Modeling digits. Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients.

PubMed

Raspopovic, J; Marcon, L; Russo, L; Sharpe, J

2014-08-01

During limb development, digits emerge from the undifferentiated mesenchymal tissue that constitutes the limb bud. It has been proposed that this process is controlled by a self-organizing Turing mechanism, whereby diffusible molecules interact to produce a periodic pattern of digital and interdigital fates. However, the identities of the molecules remain unknown. By combining experiments and modeling, we reveal evidence that a Turing network implemented by Bmp, Sox9, and Wnt drives digit specification. We develop a realistic two-dimensional simulation of digit patterning and show that this network, when modulated by morphogen gradients, recapitulates the expression patterns of Sox9 in the wild type and in perturbation experiments. Our systems biology approach reveals how a combination of growth, morphogen gradients, and a self-organizing Turing network can achieve robust and reproducible pattern formation. Copyright © 2014, American Association for the Advancement of Science.

Development of novel microfluidic platforms for neural stem cell research

NASA Astrophysics Data System (ADS)

Chung, Bonggeun

This dissertation describes the development and characterization of novel microfluidic platforms to study proliferation, differentiation, migration, and apoptosis of neural stem cells (NSCs). NSCs hold tremendous promise for fundamental biological studies and cell-based therapies in human disorders. NSCs are defined as cells that can self-renew yet maintain the ability to generate the three principal cell types of the central nervous system such as neurons, astrocytes, and oligodendrocytes. NSCs therefore have therapeutic possibilities in multiple neurodevelopmental and neurodegenerative diseases. Despite their promise, cell-based therapies are limited by the inability to precisely control their behavior in culture. Compared to traditional culture tools, microfluidic platforms can provide much greater control over cell microenvironments and optimize proliferation and differentiation conditions of cells exposed to combinatorial mixtures of growth factors. Human NSCs were cultured for more than 1 week in the microfluidic device while constantly exposed to a continuous gradient of a growth factor mixture. NSCs proliferated and differentiated in a graded and proportional fashion that varied directly with growth factor concentration. In parallel to the study of growth and differentiation of NSCs, we are interested in proliferation and apoptosis of mouse NSCs exposed to morphogen gradients. Morphogen gradients are fundamental to animal brain development. Nonetheless, much controversy remains about the mechanisms by which morphogen gradients act on the developing brain. To overcome limitations of in-vitro models of gradients, we have developed a hybrid microfluidic platform that can mimic morphogen gradient profiles. Bone morphogenetic protein (BMP) activity in the developing cortex is graded and cortical NSC responses to BMPs are highly dependent on concentration and gradient slope of BMPs. To make novel microfluidic devices integrated with multiple functions, we have also developed a microfluidic multi-injector (MMI) that can generate temporal and spatial concentration gradients. MMI consists of fluidic channels and control channels with pneumatically actuated on-chip barrier valves. Repetitive actuations of on-chip valves control pulsatile release of solution that establishes microscopic chemical gradients. The development of novel gradient-generating microfluidic platforms will help in advancing our understanding of brain development and provide a versatile tool with basic and applied studies in stem cell biology.

A computational statistics approach for estimating the spatial range of morphogen gradients

PubMed Central

Kanodia, Jitendra S.; Kim, Yoosik; Tomer, Raju; Khan, Zia; Chung, Kwanghun; Storey, John D.; Lu, Hang; Keller, Philipp J.; Shvartsman, Stanislav Y.

2011-01-01

A crucial issue in studies of morphogen gradients relates to their range: the distance over which they can act as direct regulators of cell signaling, gene expression and cell differentiation. To address this, we present a straightforward statistical framework that can be used in multiple developmental systems. We illustrate the developed approach by providing a point estimate and confidence interval for the spatial range of the graded distribution of nuclear Dorsal, a transcription factor that controls the dorsoventral pattern of the Drosophila embryo. PMID:22007136

Protein gradients in single cells induced by their coupling to "morphogen"-like diffusion

NASA Astrophysics Data System (ADS)

Nandi, Saroj Kumar; Safran, Sam A.

2018-05-01

One of the many ways cells transmit information within their volume is through steady spatial gradients of different proteins. However, the mechanism through which proteins without any sources or sinks form such single-cell gradients is not yet fully understood. One of the models for such gradient formation, based on differential diffusion, is limited to proteins with large ratios of their diffusion constants or to specific protein-large molecule interactions. We introduce a novel mechanism for gradient formation via the coupling of the proteins within a single cell with a molecule, that we call a "pronogen," whose action is similar to that of morphogens in multi-cell assemblies; the pronogen is produced with a fixed flux at one side of the cell. This coupling results in an effectively non-linear diffusion degradation model for the pronogen dynamics within the cell, which leads to a steady-state gradient of the protein concentration. We use stability analysis to show that these gradients are linearly stable with respect to perturbations.

Activin signalling and response to a morphogen gradient.

PubMed

Gurdon, J B; Harger, P; Mitchell, A; Lemaire, P

1994-10-06

Using combinations of amphibian embryo tissues, it is shown that the selection of genes expressed by a cell is determined by its distance from a source of activin, a peptide growth factor contained in vegetal cells and able to induce other cells to form mesoderm. This long-range signal spreads over at least 10 cell diameters in a few hours. It does so by passive diffusion, because it can by-pass cells that do not themselves respond to the signal nor synthesize protein. These results provide direct support for the operation of a morphogen concentration gradient in vertebrate development.

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression

PubMed Central

Verd, Berta; Crombach, Anton

2017-01-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development. PMID:28158178

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression.

PubMed

Verd, Berta; Crombach, Anton; Jaeger, Johannes

2017-02-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development.

Dense Bicoid hubs accentuate binding along the morphogen gradient

PubMed Central

Mir, Mustafa; Reimer, Armando; Haines, Jenna E.; Li, Xiao-Yong; Stadler, Michael; Garcia, Hernan

2017-01-01

Morphogen gradients direct the spatial patterning of developing embryos; however, the mechanisms by which these gradients are interpreted remain elusive. Here we used lattice light-sheet microscopy to perform in vivo single-molecule imaging in early Drosophila melanogaster embryos of the transcription factor Bicoid that forms a gradient and initiates patterning along the anteroposterior axis. In contrast to canonical models, we observed that Bicoid binds to DNA with a rapid off rate throughout the embryo such that its average occupancy at target loci is on-rate-dependent. We further observed Bicoid forming transient “hubs” of locally high density that facilitate binding as factor levels drop, including in the posterior, where we observed Bicoid binding despite vanishingly low protein levels. We propose that localized modulation of transcription factor on rates via clustering provides a general mechanism to facilitate binding to low-affinity targets and that this may be a prevalent feature of other developmental transcription factors. PMID:28982761

Color-pattern analysis of eyespots in butterfly wings: a critical examination of morphogen gradient models.

PubMed

Otaki, Joji M

2011-06-01

Butterfly wing color patterns consist of many color-pattern elements such as eyespots. It is believed that eyespot patterns are determined by a concentration gradient of a single morphogen species released by diffusion from the prospective eyespot focus in conjunction with multiple thresholds in signal-receiving cells. As alternatives to this single-morphogen model, more flexible multiple-morphogen model and induction model can be proposed. However, the relevance of these conceptual models to actual eyespots has not been examined systematically. Here, representative eyespots from nymphalid butterflies were analyzed morphologically to determine if they are consistent with these models. Measurement of ring widths of serial eyespots from a single wing surface showed that the proportion of each ring in an eyespot is quite different among homologous rings of serial eyespots of different sizes. In asymmetric eyespots, each ring is distorted to varying degrees. In extreme cases, only a portion of rings is expressed remotely from the focus. Similarly, there are many eyespots where only certain rings are deleted, added, or expanded. In an unusual case, the central area of an eyespot is composed of multiple "miniature eyespots," but the overall macroscopic eyespot structure is maintained. These results indicate that each eyespot ring has independence and flexibility to a certain degree, which is less consistent with the single-morphogen model. Considering a "periodic eyespot", which has repeats of a set of rings, damage-induced eyespots in mutants, and a scale-size distribution pattern in an eyespot, the induction model is the least incompatible with the actual eyespot diversity.

Carrier of Wingless (Cow), a Secreted Heparan Sulfate Proteoglycan, Promotes Extracellular Transport of Wingless

PubMed Central

Chang, Yung-Heng; Sun, Yi Henry

2014-01-01

Morphogens are signaling molecules that regulate growth and patterning during development by forming a gradient and activating different target genes at different concentrations. The extracellular distribution of morphogens is tightly regulated, with the Drosophila morphogen Wingless (Wg) relying on Dally-like (Dlp) and transcytosis for its distribution. However, in the absence of Dlp or endocytic activity, Wg can still move across cells along the apical (Ap) surface. We identified a novel secreted heparan sulfate proteoglycan (HSPG) that binds to Wg and promotes its extracellular distribution by increasing Wg mobility, which was thus named Carrier of Wg (Cow). Cow promotes the Ap transport of Wg, independent of Dlp and endocytosis, and this function addresses a previous gap in the understanding of Wg movement. This is the first example of a diffusible HSPG acting as a carrier to promote the extracellular movement of a morphogen. PMID:25360738

EFFECTS OF SOG ON DPP-RECEPTOR BINDING*

PubMed Central

LOU, YUAN; NIE, QING; WAN, FREDERIC Y. M.

