cellular length scale: Topics by Science.gov

Sample records for cellular length scale

Direct measurement of local material properties within living embryonic tissues

NASA Astrophysics Data System (ADS)

Serwane, Friedhelm; Mongera, Alessandro; Rowghanian, Payam; Kealhofer, David; Lucio, Adam; Hockenbery, Zachary; Campàs, Otger

The shaping of biological matter requires the control of its mechanical properties across multiple scales, ranging from single molecules to cells and tissues. Despite their relevance, measurements of the mechanical properties of sub-cellular, cellular and supra-cellular structures within living embryos pose severe challenges to existing techniques. We have developed a technique that uses magnetic droplets to measure the mechanical properties of complex fluids, including in situ and in vivo measurements within living embryos ,across multiple length and time scales. By actuating the droplets with magnetic fields and recording their deformation we probe the local mechanical properties, at any length scale we choose by varying the droplets' diameter. We use the technique to determine the subcellular mechanics of individual blastomeres of zebrafish embryos, and bridge the gap to the tissue scale by measuring the local viscosity and elasticity of zebrafish embryonic tissues. Using this technique, we show that embryonic zebrafish tissues are viscoelastic with a fluid-like behavior at long time scales. This technique will enable mechanobiology and mechano-transduction studies in vivo, including the study of diseases correlated with tissue stiffness, such as cancer.
High flexibility of DNA on short length scales probed by atomic force microscopy.

PubMed

Wiggins, Paul A; van der Heijden, Thijn; Moreno-Herrero, Fernando; Spakowitz, Andrew; Phillips, Rob; Widom, Jonathan; Dekker, Cees; Nelson, Philip C

2006-11-01

The mechanics of DNA bending on intermediate length scales (5-100 nm) plays a key role in many cellular processes, and is also important in the fabrication of artificial DNA structures, but previous experimental studies of DNA mechanics have focused on longer length scales than these. We use high-resolution atomic force microscopy on individual DNA molecules to obtain a direct measurement of the bending energy function appropriate for scales down to 5 nm. Our measurements imply that the elastic energy of highly bent DNA conformations is lower than predicted by classical elasticity models such as the worm-like chain (WLC) model. For example, we found that on short length scales, spontaneous large-angle bends are many times more prevalent than predicted by the WLC model. We test our data and model with an interlocking set of consistency checks. Our analysis also shows how our model is compatible with previous experiments, which have sometimes been viewed as confirming the WLC.
Relationship between interpersonal sensitivity and leukocyte telomere length.

PubMed

Suzuki, Akihito; Matsumoto, Yoshihiko; Enokido, Masanori; Shirata, Toshinori; Goto, Kaoru; Otani, Koichi

2017-10-10

Telomeres are repetitive DNA sequences located at the ends of chromosomes, and telomere length represents a biological marker for cellular aging. Interpersonal sensitivity, excessive sensitivity to the behavior and feelings of others, is one of the vulnerable factors to depression. In the present study, we examined the effect of interpersonal sensitivity on telomere length in healthy subjects. The subjects were 159 unrelated healthy Japanese volunteers. Mean age ± SD (range) of the subjects was 42.3 ± 7.8 (30-61) years. Interpersonal sensitivity was assessed by the Japanese version of the Interpersonal Sensitivity Measure (IPSM). Leukocyte telomere length was determined by a quantitative real-time PCR method. Higher scores of the total IPSM were significantly (β = -0.163, p = 0.038) related to shorter telomere length. In the sub-scale analysis, higher scores of timidity were significantly (β = -0.220, p = 0.044) associated with shorter telomere length. The present study suggests that subjects with higher interpersonal sensitivity have shorter leukocyte telomere length, implying that interpersonal sensitivity has an impact on cellular aging.
Fabrication of biomimetic nanomaterials and their effect on cell behavior

NASA Astrophysics Data System (ADS)

Porri, Teresa Jane

Cells in vivo respond to an intricate combination of chemical and mechanical signals. The corneal epithelium, a structure which prevents the admission of bacteria and undesirable molecules into the eye, grows on a basement membrane which presents both nanoscale topographic and adhesive chemical signals. An effective approach to biomaterials design takes advantage of the synergistic effects of the multiple cellular inputs which are available to engineer cell-substrate interactions. We have previously demonstrated the effects of nanoscale topography on a variety of corneal epithelial cell behaviors. To gain a better understanding of cell-level control in vivo, we employ a systems-level approach which looks at the effect of nanoscale topography in conjunction with a biomimetic surface chemistry. First, we discuss a novel method of fabricating nanoscale topography through templated electroless deposition of gold into PVP-coated polycarbonate membranes. This technique creates nanowires of gold with an uniform outer diameter that is dependent upon the size of the pores in the membrane used, and a nanowire length that is dependent upon the extent of etching into the polymer membrane. The gold nanowires can be modified with self-assembled monolayers (SAMs) of alkanethiols. Using these substrates, we study the effect of topographic length scale and surface chemistry on cells attached to a discontinuous nanoscale topography, and find a transition in cellular behavior at a length scale (between 600 and 2000 nm inter-wire spacing) that is commensurate with the transition length scale seen on surfaces presenting continuous grooves and ridges. Secondly, we study the effect of non-fouling peptide-modified SAMs on cellular behavior. We examine the effect of co-presented RGD and AG73 peptides and show that cell spreading is a function of the relative ratios of RGD and AG73 present on the surface. Finally, we explore the combinatorial effects of biologically relevant chemistry with anisotropic nanoscale topography with dimensions that vary from the micron to the nanoscale. We show that integrin binding, syndecan binding, and topographic length scale each independently influence epithelial cell response to nanoscale features, lending a high degree of control over cell morphologic responses.
Predicting cell viability within tissue scaffolds under equiaxial strain: multi-scale finite element model of collagen-cardiomyocytes constructs.

PubMed

Elsaadany, Mostafa; Yan, Karen Chang; Yildirim-Ayan, Eda

2017-06-01

Successful tissue engineering and regenerative therapy necessitate having extensive knowledge about mechanical milieu in engineered tissues and the resident cells. In this study, we have merged two powerful analysis tools, namely finite element analysis and stochastic analysis, to understand the mechanical strain within the tissue scaffold and residing cells and to predict the cell viability upon applying mechanical strains. A continuum-based multi-length scale finite element model (FEM) was created to simulate the physiologically relevant equiaxial strain exposure on cell-embedded tissue scaffold and to calculate strain transferred to the tissue scaffold (macro-scale) and residing cells (micro-scale) upon various equiaxial strains. The data from FEM were used to predict cell viability under various equiaxial strain magnitudes using stochastic damage criterion analysis. The model validation was conducted through mechanically straining the cardiomyocyte-encapsulated collagen constructs using a custom-built mechanical loading platform (EQUicycler). FEM quantified the strain gradients over the radial and longitudinal direction of the scaffolds and the cells residing in different areas of interest. With the use of the experimental viability data, stochastic damage criterion, and the average cellular strains obtained from multi-length scale models, cellular viability was predicted and successfully validated. This methodology can provide a great tool to characterize the mechanical stimulation of bioreactors used in tissue engineering applications in providing quantification of mechanical strain and predicting cellular viability variations due to applied mechanical strain.
Activity-dependent self-regulation of viscous length scales in biological systems

NASA Astrophysics Data System (ADS)

Nandi, Saroj Kumar

2018-05-01

The cellular cortex, which is a highly viscous thin cytoplasmic layer just below the cell membrane, controls the cell's mechanical properties, which can be characterized by a hydrodynamic length scale ℓ . Cells actively regulate ℓ via the activity of force-generating molecules, such as myosin II. Here we develop a general theory for such systems through a coarse-grained hydrodynamic approach including activity in the static description of the system providing an experimentally accessible parameter and elucidate the detailed mechanism of how a living system can actively self-regulate its hydrodynamic length scale, controlling the rigidity of the system. Remarkably, we find that ℓ , as a function of activity, behaves universally and roughly inversely proportional to the activity of the system. Our theory rationalizes a number of experimental findings on diverse systems, and comparison of our theory with existing experimental data shows good agreement.
Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length scales

PubMed Central

Hogstrom, L. J.; Guo, S. M.; Murugadoss, K.; Bathe, M.

2016-01-01

Brain function emerges from hierarchical neuronal structure that spans orders of magnitude in length scale, from the nanometre-scale organization of synaptic proteins to the macroscopic wiring of neuronal circuits. Because the synaptic electrochemical signal transmission that drives brain function ultimately relies on the organization of neuronal circuits, understanding brain function requires an understanding of the principles that determine hierarchical neuronal structure in living or intact organisms. Recent advances in fluorescence imaging now enable quantitative characterization of neuronal structure across length scales, ranging from single-molecule localization using super-resolution imaging to whole-brain imaging using light-sheet microscopy on cleared samples. These tools, together with correlative electron microscopy and magnetic resonance imaging at the nanoscopic and macroscopic scales, respectively, now facilitate our ability to probe brain structure across its full range of length scales with cellular and molecular specificity. As these imaging datasets become increasingly accessible to researchers, novel statistical and computational frameworks will play an increasing role in efforts to relate hierarchical brain structure to its function. In this perspective, we discuss several prominent experimental advances that are ushering in a new era of quantitative fluorescence-based imaging in neuroscience along with novel computational and statistical strategies that are helping to distil our understanding of complex brain structure. PMID:26855758
Brushes, cables, and anchors: recent insights into multiscale assembly and mechanics of cellular structural networks.

PubMed

Lele, Tanmay P; Kumar, Sanjay

2007-01-01

The remarkable ability of living cells to sense, process, and respond to mechanical stimuli in their environment depends on the rapid and efficient interconversion of mechanical and chemical energy at specific times and places within the cell. For example, application of force to cells leads to conformational changes in specific mechanosensitive molecules which then trigger cellular signaling cascades that may alter cellular structure, mechanics, and migration and profoundly influence gene expression. Similarly, the sensitivity of cells to mechanical stresses is governed by the composition, architecture, and mechanics of the cellular cytoskeleton and extracellular matrix (ECM), which are in turn driven by molecular-scale forces between the constituent biopolymers. Understanding how these mechanochemical systems coordinate over multiple length and time scales to produce orchestrated cell behaviors represents a fundamental challenge in cell biology. Here, we review recent advances in our understanding of these complex processes in three experimental systems: the assembly of axonal neurofilaments, generation of tensile forces by actomyosin stress fiber bundles, and mechanical control of adhesion assembly.
Cytoskeletal dynamics in fission yeast: a review of models for polarization and division

PubMed Central

Drake, Tyler; Vavylonis, Dimitrios

2010-01-01

We review modeling studies concerning cytoskeletal activity of fission yeast. Recent models vary in length and time scales, describing a range of phenomena from cellular morphogenesis to polymer assembly. The components of cytoskeleton act in concert to mediate cell-scale events and interactions such as polarization. The mathematical models reduce these events and interactions to their essential ingredients, describing the cytoskeleton by its bulk properties. On a smaller scale, models describe cytoskeletal subcomponents and how bulk properties emerge. PMID:21119765
The topology of large-scale structure. I - Topology and the random phase hypothesis. [galactic formation models

NASA Technical Reports Server (NTRS)

Weinberg, David H.; Gott, J. Richard, III; Melott, Adrian L.

1987-01-01

Many models for the formation of galaxies and large-scale structure assume a spectrum of random phase (Gaussian), small-amplitude density fluctuations as initial conditions. In such scenarios, the topology of the galaxy distribution on large scales relates directly to the topology of the initial density fluctuations. Here a quantitative measure of topology - the genus of contours in a smoothed density distribution - is described and applied to numerical simulations of galaxy clustering, to a variety of three-dimensional toy models, and to a volume-limited sample of the CfA redshift survey. For random phase distributions the genus of density contours exhibits a universal dependence on threshold density. The clustering simulations show that a smoothing length of 2-3 times the mass correlation length is sufficient to recover the topology of the initial fluctuations from the evolved galaxy distribution. Cold dark matter and white noise models retain a random phase topology at shorter smoothing lengths, but massive neutrino models develop a cellular topology.
In Vivo Protein Dynamics on the Nanometer Length Scale and Nanosecond Time Scale

DOE PAGES

Anunciado, Divina B.; Nyugen, Vyncent P.; Hurst, Gregory B.; ...

2017-04-07

Selectively labeled GroEL protein was produced in living deuterated bacterial cells to enhance its neutron scattering signal above that of the intracellular milieu. Quasi-elastic neutron scattering shows that the in-cell diffusion coefficient of GroEL was (4.7 ± 0.3) × 10 –12 m 2/s, a factor of 4 slower than its diffusion coefficient in buffer solution. Furthermore, for internal protein dynamics we see a relaxation time of (65 ± 6) ps, a factor of 2 slower compared to the protein in solution. Comparison to the literature suggests that the effective diffusivity of proteins depends on the length and time scale beingmore » probed. Retardation of in-cell diffusion compared to the buffer becomes more significant with the increasing probe length scale, suggesting that intracellular diffusion of biomolecules is nonuniform over the cellular volume. This approach outlined here enables investigation of protein dynamics within living cells to open up new lines of research using “in-cell neutron scattering” to study the dynamics of complex biomolecular systems.« less
In Vivo Protein Dynamics on the Nanometer Length Scale and Nanosecond Time Scale

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

Anunciado, Divina B.; Nyugen, Vyncent P.; Hurst, Gregory B.

Selectively labeled GroEL protein was produced in living deuterated bacterial cells to enhance its neutron scattering signal above that of the intracellular milieu. Quasi-elastic neutron scattering shows that the in-cell diffusion coefficient of GroEL was (4.7 ± 0.3) × 10 –12 m 2/s, a factor of 4 slower than its diffusion coefficient in buffer solution. Furthermore, for internal protein dynamics we see a relaxation time of (65 ± 6) ps, a factor of 2 slower compared to the protein in solution. Comparison to the literature suggests that the effective diffusivity of proteins depends on the length and time scale beingmore » probed. Retardation of in-cell diffusion compared to the buffer becomes more significant with the increasing probe length scale, suggesting that intracellular diffusion of biomolecules is nonuniform over the cellular volume. This approach outlined here enables investigation of protein dynamics within living cells to open up new lines of research using “in-cell neutron scattering” to study the dynamics of complex biomolecular systems.« less
Cellular Scaling Rules for Primate Spinal Cords

PubMed Central

Burish, Mark J.; Peebles, J. Klint; Baldwin, Mary K.; Tavares, Luciano; Kaas, Jon H.; Herculano-Houzel, Suzana

2010-01-01

The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an exponent close to 1/3. This relationship suggests that the extension, mass and number of neurons that compose the spinal cord are related to body length, rather than to body mass or surface. Moreover, we show that although brain mass increases linearly with cord mass, the number of neurons in the brain increases with the number of neurons in the spinal cord raised to the power of 1.7. This faster addition of neurons to the brain than to the spinal cord is consistent with current views on how larger brains add complexity to the processing of environmental and somatic information. PMID:20926855
Generalized theory of semiflexible polymers.

PubMed

Wiggins, Paul A; Nelson, Philip C

2006-03-01

DNA bending on length scales shorter than a persistence length plays an integral role in the translation of genetic information from DNA to cellular function. Quantitative experimental studies of these biological systems have led to a renewed interest in the polymer mechanics relevant for describing the conformational free energy of DNA bending induced by protein-DNA complexes. Recent experimental results from DNA cyclization studies have cast doubt on the applicability of the canonical semiflexible polymer theory, the wormlike chain (WLC) model, to DNA bending on biologically relevant length scales. This paper develops a theory of the chain statistics of a class of generalized semiflexible polymer models. Our focus is on the theoretical development of these models and the calculation of experimental observables. To illustrate our methods, we focus on a specific, illustrative model of DNA bending. We show that the WLC model generically describes the long-length-scale chain statistics of semiflexible polymers, as predicted by renormalization group arguments. In particular, we show that either the WLC or our present model adequately describes force-extension, solution scattering, and long-contour-length cyclization experiments, regardless of the details of DNA bend elasticity. In contrast, experiments sensitive to short-length-scale chain behavior can in principle reveal dramatic departures from the linear elastic behavior assumed in the WLC model. We demonstrate this explicitly by showing that our toy model can reproduce the anomalously large short-contour-length cyclization factors recently measured by Cloutier and Widom. Finally, we discuss the applicability of these models to DNA chain statistics in the context of future experiments.
Acculturation Predicts Negative Affect and Shortened Telomere Length.

PubMed

Ruiz, R Jeanne; Trzeciakowski, Jerome; Moore, Tiffany; Ayers, Kimberly S; Pickler, Rita H

2016-10-12

Chronic stress may accelerate cellular aging. Telomeres, protective "caps" at the end of chromosomes, modulate cellular aging and may be good biomarkers for the effects of chronic stress, including that associated with acculturation. The purpose of this analysis was to examine telomere length (TL) in acculturating Hispanic Mexican American women and to determine the associations among TL, acculturation, and psychological factors. As part of a larger cross-sectional study of 516 pregnant Hispanic Mexican American women, we analyzed DNA in blood samples (N = 56) collected at 22-24 weeks gestation for TL as an exploratory measure using monochrome multiplex quantitative telomere polymerase chain reaction (PCR). We measured acculturation with the Acculturation Rating Scale for Mexican Americans, depression with the Beck Depression Inventory, discrimination with the Experiences of Discrimination Scale, and stress with the Perceived Stress Scale. TL was negatively moderately correlated with two variables of acculturation: Anglo orientation and greater acculturation-level scores. We combined these scores for a latent variable, acculturation, and we combined depression, stress, and discrimination scores in another latent variable, "negative affectivity." Acculturation and negative affectivity were bidirectionally correlated. Acculturation significantly negatively predicted TL. Using structural equation modeling, we found the model had an excellent fit with the root mean square error of approximation estimate = .0001, comparative fit index = 1.0, Tucker-Lewis index = 1.0, and standardized root mean square residual = .05. The negative effects of acculturation on the health of Hispanic women have been previously demonstrated. Findings from this analysis suggest a link between acculturation and TL, which may indicate accelerated cellular aging associated with overall poor health outcomes. © The Author(s) 2016.
Miniaturized integration of a fluorescence microscope

PubMed Central

Ghosh, Kunal K.; Burns, Laurie D.; Cocker, Eric D.; Nimmerjahn, Axel; Ziv, Yaniv; Gamal, Abbas El; Schnitzer, Mark J.

2013-01-01

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals towards relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including semiconductor light source and sensor. This device enables high-speed cellular-level imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens. PMID:21909102
Miniaturized integration of a fluorescence microscope.

PubMed

Ghosh, Kunal K; Burns, Laurie D; Cocker, Eric D; Nimmerjahn, Axel; Ziv, Yaniv; Gamal, Abbas El; Schnitzer, Mark J

2011-09-11

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor. This device enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.
Impact of jamming on collective cell migration

NASA Astrophysics Data System (ADS)

Nnetu, Kenechukwu David; Knorr, Melanie; Pawlizak, Steve; Fuhs, Thomas; Zink, Mareike; KäS, Josef A.

2012-02-01

Multi-cellular migration plays an important role in physiological processes such as embryogenesis, cancer metastasis and tissue repair. During migration, single cells undergo cycles of extension, adhesion and retraction resulting in morphological changes. In a confluent monolayer, there are inter-cellular interactions and crowding, however, the impact of these interactions on the dynamics and elasticity of the monolayer at the multi-cellular and single cell level is not well understood. Here we study the dynamics of a confluent epithelial monolayer by simultaneously measuring cell motion at the multi-cellular and single cell level for various cell densities and tensile elasticity. At the multi-cellular level, the system exhibited spatial kinetic transitions from isotropic to anisotropic migration on long times and the velocity of the monolayer decreased with increasing cell density. Moreover, the dynamics was spatially and temporally heterogeneous. Interestingly, the dynamics was also heterogeneous in wound-healing assays and the correlation length was fitted by compressed exponential. On the single cell scale, we observed transient caging effects with increasing cage rearrangement times as the system age due to an increase in density. Also, the density dependent elastic modulus of the monolayer scaled as a weak power law. Together, these findings suggest that caging effects at the single cell level initiates a slow and heterogeneous dynamics at the multi-cellular level which is similar to the glassy dynamics of deformable colloidal systems.
Shaping the shoot: the relative contribution of cell number and cell shape to variations in internode length between parent and hybrid apple trees.

PubMed

Ripetti, V; Escoute, J; Verdeil, J L; Costes, E

2008-01-01

Genetic control of plant size and shape is a promising perspective, particularly in fruit trees, in order to select desirable genotypes. A recent study on architectural traits in an apple progeny showed that internode length was a highly heritable character. However, few studies have been devoted to internode cellular patterning in dicotyledonous stems, and the interplay between the two elementary cell processes that contribute to their length, i.e. cell division and elongation, is not fully understood. The present study aimed at unravelling their contributions in the genetic variation of internode length in a selection of F(1) and parent genotypes of apple tree, by exploring the number of cells and cell shape within mature internodes belonging to the main axes. The results highlighted that both the variables were homogeneous in samples collected either along a sagital line or along the pith width, and suggest that cell lengthening was homogeneous during internode development. They allowed the total number of cells to be estimated on the internode scale and opened up new perspectives for simplifying tissue sampling procedures for further investigations. Differences in internode length were observed between the genotypes, in particular between the parents, and partly resulted from a compensation between cell number and cell length. However, genetic variations in internode length primarily involved the number of cells, while cell length was more secondary. These results argue for an interplay between cellular and organismal control of internode shape that may involve the rib meristem.
Draft De Novo Transcriptome of the Rat Kangaroo Potorous tridactylus as a Tool for Cell Biology

PubMed Central

Udy, Dylan B.; Voorhies, Mark; Chan, Patricia P.; Lowe, Todd M.; Dumont, Sophie

2015-01-01

The rat kangaroo (long-nosed potoroo, Potorous tridactylus) is a marsupial native to Australia. Cultured rat kangaroo kidney epithelial cells (PtK) are commonly used to study cell biological processes. These mammalian cells are large, adherent, and flat, and contain large and few chromosomes—and are thus ideal for imaging intra-cellular dynamics such as those of mitosis. Despite this, neither the rat kangaroo genome nor transcriptome have been sequenced, creating a challenge for probing the molecular basis of these cellular dynamics. Here, we present the sequencing, assembly and annotation of the draft rat kangaroo de novo transcriptome. We sequenced 679 million reads that mapped to 347,323 Trinity transcripts and 20,079 Unigenes. We present statistics emerging from transcriptome-wide analyses, and analyses suggesting that the transcriptome covers full-length sequences of most genes, many with multiple isoforms. We also validate our findings with a proof-of-concept gene knockdown experiment. We expect that this high quality transcriptome will make rat kangaroo cells a more tractable system for linking molecular-scale function and cellular-scale dynamics. PMID:26252667

Draft De Novo Transcriptome of the Rat Kangaroo Potorous tridactylus as a Tool for Cell Biology.

PubMed

Udy, Dylan B; Voorhies, Mark; Chan, Patricia P; Lowe, Todd M; Dumont, Sophie

2015-01-01

The rat kangaroo (long-nosed potoroo, Potorous tridactylus) is a marsupial native to Australia. Cultured rat kangaroo kidney epithelial cells (PtK) are commonly used to study cell biological processes. These mammalian cells are large, adherent, and flat, and contain large and few chromosomes-and are thus ideal for imaging intra-cellular dynamics such as those of mitosis. Despite this, neither the rat kangaroo genome nor transcriptome have been sequenced, creating a challenge for probing the molecular basis of these cellular dynamics. Here, we present the sequencing, assembly and annotation of the draft rat kangaroo de novo transcriptome. We sequenced 679 million reads that mapped to 347,323 Trinity transcripts and 20,079 Unigenes. We present statistics emerging from transcriptome-wide analyses, and analyses suggesting that the transcriptome covers full-length sequences of most genes, many with multiple isoforms. We also validate our findings with a proof-of-concept gene knockdown experiment. We expect that this high quality transcriptome will make rat kangaroo cells a more tractable system for linking molecular-scale function and cellular-scale dynamics.
Characterization of a Setup to test the Impact of High-Amplitude Pressure Waves on Living Cells

PubMed Central

Schmidt, Mischa; Kahlert, Ulf; Wessolleck, Johanna; Maciaczyk, Donata; Merkt, Benjamin; Maciaczyk, Jaroslaw; Osterholz, Jens; Nikkhah, Guido; Steinhauser, Martin O.

2014-01-01

The impact of pressure waves on cells may provide several possible applications in biology and medicine including the direct killing of tumors, drug delivery or gene transfection. In this study we characterize the physical properties of mechanical pressure waves generated by a nanosecond laser pulse in a setup with well-defined cell culture conditions. To systematically characterize the system on the relevant length and time scales (micrometers and nanoseconds) we use photon Doppler velocimetry (PDV) and obtain velocity profiles of the cell culture vessel at the passage of the pressure wave. These profiles serve as input for numerical pressure wave simulations that help to further quantify the pressure conditions on the cellular length scale. On the biological level we demonstrate killing of glioblastoma cells and quantify experimentally the pressure threshold for cell destruction. PMID:24458018
Musculoaponeurotic Area of the Hip and Clinicophotographic Scaling System

PubMed Central

Mena-Chávez, J. Alejandro

2015-01-01

Background: With the evolution of body contouring, few innovative alternatives have been developed for cosmetic treatment in the hip area. Methods: A multicenter controlled study was conducted, including a prior review of the literature regarding the hip area. Dissections were performed on 4 male cadavers, outlining the “musculoaponeurotic area of the hip.” The area was subdivided into anterior and posterior surfaces. A clinical study was conducted in 79 patients, obtaining a scale by using the most prominent points on the sides of both thighs as the main reference. With the lines marked on photographs and the measurements, a “clinicophotographic scaling system” was designed. Results: The anterior surface corresponds to the tensor fasciae latae and its tendon as well as to the aponeurosis of the gluteus medius. The posterior surface corresponds with the iliotibial tract and the tendon insertions of the gluteus maximus. The average dimensions of the cadaver “musculoaponeurotic area of the hip” are as follows: length, 17.5 cm, and width, 11.5 cm. Using the “clinicophotographic scaling system,” the dimensions are as follows: length, 14.9 cm, and width, 10.3 cm. Conclusions: The “musculoaponeurotic area of the hip” was defined involving muscles, tendons, aponeurosis, fascia, subcutaneous cellular tissue, and skin. The borders were established using important anatomical points that determine the length and width of the area. The “clinicophotographic scaling system” was used to clinically calculate the length and width of the area. By examination and palpation, the borders and dimensions of this area could be determined. PMID:26180724
Texturing Silicon Nanowires for Highly Localized Optical Modulation of Cellular Dynamics.

PubMed

Fang, Yin; Jiang, Yuanwen; Acaron Ledesma, Hector; Yi, Jaeseok; Gao, Xiang; Weiss, Dara E; Shi, Fengyuan; Tian, Bozhi

2018-06-18

Engineered silicon-based materials can display photoelectric and photothermal responses under light illumination, which may lead to further innovations at the silicon-biology interfaces. Silicon nanowires have small radial dimensions, promising as highly localized cellular modulators, however the single crystalline form typically has limited photothermal efficacy due to the poor light absorption and fast heat dissipation. In this work, we report strategies to improve the photothermal response from silicon nanowires by introducing nanoscale textures on the surface and in the bulk. We next demonstrate high-resolution extracellular modulation of calcium dynamics in a number of mammalian cells including glial cells, neurons, and cancer cells. The new materials may be broadly used in probing and modulating electrical and chemical signals at the subcellular length scale, which is currently a challenge in the field of electrophysiology or cellular engineering.
Process-morphology scaling relations quantify self-organization in capillary densified nanofiber arrays.

PubMed

Kaiser, Ashley L; Stein, Itai Y; Cui, Kehang; Wardle, Brian L

2018-02-07

Capillary-mediated densification is an inexpensive and versatile approach to tune the application-specific properties and packing morphology of bulk nanofiber (NF) arrays, such as aligned carbon nanotubes. While NF length governs elasto-capillary self-assembly, the geometry of cellular patterns formed by capillary densified NFs cannot be precisely predicted by existing theories. This originates from the recently quantified orders of magnitude lower than expected NF array effective axial elastic modulus (E), and here we show via parametric experimentation and modeling that E determines the width, area, and wall thickness of the resulting cellular pattern. Both experiments and models show that further tuning of the cellular pattern is possible by altering the NF-substrate adhesion strength, which could enable the broad use of this facile approach to predictably pattern NF arrays for high value applications.
Quantitative Large-Scale Three-Dimensional Imaging of Human Kidney Biopsies: A Bridge to Precision Medicine in Kidney Disease.

PubMed

Winfree, Seth; Dagher, Pierre C; Dunn, Kenneth W; Eadon, Michael T; Ferkowicz, Michael; Barwinska, Daria; Kelly, Katherine J; Sutton, Timothy A; El-Achkar, Tarek M

2018-06-05

Kidney biopsy remains the gold standard for uncovering the pathogenesis of acute and chronic kidney diseases. However, the ability to perform high resolution, quantitative, molecular and cellular interrogation of this precious tissue is still at a developing stage compared to other fields such as oncology. Here, we discuss recent advances in performing large-scale, three-dimensional (3D), multi-fluorescence imaging of kidney biopsies and quantitative analysis referred to as 3D tissue cytometry. This approach allows the accurate measurement of specific cell types and their spatial distribution in a thick section spanning the entire length of the biopsy. By uncovering specific disease signatures, including rare occurrences, and linking them to the biology in situ, this approach will enhance our understanding of disease pathogenesis. Furthermore, by providing accurate quantitation of cellular events, 3D cytometry may improve the accuracy of prognosticating the clinical course and response to therapy. Therefore, large-scale 3D imaging and cytometry of kidney biopsy is poised to become a bridge towards personalized medicine for patients with kidney disease. © 2018 S. Karger AG, Basel.
Probing cooperative force generation in collective cancer invasion

NASA Astrophysics Data System (ADS)

Alobaidi, Amani A.; Xu, Yaopengxiao; Chen, Shaohua; Jiao, Yang; Sun, Bo

2017-08-01

Collective cellular dynamics in the three-dimensional extracellular matrix (ECM) plays a crucial role in many physiological processes such as cancer invasion. Both chemical and mechanical signaling support cell-cell communications on a variety of length scales, leading to collective migratory behaviors. Here we conduct experiments using 3D in vitro tumor models and develop a phenomenological model in order to probe the cooperativity of force generation in the collective invasion of breast cancer cells. In our model, cell-cell communication is characterized by a single parameter that quantifies the correlation length of cellular migration cycles. We devise a stochastic reconstruction method to generate realizations of cell colonies with specific contraction phase correlation functions and correlation length a. We find that as a increases, the characteristic size of regions containing cells with similar contraction phases grows. For small a values, the large fluctuations in individual cell contraction phases smooth out the temporal fluctuations in the time-dependent deformation field in the ECM. For large a values, the periodicity of an individual cell contraction cycle is clearly manifested in the temporal variation of the overall deformation field in the ECM. Through quantitative comparisons of the simulated and experimentally measured deformation fields, we find that the correlation length for collective force generation in the breast cancer diskoid in geometrically micropatterned ECM (DIGME) system is a≈ 25~μ \\text{m} , which is roughly twice the linear size of a single cell. One possible mechanism for this intermediate cell correlation length is the fiber-mediated stress propagation in the 3D ECM network in the DIGME system.
Interface Pattern Selection in Directional Solidification

NASA Technical Reports Server (NTRS)

Trivedi, Rohit; Tewari, Surendra N.

2001-01-01

The central focus of this research is to establish key scientific concepts that govern the selection of cellular and dendritic patterns during the directional solidification of alloys. Ground-based studies have established that the conditions under which cellular and dendritic microstructures form are precisely where convection effects are dominant in bulk samples. Thus, experimental data can not be obtained terrestrially under pure diffusive regime. Furthermore, reliable theoretical models are not yet possible which can quantitatively incorporate fluid flow in the pattern selection criterion. Consequently, microgravity experiments on cellular and dendritic growth are designed to obtain benchmark data under diffusive growth conditions that can be quantitatively analyzed and compared with the rigorous theoretical model to establish the fundamental principles that govern the selection of specific microstructure and its length scales. In the cellular structure, different cells in an array are strongly coupled so that the cellular pattern evolution is controlled by complex interactions between thermal diffusion, solute diffusion and interface effects. These interactions give infinity of solutions, and the system selects only a narrow band of solutions. The aim of this investigation is to obtain benchmark data and develop a rigorous theoretical model that will allow us to quantitatively establish the physics of this selection process.
Melt-processed polymeric cellular dosage forms for immediate drug release.

PubMed

Blaesi, Aron H; Saka, Nannaji

2015-12-28

The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.
Fabrication of cellular materials

NASA Astrophysics Data System (ADS)

Prud'homme, Robert K.; Aksay, Ilhan A.; Garg, Rajeev

1996-02-01

Nature uses cellular materials in applications requiring strength while, simultaneously, minimizing raw materials requirements. Minimizing raw materials is efficient both in terms of the energy expended by the organism to synthesize the structure and in terms of the strength- to-weight ratio of the structure. Wood is the most obvious example of cellular bio-materials, and it is the focus of other presentations in this symposium. The lightweight bone structure of birds is another excellent example where weight is a key criterion. The anchoring foot of the common muscle [Mytilus edulis] whereby it attaches itself to objects is a further example of a biological system that uses a foam to fill space and yet conserve on raw materials. In the case of the muscle the foam is water filled and the foot structure distributes stress over a larger area so that the strength of the byssal thread from which it is suspended is matched to the strength of interfacial attachment of the foot to a substrate. In these examples the synthesis and fabrication of the cellular material is directed by intercellular, genetically coded, biochemical reactions. The resulting cell sizes are microns in scale. Cellular materials at the next larger scale are created by organisms at the next higher level of integration. For example an African tree frog lays her eggs in a gas/fluid foam sack she builds on a branch overhanging a pond. The outside of the foam sack hardens in the sun and prevents water evaporation. The foam structure minimizes the amount of fluid that needs to be incorporated into the sack and minimizes its weight. However, as far as the developing eggs are concerned, they are in an aqueous medium, i.e. the continuous fluid phase of the foam. After precisely six days the eggs hatch, and the solidified outer wall re-liquefies and dumps the emerging tadpoles into the pond below. The bee honeycomb is an example of a cellular material with exquisite periodicity at millimeter length scales. The cellular structure provides strength through geometric regularity and functions as both honey storage vessels and incubators.
Child mortality, hypothalamic-pituitary-adrenal axis activity and cellular aging in mothers.

PubMed

Barha, Cindy K; Salvante, Katrina G; Hanna, Courtney W; Wilson, Samantha L; Robinson, Wendy P; Altman, Rachel M; Nepomnaschy, Pablo A

2017-01-01

Psychological challenges, including traumatic events, have been hypothesized to increase the age-related pace of biological aging. Here we test the hypothesis that psychological challenges can affect the pace of telomere attrition, a marker of cellular aging, using data from an ongoing longitudinal-cohort study of Kaqchikel Mayan women living in a population with a high frequency of child mortality, a traumatic life event. Specifically, we evaluate the associations between child mortality, maternal telomere length and the mothers' hypothalamic-pituitary-adrenal axis (HPAA), or stress axis, activity. Child mortality data were collected in 2000 and 2013. HPAA activity was assessed by quantifying cortisol levels in first morning urinary specimens collected every other day for seven weeks in 2013. Telomere length (TL) was quantified using qPCR in 55 women from buccal specimens collected in 2013. Shorter TL with increasing age was only observed in women who experienced child mortality (p = 0.015). Women with higher average basal cortisol (p = 0.007) and greater within-individual variation (standard deviation) in basal cortisol (p = 0.053) presented shorter TL. Non-parametric bootstrapping to estimate mediation effects suggests that HPAA activity mediates the effect of child mortality on TL. Our results are, thus, consistent with the hypothesis that traumatic events can influence cellular aging and that HPAA activity may play a mediatory role. Future large-scale longitudinal studies are necessary to confirm our results and further explore the role of the HPAA in cellular aging, as well as to advance our understanding of the underlying mechanisms involved.
Child mortality, hypothalamic-pituitary-adrenal axis activity and cellular aging in mothers

PubMed Central

Barha, Cindy K.; Salvante, Katrina G.; Hanna, Courtney W.; Wilson, Samantha L.; Robinson, Wendy P.; Altman, Rachel M.

2017-01-01

Psychological challenges, including traumatic events, have been hypothesized to increase the age-related pace of biological aging. Here we test the hypothesis that psychological challenges can affect the pace of telomere attrition, a marker of cellular aging, using data from an ongoing longitudinal-cohort study of Kaqchikel Mayan women living in a population with a high frequency of child mortality, a traumatic life event. Specifically, we evaluate the associations between child mortality, maternal telomere length and the mothers’ hypothalamic-pituitary-adrenal axis (HPAA), or stress axis, activity. Child mortality data were collected in 2000 and 2013. HPAA activity was assessed by quantifying cortisol levels in first morning urinary specimens collected every other day for seven weeks in 2013. Telomere length (TL) was quantified using qPCR in 55 women from buccal specimens collected in 2013. Results: Shorter TL with increasing age was only observed in women who experienced child mortality (p = 0.015). Women with higher average basal cortisol (p = 0.007) and greater within-individual variation (standard deviation) in basal cortisol (p = 0.053) presented shorter TL. Non-parametric bootstrapping to estimate mediation effects suggests that HPAA activity mediates the effect of child mortality on TL. Our results are, thus, consistent with the hypothesis that traumatic events can influence cellular aging and that HPAA activity may play a mediatory role. Future large-scale longitudinal studies are necessary to confirm our results and further explore the role of the HPAA in cellular aging, as well as to advance our understanding of the underlying mechanisms involved. PMID:28542264
Recent Advances in Transferable Coarse-Grained Modeling of Proteins

PubMed Central

Kar, Parimal; Feig, Michael

2017-01-01

Computer simulations are indispensable tools for studying the structure and dynamics of biological macromolecules. Biochemical processes occur on different scales of length and time. Atomistic simulations cannot cover the relevant spatiotemporal scales at which the cellular processes occur. To address this challenge, coarse-grained (CG) modeling of the biological systems are employed. Over the last few years, many CG models for proteins continue to be developed. However, many of them are not transferable with respect to different systems and different environments. In this review, we discuss those CG protein models that are transferable and that retain chemical specificity. We restrict ourselves to CG models of soluble proteins only. We also briefly review recent progress made in the multi-scale hybrid all-atom/coarse-grained simulations of proteins. PMID:25443957
Human mammary epithelial cells exhibit a bimodal correlated random walk pattern.

PubMed

Potdar, Alka A; Jeon, Junhwan; Weaver, Alissa M; Quaranta, Vito; Cummings, Peter T

2010-03-10

Organisms, at scales ranging from unicellular to mammals, have been known to exhibit foraging behavior described by random walks whose segments confirm to Lévy or exponential distributions. For the first time, we present evidence that single cells (mammary epithelial cells) that exist in multi-cellular organisms (humans) follow a bimodal correlated random walk (BCRW). Cellular tracks of MCF-10A pBabe, neuN and neuT random migration on 2-D plastic substrates, analyzed using bimodal analysis, were found to reveal the BCRW pattern. We find two types of exponentially distributed correlated flights (corresponding to what we refer to as the directional and re-orientation phases) each having its own correlation between move step-lengths within flights. The exponential distribution of flight lengths was confirmed using different analysis methods (logarithmic binning with normalization, survival frequency plots and maximum likelihood estimation). Because of the presence of non-uniform turn angle distribution of move step-lengths within a flight and two different types of flights, we propose that the epithelial random walk is a BCRW comprising of two alternating modes with varying degree of correlations, rather than a simple persistent random walk. A BCRW model rather than a simple persistent random walk correctly matches the super-diffusivity in the cell migration paths as indicated by simulations based on the BCRW model.
Dynamic Forces Between Two Deformable Oil Droplets in Water

NASA Astrophysics Data System (ADS)

Dagastine, Raymond R.; Manica, Rogério; Carnie, Steven L.; Chan, D. Y. C.; Stevens, Geoffrey W.; Grieser, Franz

2006-07-01

The understanding of static interactions in colloidal suspensions is well established, whereas dynamic interactions more relevant to biological and other suspended soft-matter systems are less well understood. We present the direct force measurement and quantitative theoretical description for dynamic forces for liquid droplets in another immiscible fluid. Analysis of this system demonstrates the strong link between interfacial deformation, static surface forces, and hydrodynamic drainage, which govern dynamic droplet-droplet interactions over the length scale of nanometers and over the time scales of Brownian collisions. The results and analysis have direct bearing on the control and manipulation of suspended droplets in soft-matter systems ranging from the emulsions in shampoo to cellular interactions.
Childhood adversity, social support, and telomere length among perinatal women.

PubMed

Mitchell, Amanda M; Kowalsky, Jennifer M; Epel, Elissa S; Lin, Jue; Christian, Lisa M

2018-01-01

Adverse perinatal health outcomes are heightened among women with psychosocial risk factors, including childhood adversity and a lack of social support. Biological aging could be one pathway by which such outcomes occur. However, data examining links between psychosocial factors and indicators of biological aging among perinatal women are limited. The current study examined the associations of childhood socioeconomic status (SES), childhood trauma, and current social support with telomere length in peripheral blood mononuclear cells (PBMCs) in a sample of 81 women assessed in early, mid, and late pregnancy as well as 7-11 weeks postpartum. Childhood SES was defined as perceived childhood social class and parental educational attainment. Measures included the Childhood Trauma Questionnaire, Center for Epidemiologic Studies-Depression Scale, Multidimensional Scale of Perceived Social Support, and average telomere length in PBMCs. Per a linear mixed model, telomere length did not change across pregnancy and postpartum visits; thus, subsequent analyses defined telomere length as the average across all available timepoints. ANCOVAs showed group differences by perceived childhood social class, maternal and paternal educational attainment, and current family social support, with lower values corresponding with shorter telomeres, after adjustment for possible confounds. No effects of childhood trauma or social support from significant others or friends on telomere length were observed. Findings demonstrate that while current SES was not related to telomeres, low childhood SES, independent of current SES, and low family social support were distinct risk factors for cellular aging in women. These data have relevance for understanding potential mechanisms by which early life deprivation of socioeconomic and relationship resources affect maternal health. In turn, this has potential significance for intergenerational transmission of telomere length. The predictive value of markers of biological versus chronological age on birth outcomes warrants investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Multiscale Modelling for investigating single molecule effects on the mechanics of actin filaments

NASA Astrophysics Data System (ADS)

A, Deriu Marco; C, Bidone Tamara; Laura, Carbone; Cristina, Bignardi; M, Montevecchi Franco; Umberto, Morbiducci

2011-12-01

This work presents a preliminary multiscale computational investigation of the effects of nucleotides and cations on the mechanics of actin filaments (F-actin). At the molecular level, Molecular Dynamics (MD) simulations are employed to characterize the rearrangements of the actin monomers (G-actin) in terms of secondary structures evolution in physiological conditions. At the mesoscale level, a coarse grain (CG) procedure is adopted where each monomer is represented by means of Elastic Network Modeling (ENM) technique. At the macroscale level, actin filaments up to hundreds of nanometers are assumed as isotropic and elastic beams and characterized via Rotation Translation Block (RTB) analysis. F-actin bound to adenosine triphosphate (ATP) shows a persistence length around 5 μm, while actin filaments bound to adenosine diphosphate (ADP) have a persistence length of about 3 μm. With magnesium bound to the high affinity binding site of G-actin, the persistence length of F-actin decreases to about 2 μm only in the ADP-bound form of the filament, while the same ion has no effects, in terms of stiffness variation, on the ATP-bound form of F-actin. The molecular mechanisms behind these changes in flexibility are herein elucidated. Thus, this study allows to analyze how the local binding of cations and nucleotides on G-actin induce molecular rearrangements that transmit to the overall F-actin, characterizing shifts of mechanical properties, that can be related with physiological and pathological cellular phenomena, as cell migration and spreading. Further, this study provides the basis for upcoming investigating of network and cellular remodelling at higher length scales.
Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging

PubMed Central

JONES, Christopher W.; GAMBALA, Cecilia; ESTEVES, Kyle C.; WALLACE, Maeve; SCHLESINGER, Reid; O’QUINN, Marguerite; KIDD, Laura; THEALL, Katherine P.; DRURY, Stacy S.

2017-01-01

BACKGROUND Health disparities begin early in life and persist across the life course. Despite current efforts Black women exhibit greater risk for pregnancy complications and negative perinatal outcomes compared to White women. The placenta, a complex multi-tissue organ, serves as the primary transducer of bidirectional information between the mother and fetus. Altered placental function is linked to multiple racially disparate pregnancy complications, however little is known about racial differences in molecular factors within the placenta. Several pregnancy complications, including preeclampsia and fetal growth restriction, exhibit racial disparities and are associated with shorter placental telomere length, an indicator of cellular stress and aging. Cellular senescence and telomere dynamics are linked to the molecular mechanisms associated with the onset of labor and parturition. Further, racial differences in telomere length are found in a range of different peripheral tissues. Together these factors suggest that exploration of racial differences in telomere length of the placenta may provide novel mechanistic insight into racial disparities in birth outcomes. OBJECTIVE This study examined whether telomere length measured in four distinct fetally-derived tissues were significantly different between Blacks and Whites. The study had two hypotheses: (1) that telomere length measured in different placental tissue types would be correlated and (2) that across all sampled tissues telomere length would differ by race. STUDY DESIGN In a prospective study, placental tissue samples were collected from the amnion, chorion, villus, and umbilical cord from Black and White singleton pregnancies (N=46). Telomere length was determined using monochrome multiplex quantitative real-time polymerase chain reaction in each placental tissue. Demographic and pregnancy-related data were also collected. Descriptive statistics characterized the sample overall and among Black and White women separately. The overall impact of race was assessed by multilevel mixed-effects linear regression models that included empirically relevant covariates. RESULTS Telomere length was significantly correlated across all placental tissues. Pairwise analyses of placental tissue telomere length revealed significantly longer telomere length in the amnion compared to the chorion (t=−2.06, p=0.043). Overall telomere length measured in placenta samples from Black mothers were significantly shorter than those from White mothers (β=−0.09, p=0.04). Controlling for relevant maternal and infant characteristics strengthened the significance of the observed racial differences (β=−0.12, p=0.02). Within tissue analyses revealed that the greatest difference by race was found in chorionic telomere length (t=−2.81, p=0.007). CONCLUSION These findings provide the first evidence of racial differences in placental telomere length. Telomere length was significantly shorter in placental samples derived from Black mothers compared to White. Given previous studies reporting that telomere length, cellular senescence, and telomere dynamics are molecular factors contributing to the rupture of the amniotic sac, onset of labor, and parturition, our findings of shorter telomere length in placentas from Black mothers suggests that accelerated cellular aging across placental tissues may be relevant to the increased risk of preterm delivery in Blacks. Our results suggest that racial differences in cellular aging in the placenta contribute to the earliest roots of health disparities. PMID:27865975
Direct measurement of Vorticella contraction force by micropipette deflection.

PubMed

France, Danielle; Tejada, Jonathan; Matsudaira, Paul

2017-02-01

The ciliated protozoan Vorticella convallaria is noted for its exceptionally fast adenosine triphosphate-independent cellular contraction, but direct measurements of contractile force have proven difficult given the length scale, speed, and forces involved. We used high-speed video microscopy to image live Vorticella stalled in midcontraction by deflection of an attached micropipette. Stall forces correlate with both distance contracted and the resting stalk length. Estimated isometric forces range from 95 to 177 nanonewtons (nN), or 1.12 nN·μm -1 of the stalk. Maximum velocity and work are also proportional to distance contracted. These parameters constrain proposed biochemical/physical models of the contractile mechanism. © Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
A Multi-Scale Approach to Airway Hyperresponsiveness: From Molecule to Organ

PubMed Central

Lauzon, Anne-Marie; Bates, Jason H. T.; Donovan, Graham; Tawhai, Merryn; Sneyd, James; Sanderson, Michael J.

2012-01-01

Airway hyperresponsiveness (AHR), a characteristic of asthma that involves an excessive reduction in airway caliber, is a complex mechanism reflecting multiple processes that manifest over a large range of length and time scales. At one extreme, molecular interactions determine the force generated by airway smooth muscle (ASM). At the other, the spatially distributed constriction of the branching airways leads to breathing difficulties. Similarly, asthma therapies act at the molecular scale while clinical outcomes are determined by lung function. These extremes are linked by events operating over intermediate scales of length and time. Thus, AHR is an emergent phenomenon that limits our understanding of asthma and confounds the interpretation of studies that address physiological mechanisms over a limited range of scales. A solution is a modular computational model that integrates experimental and mathematical data from multiple scales. This includes, at the molecular scale, kinetics, and force production of actin-myosin contractile proteins during cross-bridge and latch-state cycling; at the cellular scale, Ca2+ signaling mechanisms that regulate ASM force production; at the tissue scale, forces acting between contracting ASM and opposing viscoelastic tissue that determine airway narrowing; at the organ scale, the topographic distribution of ASM contraction dynamics that determine mechanical impedance of the lung. At each scale, models are constructed with iterations between theory and experimentation to identify the parameters that link adjacent scales. This modular model establishes algorithms for modeling over a wide range of scales and provides a framework for the inclusion of other responses such as inflammation or therapeutic regimes. The goal is to develop this lung model so that it can make predictions about bronchoconstriction and identify the pathophysiologic mechanisms having the greatest impact on AHR and its therapy. PMID:22701430

Ultrashort Phenomena in Biochemistry and Biological Signaling

NASA Astrophysics Data System (ADS)

Splinter, Robert

2014-11-01

In biological phenomena there are indications that within the long pulse-length of the action potential on millisecond scale, there is additional ultrashort perturbation encoding that provides the brain with detailed information about the origin (location) and physiological characteristics. The objective is to identify the mechanism-of-action providing the potential for encoding in biological signal propagation. The actual molecular processes involved in the initiation of the action potential have been identified to be in the femtosecond and pico-second scale. The depolarization process of the cellular membrane itself, leading to the onset of the actionpotential that is transmitted to the brain, however is in the millisecond timeframe. One example of the femtosecond chemical interaction is the photoresponse of bacteriorhodopsin. No clear indication for the spatial encoding has so far been verified. Further research will be required on a cellular signal analysis level to confirm or deny the spatial and physiological encoding in the signal wave-trains of intercellular communications and sensory stimuli. The pathological encoding process for cardiac depolarization is however very pronounced and validated, however this electro-chemical process is in the millisecond amplitude and frequency modulation spectrum.
High Severity Wildfire Effect On Rainfall Infiltration And Runoff: A Cellular Automata Based Simulation

NASA Astrophysics Data System (ADS)

Vergara-Blanco, J. E.; Leboeuf-Pasquier, J.; Benavides-Solorio, J. D. D.

2017-12-01

A simulation software that reproduces rainfall infiltration and runoff for a storm event in a particular forest area is presented. A cellular automaton is utilized to represent space and time. On the time scale, the simulation is composed by a sequence of discrete time steps. On the space scale, the simulation is composed of forest surface cells. The software takes into consideration rain intensity and length, individual forest cell soil absorption capacity evolution, and surface angle of inclination. The software is developed with the C++ programming language. The simulation is executed on a 100 ha area within La Primavera Forest in Jalisco, Mexico. Real soil texture for unburned terrain and high severity wildfire affected terrain is employed to recreate the specific infiltration profile. Historical rainfall data of a 92 minute event is used. The Horton infiltration equation is utilized for infiltration capacity calculation. A Digital Elevation Model (DEM) is employed to reproduce the surface topography. The DEM is displayed with a 3D mesh graph where individual surface cells can be observed. The plot colouring renders water content development at the cell level throughout the storm event. The simulation shows that the cumulative infiltration and runoff which take place at the surface cell level depend on the specific storm intensity, fluctuation and length, overall terrain topography, cell slope, and soil texture. Rainfall cumulative infiltration for unburned and high severity wildfire terrain are compared: unburned terrain exhibits a significantly higher amount of rainfall infiltration.It is concluded that a cellular automaton can be utilized with a C++ program to reproduce rainfall infiltration and runoff under diverse soil texture, topographic and rainfall conditions in a forest setting. This simulation is geared for an optimization program to pinpoint the locations of a series of forest land remediation efforts to support reforestation or to minimize runoff.
Intermediate-filaments: from disordered building blocks to well-ordered cells

NASA Astrophysics Data System (ADS)

Kornreich, Micha; Malka-Gibor, Eti; Laser-Azogui, Adi; Doron, Ofer; Avinery, Ram; Herrmann, Harald; Beck, Roy

In the past decade it was found that ~50% of human proteins contain long disordered regions, which play significant functional roles. As these regions lack a defined 3D folded structure, their ensemble conformations can be studied using polymer physics statistical-mechanics arguments. We measure the structure and mechanical response of hydrogels composed of neuronal intermediate filaments proteins. In the nervous system, these proteins provide cells with their mechanical support and shape, via interactions of their long, highly charged and disordered protein chains. We employ synchrotron small-angle X-ray scattering and various microscopy techniques to investigate such hydrogels from the nano- to the macro-scale. In contrast to previous polymer physics theories and experiments, we find that shorter and less charged chains can promote network expansion. The results are explained by intricate interactions between specific domains on the interacting chains, and also suggest a novel structural justification for the changing protein compositions observed during neuronal development. We address the following questions: Can protein disorder have an important role in cellular architecture? Can structural disorder in the micro-scale induce orientational and translational order on the macro-scale? How do the physical properties of disordered protein regions, such as charge, length, and hydrophobicity, modulate the cellular super-structure?
Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging.

PubMed

Jones, Christopher W; Gambala, Cecilia; Esteves, Kyle C; Wallace, Maeve; Schlesinger, Reid; O'Quinn, Marguerite; Kidd, Laura; Theall, Katherine P; Drury, Stacy S

2017-03-01

Health disparities begin early in life and persist across the life course. Despite current efforts, black women exhibit greater risk for pregnancy complications and negative perinatal outcomes compared with white women. The placenta, which is a complex multi-tissue organ, serves as the primary transducer of bidirectional information between the mother and fetus. Altered placental function is linked to multiple racially disparate pregnancy complications; however, little is known about racial differences in molecular factors within the placenta. Several pregnancy complications, which include preeclampsia and fetal growth restriction, exhibit racial disparities and are associated with shorter placental telomere length, which is an indicator of cellular stress and aging. Cellular senescence and telomere dynamics are linked to the molecular mechanisms that are associated with the onset of labor and parturition. Further, racial differences in telomere length are found in a range of different peripheral tissues. Together these factors suggest that exploration of racial differences in telomere length of the placenta may provide novel mechanistic insight into racial disparities in birth outcomes. This study examined whether telomere length measured in 4 distinct fetally derived tissues were significantly different between black and white women. The study had 2 hypotheses: (1) that telomere length that is measured in different placental tissue types would be correlated and (2) that across all sampled tissues telomere length would differ by race. In a prospective study, placental tissue samples were collected from the amnion, chorion, villus, and umbilical cord from black and white singleton pregnancies (N=46). Telomere length was determined with the use of monochrome multiplex quantitative real-time polymerase chain reaction in each placental tissue. Demographic and pregnancy-related data were also collected. Descriptive statistics characterized the sample overall and among black and white women separately. The overall impact of race was assessed by multilevel mixed-effects linear regression models that included empirically relevant covariates. Telomere length was correlated significantly across all placental tissues. Pairwise analyses of placental tissue telomere length revealed significantly longer telomere length in the amnion compared with the chorion (t=-2.06; P=.043). Overall telomere length measured in placenta samples from black mothers were significantly shorter than those from white mothers (β=-0.09; P=.04). Controlling for relevant maternal and infant characteristics strengthened the significance of the observed racial differences (β=-0.12; P=.02). Within tissue analyses revealed that the greatest difference by race was found in chorionic telomere length (t=-2.81; P=.007). These findings provide the first evidence of racial differences in placental telomere length. Telomere length was significantly shorter in placental samples from black mothers compared with white mothers. Given previous studies that have reported that telomere length, cellular senescence, and telomere dynamics are molecular factors that contribute to the rupture of the amniotic sac, onset of labor, and parturition, our findings of shorter telomere length in placentas from black mothers suggest that accelerated cellular aging across placental tissues may be relevant to the increased risk of preterm delivery in black pregnancies. Our results suggest that racial differences in cellular aging in the placenta contribute to the earliest roots of health disparities. Copyright © 2016 Elsevier Inc. All rights reserved.
Understanding the effect of alkyl chains of gemini cations on the physicochemical and cellular properties of polyurethane micelles.

PubMed

Pan, Zhicheng; Fang, Danxuan; Song, Yuanqing; Song, Nijia; Ding, Mingming; Li, Jiehua; Luo, Feng; Li, Jianshu; Tan, Hong; Fu, Qiang

2018-06-06

Cationic gemini quaternary ammonium (GQA) has been used as a cell internalization promoter to improve the permeability of the cell membrane and enhance the cellular uptake. However, the effect of the alkyl chain length on the cellular properties of nanocarriers has not been elucidated yet. In this study, we developed a series of polyurethane micelles containing GQAs with various alkyl chain lengths. The alteration of the gemini alkyl chain length was found to change the distribution of GQA surfactants in the micellar structure and affect the surface charge exposure, stability, and the protein absorption properties of nanocarriers. Moreover, we also clarified the role of the alkyl chain length in tumor cell internalization and macrophage uptake of polyurethane micelles. This work provides a new understanding on the effect of the GQA alkyl chain length on the physicochemical and biological properties of nanomedicines, and offers guidance on the rational design of effective drug delivery systems where the issue of functional group exposure at the micellar surface should be considered.
Tailoring Morphology and Size of Microstructure and Tensile Properties of Sn-5.5 wt.%Sb-1 wt.%(Cu,Ag) Solder Alloys

NASA Astrophysics Data System (ADS)

Dias, Marcelino; Costa, Thiago A.; Soares, Thiago; Silva, Bismarck L.; Cheung, Noé; Spinelli, José E.; Garcia, Amauri

2018-02-01

Transient directional solidification experiments, and further optical and scanning electron microscopy analyses and tensile tests, allowed the dependence of tensile properties on the micromorphology and length scale of the dendritic/cellular matrix of ternary Sn-5.5Sb-1Ag and Sn-5.5Sb-1Cu alloys to be determined. Extensive ranges of cooling rates were obtained, which permitted specific values of cooling rate for each sample examined along the length of the casting to be attributed. Very broad microstructural length scales were revealed as well as the presence of either cells or dendrites for the Ag-containing alloy. Hereafter, microstructural spacing values such as the cellular spacing, λ c, and the primary dendritic spacing, λ 1, may be correlated with thermal solidification parameters, that is, the cooling rate and the growth rate. While, for the Cu-containing Sn-Sb alloy, the β-Sn matrix is characterized only by the presence of dendritic arrangements, the Ag-containing Sn-Sb alloy is shown to have high-velocity β-Sn cells associated with high cooling rate regions, i.e., positions closer to the bottom of the alloy casting, with the remaining positions being characterized by a complex growth of β-Sn dendrites. Minor additions of Cu and Ag increase both the yield and ultimate tensile strengths when compared with the corresponding values of the binary Sn-5.5Sb alloy, with a small reduction in ductility. This has been attributed to the homogeneous distribution of the Ag3Sn and Cu6Sn5 intermetallic particles related to smaller λ 1 characterizing the dendritic zones of the ternary Sn-Sb-(Cu,Ag) alloys. In addition, the Ag-modified Sn-Sb alloy exhibited an initial wetting angle consistent with that characterizing the binary Sn-5.5Sb alloy.
Temperature and pressure tuneable swollen bicontinuous cubic phases approaching nature's length scales.

PubMed

Barriga, H M G; Tyler, A I I; McCarthy, N L C; Parsons, E S; Ces, O; Law, R V; Seddon, J M; Brooks, N J

2015-01-21

Bicontinuous cubic structures offer enormous potential in applications ranging from protein crystallisation to drug delivery systems and have been observed in cellular membrane structures. One of the current bottlenecks in understanding and exploiting these structures is that cubic scaffolds produced in vitro are considerably smaller in size than those observed in biological systems, differing by almost an order of magnitude in some cases. We have addressed this technological bottleneck and developed a methodology capable of manufacturing highly swollen bicontinuous cubic membranes with length scales approaching those seen in vivo. Crucially, these cubic systems do not require the presence of proteins. We have generated highly swollen Im3m symmetry bicontinuous cubic phases with lattice parameters of up to 480 Å, composed of ternary mixtures of monoolein, cholesterol and negatively charged lipid (DOPS or DOPG) and we have been able to tune their lattice parameters. The swollen cubic phases are highly sensitive to both temperature and pressure; these structural changes are likely to be controlled by a fine balance between lipid headgroup repulsions and lateral pressure in the hydrocarbon chain region.
Emotions and family interactions in childhood: Associations with leukocyte telomere length emotions, family interactions, and telomere length.

PubMed

Robles, Theodore F; Carroll, Judith E; Bai, Sunhye; Reynolds, Bridget M; Esquivel, Stephanie; Repetti, Rena L

2016-01-01

Conceptualizations of links between stress and cellular aging in childhood suggest that accumulating stress predicts shorter leukocyte telomere length (LTL). At the same time, several models suggest that emotional reactivity to stressors may play a key role in predicting cellular aging. Using intensive repeated measures, we tested whether exposure or emotional "reactivity" to conflict and warmth in the family were related to LTL. Children (N=39; 30 target children and 9 siblings) between 8 and 13 years of age completed daily diary questionnaires for 56 consecutive days assessing daily warmth and conflict in the marital and the parent-child dyad, and daily positive and negative mood. To assess exposure to conflict and warmth, diary scale scores were averaged over the 56 days. Mood "reactivity" was operationalized by using multilevel modeling to generate estimates of the slope of warmth or conflict scores (marital and parent-child, separately) predicting same-day mood for each individual child. After diary collection, a blood sample was collected to determine LTL. Among children aged 8-13 years, a stronger association between negative mood and marital conflict, suggesting greater negative mood reactivity to marital conflict, was related to shorter LTL (B=-1.51, p<.01). A stronger association between positive mood and marital affection, suggesting positive mood reactivity, was related to longer LTL (B=1.15, p<.05). These effects were independent of exposure to family and marital conflict and warmth, and positive and negative mood over a two-month period. To our knowledge, these findings, although cross-sectional, represent the first evidence showing that link between children's affective responses and daily family interactions may have implications for telomere length. Copyright © 2015 Elsevier Ltd. All rights reserved.
Production, properties, and applications of hydrocolloid cellular solids.

PubMed

Nussinovitch, Amos

2005-02-01

Many common synthetic and edible materials are, in fact, cellular solids. When classifying the structure of cellular solids, a few variables, such as open vs. closed cells, flexible vs. brittle cell walls, cell-size distribution, cell-wall thickness, cell shape, the uniformity of the structure of the cellular solid and the different scales of length are taken into account. Compressive stress-strain relationships of most cellular solids can be easily identified according to their characteristic sigmoid shape, reflecting three deformation mechanisms: (i) elastic distortion under small strains, (ii) collapse and/or fracture of the cell walls, and (iii) densification. Various techniques are used to produce hydrocolloid (gum) cellular solids. The products of these include (i) sponges, obtained when the drying gel contains the occasionally produced gas bubbles; (ii) sponges produced by the immobilization of microorganisms; (iii) solid foams produced by drying foamed solutions or gels containing oils, and (iv) hydrocolloid sponges produced by enzymatic reactions. The porosity of the manufactured cellular solid is subject to change and depends on its composition and the processing technique. The porosity is controlled by a range of methods and the resulting surface structures can be investigated by microscopy and analyzed using fractal methods. Models used to describe stress-strain behaviors of hydrocolloid cellular solids as well as multilayered products and composites are discussed in detail in this manuscript. Hydrocolloid cellular solids have numerous purposes, simple and complex, ranging from dried texturized fruits to carriers of vitamins and other essential micronutrients. They can also be used to control the acoustic response of specific dry food products, and have a great potential for future use in countless different fields, from novel foods and packaging to medicine and medical care, daily commodities, farming and agriculture, and the environmental, chemical, and even electronic industries.
Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres

PubMed Central

Epel, Elissa; Daubenmier, Jennifer; Moskowitz, Judith T.; Folkman, Susan; Blackburn, Elizabeth

2010-01-01

Understanding the malleable determinants of cellular aging is critical to understanding human longevity. Telomeres may provide a pathway for exploring this question. Telomeres are the protective caps at the ends of chromosomes. The length of telomeres offers insight into mitotic cell and possibly organismal longevity. Telomere length has now been linked to chronic stress exposure and depression. This raises the question of how might cellular aging be modulated by psychological functioning. We consider two psychological processes or states that are in opposition to one another--threat cognition and mindfulness--and their effects on cellular aging. Psychological stress cognitions, particularly appraisals of threat and ruminative thoughts, can lead to prolonged states of reactivity. In contrast, mindfulness meditation techniques appear to shift cognitive appraisals from threat to challenge, decrease ruminative thought, and reduce stress arousal. Mindfulness may also directly increase positive arousal states. We review data linking telomere length to cognitive stress and stress arousal and present new data linking cognitive appraisal to telomere length. Given the pattern of associations revealed so far, we propose that some forms of meditation may have salutary effects on telomere length by reducing cognitive stress and stress arousal and increasing positive states of mind and hormonal factors that may promote telomere maintenance. Aspects of this model are currently being tested in ongoing trials of mindfulness meditation. PMID:19735238
Multiscale Characterization of Engineered Cardiac Tissue Architecture.

PubMed

Drew, Nancy K; Johnsen, Nicholas E; Core, Jason Q; Grosberg, Anna

2016-11-01

In a properly contracting cardiac muscle, many different subcellular structures are organized into an intricate architecture. While it has been observed that this organization is altered in pathological conditions, the relationship between length-scales and architecture has not been properly explored. In this work, we utilize a variety of architecture metrics to quantify organization and consistency of single structures over multiple scales, from subcellular to tissue scale as well as correlation of organization of multiple structures. Specifically, as the best way to characterize cardiac tissues, we chose the orientational and co-orientational order parameters (COOPs). Similarly, neonatal rat ventricular myocytes were selected for their consistent architectural behavior. The engineered cells and tissues were stained for four architectural structures: actin, tubulin, sarcomeric z-lines, and nuclei. We applied the orientational metrics to cardiac cells of various shapes, isotropic cardiac tissues, and anisotropic globally aligned tissues. With these novel tools, we discovered: (1) the relationship between cellular shape and consistency of self-assembly; (2) the length-scales at which unguided tissues self-organize; and (3) the correlation or lack thereof between organization of actin fibrils, sarcomeric z-lines, tubulin fibrils, and nuclei. All of these together elucidate some of the current mysteries in the relationship between force production and architecture, while raising more questions about the effect of guidance cues on self-assembly function. These types of metrics are the future of quantitative tissue engineering in cardiovascular biomechanics.
DOE Office of Scientific and Technical Information (OSTI.GOV)

Boreyko, Jonathan B; Mruetusatorn, Prachya; Sarles, Stephen A

Droplet interface bilayers (DIBs) are a robust platform for studying synthetic cellular membranes; however, to date no DIBs have been produced at cellular length scales. Here, we create microscale droplet interface bilayers ( DIBs) at the interface between aqueous femtoliter-volume droplets within an oil-filled microfluidic channel. The uniquely large area-to-volume ratio of the droplets results in strong evaporation effects, causing the system to transition through three distinct regimes. First, the two adjacent droplets shrink into the shape of a single spherical droplet, where an augmented lipid bilayer partitions two hemi-spherical volumes. In the second regime, the combined effects of themore » shrinking monolayers and growing bilayer force the confined bilayer to buckle to conserve its mass. Finally, at a bending moment corresponding to a critical shear stress, the buckling bilayer fissions a vesicle to regulate its shape and stress. The DIBs produced here enable evaporation-induced bilayer dynamics reminiscent of endo- and exocytosis in cells.« less
Additively manufactured hierarchical stainless steels with high strength and ductility.

PubMed

Wang, Y Morris; Voisin, Thomas; McKeown, Joseph T; Ye, Jianchao; Calta, Nicholas P; Li, Zan; Zeng, Zhi; Zhang, Yin; Chen, Wen; Roehling, Tien Tran; Ott, Ryan T; Santala, Melissa K; Depond, Philip J; Matthews, Manyalibo J; Hamza, Alex V; Zhu, Ting

2018-01-01

Many traditional approaches for strengthening steels typically come at the expense of useful ductility, a dilemma known as strength-ductility trade-off. New metallurgical processing might offer the possibility of overcoming this. Here we report that austenitic 316L stainless steels additively manufactured via a laser powder-bed-fusion technique exhibit a combination of yield strength and tensile ductility that surpasses that of conventional 316L steels. High strength is attributed to solidification-enabled cellular structures, low-angle grain boundaries, and dislocations formed during manufacturing, while high uniform elongation correlates to a steady and progressive work-hardening mechanism regulated by a hierarchically heterogeneous microstructure, with length scales spanning nearly six orders of magnitude. In addition, solute segregation along cellular walls and low-angle grain boundaries can enhance dislocation pinning and promote twinning. This work demonstrates the potential of additive manufacturing to create alloys with unique microstructures and high performance for structural applications.
Additively manufactured hierarchical stainless steels with high strength and ductility

NASA Astrophysics Data System (ADS)

Wang, Y. Morris; Voisin, Thomas; McKeown, Joseph T.; Ye, Jianchao; Calta, Nicholas P.; Li, Zan; Zeng, Zhi; Zhang, Yin; Chen, Wen; Roehling, Tien Tran; Ott, Ryan T.; Santala, Melissa K.; Depond, Philip J.; Matthews, Manyalibo J.; Hamza, Alex V.; Zhu, Ting

2018-01-01

Many traditional approaches for strengthening steels typically come at the expense of useful ductility, a dilemma known as strength-ductility trade-off. New metallurgical processing might offer the possibility of overcoming this. Here we report that austenitic 316L stainless steels additively manufactured via a laser powder-bed-fusion technique exhibit a combination of yield strength and tensile ductility that surpasses that of conventional 316L steels. High strength is attributed to solidification-enabled cellular structures, low-angle grain boundaries, and dislocations formed during manufacturing, while high uniform elongation correlates to a steady and progressive work-hardening mechanism regulated by a hierarchically heterogeneous microstructure, with length scales spanning nearly six orders of magnitude. In addition, solute segregation along cellular walls and low-angle grain boundaries can enhance dislocation pinning and promote twinning. This work demonstrates the potential of additive manufacturing to create alloys with unique microstructures and high performance for structural applications.
Additively manufactured hierarchical stainless steels with high strength and ductility

DOE PAGES

Wang, Y. Morris; Voisin, Thomas; McKeown, Joseph T.; ...

2017-10-30

Many traditional approaches for strengthening steels typically come at the expense of useful ductility, a dilemma known as strength–ductility trade-off. New metallurgical processing might offer the possibility of overcoming this. Here we report that austenitic 316L stainless steels additively manufactured via a laser powder-bed-fusion technique exhibit a combination of yield strength and tensile ductility that surpasses that of conventional 316L steels. High strength is attributed to solidification-enabled cellular structures, low-angle grain boundaries, and dislocations formed during manufacturing, while high uniform elongation correlates to a steady and progressive work-hardening mechanism regulated by a hierarchically heterogeneous microstructure, with length scales spanning nearlymore » six orders of magnitude. In addition, solute segregation along cellular walls and low-angle grain boundaries can enhance dislocation pinning and promote twinning. This work demonstrates the potential of additive manufacturing to create alloys with unique microstructures and high performance for structural applications.« less
Additively manufactured hierarchical stainless steels with high strength and ductility

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

Wang, Y. Morris; Voisin, Thomas; McKeown, Joseph T.

Many traditional approaches for strengthening steels typically come at the expense of useful ductility, a dilemma known as strength–ductility trade-off. New metallurgical processing might offer the possibility of overcoming this. Here we report that austenitic 316L stainless steels additively manufactured via a laser powder-bed-fusion technique exhibit a combination of yield strength and tensile ductility that surpasses that of conventional 316L steels. High strength is attributed to solidification-enabled cellular structures, low-angle grain boundaries, and dislocations formed during manufacturing, while high uniform elongation correlates to a steady and progressive work-hardening mechanism regulated by a hierarchically heterogeneous microstructure, with length scales spanning nearlymore » six orders of magnitude. In addition, solute segregation along cellular walls and low-angle grain boundaries can enhance dislocation pinning and promote twinning. This work demonstrates the potential of additive manufacturing to create alloys with unique microstructures and high performance for structural applications.« less
Frontiers of optofluidics in synthetic biology.

PubMed

Tan, Cheemeng; Lo, Shih-Jie; LeDuc, Philip R; Cheng, Chao-Min

2012-10-07

The development of optofluidic-based technology has ushered in a new era of lab-on-a-chip functionality, including miniaturization of biomedical devices, enhanced sensitivity for molecular detection, and multiplexing of optical measurements. While having great potential, optofluidic devices have only begun to be exploited in many biotechnological applications. Here, we highlight the potential of integrating optofluidic devices with synthetic biological systems, which is a field focusing on creating novel cellular systems by engineering synthetic gene and protein networks. First, we review the development of synthetic biology at different length scales, ranging from single-molecule, single-cell, to cellular population. We emphasize light-sensitive synthetic biological systems that would be relevant for the integration with optofluidic devices. Next, we propose several areas for potential applications of optofluidics in synthetic biology. The integration of optofluidics and synthetic biology would have a broad impact on point-of-care diagnostics and biotechnology.
Dynamics of Active Microfilaments

NASA Astrophysics Data System (ADS)

Ling, Feng; Guo, Hanliang; Kanso, Eva

2017-11-01

Soft elastic filaments are ubiquitous in natural and artificial systems at various length scales, and their interactions within and between filaments and their environments provide a persistent source of curiosity due to both the complexity of their behaviors and the relative mathematical simplicity of their structures. Specifically, a deeper understanding of the dynamic characteristics of microscopic filaments in viscous fluids is relevant to many biophysical and physiological processes. Here we start with the Cosserat model that allows all six possible modes of deformation for an elastic rod, and focus on the case of inextensible filaments submerged in viscous fluids by ignoring inertial effects and using local resistive force theory for fluid-filament interactions. We verify our simulations against special analytic solutions and present some results on the active internal control of cilia and flagella motion. We conclude by commenting on the utility of this general framework for studying other cellular and sub-cellular physical processes such as systems involving protein filaments.
Label-free high-throughput imaging flow cytometry

NASA Astrophysics Data System (ADS)

Mahjoubfar, A.; Chen, C.; Niazi, K. R.; Rabizadeh, S.; Jalali, B.

2014-03-01

Flow cytometry is an optical method for studying cells based on their individual physical and chemical characteristics. It is widely used in clinical diagnosis, medical research, and biotechnology for analysis of blood cells and other cells in suspension. Conventional flow cytometers aim a laser beam at a stream of cells and measure the elastic scattering of light at forward and side angles. They also perform single-point measurements of fluorescent emissions from labeled cells. However, many reagents used in cell labeling reduce cellular viability or change the behavior of the target cells through the activation of undesired cellular processes or inhibition of normal cellular activity. Therefore, labeled cells are not completely representative of their unaltered form nor are they fully reliable for downstream studies. To remove the requirement of cell labeling in flow cytometry, while still meeting the classification sensitivity and specificity goals, measurement of additional biophysical parameters is essential. Here, we introduce an interferometric imaging flow cytometer based on the world's fastest continuous-time camera. Our system simultaneously measures cellular size, scattering, and protein concentration as supplementary biophysical parameters for label-free cell classification. It exploits the wide bandwidth of ultrafast laser pulses to perform blur-free quantitative phase and intensity imaging at flow speeds as high as 10 meters per second and achieves nanometer-scale optical path length resolution for precise measurements of cellular protein concentration.
Relationship between peroxisome proliferator-activated receptor alpha activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells.

