting this anisotropic characteristic, reconfigurable polarization conversion is presented first. Then the dynamic scattering performance for two kinds of sources, i.e. a plane wave and a point source, is carefully elaborated. To tailor the scattering properties, genetic algorithm, normally based on binary coding, is coupled with the scattering pattern analysis to optimize the coding matrix. Besides, inverse fast Fourier transform (IFFT) technique is also introduced to expedite the optimization process of a large metasurface. Since the coding control of each unit cell allows a local and direct modulation of EM wave, various EM phenomena including anomalous reflection, diffusion, beam steering and beam forming are successfully demonstrated by both simulations and experiments. It is worthwhile to point out that a real-time switch among these functionalities is also achieved by using a field-programmable gate array (FPGA). All the results suggest that the proposed programmable metasurface has great potentials for future applications.

A programmable metasurface with dynamic polarization, scattering and focusing control

PubMed Central

Yang, Huanhuan; Cao, Xiangyu; Yang, Fan; Gao, Jun; Xu, Shenheng; Li, Maokun; Chen, Xibi; Zhao, Yi; Zheng, Yuejun; Li, Sijia

2016-01-01

Diverse electromagnetic (EM) responses of a programmable metasurface with a relatively large scale have been investigated, where multiple functionalities are obtained on the same surface. The unit cell in the metasurface is integrated with one PIN diode, and thus a binary coded phase is realized for a single polarization. Exploiting this anisotropic characteristic, reconfigurable polarization conversion is presented first. Then the dynamic scattering performance for two kinds of sources, i.e. a plane wave and a point source, is carefully elaborated. To tailor the scattering properties, genetic algorithm, normally based on binary coding, is coupled with the scattering pattern analysis to optimize the coding matrix. Besides, inverse fast Fourier transform (IFFT) technique is also introduced to expedite the optimization process of a large metasurface. Since the coding control of each unit cell allows a local and direct modulation of EM wave, various EM phenomena including anomalous reflection, diffusion, beam steering and beam forming are successfully demonstrated by both simulations and experiments. It is worthwhile to point out that a real-time switch among these functionalities is also achieved by using a field-programmable gate array (FPGA). All the results suggest that the proposed programmable metasurface has great potentials for future applications. PMID:27774997

A programmable metasurface with dynamic polarization, scattering and focusing control.

PubMed

Yang, Huanhuan; Cao, Xiangyu; Yang, Fan; Gao, Jun; Xu, Shenheng; Li, Maokun; Chen, Xibi; Zhao, Yi; Zheng, Yuejun; Li, Sijia

2016-10-24

Diverse electromagnetic (EM) responses of a programmable metasurface with a relatively large scale have been investigated, where multiple functionalities are obtained on the same surface. The unit cell in the metasurface is integrated with one PIN diode, and thus a binary coded phase is realized for a single polarization. Exploiting this anisotropic characteristic, reconfigurable polarization conversion is presented first. Then the dynamic scattering performance for two kinds of sources, i.e. a plane wave and a point source, is carefully elaborated. To tailor the scattering properties, genetic algorithm, normally based on binary coding, is coupled with the scattering pattern analysis to optimize the coding matrix. Besides, inverse fast Fourier transform (IFFT) technique is also introduced to expedite the optimization process of a large metasurface. Since the coding control of each unit cell allows a local and direct modulation of EM wave, various EM phenomena including anomalous reflection, diffusion, beam steering and beam forming are successfully demonstrated by both simulations and experiments. It is worthwhile to point out that a real-time switch among these functionalities is also achieved by using a field-programmable gate array (FPGA). All the results suggest that the proposed programmable metasurface has great potentials for future applications.

Investigating the compatibility of PEEK polymer for the fabrication of sample cells for use in muon spin spectroscopy

NASA Astrophysics Data System (ADS)

Chandrasena, L.; McKenzie, I.; Brodovitch, J.-C.; Mozafari, M.; Cottrell, S. P.; Percival, P. W.

2014-12-01

Polyether ether ketone (PEEK) is a thermoplastic polymer with a wide range of applications due to its chemical inertness and thermal stability, and for these reasons sample cells for gas and liquid phase μSR have been constructed from PEEK. Muon levelcrossing resonance (μLCR) studies of PEEK revealed a broad, strong μLCR signal that, we hypothesize, is due to multiple overlapping resonances from the various muonium (Mu) adducts of PEEK. To investigate this, two monomer units from PEEK (4,4'-dihydroxybenzophenone and para-dimethoxybenzene) were studied in solution using transverse-field muon spin rotation (TF-μSR) and μLCR. Two different muoniated radicals were formed by Mu addition to 4,4/- dihydroxybenzophenone and one radical was formed in para-dimethoxybenzene. The μSR spectra were assigned by comparing the experimentally measured muon and proton hyperfine coupling constants with values calculated for the possible structures using Gaussian-09 software with the B3LYP functional and 6-31G basis set. Good agreement was found for cyclohexadienyl- type radicals formed by Mu addition to the benzene rings of the monomer units. We can also infer that these radicals are being formed in PEEK, and based on this we conclude that sample cells made of PEEK are unsuitable for many types of μSR experiment.

Cell-based therapeutic strategies for multiple sclerosis.

PubMed

Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

2017-11-01

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Multicenter COMPACT study of COMplications in patients with sickle cell disease and utilization of iron chelation therapy.

PubMed

Jordan, Lanetta; Adams-Graves, Patricia; Kanter-Washko, Julie; Oneal, Patricia A; Sasane, Medha; Vekeman, Francis; Bieri, Christine; Magestro, Matthew; Marcellari, Andrea; Duh, Mei Sheng

2015-03-01

Over the past few decades, lifespans of sickle cell disease (SCD) patients have increased; hence, they encounter multiple complications. Early detection, appropriate comprehensive care, and treatment may prevent or delay onset of complications. We collected longitudinal data on sickle cell disease (SCD) complication rates and associated resource utilization relative to blood transfusion patterns and iron chelation therapy (ICT) use in patients aged ≥16 years to address a gap in the literature. Medical records of 254 SCD patients ≥16 years were retrospectively reviewed at three US tertiary care centers. We classified patients into cohorts based on cumulative units of blood transfused and ICT history: <15 units, no ICT (Cohort 1 [C1]), ≥15 units, no ICT (Cohort 2 [C2]), and ≥15 units with ICT (Cohort 3 [C3]). We report SCD complication rates per patient per year; cohort comparisons use rate ratios (RRs). Cohorts had 69 (C1), 91 (C2), and 94 (C3) patients. Pain led to most hospitalizations (76%) and emergency department (ED) (82%) visits. Among transfused patients (C2+C3), those receiving ICT were less likely to experience SCD complications than those who did not (RR [95% CI] C2 vs. C3: 1.33 [1.25-1.42]). Similar trends (RR [95% CI]) were observed in ED visits and hospitalizations associated with SCD complications (C2 vs. C3, ED: 1.94 [1.70-2.21]; hospitalizations: 1.61 [1.45-1.78]), but not in outpatient visits. Although the most commonly reported SCD complication among all patients was pain, patients who received ICT were less likely to experience pain and other complications than those who did not. These results highlight the need for increased patient and provider education on the importance of comprehensive disease management.

A method for determining the conversion efficiency of multiple-cell photovoltaic devices

NASA Astrophysics Data System (ADS)

Glatfelter, Troy; Burdick, Joseph

A method for accurately determining the conversion efficiency of any multiple-cell photovoltaic device under any arbitrary reference spectrum is presented. This method makes it possible to obtain not only the short-circuit current, but also the fill factor, the open-circuit voltage, and hence the conversion efficiency of a multiple-cell device under any reference spectrum. Results are presented which allow a comparison of the I-V parameters of two-terminal, two- and three-cell tandem devices measured under a multiple-source simulator with the same parameters measured under different reference spectra. It is determined that the uncertainty in the conversion efficiency of a multiple-cell photovoltaic device obtained with this method is less than +/-3 percent.

KAMO: towards automated data processing for microcrystals.

PubMed

Yamashita, Keitaro; Hirata, Kunio; Yamamoto, Masaki

2018-05-01

In protein microcrystallography, radiation damage often hampers complete and high-resolution data collection from a single crystal, even under cryogenic conditions. One promising solution is to collect small wedges of data (5-10°) separately from multiple crystals. The data from these crystals can then be merged into a complete reflection-intensity set. However, data processing of multiple small-wedge data sets is challenging. Here, a new open-source data-processing pipeline, KAMO, which utilizes existing programs, including the XDS and CCP4 packages, has been developed to automate whole data-processing tasks in the case of multiple small-wedge data sets. Firstly, KAMO processes individual data sets and collates those indexed with equivalent unit-cell parameters. The space group is then chosen and any indexing ambiguity is resolved. Finally, clustering is performed, followed by merging with outlier rejections, and a report is subsequently created. Using synthetic and several real-world data sets collected from hundreds of crystals, it was demonstrated that merged structure-factor amplitudes can be obtained in a largely automated manner using KAMO, which greatly facilitated the structure analyses of challenging targets that only produced microcrystals. open access.

NASA Tech Briefs, April 2009

NASA Technical Reports Server (NTRS)

2009-01-01

Topics covered include: Direct-Solve Image-Based Wavefront Sensing; Use of UV Sources for Detection and Identification of Explosives; Using Fluorescent Viruses for Detecting Bacteria in Water; Gradiometer Using Middle Loops as Sensing Elements in a Low-Field SQUID MRI System; Volcano Monitor: Autonomous Triggering of In-Situ Sensors; Wireless Fluid-Level Sensors for Harsh Environments; Interference-Detection Module in a Digital Radar Receiver; Modal Vibration Analysis of Large Castings; Structural/Radiation-Shielding Epoxies; Integrated Multilayer Insulation; Apparatus for Screening Multiple Oxygen-Reduction Catalysts; Determining Aliasing in Isolated Signal Conditioning Modules; Composite Bipolar Plate for Unitized Fuel Cell/Electrolyzer Systems; Spectrum Analyzers Incorporating Tunable WGM Resonators; Quantum-Well Thermophotovoltaic Cells; Bounded-Angle Iterative Decoding of LDPC Codes; Conversion from Tree to Graph Representation of Requirements; Parallel Hybrid Vehicle Optimal Storage System; and Anaerobic Digestion in a Flooded Densified Leachbed.

Antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity.

PubMed

Shah, Nina; Martin-Antonio, Beatriz; Yang, Hong; Ku, Stephanie; Lee, Dean A; Cooper, Laurence J N; Decker, William K; Li, Sufang; Robinson, Simon N; Sekine, Takuya; Parmar, Simrit; Gribben, John; Wang, Michael; Rezvani, Katy; Yvon, Eric; Najjar, Amer; Burks, Jared; Kaur, Indreshpal; Champlin, Richard E; Bollard, Catherine M; Shpall, Elizabeth J

2013-01-01

Natural killer (NK) cells are important mediators of anti-tumor immunity and are active against several hematologic malignancies, including multiple myeloma (MM). Umbilical cord blood (CB) is a promising source of allogeneic NK cells but large scale ex vivo expansion is required for generation of clinically relevant CB-derived NK (CB-NK) cell doses. Here we describe a novel strategy for expanding NK cells from cryopreserved CB units using artificial antigen presenting feeder cells (aAPC) in a gas permeable culture system. After 14 days, mean fold expansion of CB-NK cells was 1848-fold from fresh and 2389-fold from cryopreserved CB with >95% purity for NK cells (CD56(+)/CD3(-)) and less than 1% CD3(+) cells. Though surface expression of some cytotoxicity receptors was decreased, aAPC-expanded CB-NK cells exhibited a phenotype similar to CB-NK cells expanded with IL-2 alone with respect to various inhibitory receptors, NKG2C and CD94 and maintained strong expression of transcription factors Eomesodermin and T-bet. Furthermore, CB-NK cells formed functional immune synapses with and demonstrated cytotoxicity against various MM targets. Finally, aAPC-expanded CB-NK cells showed significant in vivo activity against MM in a xenogenic mouse model. Our findings introduce a clinically applicable strategy for the generation of highly functional CB-NK cells which can be used to eradicate MM.

Localization of migraine susceptibility genes in human brain by single-cell RNA sequencing.

PubMed

Renthal, William

2018-01-01

Background Migraine is a debilitating disorder characterized by severe headaches and associated neurological symptoms. A key challenge to understanding migraine has been the cellular complexity of the human brain and the multiple cell types implicated in its pathophysiology. The present study leverages recent advances in single-cell transcriptomics to localize the specific human brain cell types in which putative migraine susceptibility genes are expressed. Methods The cell-type specific expression of both familial and common migraine-associated genes was determined bioinformatically using data from 2,039 individual human brain cells across two published single-cell RNA sequencing datasets. Enrichment of migraine-associated genes was determined for each brain cell type. Results Analysis of single-brain cell RNA sequencing data from five major subtypes of cells in the human cortex (neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells) indicates that over 40% of known migraine-associated genes are enriched in the expression profiles of a specific brain cell type. Further analysis of neuronal migraine-associated genes demonstrated that approximately 70% were significantly enriched in inhibitory neurons and 30% in excitatory neurons. Conclusions This study takes the next step in understanding the human brain cell types in which putative migraine susceptibility genes are expressed. Both familial and common migraine may arise from dysfunction of discrete cell types within the neurovascular unit, and localization of the affected cell type(s) in an individual patient may provide insight into to their susceptibility to migraine.

Annular feed air breathing fuel cell stack

DOEpatents

Wilson, Mahlon S.

1996-01-01

A stack of polymer electrolyte fuel cells is formed from a plurality of unit cells where each unit cell includes fuel cell components defining a periphery and distributed along a common axis, where the fuel cell components include a polymer electrolyte membrane, an anode and a cathode contacting opposite sides of the membrane, and fuel and oxygen flow fields contacting the anode and the cathode, respectively, wherein the components define an annular region therethrough along the axis. A fuel distribution manifold within the annular region is connected to deliver fuel to the fuel flow field in each of the unit cells. In a particular embodiment, a single bolt through the annular region clamps the unit cells together. In another embodiment, separator plates between individual unit cells have an extended radial dimension to function as cooling fins for maintaining the operating temperature of the fuel cell stack.

Solid oxide fuel cell with multi-unit construction and prismatic design

DOEpatents

McPheeters, Charles C.; Dees, Dennis W.; Myles, Kevin M.

1999-01-01

A single cell unit of a solid oxide fuel cell that is individually fabricated and sintered prior to being connected to adjacent cells to form a solid oxide fuel cell. The single cell unit is comprised of a shaped anode sheet positioned between a flat anode sheet and an anode-electrolyte-cathode (A/E/C) sheet, and a shaped cathode sheet positioned between the A/E/C sheet and a cathode-interconnect-anode (C/I/A) sheet. An alternate embodiment comprises a shaped cathode sheet positioned between an A/E/C sheet and a C/I/A sheet. The shaped sheets form channels for conducting reactant gases. Each single cell unit is individually sintered to form a finished sub-assembly. The finished sub-assemblies are connected in electrical series by interposing connective material between the end surfaces of adjacent cells, whereby individual cells may be inspected for defects and interchanged with non-defective single cell units.

Regulations and guidelines governing stem cell based products: Clinical considerations

PubMed Central

George, Bobby

2011-01-01

The use of stem cells as medicines is a promising and upcoming area of research as they may be able to help the body to regenerate damaged or lost tissue in a host of diseases like Parkinson′s, multiple sclerosis, heart disease, liver disease, spinal cord damage, cancer and many more. Translating basic stem cell research into routine therapies is a complex multi-step process which entails the challenge related to managing the expected therapeutic benefits with the potential risks while complying with the existing regulations and guidelines. While in the United States (US) and European Union (EU) regulations are in place, in India, we do not have a well-defined regulatory framework for “stem cell based products (SCBP)”. There are several areas that need to be addressed as it is quite different from that of pharmaceuticals. These range from establishing batch consistency, product stability to product safety and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspects. PMID:21897884

48 CFR 1408.802 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PLANNING REQUIRED SOURCES OF SUPPLIES AND SERVICES Acquisition of Printing and Related Supplies 1408.802... the aggregate of multiple pages. Such duplicating units shall require Departmental approval to be... to 2,500 production units in the aggregate of multiple pages. This volume standard is referred to as...

A putative siderophore-interacting protein from the marine bacterium Shewanella frigidimarina NCIMB 400: cloning, expression, purification, crystallization and X-ray diffraction analysis

PubMed Central

Trindade, Inês B.; Fonseca, Bruno M.; Matias, Pedro M.; Louro, Ricardo O.; Moe, Elin

2016-01-01

Siderophore-binding proteins (SIPs) perform a key role in iron acquisition in multiple organisms. In the genome of the marine bacterium Shewanella frigidimarina NCIMB 400, the gene tagged as SFRI_RS12295 encodes a protein from this family. Here, the cloning, expression, purification and crystallization of this protein are reported, together with its preliminary X-ray crystallographic analysis to 1.35 Å resolution. The SIP crystals belonged to the monoclinic space group P21, with unit-cell parameters a = 48.04, b = 78.31, c = 67.71 Å, α = 90, β = 99.94, γ = 90°, and are predicted to contain two molecules per asymmetric unit. Structure determination by molecular replacement and the use of previously determined ∼2 Å resolution SIP structures with ∼30% sequence identity as templates are ongoing. PMID:27599855

Just another abdominal pain? Psoas abscess-like metastasis in large cell lung cancer with adrenal insufficiency

PubMed Central

Bernardino, Vera; Val-Flores, Luis Silva; Lopes Dias, João; Bento, Luís

2015-01-01

The authors report the case of a 69-year-old man with chronic obstructive pulmonary disease and previous pulmonary tuberculosis, who presented to the emergency department with abdominal and low back pain, anorexia and weight loss, rapidly evolving into shock. An initial CT scan revealed pulmonary condensation with associated cavitation and an iliopsoas mass suggestive of a psoas abscess. He was admitted in an intensive care unit unit; after a careful examination and laboratory assessment, the aetiology was yet undisclosed. MRI showed multiple retroperitoneal lymphadenopathies, bulky nodular adrenal lesions and bilateral iliac lytic lesions. Hypocortisolism was detected and treated with steroids. A CT-guided biopsy to the psoas mass and lytic lesions identified infiltration of non-small lung carcinoma. The patient died within days. Psoas metastases and adrenal insufficiency as initial manifestations of malignancy are rare and can be misdiagnosed, particularly in the absence of a known primary tumour. PMID:26063108

Neuromyelitis Optica

MedlinePlus

... from cell to cell. NMO is different from multiple sclerosis (MS). Attacks are usually more severe in NMO ... from cell to cell. NMO is different from multiple sclerosis (MS). Attacks are usually more severe in NMO ...

Characterization of bone marrow derived mesenchymal stem cells in suspension

PubMed Central

2012-01-01

Introduction Bone marrow mesenchymal stem cells (BMMSCs) are a heterogeneous population of postnatal precursor cells with the capacity of adhering to culture dishes generating colony-forming unit-fibroblasts (CFU-F). Here we identify a new subset of BMMSCs that fail to adhere to plastic culture dishes and remain in culture suspension (S-BMMSCs). Methods To catch S-BMMSCs, we used BMMSCs-produced extracellular cell matrix (ECM)-coated dishes. Isolated S-BMMSCs were analyzed by in vitro stem cell analysis approaches, including flow cytometry, inductive multiple differentiation, western blot and in vivo implantation to assess the bone regeneration ability of S-BMMSCs. Furthermore, we performed systemic S-BMMSCs transplantation to treat systemic lupus erythematosus (SLE)-like MRL/lpr mice. Results S-BMMSCs are capable of adhering to ECM-coated dishes and showing mesenchymal stem cell characteristics with distinction from hematopoietic cells as evidenced by co-expression of CD73 or Oct-4 with CD34, forming a single colony cluster on ECM, and failure to differentiate into hematopoietic cell lineage. Moreover, we found that culture-expanded S-BMMSCs exhibited significantly increased immunomodulatory capacities in vitro and an efficacious treatment for SLE-like MRL/lpr mice by rebalancing regulatory T cells (Tregs) and T helper 17 cells (Th17) through high NO production. Conclusions These data suggest that it is feasible to improve immunotherapy by identifying a new subset BMMSCs. PMID:23083975

Structural and functional diversity in Listeria cell wall teichoic acids.

PubMed

Shen, Yang; Boulos, Samy; Sumrall, Eric; Gerber, Benjamin; Julian-Rodero, Alicia; Eugster, Marcel R; Fieseler, Lars; Nyström, Laura; Ebert, Marc-Olivier; Loessner, Martin J

2017-10-27

Wall teichoic acids (WTAs) are the most abundant glycopolymers found on the cell wall of many Gram-positive bacteria, whose diverse surface structures play key roles in multiple biological processes. Despite recent technological advances in glycan analysis, structural elucidation of WTAs remains challenging due to their complex nature. Here, we employed a combination of ultra-performance liquid chromatography-coupled electrospray ionization tandem-MS/MS and NMR to determine the structural complexity of WTAs from Listeria species. We unveiled more than 10 different types of WTA polymers that vary in their linkage and repeating units. Disparity in GlcNAc to ribitol connectivity, as well as variable O -acetylation and glycosylation of GlcNAc contribute to the structural diversity of WTAs. Notably, SPR analysis indicated that constitution of WTA determines the recognition by bacteriophage endolysins. Collectively, these findings provide detailed insight into Listeria cell wall-associated carbohydrates, and will guide further studies on the structure-function relationship of WTAs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Flow cytometry and sorting

NASA Astrophysics Data System (ADS)

Yentsch, Clarice M.

For the first time oceanographers have a tool, known as a flow cytometer and sorter, which is useful for simultaneous measurement of multiple parameters of individual cells and particles at rapid rates. We are now able to exploit the fluorescent capability of pigments and stains as signals to quantify and separate subpopulations of cells and particles in the 1.0 to 150 μm size range. Analysis rates exceed 1000 cells per second and high sensitivity is attained using laser excitation.The addition of this new technology to the ocean sciences will enable researchers to address problems which were previously intractable. The first unit, funded by the Office of Naval Research and the National Science Foundation, will be at Bigelow Laboratory for Ocean Sciences in West Boothbay Harbor, Maine, in the laboratory of Clarice M. Yentsch and David A. Phinney. In anticipation of this award, a workshop course on flow cytometry (FCM) and sorting techniques was held from October 24 through November 1, 1982, at the Bermuda Biological Station.

Lithium-Ion Cell Charge-Control Unit Developed

NASA Technical Reports Server (NTRS)

Reid, Concha M.; Manzo, Michelle A.; Buton, Robert M.; Gemeiner, Russel

2005-01-01

A lithium-ion (Li-ion) cell charge-control unit was developed as part of a Li-ion cell verification program. This unit manages the complex charging scheme that is required when Li-ion cells are charged in series. It enables researchers to test cells together as a pack, while allowing each cell to charge individually. This allows the inherent cell-to-cell variations to be addressed on a series string of cells and reduces test costs substantially in comparison to individual cell testing.

Microfocus diffraction from different regions of a protein crystal: structural variations and unit-cell polymorphism

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

Thompson, Michael C.; Cascio, Duilio; Yeates, Todd O.

Real macromolecular crystals can be non-ideal in a myriad of ways. This often creates challenges for structure determination, while also offering opportunities for greater insight into the crystalline state and the dynamic behavior of macromolecules. To evaluate whether different parts of a single crystal of a dynamic protein, EutL, might be informative about crystal and protein polymorphism, a microfocus X-ray synchrotron beam was used to collect a series of 18 separate data sets from non-overlapping regions of the same crystal specimen. A principal component analysis (PCA) approach was employed to compare the structure factors and unit cells across the datamore » sets, and it was found that the 18 data sets separated into two distinct groups, with largeRvalues (in the 40% range) and significant unit-cell variations between the members of the two groups. This categorization mapped the different data-set types to distinct regions of the crystal specimen. Atomic models of EutL were then refined against two different data sets obtained by separately merging data from the two distinct groups. A comparison of the two resulting models revealed minor but discernable differences in certain segments of the protein structure, and regions of higher deviation were found to correlate with regions where larger dynamic motions were predicted to occur by normal-mode molecular-dynamics simulations. The findings emphasize that large spatially dependent variations may be present across individual macromolecular crystals. This information can be uncovered by simultaneous analysis of multiple partial data sets and can be exploited to reveal new insights about protein dynamics, while also improving the accuracy of the structure-factor data ultimately obtained in X-ray diffraction experiments.« less

Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)

MedlinePlus

... Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key Points ...

A Systematic Analysis of 2 Monoisocentric Techniques for the Treatment of Multiple Brain Metastases.

PubMed

Narayanasamy, Ganesh; Stathakis, Sotirios; Gutierrez, Alonso N; Pappas, Evangelos; Crownover, Richard; Floyd, John R; Papanikolaou, Niko

2017-10-01

In this treatment planning study, we compare the plan quality and delivery parameters for the treatment of multiple brain metastases using 2 monoisocentric techniques: the Multiple Metastases Element from Brainlab and the RapidArc volumetric-modulated arc therapy from Varian Medical Systems. Eight patients who were treated in our institution for multiple metastases (3-7 lesions) were replanned with Multiple Metastases Element using noncoplanar dynamic conformal arcs. The same patients were replanned with the RapidArc technique in Eclipse using 4 noncoplanar arcs. Both techniques were designed using a single isocenter. Plan quality metrics (conformity index, homogeneity index, gradient index, and R 50% ), monitor unit, and the planning time were recorded. Comparison of the Multiple Metastases Element and RapidArc plans was performed using Shapiro-Wilk test, paired Student t test, and Wilcoxon signed rank test. A paired Wilcoxon signed rank test between Multiple Metastases Element and RapidArc showed comparable plan quality metrics and dose to brain. Mean ± standard deviation values of conformity index were 1.8 ± 0.7 and 1.7 ± 0.6, homogeneity index were 1.3 ± 0.1 and 1.3 ± 0.1, gradient index were 5.0 ± 1.8 and 5.1 ± 1.9, and R 50% were 4.9 ± 1.8 and 5.0 ± 1.9 for Multiple Metastases Element and RapidArc plans, respectively. Mean brain dose was 2.3 and 2.7 Gy for Multiple Metastases Element and RapidArc plans, respectively. The mean value of monitor units in Multiple Metastases Element plan was 7286 ± 1065, which is significantly lower than the RapidArc monitor units of 9966 ± 1533 ( P < .05). For the planning of multiple brain lesions to be treated with stereotactic radiosurgery, Multiple Metastases Element planning software produced equivalent conformity, homogeneity, dose falloff, and brain V 12 Gy but required significantly lower monitor units, when compared to RapidArc plans.

A Systematic Analysis of 2 Monoisocentric Techniques for the Treatment of Multiple Brain Metastases

PubMed Central

Stathakis, Sotirios; Gutierrez, Alonso N.; Pappas, Evangelos; Crownover, Richard; Floyd, John R.; Papanikolaou, Niko

2016-01-01

Background: In this treatment planning study, we compare the plan quality and delivery parameters for the treatment of multiple brain metastases using 2 monoisocentric techniques: the Multiple Metastases Element from Brainlab and the RapidArc volumetric-modulated arc therapy from Varian Medical Systems. Methods: Eight patients who were treated in our institution for multiple metastases (3-7 lesions) were replanned with Multiple Metastases Element using noncoplanar dynamic conformal arcs. The same patients were replanned with the RapidArc technique in Eclipse using 4 noncoplanar arcs. Both techniques were designed using a single isocenter. Plan quality metrics (conformity index, homogeneity index, gradient index, and R50%), monitor unit, and the planning time were recorded. Comparison of the Multiple Metastases Element and RapidArc plans was performed using Shapiro-Wilk test, paired Student t test, and Wilcoxon signed rank test. Results: A paired Wilcoxon signed rank test between Multiple Metastases Element and RapidArc showed comparable plan quality metrics and dose to brain. Mean ± standard deviation values of conformity index were 1.8 ± 0.7 and 1.7 ± 0.6, homogeneity index were 1.3 ± 0.1 and 1.3 ± 0.1, gradient index were 5.0 ± 1.8 and 5.1 ± 1.9, and R50% were 4.9 ± 1.8 and 5.0 ± 1.9 for Multiple Metastases Element and RapidArc plans, respectively. Mean brain dose was 2.3 and 2.7 Gy for Multiple Metastases Element and RapidArc plans, respectively. The mean value of monitor units in Multiple Metastases Element plan was 7286 ± 1065, which is significantly lower than the RapidArc monitor units of 9966 ± 1533 (P < .05). Conclusion: For the planning of multiple brain lesions to be treated with stereotactic radiosurgery, Multiple Metastases Element planning software produced equivalent conformity, homogeneity, dose falloff, and brain V12 Gy but required significantly lower monitor units, when compared to RapidArc plans. PMID:27612917

Abuse and Resilience in Relation to HAART Medication Adherence and HIV Viral Load Among Women with HIV in the United States

PubMed Central

Cohen, Mardge; Weber, Kathleen; Cruise, Ruth; Kelso, Gwendolyn

2014-01-01

Abstract Abuse is highly prevalent among HIV+ women, leading to behaviors, including lower adherence to highly active antiretroviral therapy (HAART) that result in poor health outcomes. Resilience (functioning competently despite adversity) may buffer the negative effects of abuse. This study investigated how resilience interacted with abuse history in relation to HAART adherence, HIV viral load (VL), and CD4+ cell count among a convenience sample of 138 HIV+ women from the Ruth M. Rothstein CORE Center/Cook County Health and Hospital Systems site of the Women's Interagency HIV Study (WIHS). Resilience was measured by the 10-item Connor-Davidson Resilience Scale (CD-RISC). HAART adherence (≥95% vs. <95% self reported usage of prescribed medication) and current or prior sexual, physical, or emotional/domestic abuse, were reported during structured interviews. HIV viral load (≥20 vs. <20 copies/mL) and CD4+ count (200 vs. <200 cells/mm) were measured with blood specimens. Multiple logistic regressions, controlling for age, race, income, enrollment wave, substance use, and depressive symptoms, indicated that each unit increase in resilience was significantly associated with an increase in the odds of having ≥95% HAART adherence and a decrease in the odds of having a detectable viral load. Resilience-Abuse interactions showed that only among HIV+ women with sexual abuse or multiple abuses did resilience significantly relate to an increase in the odds of ≥95% HAART adherence. Interventions to improve coping strategies that promote resilience among HIV+ women may be beneficial for achieving higher HAART adherence and viral suppression. PMID:24568654

CDC Grand Rounds: Improving the Lives of Persons with Sickle Cell Disease.

PubMed

Hulihan, Mary; Hassell, Kathryn L; Raphael, Jean L; Smith-Whitley, Kim; Thorpe, Phoebe

2017-11-24

Approximately 100,000 Americans have sickle cell disease (SCD), a group of recessively inherited red blood cell disorders characterized by abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in the red blood cells. Persons with hemoglobin SS or hemoglobin Sß 0 thalassemia, also known as sickle cell anemia (SCA), have the most severe form of SCD. Hemoglobin SC disease and hemoglobin Sß + thalassemia are other common forms of SCD. Red blood cells that contain sickle hemoglobin are inflexible and can stick to vessel walls, causing a blockage that slows or stops blood flow. When this happens, oxygen cannot reach nearby tissues, leading to attacks of sudden, severe pain, called pain crises, which are the clinical hallmark of SCD. The red cell sickling and poor oxygen delivery can also cause damage to the brain, spleen, eyes, lungs, liver, and multiple other organs and organ systems. These chronic complications can lead to increased morbidity, early mortality, or both. Tremendous strides in treating and preventing the complications of SCD have extended life expectancy. Now, nearly 95% of persons born with SCD in the United States reach age 18 years (1); however, adults with the most severe forms of SCD have a life span that is 20-30 years shorter than that of persons without SCD (2).

Holocentromeres in Rhynchospora are associated with genome-wide centromere-specific repeat arrays interspersed among euchromatin.

PubMed

Marques, André; Ribeiro, Tiago; Neumann, Pavel; Macas, Jiří; Novák, Petr; Schubert, Veit; Pellino, Marco; Fuchs, Jörg; Ma, Wei; Kuhlmann, Markus; Brandt, Ronny; Vanzela, André L L; Beseda, Tomáš; Šimková, Hana; Pedrosa-Harand, Andrea; Houben, Andreas

2015-11-03

Holocentric chromosomes lack a primary constriction, in contrast to monocentrics. They form kinetochores distributed along almost the entire poleward surface of the chromatids, to which spindle fibers attach. No centromere-specific DNA sequence has been found for any holocentric organism studied so far. It was proposed that centromeric repeats, typical for many monocentric species, could not occur in holocentrics, most likely because of differences in the centromere organization. Here we show that the holokinetic centromeres of the Cyperaceae Rhynchospora pubera are highly enriched by a centromeric histone H3 variant-interacting centromere-specific satellite family designated "Tyba" and by centromeric retrotransposons (i.e., CRRh) occurring as genome-wide interspersed arrays. Centromeric arrays vary in length from 3 to 16 kb and are intermingled with gene-coding sequences and transposable elements. We show that holocentromeres of metaphase chromosomes are composed of multiple centromeric units rather than possessing a diffuse organization, thus favoring the polycentric model. A cell-cycle-dependent shuffling of multiple centromeric units results in the formation of functional (poly)centromeres during mitosis. The genome-wide distribution of centromeric repeat arrays interspersing the euchromatin provides a previously unidentified type of centromeric chromatin organization among eukaryotes. Thus, different types of holocentromeres exist in different species, namely with and without centromeric repetitive sequences.

Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

MedlinePlus

... Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key Points ...

Treatment Option Overview (Plasma Cell Neoplasms Including Multiple Myeloma)

MedlinePlus

... Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key Points ...

Simulation of deleterious processes in a static-cell diode pumped alkali laser

NASA Astrophysics Data System (ADS)

Oliker, Benjamin Q.; Haiducek, John D.; Hostutler, David A.; Pitz, Greg A.; Rudolph, Wolfgang; Madden, Timothy J.

2014-02-01

The complex interactions in a diode pumped alkali laser (DPAL) gain cell provide opportunities for multiple deleterious processes to occur. Effects that may be attributable to deleterious processes have been observed experimentally in a cesium static-cell DPAL at the United States Air Force Academy [B.V. Zhdanov, J. Sell, R.J. Knize, "Multiple laser diode array pumped Cs laser with 48 W output power," Electronics Letters, 44, 9 (2008)]. The power output in the experiment was seen to go through a "roll-over"; the maximum power output was obtained with about 70 W of pump power, then power output decreased as the pump power was increased beyond this point. Research to determine the deleterious processes that caused this result has been done at the Air Force Research Laboratory utilizing physically detailed simulation. The simulations utilized coupled computational fluid dynamics (CFD) and optics solvers, which were three-dimensional and time-dependent. The CFD code used a cell-centered, conservative, finite-volume discretization of the integral form of the Navier-Stokes equations. It included thermal energy transport and mass conservation, which accounted for chemical reactions and state kinetics. Optical models included pumping, lasing, and fluorescence. The deleterious effects investigated were: alkali number density decrease in high temperature regions, convective flow, pressure broadening and shifting of the absorption lineshape including hyperfine structure, radiative decay, quenching, energy pooling, off-resonant absorption, Penning ionization, photoionization, radiative recombination, three-body recombination due to free electron and buffer gas collisions, ambipolar diffusion, thermal aberration, dissociative recombination, multi-photon ionization, alkali-hydrocarbon reactions, and electron impact ionization.

Multiple sclerosis and human T-cell lymphotropic retroviruses

NASA Astrophysics Data System (ADS)

Koprowski, Hilary; Defreitas, Elaine C.; Harper, Mary E.; Sandberg-Wollheim, Magnhild; Sheremata, William A.; Robert-Guroff, Marjorie; Saxinger, Carl W.; Feinberg, Mark B.; Wong-Staal, Flossie; Gallo, Robert C.