2007-01-01

Concentration gradients of morphogens are known to be instrumental in cell signaling and tissue patterning. Of interest here is how the presence of a competitor of BMP ligands affects cell signaling. The effects of Sog on the binding of Dpp with cell receptors are analyzed for dorsal-ventral morphogen gradient formation in vertebrate and Drosophila embryos. This prototype system includes diffusing ligands, degradation of morphogens, and cleavage of Dpp-Sog complexes by Tolloid to free up Dpp. Simple and biologically meaningful necessary and sufficient conditions for the existence of a steady state gradient configuration are established, and existence theorems are proved. For high Sog production rates (relative to the Dpp production rate), it is found that the steady state configuration exhibits a more intense Dpp-receptor concentration near the dorsal midline. Numerical simulations of the evolution of the system show that, beyond some threshold Sog production rate, the transient Dpp-receptor concentration at the dorsal midline would become more intense than that of the steady state, before subsiding and approaching a nonuniform steady state of lower magnitude. The magnitude of the transient concentration has been found to increase by several fold with increasing Sog production rate. The highly intense Dpp activity at and around the dorsal midline is consistent with available experimental observations and other analytical studies. PMID:17377624

Multiscale diffusion in the mitotic Drosophila melanogaster syncytial blastoderm

PubMed Central

Daniels, Brian R.; Rikhy, Richa; Renz, Malte; Dobrowsky, Terrence M.; Lippincott-Schwartz, Jennifer

2012-01-01

Despite the fundamental importance of diffusion for embryonic morphogen gradient formation in the early Drosophila melanogaster embryo, there remains controversy regarding both the extent and the rate of diffusion of well-characterized morphogens. Furthermore, the recent observation of diffusional “compartmentalization” has suggested that diffusion may in fact be nonideal and mediated by an as-yet-unidentified mechanism. Here, we characterize the effects of the geometry of the early syncytial Drosophila embryo on the effective diffusivity of cytoplasmic proteins. Our results demonstrate that the presence of transient mitotic membrane furrows results in a multiscale diffusion effect that has a significant impact on effective diffusion rates across the embryo. Using a combination of live-cell experiments and computational modeling, we characterize these effects and relate effective bulk diffusion rates to instantaneous diffusion coefficients throughout the syncytial blastoderm nuclear cycle phase of the early embryo. This multiscale effect may be related to the effect of interphase nuclei on effective diffusion, and thus we propose that an as-yet-unidentified role of syncytial membrane furrows is to temporally regulate bulk embryonic diffusion rates to balance the multiscale effect of interphase nuclei, which ultimately stabilizes the shapes of various morphogen gradients. PMID:22592793

Focal high cell density generates a gradient of patterns in self-organizing vascular mesenchymal cells.

PubMed

Cheng, Henry; Reddy, Aneela; Sage, Andrew; Lu, Jinxiu; Garfinkel, Alan; Tintut, Yin; Demer, Linda L

2012-01-01

In embryogenesis, structural patterns, such as vascular branching, may form via a reaction-diffusion mechanism in which activator and inhibitor morphogens guide cells into periodic aggregates. We previously found that vascular mesenchymal cells (VMCs) spontaneously aggregate into nodular structures and that morphogen pairs regulate the aggregation into patterns of spots and stripes. To test the effect of a focal change in activator morphogen on VMC pattern formation, we created a focal zone of high cell density by plating a second VMC layer within a cloning ring over a confluent monolayer. After 24 h, the ring was removed and pattern formation monitored by phase-contrast microscopy. At days 2-8, the patterns progressed from uniform distributions to swirl, labyrinthine and spot patterns. Within the focal high-density zone (HDZ) and a narrow halo zone, cells aggregated into spot patterns, whilst in the outermost zone of the plate, cells formed a labyrinthine pattern. The area occupied by aggregates was significantly greater in the outermost zone than in the HDZ or halo. The rate of pattern progression within the HDZ increased as a function of its plating density. Thus, focal differences in cell density may drive pattern formation gradients in tissue architecture, such as vascular branching. Copyright © 2012 S. Karger AG, Basel.

Decapentaplegic and growth control in the developing Drosophila wing.

PubMed

Akiyama, Takuya; Gibson, Matthew C

2015-11-19

As a central model for morphogen action during animal development, the bone morphogenetic protein 2/4 (BMP2/4)-like ligand Decapentaplegic (Dpp) is proposed to form a long-range signalling gradient that directs both growth and pattern formation during Drosophila wing disc development. While the patterning role of Dpp secreted from a stripe of cells along the anterior-posterior compartmental boundary is well established, the mechanism by which a Dpp gradient directs uniform cell proliferation remains controversial and poorly understood. Here, to determine the precise spatiotemporal requirements for Dpp during wing disc development, we use CRISPR-Cas9-mediated genome editing to generate a flippase recognition target (FRT)-dependent conditional null allele. By genetically removing Dpp from its endogenous stripe domain, we confirm the requirement of Dpp for the activation of a downstream phospho-Mothers against dpp (p-Mad) gradient and the regulation of the patterning targets spalt (sal), optomotor blind (omb; also known as bifid) and brinker (brk). Surprisingly, however, third-instar wing blade primordia devoid of compartmental dpp expression maintain relatively normal rates of cell proliferation and exhibit only mild defects in growth. These results indicate that during the latter half of larval development, the Dpp morphogen gradient emanating from the anterior-posterior compartment boundary is not directly required for wing disc growth.

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.

In vitro reconstruction of branched tubular structures from lung epithelial cells in high cell concentration gradient environment.

PubMed

Hagiwara, Masaya; Peng, Fei; Ho, Chih-Ming

2015-01-27

We have succeeded in developing hollow branching structure in vitro commonly observed in lung airway using primary lung airway epithelial cells. Cell concentration gradient is the key factor that determines production of the branching cellular structures, as optimization of this component removes the need for heterotypic culture. The higher cell concentration leads to the more production of morphogens and increases the growth rate of cells. However, homogeneous high cell concentration does not make a branching structure. Branching requires sufficient space in which cells can grow from a high concentration toward a low concentration. Simulation performed using a reaction-diffusion model revealed that long-range inhibition prevents cells from branching when they are homogeneously spread in culture environments, while short-range activation from neighboring cells leads to positive feedback. Thus, a high cell concentration gradient is required to make branching structures. Spatial distributions of morphogens, such as BMP-4, play important roles in the pattern formation. This simple yet robust system provides an optimal platform for the further study and understanding of branching mechanisms in the lung airway, and will facilitate chemical and genetic studies of lung morphogenesis programs.

Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities.

PubMed

Harfe, Brian D; Scherz, Paul J; Nissim, Sahar; Tian, Hua; McMahon, Andrew P; Tabin, Clifford J

2004-08-20

The zone of polarizing activity (ZPA) in the posterior limb bud produces Sonic Hedgehog (Shh) protein, which plays a critical role in establishing distinct fates along the anterior-posterior axis. This activity has been modeled as a concentration-dependent response to a diffusible morphogen. Using recombinase base mapping in the mouse, we determine the ultimate fate of the Shh-producing cells. Strikingly, the descendants of the Shh-producing cells encompass all cells in the two most posterior digits and also contribute to the middle digit. Our analysis suggests that, while specification of the anterior digits depends upon differential concentrations of Shh, the length of time of exposure to Shh is critical in the specification of the differences between the most posterior digits. Genetic studies of the effects of limiting accessibility of Shh within the limb support this model, in which the effect of the Shh morphogen is dictated by a temporal as well as a spatial gradient.

Formation of the long range Dpp morphogen gradient.

PubMed

Schwank, Gerald; Dalessi, Sascha; Yang, Schu-Fee; Yagi, Ryohei; de Lachapelle, Aitana Morton; Affolter, Markus; Bergmann, Sven; Basler, Konrad

2011-07-01

The TGF-β homolog Decapentaplegic (Dpp) acts as a secreted morphogen in the Drosophila wing disc, and spreads through the target tissue in order to form a long range concentration gradient. Despite extensive studies, the mechanism by which the Dpp gradient is formed remains controversial. Two opposing mechanisms have been proposed: receptor-mediated transcytosis (RMT) and restricted extracellular diffusion (RED). In these scenarios the receptor for Dpp plays different roles. In the RMT model it is essential for endocytosis, re-secretion, and thus transport of Dpp, whereas in the RED model it merely modulates Dpp distribution by binding it at the cell surface for internalization and subsequent degradation. Here we analyzed the effect of receptor mutant clones on the Dpp profile in quantitative mathematical models representing transport by either RMT or RED. We then, using novel genetic tools, experimentally monitored the actual Dpp gradient in wing discs containing receptor gain-of-function and loss-of-function clones. Gain-of-function clones reveal that Dpp binds in vivo strongly to the type I receptor Thick veins, but not to the type II receptor Punt. Importantly, results with the loss-of-function clones then refute the RMT model for Dpp gradient formation, while supporting the RED model in which the majority of Dpp is not bound to Thick veins. Together our results show that receptor-mediated transcytosis cannot account for Dpp gradient formation, and support restricted extracellular diffusion as the main mechanism for Dpp dispersal. The properties of this mechanism, in which only a minority of Dpp is receptor-bound, may facilitate long-range distribution.

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

Mathematical modelling in developmental biology.

PubMed

Vasieva, Olga; Rasolonjanahary, Manan'Iarivo; Vasiev, Bakhtier

2013-06-01

In recent decades, molecular and cellular biology has benefited from numerous fascinating developments in experimental technique, generating an overwhelming amount of data on various biological objects and processes. This, in turn, has led biologists to look for appropriate tools to facilitate systematic analysis of data. Thus, the need for mathematical techniques, which can be used to aid the classification and understanding of this ever-growing body of experimental data, is more profound now than ever before. Mathematical modelling is becoming increasingly integrated into biological studies in general and into developmental biology particularly. This review outlines some achievements of mathematics as applied to developmental biology and demonstrates the mathematical formulation of basic principles driving morphogenesis. We begin by describing a mathematical formalism used to analyse the formation and scaling of morphogen gradients. Then we address a problem of interplay between the dynamics of morphogen gradients and movement of cells, referring to mathematical models of gastrulation in the chick embryo. In the last section, we give an overview of various mathematical models used in the study of the developmental cycle of Dictyostelium discoideum, which is probably the best example of successful mathematical modelling in developmental biology.