PubMed

Rosenmai, Anna Kjerstine; Ahrens, Lutz; le Godec, Théo; Lundqvist, Johan; Oskarsson, Agneta

2018-02-01

Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target for perfluoroalkyl substances (PFASs). Little is known about the cellular uptake of PFASs and how it affects the PPARα activity. We investigated the relationship between PPARα activity and cellular concentration in HepG2 cells of 14 PFASs, including perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates and perfluorooctane sulfonamide (FOSA). Cellular concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and PPARα activity was determined in transiently transfected cells by reporter gene assay. Cellular uptake of the PFASs was low (0.04-4.1%) with absolute cellular concentrations in the range 4-2500 ng mg -1 protein. Cellular concentration of PFCAs increased with perfluorocarbon chain length up to perfluorododecanoate. PPARα activity of PFCAs increased with chain length up to perfluorooctanoate. The maximum induction of PPARα activity was similar for short-chain (perfluorobutanoate and perfluoropentanoate) and long-chain PFCAs (perfluorododecanoate and perfluorotetradecanoate) (approximately twofold). However, PPARα activities were induced at lower cellular concentrations for the short-chain homologs compared to the long-chain homologs. Perfluorohexanoate, perfluoroheptanoate, perfluorooctanoate, perfluorononanoate (PFNA) and perfluorodecanoate induced PPARα activities >2.5-fold compared to controls. The concentration-response relationships were positive for all the tested compounds, except perfluorooctane sulfonate PFOS and FOSA, and were compound-specific, as demonstrated by differences in the estimated slopes. The relationships were steeper for PFCAs with chain lengths up to and including PFNA than for the other studied PFASs. To our knowledge, this is the first report establishing relationships between PPARα activity and cellular concentration of a broad range of PFASs. Copyright © 2017 John Wiley & Sons, Ltd.

Stress appraisals and cellular aging: A key role for anticipatory threat in the relationship between psychological stress and telomere length

PubMed Central

O’Donovan, Aoife; Tomiyama, A. Janet; Lin, Jue; Puterman, Eli; Adler, Nancy E.; Kemeny, Margaret; Wolkowitz, Owen M.; Blackburn, Elizabeth H.; Epel, Elissa S.

2012-01-01

Chronic psychological stressis a risk factor formultiple diseases of aging. Accelerated cellular aging as indexed by short telomere length has emerged as a potential common biological mechanism linking various forms of psychological stress and diseases of aging. Stress appraisals determine the degree and type of biological stress responses and altered stress appraisals may be a common psychological mechanism linking psychological stress and diseases of aging. However, no previous studies have examined the relationship between stress appraisals and telomere length. We exposed chronically stressed female caregivers and non-caregiving controls (N= 50; M age = 62.14±6.10) to a standardized acute laboratory stressor and measured their anticipatory and retrospective threat and challenge appraisals of the stressor. We hypothesized that threat and challenge appraisals would be associated with shorter and longer telomere length respectively, and that chronic care giving stress would influence telomere length through altered stress appraisals. Higher anticipatory threat appraisals were associated with shorter age-adjusted telomere length (β = −.32, p = .03), but challenge appraisals and retrospective threat appraisals showed no independent association with telomere length. Caregivers reported significantly higher anticipatory (β = −.36, p = .006)and retrospective (β = −.29, p = .03) threat appraisals than controls, but similar challenge appraisals. Although there was no significant main effect of caregiver status on telomere length, care giving had a significant indirect effect on telomere length through anticipatory threat appraisals. Exaggerated anticipatory threat appraisals may be a common and modifiable psychological mechanism of psychological stress effects on cellular aging. PMID:22293459
Viscosity stratification and the aspect ratio of convection rolls

NASA Astrophysics Data System (ADS)

Morris, S. J. S.

2005-11-01

To clarify a mechanism by which earth's low--viscosity layer may increase the wavelength of mantle convection cells, we analyse the clockwise isothermal cellular motion driven by a uniform shear stress of magnitude τ applied at each end of a rectangle of height 2D and length L. The viscosity μ is a given piecewise-constant function of depth; within a low--viscosity channel of thickness d located at the top of the layer, μ=mμ1; elsewhere, within the `core', μ=μ1. We show that in the double limit d/D->0, m->0, this two--layer flow is equivalent to one in single layer of viscosity μ1 with a new boundary condition at its top representing the interaction of the channel and core flows. Let x=x*/L, y=y*/D and ψ= μ1ψ*/ τD^2. Then the stream function ψ for the core motion satisfies the b.v.p. ψyyyy+2 2̂ψxxyy+ 4̂ψxxxx=0; at |x|=1 , ψ=0, α^2ψxx=-1; at y=0 , ψ=0=ψyy; at y=1, ψyy- 2̂ψxx=0 , and ψyyy+3 2̂ψyxx= 3ɛψ. Here α=D/L and ɛ=mD^3/d^3. We find that for ɛ->0, the motion has two horizontal scales, namely D and L1= D/&1/2 ̂D. If the rectangle length L˜L1, fluid sinks at one end and rises at the other; those end flows occur on the scale D, and are connected by a long--wave flow on the scale L1. The cellular motion is closed within the low--viscosity layer. We have extended this method to treat convection rolls in a fluid of infinite Prandtl number. Our predicted heat flows agree well with those found in numerical simulations by Lenardic, Richards & Busse et al (2005) (J. Geophys. Res., to appear).
Multiscale diffusion of a molecular probe in a crowded environment: a concept

NASA Astrophysics Data System (ADS)

Currie, Megan; Thao, Chang; Timerman, Randi; Welty, Robb; Berry, Brenden; Sheets, Erin D.; Heikal, Ahmed A.

2015-08-01

Living cells are crowded with macromolecules and organelles. Yet, it is not fully understood how macromolecular crowding affects the myriad of biochemical reactions, transport and the structural stability of biomolecules that are essential to cellular function and survival. These molecular processes, with or without electrostatic interactions, in living cells are therefore expected to be distinct from those carried out in test tube in dilute solutions where excluded volumes are absent. Thus there is an urgent need to understand the macromolecular crowding effects on cellular and molecular biophysics towards quantitative cell biology. In this report, we investigated how biomimetic crowding affects both the rotational and translation diffusion of a small probe (rhodamine green, RhG). For biomimetic crowding agents, we used Ficoll-70 (synthetic polymer), bovine serum albumin and ovalbumin (proteins) at various concentrations in a buffer at room temperature. As a control, we carried out similar measurements on glycerolenriched buffer as an environment with homogeneous viscosity as a function of glycerol concentration. The corresponding bulk viscosity was measured independently to test the validity of the Stokes-Einstein model of a diffusing species undergoing a random walk. For rotational diffusion (ps-ns time scale), we used time-resolved anisotropy measurements to examine potential binding of RhG as a function of the crowding agents (surface structure and size). For translational diffusion (μs-s time scale), we used fluorescence correlation spectroscopy for single-molecule fluctuation analysis. Our results allow us to examine the diffusion model of a molecular probe in crowded environments as a function of concentration, length scale, homogeneous versus heterogeneous viscosity, size and surface structures. These biomimetic crowding studies, using non-invasive fluorescence spectroscopy methods, represent an important step towards understanding cellular biophysics and quantitative cell biology.
Bacterial chromosome organization and segregation

PubMed Central

Badrinarayanan, Anjana; Le, Tung BK; Laub, Michael T

2016-01-01

If fully stretched out, a typical bacterial chromosome would be nearly one millimeter long, or approximately 1000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length-scales, highlighting the functions of various DNA-binding proteins and impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation. PMID:26566111
Nanometer scale thermometry in a living cell

PubMed Central

Kucsko, G.; Maurer, P. C.; Yao, N. Y.; Kubo, M.; Noh, H. J.; Lo, P. K.; Park, H.; Lukin, M. D.

2014-01-01

Sensitive probing of temperature variations on nanometer scales represents an outstanding challenge in many areas of modern science and technology1. In particular, a thermometer capable of sub-degree temperature resolution over a large range of temperatures as well as integration within a living system could provide a powerful new tool for many areas of biological, physical and chemical research; possibilities range from the temperature-induced control of gene expression2–5 and tumor metabolism6 to the cell-selective treatment of disease7,8 and the study of heat dissipation in integrated circuits1. By combining local light-induced heat sources with sensitive nanoscale thermometry, it may also be possible to engineer biological processes at the sub-cellular level2–5. Here, we demonstrate a new approach to nanoscale thermometry that utilizes coherent manipulation of the electronic spin associated with nitrogen-vacancy (NV) color centers in diamond. We show the ability to detect temperature variations down to 1.8 mK (sensitivity of 9mK/Hz) in an ultra-pure bulk diamond sample. Using NV centers in diamond nanocrystals (nanodiamonds, NDs), we directly measure the local thermal environment at length scales down to 200 nm. Finally, by introducing both nanodiamonds and gold nanoparticles into a single human embryonic fibroblast, we demonstrate temperature-gradient control and mapping at the sub-cellular level, enabling unique potential applications in life sciences. PMID:23903748
Defining the hierarchical organisation of collagen VI microfibrils at nanometre to micrometre length scales.

PubMed

Godwin, Alan R F; Starborg, Tobias; Sherratt, Michael J; Roseman, Alan M; Baldock, Clair

2017-04-01

Extracellular matrix microfibrils are critical components of connective tissues with a wide range of mechanical and cellular signalling functions. Collagen VI is a heteromeric network-forming collagen which is expressed in tissues such as skin, lung, blood vessels and articular cartilage where it anchors cells into the matrix allowing for transduction of biochemical and mechanical signals. It is not understood how collagen VI is arranged into microfibrils or how these microfibrils are arranged into tissues. Therefore we have characterised the hierarchical organisation of collagen VI across multiple length scales. The frozen hydrated nanostructure of purified collagen VI microfibrils was reconstructed using cryo-TEM. The bead region has a compact hollow head and flexible tail regions linked by the collagenous interbead region. Serial block face SEM imaging coupled with electron tomography of the pericellular matrix (PCM) of murine articular cartilage revealed that the PCM has a meshwork-like organisation formed from globular densities ∼30nm in diameter. These approaches can characterise structures spanning nanometer to millimeter length scales to define the nanostructure of individual collagen VI microfibrils and the micro-structural organisation of these fibrils within tissues to help in the future design of better mimetics for tissue engineering. Cartilage is a connective tissue rich in extracellular matrix molecules and is tough and compressive to cushion the bones of joints. However, in adults cartilage is poorly repaired after injury and so this is an important target for tissue engineering. Many connective tissues contain collagen VI, which forms microfibrils and networks but we understand very little about these assemblies or the tissue structures they form. Therefore, we have use complementary imaging techniques to image collagen VI microfibrils from the nano-scale to the micro-scale in order to understand the structure and the assemblies it forms. These findings will help to inform the future design of scaffolds to mimic connective tissues in regenerative medicine applications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Effect of Small-Scale Turbulence on the Physiology and Morphology of Two Bloom-Forming Cyanobacteria.

PubMed

Xiao, Yan; Li, Zhe; Li, Chao; Zhang, Zhen; Guo, Jinsong

2016-01-01

The main goal of the present work is to test the hypothesis that small-scale turbulence affected physiological activities and the morphology of cyanobacteria in high turbulence environments. Using quantified turbulence in a stirring device, we conducted one set of experiments on cultures of two strains of cyanobacteria with different phenotypes; i.e., unicellular Microcystis flos-aquae and colonial Anabaena flos-aquae. The effect of small-scale turbulence examined varied from 0 to 8.01×10-2 m2s-3, covering the range of turbulence intensities experienced by cyanobacteria in the field. The results of photosynthesis activity and the cellular chlorophyll a in both strains did not change significantly among the turbulence levels, indicating that the potential indirect effects of a light regime under the gradient of turbulent mixing could be ignored. However, the experiments demonstrated that small-scale turbulence significantly modulated algal nutrient uptake and growth in comparison to the stagnant control. Cellular N and C of the two stains showed approximately the same responses, resulting in a similar pattern of C/N ratios. Moreover, the change in the phosphate uptake rate was similar to that of growth in two strains, which implied that growth characteristic responses to turbulence may be dependent on the P strategy, which was correlated with accumulation of polyphosphate. Additionally, our results also showed the filament length of A. flos-aquae decreased in response to high turbulence, which could favor enhancement of the nutrient uptake. These findings suggested that both M. flos-aquae and A. flos-aquae adjust their growth rates in response to turbulence levels in the ways of asynchronous cellular stoichiometry of C, N, and P, especially the phosphorus strategy, to improve the nutrient application efficiency. The fact that adaptation strategies of cyanobacteria diversely to turbulence depending on their physiological conditions presents a good example to understand the direct cause-effect relationship between hydrodynamic forces and algae.
Triangles bridge the scales: Quantifying cellular contributions to tissue deformation

NASA Astrophysics Data System (ADS)

Merkel, Matthias; Etournay, Raphaël; Popović, Marko; Salbreux, Guillaume; Eaton, Suzanne; Jülicher, Frank

2017-03-01

In this article, we propose a general framework to study the dynamics and topology of cellular networks that capture the geometry of cell packings in two-dimensional tissues. Such epithelia undergo large-scale deformation during morphogenesis of a multicellular organism. Large-scale deformations emerge from many individual cellular events such as cell shape changes, cell rearrangements, cell divisions, and cell extrusions. Using a triangle-based representation of cellular network geometry, we obtain an exact decomposition of large-scale material deformation. Interestingly, our approach reveals contributions of correlations between cellular rotations and elongation as well as cellular growth and elongation to tissue deformation. Using this triangle method, we discuss tissue remodeling in the developing pupal wing of the fly Drosophila melanogaster.
Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence.

PubMed

Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

2015-01-01

Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I.
[Geographic variation of seed morphological traits of Picea schrenkiana var. tianschanica in Tianshan Mountains, Xinjiang of Northwest China].

PubMed

Liu, Gui-Feng; Zang, Run-Guo; Liu, Hua; Bai, Zhi-Qiang; Guo, Zhong-Jun; Ding, Yi

2012-06-01

Taking the Picea schrenkiana var. tianschanica forests at three sites with different longitudes (Zhaosu, Tianchi, and Qitai) in Tianshan Mountains as the objects, the cones were collected along an altitudinal gradient to analyze the variation of their seed morphological traits (seed scale length and width, seed scale length/width ratio, seed wing length and width, seed wing length/ width ratio, seed length and width, and seed length/width ratio). All the seed traits except seed width tended to decrease with increasing altitude. The seed traits except seed wing width, seed width, and seed length/width ratio all had significant negative correlations with altitude. Seed scale length and width and seed scale length/width ratio had significant positive correlations with longitude. Seed scale length, seed scale length/width ratio, and seed wing length/width ratio had significant negative correlations with slope degree. No significant correlations were observed between the seed traits except seed wing width and the slope aspect. Altitude was the main factor affecting the seed scale length, seed scale length/width ratio, and seed wing length/width ratio.
In vivo imaging of cancer cell size and cellularity using temporal diffusion spectroscopy.

PubMed

Jiang, Xiaoyu; Li, Hua; Xie, Jingping; McKinley, Eliot T; Zhao, Ping; Gore, John C; Xu, Junzhong

2017-07-01

A temporal diffusion MRI spectroscopy based approach has been developed to quantify cancer cell size and density in vivo. A novel imaging microstructural parameters using limited spectrally edited diffusion (IMPULSED) method selects a specific limited diffusion spectral window for an accurate quantification of cell sizes ranging from 10 to 20 μm in common solid tumors. In practice, it is achieved by a combination of a single long diffusion time pulsed gradient spin echo (PGSE) and three low-frequency oscillating gradient spin echo (OGSE) acquisitions. To validate our approach, hematoxylin and eosin staining and immunostaining of cell membranes, in concert with whole slide imaging, were used to visualize nuclei and cell boundaries, and hence, enabled accurate estimates of cell size and cellularity. Based on a two compartment model (incorporating intra- and extracellular spaces), accurate estimates of cell sizes were obtained in vivo for three types of human colon cancers. The IMPULSED-derived apparent cellularities showed a stronger correlation (r = 0.81; P < 0.0001) with histology-derived cellularities than conventional ADCs (r = -0.69; P < 0.03). The IMPULSED approach samples a specific region of temporal diffusion spectra with enhanced sensitivity to length scales of 10-20 μm, and enables measurements of cell sizes and cellularities in solid tumors in vivo. Magn Reson Med 78:156-164, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.
Multispectral plasmon coupling microscopy and its application in bio-imaging

NASA Astrophysics Data System (ADS)

Wang, Hongyun

A broad range of cellular activities, including receptor mediated endocytosis, signaling and receptor clustering, involve multi-body interactions between different cellular functionalities. Many of these interactions are dynamic in nature, making optical tools the method of choice for their investigation. Conventional optical microscopy has a resolution about 300nm, limited by the diffraction of light, which is insufficient to explore processes that occur on nanometer or tens of nanometer length scales. The aim of this thesis is to develop and validate a plasmon coupling microscopy (PCM), which utilizes the distance dependent spectral properties of coupled noble metal nanoparticles (NPs) to resolve distance changes between NP labels on deeply sub-diffraction length scales. This colorimetric approach is augmented with a polarization sensitive analysis of the scattered light of individual dimers to monitor simultaneously distance and orientation changes. The distance dependent polarization anisotropy in discrete dimers is investigated experimentally and theoretically. The performed analysis reveals that the polarization anisotropy is robust even against relatively large refractive index changes. The polarization sensitive PCM is then applied to characterize the lateral spatial organization of mammalian plasma membranes by analyzing the translational and rotational motion as well as the extension of discrete NP dimers during their diffusion on lysed HeLa cell membranes. The membrane is found to be compartmentalized with typical domain sizes on the order of 70nm. The functionality of plasmon coupling based imaging method is expanded further by developing a multispectral imaging modality for a quantitative analysis of the plasmon coupling between many noble metal immunolabels in a large field of view simultaneously. This approach provides information about the spatial organization of the silver nanoparticle labels and thus of targeted EGF receptor densities on the surface of epidermoid carcinoma cells (A431). Finally, multispectral plasmon coupling microscopy is applied to investigate the uptake and subsequent intracellular spatial distribution of silver nanoparticles in murine macrophage cells (J774A.1). The studies reveal that NP uptake is mediated by scavenger receptors and that the intracellular NP association and distribution are heterogeneous among cells in a cellular ensemble. The heterogeneity is demonstrated to be correlated with the maturation status of the macrophages.
Nanofluidic interfaces in microfluidic networks

DOE PAGES

Millet, Larry J.; Doktycz, Mitchel John; Retterer, Scott T.

2015-09-24

The integration of nano- and microfluidic technologies enables the construction of tunable interfaces to physical and biological systems across relevant length scales. The ability to perform chemical manipulations of miniscule sample volumes is greatly enhanced through these technologies and extends the ability to manipulate and sample the local fluidic environments at subcellular, cellular and community or tissue scales. Here we describe the development of a flexible surface micromachining process for the creation of nanofluidic channel arrays integrated within SU-8 microfluidic networks. The use of a semi-porous, silicon rich, silicon nitride structural layer allows rapid release of the sacrificial silicon dioxidemore » during the nanochannel fabrication. Nanochannel openings that form the interface to biological samples are customized using focused ion beam milling. The compatibility of these interfaces with on-chip microbial culture is demonstrated.« less
Biomimetic surface patterning for long-term transmembrane access

PubMed Central

VanDersarl, Jules J.; Renaud, Philippe

2016-01-01

Here we present a planar patch clamp chip based on biomimetic cell membrane fusion. This architecture uses nanometer length-scale surface patterning to replicate the structure and function of membrane proteins, creating a gigaohm seal between the cell and a planar electrode array. The seal is generated passively during cell spreading, without the application of a vacuum to the cell surface. This interface can enable cell-attached and whole-cell recordings that are stable to 72 hours, and generates no visible damage to the cell. The electrodes can be very small (<5 μm) and closely packed, offering a high density platform for cellular measurement. PMID:27577519
Biomimetic surface patterning for long-term transmembrane access.

PubMed

VanDersarl, Jules J; Renaud, Philippe

2016-08-31

Here we present a planar patch clamp chip based on biomimetic cell membrane fusion. This architecture uses nanometer length-scale surface patterning to replicate the structure and function of membrane proteins, creating a gigaohm seal between the cell and a planar electrode array. The seal is generated passively during cell spreading, without the application of a vacuum to the cell surface. This interface can enable cell-attached and whole-cell recordings that are stable to 72 hours, and generates no visible damage to the cell. The electrodes can be very small (<5 μm) and closely packed, offering a high density platform for cellular measurement.
Time and length scales within a fire and implications for numerical simulation

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

TIESZEN,SHELDON R.

2000-02-02

A partial non-dimensionalization of the Navier-Stokes equations is used to obtain order of magnitude estimates of the rate-controlling transport processes in the reacting portion of a fire plume as a function of length scale. Over continuum length scales, buoyant times scales vary as the square root of the length scale; advection time scales vary as the length scale, and diffusion time scales vary as the square of the length scale. Due to the variation with length scale, each process is dominant over a given range. The relationship of buoyancy and baroclinc vorticity generation is highlighted. For numerical simulation, first principlesmore » solution for fire problems is not possible with foreseeable computational hardware in the near future. Filtered transport equations with subgrid modeling will be required as two to three decades of length scale are captured by solution of discretized conservation equations. By whatever filtering process one employs, one must have humble expectations for the accuracy obtainable by numerical simulation for practical fire problems that contain important multi-physics/multi-length-scale coupling with up to 10 orders of magnitude in length scale.« less
EDITORIAL: Proceedings of the IUTAM Symposium on Plasticity at the Micron Scale, Technical University of Denmark, 21 25 Mark 2006

NASA Astrophysics Data System (ADS)

Tvergaard, Viggo

2007-01-01

This special issue constitutes the Proceedings of the IUTAM Symposium on Plasticity at the Micron Scale, held at the Technical University of Denmark, 21-25 May 2006. The purpose of this symposium was to gather a group of leading scientists working in areas of importance to length scale dependent plasticity. This includes work on phenomenological strain gradient plasticity models, studies making use of discrete dislocation models, and even atomic level models. Experimental investigations are central to all this, as all the models focus on developing an improved understanding of real observed phenomena. The opening lecture by Professor N A Fleck, Cambridge University, discussed experimental as well as theoretical approaches. Also, recent results for the surface roughness at grain boundaries were presented based on experiments and crystal plasticity modelling. A number of presentations focused on experiments for metals at a small length scale, e.g. using indenters or a small single crystal compression test. It was found that there are causes of the size effects other than the geometrically necessary dislocations related to strain gradients. Several lectures on scale dependent phenomenological plasticity theories discussed different methods of incorporating the characteristic material length. This included lower order plasticity theories as well as higher order theories, within standard plasticity models or crystal plasticity. Differences in the ways of incorporating higher order boundary conditions were the subject of much discussion. Various methods for discrete dislocation modelling of plastic deformation were used in some of the presentations to obtain a more detailed understanding of length scale effects in metals. This included large scale computations for dislocation dynamics as well as new statistical mechanics approaches to averaging of dislocation plasticity. Furthermore, at a somewhat larger length scale, applications of scale dependent plasticity to granular media and to cellular solids were discussed. The symposium consisted of thirty-six lectures, all of which were invited based on strong expertise in the area. Some of the lectures are not represented in this special issue, mainly because of prior commitments to publish elsewhere. The international Scientific Committee responsible for the symposium comprised the following: Professor V Tvergaard (Chairman) Denmark Professor A Benallal France Professor N A Fleck UK Professor L B Freund (IUTAM Representative) USA Professor E van der Giessen The Netherlands Professor J W Hutchinson USA Professor A Needleman USA Professor B Svendsen Germany The Committee gratefully acknowledges financial support for the symposium from the International Union of Theoretical and Applied Mechanics, from Novo Nordisk A/S and from the Villum Kann Rasmussen Foundation. In the organization of all parts of the symposium the enthusiastic participation of Dr C F Niordson and Dr P Redanz was invaluable. The smooth running of the symposium also owes much to the efforts and organizational skills of Bente Andersen.
Neck linker length determines the degree of processivity in kinesin-1 and kinesin-2 motors.

PubMed

Shastry, Shankar; Hancock, William O

2010-05-25

Defining the mechanical and biochemical determinates of kinesin processivity is important for understanding how diverse kinesins are tuned for specific cellular functions. Because transmission of mechanical forces through the 14-18 amino acid neck linker domain underlies coordinated stepping, we investigated the role of neck linker length, charge, and structure in kinesin-1 and kinesin-2 motor behavior. For optimum comparison with kinesin-1, the KIF3A head and neck linker of kinesin-2 were fused to the kinesin-1 neck coil and rod. Extending the 14-residue kinesin-1 neck linker reduced processivity, and shortening the 17-residue kinesin-2 neck linker enhanced processivity. When a proline in the kinesin-2 neck linker was replaced, kinesin-1 and kinesin-2 run lengths scaled identically with neck linker length, despite moving at different speeds. In low-ionic-strength buffer, charge had a dominant effect on motor processivity, which resolves ongoing controversy regarding the effect of neck linker length on kinesin processivity. From stochastic simulations, the results are best explained by neck linker extension slowing strain-dependent detachment of the rear head along with diminishing strain-dependent inhibition of ATP binding. These results help delineate how interhead strain maximizes stepping and suggest that less processive kinesins are tuned to coordinate with other motors differently than the maximally processive kinesin-1. Copyright 2010 Elsevier Ltd. All rights reserved.
Evaluation of Interference of Cellular Phones on Electronic Apex Locators: An In Vitro Study.

PubMed

Sidhu, Preena; Shankargouda, Swapnil; Dicksit, Daniel DevaPrakash; Mahdey, Haydar Majeed; Muzaffar, Danish; Arora, Shelly

2016-04-01

Use of mobile phone has been prohibited in many hospitals to prevent interference with medical devices. Electromagnetic radiation emitted from cellular phones might interfere with electronic working length determination. The purpose of this in vitro study was to evaluate the effect of a smart phone (Samsung Galaxy Note Edge) on working length determination of electronic apex locators (EALs) Propex II and Rootor. Fifteen intact, non-carious single-rooted teeth were decoronated at the cementoenamel junction. Visually, working length was determined by using a #15 K-file under stereomicroscope (×20). The effect of cellular phones on electronic working length (EWL) was determined under 2 experimental settings: (1) in a closed room with poor signal strength and (2) in a polyclinic set up with good signal strength and 5 conditions: (1) electronically, without cellular phone in room; (2) electronically, with cellular phone in physical contact with EAL; (3) electronically, with mobile phone in physical contact with EAL and in calling mode for a period of 25 seconds; (4) electronically, mobile phone placed at a distance of 40 cm from the EAL; and (5) electronically, mobile phone placed at a distance of 40 cm and in calling mode for a period of 25 seconds. The EWL was measured 3 times per tooth under each condition. Stability of the readings was scored from 1 to 3: (1) good stability, (2) stable reading after 1 attempt, and (3) stable reading after 2 attempts. The data were compared by using analysis of variance. The EWL measurements were not influenced by the presence of cellular phone and could be determined under all experimental conditions. Within the limitations of this study, it can be concluded that mobile phones do not interfere with the EWL determination. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.
Hydrodynamics in Cell Studies

PubMed Central

2018-01-01

Hydrodynamic phenomena are ubiquitous in living organisms and can be used to manipulate cells or emulate physiological microenvironments experienced in vivo. Hydrodynamic effects influence multiple cellular properties and processes, including cell morphology, intracellular processes, cell–cell signaling cascades and reaction kinetics, and play an important role at the single-cell, multicellular, and organ level. Selected hydrodynamic effects can also be leveraged to control mechanical stresses, analyte transport, as well as local temperature within cellular microenvironments. With a better understanding of fluid mechanics at the micrometer-length scale and the advent of microfluidic technologies, a new generation of experimental tools that provide control over cellular microenvironments and emulate physiological conditions with exquisite accuracy is now emerging. Accordingly, we believe that it is timely to assess the concepts underlying hydrodynamic control of cellular microenvironments and their applications and provide some perspective on the future of such tools in in vitro cell-culture models. Generally, we describe the interplay between living cells, hydrodynamic stressors, and fluid flow-induced effects imposed on the cells. This interplay results in a broad range of chemical, biological, and physical phenomena in and around cells. More specifically, we describe and formulate the underlying physics of hydrodynamic phenomena affecting both adhered and suspended cells. Moreover, we provide an overview of representative studies that leverage hydrodynamic effects in the context of single-cell studies within microfluidic systems. PMID:29420889

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

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

Kirker, Grant; Zelinka, Sam; Gleber, Sophie -Charlotte

Ions play an important role in the growth and development of filamentous fungi, particularly in the fungal decay process of lignocellulose materials. The role of ions in wood degradation, and more broadly fungal metabolism, have implications for diverse research disciplines ranging from plant pathology and forest ecology, to wood protection. Despite the importance of ions in both enzymatic and non-enzymatic fungal decay mechanisms, the spatial distribution of ions in wood and fungal hyphae during decay is not known. Here we employ synchrotron based X-ray fluorescence microscopy (XFM) to map physiologically relevant ions, such as K, Ca, Mn, Fe, and Zn,more » in wood being decayed by the model brown rot fungus Serpula lacrymans. Two-dimensional XFM maps were obtained to study the ion spatial distributions from mm to submicron length scales in wood and hyphae. Three-dimensional ion volume reconstructions with submicron spatial resolution were also acquired of wood cell walls and fungal hyphae, and an estimation of oxalate concentration at the microscale was made. Results show that the fungus actively transports some ions, such as Fe, into the wood and controls the distribution of ions at both the bulk wood and cellular length scales. Within the fungal hyphae, ion volume reconstructions show inhomogeneous ion distributions at the micron length scale and this localization may be indicative of both physiological status and requirements or in some cases, potentially sites associated with the initiation of metal-catalyzed wood degradation. Finally, these measurements illustrate how synchrotron based XFM is uniquely qualified for probing the role of ions in the growth and metabolic processes of filamentous fungi.« less
Synchrotron-based X-ray fluorescence microscopy enables multiscale spatial visualization of ions involved in fungal lignocellulose deconstruction

DOE PAGES

Kirker, Grant; Zelinka, Sam; Gleber, Sophie -Charlotte; ...

2017-01-31

Ions play an important role in the growth and development of filamentous fungi, particularly in the fungal decay process of lignocellulose materials. The role of ions in wood degradation, and more broadly fungal metabolism, have implications for diverse research disciplines ranging from plant pathology and forest ecology, to wood protection. Despite the importance of ions in both enzymatic and non-enzymatic fungal decay mechanisms, the spatial distribution of ions in wood and fungal hyphae during decay is not known. Here we employ synchrotron based X-ray fluorescence microscopy (XFM) to map physiologically relevant ions, such as K, Ca, Mn, Fe, and Zn,more » in wood being decayed by the model brown rot fungus Serpula lacrymans. Two-dimensional XFM maps were obtained to study the ion spatial distributions from mm to submicron length scales in wood and hyphae. Three-dimensional ion volume reconstructions with submicron spatial resolution were also acquired of wood cell walls and fungal hyphae, and an estimation of oxalate concentration at the microscale was made. Results show that the fungus actively transports some ions, such as Fe, into the wood and controls the distribution of ions at both the bulk wood and cellular length scales. Within the fungal hyphae, ion volume reconstructions show inhomogeneous ion distributions at the micron length scale and this localization may be indicative of both physiological status and requirements or in some cases, potentially sites associated with the initiation of metal-catalyzed wood degradation. Finally, these measurements illustrate how synchrotron based XFM is uniquely qualified for probing the role of ions in the growth and metabolic processes of filamentous fungi.« less
Deterministic Integration of Biological and Soft Materials onto 3D Microscale Cellular Frameworks

PubMed Central

McCracken, Joselle M.; Xu, Sheng; Badea, Adina; Jang, Kyung-In; Yan, Zheng; Wetzel, David J.; Nan, Kewang; Lin, Qing; Han, Mengdi; Anderson, Mikayla A.; Lee, Jung Woo; Wei, Zijun; Pharr, Matt; Wang, Renhan; Su, Jessica; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

2018-01-01

Complex 3D organizations of materials represent ubiquitous structural motifs found in the most sophisticated forms of matter, the most notable of which are in life-sustaining hierarchical structures found in biology, but where simpler examples also exist as dense multilayered constructs in high-performance electronics. Each class of system evinces specific enabling forms of assembly to establish their functional organization at length scales not dissimilar to tissue-level constructs. This study describes materials and means of assembly that extend and join these disparate systems—schemes for the functional integration of soft and biological materials with synthetic 3D microscale, open frameworks that can leverage the most advanced forms of multilayer electronic technologies, including device-grade semiconductors such as monocrystalline silicon. Cellular migration behaviors, temporal dependencies of their growth, and contact guidance cues provided by the nonplanarity of these frameworks illustrate design criteria useful for their functional integration with living matter (e.g., NIH 3T3 fibroblast and primary rat dorsal root ganglion cell cultures). PMID:29552634
Tissue expander stimulated lengthening of arteries (TESLA) induces early endothelial cell proliferation in a novel rodent model.

PubMed

Potanos, Kristina; Fullington, Nora; Cauley, Ryan; Purcell, Patricia; Zurakowski, David; Fishman, Steven; Vakili, Khashayar; Kim, Heung Bae

2016-04-01

We examine the mechanism of aortic lengthening in a novel rodent model of tissue expander stimulated lengthening of arteries (TESLA). A rat model of TESLA was examined with a single stretch stimulus applied at the time of tissue expander insertion with evaluation of the aorta at 2, 4 and 7day time points. Measurements as well as histology and proliferation assays were performed and compared to sham controls. The aortic length was increased at all time points without histologic signs of tissue injury. Nuclear density remained unchanged despite the increase in length suggesting cellular hyperplasia. Cellular proliferation was confirmed in endothelial cell layer by Ki-67 stain. Aortic lengthening may be achieved using TESLA. The increase in aortic length can be achieved without tissue injury and results at least partially from cellular hyperplasia. Further studies are required to define the mechanisms involved in the growth of arteries under increased longitudinal stress. Copyright © 2015 Elsevier Inc. All rights reserved.
Length of intact plasma membrane determines the diffusion properties of cellular water.

PubMed

Eida, Sato; Van Cauteren, Marc; Hotokezaka, Yuka; Katayama, Ikuo; Sasaki, Miho; Obara, Makoto; Okuaki, Tomoyuki; Sumi, Misa; Nakamura, Takashi

2016-01-11

Molecular diffusion in a boundary-free medium depends only on the molecular size, the temperature, and medium viscosity. However, the critical determinant of the molecular diffusion property in inhomogeneous biological tissues has not been identified. Here, using an in vitro system and a high-resolution MR imaging technique, we show that the length of the intact plasma membrane is a major determinant of water diffusion in a controlled cellular environment and that the cell perimeter length (CPL) is sufficient to estimate the apparent diffusion coefficient (ADC) of water in any cellular environment in our experimental system (ADC = -0.21 × CPL + 1.10). We used this finding to further explain the different diffusion kinetics of cells that are dying via apoptotic or non-apoptotic cell death pathways exhibiting characteristic changes in size, nuclear and cytoplasmic architectures, and membrane integrity. These results suggest that the ADC value can be used as a potential biomarker for cell death.
Length of intact plasma membrane determines the diffusion properties of cellular water

PubMed Central

Eida, Sato; Van Cauteren, Marc; Hotokezaka, Yuka; Katayama, Ikuo; Sasaki, Miho; Obara, Makoto; Okuaki, Tomoyuki; Sumi, Misa; Nakamura, Takashi

2016-01-01

Molecular diffusion in a boundary-free medium depends only on the molecular size, the temperature, and medium viscosity. However, the critical determinant of the molecular diffusion property in inhomogeneous biological tissues has not been identified. Here, using an in vitro system and a high-resolution MR imaging technique, we show that the length of the intact plasma membrane is a major determinant of water diffusion in a controlled cellular environment and that the cell perimeter length (CPL) is sufficient to estimate the apparent diffusion coefficient (ADC) of water in any cellular environment in our experimental system (ADC = −0.21 × CPL + 1.10). We used this finding to further explain the different diffusion kinetics of cells that are dying via apoptotic or non-apoptotic cell death pathways exhibiting characteristic changes in size, nuclear and cytoplasmic architectures, and membrane integrity. These results suggest that the ADC value can be used as a potential biomarker for cell death. PMID:26750342
Accelerated Telomere Shortening in Acromegaly; IGF-I Induces Telomere Shortening and Cellular Senescence

PubMed Central

Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka

2015-01-01

Objective Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. Methods We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Results Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R 2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Conclusion Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I. PMID:26448623
Photo-thermal nanosystems for diseased cell treatment

NASA Astrophysics Data System (ADS)

Raeesi, Vahid

The prevalence of cancer and infectious disease demands for development of more effective treatment technologies. Current standard chemo- and radiotherapy for cancer offer only relative therapeutic efficacy at the cost of significant side-effects. On the other hand, resistance of microbes to current antibiotics has raised serious concern in public health sectors such as hospitals. Thermal therapy is an alternative technique that employs high temperatures to treat diseased cells via direct and indirect heat effects. Owing to its nature, this technique can offer enhanced therapeutic efficacy in local diseased regions via either mono- or combinatorial platforms and very minimal side-effects. However, existing bulk heating systems are limited in providing selective and controlled temperature rise in the desired region at tissue/cellular scales. This compromises the therapeutic efficacy of the treatment and increases the risk of off-target heating in healthy tissues. In this thesis, we propose the use of heat-generating nanoparticles to precisely target heat into small regions and study how they can be applied in cancer and bacteria treatment. Our model nanoparticle system generates heat by light stimulation. Different nanosystems based on this particle are developed and their thermal effects on therapeutic distribution are explored at tumor tissue and cellular scales. In addition, the thermal effect of these nanoparticles is utilized to overcome microbial resistance. By mechanistic understanding of nanoparticle thermal effects at different length scales, this research helps to rationalize proper design and development of heat- generating nanomedicine for cancer and microbial treatments.
Freezing-induced deformation of biomaterials in cryomedicine

NASA Astrophysics Data System (ADS)

Ozcelikkale, Altug

Cryomedicine utilizes low temperature treatments of biological proteins, cells and tissues for cryopreservation, materials processing and cryotherapy. Lack of proper understanding of cryodamage that occurs during these applications remains to be the primary bottleneck for development of successful tissue cryopreservation and cryosurgery procedures. An engineering approach based on a view of biological systems as functional biomaterials can help identify, predict and control the primary cryodamage mechanisms by developing an understanding of underlying freezing-induced biophysical processes. In particular, freezing constitutes the main structural/mechanical origin of cryodamage and results in significant deformation of biomaterials at multiple length scales. Understanding of these freezing-induced deformation processes and their effects on post-thaw biomaterial functionality is currently lacking but will be critical to engineer improved cryomedicine procedures. This dissertation addresses this problem by presenting three separate but related studies of freezing-induced deformation at multiple length scales including nanometer-scale protein fibrils, single cells and whole tissues. A combination of rigorous experimentation and computational modeling is used to characterize post-thaw biomaterial structure and properties, predict biomaterial behavior and assess its post-thaw biological functionality. Firstly, freezing-induced damage on hierarchical extracellular matrix structure of collagen is investigated at molecular, fibril and matrix levels. Results indicate to a specific kind of fibril damage due to freezing-induced expansion of intrafibrillar fluid. This is followed by a study of freezing-induced cell and tissue deformation coupled to osmotically driven cellular water transport. Computational and semi empirical modeling of these processes indicate that intracellular deformation of the cell during freezing is heterogeneous and can interfere with cellular water transport, thereby leading to previously unconsidered mechanisms of cell freezing response. In addition, cellular water transport is identified as the critical limiting factor on the amount of freezing-induced tissue deformation, particularly in native tissues with high cell densities. Finally, effects of cryopreservation on post-thaw biological functionality of collagen engineered tissue constructs is investigated where cell-matrix interactions during fibroblast migration are considered as the functional response. Simultaneous cell migration and extracellular matrix deformation are characterized. Results show diminished cell-matrix coupling by freeze/thaw accompanied by a subtle decrease in cell migration. A connection between these results and freezing-induced collagen fibril damage is also suggested. Overall, this dissertation provides new fundamental knowledge on cryodamage mechanisms and a collection of novel multi-purpose engineering tools that will open the way for rational design of cryomedicine technologies.
Buccal telomere length and its associations with cortisol, heart rate variability, heart rate, and blood pressure responses to an acute social evaluative stressor in college students.

PubMed

Woody, Alex; Hamilton, Katrina; Livitz, Irina E; Figueroa, Wilson S; Zoccola, Peggy M

2017-05-01

Understanding the relationship between stress and telomere length (a marker of cellular aging) is of great interest for reducing aging-related disease and death. One important aspect of acute stress exposure that may underlie detrimental effects on health is physiological reactivity to the stressor. This study tested the relationship between buccal telomere length and physiological reactivity (salivary cortisol reactivity and total output, heart rate (HR) variability, blood pressure, and HR) to an acute psychosocial stressor in a sample of 77 (53% male) healthy young adults. Consistent with predictions, greater reductions in HR variability (HRV) in response to a stressor and greater cortisol output during the study session were associated with shorter relative buccal telomere length (i.e. greater cellular aging). However, the relationship between cortisol output and buccal telomere length became non-significant when adjusting for medication use. Contrary to past findings and study hypotheses, associations between cortisol, blood pressure, and HR reactivity and relative buccal telomere length were not significant. Overall, these findings may indicate there are limited and mixed associations between stress reactivity and telomere length across physiological systems.
Single molecule experimentation in biological physics: exploring the living component of soft condensed matter one molecule at a time.

PubMed

Harriman, O L J; Leake, M C

2011-12-21

The soft matter of biological systems consists of mesoscopic length scale building blocks, composed of a variety of different types of biological molecules. Most single biological molecules are so small that 1 billion would fit on the full-stop at the end of this sentence, but collectively they carry out the vital activities in living cells whose length scale is at least three orders of magnitude greater. Typically, the number of molecules involved in any given cellular process at any one time is relatively small, and so real physiological events may often be dominated by stochastics and fluctuation behaviour at levels comparable to thermal noise, and are generally heterogeneous in nature. This challenging combination of heterogeneity and stochasticity is best investigated experimentally at the level of single molecules, as opposed to more conventional bulk ensemble-average techniques. In recent years, the use of such molecular experimental approaches has become significantly more widespread in research laboratories around the world. In this review we discuss recent experimental approaches in biological physics which can be applied to investigate the living component of soft condensed matter to a precision of a single molecule. © 2011 IOP Publishing Ltd Printed in the UK & the USA
Centrobin-mediated Regulation of the Centrosomal Protein 4.1-associated Protein (CPAP) Level Limits Centriole Length during Elongation Stage*

PubMed Central

Gudi, Radhika; Haycraft, Courtney J.; Bell, P. Darwin; Li, Zihai; Vasu, Chenthamarakshan

2015-01-01

Microtubule-based centrioles in the centrosome mediate accurate bipolar cell division, spindle orientation, and primary cilia formation. Cellular checkpoints ensure that the centrioles duplicate only once in every cell cycle and achieve precise dimensions, dysregulation of which results in genetic instability and neuro- and ciliopathies. The normal cellular level of centrosomal protein 4.1-associated protein (CPAP), achieved by its degradation at mitosis, is considered as one of the major mechanisms that limits centriole growth at a predetermined length. Here we show that CPAP levels and centriole elongation are regulated by centrobin. Exogenous expression of centrobin causes abnormal elongation of centrioles due to massive accumulation of CPAP in the cell. Conversely, CPAP was undetectable in centrobin-depleted cells, suggesting that it undergoes degradation in the absence of centrobin. Only the reintroduction of full-length centrobin, but not its mutant form that lacks the CPAP binding site, could restore cellular CPAP levels in centrobin-depleted cells, indicating that persistence of CPAP requires its interaction with centrobin. Interestingly, inhibition of the proteasome in centrobin-depleted cells restored the cellular and centriolar CPAP expression, suggesting its ubiquitination and proteasome-mediated degradation when centrobin is absent. Intriguingly, however, centrobin-overexpressing cells also showed proteasome-independent accumulation of ubiquitinated CPAP and abnormal, ubiquitin-positive, elongated centrioles. Overall, our results show that centrobin interacts with ubiquitinated CPAP and prevents its degradation for normal centriole elongation function. Therefore, it appears that loss of centrobin expression destabilizes CPAP and triggers its degradation to restrict the centriole length during biogenesis. PMID:25616662
Exploring the Spatial and Temporal Organization of a Cell’s Proteome

PubMed Central

Beck, Martin; Topf, Maya; Frazier, Zachary; Tjong, Harianto; Xu, Min; Zhang, Shihua; Alber, Frank

2013-01-01

To increase our current understanding of cellular processes, such as cell signaling and division, knowledge is needed about the spatial and temporal organization of the proteome at different organizational levels. These levels cover a wide range of length and time scales: from the atomic structures of macromolecules for inferring their molecular function, to the quantitative description of their abundance, and distribution in the cell. Emerging new experimental technologies are greatly increasing the availability of such spatial information on the molecular organization in living cells. This review addresses three fields that have significantly contributed to our understanding of the proteome’s spatial and temporal organization: first, methods for the structure determination of individual macromolecular assemblies, specifically the fitting of atomic structures into density maps generated from electron microscopy techniques; second, research that visualizes the spatial distributions of these complexes within the cellular context using cryo electron tomography techniques combined with computational image processing; and third, methods for the spatial modeling of the dynamic organization of the proteome, specifically those methods for simulating reaction and diffusion of proteins and complexes in crowded intracellular fluids. The long-term goal is to integrate the varied data about a proteome’s organization into a spatially explicit, predictive model of cellular processes. PMID:21094684
Early life adversity and telomere length: a meta-analysis.

PubMed

Ridout, K K; Levandowski, M; Ridout, S J; Gantz, L; Goonan, K; Palermo, D; Price, L H; Tyrka, A R

2018-04-01

Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.
A living mesoscopic cellular automaton made of skin scales.

PubMed

Manukyan, Liana; Montandon, Sophie A; Fofonjka, Anamarija; Smirnov, Stanislav; Milinkovitch, Michel C

2017-04-12

In vertebrates, skin colour patterns emerge from nonlinear dynamical microscopic systems of cell interactions. Here we show that in ocellated lizards a quasi-hexagonal lattice of skin scales, rather than individual chromatophore cells, establishes a green and black labyrinthine pattern of skin colour. We analysed time series of lizard scale colour dynamics over four years of their development and demonstrate that this pattern is produced by a cellular automaton (a grid of elements whose states are iterated according to a set of rules based on the states of neighbouring elements) that dynamically computes the colour states of individual mesoscopic skin scales to produce the corresponding macroscopic colour pattern. Using numerical simulations and mathematical derivation, we identify how a discrete von Neumann cellular automaton emerges from a continuous Turing reaction-diffusion system. Skin thickness variation generated by three-dimensional morphogenesis of skin scales causes the underlying reaction-diffusion dynamics to separate into microscopic and mesoscopic spatial scales, the latter generating a cellular automaton. Our study indicates that cellular automata are not merely abstract computational systems, but can directly correspond to processes generated by biological evolution.
A living mesoscopic cellular automaton made of skin scales

NASA Astrophysics Data System (ADS)

Manukyan, Liana; Montandon, Sophie A.; Fofonjka, Anamarija; Smirnov, Stanislav; Milinkovitch, Michel C.

2017-04-01

In vertebrates, skin colour patterns emerge from nonlinear dynamical microscopic systems of cell interactions. Here we show that in ocellated lizards a quasi-hexagonal lattice of skin scales, rather than individual chromatophore cells, establishes a green and black labyrinthine pattern of skin colour. We analysed time series of lizard scale colour dynamics over four years of their development and demonstrate that this pattern is produced by a cellular automaton (a grid of elements whose states are iterated according to a set of rules based on the states of neighbouring elements) that dynamically computes the colour states of individual mesoscopic skin scales to produce the corresponding macroscopic colour pattern. Using numerical simulations and mathematical derivation, we identify how a discrete von Neumann cellular automaton emerges from a continuous Turing reaction-diffusion system. Skin thickness variation generated by three-dimensional morphogenesis of skin scales causes the underlying reaction-diffusion dynamics to separate into microscopic and mesoscopic spatial scales, the latter generating a cellular automaton. Our study indicates that cellular automata are not merely abstract computational systems, but can directly correspond to processes generated by biological evolution.
Multi Scale Modeling of Continuous Aramid Fiber Reinforced Polymer Matrix Composites Used in Ballistic Protection Applications

DTIC Science & Technology

2014-11-16

related to identification of the type and the extent of data generated at a finer length scale to the adjacent coarser length scale, as well as seamless ...data generated at a finer length scale to the adjacent coarser length scale, as well as seamless integration of different length scales into a unified...composite laminate consisting of 32 laminae and impacted (at a 0° obliquity angle and an incident velocity of 500 m/s) by a 0.30 caliber steel
Telomere Length, Current Perceived Stress, and Urinary Stress Hormones in Women

PubMed Central

Parks, Christine G.; Miller, Diane B.; McCanlies, Erin C.; Cawthon, Richard M.; Andrew, Michael E.; DeRoo, Lisa A.; Sandler, Dale P.

2009-01-01

Telomeres are repetitive DNA sequences that cap and protect the ends of chromosomes; critically short telomeres may lead to cellular senescence or carcinogenic transformation. Previous findings suggest a link between psychosocial stress, shorter telomeres, and chronic disease risk. This cross-sectional study examined relative telomere length in relation to perceived stress and urinary stress hormones in a sample of participants (n = 647) in the National Institute of Environmental Health Sciences Sister Study, a cohort of women ages 35 to 74 years who have a sister with breast cancer. Average leukocyte telomere length was determined by quantitative PCR. Current stress was assessed using the Perceived Stress Scale and creatinine-adjusted neuroendocrine hormones in first morning urines. Linear regression models estimated differences in telomere length base pairs (bp) associated with stress measures adjusted for age, race, smoking, and obesity. Women with higher perceived stress had somewhat shorter telomeres [adjusted difference of −129bp for being at or above moderate stress levels; 95% confidence interval (CI), −292 to 33], but telomere length did not decrease monotonically with higher stress levels. Shorter telomeres were independently associated with increasing age (−27bp/year), obesity, and current smoking. Significant stress-related differences in telomere length were seen in women ages 55 years and older (−289bp; 95% CI, −519 to −59), those with recent major losses (−420bp; 95% CI, −814 to −27), and those with above-average urinary catecholamines (e.g., epinephrine: −484bp; 95% CI, −709 to −259). Although current perceived stress was only modestly associated with shorter telomeres in this broad sample of women, our findings suggest the effect of stress on telomere length may vary depending on neuroendocrine responsiveness, external stressors, and age. PMID:19190150
Derivation of large-scale cellular regulatory networks from biological time series data.

PubMed

de Bivort, Benjamin L

2010-01-01

Pharmacological agents and other perturbants of cellular homeostasis appear to nearly universally affect the activity of many genes, proteins, and signaling pathways. While this is due in part to nonspecificity of action of the drug or cellular stress, the large-scale self-regulatory behavior of the cell may also be responsible, as this typically means that when a cell switches states, dozens or hundreds of genes will respond in concert. If many genes act collectively in the cell during state transitions, rather than every gene acting independently, models of the cell can be created that are comprehensive of the action of all genes, using existing data, provided that the functional units in the model are collections of genes. Techniques to develop these large-scale cellular-level models are provided in detail, along with methods of analyzing them, and a brief summary of major conclusions about large-scale cellular networks to date.
Finite-size scaling above the upper critical dimension in Ising models with long-range interactions

NASA Astrophysics Data System (ADS)

Flores-Sola, Emilio J.; Berche, Bertrand; Kenna, Ralph; Weigel, Martin

2015-01-01

The correlation length plays a pivotal role in finite-size scaling and hyperscaling at continuous phase transitions. Below the upper critical dimension, where the correlation length is proportional to the system length, both finite-size scaling and hyperscaling take conventional forms. Above the upper critical dimension these forms break down and a new scaling scenario appears. Here we investigate this scaling behaviour by simulating one-dimensional Ising ferromagnets with long-range interactions. We show that the correlation length scales as a non-trivial power of the linear system size and investigate the scaling forms. For interactions of sufficiently long range, the disparity between the correlation length and the system length can be made arbitrarily large, while maintaining the new scaling scenarios. We also investigate the behavior of the correlation function above the upper critical dimension and the modifications imposed by the new scaling scenario onto the associated Fisher relation.

Carrier-free cellular uptake and the gene-silencing activity of the lipophilic siRNAs is strongly affected by the length of the linker between siRNA and lipophilic group.

PubMed

Petrova, Natalya S; Chernikov, Ivan V; Meschaninova, Mariya I; Dovydenko, Iiya S; Venyaminova, Aliya G; Zenkova, Marina A; Vlassov, Valentin V; Chernolovskaya, Elena L

2012-03-01

The conjugation of siRNA to molecules, which can be internalized into the cell via natural transport mechanisms, can result in the enhancement of siRNA cellular uptake. Herein, the carrier-free cellular uptake of nuclease-resistant anti-MDR1 siRNA equipped with lipophilic residues (cholesterol, lithocholic acid, oleyl alcohol and litocholic acid oleylamide) attached to the 5'-end of the sense strand via oligomethylene linker of various length was investigated. A convenient combination of H-phosphonate and phosphoramidite methods was developed for the synthesis of 5'-lipophilic conjugates of siRNAs. It was found that lipophilic siRNA are able to effectively penetrate into HEK293, HepG2 and KB-8-5 cancer cells when used in a micromolar concentration range. The efficiency of the uptake is dependent upon the type of lipophilic moiety, the length of the linker between the moiety and the siRNA and cell type. Among all the conjugates tested, the cholesterol-conjugated siRNAs with linkers containing from 6 to 10 carbon atoms demonstrate the optimal uptake and gene silencing properties: the shortening of the linker reduces the efficiency of the cellular uptake of siRNA conjugates, whereas the lengthening of the linker facilitates the uptake but retards the gene silencing effect and decreases the efficiency of the silencing.
Assessment of imaging quality in magnified phase CT of human bone tissue at the nanoscale

NASA Astrophysics Data System (ADS)

Yu, Boliang; Langer, Max; Pacureanu, Alexandra; Gauthier, Remy; Follet, Helene; Mitton, David; Olivier, Cecile; Cloetens, Peter; Peyrin, Francoise

2017-10-01

Bone properties at all length scales have a major impact on the fracture risk in disease such as osteoporosis. However, quantitative 3D data on bone tissue at the cellular scale are still rare. Here we propose to use magnified X-ray phase nano-CT to quantify bone ultra-structure in human bone, on the new setup developed on the beamline ID16A at the ESRF, Grenoble. Obtaining 3D images requires the application of phase retrieval prior to tomographic reconstruction. Phase retrieval is an ill-posed problem for which various approaches have been developed. Since image quality has a strong impact on the further quantification of bone tissue, our aim here is to evaluate different phase retrieval methods for imaging bone samples at the cellular scale. Samples from femurs of female donors were scanned using magnified phase nano-CT at voxel sizes of 120 and 30 nm with an energy of 33 keV. Four CT scans at varying sample-to-detector distances were acquired for each sample. We evaluated three phase retrieval methods adapted to these conditions: Paganin's method at single distance, Paganin's method extended to multiple distances, and the contrast transfer function (CTF) approach for pure phase objects. These methods were used as initialization to an iterative refinement step. Our results based on visual and quantitative assessment show that the use of several distances (as opposed to single one) clearly improves image quality and the two multi-distance phase retrieval methods give similar results. First results on the segmentation of osteocyte lacunae and canaliculi from such images are presented.
Active mechanics in living oocytes reveal molecular-scale force kinetics

NASA Astrophysics Data System (ADS)

Ahmed, Wylie; Fodor, Etienne; Almonacid, Maria; Bussonnier, Matthias; Verlhac, Marie-Helene; Gov, Nir; Visco, Paolo; van Wijland, Frederic; Betz, Timo

Unlike traditional materials, living cells actively generate forces at the molecular scale that change their structure and mechanical properties. This nonequilibrium activity is essential for cellular function, and drives processes such as cell division. Single molecule studies have uncovered the detailed force kinetics of isolated motor proteins in-vitro, however their behavior in-vivo has been elusive due to the complex environment inside the cell. Here, we quantify active forces and intracellular mechanics in living oocytes using in-vivo optical trapping and laser interferometry of endogenous vesicles. We integrate an experimental and theoretical framework to connect mesoscopic measurements of nonequilibrium properties to the underlying molecular- scale force kinetics. Our results show that force generation by myosin-V drives the cytoplasmic-skeleton out-of-equilibrium (at frequencies below 300 Hz) and actively softens the environment. In vivo myosin-V activity generates a force of F ~ 0 . 4 pN, with a power-stroke of length Δx ~ 20 nm and duration τ ~ 300 μs, that drives vesicle motion at vv ~ 320 nm/s. This framework is widely applicable to characterize living cells and other soft active materials.
Principal curvatures and area ratio of propagating surfaces in isotropic turbulence

NASA Astrophysics Data System (ADS)

Zheng, Tianhang; You, Jiaping; Yang, Yue

2017-10-01

We study the statistics of principal curvatures and the surface area ratio of propagating surfaces with a constant or nonconstant propagating velocity in isotropic turbulence using direct numerical simulation. Propagating surface elements initially constitute a plane to model a planar premixed flame front. When the statistics of evolving propagating surfaces reach the stationary stage, the statistical profiles of principal curvatures scaled by the Kolmogorov length scale versus the constant displacement speed scaled by the Kolmogorov velocity scale collapse at different Reynolds numbers. The magnitude of averaged principal curvatures and the number of surviving surface elements without cusp formation decrease with increasing displacement speed. In addition, the effect of surface stretch on the nonconstant displacement speed inhibits the cusp formation on surface elements at negative Markstein numbers. In order to characterize the wrinkling process of the global propagating surface, we develop a model to demonstrate that the increase of the surface area ratio is primarily due to positive Lagrangian time integrations of the area-weighted averaged tangential strain-rate term and propagation-curvature term. The difference between the negative averaged mean curvature and the positive area-weighted averaged mean curvature characterizes the cellular geometry of the global propagating surface.
Multi-scale continuum modeling of biological processes: from molecular electro-diffusion to sub-cellular signaling transduction

NASA Astrophysics Data System (ADS)

Cheng, Y.; Kekenes-Huskey, P.; Hake, J. E.; Holst, M. J.; McCammon, J. A.; Michailova, A. P.

2012-01-01

This paper presents a brief review of multi-scale modeling at the molecular to cellular scale, with new results for heart muscle cells. A finite element-based simulation package (SMOL) was used to investigate the signaling transduction at molecular and sub-cellular scales (http://mccammon.ucsd.edu/smol/, http://FETK.org) by numerical solution of the time-dependent Smoluchowski equations and a reaction-diffusion system. At the molecular scale, SMOL has yielded experimentally validated estimates of the diffusion-limited association rates for the binding of acetylcholine to mouse acetylcholinesterase using crystallographic structural data. The predicted rate constants exhibit increasingly delayed steady-state times, with increasing ionic strength, and demonstrate the role of an enzyme's electrostatic potential in influencing ligand binding. At the sub-cellular scale, an extension of SMOL solves a nonlinear, reaction-diffusion system describing Ca2+ ligand buffering and diffusion in experimentally derived rodent ventricular myocyte geometries. Results reveal the important role of mobile and stationary Ca2+ buffers, including Ca2+ indicator dye. We found that alterations in Ca2+-binding and dissociation rates of troponin C (TnC) and total TnC concentration modulate sub-cellular Ca2+ signals. The model predicts that reduced off-rate in the whole troponin complex (TnC, TnI, TnT) versus reconstructed thin filaments (Tn, Tm, actin) alters cytosolic Ca2+ dynamics under control conditions or in disease-linked TnC mutations. The ultimate goal of these studies is to develop scalable methods and theories for the integration of molecular-scale information into simulations of cellular-scale systems.
Length scale effects and multiscale modeling of thermally induced phase transformation kinetics in NiTi SMA

NASA Astrophysics Data System (ADS)

Frantziskonis, George N.; Gur, Sourav

2017-06-01

Thermally induced phase transformation in NiTi shape memory alloys (SMAs) shows strong size and shape, collectively termed length scale effects, at the nano to micrometer scales, and that has important implications for the design and use of devices and structures at such scales. This paper, based on a recently developed multiscale model that utilizes molecular dynamics (MDs) simulations at small scales and MD-verified phase field (PhF) simulations at larger scales, reports results on specific length scale effects, i.e. length scale effects in martensite phase fraction (MPF) evolution, transformation temperatures (martensite and austenite start and finish) and in the thermally cyclic transformation between austenitic and martensitic phase. The multiscale study identifies saturation points for length scale effects and studies, for the first time, the length scale effect on the kinetics (i.e. developed internal strains) in the B19‧ phase during phase transformation. The major part of the work addresses small scale single crystals in specific orientations. However, the multiscale method is used in a unique and novel way to indirectly study length scale and grain size effects on evolution kinetics in polycrystalline NiTi, and to compare the simulation results to experiments. The interplay of the grain size and the length scale effect on the thermally induced MPF evolution is also shown in this present study. Finally, the multiscale coupling results are employed to improve phenomenological material models for NiTi SMA.
Ultralight, scalable nano-architected metamaterials (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zheng, Xiaoyu R.

2017-04-01

It has been a long research and engineering pursuit to create lightweight and mechanically robust and energy efficient materials with interconnected porosity. These cellular materials are desirable for a broad range of applications including structural components, lightweight transportation, heat exchange, catalyst supports, battery electrodes and biomaterials. However, the required outstanding properties have remained elusive on lightweight materials (<10kg/m3), constrained by the inherent coupling of material properties and the lack of suitable processes to generate these artificial materials. For example, graphene aerogels have among the lowest record densities 1kg/m^3, but their strength have been degraded to tens to hundreds of Pascal (<10^-8 of that of carbon nanotubes). The attainment of low density has come with a price -- significant reduction of bulk scale properties. We present the design, manufacturing and defect tolerance study of a new class of ultralight, three-dimensional multi-functional architected materials. These 3D bulk metamaterials (polymer, metal, ceramic and combinations thereof) possess weight density comparable to that of carbon aerogel, but with over 10^4 higher stiffness and strength. By designing and studying their hierarchical architectures, material compositions and feature sizes spanning multiple length-scales, we create a wide range of decoupled material properties such as programmable stiffness, tunable strength and fracture toughness as well as programmable possion ratio. With the possibility of incorporating precise control of topological architectures across length-scale sets as well as prediction and optimization of their defect tolerance, we enter into a paradigm where nanoscale material properties can be harnessed and made accessible in large scale objects, opening a wide range of applications of these materials in energy, health care and flexible electronics.
Towards a perceptive understanding of size in cellular biology.

PubMed

Zoppè, Monica

2017-06-29

Cells are minute-typically too small to be seen by the human eye. Even so, the cellular world encompasses a range of scales, from roughly a tenth of a nanometer (10 -10 m) to a millimeter (10 -3 m) or larger, spanning seven orders of magnitude or more. Because they are so far from our experience, it is difficult for us to envision such scales. To help our imagination grasp such dimensions, I propose the adoption of a 'perceptive scale' that can facilitate a more direct experience of cellular sizes. From this, as I argue below, will stem a new perception also of biological shape, cellular space and dynamic processes.
Structure and dynamics of hyaluronic acid semidilute solutions: a dielectric spectroscopy study.

PubMed

Vuletić, T; Dolanski Babić, S; Ivek, T; Grgicin, D; Tomić, S; Podgornik, R

2010-07-01

Dielectric spectroscopy is used to investigate fundamental length scales describing the structure of hyaluronic acid sodium salt (Na-HA) semidilute aqueous solutions. In salt-free regime, the length scale of the relaxation mode detected in MHz range scales with HA concentration as c(HA)(-0.5) and corresponds to the de Gennes-Pfeuty-Dobrynin correlation length of polyelectrolytes in semidilute solution. The same scaling was observed for the case of long, genomic DNA. Conversely, the length scale of the mode detected in kilohertz range also varies with HA concentration as c(HA)(-0.5) which differs from the case of DNA (c(DNA)(-0.25)). The observed behavior suggests that the relaxation in the kilohertz range reveals the de Gennes-Dobrynin renormalized Debye screening length, and not the average size of the chain, as the pertinent length scale. Similarly, with increasing added salt the electrostatic contribution to the HA persistence length is observed to scale as the Debye length, contrary to scaling pertinent to the Odijk-Skolnick-Fixman electrostatic persistence length observed in the case of DNA. We argue that the observed features of the kilohertz range relaxation are due to much weaker electrostatic interactions that lead to the absence of Manning condensation as well as a rather high flexibility of HA as compared to DNA.
Evolutionary optimization of material properties of a tropical seed

PubMed Central

Lucas, Peter W.; Gaskins, John T.; Lowrey, Timothy K.; Harrison, Mark E.; Morrogh-Bernard, Helen C.; Cheyne, Susan M.; Begley, Matthew R.

2012-01-01

Here, we show how the mechanical properties of a thick-shelled tropical seed are adapted to permit them to germinate while preventing their predation. The seed has evolved a complex heterogeneous microstructure resulting in hardness, stiffness and fracture toughness values that place the structure at the intersection of these competing selective constraints. Analyses of different damage mechanisms inflicted by beetles, squirrels and orangutans illustrate that cellular shapes and orientations ensure damage resistance to predation forces imposed across a broad range of length scales. This resistance is shown to be around the upper limit that allows cracking the shell via internal turgor pressure (i.e. germination). Thus, the seed appears to strike an exquisitely delicate adaptive balance between multiple selection pressures. PMID:21613287
Three-dimensional micro-scale strain mapping in living biological soft tissues.

PubMed

Moo, Eng Kuan; Sibole, Scott C; Han, Sang Kuy; Herzog, Walter

2018-04-01

Non-invasive characterization of the mechanical micro-environment surrounding cells in biological tissues at multiple length scales is important for the understanding of the role of mechanics in regulating the biosynthesis and phenotype of cells. However, there is a lack of imaging methods that allow for characterization of the cell micro-environment in three-dimensional (3D) space. The aims of this study were (i) to develop a multi-photon laser microscopy protocol capable of imprinting 3D grid lines onto living tissue at a high spatial resolution, and (ii) to develop image processing software capable of analyzing the resulting microscopic images and performing high resolution 3D strain analyses. Using articular cartilage as the biological tissue of interest, we present a novel two-photon excitation imaging technique for measuring the internal 3D kinematics in intact cartilage at sub-micrometer resolution, spanning length scales from the tissue to the cell level. Using custom image processing software, we provide accurate and robust 3D micro-strain analysis that allows for detailed qualitative and quantitative assessment of the 3D tissue kinematics. This novel technique preserves tissue structural integrity post-scanning, therefore allowing for multiple strain measurements at different time points in the same specimen. The proposed technique is versatile and opens doors for experimental and theoretical investigations on the relationship between tissue deformation and cell biosynthesis. Studies of this nature may enhance our understanding of the mechanisms underlying cell mechano-transduction, and thus, adaptation and degeneration of soft connective tissues. We presented a novel two-photon excitation imaging technique for measuring the internal 3D kinematics in intact cartilage at sub-micrometer resolution, spanning from tissue length scale to cellular length scale. Using a custom image processing software (lsmgridtrack), we provide accurate and robust micro-strain analysis that allowed for detailed qualitative and quantitative assessment of the 3D tissue kinematics. The approach presented here can also be applied to other biological tissues such as meniscus and annulus fibrosus, as well as tissue-engineered tissues for the characterization of their mechanical properties. This imaging technique opens doors for experimental and theoretical investigation on the relationship between tissue deformation and cell biosynthesis. Studies of this nature may enhance our understanding of the mechanisms underlying cell mechano-transduction, and thus, adaptation and degeneration of soft connective tissues. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Computational Study of the Genomic and Epigenomic Phenomena

NASA Astrophysics Data System (ADS)

Yang, Wenjing

Biological systems are perhaps the ultimate complex systems, uniquely capable of processing and communicating information, reproducing in their lifetimes, and adapting in evolutionary time scales. My dissertation research focuses on using computational approaches to understand the biocomplexity manifested in the multitude of length scales and time scales. At the molecular and cellular level, central to the complex behavior of a biological system is the regulatory network. My research study focused on epigenetics, which is essential for multicellular organisms to establish cellular identity during development or in response to intracellular and environmental stimuli. My computational study of epigenomics is greatly facilitated by recent advances in high-throughput sequencing technology, which enables high-resolution snapshots of epigenomes and transcriptomes. Using human CD4+ T cell as a model system, the dynamical changes in epigenome and transcriptome pertinent to T cell activation were investigated at the genome scale. Going beyond traditional focus on transcriptional regulation, I provided evidences that post-transcriptional regulation may serve as a major component of the regulatory network. In addition, I explored alternative polyadenylation, another novel aspect of gene regulation, and how it cross-talks with the local chromatin structure. As the renowned theoretical biologist Theodosius Dobzhansky said eloquently, "Nothing in biology makes sense except in the light of evolution''. To better understand this ubiquitous driving force in the biological world, I went beyond molecular events in a single organism, and investigated the dynamical changes of population structure along the evolutionary time scale. To this end, we used HIV virus population dynamics in the host immune system as a model system. The evolution of HIV viral population plays a key role in AIDS immunopathogenesis with its exceptionally high mutation rate. However, the theoretical studies of the effect of recombination have been rather limited. Given the phylogenetic and experimental evidences for the high recombination rate and its important role in HIV evolution and epidemics, I established a mathematical model to study the effect of recombination, and explored the complex behavior of this dynamics system.
Universal Features of Metastable State Energies in Cellular Matter

NASA Astrophysics Data System (ADS)

Kim, Sangwoo; Wang, Yiliang; Hilgenfeldt, Sascha

2018-06-01

Mechanical equilibrium states of cellular matter are overwhelmingly metastable and separated from each other by topology changes. Using theory and simulations, it is shown that for a wide class of energy functionals in 2D, including those describing tissue cell layers, local energy differences between neighboring metastable states as well as global energy differences between initial states and ground states are governed by simple, universal relations. Knowledge of instantaneous length of an edge undergoing a T 1 transition is sufficient to predict local energy changes, while the initial edge length distribution yields a successful prediction for the global energy difference. An analytical understanding of the model parameters is provided.
Hierarchical approaches for systems modeling in cardiac development.

PubMed

Gould, Russell A; Aboulmouna, Lina M; Varner, Jeffrey D; Butcher, Jonathan T

2013-01-01

Ordered cardiac morphogenesis and function are essential for all vertebrate life. The heart begins as a simple contractile tube, but quickly grows and morphs into a multichambered pumping organ complete with valves, while maintaining regulation of blood flow and nutrient distribution. Though not identical, cardiac morphogenesis shares many molecular and morphological processes across vertebrate species. Quantitative data across multiple time and length scales have been gathered through decades of reductionist single variable analyses. These range from detailed molecular signaling pathways at the cellular levels to cardiac function at the tissue/organ levels. However, none of these components act in true isolation from others, and each, in turn, exhibits short- and long-range effects in both time and space. With the absence of a gene, entire signaling cascades and genetic profiles may be shifted, resulting in complex feedback mechanisms. Also taking into account local microenvironmental changes throughout development, it is apparent that a systems level approach is an essential resource to accelerate information generation concerning the functional relationships across multiple length scales (molecular data vs physiological function) and structural development. In this review, we discuss relevant in vivo and in vitro experimental approaches, compare different computational frameworks for systems modeling, and the latest information about systems modeling of cardiac development. Finally, we conclude with some important future directions for cardiac systems modeling. Copyright © 2013 Wiley Periodicals, Inc.
Photo- and electropatterning of hydrogel-encapsulated living cell arrays.

PubMed

Albrecht, Dirk R; Tsang, Valerie Liu; Sah, Robert L; Bhatia, Sangeeta N

2005-01-01

Living cells have the potential to serve as sensors, naturally integrating the response to stimuli to generate predictions about cell fate (e.g., differentiation, migration, proliferation, apoptosis). Miniaturized arrays of living cells further offer the capability to interrogate many cells in parallel and thereby enable high-throughput and/or combinatorial assays. However, the interface between living cells and synthetic chip platforms is a critical one wherein the cellular phenotype must be preserved to generate useful signals. While some cell types retain tissue-specific features on a flat (2-D) surface, it has become increasingly apparent that a 3-D physical environment will be required for others. In this paper, we present two independent methods for creating living cell arrays that are encapsulated within a poly(ethylene glycol)-based hydrogel to create a local 3-D microenvironment. First, 'photopatterning' selectively crosslinks hydrogel microstructures containing living cells with approximately 100 microm feature size. Second, 'electropatterning' utilizes dielectrophoretic forces to position cells within a prepolymer solution prior to crosslinking, forming cell patterns with micron resolution. We further combine these methods to obtain hierarchical control of cell positioning over length scales ranging from microns to centimeters. This level of microenvironmental control should enable the fabrication of next-generation cellular microarrays in which robust 3-D cultures of cells are presented with appropriate physical and chemical cues and, consequently, report on cellular responses that resemble in vivo behavior.
Telomere length in alcohol dependence: A role for impulsive choice and childhood maltreatment.

PubMed

Kang, Jee In; Hwang, Syung Shick; Choi, Jong Rak; Lee, Seung-Tae; Kim, Jieun; Hwang, In Sik; Kim, Hae Won; Kim, Chan-Hyung; Kim, Se Joo

2017-09-01

Telomere shortening, a marker of cellular aging, has been considered to be linked with psychosocial stress as well as with chronic alcohol consumption, possibly mediated by oxidative stress and inflammatory response. Recent findings suggested that early life adversity on telomere dynamics may be related to impulsive choice. To further our understanding of the association of impulsive choice and childhood trauma on telomere length, we examined whether delayed discounting and childhood trauma or their interaction is related to leukocyte telomere length, while controlling for multiple potential confounding variables, in patients with alcohol dependence who are considered to have higher impulsive choice and shorter telomere length. We recruited 253 male patients with chronic alcohol dependence. All participants performed the delay discounting task, and the area under curve was used as a measure of delay discounting. Steeper delay discounting represents more impulsive choices. The modified Parent-Child Conflict Tactics Scale was used to measure childhood maltreatment. In addition, confounding factors, including socio-demographic characteristics, the Alcohol Use Disorders Identification Test, the Buss-Perry Aggression Questionnaire, the Resilience Quotient, the Beck Depression Inventory, and the Beck Anxiety Inventory, were also assessed. Hierarchical regression analyses showed a significant main effect of delay discounting (β=0.161, t=2.640, p=0.009), and an interaction effect between delay discounting and childhood maltreatment on leukocyte telomere length (β=0.173, t=2.138, p=0.034). In subsequent analyses stratified by childhood maltreatment, patients with alcohol dependence and high childhood trauma showed a significant relationship between delay discounting and leukocyte telomere length (β=0.279, t=3.183, p=0.002), while those with low trauma showed no association between them. Our findings suggest that higher impulsive choice is associated with shorter telomere length, and childhood trauma may exert a moderating effect in the relationship between impulsive choice and telomere length. Copyright © 2017. Published by Elsevier Ltd.
Time scale of diffusion in molecular and cellular biology

NASA Astrophysics Data System (ADS)

Holcman, D.; Schuss, Z.