1985-11-01

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Microphotographs of cyanobacteria documenting the effects of various cell-lysis techniques

USGS Publications Warehouse

Rosen, Barry H.; Loftin, Keith A.; Smith, Christopher E.; Lane, Rachael F.; Keydel, Susan P.

2011-01-01

Cyanotoxins are a group of organic compounds biosynthesized intracellularly by many species of cyanobacteria found in surface water. The United States Environmental Protection Agency has listed cyanotoxins on the Safe Drinking Water Act's Contaminant Candidate List 3 for consideration for future regulation to protect public health. Cyanotoxins also pose a risk to humans and other organisms in a variety of other exposure scenarios. Accurate and precise analytical measurements of cyanotoxins are critical to the evaluation of concentrations in surface water to address the human health and ecosystem effects. A common approach to total cyanotoxin measurement involves cell membrane disruption to release the cyanotoxins to the dissolved phase followed by filtration to remove cellular debris. Several methods have been used historically, however no standard protocols exist to ensure this process is consistent between laboratories before the dissolved phase is measured by an analytical technique for cyanotoxin identification and quantitation. No systematic evaluation has been conducted comparing the multiple laboratory sample processing techniques for physical disruption of cell membrane or cyanotoxins recovery. Surface water samples collected from lakes, reservoirs, and rivers containing mixed assemblages of organisms dominated by cyanobacteria, as well as laboratory cultures of species-specific cyanobacteria, were used as part of this study evaluating multiple laboratory cell-lysis techniques in partnership with the U.S. Environmental Protection Agency. Evaluated extraction techniques included boiling, autoclaving, sonication, chemical treatment, and freeze-thaw. Both treated and untreated samples were evaluated for cell membrane integrity microscopically via light, epifluorescence, and epifluorescence in the presence of a DNA stain. The DNA stain, which does not permeate live cells with intact membrane structures, was used as an indicator for cyanotoxin release into the dissolved phase. Of the five techniques, sonication (at 70 percent) was most effective at complete cell destruction while QuikLyse (Trademarked) was least effective. Autoclaving, boiling, and sequential freeze-thaw were moderately effective in physical destruction of colonies and filaments.

Pathogen inactivation by riboflavin and ultraviolet light illumination accelerates the red blood cell storage lesion and promotes eryptosis.

PubMed

Qadri, Syed M; Chen, Deborah; Schubert, Peter; Perruzza, Darian L; Bhakta, Varsha; Devine, Dana V; Sheffield, William P

2017-03-01

Pathogen reduction treatment using riboflavin and ultraviolet light illumination (Mirasol) effectively reduces the risk of transfusion-transmitted infections. This treatment is currently licensed for only platelets and plasma products, while its application to whole blood (WB) to generate pathogen-inactivated red blood cells (RBCs) is under development. RBC storage lesion, constituting numerous morphologic and biochemical changes, influences RBC quality and limits shelf life. Stored RBCs further show enhanced susceptibility to RBC programmed cell death (eryptosis) characterized by increased cytosolic Ca 2+ -provoked membrane phosphatidylserine (PS) externalization. Using a "pool-and-split" approach, we examined multiple variables of RBC storage lesion and eryptosis in RBC units, derived from Mirasol-treated or untreated WB, after 4 to 42 days of storage, under blood bank conditions. In comparison to untreated RBC units, Mirasol treatment significantly altered membrane microvesiculation, supernatant hemoglobin, osmotic fragility, and intracellular adenosine triphosphate levels but did not influence membrane CD47 expression and 2,3-diphosphoglycerate levels. Mirasol-treated RBCs showed significantly higher PS exposure after 42, but not after not more than 21, days of storage, which was accompanied by enhanced cytosolic Ca 2+ activity, ceramide abundance, and oxidative stress, but not p38 kinase activation. Mirasol treatment significantly augmented PS exposure, Ca 2+ entry, and protein kinase C activation after energy depletion, a pathophysiologic cell stressor. Mirasol-treated RBCs were, however, more resistant to cell shrinkage. Prolonged storage of Mirasol-treated RBCs significantly increases the proportion of eryptotic RBCs, while even short-term storage enhances the susceptibility of RBCs to stress-induced eryptosis, which could reduce posttransfusion RBC recovery in patients. © 2016 AABB.

Recycling domains in plant cell morphogenesis: small GTPase effectors, plasma membrane signalling and the exocyst.

PubMed

Zárský, Viktor; Potocký, Martin

2010-04-01

The Rho/Rop small GTPase regulatory module is central for initiating exocytotically ACDs (active cortical domains) in plant cell cortex, and a growing array of Rop regulators and effectors are being discovered in plants. Structural membrane phospholipids are important constituents of cells as well as signals, and phospholipid-modifying enzymes are well known effectors of small GTPases. We have shown that PLDs (phospholipases D) and their product, PA (phosphatidic acid), belong to the regulators of the secretory pathway in plants. We have also shown that specific NOXs (NADPH oxidases) producing ROS (reactive oxygen species) are involved in cell growth as exemplified by pollen tubes and root hairs. Most plant cells exhibit several distinct plasma membrane domains (ACDs), established and maintained by endocytosis/exocytosis-driven membrane protein recycling. We proposed recently the concept of a 'recycling domain' (RD), uniting the ACD and the connected endosomal recycling compartment (endosome), as a dynamic spatiotemporal entity. We have described a putative GTPase-effector complex exocyst involved in exocytic vesicle tethering in plants. Owing to the multiplicity of its Exo70 subunits, this complex, along with many RabA GTPases (putative recycling endosome organizers), may belong to core regulators of RD organization in plants.

Successful choice behavior is associated with distinct and coherent network states in anterior cingulate cortex

PubMed Central

Lapish, Christopher C.; Durstewitz, Daniel; Chandler, L. Judson; Seamans, Jeremy K.

2008-01-01

Successful decision making requires an ability to monitor contexts, actions, and outcomes. The anterior cingulate cortex (ACC) is thought to be critical for these functions, monitoring and guiding decisions especially in challenging situations involving conflict and errors. A number of different single-unit correlates have been observed in the ACC that reflect the diverse cognitive components involved. Yet how ACC neurons function as an integrated network is poorly understood. Here we show, using advanced population analysis of multiple single-unit recordings from the rat ACC during performance of an ecologically valid decision-making task, that ensembles of neurons move through different coherent and dissociable states as the cognitive requirements of the task change. This organization into distinct network patterns with respect to both firing-rate changes and correlations among units broke down during trials with numerous behavioral errors, especially at choice points of the task. These results point to an underlying functional organization into cell assemblies in the ACC that may monitor choices, outcomes, and task contexts, thus tracking the animal's progression through “task space.” PMID:18708525

Genetically engineered humanized anti-ganglioside GM2 antibody against multiple organ metastasis produced by GM2-expressing small-cell lung cancer cells.

PubMed

Yamada, Tadaaki; Bando, Hideaki; Takeuchi, Shinji; Kita, Kenji; Li, Qi; Wang, Wei; Akinaga, Shiro; Nishioka, Yasuhiko; Sone, Saburo; Yano, Seiji

2011-12-01

Small-cell lung cancer (SCLC) grows rapidly and metastasizes to multiple organs. We examined the antimetastatic effects of the humanized anti-ganglioside GM2 (GM2) antibodies, BIW-8962 and KM8927, compared with the chimeric antibody KM966, in a SCID mouse model of multiple organ metastases induced by GM2-expressing SCLC cells. BIW-8962 and KM8927 induced higher antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity than KM966 against the GM2-expressing SCLC cell line SBC-3 in vitro. These humanized antibodies inhibited the production of multiple organ metastases, increased the number of apoptotic cells, and prolonged the survival of the SCID mice. Histological analyses using clinical specimens showed that SCLC cells expressed GM2. These findings suggest that humanized anti-GM2 antibodies could be therapeutically useful for controlling multiple organ metastases of GM2-expressing SCLC. © 2011 Japanese Cancer Association.

The mechanism of synthesis of a mixed-linkage (1-->3), (1-->4)beta-D-glucan in maize. Evidence for multiple sites of glucosyl transfer in the synthase complex

PubMed

Buckeridge; Vergara; Carpita

1999-08-01

We examined the mechanism of synthesis in vitro of (1-->3), (1-->4)beta-D-glucan (beta-glucan), a growth-specific cell wall polysaccharide found in grasses and cereals. beta-Glucan is composed primarily of cellotriosyl and cellotetraosyl units linked by single (1-->3)beta-linkages. The ratio of cellotriosyl and cellotetraosyl units in the native polymer is strictly controlled at between 2 and 3 in all grasses, whereas the ratios of these units in beta-glucan formed in vitro vary from 1.5 with 5 &mgr;M UDP-glucose (Glc) to over 11 with 30 mM substrate. These results support a model in which three sites of glycosyl transfer occur within the synthase complex to produce the cellobiosyl-(1-->3)-D-glucosyl units. We propose that failure to fill one of the sites results in the iterative addition of one or more cellobiosyl units to produce the longer cellodextrin units in the polymer. Variations in the UDP-Glc concentration in excised maize (Zea mays) coleoptiles did not result in wide variations in the ratios of cellotriosyl and cellotetraosyl units in beta-glucan synthesized in vivo, indicating that other factors control delivery of UDP-Glc to the synthase. In maize sucrose synthase is enriched in Golgi membranes and plasma membranes and may be involved in the control of substrate delivery to beta-glucan synthase and cellulose synthase.

Floating point only SIMD instruction set architecture including compare, select, Boolean, and alignment operations

DOEpatents

Gschwind, Michael K [Chappaqua, NY

2011-03-01

Mechanisms for implementing a floating point only single instruction multiple data instruction set architecture are provided. A processor is provided that comprises an issue unit, an execution unit coupled to the issue unit, and a vector register file coupled to the execution unit. The execution unit has logic that implements a floating point (FP) only single instruction multiple data (SIMD) instruction set architecture (ISA). The floating point vector registers of the vector register file store both scalar and floating point values as vectors having a plurality of vector elements. The processor may be part of a data processing system.

The temporal representation of the delay of dynamic iterated rippled noise with positive and negative gain by single units in the ventral cochlear nucleus.

PubMed

Sayles, Mark; Winter, Ian Michael

2007-09-26

Spike trains were recorded from single units in the ventral cochlear nucleus of the anaesthetised guinea-pig in response to dynamic iterated rippled noise with positive and negative gain. The short-term running waveform autocorrelation functions of these stimuli show peaks at integer multiples of the time-varying delay when the gain is +1, and troughs at odd-integer multiples and peaks at even-integer multiples of the time-varying delay when the gain is -1. In contrast, the short-term autocorrelation of the Hilbert envelope shows peaks at integer multiples of the time-varying delay for both positive and negative gain stimuli. A running short-term all-order interspike interval analysis demonstrates the ability of single units to represent the modulated pitch contour in their short-term interval statistics. For units with low best frequency (approximate < or = 1.1 kHz) the temporal discharge pattern reflected the waveform fine structure regardless of unit classification (Primary-like, Chopper). For higher best frequency units the pattern of response varied according to unit type. Chopper units with best frequency approximate > or = 1.1 kHz responded to envelope modulation; showing no difference between their response to stimuli with positive and negative gain. Primary-like units with best frequencies in the range 1-3 kHz were still able to represent the difference in the temporal fine structure between dynamic rippled noise with positive and negative gain. No unit with a best frequency above 3 kHz showed a response to the temporal fine structure. Chopper units in this high frequency group showed significantly greater representation of envelope modulation relative to primary-like units with the same range of best frequencies. These results show that at the level of the cochlear nucleus there exists sufficient information in the time domain to represent the time-varying pitch associated with dynamic iterated rippled noise.

Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

ClinicalTrials.gov

2017-10-23

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

HIV dynamics with multiple infections of target cells.

PubMed

Dixit, Narendra M; Perelson, Alan S

2005-06-07

The high incidence of multiple infections of cells by HIV sets the stage for rapid HIV evolution by means of recombination. Yet how HIV dynamics proceeds with multiple infections remains poorly understood. Here, we present a mathematical model that describes the dynamics of viral, target cell, and multiply infected cell subpopulations during HIV infection. Model calculations reproduce several experimental observations and provide key insights into the influence of multiple infections on HIV dynamics. We find that the experimentally observed scaling law, that the number of cells coinfected with two distinctly labeled viruses is proportional to the square of the total number of infected cells, can be generalized so that the number of triply infected cells is proportional to the cube of the number of infected cells, etc. Despite the expectation from Poisson statistics, we find that this scaling relationship only holds under certain conditions, which we predict. We also find that multiple infections do not influence viral dynamics when the rate of viral production from infected cells is independent of the number of times the cells are infected, a regime expected when viral production is limited by cellular rather than viral factors. This result may explain why extant models, which ignore multiple infections, successfully describe viral dynamics in HIV patients. Inhibiting CD4 down-modulation increases the average number of infections per cell. Consequently, altering CD4 down-modulation may allow for an experimental determination of whether viral or cellular factors limit viral production.

HIV dynamics with multiple infections of target cells

PubMed Central

Dixit, Narendra M.; Perelson, Alan S.

2005-01-01

The high incidence of multiple infections of cells by HIV sets the stage for rapid HIV evolution by means of recombination. Yet how HIV dynamics proceeds with multiple infections remains poorly understood. Here, we present a mathematical model that describes the dynamics of viral, target cell, and multiply infected cell subpopulations during HIV infection. Model calculations reproduce several experimental observations and provide key insights into the influence of multiple infections on HIV dynamics. We find that the experimentally observed scaling law, that the number of cells coinfected with two distinctly labeled viruses is proportional to the square of the total number of infected cells, can be generalized so that the number of triply infected cells is proportional to the cube of the number of infected cells, etc. Despite the expectation from Poisson statistics, we find that this scaling relationship only holds under certain conditions, which we predict. We also find that multiple infections do not influence viral dynamics when the rate of viral production from infected cells is independent of the number of times the cells are infected, a regime expected when viral production is limited by cellular rather than viral factors. This result may explain why extant models, which ignore multiple infections, successfully describe viral dynamics in HIV patients. Inhibiting CD4 down-modulation increases the average number of infections per cell. Consequently, altering CD4 down-modulation may allow for an experimental determination of whether viral or cellular factors limit viral production. PMID:15928092

Indirect rapid prototyping of sol-gel hybrid glass scaffolds for bone regeneration - Effects of organic crosslinker valence, content and molecular weight on mechanical properties.

PubMed

Hendrikx, Stephan; Kascholke, Christian; Flath, Tobias; Schumann, Dirk; Gressenbuch, Mathias; Schulze, F Peter; Hacker, Michael C; Schulz-Siegmund, Michaela

2016-04-15

We present a series of organic/inorganic hybrid sol-gel derived glasses, made from a tetraethoxysilane-derived silica sol (100% SiO2) and oligovalent organic crosslinkers functionalized with 3-isocyanatopropyltriethoxysilane. The material was susceptible to heat sterilization. The hybrids were processed into pore-interconnected scaffolds by an indirect rapid prototyping method, described here for the first time for sol-gel glass materials. A large panel of polyethylene oxide-derived 2- to 4-armed crosslinkers of molecular weights ranging between 170 and 8000Da were incorporated and their effect on scaffold mechanical properties was investigated. By multiple linear regression, 'organic content' and the 'content of ethylene oxide units in the hybrid' were identified as the main factors that determined compressive strength and modulus, respectively. In general, 3- and 4-armed crosslinkers performed better than linear molecules. Compression tests and cell culture experiments with osteoblast-like SaOS-2 cells showed that macroporous scaffolds can be produced with compressive strengths of up to 33±2MPa and with a pore structure that allows cells to grow deep into the scaffolds and form mineral deposits. Compressive moduli between 27±7MPa and 568±98MPa were obtained depending on the hybrid composition and problems associated with the inherent brittleness of sol-gel glass materials could be overcome. SaOS-2 cells showed cytocompatibility on hybrid glass scaffolds and mineral accumulation started as early as day 7. On day 14, we also found mineral accumulation on control hybrid glass scaffolds without cells, indicating a positive effect of the hybrid glass on mineral accumulation. We produced a hybrid sol-gel glass material with significantly improved mechanical properties towards an application in bone regeneration and processed the material into macroporous scaffolds of controlled architecture by indirect rapid prototyping. We were able to produce macroporous materials of relevant porosity and pore size with compressive moduli, covering the range reported for cancellous bone while an even higher compressive strength was maintained. By multiple linear regression, we identified crosslinker parameters, namely organic content and the content of ethylene oxide units in the hybrids that predominantly determined the mechanics of the hybrid materials. The scaffolds proved to be cytocompatible and induced mineralization in SaOS-2 cells. This provides new insight on the critical parameters for the design of the organic components of covalent hybrid sol-gel glasses. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bryostatin and Vincristine in B-Cell Malignancies

ClinicalTrials.gov

2013-01-10

Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Multiple Myeloma

Multiple-reflection optical gas cell

DOEpatents

Matthews, Thomas G.

1983-01-01

A multiple-reflection optical cell for Raman or fluorescence gas analysis consists of two spherical mirrors positioned transverse to a multiple-pass laser cell in a confronting plane-parallel alignment. The two mirrors are of equal diameter but possess different radii of curvature. The spacing between the mirrors is uniform and less than half of the radius of curvature of either mirror. The mirror of greater curvature possesses a small circular portal in its center which is the effective point source for conventional F1 double lens collection optics of a monochromator-detection system. Gas to be analyzed is flowed into the cell and irradiated by a multiply-reflected composite laser beam centered between the mirrors of the cell. Raman or fluorescence radiation originating from a large volume within the cell is (1) collected via multiple reflections with the cell mirrors, (2) partially collimated and (3) directed through the cell portal in a geometric array compatible with F1 collection optics.

Annular feed air breathing fuel cell stack

DOEpatents

Wilson, Mahlon S.; Neutzler, Jay K.

1997-01-01

A stack of polymer electrolyte fuel cells is formed from a plurality of unit cells where each unit cell includes fuel cell components defining a periphery and distributed along a common axis, where the fuel cell components include a polymer electrolyte membrane, an anode and a cathode contacting opposite sides of the membrane, and fuel and oxygen flow fields contacting the anode and the cathode, respectively, wherein the components define an annular region therethrough along the axis. A fuel distribution manifold within the annular region is connected to deliver fuel to the fuel flow field in each of the unit cells. The fuel distribution manifold is formed from a hydrophilic-like material to redistribute water produced by fuel and oxygen reacting at the cathode. In a particular embodiment, a single bolt through the annular region clamps the unit cells together. In another embodiment, separator plates between individual unit cells have an extended radial dimension to function as cooling fins for maintaining the operating temperature of the fuel cell stack.

Solid oxide fuel cell with multi-unit construction and prismatic design

DOEpatents

McPheeters, C.C.; Dees, D.W.; Myles, K.M.

1999-03-16

A single cell unit of a solid oxide fuel cell is described that is individually fabricated and sintered prior to being connected to adjacent cells to form a solid oxide fuel cell. The single cell unit is comprised of a shaped anode sheet positioned between a flat anode sheet and an anode-electrolyte-cathode (A/E/C) sheet, and a shaped cathode sheet positioned between the A/E/C sheet and a cathode-interconnect-anode (C/I/A) sheet. An alternate embodiment comprises a shaped cathode sheet positioned between an A/E/C sheet and a C/I/A sheet. The shaped sheets form channels for conducting reactant gases. Each single cell unit is individually sintered to form a finished sub-assembly. The finished sub-assemblies are connected in electrical series by interposing connective material between the end surfaces of adjacent cells, whereby individual cells may be inspected for defects and interchanged with non-defective single cell units. 7 figs.

Differentiation and Characterization of Myeloid Cells

PubMed Central

Gupta, Dipti; Shah, Hetavi Parag; Malu, Krishnakumar; Berliner, Nancy; Gaines, Peter

2015-01-01

Recent molecular studies of myeloid differentiation have utilized several in vitro models of myelopoiesis, generated from either ex vivo differentiated bone marrow progenitors or induced immortalized myeloid cell lines. Ex vivo differentiation begins with an enriched population of bone marrow-derived hematopoietic stem cells generated by lineage depletion and/or positive selection for CD34+ antigen (human) or Sca-1+ (mouse) cells, which are then expanded and subsequently induced in vitro in a process that recapitulates normal myeloid development. Myeloid cell lines include two human leukemic cell lines, NB-4 and HL-60, which have been demonstrated to undergo retinoic acid–induced myeloid development, however, both cell lines exhibit defects in the upregulation of late-expressed neutrophil-specific genes. Multiple murine factor–dependent cell models of myelopoiesis are also available that express the full range of neutrophil maturation markers, including: 32Dcl3 cells, which undergo G-CSF-induced myeloid maturation, EML/EPRO cells, which develop into mature neutrophils in response to cytokines and retinoic acid, and ER-Hoxb8 cells, which undergo myeloid maturation upon removal of estradial in the maintenance medium. In this unit, the induction of myeloid maturation in each of these model systems is described, including their differentiation to either neutrophils or macrophages, if applicable. Commonly used techniques to test for myeloid characteristics of developing cells are also described, including flow cytometry and real time RT-PCR. Together, these assays provide a solid foundation for in vitro investigations of myeloid development with either human or mouse models. PMID:24510620

Fresenius AS.TEC204 blood cell separator.

PubMed

Sugai, Mikiya

2003-02-01

Fresenius AS.TEC204 is a third-generation blood cell separator that incorporates the continuous centrifugal separation method and automatic control of the cell separation process. Continuous centrifugation separates cell components according to their specific gravity, and different cell components are either harvested or eliminated as needed. The interface between the red blood cell and plasma is optically detected, and the Interface Control (IFC) cooperates with different pumps, monitors and detectors to harvest required components automatically. The system is composed of three major sections; the Front Panel Unit; the Pump Unit, and the Centrifuge Unit. This unit can be used for a wide variety of clinical applications including collection of platelets, peripheral blood stem cells, bone marrow stem cells, granulocytes, mononuclear cells, and exchange of plasma or red cells, and for plasma treatment.

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

Huang, Er-Wen; Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou; Xue, Sheng-Jiang

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation,more » facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.« less

Buckling behavior of origami unit cell facets under compressive loads

NASA Astrophysics Data System (ADS)

Kshad, Mohamed Ali Emhmed; Naguib, Hani E.

2018-03-01

Origami structures as cores for sandwich structures are designed to withstand the compressive loads and to dissipate compressive energy. The deformation of the origami panels and the unit cell facets are the primary factors behind the compressive energy dissipation in origami structures. During the loading stage, the origami structures deform through the folding and unfolding process of the unit cell facets, and also through the plastic deformation of the facets. This work presents a numerical study of the buckling behavior of different origami unit cell elements under compressive loading. The studied origami configurations were Miura and Ron-Resch-like origami structures. Finite element package was used to model the origami structures. The study investigated the buckling behavior of the unit cell facets of two types of origami structures Miura origami and Ron-Resch-Like origami structures. The simulation was conducted using ANSYS finite element software, in which the model of the unit cell represented by shell elements, and the eigenvalues buckling solver was used to predict the theoretical buckling of the unit cell elements.

Approximating the stress field within the unit cell of a fabric reinforced composite using replacement elements

NASA Technical Reports Server (NTRS)

Foye, R. L.

1993-01-01

This report concerns the prediction of the elastic moduli and the internal stresses within the unit cell of a fabric reinforced composite. In the proposed analysis no restrictions or assumptions are necessary concerning yarn or tow cross-sectional shapes or paths through the unit cell but the unit cell itself must be a right hexagonal parallelepiped. All the unit cell dimensions are assumed to be small with respect to the thickness of the composite structure that it models. The finite element analysis of a unit cell is usually complicated by the mesh generation problems and the non-standard, adjacent-cell boundary conditions. This analysis avoids these problems through the use of preprogrammed boundary conditions and replacement materials (or elements). With replacement elements it is not necessary to match all the constitutional material interfaces with finite element boundaries. Simple brick-shaped elements can be used to model the unit cell structure. The analysis predicts the elastic constants and the average stresses within each constituent material of each brick element. The application and results of this analysis are demonstrated through several example problems which include a number of composite microstructures.

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

Beckman, D.E.

The structures of 0-0-dimethyl-0-(3,5,6-trichloro-2-pyridyl) phosphorothioate (Dowco 214) and dicarbonylbis(eta-cyclopentadienyl)-..mu..-carbonyl-..mu..-thiocarbonyldiiron have been solved by single crystal x-ray diffraction and use of a modified Patterson superposition technique that uses two multiple vectors to define a structural parallelogram. This method results in a simpler and more accurate shift vector position determination and a general improvement in map clarity. Dowco 214 crystallizes in the space group P/sub 1//sup -/ with a = 11.598(2) A, b = 13.619(3) A, c = 8.281(1) A, ..cap alpha.. = 94.65(1)/sup 0/, ..beta.. = 94.87(2)/sup 0/, ..gamma.. = 79.97(2)/sup 0/ and four molecules per cell (two per asymmetric unit).more » A CNDO II calculation was performed and partial charge densities assigned. The molecule contains distances between positively charged centers that correspond well to the reported anionic-esteratic distance (a possible reaction variable) in AChE. Additional reaction variables are discussed. Cp/sub 2/Fe/sub 2/(CO)/sub 3/CS crystallizes in the space group P2/sub 1//c with a = 14.508(8) A, b = 13.618(5) A, c = 15.193(7) A, ..beta.. = 110.50(6)/sup 0/ and eight molecules per unit cell (two per asymmetric unit). The compound contains both a carbonyl and thiocarbonyl bridge and ..pi..-bonded cyclopentadienyl rings that are cis to one another. The iron--iron bond length is intermediate to that of its carbonyl and thiocarbonyl analogs.« less

The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells.

PubMed

Machado-Santos, Joana; Saji, Etsuji; Tröscher, Anna R; Paunovic, Manuela; Liblau, Roland; Gabriely, Galina; Bien, Christian G; Bauer, Jan; Lassmann, Hans

2018-06-04

Multiple sclerosis is an inflammatory demyelinating disease in which active demyelination and neurodegeneration are associated with lymphocyte infiltrates in the brain. However, so far little is known regarding the phenotype and function of these infiltrating lymphocyte populations. In this study, we performed an in-depth phenotypic characterization of T and B cell infiltrates in a large set of multiple sclerosis cases with different disease and lesion stages and compared the findings with those seen in inflammatory, non-inflammatory and normal human controls. In multiple sclerosis lesions, we found a dominance of CD8+ T cells and a prominent contribution of CD20+ B cells in all disease courses and lesion stages, including acute multiple sclerosis cases with very short disease duration, while CD4+ T cells were sparse. A dominance of CD8+ T cells was also seen in other inflammatory controls, such as Rasmussen's encephalitis and viral encephalitis, but the contribution of B cells in these diseases was modest. Phenotypic analysis of the CD8+ T cells suggested that part of the infiltrating cells in active lesions proliferate, show an activated cytotoxic phenotype and are in part destroyed by apoptosis. Further characterization of the remaining cells suggest that CD8+ T cells acquire features of tissue-resident memory cells, which may be focally reactivated in active lesions of acute, relapsing and progressive multiple sclerosis, while B cells, at least in part, gradually transform into plasma cells. The loss of surface molecules involved in the egress of leucocytes from inflamed tissue, such as S1P1 or CCR7, and the upregulation of CD103 expression may be responsible for the compartmentalization of the inflammatory response in established lesions. Similar phenotypic changes of tissue-infiltrating CD8+ T cells were also seen in Rasmussen's encephalitis. Our data underline the potential importance of CD8+ T lymphocytes and B cells in the inflammatory response in established multiple sclerosis lesions. Tissue-resident T and B cells may represent guardians of previous inflammatory brain disease, which can be reactivated and sustain the inflammatory response, when they are re-exposed to their specific antigen.

Alveolar Soft Part Sarcoma Presenting as Hypervascular Adrenal Metastasis

PubMed Central

Goroshi, Manjunath; Lila, Anurag R.; Bandgar, Tushar; Shah, Nalini S.

2018-01-01

Hypervascular adrenal masses include pheochromocytoma, metastases caused by clear renal cell carcinoma/hepatocellular carcinoma. Alveolar soft part sarcoma (ASPS) causing hypervascular metastases is not described in the literature. Here, we describe the first case of ASPS presenting as hypervascular metastasis. Our case was a 23-year-old male incidentally detected right adrenal mass during the evaluation of pain in the abdomen. On computed tomography (CT), adrenal mass showed bright enhancement in early arterial phase (unenhanced Hounsfield unit [HU]-45.3; arterial phase HU-158.2). 18- flurodeoxyglucose positron emission tomography/CT showed multiple lesions and was confirmed histologically to be due to ASPS. PMID:29398970

Broadband full-color multichannel hologram with geometric metasurface.

PubMed

Qin, F F; Liu, Z Z; Zhang, Z; Zhang, Q; Xiao, J J

2018-04-30

Due to the abilities of manipulating the wavefront of light with well-controlled amplitude, and phase and polarization, optical metasurfaces are very suitable for optical holography, enabling applications with multiple functionalities and high data capacity. Here, we demonstrate encoding two- and three-dimensional full-color holographic images by an ultrathin metasurface hologram whose unit cells are subwavelength nanoslits with spatially varying orientations. We further show that it is possible to achieve full-color holographic multiplexing with such kind of geometric metasurfaces, realized by a synthetic spectrum holographic algorithm. Our results provide an efficient way to design multi-color optical display elements that are ready for fabrication.

Low-Power Differential SRAM design for SOC Based on the 25-um Technology

NASA Astrophysics Data System (ADS)

Godugunuri, Sivaprasad; Dara, Naveen; Sambasiva Nayak, R.; Nayeemuddin, Md; Singh, Yadu, Dr.; Veda, R. N. S. Sunil

2017-08-01

In recent, the SOC styles area unit the vast complicated styles in VLSI these SOC styles having important low-power operations problems, to comprehend this we tend to enforced low-power SRAM. However these SRAM Architectures critically affects the entire power of SOC and competitive space. To beat the higher than disadvantages, during this paper, a low-power differential SRAM design is planned. The differential SRAM design stores multiple bits within the same cell, operates at minimum in operation low-tension and space per bit. The differential SRAM design designed supported the 25-um technology using Tanner-EDA Tool.

The centrifuge facility - A life sciences research laboratory for Space Station Freedom

NASA Technical Reports Server (NTRS)

Fuller, Charles A.; Johnson, Catherine C.; Hargens, Alan R.

1991-01-01

The paper describes the centrifugal facility that is presently being developed by NASA for studies aboard the Space Station Freedom on the role of gravity, or its absence, at varying intensities for varying periods of time and with multiple model systems. Special attention is given to the design of the centrifuge system, the habitats designed to hold plants and animals, the glovebox system designed for experimental manipulations of the specimens, and the service unit. Studies planned for the facility will include experiments in the following disciplines: cell and developmental biology, plant biology, regulatory physiology, musculoskeletal physiology, behavior and performance, neurosciences, cardiopulmonary physiology, and environmental health and radiation.

Contribution of radon and radon daughters to respiratory cancer.

PubMed Central

Harley, N; Samet, J M; Cross, F T; Hess, T; Muller, J; Thomas, D

1986-01-01

This article reviews studies on the contribution of radon and radon daughters to respiratory cancer and proposes recommendations for further research, particularly a national radon survey. The steady-state outdoor radon concentration averages 200 pCi/m3, and indoor levels are about 4 times higher. The primary source of radon in homes is the underlying soil; entry depends on multiple variables and reduced ventilation for energy conservation increases indoor radon levels. Occupational exposures are expressed in units of radon daughter potential energy concentration or working level (WL). Cumulative exposure is the product of the working level and the time exposed. The unit for cumulative exposure is the working level month (WLM). The occupational standard for radon exposure is 4 WLM/year, and 2 WLM/year has been suggested as a guideline for remedial action in homes. Epidemiologic studies show that miners with cumulative radon daughter exposures somewhat below 100 WLM have excess lung cancer mortality. Some 3% to 8% of miners studied have developed lung cancer attributable to radon daughters. All of the underground mining studies show an increased risk of lung cancer with radon daughter exposure. All cell types of lung cancer increased with radon exposure. If radon and smoking act in a multiplicative manner, then the risk for smokers could be 10 times that for nonsmokers. The potential risk of lung cancer appears to be between 1 and 2 per 10,000/WLM, which yields a significant number of lung cancers as some 220 million persons in the United States are exposed on average to 10 to 20 WLM/lifetime. PMID:3830103

Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells.

PubMed

Sundaresan, Sinju; Meininger, Cameron A; Kang, Anthony J; Photenhauer, Amanda L; Hayes, Michael M; Sahoo, Nirakar; Grembecka, Jolanta; Cierpicki, Tomasz; Ding, Lin; Giordano, Thomas J; Else, Tobias; Madrigal, David J; Low, Malcolm J; Campbell, Fiona; Baker, Ann-Marie; Xu, Haoxing; Wright, Nicholas A; Merchant, Juanita L

2017-12-01

The multiple endocrine neoplasia, type 1 (MEN1) locus encodes the nuclear protein and tumor suppressor menin. MEN1 mutations frequently cause neuroendocrine tumors such as gastrinomas, characterized by their predominant duodenal location and local metastasis at time of diagnosis. Diffuse gastrin cell hyperplasia precedes the appearance of MEN1 gastrinomas, which develop within submucosal Brunner's glands. We investigated how menin regulates expression of the gastrin gene and induces generation of submucosal gastrin-expressing cell hyperplasia. Primary enteric glial cultures were generated from the VillinCre:Men1 FL/FL :Sst -/- mice or C57BL/6 mice (controls), with or without inhibition of gastric acid by omeprazole. Primary enteric glial cells from C57BL/6 mice were incubated with gastrin and separated into nuclear and cytoplasmic fractions. Cells were incubated with forskolin and H89 to activate or inhibit protein kinase A (a family of enzymes whose activity depends on cellular levels of cyclic AMP). Gastrin was measured in blood, tissue, and cell cultures using an ELISA. Immunoprecipitation with menin or ubiquitin was used to demonstrate post-translational modification of menin. Primary glial cells were incubated with leptomycin b and MG132 to block nuclear export and proteasome activity, respectively. We obtained human duodenal, lymph node, and pancreatic gastrinoma samples, collected from patients who underwent surgery from 1996 through 2007 in the United States or the United Kingdom. Enteric glial cells that stained positive for glial fibrillary acidic protein (GFAP+) expressed gastrin de novo through a mechanism that required PKA. Gastrin-induced nuclear export of menin via cholecystokinin B receptor (CCKBR)-mediated activation of PKA. Once exported from the nucleus, menin was ubiquitinated and degraded by the proteasome. GFAP and other markers of enteric glial cells (eg, p75 and S100B), colocalized with gastrin in human duodenal gastrinomas. MEN1-associated gastrinomas, which develop in the submucosa, might arise from enteric glial cells through hormone-dependent PKA signaling. This pathway disrupts nuclear menin function, leading to hypergastrinemia and associated sequelae. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Discrimination of taste qualities among mouse fungiform taste bud cells.