In Vitro Polarization of Colonoids to Create an Intestinal Stem Cell Compartment

PubMed Central

Attayek, Peter J.; Ahmad, Asad A.; Wang, Yuli; Williamson, Ian; Sims, Christopher E.; Magness, Scott T.; Allbritton, Nancy L.

2016-01-01

The polarity of proliferative and differentiated cellular compartments of colonic crypts is believed to be specified by gradients of key mitogens and morphogens. Indirect evidence demonstrates a tight correlation between Wnt- pathway activity and the basal-luminal patterning; however, to date there has been no direct experimental manipulation demonstrating that a chemical gradient of signaling factors can produce similar patterning under controlled conditions. In the current work, colonic organoids (colonoids) derived from cultured, multicellular organoid fragments or single stem cells were exposed in culture to steep linear gradients of two Wnt-signaling ligands, Wnt-3a and R-spondin1. The use of a genetically engineered Sox9-Sox9EGFP:CAGDsRED reporter gene mouse model and EdU-based labeling enabled crypt patterning to be quantified in the developing colonoids. Colonoids derived from multicellular fragments cultured for 5 days under a Wnt-3a or a combined Wnt-3a and R-spondin1 gradient were highly polarized with proliferative cells localizing to the region of the higher morphogen concentration. In a Wnt-3a gradient, Sox9EGFP polarization was 7.3 times greater than that of colonoids cultured in the absence of a gradient; and the extent of EdU polarization was 2.2 times greater than that in the absence of a gradient. Under a Wnt-3a/R-spondin1 gradient, Sox9EGFP polarization was 8.2 times greater than that of colonoids cultured in the absence of a gradient while the extent of EdU polarization was 10 times greater than that in the absence of a gradient. Colonoids derived from single stem cells cultured in Wnt-3a/R-spondin1 gradients were most highly polarized demonstrated by a Sox9EGFP polarization 20 times that of colonoids grown in the absence of a gradient. This data provides direct evidence that a linear gradient of Wnt signaling factors applied to colonic stem cells is sufficient to direct patterning of the colonoid unit in culture. PMID:27100890

Systems biology derived source-sink mechanism of BMP gradient formation

PubMed Central

Zinski, Joseph; Bu, Ye; Wang, Xu; Dou, Wei

2017-01-01

A morphogen gradient of Bone Morphogenetic Protein (BMP) signaling patterns the dorsoventral embryonic axis of vertebrates and invertebrates. The prevailing view in vertebrates for BMP gradient formation is through a counter-gradient of BMP antagonists, often along with ligand shuttling to generate peak signaling levels. To delineate the mechanism in zebrafish, we precisely quantified the BMP activity gradient in wild-type and mutant embryos and combined these data with a mathematical model-based computational screen to test hypotheses for gradient formation. Our analysis ruled out a BMP shuttling mechanism and a bmp transcriptionally-informed gradient mechanism. Surprisingly, rather than supporting a counter-gradient mechanism, our analyses support a fourth model, a source-sink mechanism, which relies on a restricted BMP antagonist distribution acting as a sink that drives BMP flux dorsally and gradient formation. We measured Bmp2 diffusion and found that it supports the source-sink model, suggesting a new mechanism to shape BMP gradients during development. PMID:28826472

Systems biology derived source-sink mechanism of BMP gradient formation.

PubMed

Zinski, Joseph; Bu, Ye; Wang, Xu; Dou, Wei; Umulis, David; Mullins, Mary C

2017-08-09

A morphogen gradient of Bone Morphogenetic Protein (BMP) signaling patterns the dorsoventral embryonic axis of vertebrates and invertebrates. The prevailing view in vertebrates for BMP gradient formation is through a counter-gradient of BMP antagonists, often along with ligand shuttling to generate peak signaling levels. To delineate the mechanism in zebrafish, we precisely quantified the BMP activity gradient in wild-type and mutant embryos and combined these data with a mathematical model-based computational screen to test hypotheses for gradient formation. Our analysis ruled out a BMP shuttling mechanism and a bmp transcriptionally-informed gradient mechanism. Surprisingly, rather than supporting a counter-gradient mechanism, our analyses support a fourth model, a source-sink mechanism, which relies on a restricted BMP antagonist distribution acting as a sink that drives BMP flux dorsally and gradient formation. We measured Bmp2 diffusion and found that it supports the source-sink model, suggesting a new mechanism to shape BMP gradients during development.

Application of reaction-diffusion models to cell patterning in Xenopus retina. Initiation of patterns and their biological stability.

PubMed

Shoaf, S A; Conway, K; Hunt, R K

1984-08-07

We have examined the behavior of two reaction-diffusion models, originally proposed by Gierer & Meinhardt (1972) and by Kauffman, Shymko & Trabert (1978), for biological pattern formation. Calculations are presented for pattern formation on a disc (approximating the geometry of a number of embryonic anlagen including the frog eye rudiment), emphasizing the sensitivity of patterns to changes in initial conditions and to perturbations in the geometry of the morphogen-producing space. Analysis of the linearized equations from the models enabled us to select appropriate parameters and disc size for pattern growth. A computer-implemented finite element method was used to solve the non-linear model equations reiteratively. For the Gierer-Meinhardt model, initial activation (varying in size over two orders of magnitude) of one point on the disc's edge was sufficient to generate the primary gradient. Various parts of the disc were removed (remaining only as diffusible space) from the morphogen-producing cycle to investigate the effects of cells dropping out of the cycle due to cell death or malfunction (single point removed) or differentiation (center removed), as occur in the Xenopus eye rudiment. The resulting patterns had the same general shape and amplitude as normal gradients. Nor did a two-fold increase in disc size affect the pattern-generating ability of the model. Disc fragments bearing their primary gradient patterns were fused (with gradients in opposite directions, but each parallel to the fusion line). The resulting patterns generated by the model showed many similarities to results of "compound eye" experiments in Xenopus. Similar patterns were obtained with the model of Kauffman's group (1978), but we found less stability of the pattern subject to simulations of central differentiation. However, removal of a single point from the morphogen cycle (cell death) did not result in any change. The sensitivity of the Kauffman et al. model to shape perturbations is not surprising since the model was originally designed to use shape and increasing size during growth to generate a sequence of transient patterns. However, the Gierer-Meinhardt model is remarkably stable even when subjected to a wide range of perturbations in the diffusible space, thus allowing it to cope with normal biological variability, and offering an exciting range of possibilities for reaction-diffusion models as mechanisms underlying the spatial patterns of tissue structures.

Gas1 extends the range of Hedgehog action by facilitating its signaling

PubMed Central

Martinelli, David C.; Fan, Chen-Ming

2007-01-01

Cellular signaling initiated by Hedgehog binding to Patched1 has profound importance in mammalian embryogenesis, genetic disease, and cancer. Hedgehog acts as a morphogen to specify distinctive cell fates using different concentration thresholds, but our knowledge of how the concentration gradient is interpreted into the activity gradient is incomplete. The membrane protein Growth Arrest-Specific Gene 1 (GAS1) was thought to be a negative regulator of the Hedgehog concentration gradient. Here, we report unexpected genetic evidence that Gas1 positively regulates Hedgehog signaling in multiple developmental contexts, an effect particularly noticeable at regions where Hedgehog acts at low concentration. Using a combination of in vitro cell culture and in ovo electroporation assays, we demonstrate that GAS1 acts cooperatively with Patched1 for Hedgehog binding and enhances signaling activity in a cell-autonomous manner. Our data support a model in which GAS1 helps transform the Hedgehog protein gradient into the observed activity gradient. We propose that Gas1 is an evolutionarily novel, vertebrate-specific Hedgehog pathway regulator. PMID:17504940

Perspectives on Intra- and Intercellular Trafficking of Hedgehog for Tissue Patterning

PubMed Central

Simon, Eléanor; Aguirre-Tamaral, Adrián; Aguilar, Gustavo; Guerrero, Isabel

2016-01-01

Intercellular communication is a fundamental process for correct tissue development. The mechanism of this process involves, among other things, the production and secretion of signaling molecules by specialized cell types and the capability of these signals to reach the target cells in order to trigger specific responses. Hedgehog (Hh) is one of the best-studied signaling pathways because of its importance during morphogenesis in many organisms. The Hh protein acts as a morphogen, activating its targets at a distance in a concentration-dependent manner. Post-translational modifications of Hh lead to a molecule covalently bond to two lipid moieties. These lipid modifications confer Hh high affinity to lipidic membranes, and intense studies have been carried out to explain its release into the extracellular matrix. This work reviews Hh molecule maturation, the intracellular recycling needed for its secretion and the proposed carriers to explain Hh transportation to the receiving cells. Special focus is placed on the role of specialized filopodia, also named cytonemes, in morphogen transport and gradient formation. PMID:29615597

Perspectives on Intra- and Intercellular Trafficking of Hedgehog for Tissue Patterning.

PubMed

Simon, Eléanor; Aguirre-Tamaral, Adrián; Aguilar, Gustavo; Guerrero, Isabel

2016-12-02

Intercellular communication is a fundamental process for correct tissue development. The mechanism of this process involves, among other things, the production and secretion of signaling molecules by specialized cell types and the capability of these signals to reach the target cells in order to trigger specific responses. Hedgehog (Hh) is one of the best-studied signaling pathways because of its importance during morphogenesis in many organisms. The Hh protein acts as a morphogen, activating its targets at a distance in a concentration-dependent manner. Post-translational modifications of Hh lead to a molecule covalently bond to two lipid moieties. These lipid modifications confer Hh high affinity to lipidic membranes, and intense studies have been carried out to explain its release into the extracellular matrix. This work reviews Hh molecule maturation, the intracellular recycling needed for its secretion and the proposed carriers to explain Hh transportation to the receiving cells. Special focus is placed on the role of specialized filopodia, also named cytonemes, in morphogen transport and gradient formation.