2014-05-01

Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.
Role of medium heterogeneity and viscosity contrast in miscible flow regimes and mixing zone growth: A computational pore-scale approach

NASA Astrophysics Data System (ADS)

Afshari, Saied; Hejazi, S. Hossein; Kantzas, Apostolos

2018-05-01

Miscible displacement of fluids in porous media is often characterized by the scaling of the mixing zone length with displacement time. Depending on the viscosity contrast of fluids, the scaling law varies between the square root relationship, a sign for dispersive transport regime during stable displacement, and the linear relationship, which represents the viscous fingering regime during an unstable displacement. The presence of heterogeneities in a porous medium significantly affects the scaling behavior of the mixing length as it interacts with the viscosity contrast to control the mixing of fluids in the pore space. In this study, the dynamics of the flow and transport during both unit and adverse viscosity ratio miscible displacements are investigated in heterogeneous packings of circular grains using pore-scale numerical simulations. The pore-scale heterogeneity level is characterized by the variations of the grain diameter and velocity field. The growth of mixing length is employed to identify the nature of the miscible transport regime at different viscosity ratios and heterogeneity levels. It is shown that as the viscosity ratio increases to higher adverse values, the scaling law of mixing length gradually shifts from dispersive to fingering nature up to a certain viscosity ratio and remains almost the same afterwards. In heterogeneous media, the mixing length scaling law is observed to be generally governed by the variations of the velocity field rather than the grain size. Furthermore, the normalization of mixing length temporal plots with respect to the governing parameters of viscosity ratio, heterogeneity, medium length, and medium aspect ratio is performed. The results indicate that mixing length scales exponentially with log-viscosity ratio and grain size standard deviation while the impact of aspect ratio is insignificant. For stable flows, mixing length scales with the square root of medium length, whereas it changes linearly with length during unstable flows. This scaling procedure allows us to describe the temporal variation of mixing length using a generalized curve for various combinations of the flow conditions and porous medium properties.
Length-scale dependent mechanical properties of Al-Cu eutectic alloy: Molecular dynamics based model and its experimental verification

NASA Astrophysics Data System (ADS)

Tiwary, C. S.; Chakraborty, S.; Mahapatra, D. R.; Chattopadhyay, K.

2014-05-01

This paper attempts to gain an understanding of the effect of lamellar length scale on the mechanical properties of two-phase metal-intermetallic eutectic structure. We first develop a molecular dynamics model for the in-situ grown eutectic interface followed by a model of deformation of Al-Al2Cu lamellar eutectic. Leveraging the insights obtained from the simulation on the behaviour of dislocations at different length scales of the eutectic, we present and explain the experimental results on Al-Al2Cu eutectic with various different lamellar spacing. The physics behind the mechanism is further quantified with help of atomic level energy model for different length scale as well as different strain. An atomic level energy partitioning of the lamellae and the interface regions reveals that the energy of the lamellae core are accumulated more due to dislocations irrespective of the length-scale. Whereas the energy of the interface is accumulated more due to dislocations when the length-scale is smaller, but the trend is reversed when the length-scale is large beyond a critical size of about 80 nm.
Mesoscopic Length Scale Controls the Rheology of Dense Suspensions

NASA Astrophysics Data System (ADS)

Bonnoit, Claire; Lanuza, Jose; Lindner, Anke; Clement, Eric

2010-09-01

From the flow properties of dense granular suspensions on an inclined plane, we identify a mesoscopic length scale strongly increasing with volume fraction. When the flowing layer height is larger than this length scale, a diverging Newtonian viscosity is determined. However, when the flowing layer height drops below this scale, we evidence a nonlocal effective viscosity, decreasing as a power law of the flow height. We establish a scaling relation between this mesoscopic length scale and the suspension viscosity. These results support recent theoretical and numerical results implying collective and clustered granular motion when the jamming point is approached from below.

Mesoscopic length scale controls the rheology of dense suspensions.

PubMed

Bonnoit, Claire; Lanuza, Jose; Lindner, Anke; Clement, Eric

2010-09-03

From the flow properties of dense granular suspensions on an inclined plane, we identify a mesoscopic length scale strongly increasing with volume fraction. When the flowing layer height is larger than this length scale, a diverging Newtonian viscosity is determined. However, when the flowing layer height drops below this scale, we evidence a nonlocal effective viscosity, decreasing as a power law of the flow height. We establish a scaling relation between this mesoscopic length scale and the suspension viscosity. These results support recent theoretical and numerical results implying collective and clustered granular motion when the jamming point is approached from below.
The role of plasma density scale length on the laser pulse propagation and scattering in relativistic regime

NASA Astrophysics Data System (ADS)

Pishdast, Masoud; Ghasemi, Seyed Abolfazl; Yazdanpanah, Jamal Aldin

2017-10-01

The role of plasma density scale length on two short and long laser pulse propagation and scattering in under dense plasma have been investigated in relativistic regime using 1 D PIC simulation. In our simulation, different density scale lengths and also two short and long pulse lengths with temporal pulse duration τL = 60 fs and τL = 300 fs , respectively have been used. It is found that laser pulse length and density scale length have considerable effects on the energetic electron generation. The analysis of total radiation spectrum reveals that, for short laser pulses and with reducing density scale length, more unstable electromagnetic modes grow and strong longitudinal electric field generates which leads to the generation of more energetic plasma particles. Meanwhile, the dominant scattering mechanism is Raman scattering and tends to Thomson scattering for longer laser pulse.
Quasi-Continuum Reduction of Field Theories: A Route to Seamlessly Bridge Quantum and Atomistic Length-Scales with Continuum

DTIC Science & Technology

2016-04-01

AFRL-AFOSR-VA-TR-2016-0145 Quasi-continuum reduction of field theories: A route to seamlessly bridge quantum and atomistic length-scales with...field theories: A route to seamlessly bridge quantum and atomistic length-scales with continuum Principal Investigator: Vikram Gavini Department of...calculations on tens of thousands of atoms, and enable continuing efforts towards a seamless bridging of the quantum and continuum length-scales
Influence of Stress and Antibiotic Resistance on Cell-Length Distribution in Mycobacterium tuberculosis Clinical Isolates

PubMed Central

Vijay, Srinivasan; Vinh, Dao N.; Hai, Hoang T.; Ha, Vu T. N.; Dung, Vu T. M.; Dinh, Tran D.; Nhung, Hoang N.; Tram, Trinh T. B.; Aldridge, Bree B.; Hanh, Nguyen T.; Thu, Do D. A.; Phu, Nguyen H.; Thwaites, Guy E.; Thuong, Nguyen T. T.

2017-01-01

Mycobacterial cellular variations in growth and division increase heterogeneity in cell length, possibly contributing to cell-to-cell variation in host and antibiotic stress tolerance. This may be one of the factors influencing Mycobacterium tuberculosis persistence to antibiotics. Tuberculosis (TB) is a major public health problem in developing countries, antibiotic persistence, and emergence of antibiotic resistance further complicates this problem. We wanted to investigate the factors influencing cell-length distribution in clinical M. tuberculosis strains. In parallel we examined M. tuberculosis cell-length distribution in a large set of clinical strains (n = 158) from ex vivo sputum samples, in vitro macrophage models, and in vitro cultures. Our aim was to understand the influence of clinically relevant factors such as host stresses, M. tuberculosis lineages, antibiotic resistance, antibiotic concentrations, and disease severity on the cell size distribution in clinical M. tuberculosis strains. Increased cell size and cell-to-cell variation in cell length were associated with bacteria in sputum and infected macrophages rather than liquid culture. Multidrug-resistant (MDR) strains displayed increased cell length heterogeneity compared to sensitive strains in infected macrophages and also during growth under rifampicin (RIF) treatment. Importantly, increased cell length was also associated with pulmonary TB disease severity. Supporting these findings, individual host stresses, such as oxidative stress and iron deficiency, increased cell-length heterogeneity of M. tuberculosis strains. In addition we also observed synergism between host stress and RIF treatment in increasing cell length in MDR-TB strains. This study has identified some clinical factors contributing to cell-length heterogeneity in clinical M. tuberculosis strains. The role of these cellular adaptations to host and antibiotic tolerance needs further investigation. PMID:29209302
Structure and organization of Stratocumulus fields: A network approach

NASA Astrophysics Data System (ADS)

Glassmeier, Franziska; Feingold, Graham

2017-04-01

The representation of Stratocumulus (Sc) clouds and their radiative impact is one of the large challenges for global climate models. Aerosol-cloud-precipitation interactions greatly contribute to this challenge by influencing the morphology of Sc fields: In the absence of rain, Sc are arranged in a relatively regular pattern of cloudy cells separated by cloud-free rings of down welling air ('closed cells'). Raining cloud fields, in contrast, exhibit an oscillating pattern of cloudy rings surrounding cloud free cells of negatively buoyant air caused by sedimentation and evaporation of rain ('open cells'). Surprisingly, these regular structures of open and closed cellular Sc fields and their potential for the development of new parameterizations have hardly been explored. In this contribution, we approach the organization of Sc from the perspective of a 2-dimensional random network. We find that cellular networks derived from LES simulations of open- and closed-cell Sc cases are almost indistinguishable and share the following features: (i) The distributions of nearest neighbors, or cell degree, are centered at six. This corresponds to approximately hexagonal cloud cells and is a direct mathematical consequence (Euler formula) of the triple junctions featured by Sc organization. (ii) The degree of individual cells is found to be proportional to the normalized size of the cells. This means that cell arrangement is independent of the typical cell size. (iii) Reflecting the continuously renewing dynamics of Sc fields, large (high-degree) cells tend to be neighbored by small (low-degree) cells and vice versa. These macroscopic network properties emerge independent of the state of the Sc field because the different processes governing the evolution of closed as compared to open cells correspond to topologically equivalent network dynamics. By developing a heuristic model, we show that open and closed cell dynamics can both be mimicked by versions of cell division and cell disappearance and are biased towards the expansion of smaller cells. As a conclusion of our network analysis, Sc organization can be characterized by a typical length scale and a scale-independent cell arrangement. While the typical length scale emerges from the full complexity of aerosol-cloud-precipitation-radiation interactions, cell arrangement is independent of cloud processes and its evolution could be parameterized based on our heuristic model.
Inherent length-scales of periodic solar wind number density structures

NASA Astrophysics Data System (ADS)

Viall, N. M.; Kepko, L.; Spence, H. E.

2008-07-01

We present an analysis of the radial length-scales of periodic solar wind number density structures. We converted 11 years (1995-2005) of solar wind number density data into radial length series segments and Fourier analyzed them to identify all spectral peaks with radial wavelengths between 72 (116) and 900 (900) Mm for slow (fast) wind intervals. Our window length for the spectral analysis was 9072 Mm, approximately equivalent to 7 (4) h of data for the slow (fast) solar wind. We required that spectral peaks pass both an amplitude test and a harmonic F-test at the 95% confidence level simultaneously. From the occurrence distributions of these spectral peaks for slow and fast wind, we find that periodic number density structures occur more often at certain radial length-scales than at others, and are consistently observed within each speed range over most of the 11-year interval. For the slow wind, those length-scales are L ˜ 73, 120, 136, and 180 Mm. For the fast wind, those length-scales are L ˜ 187, 270 and 400 Mm. The results argue for the existence of inherent radial length-scales in the solar wind number density.
Rapakivi texture formation via disequilibrium melting in a contact partial melt zone, Antarctica

NASA Astrophysics Data System (ADS)

Currier, R. M.

2017-12-01

In the McMurdo Dry Valleys of Antarctica, a Jurassic aged dolerite sill induced partial melting of granite in the shallow crust. The melt zone can be traced in full, from high degrees of melting (>60%) along the dolerite contact, to no apparent signs of melting, 10s of meters above the contact. Within this melt zone, the well-known rapakivi texture is found, arrested in various stages of development. High above the contact, and at low degrees of melting, K-feldspar crystals are slightly rounded and unmantled. In the lower half of the melt zone, mantles of cellular textured plagioclase appear on K-feldspar, and thicken towards the contact heat source. At the highest degrees of melting, cellular-textured plagioclase completely replaces restitic K-feldspar. Because of the complete exposure and intact context, the leading models of rapakivi texture formation can be tested against this system. The previously proposed mechanisms of subisothermal decompression, magma-mixing, and hydrothermal exsolution all fail to adequately describe rapakivi generation in this melt zone. Preferred here is a closed system model that invokes the production of a heterogeneous, disequilibrium melt through rapid heating, followed by calcium and sodium rich melt reacting in a peritectic fashion with restitic K-feldspar crystals. This peritectic reaction results in the production of plagioclase of andesine-oligoclase composition—which is consistent with not just mantles in the melt zone, but globally as well. The thickness of the mantle is diffusion limited, and thus a measure of the diffusive length scale of sodium and calcium over the time scale of melting. Thermal modeling provides a time scale of melting that is consistent with the thickness of observed mantles. Lastly, the distribution of mantled feldspars is highly ordered in this melt zone, but if it were mobilized and homogenized—mixing together cellular plagioclase, mantled feldspars, and unmantled feldspars—the result would be akin to rapakivi granites observed globally in Proterozoic systems. In essence, the melt zone is an embryonic rapakivi granite; not yet fully developed and displaying clear ties to its parental rock.
Asynchronous adaptive time step in quantitative cellular automata modeling

PubMed Central

Zhu, Hao; Pang, Peter YH; Sun, Yan; Dhar, Pawan

2004-01-01

Background The behaviors of cells in metazoans are context dependent, thus large-scale multi-cellular modeling is often necessary, for which cellular automata are natural candidates. Two related issues are involved in cellular automata based multi-cellular modeling: how to introduce differential equation based quantitative computing to precisely describe cellular activity, and upon it, how to solve the heavy time consumption issue in simulation. Results Based on a modified, language based cellular automata system we extended that allows ordinary differential equations in models, we introduce a method implementing asynchronous adaptive time step in simulation that can considerably improve efficiency yet without a significant sacrifice of accuracy. An average speedup rate of 4–5 is achieved in the given example. Conclusions Strategies for reducing time consumption in simulation are indispensable for large-scale, quantitative multi-cellular models, because even a small 100 × 100 × 100 tissue slab contains one million cells. Distributed and adaptive time step is a practical solution in cellular automata environment. PMID:15222901
Solute-specific scaling of inorganic nitrogen and phosphorus uptake in streams

NASA Astrophysics Data System (ADS)

Hall, R. O., Jr.; Baker, M. A.; Rosi-Marshall, E. J.; Tank, J. L.; Newbold, J. D.

2013-11-01

Stream ecosystem processes such as nutrient cycling may vary with stream position in the network. Using a scaling approach, we examined the relationship between stream size and nutrient uptake length, which represents the mean distance that a dissolved solute travels prior to removal from the water column. Ammonium (NH4+) uptake length increased proportionally with stream size measured as specific discharge (discharge/stream width) with a scaling exponent = 1.01. In contrast, uptake lengths for nitrate (NO3-) and soluble reactive phosphorus (SRP) increased more rapidly than increases in specific discharge (scaling exponents = 1.19 for NO3- and 1.35 for SRP). Additionally, the ratio of inorganic nitrogen (N) uptake length to SRP uptake length declined with stream size; there was relatively lower demand for SRP compared to N as stream size increased. Finally, we related the scaling of uptake length with specific discharge to that of stream length using Hack's law and downstream hydraulic geometry. Ammonium uptake length increased less than proportionally with distance from the headwaters, suggesting a strong role for larger streams and rivers in regulating nutrient transport.
Dynamic scaling for the growth of non-equilibrium fluctuations during thermophoretic diffusion in microgravity

DOE PAGES

Cerbino, Roberto; Sun, Yifei; Donev, Aleksandar; ...

2015-09-30

Diffusion processes are widespread in biological and chemical systems, where they play a fundamental role in the exchange of substances at the cellular level and in determining the rate of chemical reactions. Recently, the classical picture that portrays diffusion as random uncorrelated motion of molecules has been revised, when it was shown that giant non-equilibrium fluctuations develop during diffusion processes. Under microgravity conditions and at steady-state, non-equilibrium fluctuations exhibit scale invariance and their size is only limited by the boundaries of the system. Here in this work, we investigate the onset of non-equilibrium concentration fluctuations induced by thermophoretic diffusion inmore » microgravity, a regime not accessible to analytical calculations but of great relevance for the understanding of several natural and technological processes. A combination of state of the art simulations and experiments allows us to attain a fully quantitative description of the development of fluctuations during transient diffusion in microgravity. Both experiments and simulations show that during the onset the fluctuations exhibit scale invariance at large wave vectors. In a broader range of wave vectors simulations predict a spinodal-like growth of fluctuations, where the amplitude and length-scale of the dominant mode are determined by the thickness of the diffuse layer.« less
Appplication of statistical mechanical methods to the modeling of social networks

NASA Astrophysics Data System (ADS)

Strathman, Anthony Robert

With the recent availability of large-scale social data sets, social networks have become open to quantitative analysis via the methods of statistical physics. We examine the statistical properties of a real large-scale social network, generated from cellular phone call-trace logs. We find this network, like many other social networks to be assortative (r = 0.31) and clustered (i.e., strongly transitive, C = 0.21). We measure fluctuation scaling to identify the presence of internal structure in the network and find that structural inhomogeneity effectively disappears at the scale of a few hundred nodes, though there is no sharp cutoff. We introduce an agent-based model of social behavior, designed to model the formation and dissolution of social ties. The model is a modified Metropolis algorithm containing agents operating under the basic sociological constraints of reciprocity, communication need and transitivity. The model introduces the concept of a social temperature. We go on to show that this simple model reproduces the global statistical network features (incl. assortativity, connected fraction, mean degree, clustering, and mean shortest path length) of the real network data and undergoes two phase transitions, one being from a "gas" to a "liquid" state and the second from a liquid to a glassy state as function of this social temperature.
Dynamic scaling for the growth of non-equilibrium fluctuations during thermophoretic diffusion in microgravity

PubMed Central

Cerbino, Roberto; Sun, Yifei; Donev, Aleksandar; Vailati, Alberto

2015-01-01

Diffusion processes are widespread in biological and chemical systems, where they play a fundamental role in the exchange of substances at the cellular level and in determining the rate of chemical reactions. Recently, the classical picture that portrays diffusion as random uncorrelated motion of molecules has been revised, when it was shown that giant non-equilibrium fluctuations develop during diffusion processes. Under microgravity conditions and at steady-state, non-equilibrium fluctuations exhibit scale invariance and their size is only limited by the boundaries of the system. In this work, we investigate the onset of non-equilibrium concentration fluctuations induced by thermophoretic diffusion in microgravity, a regime not accessible to analytical calculations but of great relevance for the understanding of several natural and technological processes. A combination of state of the art simulations and experiments allows us to attain a fully quantitative description of the development of fluctuations during transient diffusion in microgravity. Both experiments and simulations show that during the onset the fluctuations exhibit scale invariance at large wave vectors. In a broader range of wave vectors simulations predict a spinodal-like growth of fluctuations, where the amplitude and length-scale of the dominant mode are determined by the thickness of the diffuse layer. PMID:26419420
Dynamic scaling for the growth of non-equilibrium fluctuations during thermophoretic diffusion in microgravity.

PubMed

Cerbino, Roberto; Sun, Yifei; Donev, Aleksandar; Vailati, Alberto

2015-09-30

Diffusion processes are widespread in biological and chemical systems, where they play a fundamental role in the exchange of substances at the cellular level and in determining the rate of chemical reactions. Recently, the classical picture that portrays diffusion as random uncorrelated motion of molecules has been revised, when it was shown that giant non-equilibrium fluctuations develop during diffusion processes. Under microgravity conditions and at steady-state, non-equilibrium fluctuations exhibit scale invariance and their size is only limited by the boundaries of the system. In this work, we investigate the onset of non-equilibrium concentration fluctuations induced by thermophoretic diffusion in microgravity, a regime not accessible to analytical calculations but of great relevance for the understanding of several natural and technological processes. A combination of state of the art simulations and experiments allows us to attain a fully quantitative description of the development of fluctuations during transient diffusion in microgravity. Both experiments and simulations show that during the onset the fluctuations exhibit scale invariance at large wave vectors. In a broader range of wave vectors simulations predict a spinodal-like growth of fluctuations, where the amplitude and length-scale of the dominant mode are determined by the thickness of the diffuse layer.
The Snakelike Chain Character of Unstructured RNA

PubMed Central

Jacobson, David R.; McIntosh, Dustin B.; Saleh, Omar A.

2013-01-01

In the absence of base-pairing and tertiary structure, ribonucleic acid (RNA) assumes a random-walk conformation, modulated by the electrostatic self-repulsion of the charged, flexible backbone. This behavior is often modeled as a Kratky-Porod “wormlike chain” (WLC) with a Barrat-Joanny scale-dependent persistence length. In this study we report measurements of the end-to-end extension of poly(U) RNA under 0.1 to 10 pN applied force and observe two distinct elastic-response regimes: a low-force, power-law regime characteristic of a chain of swollen blobs on long length scales and a high-force, salt-valence-dependent regime consistent with ion-stabilized crumpling on short length scales. This short-scale structure is additionally supported by force- and salt-dependent quantification of the RNA ion atmosphere composition, which shows that ions are liberated under stretching; the number of ions liberated increases with increasing bulk salt concentration. Both this result and the observation of two elastic-response regimes directly contradict the WLC model, which predicts a single elastic regime across all forces and, when accounting for scale-dependent persistence length, the opposite trend in ion release with salt concentration. We conclude that RNA is better described as a “snakelike chain,” characterized by smooth bending on long length scales and ion-stabilized crumpling on short length scales. In monovalent salt, these two regimes are separated by a characteristic length that scales with the Debye screening length, highlighting the determining importance of electrostatics in RNA conformation. PMID:24314087
On supervised graph Laplacian embedding CA model & kernel construction and its application

NASA Astrophysics Data System (ADS)

Zeng, Junwei; Qian, Yongsheng; Wang, Min; Yang, Yongzhong

2017-01-01

There are many methods to construct kernel with given data attribute information. Gaussian radial basis function (RBF) kernel is one of the most popular ways to construct a kernel. The key observation is that in real-world data, besides the data attribute information, data label information also exists, which indicates the data class. In order to make use of both data attribute information and data label information, in this work, we propose a supervised kernel construction method. Supervised information from training data is integrated into standard kernel construction process to improve the discriminative property of resulting kernel. A supervised Laplacian embedding cellular automaton model is another key application developed for two-lane heterogeneous traffic flow with the safe distance and large-scale truck. Based on the properties of traffic flow in China, we re-calibrate the cell length, velocity, random slowing mechanism and lane-change conditions and use simulation tests to study the relationships among the speed, density and flux. The numerical results show that the large-scale trucks will have great effects on the traffic flow, which are relevant to the proportion of the large-scale trucks, random slowing rate and the times of the lane space change.
Biophysical Discovery through the Lens of a Computational Microscope

NASA Astrophysics Data System (ADS)

Amaro, Rommie

With exascale computing power on the horizon, improvements in the underlying algorithms and available structural experimental data are enabling new paradigms for chemical discovery. My work has provided key insights for the systematic incorporation of structural information resulting from state-of-the-art biophysical simulations into protocols for inhibitor and drug discovery. We have shown that many disease targets have druggable pockets that are otherwise ``hidden'' in high resolution x-ray structures, and that this is a common theme across a wide range of targets in different disease areas. We continue to push the limits of computational biophysical modeling by expanding the time and length scales accessible to molecular simulation. My sights are set on, ultimately, the development of detailed physical models of cells, as the fundamental unit of life, and two recent achievements highlight our efforts in this arena. First is the development of a molecular and Brownian dynamics multi-scale modeling framework, which allows us to investigate drug binding kinetics in addition to thermodynamics. In parallel, we have made significant progress developing new tools to extend molecular structure to cellular environments. Collectively, these achievements are enabling the investigation of the chemical and biophysical nature of cells at unprecedented scales.
A new paradigm for atomically detailed simulations of kinetics in biophysical systems.

PubMed

Elber, Ron

2017-01-01

The kinetics of biochemical and biophysical events determined the course of life processes and attracted considerable interest and research. For example, modeling of biological networks and cellular responses relies on the availability of information on rate coefficients. Atomically detailed simulations hold the promise of supplementing experimental data to obtain a more complete kinetic picture. However, simulations at biological time scales are challenging. Typical computer resources are insufficient to provide the ensemble of trajectories at the correct length that is required for straightforward calculations of time scales. In the last years, new technologies emerged that make atomically detailed simulations of rate coefficients possible. Instead of computing complete trajectories from reactants to products, these approaches launch a large number of short trajectories at different positions. Since the trajectories are short, they are computed trivially in parallel on modern computer architecture. The starting and termination positions of the short trajectories are chosen, following statistical mechanics theory, to enhance efficiency. These trajectories are analyzed. The analysis produces accurate estimates of time scales as long as hours. The theory of Milestoning that exploits the use of short trajectories is discussed, and several applications are described.
Experimental evidence for two thermodynamic length scales in neutralized polyacrylate gels

NASA Astrophysics Data System (ADS)

Horkay, Ferenc; Hecht, Anne-Marie; Grillo, Isabelle; Basser, Peter J.; Geissler, Erik

2002-11-01

The small angle neutron scattering (SANS) behavior of fully neutralized sodium polyacrylate gels is investigated in the presence of calcium ions. Analysis of the SANS response reveals the existence of three characteristic length scales, two of which are of thermodynamic origin, while the third length is associated with the frozen-in structural inhomogeneities. This latter contribution exhibits power law behavior with a slope of about -3.6, reflecting the presence of interfaces. The osmotically active component of the scattering signal is defined by two characteristic length scales, a correlation length ξ and a persistence length L.
Long term effects of radiation exposure on telomere lengths of leukocytes and its associated biomarkers among atomic-bomb survivors.

PubMed

Lustig, Ana; Shterev, Ivo; Geyer, Susan; Shi, Alvin; Hu, Yiqun; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Maki, Mayumi; Hayashi, Ikue; Furukawa, Kyoji; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Ohishi, Waka; Nakachi, Kei; Weng, Nan-Ping; Hayashi, Tomonori

2016-06-28

Ionizing radiation (IR) is a major source of cellular damage and the immediate cellular response to IR has been well characterized. But the long-term impact of IR on cell function and its relationship with aging are not known. Here, we examined the IR effects on telomere length and other biomarkers 50 to 68 years post-exposure (two time points per person) in survivors of the atomic bombing at Hiroshima during WWII. We found that telomere length of leukocytes was inversely correlated with the dose of IR (p=0.008), and this effect was primarily found in survivors who were exposed at younger ages; specifically those <12 years old (p=0.0004). Although a dose-related retardation of telomere shortening with age was observed in the cross-sectional data, longitudinal follow-up after 11 years did not show IR exposure-related alteration of the rate of telomere shortening with age. In addition, IR diminished the associations between telomere length and selected aging biomarkers that were observed in survivors with no dose. These included uric acid metabolism, cytokines, and blood T cell counts. These findings showed long-lasting detrimental effects of IR on telomere length of leukocytes in both dose- and age-at-exposure dependent manner, and on alterations of biomarkers with aging.
Enzyme localization, crowding, and buffers collectively modulate diffusion-influenced signal transduction: Insights from continuum diffusion modeling

PubMed Central

Kekenes-Huskey, Peter M.; Eun, Changsun; McCammon, J. A.

2015-01-01

Biochemical reaction networks consisting of coupled enzymes connect substrate signaling events with biological function. Substrates involved in these reactions can be strongly influenced by diffusion “barriers” arising from impenetrable cellular structures and macromolecules, as well as interactions with biomolecules, especially within crowded environments. For diffusion-influenced reactions, the spatial organization of diffusion barriers arising from intracellular structures, non-specific crowders, and specific-binders (buffers) strongly controls the temporal and spatial reaction kinetics. In this study, we use two prototypical biochemical reactions, a Goodwin oscillator, and a reaction with a periodic source/sink term to examine how a diffusion barrier that partitions substrates controls reaction behavior. Namely, we examine how conditions representative of a densely packed cytosol, including reduced accessible volume fraction, non-specific interactions, and buffers, impede diffusion over nanometer length-scales. We find that diffusion barriers can modulate the frequencies and amplitudes of coupled diffusion-influenced reaction networks, as well as give rise to “compartments” of decoupled reactant populations. These effects appear to be intensified in the presence of buffers localized to the diffusion barrier. These findings have strong implications for the role of the cellular environment in tuning the dynamics of signaling pathways. PMID:26342355

Scaling Effects on Materials Tribology: From Macro to Micro Scale.

PubMed

Stoyanov, Pantcho; Chromik, Richard R

2017-05-18

The tribological study of materials inherently involves the interaction of surface asperities at the micro to nanoscopic length scales. This is the case for large scale engineering applications with sliding contacts, where the real area of contact is made up of small contacting asperities that make up only a fraction of the apparent area of contact. This is why researchers have sought to create idealized experiments of single asperity contacts in the field of nanotribology. At the same time, small scale engineering structures known as micro- and nano-electromechanical systems (MEMS and NEMS) have been developed, where the apparent area of contact approaches the length scale of the asperities, meaning the real area of contact for these devices may be only a few asperities. This is essentially the field of microtribology, where the contact size and/or forces involved have pushed the nature of the interaction between two surfaces towards the regime where the scale of the interaction approaches that of the natural length scale of the features on the surface. This paper provides a review of microtribology with the purpose to understand how tribological processes are different at the smaller length scales compared to macrotribology. Studies of the interfacial phenomena at the macroscopic length scales (e.g., using in situ tribometry) will be discussed and correlated with new findings and methodologies at the micro-length scale.
Scaling Effects on Materials Tribology: From Macro to Micro Scale

PubMed Central

Stoyanov, Pantcho; Chromik, Richard R.

2017-01-01

The tribological study of materials inherently involves the interaction of surface asperities at the micro to nanoscopic length scales. This is the case for large scale engineering applications with sliding contacts, where the real area of contact is made up of small contacting asperities that make up only a fraction of the apparent area of contact. This is why researchers have sought to create idealized experiments of single asperity contacts in the field of nanotribology. At the same time, small scale engineering structures known as micro- and nano-electromechanical systems (MEMS and NEMS) have been developed, where the apparent area of contact approaches the length scale of the asperities, meaning the real area of contact for these devices may be only a few asperities. This is essentially the field of microtribology, where the contact size and/or forces involved have pushed the nature of the interaction between two surfaces towards the regime where the scale of the interaction approaches that of the natural length scale of the features on the surface. This paper provides a review of microtribology with the purpose to understand how tribological processes are different at the smaller length scales compared to macrotribology. Studies of the interfacial phenomena at the macroscopic length scales (e.g., using in situ tribometry) will be discussed and correlated with new findings and methodologies at the micro-length scale. PMID:28772909
Length scale effects of friction in particle compaction using atomistic simulations and a friction scaling model

NASA Astrophysics Data System (ADS)

Stone, T. W.; Horstemeyer, M. F.

2012-09-01

The objective of this study is to illustrate and quantify the length scale effects related to interparticle friction under compaction. Previous studies have shown as the length scale of a specimen decreases, the strength of a single crystal metal or ceramic increases. The question underlying this research effort continues the thought—If there is a length scale parameter related to the strength of a material, is there a length scale parameter related to friction? To explore the length scale effects of friction, molecular dynamics (MD) simulations using an embedded atom method potential were performed to analyze the compression of two spherical FCC nickel nanoparticles at different contact angles. In the MD model study, we applied a macroscopic plastic contact formulation to determine the normal plastic contact force at the particle interfaces and used the average shear stress from the MD simulations to determine the tangential contact forces. Combining this information with the Coulomb friction law, we quantified the MD interparticle coefficient of friction and showed good agreement with experimental studies and a Discrete Element Method prediction as a function of contact angle. Lastly, we compared our MD simulation friction values to the tribological predictions of Bhushan and Nosonovsky (BN), who developed a friction scaling model based on strain gradient plasticity and dislocation-assisted sliding that included a length scale parameter. The comparison revealed that the BN elastic friction scaling model did a much better job than the BN plastic scaling model of predicting the coefficient of friction values obtained from the MD simulations.
16 CFR 321.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., mailer, book insert, free standing insert, letter, catalogue, poster, chart, billboard, public transit...-length commercial (“infomercial”), the Internet, cellular network, or any other medium. Promotional...
How much a galaxy knows about its large-scale environment?: An information theoretic perspective

NASA Astrophysics Data System (ADS)

Pandey, Biswajit; Sarkar, Suman

2017-05-01

The small-scale environment characterized by the local density is known to play a crucial role in deciding the galaxy properties but the role of large-scale environment on galaxy formation and evolution still remain a less clear issue. We propose an information theoretic framework to investigate the influence of large-scale environment on galaxy properties and apply it to the data from the Galaxy Zoo project that provides the visual morphological classifications of ˜1 million galaxies from the Sloan Digital Sky Survey. We find a non-zero mutual information between morphology and environment that decreases with increasing length-scales but persists throughout the entire length-scales probed. We estimate the conditional mutual information and the interaction information between morphology and environment by conditioning the environment on different length-scales and find a synergic interaction between them that operates up to at least a length-scales of ˜30 h-1 Mpc. Our analysis indicates that these interactions largely arise due to the mutual information shared between the environments on different length-scales.
Coarse-grained Brownian ratchet model of membrane protrusion on cellular scale.

PubMed

Inoue, Yasuhiro; Adachi, Taiji

2011-07-01

Membrane protrusion is a mechanochemical process of active membrane deformation driven by actin polymerization. Previously, Brownian ratchet (BR) was modeled on the basis of the underlying molecular mechanism. However, because the BR requires a priori load that cannot be determined without information of the cell shape, it cannot be effective in studies in which resultant shapes are to be solved. Other cellular-scale models describing the protrusion have also been suggested for modeling a whole cell; however, these models were not developed on the basis of coarse-grained physics representing the underlying molecular mechanism. Therefore, to express the membrane protrusion on the cellular scale, we propose a novel mathematical model, the coarse-grained BR (CBR), which is derived on the basis of nonequilibrium thermodynamics theory. The CBR can reproduce the BR within the limit of the quasistatic process of membrane protrusion and can estimate the protrusion velocity consistently with an effective elastic constant that represents the state of the energy of the membrane. Finally, to demonstrate the applicability of the CBR, we attempt to perform a cellular-scale simulation of migrating keratocyte in which the proposed CBR is used for the membrane protrusion model on the cellular scale. The results show that the experimentally observed shapes of the leading edge are well reproduced by the simulation. In addition, The trend of dependences of the protrusion velocity on the curvature of the leading edge, the temperature, and the substrate stiffness also agreed with the other experimental results. Thus, the CBR can be considered an appropriate cellular-scale model to express the membrane protrusion on the basis of its underlying molecular mechanism.
Size-dependent elastic/inelastic behavior of enamel over millimeter and nanometer length scales.

PubMed

Ang, Siang Fung; Bortel, Emely L; Swain, Michael V; Klocke, Arndt; Schneider, Gerold A

2010-03-01

The microstructure of enamel like most biological tissues has a hierarchical structure which determines their mechanical behavior. However, current studies of the mechanical behavior of enamel lack a systematic investigation of these hierarchical length scales. In this study, we performed macroscopic uni-axial compression tests and the spherical indentation with different indenter radii to probe enamel's elastic/inelastic transition over four hierarchical length scales, namely: 'bulk enamel' (mm), 'multiple-rod' (10's microm), 'intra-rod' (100's nm with multiple crystallites) and finally 'single-crystallite' (10's nm with an area of approximately one hydroxyapatite crystallite). The enamel's elastic/inelastic transitions were observed at 0.4-17 GPa depending on the length scale and were compared with the values of synthetic hydroxyapatite crystallites. The elastic limit of a material is important as it provides insights into the deformability of the material before fracture. At the smallest investigated length scale (contact radius approximately 20 nm), elastic limit is followed by plastic deformation. At the largest investigated length scale (contact size approximately 2 mm), only elastic then micro-crack induced response was observed. A map of elastic/inelastic regions of enamel from millimeter to nanometer length scale is presented. Possible underlying mechanisms are also discussed. (c) 2009 Elsevier Ltd. All rights reserved.
Implementation of a flow-dependent background error correlation length scale formulation in the NEMOVAR OSTIA system

NASA Astrophysics Data System (ADS)

Fiedler, Emma; Mao, Chongyuan; Good, Simon; Waters, Jennifer; Martin, Matthew

2017-04-01

OSTIA is the Met Office's Operational Sea Surface Temperature (SST) and Ice Analysis system, which produces L4 (globally complete, gridded) analyses on a daily basis. Work is currently being undertaken to replace the original OI (Optimal Interpolation) data assimilation scheme with NEMOVAR, a 3D-Var data assimilation method developed for use with the NEMO ocean model. A dual background error correlation length scale formulation is used for SST in OSTIA, as implemented in NEMOVAR. Short and long length scales are combined according to the ratio of the decomposition of the background error variances into short and long spatial correlations. The pre-defined background error variances vary spatially and seasonally, but not on shorter time-scales. If the derived length scales applied to the daily analysis are too long, SST features may be smoothed out. Therefore a flow-dependent component to determining the effective length scale has also been developed. The total horizontal gradient of the background SST field is used to identify regions where the length scale should be shortened. These methods together have led to an improvement in the resolution of SST features compared to the previous OI analysis system, without the introduction of spurious noise. This presentation will show validation results for feature resolution in OSTIA using the OI scheme, the dual length scale NEMOVAR scheme, and the flow-dependent implementation.
12 CFR 1014.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., leaflet, circular, mailer, book insert, free standing insert, letter, catalogue, poster, chart, billboard... firms, program-length commercial (“infomercial”), the internet, cellular network, or any other medium...
12 CFR 1014.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., leaflet, circular, mailer, book insert, free standing insert, letter, catalogue, poster, chart, billboard... firms, program-length commercial (“infomercial”), the internet, cellular network, or any other medium...
12 CFR 1014.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., leaflet, circular, mailer, book insert, free standing insert, letter, catalogue, poster, chart, billboard... firms, program-length commercial (“infomercial”), the internet, cellular network, or any other medium...
Novel guanidine-containing molecular transporters based on lactose scaffolds: lipophilicity effect on the intracellular organellar selectivity.

PubMed

Biswas, Goutam; Jeon, Ock-Youm; Lee, Woo Sirl; Kim, Dong-Chan; Kim, Kyong-Tai; Lee, Suho; Chang, Sunghoe; Chung, Sung-Kee

2008-01-01

We have synthesized two lactose-based molecular transporters, each containing seven guanidine residues attached to the lactose scaffold through omega-aminocarboxylate linker chains of two different lengths, and have examined their cellular uptakes and intracellular and organellar localizations in HeLa cells, as well as their tissue distributions in mice. Both molecular transporters showed higher cellular uptake efficiencies than Arg8, and wide tissue distributions including the brain. Mitochondrial localization is of special interest because of its potential relevance to "mitochondrial diseases". Interestingly, it has been found that the intracellular localization sites of the G7 molecular transporters-namely either mitochondria or lysosomes and endocytic vesicles-are largely determined by the linker chain lengths, or their associated lipophilicities.
High performance cellular level agent-based simulation with FLAME for the GPU.

PubMed

Richmond, Paul; Walker, Dawn; Coakley, Simon; Romano, Daniela

2010-05-01

Driven by the availability of experimental data and ability to simulate a biological scale which is of immediate interest, the cellular scale is fast emerging as an ideal candidate for middle-out modelling. As with 'bottom-up' simulation approaches, cellular level simulations demand a high degree of computational power, which in large-scale simulations can only be achieved through parallel computing. The flexible large-scale agent modelling environment (FLAME) is a template driven framework for agent-based modelling (ABM) on parallel architectures ideally suited to the simulation of cellular systems. It is available for both high performance computing clusters (www.flame.ac.uk) and GPU hardware (www.flamegpu.com) and uses a formal specification technique that acts as a universal modelling format. This not only creates an abstraction from the underlying hardware architectures, but avoids the steep learning curve associated with programming them. In benchmarking tests and simulations of advanced cellular systems, FLAME GPU has reported massive improvement in performance over more traditional ABM frameworks. This allows the time spent in the development and testing stages of modelling to be drastically reduced and creates the possibility of real-time visualisation for simple visual face-validation.
Coarsening of stripe patterns: variations with quench depth and scaling.

PubMed

Tripathi, Ashwani K; Kumar, Deepak

2015-02-01

The coarsening of stripe patterns when the system is evolved from random initial states is studied by varying the quench depth ε, which is a measure of distance from the transition point of the stripe phase. The dynamics of the growth of stripe order, which is characterized by two length scales, depends on the quench depth. The growth exponents of the two length scales vary continuously with ε. The decay exponents for free energy, stripe curvature, and densities of defects like grain boundaries and dislocations also show similar variation. This implies a breakdown of the standard picture of nonequilibrium dynamical scaling. In order to understand the variations with ε we propose an additional scaling with a length scale dependent on ε. The main contribution to this length scale comes from the "pinning potential," which is unique to systems where the order parameter is spatially periodic. The periodic order parameter gives rise to an ε-dependent potential, which can pin defects like grain boundaries, dislocations, etc. This additional scaling provides a compact description of variations of growth exponents with quench depth in terms of just one exponent for each of the length scales. The relaxation of free energy, stripe curvature, and the defect densities have also been related to these length scales. The study is done at zero temperature using Swift-Hohenberg equation in two dimensions.
Interactions between a fractal tree-like object and hydrodynamic turbulence: flow structure and characteristic mixing length

NASA Astrophysics Data System (ADS)

Meneveau, C. V.; Bai, K.; Katz, J.

2011-12-01

The vegetation canopy has a significant impact on various physical and biological processes such as forest microclimate, rainfall evaporation distribution and climate change. Most scaled laboratory experimental studies have used canopy element models that consist of rigid vertical strips or cylindrical rods that can be typically represented through only one or a few characteristic length scales, for example the diameter and height for cylindrical rods. However, most natural canopies and vegetation are highly multi-scale with branches and sub-branches, covering a wide range of length scales. Fractals provide a convenient idealization of multi-scale objects, since their multi-scale properties can be described in simple ways (Mandelbrot 1982). While fractal aspects of turbulence have been studied in several works in the past decades, research on turbulence generated by fractal objects started more recently. We present an experimental study of boundary layer flow over fractal tree-like objects. Detailed Particle-Image-Velocimetry (PIV) measurements are carried out in the near-wake of a fractal-like tree. The tree is a pre-fractal with five generations, with three branches and a scale reduction factor 1/2 at each generation. Its similarity fractal dimension (Mandelbrot 1982) is D ~ 1.58. Detailed mean velocity and turbulence stress profiles are documented, as well as their downstream development. We then turn attention to the turbulence mixing properties of the flow, specifically to the question whether a mixing length-scale can be identified in this flow, and if so, how it relates to the geometric length-scales in the pre-fractal object. Scatter plots of mean velocity gradient (shear) and Reynolds shear stress exhibit good linear relation at all locations in the flow. Therefore, in the transverse direction of the wake evolution, the Boussinesq eddy viscosity concept is appropriate to describe the mixing. We find that the measured mixing length increases with increasing streamwise locations. Conversely, the measured eddy viscosity and mixing length decrease with increasing elevation, which differs from eddy viscosity and mixing length behaviors of traditional boundary layers or canopies studied before. In order to find an appropriate length for the flow, several models based on the notion of superposition of scales are proposed and examined. One approach is based on spectral distributions. Another more practical approach is based on length-scale distributions evaluated using fractal geometry tools. These proposed models agree well with the measured mixing length. The results indicate that information about multi-scale clustering of branches as it occurs in fractals has to be incorporated into models of the mixing length for flows through canopies with multiple scales. The research is supported by National Science Foundation grant ATM-0621396 and AGS-1047550.
Disorder profile of nebulin encodes a vernierlike position sensor for the sliding thin and thick filaments of the skeletal muscle sarcomere

NASA Astrophysics Data System (ADS)

Wu, Ming-Chya; Forbes, Jeffrey G.; Wang, Kuan

2016-06-01

Nebulin is an about 1 μ m long intrinsically disordered scaffold for the thin filaments of skeletal muscle sarcomere. It is a multifunctional elastic protein that wraps around actin filament, stabilizes thin filaments, and regulates Ca-dependent actomyosin interactions. This study investigates whether the disorder profile of nebulin might encode guidelines for thin and thick filament interactions in the sarcomere of the skeletal muscle. The question was addressed computationally by analyzing the predicted disorder profile of human nebulin (6669 residues, ˜200 actin-binding repeats) by pondr and the periodicity of the A-band stripes (reflecting the locations of myosin-associated proteins) in the electron micrographs of the sarcomere. Using the detrended fluctuation analysis, a scale factor for the A-band stripe image data with respect to the nebulin disorder profile was determined to make the thin and thick filaments aligned to have maximum correlation. The empirical mode decomposition method was then applied to identify hidden periodicities in both the nebulin disorder profile and the rescaled A-band data. The decomposition reveals three characteristic length scales (45 nm, 100 nm, and 200 nm) that are relevant for correlational analysis. The dynamical cross-correlation analyses with moving windows at various sarcomere lengths depict a vernierlike design for both periodicities, thus enabling nebulin to sense position and fine tune sarcomere overlap. This shows that the disorder profile of scaffolding proteins may encode a guideline for cellular architecture.
Cellular Convection in a Chamber with a Warm Surface Raft

NASA Astrophysics Data System (ADS)

Whitehead, John; Shea, Erin; Behn, Mark

2011-11-01

We calculate velocity and temperature fields for Rayleigh-Benard convection in a chamber with a warm raft that can float along the top surface for Rayleigh number up to Ra=20,000. Two-dimensional, infinite Prandtl number, Boussinesq approximation equations are numerically advanced in time from a motionless state in a chamber of length L' and depth D'. We consider cases with an insulated raft and a raft of fixed temperature. Either oscillatory or stationary flow exists. The case of an insulated raft has three governing parameters: Ra, scaled chamber length L=L'/D', and scaled raft width W. For W=0 and L=1, the marginal state is at Ra=779.3. For smallest W (determined by numerical grid size) and Ra <790 the raft approaches the center monotonically in time. For 790 Ra >871 amplitude is steady, starting small and increasing with larger Ra and for Ra >871 raft movement ceases. For larger W, a range of W and Ra has raft oscillation up to Ra=20,000. Rafts in longer cavities (L=2 and 4) have almost no oscillatory behavior. With a raft of temperature Tr rather than insulating, Ra=20,000, and with internal heating, there are wider ranges of oscillating flow. Thus the presence or absence of motion is very sensitive to W, L, raft thermal properties and Ra. Reasons why are discussed.
Pulsed 86Sr-labeling and NanoSIMS imaging to study coral biomineralization at ultra-structural length scales

NASA Astrophysics Data System (ADS)

Brahmi, C.; Domart-Coulon, I.; Rougée, L.; Pyle, D. G.; Stolarski, J.; Mahoney, J. J.; Richmond, R. H.; Ostrander, G. K.; Meibom, A.

2012-09-01

A method to label marine biocarbonates is developed based on a concentration enrichment of a minor stable isotope of a trace element that is a natural component of seawater, resulting in the formation of biocarbonate with corresponding isotopic enrichments. This biocarbonate is subsequently imaged with a NanoSIMS ion microprobe to visualize the locations of the isotopic marker on sub-micrometric length scales, permitting resolution of all ultra-structural details. In this study, a scleractinian coral, Pocillopora damicornis, was labeled 3 times with 86Sr-enhanced seawater for a period of 48 h with 5 days under normal seawater conditions separating each labeling event. Two non-specific cellular stress biomarkers, glutathione-S-transferase activity and porphyrin concentration plus carbonic anhydrase, an enzymatic marker involved in the physiology of carbonate biomineralization, as well as unchanged levels of zooxanthellae photosynthesis efficiency indicate that coral physiological processes are not affected by the 86Sr-enhancement. NanoSIMS images of the 86Sr/44Ca ratio in skeleton formed during the experiment allow for a determination of the average extension rate of the two major ultra-structural components of the coral skeleton: Rapid Accretion Deposits are found to form on average about 4.5 times faster than Thickening Deposits. The method opens up new horizons in the study of biocarbonate formation because it holds the potential to observe growth of calcareous structures such as skeletons, shells, tests, spines formed by a wide range of organisms under essentially unperturbed physiological conditions.
The snakelike chain character of unstructured RNA.

PubMed

Jacobson, David R; McIntosh, Dustin B; Saleh, Omar A

2013-12-03

In the absence of base-pairing and tertiary structure, ribonucleic acid (RNA) assumes a random-walk conformation, modulated by the electrostatic self-repulsion of the charged, flexible backbone. This behavior is often modeled as a Kratky-Porod "wormlike chain" (WLC) with a Barrat-Joanny scale-dependent persistence length. In this study we report measurements of the end-to-end extension of poly(U) RNA under 0.1 to 10 pN applied force and observe two distinct elastic-response regimes: a low-force, power-law regime characteristic of a chain of swollen blobs on long length scales and a high-force, salt-valence-dependent regime consistent with ion-stabilized crumpling on short length scales. This short-scale structure is additionally supported by force- and salt-dependent quantification of the RNA ion atmosphere composition, which shows that ions are liberated under stretching; the number of ions liberated increases with increasing bulk salt concentration. Both this result and the observation of two elastic-response regimes directly contradict the WLC model, which predicts a single elastic regime across all forces and, when accounting for scale-dependent persistence length, the opposite trend in ion release with salt concentration. We conclude that RNA is better described as a "snakelike chain," characterized by smooth bending on long length scales and ion-stabilized crumpling on short length scales. In monovalent salt, these two regimes are separated by a characteristic length that scales with the Debye screening length, highlighting the determining importance of electrostatics in RNA conformation. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Gravidity is not associated with telomere length in a biracial cohort of middle-aged women: The Coronary Artery Risk Development in Young Adults (CARDIA) study

PubMed Central

Puterman, Eli; Gunderson, Erica P.; Chan, Cheeling; Hou, Lifang; Carnethon, Mercedes

2017-01-01

Objective Having experienced 2–3 births is associated with reduced mortality versus women with <2 or ≥4 births. The effect of 2–3 births on lifespan may be associated with delayed cellular aging. We hypothesized telomere length, a marker of cellular aging, would be longer in women who had 2–3 pregnancies. Methods Leukocyte telomere length was measured using quantitative real-time polymerase chain reaction in 620 women in CARDIA at the year 15 and 20 exams, expressed as the ratio of telomere repeat copy number to single-copy gene copy number (T/S). Number of pregnancies at the time of telomere length measurement was obtained (mean age = 41±0.1 years, average gravidity = 2.64±0.1 pregnancies). Participants were divided into 4 groups by number of pregnancies: 0, 1, 2–3, and ≥4, to test for differences in telomere length by gravidity group. Results The mean and SD for telomere length was 0.98 ± 0.20 T/S in the whole cohort. There were no differences in mean telomere length between groups; 0.98±0.02 T/S in women with 0 pregnancies, 1.01±0.02 T/S in women with 1 pregnancy, 0.97±0.01 T/S in women with 2–3 pregnancies, and 0.99±0.02 T/S in women with ≥4 pregnancies (p = 0.51). We defined high-risk (shorter) telomere length as ≤25th percentile, and low-risk (longer) telomere length as ≥75 percentile. There were no differences in the prevalence of high-risk or low-risk telomere length between gravidity groups. Conclusions Gravidity was not associated with telomere length in early middle age; the protective association of 2–3 births may act through other mechanisms. PMID:29049398

Gravidity is not associated with telomere length in a biracial cohort of middle-aged women: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

PubMed

Lane-Cordova, Abbi D; Puterman, Eli; Gunderson, Erica P; Chan, Cheeling; Hou, Lifang; Carnethon, Mercedes

2017-01-01

Having experienced 2-3 births is associated with reduced mortality versus women with <2 or ≥4 births. The effect of 2-3 births on lifespan may be associated with delayed cellular aging. We hypothesized telomere length, a marker of cellular aging, would be longer in women who had 2-3 pregnancies. Leukocyte telomere length was measured using quantitative real-time polymerase chain reaction in 620 women in CARDIA at the year 15 and 20 exams, expressed as the ratio of telomere repeat copy number to single-copy gene copy number (T/S). Number of pregnancies at the time of telomere length measurement was obtained (mean age = 41±0.1 years, average gravidity = 2.64±0.1 pregnancies). Participants were divided into 4 groups by number of pregnancies: 0, 1, 2-3, and ≥4, to test for differences in telomere length by gravidity group. The mean and SD for telomere length was 0.98 ± 0.20 T/S in the whole cohort. There were no differences in mean telomere length between groups; 0.98±0.02 T/S in women with 0 pregnancies, 1.01±0.02 T/S in women with 1 pregnancy, 0.97±0.01 T/S in women with 2-3 pregnancies, and 0.99±0.02 T/S in women with ≥4 pregnancies (p = 0.51). We defined high-risk (shorter) telomere length as ≤25th percentile, and low-risk (longer) telomere length as ≥75 percentile. There were no differences in the prevalence of high-risk or low-risk telomere length between gravidity groups. Gravidity was not associated with telomere length in early middle age; the protective association of 2-3 births may act through other mechanisms.
Length-scale dependent mechanical properties of Al-Cu eutectic alloy: Molecular dynamics based model and its experimental verification

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

Tiwary, C. S., E-mail: cst.iisc@gmail.com; Chattopadhyay, K.; Chakraborty, S.

2014-05-28

This paper attempts to gain an understanding of the effect of lamellar length scale on the mechanical properties of two-phase metal-intermetallic eutectic structure. We first develop a molecular dynamics model for the in-situ grown eutectic interface followed by a model of deformation of Al-Al{sub 2}Cu lamellar eutectic. Leveraging the insights obtained from the simulation on the behaviour of dislocations at different length scales of the eutectic, we present and explain the experimental results on Al-Al{sub 2}Cu eutectic with various different lamellar spacing. The physics behind the mechanism is further quantified with help of atomic level energy model for different lengthmore » scale as well as different strain. An atomic level energy partitioning of the lamellae and the interface regions reveals that the energy of the lamellae core are accumulated more due to dislocations irrespective of the length-scale. Whereas the energy of the interface is accumulated more due to dislocations when the length-scale is smaller, but the trend is reversed when the length-scale is large beyond a critical size of about 80 nm.« less
Taming active turbulence with patterned soft interfaces.

PubMed

Guillamat, P; Ignés-Mullol, J; Sagués, F

2017-09-15

Active matter embraces systems that self-organize at different length and time scales, often exhibiting turbulent flows apparently deprived of spatiotemporal coherence. Here, we use a layer of a tubulin-based active gel to demonstrate that the geometry of active flows is determined by a single length scale, which we reveal in the exponential distribution of vortex sizes of active turbulence. Our experiments demonstrate that the same length scale reemerges as a cutoff for a scale-free power law distribution of swirling laminar flows when the material evolves in contact with a lattice of circular domains. The observed prevalence of this active length scale can be understood by considering the role of the topological defects that form during the spontaneous folding of microtubule bundles. These results demonstrate an unexpected strategy for active systems to adapt to external stimuli, and provide with a handle to probe the existence of intrinsic length and time scales.Active nematics consist of self-driven components that develop orientational order and turbulent flow. Here Guillamat et al. investigate an active nematic constrained in a quasi-2D geometrical setup and show that there exists an intrinsic length scale that determines the geometry in all forcing regimes.
Air Pollution Stress and the Aging Phenotype: The Telomere Connection.

PubMed

Martens, Dries S; Nawrot, Tim S

2016-09-01

Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution in biological aging. Hallmarks of aging can be grouped into three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. At birth, the initial telomere length of a person is largely determined by environmental factors. Telomere length shortens with each cell division and exposure to air pollution as well as low residential greens space exposure is associated with shorter telomere length. Recent studies show that the estimated effects of particulate air pollution exposure on the telomere mitochondrial axis of aging may play an important role in chronic health effects of air pollution. The exposome encompasses all exposures over an entire life. As telomeres can be considered as the cellular memories of exposure to oxidative stress and inflammation, telomere maintenance may be a proxy for assessing the "exposome". If telomeres are causally related to the aging phenotype and environmental air pollution is an important determinant of telomere length, this might provide new avenues for future preventive strategies.
Evolution of time-keeping mechanisms: early emergence and adaptation to photoperiod

PubMed Central

Hut, R. A.; Beersma, D. G. M.

2011-01-01

Virtually all species have developed cellular oscillations and mechanisms that synchronize these cellular oscillations to environmental cycles. Such environmental cycles in biotic (e.g. food availability and predation risk) or abiotic (e.g. temperature and light) factors may occur on a daily, annual or tidal time scale. Internal timing mechanisms may facilitate behavioural or physiological adaptation to such changes in environmental conditions. These timing mechanisms commonly involve an internal molecular oscillator (a ‘clock’) that is synchronized (‘entrained’) to the environmental cycle by receptor mechanisms responding to relevant environmental signals (‘Zeitgeber’, i.e. German for time-giver). To understand the evolution of such timing mechanisms, we have to understand the mechanisms leading to selective advantage. Although major advances have been made in our understanding of the physiological and molecular mechanisms driving internal cycles (proximate questions), studies identifying mechanisms of natural selection on clock systems (ultimate questions) are rather limited. Here, we discuss the selective advantage of a circadian system and how its adaptation to day length variation may have a functional role in optimizing seasonal timing. We discuss various cases where selective advantages of circadian timing mechanisms have been shown and cases where temporarily loss of circadian timing may cause selective advantage. We suggest an explanation for why a circadian timing system has emerged in primitive life forms like cyanobacteria and we evaluate a possible molecular mechanism that enabled these bacteria to adapt to seasonal variation in day length. We further discuss how the role of the circadian system in photoperiodic time measurement may explain differential selection pressures on circadian period when species are exposed to changing climatic conditions (e.g. global warming) or when they expand their geographical range to different latitudes or altitudes. PMID:21690131
Supergranulation, a convective phenomenon

NASA Astrophysics Data System (ADS)

Udayashankar, Paniveni

2015-08-01

Observation of the Solar photosphere through high resolution instruments have long indicated that the surface of the Sun is not a tranquil, featureless surface but is beset with a granular appearance. These cellular velocity patterns are a visible manifestation of sub- photospheric convection currents which contribute substantially to the outward transport of energy from the deeper layers, thus maintaining the energy balance of the Sun as a whole.Convection is the chief mode of transport in the outer layers of all cool stars such as the Sun (Noyes,1982). Convection zone of thickness 30% of the Solar radius lies in the sub-photospheric layers of the Sun. Convection is revealed on four scales. On the scale of 1000 km, it is granulation and on the scale of 8-10 arcsec, it is Mesogranulation. The next hierarchial scale of convection ,Supergranules are in the range of 30-40 arcsec. The largest reported manifestation of convection in the Sun are ‘Giant Cells’or ‘Giant Granules’, on a typical length scale of about 108 m.'Supergranules' is caused by the turbulence that extends deep into the convection zone. They have a typical lifetime of about 20hr with spicules marking their boundaries. Gas rises in the centre of the supergranules and then spreads out towards the boundary and descends.Broadly speaking supergranules are characterized by the three parameters namely the length L, the lifetime T and the horizontal flow velocity vh . The interrelationships amongst these parameters can shed light on the underlying convective processes and are in agreement with the Kolmogorov theory of turbulence as applied to large scale solar convection (Krishan et al .2002 ; Paniveni et. al. 2004, 2005, 2010).References:1) Noyes, R.W., The Sun, Our Star (Harvard University Press, 1982)2) Krishan, V., Paniveni U., Singh , J., Srikanth R., 2002, MNRAS, 334/1,2303) Paniveni , U., Krishan, V., Singh, J., Srikanth, R., 2004, MNRAS, 347, 1279-12814) Paniveni , U., Krishan, V., Singh, J., Srikanth, R., 2005, Solar Physics, 231, 1-105) Paniveni , U., Krishan, V., Singh, J., Srikanth, R., 2010, MNRAS, 402, Issue 1, 424-428
Supergranular Convection

NASA Astrophysics Data System (ADS)

Udayashankar, Paniveni

2015-12-01

Observation of the Solar photosphere through high resolution instruments have long indicated that the surface of the Sun is not a tranquil, featureless surface but is beset with a granular appearance. These cellular velocity patterns are a visible manifestation of sub- photospheric convection currents which contribute substantially to the outward transport of energy from the deeper layers, thus maintaining the energy balance of the Sun as a whole.Convection is the chief mode of transport in the outer layers of all cool stars such as the Sun (Noyes,1982). Convection zone of thickness 30% of the Solar radius lies in the sub-photospheric layers of the Sun. Here the opacity is so large that heat flux transport is mainly by convection rather than by photon diffusion. Convection is revealed on four scales. On the scale of 1000 km, it is granulation and on the scale of 8-10 arcsec, it is Mesogranulation. The next hierarchial scale of convection , Supergranules are in the range of 30-40 arcsec. The largest reported manifestation of convection in the Sun are ‘Giant Cells’or ‘Giant Granules’, on a typical length scale of about 108 m.'Supergranules' is caused by the turbulence that extends deep into the convection zone. They have a typical lifetime of about 20hr with spicules marking their boundaries. Gas rises in the centre of the supergranules and then spreads out towards the boundary and descends.Broadly speaking supergranules are characterized by the three parameters namely the length L, the lifetime T and the horizontal flow velocity vh . The interrelationships amongst these parameters can shed light on the underlying convective processes and are in agreement with the Kolmogorov theory of turbulence as applied to large scale solar convection (Krishan et al .2002 ; Paniveni et. al. 2004, 2005, 2010).References:1) Noyes, R.W., The Sun, Our Star (Harvard University Press, 1982)2) Krishan, V., Paniveni U., Singh , J., Srikanth R., 2002, MNRAS, 334/1,2303) Paniveni , U., Krishan, V., Singh, J., Srikanth, R., 2004, MNRAS, 347, 1279-12814) Paniveni , U., Krishan, V., Singh, J., Srikanth, R., 2005, Solar Physics, 231, 1-105) Paniveni , U., Krishan, V., Singh, J., Srikanth, R., 2010, MNRAS, 402, Issue 1, 424-428
Association between telomere length and the risk of colorectal cancer: a meta-analysis of observational studies.

PubMed

Naing, Cho; Aung, Kyan; Lai, Pei Kuan; Mak, Joon Wah

2017-01-05

Human chromosomes are capped and stabilized by telomeres. Telomere length regulates a 'cellular mitotic clock' that defines the number of cell divisions and hence, cellular life span. This study aimed to synthesize the evidence on the association between peripheral blood leucocytes (PBL) telomere length and the risk of colorectal cancer (CRC). We searched relevant studies in electronic databases. When two or more observational studies reported the same outcome measures, we performed pooled analysis. All the analyses were performed on PBL using PCR. The odds ratio (OR) and its 95% confidence interval (CI) were used to assess the strength of association. Seven studies (with 8 datasets) were included in this meta-analysis; 3 prospective studies, 3 retrospective studies and 1 study with a separate prospective and retrospective designs. The pooled analysis of 4 prospective studies (summary OR 1.01, 95% CI: 0.77-1.34, I 2 :30%) and 4 retrospective studies (summary OR 1.65, 95% CI: 0.96-2.83, I 2 :96%) showed no relationship between PBL telomere length and the CRC risk. A subgroup analysis of 2 prospective studies exclusively on females also showed no association between PBL telomere length and the CRC risk (summary OR, 1.17, 95% CI:0.72-1.91, I 2 :57%). The current analysis is insufficient to provide evidence on the relationship between PBL telomere length and the risk of CRC. Findings suggest that there may be a complex relationship between PBL telomere length and the CRC risk or discrepancy between genetics, age of patients and clinical studies. Future well powered, large prospective studies on the relationship between telomere length and the risk of CRC, and the investigations of the biologic mechanisms are recommended.
Performance of Renormalization Group Algebraic Turbulence Model on Boundary Layer Transition Simulation

NASA Technical Reports Server (NTRS)

Ahn, Kyung H.

1994-01-01

The RNG-based algebraic turbulence model, with a new method of solving the cubic equation and applying new length scales, is introduced. An analysis is made of the RNG length scale which was previously reported and the resulting eddy viscosity is compared with those from other algebraic turbulence models. Subsequently, a new length scale is introduced which actually uses the two previous RNG length scales in a systematic way to improve the model performance. The performance of the present RNG model is demonstrated by simulating the boundary layer flow over a flat plate and the flow over an airfoil.
Current employment status, occupational category, occupational hazard exposure and job stress in relation to telomere length: the Multiethnic Study of Atherosclerosis (MESA).

PubMed

Fujishiro, Kaori; Diez-Roux, Ana V; Landsbergis, Paul A; Jenny, Nancy Swords; Seeman, Teresa

2013-08-01

Telomere length has been proposed as a biomarker of cell senescence, which is associated with a wide array of adverse health outcomes. While work is a major determinant of health, few studies have investigated the association of telomere length with various dimensions of occupation. Accelerated cellular aging could be a common pathway linking occupational exposure to several health outcomes. Leukocyte telomere length was assessed using quantitative PCR in a community-based sample of 981 individuals (age: 45-84 years). Questionnaires were used to collect information on current employment status, current or main occupation before retirement and job strain. The Occupational Resource Network (O*NET) database was linked to the questionnaire data to create five exposure measures: physical activity on the job, physical hazard exposure, interpersonal stressors, job control and job demands. Linear regression was used to estimate associations of occupational characteristics with telomere lengths after adjustment for age, sex, race, socioeconomic position and several behavioural risk factors. There were no mean differences in telomere lengths across current employment status, occupational category, job strain categories or levels of most O*NET exposure measures. There was also no evidence that being in lower status occupational categories or being exposed to higher levels of adverse physical or psychosocial exposures accelerated the association between age and telomere shortening. Cellular aging as reflected by shorter telomeres does not appear to be an important pathway linking occupation to various health outcomes.
The large-scale organization of metabolic networks

NASA Astrophysics Data System (ADS)

Jeong, H.; Tombor, B.; Albert, R.; Oltvai, Z. N.; Barabási, A.-L.

2000-10-01

In a cell or microorganism, the processes that generate mass, energy, information transfer and cell-fate specification are seamlessly integrated through a complex network of cellular constituents and reactions. However, despite the key role of these networks in sustaining cellular functions, their large-scale structure is essentially unknown. Here we present a systematic comparative mathematical analysis of the metabolic networks of 43 organisms representing all three domains of life. We show that, despite significant variation in their individual constituents and pathways, these metabolic networks have the same topological scaling properties and show striking similarities to the inherent organization of complex non-biological systems. This may indicate that metabolic organization is not only identical for all living organisms, but also complies with the design principles of robust and error-tolerant scale-free networks, and may represent a common blueprint for the large-scale organization of interactions among all cellular constituents.
Empirical scaling of the length of the longest increasing subsequences of random walks

NASA Astrophysics Data System (ADS)

Mendonça, J. Ricardo G.

2017-02-01

We provide Monte Carlo estimates of the scaling of the length L n of the longest increasing subsequences of n-step random walks for several different distributions of step lengths, short and heavy-tailed. Our simulations indicate that, barring possible logarithmic corrections, {{L}n}∼ {{n}θ} with the leading scaling exponent 0.60≲ θ ≲ 0.69 for the heavy-tailed distributions of step lengths examined, with values increasing as the distribution becomes more heavy-tailed, and θ ≃ 0.57 for distributions of finite variance, irrespective of the particular distribution. The results are consistent with existing rigorous bounds for θ, although in a somewhat surprising manner. For random walks with step lengths of finite variance, we conjecture that the correct asymptotic behavior of L n is given by \\sqrt{n}\\ln n , and also propose the form for the subleading asymptotics. The distribution of L n was found to follow a simple scaling form with scaling functions that vary with θ. Accordingly, when the step lengths are of finite variance they seem to be universal. The nature of this scaling remains unclear, since we lack a working model, microscopic or hydrodynamic, for the behavior of the length of the longest increasing subsequences of random walks.
Computational Characterization of Type I collagen-based Extra-cellular Matrix

NASA Astrophysics Data System (ADS)

Liang, Long; Jones, Christopher Allen Rucksack; Lin, Daniel; Jiao, Yang; Sun, Bo

2015-03-01

A model of extracellular matrix (ECM) of collagen fibers has been built, in which cells could communicate with distant partners via fiber-mediated long-range-transmitted stress states. The ECM is modeled as a spring-like fiber network derived from skeletonized confocal microscopy data. Different local and global perturbations have been performed on the network, each followed by an optimized global Monte-Carlo (MC) energy minimization leading to the deformed network in response to the perturbations. In the optimization, a highly efficient local energy update procedure is employed and force-directed MC moves are used, which results in a convergence to the energy minimum state 20 times faster than the commonly used random displacement trial moves in MC. Further analysis and visualization of the distribution and correlation of the resulting force network reveal that local perturbations can give rise to global impacts: the force chains formed with a linear extent much further than the characteristic length scale associated with the perturbation sites and average fiber length. This behavior provides a strong evidence for our hypothesis of fiber-mediated long-range force transmission in ECM networks and the resulting long-range cell-cell mechanical signaling. ASU Seed Grant.
Cellular responses to environmental DNA damage

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

Not Available

This volume contains the proceedings of the conference entitled Cellular Responses to Environmental DNA Damage held in Banff,Alberta December 1--6, 1991. The conference addresses various aspects of DNA repair in sessions titled DNA repair; Basic Mechanisms; Lesions; Systems; Inducible Responses; Mutagenesis; Human Population Response Heterogeneity; Intragenomic DNA Repair Heterogeneity; DNA Repair Gene Cloning; Aging; Human Genetic Disease; and Carcinogenesis. Individual papers are represented as abstracts of about one page in length.
Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder.

PubMed

Boks, Marco P; van Mierlo, Hans C; Rutten, Bart P F; Radstake, Timothy R D J; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C; Vinkers, Christiaan H; Broen, Jasper C A; Vermetten, Eric

2015-01-01

Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not confound the results. Overall, in this longitudinal study of military personnel deployed to Afghanistan we show an acceleration of ageing by trauma. However, development of PTSD symptoms was associated with telomere lengthening and reversed epigenetic ageing. These findings warrant further study of a perhaps dysfunctional compensatory cellular ageing reversal in PTSD. Copyright © 2014 Elsevier Ltd. All rights reserved.
Atomic Detail Visualization of Photosynthetic Membranes with GPU-Accelerated Ray Tracing

PubMed Central

Vandivort, Kirby L.; Barragan, Angela; Singharoy, Abhishek; Teo, Ivan; Ribeiro, João V.; Isralewitz, Barry; Liu, Bo; Goh, Boon Chong; Phillips, James C.; MacGregor-Chatwin, Craig; Johnson, Matthew P.; Kourkoutis, Lena F.; Hunter, C. Neil

2016-01-01

The cellular process responsible for providing energy for most life on Earth, namely photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. We present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. We describe the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers. PMID:27274603
Competitive intransitivity promotes species coexistence.

PubMed

Laird, Robert A; Schamp, Brandon S

2006-08-01

Using a spatially explicit cellular automaton model with local competition, we investigate the potential for varied levels of competitive intransitivity (i.e., nonhierarchical competition) to promote species coexistence. As predicted, on average, increased levels of intransitivity result in more sustained coexistence within simulated communities, although the outcome of competition also becomes increasingly unpredictable. Interestingly, even a moderate degree of intransitivity within a community can promote coexistence, in terms of both the length of time until the first competitive exclusion and the number of species remaining in the community after 500 simulated generations. These results suggest that modest levels of intransitivity in nature, such as those that are thought to be characteristic of plant communities, can contribute to coexistence and, therefore, community-scale biodiversity. We explore a potential connection between competitive intransitivity and neutral theory, whereby competitive intransitivity may represent an important mechanism for "ecological equivalence."
Electrospun nanofibres to mimic natural hierarchical structure of tissues: application in musculoskeletal regeneration.

PubMed

Sankar, Sharanya; Sharma, Chandra S; Rath, Subha N; Ramakrishna, Seeram

2018-01-01

Biomimetic scaffolds mimicking the natural hierarchical structure of tissues have recently attracted the interest of researchers and provide a promising strategy to resemble the nonhomogeneous property of tissues. This review provides an overview of the various hierarchical length scales in the native tissues of the musculoskeletal system. It further focuses on electrospinning as a technique to mimic the tissue structures with specific emphasis on bone. The effect of cellular alignment, infiltration, vascularisation, and differentiation in these nanostructures has also been discussed. An outline of the various additive manufacturing techniques in combination with electrospinning has been elaborated. The review concludes with the challenges and future directions to understand the intricacies of bottom-up approach to engineer the systems at a macroscale. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Robust nanopatterning by laser-induced dewetting of metal nanofilms.

PubMed

Favazza, Christopher; Kalyanaraman, Ramki; Sureshkumar, Radhakrishna

2006-08-28

We have observed nanopattern formation with robust and controllable spatial ordering by laser-induced dewetting in nanoscopic metal films. Pattern evolution in Co film of thickness 1≤h≤8 nm on SiO(2) was achieved under multiple pulse irradiation using a 9 ns pulse laser. Dewetting leads to the formation of cellular patterns which evolve into polygons that eventually break up into nanoparticles with unimodal size distribution and short range ordering in nearest neighbour spacing R. Spatial ordering was attributed to a hydrodynamic thin film instability and resulted in a predictable variation of R and particle diameter D with h. The length scales R and D were found to be independent of the laser energy. These results suggest that spatially ordered metal nanoparticles can be robustly assembled by laser-induced dewetting.
Tip vortices in the actuator line model

NASA Astrophysics Data System (ADS)

Martinez, Luis; Meneveau, Charles

2017-11-01

The actuator line model (ALM) is a widely used tool to represent the wind turbine blades in computational fluid dynamics without the need to resolve the full geometry of the blades. The ALM can be optimized to represent the `correct' aerodynamics of the blades by choosing an appropriate smearing length scale ɛ. This appropriate length scale creates a tip vortex which induces a downwash near the tip of the blade. A theoretical frame-work is used to establish a solution to the induced velocity created by a tip vortex as a function of the smearing length scale ɛ. A correction is presented which allows the use of a non-optimal smearing length scale but still provides the downwash which would be induced using the optimal length scale. Thanks to the National Science Foundation (NSF) who provided financial support for this research via Grants IGERT 0801471, IIA-1243482 (the WINDINSPIRE project) and ECCS-1230788.

Multi-scale Imaging of Cellular and Sub-cellular Structures using Scanning Probe Recognition Microscopy.

NASA Astrophysics Data System (ADS)

Chen, Q.; Rice, A. F.

2005-03-01

Scanning Probe Recognition Microscopy is a new scanning probe capability under development within our group to reliably return to and directly interact with a specific nanobiological feature of interest. In previous work, we have successfully recognized and classified tubular versus globular biological objects from experimental atomic force microscope images using a method based on normalized central moments [ref. 1]. In this paper we extend this work to include recognition schemes appropriate for cellular and sub-cellular structures. Globular cells containing tubular actin filaments are under investigation. Thus there are differences in external/internal shapes and scales. Continuous Wavelet Transform with a differential Gaussian mother wavelet is employed for multi- scale analysis. [ref. 1] Q. Chen, V. Ayres and L. Udpa, ``Biological Investigation Using Scanning Probe Recognition Microscopy,'' Proceedings 3rd IEEE Conference on Nanotechnology, vol. 2, p 863-865 (2003).
Nature vs nurture: interplay between the genetic control of telomere length and environmental factors.