PubMed

Yoshida, Ryusuke; Miyauchi, Aya; Yasuo, Toshiaki; Jyotaki, Masafumi; Murata, Yoshihiro; Yasumatsu, Keiko; Shigemura, Noriatsu; Yanagawa, Yuchio; Obata, Kunihiko; Ueno, Hiroshi; Margolskee, Robert F; Ninomiya, Yuzo

2009-09-15

Multiple lines of evidence from molecular studies indicate that individual taste qualities are encoded by distinct taste receptor cells. In contrast, many physiological studies have found that a significant proportion of taste cells respond to multiple taste qualities. To reconcile this apparent discrepancy and to identify taste cells that underlie each taste quality, we investigated taste responses of individual mouse fungiform taste cells that express gustducin or GAD67, markers for specific types of taste cells. Type II taste cells respond to sweet, bitter or umami tastants, express taste receptors, gustducin and other transduction components. Type III cells possess putative sour taste receptors, and have well elaborated conventional synapses. Consistent with these findings we found that gustducin-expressing Type II taste cells responded best to sweet (25/49), bitter (20/49) or umami (4/49) stimuli, while all GAD67 (Type III) taste cells examined (44/44) responded to sour stimuli and a portion of them showed multiple taste sensitivities, suggesting discrimination of each taste quality among taste bud cells. These results were largely consistent with those previously reported with circumvallate papillae taste cells. Bitter-best taste cells responded to multiple bitter compounds such as quinine, denatonium and cyclohexamide. Three sour compounds, HCl, acetic acid and citric acid, elicited responses in sour-best taste cells. These results suggest that taste cells may be capable of recognizing multiple taste compounds that elicit similar taste sensation. We did not find any NaCl-best cells among the gustducin and GAD67 taste cells, raising the possibility that salt sensitive taste cells comprise a different population.

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

PubMed

Gledhill, Karl; Guo, Zongyou; Umegaki-Arao, Noriko; Higgins, Claire A; Itoh, Munenari; Christiano, Angela M

2015-01-01

The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

Analysis of long-time operation of micro-cogeneration unit with fuel cell

NASA Astrophysics Data System (ADS)

Patsch, Marek; Čaja, Alexander

2015-05-01

Micro-cogeneration is cogeneration with small performance, with maximal electric power up to 50 kWe. On the present, there are available small micro-cogeneration units with small electric performance, about 1 kWe, which are usable also in single family houses or flats. These micro-cogeneration units operate on principle of conventional combustion engine, Stirling engine, steam engine or fuel cell. Micro-cogeneration units with fuel cells are new progressive developing type of units for single family houses. Fuel cell is electrochemical device which by oxidation-reduction reaction turn directly chemical energy of fuel to electric power, secondary products are pure water and thermal energy. The aim of paper is measuring and evaluation of operation parameters of micro-cogeneration unit with fuel cell which uses natural gas as a fuel.

Selection of transduced CD34+ progenitors and enzymatic correction of cells from Gaucher patients, with bicistronic vectors.

PubMed Central

Migita, M; Medin, J A; Pawliuk, R; Jacobson, S; Nagle, J W; Anderson, S; Amiri, M; Humphries, R K; Karlsson, S

1995-01-01

The gene transfer efficiency of human hematopoietic stem cells is still inadequate for efficient gene therapy of most disorders. To overcome this problem, a selectable retroviral vector system for gene therapy has been developed for gene therapy of Gaucher disease. We constructed a bicistronic retroviral vector containing the human glucocerebrosidase (GC) cDNA and the human small cell surface antigen CD24 (243 bp). Expression of both cDNAs was controlled by the long terminal repeat enhancer/promoter of the Molony murine leukemia virus. The CD24 selectable marker was placed downstream of the GC cDNA and its translation was enhanced by inclusion of the long 5' untranslated region of encephalomyocarditis virus internal ribosomal entry site. Virus-producing GP+envAM12 cells were created by multiple supernatant transductions to create vector producer cells. The vector LGEC has a high titer and can drive expression of GC and the cell surface antigen CD24 simultaneously in transduced NIH 3T3 cells and Gaucher skin fibroblasts. These transduced cells have been successfully separated from untransduced cells by fluorescence-activated cell sorting, based on cell surface expression of CD24. Transduced and sorted NIH 3T3 cells showed higher GC enzyme activity than the unsorted population, demonstrating coordinated expression of both genes. Fibroblasts from Gaucher patients were transduced and sorted for CD24 expression, and GC enzyme activity was measured. The transduced sorted Gaucher fibroblasts had a marked increase in enzyme activity (149%) compared with virgin Gaucher fibroblasts (17% of normal GC enzyme activity). Efficient transduction of CD34+ hematopoietic progenitors (20-40%) was accomplished and fluorescence-activated cell sorted CD24(+)-expressing progenitors generated colonies, all of which (100%) were vector positive. The sorted, CD24-expressing progenitors generated erythroid burst-forming units, colony-forming units (CFU)-granulocyte, CFU-macrophage, CFU-granulocyte/macrophage, and CFU-mix hematopoietic colonies, demonstrating their ability to differentiate into these myeloid lineages in vitro. The transduced, sorted progenitors raised the GC enzyme levels in their progeny cells manyfold compared with untransduced CD34+ progenitors. Collectively, this demonstrates the development of high titer, selectable bicistronic vectors that allow isolation of transduced hematopoietic progenitors and cells that have been metabolically corrected. Images Fig. 2 Fig. 3 PMID:8618847

Neural Stem Cell or Human Induced Pluripotent Stem Cell-derived GABA-ergic Progenitor Cell Grafting in an Animal Model of Chronic Temporal Lobe Epilepsy

PubMed Central

Upadhya, Dinesh; Hattiangady, Bharathi; Shetty, Geetha A.; Zanirati, Gabriele; Kodali, Maheedhar; Shetty, Ashok K.

2016-01-01

Grafting of neural stem cells (NSCs) or GABA-ergic progenitor cells (GPCs) into the hippocampus could offer an alternative therapy to hippocampal resection in patients with drug-resistant chronic epilepsy, which afflicts >30% of temporal lobe epilepsy (TLE) cases. Multipotent, self-renewing NSCs could be expanded from multiple regions of the developing and adult brain, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). On the other hand, GPCs could be generated from the medial and lateral ganglionic eminences of the embryonic brain and from hESCs and hiPSCs. To provide comprehensive methodologies involved in testing the efficacy of transplantation of NSCs and GPCs in a rat model of chronic TLE, NSCs derived from the rat medial ganglionic eminence (MGE) and MGE-like GPCs derived from hiPSCs are taken as examples in this unit. The topics comprise description of the required materials, reagents and equipment, methods for obtaining rat MGE-NSCs and hiPSC-derived MGE-like GPCs in culture, generation of chronically epileptic rats, intrahippocampal grafting procedure, post-grafting evaluation of the effects of grafts on spontaneous recurrent seizures and cognitive and mood impairments, analyses of the yield and the fate of graft-derived cells, and the effects of grafts on the host hippocampus. PMID:27532817

Association between number of cell phone contracts and brain tumor incidence in nineteen U.S. States.

PubMed

Lehrer, Steven; Green, Sheryl; Stock, Richard G

2011-02-01

Some concern has arisen about adverse health effects of cell phones, especially the possibility that the low power microwave-frequency signal transmitted by the antennas on handsets might cause brain tumors or accelerate the growth of subclinical tumors. We analyzed data from the Statistical Report: Primary Brain Tumors in the United States, 2000-2004 and 2007 cell phone subscription data from the Governing State and Local Sourcebook. There was a significant correlation between number of cell phone subscriptions and brain tumors in nineteen US states (r = 0.950, P < 0.001). Because increased numbers of both cell phone subscriptions and brain tumors could be due solely to the fact that some states, such as New York, have much larger populations than other states, such as North Dakota, multiple linear regression was performed with number of brain tumors as the dependent variable, cell phone subscriptions, population, mean family income and mean age as independent variables. The effect of cell phone subscriptions was significant (P = 0.017), and independent of the effect of mean family income (P = 0.894), population (P = 0.003) and age (0.499). The very linear relationship between cell phone usage and brain tumor incidence is disturbing and certainly needs further epidemiological evaluation. In the meantime, it would be prudent to limit exposure to all sources of electro-magnetic radiation.

Recycled Cell Phones - A Treasure Trove of Valuable Metals

USGS Publications Warehouse

Sullivan, Daniel E.

2006-01-01

This U.S. Geological Survey (USGS) Fact Sheet examines the potential value of recycling the metals found in obsolete cell phones. Cell phones seem ubiquitous in the United States and commonplace throughout most of the world. There were approximately 1 billion cell phones in use worldwide in 2002. In the United States, the number of cell phone subscribers increased from 340,000 in 1985 to 180 million in 2004. Worldwide, cell phone sales have increased from slightly more than 100 million units per year in 1997 to an estimated 779 million units per year in 2005. Cell phone sales are projected to exceed 1 billion units per year in 2009, with an estimated 2.6 billion cell phones in use by the end of that year. The U.S. Environmental Protection Agency estimated that, by 2005, as many as 130 million cell phones would be retired annually in the United States. The nonprofit organization INFORM, Inc., anticipated that, by 2005, a total of 500 million obsolete cell phones would have accumulated in consumers' desk drawers, store rooms, or other storage, awaiting disposal. Typically, cell phones are used for only 1 1/2 years before being replaced. Less than 1 percent of the millions of cell phones retired and discarded annually are recycled. When large numbers of cell phones become obsolete, large quantities of valuable metals end up either in storage or in landfills. The amount of metals potentially recoverable would make a significant addition to total metals recovered from recycling in the United States and would supplement virgin metals derived from mining.

Unit: Making Life Easier, Inspection Pack, National Trial Print.

ERIC Educational Resources Information Center

Australian Science Education Project, Toorak, Victoria.

As a part of the unit materials in the series produced by the Australian Science Education Project, this teacher edition is primarily composed of three sections: a core relating to a bicycle, tests, and options. The core is concerned with basic properties of a machine such as force multiplication, speed multiplication, energy dissipation, and…

Units Coordination and the Construction of Improper Fractions: A Revision of the Splitting Hypothesis

ERIC Educational Resources Information Center

Hackenberg, Amy J.

2007-01-01

This article communicates findings from a year-long constructivist teaching experiment about the relationship between four sixth-grade students' multiplicative structures and their construction of improper fractions. Students' multiplicative structures are the units coordinations that they can take as given prior to activity--i.e., the units…

Report to the House and Senate Appropriations Committees: the safety of push-pull and multiple-unit locomotive passenger rail operations

DOT National Transportation Integrated Search

2006-06-30

This report contains the results of a study by the Federal Railroad Administration (FRA) on the safety of push-pull and multiple-unit (MU) locomotive passenger rail operations. The report addresses the following two questions: (1) Based on recent acc...

Multiple gap photovoltaic device

DOEpatents

Dalal, Vikram L.

1981-01-01

A multiple gap photovoltaic device having a transparent electrical contact adjacent a first cell which in turn is adjacent a second cell on an opaque electrical contact, includes utilizing an amorphous semiconductor as the first cell and a crystalline semiconductor as the second cell.

Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma.

PubMed

Teoh, G; Anderson, K C

1997-02-01

Adhesion molecules play an important role in the growth regulation and migration of multiple myeloma (MM) cells. They mediate homing of MM cells to the bone marrow and MM cell to bone marrow stromal cell adhesion, with resultant interleukin-6 related autocrine and paracine growth and antiapoptotic affects. Their pattern of expression on tumor cells correlates with the development of plasma cell leukemia or extramedullary disease. Clinically, expression of adhesion molecules on tumor cells or in the serum has already shown prognostic utility. Finally, since adhesion molecules are involved at multiple steps in the pathogenesis of MM, therapeutic studies may target these molecules.

Multi-service small-cell cloud wired/wireless access network based on tunable optical frequency comb

NASA Astrophysics Data System (ADS)

Xiang, Yu; Zhou, Kun; Yang, Liu; Pan, Lei; Liao, Zhen-wan; Zhang, Qiang

2015-11-01

In this paper, we demonstrate a novel multi-service wired/wireless integrated access architecture of cloud radio access network (C-RAN) based on radio-over-fiber passive optical network (RoF-PON) system, which utilizes scalable multiple- frequency millimeter-wave (MF-MMW) generation based on tunable optical frequency comb (TOFC). In the baseband unit (BBU) pool, the generated optical comb lines are modulated into wired, RoF and WiFi/WiMAX signals, respectively. The multi-frequency RoF signals are generated by beating the optical comb line pairs in the small cell. The WiFi/WiMAX signals are demodulated after passing through the band pass filter (BPF) and band stop filter (BSF), respectively, whereas the wired signal can be received directly. The feasibility and scalability of the proposed multi-service wired/wireless integrated C-RAN are confirmed by the simulations.

Advances in high gradient normal conducting accelerator structures

DOE PAGES

Simakov, Evgenya Ivanovna; Dolgashev, Valery A.; Tantawi, Sami G.

2018-03-09

Here, this paper reviews the current state-of-the-art in understanding the phenomena of ultra-high vacuum radio-frequency (rf) breakdown in accelerating structures and the efforts to improve stable operation of the structures at accelerating gradients above 100 MV/m. Numerous studies have been conducted recently with the goal of understanding the dependence of the achievable accelerating gradients and breakdown rates on the frequency of operations, the geometry of the structure, material and method of fabrication, and operational temperature. Tests have been conducted with single standing wave accelerator cells as well as with the multi-cell traveling wave structures. Notable theoretical effort was directed atmore » understanding the physical mechanisms of the rf breakdown and its statistical behavior. Finally, the achievements presented in this paper are the result of the large continuous self-sustaining collaboration of multiple research institutions in the United States and worldwide.« less

Advances in high gradient normal conducting accelerator structures

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

Simakov, Evgenya Ivanovna; Dolgashev, Valery A.; Tantawi, Sami G.

Here, this paper reviews the current state-of-the-art in understanding the phenomena of ultra-high vacuum radio-frequency (rf) breakdown in accelerating structures and the efforts to improve stable operation of the structures at accelerating gradients above 100 MV/m. Numerous studies have been conducted recently with the goal of understanding the dependence of the achievable accelerating gradients and breakdown rates on the frequency of operations, the geometry of the structure, material and method of fabrication, and operational temperature. Tests have been conducted with single standing wave accelerator cells as well as with the multi-cell traveling wave structures. Notable theoretical effort was directed atmore » understanding the physical mechanisms of the rf breakdown and its statistical behavior. Finally, the achievements presented in this paper are the result of the large continuous self-sustaining collaboration of multiple research institutions in the United States and worldwide.« less

Real-World Conundrums and Biases in the Use of White Cell Growth Factors.

PubMed

Smith, Thomas J; Hillner, Bruce E

2016-01-01

We present the 2015 American Society of Clinical Oncology (ASCO) white cell growth factors, or colony-stimulating factor (CSF), guidelines, updated from 2006. One new indication has been added-dose-intense chemotherapy for bladder cancer-to accompany the existing use for dose-dense breast cancer chemotherapy. Colony-stimulating factors remain appropriate for any regimen where the risk of febrile neutropenia is about 20% per cycle and dose reduction is not appropriate. Based on new evidence from multiple trials, CSF use is no longer indicated in treatment of lymphoma unless there are special risk factors. The United States accounts for 78% of the sales of CSF. The panel approved the use of all biosimilars, but the cost savings will be small as the price is about 80% of the branded CSFs. More biosimilars at lower cost are awaited. Methods to reduce use without harm to patients, by requiring justification according to accepted guidelines, are ongoing.

Simulation of spread and control of lesions in brain.

PubMed

Thamattoor Raman, Krishna Mohan

2012-01-01

A simulation model for the spread and control of lesions in the brain is constructed using a planar network (graph) representation for the central nervous system (CNS). The model is inspired by the lesion structures observed in the case of multiple sclerosis (MS), a chronic disease of the CNS. The initial lesion site is at the center of a unit square and spreads outwards based on the success rate in damaging edges (axons) of the network. The damaged edges send out alarm signals which, at appropriate intensity levels, generate programmed cell death. Depending on the extent and timing of the programmed cell death, the lesion may get controlled or aggravated akin to the control of wild fires by burning of peripheral vegetation. The parameter phase space of the model shows smooth transition from uncontrolled situation to controlled situation. The simulations show that the model is capable of generating a wide variety of lesion growth and arrest scenarios.

Rapid learning in visual cortical networks.

PubMed

Wang, Ye; Dragoi, Valentin

2015-08-26

Although changes in brain activity during learning have been extensively examined at the single neuron level, the coding strategies employed by cell populations remain mysterious. We examined cell populations in macaque area V4 during a rapid form of perceptual learning that emerges within tens of minutes. Multiple single units and LFP responses were recorded as monkeys improved their performance in an image discrimination task. We show that the increase in behavioral performance during learning is predicted by a tight coordination of spike timing with local population activity. More spike-LFP theta synchronization is correlated with higher learning performance, while high-frequency synchronization is unrelated with changes in performance, but these changes were absent once learning had stabilized and stimuli became familiar, or in the absence of learning. These findings reveal a novel mechanism of plasticity in visual cortex by which elevated low-frequency synchronization between individual neurons and local population activity accompanies the improvement in performance during learning.

Generation of Micropatterned Substrates Using Micro Photopatterning

PubMed Central

Doyle, Andrew D.

2010-01-01

Micro photopatterning (µPP) has been developed to rapidly test and generate different patterns for extracellular matrix adsorption without being hindered with the process of making physical stamps through nanolithography techniques. It uses two-photon excitation guided through a point-scanning confocal microscope to locally photoablate poly(vinyl) alcohol (PVA) thin films in user-defined computer-controlled patterns. PVA thin films are ideal for surface blocking, being hydrophilic substrates that deter protein adsorption and cell attachment. Because gold substrates are not used during µPP, all live-cell fluorescent imaging techniques including total internal reflection fluorescence microscopy of GFP–linked proteins can be performed with minimal loss of fluorescence signal. Furthermore, because µPP does not require physical stamps for pattern generation, multiple ECMs or other proteins can be localized within microns of each other. This unit details the setup of µPP as well as giving troubleshooting techniques. PMID:20013752

Multiple pass gas absorption cell utilizing a spherical mirror opposite one or more pair of obliquely disposed flat mirrors

NASA Technical Reports Server (NTRS)

Pearson, Richard (Inventor); Lynch, Dana H. (Inventor); Gunter, William D. (Inventor)

1995-01-01

A method and apparatus for passing light bundles through a multiple pass sampling cell is disclosed. The multiple pass sampling cell includes a sampling chamber having first and second ends positioned along a longitudinal axis of the sampling cell. The sampling cell further includes an entrance opening, located adjacent the first end of the sampling cell at a first azimuthal angular position. The entrance opening permits a light bundle to pass into the sampling cell. The sampling cell also includes an exit opening at a second azimuthal angular position. The light exit permits a light bundle to pass out of the sampling cell after the light bundle has followed a predetermined path.

A compound chimeric antigen receptor strategy for targeting multiple myeloma.

PubMed

Chen, K H; Wada, M; Pinz, K G; Liu, H; Shuai, X; Chen, X; Yan, L E; Petrov, J C; Salman, H; Senzel, L; Leung, E L H; Jiang, X; Ma, Y

2018-02-01

Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

A dinoflagellate mutant with higher frequency of multiple fission.

PubMed

Lam, C M; Chong, C; Wong, J T

2001-01-01

The dinoflagellate Crypthecodinium cohnii Biecheler propagates by both binary and multiple fission. By a newly developed mutagenesis protocol based on using ethyl methanesulfonate and a cell size screening method, a cell cycle mutant, mf2, was isolated with giant cells which predominantly divide by multiple fission. The average cell size of the mutant mf2 is larger than the control C. cohnii. Cell cycle synchronization experiments suggest that mutant mf2, when compared with the control strain, has a prolonged G1 phase with a corresponding delay of the G2 + M phase.

Unit Cells

ERIC Educational Resources Information Center

Olsen, Robert C.; Tobiason, Fred L.

1975-01-01

Describes the construction of unit cells using clear plastic cubes which can be disassembled, and one inch cork balls of various colors, which can be cut in halves, quarters, or eighths, and glued on the inside face of the cube, thus simulating a unit cell. (MLH)

Beyond the Cell: Using Multiscalar Topics to Bring Interdisciplinarity into Undergraduate Cellular Biology Courses

PubMed Central

Weber, Carolyn F.

2016-01-01

Western science has grown increasingly reductionistic and, in parallel, the undergraduate life sciences curriculum has become disciplinarily fragmented. While reductionistic approaches have led to landmark discoveries, many of the most exciting scientific advances in the late 20th century have occurred at disciplinary interfaces; work at these interfaces is necessary to manage the world’s looming problems, particularly those that are rooted in cellular-level processes but have ecosystem- and even global-scale ramifications (e.g., nonsustainable agriculture, emerging infectious diseases). Managing such problems requires comprehending whole scenarios and their emergent properties as sums of their multiple facets and complex interrelationships, which usually integrate several disciplines across multiple scales (e.g., time, organization, space). This essay discusses bringing interdisciplinarity into undergraduate cellular biology courses through the use of multiscalar topics. Discussing how cellular-level processes impact large-scale phenomena makes them relevant to everyday life and unites diverse disciplines (e.g., sociology, cell biology, physics) as facets of a single system or problem, emphasizing their connections to core concepts in biology. I provide specific examples of multiscalar topics and discuss preliminary evidence that using such topics may increase students’ understanding of the cell’s position within an ecosystem and how cellular biology interfaces with other disciplines. PMID:27146162

Monopolar fuel cell stack coupled together without use of top or bottom cover plates or tie rods

NASA Technical Reports Server (NTRS)

Narayanan, Sekharipuram R. (Inventor); Valdez, Thomas I. (Inventor)

2009-01-01

A monopolar fuel cell stack comprises a plurality of sealed unit cells coupled together. Each unit cell comprises two outer cathodes adjacent to corresponding membrane electrode assemblies and a center anode plate. An inlet and outlet manifold are coupled to the anode plate and communicate with a channel therein. Fuel flows from the inlet manifold through the channel in contact with the anode plate and flows out through the outlet manifold. The inlet and outlet manifolds are arranged to couple to the inlet and outlet manifolds respectively of an adjacent one of the plurality of unit cells to permit fuel flow in common into all of the inlet manifolds of the plurality of the unit cells when coupled together in a stack and out of all of the outlet manifolds of the plurality of unit cells when coupled together in a stack.

Three-Dimensional Medical Image Analysis Using Local Dynamic Algorithm Selection on a Multiple-Instruction, Multiple-Data Architecture

DTIC Science & Technology

1989-01-01

is represented by a number, called a Hounsfield Unit (HU), which represents the attenuation within the volume relative to the attenuation of the same...volume of water. Hounsfield Unit values range from -1000 to +3000, with a value of zero assigned to the attenuation of water. A HU value of -1000...represented by a 3D array. Each array element represents a single voxel, and the value of the array entry is the corresponding scaled Hounsfield Unit value

Pituitary adenylate cyclase-activating polypeptide is a potent inhibitor of the growth of light chain-secreting human multiple myeloma cells.

PubMed

Li, Min; Cortez, Shirley; Nakamachi, Tomoya; Batuman, Vecihi; Arimura, Akira

2006-09-01

Multiple myeloma represents a malignant proliferation of plasma cells in the bone marrow, which often overproduces immunoglobulin light chains. We have shown previously that pituitary adenylate cyclase-activating polypeptide (PACAP) markedly suppresses the release of proinflammatory cytokines from light chain-stimulated human renal proximal tubule epithelial cells and prevents the resulting tubule cell injury. In this study, we have shown that PACAP suppresses the proliferation of human kappa and lambda light chain-secreting multiple myeloma-derived cells. The addition of PACAP suppressed light chain-producing myeloma cell-stimulated interleukin 6 (IL-6) secretion by the bone marrow stromal cells (BMSCs). A specific antagonist to either the human PACAP-specific receptor or the vasoactive intestinal peptide receptor attenuated the suppressive effect of PACAP on IL-6 production in the adhesion of human multiple myeloma cells to BMSCs. The secretion of IL-6 by BMSCs was completely inhibited by 10(-9) mol/L PACAP, which also attenuated the phosphorylation of both p42/44 and p38 mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappaB (NF-kappaB) activation in response to the adhesion of multiple myeloma cells to BMSCs, whereas the inhibition of p42/44 MAPK signaling attenuated PACAP action. The signaling cascades involved in the inhibitory effect of PACAP on IL-6-mediated paracrine stimulation of light chain-secreting myeloma cell growth was mediated through the suppression of p38 MAPK as well as modulation of activation of transcription factor NF-kappaB. These findings suggest that PACAP may be a new antitumor agent that directly suppresses light chain-secreting myeloma cell growth and indirectly affects tumor cell growth by modifying the bone marrow milieu of the multiple myeloma.

Cytoplasmic connection of sperm cells to the pollen vegetative cell nucleus: potential roles of the male germ unit revisited.

PubMed

McCue, Andrea D; Cresti, Mauro; Feijó, José A; Slotkin, R Keith

2011-03-01

The male germ cells of angiosperm plants are neither free-living nor flagellated and therefore are dependent on the unique structure of the pollen grain for fertilization. During angiosperm male gametogenesis, an asymmetric mitotic division produces the generative cell, which is completely enclosed within the cytoplasm of the larger pollen grain vegetative cell. Mitotic division of the generative cell generates two sperm cells that remain connected by a common extracellular matrix with potential intercellular connections. In addition, one sperm cell has a cytoplasmic projection in contact with the vegetative cell nucleus. The shared extracellular matrix of the two sperm cells and the physical association of one sperm cell to the vegetative cell nucleus forms a linkage of all the genetic material in the pollen grain, termed the male germ unit. Found in species representing both the monocot and eudicot lineages, the cytoplasmic projection is formed by vesicle formation and microtubule elongation shortly after the formation of the generative cell and tethers the male germ unit until just prior to fertilization. The cytoplasmic projection plays a structural role in linking the male germ unit, but potentially plays other important roles. Recently, it has been speculated that the cytoplasmic projection and the male germ unit may facilitate communication between the somatic vegetative cell nucleus and the germinal sperm cells, via RNA and/or protein transport. This review focuses on the nature of the sperm cell cytoplasmic projection and the potential communicative function of the male germ unit.

Stem cell treatments in China: rethinking the patient role in the global bio-economy.

PubMed

Chen, Haidan; Gottweis, Herbert

2013-05-01

The paper looks in detail at patients that were treated at one of the most discussed companies operating in the field of untried stem cell treatments, Beike Biotech of Shenzhen, China. Our data show that patients who had been treated at Beike Biotech view themselves as proactively pursuing treatment choices that are not available in their home countries. These patients typically come from a broad variety of countries: China, the United Kingdom, the United States, South Africa and Australia. Among the patients we interviewed there seemed to be both an awareness of the general risks involved in such experimental treatments and a readiness to accept those risks weighed against the possible benefits. We interpret this evidence as possibly reflecting the emergence of risk-taking patients as 'consumers' of medical options as well as the drive of patients to seek treatment options in the global arena, rather than being hindered by the ethical and regulatory constraints of their home countries. Further, we found that these patients tend to operate in more or less stable networks and groups in which they interact and cooperate closely and develop opinions and assessments of available treatment options for their ailments. These patients also perform a multiple role as patients, research subjects, and research funders because they are required to pay their way into treatment and research activities. This new social dynamics of patienthood has important implications for the ethical governance of stem cell treatments. © 2011 Blackwell Publishing Ltd.

Multiple mutant clones in blood rarely coexist

NASA Astrophysics Data System (ADS)

Dingli, David; Pacheco, Jorge M.; Traulsen, Arne

2008-02-01

Leukemias arise due to mutations in the genome of hematopoietic (blood) cells. Hematopoiesis has a multicompartment architecture, with cells exhibiting different rates of replication and differentiation. At the root of this process, one finds a small number of stem cells, and hence the description of the mutation-selection dynamics of blood cells calls for a stochastic approach. We use stochastic dynamics to investigate to which extent acquired hematopoietic disorders are associated with mutations of single or multiple genes within developing blood cells. Our analysis considers the appearance of mutations both in the stem cell compartment as well as in more committed compartments. We conclude that in the absence of genomic instability, acquired hematopoietic disorders due to mutations in multiple genes are most likely very rare events, as multiple mutations typically require much longer development times compared to those associated with a single mutation.

Multiplexed Affinity-Based Separation of Proteins and Cells Using Inertial Microfluidics.

PubMed

Sarkar, Aniruddh; Hou, Han Wei; Mahan, Alison E; Han, Jongyoon; Alter, Galit

2016-03-30

Isolation of low abundance proteins or rare cells from complex mixtures, such as blood, is required for many diagnostic, therapeutic and research applications. Current affinity-based protein or cell separation methods use binary 'bind-elute' separations and are inefficient when applied to the isolation of multiple low-abundance proteins or cell types. We present a method for rapid and multiplexed, yet inexpensive, affinity-based isolation of both proteins and cells, using a size-coded mixture of multiple affinity-capture microbeads and an inertial microfluidic particle sorter device. In a single binding step, different targets-cells or proteins-bind to beads of different sizes, which are then sorted by flowing them through a spiral microfluidic channel. This technique performs continuous-flow, high throughput affinity-separation of milligram-scale protein samples or millions of cells in minutes after binding. We demonstrate the simultaneous isolation of multiple antibodies from serum and multiple cell types from peripheral blood mononuclear cells or whole blood. We use the technique to isolate low abundance antibodies specific to different HIV antigens and rare HIV-specific cells from blood obtained from HIV+ patients.

Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe

NASA Astrophysics Data System (ADS)

Hathi, Deep; Zhou, Haiying; Bollerman-Nowlis, Alex; Shokeen, Monica; Akers, Walter J.

2016-03-01

Multiple myeloma is a plasma cell malignancy characterized by monoclonal gammopathy and osteolytic bone lesions. Multiple myeloma is most commonly diagnosed in late disease stages, presenting with pathologic fracture. Early diagnosis and monitoring of disease status may improve quality of life and long-term survival for multiple myeloma patients from what is now a devastating and fatal disease. We have developed a near-infrared targeted fluorescent molecular probe with high affinity to the α4β1 integrin receptor (VLA-4)overexpressed by a majority of multiple myeloma cells as a non-radioactive analog to PET/CT tracer currently being developed for human diagnostics. A near-infrared dye that emits about 700 nm was conjugated to a high affinity peptidomimmetic. Binding affinity and specificity for multiple myeloma cells was investigated in vitro by tissue staining and flow cytometry. After demonstration of sensitivity and specificity, preclinical optical imaging studies were performed to evaluate tumor specificity in murine subcutaneous and metastatic multiple myeloma models. The VLA-4-targeted molecular probe showed high affinity for subcutaneous MM tumor xenografts. Importantly, tumor cells specific accumulation in the bone marrow of metastatic multiple myeloma correlated with GFP signal from transfected cells. Ex vivo flow cytometry of tumor tissue and bone marrow further corroborated in vivo imaging data, demonstrating the specificity of the novel agent and potential for quantitative imaging of multiple myeloma burden in these models.

A study of the temporal stability of multiple cell vortices

NASA Technical Reports Server (NTRS)

Khorrami, Mehdi R.

1989-01-01

The effect of initial mean velocity field on the stability characteristics of longitudinal vortices is documented in detail. The temporal stability of isolated multiple cell vortices is considered. The types of vortices studied include single cell as well as two and three cell vortices. It is shown that cell multiplicity in the vortex core has drastic effects on the stability characteristics. On the basis of numerical calculations, it is concluded that the growth rates of instabilities in multiple cell vortices are substantially larger (two to threefold increases are observed) than those of a single cell vortex. It is also determined that there is a substantial increase in the effective range of axial and azimuthal wavenumbers where instabilities are present. But most importantly, there is the appearance of a variety of viscous modes of instability. In the case of vortices, these latter instabilities which highlight the importance of viscous forces have never been reported before. These effects are discussed in detail for the case of a two cell vortex.

Cortical modulation of the nucleus of the optic tract in the rabbit.

PubMed

Pettorossi, V E; Troiani, D

1983-09-01

We analyzed in rabbits the relationships between the temporooccipital nystagmogenic cortex (NGC)--the region sited at the border between cortical areas 17, 21, and 22--and the nucleus of the optic tract (NOT). Two experimental approaches were used: (a) eye movement analysis before and after electrolytic lesion of the NOT region provided an indication of the importance of the NOT for the interaction between the ocular nystagmus elicited by natural optokinetic stimulation (OKN) and the nystagmus evoked by electrical stimulation of the nystagmogenic area; (b) NOT direction-selective and velocity-sensitive units were tested with single shock or repetitive electrical stimulation of the nystagmogenic region. Single-shock stimulation evoked single or multiple spikes in 50% of NOT units analyzed and repetitive stimuli induced prolonged facilitation and inhibitory rebounds in 70% of the units tested. Comparison of orthodromic activation latencies of the NOT cells (3.2 and 6.1 ms) after cortical stimulation and of antidromic activation latencies of cortical nystagmogenic units (2.6 ms) after NOT shocks, suggested monosynaptic as well as polysynaptic connections between the temporooccipital cortex and the NOT. The existence of such cortical-NOT linkage indicates that the NOT is intercalated between the cortex and the oculomotor centers and represents the most probable site of interaction of the cortical nystagmus pathway with the optokinetic reflex arc.

Gut microbiota in multiple sclerosis: possible influence of immunomodulators.

PubMed

Cantarel, Brandi L; Waubant, Emmanuelle; Chehoud, Christel; Kuczynski, Justin; DeSantis, Todd Z; Warrington, Janet; Venkatesan, Arun; Fraser, Claire M; Mowry, Ellen M

2015-06-01

Differences in gut bacteria have been described in several autoimmune disorders. In this exploratory pilot study, we compared gut bacteria in patients with multiple sclerosis and healthy controls and evaluated the influence of glatiramer acetate and vitamin D treatment on the microbiota. Subjects were otherwise healthy white women with or without relapsing-remitting multiple sclerosis who were vitamin D insufficient. Patients with multiple sclerosis were untreated or were receiving glatiramer acetate. Subjects collected stool at baseline and after 90 days of vitamin D3 (5000 IU/d) supplementation. The abundance of operational taxonomic units was evaluated by hybridization of 16S rRNA to a DNA microarray. While there was overlap of gut bacterial communities, the abundance of some operational taxonomic units, including Faecalibacterium, was lower in patients with multiple sclerosis. Glatiramer acetate-treated patients with multiple sclerosis showed differences in community composition compared with untreated subjects, including Bacteroidaceae, Faecalibacterium, Ruminococcus, Lactobacillaceae, Clostridium, and other Clostridiales. Compared with the other groups, untreated patients with multiple sclerosis had an increase in the Akkermansia, Faecalibacterium, and Coprococcus genera after vitamin D supplementation. While overall bacterial communities were similar, specific operational taxonomic units differed between healthy controls and patients with multiple sclerosis. Glatiramer acetate and vitamin D supplementation were associated with differences or changes in the microbiota. This study was exploratory, and larger studies are needed to confirm these preliminary results.

HIF-2α-ILK Is Involved in Mesenchymal Stromal Cell Angiogenesis in Multiple Myeloma Under Hypoxic Conditions

PubMed Central

Zhang, Xiaoying; Xu, Yinhui; Liu, Hongbo; Zhao, Pan; Chen, Yafang; Yue, Zhijie; Zhang, Zhiqing; Wang, Xiaofang

2018-01-01

Mesenchymal stromal cells are proven to be likely induce the angiogenic response in multiple myeloma and thus represent an enticing target for antiangiogenesis therapies for multiple myeloma. Substantial evidence indicates that angiogenesis in multiple myeloma is complex and involves direct production of angiogenic cytokines by abnormal plasma cells and these B-cell neoplasia generated pathophysiology change within the microenvironment. In this study, we demonstrated that mesenchymal stromal cells cultured with U266/Lp-1 under hypoxic conditions resulted in an increased α-smooth muscle actin expression and high productive levels of both hypoxia-inducible factor-2α and integrin-linked kinase proteins. Moreover, inhibition of hypoxia-inducible factor-2α by Small interfering RNA (siRNA) in mesenchymal stromal cells decreased the protein levels of both α-smooth muscle actin and integrin-linked kinase after mesenchymal stromal cells cultured with U266 under hypoxic conditions. We further demonstrated that transfection of integrin-linked kinase-siRNA reduced the protein level of α-smooth muscle actin and attenuated angiogenesis in vitro by decreasing the attachment of Q-dot labeled cells and secretion of angiogenic factors. In conclusion, our research showed that mesenchymal stromal cells cultured with myeloma cells under hypoxia participated in the angiogenesis of multiple myeloma, which is regulated by the hypoxia-inducible factor-2α-integrin-linked kinase pathway. Thus, targeting integrin-linked kinase may represent an effective strategy to block hypoxia-inducible factor-2α-induced angiogenesis in the treatment of multiple myeloma. PMID:29656700

Kamishibai: A Vehicle to Multiple Literacies.