Local accumulation times for spatial difference in morphogen concentration

NASA Astrophysics Data System (ADS)

Wen, Xiaoqing; Yin, Hongwei

During development of multicellular organisms, spatial patterns of cells and tissue organizations rely on the action of morphogens, which are signaling molecules and act as dose-dependent regulators of gene expression and cellular differentiation. Since some experimental evidences have indicated that the spatial difference in morphogen concentration regulates cellular proliferation rather than this concentration profile in developing tissues, we propose spatially discrete models to describe this difference for a synthesis-diffusion-degradation process of morphogen in infinite and finite development fields, respectively. For both of models, we respectively derive analytical expressions of local accumulation times, which are required to form the steady state of the spatial difference in morphogen concentration. Our results show that the local accumulation times for the spatial difference in morphogen concentrations are different from the ones for morphogen concentration profiles.

Effects of analogues of hydra peptide morphogen on DNA synthesis in the myocardium of newborn albino rats.

PubMed

Sazonova, E N; Yakovenko, I G; Kryzhanovskaya, S Yu; Budylev, A A; Timoshin, S S

2012-01-01

DNA-synthetic activity of myocardial cells was studied by (3)H-thymidine autoradiography in newborn albino rats after intraperitoneal injection of hydra peptide morphogen and its analogues. Administration of hydra peptide morphogen stimulated proliferative activity in the myocardium. Short analogues of hydra peptide morphogen, 6C and 3C peptides, produced a similar effect. Administration of arginine-containing analogue of hydra peptide morphogen significantly reduced the number of DNA-synthesizing nuclei in the ventricular myocardium of newborn albino rats. The role of the structure of the peptide molecule in the realization of the morphogenetic effects of hydra peptide morphogen is discussed.

A Model of Controlled Growth

NASA Astrophysics Data System (ADS)

Bressan, Alberto; Lewicka, Marta

2018-03-01

We consider a free boundary problem for a system of PDEs, modeling the growth of a biological tissue. A morphogen, controlling volume growth, is produced by specific cells and then diffused and absorbed throughout the domain. The geometric shape of the growing tissue is determined by the instantaneous minimization of an elastic deformation energy, subject to a constraint on the volumetric growth. For an initial domain with C}^{2,α boundary, our main result establishes the local existence and uniqueness of a classical solution, up to a rigid motion.

Antagonistic Self-Organizing Patterning Systems Control Maintenance and Regeneration of the Anteroposterior Axis in Planarians.

PubMed

Stückemann, Tom; Cleland, James Patrick; Werner, Steffen; Thi-Kim Vu, Hanh; Bayersdorf, Robert; Liu, Shang-Yun; Friedrich, Benjamin; Jülicher, Frank; Rink, Jochen Christian

2017-02-06

Planarian flatworms maintain their body plan in the face of constant internal turnover and can regenerate from arbitrary tissue fragments. Both phenomena require self-maintaining and self-organizing patterning mechanisms, the molecular mechanisms of which remain poorly understood. We show that a morphogenic gradient of canonical Wnt signaling patterns gene expression along the planarian anteroposterior (A/P) axis. Our results demonstrate that gradient formation likely occurs autonomously in the tail and that an autoregulatory module of Wnt-mediated Wnt expression both shapes the gradient at steady state and governs its re-establishment during regeneration. Functional antagonism between the tail Wnt gradient and an unknown head patterning system further determines the spatial proportions of the planarian A/P axis and mediates mutually exclusive molecular fate choices during regeneration. Overall, our results suggest that the planarian A/P axis is patterned by self-organizing patterning systems deployed from either end that are functionally coupled by mutual antagonism. Copyright © 2017 Elsevier Inc. All rights reserved.

On the Relationships between Generative Encodings, Regularity, and Learning Abilities when Evolving Plastic Artificial Neural Networks

PubMed Central

Tonelli, Paul; Mouret, Jean-Baptiste

2013-01-01

A major goal of bio-inspired artificial intelligence is to design artificial neural networks with abilities that resemble those of animal nervous systems. It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks, and (2) synaptic plasticity, which allows neural networks to change during their lifetime. So far, these two topics have been mainly studied separately. The present paper shows that they are actually deeply connected. Using a simple operant conditioning task and a classic evolutionary algorithm, we compare three ways to encode plastic neural networks: a direct encoding, a developmental encoding inspired by computational neuroscience models, and a developmental encoding inspired by morphogen gradients (similar to HyperNEAT). Our results suggest that using a developmental encoding could improve the learning abilities of evolved, plastic neural networks. Complementary experiments reveal that this result is likely the consequence of the bias of developmental encodings towards regular structures: (1) in our experimental setup, encodings that tend to produce more regular networks yield networks with better general learning abilities; (2) whatever the encoding is, networks that are the more regular are statistically those that have the best learning abilities. PMID:24236099

Notochord-derived Shh concentrates in close association with the apically positioned basal body in neural target cells and forms a dynamic gradient during neural patterning.

PubMed

Chamberlain, Chester E; Jeong, Juhee; Guo, Chaoshe; Allen, Benjamin L; McMahon, Andrew P

2008-03-01

Sonic hedgehog (Shh) ligand secreted by the notochord induces distinct ventral cell identities in the adjacent neural tube by a concentration-dependent mechanism. To study this process, we genetically engineered mice that produce bioactive, fluorescently labeled Shh from the endogenous locus. We show that Shh ligand concentrates in close association with the apically positioned basal body of neural target cells, forming a dynamic, punctate gradient in the ventral neural tube. Both ligand lipidation and target field response influence the gradient profile, but not the ability of Shh to concentrate around the basal body. Further, subcellular analysis suggests that Shh from the notochord might traffic into the neural target field by means of an apical-to-basal-oriented microtubule scaffold. This study, in which we directly observe, measure, localize and modify notochord-derived Shh ligand in the context of neural patterning, provides several new insights into mechanisms of Shh morphogen action.

The wing and the eye: a parsimonious theory for scaling and growth control?

PubMed

Romanova-Michaelides, Maria; Aguilar-Hidalgo, Daniel; Jülicher, Frank; Gonzalez-Gaitan, Marcos

2015-01-01

How a developing organ grows and patterns to its final shape is an important question in developmental biology. Studies of growth and patterning in the Drosophila wing imaginal disc have identified a key player, the morphogen Decapentaplegic (Dpp). These studies provided insights into our understanding of growth control and scaling: expansion of the Dpp gradient correlated with the growth of the tissue. A recent report on growth of a Drosophila organ other than the wing, the eye imaginal disc, prompts a reconsideration of our models of growth control. Despite striking differences between the two, the Dpp gradient scales with the target tissues of both organs and the growth of both the wing and the eye is controlled by Dpp. The goal of this review is to discuss whether a parsimonious model of scaling and growth control can explain the relationship between the Dpp gradient and growth in these two different developmental systems. © 2015 Wiley Periodicals, Inc.

A Model for Selection of Eyespots on Butterfly Wings.

PubMed

Sekimura, Toshio; Venkataraman, Chandrasekhar; Madzvamuse, Anotida

2015-01-01

The development of eyespots on the wing surface of butterflies of the family Nympalidae is one of the most studied examples of biological pattern formation.However, little is known about the mechanism that determines the number and precise locations of eyespots on the wing. Eyespots develop around signaling centers, called foci, that are located equidistant from wing veins along the midline of a wing cell (an area bounded by veins). A fundamental question that remains unsolved is, why a certain wing cell develops an eyespot, while other wing cells do not. We illustrate that the key to understanding focus point selection may be in the venation system of the wing disc. Our main hypothesis is that changes in morphogen concentration along the proximal boundary veins of wing cells govern focus point selection. Based on previous studies, we focus on a spatially two-dimensional reaction-diffusion system model posed in the interior of each wing cell that describes the formation of focus points. Using finite element based numerical simulations, we demonstrate that variation in the proximal boundary condition is sufficient to robustly select whether an eyespot focus point forms in otherwise identical wing cells. We also illustrate that this behavior is robust to small perturbations in the parameters and geometry and moderate levels of noise. Hence, we suggest that an anterior-posterior pattern of morphogen concentration along the proximal vein may be the main determinant of the distribution of focus points on the wing surface. In order to complete our model, we propose a two stage reaction-diffusion system model, in which an one-dimensional surface reaction-diffusion system, posed on the proximal vein, generates the morphogen concentrations that act as non-homogeneous Dirichlet (i.e., fixed) boundary conditions for the two-dimensional reaction-diffusion model posed in the wing cells. The two-stage model appears capable of generating focus point distributions observed in nature. We therefore conclude that changes in the proximal boundary conditions are sufficient to explain the empirically observed distribution of eyespot focus points on the entire wing surface. The model predicts, subject to experimental verification, that the source strength of the activator at the proximal boundary should be lower in wing cells in which focus points form than in those that lack focus points. The model suggests that the number and locations of eyespot foci on the wing disc could be largely controlled by two kinds of gradients along two different directions, that is, the first one is the gradient in spatially varying parameters such as the reaction rate along the anterior-posterior direction on the proximal boundary of the wing cells, and the second one is the gradient in source values of the activator along the veins in the proximal-distal direction of the wing cell.

The VACTERL Association as a disturbance of cell fate determination.