PubMed

Harari, Yaniv; Romano, Gal-Hagit; Ungar, Lior; Kupiec, Martin

2013-11-15

Telomeres are nucleoprotein structures that cap the ends of the linear eukaryotic chromosomes, thus protecting their stability and integrity. They play important roles in DNA replication and repair and are central to our understanding of aging and cancer development. In rapidly dividing cells, telomere length is maintained by the activity of telomerase. About 400 TLM (telomere length maintenance) genes have been identified in yeast, as participants of an intricate homeostasis network that keeps telomere length constant. Two papers have recently shown that despite this extremely complex control, telomere length can be manipulated by external stimuli. These results have profound implications for our understanding of cellular homeostatic systems in general and of telomere length maintenance in particular. In addition, they point to the possibility of developing aging and cancer therapies based on telomere length manipulation.
Modeling of Ceiling Fire Spread and Thermal Radiation.

DTIC Science & Technology

1981-10-01

under a PMMA ceiling and flame lengths under an inert ceiling are found to be in reasonable agreement with full-scale behavior. Although fire spread...5 3 Flame Lengths under Full-Scale Ceilings 12 4 Correlation of Flame Length under Inert Ceilings 16 5 Correlation of Flame Length under No 234 Model...Ceilings 17 6 Correlation of Flame Length under No B8811 Model Ceilings 18 7 Correlation of Flame Length under No. 223 Model Ceilings 19 8
Natural Length Scales Shape Liquid Phase Continuity in Unsaturated Flows

NASA Astrophysics Data System (ADS)

Assouline, S.; Lehmann, P. G.; Or, D.

2015-12-01

Unsaturated flows supporting soil evaporation and internal drainage play an important role in various hydrologic and climatic processes manifested at a wide range of scales. We study inherent natural length scales that govern these flow processes and constrain the spatial range of their representation by continuum models. These inherent length scales reflect interactions between intrinsic porous medium properties that affect liquid phase continuity, and the interplay among forces that drive and resist unsaturated flow. We have defined an intrinsic length scale for hydraulic continuity based on pore size distribution that controls soil evaporation dynamics (i.e., stage 1 to stage 2 transition). This simple metric may be used to delineate upper bounds for regional evaporative losses or the depth of soil-atmosphere interactions (in the absence of plants). A similar length scale governs the dynamics of internal redistribution towards attainment of field capacity, again through its effect on hydraulic continuity in the draining porous medium. The study provides a framework for guiding numerical and mathematical models for capillary flows across different scales considering the necessary conditions for coexistence of stationarity (REV), hydraulic continuity and intrinsic capillary gradients.
Long term effects of radiation exposure on telomere lengths of leukocytes and its associated biomarkers among atomic-bomb survivors

PubMed Central

Lustig, Ana; Shterev, Ivo; Geyer, Susan; Shi, Alvin; Hu, Yiqun; Morishita, Yukari; Nagamura, Hiroko; Sasaki, Keiko; Maki, Mayumi; Hayashi, Ikue; Furukawa, Kyoji; Yoshida, Kengo; Kajimura, Junko; Kyoizumi, Seishi; Kusunoki, Yoichiro; Ohishi, Waka; Nakachi, Kei; Weng, Nan-ping; Hayashi, Tomonori

2016-01-01

Ionizing radiation (IR) is a major source of cellular damage and the immediate cellular response to IR has been well characterized. But the long-term impact of IR on cell function and its relationship with aging are not known. Here, we examined the IR effects on telomere length and other biomarkers 50 to 68 years post-exposure (two time points per person) in survivors of the atomic bombing at Hiroshima during WWII. We found that telomere length of leukocytes was inversely correlated with the dose of IR (p=0.008), and this effect was primarily found in survivors who were exposed at younger ages; specifically those <12 years old (p=0.0004). Although a dose-related retardation of telomere shortening with age was observed in the cross-sectional data, longitudinal follow-up after 11 years did not show IR exposure-related alteration of the rate of telomere shortening with age. In addition, IR diminished the associations between telomere length and selected aging biomarkers that were observed in survivors with no dose. These included uric acid metabolism, cytokines, and blood T cell counts. These findings showed long-lasting detrimental effects of IR on telomere length of leukocytes in both dose- and age-at-exposure dependent manner, and on alterations of biomarkers with aging. PMID:27102155
Label-free imaging of the native, living cellular nanoarchitecture using partial-wave spectroscopic microscopy

PubMed Central

Almassalha, Luay M.; Bauer, Greta M.; Chandler, John E.; Gladstein, Scott; Cherkezyan, Lusik; Stypula-Cyrus, Yolanda; Weinberg, Samuel; Zhang, Di; Thusgaard Ruhoff, Peder; Roy, Hemant K.; Subramanian, Hariharan; Chandel, Navdeep S.; Szleifer, Igal; Backman, Vadim

2016-01-01

The organization of chromatin is a regulator of molecular processes including transcription, replication, and DNA repair. The structures within chromatin that regulate these processes span from the nucleosomal (10-nm) to the chromosomal (>200-nm) levels, with little known about the dynamics of chromatin structure between these scales due to a lack of quantitative imaging technique in live cells. Previous work using partial-wave spectroscopic (PWS) microscopy, a quantitative imaging technique with sensitivity to macromolecular organization between 20 and 200 nm, has shown that transformation of chromatin at these length scales is a fundamental event during carcinogenesis. As the dynamics of chromatin likely play a critical regulatory role in cellular function, it is critical to develop live-cell imaging techniques that can probe the real-time temporal behavior of the chromatin nanoarchitecture. Therefore, we developed a live-cell PWS technique that allows high-throughput, label-free study of the causal relationship between nanoscale organization and molecular function in real time. In this work, we use live-cell PWS to study the change in chromatin structure due to DNA damage and expand on the link between metabolic function and the structure of higher-order chromatin. In particular, we studied the temporal changes to chromatin during UV light exposure, show that live-cell DNA-binding dyes induce damage to chromatin within seconds, and demonstrate a direct link between higher-order chromatin structure and mitochondrial membrane potential. Because biological function is tightly paired with structure, live-cell PWS is a powerful tool to study the nanoscale structure–function relationship in live cells. PMID:27702891
A novel role for the condensin II complex in cellular senescence.

PubMed

Yokoyama, Yuhki; Zhu, Hengrui; Zhang, Rugang; Noma, Ken-ichi

2015-01-01

Although cellular senescence is accompanied by global alterations in genome architecture, how the genome is restructured during the senescent processes is not well understood. Here, we show that the hCAP-H2 subunit of the condensin II complex exists as either a full-length protein or an N-terminus truncated variant (ΔN). While the full-length hCAP-H2 associates with mitotic chromosomes, the ΔN variant exists as an insoluble nuclear structure. When overexpressed, both hCAP-H2 isoforms assemble this nuclear architecture and induce senescence-associated heterochromatic foci (SAHF). The hCAP-H2ΔN protein accumulates as cells approach senescence, and hCAP-H2 knockdown inhibits oncogene-induced senescence. This study identifies a novel mechanism whereby condensin drives senescence via nuclear/genomic reorganization.
Proteome-scale human interactomics

PubMed Central

Luck, Katja; Sheynkman, Gloria M.; Zhang, Ivy; Vidal, Marc

2017-01-01

Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome-scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life. PMID:28284537
Failure analysis of fuel cell electrodes using three-dimensional multi-length scale X-ray computed tomography

NASA Astrophysics Data System (ADS)

Pokhrel, A.; El Hannach, M.; Orfino, F. P.; Dutta, M.; Kjeang, E.

2016-10-01

X-ray computed tomography (XCT), a non-destructive technique, is proposed for three-dimensional, multi-length scale characterization of complex failure modes in fuel cell electrodes. Comparative tomography data sets are acquired for a conditioned beginning of life (BOL) and a degraded end of life (EOL) membrane electrode assembly subjected to cathode degradation by voltage cycling. Micro length scale analysis shows a five-fold increase in crack size and 57% thickness reduction in the EOL cathode catalyst layer, indicating widespread action of carbon corrosion. Complementary nano length scale analysis shows a significant reduction in porosity, increased pore size, and dramatically reduced effective diffusivity within the remaining porous structure of the catalyst layer at EOL. Collapsing of the structure is evident from the combination of thinning and reduced porosity, as uniquely determined by the multi-length scale approach. Additionally, a novel image processing based technique developed for nano scale segregation of pore, ionomer, and Pt/C dominated voxels shows an increase in ionomer volume fraction, Pt/C agglomerates, and severe carbon corrosion at the catalyst layer/membrane interface at EOL. In summary, XCT based multi-length scale analysis enables detailed information needed for comprehensive understanding of the complex failure modes observed in fuel cell electrodes.
Cellular senescence in the Penna model of aging

NASA Astrophysics Data System (ADS)

Periwal, Avikar

2013-11-01

Cellular senescence is thought to play a major role in age-related diseases, which cause nearly 67% of all human deaths worldwide. Recent research in mice showed that exercising mice had higher levels of telomerase, an enzyme that helps maintain telomere length, than nonexercising mice. A commonly used model for biological aging was proposed by Penna. I propose a modification of the Penna model that incorporates cellular senescence and find an analytical steady-state solution following Coe, Mao, and Cates [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.89.288103 89, 288103 (2002)]. I find that models corresponding to delayed cellular senescence have younger populations that live longer. I fit the model to the United Kingdom's death distribution, which the original Penna model cannot do.
Formalizing Knowledge in Multi-Scale Agent-Based Simulations

PubMed Central

Somogyi, Endre; Sluka, James P.; Glazier, James A.

2017-01-01

Multi-scale, agent-based simulations of cellular and tissue biology are increasingly common. These simulations combine and integrate a range of components from different domains. Simulations continuously create, destroy and reorganize constituent elements causing their interactions to dynamically change. For example, the multi-cellular tissue development process coordinates molecular, cellular and tissue scale objects with biochemical, biomechanical, spatial and behavioral processes to form a dynamic network. Different domain specific languages can describe these components in isolation, but cannot describe their interactions. No current programming language is designed to represent in human readable and reusable form the domain specific knowledge contained in these components and interactions. We present a new hybrid programming language paradigm that naturally expresses the complex multi-scale objects and dynamic interactions in a unified way and allows domain knowledge to be captured, searched, formalized, extracted and reused. PMID:29338063
Formalizing Knowledge in Multi-Scale Agent-Based Simulations.

PubMed

Somogyi, Endre; Sluka, James P; Glazier, James A

2016-10-01

Multi-scale, agent-based simulations of cellular and tissue biology are increasingly common. These simulations combine and integrate a range of components from different domains. Simulations continuously create, destroy and reorganize constituent elements causing their interactions to dynamically change. For example, the multi-cellular tissue development process coordinates molecular, cellular and tissue scale objects with biochemical, biomechanical, spatial and behavioral processes to form a dynamic network. Different domain specific languages can describe these components in isolation, but cannot describe their interactions. No current programming language is designed to represent in human readable and reusable form the domain specific knowledge contained in these components and interactions. We present a new hybrid programming language paradigm that naturally expresses the complex multi-scale objects and dynamic interactions in a unified way and allows domain knowledge to be captured, searched, formalized, extracted and reused.
Engineering Cyanobacterial Cell Morphology for Enhanced Recovery and Processing of Biomass.

PubMed

Jordan, Adam; Chandler, Jenna; MacCready, Joshua S; Huang, Jingcheng; Osteryoung, Katherine W; Ducat, Daniel C

2017-05-01

Cyanobacteria are emerging as alternative crop species for the production of fuels, chemicals, and biomass. Yet, the success of these microbes depends on the development of cost-effective technologies that permit scaled cultivation and cell harvesting. Here, we investigate the feasibility of engineering cell morphology to improve biomass recovery and decrease energetic costs associated with lysing cyanobacterial cells. Specifically, we modify the levels of Min system proteins in Synechococcus elongatus PCC 7942. The Min system has established functions in controlling cell division by regulating the assembly of FtsZ, a tubulin-like protein required for defining the bacterial division plane. We show that altering the expression of two FtsZ-regulatory proteins, MinC and Cdv3, enables control over cell morphology by disrupting FtsZ localization and cell division without preventing continued cell growth. By varying the expression of these proteins, we can tune the lengths of cyanobacterial cells across a broad dynamic range, anywhere from an ∼20% increased length (relative to the wild type) to near-millimeter lengths. Highly elongated cells exhibit increased rates of sedimentation under low centrifugal forces or by gravity-assisted settling. Furthermore, hyperelongated cells are also more susceptible to lysis through the application of mild physical stress. Collectively, these results demonstrate a novel approach toward decreasing harvesting and processing costs associated with mass cyanobacterial cultivation by altering morphology at the cellular level. IMPORTANCE We show that the cell length of a model cyanobacterial species can be programmed by rationally manipulating the expression of protein factors that suppress cell division. In some instances, we can increase the size of these cells to near-millimeter lengths with this approach. The resulting elongated cells have favorable properties with regard to cell harvesting and lysis. Furthermore, cells treated in this manner continue to grow rapidly at time scales similar to those of uninduced controls. To our knowledge, this is the first reported example of engineering the cell morphology of cyanobacteria or algae to make them more compatible with downstream processing steps that present economic barriers to their use as alternative crop species. Therefore, our results are a promising proof-of-principle for the use of morphology engineering to increase the cost-effectiveness of the mass cultivation of cyanobacteria for various sustainability initiatives. Copyright © 2017 American Society for Microbiology.
F19. TELOMERE SHORTENING IN YOUNG PEOPLE WITH FIRST EPISODE PSYCHOSIS: A 12-MONTH FOLLOW-UP STUDY

PubMed Central

Fraguas, David; Recio, Sandra; Diaz-Caneja, Covadonga M; Blasco, Maria A; Moisés, Ana Carolina; Arango, Celso

2018-01-01

Abstract Background Short telomere length is a biomarker of cell oxidation and aging. Patients with first-episode psychosis (FEP) have been reported to have shorter telomeres than healthy controls (HC), suggesting that there is a premature and accelerated cellular aging in FEP. However, there are not data on longitudinal changes of telomere length in people with FEP relative to HC. We present preliminary results on 1-year longitudinal changes in peripheral blood mononuclear cells (PBMCs) telomere length and the proportion of PBMCs with short telomeres in young people with FEP and HC. Methods 16 young patients with FEP (43.8% female, mean age 17.9 years) and 21 young HC (61.9% female, mean age 16.6 years) were enrolled in the study. PBMCs telomere length and the proportion of PBMCs with short telomeres (i.e. <3kb) were determined using high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) at baseline (16 patients with FEP and 21 HC) and 12-month follow-up (4 patients with FEP and 4 HC). Results At baseline, we did not find significant differences in telomere length nor in proportion of PBMCs with short telomeres between FEP patients and HC. During the one-year follow-up, we found a significantly greater loss of telomere length (p=0.019; explained variance=69.7%) and a non-significantly trend for greater increase in the proportion of PBMCs with short telomeres (p=0.097; explained variance=45.5%) in patients with FEP than in HC. Discussion Telomere length changes during the first years of the illness can represent an early marker of accelerated cellular aging in patients with first-episode psychosis.
Λ(t)CDM model as a unified origin of holographic and agegraphic dark energy models

NASA Astrophysics Data System (ADS)

Chen, Yun; Zhu, Zong-Hong; Xu, Lixin; Alcaniz, J. S.

2011-04-01

Motivated by the fact that any nonzero Λ can introduce a length scale or a time scale into Einstein's theory, r=ct=3/|Λ|. Conversely, any cosmological length scale or time scale can introduce a Λ(t), Λ(t)=3/rΛ2(t)=3/(c2tΛ2(t)). In this Letter, we investigate the time varying Λ(t) corresponding to the length scales, including the Hubble horizon, the particle horizon and the future event horizon, and the time scales, including the age of the universe and the conformal time. It is found out that, in this scenario, the Λ(t)CDM model can be taken as the unified origin of the holographic and agegraphic dark energy models with interaction between the matter and the dark energy, where the interacting term is determined by Q=-ρ. We place observational constraints on the Λ(t)CDM models originating from different cosmological length scales and time scales with the recently compiled “Union2 compilation” which consists of 557 Type Ia supernovae (SNIa) covering a redshift range 0.015⩽z⩽1.4. In conclusion, an accelerating expansion universe can be derived in the cases taking the Hubble horizon, the future event horizon, the age of the universe and the conformal time as the length scale or the time scale.
Similarity and Scale Invariance of Velocity and Temperature Structure Functions within and above Dense Canopies

NASA Astrophysics Data System (ADS)

Ghannam, K.; Katul, G. G.; Chamecki, M.

2016-12-01

The scale-wise properties of turbulent flow statistics are conventionally quantified using the structure function D_ss (r)= <〖(Δs)〗^2 > describing velocity (s=u) or scalar (s=c) concentration increments Δs=s(x+r)-s(x) at various scales or separation distances r, where <.> is Reynolds averaging over coordinates of statistical homogeneity. For locally homogeneous and isotropic turbulence, the structure function can unfold statistical invariance of the form D_ss (βr)=β^p D_ss (r) as has been demonstrated by Kolmogorov's theory for the inertial subrange in the absence of intermittency corrections. For scales larger than inertial, scale invariance need not hold though universal scaling properties can still emerge provided an appropriate length and velocity scales are identified. One recent study on the structure function of the streamwise velocity (s=u) in smooth and rough wall-bounded flows argued that a logarithmic scaling of the form D_ss/(u_*^2 )=A+B ln(r/l_ɛ ) exists at any height z above the wall (or roughness elements), with,l_ɛ,〖 u〗_*, A and B being a dissipation length scale, the friction velocity, and two similarity constants to be determined. Whether this scaling is valid across all atmospheric stability regimes in the roughness sublayer (RSL) and the possible co-existence of length scales other than l_ɛ that collapse D_ss (r) for velocity and temperature frames the scope of this work. Using year-round field measurements within and above an Amazonian canopy, the work here explores the aforementioned scaling for the streamwise (s=u) and vertical velocity (s=w) components, along with its extension to active scalars (s=T, the air temperature) inside canopies and in the RSL above canopies. While the premise is that a length scale such as l_ɛ may serve as a master closure length scale for turbulent momentum and heat flux budgets, the role of the vorticity thickness, the Obukhov length, the adjustment length scale, and height z are also explored for various scale (or r) regimes. Because the RSL blends D_ss (r) from its form inside the canopy to its form in the well-studied atmospheric surface layer, the scaling laws derived here offer a new perspective on the thickness of the RSL for momentum and scalars and its variations with atmospheric stability.
Constant Stress Drop Fits Earthquake Surface Slip-Length Data

NASA Astrophysics Data System (ADS)

Shaw, B. E.

2011-12-01

Slip at the surface of the Earth provides a direct window into the earthquake source. A longstanding controversy surrounds the scaling of average surface slip with rupture length, which shows the puzzling feature of continuing to increase with rupture length for lengths many times the seismogenic width. Here we show that a more careful treatment of how ruptures transition from small circular ruptures to large rectangular ruptures combined with an assumption of constant stress drop provides a new scaling law for slip versus length which (1) does an excellent job fitting the data, (2) gives an explanation for the large crossover lengthscale at which slip begins to saturate, and (3) supports constant stress drop scaling which matches that seen for small earthquakes. We additionally discuss how the new scaling can be usefully applied to seismic hazard estimates.
Current employment status, occupational category, occupational hazard exposure, and job stress in relation to telomere length: The Multiethnic Study of Atherosclerosis (MESA)

PubMed Central

Fujishiro, Kaori; Diez-Roux, Ana V; Landsbergis, Paul; Jenny, Nancy Swords; Seeman, Teresa

2014-01-01

Objective Telomere length has been proposed as a biomarker of cell senescence, which is associated with a wide array of adverse health outcomes. While work is a major determinant of health, few studies have investigated the association of telomere length with various dimensions of occupation. Accelerated cellular aging could be a common pathway linking occupational exposure to several health outcomes. Methods Leukocyte telomere length was assessed using quantitative polymerase chain reaction (Q-PCR) in a community-based sample of 981 individuals (age: 45–84 years old). Questionnaires were used to collect information on current employment status, current or main occupation before retirement, and job strain. The O*NET (Occupational Resource Network) database was linked to the questionnaire data to create 5 exposure measures: physical activity on the job, physical hazard exposure, interpersonal stressors, job control, and job demands. Linear regression was used to estimate associations of occupational characteristics with telomere lengths after adjustment for age, sex, race, socioeconomic position, and several behavioral risk factors. Results There were no mean differences in telomere lengths across current employment status, occupational category, job strain categories or levels of most O*NET exposure measures. There was also no evidence that being in lower status occupational categories or being exposed to higher levels of adverse physical or psychosocial exposures accelerated the association between age and telomere shortening. Conclusions Cellular aging as reflected by shorter telomeres does not appear to be an important pathway linking occupation to various health outcomes. PMID:23686115
Proteome-Scale Human Interactomics.

PubMed

Luck, Katja; Sheynkman, Gloria M; Zhang, Ivy; Vidal, Marc

2017-05-01

Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life. Copyright © 2017 Elsevier Ltd. All rights reserved.
Driven, underdamped Frenkel-Kontorova model on a quasiperiodic substrate

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

Vanossi, A.; Ro''der, J.; Bishop, A. R.

2001-01-01

We consider the underdamped dynamics of a chain of atoms subject to a dc driving force and a quasiperiodic substrate potential. The system has three inherent length scales which we take to be mutually incommensurate. We find that when the length scales are related by the spiral mean (a cubic irrational) there exists a value of the interparticle interaction strength above which the static friction is zero. When the length scales are related by the golden mean (a quadratic irrational) the static friction is always nonzero. >From considerations based on the connection of this problem to standard map theory, wemore » postulate that zero static friction is generally possible for incommensurate ratios of the length scales involved. However, when the length scales are quadratic irrationals, or have some commensurability with each other, the static friction will be nonzero for all choices of interaction parameters. We also comment on the nature of the depinning mechanisms and the steady states achieved by the moving chain.« less

Brillouin Scattering of Picosecond Laser Pulses in Preformed, Short-Scale-Length Plasmas

NASA Astrophysics Data System (ADS)

Gaeris, A. C.; Fisher, Y.; Delettrez, J. A.; Meyerhofer, D. D.

1996-11-01

Brillouin scattering (BS) has been studied in short-scale-length, preformed plasmas. The backscattered and specularly reflected light resulting from the interaction of high-power picosecond pulses with preformed silicon plasmas has been measured. A first laser pulse forms a short-scale-length plasma -- without significant BS -- while a second delayed pulse interacts with an expanded, drifting underdense region of the plasma with density scale length (0 <= Ln <= 600 λ _L). The pulses are generated at λ L = 1054 nm, with intensities up to 10^16 W/cm^2. The backscattered light spectra, threshold intensities, and enhanced reflectivities have been determined for different plasma-density scale lengths and are compared to Liu, Rosenbluth, and White's(C. S. Liu, M. N. Rosenbluth, and R. B. White, Phys. Fluids 17, 1211 (1974).) WKB treatment of stimulated Brillouin scattering in inhomogeneous drifting plasmas. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460.
Experiments on integral length scale control in atmospheric boundary layer wind tunnel

NASA Astrophysics Data System (ADS)

Varshney, Kapil; Poddar, Kamal

2011-11-01

Accurate predictions of turbulent characteristics in the atmospheric boundary layer (ABL) depends on understanding the effects of surface roughness on the spatial distribution of velocity, turbulence intensity, and turbulence length scales. Simulation of the ABL characteristics have been performed in a short test section length wind tunnel to determine the appropriate length scale factor for modeling, which ensures correct aeroelastic behavior of structural models for non-aerodynamic applications. The ABL characteristics have been simulated by using various configurations of passive devices such as vortex generators, air barriers, and slot in the test section floor which was extended into the contraction cone. Mean velocity and velocity fluctuations have been measured using a hot-wire anemometry system. Mean velocity, turbulence intensity, turbulence scale, and power spectral density of velocity fluctuations have been obtained from the experiments for various configuration of the passive devices. It is shown that the integral length scale factor can be controlled using various combinations of the passive devices.
Fluctuations and differential contraction during regeneration of Hydra vulgaris tissue toroids

NASA Astrophysics Data System (ADS)

Krahe, Michael; Wenzel, Iris; Lin, Kao-Nung; Fischer, Julia; Goldmann, Joseph; Kästner, Markus; Fütterer, Claus

2013-03-01

We studied regenerating bilayered tissue toroids dissected from Hydra vulgaris polyps and relate our macroscopic observations to the dynamics of force-generating mesoscopic cytoskeletal structures. Tissue fragments undergo a specific toroid-spheroid folding process leading to complete regeneration towards a new organism. The time scale of folding is too fast for biochemical signalling or morphogenetic gradients, which forced us to assume purely mechanical self-organization. The initial pattern selection dynamics was studied by embedding toroids into hydro-gels, allowing us to observe the deformation modes over longer periods of time. We found increasing mechanical fluctuations which break the toroidal symmetry, and discuss the evolution of their power spectra for various gel stiffnesses. Our observations are related to single-cell studies which explain the mechanical feasibility of the folding process. In addition, we observed switching of cells from a tissue bound to a migrating state after folding failure as well as in tissue injury. We found a supra-cellular actin ring assembled along the toroid's inner edge. Its contraction can lead to the observed folding dynamics as we could confirm by finite element simulations. This actin ring in the inner cell layer is assembled by myosin-driven length fluctuations of supra-cellular F-actin bundles (myonemes) in the outer cell layer. This paper is dedicated to Malcolm Steinberg.
Reynolds number scaling of straining motions in turbulence

NASA Astrophysics Data System (ADS)

Elsinga, Gerrit; Ishihara, T.; Goudar, M. V.; da Silva, C. B.; Hunt, J. C. R.

2017-11-01

Strain is an important fluid motion in turbulence as it is associated with the kinetic energy dissipation rate, vorticity stretching, and the dispersion of passive scalars. The present study investigates the scaling of the turbulent straining motions by evaluating the flow in the eigenframe of the local strain-rate tensor. The analysis is based on DNS of homogeneous isotropic turbulence covering a Reynolds number range Reλ = 34.6 - 1131. The resulting flow pattern reveals a shear layer containing tube-like vortices and a dissipation sheet, which both scale on the Kolmogorov length scale, η. The vorticity stretching motions scale on the Taylor length scale, while the flow outside the shear layer scales on the integral length scale. These scaling results are consistent with those in wall-bounded flow, which suggests a quantitative universality between the different flows. The overall coherence length of the vorticity is 120 η in all directions, which is considerably larger than the typical size of individual vortices, and reflects the importance of spatial organization at the small scales. Transitions in flow structure are identified at Reλ 45 and 250. Below these respective Reynolds numbers, the small-scale motions and the vorticity stretching motions appear underdeveloped.
A Compact Synchronous Cellular Model of Nonlinear Calcium Dynamics: Simulation and FPGA Synthesis Results.

PubMed

Soleimani, Hamid; Drakakis, Emmanuel M

2017-06-01

Recent studies have demonstrated that calcium is a widespread intracellular ion that controls a wide range of temporal dynamics in the mammalian body. The simulation and validation of such studies using experimental data would benefit from a fast large scale simulation and modelling tool. This paper presents a compact and fully reconfigurable cellular calcium model capable of mimicking Hopf bifurcation phenomenon and various nonlinear responses of the biological calcium dynamics. The proposed cellular model is synthesized on a digital platform for a single unit and a network model. Hardware synthesis, physical implementation on FPGA, and theoretical analysis confirm that the proposed cellular model can mimic the biological calcium behaviors with considerably low hardware overhead. The approach has the potential to speed up large-scale simulations of slow intracellular dynamics by sharing more cellular units in real-time. To this end, various networks constructed by pipelining 10 k to 40 k cellular calcium units are compared with an equivalent simulation run on a standard PC workstation. Results show that the cellular hardware model is, on average, 83 times faster than the CPU version.
New Roles of the Primary Cilium in Autophagy

PubMed Central

Ávalos, Yenniffer; Peña-Oyarzun, Daniel; Budini, Mauricio

2017-01-01

The primary cilium is a nonmotile organelle that emanates from the surface of multiple cell types and receives signals from the environment to regulate intracellular signaling pathways. The presence of cilia, as well as their length, is important for proper cell function; shortened, elongated, or absent cilia are associated with pathological conditions. Interestingly, it has recently been shown that the molecular machinery involved in autophagy, the process of recycling of intracellular material to maintain cellular and tissue homeostasis, participates in ciliogenesis. Cilium-dependent signaling is necessary for autophagosome formation and, conversely, autophagy regulates both ciliogenesis and cilium length by degrading specific ciliary proteins. Here, we will discuss the relationship that exists between the two processes at the cellular and molecular level, highlighting what is known about the effects of ciliary dysfunction in the control of energy homeostasis in some ciliopathies. PMID:28913352
New Roles of the Primary Cilium in Autophagy.

PubMed

Ávalos, Yenniffer; Peña-Oyarzun, Daniel; Budini, Mauricio; Morselli, Eugenia; Criollo, Alfredo

2017-01-01

The primary cilium is a nonmotile organelle that emanates from the surface of multiple cell types and receives signals from the environment to regulate intracellular signaling pathways. The presence of cilia, as well as their length, is important for proper cell function; shortened, elongated, or absent cilia are associated with pathological conditions. Interestingly, it has recently been shown that the molecular machinery involved in autophagy, the process of recycling of intracellular material to maintain cellular and tissue homeostasis, participates in ciliogenesis. Cilium-dependent signaling is necessary for autophagosome formation and, conversely, autophagy regulates both ciliogenesis and cilium length by degrading specific ciliary proteins. Here, we will discuss the relationship that exists between the two processes at the cellular and molecular level, highlighting what is known about the effects of ciliary dysfunction in the control of energy homeostasis in some ciliopathies.
Altered cellular kinetics in growth plate according to alterations in weight bearing.

PubMed

Park, Hoon; Kong, Sun Young; Kim, Hyun Woo; Yang, Ick Hwan

2012-05-01

To examine the effects of change in weight bearing on the growth plate metabolism, a simulated animal model of weightlessness was introduced and the chondrocytes' cellular kinetics was evaluated. Unloading condition on the hind-limb of Sprague-Dawley rats was created by fixing a tail and lifting the hind-limb. Six rats aged 6 weeks old were assigned to each group of unloading, reloading, and control groups of unloading or reloading. Unloading was maintained for three weeks, and then reloading was applied for another one week thereafter. Histomorphometry for the assessment of vertical length of the growth plate, 5-bromo-2'-deoxyuridin immunohistochemistry for cellular kinetics, and biotin nick end labeling transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay for chondrocytes apoptosis in the growth plate were performed. The vertical length of the growth plate and the proliferative potential of chondrocytes were decreased in the unloading group compared to those of control groups. Inter-group differences were more significant in the proliferative and hypertrophic zones. Reloading increased the length of growth plate and proliferative potential of chondrocytes. However, apoptotic changes in the growth plate were not affected by the alterations of weight bearing. Alterations in the weight bearing induced changes in the chondrocytic proliferative potential of the growth plate, however, had no effects on the apoptosis. This may explain why non-weight bearing in various clinical situations hampers normal longitudinal bone growth. Further studies on the factors for reversibility of chondrocytic proliferation upon variable mechanical stresses are needed.
Mesoscale computational studies of membrane bilayer remodeling by curvature-inducing proteins

PubMed Central

Ramakrishnan, N.; Sunil Kumar, P. B.; Radhakrishnan, Ravi

2014-01-01

Biological membranes constitute boundaries of cells and cell organelles. These membranes are soft fluid interfaces whose thermodynamic states are dictated by bending moduli, induced curvature fields, and thermal fluctuations. Recently, there has been a flood of experimental evidence highlighting active roles for these structures in many cellular processes ranging from trafficking of cargo to cell motility. It is believed that the local membrane curvature, which is continuously altered due to its interactions with myriad proteins and other macromolecules attached to its surface, holds the key to the emergent functionality in these cellular processes. Mechanisms at the atomic scale are dictated by protein-lipid interaction strength, lipid composition, lipid distribution in the vicinity of the protein, shape and amino acid composition of the protein, and its amino acid contents. The specificity of molecular interactions together with the cooperativity of multiple proteins induce and stabilize complex membrane shapes at the mesoscale. These shapes span a wide spectrum ranging from the spherical plasma membrane to the complex cisternae of the Golgi apparatus. Mapping the relation between the protein-induced deformations at the molecular scale and the resulting mesoscale morphologies is key to bridging cellular experiments across the various length scales. In this review, we focus on the theoretical and computational methods used to understand the phenomenology underlying protein-driven membrane remodeling. Interactions at the molecular scale can be computationally probed by all atom and coarse grained molecular dynamics (MD, CGMD), as well as dissipative particle dynamics (DPD) simulations, which we only describe in passing. We choose to focus on several continuum approaches extending the Canham - Helfrich elastic energy model for membranes to include the effect of curvature-inducing proteins and explore the conformational phase space of such systems. In this description, the protein is expressed in the form of a spontaneous curvature field. The approaches include field theoretical methods limited to the small deformation regime, triangulated surfaces and particle-based computational models to investigate the large-deformation regimes observed in the natural state of many biological membranes. Applications of these methods to understand the properties of biological membranes in homogeneous and inhomogeneous environments of proteins, whose underlying curvature fields are either isotropic or anisotropic, are discussed. The diversity in the curvature fields elicits a rich variety of morphological states, including tubes, discs, branched tubes, and caveola. Mapping the thermodynamic stability of these states as a function of tuning parameters such as concentration and strength of curvature induction of the proteins is discussed. The relative stabilities of these self-organized shapes are examined through free-energy calculations. The suite of methods discussed here can be tailored to applications in specific cellular settings such as endocytosis during cargo trafficking and tubulation of filopodial structures in migrating cells, which makes these methods a powerful complement to experimental studies. PMID:25484487
Mesoscale computational studies of membrane bilayer remodeling by curvature-inducing proteins.

PubMed

Ramakrishnan, N; Sunil Kumar, P B; Radhakrishnan, Ravi

2014-10-01

Biological membranes constitute boundaries of cells and cell organelles. These membranes are soft fluid interfaces whose thermodynamic states are dictated by bending moduli, induced curvature fields, and thermal fluctuations. Recently, there has been a flood of experimental evidence highlighting active roles for these structures in many cellular processes ranging from trafficking of cargo to cell motility. It is believed that the local membrane curvature, which is continuously altered due to its interactions with myriad proteins and other macromolecules attached to its surface, holds the key to the emergent functionality in these cellular processes. Mechanisms at the atomic scale are dictated by protein-lipid interaction strength, lipid composition, lipid distribution in the vicinity of the protein, shape and amino acid composition of the protein, and its amino acid contents. The specificity of molecular interactions together with the cooperativity of multiple proteins induce and stabilize complex membrane shapes at the mesoscale. These shapes span a wide spectrum ranging from the spherical plasma membrane to the complex cisternae of the Golgi apparatus. Mapping the relation between the protein-induced deformations at the molecular scale and the resulting mesoscale morphologies is key to bridging cellular experiments across the various length scales. In this review, we focus on the theoretical and computational methods used to understand the phenomenology underlying protein-driven membrane remodeling. Interactions at the molecular scale can be computationally probed by all atom and coarse grained molecular dynamics (MD, CGMD), as well as dissipative particle dynamics (DPD) simulations, which we only describe in passing. We choose to focus on several continuum approaches extending the Canham - Helfrich elastic energy model for membranes to include the effect of curvature-inducing proteins and explore the conformational phase space of such systems. In this description, the protein is expressed in the form of a spontaneous curvature field. The approaches include field theoretical methods limited to the small deformation regime, triangulated surfaces and particle-based computational models to investigate the large-deformation regimes observed in the natural state of many biological membranes. Applications of these methods to understand the properties of biological membranes in homogeneous and inhomogeneous environments of proteins, whose underlying curvature fields are either isotropic or anisotropic, are discussed. The diversity in the curvature fields elicits a rich variety of morphological states, including tubes, discs, branched tubes, and caveola. Mapping the thermodynamic stability of these states as a function of tuning parameters such as concentration and strength of curvature induction of the proteins is discussed. The relative stabilities of these self-organized shapes are examined through free-energy calculations. The suite of methods discussed here can be tailored to applications in specific cellular settings such as endocytosis during cargo trafficking and tubulation of filopodial structures in migrating cells, which makes these methods a powerful complement to experimental studies.
Mesoscale computational studies of membrane bilayer remodeling by curvature-inducing proteins

NASA Astrophysics Data System (ADS)

Ramakrishnan, N.; Sunil Kumar, P. B.; Radhakrishnan, Ravi

2014-10-01

Biological membranes constitute boundaries of cells and cell organelles. These membranes are soft fluid interfaces whose thermodynamic states are dictated by bending moduli, induced curvature fields, and thermal fluctuations. Recently, there has been a flood of experimental evidence highlighting active roles for these structures in many cellular processes ranging from trafficking of cargo to cell motility. It is believed that the local membrane curvature, which is continuously altered due to its interactions with myriad proteins and other macromolecules attached to its surface, holds the key to the emergent functionality in these cellular processes. Mechanisms at the atomic scale are dictated by protein-lipid interaction strength, lipid composition, lipid distribution in the vicinity of the protein, shape and amino acid composition of the protein, and its amino acid contents. The specificity of molecular interactions together with the cooperativity of multiple proteins induce and stabilize complex membrane shapes at the mesoscale. These shapes span a wide spectrum ranging from the spherical plasma membrane to the complex cisternae of the Golgi apparatus. Mapping the relation between the protein-induced deformations at the molecular scale and the resulting mesoscale morphologies is key to bridging cellular experiments across various length scales. In this review, we focus on the theoretical and computational methods used to understand the phenomenology underlying protein-driven membrane remodeling. Interactions at the molecular scale can be computationally probed by all atom and coarse grained molecular dynamics (MD, CGMD), as well as dissipative particle dynamics (DPD) simulations, which we only describe in passing. We choose to focus on several continuum approaches extending the Canham-Helfrich elastic energy model for membranes to include the effect of curvature-inducing proteins and explore the conformational phase space of such systems. In this description, the protein is expressed in the form of a spontaneous curvature field. The approaches include field theoretical methods limited to the small deformation regime, triangulated surfaces and particle-based computational models to investigate the large-deformation regimes observed in the natural state of many biological membranes. Applications of these methods to understand the properties of biological membranes in homogeneous and inhomogeneous environments of proteins, whose underlying curvature fields are either isotropic or anisotropic, are discussed. The diversity in the curvature fields elicits a rich variety of morphological states, including tubes, discs, branched tubes, and caveola. Mapping the thermodynamic stability of these states as a function of tuning parameters such as concentration and strength of curvature induction of the proteins is discussed. The relative stabilities of these self-organized shapes are examined through free-energy calculations. The suite of methods discussed here can be tailored to applications in specific cellular settings such as endocytosis during cargo trafficking and tubulation of filopodial structures in migrating cells, which makes these methods a powerful complement to experimental studies.
Influence of Turbulent Flow and Fractal Scaling on Effective Permeability of Fracture Network

NASA Astrophysics Data System (ADS)

Zhu, J.

2017-12-01

A new approach is developed to calculate hydraulic gradient dependent effective permeability of a fractal fracture network where both laminar and turbulent flows may occur in individual fractures. A critical fracture length is used to distinguish flow characteristics in individual fractures. The developed new solutions can be used for the case of a general scaling relationship, an extension to the linear scaling. We examine the impact on the effective permeability of the network of fractal fracture network characteristics, which include the fractal scaling coefficient and exponent, fractal dimension, ratio of minimum over maximum fracture lengths. Results demonstrate that the developed solution can explain more variations of the effective permeability in relation to the fractal dimensions estimated from the field observations. At high hydraulic gradient the effective permeability decreases with the fractal scaling exponent, but increases with the fractal scaling exponent at low gradient. The effective permeability increases with the scaling coefficient, fractal dimension, fracture length ratio and maximum fracture length.
End-monomer Dynamics in Semiflexible Polymers

PubMed Central

Hinczewski, Michael; Schlagberger, Xaver; Rubinstein, Michael; Krichevsky, Oleg; Netz, Roland R.

2009-01-01

Spurred by an experimental controversy in the literature, we investigate the end-monomer dynamics of semiflexible polymers through Brownian hydrodynamic simulations and dynamic mean-field theory. Precise experimental observations over the last few years of end-monomer dynamics in the diffusion of double-stranded DNA have given conflicting results: one study indicated an unexpected Rouse-like scaling of the mean squared displacement (MSD) 〈r2(t)〉 ~ t1/2 at intermediate times, corresponding to fluctuations at length scales larger than the persistence length but smaller than the coil size; another study claimed the more conventional Zimm scaling 〈r2(t)〉 ~ t2/3 in the same time range. Using hydrodynamic simulations, analytical and scaling theories, we find a novel intermediate dynamical regime where the effective local exponent of the end-monomer MSD, α(t) = d log〈r2(t)〉/d log t, drops below the Zimm value of 2/3 for sufficiently long chains. The deviation from the Zimm prediction increases with chain length, though it does not reach the Rouse limit of 1/2. The qualitative features of this intermediate regime, found in simulations and in an improved mean-field theory for semiflexible polymers, in particular the variation of α(t) with chain and persistence lengths, can be reproduced through a heuristic scaling argument. Anomalously low values of the effective exponent α are explained by hydrodynamic effects related to the slow crossover from dynamics on length scales smaller than the persistence length to dynamics on larger length scales. PMID:21359118
Combining the Finite Element Method with Structural Connectome-based Analysis for Modeling Neurotrauma: Connectome Neurotrauma Mechanics

PubMed Central

Kraft, Reuben H.; Mckee, Phillip Justin; Dagro, Amy M.; Grafton, Scott T.

2012-01-01

This article presents the integration of brain injury biomechanics and graph theoretical analysis of neuronal connections, or connectomics, to form a neurocomputational model that captures spatiotemporal characteristics of trauma. We relate localized mechanical brain damage predicted from biofidelic finite element simulations of the human head subjected to impact with degradation in the structural connectome for a single individual. The finite element model incorporates various length scales into the full head simulations by including anisotropic constitutive laws informed by diffusion tensor imaging. Coupling between the finite element analysis and network-based tools is established through experimentally-based cellular injury thresholds for white matter regions. Once edges are degraded, graph theoretical measures are computed on the “damaged” network. For a frontal impact, the simulations predict that the temporal and occipital regions undergo the most axonal strain and strain rate at short times (less than 24 hrs), which leads to cellular death initiation, which results in damage that shows dependence on angle of impact and underlying microstructure of brain tissue. The monotonic cellular death relationships predict a spatiotemporal change of structural damage. Interestingly, at 96 hrs post-impact, computations predict no network nodes were completely disconnected from the network, despite significant damage to network edges. At early times () network measures of global and local efficiency were degraded little; however, as time increased to 96 hrs the network properties were significantly reduced. In the future, this computational framework could help inform functional networks from physics-based structural brain biomechanics to obtain not only a biomechanics-based understanding of injury, but also neurophysiological insight. PMID:22915997
Role of environmental and antibiotic stress on Staphylococcus epidermidis biofilm microstructure.

PubMed

Stewart, Elizabeth J; Satorius, Ashley E; Younger, John G; Solomon, Michael J

2013-06-11

Cellular clustering and separation of Staphylococcus epidermidis surface adherent biofilms were found to depend significantly on both antibiotic and environmental stress present during growth under steady flow. Image analysis techniques common to colloidal science were applied to image volumes acquired with high-resolution confocal laser scanning microscopy to extract spatial positions of individual bacteria in volumes of size ~30 × 30 × 15 μm(3). The local number density, cluster distribution, and radial distribution function were determined at each condition by analyzing the statistics of the bacterial spatial positions. Environmental stressors of high osmotic pressure (776 mM NaCl) and sublethal antibiotic dose (1.9 μg/mL vancomycin) decreased the average bacterial local number density 10-fold. Device-associated bacterial biofilms are frequently exposed to these environmental and antibiotic stressors while undergoing flow in the bloodstream. Characteristic density phenotypes associated with low, medium, and high local number densities were identified in unstressed S. epidermidis biofilms, while stressed biofilms contained medium- and low-density phenotypes. All biofilms exhibited clustering at length scales commensurate with cell division (~1.0 μm). However, density phenotypes differed in cellular connectivity at the scale of ~6 μm. On this scale, nearly all cells in the high- and medium-density phenotypes were connected into a single cluster with a structure characteristic of a densely packed disordered fluid. However, in the low-density phenotype, the number of clusters was greater, equal to 4% of the total number of cells, and structures were fractal in nature with d(f) =1.7 ± 0.1. The work advances the understanding of biofilm growth, informs the development of predictive models of transport and mechanical properties of biofilms, and provides a method for quantifying the kinetics of bacterial surface colonization as well as biofilm fracture and fragmentation.
Mechanobiological induction of long-range contractility by diffusing biomolecules and size scaling in cell assemblies

NASA Astrophysics Data System (ADS)

Dasbiswas, K.; Alster, E.; Safran, S. A.

2016-06-01

Mechanobiological studies of cell assemblies have generally focused on cells that are, in principle, identical. Here we predict theoretically the effect on cells in culture of locally introduced biochemical signals that diffuse and locally induce cytoskeletal contractility which is initially small. In steady-state, both the concentration profile of the signaling molecule as well as the contractility profile of the cell assembly are inhomogeneous, with a characteristic length that can be of the order of the system size. The long-range nature of this state originates in the elastic interactions of contractile cells (similar to long-range “macroscopic modes” in non-living elastic inclusions) and the non-linear diffusion of the signaling molecules, here termed mechanogens. We suggest model experiments on cell assemblies on substrates that can test the theory as a prelude to its applicability in embryo development where spatial gradients of morphogens initiate cellular development.
Atomic detail visualization of photosynthetic membranes with GPU-accelerated ray tracing

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

Stone, John E.; Sener, Melih; Vandivort, Kirby L.

The cellular process responsible for providing energy for most life on Earth, namely, photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. In this paper, we present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. Finally, we describemore » the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers.« less
Multiscale Modeling of Virus Entry via Receptor-Mediated Endocytosis

NASA Astrophysics Data System (ADS)

Liu, Jin

2012-11-01

Virus infections are ubiquitous and remain major threats to human health worldwide. Viruses are intracellular parasites and must enter host cells to initiate infection. Receptor-mediated endocytosis is the most common entry pathway taken by viruses, the whole process is highly complex and dictated by various events, such as virus motions, membrane deformations, receptor diffusion and ligand-receptor reactions, occurring at multiple length and time scales. We develop a multiscale model for virus entry through receptor-mediated endocytosis. The binding of virus to cell surface is based on a mesoscale three dimensional stochastic adhesion model, the internalization (endocytosis) of virus and cellular membrane deformation is based on the discretization of Helfrich Hamiltonian in a curvilinear space using Monte Carlo method. The multiscale model is based on the combination of these two models. We will implement this model to study the herpes simplex virus entry into B78 cells and compare the model predictions with experimental measurements.
Localization-delocalization transition in a system of quantum kicked rotors.

PubMed

Creffield, C E; Hur, G; Monteiro, T S

2006-01-20

The quantum dynamics of atoms subjected to pairs of closely spaced delta kicks from optical potentials are shown to be quite different from the well-known paradigm of quantum chaos, the single delta-kick system. We find the unitary matrix has a new oscillating band structure corresponding to a cellular structure of phase space and observe a spectral signature of a localization-delocalization transition from one cell to several. We find that the eigenstates have localization lengths which scale with a fractional power L approximately h(-0.75) and obtain a regime of near-linear spectral variances which approximate the "critical statistics" relation summation2(L) approximately or equal to chi(L) approximately 1/2 (1-nu)L, where nu approximately 0.75 is related to the fractal classical phase-space structure. The origin of the nu approximately 0.75 exponent is analyzed.
Atomic detail visualization of photosynthetic membranes with GPU-accelerated ray tracing

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

Stone, John E.; Sener, Melih; Vandivort, Kirby L.

The cellular process responsible for providing energy for most life on Earth, namely, photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. We present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. We describe the techniques that weremore » used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers.« less

Atomic detail visualization of photosynthetic membranes with GPU-accelerated ray tracing

DOE PAGES

Stone, John E.; Sener, Melih; Vandivort, Kirby L.; ...

2015-12-12

The cellular process responsible for providing energy for most life on Earth, namely, photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. In this paper, we present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. Finally, we describemore » the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers.« less
Optical imaging of localized chemical events using programmable diamond quantum nanosensors

NASA Astrophysics Data System (ADS)

Rendler, Torsten; Neburkova, Jitka; Zemek, Ondrej; Kotek, Jan; Zappe, Andrea; Chu, Zhiqin; Cigler, Petr; Wrachtrup, Jörg

2017-03-01

Development of multifunctional nanoscale sensors working under physiological conditions enables monitoring of intracellular processes that are important for various biological and medical applications. By attaching paramagnetic gadolinium complexes to nanodiamonds (NDs) with nitrogen-vacancy (NV) centres through surface engineering, we developed a hybrid nanoscale sensor that can be adjusted to directly monitor physiological species through a proposed sensing scheme based on NV spin relaxometry. We adopt a single-step method to measure spin relaxation rates enabling time-dependent measurements on changes in pH or redox potential at a submicrometre-length scale in a microfluidic channel that mimics cellular environments. Our experimental data are reproduced by numerical simulations of the NV spin interaction with gadolinium complexes covering the NDs. Considering the versatile engineering options provided by polymer chemistry, the underlying mechanism can be expanded to detect a variety of physiologically relevant species and variables.
An optical conveyor for molecules.

PubMed

Weinert, Franz M; Braun, Dieter

2009-12-01

Trapping single ions under vacuum allows for precise spectroscopy in atomic physics. The confinement of biological molecules in bulk water is hindered by the lack of comparably strong forces. Molecules have been immobilized to surfaces, however often with detrimental effects on their function. Here, we optically trap molecules by creating the microscale analogue of a conveyor belt: a bidirectional flow is combined with a perpendicular thermophoretic molecule drift. Arranged in a toroidal geometry, the conveyor accumulates a hundredfold excess of 5-base DNA within seconds. The concentrations of the trapped DNA scale exponentially with length, reaching trapping potential depths of 14 kT for 50 bases. The mechanism does not require microfluidics, electrodes, or surface modifications. As a result, the trap can be dynamically relocated. The optical conveyor can be used to enhance diffusion-limited surface reactions, redirect cellular signaling, observe individual biomolecules over a prolonged time, or approach single-molecule chemistry in bulk water.
Early Hits and Long-Term Consequences: Tracking the Lasting Impact of Prenatal Smoke Exposure on Telomere Length in Children

PubMed Central

McKasson, Sarah; Mabile, Emily; Dunaway, Lauren F.; Drury, Stacy S.

2013-01-01

We examined the association between telomere length and prenatal tobacco exposure (PTE) in 104 children aged 4 to 14 years. Salivary telomere length (STL) was determined from salivary DNA using quantitative polymerase chain reaction. Of the children, 18% had maternal reported PTE. Mean STL was significantly lower among children with PTE (6.4 vs 7.5, P < .05). Findings extend the literature demonstrating the negative long-term effects of PTE to include a cellular marker of aging linked to multiple negative health outcomes. PMID:23927510
Rayleigh instability at small length scales.

PubMed

Gopan, Nandu; Sathian, Sarith P

2014-09-01

The Rayleigh instability (also called the Plateau-Rayleigh instability) of a nanosized liquid propane thread is investigated using molecular dynamics (MD). The validity of classical predictions at small length scales is verified by comparing the temporal evolution of liquid thread simulated by MD against classical predictions. Previous works have shown that thermal fluctuations become dominant at small length scales. The role and influence of the stochastic nature of thermal fluctuations in determining the instability at small length scale is also investigated. Thermal fluctuations are seen to dominate and accelerate the breakup process only during the last stages of breakup. The simulations also reveal that the breakup profile of nanoscale threads undergo modification due to reorganization of molecules by the evaporation-condensation process.
Coupled pulsating and cellular structure in the propagation of globally planar detonations in free space

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

Han, Wenhu; Key Laboratory for Thermal Science and Power Engineering of Ministry of Education, Department of Thermal Engineering, Tsinghua University, Beijing 100084; Gao, Yang, E-mail: gaoyang-00@mails.tsinghua.edu.cn

The globally planar detonation in free space is numerically simulated, with particular interest to understand and quantify the emergence and evolution of the one-dimensional pulsating instability and the two-dimensional cellular structure which is inherently also affected by pulsating instability. It is found that the pulsation includes three stages: rapid decay of the overdrive, approach to the Chapman-Jouguet state and emergence of weak pulsations, and the formation of strong pulsations; while evolution of the cellular structure also exhibits distinct behavior at these three stages: no cell formation, formation of small-scale, irregular cells, and formation of regular cells of a larger scale.more » Furthermore, the average shock pressure in the detonation front consists of fine-scale oscillations reflecting the collision dynamics of the triple-shock structure and large-scale oscillations affected by the global pulsation. The common stages of evolution between the cellular structure and the pulsating behavior, as well as the existence of shock-front pressure oscillation, suggest highly correlated mechanisms between them. Detonations with period doubling, period quadrupling, and chaotic amplitudes were also observed and studied for progressively increasing activation energies.« less
Cellular Factors Shape 3D Genome Landscape

Cancer.gov

Researchers, using novel large-scale imaging technology, have mapped the spatial location of individual genes in the nucleus of human cells and identified 50 cellular factors required for the proper 3D positioning of genes. These spatial locations play important roles in gene expression, DNA repair, genome stability, and other cellular activities.
Excess entropy scaling for the segmental and global dynamics of polyethylene melts.

PubMed

Voyiatzis, Evangelos; Müller-Plathe, Florian; Böhm, Michael C

2014-11-28

The range of validity of the Rosenfeld and Dzugutov excess entropy scaling laws is analyzed for unentangled linear polyethylene chains. We consider two segmental dynamical quantities, i.e. the bond and the torsional relaxation times, and two global ones, i.e. the chain diffusion coefficient and the viscosity. The excess entropy is approximated by either a series expansion of the entropy in terms of the pair correlation function or by an equation of state for polymers developed in the context of the self associating fluid theory. For the whole range of temperatures and chain lengths considered, the two estimates of the excess entropy are linearly correlated. The scaled bond and torsional relaxation times fall into a master curve irrespective of the chain length and the employed scaling scheme. Both quantities depend non-linearly on the excess entropy. For a fixed chain length, the reduced diffusion coefficient and viscosity scale linearly with the excess entropy. An empirical reduction to a chain length-independent master curve is accessible for both dynamic quantities. The Dzugutov scheme predicts an increased value of the scaled diffusion coefficient with increasing chain length which contrasts physical expectations. The origin of this trend can be traced back to the density dependence of the scaling factors. This finding has not been observed previously for Lennard-Jones chain systems (Macromolecules, 2013, 46, 8710-8723). Thus, it limits the applicability of the Dzugutov approach to polymers. In connection with diffusion coefficients and viscosities, the Rosenfeld scaling law appears to be of higher quality than the Dzugutov approach. An empirical excess entropy scaling is also proposed which leads to a chain length-independent correlation. It is expected to be valid for polymers in the Rouse regime.
Scaling in Free-Swimming Fish and Implications for Measuring Size-at-Time in the Wild

PubMed Central

Broell, Franziska; Taggart, Christopher T.

2015-01-01

This study was motivated by the need to measure size-at-age, and thus growth rate, in fish in the wild. We postulated that this could be achieved using accelerometer tags based first on early isometric scaling models that hypothesize that similar animals should move at the same speed with a stroke frequency that scales with length-1, and second on observations that the speed of primarily air-breathing free-swimming animals, presumably swimming ‘efficiently’, is independent of size, confirming that stroke frequency scales as length-1. However, such scaling relations between size and swimming parameters for fish remain mostly theoretical. Based on free-swimming saithe and sturgeon tagged with accelerometers, we introduce a species-specific scaling relationship between dominant tail beat frequency (TBF) and fork length. Dominant TBF was proportional to length-1 (r2 = 0.73, n = 40), and estimated swimming speed within species was independent of length. Similar scaling relations accrued in relation to body mass-0.29. We demonstrate that the dominant TBF can be used to estimate size-at-time and that accelerometer tags with onboard processing may be able to provide size-at-time estimates among free-swimming fish and thus the estimation of growth rate (change in size-at-time) in the wild. PMID:26673777
Genetic parameters for different growth scales in GIFT strain of Nile tilapia (Oreochromis niloticus).

PubMed

He, J; Gao, H; Xu, P; Yang, R

2015-12-01

Body weight, length, width and depth at two growth stages were observed for a total of 5015 individuals of GIFT strain, along with a pedigree including 5588 individuals from 104 sires and 162 dams was collected. Multivariate animal models and a random regression model were used to genetically analyse absolute and relative growth scales of these growth traits. In absolute growth scale, the observed growth traits had moderate heritabilities ranging from 0.321 to 0.576, while pairwise ratios between body length, width and depth were lowly inherited and maximum heritability was only 0.146 for length/depth. All genetic correlations were above 0.5 between pairwise growth traits and genetic correlation between length/width and length/depth varied between both growth stages. Based on those estimates, selection index of multiple traits of interest can be formulated in future breeding program to improve genetically body weight and morphology of the GIFT strain. In relative growth scale, heritabilities in relative growths of body length, width and depth to body weight were 0.257, 0.412 and 0.066, respectively, while genetic correlations among these allometry scalings were above 0.8. Genetic analysis for joint allometries of body weight to body length, width and depth will contribute to genetically regulate the growth rate between body shape and body weight. © 2015 Blackwell Verlag GmbH.
Desert bird associations with broad-scale boundary length: Applications in avian conservation

USGS Publications Warehouse

Gutzwiller, K.J.; Barrow, W.C.

2008-01-01

1. Current understanding regarding the effects of boundaries on bird communities has originated largely from studies of forest-non-forest boundaries in mesic systems. To assess whether broad-scale boundary length can affect bird community structure in deserts, and to identify patterns and predictors of species' associations useful in avian conservation, we studied relations between birds and boundary-length variables in Chihuahuan Desert landscapes. Operationally, a boundary was the border between two adjoining land covers, and broad-scale boundary length was the total length of such borders in a large area. 2. Within 2-km radius areas, we measured six boundary-length variables. We analysed bird-boundary relations for 26 species, tested for assemblage-level patterns in species' associations with boundary-length variables, and assessed whether body size, dispersal ability and cowbird-host status were correlates of these associations. 3. The abundances or occurrences of a significant majority of species were associated with boundary-length variables, and similar numbers of species were related positively and negatively to boundary-length variables. 4. Disproportionately small numbers of species were correlated with total boundary length, land-cover boundary length and shrubland-grassland boundary length (variables responsible for large proportions of boundary length). Disproportionately large numbers of species were correlated with roadside boundary length and riparian vegetation-grassland boundary length (variables responsible for small proportions of boundary length). Roadside boundary length was associated (positively and negatively) with the most species. 5. Species' associations with boundary-length variables were not correlated with body size, dispersal ability or cowbird-host status. 6. Synthesis and applications. For the species we studied, conservationists can use the regressions we report as working models to anticipate influences of boundary-length changes on bird abundance and occurrence, and to assess avifaunal composition for areas under consideration for protection. Boundary-length variables associated with a disproportionate or large number of species can be used as foci for landscape management. Assessing the underlying causes of bird-boundary relations may improve the prediction accuracy of associated models. We therefore advocate local- and broad-scale manipulative experiments involving the boundary types with which species were correlated, as indicated by the regressions. ?? 2008 The Authors.
Resolving Properties of Polymers and Nanoparticle Assembly through Coarse-Grained Computational Studies.

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

Grest, Gary S.

2017-09-01

Coupled length and time scales determine the dynamic behavior of polymers and polymer nanocomposites and underlie their unique properties. To resolve the properties over large time and length scales it is imperative to develop coarse grained models which retain the atomistic specificity. Here we probe the degree of coarse graining required to simultaneously retain significant atomistic details a nd access large length and time scales. The degree of coarse graining in turn sets the minimum length scale instrumental in defining polymer properties and dynamics. Using polyethylene as a model system, we probe how the coarse - graining scale affects themore » measured dynamics with different number methylene group s per coarse - grained beads. Using these models we simulate polyethylene melts for times over 500 ms to study the viscoelastic properties of well - entangled polymer melts and large nanoparticle assembly as the nanoparticles are driven close enough to form nanostructures.« less
Effect of length scale on mechanical properties of Al-Cu eutectic alloy

NASA Astrophysics Data System (ADS)

Tiwary, C. S.; Roy Mahapatra, D.; Chattopadhyay, K.

2012-10-01

This paper attempts a quantitative understanding of the effect of length scale on two phase eutectic structure. We first develop a model that considers both the elastic and plastic properties of the interface. Using Al-Al2Cu lamellar eutectic as model system, the parameters of the model were experimentally determined using indentation technique. The model is further validated using the results of bulk compression testing of the eutectics having different length scales.
Energy Spectra of Higher Reynolds Number Turbulence by the DNS with up to 122883 Grid Points

NASA Astrophysics Data System (ADS)

Ishihara, Takashi; Kaneda, Yukio; Morishita, Koji; Yokokawa, Mitsuo; Uno, Atsuya

2014-11-01

Large-scale direct numerical simulations (DNS) of forced incompressible turbulence in a periodic box with up to 122883 grid points have been performed using K computer. The maximum Taylor-microscale Reynolds number Rλ, and the maximum Reynolds number Re based on the integral length scale are over 2000 and 105, respectively. Our previous DNS with Rλ up to 1100 showed that the energy spectrum has a slope steeper than - 5 / 3 (the Kolmogorov scaling law) by factor 0 . 1 at the wavenumber range (kη < 0 . 03). Here η is the Kolmogorov length scale. Our present DNS at higher resolutions show that the energy spectra with different Reynolds numbers (Rλ > 1000) are well normalized not by the integral length-scale but by the Kolmogorov length scale, at the wavenumber range of the steeper slope. This result indicates that the steeper slope is not inherent character in the inertial subrange, and is affected by viscosity.
Resolving Dynamic Properties of Polymers through Coarse-Grained Computational Studies

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

Salerno, K. Michael; Agrawal, Anupriya; Perahia, Dvora

2016-02-05

Coupled length and time scales determine the dynamic behavior of polymers and underlie their unique viscoelastic properties. To resolve the long-time dynamics it is imperative to determine which time and length scales must be correctly modeled. In this paper, we probe the degree of coarse graining required to simultaneously retain significant atomistic details and access large length and time scales. The degree of coarse graining in turn sets the minimum length scale instrumental in defining polymer properties and dynamics. Using linear polyethylene as a model system, we probe how the coarse-graining scale affects the measured dynamics. Iterative Boltzmann inversion ismore » used to derive coarse-grained potentials with 2–6 methylene groups per coarse-grained bead from a fully atomistic melt simulation. We show that atomistic detail is critical to capturing large-scale dynamics. Finally, using these models we simulate polyethylene melts for times over 500 μs to study the viscoelastic properties of well-entangled polymer melts.« less
Electropolishing effect on roughness metrics of ground stainless steel: a length scale study

NASA Astrophysics Data System (ADS)

Nakar, Doron; Harel, David; Hirsch, Baruch

2018-03-01

Electropolishing is a widely-used electrochemical surface finishing process for metals. The electropolishing of stainless steel has vast commercial application, such as improving corrosion resistance, improving cleanness, and brightening. The surface topography characterization is performed using several techniques with different lateral resolutions and length scales, from atomic force microscopy in the nano-scale (<0.1 µm) to stylus and optical profilometry in the micro- and mesoscales (0.1 µm-1 mm). This paper presents an experimental length scale study of the surface texture of ground stainless steel followed by an electropolishing process in the micro and meso lateral scales. Both stylus and optical profilometers are used, and multiple cut-off lengths of the standard Gaussian filter are adopted. While the commonly used roughness amplitude parameters (Ra, Rq and Rz) fail to characterize electropolished textures, the root mean square slope (RΔq) is found to better describe the electropolished surfaces and to be insensitive to scale.
Length scales and pinning of interfaces

PubMed Central

Tan, Likun

2016-01-01

The pinning of interfaces and free discontinuities by defects and heterogeneities plays an important role in a variety of phenomena, including grain growth, martensitic phase transitions, ferroelectricity, dislocations and fracture. We explore the role of length scale on the pinning of interfaces and show that the width of the interface relative to the length scale of the heterogeneity can have a profound effect on the pinning behaviour, and ultimately on hysteresis. When the heterogeneity is large, the pinning is strong and can lead to stick–slip behaviour as predicted by various models in the literature. However, when the heterogeneity is small, we find that the interface may not be pinned in a significant manner. This shows that a potential route to making materials with low hysteresis is to introduce heterogeneities at a length scale that is small compared with the width of the phase boundary. Finally, the intermediate setting where the length scale of the heterogeneity is comparable to that of the interface width is characterized by complex interactions, thereby giving rise to a non-monotone relationship between the relative heterogeneity size and the critical depinning stress. PMID:27002068
Current sheet extension and reconnection scaling in collisionless, hyperresistive, Hall MHD

NASA Astrophysics Data System (ADS)

Sullivan, B. P.; Bhattacharjee, A.; Huang, Y. M.

2009-11-01

We present Sweet-Parker type scaling arguments in the context of collisionless, hyper-resistive, Hall magnetohyrdodynamics (MHD). The predicted steady state scalings are consistent with those found by Chac'on et al. [PRL 99, 235001 (2007)], and Uzdensky, [PoP 16, 040702 (2009)], though our methods differ slightly. As with those studies, no prediction of electron dissipation region length is made. Numerical experiments confirm that both cusp like & extended geometries are realizable. Importantly, the length of the electron dissipation region (taken as a parameter by several recent studies) is found to depend on the level of hyper-resistivity. Although hyper-resistivity can produce modestly extended dissipation regions, the dissipation regions observed here are much shorter than those seen in many kinetic studies. The thickness of the dissipation region scales in a similar way as the length,so that the reconnection rate is not strongly sensitive to the level of hyperresistivity. The length of the electron dissipation region depends on electron inertia as well.The limitations of scaling theories that do not predict the length of the electron dissipation region are emphasized.
Multi-Scale Modeling in Morphogenesis: A Critical Analysis of the Cellular Potts Model

PubMed Central

Voss-Böhme, Anja

2012-01-01

Cellular Potts models (CPMs) are used as a modeling framework to elucidate mechanisms of biological development. They allow a spatial resolution below the cellular scale and are applied particularly when problems are studied where multiple spatial and temporal scales are involved. Despite the increasing usage of CPMs in theoretical biology, this model class has received little attention from mathematical theory. To narrow this gap, the CPMs are subjected to a theoretical study here. It is asked to which extent the updating rules establish an appropriate dynamical model of intercellular interactions and what the principal behavior at different time scales characterizes. It is shown that the longtime behavior of a CPM is degenerate in the sense that the cells consecutively die out, independent of the specific interdependence structure that characterizes the model. While CPMs are naturally defined on finite, spatially bounded lattices, possible extensions to spatially unbounded systems are explored to assess to which extent spatio-temporal limit procedures can be applied to describe the emergent behavior at the tissue scale. To elucidate the mechanistic structure of CPMs, the model class is integrated into a general multiscale framework. It is shown that the central role of the surface fluctuations, which subsume several cellular and intercellular factors, entails substantial limitations for a CPM's exploitation both as a mechanistic and as a phenomenological model. PMID:22984409
Dimensions of religious involvement and leukocyte telomere length.

PubMed

Hill, Terrence D; Ellison, Christopher G; Burdette, Amy M; Taylor, John; Friedman, Katherine L

2016-08-01

Although numerous studies suggest that religious involvement is associated with a wide range of favorable health outcomes, it is unclear whether this general pattern extends to cellular aging. In this paper, we tested whether leukocyte telomere length varies according to several dimensions of religious involvement. We used cross-sectional data from the Nashville Stress and Health Study (2011-2014), a large probability sample of 1252 black and white adults aged 22 to 69 living in Davidson County, TN, USA. Leukocyte telomere length was measured using the monochrome multiplex quantitative polymerase chain reaction method with albumin as the single-copy reference sequence. Dimensions of religious involvement included religiosity, religious support, and religious coping. Our multivariate analyses showed that religiosity (an index of religious attendance, prayer frequency, and religious identity) was positively associated with leukocyte telomere length, even with adjustments for religious support, religious coping, age, gender, race, education, employment status, income, financial strain, stressful life events, marital status, family support, friend support, depressive symptoms, smoking, heavy drinking, and allostatic load. Unlike religiosity, religious support and religious coping were unrelated to leukocyte telomere length across models. Depressive symptoms, smoking, heavy drinking, and allostatic load failed to explain any of the association between religiosity and telomere length. To our knowledge, this is the first population-based study to link religious involvement and cellular aging. Although our data suggest that adults who frequently attend religious services, pray with regularity, and consider themselves to be religious tend to exhibit longer telomeres than those who attend and pray less frequently and do not consider themselves to be religious, additional research is needed to establish the mechanisms underlying this association. Copyright © 2016 Elsevier Ltd. All rights reserved.

Marital Disruption is Associated with Shorter Salivary Telomere Length in a Probability Sample of Older Adults

PubMed Central

Whisman, Mark A.; Robustelli, Briana L.; Sbarra, David A.

2016-01-01

Rationale Marital disruption (i.e., marital separation, divorce) is associated with a wide range of poor mental and physical health outcomes, including increased risk for all-cause mortality. One biological intermediary that may help explain the association between marital disruption and poor health is accelerated cellular aging. Objective This study examines the association between marital disruption and salivary telomere length in a United States probability sample of adults ≥ 50 years of age. Method Participants were 3,526 individuals who participated in the 2008 wave of the Health and Retirement Study. Telomere length assays were performed using quantitative real-time polymerase chain reaction (qPCR) on DNA extracted from saliva samples. Health and lifestyle factors, traumatic and stressful life events, and neuroticism were assessed via self-report. Linear regression analyses were conducted to examine the associations between predictor variables and salivary telomere length. Results Based on their marital status data in the 2006 wave, people who were separated or divorced had shorter salivary telomeres than people who were continuously married or had never been married, and the association between marital disruption and salivary telomere length was not moderated by gender or neuroticism. Furthermore, the association between marital disruption and salivary telomere length remained statistically significant after adjusting for demographic and socioeconomic variables, neuroticism, cigarette use, body mass, traumatic life events, and other stressful life events. Additionally, results revealed that currently married adults with a history of divorce evidenced shorter salivary telomeres than people who were continuously married or never married. Conclusion Accelerated cellular aging, as indexed by telomere shortening, may be one pathway through which marital disruption is associated with morbidity and mortality. PMID:27062452
Pharmacological efficacy of anti-IL-1β scFv, Fab and full-length antibodies in treatment of rheumatoid arthritis.

PubMed

Qi, Jianying; Ye, Xianlong; Ren, Guiping; Kan, Fangming; Zhang, Yu; Guo, Mo; Zhang, Zhiyi; Li, Deshan

2014-02-01

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that mainly causes the synovial joint inflammation and cartilage destruction. Interleukin-1β (IL-1β) is an important proinflammatory cytokine involved in the pathogenesis of RA. In this study, we constructed and expressed anti-IL-1β-full-length antibody in CHO-K1-SV, anti-IL-1β-Fab and anti-IL-1β-scFv in Rosetta. We compared the therapeutic efficacy of three anti-IL-1β antibodies for CIA mice. Mice with CIA were subcutaneously injected with humanized anti-IL-1β-scFv, anti-IL-1β-Fab or anti-IL-1β-full-length antibody. The effects of treatment were determined by arthritis severity score, autoreactive humoral, cellular immune responses, histological lesion and cytokines production. Compared with anti-IL-1β-scFv treatments, anti-IL-1β-Fab and anti-IL-1β-full-length antibody therapy resulted in more significant effect in alleviating the severity of arthritis by preventing bone damage and cartilage destruction, reducing humoral and cellular immune responses, and down-regulating the expression of IL-1β, IL-6, IL-2, IFN-γ, TNF-α and MMP-3 in inflammatory tissue. The therapeutic effects of anti-IL-1β-Fab and anti-IL-1β-full-length antibodies on CIA mice had no significant difference. However, production of anti-IL-1β-full-length antibody in eukaryotic system is, in general, time-consuming and more expensive than that of anti-IL-1β-Fab in prokaryotic systems. In conclusion, as a small molecule antibody, anti-IL-1β-Fab is an ideal candidate for RA therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.
Marital disruption is associated with shorter salivary telomere length in a probability sample of older adults.

PubMed

Whisman, Mark A; Robustelli, Briana L; Sbarra, David A

2016-05-01

Marital disruption (i.e., marital separation, divorce) is associated with a wide range of poor mental and physical health outcomes, including increased risk for all-cause mortality. One biological intermediary that may help explain the association between marital disruption and poor health is accelerated cellular aging. This study examines the association between marital disruption and salivary telomere length in a United States probability sample of adults ≥50 years of age. Participants were 3526 individuals who participated in the 2008 wave of the Health and Retirement Study. Telomere length assays were performed using quantitative real-time polymerase chain reaction (qPCR) on DNA extracted from saliva samples. Health and lifestyle factors, traumatic and stressful life events, and neuroticism were assessed via self-report. Linear regression analyses were conducted to examine the associations between predictor variables and salivary telomere length. Based on their marital status data in the 2006 wave, people who were separated or divorced had shorter salivary telomeres than people who were continuously married or had never been married, and the association between marital disruption and salivary telomere length was not moderated by gender or neuroticism. Furthermore, the association between marital disruption and salivary telomere length remained statistically significant after adjusting for demographic and socioeconomic variables, neuroticism, cigarette use, body mass, traumatic life events, and other stressful life events. Additionally, results revealed that currently married adults with a history of divorce evidenced shorter salivary telomeres than people who were continuously married or never married. Accelerated cellular aging, as indexed by telomere shortening, may be one pathway through which marital disruption is associated with morbidity and mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.
Minimal Length Scale Scenarios for Quantum Gravity.

PubMed

Hossenfelder, Sabine

2013-01-01

We review the question of whether the fundamental laws of nature limit our ability to probe arbitrarily short distances. First, we examine what insights can be gained from thought experiments for probes of shortest distances, and summarize what can be learned from different approaches to a theory of quantum gravity. Then we discuss some models that have been developed to implement a minimal length scale in quantum mechanics and quantum field theory. These models have entered the literature as the generalized uncertainty principle or the modified dispersion relation, and have allowed the study of the effects of a minimal length scale in quantum mechanics, quantum electrodynamics, thermodynamics, black-hole physics and cosmology. Finally, we touch upon the question of ways to circumvent the manifestation of a minimal length scale in short-distance physics.
A new length scale for quantum gravity: A resolution of the black hole information loss paradox

NASA Astrophysics Data System (ADS)

Singh, Tejinder P.

We show why and how Compton wavelength and Schwarzschild radius should be combined into one single new length scale, which we call the Compton-Schwarzschild length. Doing so offers a resolution of the black hole information loss paradox, and suggests Planck mass remnant black holes as candidates for dark matter. It also compels us to introduce torsion, and identify the Dirac field with a complex torsion field. Dirac equation and Einstein equations, are shown to be mutually dual limiting cases of an underlying gravitation theory which involves the Compton-Schwarzschild length scale, and includes a complex torsion field.
Multi-classification of cell deformation based on object alignment and run length statistic.

PubMed

Li, Heng; Liu, Zhiwen; An, Xing; Shi, Yonggang

2014-01-01

Cellular morphology is widely applied in digital pathology and is essential for improving our understanding of the basic physiological processes of organisms. One of the main issues of application is to develop efficient methods for cell deformation measurement. We propose an innovative indirect approach to analyze dynamic cell morphology in image sequences. The proposed approach considers both the cellular shape change and cytoplasm variation, and takes each frame in the image sequence into account. The cell deformation is measured by the minimum energy function of object alignment, which is invariant to object pose. Then an indirect analysis strategy is employed to overcome the limitation of gradual deformation by run length statistic. We demonstrate the power of the proposed approach with one application: multi-classification of cell deformation. Experimental results show that the proposed method is sensitive to the morphology variation and performs better than standard shape representation methods.
The electrostatic persistence length of polymers beyond the OSF limit.