ERIC Educational Resources Information Center

Lee, Gretchen

2003-01-01

Outlines how the author and her fellow history teacher used kamishibai storyboards (a type of folk art common in Japan before World War II) in an integrated unit on Egypt to make textbook reading more meaningful to students. Notes that in order to complete the unit, students had to use multiple literacy skills as they combined textbook reading…

A Case Study of Resources Management Planning with Multiple Objectives and Projects

Treesearch

David L. Peterson; David G. Silsbee; Daniel L. Schmoldt

1995-01-01

Each National Park Service unit in the United States produces a resources management plan (RMP) every four years or less. The plans commit budgets and personnel to specific projects for four years, but they are prepared with little quantitative and analytical rigor and without formal decisionmaking tools. We have previously described a multiple objective planning...

"I Want to Do Things with Languages": A Male Karenni Refugee's Reconstructing Multilingual Capital

ERIC Educational Resources Information Center

Duran, Chatwara Suwannamai

2016-01-01

This article discusses how a male Karenni refugee in the United States has constructed multilingual capital along the way of his multiple movements across national borders. As a member of an ethnic minority group in three different countries (Burma, Thailand, and the United States), he has invested in learning multiple languages throughout the…

Hydrogen Fuel Cell Performance as Telecommunications Backup Power in the United States

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

Kurtz, Jennifer; Saur, Genevieve; Sprik, Sam

2015-03-01

Working in collaboration with the U.S. Department of Energy (DOE) and industry project partners, the National Renewable Energy Laboratory (NREL) acts as the central data repository for the data collected from real-world operation of fuel cell backup power systems. With American Recovery and Reinvestment Act of 2009 (ARRA) co-funding awarded through DOE's Fuel Cell Technologies Office, more than 1,300 fuel cell units were deployed over a three-plus-year period in stationary, material handling equipment, auxiliary power, and backup power applications. This surpassed a Fuel Cell Technologies Office ARRA objective to spur commercialization of an early market technology by installing 1,000 fuelmore » cell units across several different applications, including backup power. By December 2013, 852 backup power units out of 1,330 fuel cell units deployed were providing backup service, mainly for telecommunications towers. For 136 of the fuel cell backup units, project participants provided detailed operational data to the National Fuel Cell Technology Evaluation Center for analysis by NREL's technology validation team. NREL analyzed operational data collected from these government co-funded demonstration projects to characterize key fuel cell backup power performance metrics, including reliability and operation trends, and to highlight the business case for using fuel cells in these early market applications. NREL's analyses include these critical metrics, along with deployment, U.S. grid outage statistics, and infrastructure operation.« less

Rationally Designed Peptidomimetic Modulators of Aβ Toxicity in Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Rajasekhar, K.; Suresh, S. N.; Manjithaya, Ravi; Govindaraju, T.

2015-01-01

Alzheimer's disease is one of the devastating illnesses mankind is facing in the 21st century. The main pathogenic event in Alzheimer's disease is believed to be the aggregation of the β-amyloid (Aβ) peptides into toxic aggregates. Molecules that interfere with this process may act as therapeutic agents for the treatment of the disease. Use of recognition unit based peptidomimetics as inhibitors are a promising approach, as they exhibit greater protease stability compared to natural peptides. Here, we present peptidomimetic inhibitors of Aβ aggregation designed based on the KLVFF (P1) sequence that is known to bind Aβ aggregates. We improved inhibition efficiency of P1 by introducing multiple hydrogen bond donor-acceptor moieties (thymine/barbiturate) at the N-terminal (P2 and P3), and blood serum stability by modifying the backbone by incorporating sarcosine (N-methylglycine) units at alternate positions (P4 and P5). The peptidomimetics showed moderate to good activity in both inhibition and dissolution of Aβ aggregates as depicted by thioflavin assay, circular dichroism (CD) measurements and microscopy (TEM). The activity of P4 and P5 were studied in a yeast cell model showing Aβ toxicity. P4 and P5 could rescue yeast cells from Aβ toxicity and Aβ aggregates were cleared by the process of autophagy.

Preliminary X-ray data analysis of crystalline hibiscus chlorotic ringspot virus

PubMed Central

Cheng, Ao; Speir, Jeffrey A.; Yuan, Y. Adam; Johnson, John E.; Wong, Sek-Man

2009-01-01

Hibiscus chlorotic ringspot virus (HCRSV) is a positive-sense monopartite single-stranded RNA virus that belongs to the Carmovirus genus of the Tombusviridae family, which includes carnation mottle virus (CarMV). The HCRSV virion has a 30 nm diameter icosahedral capsid with T = 3 quasi-symmetry containing 180 copies of a 38 kDa coat protein (CP) and encapsidates a full-length 3.9 kb genomic RNA. Authentic virus was harvested from infected host kenaf leaves and was purified by saturated ammonium sulfate precipitation, sucrose density-gradient centrifugation and anion-exchange chromatography. Virus crystals were grown in multiple conditions; one of the crystals diffracted to 3.2 Å resolution and allowed the collection of a partial data set. The crystal belonged to space group R32, with unit-cell parameters a = b = 336.4, c = 798.5 Å. Packing considerations and rotation-function analysis determined that there were three particles per unit cell, all of which have the same orientation and fixed positions, and resulted in tenfold noncrystallography symmetry for real-space averaging. The crystals used for the structure determination of southern bean mosaic virus (SBMV) have nearly identical characteristics. Together, these findings will greatly aid the high-resolution structure determination of HCRSV. PMID:19478438

Preliminary X-ray Data Analysis of Crystalline Hibiscus Chlorotic Ringspot Virus

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

Cheng, A.; Speir, J; Yuan, Y

Hibiscus chlorotic ringspot virus (HCRSV) is a positive-sense monopartite single-stranded RNA virus that belongs to the Carmovirus genus of the Tombusviridae family, which includes carnation mottle virus (CarMV). The HCRSV virion has a 30 nm diameter icosahedral capsid with T = 3 quasi-symmetry containing 180 copies of a 38 kDa coat protein (CP) and encapsidates a full-length 3.9 kb genomic RNA. Authentic virus was harvested from infected host kenaf leaves and was purified by saturated ammonium sulfate precipitation, sucrose density-gradient centrifugation and anion-exchange chromatography. Virus crystals were grown in multiple conditions; one of the crystals diffracted to 3Synchrotron .2 Amore » resolution and allowed the collection of a partial data set. The crystal belonged to space group R32, with unit-cell parameters a = b = 336.4, c = 798.5 . Packing considerations and rotation-function analysis determined that there were three particles per unit cell, all of which have the same orientation and fixed positions, and resulted in tenfold noncrystallography symmetry for real-space averaging. The crystals used for the structure determination of southern bean mosaic virus (SBMV) have nearly identical characteristics. Together, these findings will greatly aid the high-resolution structure determination of HCRSV.« less

Iron Supplementation Decreases Severity of Allergic Inflammation in Murine Lung

PubMed Central

Hale, Laura P.; Kant, Erin Potts; Greer, Paula K.; Foster, W. Michael

2012-01-01

The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans. PMID:23029172

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies.

PubMed

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A

2017-08-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies

PubMed Central

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A.

2017-01-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy. PMID:28817344

The impact of embedding multiple modes of representation on student construction of chemistry knowledge

NASA Astrophysics Data System (ADS)

McDermott, Mark Andrew

2009-12-01

This study was designed to examine the impact of embedding multiple modes of representing science information on student conceptual understanding in science. Multiple representations refer to utilizing charts, graphs, diagrams, and other types of representations to communicate scientific information. This study investigated the impact of encouraging students to embed or integrate the multiple modes with text in end of unit writing-to-learn activities. A quasi-experimental design with four separate sites consisting of intact chemistry classes taught by different teachers at each site was utilized. At each site, approximately half of the classes were designated treatment classes and students in these classes participated in activities designed to encourage strategies to embed multiple modes within text in student writing. The control classes did not participate in these activities. All classes participated in identical end of unit writing tasks in which they were required to use at least one mode other than text, followed by identical end of unit assessments. This progression was then repeated for a second consecutive unit of study. Analysis of quantitative data indicated that in several cases, treatment classes significantly outperformed control classes both on measures of embeddedness in writing and on end of unit assessment measures. In addition, analysis at the level of individual students indicated significant positive correlations in many cases between measures of student embeddedness in writing and student performance on end of unit assessments. Three factors emerged as critical in increasing the likelihood of benefit for students from these types of activities. First, the level of teacher implementation and emphasis on the embeddedness lessons was linked to the possibility of conceptual benefit. Secondly, students participating in two consecutive lessons appeared to receive greater benefit during the second unit, inferring a cumulative benefit. Finally, differential impact of the degree of embeddedness on student performance was noted based on student's level of science ability prior to the initiation of study procedures.

Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments

PubMed Central

Goodell, Margaret A.; Nguyen, Hoang; Shroyer, Noah

2017-01-01

Somatic stem cells replenish many tissues throughout life to repair damage and to maintain tissue homeostasis. Stem cell function is frequently described as following a hierarchical model in which a single master cell undergoes self-renewal and differentiation into multiple cell types and is responsible for most regenerative activity. However, recent data from studies on blood, skin and intestinal epithelium all point to the concomitant action of multiple types of stem cells with distinct everyday roles. Under stress conditions such as acute injury, the surprising developmental flexibility of these stem cells enables them to adapt to diverse roles and to acquire different regeneration capabilities. This paradigm shift raises many new questions about the developmental origins, inter-relationships and molecular regulation of these multiple stem cell types. PMID:25907613

Importance of Unit Cells in Accurate Evaluation of the Characteristics of Graphene

NASA Astrophysics Data System (ADS)

Sabzyan, Hassan; Sadeghpour, Narges

2016-04-01

Effects of the size of the unit cell on energy, atomic charges, and phonon frequencies of graphene at the Γ point of the Brillouin zone are studied in the absence and presence of an electric field using density functional theory (DFT) methods (LDA and DFT-PBE functionals with Goedecker-Teter-Hutter (GTH) and Troullier-Martins (TM) norm-conserving pseudopotentials). Two types of unit cells containing nC=4-28 carbon atoms are considered. Results show that stability of graphene increases with increasing size of the unit cell. Energy, atomic charges, and phonon frequencies all converge above nC=24 for all functional-pseudopotentials used. Except for the LDA-GTH calculations, application of an electric field of 0.4 and 0.9 V/nm strengths does not change the trends with the size of the unit cell but instead slightly decreases the binding energy of graphene. Results of this study show that the choice of unit cell size and type is critical for calculation of reliable characteristics of graphene.

Gene therapy of uterine leiomyoma: adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir treatment inhibits growth of human and rat leiomyoma cells in vitro and in a nude mouse model.

PubMed

Salama, S A; Kamel, M; Christman, G; Wang, H Q; Fouad, H M; Al-Hendy, A

2007-01-01

Uterine leiomyomas (LM) affect a high percentage of reproductive-age women. They develop as discrete, well-defined tumors that are easily accessible with imaging techniques--making this disease ideal for localized gene therapy approaches. In this study, we determined the efficacy of adenovirus-mediated herpes simplex virus thymidine kinase gene transfer in combination with ganciclovir (Ad-TK/GCV) as a potential therapy for LM. Rat ELT-3 LM cells and human LM cells were transfected with different multiplicity of infections (10-100 plaque forming units [PFU]/cell) of Ad-TK and treated with GCV (5, 10, or 20 microg/ml) for 5 days. To test the bystander effect, Ad-TK-transfected ELT-3 cells (100 PFU/cell) or LM cells (10 PFU/cell) were cocultured with corresponding nontransfected cells at increasing percentages and treated with GCV followed by cell counting. In ELT-3 cells transfected with Ad-TK/GCV (10, 20, 50, or 100 PFU/cell), the cell count was reduced by 24, 42, 77, and 87%, respectively, compared with the control cells (transfected with Ad-Lac Z/GCV). Similarly, in LM cells transfected with Ad-TK/GCV (10, 50, or 100 PFU/cell), the cell count was reduced by 31, 62, and 82%, respectively, compared with the control. A strong bystander effect was noted in both ELT-3 and LM cells with significant killing (p = 0.001) at a ratio of infected:uninfected cells of only 1:99 and maximal killing at 1:4. This study demonstrates the potential efficacy of the Ad-TK/GCV gene therapy approach as a viable nonsurgical alternative treatment for uterine LM.

Integrative multicellular biological modeling: a case study of 3D epidermal development using GPU algorithms

PubMed Central

2010-01-01

Background Simulation of sophisticated biological models requires considerable computational power. These models typically integrate together numerous biological phenomena such as spatially-explicit heterogeneous cells, cell-cell interactions, cell-environment interactions and intracellular gene networks. The recent advent of programming for graphical processing units (GPU) opens up the possibility of developing more integrative, detailed and predictive biological models while at the same time decreasing the computational cost to simulate those models. Results We construct a 3D model of epidermal development and provide a set of GPU algorithms that executes significantly faster than sequential central processing unit (CPU) code. We provide a parallel implementation of the subcellular element method for individual cells residing in a lattice-free spatial environment. Each cell in our epidermal model includes an internal gene network, which integrates cellular interaction of Notch signaling together with environmental interaction of basement membrane adhesion, to specify cellular state and behaviors such as growth and division. We take a pedagogical approach to describing how modeling methods are efficiently implemented on the GPU including memory layout of data structures and functional decomposition. We discuss various programmatic issues and provide a set of design guidelines for GPU programming that are instructive to avoid common pitfalls as well as to extract performance from the GPU architecture. Conclusions We demonstrate that GPU algorithms represent a significant technological advance for the simulation of complex biological models. We further demonstrate with our epidermal model that the integration of multiple complex modeling methods for heterogeneous multicellular biological processes is both feasible and computationally tractable using this new technology. We hope that the provided algorithms and source code will be a starting point for modelers to develop their own GPU implementations, and encourage others to implement their modeling methods on the GPU and to make that code available to the wider community. PMID:20696053

Phenotypic Changes and Impaired Function of Peripheral γδ T Cells in Patients With Sepsis.

PubMed

Liao, Xue-Lian; Feng, Ting; Zhang, Jiang-Qian; Cao, Xing; Wu, Qi-Hong; Xie, Zhi-Chao; Kang, Yan; Li, Hong

2017-09-01

Recent studies demonstrated the significant loss of gamma delta T (γδ T) cells in patients with sepsis. Given the distinct functions of γδ T cells in human anti-infection immunity, we are interested in evaluating the phenotype and function of peripheral γδ T cells in septic patients and determining their prognostic implication. This prospective study has been conducted in three intensive care units of a university hospital. During the period from October 2014 to June 2015, we enrolled 107 patients who were consecutively admitted and diagnosed with severe sepsis or septic shock (excluding previous immunosuppression) and 45 healthy controls. Using flow cytometry, we analyzed the in vivo percentage of γδ T cells in cluster of differentiation (CD)3 cells from peripheral blood mononuclear cells as well as their expression of surface markers (CD69, natural-killer group 2 member D [NKG2D], programmed death receptor 1 [PD-1]) and intracellular cytokines (interferon-γ [IFN-γ], interleukin [IL]-17, IL-10, transforming growth factor-β [TGF-β]). Then we further evaluated the different responses of γδ T cells after the antigen stimulation ex vivo by measuring CD69 and IFN-γ expression. Lastly, we conducted the multiple logistic regressions to analyze the risk factor for prognosis. Compared with control group, γδ T cells in septic patients displayed a decrease in percentage, increase in CD69, decrease in NKG2D, and increase in cytokine expression (pro-inflammatory IFN-γ, IL-17, anti-inflammatory IL-10, TGF-β) in vivo. After the antigen stimulation ex vivo, both CD69 and IFN-γ expression in γδ T cells were significantly lower in septic patients than control group. Importantly, the decrease in CD69 and IFN-γ expression was more pronounced in non-survivors than survivors. Multiple logistic regression analysis revealed that lower expression of IFN-γ after stimulation is a dependent risk factor that associated with patient 28-day death in septic patients (OR: 0.908 [95% CI: 0.853-0.966]). Septic patients showed altered phenotype and function of γδ T cells. The impaired IFN-γ expression by γδ T cells after the antigen stimulation is associated with mortality in septic patients.

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.

Susceptibility to viral infection is enhanced by stable expression of 3A or 3AB proteins from foot-and-mouth disease virus

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

Rosas, Maria F.; Vieira, Yuri A.; Postigo, Raul

2008-10-10

The foot-and-mouth disease virus (FMDV) 3A protein is involved in virulence and host range. A distinguishing feature of FMDV 3B among picornaviruses is that three non-identical copies are encoded in the viral RNA and required for optimal replication in cell culture. Here, we have studied the involvement of the 3AB region on viral infection using constitutive and transient expression systems. BHK-21 stably transformed clones expressed low levels of FMDV 3A or 3A(B) proteins in the cell cytoplasm. Transformed cells stably expressing these proteins did not exhibit inner cellular rearrangements detectable by electron microscope analysis. Upon FMDV infection, clones expressing eithermore » 3A alone or 3A(B) proteins showed a significant increase in the percentage of infected cells, the number of plaque forming units and the virus yield. The 3A-enhancing effect was specific for FMDV as no increase in viral multiplication was observed in transformed clones infected with another picornavirus, encephalomyocarditis virus, or the negative-strand RNA virus vesicular stomatitis virus. A potential role of 3A protein in viral RNA translation was discarded by the lack of effect on FMDV IRES-dependent translation. Increased viral susceptibility was not caused by a released factor; neither the supernatant of transformed clones nor the addition of purified 3A protein to the infection medium was responsible for this effect. Unlike stable expression, high levels of 3A or 3A(B) protein transient expression led to unspecific inhibition of viral infection. Therefore, the effect observed on viral yield, which inversely correlated with the intracellular levels of 3A protein, suggests a transacting role operating on the FMDV multiplication cycle.« less

Associative list processing unit

DOEpatents

Hemmert, Karl Scott; Underwood, Keith D.

2013-01-29

An associative list processing unit and method comprising employing a plurality of prioritized cell blocks and permitting inserts to occur in a single clock cycle if all of the cell blocks are not full. Also, an associative list processing unit and method comprising employing a plurality of prioritized cell blocks and using a tree of prioritized multiplexers descending from the plurality of cell blocks.

MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis

PubMed Central

Qiu, Jing-Xin; Kim, Edward J.; Yu, Ai-Ming

2016-01-01

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Better understanding of pancreatic cancer biology may help identify new oncotargets towards more effective therapies. This study investigated the mechanistic actions of microRNA-1291 (miR-1291) in the suppression of pancreatic tumorigenesis. Our data showed that miR-1291 was downregulated in a set of clinical pancreatic carcinoma specimens and human pancreatic cancer cell lines. Restoration of miR-1291 expression inhibited pancreatic cancer cell proliferation, which was associated with cell cycle arrest and enhanced apoptosis. Furthermore, miR-1291 sharply suppressed the tumorigenicity of PANC-1 cells in mouse models. A proteomic profiling study revealed 32 proteins altered over 2-fold in miR-1291-expressing PANC-1 cells that could be assembled into multiple critical pathways for cancer. Among them anterior gradient 2 (AGR2) was reduced to the greatest degree. Through computational and experimental studies we further identified that forkhead box protein A2 (FOXA2), a transcription factor governing AGR2 expression, was a direct target of miR-1291. These results connect miR-1291 to the FOXA2-AGR2 regulatory pathway in the suppression of pancreatic cancer cell proliferation and tumorigenesis, providing new insight into the development of miRNA-based therapy to combat pancreatic cancer. PMID:27322206

Theta phase precession of grid and place cell firing in open environments

PubMed Central

Jeewajee, A.; Barry, C.; Douchamps, V.; Manson, D.; Lever, C.; Burgess, N.

2014-01-01

Place and grid cells in the rodent hippocampal formation tend to fire spikes at successively earlier phases relative to the local field potential theta rhythm as the animal runs through the cell's firing field on a linear track. However, this ‘phase precession’ effect is less well characterized during foraging in two-dimensional open field environments. Here, we mapped runs through the firing fields onto a unit circle to pool data from multiple runs. We asked which of seven behavioural and physiological variables show the best circular–linear correlation with the theta phase of spikes from place cells in hippocampal area CA1 and from grid cells from superficial layers of medial entorhinal cortex. The best correlate was the distance to the firing field peak projected onto the animal's current running direction. This was significantly stronger than other correlates, such as instantaneous firing rate and time-in-field, but similar in strength to correlates with other measures of distance travelled through the firing field. Phase precession was stronger in place cells than grid cells overall, and robust phase precession was seen in traversals through firing field peripheries (although somewhat less than in traversals through the centre), consistent with phase coding of displacement along the current direction. This type of phase coding, of place field distance ahead of or behind the animal, may be useful for allowing calculation of goal directions during navigation. PMID:24366140

Teaching About Genetics and Sickle Cell Disease In Fifth Grade.

PubMed

Day, Lucille Lang; Murray, Eileen; Treadwell, Marsha J; Lubin, Bertram H

2015-02-01

We are grateful to Laura McVittie Gray for her work on the development of the student activities described in this article. This work was made possible by a Science Education Partnership Award (SEPA), Grant Number R25RR020449, from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Additional support for this SEPA-funded project was provided by Grant Number UL1RR024131-01 from NCRR. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. A 5-lesson, 5th-grade instructional unit, "Genetics and Sickle Cell Disease," was developed and tested as part of a 40-lesson curriculum entitled SEEK (Science Exploration, Excitement, and Knowledge): A Curriculum in Health and Biomedical Science for Diverse 4th and 5th Grade Students. The genetics lessons include hands-on activities (e.g., DNA extraction from cheek cells), a simulated plant genetics experiment, and a classroom visit by a person with sickle cell disease, as well as by a health care practitioner who works with sickle cell patients or a scientist specializing in genetics. The unit was tested with 82 5th-grade students at public elementary schools in Oakland, CA; 96% were racial and ethnic minorities. The comparison group consisted of 84 5th-grade Oakland students racially/ ethnically, academically, and socio-economically matched to those in the experimental group. Both groups completed a 20-question, multiple-choice pre/posttest covering science concepts, scientific process, lifestyle choices, and careers. The experimental group showed significant improvement on 13 of 20 questions (P<.05, t-tests) and on the test as a whole, whereas the comparison group did not show significant improvement either on any of the questions or on the test as a whole. The experimental group improved on 10 concept questions, 2 scientific process questions, and 1 lifestyle question. Teachers rated the educational value of the unit as 9.5 on a scale from 1 (low) to 10 (high). These results show that genetics and sickle cell disease can be taught successfully in 5th grade, although they are not typically covered at this level. © 2015 National Medical Association. Published by Elsevier Inc. All rights reserved.

Mechanism for multiplicity of steady states with distinct cell concentration in continuous culture of mammalian cells.

PubMed

Yongky, Andrew; Lee, Jongchan; Le, Tung; Mulukutla, Bhanu Chandra; Daoutidis, Prodromos; Hu, Wei-Shou

2015-07-01

Continuous culture for the production of biopharmaceutical proteins offers the possibility of steady state operations and thus more consistent product quality and increased productivity. Under some conditions, multiplicity of steady states has been observed in continuous cultures of mammalian cells, wherein with the same dilution rate and feed nutrient composition, steady states with very different cell and product concentrations may be reached. At those different steady states, cells may exhibit a high glycolysis flux with high lactate production and low cell concentration, or a low glycolysis flux with low lactate and high cell concentration. These different steady states, with different cell concentration, also have different productivity. Developing a mechanistic understanding of the occurrence of steady state multiplicity and devising a strategy to steer the culture toward the desired steady state is critical. We establish a multi-scale kinetic model that integrates a mechanistic intracellular metabolic model and cell growth model in a continuous bioreactor. We show that steady state multiplicity exists in a range of dilution rate in continuous culture as a result of the bistable behavior in glycolysis. The insights from the model were used to devise strategies to guide the culture to the desired steady state in the multiple steady state region. The model provides a guideline principle in the design of continuous culture processes of mammalian cells. © 2015 Wiley Periodicals, Inc.

Ultrafast frequency-agile terahertz devices using methylammonium lead halide perovskites

PubMed Central

Chanana, Ashish; Liu, Xiaojie; Vardeny, Zeev Valy

2018-01-01

The ability to control the response of metamaterial structures can facilitate the development of new terahertz devices, with applications in spectroscopy and communications. We demonstrate ultrafast frequency-agile terahertz metamaterial devices that enable such a capability, in which multiple perovskites can be patterned in each unit cell with micrometer-scale precision. To accomplish this, we developed a fabrication technique that shields already deposited perovskites from organic solvents, allowing for multiple perovskites to be patterned in close proximity. By doing so, we demonstrate tuning of the terahertz resonant response that is based not only on the optical pump fluence but also on the optical wavelength. Because polycrystalline perovskites have subnanosecond photocarrier recombination lifetimes, switching between resonances can occur on an ultrafast time scale. The use of multiple perovskites allows for new functionalities that are not possible using a single semiconducting material. For example, by patterning one perovskite in the gaps of split-ring resonators and bringing a uniform thin film of a second perovskite in close proximity, we demonstrate tuning of the resonant response using one optical wavelength and suppression of the resonance using a different optical wavelength. This general approach offers new capabilities for creating tunable terahertz devices. PMID:29736416

Ultrafast frequency-agile terahertz devices using methylammonium lead halide perovskites.

PubMed

Chanana, Ashish; Liu, Xiaojie; Zhang, Chuang; Vardeny, Zeev Valy; Nahata, Ajay

2018-05-01

The ability to control the response of metamaterial structures can facilitate the development of new terahertz devices, with applications in spectroscopy and communications. We demonstrate ultrafast frequency-agile terahertz metamaterial devices that enable such a capability, in which multiple perovskites can be patterned in each unit cell with micrometer-scale precision. To accomplish this, we developed a fabrication technique that shields already deposited perovskites from organic solvents, allowing for multiple perovskites to be patterned in close proximity. By doing so, we demonstrate tuning of the terahertz resonant response that is based not only on the optical pump fluence but also on the optical wavelength. Because polycrystalline perovskites have subnanosecond photocarrier recombination lifetimes, switching between resonances can occur on an ultrafast time scale. The use of multiple perovskites allows for new functionalities that are not possible using a single semiconducting material. For example, by patterning one perovskite in the gaps of split-ring resonators and bringing a uniform thin film of a second perovskite in close proximity, we demonstrate tuning of the resonant response using one optical wavelength and suppression of the resonance using a different optical wavelength. This general approach offers new capabilities for creating tunable terahertz devices.

T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention.

PubMed

van Langelaar, Jamie; van der Vuurst de Vries, Roos M; Janssen, Malou; Wierenga-Wolf, Annet F; Spilt, Isis M; Siepman, Theodora A; Dankers, Wendy; Verjans, Georges M G M; de Vries, Helga E; Lubberts, Erik; Hintzen, Rogier Q; van Luijn, Marvin M

2018-05-01

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3-) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6-CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4-) expressed the highest very late antigen-4 levels and selectively accumulated in natalizumab-treated patients who remained free of clinical relapses. This was not found in patients who experienced relapses during natalizumab treatment. The enhanced potential of Th17.1 cells to infiltrate the central nervous system was supported by their predominance in cerebrospinal fluid of early multiple sclerosis patients and their preferential transmigration across human brain endothelial layers. These findings reveal a dominant contribution of Th1-like Th17 subpopulations, in particular Th17.1 cells, to clinical disease activity and provide a strong rationale for more specific and earlier use of T cell-targeted therapy in multiple sclerosis.

Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Patient Version

Cancer.gov

Plasma cell neoplasms occur when abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. Multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are different types of plasma cell neoplasms. Find out about risk factors, symptoms, diagnostic tests, prognosis, and treatment for these diseases.

Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma.

PubMed

Drent, Esther; Groen, Richard W J; Noort, Willy A; Themeli, Maria; Lammerts van Bueren, Jeroen J; Parren, Paul W H I; Kuball, Jürgen; Sebestyen, Zsolt; Yuan, Huipin; de Bruijn, Joost; van de Donk, Niels W C J; Martens, Anton C M; Lokhorst, Henk M; Mutis, Tuna

2016-05-01

Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy. Prompted by this, we used three different CD38 antibody sequences to generate second-generation retroviral CD38-chimeric antigen receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients. We then evaluated the preclinical efficacy and safety of the transduced T cells. Irrespective of the donor and antibody sequence, CD38-chimeric antigen receptor-transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite becoming CD38-negative during culture. CD38-chimeric antigen receptor-transduced T cells also displayed significant anti-tumor effects in a xenotransplant model, in which multiple myeloma tumors were grown in a human bone marrow-like microenvironment. CD38-chimeric antigen receptor-transduced T cells also appeared to lyse the CD38(+) fractions of CD34(+) hematopoietic progenitor cells, monocytes, natural killer cells, and to a lesser extent T and B cells but did not inhibit the outgrowth of progenitor cells into various myeloid lineages and, furthermore, were effectively controllable with a caspase-9-based suicide gene. These results signify the potential importance of CD38-chimeric antigen receptor-transduced T cells as therapeutic tools for CD38(+) malignancies and warrant further efforts to diminish the undesired effects of this immunotherapy using appropriate strategies. Copyright© Ferrata Storti Foundation.

The use of in vitro transcription to probe regulatory functions of viral protein domains.

PubMed

Loewenstein, Paul M; Song, Chao-Zhong; Green, Maurice

2007-01-01

Adenoviruses (Ads), like other DNA tumor viruses, have evolved specific regulatory genes that facilitate virus replication by controlling the transcription of other viral genes as well as that of key cellular genes. In this regard, the E1A transcription unit contains multiple protein domains that can transcriptionally activate or repress cellular genes involved in the regulation of cell proliferation and cell differentiation. Studies using in vitro transcription have provided a basis for a molecular understanding of the interaction of viral regulatory proteins with the transcriptional machinery of the cell and continue to inform our understanding of transcription regulation. This chapter provides examples of the use of in vitro transcription to analyze transcriptional activation and transcriptional repression by purified, recombinant Ad E1A protein domains and single amino acid substitution mutants as well as the use of protein-affinity chromatography to identify host cell transcription factors involved in viral transcriptional regulation. A detailed description is provided of the methodology to prepare nuclear transcription extract, to prepare biologically active protein domains, to prepare affinity depleted transcription extracts, and to analyze transcription by primer extension and by run-off assay using naked DNA templates.

Expansion and concatenation of nonmuscle myosin IIA filaments drive cellular contractile system formation during interphase and mitosis

PubMed Central

Fenix, Aidan M.; Taneja, Nilay; Buttler, Carmen A.; Lewis, John; Van Engelenburg, Schuyler B.; Ohi, Ryoma; Burnette, Dylan T.

2016-01-01

Cell movement and cytokinesis are facilitated by contractile forces generated by the molecular motor, nonmuscle myosin II (NMII). NMII molecules form a filament (NMII-F) through interactions of their C-terminal rod domains, positioning groups of N-terminal motor domains on opposite sides. The NMII motors then bind and pull actin filaments toward the NMII-F, thus driving contraction. Inside of crawling cells, NMIIA-Fs form large macromolecular ensembles (i.e., NMIIA-F stacks), but how this occurs is unknown. Here we show NMIIA-F stacks are formed through two non–mutually exclusive mechanisms: expansion and concatenation. During expansion, NMIIA molecules within the NMIIA-F spread out concurrent with addition of new NMIIA molecules. Concatenation occurs when multiple NMIIA-Fs/NMIIA-F stacks move together and align. We found that NMIIA-F stack formation was regulated by both motor activity and the availability of surrounding actin filaments. Furthermore, our data showed expansion and concatenation also formed the contractile ring in dividing cells. Thus interphase and mitotic cells share similar mechanisms for creating large contractile units, and these are likely to underlie how other myosin II–based contractile systems are assembled. PMID:26960797

The "Growing" Reality of the Neurological Complications of Global "Stem Cell Tourism".

PubMed

Julian, Katie; Yuhasz, Nick; Hollingsworth, Ethan; Imitola, Jaime

2018-04-01

"Stem cell tourism" is defined as the unethical practice of offering unproven cellular preparations to patients suffering from various medical conditions. This phenomenon is rising in the field of neurology as patients are requesting information and opportunities for treatment with stem cells for incurable conditions such as multiple sclerosis and amyotrophic lateral sclerosis, despite their clinical research and experimental designation. Here, we review the recent trends in "stem cell tourism" in both the United States and abroad, and discuss the recent reports of neurological complications from these activities. Finally, we frame critical questions for the field of neurology regarding training in the ethical, legal, and societal issues of the global "stem cell tourism," as well as suggest strategies to alleviate this problem. Although there are ongoing legitimate clinical trials with stem cells for neurological diseases, procedures offered by "stem cell clinics" cannot be defined as clinical research. They lack the experimental and state-of-the-art framework defined by peers and the FDA that focus on human research that safeguard the protection of human subjects against economical exploitation, unwanted side effects, and futility of unproven procedures. "Stem cell tourism" ultimately exploits therapeutic hope of patients and families with incurable neurological diseases and can put in danger the legitimacy of stem cell research as a whole. We posit that an improvement in education, regulation, legislation, and involvement of authorities in global health in neurology and neurosurgery is required. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Structural and experimental investigations of the functional anatomy and the turgor of the notochord in the larval tail of anuran tadpoles.

PubMed

Platz, Franz

2006-07-01

The premetamorphotic morphology and metamorphotic degeneration of the tail notochord of anuran tadpoles has been investigated. For this purpose the functional anatomy and origin of the notochord turgor was analysed in 10 species macroscopically and using light, transmission and scanning electron microscopic techniques. The notochord consists of the fibrous notochord sheath, which surrounds the notochord cells. Within the sheath these cells form a net-like unit. The inner cells are derived from the marginal notochord cells (chordoblasts). They are protected from mechanical overload by intracellular filaments and desmosomes. Due to their vacuoles, which are filled with a hyaline liquid, they have a constant volume but are deformable. Dissolved substances may pass from the vascularized fin to the notochord cells. The transport from marginal to inner cells occurs via cytopempsis and micropinocytosis. The morphological correlation of this process consists of multiple membrane invaginations and intracellular vesicles. Within the notochord cells a high turgor pressure has been observed. During metamorphosis the membrane vesiculation persists and the notochord cells degenerate. Due to the loss of turgor pressure the tight consistency of the notochord is lost. The collagen filaments and the elastic membrane of the notochord sheath dissolve. Notochord cells with their filaments, high turgor pressure and their central vacuole can function as a combined mechanical and physiological system, which is adaptable to the needs of pressure, compression, tensile and bending forces.