PubMed

Lubinsky, Mark

2015-11-01

Cases diagnosed as the VACTERL Association are heterogeneous, and can involve other associations arising from different developmental processes with midline effects. However, these often lack the classic radial ray anomalies that help make VACTERL distinct. A more specific association can be delineated based on teratogenic disturbances affecting vulnerabilities associated with the establishment of cell fate through positional information, with two basic weaknesses: (i) The midline, where topological properties such as reduced lateral information should make information losses more likely; (ii) Increased distal sensitivity at the end of a morphogen gradient in the limbs, where both duplications and deficiencies can arise from similar disturbances. Vertebral, cardiac, anal-rectal, and tracheo-esophaeal findings are primary midline derivatives. While the kidneys are bilateral, they can be influenced by the midline, although there may also be effects on the ureteral buds as distal structures. The pre-axial area is the most distal in limb development, giving radial/tibial deficiencies and duplications. Alternatively, spina bifida and orofacial clefts originate from bilateral structures that are less likely to be affected by problems with midline determination, explaining the rarity of these disorders with VACTERL. Suggested human genetic models typically involve the midline, but lack radial findings, and true Mendelian forms are rare. However, developmental genes such as Sonic Hedgehog may have a pathogenetic role without being causal. © 2015 Wiley Periodicals, Inc.

Evolution-development congruence in pattern formation dynamics: Bifurcations in gene expression and regulation of networks structures.

PubMed

Kohsokabe, Takahiro; Kaneko, Kunihiko

2016-01-01

Search for possible relationships between phylogeny and ontogeny is important in evolutionary-developmental biology. Here we uncover such relationships by numerical evolution and unveil their origin in terms of dynamical systems theory. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell-to-cell interaction under external morphogen gradient, gene regulation networks are evolved under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Both in the evolution and development pattern changes consist of several epochs where stripes are formed in a short time, while for other temporal regimes, pattern hardly changes. In evolution, these quasi-stationary regimes are generations needed to hit relevant mutations, while in development, they are due to some gene expression that varies slowly and controls the pattern change. The morphogenesis is regulated by combinations of feedback or feedforward regulations, where the upstream feedforward network reads the external morphogen gradient, and generates a pattern used as a boundary condition for the later patterns. The ordering from up to downstream is common in evolution and development, while the successive epochal changes in development and evolution are represented as common bifurcations in dynamical-systems theory, which lead to the evolution-development congruence. Mechanism of exceptional violation of the congruence is also unveiled. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution Published by Wiley Periodicals, Inc.

Evolution‐development congruence in pattern formation dynamics: Bifurcations in gene expression and regulation of networks structures

PubMed Central

Kohsokabe, Takahiro

2016-01-01

ABSTRACT Search for possible relationships between phylogeny and ontogeny is important in evolutionary‐developmental biology. Here we uncover such relationships by numerical evolution and unveil their origin in terms of dynamical systems theory. By representing developmental dynamics of spatially located cells with gene expression dynamics with cell‐to‐cell interaction under external morphogen gradient, gene regulation networks are evolved under mutation and selection with the fitness to approach a prescribed spatial pattern of expressed genes. For most numerical evolution experiments, evolution of pattern over generations and development of pattern by an evolved network exhibit remarkable congruence. Both in the evolution and development pattern changes consist of several epochs where stripes are formed in a short time, while for other temporal regimes, pattern hardly changes. In evolution, these quasi‐stationary regimes are generations needed to hit relevant mutations, while in development, they are due to some gene expression that varies slowly and controls the pattern change. The morphogenesis is regulated by combinations of feedback or feedforward regulations, where the upstream feedforward network reads the external morphogen gradient, and generates a pattern used as a boundary condition for the later patterns. The ordering from up to downstream is common in evolution and development, while the successive epochal changes in development and evolution are represented as common bifurcations in dynamical‐systems theory, which lead to the evolution‐development congruence. Mechanism of exceptional violation of the congruence is also unveiled. Our results provide a new look on developmental stages, punctuated equilibrium, developmental bottlenecks, and evolutionary acquisition of novelty in morphogenesis. J. Exp. Zool. (Mol. Dev. Evol.) 326B:61–84, 2016. © 2015 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution Published by Wiley Periodicals, Inc. PMID:26678220

Linear signaling in the Toll-Dorsal pathway of Drosophila: activated Pelle kinase specifies all threshold outputs of gene expression while the bHLH protein Twist specifies a subset.

PubMed

Stathopoulos, Angelike; Levine, Michael

2002-07-01

Differential activation of the Toll receptor leads to the formation of a broad Dorsal nuclear gradient that specifies at least three patterning thresholds of gene activity along the dorsoventral axis of precellular embryos. We investigate the activities of the Pelle kinase and Twist basic helix-loop-helix (bHLH) transcription factor in transducing Toll signaling. Pelle functions downstream of Toll to release Dorsal from the Cactus inhibitor. Twist is an immediate-early gene that is activated upon entry of Dorsal into nuclei. Transgenes misexpressing Pelle and Twist were introduced into different mutant backgrounds and the patterning activities were visualized using various target genes that respond to different thresholds of Toll-Dorsal signaling. These studies suggest that an anteroposterior gradient of Pelle kinase activity is sufficient to generate all known Toll-Dorsal patterning thresholds and that Twist can function as a gradient morphogen to establish at least two distinct dorsoventral patterning thresholds. We discuss how the Dorsal gradient system can be modified during metazoan evolution and conclude that Dorsal-Twist interactions are distinct from the interplay between Bicoid and Hunchback, which pattern the anteroposterior axis.

Dpp signaling inhibits proliferation in the Drosophila wing by Omb-dependent regional control of bantam.

PubMed

Zhang, Xubo; Luo, Dan; Pflugfelder, Gert O; Shen, Jie

2013-07-01

The control of organ growth is a fundamental aspect of animal development but remains poorly understood. The morphogen Dpp has long been considered as a general promoter of cell proliferation during Drosophila wing development. It is an ongoing debate whether the Dpp gradient is required for the uniform cell proliferation observed in the wing imaginal disc. Here, we investigated how the Dpp signaling pathway regulates proliferation during wing development. By systematic manipulation of Dpp signaling we observed that it controls proliferation in a region-specific manner: Dpp, via omb, promoted proliferation in the lateral and repressed proliferation in the medial wing disc. Omb controlled the regional proliferation rate by oppositely regulating transcription of the microRNA gene bantam in medial versus lateral wing disc. However, neither the Dpp nor Omb gradient was essential for uniform proliferation along the anteroposterior axis.

Boundary Dpp promotes growth of medial and lateral regions of the Drosophila wing.

PubMed

Barrio, Lara; Milán, Marco

2017-07-04

The gradient of Decapentaplegic (Dpp) in the Drosophila wing has served as a paradigm to characterize the role of morphogens in regulating patterning. However, the role of this gradient in regulating tissue size is a topic of intense debate as proliferative growth is homogenous. Here, we combined the Gal4/UAS system and a temperature-sensitive Gal80 molecule to induce RNAi-mediated depletion of dpp and characterise the spatial and temporal requirement of Dpp in promoting growth. We show that Dpp emanating from the AP compartment boundary is required throughout development to promote growth by regulating cell proliferation and tissue size. Dpp regulates growth and proliferation rates equally in central and lateral regions of the developing wing appendage and reduced levels of Dpp affects similarly the width and length of the resulting wing. We also present evidence supporting the proposal that graded activity of Dpp is not an absolute requirement for wing growth.

Synthesis and materialization of a reaction-diffusion French flag pattern

NASA Astrophysics Data System (ADS)

Zadorin, Anton S.; Rondelez, Yannick; Gines, Guillaume; Dilhas, Vadim; Urtel, Georg; Zambrano, Adrian; Galas, Jean-Christophe; Estevez-Torres, André

2017-10-01

During embryo development, patterns of protein concentration appear in response to morphogen gradients. These patterns provide spatial and chemical information that directs the fate of the underlying cells. Here, we emulate this process within non-living matter and demonstrate the autonomous structuration of a synthetic material. First, we use DNA-based reaction networks to synthesize a French flag, an archetypal pattern composed of three chemically distinct zones with sharp borders whose synthetic analogue has remained elusive. A bistable network within a shallow concentration gradient creates an immobile, sharp and long-lasting concentration front through a reaction-diffusion mechanism. The combination of two bistable circuits generates a French flag pattern whose 'phenotype' can be reprogrammed by network mutation. Second, these concentration patterns control the macroscopic organization of DNA-decorated particles, inducing a French flag pattern of colloidal aggregation. This experimental framework could be used to test reaction-diffusion models and fabricate soft materials following an autonomous developmental programme.

Response of bone marrow stromal cells to graded co-electrospun scaffolds and its implications for engineering the ligament-bone interface.

PubMed

Samavedi, Satyavrata; Guelcher, Scott A; Goldstein, Aaron S; Whittington, Abby R

2012-11-01

Biomaterial scaffolds with gradients in architecture, mechanical and chemical properties have the potential to improve the osseointegration of ligament grafts by recapitulating phenotypic gradients that exist at the natural ligament-bone (L-B) interface. Towards the larger goal of regenerating the L-B interface, this in vitro study was performed to investigate the potential of two scaffolds with mineral gradients in promoting a spatial gradient of osteoblastic differentiation. Specifically, the first graded scaffold was fabricated by co-electrospinning two polymer solutions (one doped with nano-hydroxyapatite particles) from offset spinnerets, while the second was created by immersing the first scaffold in a 5 × simulated body fluid. Rat bone marrow stromal cells, cultured in the presence of osteogenic supplements, were found to be metabolically active on all regions of both scaffolds after 1 and 7 days of culture. Gene expression of bone morphogenic protein-2 and osteopontin was elevated on mineral-containing regions as compared to regions without mineral, while the expression of alkaline phosphatase mRNA revealed the opposite trend. Finally, the presence of osteopontin and bone sialoprotein confirmed osteoblastic phenotypic maturation by day 28. This study indicates that co-electrospun scaffolds with gradients in mineral content can guide the formation of phenotypic gradients and may thus promote the regeneration of the L-B interface. Copyright © 2012 Elsevier Ltd. All rights reserved.