PubMed

Everaers, R; Milchev, A; Yamakov, V

2002-05-01

We use large-scale Monte Carlo simulations to test scaling theories for the electrostatic persistence length l(e) of isolated, uniformly charged polymers with Debye-Hückel intrachain interactions in the limit where the screening length kappa(-1) exceeds the intrinsic persistence length of the chains. Our simulations cover a significantly larger part of the parameter space than previous studies. We observe no significant deviations from the prediction l(e) proportional to kappa(-2) by Khokhlov and Khachaturian which is based on applying the Odijk-Skolnick-Fixman theories of electrostatic bending rigidity and electrostatically excluded volume to the stretched de Gennes-Pincus-Velasco-Brochard polyelectrolyte blob chain. A linear or sublinear dependence of the persistence length on the screening length can be ruled out. We show that previous results pointing into this direction are due to a combination of excluded-volume and finite chain length effects. The paper emphasizes the role of scaling arguments in the development of useful representations for experimental and simulation data.
Amplification and chromosomal dispersion of human endogenous retroviral sequences

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

Steele, P.E.; Martin, M.A.; Rabson, A.B.

1986-09-01

Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification andmore » dispersion events may be linked.« less
DNA confinement in nanochannels: physics and biological applications

NASA Astrophysics Data System (ADS)

Reisner, Walter; Pedersen, Jonas N.; Austin, Robert H.

2012-10-01

DNA is the central storage molecule of genetic information in the cell, and reading that information is a central problem in biology. While sequencing technology has made enormous advances over the past decade, there is growing interest in platforms that can readout genetic information directly from long single DNA molecules, with the ultimate goal of single-cell, single-genome analysis. Such a capability would obviate the need for ensemble averaging over heterogeneous cellular populations and eliminate uncertainties introduced by cloning and molecular amplification steps (thus enabling direct assessment of the genome in its native state). In this review, we will discuss how the information contained in genomic-length single DNA molecules can be accessed via physical confinement in nanochannels. Due to self-avoidance interactions, DNA molecules will stretch out when confined in nanochannels, creating a linear unscrolling of the genome along the channel for analysis. We will first review the fundamental physics of DNA nanochannel confinement—including the effect of varying ionic strength—and then discuss recent applications of these systems to genomic mapping. Apart from the intense biological interest in extracting linear sequence information from elongated DNA molecules, from a physics view these systems are fascinating as they enable probing of single-molecule conformation in environments with dimensions that intersect key physical length-scales in the 1 nm to 100 µm range.
DNA confinement in nanochannels: physics and biological applications.

PubMed

Reisner, Walter; Pedersen, Jonas N; Austin, Robert H

2012-10-01

DNA is the central storage molecule of genetic information in the cell, and reading that information is a central problem in biology. While sequencing technology has made enormous advances over the past decade, there is growing interest in platforms that can readout genetic information directly from long single DNA molecules, with the ultimate goal of single-cell, single-genome analysis. Such a capability would obviate the need for ensemble averaging over heterogeneous cellular populations and eliminate uncertainties introduced by cloning and molecular amplification steps (thus enabling direct assessment of the genome in its native state). In this review, we will discuss how the information contained in genomic-length single DNA molecules can be accessed via physical confinement in nanochannels. Due to self-avoidance interactions, DNA molecules will stretch out when confined in nanochannels, creating a linear unscrolling of the genome along the channel for analysis. We will first review the fundamental physics of DNA nanochannel confinement--including the effect of varying ionic strength--and then discuss recent applications of these systems to genomic mapping. Apart from the intense biological interest in extracting linear sequence information from elongated DNA molecules, from a physics view these systems are fascinating as they enable probing of single-molecule conformation in environments with dimensions that intersect key physical length-scales in the 1 nm to 100 µm range.
A Semi-Automatic Method for Image Analysis of Edge Dynamics in Living Cells

PubMed Central

Huang, Lawrence; Helmke, Brian P.

2011-01-01

Spatial asymmetry of actin edge ruffling contributes to the process of cell polarization and directional migration, but mechanisms by which external cues control actin polymerization near cell edges remain unclear. We designed a quantitative image analysis strategy to measure the spatiotemporal distribution of actin edge ruffling. Time-lapse images of endothelial cells (ECs) expressing mRFP-actin were segmented using an active contour method. In intensity line profiles oriented normal to the cell edge, peak detection identified the angular distribution of polymerized actin within 1 µm of the cell edge, which was localized to lamellipodia and edge ruffles. Edge features associated with filopodia and peripheral stress fibers were removed. Circular statistical analysis enabled detection of cell polarity, indicated by a unimodal distribution of edge ruffles. To demonstrate the approach, we detected a rapid, nondirectional increase in edge ruffling in serum-stimulated ECs and a change in constitutive ruffling orientation in quiescent, nonpolarized ECs. Error analysis using simulated test images demonstrate robustness of the method to variations in image noise levels, edge ruffle arc length, and edge intensity gradient. These quantitative measurements of edge ruffling dynamics enable investigation at the cellular length scale of the underlying molecular mechanisms regulating actin assembly and cell polarization. PMID:21643526
Micro-scale and meso-scale architectural cues cooperate and compete to direct aligned tissue formation

PubMed Central

Gilchrist, Christopher L.; Ruch, David S.; Little, Dianne; Guilak, Farshid

2014-01-01

Tissue and biomaterial microenvironments provide architectural cues that direct important cell behaviors including cell shape, alignment, migration, and resulting tissue formation. These architectural features may be presented to cells across multiple length scales, from nanometers to millimeters in size. In this study, we examined how architectural cues at two distinctly different length scales, “micro-scale” cues on the order of ~1–2 μm, and “meso-scale” cues several orders of magnitude larger (>100 μm), interact to direct aligned neo-tissue formation. Utilizing a micro-photopatterning (μPP) model system to precisely arrange cell-adhesive patterns, we examined the effects of substrate architecture at these length scales on human mesenchymal stem cell (hMSC) organization, gene expression, and fibrillar collagen deposition. Both micro- and meso-scale architectures directed cell alignment and resulting tissue organization, and when combined, meso cues could enhance or compete against micro-scale cues. As meso boundary aspect ratios were increased, meso-scale cues overrode micro-scale cues and controlled tissue alignment, with a characteristic critical width (~500 μm) similar to boundary dimensions that exist in vivo in highly aligned tissues. Meso-scale cues acted via both lateral confinement (in a cell-density-dependent manner) and by permitting end-to-end cell arrangements that yielded greater fibrillar collagen deposition. Despite large differences in fibrillar collagen content and organization between μPP architectural conditions, these changes did not correspond with changes in gene expression of key matrix or tendon-related genes. These findings highlight the complex interplay between geometric cues at multiple length scales and may have implications for tissue engineering strategies, where scaffold designs that incorporate cues at multiple length scales could improve neo-tissue organization and resulting functional outcomes. PMID:25263687
Matrix metalloproteinase 9 and cellular fibronectin plasma concentrations are predictors of the composite endpoint of length of stay and death in the intensive care unit after severe traumatic brain injury

PubMed Central

2012-01-01

Background The relationship between severe traumatic brain injury (TBI) and blood levels of matrix metalloproteinase-9 (MMP-9) or cellular fibronectin (c-Fn) has never been reported. In this study, we aimed to assess whether plasma concentrations of MMP-9 and c-Fn could have predictive values for the composite endpoint of intensive care unit (ICU) length of stay (LOS) of survivors and mortality after severe TBI. Secondary outcomes were the state of consciousness measured with the Glasgow Coma Scale (GCS) of survivors at 14 days and Glasgow Outcome Scale Extended (GOSE) at 3 months. Methods Forty-nine patients with abbreviated injury scores of the head region ≥ 4 were included. Blood was sampled at 6, 12, 24 and 48 hours after injury. MMP-9 and c-Fn concentrations were measured by ELISA. The values of MMP-9 and c-Fn, and, for comparison, the value of the GCS on the field of the accident (fGCS), as predictors of the composite outcome of ICU LOS and death were assessed by logistic regression. Results There was a linear relationship between maximal MMP-9 concentration, measured during the 6-12-hour period, and maximal c-Fn concentration, measured during the 24-48-hour period. The risk of staying longer than 9 days in the ICU or of dying was increased in patients with a maximal early MMP-9 concentration ≥ 21.6 ng/ml (OR = 5.0; 95% CI: 1.3 to 18.6; p = 0.02) or with a maximal late c-Fn concentration ≥ 7.7 μg/ml (OR = 5.4; 95% CI: 1.4 to 20.8; p = 0.01). A similar risk association was observed with fGCS ≤8 (OR, 4.4; 95% CI, 1.2-15.8; p = 0.02). No relationship was observed between MMP-9, c-Fn concentrations or fGCS and the GCS at 14 days of survivors and GOSE at 3 months. Conclusions Plasma MMP-9 and c-Fn concentrations in the first 48 hours after injury are predictive for the composite endpoint of ICU LOS and death after severe TBI but not for consciousness at 14 days and outcome at 3 months. PMID:23249478
On the saturation of the refractive index structure function. II - Influence of the correlation length on astronomical 'seeing'

NASA Technical Reports Server (NTRS)

Venkatakrishnan, P.

1987-01-01

A physical length scale in the wavefront corresponding to the parameter (r sub 0) characterizing the loss in detail in a long exposure image is identified, and the influence of the correlation scale of turbulence as r sub 0 approaches this scale is shown. Allowing for the effect of 2-point correlations in the fluctuations of the refractive index, Venkatakrishnan and Chatterjee (1987) proposed a modified law for the phase structure function. It is suggested that the departure of the phase structure function from the 5/3 power law for length scales in the wavefront approaching the correlation scale of turbulence may lead to better 'seeing' at longer wavelengths.
Solar potential scaling and the urban road network topology

NASA Astrophysics Data System (ADS)

Najem, Sara

2017-01-01

We explore the scaling of cities' solar potentials with their number of buildings and reveal a latent dependence between the solar potential and the length of the corresponding city's road network. This scaling is shown to be valid at the grid and block levels and is attributed to a common street length distribution. Additionally, we compute the buildings' solar potential correlation function and length in order to determine the set of critical exponents typifying the urban solar potential universality class.
Scale effects between body size and limb design in quadrupedal mammals.

PubMed

Kilbourne, Brandon M; Hoffman, Louwrens C

2013-01-01

Recently the metabolic cost of swinging the limbs has been found to be much greater than previously thought, raising the possibility that limb rotational inertia influences the energetics of locomotion. Larger mammals have a lower mass-specific cost of transport than smaller mammals. The scaling of the mass-specific cost of transport is partly explained by decreasing stride frequency with increasing body size; however, it is unknown if limb rotational inertia also influences the mass-specific cost of transport. Limb length and inertial properties--limb mass, center of mass (COM) position, moment of inertia, radius of gyration, and natural frequency--were measured in 44 species of terrestrial mammals, spanning eight taxonomic orders. Limb length increases disproportionately with body mass via positive allometry (length ∝ body mass(0.40)); the positive allometry of limb length may help explain the scaling of the metabolic cost of transport. When scaled against body mass, forelimb inertial properties, apart from mass, scale with positive allometry. Fore- and hindlimb mass scale according to geometric similarity (limb mass ∝ body mass(1.0)), as do the remaining hindlimb inertial properties. The positive allometry of limb length is largely the result of absolute differences in limb inertial properties between mammalian subgroups. Though likely detrimental to locomotor costs in large mammals, scale effects in limb inertial properties appear to be concomitant with scale effects in sensorimotor control and locomotor ability in terrestrial mammals. Across mammals, the forelimb's potential for angular acceleration scales according to geometric similarity, whereas the hindlimb's potential for angular acceleration scales with positive allometry.
Scale Effects between Body Size and Limb Design in Quadrupedal Mammals

PubMed Central

Kilbourne, Brandon M.; Hoffman, Louwrens C.

2013-01-01

Recently the metabolic cost of swinging the limbs has been found to be much greater than previously thought, raising the possibility that limb rotational inertia influences the energetics of locomotion. Larger mammals have a lower mass-specific cost of transport than smaller mammals. The scaling of the mass-specific cost of transport is partly explained by decreasing stride frequency with increasing body size; however, it is unknown if limb rotational inertia also influences the mass-specific cost of transport. Limb length and inertial properties – limb mass, center of mass (COM) position, moment of inertia, radius of gyration, and natural frequency – were measured in 44 species of terrestrial mammals, spanning eight taxonomic orders. Limb length increases disproportionately with body mass via positive allometry (length ∝ body mass0.40); the positive allometry of limb length may help explain the scaling of the metabolic cost of transport. When scaled against body mass, forelimb inertial properties, apart from mass, scale with positive allometry. Fore- and hindlimb mass scale according to geometric similarity (limb mass ∝ body mass1.0), as do the remaining hindlimb inertial properties. The positive allometry of limb length is largely the result of absolute differences in limb inertial properties between mammalian subgroups. Though likely detrimental to locomotor costs in large mammals, scale effects in limb inertial properties appear to be concomitant with scale effects in sensorimotor control and locomotor ability in terrestrial mammals. Across mammals, the forelimb's potential for angular acceleration scales according to geometric similarity, whereas the hindlimb's potential for angular acceleration scales with positive allometry. PMID:24260117
The prospects of transition metal dichalcogenides for ultimately scaled CMOS

NASA Astrophysics Data System (ADS)

Thiele, S.; Kinberger, W.; Granzner, R.; Fiori, G.; Schwierz, F.

2018-05-01

MOSFET gate length scaling has been a main source of progress in digital electronics for decades. Today, researchers still spend considerable efforts on reducing the gate length and on developing ultimately scaled MOSFETs, thereby exploring both new device architectures and alternative channel materials beyond Silicon such as two-dimensional TMDs (transition metal dichalcogenide). On the other hand, the envisaged scaling scenario for the next 15 years has undergone a significant change recently. While the 2013 ITRS edition required a continuation of aggressive gate length scaling for at least another 15 years, the 2015 edition of the ITRS suggests a deceleration and eventually a levelling off of gate length scaling and puts more emphasis on alternative options such as pitch scaling to keep Moore's Law alive. In the present paper, future CMOS scaling is discussed in the light of emerging two-dimensional MOSFET channel, in particular two-dimensional TMDs. To this end, the scaling scenarios of the 2013 and 2015 ITRS editions are considered and the scaling potential of TMD MOSFETs is investigated by means of quantum-mechanical device simulations. It is shown that for ultimately scaled MOSFETs as required in the 2013 ITRS, the heavy carrier effective masses of the Mo- and W-based TMDs are beneficial for the suppression of direct source-drain tunneling, while to meet the significantly relaxed scaling targets of the 2016 ITRS heavy-effective-mass channels are not needed.
Application of Elastography for the Noninvasive Assessment of Biomechanics in Engineered Biomaterials and Tissues

PubMed Central

Kim, Woong; Ferguson, Virginia L.; Borden, Mark; Neu, Corey P.

2016-01-01

The elastic properties of engineered biomaterials and tissues impact their post-implantation repair potential and structural integrity, and are critical to help regulate cell fate and gene expression. The measurement of properties (e.g., stiffness or shear modulus) can be attained using elastography, which exploits noninvasive imaging modalities to provide functional information of a material indicative of the regeneration state. In this review, we outline the current leading elastography methodologies available to characterize the properties of biomaterials and tissues suitable for repair and mechanobiology research. We describe methods utilizing magnetic resonance, ultrasound, and optical coherent elastography, highlighting their potential for longitudinal monitoring of implanted materials in vivo, in addition to spatiotemporal limits of each method for probing changes in cell-laden constructs. Micro-elastography methods now allow acquisitions at length scales approaching 5–100 μm in two and three dimensions. Many of the methods introduced in this review are therefore capable of longitudinal monitoring in biomaterials and tissues approaching the cellular scale. However, critical factors such as anisotropy, heterogeneity and viscoelasity—inherent in many soft tissues—are often not fully described and therefore require further advancements and future developments. PMID:26790865
Time evolution of shear-induced particle margination and migration in a cellular suspension

NASA Astrophysics Data System (ADS)

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

2016-11-01

The inhomogeneous center-of-mass distributions of red blood cells and platelets normal to the flow direction in small vessels play a significant role in hemostasis and drug delivery. Under pressure-driven flow in channels, the migration of deformable red blood cells at steady state is characterized by a cell-free or Fahraeus-Lindqvist layer near the vessel wall. Rigid particles such as platelets, however, "marginate" and thus develop a near-wall excess concentration. In order to evaluate the role of branching and design suitable microfluidic devices, it is important to investigate the time evolution of particle margination and migration from a non-equilibrium state and determine the corresponding entrance lengths. From a mechanistic point of view, deformability-induced hydrodynamic lift and shear-induced diffusion are essential mechanisms for the cross-flow migration and margination. In this talk, we determine the concentration distribution of red blood cells and platelets by solving coupled Boltzmann advection-diffusion equations for both species and explore their time evolution. We verify our model by comparing with large-scale, multi-cell simulations and experiments. Our Boltzmann collision theory serves as a fast alternative to large-scale simulations.

Mathematical and computational approaches can complement experimental studies of host-pathogen interactions.

PubMed

Kirschner, Denise E; Linderman, Jennifer J

2009-04-01

In addition to traditional and novel experimental approaches to study host-pathogen interactions, mathematical and computer modelling have recently been applied to address open questions in this area. These modelling tools not only offer an additional avenue for exploring disease dynamics at multiple biological scales, but also complement and extend knowledge gained via experimental tools. In this review, we outline four examples where modelling has complemented current experimental techniques in a way that can or has already pushed our knowledge of host-pathogen dynamics forward. Two of the modelling approaches presented go hand in hand with articles in this issue exploring fluorescence resonance energy transfer and two-photon intravital microscopy. Two others explore virtual or 'in silico' deletion and depletion as well as a new method to understand and guide studies in genetic epidemiology. In each of these examples, the complementary nature of modelling and experiment is discussed. We further note that multi-scale modelling may allow us to integrate information across length (molecular, cellular, tissue, organism, population) and time (e.g. seconds to lifetimes). In sum, when combined, these compatible approaches offer new opportunities for understanding host-pathogen interactions.
The Role of Endocytosis during Morphogenetic Signaling

PubMed Central

Gonzalez-Gaitan, Marcos; Jülicher, Frank

2014-01-01

Morphogens are signaling molecules that are secreted by a localized source and spread in a target tissue where they are involved in the regulation of growth and patterning. Both the activity of morphogenetic signaling and the kinetics of ligand spreading in a tissue depend on endocytosis and intracellular trafficking. Here, we review quantitative approaches to study how large-scale morphogen profiles and signals emerge in a tissue from cellular trafficking processes and endocytic pathways. Starting from the kinetics of endosomal networks, we discuss the role of cellular trafficking and receptor dynamics in the formation of morphogen gradients. These morphogen gradients scale during growth, which implies that overall tissue size influences cellular trafficking kinetics. Finally, we discuss how such morphogen profiles can be used to control tissue growth. We emphasize the role of theory in efforts to bridge between scales. PMID:24984777
Towards mechanism-based simulation of impact damage using exascale computing

NASA Astrophysics Data System (ADS)

Shterenlikht, Anton; Margetts, Lee; McDonald, Samuel; Bourne, Neil K.

2017-01-01

Over the past 60 years, the finite element method has been very successful in modelling deformation in engineering structures. However the method requires the definition of constitutive models that represent the response of the material to applied loads. There are two issues. Firstly, the models are often difficult to define. Secondly, there is often no physical connection between the models and the mechanisms that accommodate deformation. In this paper, we present a potentially disruptive two-level strategy which couples the finite element method at the macroscale with cellular automata at the mesoscale. The cellular automata are used to simulate mechanisms, such as crack propagation. The stress-strain relationship emerges as a continuum mechanics scale interpretation of changes at the micro- and meso-scales. Iterative two-way updating between the cellular automata and finite elements drives the simulation forward as the material undergoes progressive damage at high strain rates. The strategy is particularly attractive on large-scale computing platforms as both methods scale well on tens of thousands of CPUs.
A variable mixing-length ratio for convection theory

NASA Technical Reports Server (NTRS)

Chan, K. L.; Wolff, C. L.; Sofia, S.

1981-01-01

It is argued that a natural choice for the local mixing length in the mixing-length theory of convection has a value proportional to the local density scale height of the convective bubbles. The resultant variable mixing-length ratio (the ratio between the mixing length and the pressure scale height) of this theory is enhanced in the superadiabatic region and approaches a constant in deeper layers. Numerical tests comparing the new mixing length successfully eliminate most of the density inversion that typically plagues conventional results. The new approach also seems to indicate the existence of granular motion at the top of the convection zone.
An Efficient and Imperfect Model for Gravel-Bed Braided River Morphodynamics: Numerical Simulations as Exploratory Tools

NASA Astrophysics Data System (ADS)

Kasprak, A.; Brasington, J.; Hafen, K.; Wheaton, J. M.

2015-12-01

Numerical models that predict channel evolution through time are an essential tool for investigating processes that occur over timescales which render field observation intractable. However, available morphodynamic models generally take one of two approaches to the complex problem of computing morphodynamics, resulting in oversimplification of the relevant physics (e.g. cellular models) or faithful, yet computationally intensive, representations of the hydraulic and sediment transport processes at play. The practical implication of these approaches is that river scientists must often choose between unrealistic results, in the case of the former, or computational demands that render modeling realistic spatiotemporal scales of channel evolution impossible. Here we present a new modeling framework that operates at the timescale of individual competent flows (e.g. floods), and uses a highly-simplified sediment transport routine that moves volumes of material according to morphologically-derived characteristic transport distances, or path lengths. Using this framework, we have constructed an open-source morphodynamic model, termed MoRPHED, which is here applied, and its validity investigated, at timescales ranging from a single event to a decade on two braided rivers in the UK and New Zealand. We do not purport that MoRPHED is the best, nor even an adequate, tool for modeling braided river dynamics at this range of timescales. Rather, our goal in this research is to explore the utility, feasibility, and sensitivity of an event-scale, path-length-based modeling framework for predicting braided river dynamics. To that end, we further explore (a) which processes are naturally emergent and which must be explicitly parameterized in the model, (b) the sensitivity of the model to the choice of particle travel distance, and (c) whether an event-scale model timestep is adequate for producing braided channel dynamics. The results of this research may inform techniques for future morphodynamic modeling that seeks to maximize computational resources while modeling fluvial dynamics at the timescales of change.
Assessing self-care and social function using a computer adaptive testing version of the pediatric evaluation of disability inventory.

PubMed

Coster, Wendy J; Haley, Stephen M; Ni, Pengsheng; Dumas, Helene M; Fragala-Pinkham, Maria A

2008-04-01

To examine score agreement, validity, precision, and response burden of a prototype computer adaptive testing (CAT) version of the self-care and social function scales of the Pediatric Evaluation of Disability Inventory compared with the full-length version of these scales. Computer simulation analysis of cross-sectional and longitudinal retrospective data; cross-sectional prospective study. Pediatric rehabilitation hospital, including inpatient acute rehabilitation, day school program, outpatient clinics; community-based day care, preschool, and children's homes. Children with disabilities (n=469) and 412 children with no disabilities (analytic sample); 38 children with disabilities and 35 children without disabilities (cross-validation sample). Not applicable. Summary scores from prototype CAT applications of each scale using 15-, 10-, and 5-item stopping rules; scores from the full-length self-care and social function scales; time (in seconds) to complete assessments and respondent ratings of burden. Scores from both computer simulations and field administration of the prototype CATs were highly consistent with scores from full-length administration (r range, .94-.99). Using computer simulation of retrospective data, discriminant validity, and sensitivity to change of the CATs closely approximated that of the full-length scales, especially when the 15- and 10-item stopping rules were applied. In the cross-validation study the time to administer both CATs was 4 minutes, compared with over 16 minutes to complete the full-length scales. Self-care and social function score estimates from CAT administration are highly comparable with those obtained from full-length scale administration, with small losses in validity and precision and substantial decreases in administration time.
Is central dogma a global property of cellular information flow?

PubMed Central

Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

2012-01-01

The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcripts to proteins show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale, and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information. PMID:23189060
Is central dogma a global property of cellular information flow?

PubMed

Piras, Vincent; Tomita, Masaru; Selvarajoo, Kumar

2012-01-01

The central dogma of molecular biology has come under scrutiny in recent years. Here, we reviewed high-throughput mRNA and protein expression data of Escherichia coli, Saccharomyces cerevisiae, and several mammalian cells. At both single cell and population scales, the statistical comparisons between the entire transcriptomes and proteomes show clear correlation structures. In contrast, the pair-wise correlations of single transcripts to proteins show nullity. These data suggest that the organizing structure guiding cellular processes is observed at omics-wide scale, and not at single molecule level. The central dogma, thus, globally emerges as an average integrated flow of cellular information.
Irradiation With Carbon Ion Beams Induces Apoptosis, Autophagy, and Cellular Senescence in a Human Glioma-Derived Cell Line

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

Jinno-Oue, Atsushi; Shimizu, Nobuaki; 21st Century Center of Excellence Program for Biomedical Research Using Accelerator Technology, Maebashi, Gunma

2010-01-15

Purpose: We examined biological responses of human glioma cells to irradiation with carbon ion beams (C-ions). Methods and Materials: A human glioma-derived cell line, NP-2, was irradiated with C-ions. Apoptotic cell nuclei were stained with Hoechst 33342. Induction of autophagy was examined either by staining cells with monodansylcadaverine (MDC) or by Western blotting to detect conversion of microtuble-associated protein light chain 3 (MAP-LC3) (LC3-I) to the membrane-bound form (LC3-II). Cellular senescence markers including induction of senescence-associated beta-galactosidase (SA-beta-gal) were examined. The mean telomere length of irradiated cells was determined by Southern blot hybridization. Expression of tumor suppressor p53 and cyclin/cyclin-dependentmore » kinase inhibitor p21{sup WAF1/CIP1} in the irradiated cells was analyzed by Western blotting. Results: When NP-2 cells were irradiated with C-ions at 6 Gy, the major population of the cells died of apoptosis and autophagy. The residual fraction of attached cells (<1% of initially irradiated cells) could not form a colony: however, they showed a morphological phenotype consistent with cellular senescence, that is, enlarged and flattened appearance. The senescent nature of these attached cells was further indicated by staining for SA-beta-gal. The mean telomere length was not changed after irradiation with C-ions. Phosphorylation of p53 at serine 15 as well as the expression of p21{sup WAF1/CIP1} was induced in NP-2 cells after irradiation. Furthermore, we found that irradiation with C-ions induced cellular senescence in a human glioma cell line lacking functional p53. Conclusions: Irradiation with C-ions induced apoptosis, autophagy, and cellular senescence in human glioma cells.« less
Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration

PubMed Central

Le Maitre, Christine Lyn; Freemont, Anthony John; Hoyland, Judith Alison

2007-01-01

Current evidence implicates intervertebral disc degeneration as a major cause of low back pain, although its pathogenesis is poorly understood. Numerous characteristic features of disc degeneration mimic those seen during ageing but appear to occur at an accelerated rate. We hypothesised that this is due to accelerated cellular senescence, which causes fundamental changes in the ability of disc cells to maintain the intervertebral disc (IVD) matrix, thus leading to IVD degeneration. Cells isolated from non-degenerate and degenerate human tissue were assessed for mean telomere length, senescence-associated β-galactosidase (SA-β-gal), and replicative potential. Expression of P16INK4A (increased in cellular senescence) was also investigated in IVD tissue by means of immunohistochemistry. RNA from tissue and cultured cells was used for real-time polymerase chain reaction analysis for matrix metalloproteinase-13, ADAMTS 5 (a disintegrin and metalloprotease with thrombospondin motifs 5), and P16INK4A. Mean telomere length decreased with age in cells from non-degenerate tissue and also decreased with progressive stages of degeneration. In non-degenerate discs, there was an age-related increase in cellular expression of P16INK4A. Cells from degenerate discs (even from young patients) exhibited increased expression of P16INK4A, increased SA-β-gal staining, and a decrease in replicative potential. Importantly, there was a positive correlation between P16INK4A and matrix-degrading enzyme gene expression. Our findings indicate that disc cell senescence occurs in vivo and is accelerated in IVD degeneration. Furthermore, the senescent phenotype is associated with increased catabolism, implicating cellular senescence in the pathogenesis of IVD degeneration. PMID:17498290
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
Risky family processes prospectively forecast shorter telomere length mediated through negative emotions.

PubMed

Brody, Gene H; Yu, Tianyi; Shalev, Idan

2017-05-01

This study was designed to examine prospective associations of risky family environments with subsequent levels of negative emotions and peripheral blood mononuclear cell telomere length (TL), a marker of cellular aging. A second purpose was to determine whether negative emotions mediate the hypothesized link between risky family processes and diminished telomere length. Participants were 293 adolescents (age 17 years at the first assessment) and their primary caregivers. Caregivers provided data on risky family processes when the youths were age 17 years, youths reported their negative emotions at age 18 years, and youths' TL was assayed from a blood sample at age 22 years. The results revealed that (a) risky family processes forecast heightened negative emotions (β = .316, p < .001) and diminished TL (β = -.199, p = .003) among youths, (b) higher levels of negative emotions forecast shorter TL (β = -.187, p = .012), and (c) negative emotions served as a mediator connecting risky family processes with diminished TL (indirect effect = -0.012, 95% CI [-0.036, -0.002]). These findings are consistent with the hypothesis that risky family processes presage premature cellular aging through effects on negative emotions, with potential implications for lifelong health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
Template-assisted fabrication of protein nanocapsules

NASA Astrophysics Data System (ADS)

Dougherty, Shelley A.; Liang, Jianyu; Kowalik, Timothy F.

2009-02-01

Bionanomaterials have recently begun to spark a great amount of interest and could potentially revolutionize biomedical research. Nanoparticles, nanocapsules, and nanotubular structures are becoming attractive options in drug and gene delivery. The size of the delivery vehicles greatly impacts cellular uptake and makes it highly desirable to precisely control the diameter and length of nanocarriers to make uniform nanoparticles at low cost. Carbon nanotubes have shown great potential within the field of drug and gene delivery. However, their insolubility and cytotoxicity could severely delay FDA approval. A desirable alternative would be to fabricate nanostructures from biomaterials such as proteins, peptides, or liposomes, which are already FDA approved. In this article we demonstrate the preparation of protein nanocapsules with both ends sealed using a template-assisted alternate immersion method combined with controlled cleaving. Glucose oxidase nanocapsules with controllable diameter, wall thickness, and length were fabricated and characterized with SEM and TEM. The biochemical activity of glucose oxidase in the form of nanocapsules after processing was confirmed using UV spectrometry. Our future work will explore proteins suitable for drug encapsulation and cellular uptake and will focus on optimizing the cleaving process to gain precise control over the length of the nanocapsules.
Risky Family Processes Prospectively Forecast Shorter Telomere Length Mediated through Negative Emotions

PubMed Central

Brody, Gene H.; Yu, Tianyi; Shalev, Idan

2016-01-01

Objective This study was designed to examine prospective associations of risky family environments with subsequent levels of negative emotions and peripheral blood mononuclear cell telomere length (TL), a marker of cellular aging. A second purpose was to determine whether negative emotions mediate the hypothesized link between risky family processes and diminished telomere length. Methods Participants were 293 adolescents (age 17 years at the first assessment) and their primary caregivers. Caregivers provided data on risky family processes when the youths were age 17 years, youths reported their negative emotions at age 18 years, and youths’ TL was assayed from a blood sample at age 22 years. Results The results revealed that (a) risky family processes forecast heightened negative emotions (β = .316, p < .001) and diminished TL (β = −.199, p = .003) among youths, (b) higher levels of negative emotions forecast shorter TL (β = −.187, p = .012), and (c) negative emotions served as a mediator connecting risky family processes with diminished TL (indirect effect = −0.012, 95% CI [−0.036, −0.002]). Conclusions These findings are consistent with the hypothesis that risky family processes presage premature cellular aging through effects on negative emotions, with potential implications for lifelong health. PMID:27831704
The dynamics of oceanic fronts. Part 1: The Gulf Stream

NASA Technical Reports Server (NTRS)

Kao, T. W.

1970-01-01

The establishment and maintenance of the mean hydrographic properties of large scale density fronts in the upper ocean is considered. The dynamics is studied by posing an initial value problem starting with a near surface discharge of buoyant water with a prescribed density deficit into an ambient stationary fluid of uniform density. The full time dependent diffusion and Navier-Stokes equations for a constant Coriolis parameter are used in this study. Scaling analysis reveals three independent length scales of the problem, namely a radius of deformation or inertial length scale, Lo, a buoyance length scale, ho, and a diffusive length scale, hv. Two basic dimensionless parameters are then formed from these length scales, the thermal (or more precisely, the densimetric) Rossby number, Ro = Lo/ho and the Ekman number, E = hv/ho. The governing equations are then suitably scaled and the resulting normalized equations are shown to depend on E alone for problems of oceanic interest. Under this scaling, the solutions are similar for all Ro. It is also shown that 1/Ro is a measure of the frontal slope. The governing equations are solved numerically and the scaling analysis is confirmed. The solution indicates that an equilibrium state is established. The front can then be rendered stationary by a barotropic current from a larger scale along-front pressure gradient. In that quasisteady state, and for small values of E, the main thermocline and the inclined isopycnics forming the front have evolved, together with the along-front jet. Conservation of potential vorticity is also obtained in the light water pool. The surface jet exhibits anticyclonic shear in the light water pool and cyclonic shear across the front.
Rating disease progression of Friedreich’s ataxia by the International Cooperative Ataxia Rating Scale: analysis of a 603-patient database

PubMed Central

Coppard, Nicholas; Cooper, Jonathon M.; Delatycki, Martin B.; Dürr, Alexandra; Di Prospero, Nicholas A.; Giunti, Paola; Lynch, David R.; Schulz, J. B.; Rummey, Christian; Meier, Thomas

2013-01-01

The aim of this cross-sectional study was to analyse disease progression in Friedreich’s ataxia as measured by the International Cooperative Ataxia Rating Scale. Single ratings from 603 patients with Friedreich’s ataxia were analysed as a function of disease duration, age of onset and GAA repeat lengths. The relative contribution of items and subscales to the total score was studied as a function of disease progression. In addition, the scaling properties were assessed using standard statistical measures. Average total scale progression per year depends on the age of disease onset, the time since diagnosis and the GAA repeat length. The age of onset inversely correlates with increased GAA repeat length. For patients with an age of onset ≤14 years associated with a longer repeat length, the average yearly rate of decline was 2.5 ± 0.18 points in the total International Cooperative Ataxia Rating Scale for the first 20 years of disease duration, whereas patients with a later onset progress more slowly (1.8 ± 0.27 points/year). Ceiling effects in posture, gait and lower limb scale items lead to a reduced sensitivity of the scale in the severely affected population with a total score of >60 points. Psychometric scaling analysis shows generally favourable properties for the total scale, but the subscale grouping could be improved. This cross-sectional study provides a detailed characterization of the International Cooperative Ataxia Rating Scale. The analysis further provides rates of change separated for patients with early and late disease onset, which is driven by the GAA repeat length. Differences in the subscale dynamics merit consideration in the design of future clinical trials applying this scale as a neurological assessment instrument in Friedreich’s ataxia. PMID:23365101
Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

NASA Astrophysics Data System (ADS)

Chaplain, Mark A. J.; Powathil, Gibin G.

Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.
Multiscale Modelling of Cancer Progression and Treatment Control: The Role of Intracellular Heterogeneities in Chemotherapy Treatment

NASA Astrophysics Data System (ADS)

Chaplain, Mark A. J.; Powathil, Gibin G.

2015-04-01

Cancer is a complex, multiscale process involving interactions at intracellular, intercellular and tissue scales that are in turn susceptible to microenvironmental changes. Each individual cancer cell within a cancer cell mass is unique, with its own internal cellular pathways and biochemical interactions. These interactions contribute to the functional changes at the cellular and tissue scale, creating a heterogenous cancer cell population. Anticancer drugs are effective in controlling cancer growth by inflicting damage to various target molecules and thereby triggering multiple cellular and intracellular pathways, leading to cell death or cell-cycle arrest. One of the major impediments in the chemotherapy treatment of cancer is drug resistance driven by multiple mechanisms, including multi-drug and cell-cycle mediated resistance to chemotherapy drugs. In this article, we discuss two hybrid multiscale modelling approaches, incorporating multiple interactions involved in the sub-cellular, cellular and microenvironmental levels to study the effects of cell-cycle, phase-specific chemotherapy on the growth and progression of cancer cells.
A Two-length Scale Turbulence Model for Single-phase Multi-fluid Mixing

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

Schwarzkopf, J. D.; Livescu, D.; Baltzer, J. R.

2015-09-08

A two-length scale, second moment turbulence model (Reynolds averaged Navier-Stokes, RANS) is proposed to capture a wide variety of single-phase flows, spanning from incompressible flows with single fluids and mixtures of different density fluids (variable density flows) to flows over shock waves. The two-length scale model was developed to address an inconsistency present in the single-length scale models, e.g. the inability to match both variable density homogeneous Rayleigh-Taylor turbulence and Rayleigh-Taylor induced turbulence, as well as the inability to match both homogeneous shear and free shear flows. The two-length scale model focuses on separating the decay and transport length scales,more » as the two physical processes are generally different in inhomogeneous turbulence. This allows reasonable comparisons with statistics and spreading rates over such a wide range of turbulent flows using a common set of model coefficients. The specific canonical flows considered for calibrating the model include homogeneous shear, single-phase incompressible shear driven turbulence, variable density homogeneous Rayleigh-Taylor turbulence, Rayleigh-Taylor induced turbulence, and shocked isotropic turbulence. The second moment model shows to compare reasonably well with direct numerical simulations (DNS), experiments, and theory in most cases. The model was then applied to variable density shear layer and shock tube data and shows to be in reasonable agreement with DNS and experiments. Additionally, the importance of using DNS to calibrate and assess RANS type turbulence models is highlighted.« less
Microphase separation of comb copolymers with two different lengths of side chains

NASA Astrophysics Data System (ADS)

Aliev, M. A.; Kuzminyh, N. Yu.

2009-10-01

The phase behavior of the monodisperse AB comb copolymer melt contained the macromolecules of special architecture is discussed. Each macromolecule is assumed to be composed of two comb blocks which differ in numbers of side chains and numbers of monomer units in these chains. It is shown (by analysis of the structure factor of the melt) that microphase separation at two different length scales in the melt is possible. The large and small length scales correspond to separation between comb blocks and separation between monomer units in repeating fragments of blocks, respectively. The classification diagrams indicated which length scale is favored for a given parameters of chemical structure of macromolecules are constructed.

Radial distribution of dust, stars, gas, and star-formation rate in DustPedia⋆ face-on galaxies

NASA Astrophysics Data System (ADS)

Casasola, V.; Cassarà, L. P.; Bianchi, S.; Verstocken, S.; Xilouris, E.; Magrini, L.; Smith, M. W. L.; De Looze, I.; Galametz, M.; Madden, S. C.; Baes, M.; Clark, C.; Davies, J.; De Vis, P.; Evans, R.; Fritz, J.; Galliano, F.; Jones, A. P.; Mosenkov, A. V.; Viaene, S.; Ysard, N.

2017-09-01

Aims: The purpose of this work is the characterization of the radial distribution of dust, stars, gas, and star-formation rate (SFR) in a sub-sample of 18 face-on spiral galaxies extracted from the DustPedia sample. Methods: This study is performed by exploiting the multi-wavelength DustPedia database, from ultraviolet (UV) to sub-millimeter bands, in addition to molecular (12CO) and atomic (Hi) gas maps and metallicity abundance information available in the literature. We fitted the surface-brightness profiles of the tracers of dust and stars, the mass surface-density profiles of dust, stars, molecular gas, and total gas, and the SFR surface-density profiles with an exponential curve and derived their scale-lengths. We also developed a method to solve for the CO-to-H2 conversion factor (αCO) per galaxy by using dust- and gas-mass profiles. Results: Although each galaxy has its own peculiar behavior, we identified a common trend of the exponential scale-lengths versus wavelength. On average, the scale-lengths normalized to the B-band 25 mag/arcsec2 radius decrease from UV to 70 μm, from 0.4 to 0.2, and then increase back up to 0.3 at 500 microns. The main result is that, on average, the dust-mass surface-density scale-length is about 1.8 times the stellar one derived from IRAC data and the 3.6 μm surface brightness, and close to that in the UV. We found a mild dependence of the scale-lengths on the Hubble stage T: the scale-lengths of the Herschel bands and the 3.6 μm scale-length tend to increase from earlier to later types, the scale-length at 70 μm tends to be smaller than that at longer sub-mm wavelength with ratios between longer sub-mm wavelengths and 70 μm that decrease with increasing T. The scale-length ratio of SFR and stars shows a weak increasing trend towards later types. Our αCO determinations are in the range (0.3-9) M⊙ pc-2 (K km s-1)-1, almost invariant by using a fixed dust-to-gas ratio mass (DGR) or a DGR depending on metallicity gradient. DustPedia is a project funded by the EU under the heading "Exploitation of space science and exploration data". It has the primary goal of exploiting existing data in the Herschel Space Observatory and Planck Telescope databases.
Creation of current filaments in the solar corona

NASA Technical Reports Server (NTRS)

Mikic, Z.; Schnack, D. D.; Van Hoven, G.

1989-01-01

It has been suggested that the solar corona is heated by the dissipation of electric currents. The low value of the resistivity requires the magnetic field to have structure at very small length scales if this mechanism is to work. In this paper it is demonstrated that the coronal magnetic field acquires small-scale structure through the braiding produced by smooth, randomly phased, photospheric flows. The current density develops a filamentary structure and grows exponentially in time. Nonlinear processes in the ideal magnetohydrodynamic equations produce a cascade effect, in which the structure introduced by the flow at large length scales is transferred to smaller scales. If this process continues down to the resistive dissipation length scale, it would provide an effective mechanism for coronal heating.
Endoscopic probe optics for spectrally encoded confocal microscopy.

PubMed

Kang, Dongkyun; Carruth, Robert W; Kim, Minkyu; Schlachter, Simon C; Shishkov, Milen; Woods, Kevin; Tabatabaei, Nima; Wu, Tao; Tearney, Guillermo J

2013-01-01

Spectrally encoded confocal microscopy (SECM) is a form of reflectance confocal microscopy that can achieve high imaging speeds using relatively simple probe optics. Previously, the feasibility of conducting large-area SECM imaging of the esophagus in bench top setups has been demonstrated. Challenges remain, however, in translating SECM into a clinically-useable device; the tissue imaging performance should be improved, and the probe size needs to be significantly reduced so that it can fit into luminal organs of interest. In this paper, we report the development of new SECM endoscopic probe optics that addresses these challenges. A custom water-immersion aspheric singlet (NA = 0.5) was developed and used as the objective lens. The water-immersion condition was used to reduce the spherical aberrations and specular reflection from the tissue surface, which enables cellular imaging of the tissue deep below the surface. A custom collimation lens and a small-size grating were used along with the custom aspheric singlet to reduce the probe size. A dual-clad fiber was used to provide both the single- and multi- mode detection modes. The SECM probe optics was made to be 5.85 mm in diameter and 30 mm in length, which is small enough for safe and comfortable endoscopic imaging of the gastrointestinal tract. The lateral resolution was 1.8 and 2.3 µm for the single- and multi- mode detection modes, respectively, and the axial resolution 11 and 17 µm. SECM images of the swine esophageal tissue demonstrated the capability of this device to enable the visualization of characteristic cellular structural features, including basal cell nuclei and papillae, down to the imaging depth of 260 µm. These results suggest that the new SECM endoscopic probe optics will be useful for imaging large areas of the esophagus at the cellular scale in vivo.
Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes.

PubMed

Ivarsson, Ylva; Arnold, Roland; McLaughlin, Megan; Nim, Satra; Joshi, Rakesh; Ray, Debashish; Liu, Bernard; Teyra, Joan; Pawson, Tony; Moffat, Jason; Li, Shawn Shun-Cheng; Sidhu, Sachdev S; Kim, Philip M

2014-02-18

The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain-SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between full-length Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit α-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host-virus protein-protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen-host protein-protein interactions.
Fabrication, Characterization, And Deformation of 3D Structural Meta-Materials

NASA Astrophysics Data System (ADS)

Montemayor, Lauren C.

Current technological advances in fabrication methods have provided pathways to creating architected structural meta-materials similar to those found in natural organisms that are structurally robust and lightweight, such as diatoms. Structural meta-materials are materials with mechanical properties that are determined by material properties at various length scales, which range from the material microstructure (nm) to the macro-scale architecture (mum -- mm). It is now possible to exploit material size effect, which emerge at the nanometer length scale, as well as structural effects to tune the material properties and failure mechanisms of small-scale cellular solids, such as nanolattices. This work demonstrates the fabrication and mechanical properties of 3-dimensional hollow nanolattices in both tension and compression. Hollow gold nanolattices loaded in uniaxial compression demonstrate that strength and stiffness vary as a function of geometry and tube wall thickness. Structural effects were explored by increasing the unit cell angle from 30° to 60° while keeping all other parameters constant; material size effects were probed by varying the tube wall thickness, t, from 200nm to 635nm, at a constant relative density and grain size. In-situ uniaxial compression experiments reveal an order-of-magnitude increase in yield stress and modulus in nanolattices with greater lattice angles, and a 150% increase in the yield strength without a concomitant change in modulus in thicker-walled nanolattices for fixed lattice angles. These results imply that independent control of structural and material size effects enables tunability of mechanical properties of 3-dimensional architected meta-materials and highlight the importance of material, geometric, and microstructural effects in small-scale mechanics. This work also explores the flaw tolerance of 3D hollow-tube alumina kagome nanolattices with and without pre-fabricated notches, both in experiment and simulation. Experiments demonstrate that the hollow kagome nanolattices in uniaxial tension always fail at the same load when the ratio of notch length (a) to sample width (w) is no greater than 1/3, with no correlation between failure occurring at or away from the notch. For notches with (a/w) > 1/3, the samples fail at lower peak loads and this is attributed to the increased compliance as fewer unit cells span the un-notched region. Finite element simulations of the kagome tension samples show that the failure is governed by tensile loading for (a/w) < 1/3 but as ( a/w) increases, bending begins to play a significant role in the failure. This work explores the flaw sensitivity of hollow alumina kagome nanolattices in tension, using experiments and simulations, and demonstrates that the discrete-continuum duality of architected structural meta-materials gives rise to their flaw insensitivity even when made entirely of intrinsically brittle materials.
Constitutive Models for the Force-Extension Behavior of Biological Filaments

NASA Astrophysics Data System (ADS)

Palmer, J. S.; Castro, C. E.; Arslan, M.; Boyce, M. C.

Biopolymer filaments form the molecular backbone of biological structures throughout the body. The biomechanical response of single filaments yields insight into their individual behavior at the molecular level as well as their concerted networked behavior at the cellular and tissue scales. This paper focuses on modeling approaches for axial force vs. extension behavior of single biopolymer filaments within three stiffness regimes: flexible, semiflexible, and stiff. The end-to-end force-extension behaviors of flexible and semiflexible filaments arise as a result of a reduction in configurational space as the filament is straightened and are captured with entropic models including the freely jointed chain model and the worm-like chain model. As the filament is straightened and the end-to-end distance approaches the filament contour length, the contour length is directly axially extended and an internal energy contribution governs the force-extension behavior in this limiting extension regime. On the other hand, for stiff filaments in originally crimped or kinked configurations, the end-to-end force vs. extension behavior results from the unbending (straightening) of the crimped configuration as governed by an internal energy based elastica approximation which is also complemented by an axial stretching contribution once the end-to-end distance approaches the contour length of the filament. Simplified, analytical force-extension relationships are developed for the worm-like chain model for semiflexible filaments, and for the Euler elastica model for stiffer, wavy fibers. For the case of flexible molecules containing modular folded domains, the influence of force-induced unfolding on the force-extension behavior of single molecules and assemblies of multiple molecules is also presented.
Wavelet Imaging on Multiple Scales (WIMS) reveals focal adhesion distributions, dynamics and coupling between actomyosin bundle stability

PubMed Central

Toplak, Tim; Palmieri, Benoit; Juanes-García, Alba; Vicente-Manzanares, Miguel; Grant, Martin; Wiseman, Paul W.

2017-01-01

We introduce and use Wavelet Imaging on Multiple Scales (WIMS) as an improvement to fluorescence correlation spectroscopy to measure physical processes and features that occur across multiple length scales. In this study, wavelet transforms of cell images are used to characterize molecular dynamics at the cellular and subcellular levels (i.e. focal adhesions). We show the usefulness of the technique by applying WIMS to an image time series of a migrating osteosarcoma cell expressing fluorescently labelled adhesion proteins, which allows us to characterize different components of the cell ranging from optical resolution scale through to focal adhesion and whole cell size scales. Using WIMS we measured focal adhesion numbers, orientation and cell boundary velocities for retraction and protrusion. We also determine the internal dynamics of individual focal adhesions undergoing assembly, disassembly or elongation. Thus confirming as previously shown, WIMS reveals that the number of adhesions and the area of the protruding region of the cell are strongly correlated, establishing a correlation between protrusion size and adhesion dynamics. We also apply this technique to characterize the behavior of adhesions, actin and myosin in Chinese hamster ovary cells expressing a mutant form of myosin IIB (1935D) that displays decreased filament stability and impairs front-back cell polarity. We find separate populations of actin and myosin at each adhesion pole for both the mutant and wild type form. However, we find these populations move rapidly inwards toward one another in the mutant case in contrast to the cells that express wild type myosin IIB where those populations remain stationary. Results obtained with these two systems demonstrate how WIMS has the potential to reveal novel correlations between chosen parameters that belong to different scales. PMID:29049414
Scale effects in crystal plasticity

NASA Astrophysics Data System (ADS)

Padubidri Janardhanachar, Guruprasad

The goal of this research work is to further the understanding of crystal plasticity, particularly at reduced structural and material length scales. Fundamental understanding of plasticity is central to various challenges facing design and manufacturing of materials for structural and electronic device applications. The development of microstructurally tailored advanced metallic materials with enhanced mechanical properties that can withstand extremes in stress, strain, and temperature, will aid in increasing the efficiency of power generating systems by allowing them to work at higher temperatures and pressures. High specific strength materials can lead to low fuel consumption in transport vehicles. Experiments have shown that enhanced mechanical properties can be obtained in materials by constraining their size, microstructure (e.g. grain size), or both for various applications. For the successful design of these materials, it is necessary to have a thorough understanding of the influence of different length scales and evolving microstructure on the overall behavior. In this study, distinction is made between the effect of structural and material length scale on the mechanical behavior of materials. A length scale associated with an underlying physical mechanism influencing the mechanical behavior can overlap with either structural length scales or material length scales. If it overlaps with structural length scales, then the material is said to be dimensionally constrained. On the other hand, if it overlaps with material length scales, for example grain size, then the material is said to be microstructurally constrained. The objectives of this research work are: (1) to investigate scale and size effects due to dimensional constraints; (2) to investigate size effects due to microstructural constraints; and (3) to develop a size dependent hardening model through coarse graining of dislocation dynamics. A discrete dislocation dynamics (DDD) framework where the scale of analysis is intermediate between a fully discretized (e.g. atomistic) and fully continuum is used for this study. This mesoscale tool allows to address all the stated objectives of this study within a single framework. Within this framework, the effect of structural and the material length scales are naturally accounted for in the simulations and need not be specified in an ad hoc manner, as in some continuum models. It holds the promise of connecting the evolution of the defect microstructure to the effective response of the crystal. Further, it provides useful information to develop physically motivated continuum models to model size effects in materials. The contributions of this study are: (a) provides a new interpretation of mechanical size effect due to only dimensional constraint using DDD; (b) a development of an experimentally validated DDD simulation methodology to model Cu micropillars; (c) a coarse graining technique using DDD to develop a phenomenological model to capture size effect on strain hardening; and (d) a development of a DDD framework for polycrystals to investigate grain size effect on yield strength and strain hardening.
Organ size control via hydraulically gated oscillations.

PubMed

Ruiz-Herrero, Teresa; Alessandri, Kévin; Gurchenkov, Basile V; Nassoy, Pierre; Mahadevan, L

2017-12-01

Hollow vesicular tissues of various sizes and shapes arise in biological organs such as ears, guts, hearts, brains and even entire organisms. Regulating their size and shape is crucial for their function. Although chemical signaling has been thought to play a role in the regulation of cellular processes that feed into larger scales, it is increasingly recognized that mechanical forces are involved in the modulation of size and shape at larger length scales. Motivated by a variety of examples of tissue cyst formation and size control that show simultaneous growth and size oscillations, we create a minimal theoretical framework for the growth and dynamics of a soft, fluid-permeable, spherical shell. We show that these shells can relieve internal pressure by bursting intermittently, shrinking and re-growing, providing a simple mechanism by which hydraulically gated oscillations can regulate size. To test our theory, we develop an in vitro experimental set-up to monitor the growth and oscillations of a hollow tissue spheroid growing freely or when confined. A simple generalization of our theory to account for irreversible deformations allows us to explain the time scales and the amplitudes of oscillations in terms of the geometry and mechanical properties of the tissue shells. Taken together, our theory and experimental observations show how soft hydraulics can regulate the size of growing tissue shells. © 2017. Published by The Company of Biologists Ltd.
Electrostatically Driven Assembly of Charged Amphiphiles Forming Crystallized Membranes, Vesicles and Nanofiber Arrays

NASA Astrophysics Data System (ADS)

Leung, Cheuk Yui Curtis

Charged amphiphilic molecules can self-assemble into a large variety of objects including membranes, vesicles and fibers. These micro to nano-scale structures have been drawing increasing attention due to their broad applications, especially in biotechnology and biomedicine. In this dissertation, three self-assembled systems were investigated: +3/-1 self-assembled catanionic membranes, +2/-1 self-assembled catanionic membranes and +1 self-assembled nanofibers. Transmission electron microscopy (TEM) combined with synchrotron small and wide angle x-ray scattering (SAXS and WAXS) were used to characterize the coassembled structures from the mesoscopic to nanometer scale. We designed a system of +3 and -1 ionic amphiphiles that coassemble into crystalline ionic bilayer vesicles with large variety of geometries that resemble polyhedral cellular crystalline shells and archaea wall envelopes. The degree of ionization of the amphiphiles and their intermolecular electrostatic interactions can be controlled by varying pH. The molecular packing of these membranes showed a hexagonal to rectangular-C to hexagonal phase transition with increasing pH, resulting in significant changes to the membrane morphology. A similar mixture of +2 and -1 ionic amphiphiles was also investigated. In addition to varying pH, which controls the headgroup attractions, we also adjust the tail length of the amphiphiles to control the van der Waals interactions between the tails. A 2D phase diagram was developed to show how pH and tail length can be used to control the intermolecular packing within the membranes. Another system of self-assembled nanofiber network formed by positively charged amphiphiles was also studied. These highly charged fibers repel each other and are packed in hexagonal lattice with lattice constant at least eight times of the fiber diameter. The d-spacing and the crystal structure can be controlled by varying the solution concentration and temperature.
Cellular convection in a chamber with a warm surface raft

NASA Astrophysics Data System (ADS)

Whitehead, J. A.; Shea, Erin; Behn, Mark D.

2011-10-01

We calculate velocity and temperature fields for Rayleigh-Benard convection in a chamber with a warm raft that floats along the top surface for Rayleigh number up to Ra = 20 000. Two-dimensional, infinite Prandtl number, Boussinesq approximation equations are numerically advanced in time from a motionless state in a chamber of length L' and depth D'. We consider cases with an insulated raft and a raft of fixed temperature. Either oscillatory or stationary flow exists. In the case with an insulated raft over a fluid, there are only three parameters that govern the system: Rayleigh number (Ra), scaled chamber length (L = L'/D'), and scaled raft width (W). For W = 0 and L = 1, linear theory shows that the marginal state without a raft is at a Rayleigh number of 23π4=779.3, but we find that for the smallest W (determined by numerical grid size) the raft approaches the center monotonically in time for Ra<790. For 790871. For larger raft widths, there is a range of W that produces raft oscillation at each Ra up to 20 000. Rafts in longer cavities (L = 2 and 4) have almost no oscillatory behavior. With a raft of temperature set to different values of Tr rather than insulating, a fixed Rayleigh number Ra =20000, a square chamber (L = 1), fixed raft width, and with internal heat generation, there are two ranges of oscillating flow.
Severely impaired bone material quality in Chihuahua zebrafish resembles classical dominant human osteogenesis imperfecta.

PubMed

Fiedler, Imke A K; Schmidt, Felix N; Wölfel, Eva M; Plumeyer, Christine; Milovanovic, Petar; Gioia, Roberta; Tonelli, Francesca; Bale, Hrishikesh A; Jähn, Katharina; Besio, Roberta; Forlino, Antonella; Busse, Björn

2018-04-17

Excessive skeletal deformations and brittle fractures in the vast majority of patients suffering from osteogenesis imperfecta (OI) are a result of substantially reduced bone quality. Since the mechanical competence of bone is dependent on the tissue characteristics at small length scales, it is of crucial importance to assess how osteogenesis imperfecta manifests at the micro- and nanoscale of bone. In this context, the Chihuahua (Chi/ +) zebrafish, carrying a heterozygous glycine substitution in the α1 chain of collagen type I, has recently been proposed as suitable animal model of classical dominant OI, showing skeletal deformities, altered mineralization patterns and a smaller body size. This study assessed the bone quality properties of Chi/+ at multiple length scales using micro-computed tomography (micro-CT), histomorphometry, quantitative back-scattered electron imaging, Fourier transform infrared spectroscopy, nanoindentation and X-ray microscopy. At the skeletal level, Chi/+ display smaller body size, deformities and fracture calli in the ribs. Morphological changes at the whole bone level showed that the vertebrae in Chi/+ had a smaller size, smaller thickness and distorted shape. At the tissue level, Chi/+ displayed a higher degree of mineralization, lower collagen maturity, lower mineral maturity, altered osteoblast morphology, and lower osteocyte lacunar density compared to WT. The alterations in the cellular, compositional and structural properties of Chi/+ bones bear an explanation for the impaired local mechanical properties, which promote an increase in overall bone fragility in Chi/ +. The quantitative assessment of bone quality in Chi/+ thus further validates this mutant as an important model reflecting osseous characteristics associated with human classical dominant osteogenesis imperfecta. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Aerosol based direct-write micro-additive fabrication method for sub-mm 3D metal-dielectric structures

NASA Astrophysics Data System (ADS)

Rahman, Taibur; Renaud, Luke; Heo, Deuk; Renn, Michael; Panat, Rahul

2015-10-01

The fabrication of 3D metal-dielectric structures at sub-mm length scale is highly important in order to realize low-loss passives and GHz wavelength antennas with applications in wearable and Internet-of-Things (IoT) devices. The inherent 2D nature of lithographic processes severely limits the available manufacturing routes to fabricate 3D structures. Further, the lithographic processes are subtractive and require the use of environmentally harmful chemicals. In this letter, we demonstrate an additive manufacturing method to fabricate 3D metal-dielectric structures at sub-mm length scale. A UV curable dielectric is dispensed from an Aerosol Jet system at 10-100 µm length scale and instantaneously cured to build complex 3D shapes at a length scale <1 mm. A metal nanoparticle ink is then dispensed over the 3D dielectric using a combination of jetting action and tilted dispense head, also using the Aerosol Jet technique and at a length scale 10-100 µm, followed by the nanoparticle sintering. Simulation studies are carried out to demonstrate the feasibility of using such structures as mm-wave antennas. The manufacturing method described in this letter opens up the possibility of fabricating an entirely new class of custom-shaped 3D structures at a sub-mm length scale with potential applications in 3D antennas and passives.
WE-DE-202-02: Are Track Structure Simulations Truly Needed for Radiobiology at the Cellular and Tissue Levels?

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

Stewart, R.

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less
Accurate aging of juvenile salmonids using fork lengths

USGS Publications Warehouse

Sethi, Suresh; Gerken, Jonathon; Ashline, Joshua

2017-01-01

Juvenile salmon life history strategies, survival, and habitat interactions may vary by age cohort. However, aging individual juvenile fish using scale reading is time consuming and can be error prone. Fork length data are routinely measured while sampling juvenile salmonids. We explore the performance of aging juvenile fish based solely on fork length data, using finite Gaussian mixture models to describe multimodal size distributions and estimate optimal age-discriminating length thresholds. Fork length-based ages are compared against a validation set of juvenile coho salmon, Oncorynchus kisutch, aged by scales. Results for juvenile coho salmon indicate greater than 95% accuracy can be achieved by aging fish using length thresholds estimated from mixture models. Highest accuracy is achieved when aged fish are compared to length thresholds generated from samples from the same drainage, time of year, and habitat type (lentic versus lotic), although relatively high aging accuracy can still be achieved when thresholds are extrapolated to fish from populations in different years or drainages. Fork length-based aging thresholds are applicable for taxa for which multiple age cohorts coexist sympatrically. Where applicable, the method of aging individual fish is relatively quick to implement and can avoid ager interpretation bias common in scale-based aging.
Social Isolation Shortens Telomeres in African Grey Parrots (Psittacus erithacus erithacus)

PubMed Central

Aydinonat, Denise; Penn, Dustin J.; Smith, Steve; Moodley, Yoshan; Hoelzl, Franz; Knauer, Felix; Schwarzenberger, Franz

2014-01-01

Telomeres, the caps of eukaryotic chromosomes, control chromosome stability and cellular senescence, but aging and exposure to chronic stress are suspected to cause attrition of telomere length. We investigated the effect of social isolation on telomere length in the highly social and intelligent African Grey parrot (Psittacus erithacus erithacus). Our study population consisted of single-housed (n = 26) and pair-housed (n = 19) captive individuals between 0.75 to 45 years of age. Relative telomere length of erythrocyte DNA was measured by quantitative real-time PCR. We found that telomere length declined with age (p<0.001), and socially isolated parrots had significantly shorter telomeres compared to pair-housed birds (p<0.001) – even among birds of similar ages. Our findings provide the first evidence that social isolation affects telomere length, which supports the hypothesis that telomeres provide a biomarker indicating exposure to chronic stress. PMID:24705445
Porotic paradox: distribution of cortical bone pore sizes at nano- and micro-levels in healthy vs. fragile human bone.

PubMed

Milovanovic, Petar; Vukovic, Zorica; Antonijevic, Djordje; Djonic, Danijela; Zivkovic, Vladimir; Nikolic, Slobodan; Djuric, Marija

2017-05-01

Bone is a remarkable biological nanocomposite material showing peculiar hierarchical organization from smaller (nano, micro) to larger (macro) length scales. Increased material porosity is considered as the main feature of fragile bone at larger length-scales. However, there is a shortage of quantitative information on bone porosity at smaller length-scales, as well as on the distribution of pore sizes in healthy vs. fragile bone. Therefore, here we investigated how healthy and fragile bones differ in pore volume and pore size distribution patterns, considering a wide range of mostly neglected pore sizes from nano to micron-length scales (7.5 to 15000 nm). Cortical bone specimens from four young healthy women (age: 35 ± 6 years) and five women with bone fracture (age: 82 ± 5 years) were analyzed by mercury porosimetry. Our findings showed that, surprisingly, fragile bone demonstrated lower pore volume at the measured scales. Furtnermore, pore size distribution showed differential patterns between healthy and fragile bones, where healthy bone showed especially high proportion of pores between 200 and 15000 nm. Therefore, although fragile bones are known for increased porosity at macroscopic level and level of tens or hundreds of microns as firmly established in the literature, our study with a unique assessment range of nano-to micron-sized pores reveal that osteoporosis does not imply increased porosity at all length scales. Our thorough assessment of bone porosity reveals a specific distribution of porosities at smaller length-scales and contributes to proper understanding of bone structure which is important for designing new biomimetic bone substitute materials.
Assessing self-care and social function using a computer adaptive testing version of the Pediatric Evaluation of Disability Inventory Accepted for Publication, Archives of Physical Medicine and Rehabilitation

PubMed Central

Coster, Wendy J.; Haley, Stephen M.; Ni, Pengsheng; Dumas, Helene M.; Fragala-Pinkham, Maria A.

2009-01-01

Objective To examine score agreement, validity, precision, and response burden of a prototype computer adaptive testing (CAT) version of the Self-Care and Social Function scales of the Pediatric Evaluation of Disability Inventory (PEDI) compared to the full-length version of these scales. Design Computer simulation analysis of cross-sectional and longitudinal retrospective data; cross-sectional prospective study. Settings Pediatric rehabilitation hospital, including inpatient acute rehabilitation, day school program, outpatient clinics; community-based day care, preschool, and children’s homes. Participants Four hundred sixty-nine children with disabilities and 412 children with no disabilities (analytic sample); 38 children with disabilities and 35 children without disabilities (cross-validation sample). Interventions Not applicable. Main Outcome Measures Summary scores from prototype CAT applications of each scale using 15-, 10-, and 5-item stopping rules; scores from the full-length Self-Care and Social Function scales; time (in seconds) to complete assessments and respondent ratings of burden. Results Scores from both computer simulations and field administration of the prototype CATs were highly consistent with scores from full-length administration (all r’s between .94 and .99). Using computer simulation of retrospective data, discriminant validity and sensitivity to change of the CATs closely approximated that of the full-length scales, especially when the 15- and 10-item stopping rules were applied. In the cross-validation study the time to administer both CATs was 4 minutes, compared to over 16 minutes to complete the full-length scales. Conclusions Self-care and Social Function score estimates from CAT administration are highly comparable to those obtained from full-length scale administration, with small losses in validity and precision and substantial decreases in administration time. PMID:18373991
Hierarchical roughness of sticky and non-sticky superhydrophobic surfaces

NASA Astrophysics Data System (ADS)

Raza, Muhammad; Kooij, Stefan; van Silfhout, Arend; Zandvliet, Harold; Poelsema, Bene

2011-11-01

The importance of superhydrophobic substrates (contact angle >150° with sliding angle <10°) in modern technology is undeniable. We present a simple colloidal route to manufacture superstructured arrays with single- and multi-length-scaled roughness to obtain sticky and non-sticky superhydrophobic surfaces. The largest length scale is provided by (multi-)layers of silica spheres (1 μm, 500nm and 150nm diameter). Decoration with gold nanoparticles (14nm, 26nm and 47nm) gives rise to a second length scale. To lower the surface energy, gold nanoparticles are functionalized with dodecanethiol and the silica spheres by perfluorooctyltriethoxysilane. The morphology was examined by helium ion microscopy (HIM), while wettability measurements were performed by using the sessile drop method. We conclude that wettability can be controlled by changing the surface chemistry and/or length scales of the structures. To achieve truly non-sticky superhydrophobic surfaces, hierarchical roughness plays a vital role.
On the physics of electron ejection from laser-irradiated overdense plasmas

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

Thévenet, M.; Vincenti, H.; Faure, J.

2016-06-15

Using 1D and 2D PIC simulations, we describe and model the backward ejection of electron bunches when a laser pulse reflects off an overdense plasma with a short density gradient on its front side. The dependence on the laser intensity and gradient scale length is studied. It is found that during each laser period, the incident laser pulse generates a large charge-separation field, or plasma capacitor, which accelerates an attosecond bunch of electrons toward vacuum. This process is maximized for short gradient scale lengths and collapses when the gradient scale length is comparable to the laser wavelength. We develop amore » model that reproduces the electron dynamics and the dependence on laser intensity and gradient scale length. This process is shown to be strongly linked with high harmonic generation via the Relativistic Oscillating Mirror mechanism.« less

Scale effects and morphological diversification in hindlimb segment mass proportions in neognath birds.

PubMed

Kilbourne, Brandon M

2014-01-01

In spite of considerable work on the linear proportions of limbs in amniotes, it remains unknown whether differences in scale effects between proximal and distal limb segments has the potential to influence locomotor costs in amniote lineages and how changes in the mass proportions of limbs have factored into amniote diversification. To broaden our understanding of how the mass proportions of limbs vary within amniote lineages, I collected data on hindlimb segment masses - thigh, shank, pes, tarsometatarsal segment, and digits - from 38 species of neognath birds, one of the most speciose amniote clades. I scaled each of these traits against measures of body size (body mass) and hindlimb size (hindlimb length) to test for departures from isometry. Additionally, I applied two parameters of trait evolution (Pagel's λ and δ) to understand patterns of diversification in hindlimb segment mass in neognaths. All segment masses are positively allometric with body mass. Segment masses are isometric with hindlimb length. When examining scale effects in the neognath subclade Land Birds, segment masses were again positively allometric with body mass; however, shank, pedal, and tarsometatarsal segment masses were also positively allometric with hindlimb length. Methods of branch length scaling to detect phylogenetic signal (i.e., Pagel's λ) and increasing or decreasing rates of trait change over time (i.e., Pagel's δ) suffer from wide confidence intervals, likely due to small sample size and deep divergence times. The scaling of segment masses appears to be more strongly related to the scaling of limb bone mass as opposed to length, and the scaling of hindlimb mass distribution is more a function of scale effects in limb posture than proximo-distal differences in the scaling of limb segment mass. Though negative allometry of segment masses appears to be precluded by the need for mechanically sound limbs, the positive allometry of segment masses relative to body mass may underlie scale effects in stride frequency and length between smaller and larger neognaths. While variation in linear proportions of limbs appear to be governed by developmental mechanisms, variation in mass proportions does not appear to be constrained so.
Scale effects and morphological diversification in hindlimb segment mass proportions in neognath birds

PubMed Central

2014-01-01

Introduction In spite of considerable work on the linear proportions of limbs in amniotes, it remains unknown whether differences in scale effects between proximal and distal limb segments has the potential to influence locomotor costs in amniote lineages and how changes in the mass proportions of limbs have factored into amniote diversification. To broaden our understanding of how the mass proportions of limbs vary within amniote lineages, I collected data on hindlimb segment masses – thigh, shank, pes, tarsometatarsal segment, and digits – from 38 species of neognath birds, one of the most speciose amniote clades. I scaled each of these traits against measures of body size (body mass) and hindlimb size (hindlimb length) to test for departures from isometry. Additionally, I applied two parameters of trait evolution (Pagel’s λ and δ) to understand patterns of diversification in hindlimb segment mass in neognaths. Results All segment masses are positively allometric with body mass. Segment masses are isometric with hindlimb length. When examining scale effects in the neognath subclade Land Birds, segment masses were again positively allometric with body mass; however, shank, pedal, and tarsometatarsal segment masses were also positively allometric with hindlimb length. Methods of branch length scaling to detect phylogenetic signal (i.e., Pagel’s λ) and increasing or decreasing rates of trait change over time (i.e., Pagel’s δ) suffer from wide confidence intervals, likely due to small sample size and deep divergence times. Conclusions The scaling of segment masses appears to be more strongly related to the scaling of limb bone mass as opposed to length, and the scaling of hindlimb mass distribution is more a function of scale effects in limb posture than proximo-distal differences in the scaling of limb segment mass. Though negative allometry of segment masses appears to be precluded by the need for mechanically sound limbs, the positive allometry of segment masses relative to body mass may underlie scale effects in stride frequency and length between smaller and larger neognaths. While variation in linear proportions of limbs appear to be governed by developmental mechanisms, variation in mass proportions does not appear to be constrained so. PMID:24876886
Neandertal clavicle length

PubMed Central

Trinkaus, Erik; Holliday, Trenton W.; Auerbach, Benjamin M.

2014-01-01

The Late Pleistocene archaic humans from western Eurasia (the Neandertals) have been described for a century as exhibiting absolutely and relatively long clavicles. This aspect of their body proportions has been used to distinguish them from modern humans, invoked to account for other aspects of their anatomy and genetics, used in assessments of their phylogenetic polarities, and used as evidence for Late Pleistocene population relationships. However, it has been unclear whether the usual scaling of Neandertal clavicular lengths to their associated humeral lengths reflects long clavicles, short humeri, or both. Neandertal clavicle lengths, along with those of early modern humans and latitudinally diverse recent humans, were compared with both humeral lengths and estimated body masses (based on femoral head diameters). The Neandertal do have long clavicles relative their humeri, even though they fall within the ranges of variation of early and recent humans. However, when scaled to body masses, their humeral lengths are relatively short, and their clavicular lengths are indistinguishable from those of Late Pleistocene and recent modern humans. The few sufficiently complete Early Pleistocene Homo clavicles seem to have relative lengths also well within recent human variation. Therefore, appropriately scaled clavicular length seems to have varied little through the genus Homo, and it should not be used to account for other aspects of Neandertal biology or their phylogenetic status. PMID:24616525
Converging cellular themes for the hereditary spastic paraplegias.