PRODUCTION AND CHARACTERIZATION OF MULTIPLE-LAYERED POPULATIONS OF ANIMAL CELLS

PubMed Central

Kruse, Paul F.; Miedema, Ed

1965-01-01

Dense populations containing 129 x 106 Jensen sarcoma, 134 x 106 DON Chinese hamster, 28.9 x 106 WI-38 human diploid, 61.8 x 106 HEp-2 human carcinoma, and 67.4 x 106 WISH human amnion cells were produced from dilute inocula, 0.85 to 5.33 x 106, in 7 to 8 days in a perfusion system using replicate T-60 flasks. Perfusion rates as high as 560 ml medium/day/T-60 were required to maintain pH (to ca ±0.1 unit) and adequate nutrient supplies. The cell densities encountered are described by the term "monolayer equivalents" (M.E.), defined as number of cells per culture divided by number of cells in a monolayer. The M.E.'s for T-60 cultures containing unusually dense populations of 40 x 106 WI-38 and 250 x 106 DON cells (9-day perfusion) were 5 and 17, respectively, and numbers of cells in illustrations of stained cross-sections of membranes from these cultures were in excellent agreement. Threshold M.E.'s exist below which proliferation is the chief cellular activity and above which one or more cell functions may predominate even though proliferation persists. Cellular nutrition and metabolism may change with changes in M.E., as illustrated in different patterns of glutamic acid, proline, and glycine utilization or production in dense vs. dilute WI-38 cell populations. The results indicated that the role of contact inhibition phenomena in arresting cellular proliferation was diminished in perfusion system environments. PMID:5884626

Correlating Polymer Crystals via Self-Induced Nucleation

NASA Astrophysics Data System (ADS)

Reiter, Günter

Crystallizable polymers often form multiple stacks of uniquely oriented lamellae, which have good registry despite being separated by amorphous fold surfaces. These correlations require multiple synchronized, yet unidentified, nucleation events. Here, we demonstrate that in thin films of isotactic polystyrene, the probability of generating correlated lamellae is controlled by the branched morphology of a single primary lamella. The nucleation density ns of secondary lamellae is found to be dependent on the width of the branches of the primary lamella. This relation is independent of molecular weight, crystallization temperature, and film thickness. We propose a nucleation mechanism based on the insertion of polymers into a branched primary lamellar crystal. Even in single crystals, characterized by faceted structures with a well-defined envelope reflecting the underlying crystal unit cell, polymers are folded and thus in a meta-stable state. Annealing such meta-stable single crystals allowed to unveil the initial morphological framework of a dendritic single crystal, i.e. the initial stages of growth.

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

PubMed

Andlauer, Till F M; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A; Loleit, Verena; Luessi, Felix; Meuth, Sven G; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

2016-06-01

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

New methods for indexing multi-lattice diffraction data

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

Gildea, Richard J.; Waterman, David G.; CCP4, Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot OX11 0FA

2014-10-01

A new indexing method is presented which is capable of indexing multiple crystal lattices from narrow wedges of data. The efficacy of this method is demonstrated with both semi-synthetic multi-lattice data and real multi-lattice data recorded from microcrystals of ∼1 µm in size. A new indexing method is presented which is capable of indexing multiple crystal lattices from narrow wedges of diffraction data. The method takes advantage of a simplification of Fourier transform-based methods that is applicable when the unit-cell dimensions are known a priori. The efficacy of this method is demonstrated with both semi-synthetic multi-lattice data and real multi-latticemore » data recorded from crystals of ∼1 µm in size, where it is shown that up to six lattices can be successfully indexed and subsequently integrated from a 1° wedge of data. Analysis is presented which shows that improvements in data-quality indicators can be obtained through accurate identification and rejection of overlapping reflections prior to scaling.« less

Ultra-Thin Multi-Band Polarization-Insensitive Microwave Metamaterial Absorber Based on Multiple-Order Responses Using a Single Resonator Structure

PubMed Central

Cheng, Zheng Ze; Mao, Xue Song; Gong, Rong Zhou

2017-01-01

We design an ultra-thin multi-band polarization-insensitive metamaterial absorber (MMA) using a single circular sector resonator (CSR) structure in the microwave region. Simulated results show that the proposed MMA has three distinctive absorption peaks at 3.35 GHz, 8.65 GHz, and 12.44 GHz, with absorbance of 98.8%, 99.7%, and 98.3%, respectively, which agree well with an experiment. Simulated surface current distributions of the unit-cell structure reveal that the triple-band absorption mainly originates from multiple-harmonic magnetic resonance. The proposed triple-band MMA can remain at a high absorption level for all polarization of both transverse-electric (TE) and transverse-magnetic (TM) modes under normal incidence. Moreover, by further optimizing the geometric parameters of the CSRs, four-band and five-band MMAs can also be obtained. Thus, our design will have potential application in detection, sensing, and stealth technology. PMID:29077036

Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

PubMed Central

Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A.; Loleit, Verena; Luessi, Felix; Meuth, Sven G.; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H.; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O.; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B.; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M.; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M.; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

2016-01-01

We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID:27386562

Design and implementation of a hybrid MPI-CUDA model for the Smith-Waterman algorithm.

PubMed

Khaled, Heba; Faheem, Hossam El Deen Mostafa; El Gohary, Rania

2015-01-01

This paper provides a novel hybrid model for solving the multiple pair-wise sequence alignment problem combining message passing interface and CUDA, the parallel computing platform and programming model invented by NVIDIA. The proposed model targets homogeneous cluster nodes equipped with similar Graphical Processing Unit (GPU) cards. The model consists of the Master Node Dispatcher (MND) and the Worker GPU Nodes (WGN). The MND distributes the workload among the cluster working nodes and then aggregates the results. The WGN performs the multiple pair-wise sequence alignments using the Smith-Waterman algorithm. We also propose a modified implementation to the Smith-Waterman algorithm based on computing the alignment matrices row-wise. The experimental results demonstrate a considerable reduction in the running time by increasing the number of the working GPU nodes. The proposed model achieved a performance of about 12 Giga cell updates per second when we tested against the SWISS-PROT protein knowledge base running on four nodes.

Lithological and Surface Geometry Joint Inversions Using Multi-Objective Global Optimization Methods

NASA Astrophysics Data System (ADS)

Lelièvre, Peter; Bijani, Rodrigo; Farquharson, Colin

2016-04-01

Geologists' interpretations about the Earth typically involve distinct rock units with contacts (interfaces) between them. In contrast, standard minimum-structure geophysical inversions are performed on meshes of space-filling cells (typically prisms or tetrahedra) and recover smoothly varying physical property distributions that are inconsistent with typical geological interpretations. There are several approaches through which mesh-based minimum-structure geophysical inversion can help recover models with some of the desired characteristics. However, a more effective strategy may be to consider two fundamentally different types of inversions: lithological and surface geometry inversions. A major advantage of these two inversion approaches is that joint inversion of multiple types of geophysical data is greatly simplified. In a lithological inversion, the subsurface is discretized into a mesh and each cell contains a particular rock type. A lithological model must be translated to a physical property model before geophysical data simulation. Each lithology may map to discrete property values or there may be some a priori probability density function associated with the mapping. Through this mapping, lithological inverse problems limit the parameter domain and consequently reduce the non-uniqueness from that presented by standard mesh-based inversions that allow physical property values on continuous ranges. Furthermore, joint inversion is greatly simplified because no additional mathematical coupling measure is required in the objective function to link multiple physical property models. In a surface geometry inversion, the model comprises wireframe surfaces representing contacts between rock units. This parameterization is then fully consistent with Earth models built by geologists, which in 3D typically comprise wireframe contact surfaces of tessellated triangles. As for the lithological case, the physical properties of the units lying between the contact surfaces are set to a priori values. The inversion is tasked with calculating the geometry of the contact surfaces instead of some piecewise distribution of properties in a mesh. Again, no coupling measure is required and joint inversion is simplified. Both of these inverse problems involve high nonlinearity and discontinuous or non-obtainable derivatives. They can also involve the existence of multiple minima. Hence, one can not apply the standard descent-based local minimization methods used to solve typical minimum-structure inversions. Instead, we are applying Pareto multi-objective global optimization (PMOGO) methods, which generate a suite of solutions that minimize multiple objectives (e.g. data misfits and regularization terms) in a Pareto-optimal sense. Providing a suite of models, as opposed to a single model that minimizes a weighted sum of objectives, allows a more complete assessment of the possibilities and avoids the often difficult choice of how to weight each objective. While there are definite advantages to PMOGO joint inversion approaches, the methods come with significantly increased computational requirements. We are researching various strategies to ameliorate these computational issues including parallelization and problem dimension reduction.

A multiple p-n junction structure obtained from as-grown Czochralski silicon crystals by heat treatment - Application to solar cells

NASA Technical Reports Server (NTRS)

Chi, J. Y.; Gatos, H. C.; Mao, B. Y.

1980-01-01

Multiple p-n junctions have been prepared in as-grown Czochralski p-type silicon through overcompensation near the oxygen periodic concentration maxima by oxygen thermal donors generated during heat treatment at 450 C. Application of the multiple p-n-junction configuration to photovoltaic energy conversion has been investigated. A new solar-cell structure based on multiple p-n-junctions was developed. Theoretical analysis showed that a significant increase in collection efficiency over the conventional solar cells can be achieved.

Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units.

PubMed

Robert, Mark E; Linthicum, Fred H

2016-01-01

Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3-dimensional reconstruction software to identify double-counted count units. For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-µm sections. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Mechanical properties of regular porous biomaterials made from truncated cube repeating unit cells: Analytical solutions and computational models.

PubMed

Hedayati, R; Sadighi, M; Mohammadi-Aghdam, M; Zadpoor, A A

2016-03-01

Additive manufacturing (AM) has enabled fabrication of open-cell porous biomaterials based on repeating unit cells. The micro-architecture of the porous biomaterials and, thus, their physical properties could then be precisely controlled. Due to their many favorable properties, porous biomaterials manufactured using AM are considered as promising candidates for bone substitution as well as for several other applications in orthopedic surgery. The mechanical properties of such porous structures including static and fatigue properties are shown to be strongly dependent on the type of the repeating unit cell based on which the porous biomaterial is built. In this paper, we study the mechanical properties of porous biomaterials made from a relatively new unit cell, namely truncated cube. We present analytical solutions that relate the dimensions of the repeating unit cell to the elastic modulus, Poisson's ratio, yield stress, and buckling load of those porous structures. We also performed finite element modeling to predict the mechanical properties of the porous structures. The analytical solution and computational results were found to be in agreement with each other. The mechanical properties estimated using both the analytical and computational techniques were somewhat higher than the experimental data reported in one of our recent studies on selective laser melted Ti-6Al-4V porous biomaterials. In addition to porosity, the elastic modulus and Poisson's ratio of the porous structures were found to be strongly dependent on the ratio of the length of the inclined struts to that of the uninclined (i.e. vertical or horizontal) struts, α, in the truncated cube unit cell. The geometry of the truncated cube unit cell approaches the octahedral and cube unit cells when α respectively approaches zero and infinity. Consistent with those geometrical observations, the analytical solutions presented in this study approached those of the octahedral and cube unit cells when α approached respectively 0 and infinity. Copyright © 2015 Elsevier B.V. All rights reserved.

Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma.

PubMed

Simonsen, Trude G; Gaustad, Jon-Vidar; Rofstad, Einar K

2016-06-01

A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

14 CFR 29.511 - Ground load: unsymmetrical loads on multiple-wheel units.

Code of Federal Regulations, 2010 CFR

2010-01-01

... gear units, 60 percent of the total ground reaction for the gear unit must be applied to one wheel and... specified load for the gear unit must be applied to either wheel except that the vertical ground reaction...

14 CFR 29.511 - Ground load: unsymmetrical loads on multiple-wheel units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... gear units, 60 percent of the total ground reaction for the gear unit must be applied to one wheel and... specified load for the gear unit must be applied to either wheel except that the vertical ground reaction...

A Unit Cell Laboratory Experiment: Marbles, Magnets, and Stacking Arrangements

ERIC Educational Resources Information Center

Collins, David C.

2011-01-01

An undergraduate first-semester general chemistry laboratory experiment introducing face-centered, body-centered, and simple cubic unit cells is presented. Emphasis is placed on the stacking arrangement of solid spheres used to produce a particular unit cell. Marbles and spherical magnets are employed to prepare each stacking arrangement. Packing…

Downregulation of Cinnamoyl-Coenzyme A Reductase in Poplar: Multiple-Level Phenotyping Reveals Effects on Cell Wall Polymer Metabolism and Structure[W

PubMed Central

Leplé, Jean-Charles; Dauwe, Rebecca; Morreel, Kris; Storme, Véronique; Lapierre, Catherine; Pollet, Brigitte; Naumann, Annette; Kang, Kyu-Young; Kim, Hoon; Ruel, Katia; Lefèbvre, Andrée; Joseleau, Jean-Paul; Grima-Pettenati, Jacqueline; De Rycke, Riet; Andersson-Gunnerås, Sara; Erban, Alexander; Fehrle, Ines; Petit-Conil, Michel; Kopka, Joachim; Polle, Andrea; Messens, Eric; Sundberg, Björn; Mansfield, Shawn D.; Ralph, John; Pilate, Gilles; Boerjan, Wout

2007-01-01

Cinnamoyl-CoA reductase (CCR) catalyzes the penultimate step in monolignol biosynthesis. We show that downregulation of CCR in transgenic poplar (Populus tremula × Populus alba) was associated with up to 50% reduced lignin content and an orange-brown, often patchy, coloration of the outer xylem. Thioacidolysis, nuclear magnetic resonance (NMR), immunocytochemistry of lignin epitopes, and oligolignol profiling indicated that lignin was relatively more reduced in syringyl than in guaiacyl units. The cohesion of the walls was affected, particularly at sites that are generally richer in syringyl units in wild-type poplar. Ferulic acid was incorporated into the lignin via ether bonds, as evidenced independently by thioacidolysis and by NMR. A synthetic lignin incorporating ferulic acid had a red-brown coloration, suggesting that the xylem coloration was due to the presence of ferulic acid during lignification. Elevated ferulic acid levels were also observed in the form of esters. Transcript and metabolite profiling were used as comprehensive phenotyping tools to investigate how CCR downregulation impacted metabolism and the biosynthesis of other cell wall polymers. Both methods suggested reduced biosynthesis and increased breakdown or remodeling of noncellulosic cell wall polymers, which was further supported by Fourier transform infrared spectroscopy and wet chemistry analysis. The reduced levels of lignin and hemicellulose were associated with an increased proportion of cellulose. Furthermore, the transcript and metabolite profiling data pointed toward a stress response induced by the altered cell wall structure. Finally, chemical pulping of wood derived from 5-year-old, field-grown transgenic lines revealed improved pulping characteristics, but growth was affected in all transgenic lines tested. PMID:18024569

NMR study of methane + ethane structure I hydrate decomposition.

PubMed

Dec, Steven F; Bowler, Kristen E; Stadterman, Laura L; Koh, Carolyn A; Sloan, E Dendy

2007-05-24

The thermally activated decomposition of methane + ethane structure I hydrate was studied with use of 13C magic-angle spinning (MAS) NMR as a function of composition and temperature. The observed higher decomposition rate of large sI cages initially filled with ethane gas can be described in terms of a model where a distribution of sI unit cells exists such that a particular unit cell contains zero, one, or two methane molecules in the unit cell; this distribution of unit cells is combined to form the observed equilibrium composition. In this model, unit cells with zero methane molecules are the least stable and decompose more rapidly than those populated with one or two methane molecules leading to the observed overall faster decomposition rate of the large cages containing ethane molecules.

Pharmacokinetics-on-a-Chip Using Label-Free SERS Technique for Programmable Dual-Drug Analysis.

PubMed

Fei, Jiayuan; Wu, Lei; Zhang, Yizhi; Zong, Shenfei; Wang, Zhuyuan; Cui, Yiping

2017-06-23

Synergistic effects of dual or multiple drugs have attracted great attention in medical fields, especially in cancer therapies. We provide a programmable microfluidic platform for pharmacokinetic detection of multiple drugs in multiple cells. The well-designed microfluidic platform includes two 2 × 3 microarrays of cell chambers, two gradient generators, and several pneumatic valves. Through the combined use of valves and gradient generators, each chamber can be controlled to infuse different kinds of living cells and drugs with specific concentrations as needed. In our experiments, 6-mercaptopurine (6MP) and methimazole (MMI) were chosen as two drug models and their pharmacokinetic parameters in different living cells were monitored through intracellular SERS spectra, which reflected the molecular structure of these drugs. The dynamic change of SERS fingerprints from 6MP and MMI molecules were recorded during drug metabolism in living cells. The results indicated that both 6MP and MMI molecules were diffused into the cells within 4 min and excreted out after 36 h. Moreover, the intracellular distribution of these drugs was monitored through SERS mapping. Thus, our microfluidic platform simultaneously accomplishes the functions to monitor pharmacokinetic action, distribution, and fingerprint of multiple drugs in multiple cells. Owing to its real-time, rapid-speed, high-precision, and programmable capability of multiple-drug and multicell analysis, such a microfluidic platform has great potential in drug design and development.

Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats.

PubMed

Omori, Yoshinori; Honmou, Osamu; Harada, Kuniaki; Suzuki, Junpei; Houkin, Kiyohiro; Kocsis, Jeffery D

2008-10-21

The systemic injection of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has therapeutic benefits after cerebral artery occlusion in rats, and may have multiple therapeutic effects at various sites and times within the lesion as the cells respond to a particular pathological microenvironment. However, the comparative therapeutic benefits of multiple injections of hMSCs at different time points after cerebral artery occlusion in rats remain unclear. In this study, we induced middle cerebral artery occlusion (MCAO) in rats using intra-luminal vascular occlusion, and infused hMSCs intravenously at a single 6 h time point (low and high cell doses) and various multiple time points after MCAO. From MRI analyses lesion volume was reduced in all hMSC cell injection groups as compared to serum alone injections. However, the greatest therapeutic benefit was achieved following a single high cell dose injection at 6 h post-MCAO, rather than multiple lower cell infusions over multiple time points. Three-dimensional analysis of capillary vessels in the lesion indicated that the capillary volume was equally increased in all of the cell-injected groups. Thus, differences in functional outcome in the hMSC transplantation subgroups are not likely the result of differences in angiogenesis, but rather from differences in neuroprotective effects.

Solar energy conversion through the interaction of plasmons with tunnel junctions. Part A: Solar cell analysis. Part B: Photoconductor analysis

NASA Technical Reports Server (NTRS)

Welsh, P. E.; Schwartz, R. J.

1988-01-01

A solar cell utilizing guided optical waves and tunnel junctions was analyzed to determine its feasibility. From this analysis, it appears that the limits imposed upon conventional multiple cell systems also limit this solar cell. Due to this limitation, it appears that the relative simplicity of the conventional multiple cell systems over the solar cell make the conventional multiple cell systems the more promising candidate for improvement. It was discovered that some superlattice structures studied could be incorporated into an infrared photodetector. This photoconductor appears to be promising as a high speed, sensitive (high D sup star sub BLIP) detector in the wavelength range from 15 to over 100 micrometers.

A critical examination of the numerology of antigen-binding cells: evidence for multiple receptor specificities on single cells.

PubMed

Miller, A

1977-01-01

The data available from other laboratories as well as our own on the frequency of cells recognizing major histocompatibility antigens or conventional protein and hapten antigens is critically evaluated. The frequency of specific binding for a large number of antigens is sufficiently high to support the idea that at least part of the antigen-binding cell population must have multiple specificities. Our results suggest that these multiple specific cells result from single cells synthesizing and displaying as many as 50-100 species of receptor, each at a frequency of 10(4) per cell. A model involving gene expansion of constant-region genes is suggested and some auxilliary evidence consistent with such C-gene expansion is presented.

Recapitulating the History of Sickle-Cell Anemia Research: Improving Students' NOS Views Explicitly and Reflectively

NASA Astrophysics Data System (ADS)

Howe, Eric Michael; Wÿss Rudge, David

This paper provides an argument in favor of a specific pedagogical method of using the history of science to help students develop more informed views about nature of science (NOS) issues. The paper describes a series of lesson plans devoted to encouraging students to engage, unbeknownst to them, in similar reasoning that led scientists to understand sickle-cell anemia from the perspective of multiple subdisciplines in biology. Students pursue their understanding of a "mystery disease"; by means of a series of open-ended problems that invite them to discuss it from the perspective of anatomy, physiology, ecology, evolution, and molecular and cell biology. Throughout this unit, instructors incorporate techniques that invite students to explicitly and reflectively discuss various NOS issues with reference to this example and more generally. It is argued on the grounds of constructivist tenets that this pedagogy has substantial advantages over more implicit approaches. The findings of an empirical study using an open-ended survey and follow-up, semi-structured interviews to assess students' pre- and post-instruction NOS conceptions support the efficacy of this approach.

The clypeal gland: a new exocrine gland in termite imagoes (Isoptera: Serritermitidae, Rhinotermitidae, Termitidae).

PubMed

Křížková, Barbora; Bourguignon, Thomas; Vytisková, Blahoslava; Sobotník, Jan

2014-11-01

Social insects possess a rich set of exocrine organs producing diverse pheromones and defensive compounds. This is especially true for termite imagoes, which are equipped with several glands producing, among others, sex pheromones and defensive compounds protecting imagoes during the dispersal flight and colony foundation. Here, we describe the clypeal gland, a new termite exocrine organ occurring in the labro-clypeal region of imagoes of most Rhinotermitidae, Serritermitidae and Termitidae species. The clypeal gland of Coptotermes testaceus consists of class 1 (modified epidermal cell) and class 3 (bicellular gland unit) secretory cells. Ultrastructural features suggest that the gland secretes volatile compounds and proteins, probably after starting the reproduction. One peculiar feature of the gland is the presence of multiple secretory canals in a single canal cell, a feature never observed before in other insect glands. Although the function of the gland remains unknown, we hypothesize that it could produce secretion signalling the presence of functional reproductives or their need to be fed. Copyright © 2014 Elsevier Ltd. All rights reserved.

The pedagogical potential of drawing and writing in a primary science multimodal unit

NASA Astrophysics Data System (ADS)

Wilson, Rachel E.; Bradbury, Leslie U.

2016-11-01

In consideration of the potential of drawing and writing as assessment and learning tools, we explored how early primary students used these modes to communicate their science understandings. The context for this study was a curricular unit that incorporated multiple modes of representation in both the presentation of information and production of student understanding with a focus on the structure and function of carnivorous plants (CPs). Two science teacher educators and two first-grade teachers in the United States co-planned and co-taught a multimodal science unit on CP structure and function that included multiple representations of Venus flytraps (VFTs): physical specimens, photographs, videos, text, and discussions. Pre- and post-assessment student drawings and writings were statistically compared to note significant changes, and pre- and post-assessment writings were qualitatively analysed to note themes in student ideas. Results indicate that students increased their knowledge of VFT structure and function and synthesised information from multiple modes. While students included more structures of the VFT in their drawings, they were better able to describe the functions of structures in their writings. These results suggest the benefits for student learning and assessment of having early primary students represent their science understandings in multiple modes.

Striate cortical contribution to the transcorneal electrically evoked response of the visual system.

PubMed

Shimazu, K; Miyake, Y; Fukatsu, Y; Watanabe, S

1996-01-01

Analyses of current-source-density (CSD) and multiple unit activity (MUA) in area 17 of the cat were performed to determine the sources of the cortical transcorneal electrically evoked response. Cortical field potential, CSD and MUA profiles were obtained with multi-electrodes. CSD findings include: current sinks (inward cell membrane current) within 20 ms latency, in layers 4 and 6 of the striate cortex; current sinks corresponding to N3 (negative component of the EER; latency, 35 ms) in layer 4 and lower layer 3 with current sources (outward cell membrane current) for N3 in the supragranular layers; current sinks with latency over 40 ms in the supragranular layers. In the layers 4 and 6, simultaneous MUA was seen. When the stimulus frequency was increased or with dual stimulation, the N3 current sinks were decreased. This indicates that N1 (latency, 9 ms) and N2 (latency, 20 ms) reflect near-field potentials in layers 4 and 6, generated by geniculocortical afferents, and that N3 is a post- and polysynaptic component. It is also suggested that dipoles composed of cell bodies and the apical dendrites of pyramidal cells of layer 3, generated by satellite cells in layer 4, play a major role in generating N3.

40 CFR Appendix A to Part 76 - Phase I Affected Coal-Fired Utility Units With Group 1 or Cell Burner Boilers

Code of Federal Regulations, 2011 CFR

2011-07-01

... Units With Group 1 or Cell Burner Boilers A Appendix A to Part 76 Protection of Environment... 1 or Cell Burner Boilers Table 1—Phase I Tangentially Fired Units State Plant Unit Operator ALABAMA... TOWER 9 CEN ILLINOIS PUB SER. INDIANA CULLEY 2 STHERN IND GAS & EL. INDIANA CULLEY 3 STHERN IND GAS & EL...

Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Health Professional Version

Cancer.gov

Plasma cell neoplasms (including multiple myeloma) treatment include observation, chemotherapy, radiation, stem cell rescue, targeted, and supportive therapies. Corticosteroids and immunomodulatory drugs may be used. Get detailed treatment information in this summary for clinicians.

Plasma Cell Neoplasms (Including Multiple Myeloma)—Health Professional Version

Cancer.gov

There are several types of plasma cell neoplasms, including monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma. Find evidence-based information on plasma cell neoplasms treatment, research, and statistics.

Heterogeneity of clonogenic cells in acute myeloblastic leukemia.

PubMed Central

Sabbath, K D; Ball, E D; Larcom, P; Davis, R B; Griffin, J D

1985-01-01

The expression of differentiation-associated surface antigens by the clonogenic leukemic cells from 20 patients with acute myeloblastic leukemia (AML) was studied with a panel of seven cytotoxic monoclonal antibodies (anti-Ia, -MY9, -PM-81, -AML-2-23, -Mol, -Mo2, and -MY3). The surface antigen phenotypes of the clonogenic cells were compared with the phenotypes of the whole leukemic cell population, and with the phenotypes of normal hematopoietic progenitor cells. In each case the clonogenic leukemic cells were found within a distinct subpopulation that was less "differentiated" than the total cell population. Clonogenic leukemic cells from different patients could be divided into three phenotype groups. In the first group (7 of 20 cases), the clonogenic cells expressed surface antigens characteristic of the normal multipotent colony-forming cell (Ia, MY9). These cases tended to have "undifferentiated" (FAB M1) morphology, and the total cell population generally lacked expression of "late" monocyte antigens such as MY3 and Mo2. A second group (seven cases) of clonogenic cells expressed surface antigens characteristic of an "early" (day 14) colony-forming unit granulocyte-monocyte (CFU-GM), and a third group (six cases) was characteristic of a "late" (day 7) CFU-GM. The cases in these latter two groups tended to have myelomonocytic (FAB M4) morphology and to express monocyte surface antigens. These results suggest that the clonogenic cells are a distinct subpopulation in all cases of AML, and may be derived from normal hematopoietic progenitor cells at multiple points in the differentiation pathway. The results further support the possibility that selected monoclonal antibodies have the potential to purge leukemic clonogenic cells from bone marrow in some AML patients without eliminating critical normal progenitor cells. PMID:3855866

Heterogeneity of clonogenic cells in acute myeloblastic leukemia.

PubMed

Sabbath, K D; Ball, E D; Larcom, P; Davis, R B; Griffin, J D

1985-02-01

The expression of differentiation-associated surface antigens by the clonogenic leukemic cells from 20 patients with acute myeloblastic leukemia (AML) was studied with a panel of seven cytotoxic monoclonal antibodies (anti-Ia, -MY9, -PM-81, -AML-2-23, -Mol, -Mo2, and -MY3). The surface antigen phenotypes of the clonogenic cells were compared with the phenotypes of the whole leukemic cell population, and with the phenotypes of normal hematopoietic progenitor cells. In each case the clonogenic leukemic cells were found within a distinct subpopulation that was less "differentiated" than the total cell population. Clonogenic leukemic cells from different patients could be divided into three phenotype groups. In the first group (7 of 20 cases), the clonogenic cells expressed surface antigens characteristic of the normal multipotent colony-forming cell (Ia, MY9). These cases tended to have "undifferentiated" (FAB M1) morphology, and the total cell population generally lacked expression of "late" monocyte antigens such as MY3 and Mo2. A second group (seven cases) of clonogenic cells expressed surface antigens characteristic of an "early" (day 14) colony-forming unit granulocyte-monocyte (CFU-GM), and a third group (six cases) was characteristic of a "late" (day 7) CFU-GM. The cases in these latter two groups tended to have myelomonocytic (FAB M4) morphology and to express monocyte surface antigens. These results suggest that the clonogenic cells are a distinct subpopulation in all cases of AML, and may be derived from normal hematopoietic progenitor cells at multiple points in the differentiation pathway. The results further support the possibility that selected monoclonal antibodies have the potential to purge leukemic clonogenic cells from bone marrow in some AML patients without eliminating critical normal progenitor cells.

Adaptive Digital Signature Design and Short-Data-Record Adaptive Filtering

DTIC Science & Technology

2008-04-01

rate BPSK binary phase shift keying CA − CFAR cell averaging− constant false alarm rate CDMA code − division multiple − access CFAR constant false...Cotae, “Spreading sequence design for multiple cell synchronous DS-CDMA systems under total weighted squared correlation criterion,” EURASIP Journal...415-428, Mar. 2002. [6] P. Cotae, “Spreading sequence design for multiple cell synchronous DS-CDMA systems under total weighted squared correlation

Stationary Size Distributions of Growing Cells with Binary and Multiple Cell Division

NASA Astrophysics Data System (ADS)

Rading, M. M.; Engel, T. A.; Lipowsky, R.; Valleriani, A.

2011-10-01

Populations of unicellular organisms that grow under constant environmental conditions are considered theoretically. The size distribution of these cells is calculated analytically, both for the usual process of binary division, in which one mother cell produces always two daughter cells, and for the more complex process of multiple division, in which one mother cell can produce 2 n daughter cells with n=1,2,3,… . The latter mode of division is inspired by the unicellular algae Chlamydomonas reinhardtii. The uniform response of the whole population to different environmental conditions is encoded in the individual rates of growth and division of the cells. The analytical treatment of the problem is based on size-dependent rules for cell growth and stochastic transition processes for cell division. The comparison between binary and multiple division shows that these different division processes lead to qualitatively different results for the size distribution and the population growth rates.

Immune Tolerance in Multiple Sclerosis

PubMed Central

Goverman, Joan M.

2011-01-01

Summary Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T-cell tolerance to myelin antigens and to understand how some myelin-specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin-specific T cells, as most myelin-specific T cells are eliminated by clonal deletion in the thymus. Self-reactive T cells that escape central tolerance are generally capable only of low-avidity interactions with antigen-presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin-specific T cells have been indentified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4+ myelin-specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8+ myelin-specific T cells. PMID:21488900

[Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of multiple myeloma cells].

PubMed

Li, Lixuan; Li, Jia

2015-05-01

To study the effects of lentivirus-mediated short hairpin RNA (shRNA) silencing of lysosome-associated membrane protein type 2A (LAMP2A) expression on the proliferation of multiple myeloma cells. The constructed shRNA lentiviral vector was applied to infect human multiple myeloma cell line MM.1S, and stable expression cell line was obtained by puromycin screening. Western blotting was used to verify the inhibitory effect on LAMP2A protein expression. MTT assay was conducted to detect the effect of knocked-down LAMP2A on MM.1S cell proliferation, and the anti-tumor potency of suberoylanilide hydroxamic acid (SAHA) against the obtained MM.1S LAMP2A(shRNA) stable cell line. Lactate assay was performed to observe the impact of low LAMP2A expression on cell glycolysis. The stable cell line with low LAMP2A expression were obtained with the constructed human LAMP2A-shRNA lentiviral vector. Down-regulation of LAMP2A expression significantly inhibited MM.1S cell proliferation and enhanced the anti-tumor activity of SAHA. Interestingly, decreased LAMP2A expression also inhibited MM.1S cell lactic acid secretion. Down-regulation of LAMP2A expression could inhibit cell proliferation in multiple myeloma cells.

Relationship between unit cell type and porosity and the fatigue behavior of selective laser melted meta-biomaterials.

PubMed

Amin Yavari, S; Ahmadi, S M; Wauthle, R; Pouran, B; Schrooten, J; Weinans, H; Zadpoor, A A

2015-03-01

Meta-materials are structures when their small-scale properties are considered, but behave as materials when their homogenized macroscopic properties are studied. There is an intimate relationship between the design of the small-scale structure and the homogenized properties of such materials. In this article, we studied that relationship for meta-biomaterials that are aimed for biomedical applications, otherwise known as meta-biomaterials. Selective laser melted porous titanium (Ti6Al4V ELI) structures were manufactured based on three different types of repeating unit cells, namely cube, diamond, and truncated cuboctahedron, and with different porosities. The morphological features, static mechanical properties, and fatigue behavior of the porous biomaterials were studied with a focus on their fatigue behavior. It was observed that, in addition to static mechanical properties, the fatigue properties of the porous biomaterials are highly dependent on the type of unit cell as well as on porosity. None of the porous structures based on the cube unit cell failed after 10(6) loading cycles even when the applied stress reached 80% of their yield strengths. For both other unit cells, higher porosities resulted in shorter fatigue lives for the same level of applied stress. When normalized with respect to their yield stresses, the S-N data points of structures with different porosities very well (R(2)>0.8) conformed to one single power law specific to the type of the unit cell. For the same level of normalized applied stress, the truncated cuboctahedron unit cell resulted in a longer fatigue life as compared to the diamond unit cell. In a similar comparison, the fatigue lives of the porous structures based on both truncated cuboctahedron and diamond unit cells were longer than that of the porous structures based on the rhombic dodecahedron unit cell (determined in a previous study). The data presented in this study could serve as a basis for design of porous biomaterials as well as for corroboration of relevant analytical and computational models. Copyright © 2014 Elsevier Ltd. All rights reserved.

Just another abdominal pain? Psoas abscess-like metastasis in large cell lung cancer with adrenal insufficiency.

PubMed

Bernardino, Vera; Val-Flores, Luis Silva; Dias, João Lopes; Bento, Luís

2015-06-10

The authors report the case of a 69-year-old man with chronic obstructive pulmonary disease and previous pulmonary tuberculosis, who presented to the emergency department with abdominal and low back pain, anorexia and weight loss, rapidly evolving into shock. An initial CT scan revealed pulmonary condensation with associated cavitation and an iliopsoas mass suggestive of a psoas abscess. He was admitted in an intensive care unit unit; after a careful examination and laboratory assessment, the aetiology was yet undisclosed. MRI showed multiple retroperitoneal lymphadenopathies, bulky nodular adrenal lesions and bilateral iliac lytic lesions. Hypocortisolism was detected and treated with steroids. A CT-guided biopsy to the psoas mass and lytic lesions identified infiltration of non-small lung carcinoma. The patient died within days. Psoas metastases and adrenal insufficiency as initial manifestations of malignancy are rare and can be misdiagnosed, particularly in the absence of a known primary tumour. 2015 BMJ Publishing Group Ltd.

Evaluation of Marijuana Compounds on Neuroimmune Endpoints in Experimental Autoimmune Encephalomyelitis.

PubMed

Kaplan, Barbara L F

2018-02-21

Cannabinoid compounds refer to a group of more than 60 plant-derived compounds in Cannabis sativa, more commonly known as marijuana. Exposure to marijuana and cannabinoid compounds has been increasing due to increased societal acceptance for both recreational and possible medical use. Cannabinoid compounds suppress immune function, and while this could compromise one's ability to fight infections, immune suppression is the desired effect for therapies for autoimmune diseases. It is critical, therefore, to understand the effects and mechanisms by which cannabinoid compounds alter immune function, especially immune responses induced in autoimmune disease. Therefore, this unit will describe induction and assessment of the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and its potential alteration by cannabinoid compounds. The unit includes three approaches to induce EAE, two of which provide correlations to two forms of MS, and the third specifically addresses the role of autoreactive T cells in EAE. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Biosynthetic elongation of isolated teichuronic acid polymers via glucosyl- and N-acetylmannosaminuronosyltransferases from solubilized cytoplasmic membrane fragments of Micrococcus luteus.