Novel Metrics to Characterize Embryonic Elongation of the Nematode Caenorhabditis elegans.

PubMed

Martin, Emmanuel; Rocheleau-Leclair, Olivier; Jenna, Sarah

2016-03-28

Dissecting the signaling pathways that control the alteration of morphogenic processes during embryonic development requires robust and sensitive metrics. Embryonic elongation of the nematode Caenorhabditis elegans is a late developmental stage consisting of the elongation of the embryo along its longitudinal axis. This developmental stage is controlled by intercellular communication between hypodermal cells and underlying body-wall muscles. These signaling mechanisms control the morphology of hypodermal cells by remodeling the cytoskeleton and the cell-cell junctions. Measurement of embryonic lethality and developmental arrest at larval stages as well as alteration of cytoskeleton and cell-cell adhesion structures in hypodermal and muscle cells are classical phenotypes that have been used for more than 25 years to dissect these signaling pathways. Recent studies required the development of novel metrics specifically targeting either early or late elongation and characterizing morphogenic defects along the antero-posterior axis of the embryo. Here, we provide detailed protocols enabling the accurate measurement of the length and the width of the elongating embryos as well as the length of synchronized larvae. These methods constitute useful tools to identify genes controlling elongation, to assess whether these genes control both early and late phases of this stage and are required evenly along the antero-posterior axis of the embryo.

Positive modulator of bone morphogenic protein-2

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

Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Positive modulator of bone morphogenic protein-2

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2009-01-27

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Messages Do Diffuse Faster than Messengers: Reconciling Disparate Estimates of the Morphogen Bicoid Diffusion Coefficient

PubMed Central

Sigaut, Lorena; Pearson, John E.; Colman-Lerner, Alejandro; Ponce Dawson, Silvina

2014-01-01

The gradient of Bicoid (Bcd) is key for the establishment of the anterior-posterior axis in Drosophila embryos. The gradient properties are compatible with the SDD model in which Bcd is synthesized at the anterior pole and then diffuses into the embryo and is degraded with a characteristic time. Within this model, the Bcd diffusion coefficient is critical to set the timescale of gradient formation. This coefficient has been measured using two optical techniques, Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Correlation Spectroscopy (FCS), obtaining estimates in which the FCS value is an order of magnitude larger than the FRAP one. This discrepancy raises the following questions: which estimate is "correct''; what is the reason for the disparity; and can the SDD model explain Bcd gradient formation within the experimentally observed times? In this paper, we use a simple biophysical model in which Bcd diffuses and interacts with binding sites to show that both the FRAP and the FCS estimates may be correct and compatible with the observed timescale of gradient formation. The discrepancy arises from the fact that FCS and FRAP report on different effective (concentration dependent) diffusion coefficients, one of which describes the spreading rate of the individual Bcd molecules (the messengers) and the other one that of their concentration (the message). The latter is the one that is more relevant for the gradient establishment and is compatible with its formation within the experimentally observed times. PMID:24901638

Messages do diffuse faster than messengers: reconciling disparate estimates of the morphogen bicoid diffusion coefficient.

PubMed

Sigaut, Lorena; Pearson, John E; Colman-Lerner, Alejandro; Ponce Dawson, Silvina

2014-06-01

The gradient of Bicoid (Bcd) is key for the establishment of the anterior-posterior axis in Drosophila embryos. The gradient properties are compatible with the SDD model in which Bcd is synthesized at the anterior pole and then diffuses into the embryo and is degraded with a characteristic time. Within this model, the Bcd diffusion coefficient is critical to set the timescale of gradient formation. This coefficient has been measured using two optical techniques, Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Correlation Spectroscopy (FCS), obtaining estimates in which the FCS value is an order of magnitude larger than the FRAP one. This discrepancy raises the following questions: which estimate is "correct''; what is the reason for the disparity; and can the SDD model explain Bcd gradient formation within the experimentally observed times? In this paper, we use a simple biophysical model in which Bcd diffuses and interacts with binding sites to show that both the FRAP and the FCS estimates may be correct and compatible with the observed timescale of gradient formation. The discrepancy arises from the fact that FCS and FRAP report on different effective (concentration dependent) diffusion coefficients, one of which describes the spreading rate of the individual Bcd molecules (the messengers) and the other one that of their concentration (the message). The latter is the one that is more relevant for the gradient establishment and is compatible with its formation within the experimentally observed times.

Fucoidan promotes early step of cardiac differentiation from human embryonic stem cells and long-term maintenance of beating areas.

PubMed

Hamidi, Sofiane; Letourneur, Didier; Aid-Launais, Rachida; Di Stefano, Antonio; Vainchenker, William; Norol, Françoise; Le Visage, Catherine

2014-04-01

Somatic stem cells require specific niches and three-dimensional scaffolds provide ways to mimic this microenvironment. Here, we studied a scaffold based on Fucoidan, a sulfated polysaccharide known to influence morphogen gradients during embryonic development, to support human embryonic stem cells (hESCs) differentiation toward the cardiac lineage. A macroporous (pore 200 μm) Fucoidan scaffold was selected to support hESCs attachment and proliferation. Using a protocol based on the cardiogenic morphogen bone morphogenic protein 2 (BMP2) and transforming growth factor (TGFβ) followed by tumor necrosis factor (TNFα), an effector of cardiopoietic priming, we examined the cardiac differentiation in the scaffold compared to culture dishes and embryoid bodies (EBs). At day 8, Fucoidan scaffolds supported a significantly higher expression of the 3 genes encoding for transcription factors marking the early step of embryonic cardiac differentiation NKX2.5 (p<0.05), MEF2C (p<0.01), and GATA4 (p<0.01), confirmed by flow cytometry analysis for MEF2C and NKX2.5. The ability of Fucoidan scaffolds to locally concentrate and slowly release TGFβ and TNFα was confirmed by Luminex technology. We also found that Fucoidan scaffolds supported the late stage of embryonic cardiac differentiation marked by a significantly higher atrial natriuretic factor (ANF) expression (p<0.001), although only rare beating areas were observed. We postulated that absence of mechanical stress in the soft hydrogel impaired sarcomere formation, as confirmed by molecular analysis of the cardiac muscle myosin MYH6 and immunohistological staining of sarcomeric α-actinin. Nevertheless, Fucoidan scaffolds contributed to the development of thin filaments connecting beating areas through promotion of smooth muscle cells, thus enabling maintenance of beating areas for up to 6 months. In conclusion, Fucoidan scaffolds appear as a very promising biomaterial to control cardiac differentiation from hESCs that could be further combined with mechanical stress to promote sarcomere formation at terminal stages of differentiation.

Pre-procambial cells are niches for pluripotent and totipotent stem-like cells for organogenesis and somatic embryogenesis in the peach palm: a histological study.

PubMed

de Almeida, Marcilio; de Almeida, Cristina Vieira; Mendes Graner, Erika; Ebling Brondani, Gilvano; Fiori de Abreu-Tarazi, Monita

2012-08-01

The direct induction of adventitious buds and somatic embryos from explants is a morphogenetic process that is under the influence of exogenous plant growth regulators and its interactions with endogenous phytohormones. We performed an in vitro histological analysis in peach palm (Bactris gasipaes Kunth) shoot apexes and determined that the positioning of competent cells and their interaction with neighboring cells, under the influence of combinations of exogenously applied growth regulators (NAA/BAP and NAA/TDZ), allows the pre-procambial cells (PPCs) to act in different morphogenic pathways to establish niche competent cells. It is likely that there has been a habituation phenomenon during the regeneration and development of the microplants. This includes promoting the tillering of primary or secondary buds due to culturing in the absence of NAA/BAP or NAA/TDZ after a period in the presence of these growth regulators. Histological analyses determined that the adventitious roots were derived from the dedifferentiation of the parenchymal cells located in the basal region of the adventitious buds, with the establishment of rooting pole, due to an auxin gradient. Furthermore, histological and histochemical analyses allowed us to characterize how the PPCs provide niches for multipotent, pluripotent and totipotent stem-like cells for vascular differentiation, organogenesis and somatic embryogenesis in the peach palm. The histological and histochemical analyses also allowed us to detect the unicellular or multicellular origin of somatic embryogenesis. Therefore, our results indicate that the use of growth regulators in microplants can lead to habituation and to different morphogenic pathways leading to potential niche establishment, depending on the positioning of the competent cells and their interaction with neighboring cells. Our results indicate that the use of growth regulators in microplants can lead to habituation and to different morphogenic pathways leading to potential niche establishment, depending on the positioning of the competent cells and their interaction with neighboring cells.

Microfluidic device generating stable concentration gradients for long term cell culture: application to Wnt3a regulation of β-catenin signaling.