PubMed

Blackstone, Craig

2018-05-10

Hereditary spastic paraplegias (HSPs) are neurologic disorders characterized by prominent lower-extremity spasticity, resulting from a length-dependent axonopathy of corticospinal upper motor neurons. They are among the most genetically-diverse neurologic disorders, with >80 distinct genetic loci and over 60 identified genes. Studies investigating the molecular pathogenesis underlying HSPs have emphasized the importance of converging cellular pathogenic themes in the most common forms of HSP, providing compelling targets for therapy. Most notably, these include organelle shaping and biogenesis as well as membrane and cargo trafficking. Published by Elsevier Ltd.
A study for bank effect on ship traffic in narrow water channels using cellular automata

NASA Astrophysics Data System (ADS)

Sun, Zhuo; Cong, Shuang; Pan, Junnan; Zheng, Jianfeng

2017-12-01

In narrow water channels, bank might affect nearby ships due to hydrodynamic forces (bank effect). To avoid accidents, different sailing rules (i.e., lane-changing, speed control) are required. In this paper, a two-lane cellular automata model is proposed to evaluate such phenomena. Numerical experiments show that ships will form a “slow-moving chunk” in the bank area, which will significantly block the flux. As further study demonstrated to alleviate bank effect, ship speed and bank length should be controlled.
Chemical Imaging of the Cell Membrane by NanoSIMS

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

Weber, P K; Kraft, M L; Frisz, J F

2010-02-23

The existence of lipid microdomains and their role in cell membrane organization are currently topics of great interest and controversy. The cell membrane is composed of a lipid bilayer with embedded proteins that can flow along the two-dimensional surface defined by the membrane. Microdomains, known as lipid rafts, are believed to play a central role in organizing this fluid system, enabling the cell membrane to carry out essential cellular processes, including protein recruitment and signal transduction. Lipid rafts are also implicated in cell invasion by pathogens, as in the case of the HIV. Therefore, understanding the role of lipid raftsmore » in cell membrane organization not only has broad scientific implications, but also has practical implications for medical therapies. One of the major limitations on lipid organization research has been the inability to directly analyze lipid composition without introducing artifacts and at the relevant length-scales of tens to hundreds of nanometers. Fluorescence microscopy is widely used due to its sensitivity and specificity to the labeled species, but only the labeled components can be observed, fluorophores can alter the behavior of the lipids they label, and the length scales relevant to imaging cell membrane domains are between that probed by fluorescence resonance energy transfer (FRET) imaging (<10 nm) and the diffraction limit of light. Topographical features can be imaged on this length scale by atomic force microscopy (AFM), but the chemical composition of the observed structures cannot be determined. Immuno-labeling can be used to study the distribution of membrane proteins at high resolution, but not lipid composition. We are using imaging mass spectrometry by secondary ion mass spectrometry (SIMS) in concert with other high resolution imaging methods to overcome these limitations. The experimental approach of this project is to combine molecule-specific stable isotope labeling with high-resolution SIMS using a Cameca NanoSIMS 50 to probe membrane organization and test microdomain hypotheses. The NanoSIMS is an imaging secondary ion mass spectrometer with an unprecedented combination of spatial resolution, sensitivity and mass specificity. It has 50 nm lateral resolution and is capable of detecting 1 in 20 nitrogen atoms while excluding near-neighbor isobaric interferences. The tightly focused cesium ion beam is rastered across the sample to produce simultaneous, quantitative digital images of up to five different masses. By labeling each specific components of a membrane with a unique rare stable isotope or element and mapping the location of the labels with the NanoSIMS, the location of the each labeled component can be determined and quantified. This new approach to membrane composition analysis allows molecular interactions of biological membranes to be probed at length-scales relevant to lipid rafts (10s to 100s of nm) that were not previously possible. Results from our most recent experiments analyzing whole cells will be presented.« less
Spatial confinement of active microtubule networks induces large-scale rotational cytoplasmic flow

PubMed Central

Suzuki, Kazuya; Miyazaki, Makito; Takagi, Jun; Itabashi, Takeshi; Ishiwata, Shin’ichi

2017-01-01

Collective behaviors of motile units through hydrodynamic interactions induce directed fluid flow on a larger length scale than individual units. In cells, active cytoskeletal systems composed of polar filaments and molecular motors drive fluid flow, a process known as cytoplasmic streaming. The motor-driven elongation of microtubule bundles generates turbulent-like flow in purified systems; however, it remains unclear whether and how microtubule bundles induce large-scale directed flow like the cytoplasmic streaming observed in cells. Here, we adopted Xenopus egg extracts as a model system of the cytoplasm and found that microtubule bundle elongation induces directed flow for which the length scale and timescale depend on the existence of geometrical constraints. At the lower activity of dynein, kinesins bundle and slide microtubules, organizing extensile microtubule bundles. In bulk extracts, the extensile bundles connected with each other and formed a random network, and vortex flows with a length scale comparable to the bundle length continually emerged and persisted for 1 min at multiple places. When the extracts were encapsulated in droplets, the extensile bundles pushed the droplet boundary. This pushing force initiated symmetry breaking of the randomly oriented bundle network, leading to bundles aligning into a rotating vortex structure. This vortex induced rotational cytoplasmic flows on the length scale and timescale that were 10- to 100-fold longer than the vortex flows emerging in bulk extracts. Our results suggest that microtubule systems use not only hydrodynamic interactions but also mechanical interactions to induce large-scale temporally stable cytoplasmic flow. PMID:28265076
Polymer Physics Prize Talk

NASA Astrophysics Data System (ADS)

Olvera de La Cruz, Monica

Polymer electrolytes have been particularly difficult to describe theoretically given the large number of disparate length scales involved in determining their physical properties. The Debye length, the Bjerrum length, the ion size, the chain length, and the distance between the charges along their backbones determine their structure and their response to external fields. We have developed an approach that uses multi-scale calculations with the capability of demonstrating the phase behavior of polymer electrolytes and of providing a conceptual understanding of how charge dictates nano-scale structure formation. Moreover, our molecular dynamics simulations have provided an understanding of the coupling of their conformation to their dynamics, which is crucial to design self-assembling materials, as well as to explore the dynamics of complex electrolytes for energy storage and conversion applications.
A new species of the genus Capoeta Valenciennes, 1842 from the Caspian Sea basin in Iran (Teleostei, Cyprinidae)

PubMed Central

Jouladeh-Roudbar, Arash; Eagderi, Soheil; Ghanavi, Hamid Reza; Doadrio, Ignacio

2017-01-01

Abstract A new species of algae-scraping cyprinid of the genus Capoeta Valenciennes, 1842 is described from the Kheyroud River, located in the southern part of the Caspian Sea basin in Iran. The species differs from other members of this genus by a combination of the following characters: one pair of barbels; predorsal length equal to postdorsal length; maxillary barbel slightly smaller than eye’s horizontal diameter and reach to posterior margin of orbit; intranasal length slightly shorter than snout length; lateral line with 46–54 scales; 7–9 scales between dorsal-fin origin and lateral line, and 6–7 scales between anal-fin origin and lateral line. PMID:28769726
Control of fluxes in metabolic networks

PubMed Central

Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

2016-01-01

Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. PMID:27197218
Motion of Molecular Probes and Viscosity Scaling in Polyelectrolyte Solutions at Physiological Ionic Strength

PubMed Central

Sozanski, Krzysztof; Wisniewska, Agnieszka; Kalwarczyk, Tomasz; Sznajder, Anna; Holyst, Robert

2016-01-01

We investigate transport properties of model polyelectrolyte systems at physiological ionic strength (0.154 M). Covering a broad range of flow length scales—from diffusion of molecular probes to macroscopic viscous flow—we establish a single, continuous function describing the scale dependent viscosity of high-salt polyelectrolyte solutions. The data are consistent with the model developed previously for electrically neutral polymers in a good solvent. The presented approach merges the power-law scaling concepts of de Gennes with the idea of exponential length scale dependence of effective viscosity in complex liquids. The result is a simple and applicable description of transport properties of high-salt polyelectrolyte solutions at all length scales, valid for motion of single molecules as well as macroscopic flow of the complex liquid. PMID:27536866
DOE Office of Scientific and Technical Information (OSTI.GOV)

Mamontov, Eugene; Zolnierczuk, Piotr A.; Ohl, Michael E.

Using neutron spin-echo and backscattering spectroscopy, we have found that at low temperatures water molecules in an aqueous solution engage in center-of-mass dynamics that are different from both the main structural relaxations and the well-known localized motions in the transient cages of the nearest neighbor molecules. While the latter localized motions are known to take place on the picosecond time scale and Angstrom length scale, the slower motions that we have observed are found on the nanosecond time scale and nanometer length scale. They are associated with the slow secondary relaxations, or excess wing dynamics, in glass-forming liquids. Our approach,more » therefore, can be applied to probe the characteristic length scale of the dynamic entities associated with slow dynamics in glass-forming liquids, which presently cannot be studied by other experimental techniques.« less
Correlation lengths in hydrodynamic models of active nematics.

PubMed

Hemingway, Ewan J; Mishra, Prashant; Marchetti, M Cristina; Fielding, Suzanne M

2016-09-28

We examine the scaling with activity of the emergent length scales that control the nonequilibrium dynamics of an active nematic liquid crystal, using two popular hydrodynamic models that have been employed in previous studies. In both models we find that the chaotic spatio-temporal dynamics in the regime of fully developed active turbulence is controlled by a single active scale determined by the balance of active and elastic stresses, regardless of whether the active stress is extensile or contractile in nature. The observed scaling of the kinetic energy and enstrophy with activity is consistent with our single-length scale argument and simple dimensional analysis. Our results provide a unified understanding of apparent discrepancies in the previous literature and demonstrate that the essential physics is robust to the choice of model.
Biochemical basis for the biological clock

NASA Technical Reports Server (NTRS)

Morre, D. James; Chueh, Pin-Ju; Pletcher, Jake; Tang, Xiaoyu; Wu, Lian-Ying; Morre, Dorothy M.

2002-01-01

NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.
PSYCHIATRIC DISORDERS AND LEUKOCYTE TELOMERE LENGTH: UNDERLYING MECHANISMS LINKING MENTAL ILLNESS WITH CELLULAR AGING

PubMed Central

Lindqvist, Daniel; Epel, Elissa S.; Mellon, Synthia H.; Penninx, Brenda W.; Révész, Dóra; Verhoeven, Josine E.; Reus, Victor I.; Lin, Jue; Mahan, Laura; Hough, Christina M.; Rosser, Rebecca; Bersani, F. Saverio; Blackburn, Elizabeth H.; Wolkowitz, Owen M.

2015-01-01

Many psychiatric illnesses are associated with early mortality and with an increased risk of developing physical diseases that are more typically seen in the elderly. Moreover, certain psychiatric illnesses may be associated with accelerated cellular aging, evidenced by shortened leukocyte telomere length (LTL), which could underlie this association. Shortened LTL reflects a cell’s mitotic history and cumulative exposure to inflammation and oxidation as well as the availability of telomerase, a telomere-lengthening enzyme. Critically short telomeres can cause cells to undergo senescence, apoptosis or genomic instability, and shorter LTL correlates with poorer health and predicts mortality. Emerging data suggest that LTL may be reduced in certain psychiatric illnesses, perhaps in proportion to exposure to the psychiatric illnesses, although conflicting data exist. Telomerase has been less well characterized in psychiatric illnesses, but a role in depression and in antidepressant and neurotrophic effects has been suggested by preclinical and clinical studies. In this article, studies on LTL and telomerase activity in psychiatric illnesses are critically reviewed, potential mediators are discussed, and future directions are suggested. A deeper understanding of cellular aging in psychiatric illnesses could lead to re-conceptualizing them as systemic illnesses with manifestations inside and outside the brain and could identify new treatment targets. PMID:25999120
The length of the glaciers in the world - a straightforward method for the automated calculation of glacier center lines

NASA Astrophysics Data System (ADS)

Machguth, H.; Huss, M.

2014-05-01

Glacier length is an important measure of glacier geometry but global glacier inventories are mostly lacking length data. Only recently semi-automated approaches to measure glacier length have been developed and applied regionally. Here we present a first global assessment of glacier length using a fully automated method based on glacier surface slope, distance to the glacier margins and a set of trade-off functions. The method is developed for East Greenland, evaluated for the same area as well as for Alaska, and eventually applied to all ∼200 000 glaciers around the globe. The evaluation highlights accurately calculated glacier length where DEM quality is good (East Greenland) and limited precision on low quality DEMs (parts of Alaska). Measured length of very small glaciers is subject to a certain level of ambiguity. The global calculation shows that only about 1.5% of all glaciers are longer than 10 km with Bering Glacier (Alaska/Canada) being the longest glacier in the world at a length of 196 km. Based on model output we derive global and regional area-length scaling laws. Differences among regional scaling parameters appear to be related to characteristics of topography and glacier mass balance. The present study adds glacier length as a central parameter to global glacier inventories. Global and regional scaling laws might proof beneficial in conceptual glacier models.
The length of the world's glaciers - a new approach for the global calculation of center lines

NASA Astrophysics Data System (ADS)

Machguth, H.; Huss, M.

2014-09-01

Glacier length is an important measure of glacier geometry. Nevertheless, global glacier inventories are mostly lacking length data. Only recently semi-automated approaches to measure glacier length have been developed and applied regionally. Here we present a first global assessment of glacier length using an automated method that relies on glacier surface slope, distance to the glacier margins and a set of trade-off functions. The method is developed for East Greenland, evaluated for East Greenland as well as for Alaska and eventually applied to all ~ 200 000 glaciers around the globe. The evaluation highlights accurately calculated glacier length where digital elevation model (DEM) quality is high (East Greenland) and limited accuracy on low-quality DEMs (parts of Alaska). Measured length of very small glaciers is subject to a certain level of ambiguity. The global calculation shows that only about 1.5% of all glaciers are longer than 10 km, with Bering Glacier (Alaska/Canada) being the longest glacier in the world at a length of 196 km. Based on the output of our algorithm we derive global and regional area-length scaling laws. Differences among regional scaling parameters appear to be related to characteristics of topography and glacier mass balance. The present study adds glacier length as a key parameter to global glacier inventories. Global and regional scaling laws might prove beneficial in conceptual glacier models.
WE-AB-204-12: Dosimetry at the Sub-Cellular Scale of Auger-Electron Emitter 99m-Tc in a Mouse Single Thyroid Follicle Model

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

Taborda, A; Benabdallah, N; Desbree, A

2015-06-15

Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres ofmore » unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single thyroid follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse thyroid follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell’s nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can’t be neglected. The obtained S-values of Auger-electron emitting 99m-Tc radionuclide will be presented and discussed.« less
Multi-Scale Structure of Coacervates formed by Oppositely Charged Polyelectrolytes

NASA Astrophysics Data System (ADS)

Rubinstein, Michael

We develop a scaling model of coacervates formed by oppositely charged polyelectrolytes and demonstrate that they self-organize into multi-scale structures. The intramolecular electrostatic interactions in dilute polyanion or polycation solutions are characterized by the electrostatic blobs with size D- and D+ respectively, that repel neighboring blobs on the same chains with electrostatic energy on the order of thermal energy kT . After mixing, electrostatic intramolecular repulsion of polyelectrolytes with higher charged density, say polyanions, keeps these polyanions in coacervates aligned into stretched arrays of electrostatic blobs of size D-
Perspectives on integrated modeling of transport processes in semiconductor crystal growth

NASA Technical Reports Server (NTRS)

Brown, Robert A.

1992-01-01

The wide range of length and time scales involved in industrial scale solidification processes is demonstrated here by considering the Czochralski process for the growth of large diameter silicon crystals that become the substrate material for modern microelectronic devices. The scales range in time from microseconds to thousands of seconds and in space from microns to meters. The physics and chemistry needed to model processes on these different length scales are reviewed.

Vernier effect-based multiplication of the Sagnac beating frequency in ring laser gyroscope sensors

NASA Astrophysics Data System (ADS)

Adib, George A.; Sabry, Yasser M.; Khalil, Diaa

2018-02-01

A multiplication method of the Sagnac effect scale factor in ring laser gyroscopes is presented based on the Vernier effect of a dual-coupler passive ring resonator coupled to the active ring. The multiplication occurs when the two rings have comparable lengths or integer multiples and their scale factors have opposite signs. In this case, and when the rings have similar areas, the scale factor is multiplied by ratio of their length to their length difference. The scale factor of the presented configuration is derived analytically and the lock-in effect is analyzed. The principle is demonstrated using optical fiber rings and semiconductor optical amplifier as gain medium. A scale factor multiplication by about 175 is experimentally measured, demonstrating larger than two orders of magnitude enhancement in the Sagnac effect scale factor for the first time in literature, up to the authors' knowledge.
Mesoporous silica nanoparticles functionalized with hyaluronic acid. Effect of the biopolymer chain length on cell internalization.

PubMed

Nairi, Valentina; Magnolia, Silvia; Piludu, Marco; Nieddu, Mariella; Caria, Cristian Antonio; Sogos, Valeria; Vallet-Regì, Maria; Monduzzi, Maura; Salis, Andrea

2018-02-12

Mesoporous silica nanoparticles (MSNs) were functionalized with amino groups (MSN-NH 2 ) and then with hyaluronic acid, a biocompatible biopolymer which can be recognized by CD44 receptors in tumor cells, to obtain a targeting drug delivery system. To this purpose, three hyaluronic acid samples differing for the molecular weight, namely HA S (8-15 kDa), HA M (30-50 kDa) and HA L (90-130 kDa), were used. The MSN-HA S , MSN-HA M , and MSN-HA L materials were characterized through zeta potential and dynamic light scattering measurements at pH = 7.4 and T = 37 °C to simulate physiological conditions. While zeta potential showed an increasing negative value with the increase of the HA chain length, an anomalous value of the hydrodynamic diameter was observed for MSN-HA L , which was smaller than that of MSN-HA S and MSN-HA M samples. The cellular uptake of MSN-HA samples on HeLa cells at 37 °C was studied by optical and electron microscopy. HA chain length affected significantly the cellular uptake that occurred at a higher extent for MSN-NH 2 and MSN-HA S than for MSN-HA M and MSN-HA L samples. Cellular uptake experiments carried out at 4 °C showed that the internalization process was inhibited for MSN-HA samples but not for MSN-NH 2 . This suggests the occurrence of two different mechanisms of internalization. For MSN-NH 2 the uptake is mainly driven by the attractive electrostatic interaction with membrane phospholipids, while MSN-HA internalization involves CD44 receptors overexpressed in HeLa cells. Copyright © 2018 Elsevier B.V. All rights reserved.
Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin-functionalized nanoparticle formulation for targeted delivery of anticancer drugs.

PubMed

Zhao, Jing; Feng, Si-Shen

2014-03-01

Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has become one of the most important strategies in drug targeting. We have developed in our previous work nanoparticles of a mixture of two vitamin E TPGS based copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth factor receptor 2 (HER2) overexpression. In this research, we investigated the effects of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation method and characterized for their size and size distribution, drug loading, surface morphology, surface charge and surface chemistry as well as in vitro drug release profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided a theoretical explanation from surface mechanics and thermodynamics for endocytosis of nanoparticles. Copyright © 2014 Elsevier Ltd. All rights reserved.
Persistence length of collagen molecules based on nonlocal viscoelastic model.

PubMed

Ghavanloo, Esmaeal

2017-12-01

Persistence length is one of the most interesting properties of a molecular chain, which is used to describe the stiffness of a molecule. The experimentally measured values of the persistence length of the collagen molecule are widely scattered from 14 to 180 nm. Therefore, an alternative approach is highly desirable to predict the persistence length of a molecule and also to explain the experimental results. In this paper, a nonlocal viscoelastic model is developed to obtain the persistence length of the collagen molecules in solvent. A new explicit formula is proposed for the persistence length of the molecule with the consideration of the small-scale effect, viscoelastic properties of the molecule, loading frequency, and viscosity of the solvent. The presented model indicates that there exists a range of molecule lengths in which the persistence length strongly depends on the frequency and spatial mode of applied loads, small-scale effect, and viscoelastic properties of the collagen.
Anomalous dispersion in correlated porous media: a coupled continuous time random walk approach

NASA Astrophysics Data System (ADS)

Comolli, Alessandro; Dentz, Marco

2017-09-01

We study the causes of anomalous dispersion in Darcy-scale porous media characterized by spatially heterogeneous hydraulic properties. Spatial variability in hydraulic conductivity leads to spatial variability in the flow properties through Darcy's law and thus impacts on solute and particle transport. We consider purely advective transport in heterogeneity scenarios characterized by broad distributions of heterogeneity length scales and point values. Particle transport is characterized in terms of the stochastic properties of equidistantly sampled Lagrangian velocities, which are determined by the flow and conductivity statistics. The persistence length scales of flow and transport velocities are imprinted in the spatial disorder and reflect the distribution of heterogeneity length scales. Particle transitions over the velocity length scales are kinematically coupled with the transition time through velocity. We show that the average particle motion follows a coupled continuous time random walk (CTRW), which is fully parameterized by the distribution of flow velocities and the medium geometry in terms of the heterogeneity length scales. The coupled CTRW provides a systematic framework for the investigation of the origins of anomalous dispersion in terms of heterogeneity correlation and the distribution of conductivity point values. We derive analytical expressions for the asymptotic scaling of the moments of the spatial particle distribution and first arrival time distribution (FATD), and perform numerical particle tracking simulations of the coupled CTRW to capture the full average transport behavior. Broad distributions of heterogeneity point values and lengths scales may lead to very similar dispersion behaviors in terms of the spatial variance. Their mechanisms, however are very different, which manifests in the distributions of particle positions and arrival times, which plays a central role for the prediction of the fate of dissolved substances in heterogeneous natural and engineered porous materials. Contribution to the Topical Issue "Continuous Time Random Walk Still Trendy: Fifty-year History, Current State and Outlook", edited by Ryszard Kutner and Jaume Masoliver.
Self-organization versus Watchmaker: ambiguity of molecular recognition and design charts of cellular circuitry.

PubMed

Kurakin, Alexei

2007-01-01

A large body of experimental evidence indicates that the specific molecular interactions and/or chemical conversions depicted as links in the conventional diagrams of cellular signal transduction and metabolic pathways are inherently probabilistic, ambiguous and context-dependent. Being the inevitable consequence of the dynamic nature of protein structure in solution, the ambiguity of protein-mediated interactions and conversions challenges the conceptual adequacy and practical usefulness of the mechanistic assumptions and inferences embodied in the design charts of cellular circuitry. It is argued that the reconceptualization of molecular recognition and cellular organization within the emerging interpretational framework of self-organization, which is expanded here to include such concepts as bounded stochasticity, evolutionary memory, and adaptive plasticity offers a significantly more adequate representation of experimental reality than conventional mechanistic conceptions do. Importantly, the expanded framework of self-organization appears to be universal and scale-invariant, providing conceptual continuity across multiple scales of biological organization, from molecules to societies. This new conceptualization of biological phenomena suggests that such attributes of intelligence as adaptive plasticity, decision-making, and memory are enforced by evolution at different scales of biological organization and may represent inherent properties of living matter. (c) 2007 John Wiley & Sons, Ltd.
Phase and vortex correlations in superconducting Josephson-junction arrays at irrational magnetic frustration.

PubMed

Granato, Enzo

2008-07-11

Phase coherence and vortex order in a Josephson-junction array at irrational frustration are studied by extensive Monte Carlo simulations using the parallel-tempering method. A scaling analysis of the correlation length of phase variables in the full equilibrated system shows that the critical temperature vanishes with a power-law divergent correlation length and critical exponent nuph, in agreement with recent results from resistivity scaling analysis. A similar scaling analysis for vortex variables reveals a different critical exponent nuv, suggesting that there are two distinct correlation lengths associated with a decoupled zero-temperature phase transition.
Thermal diffusivity study of aged Li-ion batteries using flash method

NASA Astrophysics Data System (ADS)

Nagpure, Shrikant C.; Dinwiddie, Ralph; Babu, S. S.; Rizzoni, Giorgio; Bhushan, Bharat; Frech, Tim

Advanced Li-ion batteries with high energy and power density are fast approaching compatibility with automotive demands. While the mechanism of operation of these batteries is well understood, the aging mechanisms are still under investigation. Investigation of aging mechanisms in Li-ion batteries becomes very challenging, as aging does not occur due to a single process, but because of multiple physical processes occurring at the same time in a cascading manner. As the current characterization techniques such as Raman spectroscopy, X-ray diffraction, and atomic force microscopy are used independent of each other they do not provide a comprehensive understanding of material degradation at different length (nm 2 to m 2) scales. Thus to relate the damage mechanisms of the cathode at mm length scale to micro/nanoscale, data at an intermediate length scale is needed. As such, we demonstrate here the use of thermal diffusivity analysis by flash method to bridge the gap between different length scales. In this paper we present the thermal diffusivity analysis of an unaged and aged cell. Thermal diffusivity analysis maps the damage to the cathode samples at millimeter scale lengths. Based on these maps we also propose a mechanism leading to the increase of the thermal diffusivity as the cells are aged.
Accelerated aging in adults with knee osteoarthritis pain: consideration for frequency, intensity, time, and total pain sites

PubMed Central

Sibille, Kimberly T.; Chen, Huaihou; Bartley, Emily J.; Riley, Joseph; Glover, Toni L.; King, Christopher D.; Zhang, Hang; Cruz-Almeida, Yenisel; Goodin, Burel R.; Sotolongo, Adriana; Petrov, Megan E.; Herbert, Matthew; Bulls, Hailey W.; Edberg, Jeffrey C.; Staud, Roland; Redden, David; Bradley, Laurence A.; Fillingim, Roger B.

2017-01-01

Abstract Introduction: Individuals with osteoarthritis (OA) show increased morbidity and mortality. Telomere length, a measure of cellular aging, predicts increased morbidity and mortality. Telomeres shorten with persisting biological and psychosocial stress. Living with chronic OA pain is stressful. Previous research exploring telomere length in people with OA has produced inconsistent results. Considering pain severity may clarify the relationship between OA and telomeres. Objectives: We hypothesized that individuals with high OA chronic pain severity would have shorter telomeres than those with no or low chronic pain severity. Methods: One hundred thirty-six adults, ages 45 to 85 years old, with and without symptomatic knee OA were included in the analysis. Peripheral blood leukocyte telomere length was measured, and demographic, clinical, and functional data were collected. Participants were categorized into 5 pain severity groups based on an additive index of frequency, intensity, time or duration, and total number of pain sites (FITT). Covariates included age, sex, race or ethnicity, study site, and knee pain status. Results: The no or low chronic pain severity group had significantly longer telomeres compared with the high pain severity group, P = 0.025. A significant chronic pain severity dose response emerged for telomere length, P = 0.034. The FITT chronic pain severity index was highly correlated with the clinical and functional OA pain measures. However, individual clinical and functional measures were not associated with telomere length. Conclusion: Results demonstrate accelerated cellular aging with high knee OA chronic pain severity and provide evidence for the potential utility of the FITT chronic pain severity index in capturing the biological burden of chronic pain. PMID:29392207
Lead Scales for X-Radiographs

NASA Technical Reports Server (NTRS)

Burley, Richard K.; Adams, James F.

1987-01-01

Indentations made by typing on lead tape. Lead scales for inclusion in x-radiographs as length and position references created by repeatedly imprinting character like upper-case I, L, or V, or lower-case L into lead tape with typewriter. Character pitch of typewriter serves as length reference for scale. Thinning of tape caused by impacts of type shows up dark in radiograph.
Length and area equivalents for interpreting wildland resource maps

Treesearch

Elliot L. Amidon; Marilyn S. Whitfield

1969-01-01

Map users must refer to an appropriate scale in interpreting wildland resource maps. Length and area equivalents for nine map scales commonly used have been computed. For each scale a 1-page table consists of map-to-ground equivalents, buffer strip or road widths, and cell dimensions required for a specified acreage. The conversion factors are stored in a Fortran...
Fall risk assessment: retrospective analysis of Morse Fall Scale scores in Portuguese hospitalized adult patients.

PubMed

Sardo, Pedro Miguel Garcez; Simões, Cláudia Sofia Oliveira; Alvarelhão, José Joaquim Marques; Simões, João Filipe Fernandes Lindo; Melo, Elsa Maria de Oliveira Pinheiro de

2016-08-01

The Morse Fall Scale is used in several care settings for fall risk assessment and supports the implementation of preventive nursing interventions. Our work aims to analyze the Morse Fall Scale scores of Portuguese hospitalized adult patients in association with their characteristics, diagnoses and length of stay. Retrospective cohort analysis of Morse Fall Scale scores of 8356 patients hospitalized during 2012. Data were associated to age, gender, type of admission, specialty units, length of stay, patient discharge, and ICD-9 diagnosis. Elderly patients, female, with emergency service admission, at medical units and/or with longer length of stays were more frequently included in the risk group for falls. ICD-9 diagnosis may also be an important risk factor. More than a half of hospitalized patients had "medium" to "high" risk of falling during the length of stay, which determines the implementation and maintenance of protocoled preventive nursing interventions throughout hospitalization. There are several fall risk factors not assessed by Morse Fall Scale. There were no statistical differences in Morse Fall Scale score between the first and the last assessment. Copyright © 2015 Elsevier Inc. All rights reserved.
Effect of artificial length scales in large eddy simulation of a neutral atmospheric boundary layer flow: A simple solution to log-layer mismatch

NASA Astrophysics Data System (ADS)

Chatterjee, Tanmoy; Peet, Yulia T.

2017-07-01

A large eddy simulation (LES) methodology coupled with near-wall modeling has been implemented in the current study for high Re neutral atmospheric boundary layer flows using an exponentially accurate spectral element method in an open-source research code Nek 5000. The effect of artificial length scales due to subgrid scale (SGS) and near wall modeling (NWM) on the scaling laws and structure of the inner and outer layer eddies is studied using varying SGS and NWM parameters in the spectral element framework. The study provides an understanding of the various length scales and dynamics of the eddies affected by the LES model and also the fundamental physics behind the inner and outer layer eddies which are responsible for the correct behavior of the mean statistics in accordance with the definition of equilibrium layers by Townsend. An economical and accurate LES model based on capturing the near wall coherent eddies has been designed, which is successful in eliminating the artificial length scale effects like the log-layer mismatch or the secondary peak generation in the streamwise variance.
Progress in long scale length laser plasma interactions

NASA Astrophysics Data System (ADS)

Glenzer, S. H.; Arnold, P.; Bardsley, G.; Berger, R. L.; Bonanno, G.; Borger, T.; Bower, D. E.; Bowers, M.; Bryant, R.; Buckman, S.; Burkhart, S. C.; Campbell, K.; Chrisp, M. P.; Cohen, B. I.; Constantin, C.; Cooper, F.; Cox, J.; Dewald, E.; Divol, L.; Dixit, S.; Duncan, J.; Eder, D.; Edwards, J.; Erbert, G.; Felker, B.; Fornes, J.; Frieders, G.; Froula, D. H.; Gardner, S. D.; Gates, C.; Gonzalez, M.; Grace, S.; Gregori, G.; Greenwood, A.; Griffith, R.; Hall, T.; Hammel, B. A.; Haynam, C.; Heestand, G.; Henesian, M.; Hermes, G.; Hinkel, D.; Holder, J.; Holdner, F.; Holtmeier, G.; Hsing, W.; Huber, S.; James, T.; Johnson, S.; Jones, O. S.; Kalantar, D.; Kamperschroer, J. H.; Kauffman, R.; Kelleher, T.; Knight, J.; Kirkwood, R. K.; Kruer, W. L.; Labiak, W.; Landen, O. L.; Langdon, A. B.; Langer, S.; Latray, D.; Lee, A.; Lee, F. D.; Lund, D.; MacGowan, B.; Marshall, S.; McBride, J.; McCarville, T.; McGrew, L.; Mackinnon, A. J.; Mahavandi, S.; Manes, K.; Marshall, C.; Menapace, J.; Mertens, E.; Meezan, N.; Miller, G.; Montelongo, S.; Moody, J. D.; Moses, E.; Munro, D.; Murray, J.; Neumann, J.; Newton, M.; Ng, E.; Niemann, C.; Nikitin, A.; Opsahl, P.; Padilla, E.; Parham, T.; Parrish, G.; Petty, C.; Polk, M.; Powell, C.; Reinbachs, I.; Rekow, V.; Rinnert, R.; Riordan, B.; Rhodes, M.; Roberts, V.; Robey, H.; Ross, G.; Sailors, S.; Saunders, R.; Schmitt, M.; Schneider, M. B.; Shiromizu, S.; Spaeth, M.; Stephens, A.; Still, B.; Suter, L. J.; Tietbohl, G.; Tobin, M.; Tuck, J.; Van Wonterghem, B. M.; Vidal, R.; Voloshin, D.; Wallace, R.; Wegner, P.; Whitman, P.; Williams, E. A.; Williams, K.; Winward, K.; Work, K.; Young, B.; Young, P. E.; Zapata, P.; Bahr, R. E.; Seka, W.; Fernandez, J.; Montgomery, D.; Rose, H.

2004-12-01

The first experiments on the National Ignition Facility (NIF) have employed the first four beams to measure propagation and laser backscattering losses in large ignition-size plasmas. Gas-filled targets between 2 and 7 mm length have been heated from one side by overlapping the focal spots of the four beams from one quad operated at 351 nm (3ω) with a total intensity of 2 × 1015 W cm-2. The targets were filled with 1 atm of CO2 producing up to 7 mm long homogeneously heated plasmas with densities of ne = 6 × 1020 cm-3 and temperatures of Te = 2 keV. The high energy in an NIF quad of beams of 16 kJ, illuminating the target from one direction, creates unique conditions for the study of laser-plasma interactions at scale lengths not previously accessible. The propagation through the large-scale plasma was measured with a gated x-ray imager that was filtered for 3.5 keV x-rays. These data indicate that the beams interact with the full length of this ignition-scale plasma during the last ~1 ns of the experiment. During that time, the full aperture measurements of the stimulated Brillouin scattering and stimulated Raman scattering show scattering into the four focusing lenses of 3% for the smallest length (~2 mm), increasing to 10-12% for ~7 mm. These results demonstrate the NIF experimental capabilities and further provide a benchmark for three-dimensional modelling of the laser-plasma interactions at ignition-size scale lengths.
Fundamental Scaling Laws in Nanophotonics

PubMed Central

Liu, Ke; Sun, Shuai; Majumdar, Arka; Sorger, Volker J.

2016-01-01

The success of information technology has clearly demonstrated that miniaturization often leads to unprecedented performance, and unanticipated applications. This hypothesis of “smaller-is-better” has motivated optical engineers to build various nanophotonic devices, although an understanding leading to fundamental scaling behavior for this new class of devices is missing. Here we analyze scaling laws for optoelectronic devices operating at micro and nanometer length-scale. We show that optoelectronic device performance scales non-monotonically with device length due to the various device tradeoffs, and analyze how both optical and electrical constrains influence device power consumption and operating speed. Specifically, we investigate the direct influence of scaling on the performance of four classes of photonic devices, namely laser sources, electro-optic modulators, photodetectors, and all-optical switches based on three types of optical resonators; microring, Fabry-Perot cavity, and plasmonic metal nanoparticle. Results show that while microrings and Fabry-Perot cavities can outperform plasmonic cavities at larger length-scales, they stop working when the device length drops below 100 nanometers, due to insufficient functionality such as feedback (laser), index-modulation (modulator), absorption (detector) or field density (optical switch). Our results provide a detailed understanding of the limits of nanophotonics, towards establishing an opto-electronics roadmap, akin to the International Technology Roadmap for Semiconductors. PMID:27869159
Fundamental Scaling Laws in Nanophotonics.

PubMed

Liu, Ke; Sun, Shuai; Majumdar, Arka; Sorger, Volker J

2016-11-21

The success of information technology has clearly demonstrated that miniaturization often leads to unprecedented performance, and unanticipated applications. This hypothesis of "smaller-is-better" has motivated optical engineers to build various nanophotonic devices, although an understanding leading to fundamental scaling behavior for this new class of devices is missing. Here we analyze scaling laws for optoelectronic devices operating at micro and nanometer length-scale. We show that optoelectronic device performance scales non-monotonically with device length due to the various device tradeoffs, and analyze how both optical and electrical constrains influence device power consumption and operating speed. Specifically, we investigate the direct influence of scaling on the performance of four classes of photonic devices, namely laser sources, electro-optic modulators, photodetectors, and all-optical switches based on three types of optical resonators; microring, Fabry-Perot cavity, and plasmonic metal nanoparticle. Results show that while microrings and Fabry-Perot cavities can outperform plasmonic cavities at larger length-scales, they stop working when the device length drops below 100 nanometers, due to insufficient functionality such as feedback (laser), index-modulation (modulator), absorption (detector) or field density (optical switch). Our results provide a detailed understanding of the limits of nanophotonics, towards establishing an opto-electronics roadmap, akin to the International Technology Roadmap for Semiconductors.
Fundamental Scaling Laws in Nanophotonics

NASA Astrophysics Data System (ADS)

Liu, Ke; Sun, Shuai; Majumdar, Arka; Sorger, Volker J.

2016-11-01

The success of information technology has clearly demonstrated that miniaturization often leads to unprecedented performance, and unanticipated applications. This hypothesis of “smaller-is-better” has motivated optical engineers to build various nanophotonic devices, although an understanding leading to fundamental scaling behavior for this new class of devices is missing. Here we analyze scaling laws for optoelectronic devices operating at micro and nanometer length-scale. We show that optoelectronic device performance scales non-monotonically with device length due to the various device tradeoffs, and analyze how both optical and electrical constrains influence device power consumption and operating speed. Specifically, we investigate the direct influence of scaling on the performance of four classes of photonic devices, namely laser sources, electro-optic modulators, photodetectors, and all-optical switches based on three types of optical resonators; microring, Fabry-Perot cavity, and plasmonic metal nanoparticle. Results show that while microrings and Fabry-Perot cavities can outperform plasmonic cavities at larger length-scales, they stop working when the device length drops below 100 nanometers, due to insufficient functionality such as feedback (laser), index-modulation (modulator), absorption (detector) or field density (optical switch). Our results provide a detailed understanding of the limits of nanophotonics, towards establishing an opto-electronics roadmap, akin to the International Technology Roadmap for Semiconductors.
Cofilin-2 controls actin filament length in muscle sarcomeres

PubMed Central

Kremneva, Elena; Makkonen, Maarit H.; Skwarek-Maruszewska, Aneta; Gateva, Gergana; Michelot, Alphee; Dominguez, Roberto; Lappalainen, Pekka

2014-01-01

SUMMARY ADF/cofilins drive cytoskeletal dynamics by promoting the disassembly of ‘aged’ ADP-actin filaments. Mammals express several ADF/cofilin isoforms, but their specific biochemical activities and cellular functions have not been studied in detail. Here we demonstrate that the muscle-specific isoform cofilin-2 promotes actin filament disassembly in sarcomeres to control the precise length of thin filaments in the contractile apparatus. In contrast to other isoforms, cofilin-2 efficiently binds and disassembles both ADP- and ATP/ADP-Pi-actin filaments. We mapped surface-exposed cofilin-2-specific residues required for ATP-actin binding and propose that these residues function as an ‘actin nucleotide-state sensor’ among ADF/cofilins. The results suggest that cofilin-2 evolved specific biochemical and cellular properties allowing it to control actin dynamics in sarcomeres, where filament pointed ends may contain a mixture of ADP- and ATP/ADP-Pi-actin subunits. Our findings also offer a rationale for why cofilin-2 mutations in humans lead to myopathies. PMID:25373779
Synthesis of Lipidated Proteins.

PubMed

Mejuch, Tom; Waldmann, Herbert

2016-08-17

Protein lipidation is one of the major post-translational modifications (PTM) of proteins. The attachment of the lipid moiety frequently determines the localization and the function of the lipoproteins. Lipidated proteins participate in many essential biological processes in eukaryotic cells, including vesicular trafficking, signal transduction, and regulation of the immune response. Malfunction of these cellular processes usually leads to various diseases such as cancer. Understanding the mechanism of cellular signaling and identifying the protein-protein and protein-lipid interactions in which the lipoproteins are involved is a crucial task. To achieve these goals, fully functional lipidated proteins are required. However, access to lipoproteins by means of standard expression is often rather limited. Therefore, semisynthetic methods, involving the synthesis of lipidated peptides and their subsequent chemoselective ligation to yield full-length lipoproteins, were developed. In this Review we summarize the commonly used methods for lipoprotein synthesis and the development of the corresponding chemoselective ligation techniques. Several key studies involving full-length semisynthetic lipidated Ras, Rheb, and LC3 proteins are presented.
Long-range allosteric signaling in red light–regulated diguanylyl cyclases

PubMed Central

Gourinchas, Geoffrey; Etzl, Stefan; Göbl, Christoph; Vide, Uršula; Madl, Tobias; Winkler, Andreas

2017-01-01

Nature has evolved an astonishingly modular architecture of covalently linked protein domains with diverse functionalities to enable complex cellular networks that are critical for cell survival. The coupling of sensory modules with enzymatic effectors allows direct allosteric regulation of cellular signaling molecules in response to diverse stimuli. We present molecular details of red light–sensing bacteriophytochromes linked to cyclic dimeric guanosine monophosphate–producing diguanylyl cyclases. Elucidation of the first crystal structure of a full-length phytochrome with its enzymatic effector, in combination with the characterization of light-induced changes in conformational dynamics, reveals how allosteric light regulation is fine-tuned by the architecture and composition of the coiled-coil sensor-effector linker and also the central helical spine. We anticipate that consideration of molecular principles of sensor-effector coupling, going beyond the length of the characteristic linker, and the appreciation of dynamically driven allostery will open up new directions for the design of novel red light–regulated optogenetic tools. PMID:28275738

Cellular metabolic rates from primary dermal fibroblast cells isolated from birds of different body masses.

PubMed

Jimenez, Ana Gabriela; Williams, Joseph B

2014-10-01

The rate of metabolism is the speed at which organisms use energy, an integration of energy transformations within the body; it governs biological processes that influence rates of growth and reproduction. Progress at understanding functional linkages between whole organism metabolic rate and underlying mechanisms that influence its magnitude has been slow despite the central role this issue plays in evolutionary and physiological ecology. Previous studies that have attempted to relate how cellular processes translate into whole-organism physiology have done so over a range of body masses of subjects. However, the data still remains controversial when observing metabolic rates at the cellular level. To bridge the gap between these ideas, we examined cellular metabolic rate of primary dermal fibroblasts isolated from 49 species of birds representing a 32,000-fold range in body masses to test the hypothesis that metabolic rate of cultured cells scales with body size. We used a Seahorse XF-96 Extracellular flux analyzer to measure cellular respiration in fibroblasts. Additionally, we measured fibroblast size and mitochondrial content. We found no significant correlation between cellular metabolic rate, cell size, or mitochondrial content and body mass. Additionally, there was a significant relationship between cellular basal metabolic rate and proton leak in these cells. We conclude that metabolic rate of cells isolated in culture does not scale with body mass, but cellular metabolic rate is correlated to growth rate in birds. Copyright © 2014 Elsevier Inc. All rights reserved.
Vertical length scale selection for pancake vortices in strongly stratified viscous fluids

NASA Astrophysics Data System (ADS)

Godoy-Diana, Ramiro; Chomaz, Jean-Marc; Billant, Paul

2004-04-01

The evolution of pancake dipoles of different aspect ratio is studied in a stratified tank experiment. Two cases are reported here for values of the dipole initial aspect ratio alpha_0 = L_v/L_h (where L_v and L_h are vertical and horizontal length scales, respectively) of alpha_0 = 0.4 (case I) and alpha_0 = 1.2 (case II). In the first case, the usual decay scenario is observed where the dipole diffuses slowly with a growing thickness and a decaying circulation. In case II, we observed a regime where the thickness of the dipole decreases and the circulation in the horizontal mid-plane of the vortices remains constant. We show that this regime where the vertical length scale decreases can be explained by the shedding of two boundary layers at the top and bottom of the dipole that literally peel off vorticity layers. Horizontal advection and vertical diffusion cooperate in this regime and the decrease towards the viscous vertical length scale delta = L_hRe(-1/2) occurs on a time scale alpha_0 Re(1/2) T_A, T_A being the advection time L_h/U. From a scaling analysis of the equations for a stratified viscous fluid in the Boussinesq approximation, two dominant balances depending on the parameter R = ReF_h(2) are discussed, where F_h = U/NL_h is the horizontal Froude number and Re = UL_h/nu is the Reynolds number, U, N and nu being, respectively, the translation speed of the dipole, the Brunt Väisälä frequency and the kinematic viscosity. When R≫ 1 the vertical length scale is determined by buoyancy effects to be of order L_b = U/N. The experiments presented in this paper pertain to the case of small R, where viscous effects govern the selection of the vertical length scale. We show that if initially L_v ≤ delta, the flow diffuses on the vertical (case I), while if L_v ≫ delta (case II), vertically sheared horizontal advection decreases the vertical length scale down to delta. This viscous regime may explain results from experiments and numerical simulations on the late evolution of stratified flows where the decay is observed to be independent of the buoyancy frequency N.
Coupling biomechanics to a cellular level model: an approach to patient-specific image driven multi-scale and multi-physics tumor simulation.

PubMed

May, Christian P; Kolokotroni, Eleni; Stamatakos, Georgios S; Büchler, Philippe

2011-10-01

Modeling of tumor growth has been performed according to various approaches addressing different biocomplexity levels and spatiotemporal scales. Mathematical treatments range from partial differential equation based diffusion models to rule-based cellular level simulators, aiming at both improving our quantitative understanding of the underlying biological processes and, in the mid- and long term, constructing reliable multi-scale predictive platforms to support patient-individualized treatment planning and optimization. The aim of this paper is to establish a multi-scale and multi-physics approach to tumor modeling taking into account both the cellular and the macroscopic mechanical level. Therefore, an already developed biomodel of clinical tumor growth and response to treatment is self-consistently coupled with a biomechanical model. Results are presented for the free growth case of the imageable component of an initially point-like glioblastoma multiforme tumor. The composite model leads to significant tumor shape corrections that are achieved through the utilization of environmental pressure information and the application of biomechanical principles. Using the ratio of smallest to largest moment of inertia of the tumor material to quantify the effect of our coupled approach, we have found a tumor shape correction of 20% by coupling biomechanics to the cellular simulator as compared to a cellular simulation without preferred growth directions. We conclude that the integration of the two models provides additional morphological insight into realistic tumor growth behavior. Therefore, it might be used for the development of an advanced oncosimulator focusing on tumor types for which morphology plays an important role in surgical and/or radio-therapeutic treatment planning. Copyright © 2011 Elsevier Ltd. All rights reserved.
Scaling of cell size in cellular instabilities of nonpremixed jet flames

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

Lo Jacono, D.; Monkewitz, P.A.

2007-10-15

Systematic experiments have been undertaken to study the parameter dependence of cellular instability and in particular the scaling of the resulting cell size in CO{sub 2}-diluted H{sub 2}-O{sub 2} jet diffusion flames. Cellular flames are known to arise near the extinction limit when reactant Lewis numbers are relatively low. The Lewis numbers of the investigated near-extinction mixtures, based on the initial mixture strength {phi}{sub m} and ambient conditions, varied in the ranges [1.1-1.3] for oxygen and [0.25-0.29] for hydrogen ({phi}{sub m} is defined here as the fuel-to-oxygen mass ratio, normalized by the stoichiometric ratio). The experiments were carried out bothmore » in an axisymmetric jet (AJ) burner and in a two-dimensional slot burner known as a Wolfhard-Parker (WP) burner with an oxidizer co-flow (mostly 100% O{sub 2}) of fixed low velocity. First, the region of cellular flames adjacent to the extinction limit was characterized in terms of initial H{sub 2} concentration and fuel jet velocity, with all other parameters fixed. Then, the wavelength of the cellular instability, i.e., the cell size, was determined as a function of the fuel jet velocity and the initial mixture strength {phi}{sub m}. For conditions not too close to extinction, this wavelength is found to increase with the square root of the vorticity thickness of the jet shear layer and roughly the 1/5 power of {phi}{sub m}. Very close to extinction, this scaling breaks down and will likely switch to a scaling with the flame thickness, i.e., involving the Damkoehler number. (author)« less
A modification in the technique of computing average lengths from the scales of fishes

USGS Publications Warehouse

Van Oosten, John

1953-01-01

In virtually all the studies that employ scales, otollths, or bony structures to obtain the growth history of fishes, it has been the custom to compute lengths for each individual fish and from these data obtain the average growth rates for any particular group. This method involves a considerable amount of mathematical manipulation, time, and effort. Theoretically it should be possible to obtain the same information simply by averaging the scale measurements for each year of life and the length of the fish employed and computing the average lengths from these data. This method would eliminate all calculations for individual fish. Although Van Oosten (1929: 338) pointed out many years ago the validity of this method of computation, his statements apparently have been overlooked by subsequent investigators.
A nomograph for the computation of the growth of fish from scale measurements

USGS Publications Warehouse

Hile, Ralph

1950-01-01

Directions are given for the construction and operation of a nomograph that can be employed for the computation of the growth of fish from scale measurements regardless of the nature of the body-scale relationship, so long as that relationship is known. The essential feature of the nomograph that makes rapid calculations possible is a ruler on which the graduations are in terms of length with the distance of each length graduation from the O graduation equal to the corresponding theoretical scale measurement. The chief advantage of the nomograph lies in the fact that the calculation of the lengths for all years of life of an individual fish requires only one setting of the single movable part.
Probing sub-alveolar length scales with hyperpolarized-gas diffusion NMR

NASA Astrophysics Data System (ADS)

Miller, Wilson; Carl, Michael; Mooney, Karen; Mugler, John; Cates, Gordon

2009-05-01

Diffusion MRI of the lung is a promising technique for detecting alterations of normal lung microstructure in diseases such as emphysema. The length scale being probed using this technique is related to the time scale over which the helium-3 or xenon-129 diffusion is observed. We have developed new MR pulse sequence methods for making diffusivity measurements at sub-millisecond diffusion times, allowing one to probe smaller length scales than previously possible in-vivo, and opening the possibility of making quantitative measurements of the ratio of surface area to volume (S/V) in the lung airspaces. The quantitative accuracy of simulated and experimental measurements in microstructure phantoms will be discussed, and preliminary in-vivo results will be presented.
Cellular scaling rules for the brain of afrotherians

PubMed Central

Neves, Kleber; Ferreira, Fernanda M.; Tovar-Moll, Fernanda; Gravett, Nadine; Bennett, Nigel C.; Kaswera, Consolate; Gilissen, Emmanuel; Manger, Paul R.; Herculano-Houzel, Suzana

2014-01-01

Quantitative analysis of the cellular composition of rodent, primate and eulipotyphlan brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in evolution in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of afrotherians, believed to be the first clade to radiate from the common eutherian ancestor. We find that afrotherians share non-neuronal scaling rules with rodents, primates and eulipotyphlans, as well as the coordinated scaling of numbers of neurons in the cerebral cortex and cerebellum. Afrotherians share with rodents and eulipotyphlans, but not with primates, the scaling of number of neurons in the cortex and in the cerebellum as a function of the number of neurons in the rest of the brain. Afrotheria also share with rodents and eulipotyphlans the neuronal scaling rules that apply to the cerebral cortex. Afrotherians share with rodents, but not with eulipotyphlans nor primates, the neuronal scaling rules that apply to the cerebellum. Importantly, the scaling of the folding index of the cerebral cortex with the number of neurons in the cerebral cortex is not shared by either afrotherians, rodents, or primates. The sharing of some neuronal scaling rules between afrotherians and rodents, and of some additional features with eulipotyphlans and primates, raise the interesting possibility that these shared characteristics applied to the common eutherian ancestor. In turn, the clade-specific characteristics that relate to the distribution of neurons along the surface of the cerebral cortex and to its degree of gyrification suggest that these characteristics compose an evolutionarily plastic suite of features that may have defined and distinguished mammalian groups in evolution. PMID:24596544
Towards a comprehensive understanding of emerging dynamics and function of pancreatic islets: A complex network approach. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

NASA Astrophysics Data System (ADS)

Loppini, Alessandro

2018-03-01

Complex network theory represents a comprehensive mathematical framework to investigate biological systems, ranging from sub-cellular and cellular scales up to large-scale networks describing species interactions and ecological systems. In their exhaustive and comprehensive work [1], Gosak et al. discuss several scenarios in which the network approach was able to uncover general properties and underlying mechanisms of cells organization and regulation, tissue functions and cell/tissue failure in pathology, by the study of chemical reaction networks, structural networks and functional connectivities.
Functional Implications of Novel Human Acid Sphingomyelinase Splice Variants

PubMed Central

Rhein, Cosima; Tripal, Philipp; Seebahn, Angela; Konrad, Alice; Kramer, Marcel; Nagel, Christine; Kemper, Jonas; Bode, Jens; Mühle, Christiane; Gulbins, Erich; Reichel, Martin; Becker, Cord-Michael; Kornhuber, Johannes

2012-01-01

Background Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity. Methodology/Principal Findings We identified three novel ASM splice variants in human cells, termed ASM-5, -6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models. Conclusions/Significance These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity. PMID:22558155
Feasibility analysis of large length-scale thermocapillary flow experiment for the International Space Station

NASA Astrophysics Data System (ADS)

Alberts, Samantha J.

The investigation of microgravity fluid dynamics emerged out of necessity with the advent of space exploration. In particular, capillary research took a leap forward in the 1960s with regards to liquid settling and interfacial dynamics. Due to inherent temperature variations in large spacecraft liquid systems, such as fuel tanks, forces develop on gas-liquid interfaces which induce thermocapillary flows. To date, thermocapillary flows have been studied in small, idealized research geometries usually under terrestrial conditions. The 1 to 3m lengths in current and future large tanks and hardware are designed based on hardware rather than research, which leaves spaceflight systems designers without the technological tools to effectively create safe and efficient designs. This thesis focused on the design and feasibility of a large length-scale thermocapillary flow experiment, which utilizes temperature variations to drive a flow. The design of a helical channel geometry ranging from 1 to 2.5m in length permits a large length-scale thermocapillary flow experiment to fit in a seemingly small International Space Station (ISS) facility such as the Fluids Integrated Rack (FIR). An initial investigation determined the proposed experiment produced measurable data while adhering to the FIR facility limitations. The computational portion of this thesis focused on the investigation of functional geometries of fuel tanks and depots using Surface Evolver. This work outlines the design of a large length-scale thermocapillary flow experiment for the ISS FIR. The results from this work improve the understanding thermocapillary flows and thus improve technological tools for predicting heat and mass transfer in large length-scale thermocapillary flows. Without the tools to understand the thermocapillary flows in these systems, engineers are forced to design larger, heavier vehicles to assure safety and mission success.
Turbulent kinetic energy and a possible hierarchy of length scales in a generalization of the Navier-Stokes alpha theory.

PubMed

Fried, Eliot; Gurtin, Morton E

2007-05-01

We present a continuum-mechanical formulation and generalization of the Navier-Stokes alpha theory based on a general framework for fluid-dynamical theories with gradient dependencies. Our flow equation involves two additional problem-dependent length scales alpha and beta. The first of these scales enters the theory through the internal kinetic energy, per unit mass, alpha2|D|2, where D is the symmetric part of the gradient of the filtered velocity. The remaining scale is associated with a dissipative hyperstress which depends linearly on the gradient of the filtered vorticity. When alpha and beta are equal, our flow equation reduces to the Navier-Stokes alpha equation. In contrast to the original derivation of the Navier-Stokes alpha equation, which relies on Lagrangian averaging, our formulation delivers boundary conditions. For a confined flow, our boundary conditions involve an additional length scale l characteristic of the eddies found near walls. Based on a comparison with direct numerical simulations for fully developed turbulent flow in a rectangular channel of height 2h, we find that alphabeta approximately Re(0.470) and lh approximately Re(-0.772), where Re is the Reynolds number. The first result, which arises as a consequence of identifying the internal kinetic energy with the turbulent kinetic energy, indicates that the choice alpha=beta required to reduce our flow equation to the Navier-Stokes alpha equation is likely to be problematic. The second result evinces the classical scaling relation eta/L approximately Re(-3/4) for the ratio of the Kolmogorov microscale eta to the integral length scale L . The numerical data also suggests that l < or = beta . We are therefore led to conjecture a tentative hierarchy, l < or = beta < alpha , involving the three length scales entering our theory.
Generating and controlling homogeneous air turbulence using random jet arrays

NASA Astrophysics Data System (ADS)

Carter, Douglas; Petersen, Alec; Amili, Omid; Coletti, Filippo

2016-12-01

The use of random jet arrays, already employed in water tank facilities to generate zero-mean-flow homogeneous turbulence, is extended to air as a working fluid. A novel facility is introduced that uses two facing arrays of individually controlled jets (256 in total) to force steady homogeneous turbulence with negligible mean flow, shear, and strain. Quasi-synthetic jet pumps are created by expanding pressurized air through small straight nozzles and are actuated by fast-response low-voltage solenoid valves. Velocity fields, two-point correlations, energy spectra, and second-order structure functions are obtained from 2D PIV and are used to characterize the turbulence from the integral-to-the Kolmogorov scales. Several metrics are defined to quantify how well zero-mean-flow homogeneous turbulence is approximated for a wide range of forcing and geometric parameters. With increasing jet firing time duration, both the velocity fluctuations and the integral length scales are augmented and therefore the Reynolds number is increased. We reach a Taylor-microscale Reynolds number of 470, a large-scale Reynolds number of 74,000, and an integral-to-Kolmogorov length scale ratio of 680. The volume of the present homogeneous turbulence, the largest reported to date in a zero-mean-flow facility, is much larger than the integral length scale, allowing for the natural development of the energy cascade. The turbulence is found to be anisotropic irrespective of the distance between the jet arrays. Fine grids placed in front of the jets are effective at modulating the turbulence, reducing both velocity fluctuations and integral scales. Varying the jet-to-jet spacing within each array has no effect on the integral length scale, suggesting that this is dictated by the length scale of the jets.
Engineering behavior of small-scale foundation piers constructed from alternative materials

NASA Astrophysics Data System (ADS)

Prokudin, Maxim Mikhaylovich

Testing small-scale prototype pier foundations to evaluate engineering behavior is an alternative to full-scale testing that facilitates testing of several piers and pier groups at relatively low cost. In this study, various pier systems and pier groups at one tenth scale were subjected to static vertical loading under controlled conditions to evaluate stiffness, bearing capacity, and group efficiency. Pier length, material properties and methods of installation were evaluated. Pier length to diameter ratios varied between four and eight. A unique soil pit with dimensions of 2.1 m in width, 1.5 m in length and 2.0 m in depth was designed to carry out this research. The test pit was filled with moisture conditioned and compacted Western Iowa loess. A special load test frame was designed and fabricated to provide up to 25,000 kg vertical reaction force for load testing. A load cell and displacement instrumentation was setup to capture the load test data. Alternative materials to conventional cement concrete were studied. The pier materials evaluated in this study included compacted aggregate, cement stabilized silt, cementitious grouts, and fiber reinforced silt. Key findings from this study demonstrated that (1) the construction method influences the behavior of aggregate piers, (2) the composition of the pier has a significant impact on the stiffness, (3) group efficiencies were found to be a function of pier length and pier material, (4) in comparison to full-scale testing the scaled piers were found to produce a stiffer response with load-settlement and bearing capacities to be similar. Further, although full-scale test results were not available for all pier materials, the small-scale testing provided a means for comparing results between pier systems. Finally, duplicate pier tests for a given length and material were found to be repeatable.
Asymptotic Expansion Homogenization for Multiscale Nuclear Fuel Analysis

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

Hales, J. D.; Tonks, M. R.; Chockalingam, K.

2015-03-01

Engineering scale nuclear fuel performance simulations can benefit by utilizing high-fidelity models running at a lower length scale. Lower length-scale models provide a detailed view of the material behavior that is used to determine the average material response at the macroscale. These lower length-scale calculations may provide insight into material behavior where experimental data is sparse or nonexistent. This multiscale approach is especially useful in the nuclear field, since irradiation experiments are difficult and expensive to conduct. The lower length-scale models complement the experiments by influencing the types of experiments required and by reducing the total number of experiments needed.more » This multiscale modeling approach is a central motivation in the development of the BISON-MARMOT fuel performance codes at Idaho National Laboratory. These codes seek to provide more accurate and predictive solutions for nuclear fuel behavior. One critical aspect of multiscale modeling is the ability to extract the relevant information from the lower length-scale sim- ulations. One approach, the asymptotic expansion homogenization (AEH) technique, has proven to be an effective method for determining homogenized material parameters. The AEH technique prescribes a system of equations to solve at the microscale that are used to compute homogenized material constants for use at the engineering scale. In this work, we employ AEH to explore the effect of evolving microstructural thermal conductivity and elastic constants on nuclear fuel performance. We show that the AEH approach fits cleanly into the BISON and MARMOT codes and provides a natural, multidimensional homogenization capability.« less
Computed tomography-based diagnosis of diffuse compensatory enlargement of coronary arteries using scaling power laws.

PubMed

Huo, Yunlong; Choy, Jenny Susana; Wischgoll, Thomas; Luo, Tong; Teague, Shawn D; Bhatt, Deepak L; Kassab, Ghassan S

2013-04-06

Glagov's positive remodelling in the early stages of coronary atherosclerosis often results in plaque rupture and acute events. Because positive remodelling is generally diffused along the epicardial coronary arterial tree, it is difficult to diagnose non-invasively. Hence, the objective of the study is to assess the use of scaling power law for the diagnosis of positive remodelling of coronary arteries based on computed tomography (CT) images. Epicardial coronary arterial trees were reconstructed from CT scans of six Ossabaw pigs fed on a high-fat, high-cholesterol, atherogenic diet for eight months as well as the same number of body-weight-matched farm pigs fed on a lean chow (101.9±16.1 versus 91.5±13.1 kg). The high-fat diet Ossabaw pig model showed diffuse positive remodelling of epicardial coronary arteries. Good fit of measured coronary data to the length-volume scaling power law ( where L(c) and V(c) are crown length and volume) were found for both the high-fat and control groups (R(2) = 0.95±0.04 and 0.99±0.01, respectively). The coefficient, K(LV), decreased significantly in the high-fat diet group when compared with the control (14.6±2.6 versus 40.9±5.6). The flow-length scaling power law, however, was nearly unaffected by the positive remodelling. The length-volume and flow-length scaling power laws were preserved in epicardial coronary arterial trees after positive remodelling. K(LV) < 18 in the length-volume scaling relation is a good index of positive remodelling of coronary arteries. These findings provide a clinical rationale for simple, accurate and non-invasive diagnosis of positive remodelling of coronary arteries, using conventional CT scans.
An outlook review: mechanochromic materials and their potential for biological and healthcare applications.

PubMed

Jiang, Ying

2014-12-01

Macroscopic mechanical perturbations have been observed to result in optical changes for certain compounds and composite materials. This phenomenon could originate from chemical and physical changes across various length scales, from the rearrangement of chemical bonds to alteration of molecular domains on the order of several hundred nanometers. This review classifies the mechanisms and surveys of how each class of mechanochromic materials has been, and can potentially be applied in biological and healthcare innovations. The study of cellular and molecular responses to mechanical forces in biological systems is an emerging field; there is potential in applying mechanochromic principles and material systems for probing biological systems. On the other hand, application of mechanochromic materials for medical and healthcare consumer products has been described in a wide variety of concepts and inventions. It is hopeful that further understanding of mechanochromism and material innovations would initiate concrete, impactful studies in biological systems soon. Copyright © 2014 Elsevier B.V. All rights reserved.
Self-Organization of Embryonic Genetic Oscillators into Spatiotemporal Wave Patterns

PubMed Central

Tsiairis, Charisios D.; Aulehla, Alexander

2016-01-01

Summary In vertebrate embryos, somites, the precursor of vertebrae, form from the presomitic mesoderm (PSM), which is composed of cells displaying signaling oscillations. Cellular oscillatory activity leads to periodic wave patterns in the PSM. Here, we address the origin of such complex wave patterns. We employed an in vitro randomization and real-time imaging strategy to probe for the ability of cells to generate order from disorder. We found that, after randomization, PSM cells self-organized into several miniature emergent PSM structures (ePSM). Our results show an ordered macroscopic spatial arrangement of ePSM with evidence of an intrinsic length scale. Furthermore, cells actively synchronize oscillations in a Notch-signaling-dependent manner, re-establishing wave-like patterns of gene activity. We demonstrate that PSM cells self-organize by tuning oscillation dynamics in response to surrounding cells, leading to collective synchronization with an average frequency. These findings reveal emergent properties within an ensemble of coupled genetic oscillators. PMID:26871631
Macro-SICM: A Scanning Ion Conductance Microscope for Large-Range Imaging.

PubMed

Schierbaum, Nicolas; Hack, Martin; Betz, Oliver; Schäffer, Tilman E

2018-04-17

The scanning ion conductance microscope (SICM) is a versatile, high-resolution imaging technique that uses an electrolyte-filled nanopipet as a probe. Its noncontact imaging principle makes the SICM uniquely suited for the investigation of soft and delicate surface structures in a liquid environment. The SICM has found an ever-increasing number of applications in chemistry, physics, and biology. However, a drawback of conventional SICMs is their relatively small scan range (typically 100 μm × 100 μm in the lateral and 10 μm in the vertical direction). We have developed a Macro-SICM with an exceedingly large scan range of 25 mm × 25 mm in the lateral and 0.25 mm in the vertical direction. We demonstrate the high versatility of the Macro-SICM by imaging at different length scales: from centimeters (fingerprint, coin) to millimeters (bovine tongue tissue, insect wing) to micrometers (cellular extensions). We applied the Macro-SICM to the study of collective cell migration in epithelial wound healing.
Characterization of RNase MRP RNA and novel snoRNAs from Giardia intestinalis and Trichomonas vaginalis

PubMed Central

2011-01-01

Background Eukaryotic cells possess a complex network of RNA machineries which function in RNA-processing and cellular regulation which includes transcription, translation, silencing, editing and epigenetic control. Studies of model organisms have shown that many ncRNAs of the RNA-infrastructure are highly conserved, but little is known from non-model protists. In this study we have conducted a genome-scale survey of medium-length ncRNAs from the protozoan parasites Giardia intestinalis and Trichomonas vaginalis. Results We have identified the previously 'missing' Giardia RNase MRP RNA, which is a key ribozyme involved in pre-rRNA processing. We have also uncovered 18 new H/ACA box snoRNAs, expanding our knowledge of the H/ACA family of snoRNAs. Conclusions Results indicate that Giardia intestinalis and Trichomonas vaginalis, like their distant multicellular relatives, contain a rich infrastructure of RNA-based processing. From here we can investigate the evolution of RNA processing networks in eukaryotes. PMID:22053856

Synthetic Biomaterials to Rival Nature's Complexity-a Path Forward with Combinatorics, High-Throughput Discovery, and High-Content Analysis.

PubMed

Zhang, Douglas; Lee, Junmin; Kilian, Kristopher A

2017-10-01

Cells in tissue receive a host of soluble and insoluble signals in a context-dependent fashion, where integration of these cues through a complex network of signal transduction cascades will define a particular outcome. Biomaterials scientists and engineers are tasked with designing materials that can at least partially recreate this complex signaling milieu towards new materials for biomedical applications. In this progress report, recent advances in high throughput techniques and high content imaging approaches that are facilitating the discovery of efficacious biomaterials are described. From microarrays of synthetic polymers, peptides and full-length proteins, to designer cell culture systems that present multiple biophysical and biochemical cues in tandem, it is discussed how the integration of combinatorics with high content imaging and analysis is essential to extracting biologically meaningful information from large scale cellular screens to inform the design of next generation biomaterials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Connectivity-driven white matter scaling and folding in primate cerebral cortex

PubMed Central

Herculano-Houzel, Suzana; Mota, Bruno; Kaas, Jon H.

2010-01-01

Larger brains have an increasingly folded cerebral cortex whose white matter scales up faster than the gray matter. Here we analyze the cellular composition of the subcortical white matter in 11 primate species, including humans, and one Scandentia, and show that the mass of the white matter scales linearly across species with its number of nonneuronal cells, which is expected to be proportional to the total length of myelinated axons in the white matter. This result implies that the average axonal cross-section area in the white matter, a, does not scale significantly with the number of neurons in the gray matter, N. The surface area of the white matter increases with N0.87, not N1.0. Because this surface can be defined as the product of N, a, and the fraction n of cortical neurons connected through the white matter, we deduce that connectivity decreases in larger cerebral cortices as a slowly diminishing fraction of neurons, which varies with N−0.16, sends myelinated axons into the white matter. Decreased connectivity is compatible with previous suggestions that neurons in the cerebral cortex are connected as a small-world network and should slow down the increase in global conduction delay in cortices with larger numbers of neurons. Further, a simple model shows that connectivity and cortical folding are directly related across species. We offer a white matter-based mechanism to account for increased cortical folding across species, which we propose to be driven by connectivity-related tension in the white matter, pulling down on the gray matter. PMID:20956290
Elliptic Length Scales in Laminar, Two-Dimensional Supersonic Flows

DTIC Science & Technology

2015-06-01

sophisticated computational fluid dynamics ( CFD ) methods. Additionally, for 3D interactions, the length scales would require determination in spanwise as well...Manna, M. “Experimental, Analytical, and Computational Methods Applied to Hypersonic Compression Ramp Flows,” AIAA Journal, Vol. 32, No. 2, Feb. 1994
Many-body localization transition: Schmidt gap, entanglement length, and scaling

NASA Astrophysics Data System (ADS)

Gray, Johnnie; Bose, Sougato; Bayat, Abolfazl

2018-05-01

Many-body localization has become an important phenomenon for illuminating a potential rift between nonequilibrium quantum systems and statistical mechanics. However, the nature of the transition between ergodic and localized phases in models displaying many-body localization is not yet well understood. Assuming that this is a continuous transition, analytic results show that the length scale should diverge with a critical exponent ν ≥2 in one-dimensional systems. Interestingly, this is in stark contrast with all exact numerical studies which find ν ˜1 . We introduce the Schmidt gap, new in this context, which scales near the transition with an exponent ν >2 compatible with the analytical bound. We attribute this to an insensitivity to certain finite-size fluctuations, which remain significant in other quantities at the sizes accessible to exact numerical methods. Additionally, we find that a physical manifestation of the diverging length scale is apparent in the entanglement length computed using the logarithmic negativity between disjoint blocks.
A phenomenological description of space-time noise in quantum gravity.

PubMed

Amelino-Camelia, G

2001-04-26

Space-time 'foam' is a geometric picture of the smallest size scales in the Universe, which is characterized mainly by the presence of quantum uncertainties in the measurement of distances. All quantum-gravity theories should predict some kind of foam, but the description of the properties of this foam varies according to the theory, thereby providing a possible means of distinguishing between such theories. I previously showed that foam-induced distance fluctuations would introduce a new source of noise to the measurements of gravity-wave interferometers, but the theories are insufficiently developed to permit detailed predictions that would be of use to experimentalists. Here I propose a phenomenological approach that directly describes space-time foam, and which leads naturally to a picture of distance fluctuations that is independent of the details of the interferometer. The only unknown in the model is the length scale that sets the overall magnitude of the effect, but recent data already rule out the possibility that this length scale could be identified with the 'string length' (10-34 m < Ls < 10-33 m). Length scales even smaller than the 'Planck length' (LP approximately 10-35 m) will soon be probed experimentally.
Geostatistics and the representative elementary volume of gamma ray tomography attenuation in rocks cores

USGS Publications Warehouse

Vogel, J.R.; Brown, G.O.

2003-01-01

Semivariograms of samples of Culebra Dolomite have been determined at two different resolutions for gamma ray computed tomography images. By fitting models to semivariograms, small-scale and large-scale correlation lengths are determined for four samples. Different semivariogram parameters were found for adjacent cores at both resolutions. Relative elementary volume (REV) concepts are related to the stationarity of the sample. A scale disparity factor is defined and is used to determine sample size required for ergodic stationarity with a specified correlation length. This allows for comparison of geostatistical measures and representative elementary volumes. The modifiable areal unit problem is also addressed and used to determine resolution effects on correlation lengths. By changing resolution, a range of correlation lengths can be determined for the same sample. Comparison of voxel volume to the best-fit model correlation length of a single sample at different resolutions reveals a linear scaling effect. Using this relationship, the range of the point value semivariogram is determined. This is the range approached as the voxel size goes to zero. Finally, these results are compared to the regularization theory of point variables for borehole cores and are found to be a better fit for predicting the volume-averaged range.
The Virtual Cell Animation Collection: Tools for Teaching Molecular and Cellular Biology

PubMed Central

Reindl, Katie M.; White, Alan R.; Johnson, Christina; Vender, Bradley; Slator, Brian M.; McClean, Phillip

2015-01-01

A cell is a minifactory in which structures and molecules are assembled, rearranged, disassembled, packaged, sorted, and transported. Because cellular structures and molecules are invisible to the human eye, students often have difficulty conceptualizing the dynamic nature of cells that function at multiple scales across time and space. To represent these dynamic cellular processes, the Virtual Cell Productions team at North Dakota State University develops freely available multimedia materials to support molecular and cellular biology learning inside and outside the high school and university classroom. PMID:25856580
Adult Chinese as a Second Language Learners' Willingness to Communicate in Chinese: Effects of Cultural, Affective, and Linguistic Variables.

PubMed

Liu, Meihua

2017-06-01

The present research explored the effects of cultural, affective, and linguistic variables on adult Chinese as a second language learners' willingness to communicate in Chinese. One hundred and sixty-two Chinese as a second language learners from a Chinese university answered the Willingness to Communicate in Chinese Scale, the Intercultural Sensitivity Scale, Chinese Speaking Anxiety Scale, Chinese Learning Motivation Scale, Use of Chinese Profile, as well as the Background Questionnaire. The major findings were as follows: (1) the Willingness to Communicate in Chinese Scales were significantly negatively correlated with Chinese Speaking Anxiety Scale but positively correlated with length of stay in China and (2) Chinese Speaking Anxiety Scale was a powerful negative predictor for the overall willingness to communicate in Chinese and the Willingness to Communicate in Chinese Scales, followed by length of stay in China, Chinese Learning Motivation Scale, interaction attentiveness, and Chinese proficiency level. Apparently, students' willingness to communicate in Chinese is largely determined by their Chinese Speaking Anxiety Scale level and length of stay in China, mediated by other variables such as Chinese proficiency level and intercultural communication sensitivity level.
Magnesite Dissolution Rates Across Scales: Role of Spatial Heterogeneity, Equilibrium Lengths, and Reactive Time Scales

NASA Astrophysics Data System (ADS)

Wen, H.; Li, L.

2017-12-01

This work develops a general rate law for magnesite dissolution in heterogeneous media under variable flow and length conditions, expanding the previous work under one particular flow and length conditions (Wen and Li, 2017). We aim to answer: 1) How does spatial heterogeneity influence the time and length scales to reach equilibrium? 2) How do relative timescales of advection, diffusion/dispersion, and reactions influence dissolution rates under variable flow and length conditions? We carried out 640 Monte-Carlo numerical experiments of magnesite dissolution within quartz matrix with heterogeneity characterized by permeability variance and correlation length under a range of length and flow velocity. A rate law Rhete = kAT(1-exp(τeq,m/τa))(1-exp(- Lβ))^α was developed. The former part is rates in equivalent homogeneous media kAT(1-exp(τeq,m/τa)), depending on rate constant k, magnesite surface area AT, and relative timescales of reactions τeq,m and advection τa. The latter term (1-exp(- Lβ))^α is the heterogeneity factor χ that quantifies the deviation of heterogeneous media from its homogeneous counterpart. The term has a scaling factor, called reactive transport number β=τa/(τad,r+τeq,m), for domain length L, and the geostatistical characteristics of heterogeneity α. The β quantifies the relative timescales of advection at the domain scale τa versus the advective-diffusive-dispersive transport time out of reactive zones τad,r and reaction time τeq,m. The χ is close to 1 and is insignificant under long residence time conditions (low flow velocity and / or long length) where the residence time is longer than the time needed for Mg to dissolve and transport out of reactive zones (τad,r+τeq,m) so that equilibrium is reached and homogenization occurs. In contrast, χ deviates from 1 and is significant only when β is small, which occurs at short length or fast flow where timescales of reactive transport in reactive zones are much longer than the global residence time so that reactive transport is the limiting step. These findings demonstrate that dissolution rates in heterogeneous media reach asymptotic values in homogeneous media at "sufficiently" long lengths. Wen, H. and Li, L. (2017) An upscaled rate law for magnesite dissolution in heterogeneous porous media. Geochimica et Cosmochimica Acta 210, 289-305.
Hydrodynamic simulations of long-scale-length two-plasmon-decay experiments at the Omega Laser Facility

NASA Astrophysics Data System (ADS)

Hu, S. X.; Michel, D. T.; Edgell, D. H.; Froula, D. H.; Follett, R. K.; Goncharov, V. N.; Myatt, J. F.; Skupsky, S.; Yaakobi, B.