PubMed Central

Hildebrandt, K M; Anderson, J S

1990-01-01

Cytoplasmic membrane fragments of Micrococcus luteus catalyze in vitro biosynthesis of teichuronic acid from uridine diphosphate D-glucose (UDP-glucose), uridine diphosphate N-acetyl-D-mannosaminuronic acid (UDP-ManNAcA), and uridine diphosphate N-acetyl-D-glucosamine. Membrane fragments solubilized with Thesit (dodecyl alcohol polyoxyethylene ether) can utilize UDP-glucose and UDP-ManNAcA to effect elongation of teichuronic acid isolated from native cell walls. When UDP-glucose is the only substrate supplied, the detergent-solubilized glucosyltransferase incorporates a single glucosyl residue onto each teichuronic acid acceptor. When both UDP-glucose and UDP-ManNAcA are supplied, the glucosyltransferase and the N-acetylmannosaminuronosyltransferase act cooperatively to elongate the teichuronic acid acceptor by multiple additions of the disaccharide repeat unit. As shown by polyacrylamide gel electrophoresis, low-molecular-weight fractions of teichuronic acid are converted to higher-molecular-weight polymers by the addition of as many as 17 disaccharide repeat units. Images PMID:2118507

Efficient Generation of Somatic Cell Nuclear Transfer-Competent Porcine Cells with Mutated Alleles at Multiple Target Loci by Using CRISPR/Cas9 Combined with Targeted Toxin-Based Selection System.

PubMed

Sato, Masahiro; Miyoshi, Kazuchika; Nakamura, Shingo; Ohtsuka, Masato; Sakurai, Takayuki; Watanabe, Satoshi; Kawaguchi, Hiroaki; Tanimoto, Akihide

2017-12-04

The recent advancement in genome editing such a CRISPR/Cas9 system has enabled isolation of cells with knocked multiple alleles through a one-step transfection. Somatic cell nuclear transfer (SCNT) has been frequently employed as one of the efficient tools for the production of genetically modified (GM) animals. To use GM cells as SCNT donor, efficient isolation of transfectants with mutations at multiple target loci is often required. The methods for the isolation of such GM cells largely rely on the use of drug selection-based approach using selectable genes; however, it is often difficult to isolate cells with mutations at multiple target loci. In this study, we used a novel approach for the efficient isolation of porcine cells with at least two target loci mutations by one-step introduction of CRISPR/Cas9-related components. A single guide (sg) RNA targeted to GGTA1 gene, involved in the synthesis of cell-surface α-Gal epitope (known as xenogenic antigen), is always a prerequisite. When the transfected cells were reacted with toxin-labeled BS-I-B₄ isolectin for 2 h at 37 C to eliminate α-Gal epitope-expressing cells, the surviving clones lacked α-Gal epitope expression and were highly expected to exhibit induced mutations at another target loci. Analysis of these α-Gal epitope-negative surviving cells demonstrated a 100% occurrence of genome editing at target loci. SCNT using these cells as donors resulted in the production of cloned blastocysts with the genotype similar to that of the donor cells used. Thus, this novel system will be useful for SCNT-mediated acquisition of GM cloned piglets, in which multiple target loci may be mutated.

A Modular Approach to Arithmetic and Logic Unit Design on a Reconfigurable Hardware Platform for Educational Purpose

NASA Astrophysics Data System (ADS)

Oztekin, Halit; Temurtas, Feyzullah; Gulbag, Ali

The Arithmetic and Logic Unit (ALU) design is one of the important topics in Computer Architecture and Organization course in Computer and Electrical Engineering departments. There are ALU designs that have non-modular nature to be used as an educational tool. As the programmable logic technology has developed rapidly, it is feasible that ALU design based on Field Programmable Gate Array (FPGA) is implemented in this course. In this paper, we have adopted the modular approach to ALU design based on FPGA. All the modules in the ALU design are realized using schematic structure on Altera's Cyclone II Development board. Under this model, the ALU content is divided into four distinct modules. These are arithmetic unit except for multiplication and division operations, logic unit, multiplication unit and division unit. User can easily design any size of ALU unit since this approach has the modular nature. Then, this approach was applied to microcomputer architecture design named BZK.SAU.FPGA10.0 instead of the current ALU unit.

Band structures in fractal grading porous phononic crystals

NASA Astrophysics Data System (ADS)

Wang, Kai; Liu, Ying; Liang, Tianshu; Wang, Bin

2018-05-01

In this paper, a new grading porous structure is introduced based on a Sierpinski triangle routine, and wave propagation in this fractal grading porous phononic crystal is investigated. The influences of fractal hierarchy and porosity on the band structures in fractal graidng porous phononic crystals are clarified. Vibration modes of unit cell at absolute band gap edges are given to manifest formation mechanism of absolute band gaps. The results show that absolute band gaps are easy to form in fractal structures comparatively to the normal ones with the same porosity. Structures with higher fractal hierarchies benefit multiple wider absolute band gaps. This work provides useful guidance in design of fractal porous phononic crystals.

Cellular generators of the cortical auditory evoked potential initial component.

PubMed

Steinschneider, M; Tenke, C E; Schroeder, C E; Javitt, D C; Simpson, G V; Arezzo, J C; Vaughan, H G

1992-01-01

Cellular generators of the initial cortical auditory evoked potential (AEP) component were determined by analyzing laminar profiles of click-evoked AEPs, current source density, and multiple unit activity (MUA) in primary auditory cortex of awake monkeys. The initial AEP component is a surface-negative wave, N8, that peaks at 8-9 msec and inverts in polarity below lamina 4. N8 is generated by a lamina 4 current sink and a deeper current source. Simultaneous MUA is present from lower lamina 3 to the subjacent white matter. Findings indicate that thalamocortical afferents are a generator of N8 and support a role for lamina 4 stellate cells. Relationships to the human AEP are discussed.

A multi-responsive water-driven actuator with instant and powerful performance for versatile applications

NASA Astrophysics Data System (ADS)

Mu, Jiuke; Hou, Chengyi; Zhu, Bingjie; Wang, Hongzhi; Li, Yaogang; Zhang, Qinghong

2015-03-01

Mechanical actuators driven by water that respond to multiple stimuli, exhibit fast responses and large deformations, and generate high stress have potential in artificial muscles, motors, and generators. Meeting all these requirements in a single device remains a challenge. We report a graphene monolayer paper that undergoes reversible deformation. Its graphene oxide cells wrinkle and extend in response to water desorption and absorption, respectively. Its fast (~0.3 s), powerful (>100 MPa output stress, 7.5 × 105 N kg-1 unit mass force), and controllable actuation can be triggered by moisture, heat, and light. The graphene monolayer paper has potential in artificial muscles, robotic hands, and electromagnetic-free generators.

Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of macrophage growth locus A (MglA) protein from Francisella tularensis

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

Subburaman, P.; Austin, B.P.; Shaw, G.X.

2010-11-03

Francisella tularensis, a potential bioweapon, causes a rare infectious disease called tularemia in humans and animals. The macrophage growth locus A (MglA) protein from F. tularensis associates with RNA polymerase to positively regulate the expression of multiple virulence factors that are required for its survival and replication within macrophages. The MglA protein was overproduced in Escherichia coli, purified and crystallized. The crystals diffracted to 7.5 {angstrom} resolution at the Advanced Photon Source, Argonne National Laboratory and belonged to the hexagonal space group P6{sub 1} or P6{sub 5}, with unit-cell parameters a = b = 125, c = 54 {angstrom}.

Multiband frequency-reconfigurable antenna using metamaterial structure of electromagnetic band gap

NASA Astrophysics Data System (ADS)

Dewan, Raimi; Rahim, M. K. A.; Himdi, Mohamed; Hamid, M. R.; Majid, H. A.; Jalil, M. E.

2017-01-01

A metamaterial of electromagnetic band gap (EBG) is incorporated to an antenna for frequency reconfigurability is proposed. The EBG consists of two identical unit cells that provide multiple band gaps at 1.88-1.94, 2.25-2.44, 2.67-2.94, 3.52-3.54, and 5.04-5.70 GHz with different EBG configurations. Subsequently, the antenna is incorporated with EBG. The corresponding incorporated structure successfully achieves various reconfigurable frequencies at 1.60, 1.91, 2.41, 3.26, 2.87, 5.21, and 5.54 GHz. The antenna has the potential to be implemented for Bluetooth, Wi-Fi, WiMAX, LTE, and cognitive radio applications.

EnviroAtlas - Average Annual Precipitation 1981-2010 by HUC12 for the Conterminous United States

EPA Pesticide Factsheets

This EnviroAtlas dataset provides the average annual precipitation by 12-digit Hydrologic Unit (HUC). The values were estimated from maps produced by the PRISM Climate Group, Oregon State University. The original data was at the scale of 800 m grid cells representing average precipitation from 1981-2010 in mm. The data was converted to inches of precipitation and then zonal statistics were estimated for a final value of average annual precipitation for each 12 digit HUC. For more information about the original dataset please refer to the PRISM website at http://www.prism.oregonstate.edu/. This dataset was produced by the US EPA to support research and online mapping activities related to EnviroAtlas. EnviroAtlas (https://www.epa.gov/enviroatlas) allows the user to interact with a web-based, easy-to-use, mapping application to view and analyze multiple ecosystem services for the contiguous United States. The dataset is available as downloadable data (https://edg.epa.gov/data/Public/ORD/EnviroAtlas) or as an EnviroAtlas map service. Additional descriptive information about each attribute in this dataset can be found in its associated EnviroAtlas Fact Sheet (https://www.epa.gov/enviroatlas/enviroatlas-fact-sheets).

Competitive Stem Cell Recruitment by Multiple Cytotactic Cues

PubMed Central

Mendelson, Avital; Cheung, Yukkee; Paluch, Kamila; Chen, Mo; Kong, Kimi; Tan, Jiali; Dong, Ziming; Sia, Samuel K.; Mao, Jeremy J.

2014-01-01

A multitude of cytotactic cues direct cell migration in development, cancer metastasis and wound healing. However, our understanding of cell motility remains fragmented partially because current migration devices only allow the study of independent factors. We developed a cell motility assay that allows competitive recruitment of a given cell population simultaneously by gradients of multiple cytotactic cues, observable under real-time imaging. Well-defined uniform gradients of cytotactic cues can be independently generated and sustained in each channel. As a case study, bone marrow mesenchymal stem/stromal cells (MSCs) were exposed to 15 cytokines that are commonly present in arthritis. Cytokines that induced robust recruitment of MSCs in multiple groups were selected to ‘compete’ in a final round to yield the most chemotactic factor(s) based on cell migration numbers, distances, migration indices and motility over time. The potency of a given cytokine in competition frequently differed from its individual action, substantiating the need to test multiple cytokines concurrently due to synergistic or antagonistic effects. This new device has the rare capacity to screen molecules that induce cell migration in cancer therapy, drug development and tissue regeneration. PMID:23364311

ATP release from freshly isolated guinea-pig bladder urothelial cells: a quantification and study of the mechanisms involved.

PubMed

McLatchie, Linda M; Fry, Christopher H

2015-06-01

To quantify the amount of ATP released from freshly isolated bladder urothelial cells, study its control by intracellular and extracellular calcium and identify the pathways responsible for its release. Urothelial cells were isolated from male guinea-pig urinary bladders and stimulated to release ATP by imposition of drag forces by repeated pipetting. ATP was measured using a luciferin-luciferase assay and the effects of modifying internal and external calcium concentration and blockers of potential release pathways studied. Freshly isolated guinea-pig urothelial cells released ATP at a mean (sem) rate of 1.9 (0.1) pmoles/mm(2) cell membrane, corresponding to about 700 pmoles/g of tissue, and about half [49 (6)%, n = 9) of the available cell ATP. This release was reduced to a mean (sem) of 0.46 (0.08) pmoles/mm(2) (160 pmoles/g) with 1.8 mm external calcium, and was increased about two-fold by increasing intracellular calcium. The release from umbrella cells was not significantly different from a mixed intermediate and basal cell population, suggesting that all three groups of cells release a similar amount of ATP per unit area. ATP release was reduced by ≈ 50% by agents that block pannexin and connexin hemichannels. It is suggested that the remainder may involve vesicular release. A significant fraction of cellular ATP is released from isolated urothelial cells by imposing drag forces that cause minimal loss of cell viability. This release involves multiple release pathways, including hemichannels and vesicular release. © 2014 The Authors BJU International © 2014 BJU International.

Risk Factors and Outcomes Related to Pediatric Intensive Care Unit Admission after Hematopoietic Stem Cell Transplantation: A Single-Center Experience.

PubMed

Pillon, Marta; Amigoni, Angela; Contin, Annaelena; Cattelan, Manuela; Carraro, Elisa; Campagnano, Emiliana; Tumino, Manuela; Calore, Elisabetta; Marzollo, Antonio; Mainardi, Chiara; Boaro, Maria Paola; Nizzero, Marta; Pettenazzo, Andrea; Basso, Giuseppe; Messina, Chiara

2017-08-01

To describe incidence, causes, and outcomes related to pediatric intensive care unit (PICU) admission for patients undergoing hematopoietic stem cell transplantation (HSCT), we investigated the risk factors predisposing to PICU admission and prognostic factors in terms of patient survival. From October 1998 to April 2015, 496 children and young adults (0 to 23 years) underwent transplantation in the HSCT unit. Among them, 70 (14.1%) were admitted to PICU. The 3-year cumulative incidence of PICU admission was 14.3%. The main causes of PICU admission were respiratory failure (36%), multiple organ failure (16%), and septic shock (13%). The overall 90-day cumulative probability of survival after PICU admission was 34.3% (95% confidence interval, 24.8% to 47.4%). In multivariate analysis, risk factors predisposing to PICU admission were allogeneic HSCT (versus autologous HSCT, P = .030) and second or third HSCT (P = .018). Characteristics significantly associated with mortality were mismatched HSCT (P = .011), relapse of underlying disease before PICU admission (P < .001), acute respiratory distress syndrome at admission (P = .012), hepatic failure at admission (P = .021), and need for invasive ventilation during PICU course (P < .001). Our data indicate which patients have a high risk for PICU admission after HSCT and for dismal outcomes after PICU stay. These findings may provide support for the clinical decision-making process on the opportunity of PICU admission for severely compromised patients after HSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Establishment of an unrelated umbilical cord blood bank qualification program: ensuring quality while meeting Food and Drug Administration vendor qualification requirements.

PubMed

Rabe, Fran; Kadidlo, Diane; Van Orsow, Lisa; McKenna, David

2013-10-01

Qualification of a cord blood bank (CBB) is a complex process that includes evaluation of multiple aspects of donor screening and testing, processing, accreditation and approval by professional cell therapy groups, and results of received cord blood units. The University of Minnesota Medical Center Cell Therapy Laboratory has established a CBB vendor qualification process to ensure the CBB meets established regulatory and quality requirements. The deployed qualification of CBBs is based on retrospective and prospective review of the CBB. Forty-one CBBs were evaluated retrospectively: seven CBBs were disqualified based on failed quality control (QC) results. Eight CBBs did not meet the criteria for retrospective qualification because fewer than 3 cord blood units were received and the CBB was not accredited. As of March 2012, three US and one non-US CBBs have been qualified prospectively. One CBB withdrew from the qualification process after successful completion of the comprehensive survey and subsequent failure of the provided QC unit to pass the minimum criteria. One CBB failed the prospective qualification process based on processing methods that were revealed during the paper portion of the evaluation. A CBB qualification process is necessary for a transplant center to manage the qualification of the large number of CBBs needed to support a umbilical cord blood transplantation program. A transplant center that has utilized cord blood for a number of years before implementation of a qualification process should use a retrospective qualification process along with a prospective process. © 2013 American Association of Blood Banks.

Three-dimensional high-entropy alloy-polymer composite nanolattices that overcome the strength-recoverability trade-off.

PubMed

Zhang, Xuan; Yao, Jiahao; Liu, Bin; Yan, Jun; Lu, Lei; Li, Yi; Gao, Huajian; Li, Xiaoyan

2018-06-14

Mechanical metamaterials with three-dimensional micro- and nano-architectures exhibit unique mechanical properties, such as high specific modulus, specific strength and energy absorption. However, a conflict exists between strength and recoverability in nearly all the mechanical metamaterials reported recently, in particular the architected micro-/nanolattices, which restricts the applications of these materials in energy storage/absorption and mechanical actuation. Here, we demonstrated the fabrication of three-dimensional architected composite nanolattices that overcome the strength-recoverability trade-off. The nanolattices under study are made up of a high entropy alloy coated (14.2-126.1 nm in thickness) polymer strut (approximately 260 nm in the characteristic size) fabricated via two-photon lithography and magnetron sputtering deposition. In situ uniaxial compression inside a scanning electron microscope showed that these composite nanolattices exhibit a high specific strength of 0.027 MPa/kg m3, an ultra-high energy absorption per unit volume of 4.0 MJ/m3, and nearly complete recovery after compression under strains exceeding 50%, thus overcoming the traditional strength-recoverability trade-off. During multiple compression cycles, the composite nanolattices exhibit a high energy loss coefficient (converged value after multiple cycles) of 0.5-0.6 at a compressive strain beyond 50%, surpassing the coefficients of all the micro-/nanolattices fabricated recently. Our experiments also revealed that for a given unit cell size, the composite nanolattices coated with a high entropy alloy with thickness in the range of 14-50 nm have the optimal specific modulus, specific strength and energy absorption per unit volume, which is related to a transition of the dominant deformation mechanism from local buckling to brittle fracture of the struts.

Pituitary adenylate cyclase-activating polypeptide (PACAP) contributes to the proliferation of hematopoietic progenitor cells in murine bone marrow via PACAP-specific receptor

PubMed Central

Xu, Zhifang; Ohtaki, Hirokazu; Watanabe, Jun; Miyamoto, Kazuyuki; Murai, Norimitsu; Sasaki, Shun; Matsumoto, Minako; Hashimoto, Hitoshi; Hiraizumi, Yutaka; Numazawa, Satoshi; Shioda, Seiji

2016-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP, encoded by adcyap1) plays an important role in ectodermal development. However, the involvement of PACAP in the development of other germ layers is still unclear. This study assessed the expression of a PACAP-specific receptor (PAC1) gene and protein in mouse bone marrow (BM). Cells strongly expressing PAC1+ were large in size, had oval nuclei, and merged with CD34+ cells, suggesting that the former were hematopoietic progenitor cells (HPCs). Compared with wild-type mice, adcyap1−/− mice exhibited lower multiple potential progenitor cell populations and cell frequency in the S-phase of the cell cycle. Exogenous PACAP38 significantly increased the numbers of colony forming unit-granulocyte/macrophage progenitor cells (CFU-GM) with two peaks in semi-solid culture. PACAP also increased the expression of cyclinD1 and Ki67 mRNAs. These increases were completely and partially inhibited by the PACAP receptor antagonists, PACAP6-38 and VIP6-28, respectively. Little or no adcyap1 was expressed in BM and the number of CFU-GM colonies was similar in adcyap1−/− and wild-type mice. However, PACAP mRNA and protein were expressed in paravertebral sympathetic ganglia, which innervate tibial BM, and in the sympathetic fibers of BM cavity. These results suggested that sympathetic nerve innervation may be responsible for PACAP-regulated hematopoiesis in BM, mainly via PAC1. PMID:26925806

Multiple Testing in the Context of Gene Discovery in Sickle Cell Disease Using Genome-Wide Association Studies.

PubMed

Kuo, Kevin H M

2017-01-01

The issue of multiple testing, also termed multiplicity, is ubiquitous in studies where multiple hypotheses are tested simultaneously. Genome-wide association study (GWAS), a type of genetic association study that has gained popularity in the past decade, is most susceptible to the issue of multiple testing. Different methodologies have been employed to address the issue of multiple testing in GWAS. The purpose of the review is to examine the methodologies employed in dealing with multiple testing in the context of gene discovery using GWAS in sickle cell disease complications.

Adjustment of Measurements with Multiplicative Errors: Error Analysis, Estimates of the Variance of Unit Weight, and Effect on Volume Estimation from LiDAR-Type Digital Elevation Models

PubMed Central

Shi, Yun; Xu, Peiliang; Peng, Junhuan; Shi, Chuang; Liu, Jingnan

2014-01-01

Modern observation technology has verified that measurement errors can be proportional to the true values of measurements such as GPS, VLBI baselines and LiDAR. Observational models of this type are called multiplicative error models. This paper is to extend the work of Xu and Shimada published in 2000 on multiplicative error models to analytical error analysis of quantities of practical interest and estimates of the variance of unit weight. We analytically derive the variance-covariance matrices of the three least squares (LS) adjustments, the adjusted measurements and the corrections of measurements in multiplicative error models. For quality evaluation, we construct five estimators for the variance of unit weight in association of the three LS adjustment methods. Although LiDAR measurements are contaminated with multiplicative random errors, LiDAR-based digital elevation models (DEM) have been constructed as if they were of additive random errors. We will simulate a model landslide, which is assumed to be surveyed with LiDAR, and investigate the effect of LiDAR-type multiplicative error measurements on DEM construction and its effect on the estimate of landslide mass volume from the constructed DEM. PMID:24434880

Hardware device binding and mutual authentication

DOEpatents

Hamlet, Jason R; Pierson, Lyndon G

2014-03-04

Detection and deterrence of device tampering and subversion by substitution may be achieved by including a cryptographic unit within a computing device for binding multiple hardware devices and mutually authenticating the devices. The cryptographic unit includes a physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a binding PUF value. The cryptographic unit uses the binding PUF value during an enrollment phase and subsequent authentication phases. During a subsequent authentication phase, the cryptographic unit uses the binding PUF values of the multiple hardware devices to generate a challenge to send to the other device, and to verify a challenge received from the other device to mutually authenticate the hardware devices.

A Phthalimide Derivative That Inhibits Centrosomal Clustering Is Effective on Multiple Myeloma

PubMed Central

Shiheido, Hirokazu; Terada, Fukiko; Tabata, Noriko; Hayakawa, Ichigo; Matsumura, Nobutaka; Takashima, Hideaki; Ogawa, Yoko; Du, Wenlin; Yamada, Taketo; Shoji, Mitsuru; Sugai, Takeshi; Doi, Nobuhide; Iijima, Shiro; Hattori, Yutaka; Yanagawa, Hiroshi

2012-01-01

Despite the introduction of newly developed drugs such as lenalidomide and bortezomib, patients with multiple myeloma are still difficult to treat and have a poor prognosis. In order to find novel drugs that are effective for multiple myeloma, we tested the antitumor activity of 29 phthalimide derivatives against several multiple myeloma cell lines. Among these derivatives, 2-(2,6-diisopropylphenyl)-5-amino-1H-isoindole-1,3- dione (TC11) was found to be a potent inhibitor of tumor cell proliferation and an inducer of apoptosis via activation of caspase-3, 8 and 9. This compound also showed in vivo activity against multiple myeloma cell line KMS34 tumor xenografts in ICR/SCID mice. By means of mRNA display selection on a microfluidic chip, the target protein of TC11 was identified as nucleophosmin 1 (NPM). Binding of TC11 and NPM monomer was confirmed by surface plasmon resonance. Immunofluorescence and NPM knockdown studies in HeLa cells suggested that TC11 inhibits centrosomal clustering by inhibiting the centrosomal-regulatory function of NPM, thereby inducing multipolar mitotic cells, which undergo apoptosis. NPM may become a novel target for development of antitumor drugs active against multiple myeloma. PMID:22761710

[Pooled Umbilical Cord Blood Plasma for Culturing UCMSC and Ex Vivo Expanding Umbilical Cord Blood CD34⁺ Cells].

PubMed

Wu, Jie-Ying; Lu, Yan; Chen, Jin-Song; Wu, Shao-Qing; Tang, Xue-Wei; Li, Yan

2015-08-01

To investigate the feasibility of umbilical cord blood plasma (UCP) as a replacement for fetal bovine serum (FBS) for culturing mesenchymal stem cells (MSC) derived from umbilical cord, and to observe the supporting effects of these cells (served as a feeder layer) on ex vivo expanding of human umbilical cord blood CD34(+) cells. Umbilical cord blood (UCB) units were suitable if the Guangzhou cord blood bank donor selection criteria strictly were fulfilled. UCP were ready to use after the collection from the plasma depletion/reduction during the processing and pooling of suitable UCB units (at least 30 units were screened for pathogens and microorganisms, and qualified). Umbilical cord mesenchymal stem cells (UCMSC) were harvested from the umbilical cord tissue of health full-term newborns after delivery by enzyme digestion and divided into 3 groups: group 1 and 2 were cultured in the presence of DMEM/F12 containing either FBS or UCP; and group 3 was cultured in serum-free medium (StemPro® MSC SFM CTS™). Morphology, proliferation and surface marker expression were examined by flow cytometry, and the differentiation toward adipogenic and osteogenic lineages was used for investigating the effect of media on UCMSC after 3-5 passages. Next, the cells cultured in the three different media were cryopreserved and thawed, then prepared as feeder layers with the name of UCMSC(FBS), UCMSC(UCP), and UCMSC(SFM), respectively. The CD34⁺ cells were separated from UCB by magnetic activated cell sorting (MACS) and divided into 4 groups cultured in StemPro(-34) SFM medium added with hematopoietic cytokine combination (StemSpan® CC100). The control group included only CD34⁺ cells as group A (blank control) and experimental groups included UCMSC(FBS) + CD34⁺ cells as group B, UCMSC(UCP) + CD34⁺ cells as group C, UCMSC(SFM) + CD34⁺ cells as group D, and cells in all groups were cultured ex vivo for 7 days. The nucleated cell (NC) number was counted by cell counter, CD34⁺ cells were measured by flow cytometry, and clonogenic assay was conducted at day 0 and 7 of culture. The expansion efficiency was assessed. The morphology (spindle-shaped and plastic-adherent), the immunophenotype (high positive percentage of CD73, CD90, CD105 and CD166) and the differentiation potential (osteogenic and adipogenic) were almost indistinguishable among the cells cultured in any of these three media except for the expression of CD105 in group 3 (serum-free medium) was lower than that in other 2 groups (P < 0.05). UCMSC grown in UCP medium demonstrated significantly higher proliferation rates than that in media containing FBS or commercial serum-free supplement (P < 0.05). After co-culture for 7 days, the CD34⁺ cell percentage decreased in all the groups, while NC were amplified effectively and the CD34⁺ cell number increased with the same order as group C or D group B or A (control group) (P < 0.05). As compared with the colony-forming unit (CFU) number at day 0, there was no significant difference in the expansion multiple between group C and D, while the expansion of CFU in group C were higher than that in group B and A. The UCP can be used as a better animal-free serum supplement for growth, maintenance and differentiation of UCMSC, thus would be a safe choice for clinical-scale production of human MSC.

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells

PubMed Central

Gledhill, Karl; Guo, Zongyou; Umegaki-Arao, Noriko; Higgins, Claire A.; Itoh, Munenari; Christiano, Angela M.

2015-01-01

The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes. PMID:26308443

Impact of genetic targets on therapy in head and neck squamous cell carcinoma.

PubMed

Chaikhoutdinov, Irina; Goldenberg, David

2013-01-01

Despite advances in surgical technique, radiation therapy and chemotherapy, the mortality from head and neck squamous cell carcinoma (HNSCC) has not improved significantly. Squamous cell carcinoma is caused by tobacco use, alcohol consumption and infection with high-risk types of human papillomavirus. It is the 6th most common cancer in the world, with upwards of 45,000 new cases reported yearly in the United States alone.In recent years, there has been a significant increase in the understanding of the molecular and genetic pathogenesis of head and neck cancer, shedding light on the unexpected heterogeneity of the disease. Genetic analysis has led to new classification schemes for HNSCC, with different subgroups exhibiting different prognoses. In addition, multiple targets in aberrant signaling pathways have been identified using increasingly sophisticated bio-informatics tools. Advances in technology have allowed for novel delivery mechanisms to introduce genetic material into cells to produce a therapeutic effect by targeting cancer cells via a number of different approaches.A pressing need to develop novel therapies to augment current treatment modalities has led to a number of translational studies involving gene therapy in the treatment of HNSCC. This article will focus on a review of the most recent developments in molecular biology of head and neck squamous cell carcinoma in regards to possible targets for gene therapy, as well as the array of novel therapeutic strategies directed at these targets.

APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair

PubMed Central

Nowarski, Roni; Wilner, Ofer I.; Cheshin, Ori; Shahar, Or D.; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S.; Goldberg, Michal; Willner, Itamar

2012-01-01

APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy. PMID:22645179

APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair.

PubMed

Nowarski, Roni; Wilner, Ofer I; Cheshin, Ori; Shahar, Or D; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S; Goldberg, Michal; Willner, Itamar; Kotler, Moshe

2012-07-12

APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.

Cost comparison of methods for preparation of neonatal red cell aliquots.

PubMed

Lechuga, Diana; Thompson, Christina

2007-01-01

The purpose of this study was to compare the preparation costs of two common methods used for neonatal red blood cell transfusion aliquots. Three months of data from a Level 2 and Level 3 neonatal intensive care unit (NICU) were used to determine the comparative cost for red cell aliquot transfusions using an eight bag aliquot/transfer system or the syringe set system. Using leuko-poor red blood cell blood collected in Adsol and containing approximately 320 ml of red blood cells and supernatant solution, the average cost of neonatal transfusion aliquots was determined using the Charter Medical syringe set and the Charter Medical eight bag aliquot/transfer system. A total of 126 red blood cell transfusion aliquots were used over the three month period. The amount transfused with each aliquot ranged from 5.0 ml - 55.0 ml with an average of 24.0 ml per aliquot. The cost per aliquot using the eight aliquot/transfer set was calculated as $36.25 and the cost per aliquot using the syringe set cost was calculated as $30.71. Additional benefits observed with the syringe set included decreased blood waste. When comparing Charter Medical multiple aliquot bag sets and the Charter Medical syringe aliquot system to provide neonatal transfusions, the use of the syringe system decreased blood waste and proved more cost effective.

The Psychosocial Development and Increased Fluency of Users of the SpeechEasyRTM Device: A Multiple Unit Case Study

ERIC Educational Resources Information Center

Horgan, David James

2010-01-01

This dissertation study explored the efficacy of the SpeechEasy[R] device for individuals who are gainfully employed stutterers and who participated in workplace education learning activities. This study attempted to fill a gap in the literature regarding efficacy of the SpeechEasy[R] device. It employed a qualitative multiple unit case study…

Transfusion-transmitted malaria masquerading as sickle cell crisis with multisystem organ failure.

PubMed

Maier, Cheryl L; Gross, Phillip J; Dean, Christina L; Chonat, Satheesh; Ip, Andrew; McLemore, Morgan; El Rassi, Fuad; Stowell, Sean R; Josephson, Cassandra D; Fasano, Ross M

2018-06-01

Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF). An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain. He received monthly blood transfusions as stroke prophylaxis. A source of infection was not readily identified, but treatment was initiated with continuous intravenous fluids and empiric antibiotics. The patient developed acute renal failure, acute hypoxic respiratory failure, and shock. He underwent red blood cell (RBC) exchange transfusion followed by therapeutic plasma exchange and continuous veno-venous hemodialysis. A manual peripheral blood smear revealed intraerythrocytic inclusions suggestive of Plasmodium, and molecular studies confirmed Plasmodium falciparum infection. Intravenous artesunate was given daily for 1 week. A look-back investigation involving two hospitals, multiple blood suppliers, and state and federal public health departments identified the source of malaria as a unit of RBCs transfused 2 weeks prior to admission. Clinical suspicion for transfusion-related adverse events, including hemolytic transfusion reactions and transfusion-transmitted infections, should be high in typically and atypically immunocompromised patient populations (like SCD), especially those on chronic transfusion protocols. Manual blood smear review aids in the evaluation of patients with SCD presenting with severe vaso-occlusive crisis and MSOF and can alert clinicians to the need for initiating aggressive therapy like RBC exchange and artesunate therapy. © 2018 AABB.

Synergistic Effects of Multiple Natural Products in Pancreatic Cancer Cells

PubMed Central

Wang, Zhiwei; Desmoulin, Sita; Banerjee, Sanjeev; Kong, Dejuan; Li, Yiwei; Deraniyagala, Rohan L; Abbruzzese, James; Sarkar, Fazlul H.

2008-01-01

Pancreatic cancer (PC) remains the fourth most common cause of cancer related death in the United States. Therefore, novel strategies for the prevention and treatment are urgently needed. Numerous dietary and pharmacological agents have been proposed as alternative strategies for the prevention and/or treatment of PC. Isoflavone is a prominent flavonoid found in soy products and has been proposed to be responsible for lowering the incidence of PC in Asians. Similarly, curcumin, an active ingredient of turmeric, that inhibits growth of malignant neoplasms, has a promising role in the prevention and/or treatment of PC. Here we examined whether isoflavone together with curcumin could elicit a greater inhibition of growth of PC cells than either agent alone, and also sought to determine the molecular mechanism of action. We found that the inhibition of cell growth and induction of apoptosis was significantly greater in the combination group than that could be achieved by either agent alone. These changes were associated with decreased Notch-1 expression and DNA binding activity of NF-κB and its target genes such as Cyclin D1, Bcl-2, and Bcl-xL. Moreover, we found that the combination of four natural agents at lower concentration was much more effective. Collectively, our results suggest that diet containing multiple natural products should be preferable over single agents for the prevention and/or treatment of PC. The superior effects of the combinatorial treatment could partly be attributed to the inhibition of constitutive activation of Notch-1 and NF-κB signaling pathways. PMID:18640131

Ex Vivo Expanded Natural Killer Cells Demonstrate Robust Proliferation In Vivo In High-Risk Relapsed Multiple Myeloma Patients

PubMed Central

Szmania, Susann; Lapteva, Natalia; Garg, Tarun; Greenway, Amy; Lingo, Joshuah; Nair, Bijay; Stone, Katie; Woods, Emily; Khan, Junaid; Stivers, Justin; Panozzo, Susan; Campana, Dario; Bellamy, William T.; Robbins, Molly; Epstein, Joshua; Yaccoby, Shmuel; Waheed, Sarah; Gee, Adrian; Cottler-Fox, Michele; Rooney, Cliona; Barlogie, Bart; van Rhee, Frits

2015-01-01

Highly activated/expanded natural killer (NK) cells can be generated via stimulation with the HLA-deficient cell line K562 genetically modified to express 41BB-ligand and membrane-bound interleukin (IL)15. We tested the safety, persistence and activity of expanded NK cells generated from myeloma patients (auto-NK) or haplo-identical family donors (allo-NK) in heavily pretreated patients with high-risk relapsing myeloma. The preparative regimen comprised bortezomib only or bortezomib and immunosuppression with cyclophosphamide, dexamethasone and fludarabine. NK cells were shipped overnight either cryopreserved or fresh. In 8 patients, up to 1×108 NK cells/kg were infused on day 0 and followed by daily administrations of IL2. Significant in vivo expansion was observed only in the 5 patients receiving fresh products, peaking at or near day 7, with the highest NK cell counts in 2 subjects who received cells produced in a high concentration of IL2 (500 units/mL). Seven days after infusion, donor NK cells comprised > 90% of circulating leukocytes in fresh allo-NK cell recipients, and cytolytic activity against allogeneic myeloma targets was retained in vitro. Among the 7 evaluable patients, there were no serious adverse events that could be related to NK cell infusion. One patient had a partial response and in another the tempo of disease progression decreased; neither patient required further therapy for 6 months. In the 5 remaining patients, disease progression was not affected by NK cell infusion. In conclusion, infusion of large numbers of expanded NK cells was feasible and safe; infusing fresh cells was critical to their expansion in vivo. PMID:25415285

Composite stabilizer unit

DOEpatents

Ebaugh, Larry R.; Sadler, Collin P.; Carter, Gary D.