PubMed

Cimetta, Elisa; Cannizzaro, Christopher; James, Richard; Biechele, Travis; Moon, Randall T; Elvassore, Nicola; Vunjak-Novakovic, Gordana

2010-12-07

In developing tissues, proteins and signaling molecules present themselves in the form of concentration gradients, which determine the fate specification and behavior of the sensing cells. To mimic these conditions in vitro, we developed a microfluidic device designed to generate stable concentration gradients at low hydrodynamic shear and allowing long term culture of adhering cells. The gradient forms in a culture space between two parallel laminar flow streams of culture medium at two different concentrations of a given morphogen. The exact algorithm for defining the concentration gradients was established with the aid of mathematical modeling of flow and mass transport. Wnt3a regulation of β-catenin signaling was chosen as a case study. The highly conserved Wnt-activated β-catenin pathway plays major roles in embryonic development, stem cell proliferation and differentiation. Wnt3a stimulates the activity of β-catenin pathway, leading to translocation of β-catenin to the nucleus where it activates a series of target genes. We cultured A375 cells stably expressing a Wnt/β-catenin reporter driving the expression of Venus, pBARVS, inside the microfluidic device. The extent to which the β-catenin pathway was activated in response to a gradient of Wnt3a was assessed in real time using the BARVS reporter gene. On a single cell level, the β-catenin signaling was proportionate to the concentration gradient of Wnt3a; we thus propose that the modulation of Wnt3a gradients in real time can provide new insights into the dynamics of β-catenin pathway, under conditions that replicate some aspects of the actual cell-tissue milieu. Our device thus offers a highly controllable platform for exploring the effects of concentration gradients on cultured cells.

Spatial transcriptomics: paving the way for tissue-level systems biology.

PubMed

Moor, Andreas E; Itzkovitz, Shalev

2017-08-01

The tissues in our bodies are complex systems composed of diverse cell types that often interact in highly structured repeating anatomical units. External gradients of morphogens, directional blood flow, as well as the secretion and absorption of materials by cells generate distinct microenvironments at different tissue coordinates. Such spatial heterogeneity enables optimized function through division of labor among cells. Unraveling the design principles that govern this spatial division of labor requires techniques to quantify the entire transcriptomes of cells while accounting for their spatial coordinates. In this review we describe how recent advances in spatial transcriptomics open the way for tissue-level systems biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro maturation of Drosophila melanogaster Spätzle protein with refolded Easter reveals a novel cleavage site within the prodomain.

PubMed

Ursel, Christian; Fandrich, Uwe; Hoffmann, Anita; Sieg, Torsten; Ihling, Christian; Stubbs, Milton T

2013-08-01

Dorsoventral patterning during Drosophila melanogaster embryogenesis is mediated by a well-defined gradient of the mature NGF-like ligand Spätzle. Easter, the ultimate protease of a ventrally-restricted serine protease cascade, plays a key role in the regulation of the morphogenic gradient, catalyzing the activation cleavage of proSpätzle. As a result of alternative splicing, proSpätzle exists in multiple isoforms, almost all of which differ only in their prodomain. Although this domain is unstructured in isolation, it has a stabilizing influence on the mature cystine knot domain and is involved in the binding to the Toll receptor. Here, we report the expression and refolding of Easter, and show that the renatured enzyme performs the activation cleavage of two Spätzle isoforms. We determine the affinity of the prodomain for the cystine knot domain, and show that Easter performs a previously unknown secondary cleavage in each prodomain.

Dampened regulates the activating potency of Bicoid and the embryonic patterning outcome in Drosophila

PubMed Central

Liu, Junbo; Ma, Jun

2014-01-01

The Drosophila morphogen gradient of Bicoid (Bcd) initiates anterior-posterior (AP) patterning, but it is poorly understood how its ability to activate a target gene may impact this process. Here we report an F-box protein, Dampened (Dmpd) as a nuclear co-factor of Bcd that can enhance its activating potency. We establish a quantitative platform to specifically investigate two parameters of a Bcd target gene response, expression amplitude and boundary position. We show that embryos lacking Dmpd have a reduced amplitude of Bcd-activated hunchback (hb) expression at a critical time of development. This is due to a reduced Bcd-dependent transcribing probability. This defect is faithfully propagated further downstream of the AP patterning network to alter the spatial characteristics of even-skipped (eve) stripes. Thus, unlike another Bcd-interacting F-box protein Fates-shifted (Fsd), which controls AP patterning through regulating the Bcd gradient profile, Dmpd achieves its patterning role through regulating the activating potency of Bcd. PMID:24336107

Boundary Dpp promotes growth of medial and lateral regions of the Drosophila wing

PubMed Central

Barrio, Lara; Milán, Marco

2017-01-01

The gradient of Decapentaplegic (Dpp) in the Drosophila wing has served as a paradigm to characterize the role of morphogens in regulating patterning. However, the role of this gradient in regulating tissue size is a topic of intense debate as proliferative growth is homogenous. Here, we combined the Gal4/UAS system and a temperature-sensitive Gal80 molecule to induce RNAi-mediated depletion of dpp and characterise the spatial and temporal requirement of Dpp in promoting growth. We show that Dpp emanating from the AP compartment boundary is required throughout development to promote growth by regulating cell proliferation and tissue size. Dpp regulates growth and proliferation rates equally in central and lateral regions of the developing wing appendage and reduced levels of Dpp affects similarly the width and length of the resulting wing. We also present evidence supporting the proposal that graded activity of Dpp is not an absolute requirement for wing growth. DOI: http://dx.doi.org/10.7554/eLife.22013.001 PMID:28675372

Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc.

PubMed

Chen, Weitao; Huang, Hai; Hatori, Ryo; Kornberg, Thomas B

2017-09-01

Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression, and analyzed the movement and colocalization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes. Hh:GFP moved to basal subcellular locations prior to release from posterior compartment cells that express it, and was taken up by basal cytonemes that extend to the source cells. Hh and Ptc were present in puncta that moved along the basal cytonemes and formed characteristic apical-basal distributions in the anterior compartment cells. The basal cytonemes required diaphanous , SCAR , N euroglian and S ynaptobrevin , and both the Hh gradient and Hh signaling declined under conditions in which the cytonemes were compromised. These findings show that in the wing disc, Hh distributions and signaling are dependent upon basal release and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion was obtained. © 2017. Published by The Company of Biologists Ltd.

Mechanochemical Symmetry Breaking in Hydra Aggregates

PubMed Central

Mercker, Moritz; Köthe, Alexandra; Marciniak-Czochra, Anna

2015-01-01

Tissue morphogenesis comprises the self-organized creation of various patterns and shapes. Although detailed underlying mechanisms are still elusive in many cases, an increasing amount of experimental data suggests that chemical morphogen and mechanical processes are strongly coupled. Here, we develop and test a minimal model of the axis-defining step (i.e., symmetry breaking) in aggregates of the Hydra polyp. Based on previous findings, we combine osmotically driven shape oscillations with tissue mechanics and morphogen dynamics. We show that the model incorporating a simple feedback loop between morphogen patterning and tissue stretch reproduces a wide range of experimental data. Finally, we compare different hypothetical morphogen patterning mechanisms (Turing, tissue-curvature, and self-organized criticality). Our results suggest the experimental investigation of bigger (i.e., multiple head) aggregates as a key step for a deeper understanding of mechanochemical symmetry breaking in Hydra. PMID:25954896

A gradient of auxin and auxin-dependent transcription precedes tropic growth responses.

PubMed

Esmon, C Alex; Tinsley, Amanda G; Ljung, Karin; Sandberg, Goran; Hearne, Leonard B; Liscum, Emmanuel

2006-01-03

Plants, although sessile, can reorient growth axes in response to changing environmental conditions. Phototropism and gravitropism represent adaptive growth responses induced by changes in light direction and growth axis orientation relative to gravitational direction, respectively. The nearly 80-year-old Cholodny-Went theory [Went, F. W. & Thimann, K. V. (1937) Phytohormones (Macmillan, New York)] predicts that formation of a gradient of the plant morphogen auxin is central to the establishment of tropic curvature. Loss of tropic responses in seedling stems of Arabidopsis thaliana mutants lacking the auxin-regulated transcriptional activator NPH4/ARF7 has further suggested that a gradient of gene expression represents an essential output from the auxin gradient. Yet the molecular identities of such output components, which are likely to encode proteins directly involved in growth control, have remained elusive. Here we report the discovery of a suite of tropic stimulus-induced genes in Brassica oleracea that are responsive to an auxin gradient and exhibit morphologically graded expression concomitant with, or before, observable curvature responses. These results provide compelling molecular support for the Cholodny-Went theory and suggest that morphologically graded transcription represents an important mechanism for interpreting tropically stimulated gradients of auxin. Intriguingly, two of the tropic stimulus-induced genes, EXPA1 and EXPA8, encode enzymes involved in cell wall extension, a response prerequisite for differential growth leading to curvatures, and are up-regulated before curvature in the flank that will elongate. This observation suggests that morphologically graded transcription likely leads to the graded expression of proteins whose activities can directly regulate the establishment and modulation of tropic curvatures.

Permissive and instructive anterior patterning rely on mRNA localization in the wasp embryo.

PubMed

Brent, Ava E; Yucel, Gozde; Small, Stephen; Desplan, Claude

2007-03-30

The long-germ mode of embryogenesis, in which segments arise simultaneously along the anteriorposterior axis, has evolved several times in different lineages of the holometabolous, or fully metamorphosing, insects. Drosophila's long-germ fate map is established largely by the activity of the dipteran-specific Bicoid (Bcd) morphogen gradient, which operates both instructively and permissively to accomplish anterior patterning. By contrast, all nondipteran long-germ insects must achieve anterior patterning independently of bcd. We show that bcd's permissive function is mimicked in the wasp by a maternal repression system in which anterior localization of the wasp ortholog of giant represses anterior expression of the trunk gap genes so that head and thorax can properly form.

Sensory hair cell development and regeneration: similarities and differences

PubMed Central

Atkinson, Patrick J.; Huarcaya Najarro, Elvis; Sayyid, Zahra N.; Cheng, Alan G.