2013-03-01

Direct-drive-ignition designs with plastic CH ablators create plasmas of long density scale lengths (Ln ≥ 500 μm) at the quarter-critical density (Nqc) region of the driving laser. The two-plasmon-decay (TPD) instability can exceed its threshold in such long-scale-length plasmas (LSPs). To investigate the scaling of TPD-induced hot electrons to laser intensity and plasma conditions, a series of planar experiments have been conducted at the Omega Laser Facility with 2-ns square pulses at the maximum laser energies available on OMEGA and OMEGA EP. Radiation-hydrodynamic simulations have been performed for these LSP experiments using the two-dimensional hydrocode draco. The simulated hydrodynamic evolution of such long-scale-length plasmas has been validated with the time-resolved full-aperture backscattering and Thomson-scattering measurements. draco simulations for CH ablator indicate that (1) ignition-relevant long-scale-length plasmas of Ln approaching ˜400 μm have been created; (2) the density scale length at Nqc scales as Ln(μm)≃(RDPP×I1/4/2); and (3) the electron temperature Te at Nqc scales as Te(keV)≃0.95×√I , with the incident intensity (I) measured in 1014 W/cm2 for plasmas created on both OMEGA and OMEGA EP configurations with different-sized (RDPP) distributed phase plates. These intensity scalings are in good agreement with the self-similar model predictions. The measured conversion fraction of laser energy into hot electrons fhot is found to have a similar behavior for both configurations: a rapid growth [fhot≃fc×(Gc/4)6 for Gc < 4] followed by a saturation of the form, fhot≃fc×(Gc/4)1.2 for Gc ≥ 4, with the common wave gain is defined as Gc=3 × 10-2×IqcLnλ0/Te, where the laser intensity contributing to common-wave gain Iqc, Ln, Te at Nqc, and the laser wavelength λ0 are, respectively, measured in [1014 W/cm2], [μm], [keV], and [μm]. The saturation level fc is observed to be fc ≃ 10-2 at around Gc ≃ 4. The hot-electron temperature scales roughly linear with Gc. Furthermore, to mitigate TPD instability in long-scale-length plasmas, different ablator materials such as saran and aluminum have been investigated on OMEGA EP. Hot-electron generation has been reduced by a factor of 3-10 for saran and aluminum plasmas, compared to the CH case at the same incident laser intensity. draco simulations suggest that saran might be a better ablator for direct-drive-ignition designs as it balances TPD mitigation with an acceptable hydro-efficiency.
Colony-Level Differences in the Scaling Rules Governing Wood Ant Compound Eye Structure.

PubMed

Perl, Craig D; Niven, Jeremy E

2016-04-12

Differential organ growth during development is essential for adults to maintain the correct proportions and achieve their characteristic shape. Organs scale with body size, a process known as allometry that has been studied extensively in a range of organisms. Such scaling rules, typically studied from a limited sample, are assumed to apply to all members of a population and/or species. Here we study scaling in the compound eyes of workers of the wood ant, Formica rufa, from different colonies within a single population. Workers' eye area increased with body size in all the colonies showing a negative allometry. However, both the slope and intercept of some allometric scaling relationships differed significantly among colonies. Moreover, though mean facet diameter and facet number increased with body size, some colonies primarily increased facet number whereas others increased facet diameter, showing that the cellular level processes underlying organ scaling differed among colonies. Thus, the rules that govern scaling at the organ and cellular levels can differ even within a single population.
Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

PubMed Central

Kazu, Rodrigo S.; Maldonado, José; Mota, Bruno; Manger, Paul R.; Herculano-Houzel, Suzana

2014-01-01

Quantitative analysis of the cellular composition of rodent, primate, insectivore, and afrotherian brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share non-neuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are, however, distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires, and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex. PMID:25429261
Procedure for Determining Turbulence Length Scales Using Hotwire Anemometry

NASA Technical Reports Server (NTRS)

El-Gabry, Lamyaa A.; Thurman, Douglas R.; Poinsatte, Philip E.

2014-01-01

Hotwire anemometers are used to measure instantaneous velocity from which the mean velocity and the velocity fluctuation can be determined. Using a hotwire system, it is possible to deduce not only the velocity components and their fluctuation but to also analyze the energy spectra and from that the turbulence length scales. In this experiment, hotwire anemometry is used to measure the flow field turbulence for an array of film cooling holes. The objective of this paper is to document the procedure that is used to reduce the instantaneous velocity measurements to determine the turbulence length scales using data from the film-cooling experiments to illustrate the procedure.
Factors affecting length of stay in forensic hospital setting: need for therapeutic security and course of admission.

PubMed

Davoren, Mary; Byrne, Orla; O'Connell, Paul; O'Neill, Helen; O'Reilly, Ken; Kennedy, Harry G

2015-11-23

Patients admitted to a secure forensic hospital are at risk of a long hospital stay. Forensic hospital beds are a scarce and expensive resource and ability to identify the factors predicting length of stay at time of admission would be beneficial. The DUNDRUM-1 triage security scale and DUNDRUM-2 triage urgency scale are designed to assess need for therapeutic security and urgency of that need while the HCR-20 predicts risk of violence. We hypothesized that items on the DUNDRUM-1 and DUNDRUM-2 scales, rated at the time of pre-admission assessment, would predict length of stay in a medium secure forensic hospital setting. This is a prospective study. All admissions to a medium secure forensic hospital setting were collated over a 54 month period (n = 279) and followed up for a total of 66 months. Each patient was rated using the DUNDRUM-1 triage security scale and DUNDRUM-2 triage urgency scale as part of a pre-admission assessment (n = 279) and HCR-20 within 2 weeks of admission (n = 187). Episodes of harm to self, harm to others and episodes of seclusion whilst an in-patient were collated. Date of discharge was noted for each individual. Diagnosis at the time of pre-admission assessment (adjustment disorder v other diagnosis), predicted legal status (sentenced v mental health order) and items on the DUNDRUM-1 triage security scale and the DUNDRUM-2 triage urgency scale, also rated at the time of pre-admission assessment, predicted length of stay in the forensic hospital setting. Need for seclusion following admission also predicted length of stay. These findings may form the basis for a structured professional judgment instrument, rated prior to or at time of admission, to assist in estimating length of stay for forensic patients. Such a tool would be useful to clinicians, service planners and commissioners given the high cost of secure psychiatric care.
Recent assimilation developments of FOAM the Met Office ocean forecast system

NASA Astrophysics Data System (ADS)

Lea, Daniel; Martin, Matthew; Waters, Jennifer; Mirouze, Isabelle; While, James; King, Robert

2015-04-01

FOAM is the Met Office's operational ocean forecasting system. This system comprises a range of models from a 1/4 degree resolution global to 1/12 degree resolution regional models and shelf seas models at 7 km resolution. The system is made up of the ocean model NEMO (Nucleus for European Modeling of the Ocean), the Los Alomos sea ice model CICE and the NEMOVAR assimilation run in 3D-VAR FGAT mode. Work is ongoing to transition to both a higher resolution global ocean model at 1/12 degrees and to run FOAM in coupled models. The FOAM system generally performs well. One area of concern however is the performance in the tropics where spurious oscillations and excessive vertical velocity gradients are found after assimilation. NEMOVAR includes a balance operator which in the extra-tropics uses geostrophic balance to produce velocity increments which balance the density increments applied. In the tropics, however, the main balance is between the pressure gradients produced by the density gradient and the applied wind stress. A scheme is presented which aims to maintain this balance when increments are applied. Another issue in FOAM is that there are sometimes persistent temperature and salinity errors which are not effectively corrected by the assimilation. The standard NEMOVAR has a single correlation length scale based on the local Rossby radius. This means that observations in the extra tropics have influence on the model only on short length-scales. In order to maximise the information extracted from the observations and to correct large scale model biases a multiple correlation length-scale scheme has been developed. This includes a larger length scale which spreads observation information further. Various refinements of the scheme are also explored including reducing the longer length scale component at the edge of the sea ice and in areas with high potential vorticity gradients. A related scheme which varies the correlation length scale in the shelf seas is also described.
Visualizing chemical functionality in plant cell walls

DOE PAGES

Zeng, Yining; Himmel, Michael E.; Ding, Shi-You

2017-11-30

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructivelymore » and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition - especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.« less
How deep cells feel: Mean-field Computations and Experiments

NASA Astrophysics Data System (ADS)

Buxboim, Amnon; Sen, Shamik; Discher, Dennis E.

2009-03-01

Most cells in solid tissues exert contractile forces that mechanically couple them to elastic surroundings and that significantly influence cell adhesion, cytoskeletal organization and differentiation. However, strains within the depths of matrices are often unclear and are likely relevant to thin matrices, such as basement membranes, relative to cell size as well as to defining how far cells can ``feel.'' We present experimental results for cell spreading on thin, ligand- coated gels and for prestress in stem cells in relation to gel stiffness. Matrix thickness affects cell spread area, focal adhesions and cytoskeleton organization in stem cells, which we will compare to differentiated cells. We introduce a finite element computation to estimate the elastostatic deformations within the matrix on which a cell is placed. Interfacial strains between cell and matrix show large deviations only when soft matrices are a fraction of cell dimensions, proving consistent with experiments. 3-D cell morphologies that model stem cell-derived neurons, myoblasts, and osteoblasts show that a cylinder-shaped myoblast induces the highest strains, consistent with the prominent contractility of muscle. Groups of such cells show a weak crosstalk via matrix strains only when cells are much closer than a cell-width. Cells thus feel on length scales closer to that of adhesions than on cellular scales.
Visualizing chemical functionality in plant cell walls

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

Zeng, Yining; Himmel, Michael E.; Ding, Shi-You

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructivelymore » and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition - especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.« less
Visualizing chemical functionality in plant cell walls.

PubMed

Zeng, Yining; Himmel, Michael E; Ding, Shi-You

2017-01-01

Understanding plant cell wall cross-linking chemistry and polymeric architecture is key to the efficient utilization of biomass in all prospects from rational genetic modification to downstream chemical and biological conversion to produce fuels and value chemicals. In fact, the bulk properties of cell wall recalcitrance are collectively determined by its chemical features over a wide range of length scales from tissue, cellular to polymeric architectures. Microscopic visualization of cell walls from the nanometer to the micrometer scale offers an in situ approach to study their chemical functionality considering its spatial and chemical complexity, particularly the capabilities of characterizing biomass non-destructively and in real-time during conversion processes. Microscopic characterization has revealed heterogeneity in the distribution of chemical features, which would otherwise be hidden in bulk analysis. Key microscopic features include cell wall type, wall layering, and wall composition-especially cellulose and lignin distributions. Microscopic tools, such as atomic force microscopy, stimulated Raman scattering microscopy, and fluorescence microscopy, have been applied to investigations of cell wall structure and chemistry from the native wall to wall treated by thermal chemical pretreatment and enzymatic hydrolysis. While advancing our current understanding of plant cell wall recalcitrance and deconstruction, microscopic tools with improved spatial resolution will steadily enhance our fundamental understanding of cell wall function.
Combined Multidimensional Microscopy as a Histopathology Imaging Tool.

PubMed

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

2017-02-01

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

Universality from disorder in the random-bond Blume-Capel model

NASA Astrophysics Data System (ADS)

Fytas, N. G.; Zierenberg, J.; Theodorakis, P. E.; Weigel, M.; Janke, W.; Malakis, A.

2018-04-01

Using high-precision Monte Carlo simulations and finite-size scaling we study the effect of quenched disorder in the exchange couplings on the Blume-Capel model on the square lattice. The first-order transition for large crystal-field coupling is softened to become continuous, with a divergent correlation length. An analysis of the scaling of the correlation length as well as the susceptibility and specific heat reveals that it belongs to the universality class of the Ising model with additional logarithmic corrections which is also observed for the Ising model itself if coupled to weak disorder. While the leading scaling behavior of the disordered system is therefore identical between the second-order and first-order segments of the phase diagram of the pure model, the finite-size scaling in the ex-first-order regime is affected by strong transient effects with a crossover length scale L*≈32 for the chosen parameters.
Correspondence: Reply to ‘Phantom phonon localization in relaxors’

DOE PAGES

Manley, Michael E.; Abernathy, Douglas L.; Budai, John D.

2017-12-05

The Correspondence by Gehring et al. mistakes Anderson phonon localization for the concept of an atomic-scale local mode. An atomic-scale local mode refers to a single atom vibrating on its own within a crystal. Such a local mode will have an almost flat intensity profile, but this is not the same as phonon localization. Anderson localization is a wave interference effect in a disordered system that results in waves becoming spatially localized. The length scale of the localized waves is set by the wavelength, which is approximately 2 nm in this case. This larger length scale in real space meansmore » narrower intensity profiles in reciprocal space. Here, we conclude that the claims in the Correspondence by Gehring et al. are incorrect because they mistakenly assume that the length scale for Anderson localization is atomic, and because the experimental observations rule out multiple scattering as the origin.« less
Correspondence: Reply to ‘Phantom phonon localization in relaxors’

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

Manley, Michael E.; Abernathy, Douglas L.; Budai, John D.

The Correspondence by Gehring et al. mistakes Anderson phonon localization for the concept of an atomic-scale local mode. An atomic-scale local mode refers to a single atom vibrating on its own within a crystal. Such a local mode will have an almost flat intensity profile, but this is not the same as phonon localization. Anderson localization is a wave interference effect in a disordered system that results in waves becoming spatially localized. The length scale of the localized waves is set by the wavelength, which is approximately 2 nm in this case. This larger length scale in real space meansmore » narrower intensity profiles in reciprocal space. Here, we conclude that the claims in the Correspondence by Gehring et al. are incorrect because they mistakenly assume that the length scale for Anderson localization is atomic, and because the experimental observations rule out multiple scattering as the origin.« less
Flexible chain molecules in the marginal and concentrated regimes: universal static scaling laws and cross-over predictions.

PubMed

Laso, Manuel; Karayiannis, Nikos Ch

2008-05-07

We present predictions for the static scaling exponents and for the cross-over polymer volumetric fractions in the marginal and concentrated solution regimes. Corrections for finite chain length are made. Predictions are based on an analysis of correlated fluctuations in density and chain length, in a semigrand ensemble in which mers and solvent sites exchange identities. Cross-over volumetric fractions are found to be chain length independent to first order, although reciprocal-N corrections are also estimated. Predicted scaling exponents and cross-over regimes are compared with available data from extensive off-lattice Monte Carlo simulations [Karayiannis and Laso, Phys. Rev. Lett. 100, 050602 (2008)] on freely jointed, hard-sphere chains of average lengths from N=12-500 and at packing densities from dilute ones up to the maximally random jammed state.
Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7.

PubMed

Gullett, Jessica M; Bible, Amber; Alexandre, Gladys

2017-07-01

Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense , Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. Copyright © 2017 American Society for Microbiology.
Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7

PubMed Central

Gullett, Jessica M.

2017-01-01

ABSTRACT Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense, Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. PMID:28416707
Effect of von Karman Vortex Shedding on Regular and Open-slit V-gutter Stabilized Turbulent Premixed Flames

DTIC Science & Technology

2012-04-01

Both flame lengths shrink and large scale disruptions occur downstream with vortex shedding carrying reaction zones. Flames in both flameholders...9) the flame structure changes dramatically for both regular and open-slit V-gutter. Both flame lengths shrink and large scale disruptions occur...reduces the flame length . However, qualitatively the open-slit V-gutter appears to be more sensitive than the regular V-gutter. Both flames remain
Evaluation of removal of the size effect using data scaling and elliptic Fourier descriptors in otolith shape analysis, exemplified by the discrimination of two yellow croaker stocks along the Chinese coast

NASA Astrophysics Data System (ADS)

Zhao, Bo; Liu, Jinhu; Song, Junjie; Cao, Liang; Dou, Shuozeng

2017-11-01

Removal of the length effect in otolith shape analysis for stock identification using length scaling is an important issue; however, few studies have attempted to investigate the effectiveness or weakness of this methodology in application. The aim of this study was to evaluate whether commonly used size scaling methods and normalized elliptic Fourier descriptors (NEFDs) could effectively remove the size effect of fish in stock discrimination. To achieve this goal, length groups from two known geographical stocks of yellow croaker, Larimichthys polyactis, along the Chinese coast (five groups from the Changjiang River estuary of the East China Sea and three groups from the Bohai Sea) were subjected to otolith shape analysis. The results indicated that the variation of otolith shape caused by intra-stock fish length might exceed that due to inter-stock geographical separation, even when otolith shape variables are standardized with length scaling methods. This variation could easily result in misleading stock discrimination through otolith shape analysis. Therefore, conclusions about fish stock structure should be carefully drawn from otolith shape analysis because the observed discrimination may primarily be due to length effects, rather than differences among stocks. The application of multiple methods, such as otoliths shape analysis combined with elemental fingering, tagging or genetic analysis, is recommended for sock identification.
Microtubule Dynamics Scale with Cell Size to Set Spindle Length and Assembly Timing.

PubMed

Lacroix, Benjamin; Letort, Gaëlle; Pitayu, Laras; Sallé, Jérémy; Stefanutti, Marine; Maton, Gilliane; Ladouceur, Anne-Marie; Canman, Julie C; Maddox, Paul S; Maddox, Amy S; Minc, Nicolas; Nédélec, François; Dumont, Julien

2018-05-21

Successive cell divisions during embryonic cleavage create increasingly smaller cells, so intracellular structures must adapt accordingly. Mitotic spindle size correlates with cell size, but the mechanisms for this scaling remain unclear. Using live cell imaging, we analyzed spindle scaling during embryo cleavage in the nematode Caenorhabditis elegans and sea urchin Paracentrotus lividus. We reveal a common scaling mechanism, where the growth rate of spindle microtubules scales with cell volume, which explains spindle shortening. Spindle assembly timing is, however, constant throughout successive divisions. Analyses in silico suggest that controlling the microtubule growth rate is sufficient to scale spindle length and maintain a constant assembly timing. We tested our in silico predictions to demonstrate that modulating cell volume or microtubule growth rate in vivo induces a proportional spindle size change. Our results suggest that scalability of the microtubule growth rate when cell size varies adapts spindle length to cell volume. Copyright © 2018 Elsevier Inc. All rights reserved.
Multi-Length Scale-Enriched Continuum-Level Material Model for Kevlar (registered trademark)-Fiber-Reinforced Polymer-Matrix Composites

DTIC Science & Technology

2013-03-01

of coarser-scale materials and structures containing Kevlar fibers (e.g., yarns, fabrics, plies, lamina, and laminates ). Journal of Materials...Multi-Length Scale-Enriched Continuum-Level Material Model for Kevlar -Fiber-Reinforced Polymer-Matrix Composites M. Grujicic, B. Pandurangan, J.S...extensive set of molecular-level computational analyses regarding the role of various microstructural/morphological defects on the Kevlar fiber
Underscreening in concentrated electrolytes.

PubMed

Lee, Alpha A; Perez-Martinez, Carla S; Smith, Alexander M; Perkin, Susan

2017-07-01

Screening of a surface charge by an electrolyte and the resulting interaction energy between charged objects is of fundamental importance in scenarios from bio-molecular interactions to energy storage. The conventional wisdom is that the interaction energy decays exponentially with object separation and the decay length is a decreasing function of ion concentration; the interaction is thus negligible in a concentrated electrolyte. Contrary to this conventional wisdom, we have shown by surface force measurements that the decay length is an increasing function of ion concentration and Bjerrum length for concentrated electrolytes. In this paper we report surface force measurements to test directly the scaling of the screening length with Bjerrum length. Furthermore, we identify a relationship between the concentration dependence of this screening length and empirical measurements of activity coefficient and differential capacitance. The dependence of the screening length on the ion concentration and the Bjerrum length can be explained by a simple scaling conjecture based on the physical intuition that solvent molecules, rather than ions, are charge carriers in a concentrated electrolyte.
Scaling and functional morphology in strigiform hind limbs

PubMed Central

Madan, Meena A.; Rayfield, Emily J.; Bright, Jen A.

2017-01-01

Strigiformes are an order of raptorial birds consisting exclusively of owls: the Tytonidae (barn owls) and the Strigidae (true owls), united by a suite of adaptations aiding a keen predatory lifestyle, including robust hind limb elements modified for grip strength. To assess variation in hind limb morphology, we analysed how the dimensions of the major hind limb elements in subfossil and modern species scaled with body mass. Comparing hind limb element length, midshaft width, and robusticity index (RI: ratio of midshaft width to maximum length) to body mass revealed that femoral and tibiotarsal width scale with isometry, whilst length scales with negative allometry, and close to elastic similarity in the tibiotarsus. In contrast, tarsometatarsus width shows strong positive allometry with body mass, whilst length shows strong negative allometry. Furthermore, the tarsometatarsi RI scales allometrically to mass0.028, whilst a weak relationship exists in femora (mass0.004) and tibiotarsi (mass0.004). Our results suggest that tarsometatarsi play a more substantial functional role than tibiotarsi and femora. Given the scaling relationship between tarsometatarsal width and robusticity to body mass, it may be possible to infer the body mass of prehistoric owls by analysing tarsometatarsi, an element that is frequently preserved in the fossil record of owls. PMID:28327549
Control of fluxes in metabolic networks.

PubMed

Basler, Georg; Nikoloski, Zoran; Larhlimi, Abdelhalim; Barabási, Albert-László; Liu, Yang-Yu

2016-07-01

Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coli, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. © 2016 Basler et al.; Published by Cold Spring Harbor Laboratory Press.
Sheaths: A Comparison of Magnetospheric, ICME, and Heliospheric Sheaths

NASA Technical Reports Server (NTRS)

Sibeck, D. G.; Richardson, J. D.; Liu, W.

2007-01-01

When a supersonic flow encounters an obstacles, shocks form to divert the flow around the obstacle. The region between the shock and the obstacle is the sheath, where the supersonic flow is compressed, heated, decelerated, and deflected. Supersonic flows, obstacles, and thus sheaths are observed on many scales throughout the Universe. We compare three examples seen in the heliosphere, illustrating the interaction of the solar wind with obstacles of three very different scales lengths. Magnetosheaths form behind planetary bow shocks on scales ranging from tens to 100 planetary radii. ICME sheath form behind shocks driven by solar disturbances on scale lengths of a few to tens of AU. The heliosheath forms behind the termination shock due to the obstacle presented by the interstellar medium on scale lengths of tens to a hundred AU. Despite this range in scales some common features have been observed. Magnetic holes, possibly due to mirror mode waves, have been observed in all three of these sheaths. Plasma depletion layers are observed in planetary and ICME sheaths. Other features observed in some sheaths are wave activity (ion cyclotron, plasma), energetic particles, transmission of Alfven waves/shocks, tangential discontinuities turbulence behind quasi-parallel shocks, standing slow mode waves, and reconnection on the obstacle boundary. We compare these sheath regions, discussing similarities and differences and how these may relate to the scale lengths of these regions.
WE-DE-202-00: Connecting Radiation Physics with Computational Biology

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

NONE

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less
DOE Office of Scientific and Technical Information (OSTI.GOV)

McMahon, S.

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less
WE-DE-202-01: Connecting Nanoscale Physics to Initial DNA Damage Through Track Structure Simulations

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

Schuemann, J.

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less
A comprehensive allometric analysis of 2nd digit length to 4th digit length in humans.

PubMed

Lolli, Lorenzo; Batterham, Alan M; Kratochvíl, Lukáš; Flegr, Jaroslav; Weston, Kathryn L; Atkinson, Greg

2017-06-28

It has been widely reported that men have a lower ratio of the 2nd and 4th human finger lengths (2D : 4D). Size-scaling ratios, however, have the seldom-appreciated potential for providing biased estimates. Using an information-theoretic approach, we compared 12 candidate models, with different assumptions and error structures, for scaling untransformed 2D to 4D lengths from 154 men and 262 women. In each hand, the two-parameter power function and the straight line with intercept models, both with normal, homoscedastic error, were superior to the other models and essentially equivalent to each other for normalizing 2D to 4D lengths. The conventional 2D : 4D ratio biased relative 2D length low for the generally bigger hands of men, and vice versa for women, thereby leading to an artefactual indication that mean relative 2D length is lower in men than women. Conversely, use of the more appropriate allometric or linear regression models revealed that mean relative 2D length was, in fact, greater in men than women. We conclude that 2D does not vary in direct proportion to 4D for both men and women, rendering the use of the simple 2D : 4D ratio inappropriate for size-scaling purposes and intergroup comparisons. © 2017 The Author(s).
Diffusion and scaling during early embryonic pattern formation.

PubMed

Gregor, Thomas; Bialek, William; de Ruyter van Steveninck, Rob R; Tank, David W; Wieschaus, Eric F

2005-12-20

Development of spatial patterns in multicellular organisms depends on gradients in the concentration of signaling molecules that control gene expression. In the Drosophila embryo, Bicoid (Bcd) morphogen controls cell fate along 70% of the anteroposterior axis but is translated from mRNA localized at the anterior pole. Gradients of Bcd and other morphogens are thought to arise through diffusion, but this basic assumption has never been rigorously tested in living embryos. Furthermore, because diffusion sets a relationship between length and time scales, it is hard to see how patterns of gene expression established by diffusion would scale proportionately as egg size changes during evolution. Here, we show that the motion of inert molecules through the embryo is well described by the diffusion equation on the relevant length and time scales, and that effective diffusion constants are essentially the same in closely related dipteran species with embryos of very different size. Nonetheless, patterns of gene expression in these different species scale with egg length. We show that this scaling can be traced back to scaling of the Bcd gradient itself. Our results, together with constraints imposed by the time scales of development, suggest that the mechanism for scaling is a species-specific adaptation of the Bcd lifetime.
Permeability from complex conductivity: an evaluation of polarization magnitude versus relaxation time based geophysical length scales

NASA Astrophysics Data System (ADS)

Slater, L. D.; Robinson, J.; Weller, A.; Keating, K.; Robinson, T.; Parker, B. L.

2017-12-01

Geophysical length scales determined from complex conductivity (CC) measurements can be used to estimate permeability k when the electrical formation factor F describing the ratio between tortuosity and porosity is known. Two geophysical length scales have been proposed: [1] the imaginary conductivity σ" normalized by the specific polarizability cp; [2] the time constant τ multiplied by a diffusion coefficient D+. The parameters cp and D+ account for the control of fluid chemistry and/or varying minerology on the geophysical length scale. We evaluated the predictive capability of two recently presented CC permeability models: [1] an empirical formulation based on σ"; [2] a mechanistic formulation based on τ;. The performance of the CC models was evaluated against measured permeability; this performance was also compared against that of well-established k estimation equations that use geometric length scales to represent the pore scale properties controlling fluid flow. Both CC models predict permeability within one order of magnitude for a database of 58 sandstone samples, with the exception of those samples characterized by high pore volume normalized surface area Spor and more complex mineralogy including significant dolomite. Variations in cp and D+ likely contribute to the poor performance of the models for these high Spor samples. The ultimate value of such geophysical models for permeability prediction lies in their application to field scale geophysical datasets. Two observations favor the implementation of the σ" based model over the τ based model for field-scale estimation: [1] the limited range of variation in cp relative to D+; [2] σ" is readily measured using field geophysical instrumentation (at a single frequency) whereas τ requires broadband spectral measurements that are extremely challenging and time consuming to accurately measure in the field. However, the need for a reliable estimate of F remains a major obstacle to the field-scale implementation of either of the CC permeability models for k estimation.

Seasonal and gender-related differences in morphometric features and cellular and biochemical parameters of Carcinus aestuarii from the Lagoon of Venice.

PubMed

Matozzo, Valerio; Boscolo, Alice; Marin, Maria Gabriella

2013-08-01

In this study, the seasonal variations in the morphometric features and in the cellular and biochemical parameters of the haemolymph were investigated in both male and female crabs (Carcinus aestuarii). Crabs were seasonally (November 2010-August 2011) collected from the Lagoon of Venice, and the moult stage, weight, width and length of the carapace, and width and length of the bigger chela were evaluated. In addition, the total haemocyte count (THC), haemocyte diameter and volume, haemolymph glucose and total protein levels, and haemolymph phenoloxidase (PO) and N-acetyl-β-glucosaminidase (NAG) activities were measured. The results demonstrated that the collected crabs were all in the intermoult stage and that the males were bigger than the females. A two-way ANOVA revealed a significant effect of season on the THC and the haemocyte volume and a significant influence of gender on the haemocyte diameter. Season and gender significantly affected the haemolymph glucose concentration, whereas haemolymph protein levels were dependent only on the season. In addition, both season and gender significantly influenced the PO and NAG activities in the haemolymph. Overall, the results demonstrated that crab morphometric features as well as haemolymph cellular and biochemical parameters varied markedly as a function of both season and gender. Copyright © 2013 Elsevier Ltd. All rights reserved.
Mid-tropospheric Spectral Length-scale Analysis of Many Constituents from Aircraft, Satellite and Model Results During the 2013 SENEX Field Study.

NASA Astrophysics Data System (ADS)

McKeen, S. A.; Angevine, W. M.; Ahmadov, R.; Frost, G. J.; Kim, S. W.; Cui, Y.; McDonald, B.; Trainer, M.; Holloway, J. S.; Ryerson, T. B.; Peischl, J.; Gambacorta, A.; Barnet, C. D.; Smith, N.; Pierce, R. B.

2016-12-01

This study presents preliminary comparisons of satellite, aircraft, and model variance spectra for meteorological, thermodynamic and gas-phase species collected during the 2013 Southeastern Nexus Air Quality Experiment (SENEX). Fourier analysis of 8 constituents collected at 1 Hz by the NOAA W-P3 aircraft in the 25 to 200 km length-scale range exhibit properties consistent with previous scale dependence studies: when spectra are averaged over several 500 mb flight legs, very linear dependence is found on log-log plots of spectral density versus inverse length-scale. Derived slopes for wind speed, temperature, H2O, CO, CO2, CH4, NOy and O3 all fall within ±30% and close to the slope of -5/3 predicted from dimensional scaling theory of isotropic turbulence. Qualitative differences are seen when a similar analysis, without quality control, is applied to a preliminary set of NUCAPS satellite retrievals over the continental U.S. during SENEX. While 500mb water vapor and column integrated water show slopes close to the -5/3 value in the 200 to 1000 km length-scale range, other quantities show significantly shallower slopes, suggesting the need for rigorous quality control. Results from WRF-Chem regional air quality model simulations at 500mb show the model is unable to account for variance on length-scales less than 6ΔX, where ΔX is the model horizontal resolution (12km). Comparisons with satellite data in the 200 to 1000km range show slopes consistent with the -5/3 power law for species such as CO, CH4 and CO2 that do not undergo reinitialization, suggesting potential for future application.
A tool for multi-scale modelling of the renal nephron

PubMed Central

Nickerson, David P.; Terkildsen, Jonna R.; Hamilton, Kirk L.; Hunter, Peter J.

2011-01-01

We present the development of a tool, which provides users with the ability to visualize and interact with a comprehensive description of a multi-scale model of the renal nephron. A one-dimensional anatomical model of the nephron has been created and is used for visualization and modelling of tubule transport in various nephron anatomical segments. Mathematical models of nephron segments are embedded in the one-dimensional model. At the cellular level, these segment models use models encoded in CellML to describe cellular and subcellular transport kinetics. A web-based presentation environment has been developed that allows the user to visualize and navigate through the multi-scale nephron model, including simulation results, at the different spatial scales encompassed by the model description. The Zinc extension to Firefox is used to provide an interactive three-dimensional view of the tubule model and the native Firefox rendering of scalable vector graphics is used to present schematic diagrams for cellular and subcellular scale models. The model viewer is embedded in a web page that dynamically presents content based on user input. For example, when viewing the whole nephron model, the user might be presented with information on the various embedded segment models as they select them in the three-dimensional model view. Alternatively, the user chooses to focus the model viewer on a cellular model located in a particular nephron segment in order to view the various membrane transport proteins. Selecting a specific protein may then present the user with a description of the mathematical model governing the behaviour of that protein—including the mathematical model itself and various simulation experiments used to validate the model against the literature. PMID:22670210
Explaining the length threshold of polyglutamine aggregation

NASA Astrophysics Data System (ADS)

De Los Rios, Paolo; Hafner, Marc; Pastore, Annalisa

2012-06-01

The existence of a length threshold, of about 35 residues, above which polyglutamine repeats can give rise to aggregation and to pathologies, is one of the hallmarks of polyglutamine neurodegenerative diseases such as Huntington’s disease. The reason why such a minimal length exists at all has remained one of the main open issues in research on the molecular origins of such classes of diseases. Following the seminal proposals of Perutz, most research has focused on the hunt for a special structure, attainable only above the minimal length, able to trigger aggregation. Such a structure has remained elusive and there is growing evidence that it might not exist at all. Here we review some basic polymer and statistical physics facts and show that the existence of a threshold is compatible with the modulation that the repeat length imposes on the association and dissociation rates of polyglutamine polypeptides to and from oligomers. In particular, their dramatically different functional dependence on the length rationalizes the very presence of a threshold and hints at the cellular processes that might be at play, in vivo, to prevent aggregation and the consequent onset of the disease.
Integrated Circuit-Based Biofabrication with Common Biomaterials for Probing Cellular Biomechanics.

PubMed

Sung, Chun-Yen; Yang, Chung-Yao; Yeh, J Andrew; Cheng, Chao-Min

2016-02-01

Recent advances in bioengineering have enabled the development of biomedical tools with modifiable surface features (small-scale architecture) to mimic extracellular matrices and aid in the development of well-controlled platforms that allow for the application of mechanical stimulation for studying cellular biomechanics. An overview of recent developments in common biomaterials that can be manufactured using integrated circuit-based biofabrication is presented. Integrated circuit-based biofabrication possesses advantages including mass and diverse production capacities for fabricating in vitro biomedical devices. This review highlights the use of common biomaterials that have been most frequently used to study cellular biomechanics. In addition, the influence of various small-scale characteristics on common biomaterial surfaces for a range of different cell types is discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.
Electron Profile Stiffness and Critical Gradient Length Studies in the Alcator C-Mod Tokamak

NASA Astrophysics Data System (ADS)

Houshmandyar, Saeid; Hatch, David R.; Liao, Kenneth T.; Zhao, Bingzhe; Phillips, Perry E.; Rowan, William L.; Cao, Norman; Ernst, Darin R.; Rice, John E.

2017-10-01

Electron temperature profile stiffness was investigated at Alcator C-Mod L-mode discharges. Electrons were heated by ion cyclotron range of frequencies (ICRF) through minority heating. The intent of the heating mechanism was to vary the heat flux and simultaneously, gradually change the local gradient. The electron temperature gradient scale length (LTe- 1 = | ∇Te |/Te) was accurately measured through a novel technique, using the high-resolution radiometer ECE diagnostic. The TRANSP power balance analysis (Q/QGB) and the measured scale length (a/LTe) result in critical scale length measurements at all major radius locations. These measurements suggest that the profiles are already at the critical values. Furthermore, the dependence of the stiffness on plasma rotation and magnetic shear will be discussed. In order to understand the underlying mechanism of turbulence for these discharges, simulations using the gyrokinetic code, GENE, were carried out. For linear runs at electron scales, it was found that the largest growth rates are very sensitive to a/LTe variation, which suggests the presence of ETG modes, while the sensitivity studies in the ion scales indicate ITG/TEM modes. Supported by USDoE awards DE-FG03-96ER54373 and DE-FC02-99ER54512.
The correlation function for density perturbations in an expanding universe. I - Linear theory

NASA Technical Reports Server (NTRS)

Mcclelland, J.; Silk, J.

1977-01-01

The evolution of the two-point correlation function for adiabatic density perturbations in the early universe is studied. Analytical solutions are obtained for the evolution of linearized spherically symmetric adiabatic density perturbations and the two-point correlation function for these perturbations in the radiation-dominated portion of the early universe. The results are then extended to the regime after decoupling. It is found that: (1) adiabatic spherically symmetric perturbations comparable in scale with the maximum Jeans length would survive the radiation-dominated regime; (2) irregular fluctuations are smoothed out up to the scale of the maximum Jeans length in the radiation era, but regular fluctuations might survive on smaller scales; (3) in general, the only surviving structures for irregularly shaped adiabatic density perturbations of arbitrary but finite scale in the radiation regime are the size of or larger than the maximum Jeans length in that regime; (4) infinite plane waves with a wavelength smaller than the maximum Jeans length but larger than the critical dissipative damping scale could survive the radiation regime; and (5) black holes would also survive the radiation regime and might accrete sufficient mass after decoupling to nucleate the formation of galaxies.
Connecting macroscopic dynamics with microscopic properties in active microtubule network contraction

NASA Astrophysics Data System (ADS)

Foster, Peter J.; Yan, Wen; Fürthauer, Sebastian; Shelley, Michael J.; Needleman, Daniel J.

2017-12-01

The cellular cytoskeleton is an active material, driven out of equilibrium by molecular motor proteins. It is not understood how the collective behaviors of cytoskeletal networks emerge from the properties of the network’s constituent motor proteins and filaments. Here we present experimental results on networks of stabilized microtubules in Xenopus oocyte extracts, which undergo spontaneous bulk contraction driven by the motor protein dynein, and investigate the effects of varying the initial microtubule density and length distribution. We find that networks contract to a similar final density, irrespective of the length of microtubules or their initial density, but that the contraction timescale varies with the average microtubule length. To gain insight into why this microscopic property influences the macroscopic network contraction time, we developed simulations where microtubules and motors are explicitly represented. The simulations qualitatively recapitulate the variation of contraction timescale with microtubule length, and allowed stress contributions from different sources to be estimated and decoupled.
A multi-resolution analysis of lidar-DTMs to identify geomorphic processes from characteristic topographic length scales

NASA Astrophysics Data System (ADS)

Sangireddy, H.; Passalacqua, P.; Stark, C. P.

2013-12-01

Characteristic length scales are often present in topography, and they reflect the driving geomorphic processes. The wide availability of high resolution lidar Digital Terrain Models (DTMs) allows us to measure such characteristic scales, but new methods of topographic analysis are needed in order to do so. Here, we explore how transitions in probability distributions (pdfs) of topographic variables such as (log(area/slope)), defined as topoindex by Beven and Kirkby[1979], can be measured by Multi-Resolution Analysis (MRA) of lidar DTMs [Stark and Stark, 2001; Sangireddy et al.,2012] and used to infer dominant geomorphic processes such as non-linear diffusion and critical shear. We show this correlation between dominant geomorphic processes to characteristic length scales by comparing results from a landscape evolution model to natural landscapes. The landscape evolution model MARSSIM Howard[1994] includes components for modeling rock weathering, mass wasting by non-linear creep, detachment-limited channel erosion, and bedload sediment transport. We use MARSSIM to simulate steady state landscapes for a range of hillslope diffusivity and critical shear stresses. Using the MRA approach, we estimate modal values and inter-quartile ranges of slope, curvature, and topoindex as a function of resolution. We also construct pdfs at each resolution and identify and extract characteristic scale breaks. Following the approach of Tucker et al.,[2001], we measure the average length to channel from ridges, within the GeoNet framework developed by Passalacqua et al.,[2010] and compute pdfs for hillslope lengths at each scale defined in the MRA. We compare the hillslope diffusivity used in MARSSIM against inter-quartile ranges of topoindex and hillslope length scales, and observe power law relationships between the compared variables for simulated landscapes at steady state. We plot similar measures for natural landscapes and are able to qualitatively infer the dominant geomorphic processes. Also, we explore the variability in hillslope length scales as a function of hillslope diffusivity coefficients and critical shear stress in natural landscapes and show that we can infer signatures of dominant geomorphic processes by analyzing characteristic topographic length scales present in topography. References: Beven, K. and Kirkby, M. J.: A physically based variable contributing area model of basin hydrology, Hydrol. Sci. Bull., 24, 43-69, 1979 Howard, A. D. (1994). A detachment-limited model of drainage basin evolution.Water resources research, 30(7), 2261-2285. Passalacqua, P., Do Trung, T., Foufoula Georgiou, E., Sapiro, G., & Dietrich, W. E. (2010). A geometric framework for channel network extraction from lidar: Nonlinear diffusion and geodesic paths. Journal of Geophysical. Research: Earth Surface (2003-2012), 115(F1). Sangireddy, H., Passalacqua, P., Stark, C.P.(2012). Multi-resolution estimation of lidar-DTM surface flow metrics to identify characteristic topographic length scales, EP13C-0859: AGU Fall meeting 2012. Stark, C. P., & Stark, G. J. (2001). A channelization model of landscape evolution. American Journal of Science, 301(4-5), 486-512. Tucker, G. E., Catani, F., Rinaldo, A., & Bras, R. L. (2001). Statistical analysis of drainage density from digital terrain data. Geomorphology, 36(3), 187-202.
Gorilla and Orangutan Brains Conform to the Primate Cellular Scaling Rules: Implications for Human Evolution

PubMed Central

Herculano-Houzel, Suzana; Kaas, Jon H.

2011-01-01

Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they apply to simians, great apes and modern humans alike), the Colobinae and Pongidae lineages favored marked increases in body size rather than brain size from the common ancestor with the Homo lineage, while the Homo lineage seems to have favored a large brain instead of a large body, possibly due to the metabolic limitations to having both. PMID:21228547
Gorilla and orangutan brains conform to the primate cellular scaling rules: implications for human evolution.

PubMed

Herculano-Houzel, Suzana; Kaas, Jon H

2011-01-01

Gorillas and orangutans are primates at least as large as humans, but their brains amount to about one third of the size of the human brain. This discrepancy has been used as evidence that the human brain is about 3 times larger than it should be for a primate species of its body size. In contrast to the view that the human brain is special in its size, we have suggested that it is the great apes that might have evolved bodies that are unusually large, on the basis of our recent finding that the cellular composition of the human brain matches that expected for a primate brain of its size, making the human brain a linearly scaled-up primate brain in its number of cells. To investigate whether the brain of great apes also conforms to the primate cellular scaling rules identified previously, we determine the numbers of neuronal and other cells that compose the orangutan and gorilla cerebella, use these numbers to calculate the size of the brain and of the cerebral cortex expected for these species, and show that these match the sizes described in the literature. Our results suggest that the brains of great apes also scale linearly in their numbers of neurons like other primate brains, including humans. The conformity of great apes and humans to the linear cellular scaling rules that apply to other primates that diverged earlier in primate evolution indicates that prehistoric Homo species as well as other hominins must have had brains that conformed to the same scaling rules, irrespective of their body size. We then used those scaling rules and published estimated brain volumes for various hominin species to predict the numbers of neurons that composed their brains. We predict that Homo heidelbergensis and Homo neanderthalensis had brains with approximately 80 billion neurons, within the range of variation found in modern Homo sapiens. We propose that while the cellular scaling rules that apply to the primate brain have remained stable in hominin evolution (since they apply to simians, great apes and modern humans alike), the Colobinae and Pongidae lineages favored marked increases in body size rather than brain size from the common ancestor with the Homo lineage, while the Homo lineage seems to have favored a large brain instead of a large body, possibly due to the metabolic limitations to having both. Copyright © 2011 S. Karger AG, Basel.
Rational Design of Semiconductor Nanostructures for Functional Subcellular Interfaces.

PubMed

Parameswaran, Ramya; Tian, Bozhi

2018-05-15

One of the fundamental questions guiding research in the biological sciences is how cellular systems process complex physical and environmental cues and communicate with each other across multiple length scales. Importantly, aberrant signal processing in these systems can lead to diseases that can have devastating impacts on human lives. Biophysical studies in the past several decades have demonstrated that cells can respond to not only biochemical cues but also mechanical and electrical ones. Thus, the development of new materials that can both sense and modulate all of these pathways is necessary. Semiconducting nanostructures are an emerging class of discovery platforms and tools that can push the limits of our ability to modulate and sense biological behaviors for both fundamental research and clinical applications. These materials are of particular interest for interfacing with cellular systems due to their matched dimension with subcellular components (e.g., cytoskeletal filaments), and easily tunable properties in the electrical, optical and mechanical regimes. Rational design via traditional or new approaches, such as nanocasting and mesoscale chemical lithography, can allow us to control micro- and nanoscale features in nanowires to achieve new biointerfaces. Both processes endogenous to the target cell and properties of the material surface dictate the character of these interfaces. In this Account, we focus on (1) approaches for the rational design of semiconducting nanowires that exhibit unique structures for biointerfaces, (2) recent fundamental discoveries that yield robust biointerfaces at the subcellular level, (3) intracellular electrical and mechanical sensing, and (4) modulation of cellular behaviors through material topography and remote physical stimuli. In the first section, we discuss new approaches for the synthetic control of micro- and nanoscale features of these materials. In the second section, we focus on achieving biointerfaces with these rationally designed materials either intra- or extracellularly. We last delve into the use of these materials in sensing mechanical forces and electrical signals in various cellular systems as well as in instructing cellular behaviors. Future research in this area may shift the paradigm in fundamental biophysical research and biomedical applications through (1) the design and synthesis of new semiconductor-based materials and devices that interact specifically with targeted cells, (2) the clarification of many developmental, physiological, and anatomical aspects of cellular communications, (3) an understanding of how signaling between cells regulates synaptic development (e.g., information like this would offer new insight into how the nervous system works and provide new targets for the treatment of neurological diseases), (4) and the creation of new cellular materials that have the potential to open up completely new areas of application, such as in hybrid information processing systems.
Detection of submicron scale cracks and other surface anomalies using positron emission tomography

DOEpatents

Cowan, Thomas E.; Howell, Richard H.; Colmenares, Carlos A.

2004-02-17

Detection of submicron scale cracks and other mechanical and chemical surface anomalies using PET. This surface technique has sufficient sensitivity to detect single voids or pits of sub-millimeter size and single cracks or fissures of millimeter size; and single cracks or fissures of millimeter-scale length, micrometer-scale depth, and nanometer-scale length, micrometer-scale depth, and nanometer-scale width. This technique can also be applied to detect surface regions of differing chemical reactivity. It may be utilized in a scanning or survey mode to simultaneously detect such mechanical or chemical features over large interior or exterior surface areas of parts as large as about 50 cm in diameter. The technique involves exposing a surface to short-lived radioactive gas for a time period, removing the excess gas to leave a partial monolayer, determining the location and shape of the cracks, voids, porous regions, etc., and calculating the width, depth, and length thereof. Detection of 0.01 mm deep cracks using a 3 mm detector resolution has been accomplished using this technique.
Computational Modeling of Fluctuations in Energy and Metabolic Pathways of Methanogenic Archaea

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

Luthey-Schulten, Zaida

The methanogenic archaea, anaerobic microbes that convert CO2 and H2 and/or other small organic fermentation products into methane, play an unusually large role in the global carbon cycle. As they perform the final step in the anaerobic breakdown of biomass, methanogens are a biogenic source of an estimated one billion tons methane each year. Depending on the location, produced methane can be considered as either a greenhouse gas (agricultural byproduct), sequestered carbon storage (methane hydrate deposits), or a potential energy source (organic wastewater treatment). These microbes therefore represent an important target for biotechnology applications. Computational models of methanogens with predictivemore » power are useful aids in the adaptation of methanogenic systems, but need to connect processes of wide-ranging time and length scales. In this project, we developed several computational methodologies for modeling the dynamic behavior of entire cells that connects stochastic reaction-diffusion dynamics of individual biochemical pathways with genome-scale modeling of metabolic networks. While each of these techniques were in the realm of well-defined computational methods, here we integrated them to develop several entirely new approaches to systems biology. The first scientific aim of the project was to model how noise in a biochemical pathway propagates into cellular phenotypes. Genetic circuits have been optimized by evolution to regulate molecular processes despite stochastic noise, but the effect of such noise on a cellular biochemical networks is currently unknown. An integrated stochastic/systems model of Escherichia coli species was created to analyze how noise in protein expression gives—and therefore noise in metabolic fluxes—gives rise to multiple cellular phenotype in isogenic population. After the initial work developing and validating methods that allow characterization of the heterogeneity in the model organism E. coli, the project shifted toward investigations of the methanogen Methanosarcina acetivorans. By integrating an unprecedented transcriptomics dataset for growth of the methanogen on many substrates with an in silico model, heterogeneity in metabolic pathway usage and methane production were examined. This lent insight into the physiological requirements of the organism under different environmental conditions and uncovered the unique regulatory role that mRNA half-life has in shaping metabolic flux distributions in this organism.« less
Multiple scales and phases in discrete chains with application to folded proteins

NASA Astrophysics Data System (ADS)

Sinelnikova, A.; Niemi, A. J.; Nilsson, Johan; Ulybyshev, M.

2018-05-01

Chiral heteropolymers such as large globular proteins can simultaneously support multiple length scales. The interplay between the different scales brings about conformational diversity, determines the phase properties of the polymer chain, and governs the structure of the energy landscape. Most importantly, multiple scales produce complex dynamics that enable proteins to sustain live matter. However, at the moment there is incomplete understanding of how to identify and distinguish the various scales that determine the structure and dynamics of a complex protein. Here we address this impending problem. We develop a methodology with the potential to systematically identify different length scales, in the general case of a linear polymer chain. For this we introduce and analyze the properties of an order parameter that can both reveal the presence of different length scales and can also probe the phase structure. We first develop our concepts in the case of chiral homopolymers. We introduce a variant of Kadanoff's block-spin transformation to coarse grain piecewise linear chains, such as the C α backbone of a protein. We derive analytically, and then verify numerically, a number of properties that the order parameter can display, in the case of a chiral polymer chain. In particular, we propose that in the case of a chiral heteropolymer the order parameter can reveal traits of several different phases, contingent on the length scale at which it is scrutinized. We confirm that this is the case with crystallographic protein structures in the Protein Data Bank. Thus our results suggest relations between the scales, the phases, and the complexity of folding pathways.
Fire Hazards from Combustible Ammunition, Methodology Development. Phase I

DTIC Science & Technology

1980-06-01

5.3 Flame Length , Flame Diameter and Mass Burning Rate 37 5.4 Flame Emissive Power 41 5.5 Fire Plume Axial Gas Velocity 41 5.6 Flame Temperature...B.2 Exit Velocity 93 B.3 Rate of Energy Flow 93 B.4 Chamber Characteristics 94 B.5 Flame Length 95 B.6 Flame Lift Angle 95 B.7 Summary 97...Viewing Flame in Test Series 5 17. Flame Length Scaling 18. Scaling Trends for Mass Burning Rate 19. Effective Flame Emissive Power versus Flame
Allometry of sexual size dimorphism in turtles: a comparison of mass and length data.

PubMed

Regis, Koy W; Meik, Jesse M

2017-01-01

The macroevolutionary pattern of Rensch's Rule (positive allometry of sexual size dimorphism) has had mixed support in turtles. Using the largest carapace length dataset and only large-scale body mass dataset assembled for this group, we determine (a) whether turtles conform to Rensch's Rule at the order, suborder, and family levels, and (b) whether inferences regarding allometry of sexual size dimorphism differ based on choice of body size metric used for analyses. We compiled databases of mean body mass and carapace length for males and females for as many populations and species of turtles as possible. We then determined scaling relationships between males and females for average body mass and straight carapace length using traditional and phylogenetic comparative methods. We also used regression analyses to evalutate sex-specific differences in the variance explained by carapace length on body mass. Using traditional (non-phylogenetic) analyses, body mass supports Rensch's Rule, whereas straight carapace length supports isometry. Using phylogenetic independent contrasts, both body mass and straight carapace length support Rensch's Rule with strong congruence between metrics. At the family level, support for Rensch's Rule is more frequent when mass is used and in phylogenetic comparative analyses. Turtles do not differ in slopes of sex-specific mass-to-length regressions and more variance in body size within each sex is explained by mass than by carapace length. Turtles display Rensch's Rule overall and within families of Cryptodires, but not within Pleurodire families. Mass and length are strongly congruent with respect to Rensch's Rule across turtles, and discrepancies are observed mostly at the family level (the level where Rensch's Rule is most often evaluated). At macroevolutionary scales, the purported advantages of length measurements over weight are not supported in turtles.
Image-Based Measurement of H2O2 Reaction-Diffusion in Wounded Zebrafish Larvae.

PubMed

Jelcic, Mark; Enyedi, Balázs; Xavier, João B; Niethammer, Philipp

2017-05-09

Epithelial injury induces rapid recruitment of antimicrobial leukocytes to the wound site. In zebrafish larvae, activation of the epithelial NADPH oxidase Duox at the wound margin is required early during this response. Before injury, leukocytes are near the vascular region, that is, ∼100-300 μm away from the injury site. How Duox establishes long-range signaling to leukocytes is unclear. We conceived that extracellular hydrogen peroxide (H 2 O 2 ) generated by Duox diffuses through the tissue to directly regulate chemotactic signaling in these cells. But before it can oxidize cellular proteins, H 2 O 2 must get past the antioxidant barriers that protect the cellular proteome. To test whether, or on which length scales this occurs during physiological wound signaling, we developed a computational method based on reaction-diffusion principles that infers H 2 O 2 degradation rates from intravital H 2 O 2 -biosensor imaging data. Our results indicate that at high tissue H 2 O 2 levels the peroxiredoxin-thioredoxin antioxidant chain becomes overwhelmed, and H 2 O 2 degradation stalls or ceases. Although the wound H 2 O 2 gradient reaches deep into the tissue, it likely overcomes antioxidant barriers only within ∼30 μm of the wound margin. Thus, Duox-mediated long-range signaling may require other spatial relay mechanisms besides extracellular H 2 O 2 diffusion. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Molecular simulation investigation of the nanorheology of an entangled polymer melt

NASA Astrophysics Data System (ADS)

Karim, Mir; Khare, Rajesh; Indei, Tsutomu; Schieber, Jay

2014-03-01

Knowledge of the ``local rheology'' is important for viscoelastic systems that contain significant structural and dynamic heterogeneities, such as cellular and extra-cellular crowded environments. For homogeneous viscoelastic media, a study of probe particle motion provides information on the microstructural evolution of the medium in response to the probe particle motion. Over the last two decades, probe particle rheology has emerged as a leading experimental technique for capturing local rheology of complex fluids. In recent work [M. Karim, S. C. Kohale, T. Indei, J. D. Schieber, and R. Khare, Phys. Rev. E86, 051501 (2012)], we showed that this approach can be used in molecular dynamics (MD) simulations to study the nanoscale viscoelastic properties of an unentangled polymer melt; an important conclusion of that work was that medium and particle inertia play a crucial role in analysis of the particle rheology simulation data. MD simulations have a natural advantage that they enable study of deformation and dynamics over a small length scale around the moving probe particle. In this work, the approach is extended to compare the motion of a nanoscale probe in melts of entangled and unentangled chains. The simulations will be used to elucidate the differences between the local responses of these media to the probe particle motion. In particular, results will be presented for the differences in the resultant velocity and stress fields as well as any possible structural asymmetry developed around the moving probe particle in the entangled and unentangled cases.
Carbon nanotubes' surface chemistry determines their potency as vaccine nanocarriers in vitro and in vivo

PubMed Central

Hassan, Hatem A.F.M.; Smyth, Lesley; Rubio, Noelia; Ratnasothy, Kulachelvy; Wang, Julie T.-W.; Bansal, Sukhvinder S.; Summers, Huw D.; Diebold, Sandra S.; Lombardi, Giovanna; Al-Jamal, Khuloud T.

2016-01-01

Carbon nanotubes (CNTs) have shown marked capabilities in enhancing antigen delivery to antigen presenting cells. However, proper understanding of how altering the physical properties of CNTs may influence antigen uptake by antigen presenting cells, such as dendritic cells (DCs), has not been established yet. We hypothesized that altering the physical properties of multi-walled CNTs (MWNTs)-antigen conjugates, e.g. length and surface charge, can affect the internalization of MWNT-antigen by DCs, hence the induced immune response potency. For this purpose, pristine MWNTs (p-MWNTs) were exposed to various chemical reactions to modify their physical properties then conjugated to ovalbumin (OVA), a model antigen. The yielded MWNTs-OVA conjugates were long MWNT-OVA (~ 386 nm), bearing net positive charge (5.8 mV), or short MWNTs-OVA (~ 122 nm) of increasing negative charges (− 23.4, − 35.8 or − 39 mV). Compared to the short MWNTs-OVA bearing high negative charges, short MWNT-OVA with the lowest negative charge demonstrated better cellular uptake and OVA-specific immune response both in vitro and in vivo. However, long positively-charged MWNT-OVA showed limited cellular uptake and OVA specific immune response in contrast to short MWNT-OVA displaying the least negative charge. We suggest that reduction in charge negativity of MWNT-antigen conjugate enhances cellular uptake and thus the elicited immune response intensity. Nevertheless, length of MWNT-antigen conjugate might also affect the cellular uptake and immune response potency; highlighting the importance of physical properties as a consideration in designing a MWNT-based vaccine delivery system. PMID:26802552

Growing Up Or Growing Old? Cellular Aging Linked With Testosterone Reactivity To Stress In Youth

PubMed Central

Drury, Stacy S.; Shirtcliff, Elizabeth A.; Shachet, Andrew; Phan, Jenny; Mabile, Emily; Brett, Zoë H.; Wren, Michael; Esteves, Kyle; Theall, Katherine P.

2014-01-01

Background Given the established relation between testosterone and aging in older adults, we tested whether buccal telomere length (TL), an established cellular biomarker of aging, was associated with testosterone levels in youth. Methods Children, mean age 10.2 years, were recruited from the greater New Orleans area and salivary testosterone was measured during both an acute stressor and diurnally. Buccal TL was measured using monochrome multiplex quantitative real-time PCR (MMQ-PCR). Testosterone and telomere length data was available on 77 individuals. The association between buccal TL and testosterone was tested using multivariate Generalized Estimating Equations (GEE) to account for clustering of children within families. Results Greater peak testosterone levels (β=-0.87, p < 0.01) and slower recovery (β=-0.56, p < 0.01) and reactivity (β = -1.22, p < 0.01) following a social stressor were significantly associated with shorter buccal TL after controlling for parental age at conception, child age, sex, sociodemographic factors and puberty. No association was initially present between diurnal measurements of testosterone or morning basal testosterone levels and buccal TL. Sex significantly moderated the relation between testosterone reactivity and buccal TL. Conclusions The association between testosterone and buccal TL supports gonadal maturation as a developmentally sensitive biomarker of aging within youth. As stress levels of testosterone were significantly associated with buccal TL, these findings are consistent with the growing literature linking stress exposure and accelerated maturation. The lack of association of diurnal testosterone or morning basal levels with buccal TL bolsters the notion of a shared stress-related maturational mechanism between cellular stress and the hypothalamic pituitary gonadal (HPG) axis. These data provide novel evidence supporting the interaction of aging, physiologic stress and cellular processes as an underlying mechanism linking negative health outcomes and early life stress. PMID:25010187
Understanding the Cellular Function of TRPV2 Channel through Generation of Specific Monoclonal Antibodies

PubMed Central

Cohen, Matthew R.; Huynh, Kevin W.; Cawley, Daniel; Moiseenkova-Bell, Vera Y.

2013-01-01

Transient receptor potential vanilloid 2 (TRPV2) is a Ca2+-permeable nonselective cation channel proposed to play a critical role in a wide array of cellular processes. Although TRPV2 surface expression was originally determined to be sensitive to growth factor signaling, regulated trafficking of TRPV2 has remained controversial. TRPV2 has proven difficult to study due to the lack of specific pharmacological tools to modulate channel activity; therefore, most studies of the cellular function of TRPV2 rely on immuno-detection techniques. Polyclonal antibodies against TRPV2 have not been properly validated and characterized, which may contribute to conflicting results regarding its function in the cell. Here, we developed monoclonal antibodies using full-length TRPV2 as an antigen. Extensive characterization of these antibodies and comparison to commonly used commercially available TRPV2 antibodies revealed that while monoclonal antibodies generated in our laboratory were suitable for detection of endogenous TRPV2 by western blot, immunoprecipitation and immunocytochemistry, the commercially available polyclonal antibodies we tested were not able to recognize endogenous TRPV2. We used our newly generated and validated TRPV2 antibodies to determine the effects of insulin-like growth factor 1 (IGF-1) on TRPV2 surface expression in heterologous and endogenous expression systems. We found that IGF-1 had little to no effect on trafficking and plasma membrane expression of TRPV2. Overall, these new TRPV2 monoclonal antibodies served to dispel the controversy of the effects of IGF-1 on TRPV2 plasma membrane expression and will clarify the role TRPV2 plays in cellular function. Furthermore, our strategy of using full-length tetrameric TRP channels may allow for the generation of antibodies against other TRP channels of unclear function. PMID:24392006
Understanding the cellular function of TRPV2 channel through generation of specific monoclonal antibodies.

PubMed

Cohen, Matthew R; Huynh, Kevin W; Cawley, Daniel; Moiseenkova-Bell, Vera Y

2013-01-01

Transient receptor potential vanilloid 2 (TRPV2) is a Ca(2+)-permeable nonselective cation channel proposed to play a critical role in a wide array of cellular processes. Although TRPV2 surface expression was originally determined to be sensitive to growth factor signaling, regulated trafficking of TRPV2 has remained controversial. TRPV2 has proven difficult to study due to the lack of specific pharmacological tools to modulate channel activity; therefore, most studies of the cellular function of TRPV2 rely on immuno-detection techniques. Polyclonal antibodies against TRPV2 have not been properly validated and characterized, which may contribute to conflicting results regarding its function in the cell. Here, we developed monoclonal antibodies using full-length TRPV2 as an antigen. Extensive characterization of these antibodies and comparison to commonly used commercially available TRPV2 antibodies revealed that while monoclonal antibodies generated in our laboratory were suitable for detection of endogenous TRPV2 by western blot, immunoprecipitation and immunocytochemistry, the commercially available polyclonal antibodies we tested were not able to recognize endogenous TRPV2. We used our newly generated and validated TRPV2 antibodies to determine the effects of insulin-like growth factor 1 (IGF-1) on TRPV2 surface expression in heterologous and endogenous expression systems. We found that IGF-1 had little to no effect on trafficking and plasma membrane expression of TRPV2. Overall, these new TRPV2 monoclonal antibodies served to dispel the controversy of the effects of IGF-1 on TRPV2 plasma membrane expression and will clarify the role TRPV2 plays in cellular function. Furthermore, our strategy of using full-length tetrameric TRP channels may allow for the generation of antibodies against other TRP channels of unclear function.
Mechanism for CCC DNA synthesis in hepadnaviruses.

PubMed

Sohn, Ji A; Litwin, Samuel; Seeger, Christoph

2009-11-30

Hepadnavirus replication requires the synthesis of a covalently closed circular (CCC) DNA from the relaxed circular (RC) viral genome by an unknown mechanism. CCC DNA formation could require enzymatic activities of the viral reverse transcriptase (RT), or cellular DNA repair enzymes, or both. Physical mapping of the 5' and 3' ends of RC DNA and sequence analysis of CCC DNA revealed that CCC DNA synthesis requires the removal of the RT and an RNA oligomer from the 5' ends of minus and plus strand DNA, respectively, removal of sequences from the terminally redundant minus strand, completion of the less than full-length plus strand, and ligation of the ends. Two models have been proposed that could explain CCC DNA formation. The first (model 1) invokes a role for the RT to catalyze a cleavage-ligation reaction leading to the formation of a unit length minus strand in CCC DNA and a DNA repair reaction for the completion and ligation of plus strand DNA; the second (model 2) predicts that CCC DNA formation depends entirely on cellular DNA repair enzymes. To determine which mechanism is utilized, we developed cell lines expressing duck hepatitis B virus genomes carrying mutations permitting us to follow the fate of viral DNA sequences during their conversion from RC to CCC DNA. Our results demonstrated that the oligomer at the 5' end of minus strand DNA is completely or at least partially removed prior to CCC DNA synthesis. The results indicated that both RC DNA strands undergo DNA repair reactions carried out by the cellular DNA repair machinery as predicted by model 2. Thus, our study provided the basis for the identification of the cellular components required for CCC DNA formation.
Microengineering of cellular interactions.

PubMed

Folch, A; Toner, M

2000-01-01

Tissue function is modulated by an intricate architecture of cells and biomolecules on a micrometer scale. Until now, in vitro cellular interactions were mainly studied by random seeding over homogeneous substrates. Although this strategy has led to important discoveries, it is clearly a nonoptimal analog of the in vivo scenario. With the incorporation--and adaptation--of microfabrication technology into biology, it is now possible to design surfaces that reproduce some of the aspects of that architecture. This article reviews past research on the engineering of cell-substrate, cell-cell, and cell-medium interactions on the micrometer scale.
VizieR Online Data Catalog: CALIFA galaxies observational hints (Ruiz-Lara+, 2017)

NASA Astrophysics Data System (ADS)

Ruiz-Lara, T.; Perez, I.; Florido, E.; Sanchez-Blazquez, P.; Mendez-Abreu, J.; Sanchez-Menguiano, L.; Sanchez, S. F.; Lyubenova, M.; Falcon-Barroso, J.; van de Ven, G.; Marino, R. A.; de Lorenzo-Caceres, A.; Catalan-Torrecilla, C.; Costantin, L.; Bland-Hawthorn, J.; Galbany, L.; Garcia-Benito, R.; Husemann, B.; Kehrig, C.; Marquez, I.; Mast, D.; Walcher, C. J.; Zibetti, S.; Ziegle, B.; Califa Team

2017-05-01

Characterisation of the sample of galaxies under analysis in the paper. The sample comprises 214 galaxies from the CALIFA survey. For each galaxy the name, equatorial coordinates, morphological type, presence of a bar, surface brightness profile type, inner disc scale length (kpc), outer disc scale length (kpc), and break radius in units of the inner disc scale length are given. Columns (1), (2), (3), and (4) from the CALIFA general sample characterisation (Walcher et al., 2014A&A...569A...1W). Columns (5), (6), (7), (8), (9), and (10) from the 2D decomposition performed in Mendez-Abreu et al. (2017, Cat. J/A+A/598/A32). (1 data file).
Toward power scaling in an acetylene mid-infrared hollow-core optical fiber gas laser: effects of pressure, fiber length, and pump power

NASA Astrophysics Data System (ADS)

Weerasinghe, H. W. Kushan; Dadashzadeh, Neda; Thirugnanasambandam, Manasadevi P.; Debord, Benoît.; Chafer, Matthieu; Gérôme, Frédéric; Benabid, Fetah; Corwin, Kristan L.; Washburn, Brian R.

2018-02-01

The effect of gas pressure, fiber length, and optical pump power on an acetylene mid-infrared hollow-core optical fiber gas laser (HOFGLAS) is experimentally determined in order to scale the laser to higher powers. The absorbed optical power and threshold power are measured for different pressures providing an optimum pressure for a given fiber length. We observe a linear dependence of both absorbed pump energy and lasing threshold for the acetylene HOFGLAS, while maintaining a good mode quality with an M-squared of 1.15. The threshold and mode behavior are encouraging for scaling to higher pressures and pump powers.
Infrared length scale and extrapolations for the no-core shell model

DOE PAGES

Wendt, K. A.; Forssén, C.; Papenbrock, T.; ...

2015-06-03

In this paper, we precisely determine the infrared (IR) length scale of the no-core shell model (NCSM). In the NCSM, the A-body Hilbert space is truncated by the total energy, and the IR length can be determined by equating the intrinsic kinetic energy of A nucleons in the NCSM space to that of A nucleons in a 3(A-1)-dimensional hyper-radial well with a Dirichlet boundary condition for the hyper radius. We demonstrate that this procedure indeed yields a very precise IR length by performing large-scale NCSM calculations for 6Li. We apply our result and perform accurate IR extrapolations for bound statesmore » of 4He, 6He, 6Li, and 7Li. Finally, we also attempt to extrapolate NCSM results for 10B and 16O with bare interactions from chiral effective field theory over tens of MeV.« less
Combined single crystal polarized XAFS and XRD at high pressure: probing the interplay between lattice distortions and electronic order at multiple length scales in high T c cuprates

DOE PAGES

Fabbris, G.; Hücker, M.; Gu, G. D.; ...

2016-07-14

Some of the most exotic material properties derive from electronic states with short correlation length (~10-500 Å), suggesting that the local structural symmetry may play a relevant role in their behavior. In this study, we discuss the combined use of polarized x-ray absorption fine structure and x-ray diffraction at high pressure as a powerful method to tune and probe structural and electronic orders at multiple length scales. Besides addressing some of the technical challenges associated with such experiments, we illustrate this approach with results obtained in the cuprate La 1.875Ba 0.125CuO 4, in which the response of electronic order tomore » pressure can only be understood by probing the structure at the relevant length scales.« less
Nano-scaled graphene platelets with a high length-to-width aspect ratio

DOEpatents

Zhamu, Aruna; Guo, Jiusheng; Jang, Bor Z.

2010-09-07

This invention provides a nano-scaled graphene platelet (NGP) having a thickness no greater than 100 nm and a length-to-width ratio no less than 3 (preferably greater than 10). The NGP with a high length-to-width ratio can be prepared by using a method comprising (a) intercalating a carbon fiber or graphite fiber with an intercalate to form an intercalated fiber; (b) exfoliating the intercalated fiber to obtain an exfoliated fiber comprising graphene sheets or flakes; and (c) separating the graphene sheets or flakes to obtain nano-scaled graphene platelets. The invention also provides a nanocomposite material comprising an NGP with a high length-to-width ratio. Such a nanocomposite can become electrically conductive with a small weight fraction of NGPs. Conductive composites are particularly useful for shielding of sensitive electronic equipment against electromagnetic interference (EMI) or radio frequency interference (RFI), and for electrostatic charge dissipation.
Real-time Visualization of Tissue Dynamics during Embryonic Development and Malignant Transformation

NASA Astrophysics Data System (ADS)

Yamada, Kenneth

Tissues undergo dramatic changes in organization during embryonic development, as well as during cancer progression and invasion. Recent advances in microscopy now allow us to visualize and track directly the dynamic movements of tissues, their constituent cells, and cellular substructures. This behavior can now be visualized not only in regular tissue culture on flat surfaces (`2D' environments), but also in a variety of 3D environments that may provide physiological cues relevant to understanding dynamics within living organisms. Acquisition of imaging data using various microscopy modalities will provide rich opportunities for determining the roles of physical factors and for computational modeling of complex processes in living tissues. Direct visualization of real-time motility is providing insight into biology spanning multiple spatio-temporal scales. Many cells in our body are known to be in contact with connective tissue and other forms of extracellular matrix. They do so through microscopic cellular adhesions that bind to matrix proteins. In particular, fluorescence microscopy has revealed that cells dynamically probe and bend the matrix at the sites of cell adhesions, and that 3D matrix architecture, stiffness, and elasticity can each regulate migration of the cells. Conversely, cells remodel their local matrix as organs form or tumors invade. Cancer cells can invade tissues using microscopic protrusions that degrade the surrounding matrix; in this case, the local matrix protein concentration is more important for inducing the micro-invasive protrusions than stiffness. On the length scales of tissues, transiently high rates of individual cell movement appear to help establish organ architecture. In fact, isolated cells can self-organize to form tissue structures. In all of these cases, in-depth real-time visualization will ultimately provide the extensive data needed for computer modeling and for testing hypotheses in which physical forces interact closely with cell signaling to form organs or promote tumor invasion.
Flow and diffusion in channel-guided cell migration.

PubMed

Marel, Anna-Kristina; Zorn, Matthias; Klingner, Christoph; Wedlich-Söldner, Roland; Frey, Erwin; Rädler, Joachim O

2014-09-02

Collective migration of mechanically coupled cell layers is a notable feature of wound healing, embryonic development, and cancer progression. In confluent epithelial sheets, the dynamics have been found to be highly heterogeneous, exhibiting spontaneous formation of swirls, long-range correlations, and glass-like dynamic arrest as a function of cell density. In contrast, the flow-like properties of one-sided cell-sheet expansion in confining geometries are not well understood. Here, we studied the short- and long-term flow of Madin-Darby canine kidney (MDCK) cells as they moved through microchannels. Using single-cell tracking and particle image velocimetry (PIV), we found that a defined averaged stationary cell current emerged that exhibited a velocity gradient in the direction of migration and a plug-flow-like profile across the advancing sheet. The observed flow velocity can be decomposed into a constant term of directed cell migration and a diffusion-like contribution that increases with density gradient. The diffusive component is consistent with the cell-density profile and front propagation speed predicted by the Fisher-Kolmogorov equation. To connect diffusion-mediated transport to underlying cellular motility, we studied single-cell trajectories and occurrence of vorticity. We discovered that the directed large-scale cell flow altered fluctuations in cellular motion at short length scales: vorticity maps showed a reduced frequency of swirl formation in channel flow compared with resting sheets of equal cell density. Furthermore, under flow, single-cell trajectories showed persistent long-range, random-walk behavior superimposed on drift, whereas cells in resting tissue did not show significant displacements with respect to neighboring cells. Our work thus suggests that active cell migration manifests itself in an underlying, spatially uniform drift as well as in randomized bursts of short-range correlated motion that lead to a diffusion-mediated transport. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.
Microstructural evolution during the homogenization heat treatment of 6XXX and 7XXX aluminum alloys

NASA Astrophysics Data System (ADS)

Priya, Pikee

Homogenization heat treatment of as-cast billets is an important step in the processing of aluminum extrusions. Microstructural evolution during homogenization involves elimination of the eutectic morphology by spheroidisation of the interdendritic phases, minimization of the microsegregation across the grains through diffusion, dissolution of the low-melting phases, which enhances the surface finish of the extrusions, and precipitation of nano-sized dispersoids (for Cr-, Zr-, Mn-, Sc-containing alloys), which inhibit grain boundary motion to prevent recrystallization. Post-homogenization cooling reprecipitates some of the phases, changing the flow stress required for subsequent extrusion. These precipitates, however, are deleterious for the mechanical properties of the alloy and also hamper the age-hardenability and are hence dissolved during solution heat treatment. Microstructural development during homogenization and subsequent cooling occurs both at the length scale of the Secondary Dendrite Arm Spacing (SDAS) in micrometers and dispersoids in nanometers. Numerical tools to simulate microstructural development at both the length scales have been developed and validated against experiments. These tools provide easy and convenient means to study the process. A Cellular Automaton-Finite Volume-based model for evolution of interdendritic phases is coupled with a Particle Size Distribution-based model for precipitation of dispersoids across the grain. This comprehensive model has been used to study the effect of temperature, composition, as-cast microstructure, and cooling rates during post-homogenization quenching on microstructural evolution. The numerical study has been complimented with experiments involving Scanning Electron Microscopy, Energy Dispersive Spectroscopy, X-Ray Diffraction and Differential Scanning Calorimetry and a good agreement has with numerical results has been found. The current work aims to study the microstructural evolution during homogenization heat treatment at both length scales which include the (i) dissolution and transformation of the as-cast secondary phases; (ii) precipitation of dispersoids; and (iii) reprecipitation of some of the secondary phases during post-homogenization cooling. The kinetics of the phase transformations are mostly diffusion controlled except for the eta to S phase transformation in 7XXX alloys which is interface reaction rate controlled which has been implemented using a novel approach. Recommendations for homogenization temperature, time, cooling rates and compositions are made for Al-Si-Mg-Fe-Mn and Al-Zn-Cu-Mg-Zr alloys. The numerical model developed has been applied for a through process solidification-homogenization modeling of a Direct-Chill cast AA7050 cylindrical billet to study the radial variation of microstructure after solidification, homogenization and post-homogenization cooling.
Multiresolution analysis of characteristic length scales with high-resolution topographic data

NASA Astrophysics Data System (ADS)

Sangireddy, Harish; Stark, Colin P.; Passalacqua, Paola

2017-07-01

Characteristic length scales (CLS) define landscape structure and delimit geomorphic processes. Here we use multiresolution analysis (MRA) to estimate such scales from high-resolution topographic data. MRA employs progressive terrain defocusing, via convolution of the terrain data with Gaussian kernels of increasing standard deviation, and calculation at each smoothing resolution of (i) the probability distributions of curvature and topographic index (defined as the ratio of slope to area in log scale) and (ii) characteristic spatial patterns of divergent and convergent topography identified by analyzing the curvature of the terrain. The MRA is first explored using synthetic 1-D and 2-D signals whose CLS are known. It is then validated against a set of MARSSIM (a landscape evolution model) steady state landscapes whose CLS were tuned by varying hillslope diffusivity and simulated noise amplitude. The known CLS match the scales at which the distributions of topographic index and curvature show scaling breaks, indicating that the MRA can identify CLS in landscapes based on the scaling behavior of topographic attributes. Finally, the MRA is deployed to measure the CLS of five natural landscapes using meter resolution digital terrain model data. CLS are inferred from the scaling breaks of the topographic index and curvature distributions and equated with (i) small-scale roughness features and (ii) the hillslope length scale.
Length scales involved in decoherence of trapped bosons by buffer-gas scattering

NASA Astrophysics Data System (ADS)

Gilz, Lukas; Rico-Pérez, Luis; Anglin, James R.