1992-01-01

An improved fin stabilized projectile including multiple stabilizer fins upon a stabilizer unit situated at the aft end of the projectile is provided, the improvement wherein the stabilizer fins are joined into the stabillizer unit by an injection molded engineering grade polymer.

Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition

PubMed Central

Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara Mª; Teixidó, Montserrat; Gimenez, Mª Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Bladé, Joan; de Larrea, Carlos Fernández

2017-01-01

The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1–4%, 5–20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6–9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×109/L vs. 214×109/L, P<0.0001) and higher bone marrow plasma cells (median 53% vs. 36%, P=0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia. PMID:28255016

Unit: Cells, Inspection Set, National Trial Print.

ERIC Educational Resources Information Center

Australian Science Education Project, Toorak, Victoria.

This trial version of a unit is the series being produced by the Australian Science Education Project provides instructions for students to prepare a variety of cell types and examine them with microscopes. It also gives some information about the variety and function of cells. The core of the unit, which all students are expected to complete,…

The effectiveness of computer-generated 3D animations in inquiry chemistry laboratory

NASA Astrophysics Data System (ADS)

Theall, Rachel Morgan

It has been shown that students need a molecular-level understanding of substances in order to comprehend chemistry. For solid structures, atomic-level understanding requires students to learn additional and different concepts than for other states of matter. To aid understanding, animations were created to model unit cell structures and depict the properties of unit cells. In order to determine if these animations are helpful to students, they were tested during a laboratory exercise in which students had previously been using model kits and images from textbooks to learn about solid structures. Students evaluated in this study were from two lecture sections of general chemistry, one that routinely used animations during lecture and one that used a more traditional lecture format that did not include animations or models. Twelve laboratory sections of these lectures, taught by six different instructors each teaching two sections, were chosen for participation. One section for each instructor was given the animations as an optional tool for completing the laboratory assignment, which consisted of questions about unit cells and crystal structures. The results of the study indicate that students who looked at the animations performed significantly better on the assignment. For the control group, students who routinely viewed multiple representations of chemistry in lecture performed significantly better on the lab assignment than students in the lecture section where chemistry concepts were only presented on the chalkboard and overhead projector. Students in the traditional lecture section also had significantly less appreciation for the model kits used in the laboratory than students in the other lecture section. Observations of students in the lab combined with statistical results led to the revision of the solid structures investigation. Additional animations were created and inserted into the module that covered areas where students indicated more help was needed. Movies of "real life" chemistry were also incorporated into the module to help students relate the investigation to prior knowledge.

Automated platform for designing multiple robot work cells

NASA Astrophysics Data System (ADS)

Osman, N. S.; Rahman, M. A. A.; Rahman, A. A. Abdul; Kamsani, S. H.; Bali Mohamad, B. M.; Mohamad, E.; Zaini, Z. A.; Rahman, M. F. Ab; Mohamad Hatta, M. N. H.

2017-06-01

Designing the multiple robot work cells is very knowledge-intensive, intricate, and time-consuming process. This paper elaborates the development process of a computer-aided design program for generating the multiple robot work cells which offer a user-friendly interface. The primary purpose of this work is to provide a fast and easy platform for less cost and human involvement with minimum trial and errors adjustments. The automated platform is constructed based on the variant-shaped configuration concept with its mathematical model. A robot work cell layout, system components, and construction procedure of the automated platform are discussed in this paper where integration of these items will be able to automatically provide the optimum robot work cell design according to the information set by the user. This system is implemented on top of CATIA V5 software and utilises its Part Design, Assembly Design, and Macro tool. The current outcomes of this work provide a basis for future investigation in developing a flexible configuration system for the multiple robot work cells.

Finite-size correction scheme for supercell calculations in Dirac-point two-dimensional materials.

PubMed

Rocha, C G; Rocha, A R; Venezuela, P; Garcia, J H; Ferreira, M S

2018-06-19

Modern electronic structure calculations are predominantly implemented within the super cell representation in which unit cells are periodically arranged in space. Even in the case of non-crystalline materials, defect-embedded unit cells are commonly used to describe doped structures. However, this type of computation becomes prohibitively demanding when convergence rates are sufficiently slow and may require calculations with very large unit cells. Here we show that a hitherto unexplored feature displayed by several 2D materials may be used to achieve convergence in formation- and adsorption-energy calculations with relatively small unit-cell sizes. The generality of our method is illustrated with Density Functional Theory calculations for different 2D hosts doped with different impurities, all of which providing accuracy levels that would otherwise require enormously large unit cells. This approach provides an efficient route to calculating the physical properties of 2D systems in general but is particularly suitable for Dirac-point materials doped with impurities that break their sublattice symmetry.

V-band electronically reconfigurable metamaterial

NASA Astrophysics Data System (ADS)

Radisic, Vesna; Hester, Jimmy G.; Nguyen, Vinh N.; Caira, Nicholas W.; DiMarzio, Donald; Hilgeman, Theodore; Larouche, Stéphane; Kaneshiro, Eric; Gutierrez-Aitken, Augusto

2017-04-01

In this work, we report on a reconfigurable V-band metamaterial fabricated using an InP heterojunction bipolar transistor production process. As designed and fabricated, the implementation uses complementary split ring resonators (cSRRs) and Schottky diodes in both single unit cell and three unit cell monolithic microwave integrated circuits. Each unit cell has two diodes embedded within the gaps of the cSRRs. Reconfigurability is achieved by applying an external bias that turns the diodes on and off, which effectively controls the resonant property of the structure. In order to measure the metamaterial properties, the unit cells are fed and followed by transmission lines. Measured data show good agreement with simulations and demonstrate that the metamaterial structure exhibits resonance at around 65 GHz that can be switched on and off. The three-unit cell transmission line metamaterial shows a deeper resonance and a larger phase change than a single cell, as expected. These are the first reported reconfigurable metamaterials operating at the V-band using the InP high speed device fabrication process.

[The cell theory. Progress in studies on cell-cell communications].

PubMed

Brodskiĭ, V Ia

2009-01-01

Current data confirm the fundamental statement of the cell theory concerning the cell reproduction in a series of generations (omnis cellula e cellula). Cell communities or ensembles integrated by the signaling systems established in prokaryotes and protists and functioning in multicellular organisms including mammals are considered as the structural and functional unit of a multicellular organism. The cell is an elementary unit of life and basis of organism development and functioning. At the same time, the adult organism is not just a totality of cells. Multinucleated cells in some tissues, syncytial structure, and structural-functional units of organs are adaptations for optimal functioning of the multicellular organism and manifestations of cell-cell communications in development and definitive functioning. The cell theory was supplemented and developed by studies on cell-cell communications; however, these studies do not question the main generalizations of the theory.

Beyond Adapting to Climate Change: Embedding Adaptation in Responses to Multiple Threats and Stresses

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

Wilbanks, Thomas J; Kates, Dr. Robert W.

2010-01-01

Climate change impacts are already being experienced in every region of the United States and every part of the world most severely in Arctic regions and adaptation is needed now. Although climate change adaptation research is still in its infancy, significant adaptation planning in the United States has already begun in a number of localities. This article seeks to broaden the adaptation effort by integrating it with broader frameworks of hazards research, sustainability science, and community and regional resilience. To extend the range of experience, we draw from ongoing case studies in the Southeastern United States and the environmental historymore » of New Orleans to consider the multiple threats and stresses that all communities and regions experience. Embedding climate adaptation in responses to multiple threats and stresses helps us to understand climate change impacts, themselves often products of multiple stresses, to achieve community acceptance of needed adaptations as co-benefits of addressing multiple threats, and to mainstream the process of climate adaptation through the larger envelope of social relationships, communication channels, and broad-based awareness of needs for risk management that accompany community resilience.« less

Effect of blood transfusion on outcome after major burn injury: a multicenter study.

PubMed

Palmieri, Tina L; Caruso, Daniel M; Foster, Kevin N; Cairns, Bruce A; Peck, Michael D; Gamelli, Richard L; Mozingo, David W; Kagan, Richard J; Wahl, Wendy; Kemalyan, Nathan A; Fish, Joel S; Gomez, Manuel; Sheridan, Robert L; Faucher, Lee D; Latenser, Barbara A; Gibran, Nicole S; Klein, Robert L; Solem, Lynn D; Saffle, Jeffrey R; Morris, Stephen E; Jeng, James C; Voigt, David; Howard, Pamela A; Molitor, Fred; Greenhalgh, David G

2006-06-01

To delineate blood transfusion practices and outcomes in patients with major burn injury. Patients with major burn injury frequently require multiple blood transfusions; however, the effect of blood transfusion after major burn injury has had limited study. Multicenter retrospective cohort analysis. Regional burn centers throughout the United States and Canada. Patients admitted to a participating burn center from January 1 through December 31, 2002, with acute burn injuries of >or=20% total body surface area. Outcome measurements included mortality, number of infections, length of stay, units of blood transfused in and out of the operating room, number of operations, and anticoagulant use. A total of 21 burn centers contributed data on 666 patients; 79% of patients survived and received a mean of 14 units of packed red blood cells during their hospitalization. Mortality was related to patient age, total body surface area burn, inhalation injury, number of units of blood transfused outside the operating room, and total number of transfusions. The number of infections per patient increased with each unit of blood transfused (odds ratio, 1.13; p<.001). Patients on anticoagulation during hospitalization received more blood than patients not on anticoagulation (16.3+/-1.5 vs. 12.3+/-1.5, p<.001). The number of transfusions received was associated with mortality and infectious episodes in patients with major burns even after factoring for indices of burn severity. The utilization of blood products in the treatment of major burn injury should be reserved for patients with a demonstrated physiologic need.

Multiple Child Care Arrangements and Child Well Being: Early Care Experiences in Australia

ERIC Educational Resources Information Center

Claessens, Amy; Chen, Jen-Hao

2013-01-01

Nearly one quarter of Australian children under the age of 5 experience multiple non-parental child care arrangements. Research focused on the relationship between multiple child care arrangements and child socioemotional development is limited, particularly in Australia. Evidence from the United States and Europe has linked multiple child care…

Multiple emulsions as effective platforms for controlled anti-cancer drug delivery.

PubMed

Dluska, Ewa; Markowska-Radomska, Agnieszka; Metera, Agata; Tudek, Barbara; Kosicki, Konrad

2017-09-01

Developing pH-responsive multiple emulsion platforms for effective glioblastoma multiforme therapy with reduced toxicity, a drug release study and modeling. Cancer cell line: U87 MG, multiple emulsions with pH-responsive biopolymer and encapsulated doxorubicin (DOX); preparation of multiple emulsions in a Couette-Taylor flow biocontactor, in vitro release study of DOX (fluorescence intensity analysis), in vitro cytotoxicity study (alamarBlue cell viability assay) and numerical simulation of DOX release rates. The multiple emulsions offered a high DOX encapsulation efficiency (97.4 ± 1%) and pH modulated release rates of a drug. Multiple emulsions with a low concentration of DOX (0.02 μM) exhibited broadly advanced cell (U87 MG) cytotoxicity than free DOX solution used at the same concentration. Emulsion platforms could be explored for potential delivery of chemotherapeutics in glioblastoma multiforme therapy.

Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells

PubMed Central

Jang, Jinsil; Jeong, Soo-Jin; Kwon, Hee-Young; Jung, Ji Hoon; Sohn, Eun Jung; Lee, Hyo-Jung; Kim, Ji-Hyun; Kim, Sun-Hee; Kim, Jin Hyoung; Kim, Sung-Hoon

2013-01-01

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells. PMID:23818927

Presence of multiple sites containing polar material in spherical Escherichia coli cells that lack MreB.

PubMed

Nilsen, Trine; Yan, Arthur W; Gale, Gregory; Goldberg, Marcia B

2005-09-01

In rod-shaped bacteria, certain proteins are specifically localized to the cell poles. The nature of the positional information that leads to the proper localization of these proteins is unclear. In a screen for factors required for the localization of the Shigella sp. actin assembly protein IcsA to the bacterial pole, a mutant carrying a transposon insertion in mreB displayed altered targeting of IcsA. The phenotype of cells containing a transposon insertion in mreB was indistinguishable from that of cells containing a nonpolar mutation in mreB or that of wild-type cells treated with the MreB inhibitor A22. In cells lacking MreB, a green fluorescent protein (GFP) fusion to a cytoplasmic derivative of IcsA localized to multiple sites. Secreted full-length native IcsA was present in multiple faint patches on the surfaces of these cells in a pattern similar to that seen for the cytoplasmic IcsA-GFP fusion. EpsM, the polar Vibrio cholerae inner membrane protein, also localized to multiple sites in mreB cells and colocalized with IcsA, indicating that localization to multiple sites is not unique to IcsA. Our results are consistent with the requirement, either direct or indirect, for MreB in the restriction of certain polar material to defined sites within the cell and, in the absence of MreB, with the formation of ectopic sites containing polar material.

Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells.

PubMed

Jang, Jinsil; Jeong, Soo-Jin; Kwon, Hee-Young; Jung, Ji Hoon; Sohn, Eun Jung; Lee, Hyo-Jung; Kim, Ji-Hyun; Kim, Sun-Hee; Kim, Jin Hyoung; Kim, Sung-Hoon

2013-01-01

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.

MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells

PubMed Central

Brito, Jose L.R.; Walker, Brian; Jenner, Matthew; Dickens, Nicholas J.; Brown, Nicola J.M.; Ross, Fiona M.; Avramidou, Athanasia; Irving, Julie A.E.; Gonzalez, David; Davies, Faith E.; Morgan, Gareth J.

2009-01-01

Background The recurrent immunoglobulin translocation, t(4;14)(p16;q32) occurs in 15% of multiple myeloma patients and is associated with poor prognosis, through an unknown mechanism. The t(4;14) up-regulates fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET) genes. The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear. Design and Methods The expression of MMSET was analyzed using a novel antibody. The involvement of MMSET in t(4;14) myelomagenesis was assessed by small interfering RNA mediated knockdown combined with several biological assays. In addition, the differential gene expression of MMSET-induced knockdown was analyzed with expression microarrays. MMSET gene targets in primary patient material was analyzed by expression microarrays. Results We found that MMSET isoforms are expressed in multiple myeloma cell lines, being exclusively up-regulated in t(4;14)-positive cells. Suppression of MMSET expression affected cell proliferation by both decreasing cell viability and cell cycle progression of cells with the t(4;14) translocation. These findings were associated with reduced expression of genes involved in the regulation of cell cycle progression (e.g. CCND2, CCNG1, BRCA1, AURKA and CHEK1), apoptosis (CASP1, CASP4 and FOXO3A) and cell adhesion (ADAM9 and DSG2). Furthermore, we identified genes involved in the latter processes that were differentially expressed in t(4;14) multiple myeloma patient samples. Conclusions In conclusion, dysregulation of MMSET affects the expression of several genes involved in the regulation of cell cycle progression, cell adhesion and survival. PMID:19059936

Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis

PubMed Central

Lovato, Laura; Willis, Simon N.; Rodig, Scott J.; Caron, Tyler; Almendinger, Stefany E.; Howell, Owain W.; Reynolds, Richard; Hafler, David A.

2011-01-01

In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis. PMID:21216828

Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis.

PubMed

Lovato, Laura; Willis, Simon N; Rodig, Scott J; Caron, Tyler; Almendinger, Stefany E; Howell, Owain W; Reynolds, Richard; O'Connor, Kevin C; Hafler, David A

2011-02-01

In the central nervous system of patients with multiple sclerosis, B cell aggregates populate the meninges, raising the central question as to whether these structures relate to the B cell infiltrates found in parenchymal lesions or instead, represent a separate central nervous system immune compartment. We characterized the repertoires derived from meningeal B cell aggregates and the corresponding parenchymal infiltrates from brain tissue derived primarily from patients with progressive multiple sclerosis. The majority of expanded antigen-experienced B cell clones derived from meningeal aggregates were also present in the parenchyma. We extended this investigation to include 20 grey matter specimens containing meninges, 26 inflammatory plaques, 19 areas of normal appearing white matter and cerebral spinal fluid. Analysis of 1833 B cell receptor heavy chain variable region sequences demonstrated that antigen-experienced clones were consistently shared among these distinct compartments. This study establishes a relationship between extraparenchymal lymphoid tissue and parenchymal infiltrates and defines the arrangement of B cell clones that populate the central nervous system of patients with multiple sclerosis.

Long-Term Quality Control Program Plan for Cord Blood Banks in Korea: A Pilot Study for Cryopreservation Stability.

PubMed

Seo, Soo Hyun; Shin, Sue; Roh, Eun Youn; Song, Eun Young; Oh, Sohee; Kim, Byoung Jae; Yoon, Jong Hyun

2017-03-01

Maintaining the quality of cryopreserved cord blood is crucial. In this pilot study, we describe the results of the internal quality control program for a cord blood bank thus far. Donated cord blood units unsuitable for transplantation were selected for internal quality control once a month. One unit of cord blood, aliquoted into 21 capillaries, was cryopreserved and thawed annually to analyze the total nucleated cell count, CD34⁺ cell count, cell viability test, and colony-forming units assay. No significant differences in the variables (total nucleated cell count, cell viability, CD34⁺ cell count) were observed between samples cryopreserved for one and two years. Upon comparing the variables before cryopreservation and post thawing with the capillaries of one year of storage, cell viability and CD34⁺ cell counts decreased significantly. The use of cord blood samples in capillaries, which can be easily stored for a long period, was similar to the methods used for testing segments attached to the cord blood unit. The results of this study may be useful for determining the period during which the quality of cryopreserved cord blood units used for transplantation is maintained.

Long-Term Quality Control Program Plan for Cord Blood Banks in Korea: A Pilot Study for Cryopreservation Stability

PubMed Central

Seo, Soo Hyun; Shin, Sue; Roh, Eun Youn; Song, Eun Young; Oh, Sohee; Kim, Byoung Jae

2017-01-01

Background Maintaining the quality of cryopreserved cord blood is crucial. In this pilot study, we describe the results of the internal quality control program for a cord blood bank thus far. Methods Donated cord blood units unsuitable for transplantation were selected for internal quality control once a month. One unit of cord blood, aliquoted into 21 capillaries, was cryopreserved and thawed annually to analyze the total nucleated cell count, CD34+ cell count, cell viability test, and colony-forming units assay. Results No significant differences in the variables (total nucleated cell count, cell viability, CD34+ cell count) were observed between samples cryopreserved for one and two years. Upon comparing the variables before cryopreservation and post thawing with the capillaries of one year of storage, cell viability and CD34+ cell counts decreased significantly. The use of cord blood samples in capillaries, which can be easily stored for a long period, was similar to the methods used for testing segments attached to the cord blood unit. Conclusions The results of this study may be useful for determining the period during which the quality of cryopreserved cord blood units used for transplantation is maintained. PMID:28028998

Spotlight on elotuzumab in the treatment of multiple myeloma: the evidence to date

PubMed Central

Weisel, Katja

2016-01-01

Despite advances in the treatment of multiple myeloma, it remains an incurable disease, with relapses and resistances frequently observed. Recently, immunotherapies, in particular, monoclonal antibodies, have become important treatment options in anticancer therapies. Elotuzumab is a humanized monoclonal antibody to signaling lymphocytic activation molecule F7, which is highly expressed on myeloma cells and, to a lower extent, on selected leukocyte subsets such as natural killer cells. By directly activating natural killer cells and by antibody-dependent cell-mediated cytotoxicity, elotuzumab exhibits a dual mechanism of action leading to myeloma cell death with minimal effects on normal tissue. In several nonclinical models of multiple myeloma, elotuzumab was effective as a single agent and in combination with standard myeloma treatments, supporting the use of elotuzumab in patients. In combination with lenalidomide and dexamethasone, elotuzumab showed a significant increase in tumor response rates and progression-free survival in patients with relapsed and/or refractory multiple myeloma. This review summarizes the nonclinical and clinical development of elotuzumab as a single agent and in combination with established therapies for the treatment of multiple myeloma. PMID:27785050

Unprecedented linking of two polyoxometalate units with a metal-metal multiple bond.

PubMed

Sokolov, Maxim N; Korenev, Vladimir S; Izarova, Natalya V; Peresypkina, Eugenia V; Vicent, Cristian; Fedin, Vladimir P

2009-03-02

The reaction of (Bu(4)N)(2)[Re(2)Cl(8)] with lacunary Keggin polyoxometalate K(7)[PW(11)O(39)] in water produces a new dumbbell-shaped heteropolyoxometalate anion, [Re(2)(PW(11)O(39))(2)](8-), whose structure contains a central Re(2) core with a quadruple bond between Re atoms (Re-Re 2.25 A), coordinated to two polyoxometalate units. This complex represents the first example of the direct linking of two polyoxometalate units via a metal-metal multiple bond. The compounds were characterized by X-ray analysis, IR, and electrospray ionization mass spectrometry.

System, Apparatus, and Method for Active Debris Removal

NASA Technical Reports Server (NTRS)

Hickey, Christopher J. (Inventor); Spehar, Peter T. (Inventor); Griffith, Sr., Anthony D. (Inventor); Kohli, Rajiv (Inventor); Burns, Susan H. (Inventor); Gruber, David J. (Inventor); Lee, David E. (Inventor); Robinson, Travis M. (Inventor); Damico, Stephen J. (Inventor); Smith, Jason T. (Inventor)

2017-01-01

Systems, apparatuses, and methods for removal of orbital debris are provided. In one embodiment, an apparatus includes a spacecraft control unit configured to guide and navigate the apparatus to a target. The apparatus also includes a dynamic object characterization unit configured to characterize movement, and a capture feature, of the target. The apparatus further includes a capture and release unit configured to capture a target and deorbit or release the target. The collection of these apparatuses is then employed as multiple, independent and individually operated vehicles launched from a single launch vehicle for the purpose of disposing of multiple debris objects.

Polycistronic tRNA and CRISPR guide-RNA enables highly efficient multiplexed genome engineering in human cells

PubMed Central

Dong, Fengping; Xie, Kabin; Chen, Yueying; Yang, Yinong; Mao, Yingwei

2016-01-01

CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides a potential tool to introduce multiple mutations in a genome. To mimic complicated genomic variants in human diseases, such as multiple gene deletions or mutations, two or more small guide RNAs (sgRNAs) need to be introduced all together. This can be achieved by separate Pol III promoters in a construct. However, limited enzyme sites and increased insertion size lower the efficiency to make a construct. Here, we report a strategy to quickly assembly multiple sgRNAs in one construct using a polycistronic-tRNA-gRNA (PTG) strategy. Taking advantage of the endogenous tRNA processing system in mammalian cells, we efficiently express multiple sgRNAs driven using only one Pol III promoter. Using an all-in-one construct carrying PTG, we disrupt the deacetylase domain in multiple histone deacetylases (HDACs) in human cells simultaneously. We demonstrate that multiple HDAC deletions significantly affect the activation of the Wnt-signaling pathway. Thus, this method enables to efficiently target multiple genes and provide a useful tool to establish mutated cells mimicking human diseases. PMID:27890617

Polycistronic tRNA and CRISPR guide-RNA enables highly efficient multiplexed genome engineering in human cells.

PubMed

Dong, Fengping; Xie, Kabin; Chen, Yueying; Yang, Yinong; Mao, Yingwei

2017-01-22

CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides a potential tool to introduce multiple mutations in a genome. To mimic complicated genomic variants in human diseases, such as multiple gene deletions or mutations, two or more small guide RNAs (sgRNAs) need to be introduced all together. This can be achieved by separate Pol III promoters in a construct. However, limited enzyme sites and increased insertion size lower the efficiency to make a construct. Here, we report a strategy to quickly assembly multiple sgRNAs in one construct using a polycistronic-tRNA-gRNA (PTG) strategy. Taking advantage of the endogenous tRNA processing system in mammalian cells, we efficiently express multiple sgRNAs driven using only one Pol III promoter. Using an all-in-one construct carrying PTG, we disrupt the deacetylase domain in multiple histone deacetylases (HDACs) in human cells simultaneously. We demonstrate that multiple HDAC deletions significantly affect the activation of the Wnt-signaling pathway. Thus, this method enables to efficiently target multiple genes and provide a useful tool to establish mutated cells mimicking human diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Hydrogen storage and integrated fuel cell assembly

DOEpatents

Gross, Karl J.

2010-08-24

Hydrogen is stored in materials that absorb and desorb hydrogen with temperature dependent rates. A housing is provided that allows for the storage of one or more types of hydrogen-storage materials in close thermal proximity to a fuel cell stack. This arrangement, which includes alternating fuel cell stack and hydrogen-storage units, allows for close thermal matching of the hydrogen storage material and the fuel cell stack. Also, the present invention allows for tailoring of the hydrogen delivery by mixing different materials in one unit. Thermal insulation alternatively allows for a highly efficient unit. Individual power modules including one fuel cell stack surrounded by a pair of hydrogen-storage units allows for distribution of power throughout a vehicle or other electric power consuming devices.

Extraction of Carbon Dioxide and Hydrogen from Seawater by an Electrochemical Acidification Cell. Part 3. Scaled-up Mobile Unit Studies (Calendar Year 2011)

DTIC Science & Technology

2012-05-30

Electrochemical Acidification Cell Part III: Scaled-up Mobile Unit Studies (Calendar Year 2011) May 30, 2012 Approved for public release; distribution is...Hydrogen from Seawater by an Electrochemical Acidification Cell Part III: Scaled-up Mobile Unit Studies (Calendar Year 2011) Heather D. Willauer, Dennis R...Unclassified Unlimited Unclassified Unlimited Unclassified Unlimited 41 Heather D. Willauer (202) 767-2673 Electrochemical acidification cell Carbon

SMEX-Lite Modular Solar Array Architecture

NASA Technical Reports Server (NTRS)

Lyons, John

2002-01-01

For the most part, Goddard solar arrays have been custom designs that are unique to each mission. The solar panel design has been frozen prior to issuing an RFP for their procurement. There has typically been 6-9 months between RFP release and contract award, followed by an additional 24 months for performance of the contract. For Small Explorer (SMEX) missions, with three years between mission definition and launch, this has been a significant problem. The SMEX solar panels have been sufficiently small that the contract performance period has been reduced to 12-15 months. The bulk of this time is used up in the final design definition and fabrication of flight solar cell assemblies. Even so, it has been virtually impossible to have the spacecraft design at a level of maturity sufficient to freeze the solar panel geometry and release the RFP in time to avoid schedule problems with integrating the solar panels to the spacecraft. With that in mind, the SMEX-Lite project team developed a modular architecture for the assembly of solar arrays to greatly reduce the cost and schedule associated with the development of a mission- specific solar array. In the modular architecture, solar cells are fabricated onto small substrate panels. This modular panel (approximately 8.5" x 17" in this case) becomes the building block for constructing solar arrays for multiple missions with varying power requirements and geometrical arrangements. The mechanical framework that holds these modules together as a solar array is the only mission-unique design, changing in size and shape as required for each mission. There are several advantages to this approach. First, the typical solar array development cycle requires a mission unique design, procurement, and qualification including a custom qualification panel. With the modular architecture, a single qualification of the SMEX-Lite modules and the associated mechanical framework in a typical configuration provided a qualification by similarity to multiple missions. It then becomes possible to procure solar array modules in advance of mission definition and respond quickly and inexpensively to a selected mission's unique requirements. The solar array modular architecture allows the procurement of solar array modules before the array geometry has been frozen. This reduces the effect of procurement lead-time on the mission integration and test flow by as much as 50%. Second, by spreading the non-recurring costs over multiple missions, the cost per unit area is also reduced. In the case of the SMEX-Lite procurement, this reduction was by about one third of the cost per unit area compared to previous SMEX mission-unique procurements. Third, the modular architecture greatly facilitates the infusion of new solar cell technologies into flight programs as these technologies become available. New solar cell technologies need only be fabricated onto a standard-sized module to be incorporated into the next available mission. The modular solar array can be flown in a mixed configuration with some new and some standard cell technologies. Since each module has its own wiring terminals, the array can be arranged as desired electrically with little impact to cost and schedule. The solar array modular architecture does impose some additional constraints on systems and subsystem engineers. First, they must work with discrete solar array modules rather than size the array to fit exactly within an available envelope. The array area is constrained to an integer multiple of the module area. Second, the modular design is optimized for space radiation and thermal environments not greatly different from a typical SMEX LEO environment. For example, a mission with a highly elliptical orbit (e.g., Polar, SMEX/FAST) would require thicker coverglasses to protect the solar cells from the more intense radiation environment.

Beyond CD34+ cell dose: impact of method of peripheral blood hematopoietic stem cell mobilization (granulocyte-colony-stimulating factor [G-CSF], G-CSF plus plerixafor, or cyclophosphamide G-CSF/granulocyte-macrophage [GM]-CSF) on number of colony-forming unit-GM, engraftment, and Day +100 hematopoietic graft function.

PubMed

Alexander, Erin T; Towery, Jeanne A; Miller, Ashley N; Kramer, Cindy; Hogan, Kathy R; Squires, Jerry E; Stuart, Robert K; Costa, Luciano J

2011-09-01

The dose of CD34+ cells/kg in the mobilized peripheral blood product is the main determinant of neutrophil and platelet (PLT) engraftment after autologous hematopoietic stem cell transplantation (AHSCT). Whether the method of mobilization, namely, granulocyte-colony-stimulating factor (G-CSF) alone (G), G-CSF plus plerixafor (G+P), or cyclophosphamide + G/granulocyte-macrophage (GM)-CSF (Cy+G/GM), independently affects number of colony-forming unit (CFU)-GM, engraftment, and hematopoietic graft function is unknown. We used a database of AHSCT patients with multiple myeloma or lymphoma to identify three groups with different mobilization strategies receiving transplantation with similar CD34+ cell doses. Groups were compared in terms of CFU-GM, ratio of CFU-GM/CD34+, engraftment of neutrophils and PLTs, and hematopoietic graft function on Day +100. Ninety-six patients were included in the analysis, 26 G, 32 G+P, and 38 Cy+G/GM, with median cell doses of 4.21 × 10(6) , 4.11 × 10(6) , and 4.67 × 10(6) CD34+/kg, respectively (p = 0.433). There was no significant difference in number of CFU-GM between the three groups; however, the ratio of CFU-GM/CD34+ was significantly lower for G+P (p = 0.008). Median time for neutrophil engraftment was 13 days in G+P and 12 days in G and Cy+G/GM (p = 0.028), while PLT engraftment happened at a median of 14.5 days in G+P versus 12 days in G and 11 days in Cy+G/GM (p = 0.012). There was no difference in hematopoietic graft function at Day +100. Plerixafor-based mobilization is associated with slightly reduced number of CFU-GM and minimal delay in engraftment that is independent of CD34+ cell dose. Hematopoietic graft function on Day 100 is not affected by mobilization strategy. © 2011 American Association of Blood Banks.

Regulation of epidermal cell fate in Arabidopsis roots: the importance of multiple feedback loops

PubMed Central

Schiefelbein, John; Huang, Ling; Zheng, Xiaohua

2014-01-01

The specification of distinct cell types in multicellular organisms is accomplished via establishment of differential gene expression. A major question is the nature of the mechanisms that establish this differential expression in time and space. In plants, the formation of the hair and non-hair cell types in the root epidermis has been used as a model to understand regulation of cell specification. Recent findings show surprising complexity in the number and the types of regulatory interactions between the multiple transcription factor genes/proteins influencing root epidermis cell fate. Here, we describe this regulatory network and the importance of the multiple feedback loops for its establishment and maintenance. PMID:24596575

Chemical complexity and source of the White River Ash, Alaska and Yukon

USGS Publications Warehouse

Preece, S.J.; McGimsey, Robert G.; Westgate, J.A.; Pearce, N.J.G.; Hartmann, W.K.; Perkins, W.T.

2014-01-01

The White River Ash, a prominent stratigraphic marker bed in Alaska (USA) and Yukon (Canada), consists of multiple compositional units belonging to two geochemical groups. The compositional units are characterized using multiple criteria, with combined glass and ilmenite compositions being the best discriminators. Two compositional units compose the northern group (WRA-Na and WRA-Nb), and two units are present in the eastern group (WRA-Ea and the younger, WRA-Eb). In the proximal area, the ca. 1900 yr B.P. (Lerbekmo et al., 1975) WRA-Na displays reverse zoning in the glass phase and systematic changes in ilmenite composition and estimated oxygen fugacity from the base to the top of the unit. The eruption probably tapped different magma batches or bodies within the magma reservoir with limited mixing or mingling between them. The 1147 cal yr B.P. (calibrated years, approximately equivalent to calendric years) (Clague et al., 1995) WRA-Ea eruption is only weakly zoned, but pumices with different glass compositions are present, along with gray and white intermingled glass in individual pumice clasts, indicating the presence of multiple magmatic bodies or layers. All White River Ash products are high-silica adakites and are sourced from the Mount Churchill magmatic system.

Wide-angle, polarization-insensitive and broadband absorber based on eight-fold symmetric SRRs metamaterial

NASA Astrophysics Data System (ADS)

Wu, Dong; Liu, Yumin; Yu, Zhongyuan; Chen, Lei; Ma, Rui; Li, Yutong; Li, Ruifang; Ye, Han

2016-12-01

In this paper, we propose a novel three dimensional metamaterial design with eight-fold rotational symmetry that shows a polarization-insensitive, wide-angle and broadband perfect absorption in the microwave band. By simulation, the polarization-insensitive absorption is over 90% between 26.9 GHz to 32.9 GHz, and the broadband absorption remains a good absorption performance to a wide incident angles for both TE and TM polarizations. The magnetic field distribution are investigated to interpret the physical mechanism of broadband absorption. The broadband absorption is based on overlapping the multiple magnetic resonances at the neighboring frequencies by coupling effects of multiple metallic split-ring resonators (SRRs). Moreover, it is demonstrate that the designed structure can be extended to other frequencies by scale down the size of the unit cell, such as the visible frequencies. The simulated results show that the absorption of the smaller absorber is above 90% in the frequency range from 467 THz to 765 THz(392-642 nm), which include orange to purple light in visible region(400-760nm). The wide-angle and polarization-insensitive stabilities of the smaller absorber is also demonstrated at visible region. The proposed work provides a new design of realization of a polarization-insensitive, wide-angle and broadband absorber ranging different frequency bands, and such a structure has potential application in the fields of solar cell, imaging and detection.

Immunoglobulin G4-related acquired hemophilia: A case report

PubMed Central

Li, Xiaoyan; Duan, Wei; Zhu, Xiang; Xu, Jianying

2016-01-01

Acquired hemophilia A (AHA) is a relatively rare and life-threatening bleeding disorder whose pathogenesis is not completely understood. The present study reports a rare case of immunogubulin (IgG)4-related AHA with multisystemic involvement. A 55-year old male patient presented with symptoms of bronchial asthma and multiple subdermal hematomas. Chest computed tomography showed multiple diffuse nodular lesions with thickening of bronchovascular bundles, and scattered high-density spots in both lung lobes. Laboratory investigations showed increased activated partial prothrombin time (120.0 sec), a markedly decreased factor VIII (FVIII) activity (0.5%), a high-titer of FVIII inhibitor (27.2 Bethesda units/ml) and a marked increase in serum IgG4 (>4.03 g/l) level. Left inguinal lymph node biopsy revealed capsular thickening with marked lymphoplasmacytic infiltration, occlusive phlebitis and irregular fibrosis. Immunostaining revealed numerous IgG4-positive plasma cells (>100 cells/human plasma fibronectin) in the nodular lesions, with an IgG4/IgG ratio of >40%. The symptoms were markedly alleviated following corticosteroid therapy. The current study presents the first reported case of a rare IgG4-related AHA that presented with unusual clinical features and multisystemic involvement. The patient responded well to corticosteroid therapy. Documentation of such rare cases will help in characterizing the pathogenesis, and prompt recognition and timely treatment of this rare disorder. PMID:28105131

Relative Performance of Lindgren Multiple-Funnel, Intercept Panel, and Colossus Pipe Traps in Catching Cerambycidae and Associated Species in the Southeastern United States

Treesearch

Daniel R. Miller; Christopher M. Crowe

2011-01-01

In 2004, we evaluated the relative performance of 8-unit Lindgren multiple-funnel (funnel), Intercept panel (panel), and Colossus pipe (pipe) traps, baited with ethanol and -pinene lures, in catching saproxylic beetles (Coleoptera) in pine stands in northern Florida and western South Carolina. Panel traps were as good as, if not better than, funnel and pipe...

Sorafenib in Treating Patients With Metastatic or Unresectable Solid Tumors, Multiple Myeloma, or Non-Hodgkin's Lymphoma With or Without Impaired Liver or Kidney Function

ClinicalTrials.gov

2013-01-04

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenström Macroglobulinemia

Effect of the orthoquinone moiety in 9,10-phenanthrenequinone on its ability to induce apoptosis in HCT-116 and HL-60 cells.

PubMed

Hatae, Noriyuki; Nakamura, Jun; Okujima, Tetsuo; Ishikura, Minoru; Abe, Takumi; Hibino, Satoshi; Choshi, Tominari; Okada, Chiaki; Yamada, Hiroko; Uno, Hidemitsu; Toyota, Eiko

2013-08-15

9,10-Phenanthrenequinone (9,10-PQ) is one of the most abundant quinones among diesel exhaust particulates. Recent data have suggested that quinones induce apoptosis in immune, epithelial and tumor cells, leading to respirator illness; however, the mechanisms by which quinones induce apoptosis and the structure required for this remain unknown. We studied the antitumor activity of 9,10-PQ analogs against two human tumor cell lines, HCT-116 colon tumor cells and HL-60 promyelocytic leukemia cells. The loss of the cis-orthoquinone unit in 9,10-PQ abrogated its ability to induce apoptosis in the two tumor cell lines, and the LC50 values of these analogs were indicated over 10 μM. An analog of 9,10-PQ in which the biaryl unit had been deleted displayed a reduced ability to induce tumor cell apoptosis, while the analogs 1,10-phenanthroline-5,6-dione (9) and pyrene-4,5-dione (10), which also had modified biaryl units, exhibited increased tumor cell apoptotic activity. The cis-orthoquinone unit in 9,10-PQ was identified as essential for its ability to induce apoptosis in tumor cells, and its biaryl unit is also considered to influence orthoquinone-mediated apoptotic activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

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

Webb, Carol F., E-mail: carol-webb@omrf.org; Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights:more » • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.« less

Lattice-structures and constructs with designed thermal expansion coefficients

DOEpatents

Spadaccini, Christopher; Hopkins, Jonathan

2014-10-28

A thermal expansion-managed lattice structure having a plurality of unit cells each having flexure bearing-mounted tabs supported on a base and actuated by thermal expansion of an actuator having a thermal expansion coefficient greater than the base and arranged so that the tab is inwardly displaced into a base cavity. The flexure bearing-mounted tabs are connected to other flexure-bearing-mounted tabs of adjacent unit cells so that the adjacent unit cells are spaced from each other to accommodate thermal expansion of individual unit cells while maintaining a desired bulk thermal expansion coefficient of the lattice structure as a whole.

Polarization splitting phenomenon of photonic crystals constructed by two-fold rotationally symmetric unit-cells

NASA Astrophysics Data System (ADS)

Yasa, U. G.; Giden, I. H.; Turduev, M.; Kurt, H.

2017-09-01

We present an intrinsic polarization splitting characteristic of low-symmetric photonic crystals (PCs) formed by unit-cells with C 2 rotational symmetry. This behavior emerges from the polarization sensitive self-collimation effect for both transverse-magnetic (TM) and transverse-electric (TE) modes depending on the rotational orientations of the unit-cell elements. Numerical analyzes are performed in both frequency and time domains for different types of square lattice two-fold rotational symmetric PC structures. At incident wavelength of λ = 1550 nm, high polarization extinction ratios with ˜26 dB (for TE polarization) and ˜22 dB (for TM polarization) are obtained with an operating bandwidth of 59 nm. Moreover, fabrication feasibilities of the designed structure are analyzed to evaluate their robustness in terms of the unit-cell orientation: for the selected PC unit-cell composition, corresponding extinction ratios for both polarizations still remain to be over 18 dB for the unit-cell rotation interval of θ = [40°-55°]. Taking all these advantages, two-fold rotationally symmetric PCs could be considered as an essential component in photonic integrated circuits for polarization control of light.

Photocarcinogenesis study of aloe vera [CAS NO. 481-72-1(Aloe-emodin)] in SKH-1 mice (simulated solar light and topical application study).

PubMed

2010-09-01

The popular recognition of the Aloe barbadensis Miller (Aloe vera) plant as a therapeutic dermatologic agent has led to the widespread incorporation of Aloe vera leaf extracts in skincare products. Studies have suggested that Aloe vera in skincare preparations may enhance the induction of skin cancer by ultraviolet radiation. A 1-year study was conducted in mice to determine whether the topical application of creams containing Aloe vera plant extracts (aloe gel, whole leaf, or decolorized whole leaf) or creams containing aloe-emodin would enhance the photocarcinogenicity of simulated solar light (SSL). 1-YEAR STUDY: groups of 36 male and 36 female Crl:SKH-1 (hr -/hr -) hairless mice received topical applications of control cream or creams containing 3% or 6% (w/w) aloe gel, whole leaf, or decolorized whole leaf or 7.46 or 74.6 µg/g aloe-emodin to the dorsal skin region each weekday morning. The mice were irradiated with SSL emitted from filtered 6 kW xenon arc lamps each weekday afternoon. The topical applications of creams and irradiance exposures were conducted 5 days per week for a period of 40 weeks. A 12-week recovery/observation period followed the 40-week treatment/exposure period. Additional groups of 36 male and 36 female mice received no cream and were exposed to 0.00, 6.85, 13.70, or 20.55 mJ⋅CIE/cm2 SSL per day. Mice that received no cream treatment and were exposed to increasing levels of SSL showed significant SSL exposure-dependent decreases in survival and significant increases in the in-life observations of skin lesion onset, incidence, and multiplicity, and significant SSL exposure-dependent increases in the incidences and multiplicities of histopathology-determined squamous cell nonneoplastic skin lesions (squamous hyperplasia and focal atypical hyperplasia) and squamous cell neoplasms (papilloma, carcinoma in situ, and/or carcinoma). Squamous cell neoplasms were not detected in mice that received no SSL exposure. The topical treatment with the control cream of mice that were exposed to SSL did not impart a measurable effect when compared with comparable measurements in mice that received no cream treatment and were exposed to the same level of SSL, suggesting that the control cream used in these studies did not alter the efficiency of the SSL delivered to mice or the tolerability of mice to SSL. The application of aloe gel creams to mice had no effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. The administration of aloe gel creams to male mice had no effect on the incidences or multiplicities of histopathology-determined squamous cell nonneoplastic skin lesions or neoplasms. Female mice treated with aloe gel creams (3% and 6%) had significantly increased multiplicities of squamous cell neoplasms. There were no treatment-related effects on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity in mice treated with the whole leaf creams. In male mice exposed to SSL and treated with the 6% whole leaf cream, a significant increase was observed in the multiplicity of squamous cell neoplasms. Female mice exposed to SSL and treated with the 3% whole leaf creams had significantly decreased multiplicity of squamous cell nonneoplastic lesions and significantly increased multiplicity of squamous cell neoplasms. Female mice exposed to SSL and treated with the 6% whole leaf cream had significantly decreased multiplicity of squamous cell nonneoplastic lesions. The application of decolorized whole leaf creams to mice had no effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. Male mice administered the 3% decolorized whole leaf cream had significantly increased multiplicity of squamous cell neoplasms. Female mice administered the 3% decolorized whole leaf cream had significantly decreased multiplicity of squamous cell nonneoplastic skin lesions and significantly increased multiplicity of squamous cell neoplasms. In female mice that received the 6% decolorized whole leaf cream, there was a significant increase in the multiplicity of squamous cell neoplasms. As with the Aloe vera plant extracts, the application of aloe-emodin creams to mice had no measurable effect on body weights, survival, or the in-life observations of skin lesion onset, incidence, or multiplicity. The administration of aloe-emodin creams to male mice had no effect on the incidence or multiplicity of histopathology-determined nonneoplastic skin lesions or squamous cell neoplasms. Female mice treated with the 74.6 µg/g aloe-emodin cream had significantly decreased multiplicity of histopathology-determined squamous cell nonneoplastic skin lesions and significantly increased multiplicity of squamous cell neoplasms. these experiments investigated the potential of topical application of creams containing extracts of Aloe barbadensis Miller plant (aloe gel, whole leaf, or decolorized whole leaf) or aloe-emodin to alter the photocarcinogenic activity of filtered xenon arc simulated solar light (SSL) in male and female SKH-1 hairless mice. Data on skin lesions were collected both on digital images during the in-life phase and by histopathologic evaluation at necropsy. No effects of creams upon SSL-induced skin lesions were identified from data collected during the in-life phase. ALOE GEL OR ALOE-EMODIN: under the conditions of these studies, there was a weak enhancing effect of aloe gel or aloe-emodin on the photocarcinogenic activity of SSL in female but not in male SKH-1 mice based on an increase in the multiplicity of histopathologically-determined squamous cell neoplasms. under the conditions of these studies, there was a weak enhancing effect of aloe whole leaf or decolorized whole leaf on the photocarcinogenic activity of SSL in both male and female SKH-1 mice based on an increase in the multiplicity of histopathologically-determined squamous cell neoplasms.

Fuel cell programs in the United States for stationary power applications

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

Singer, M.

1996-04-01

The Department of Energy (DOE), Office of Fossil Energy, is participating with the private sector in sponsoring the development of molten carbonate fuel cell (MCFC) and solid oxide fuel cell (SOFC) technologies for application in the utility, commercial and industrial sectors. Phosphoric acid fuel cell (PAFC) development was sponsored by the Office of Fossil Energy in previous years and is now being commercialized by the private sector. Private sector participants with the Department of Energy include the Electric Power Research Institute (EPRI), the Gas Research institute (GRI), electric and gas utilities, universities, manufacturing companies and their suppliers. through continued governmentmore » and private sector support, fuel cell systems are emerging power generation technologies which are expected to have significant worldwide impacts. An industry with annual sales of over a billion dollars is envisioned early in the 21st century. PAFC power plants have begun to enter the marketplace and MCFC and SOFC power plants are expected to be ready to enter the marketplace in the late 1990s. In support of the efficient and effective use of our natural resources, the fuel cell program seeks to increase energy efficiency and economic effectiveness of power generation. This is to be accomplished through effectiveness of power generation. This is accomplished through the development and commercialization of cost-effective, efficient and environmentally desirable fuel cell systems which will operate on fossil fuels in multiple and end use sectors.« less

High Frequency, Sustained T Cell Responses to PARV4 Suggest Viral Persistence In Vivo

PubMed Central

Simmons, Ruth; Sharp, Colin; Sims, Stuart; Kloverpris, Henrik; Goulder, Philip; Simmonds, Peter; Bowness, Paul; Klenerman, Paul

2011-01-01

Background. Parvovirus 4 (PARV4) is a recently identified human virus that has been found in livers of patients infected with hepatitis C virus (HCV) and in bone marrow of individuals infected with human immunodeficiency virus (HIV). T cells are important in controlling viruses but may also contribute to disease pathogenesis. The interaction of PARV4 with the cellular immune system has not been described. Consequently, we investigated whether T cell responses to PARV4 could be detected in individuals exposed to blood-borne viruses. Methods. Interferon γ (IFN-γ) enzyme-linked immunospot assay, intracellular cytokine staining, and a tetrameric HLA-A*0201–peptide complex were used to define the lymphocyte populations responding to PARV4 NS peptides in 88 HCV-positive and 13 HIV-positive individuals. Antibody responses were tested using a recently developed PARV4 enzyme-linked immunosorbent assay. Results. High-frequency T cell responses against multiple PARV4 NS peptides and antibodies were observed in 26% of individuals. Typical responses to the NS pools were >1000 spot-forming units per million peripheral blood mononuclear cells. Conclusions. PARV4 infection is common in individuals exposed to blood-borne viruses and elicits strong T cell responses, a feature typically associated with persistent, contained infections such as cytomegalovirus. Persistence of PARV4 viral antigen in tissue in HCV-positive and HIV-positive individuals and/or the associated activated antiviral T cell response may contribute to disease pathogenesis. PMID:21502079

Quantitative Analysis of Complex Glioma Cell Migration on Electrospun Polycaprolactone Using Time-Lapse Microscopy

PubMed Central

Johnson, Jed; Nowicki, M. Oskar; Lee, Carol H.; Chiocca, E. Antonio; Viapiano, Mariano S.; Lawler, Sean E.

2009-01-01

Malignant gliomas are the most common tumors originating within the central nervous system and account for over 15,000 deaths annually in the United States. The median survival for glioblastoma, the most common and aggressive of these tumors, is only 14 months. Therapeutic strategies targeting glioma cells migrating away from the tumor core are currently hampered by the difficulty of reproducing migration in the neural parenchyma in vitro. We utilized a tissue engineering approach to develop a physiologically relevant model of glioma cell migration. This revealed that glioma cells display dramatic differences in migration when challenged by random versus aligned electrospun poly-ɛ-caprolactone nanofibers. Cells on aligned fibers migrated at an effective velocity of 4.2 ± 0.39 μm/h compared to 0.8 ± 0.08 μm/h on random fibers, closely matching in vivo models and prior observations of glioma spread in white versus gray matter. Cells on random fibers exhibited extension along multiple fiber axes that prevented net motion; aligned fibers promoted a fusiform morphology better suited to infiltration. Time-lapse microscopy revealed that the motion of individual cells was complex and was influenced by cell cycle and local topography. Glioma stem cell–containing neurospheres seeded on random fibers did not show cell detachment and retained their original shape; on aligned fibers, cells detached and migrated in the fiber direction over a distance sixfold greater than the perpendicular direction. This chemically and physically flexible model allows time-lapse analysis of glioma cell migration while recapitulating in vivo cell morphology, potentially allowing identification of physiological mediators and pharmacological inhibitors of invasion. PMID:19199562

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting

PubMed Central

Ma, Xuanyi; Qu, Xin; Zhu, Wei; Li, Yi-Shuan; Yuan, Suli; Zhang, Hong; Liu, Justin; Wang, Pengrui; Lai, Cheuk Sun Edwin; Zanella, Fabian; Feng, Gen-Sheng; Sheikh, Farah; Chien, Shu; Chen, Shaochen

2016-01-01

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling. PMID:26858399

Photoreceptor Cells With Profound Structural Deficits Can Support Useful Vision in Mice

PubMed Central

Thompson, Stewart; Blodi, Frederick R.; Lee, Swan; Welder, Chris R.; Mullins, Robert F.; Tucker, Budd A.; Stasheff, Steven F.; Stone, Edwin M.

2014-01-01

Purpose. In animal models of degenerative photoreceptor disease, there has been some success in restoring photoreception by transplanting stem cell–derived photoreceptor cells into the subretinal space. However, only a small proportion of transplanted cells develop extended outer segments, considered critical for photoreceptor cell function. The purpose of this study was to determine whether photoreceptor cells that lack a fully formed outer segment could usefully contribute to vision. Methods. Retinal and visual function was tested in wild-type and Rds mice at 90 days of age (RdsP90). Photoreceptor cells of mice homozygous for the Rds mutation in peripherin 2 never develop a fully formed outer segment. The electroretinogram and multielectrode recording of retinal ganglion cells were used to test retinal responses to light. Three distinct visual behaviors were used to assess visual capabilities: the optokinetic tracking response, the discrimination-based visual water task, and a measure of the effect of vision on wheel running. Results. RdsP90 mice had reduced but measurable electroretinogram responses to light, and exhibited light-evoked responses in multiple types of retinal ganglion cells, the output neurons of the retina. In optokinetic and discrimination-based tests, acuity was measurable but reduced, most notably when contrast was decreased. The wheel running test showed that RdsP90 mice needed 3 log units brighter luminance than wild type to support useful vision (10 cd/m2). Conclusions. Photoreceptors that lack fully formed outer segments can support useful vision. This challenges the idea that normal cellular structure needs to be completely reproduced for transplanted cells to contribute to useful vision. PMID:24569582

Production and characterization of multiple-layered populations of animal cells.

PubMed

Kruse, P F; Miedema, E

1965-11-01

Dense populations containing 129 x 10(6) Jensen sarcoma, 134 x 10(6) DON Chinese hamster, 28.9 x 10(6) WI-38 human diploid, 61.8 x 10(6) HEp-2 human carcinoma, and 67.4 x 10(6) WISH human amnion cells were produced from dilute inocula, 0.85 to 5.33 x 10(6), in 7 to 8 days in a perfusion system using replicate T-60 flasks. Perfusion rates as high as 560 ml medium/day/T-60 were required to maintain pH (to ca +/-0.1 unit) and adequate nutrient supplies. The cell densities encountered are described by the term "monolayer equivalents" (M.E.), defined as number of cells per culture divided by number of cells in a monolayer. The M.E.'s for T-60 cultures containing unusually dense populations of 40 x 10(6) WI-38 and 250 x 10(6) DON cells (9-day perfusion) were 5 and 17, respectively, and numbers of cells in illustrations of stained cross-sections of membranes from these cultures were in excellent agreement. Threshold M.E.'s exist below which proliferation is the chief cellular activity and above which one or more cell functions may predominate even though proliferation persists. Cellular nutrition and metabolism may change with changes in M.E., as illustrated in different patterns of glutamic acid, proline, and glycine utilization or production in dense vs. dilute WI-38 cell populations. The results indicated that the role of contact inhibition phenomena in arresting cellular proliferation was diminished in perfusion system environments.

Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting.

PubMed

Ma, Xuanyi; Qu, Xin; Zhu, Wei; Li, Yi-Shuan; Yuan, Suli; Zhang, Hong; Liu, Justin; Wang, Pengrui; Lai, Cheuk Sun Edwin; Zanella, Fabian; Feng, Gen-Sheng; Sheikh, Farah; Chien, Shu; Chen, Shaochen

2016-02-23

The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.

Concept of multiple-cell cavity for axion dark matter search

NASA Astrophysics Data System (ADS)

Jeong, Junu; Youn, SungWoo; Ahn, Saebyeok; Kim, Jihn E.; Semertzidis, Yannis K.

2018-02-01

In cavity-based axion dark matter search experiments exploring high mass regions, multiple-cavity design is under consideration as a method to increase the detection volume within a given magnet bore. We introduce a new idea, referred to as a multiple-cell cavity, which provides various benefits including a larger detection volume, simpler experimental setup, and easier phase-matching mechanism. We present the characteristics of this concept and demonstrate the experimental feasibility with an example of a double-cell cavity.

Multi-floor cascading ferroelectric nanostructures: multiple data writing-based multi-level non-volatile memory devices

NASA Astrophysics Data System (ADS)

Hyun, Seung; Kwon, Owoong; Lee, Bom-Yi; Seol, Daehee; Park, Beomjin; Lee, Jae Yong; Lee, Ju Hyun; Kim, Yunseok; Kim, Jin Kon

2016-01-01

Multiple data writing-based multi-level non-volatile memory has gained strong attention for next-generation memory devices to quickly accommodate an extremely large number of data bits because it is capable of storing multiple data bits in a single memory cell at once. However, all previously reported devices have failed to store a large number of data bits due to the macroscale cell size and have not allowed fast access to the stored data due to slow single data writing. Here, we introduce a novel three-dimensional multi-floor cascading polymeric ferroelectric nanostructure, successfully operating as an individual cell. In one cell, each floor has its own piezoresponse and the piezoresponse of one floor can be modulated by the bias voltage applied to the other floor, which means simultaneously written data bits in both floors can be identified. This could achieve multi-level memory through a multiple data writing process.Multiple data writing-based multi-level non-volatile memory has gained strong attention for next-generation memory devices to quickly accommodate an extremely large number of data bits because it is capable of storing multiple data bits in a single memory cell at once. However, all previously reported devices have failed to store a large number of data bits due to the macroscale cell size and have not allowed fast access to the stored data due to slow single data writing. Here, we introduce a novel three-dimensional multi-floor cascading polymeric ferroelectric nanostructure, successfully operating as an individual cell. In one cell, each floor has its own piezoresponse and the piezoresponse of one floor can be modulated by the bias voltage applied to the other floor, which means simultaneously written data bits in both floors can be identified. This could achieve multi-level memory through a multiple data writing process. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07377d

Reproduction of the FC/DFC units in nucleoli.

PubMed

Smirnov, Evgeny; Hornáček, Matúš; Kováčik, Lubomír; Mazel, Tomáš; Schröfel, Adam; Svidenská, Silvie; Skalníková, Magdalena; Bartová, Eva; Cmarko, Dušan; Raška, Ivan

2016-04-25

The essential structural components of the nucleoli, Fibrillar Centers (FC) and Dense Fibrillar Components (DFC), together compose FC/DFC units, loci of rDNA transcription and early RNA processing. In the present study we followed cell cycle related changes of these units in 2 human sarcoma derived cell lines with stable expression of RFP-PCNA (the sliding clamp protein) and GFP-RPA43 (a subunit of RNA polymerase I, pol I) or GFP-fibrillarin. Correlative light and electron microscopy analysis showed that the pol I and fibrillarin positive nucleolar beads correspond to individual FC/DFC units. In vivo observations showed that at early S phase, when transcriptionally active ribosomal genes were replicated, the number of the units in each cell increased by 60-80%. During that period the units transiently lost pol I, but not fibrillarin. Then, until the end of interphase, number of the units did not change, and their duplication was completed only after the cell division, by mid G1 phase. This peculiar mode of reproduction suggests that a considerable subset of ribosomal genes remain transcriptionally silent from mid S phase to mitosis, but become again active in the postmitotic daughter cells.

Controlling Energy Radiations of Electromagnetic Waves via Frequency Coding Metamaterials.

PubMed

Wu, Haotian; Liu, Shuo; Wan, Xiang; Zhang, Lei; Wang, Dan; Li, Lianlin; Cui, Tie Jun

2017-09-01

Metamaterials are artificial structures composed of subwavelength unit cells to control electromagnetic (EM) waves. The spatial coding representation of metamaterial has the ability to describe the material in a digital way. The spatial coding metamaterials are typically constructed by unit cells that have similar shapes with fixed functionality. Here, the concept of frequency coding metamaterial is proposed, which achieves different controls of EM energy radiations with a fixed spatial coding pattern when the frequency changes. In this case, not only different phase responses of the unit cells are considered, but also different phase sensitivities are also required. Due to different frequency sensitivities of unit cells, two units with the same phase response at the initial frequency may have different phase responses at higher frequency. To describe the frequency coding property of unit cell, digitalized frequency sensitivity is proposed, in which the units are encoded with digits "0" and "1" to represent the low and high phase sensitivities, respectively. By this merit, two degrees of freedom, spatial coding and frequency coding, are obtained to control the EM energy radiations by a new class of frequency-spatial coding metamaterials. The above concepts and physical phenomena are confirmed by numerical simulations and experiments.

Community-acquired respiratory infections are common in patients with non-Hodgkin lymphoma and multiple myeloma.

PubMed

Lavi, Noa; Avivi, Irit; Kra-Oz, Zipora; Oren, Ilana; Hardak, Emilia

2018-07-01

Available data suggest that respiratory infections are associated with increased morbidity and mortality in patients hospitalized due to acute leukemia and allogeneic stem cell transplantation (allo-SCT). However, the precise incidence, risk factors, and severity of respiratory infection, mainly community-acquired, in patients with lymphoma and multiple myeloma (MM) are not fully determined. The current study aimed to investigate risk factors for respiratory infections and their clinical significance in patients with B cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) in the first year of diagnosis. Data of consecutive patients diagnosed with NHL or MM and treated at the Rambam Hematology Inpatient and Outpatient Units between 01/2011 and 03/2012 were evaluated. Information regarding anticancer treatment, incidence and course of respiratory infections, and infection-related outcomes was analyzed. One hundred and sixty episodes of respiratory infections were recorded in 103 (49%) of 211 (73-MM, 138-NHL) patients; 126 (79%) episodes were community-acquired, 47 (29%) of them required hospitalization. In univariate analysis, age < 60 years, MM diagnosis, and autologous SCT increased the respiratory infection risk (P = 0.058, 0.038, and 0.001, respectively). Ninety episodes (56% of all respiratory episodes) were examined for viral pathogens. Viral infections were documented in 25/90 (28%) episodes, 21 (84%) of them were community-acquired, requiring hospitalization in 5 (24%) cases. Anti-flu vaccination was performed in 119 (56%) patients. Two of the six patients diagnosed with influenza were vaccinated. Respiratory infections, including viral ones, are common in NHL and MM. Most infections are community-acquired and have a favorable outcome. Rapid identification of viral pathogens allows avoiding antibiotic overuse in this patient population.

UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep

ClinicalTrials.gov

2017-12-03

Acute Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia/Lymphoma; Burkitt's Lymphoma; Natural Killer Cell Malignancies; Chronic Myelogenous Leukemia; Myelodysplastic Syndrome; Large-cell Lymphoma; Hodgkin Lymphoma; Multiple Myeloma; Relapsed Chronic Lymphocytic Leukemia; Relapsed Small Lymphocytic Lymphoma; Marginal Zone B-cell Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle-cell Lymphoma; Prolymphocytic Leukemia; Bone Marrow Failure Syndromes; Myeloproliferative Neoplasms/Myelofibrosis; Biphenotypic/Undifferentiated/Prolymphocytic Leukemias; MRD Positive Leukemia; Leukemia or MDS in Aplasia; Relapsed T-Cell Lymphoma; Relapsed Multiple Myeloma; Plasma Cell Leukemia

Sickle red cell adhesion: many issues and some answers.

PubMed

Kaul, D K

2008-01-01

Among multiple pathologies associated with sickle cell disease, sickle red cell-endothelial interaction has been implicated as a potential initiating mechanism in vaso-occlusive events that characterize this disease. Vast literature exists on various aspects of sickle red cell adhesion, but many issues remain unresolved, especially pertaining to the role of sickle red cell heterogeneity, the relative role of multiple adhesion mechanisms and targets of antiadhesive therapy. This review briefly analyzes these issues.

The extraction of simple relationships in growth factor-specific multiple-input and multiple-output systems in cell-fate decisions by backward elimination PLS regression.

PubMed

Akimoto, Yuki; Yugi, Katsuyuki; Uda, Shinsuke; Kudo, Takamasa; Komori, Yasunori; Kubota, Hiroyuki; Kuroda, Shinya

2013-01-01

Cells use common signaling molecules for the selective control of downstream gene expression and cell-fate decisions. The relationship between signaling molecules and downstream gene expression and cellular phenotypes is a multiple-input and multiple-output (MIMO) system and is difficult to understand due to its complexity. For example, it has been reported that, in PC12 cells, different types of growth factors activate MAP kinases (MAPKs) including ERK, JNK, and p38, and CREB, for selective protein expression of immediate early genes (IEGs) such as c-FOS, c-JUN, EGR1, JUNB, and FOSB, leading to cell differentiation, proliferation and cell death; however, how multiple-inputs such as MAPKs and CREB regulate multiple-outputs such as expression of the IEGs and cellular phenotypes remains unclear. To address this issue, we employed a statistical method called partial least squares (PLS) regression, which involves a reduction of the dimensionality of the inputs and outputs into latent variables and a linear regression between these latent variables. We measured 1,200 data points for MAPKs and CREB as the inputs and 1,900 data points for IEGs and cellular phenotypes as the outputs, and we constructed the PLS model from these data. The PLS model highlighted the complexity of the MIMO system and growth factor-specific input-output relationships of cell-fate decisions in PC12 cells. Furthermore, to reduce the complexity, we applied a backward elimination method to the PLS regression, in which 60 input variables were reduced to 5 variables, including the phosphorylation of ERK at 10 min, CREB at 5 min and 60 min, AKT at 5 min and JNK at 30 min. The simple PLS model with only 5 input variables demonstrated a predictive ability comparable to that of the full PLS model. The 5 input variables effectively extracted the growth factor-specific simple relationships within the MIMO system in cell-fate decisions in PC12 cells.

Logistics and Capability Implications of a Bradley Fighting Vehicle with a Fuel Cell Auxiliary Power Unit

DTIC Science & Technology

2003-10-13

04ANNUAL-524 Logistics and Capability Implications of a Bradley Fighting Vehicle with a Fuel Cell Auxiliary Power Unit Joseph Conover, Harry...used or the main engines are restarted. Integration of a solid oxide fuel cell (SOFC) auxiliary power unit into a military vehicle has the...presented which show the fuel usage and capability impacts of incorporating a fuel cell APU into the electrical system of a Bradley M2A3 Diesel

Fluorescent-Magnetic-Biotargeting Multifunctional Nanobioprobes for Detecting and Isolating Multiple Types of Tumor Cells

PubMed Central

Song, Er-Qun; Hu, Jun; Wen, Cong-Ying; Tian, Zhi-Quan; Yu, Xu; Zhang, Zhi-Ling; Shi, Yun-Bo; Pang, Dai-Wen

2011-01-01

Fluorescent-magnetic-biotargeting multifunctional nanobioprobes (FMBMNs) have attracted great attention in recent years due to their increasing, important applications in biomedical research, clinical diagnosis, and biomedicine. We have previously developed such nanobioprobes for the detection and isolation of a single kind of tumor cells. Detection and isolation of multiple tumor markers or tumor cells from complex samples sensitively and with high efficiency is critical for the early diagnosis of tumors, especially malignant tumors or cancers, which will improve clinical diagnosis outcomes and help to select effective treatment approaches. Here, we expanded the application of the monoclonal antibody (mAb)-coupled FMBMNs for multiplexed assays. Multiple types of cancer cells, such as leukemia cells and prostate cancer cells, were detected and collected from mixed samples within 25 minutes by using a magnet and an ordinary fluorescence microscope. The capture efficiencies of mAb-coupled FMBMNs for the above mentioned two types of cells were 96% and 97% respectively. Furthermore, by using the mAb-coupled FMBMNs, specific and sensitive detection and rapid separation of a small number of spiked leukemia cells and prostate cancer cells in a large population of cultured normal cells (about 0.01% were tumor cells) were achieved simply and inexpensively without any sample pretreatment before cell analysis. Therefore, mAb-coupled multicolour FMBMNs may be used for very sensitive detection and rapid isolation of multiple cancer cells in biomedical research and medical diagnostics. PMID:21250650

Prognostic impact of circulating plasma cells in patients with multiple myeloma: implications for plasma cell leukemia definition.

PubMed

Granell, Miquel; Calvo, Xavier; Garcia-Guiñón, Antoni; Escoda, Lourdes; Abella, Eugènia; Martínez, Clara Mª; Teixidó, Montserrat; Gimenez, Mª Teresa; Senín, Alicia; Sanz, Patricia; Campoy, Desirée; Vicent, Ana; Arenillas, Leonor; Rosiñol, Laura; Sierra, Jorge; Bladé, Joan; de Larrea, Carlos Fernández

2017-06-01

The presence of circulating plasma cells in patients with multiple myeloma is considered a marker for highly proliferative disease. In the study herein, the impact of circulating plasma cells assessed by cytology on survival of patients with multiple myeloma was analyzed. Wright-Giemsa stained peripheral blood smears of 482 patients with newly diagnosed myeloma or plasma cell leukemia were reviewed and patients were classified into 4 categories according to the percentage of circulating plasma cells: 0%, 1-4%, 5-20%, and plasma cell leukemia with the following frequencies: 382 (79.2%), 83 (17.2%), 12 (2.5%) and 5 (1.0%), respectively. Median overall survival according to the circulating plasma cells group was 47, 50, 6 and 14 months, respectively. At multivariate analysis, the presence of 5 to 20% circulating plasma cells was associated with a worse overall survival (relative risk 4.9, 95% CI 2.6-9.3) independently of age, creatinine, the Durie-Salmon system stage and the International Staging System (ISS) stage. Patients with ≥5% circulating plasma cells had lower platelet counts (median 86×10 9 /L vs 214×10 9 /L, P <0.0001) and higher bone marrow plasma cells (median 53% vs 36%, P =0.004). The presence of ≥5% circulating plasma cells in patients with multiple myeloma has a similar adverse prognostic impact as plasma cell leukemia. Copyright© Ferrata Storti Foundation.

Single cell multiplexed assay for proteolytic activity using droplet microfluidics.

PubMed

Ng, Ee Xien; Miller, Miles A; Jing, Tengyang; Chen, Chia-Hung

2016-07-15

Cellular enzymes interact in a post-translationally regulated fashion to govern individual cell behaviors, yet current platform technologies are limited in their ability to measure multiple enzyme activities simultaneously in single cells. Here, we developed multi-color Förster resonance energy transfer (FRET)-based enzymatic substrates and use them in a microfluidics platform to simultaneously measure multiple specific protease activities from water-in-oil droplets that contain single cells. By integrating the microfluidic platform with a computational analytical method, Proteolytic Activity Matrix Analysis (PrAMA), we are able to infer six different protease activity signals from individual cells in a high throughput manner (~100 cells/experimental run). We characterized protease activity profiles at single cell resolution for several cancer cell lines including breast cancer cell line MDA-MB-231, lung cancer cell line PC-9, and leukemia cell line K-562 using both live-cell and in-situ cell lysis assay formats, with special focus on metalloproteinases important in metastasis. The ability to measure multiple proteases secreted from or expressed in individual cells allows us to characterize cell heterogeneity and has potential applications including systems biology, pharmacology, cancer diagnosis and stem cell biology. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamic equilibrium of heterogeneous and interconvertible multipotent hematopoietic cell subsets

PubMed Central

Weston, Wendy; Zayas, Jennifer; Perez, Ruben; George, John; Jurecic, Roland

2014-01-01

Populations of hematopoietic stem cells and progenitors are quite heterogeneous and consist of multiple cell subsets with distinct phenotypic and functional characteristics. Some of these subsets also appear to be interconvertible and oscillate between functionally distinct states. The multipotent hematopoietic cell line EML has emerged as a unique model to study the heterogeneity and interconvertibility of multipotent hematopoietic cells. Here we describe extensive phenotypic and functional heterogeneity of EML cells which stems from the coexistence of multiple cell subsets. Each of these subsets is phenotypically and functionally heterogeneous, and displays distinct multilineage differentiation potential, cell cycle profile, proliferation kinetics, and expression pattern of HSC markers and some of the key lineage-associated transcription factors. Analysis of their maintenance revealed that on a population level all EML cell subsets exhibit cell-autonomous interconvertible properties, with the capacity to generate all other subsets and re-establish complete parental EML cell population. Moreover, all EML cell subsets generated during multiple cell generations maintain their distinct phenotypic and functional signatures and interconvertible properties. The model of EML cell line suggests that interconvertible multipotent hematopoietic cell subsets coexist in a homeostatically maintained dynamic equilibrium which is regulated by currently unknown cell-intrinsic mechanisms. PMID:24903657