2014-05-01

We ask and answer a basic question about the length scales involved in quantum decoherence: how far apart in space do two parts of a quantum system have to be before a common quantum environment decoheres them as if they were entirely separate? We frame this question specifically in a cold atom context. How far apart do two populations of bosons have to be before an environment of thermal atoms of a different species ("buffer gas") responds to their two particle numbers separately? An initial guess for this length scale is the thermal coherence length of the buffer gas; we show that a standard Born-Markov treatment partially supports this guess, but predicts only inverse-square saturation of decoherence rates with distance, and not the much more abrupt Gaussian behavior of the buffer gas's first-order coherence. We confirm this Born-Markov result with a more rigorous theory, based on an exact solution of a two-scatterer scattering problem, which also extends the result beyond weak scattering. Finally, however, we show that when interactions within the buffer-gas reservoir are taken into account, an abrupt saturation of the decoherence rate does occur, exponentially on the length scale of the buffer gas's mean free path.
The scaling structure of the global road network

PubMed Central

Giometto, Andrea; Shai, Saray; Bertuzzo, Enrico; Mucha, Peter J.; Rinaldo, Andrea

2017-01-01

Because of increasing global urbanization and its immediate consequences, including changes in patterns of food demand, circulation and land use, the next century will witness a major increase in the extent of paved roads built worldwide. To model the effects of this increase, it is crucial to understand whether possible self-organized patterns are inherent in the global road network structure. Here, we use the largest updated database comprising all major roads on the Earth, together with global urban and cropland inventories, to suggest that road length distributions within croplands are indistinguishable from urban ones, once rescaled to account for the difference in mean road length. Such similarity extends to road length distributions within urban or agricultural domains of a given area. We find two distinct regimes for the scaling of the mean road length with the associated area, holding in general at small and at large values of the latter. In suitably large urban and cropland domains, we find that mean and total road lengths increase linearly with their domain area, differently from earlier suggestions. Scaling regimes suggest that simple and universal mechanisms regulate urban and cropland road expansion at the global scale. As such, our findings bear implications for global road infrastructure growth based on land-use change and for planning policies sustaining urban expansions. PMID:29134071
The scaling structure of the global road network.

PubMed

Strano, Emanuele; Giometto, Andrea; Shai, Saray; Bertuzzo, Enrico; Mucha, Peter J; Rinaldo, Andrea

2017-10-01

Because of increasing global urbanization and its immediate consequences, including changes in patterns of food demand, circulation and land use, the next century will witness a major increase in the extent of paved roads built worldwide. To model the effects of this increase, it is crucial to understand whether possible self-organized patterns are inherent in the global road network structure. Here, we use the largest updated database comprising all major roads on the Earth, together with global urban and cropland inventories, to suggest that road length distributions within croplands are indistinguishable from urban ones, once rescaled to account for the difference in mean road length. Such similarity extends to road length distributions within urban or agricultural domains of a given area. We find two distinct regimes for the scaling of the mean road length with the associated area, holding in general at small and at large values of the latter. In suitably large urban and cropland domains, we find that mean and total road lengths increase linearly with their domain area, differently from earlier suggestions. Scaling regimes suggest that simple and universal mechanisms regulate urban and cropland road expansion at the global scale. As such, our findings bear implications for global road infrastructure growth based on land-use change and for planning policies sustaining urban expansions.
Diffusion-limited mixing by incompressible flows

NASA Astrophysics Data System (ADS)

Miles, Christopher J.; Doering, Charles R.

2018-05-01

Incompressible flows can be effective mixers by appropriately advecting a passive tracer to produce small filamentation length scales. In addition, diffusion is generally perceived as beneficial to mixing due to its ability to homogenize a passive tracer. However we provide numerical evidence that, in cases where advection and diffusion are both actively present, diffusion may produce negative effects by limiting the mixing effectiveness of incompressible optimal flows. This limitation appears to be due to the presence of a limiting length scale given by a generalised Batchelor length (Batchelor 1959 J. Fluid Mech. 5 113–33). This length scale limitation may in turn affect long-term mixing rates. More specifically, we consider local-in-time flow optimisation under energy and enstrophy flow constraints with the objective of maximising the mixing rate. We observe that, for enstrophy-bounded optimal flows, the strength of diffusion may not impact the long-term mixing rate. For energy-constrained optimal flows, however, an increase in the strength of diffusion can decrease the mixing rate. We provide analytical lower bounds on mixing rates and length scales achievable under related constraints (point-wise bounded speed and rate-of-strain) by extending the work of Lin et al (2011 J. Fluid Mech. 675 465–76) and Poon (1996 Commun. PDE 21 521–39).
Multi-window PIV measurements around a breathing manikin

NASA Astrophysics Data System (ADS)

Marr, David

2005-11-01

The presented work includes multi-scale measurements via a stereo article Image Velocimetry (PIV) system to view a pair of two-component windows of dissimilar scale using a varied focal length. These measurements are taken in the breathing zone of an isothermal breathing manikin (from mouth) in an environmental chamber of average office cubicle dimensions without ventilation and are analogous to an oscillatory jet. From these phase-averaged measurements, we can extract information concerning length scales, turbulence quantities and low dimensional information in order to both determine correlation between data at different length scales as well as continuing research in exposure assessment for the indoor environment. In this talk we will present these turbulence quantities and interpret their influence on the breathing zone. While the largest scale is that of the room itself, we find that the relevant spatial scales associated with the breathing zone are much lower in magnitude. In future experiments, we will expand the multi window PIV technique to include PIV window configured to obtain scales of order the cubicle simultaneously with those of the breathing zone. This will aid in our understanding of the combined impact of these multiple scales on occupant exposure in the indoor environment.
Bridging the Gap Between Large-scale Data Sets and Analyses: Semi-automated Methods to Facilitate Length Polymorphism Scoring and Data Analyses.

EPA Science Inventory

Amplified fragment length polymorphism (AFLP) markers can be developed more quickly and at a lower cost than microsatellite and single nucleotide polymorphism markers, which makes them ideal markers for large-scale studies of understudied taxa — such as species at risk. However,...

Temporal length-scale cascade and expansion rate on planar liquid jet instability

NASA Astrophysics Data System (ADS)

Sirignano, William; Zandian, Arash; Hussain, Fazle

2016-11-01

Using the local radius of curvature of the surface and the local transverse dimension of the two-phase (i.e., spray) domain as length scales, we obtained two PDFs over a wide range of length-scales at different times and for different Reynolds and Weber (We) numbers. The PDFs were developed via post-processing of DNS Navier-Stokes results for a 3D planar liquid sheet segment with level-set and Volume-of-Fluid surface tracking, giving better statistical data for the length scales compared to the former methods. The radius PDF shows that, with increasing We , the average radius of curvature decreases, number of small droplets increases, and cascade occurs at a faster rate. In time, the mean of the radius PDF decreases while the rms increases. The other PDF represents the spray expansion in a more realistic and meaningful form, showing that the spray angle is larger at higher We and density-ratios. Both the mean and the rms of the spray-size PDF increase with time. The PDFs also track the transitions between symmetric and anti-symmetric modes.
Entropically Stabilized Colloidal Crystals Hold Entropy in Collective Modes

NASA Astrophysics Data System (ADS)

Antonaglia, James; van Anders, Greg; Glotzer, Sharon

Ordered structures can be stabilized by entropy if the system has more ordered microstates available than disordered ones. However, ``locating'' the entropy in an ordered system is challenging because entropic ordering is necessarily a collective effort emerging from the interactions of large numbers of particles. Yet, we can characterize these crystals using simple traditional tools, because entropically stabilized crystals exhibit collective motion and effective stiffness. For a two-dimensional system of hard hexagons, we calculate the dispersion relations of both vibrational and librational collective modes. We find the librational mode is gapped, and the gap provides an emergent, macroscopic, and density-dependent length scale. We quantify the entropic contribution of each collective mode and find that below this length scale, the dominant entropic contributions are librational, and above this length scale, vibrations dominate. This length scale diverges in the high-density limit, so entropy is found predominantly in libration near dense packing. National Science Foundation Graduate Research Fellowship Program Grant No. DGE 1256260, Advanced Research Computing at the University of Michigan, Ann Arbor, and the Simons Foundation.
Flow field topology of transient mixing driven by buoyancy

NASA Technical Reports Server (NTRS)

Duval, Walter M B.

2004-01-01

Transient mixing driven by buoyancy occurs through the birth of a symmetric Rayleigh-Taylor morphology (RTM) structure for large length scales. Beyond its critical bifurcation the RTM structure exhibits self-similarity and occurs on smaller and smaller length scales. The dynamics of the RTM structure, its nonlinear growth and internal collision, show that its genesis occurs from an explosive bifurcation which leads to the overlap of resonance regions in phase space. This event shows the coexistence of regular and chaotic regions in phase space which is corroborated with the existence of horseshoe maps. A measure of local chaos given by the topological entropy indicates that as the system evolves there is growth of uncertainty. Breakdown of the dissipative RTM structure occurs during the transition from explosive to catastrophic bifurcation; this event gives rise to annihilation of the separatrices which drives overlap of resonance regions. The global bifurcation of explosive and catastrophic events in phase space for the large length scale of the RTM structure serves as a template for which mixing occurs on smaller and smaller length scales. Copyright 2004 American Institute of Physics.
Accurate atomistic potentials and training sets for boron-nitride nanostructures

NASA Astrophysics Data System (ADS)

Tamblyn, Isaac

Boron nitride nanotubes exhibit exceptional structural, mechanical, and thermal properties. They are optically transparent and have high thermal stability, suggesting a wide range of opportunities for structural reinforcement of materials. Modeling can play an important role in determining the optimal approach to integrating nanotubes into a supporting matrix. Developing accurate, atomistic scale models of such nanoscale interfaces embedded within composites is challenging, however, due to the mismatch of length scales involved. Typical nanotube diameters range from 5-50 nm, with a length as large as a micron (i.e. a relevant length-scale for structural reinforcement). Unlike their carbon-based counterparts, well tested and transferable interatomic force fields are not common for BNNT. In light of this, we have developed an extensive training database of BN rich materials, under conditions relevant for BNNT synthesis and composites based on extensive first principles molecular dynamics simulations. Using this data, we have produced an artificial neural network potential capable of reproducing the accuracy of first principles data at significantly reduced computational cost, allowing for accurate simulation at the much larger length scales needed for composite design.
Critical behavior of the order-disorder phase transition in β -brass investigated by x-ray scattering

NASA Astrophysics Data System (ADS)

Madsen, A.; Als-Nielsen, J.; Hallmann, J.; Roth, T.; Lu, W.

2016-07-01

β -brass exhibits an archetypical example of an order-disorder transition with a critical behavior that was previously investigated by neutron scattering. The data were well described by the three-dimensional (3d) Ising model but the relatively crude experimental resolution prevented an in-depth examination of the single-length scaling hypothesis, a cornerstone in the theory of critical phenomena. With the development of synchrotron x-ray experiments, high-resolution data could be recorded and surprisingly it was found that the single-length scaling did not hold in most critical systems, possibly due to strain originating from surface defects and/or impurities. In this paper we demonstrate single-length critical behavior using high-resolution x-ray scattering in β -brass. The investigations confirm that β -brass behaves like a 3d Ising system over a wide range of length scales comprising correlated clusters of millions of atoms. To vary the surface sensitivity, experiments have been performed both in Bragg reflection and Laue transmission geometries but without any substantial differences observed in the scaling and critical behavior.
A rational approach to the use of Prandtl's mixing length model in free turbulent shear flow calculations

NASA Technical Reports Server (NTRS)

Rudy, D. H.; Bushnell, D. M.

1973-01-01

Prandtl's basic mixing length model was used to compute 22 test cases on free turbulent shear flows. The calculations employed appropriate algebraic length scale equations and single values of mixing length constant for planar and axisymmetric flows, respectively. Good agreement with data was obtained except for flows, such as supersonic free shear layers, where large sustained sensitivity changes occur. The inability to predict the more gradual mixing in these flows is tentatively ascribed to the presence of a significant turbulence-induced transverse static pressure gradient which is neglected in conventional solution procedures. Some type of an equation for length scale development was found to be necessary for successful computation of highly nonsimilar flow regions such as jet or wake development from thick wall flows.
The Electrostatic Screening Length in Concentrated Electrolytes Increases with Concentration.

PubMed

Smith, Alexander M; Lee, Alpha A; Perkin, Susan

2016-06-16

According to classical electrolyte theories interactions in dilute (low ion density) electrolytes decay exponentially with distance, with the Debye screening length the characteristic length scale. This decay length decreases monotonically with increasing ion concentration due to effective screening of charges over short distances. Thus, within the Debye model no long-range forces are expected in concentrated electrolytes. Here we reveal, using experimental detection of the interaction between two planar charged surfaces across a wide range of electrolytes, that beyond the dilute (Debye-Hückel) regime the screening length increases with increasing concentration. The screening lengths for all electrolytes studied-including aqueous NaCl solutions, ionic liquids diluted with propylene carbonate, and pure ionic liquids-collapse onto a single curve when scaled by the dielectric constant. This nonmonotonic variation of the screening length with concentration, and its generality across ionic liquids and aqueous salt solutions, demonstrates an important characteristic of concentrated electrolytes of substantial relevance from biology to energy storage.
Length scale hierarchy and spatiotemporal change of alluvial morphologies over the Selenga River delta, Russia

NASA Astrophysics Data System (ADS)

Dong, T. Y.; Nittrouer, J.; McElroy, B. J.; Ma, H.; Czapiga, M. J.; Il'icheva, E.; Pavlov, M.; Parker, G.

2017-12-01

The movement of water and sediment in natural channels creates various types of alluvial morphologies that span length scales from dunes to deltas. The behavior of these morphologies is controlled microscopically by hydrodynamic conditions and bed material size, and macroscopically by hydrologic and geological settings. Alluvial morphologies can be modeled as either diffusive or kinematic waves, in accordance with their respective boundary conditions. Recently, it has been shown that the difference between these two dynamic behaviors of alluvial morphologies can be characterized by the backwater number, which is a dimensionless value normalizing the length scale of a morphological feature to its local hydrodynamic condition. Application of the backwater number has proven useful for evaluating the size of morphologies, including deltas (e.g., by assessing the preferential avulsion location of a lobe), and for comparing bedform types across different fluvial systems. Yet two critical questions emerge when applying the backwater number: First, how do different types of alluvial morphologies compare within a single deltaic system, where there is a hydrodynamic transition from uniform to non-uniform flow? Second, how do different types of morphologies evolve temporally within a system as a function of changing water discharge? This study addresses these questions by compiling and analyzing field data from the Selenga River delta, Russia, which include measurements of flow velocity, channel geometry, bed material grain size, and channel slope, as well as length scales of various morphologies, including dunes, island bars, meanders, bifurcations, and delta lobes. Data analyses reveal that the length scale of morphologies decrease and the backwater number increases as flow transitions from uniform to non-uniform conditions progressing downstream. It is shown that the evaluated length scale hierarchy and planform distribution of different morphologies can be used to estimate slope, shear velocity and sediment flux within this depositional system. The findings from this research can be applied to evaluate spatially and temporally varying morphodynamic conditions, based on structures measured from both modern systems and ancient sedimentary records.
Measurement of Two-Plasmon-Decay Dependence on Plasma Density Scale Length

NASA Astrophysics Data System (ADS)

Haberberger, D.

2013-10-01

An accurate understanding of the plasma scale-length (Lq) conditions near quarter-critical density is important in quantifying the hot electrons generated by the two-plasmon-decay (TPD) instability in long-scale-length plasmas. A novel target platform was developed to vary the density scale length and an innovative diagnostic was implemented to measure the density profiles above 1021 cm-3 where TPD is expected to have the largest growth. A series of experiments was performed using the four UV (351-nm) beams on OMEGA EP that varied the Lq by changing the radius of curvature of the target while maintaining a constant Iq/Tq. The fraction of laser energy converted to hot electrons (fhot) was observed to increase rapidly from 0.005% to 1% by increasing the plasma scale length from 130 μm to 300 μm, corresponding to target diameters of 0.4 mm to 8 mm. A new diagnostic was developed based on refractometry using angular spectral filters to overcome the large phase accumulation in standard interferometric techniques. The angular filter refractometer measures the refraction angles of a 10-ps, 263-nm probe laser after propagating through the plasma. An angular spectral filter is used in the Fourier plane of the probe beam, where the refractive angles of the rays are mapped to space. The edges of the filter are present in the image plane and represent contours of constant refraction angle. These contours are used to infer the phase of the probe beam, which are used to calculate the plasma density profile. In long-scale-length plasmas, the diagnostic currently measures plasma densities from ~1019 cm-3 to ~2 × 1021 cm-3. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944. In collaboration with D. H. Edgell, S. X. Hu, S. Ivancic, R. Boni, C. Dorrer, and D. H. Froula (Laboratory for Laser Energetics, U. of Rochester).
The accuracy of climate models' simulated season lengths and the effectiveness of grid scale correction factors

DOE PAGES

Winterhalter, Wade E.

2011-09-01

Global climate change is expected to impact biological populations through a variety of mechanisms including increases in the length of their growing season. Climate models are useful tools for predicting how season length might change in the future. However, the accuracy of these models tends to be rather low at regional geographic scales. Here, I determined the ability of several atmosphere and ocean general circulating models (AOGCMs) to accurately simulate historical season lengths for a temperate ectotherm across the continental United States. I also evaluated the effectiveness of regional-scale correction factors to improve the accuracy of these models. I foundmore » that both the accuracy of simulated season lengths and the effectiveness of the correction factors to improve the model's accuracy varied geographically and across models. These results suggest that regional specific correction factors do not always adequately remove potential discrepancies between simulated and historically observed environmental parameters. As such, an explicit evaluation of the correction factors' effectiveness should be included in future studies of global climate change's impact on biological populations.« less
Modeling Near-Crack-Tip Plasticity from Nano- to Micro-Scales

NASA Technical Reports Server (NTRS)

Glaessgen, Edward H.; Saether, Erik; Hochhalter, Jake D.; Yamakov, Vesselin I.

2010-01-01

Several efforts that are aimed at understanding the plastic deformation mechanisms related to crack propagation at the nano-, meso- and micro-length scales including atomistic simulation, discrete dislocation plasticity, strain gradient plasticity and crystal plasticity are discussed. The paper focuses on discussion of newly developed methodologies and their application to understanding damage processes in aluminum and its alloys. Examination of plastic mechanisms as a function of increasing length scale illustrates increasingly complex phenomena governing plasticity
Chondrocyte Deformations as a Function of Tibiofemoral Joint Loading Predicted by a Generalized High-Throughput Pipeline of Multi-Scale Simulations

PubMed Central

Sibole, Scott C.; Erdemir, Ahmet

2012-01-01

Cells of the musculoskeletal system are known to respond to mechanical loading and chondrocytes within the cartilage are not an exception. However, understanding how joint level loads relate to cell level deformations, e.g. in the cartilage, is not a straightforward task. In this study, a multi-scale analysis pipeline was implemented to post-process the results of a macro-scale finite element (FE) tibiofemoral joint model to provide joint mechanics based displacement boundary conditions to micro-scale cellular FE models of the cartilage, for the purpose of characterizing chondrocyte deformations in relation to tibiofemoral joint loading. It was possible to identify the load distribution within the knee among its tissue structures and ultimately within the cartilage among its extracellular matrix, pericellular environment and resident chondrocytes. Various cellular deformation metrics (aspect ratio change, volumetric strain, cellular effective strain and maximum shear strain) were calculated. To illustrate further utility of this multi-scale modeling pipeline, two micro-scale cartilage constructs were considered: an idealized single cell at the centroid of a 100×100×100 μm block commonly used in past research studies, and an anatomically based (11 cell model of the same volume) representation of the middle zone of tibiofemoral cartilage. In both cases, chondrocytes experienced amplified deformations compared to those at the macro-scale, predicted by simulating one body weight compressive loading on the tibiofemoral joint. In the 11 cell case, all cells experienced less deformation than the single cell case, and also exhibited a larger variance in deformation compared to other cells residing in the same block. The coupling method proved to be highly scalable due to micro-scale model independence that allowed for exploitation of distributed memory computing architecture. The method’s generalized nature also allows for substitution of any macro-scale and/or micro-scale model providing application for other multi-scale continuum mechanics problems. PMID:22649535
Thermosolutal convection during cellular arrayed growth of Pb-Sn alloys

NASA Technical Reports Server (NTRS)

Tewari, S. N.; Shah, Rajesh; Chopra, M. A.

1993-01-01

Thermosolutal convection caused by the solute build up ahead of the growing arrays of cells and dendrites results in macrosegregation along the length of the Pb-Sn alloy (10 to 58 wt pct Sn) specimens when they are directionally solidified in a positive thermal gradient (melt on top, solid below, and gravity pointing down). At a constant thermal gradient, the extent of macrosegregation increases with decreasing growth speed as the microstructure changes from dendritic, to cellular and to planar. An empirical parameter, effective partition coefficient, obtained from the dependence of the longitudinal macrosegregation on fraction distance solidified can be used to represent the extent of macrosegregation.
A cellular automata approach to estimate incident-related travel time on Interstate 66 in near real time : final contract report.

DOT National Transportation Integrated Search

2010-03-01

Incidents account for a large portion of all congestion and a need clearly exists for tools to predict and estimate incident effects. This study examined (1) congestion back propagation to estimate the length of the queue and travel time from upstrea...
Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

DTIC Science & Technology

2010-09-01

quantitative PCR (10) or with a chemiluminescent-based slot blot assay that measures telomere DNA content, a proxy of telomere length (9, 11, 12). These...Subhawong AP, Subhawong T, Nassar H, et al. Most basal-like breast carcinomas demonstrate the same Rb-/p16+ immunophenotype as the HPV -related poorly
Actin kinetics shapes cortical network structure and mechanics

PubMed Central

Fritzsche, Marco; Erlenkämper, Christoph; Moeendarbary, Emad; Charras, Guillaume; Kruse, Karsten

2016-01-01

The actin cortex of animal cells is the main determinant of cellular mechanics. The continuous turnover of cortical actin filaments enables cells to quickly respond to stimuli. Recent work has shown that most of the cortical actin is generated by only two actin nucleators, the Arp2/3 complex and the formin Diaph1. However, our understanding of their interplay, their kinetics, and the length distribution of the filaments that they nucleate within living cells is poor. Such knowledge is necessary for a thorough comprehension of cellular processes and cell mechanics from basic polymer physics principles. We determined cortical assembly rates in living cells by using single-molecule fluorescence imaging in combination with stochastic simulations. We find that formin-nucleated filaments are, on average, 10 times longer than Arp2/3-nucleated filaments. Although formin-generated filaments represent less than 10% of all actin filaments, mechanical measurements indicate that they are important determinants of cortical elasticity. Tuning the activity of actin nucleators to alter filament length distribution may thus be a mechanism allowing cells to adjust their macroscopic mechanical properties to their physiological needs. PMID:27152338
Actin kinetics shapes cortical network structure and mechanics.

PubMed

Fritzsche, Marco; Erlenkämper, Christoph; Moeendarbary, Emad; Charras, Guillaume; Kruse, Karsten

2016-04-01

The actin cortex of animal cells is the main determinant of cellular mechanics. The continuous turnover of cortical actin filaments enables cells to quickly respond to stimuli. Recent work has shown that most of the cortical actin is generated by only two actin nucleators, the Arp2/3 complex and the formin Diaph1. However, our understanding of their interplay, their kinetics, and the length distribution of the filaments that they nucleate within living cells is poor. Such knowledge is necessary for a thorough comprehension of cellular processes and cell mechanics from basic polymer physics principles. We determined cortical assembly rates in living cells by using single-molecule fluorescence imaging in combination with stochastic simulations. We find that formin-nucleated filaments are, on average, 10 times longer than Arp2/3-nucleated filaments. Although formin-generated filaments represent less than 10% of all actin filaments, mechanical measurements indicate that they are important determinants of cortical elasticity. Tuning the activity of actin nucleators to alter filament length distribution may thus be a mechanism allowing cells to adjust their macroscopic mechanical properties to their physiological needs.
Efficient and Extensible Quasi-Explicit Modular Nonlinear Multiscale Battery Model: GH-MSMD

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

Kim, Gi-Heon; Smith, Kandler; Lawrence-Simon, Jake

Complex physics and long computation time hinder the adoption of computer aided engineering models in the design of large-format battery cells and systems. A modular, efficient battery simulation model -- the multiscale multidomain (MSMD) model -- was previously introduced to aid the scale-up of Li-ion material and electrode designs to complete cell and pack designs, capturing electrochemical interplay with 3-D electronic current pathways and thermal response. Here, this paper enhances the computational efficiency of the MSMD model using a separation of time-scales principle to decompose model field variables. The decomposition provides a quasi-explicit linkage between the multiple length-scale domains andmore » thus reduces time-consuming nested iteration when solving model equations across multiple domains. In addition to particle-, electrode- and cell-length scales treated in the previous work, the present formulation extends to bus bar- and multi-cell module-length scales. We provide example simulations for several variants of GH electrode-domain models.« less
Efficient and Extensible Quasi-Explicit Modular Nonlinear Multiscale Battery Model: GH-MSMD

DOE PAGES

Kim, Gi-Heon; Smith, Kandler; Lawrence-Simon, Jake; ...

2017-03-24

Complex physics and long computation time hinder the adoption of computer aided engineering models in the design of large-format battery cells and systems. A modular, efficient battery simulation model -- the multiscale multidomain (MSMD) model -- was previously introduced to aid the scale-up of Li-ion material and electrode designs to complete cell and pack designs, capturing electrochemical interplay with 3-D electronic current pathways and thermal response. Here, this paper enhances the computational efficiency of the MSMD model using a separation of time-scales principle to decompose model field variables. The decomposition provides a quasi-explicit linkage between the multiple length-scale domains andmore » thus reduces time-consuming nested iteration when solving model equations across multiple domains. In addition to particle-, electrode- and cell-length scales treated in the previous work, the present formulation extends to bus bar- and multi-cell module-length scales. We provide example simulations for several variants of GH electrode-domain models.« less
The dynamics of oceanic fronts. I - The Gulf Stream

NASA Technical Reports Server (NTRS)

Kao, T. W.

1980-01-01

The establishment and maintenance of the mean hydrographic properties of large-scale density fronts in the upper ocean is considered. The dynamics is studied by posing an initial value problem starting with a near-surface discharge of buoyant water with a prescribed density deficit into an ambient stationary fluid of uniform density; full time dependent diffusion and Navier-Stokes equations are then used with constant eddy diffusion and viscosity coefficients, together with a constant Coriolis parameter. Scaling analysis reveals three independent scales of the problem including the radius of deformation of the inertial length, buoyancy length, and diffusive length scales. The governing equations are then suitably scaled and the resulting normalized equations are shown to depend on the Ekman number alone for problems of oceanic interest. It is concluded that the mean Gulf Stream dynamics can be interpreted in terms of a solution of the Navier-Stokes and diffusion equations, with the cross-stream circulation responsible for the maintenance of the front; this mechanism is suggested for the maintenance of the Gulf Stream dynamics.

Using cell deformation and motion to predict forces and collective behavior in morphogenesis.

PubMed

Merkel, Matthias; Manning, M Lisa

2017-07-01

In multi-cellular organisms, morphogenesis translates processes at the cellular scale into tissue deformation at the scale of organs and organisms. To understand how biochemical signaling regulates tissue form and function, we must understand the mechanical forces that shape cells and tissues. Recent progress in developing mechanical models for tissues has led to quantitative predictions for how cell shape changes and polarized cell motility generate forces and collective behavior on the tissue scale. In particular, much insight has been gained by thinking about biological tissues as physical materials composed of cells. Here we review these advances and discuss how they might help shape future experiments in developmental biology. Copyright © 2016 Elsevier Ltd. All rights reserved.
Scale and time dependence of serial correlations in word-length time series of written texts

NASA Astrophysics Data System (ADS)

Rodriguez, E.; Aguilar-Cornejo, M.; Femat, R.; Alvarez-Ramirez, J.

2014-11-01

This work considered the quantitative analysis of large written texts. To this end, the text was converted into a time series by taking the sequence of word lengths. The detrended fluctuation analysis (DFA) was used for characterizing long-range serial correlations of the time series. To this end, the DFA was implemented within a rolling window framework for estimating the variations of correlations, quantified in terms of the scaling exponent, strength along the text. Also, a filtering derivative was used to compute the dependence of the scaling exponent relative to the scale. The analysis was applied to three famous English-written literary narrations; namely, Alice in Wonderland (by Lewis Carrol), Dracula (by Bram Stoker) and Sense and Sensibility (by Jane Austen). The results showed that high correlations appear for scales of about 50-200 words, suggesting that at these scales the text contains the stronger coherence. The scaling exponent was not constant along the text, showing important variations with apparent cyclical behavior. An interesting coincidence between the scaling exponent variations and changes in narrative units (e.g., chapters) was found. This suggests that the scaling exponent obtained from the DFA is able to detect changes in narration structure as expressed by the usage of words of different lengths.
Diffusion and scaling during early embryonic pattern formation

PubMed Central

Gregor, Thomas; Bialek, William; van Steveninck, Rob R. de Ruyter; Tank, David W.; Wieschaus, Eric F.

2005-01-01

Development of spatial patterns in multicellular organisms depends on gradients in the concentration of signaling molecules that control gene expression. In the Drosophila embryo, Bicoid (Bcd) morphogen controls cell fate along 70% of the anteroposterior axis but is translated from mRNA localized at the anterior pole. Gradients of Bcd and other morphogens are thought to arise through diffusion, but this basic assumption has never been rigorously tested in living embryos. Furthermore, because diffusion sets a relationship between length and time scales, it is hard to see how patterns of gene expression established by diffusion would scale proportionately as egg size changes during evolution. Here, we show that the motion of inert molecules through the embryo is well described by the diffusion equation on the relevant length and time scales, and that effective diffusion constants are essentially the same in closely related dipteran species with embryos of very different size. Nonetheless, patterns of gene expression in these different species scale with egg length. We show that this scaling can be traced back to scaling of the Bcd gradient itself. Our results, together with constraints imposed by the time scales of development, suggest that the mechanism for scaling is a species-specific adaptation of the Bcd lifetime. PMID:16352710
Double-exponential decay of orientational correlations in semiflexible polyelectrolytes.

PubMed

Bačová, P; Košovan, P; Uhlík, F; Kuldová, J; Limpouchová, Z; Procházka, K

2012-06-01

In this paper we revisited the problem of persistence length of polyelectrolytes. We performed a series of Molecular Dynamics simulations using the Debye-Hückel approximation for electrostatics to test several equations which go beyond the classical description of Odijk, Skolnick and Fixman (OSF). The data confirm earlier observations that in the limit of large contour separations the decay of orientational correlations can be described by a single-exponential function and the decay length can be described by the OSF relation. However, at short countour separations the behaviour is more complex. Recent equations which introduce more complicated expressions and an additional length scale could describe the results very well on both the short and the long length scale. The equation of Manghi and Netz when used without adjustable parameters could capture the qualitative trend but deviated in a quantitative comparison. Better quantitative agreement within the estimated error could be obtained using three equations with one adjustable parameter: 1) the equation of Manghi and Netz; 2) the equation proposed by us in this paper; 3) the equation proposed by Cannavacciuolo and Pedersen. Two characteristic length scales can be identified in the data: the intrinsic or bare persistence length and the electrostatic persistence length. All three equations use a single parameter to describe a smooth crossover from the short-range behaviour dominated by the intrinsic stiffness of the chain to the long-range OSF-like behaviour.
Multi-scale Modeling of Chromosomal DNA in Living Cells

NASA Astrophysics Data System (ADS)

Spakowitz, Andrew

The organization and dynamics of chromosomal DNA play a pivotal role in a range of biological processes, including gene regulation, homologous recombination, replication, and segregation. Establishing a quantitative theoretical model of DNA organization and dynamics would be valuable in bridging the gap between the molecular-level packaging of DNA and genome-scale chromosomal processes. Our research group utilizes analytical theory and computational modeling to establish a predictive theoretical model of chromosomal organization and dynamics. In this talk, I will discuss our efforts to develop multi-scale polymer models of chromosomal DNA that are both sufficiently detailed to address specific protein-DNA interactions while capturing experimentally relevant time and length scales. I will demonstrate how these modeling efforts are capable of quantitatively capturing aspects of behavior of chromosomal DNA in both prokaryotic and eukaryotic cells. This talk will illustrate that capturing dynamical behavior of chromosomal DNA at various length scales necessitates a range of theoretical treatments that accommodate the critical physical contributions that are relevant to in vivo behavior at these disparate length and time scales. National Science Foundation, Physics of Living Systems Program (PHY-1305516).
Optimizing eukaryotic cell hosts for protein production through systems biotechnology and genome-scale modeling.

PubMed

Gutierrez, Jahir M; Lewis, Nathan E

2015-07-01

Eukaryotic cell lines, including Chinese hamster ovary cells, yeast, and insect cells, are invaluable hosts for the production of many recombinant proteins. With the advent of genomic resources, one can now leverage genome-scale computational modeling of cellular pathways to rationally engineer eukaryotic host cells. Genome-scale models of metabolism include all known biochemical reactions occurring in a specific cell. By describing these mathematically and using tools such as flux balance analysis, the models can simulate cell physiology and provide targets for cell engineering that could lead to enhanced cell viability, titer, and productivity. Here we review examples in which metabolic models in eukaryotic cell cultures have been used to rationally select targets for genetic modification, improve cellular metabolic capabilities, design media supplementation, and interpret high-throughput omics data. As more comprehensive models of metabolism and other cellular processes are developed for eukaryotic cell culture, these will enable further exciting developments in cell line engineering, thus accelerating recombinant protein production and biotechnology in the years to come. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Ultrahigh-resolution optical coherence elastography through a micro-endoscope: towards in vivo imaging of cellular-scale mechanics

PubMed Central

Fang, Qi; Curatolo, Andrea; Wijesinghe, Philip; Yeow, Yen Ling; Hamzah, Juliana; Noble, Peter B.; Karnowski, Karol; Sampson, David D.; Ganss, Ruth; Kim, Jun Ki; Lee, Woei M.; Kennedy, Brendan F.

2017-01-01

In this paper, we describe a technique capable of visualizing mechanical properties at the cellular scale deep in living tissue, by incorporating a gradient-index (GRIN)-lens micro-endoscope into an ultrahigh-resolution optical coherence elastography system. The optical system, after the endoscope, has a lateral resolution of 1.6 µm and an axial resolution of 2.2 µm. Bessel beam illumination and Gaussian mode detection are used to provide an extended depth-of-field of 80 µm, which is a 4-fold improvement over a fully Gaussian beam case with the same lateral resolution. Using this system, we demonstrate quantitative elasticity imaging of a soft silicone phantom containing a stiff inclusion and a freshly excised malignant murine pancreatic tumor. We also demonstrate qualitative strain imaging below the tissue surface on in situ murine muscle. The approach we introduce here can provide high-quality extended-focus images through a micro-endoscope with potential to measure cellular-scale mechanics deep in tissue. We believe this tool is promising for studying biological processes and disease progression in vivo. PMID:29188108
Measurements of the Influence of Integral Length Scale on Stagnation Region Heat Transfer

NASA Technical Reports Server (NTRS)

Vanfossen, G. James; Ching, Chang Y.

1994-01-01

The purpose was twofold: first, to determine if a length scale existed that would cause the greatest augmentation in stagnation region heat transfer for a given turbulence intensity and second, to develop a prediction tool for stagnation heat transfer in the presence of free stream turbulence. Toward this end, a model with a circular leading edge was fabricated with heat transfer gages in the stagnation region. The model was qualified in a low turbulence wind tunnel by comparing measurements with Frossling's solution for stagnation region heat transfer in a laminar free stream. Five turbulence generating grids were fabricated; four were square mesh, biplane grids made from square bars. Each had identical mesh to bar width ratio but different bar widths. The fifth grid was an array of fine parallel wires that were perpendicular to the axis of the cylindrical leading edge. Turbulence intensity and integral length scale were measured as a function of distance from the grids. Stagnation region heat transfer was measured at various distances downstream of each grid. Data were taken at cylinder Reynolds numbers ranging from 42,000 to 193,000. Turbulence intensities were in the range 1.1 to 15.9 percent while the ratio of integral length scale to cylinder diameter ranged from 0.05 to 0.30. Stagnation region heat transfer augmentation increased with decreasing length scale. An optimum scale was not found. A correlation was developed that fit heat transfer data for the square bar grids to within +4 percent. The data from the array of wires were not predicted by the correlation; augmentation was higher for this case indicating that the degree of isotropy in the turbulent flow field has a large effect on stagnation heat transfer. The data of other researchers are also compared with the correlation.
Pollutant Dispersion in Boundary Layers Exposed to Rural-to-Urban Transitions: Varying the Spanwise Length Scale of the Roughness

NASA Astrophysics Data System (ADS)

Tomas, J. M.; Eisma, H. E.; Pourquie, M. J. B. M.; Elsinga, G. E.; Jonker, H. J. J.; Westerweel, J.

2017-05-01

Both large-eddy simulations (LES) and water-tunnel experiments, using simultaneous stereoscopic particle image velocimetry and laser-induced fluorescence, have been used to investigate pollutant dispersion mechanisms in regions where the surface changes from rural to urban roughness. The urban roughness was characterized by an array of rectangular obstacles in an in-line arrangement. The streamwise length scale of the roughness was kept constant, while the spanwise length scale was varied by varying the obstacle aspect ratio l / h between 1 and 8, where l is the spanwise dimension of the obstacles and h is the height of the obstacles. Additionally, the case of two-dimensional roughness (riblets) was considered in LES. A smooth-wall turbulent boundary layer of depth 10 h was used as the approaching flow, and a line source of passive tracer was placed 2 h upstream of the urban canopy. The experimental and numerical results show good agreement, while minor discrepancies are readily explained. It is found that for l/h=2 the drag induced by the urban canopy is largest of all considered cases, and is caused by a large-scale secondary flow. In addition, due to the roughness transition the vertical advective pollutant flux is the main ventilation mechanism in the first three streets. Furthermore, by means of linear stochastic estimation the mean flow structure is identified that is responsible for street-canyon ventilation for the sixth street and onwards. Moreover, it is shown that the vertical length scale of this structure increases with increasing aspect ratio of the obstacles in the canopy, while the streamwise length scale does not show a similar trend.
Dynamics of an elastic sphere containing a thin creeping region and immersed in an acoustic region for similar viscous-elastic and acoustic time- and length-scales

NASA Astrophysics Data System (ADS)

Gat, Amir; Friedman, Yonathan

2017-11-01

The characteristic time of low-Reynolds number fluid-structure interaction scales linearly with the ratio of fluid viscosity to solid Young's modulus. For sufficiently large values of Young's modulus, both time- and length-scales of the viscous-elastic dynamics may be similar to acoustic time- and length-scales. However, the requirement of dominant viscous effects limits the validity of such regimes to micro-configurations. We here study the dynamics of an acoustic plane wave impinging on the surface of a layered sphere, immersed within an inviscid fluid, and composed of an inner elastic sphere, a creeping fluid layer and an external elastic shell. We focus on configurations with similar viscous-elastic and acoustic time- and length-scales, where the viscous-elastic speed of interaction between the creeping layer and the elastic regions is similar to the speed of sound. By expanding the linearized spherical Reynolds equation into the relevant spectral series solution for the hyperbolic elastic regions, a global stiffness matrix of the layered elastic sphere was obtained. This work relates viscous-elastic dynamics to acoustic scattering and may pave the way to the design of novel meta-materials with unique acoustic properties. ISF 818/13.
Dependence of displacement-length scaling relations for fractures and deformation bands on the volumetric changes across them

USGS Publications Warehouse

Schultz, R.A.; Soliva, R.; Fossen, H.; Okubo, C.H.; Reeves, D.M.

2008-01-01

Displacement-length data from faults, joints, veins, igneous dikes, shear deformation bands, and compaction bands define two groups. The first group, having a power-law scaling relation with a slope of n = 1 and therefore a linear dependence of maximum displacement and discontinuity length (Dmax = ??L), comprises faults and shear (non-compactional or non-dilational) deformation bands. These shearing-mode structures, having shearing strains that predominate over volumetric strains across them, grow under conditions of constant driving stress, with the magnitude of near-tip stress on the same order as the rock's yield strength in shear. The second group, having a power-law scaling relation with a slope of n = 0.5 and therefore a dependence of maximum displacement on the square root of discontinuity length (Dmax = ??L0.5), comprises joints, veins, igneous dikes, cataclastic deformation bands, and compaction bands. These opening- and closing-mode structures grow under conditions of constant fracture toughness, implying significant amplification of near-tip stress within a zone of small-scale yielding at the discontinuity tip. Volumetric changes accommodated by grain fragmentation, and thus control of propagation by the rock's fracture toughness, are associated with scaling of predominantly dilational and compactional structures with an exponent of n = 0.5. ?? 2008 Elsevier Ltd.
CNT Based Artificial Hair Sensors for Predictable Boundary Layer Air Flow Sensing (Postscript)

DTIC Science & Technology

2016-11-07

hairs. The moment sensitivity is shown to scale inversely with the CNT length and stiffness to a typical maximum of 1.3 ± 0.4% resistance change nN−1...determined air flow is obtained using theory and measurement for various lengths of hairs. The moment sensitivity is shown to scale inversely with the
Magnetic field line random walk in two-dimensional dynamical turbulence

NASA Astrophysics Data System (ADS)

Wang, J. F.; Qin, G.; Ma, Q. M.; Song, T.; Yuan, S. B.

2017-08-01

The field line random walk (FLRW) of magnetic turbulence is one of the important topics in plasma physics and astrophysics. In this article, by using the field line tracing method, the mean square displacement (MSD) of FLRW is calculated on all possible length scales for pure two-dimensional turbulence with the damping dynamical model. We demonstrate that in order to describe FLRW with the damping dynamical model, a new dimensionless quantity R is needed to be introduced. On different length scales, dimensionless MSD shows different relationships with the dimensionless quantity R. Although the temporal effect affects the MSD of FLRW and even changes regimes of FLRW, it does not affect the relationship between the dimensionless MSD and dimensionless quantity R on all possible length scales.
Emergence of linear elasticity from the atomistic description of matter

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

Cakir, Abdullah, E-mail: acakir@ntu.edu.sg; Pica Ciamarra, Massimo; Dipartimento di Scienze Fisiche, CNR–SPIN, Università di Napoli Federico II, I-80126 Napoli

2016-08-07

We investigate the emergence of the continuum elastic limit from the atomistic description of matter at zero temperature considering how locally defined elastic quantities depend on the coarse graining length scale. Results obtained numerically investigating different model systems are rationalized in a unifying picture according to which the continuum elastic limit emerges through a process determined by two system properties, the degree of disorder, and a length scale associated to the transverse low-frequency vibrational modes. The degree of disorder controls the emergence of long-range local shear stress and shear strain correlations, while the length scale influences the amplitude of themore » fluctuations of the local elastic constants close to the jamming transition.« less
Communication and wiring in the cortical connectome

PubMed Central

Budd, Julian M. L.; Kisvárday, Zoltán F.

2012-01-01

In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimize communication there is a trade-off between spatial (construction) and temporal (routing) costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fiber tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for cortical wiring patterns. PMID:23087619
Using large eddy simulations to reveal the size, strength, and phase of updraft and downdraft cores of an Arctic mixed-phase stratocumulus cloud

DOE PAGES

Roesler, Erika L.; Posselt, Derek J.; Rood, Richard B.

2017-04-06

Three-dimensional large eddy simulations (LES) are used to analyze a springtime Arctic mixed-phase stratocumulus observed on 26 April 2008 during the Indirect and Semi-Direct Aerosol Campaign. Two subgrid-scale turbulence parameterizations are compared. The first scheme is a 1.5-order turbulent kinetic energy (1.5-TKE) parameterization that has been previously applied to boundary layer cloud simulations. The second scheme, Cloud Layers Unified By Binormals (CLUBB), provides higher-order turbulent closure with scale awareness. The simulations, in comparisons with observations, show that both schemes produce the liquid profiles within measurement variability but underpredict ice water mass and overpredict ice number concentration. The simulation using CLUBBmore » underpredicted liquid water path more than the simulation using the 1.5-TKE scheme, so the turbulent length scale and horizontal grid box size were increased to increase liquid water path and reduce dissipative energy. The LES simulations show this stratocumulus cloud to maintain a closed cellular structure, similar to observations. The updraft and downdraft cores self-organize into a larger meso-γ-scale convective pattern with the 1.5-TKE scheme, but the cores remain more isotropic with the CLUBB scheme. Additionally, the cores are often composed of liquid and ice instead of exclusively containing one or the other. Furthermore, these results provide insight into traditionally unresolved and unmeasurable aspects of an Arctic mixed-phase cloud. From analysis, this cloud's updraft and downdraft cores appear smaller than other closed-cell stratocumulus such as midlatitude stratocumulus and Arctic autumnal mixed-phase stratocumulus due to the weaker downdrafts and lower precipitation rates.« less
Cold Ion Demagnetization near the X-line of Magnetic Reconnection

NASA Technical Reports Server (NTRS)

Toledo-Redondo, Serio; Andre, Mats; Khotyaintsev, Yuri V.; Vaivads, Andris; Walsh, Andrew; Li, Wenya; Graham, Daniel B.; Lavraud, Benoit; Masson, Arnaud; Aunai, Nicolas;

2016-01-01

Although the effects of magnetic reconnection in magnetospheres can be observed at planetary scales, reconnection is initiated at electron scales in a plasma. Surrounding the electron diffusion region, there is an Ion-Decoupling Region (IDR) of the size of the ion length scales (inertial length and gyroradius). Reconnection at the Earths magnetopause often includes cold magnetospheric (few tens of eV), hot magnetospheric (10 keV), and magnetosheath (1 keV) ions, with different gyroradius length scales. We report observations of a subregion inside the IDR of the size of the cold ion population gyroradius (approx. 15 km) where the cold ions are demagnetized and accelerated parallel to the Hall electric field. Outside the subregion, cold ions follow the E x B motion together with electrons, while hot ions are demagnetized. We observe a sharp cold ion density gradient separating the two regions, which we identify as the cold and hot IDRs.

Dependence of exponents on text length versus finite-size scaling for word-frequency distributions

NASA Astrophysics Data System (ADS)

Corral, Álvaro; Font-Clos, Francesc

2017-08-01

Some authors have recently argued that a finite-size scaling law for the text-length dependence of word-frequency distributions cannot be conceptually valid. Here we give solid quantitative evidence for the validity of this scaling law, using both careful statistical tests and analytical arguments based on the generalized central-limit theorem applied to the moments of the distribution (and obtaining a novel derivation of Heaps' law as a by-product). We also find that the picture of word-frequency distributions with power-law exponents that decrease with text length [X. Yan and P. Minnhagen, Physica A 444, 828 (2016), 10.1016/j.physa.2015.10.082] does not stand with rigorous statistical analysis. Instead, we show that the distributions are perfectly described by power-law tails with stable exponents, whose values are close to 2, in agreement with the classical Zipf's law. Some misconceptions about scaling are also clarified.
Cold ion demagnetization near the X-line of magnetic reconnection

NASA Astrophysics Data System (ADS)

Toledo-Redondo, Sergio; André, Mats; Khotyaintsev, Yuri V.; Vaivads, Andris; Walsh, Andrew; Li, Wenya; Graham, Daniel B.; Lavraud, Benoit; Masson, Arnaud; Aunai, Nicolas; Divin, Andrey; Dargent, Jeremy; Fuselier, Stephen; Gershman, Daniel J.; Dorelli, John; Giles, Barbara; Avanov, Levon; Pollock, Craig; Saito, Yoshifumi; Moore, Thomas E.; Coffey, Victoria; Chandler, Michael O.; Lindqvist, Per-Arne; Torbert, Roy; Russell, Christopher T.

2016-07-01

Although the effects of magnetic reconnection in magnetospheres can be observed at planetary scales, reconnection is initiated at electron scales in a plasma. Surrounding the electron diffusion region, there is an Ion-Decoupling Region (IDR) of the size of the ion length scales (inertial length and gyroradius). Reconnection at the Earth's magnetopause often includes cold magnetospheric (few tens of eV), hot magnetospheric (10 keV), and magnetosheath (1 keV) ions, with different gyroradius length scales. We report observations of a subregion inside the IDR of the size of the cold ion population gyroradius (˜15 km) where the cold ions are demagnetized and accelerated parallel to the Hall electric field. Outside the subregion, cold ions follow the E × B motion together with electrons, while hot ions are demagnetized. We observe a sharp cold ion density gradient separating the two regions, which we identify as the cold and hot IDRs.
Benchmarking sheath subgrid boundary conditions for macroscopic-scale simulations

NASA Astrophysics Data System (ADS)

Jenkins, T. G.; Smithe, D. N.

2015-02-01

The formation of sheaths near metallic or dielectric-coated wall materials in contact with a plasma is ubiquitous, often giving rise to physical phenomena (sputtering, secondary electron emission, etc) which influence plasma properties and dynamics both near and far from the material interface. In this paper, we use first-principles PIC simulations of such interfaces to formulate a subgrid sheath boundary condition which encapsulates fundamental aspects of the sheath behavior at the interface. Such a boundary condition, based on the capacitive behavior of the sheath, is shown to be useful in fluid simulations wherein sheath scale lengths are substantially smaller than scale lengths for other relevant physical processes (e.g. radiofrequency wavelengths), in that it enables kinetic processes associated with the presence of the sheath to be numerically modeled without explicit resolution of spatial and temporal sheath scales such as electron Debye length or plasma frequency.

Multiscale Porosity and Mechanical Properties of Mancos Shale: Evaluation of REV and Scale Separation

NASA Astrophysics Data System (ADS)

Heath, J. E.; Dewers, T. A.; Yoon, H.; Mozley, P.

2016-12-01

Heterogeneity from the nanometer to core and larger length scales is a major challenge to understanding coupled processes in shale. To develop methods to address this challenge, we present application of high throughput multi-beam scanning electron microscopy (mSEM) and nano-to-micro-scale mechanics to the Mancos Shale. We use a 61-beam mSEM to collect 6 nm resolution SEM images at the scale of several square millimeters. These images are analyzed for pore size and shape characteristics including spatial correlation and structure. Nano-indentation, micropillar compression, and axisymmetric testing at multiple length scales allows for examining the influence of sampling size on mechanical response. The combined data set is used to: investigate representative elementary volumes (and areas for the 2D images) for the Mancos Shale; determine if scale separation occurs; and determine if transport and mechanical properties at a given length scale can be statistically defined. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.
Effects of axisymmetric contractions on turbulence of various scales

NASA Technical Reports Server (NTRS)

Tan-Atichat, J.; Nagib, H. M.; Drubka, R. E.

1980-01-01

Digitally acquired and processed results from an experimental investigation of grid generated turbulence of various scales through and downstream of nine matched cubic contour contractions ranging in area ratio from 2 to 36, and in length to inlet diameter ratio from 0.25 to 1.50 are reported. An additional contraction with a fifth order contour was also utilized for studying the shape effect. Thirteen homogeneous and nearly isotropic test flow conditions with a range of turbulence intensities, length scales and Reynolds numbers were generated and used to examine the sensitivity of the contractions to upstream turbulence. The extent to which the turbulence is altered by the contraction depends on the incoming turbulence scales, the total strain experienced by the fluid, as well as the contraction ratio and the strain rate. Varying the turbulence integral scale influences the transverse turbulence components more than the streamwise component. In general, the larger the turbulence scale, the lesser the reduction in the turbulence intensity of the transverse components. Best agreement with rapid distortion theory was obtained for large scale turbulence, where viscous decay over the contraction length was negligible, or when a first order correction for viscous decay was applied to the results.
A network approach to the geometric structure of shallow cloud fields

NASA Astrophysics Data System (ADS)

Glassmeier, F.; Feingold, G.

2017-12-01

The representation of shallow clouds and their radiative impact is one of the largest challenges for global climate models. While the bulk properties of cloud fields, including effects of organization, are a very active area of research, the potential of the geometric arrangement of cloud fields for the development of new parameterizations has hardly been explored. Self-organized patterns are particularly evident in the cellular structure of Stratocumulus (Sc) clouds so readily visible in satellite imagery. Inspired by similar patterns in biology and physics, we approach pattern formation in Sc fields from the perspective of natural cellular networks. Our network analysis is based on large-eddy simulations of open- and closed-cell Sc cases. We find the network structure to be neither random nor characteristic to natural convection. It is independent of macroscopic cloud fields properties like the Sc regime (open vs closed) and its typical length scale (boundary layer height). The latter is a consequence of entropy maximization (Lewis's Law with parameter 0.16). The cellular pattern is on average hexagonal, where non-6 sided cells occur according to a neighbor-number distribution variance of about 2. Reflecting the continuously renewing dynamics of Sc fields, large (many-sided) cells tend to neighbor small (few-sided) cells (Aboav-Weaire Law with parameter 0.9). These macroscopic network properties emerge independent of the Sc regime because the different processes governing the evolution of closed as compared to open cells correspond to topologically equivalent network dynamics. By developing a heuristic model, we show that open and closed cell dynamics can both be mimicked by versions of cell division and cell disappearance and are biased towards the expansion of smaller cells. This model offers for the first time a fundamental and universal explanation for the geometric pattern of Sc clouds. It may contribute to the development of advanced Sc parameterizations. As an outlook, we discuss how a similar network approach can be applied to describe and quantify the geometric structure of shallow cumulus cloud fields.
Lagrangian Formulation of a Magnetostatic Field in the Presence of a Minimal Length Scale Based on the Kempf Algebra

NASA Astrophysics Data System (ADS)

Moayedi, S. K.; Setare, M. R.; Khosropour, B.

2013-11-01

In the 1990s, Kempf and his collaborators Mangano and Mann introduced a D-dimensional (β, β‧)-two-parameter deformed Heisenberg algebra which leads to an isotropic minimal length (\\triangle Xi)\\min = \\hbar √ {Dβ +β '}, \\forall i\\in \\{1, 2, ..., D\\}. In this work, the Lagrangian formulation of a magnetostatic field in three spatial dimensions (D = 3) described by Kempf algebra is presented in the special case of β‧ = 2β up to the first-order over β. We show that at the classical level there is a similarity between magnetostatics in the presence of a minimal length scale (modified magnetostatics) and the magnetostatic sector of the Abelian Lee-Wick model in three spatial dimensions. The integral form of Ampere's law and the energy density of a magnetostatic field in the modified magnetostatics are obtained. Also, the Biot-Savart law in the modified magnetostatics is found. By studying the effect of minimal length corrections to the gyromagnetic moment of the muon, we conclude that the upper bound on the isotropic minimal length scale in three spatial dimensions is 4.42×10-19 m. The relationship between magnetostatics with a minimal length and the Gaete-Spallucci nonlocal magnetostatics [J. Phys. A: Math. Theor. 45, 065401 (2012)] is investigated.
The Conductance of Porphyrin-Based Molecular Nanowires Increases with Length.

PubMed

Algethami, Norah; Sadeghi, Hatef; Sangtarash, Sara; Lambert, Colin J

2018-06-13

High electrical conductance molecular nanowires are highly desirable components for future molecular-scale circuitry, but typically molecular wires act as tunnel barriers and their conductance decays exponentially with length. Here, we demonstrate that the conductance of fused-oligo-porphyrin nanowires can be either length independent or increase with length at room temperature. We show that this negative attenuation is an intrinsic property of fused-oligo-porphyrin nanowires, but its manifestation depends on the electrode material or anchor groups. This highly desirable, nonclassical behavior signals the quantum nature of transport through such wires. It arises because with increasing length the tendency for electrical conductance to decay is compensated by a decrease in their highest occupied molecular orbital-lowest unoccupied molecular orbital gap. Our study reveals the potential of these molecular wires as interconnects in future molecular-scale circuitry.
Computer Modeling of the Earliest Cellular Structures and Functions

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Chipot, Christophe; Schweighofer, Karl

2000-01-01

In the absence of extinct or extant record of protocells (the earliest ancestors of contemporary cells). the most direct way to test our understanding of the origin of cellular life is to construct laboratory models of protocells. Such efforts are currently underway in the NASA Astrobiology Program. They are accompanied by computational studies aimed at explaining self-organization of simple molecules into ordered structures and developing designs for molecules that perform proto-cellular functions. Many of these functions, such as import of nutrients, capture and storage of energy. and response to changes in the environment are carried out by proteins bound to membrane< We will discuss a series of large-scale, molecular-level computer simulations which demonstrate (a) how small proteins (peptides) organize themselves into ordered structures at water-membrane interfaces and insert into membranes, (b) how these peptides aggregate to form membrane-spanning structures (eg. channels), and (c) by what mechanisms such aggregates perform essential proto-cellular functions, such as proton transport of protons across cell walls, a key step in cellular bioenergetics. The simulations were performed using the molecular dynamics method, in which Newton's equations of motion for each item in the system are solved iteratively. The problems of interest required simulations on multi-nanosecond time scales, which corresponded to 10(exp 6)-10(exp 8) time steps.
Enterococcus faecalis Responds to Individual Exogenous Fatty Acids Independently of Their Degree of Saturation or Chain Length

PubMed Central

2017-01-01

ABSTRACT Enterococcus faecalis is a commensal of the human gastrointestinal tract that can persist in the external environment and is a leading cause of hospital-acquired infections. Given its diverse habitats, the organism has developed numerous strategies to survive a multitude of environmental conditions. Previous studies have demonstrated that E. faecalis will incorporate fatty acids from bile and serum into its membrane, resulting in an induced tolerance to membrane-damaging agents. To discern whether all fatty acids induce membrane stress protection, we examined how E. faecalis responded to individually supplied fatty acids. E. faecalis readily incorporated fatty acids 14 to 18 carbons in length into its membrane but poorly incorporated fatty acids shorter or longer than this length. Supplementation with saturated fatty acids tended to increase generation time and lead to altered cellular morphology in most cases. Further, exogenously supplied saturated fatty acids did not induce tolerance to the membrane-damaging antibiotic daptomycin. Supplementation with unsaturated fatty acids produced variable growth effects, with some impacting generation time and morphology. Exogenously supplied unsaturated fatty acids that are normally produced by E. faecalis and those that are found in bile or serum could restore growth in the presence of a fatty acid biosynthetic inhibitor. However, only the eukaryote-derived fatty acids oleic acid and linoleic acid provided protection from daptomycin. Thus, exogenous fatty acids do not lead to a common physiological effect on E. faecalis. The organism responds uniquely to each, and only host-derived fatty acids induce membrane protection. IMPORTANCE Enterococcus faecalis is a commonly acquired hospital infectious agent with resistance to many antibiotics, including those that target its cellular membrane. We previously demonstrated that E. faecalis will incorporate fatty acids found in human fluids, like serum, into its cellular membrane, thereby altering its membrane composition. In turn, the organism is better able to survive membrane-damaging agents, including the antibiotic daptomycin. We examined fatty acids commonly found in serum and those normally produced by E. faecalis to determine which fatty acids can induce protection from membrane damage. Supplementation with individual fatty acids produced a myriad of different effects on cellular growth, morphology, and stress response. However, only host-derived unsaturated fatty acids provided stress protection. Future studies are aimed at understanding how these specific fatty acids induce protection from membrane damage. PMID:29079613
Full-Scale Numerical Modeling of Turbulent Processes in the Earth's Ionosphere

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

Eliasson, B.; Stenflo, L.; Department of Physics, Linkoeping University, SE-581 83 Linkoeping

2008-10-15

We present a full-scale simulation study of ionospheric turbulence by means of a generalized Zakharov model based on the separation of variables into high-frequency and slow time scales. The model includes realistic length scales of the ionospheric profile and of the electromagnetic and electrostatic fields, and uses ionospheric plasma parameters relevant for high-latitude radio facilities such as Eiscat and HAARP. A nested grid numerical method has been developed to resolve the different length-scales, while avoiding severe restrictions on the time step. The simulation demonstrates the parametric decay of the ordinary mode into Langmuir and ion-acoustic waves, followed by a Langmuirmore » wave collapse and short-scale caviton formation, as observed in ionospheric heating experiments.« less
Metabolic Conversion of Ceramides in HeLa Cells - A Cholesteryl Phosphocholine Delivery Approach

PubMed Central

Kjellberg, Matti A.; Lönnfors, Max; Slotte, J. Peter; Mattjus, Peter

2015-01-01

Ceramides can be delivered to cultured cells without solvents in the form of complexes with cholesteryl phosphocholine. We have analysed the delivery of three different radiolabeled D-erythro-ceramides (C6-Cer, C10-Cer and C16-Cer) to HeLa cells, and followed their metabolism as well as the cell viability. We found that all three ceramides were successfully taken up by HeLa cells when complexed to CholPC in an equimolar ratio, and show that the ceramides show different rates of cellular uptake and metabolic fate. The C6-Cer had the highest incorporation rate, followed by C10-Cer and C16-Cer, respectively. The subsequent effect on cell viability strongly correlated with the rate of incorporation, where C6-Cer had the strongest apoptotic effects. Low-dose (1 μM) treatment with C6-Cer favoured conversion of the precursor to sphingomyelin, whereas higher concentrations (25–100 μM) yielded increased conversion to C6-glucosylceramide. Similar results were obtained for C10-Cer. In the lower-dose C16-Cer experiments, most of the precursor was degraded, whereas at high-dose concentrations the precursor remained un-metabolized. Using this method, we demonstrate that ceramides with different chain lengths clearly exhibit varying rates of cellular uptake. The cellular fate of the externally delivered ceramides are clearly connected to their rate of incorporation and their subsequent effects on cell viability may be in part determined by their chain length. PMID:26599810
α-Synuclein and huntingtin exon 1 amyloid fibrils bind laterally to the cellular membrane.

PubMed

Monsellier, Elodie; Bousset, Luc; Melki, Ronald

2016-01-13

Fibrillar aggregates involved in neurodegenerative diseases have the ability to spread from one cell to another in a prion-like manner. The underlying molecular mechanisms, in particular the binding mode of the fibrils to cell membranes, are poorly understood. In this work we decipher the modality by which aggregates bind to the cellular membrane, one of the obligatory steps of the propagation cycle. By characterizing the binding properties of aggregates made of α-synuclein or huntingtin exon 1 protein displaying similar composition and structure but different lengths to mammalian cells we demonstrate that in both cases aggregates bind laterally to the cellular membrane, with aggregates extremities displaying little or no role in membrane binding. Lateral binding to artificial liposomes was also observed by transmission electron microscopy. In addition we show that although α-synuclein and huntingtin exon 1 fibrils bind both laterally to the cellular membrane, their mechanisms of interaction differ. Our findings have important implications for the development of future therapeutic tools that aim to block protein aggregates propagation in the brain.
α-Synuclein and huntingtin exon 1 amyloid fibrils bind laterally to the cellular membrane

PubMed Central

Monsellier, Elodie; Bousset, Luc; Melki, Ronald

2016-01-01

Fibrillar aggregates involved in neurodegenerative diseases have the ability to spread from one cell to another in a prion-like manner. The underlying molecular mechanisms, in particular the binding mode of the fibrils to cell membranes, are poorly understood. In this work we decipher the modality by which aggregates bind to the cellular membrane, one of the obligatory steps of the propagation cycle. By characterizing the binding properties of aggregates made of α-synuclein or huntingtin exon 1 protein displaying similar composition and structure but different lengths to mammalian cells we demonstrate that in both cases aggregates bind laterally to the cellular membrane, with aggregates extremities displaying little or no role in membrane binding. Lateral binding to artificial liposomes was also observed by transmission electron microscopy. In addition we show that although α-synuclein and huntingtin exon 1 fibrils bind both laterally to the cellular membrane, their mechanisms of interaction differ. Our findings have important implications for the development of future therapeutic tools that aim to block protein aggregates propagation in the brain. PMID:26757959
Effect of chemical composition and microstructure on the mechanical behavior of fish scales from Megalops Atlanticus.

PubMed

Gil-Duran, S; Arola, D; Ossa, E A

2016-03-01

This paper presents an experimental study of the composition, microstructure and mechanical behavior of scales from the Megalops Atlanticus (Atlantic tarpon). The microstructure and composition were evaluated by Scanning Electron Microscopy (SEM) and RAMAN spectroscopy, respectively. The mechanical properties were evaluated in uniaxial tension as a function of position along the length of the fish (head, mid-length and tail). Results showed that the scales are composed of collagen and hydroxyapatite, and these constituents are distributed within three well-defined layers from the bottom to the top of the scale. The proportion of these layers with respect to the total scale thickness varies radially. The collagen fibers are arranged in plies with different orientations and with preferred orientation in the longitudinal direction of the fish. Results from the tensile tests showed that scales from Megalops Atlanticus exhibit variations in the elastic modulus as a function of body position. Additional testing performed with and without the highly mineralized top layers of the scale revealed that the mechanical behavior is anisotropic and that the highest strength was exhibited along the fish length. Furthermore, removing the top mineralized layers resulted in an increase in the tensile strength of the scale. Copyright © 2015 Elsevier Ltd. All rights reserved.
Molecular insights into human daily behavior

PubMed Central

Brown, Steven A.; Kunz, Dieter; Dumas, Amelie; Westermark, Pål O.; Vanselow, Katja; Tilmann-Wahnschaffe, Amely; Herzel, Hanspeter; Kramer, Achim

2008-01-01

Human beings exhibit wide variation in their timing of daily behavior. We and others have suggested previously that such differences might arise because of alterations in the period length of the endogenous human circadian oscillator. Using dermal fibroblast cells from skin biopsies of 28 subjects of early and late chronotype (11 “larks” and 17 “owls”), we have studied the circadian period lengths of these two groups, as well as their ability to phase-shift and entrain to environmental and chemical signals. We find not only period length differences between the two classes, but also significant changes in the amplitude and phase-shifting properties of the circadian oscillator among individuals with identical “normal” period lengths. Mathematical modeling shows that these alterations could also account for the extreme behavioral phenotypes of these subjects. We conclude that human chronotype may be influenced not only by the period length of the circadian oscillator, but also by cellular components that affect its amplitude and phase. In many instances, these changes can be studied at the molecular level in primary dermal cells. PMID:18227513
Role of Fiber Length on Phagocytosis & Inflammatory Response

NASA Astrophysics Data System (ADS)

Turkevich, Leonid; Stark, Carahline; Champion, Julie

2014-03-01

Asbestos fibers have long been associated with lung cancer death. The inability of immune cells (e.g. macrophages) to effectively remove asbestos leads to chronic inflammation and disease. This study examines the role of fiber length on toxicity at the cellular level using model glass fibers. A major challenge is obtaining single diameter fibers but differing in length. Samples of 1 micron diameter fibers with different length distributions were prepared: short fibers (less than 15 microns) by aggressive crushing, and long fibers (longer than 15 microns) by successive sedimentation. Time-lapse video microscopy monitored the interaction of MH-S murine alveolar macrophages with the fibers: short fibers were easily internalized by the macrophages, but long fibers resisted internalization over many hours. Production of TNF- α (tumor necrosis factor alpha), a general inflammatory secreted cytokine, and Cox-2 (cyclo-oxygenase-2), an enzyme that produces radicals, each exhibited a dose-dependence that was greater for long than for short fibers. These results corroborate the importance of fiber length in both physical and biochemical cell response and support epidemiological observations of higher toxicity for longer fibers.
Hydrological Storage Length Scales Represented by Remote Sensing Estimates of Soil Moisture and Precipitation

NASA Astrophysics Data System (ADS)

Akbar, Ruzbeh; Short Gianotti, Daniel; McColl, Kaighin A.; Haghighi, Erfan; Salvucci, Guido D.; Entekhabi, Dara

2018-03-01

The soil water content profile is often well correlated with the soil moisture state near the surface. They share mutual information such that analysis of surface-only soil moisture is, at times and in conjunction with precipitation information, reflective of deeper soil fluxes and dynamics. This study examines the characteristic length scale, or effective depth Δz, of a simple active hydrological control volume. The volume is described only by precipitation inputs and soil water dynamics evident in surface-only soil moisture observations. To proceed, first an observation-based technique is presented to estimate the soil moisture loss function based on analysis of soil moisture dry-downs and its successive negative increments. Then, the length scale Δz is obtained via an optimization process wherein the root-mean-squared (RMS) differences between surface soil moisture observations and its predictions based on water balance are minimized. The process is entirely observation-driven. The surface soil moisture estimates are obtained from the NASA Soil Moisture Active Passive (SMAP) mission and precipitation from the gauge-corrected Climate Prediction Center daily global precipitation product. The length scale Δz exhibits a clear east-west gradient across the contiguous United States (CONUS), such that large Δz depths (>200 mm) are estimated in wetter regions with larger mean precipitation. The median Δz across CONUS is 135 mm. The spatial variance of Δz is predominantly explained and influenced by precipitation characteristics. Soil properties, especially texture in the form of sand fraction, as well as the mean soil moisture state have a lesser influence on the length scale.
Deformation and Failure Mechanisms of Shape Memory Alloys

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

Daly, Samantha Hayes

2015-04-15

The goal of this research was to understand the fundamental mechanics that drive the deformation and failure of shape memory alloys (SMAs). SMAs are difficult materials to characterize because of the complex phase transformations that give rise to their unique properties, including shape memory and superelasticity. These phase transformations occur across multiple length scales (one example being the martensite-austenite twinning that underlies macroscopic strain localization) and result in a large hysteresis. In order to optimize the use of this hysteretic behavior in energy storage and damping applications, we must first have a quantitative understanding of this transformation behavior. Prior resultsmore » on shape memory alloys have been largely qualitative (i.e., mapping phase transformations through cracked oxide coatings or surface morphology). The PI developed and utilized new approaches to provide a quantitative, full-field characterization of phase transformation, conducting a comprehensive suite of experiments across multiple length scales and tying these results to theoretical and computational analysis. The research funded by this award utilized new combinations of scanning electron microscopy, diffraction, digital image correlation, and custom testing equipment and procedures to study phase transformation processes at a wide range of length scales, with a focus at small length scales with spatial resolution on the order of 1 nanometer. These experiments probe the basic connections between length scales during phase transformation. In addition to the insights gained on the fundamental mechanisms driving transformations in shape memory alloys, the unique experimental methodologies developed under this award are applicable to a wide range of solid-to-solid phase transformations and other strain localization mechanisms.« less
The scaling of urban surface water abundance and impairment with city size

NASA Astrophysics Data System (ADS)

Steele, M. K.

2018-03-01

Urbanization alters surface water compared to nonurban landscapes, yet little is known regarding how basic aquatic ecosystem characteristics, such as the abundance and impairment of surface water, differ with population size or regional context. This study examined the abundance, scaling, and impairment of surface water by quantifying the stream length, water body area, and impaired stream length for 3520 cities in the United States with populations from 2500 to 18 million. Stream length, water body area, and impaired stream length were quantified using the National Hydrography Dataset and the EPA's 303(d) list. These metrics were scaled with population and city area using single and piecewise power-law models and related to biophysical factors (precipitation, topography) and land cover. Results show that abundance of stream length and water body area in cities actually increases with city area; however, the per person abundance decreases with population size. Relative to population, impaired stream length did not increase until city populations were > 25,000 people, then scaled linearly with population. Some variation in abundance and impairment was explained by biophysical context and land cover. Development intensity correlated with stream density and impairment; however, those relationships depended on the orientation of the land covers. When high intensity development occupied the local elevation highs (+ 15 m) and undeveloped land the elevation lows, the percentage of impaired streams was less than the opposite land cover orientation (- 15 m) or very flat land. These results show that surface water abundance and impairment across contiguous US cities are influenced by city size and by biophysical setting interacting with land cover intensity.
Spindles and active vortices in a model of confined filament-motor mixtures.

PubMed

Head, David A; Briels, Wj; Gompper, Gerhard

2011-11-16

Robust self-organization of subcellular structures is a key principle governing the dynamics and evolution of cellular life. In fission yeast cells undergoing division, the mitotic spindle spontaneously emerges from the interaction of microtubules, motor proteins and the confining cell walls, and asters and vortices have been observed to self-assemble in quasi-two dimensional microtubule-kinesin assays. There is no clear microscopic picture of the role of the active motors driving this pattern formation, and the relevance of continuum modeling to filament-scale structures remains uncertain. Here we present results of numerical simulations of a discrete filament-motor protein model confined to a pressurised cylindrical box. Stable spindles, nematic configurations, asters and high-density semi-asters spontaneously emerge, the latter pair having also been observed in cytosol confined within emulsion droplets. State diagrams are presented delineating each stationary state as the pressure, motor speed and motor density are varied. We further highlight a parameter regime where vortices form exhibiting collective rotation of all filaments, but have a finite life-time before contracting to a semi-aster. Quantifying the distribution of life-times suggests this contraction is a Poisson process. Equivalent systems with fixed volume exhibit persistent vortices with stochastic switching in the direction of rotation, with switching times obeying similar statistics to contraction times in pressurised systems. Furthermore, we show that increasing the detachment rate of motors from filament plus-ends can both destroy vortices and turn some asters into vortices. We have shown that discrete filament-motor protein models provide new insights into the stationary and dynamical behavior of active gels and subcellular structures, because many phenomena occur on the length-scale of single filaments. Based on our findings, we argue the need for a deeper understanding of the microscopic activities underpinning macroscopic self-organization in active gels and urge further experiments to help bridge these lengths.
In Situ Spatiotemporal Mapping of Flow Fields around Seeded Stem Cells at the Subcellular Length Scale

PubMed Central

Song, Min Jae; Dean, David; Knothe Tate, Melissa L.

2010-01-01

A major hurdle to understanding and exploiting interactions between the stem cell and its environment is the lack of a tool for precise delivery of mechanical cues concomitant to observing sub-cellular adaptation of structure. These studies demonstrate the use of microscale particle image velocimetry (μ-PIV) for in situ spatiotemporal mapping of flow fields around mesenchymal stem cells, i.e. murine embryonic multipotent cell line C3H10T1/2, at the subcellular length scale, providing a tool for real time observation and analysis of stem cell adaptation to the prevailing mechanical milieu. In the absence of cells, computational fluid dynamics (CFD) predicts flow regimes within 12% of μ-PIV measures, achieving the technical specifications of the chamber and the flow rates necessary to deliver target shear stresses at a particular height from the base of the flow chamber. However, our μ-PIV studies show that the presence of cells per se as well as the density at which cells are seeded significantly influences local flow fields. Furthermore, for any given cell or cell seeding density, flow regimes vary significantly along the vertical profile of the cell. Hence, the mechanical milieu of the stem cell exposed to shape changing shear stresses, induced by fluid drag, varies with respect to proximity of surrounding cells as well as with respect to apical height. The current study addresses a previously unmet need to predict and observe both flow regimes as well as mechanoadaptation of cells in flow chambers designed to deliver precisely controlled mechanical signals to live cells. An understanding of interactions and adaptation in response to forces at the interface between the surface of the cell and its immediate local environment may be key for de novo engineering of functional tissues from stem cell templates as well as for unraveling the mechanisms underlying multiscale development, growth and adaptation of organisms. PMID:20862249
An Item Response Unfolding Model for Graphic Rating Scales

ERIC Educational Resources Information Center

Liu, Ying

2009-01-01

The graphic rating scale, a measurement tool used in many areas of psychology, usually takes a form of a fixed-length line segment, with both ends bounded and labeled as extreme responses. The raters mark somewhere on the line, and the length of the line segment from one endpoint to the mark is taken as the measure. An item response unfolding…

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