2015-01-01

Sensory hair cells are mechanoreceptors of the auditory and vestibular systems and are crucial for hearing and balance. In adult mammals, auditory hair cells are unable to regenerate, and damage to these cells results in permanent hearing loss. By contrast, hair cells in the chick cochlea and the zebrafish lateral line are able to regenerate, prompting studies into the signaling pathways, morphogen gradients and transcription factors that regulate hair cell development and regeneration in various species. Here, we review these findings and discuss how various signaling pathways and factors function to modulate sensory hair cell development and regeneration. By comparing and contrasting development and regeneration, we also highlight the utility and limitations of using defined developmental cues to drive mammalian hair cell regeneration. PMID:25922522

ATP oscillations mediate inductive action of FGF and Shh signalling on prechondrogenic condensation.

PubMed

Kwon, Hyuck Joon

2013-01-01

Skeletal patterns are prefigured by prechondrogenic condensation. Morphogens such as fibroblast growth factor (FGF) and sonic hedgehog (Shh) specify the skeletal patterns in limb development. However, how morphogens regulate prechondrogenic condensation has remained unclear. Recently, it was demonstrated that synchronized Adenosine triphosphate (ATP) oscillations play a critical role in prechondrogenic condensation. Thus, the present study has focused on whether ATP oscillations mediate the actions of major developmental morphogens such as FGF and Shh on prechondrogenic condensation. It has been shown that both FGF and Shh signalling promoted cellular condensation but not chondrogenic differentiation and also induced ATP oscillations. In addition, blockage of FGF and Shh signalling prevented both ATP oscillations and prechondrogenic condensation. Furthermore, it was found that inhibition of ATP oscillations suppressed FGF/Shh-induced prechondrogenic condensation. These results indicate that ATP oscillations mediate the actions of FGF and Shh signalling on prechondrogenic condensation. This study proposes that morphogens organize skeletal patterns via ATP oscillations. Copyright © 2012 John Wiley & Sons, Ltd.

JAK/STAT controls organ size and fate specification by regulating morphogen production and signalling

PubMed Central

Recasens-Alvarez, Carles; Ferreira, Ana; Milán, Marco

2017-01-01

A stable pool of morphogen-producing cells is critical for the development of any organ or tissue. Here we present evidence that JAK/STAT signalling in the Drosophila wing promotes the cycling and survival of Hedgehog-producing cells, thereby allowing the stable localization of the nearby BMP/Dpp-organizing centre in the developing wing appendage. We identify the inhibitor of apoptosis dIAP1 and Cyclin A as two critical genes regulated by JAK/STAT and contributing to the growth of the Hedgehog-expressing cell population. We also unravel an early role of JAK/STAT in guaranteeing Wingless-mediated appendage specification, and a later one in restricting the Dpp-organizing activity to the appendage itself. These results unveil a fundamental role of the conserved JAK/STAT pathway in limb specification and growth by regulating morphogen production and signalling, and a function of pro-survival cues and mitogenic signals in the regulation of the pool of morphogen-producing cells in a developing organ. PMID:28045022

Dancing with Hormones: A Current Perspective of Nitrate Signaling and Regulation in Arabidopsis

PubMed Central

Guan, Peizhu

2017-01-01

In nature and agriculture, nitrate availability is a main environmental cue for plant growth, development and stress responses. Nitrate signaling and regulation are hence at the center of communications between plant intrinsic programs and the environment. It is also well known that endogenous phytohormones play numerous critical roles in integrating extrinsic cues and intrinsic responses, regulating and refining almost all aspects of plant growth, development and stress responses. Therefore, interaction between nitrate and phytohormones, such as auxins, cytokinins, abscisic acid, gibberellins, and ethylene, is prevalent. The growing evidence indicates that biosynthesis, de-conjugation, transport, and signaling of hormones are partly controlled by nitrate signaling. Recent advances with nitrate signaling and transcriptional regulation in Arabidopsis give rise to new paradigms. Given the comprehensive nitrate transport, sensing, signaling and regulations at the level of the cell and organism, nitrate itself is a local and long-distance signal molecule, conveying N status at the whole-plant level. A direct molecular link between nitrate signaling and cell cycle progression was revealed with TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR1-20 (TCP20) – NIN-LIKE PROTEIN 6/7 (NLP6/7) regulatory nexus. NLPs are key regulators of nitrogen responses in plants. TCPs function as the main regulators of plant morphology and architecture, with the emerging role as integrators of plant developmental responses to the environment. By analogy with auxin being proposed as a plant morphogen, nitrate may be an environmental morphogen. The morphogen-gradient-dependent and cell-autonomous mechanisms of nitrate signaling and regulation are an integral part of cell growth and cell identification. This is especially true in root meristem growth that is regulated by intertwined nitrate, phytohormones, and glucose-TOR signaling pathways. Furthermore, the nitrate transcriptional hierarchy is emerging. Nitrate regulators in primary nitrate signaling can individually and combinatorially control downstream transcriptional networks and hormonal pathways for signal propagation and amplification. Under the new paradigms, nitrate-induced hormone metabolism and signaling deserve fresh examination. The close interplay and convergent regulation of nitrate and hormonal signaling at morphological, physiological, and molecular levels have significant effects on important agronomic traits, especially nutrient-dependent adaptive root system growth and architecture. PMID:29033968

Physiologically induced color-pattern changes in butterfly wings: mechanistic and evolutionary implications.

PubMed

Otaki, Joji M

2008-07-01

A mechanistic understanding of the butterfly wing color-pattern determination can be facilitated by experimental pattern changes. Here I review physiologically induced color-pattern changes in nymphalid butterflies and their mechanistic and evolutionary implications. A type of color-pattern change can be elicited by elemental changes in size and position throughout the wing, as suggested by the nymphalid groundplan. These changes of pattern elements are bi-directional and bi-sided dislocation toward or away from eyespot foci and in both proximal and distal sides of the foci. The peripheral elements are dislocated even in the eyespot-less compartments. Anterior spots are more severely modified, suggesting the existence of an anterior-posterior gradient. In one species, eyespots are transformed into white spots with remnant-like orange scales, and such patterns emerge even at the eyespot-less "imaginary" foci. A series of these color-pattern modifications probably reveal "snap-shots" of a dynamic morphogenic signal due to heterochronic uncoupling between the signaling and reception steps. The conventional gradient model can be revised to account for these observed color-pattern changes.

Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates

PubMed Central

Chen, Miao-Hsueh; Li, Ya-Jun; Kawakami, Takatoshi; Xu, Shan-Mei; Chuang, Pao-Tien

2004-01-01

Hedgehog (Hh) signaling plays a major role in multiple aspects of embryonic development. A key issue in Hh signaling is to elucidate the molecular mechanism by which a Hh protein morphogen gradient is formed despite its membrane association. In this study, we used a combination of genetic, cellular, and biochemical approaches to address the role of lipid modifications in long-range vertebrate Hh signaling. Our molecular analysis of knockout mice deficient in Skn, the murine homolog of the Drosophila ski gene, which catalyzes Hh palmitoylation, and gene-targeted mice producing a nonpalmitoylated form of Shh indicates that Hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos. Furthermore, our biochemical data show that Hh lipid modifications are required for producing a soluble multimeric protein complex, which constitutes the major active component for Hh signaling. These results suggest that soluble Hh multimeric complex travels in the morphogenetic field to activate Hh signaling in distant Hh-responsive cells. PMID:15075292

Sonic Hedgehog functions through dynamic changes in temporal competence in the developing ventral telencephalon

PubMed Central

Sousa, Vitor H.; Fishell, Gord

2010-01-01

Morphogens act during development to provide graded spatial information that controls patterning and cell lineage specification in the nervous system. The role of morphogen signaling in instructing the expression of downstream effector transcription factors has been well established. However, a key requirement for morphogen signaling is the existence of functional intracellular machinery able to mediate the appropriate response in target cells. Here we suggest that dynamic changes in the temporal responses to Shh in the developing ventral telencephalon occur through alterations in progenitor competence. We suggest these developmental changes in competence are mediated by a transcriptional mechanism that intrinsically integrates information from the distinct signaling pathways that act to pattern the telencephalic neuroepithelium. PMID:20466536

Application of gradient elasticity to benchmark problems of beam vibrations

NASA Astrophysics Data System (ADS)

Kateb, K. M.; Almitani, K. H.; Alnefaie, K. A.; Abu-Hamdeh, N. H.; Papadopoulos, P.; Askes, H.; Aifantis, E. C.

2016-04-01

The gradient approach, specifically gradient elasticity theory, is adopted to revisit certain typical configurations on mechanical vibrations. New results on size effects and scale-dependent behavior not captured by classical elasticity are derived, aiming at illustrating the usefulness of this approach to applications in advanced technologies. In particular, elastic prismatic straight beams in bending are discussed using two different governing equations: the gradient elasticity bending moment equation (fourth order) and the gradient elasticity deflection equation (sixth order). Different boundary/support conditions are examined. One problem considers the free vibrations of a cantilever beam loaded by an end force. A second problem is concerned with a simply supported beam disturbed by a concentrated force in the middle of the beam. Both problems are solved analytically. Exact free vibration frequencies and mode shapes are derived and presented. The difference between the gradient elasticity solution and its classical counterpart is revealed. The size ratio c/L (c denotes internal length and L is the length of the beam) induces significant effects on vibration frequencies. For both beam configurations, it turns out that as the ratio c/L increases, the vibration frequencies decrease, a fact which implies lower beam stiffness. Numerical examples show this behavior explicitly and recover the classical vibration behavior for vanishing size ratio c/L.

Thermoelastic response of metal matrix composites with large-diameter fibers subjected to thermal gradients

NASA Technical Reports Server (NTRS)

Aboudi, Jacob; Pindera, Marek-Jerzy; Arnold, Steven M.

1993-01-01

A new micromechanical theory is presented for the response of heterogeneous metal matrix composites subjected to thermal gradients. In contrast to existing micromechanical theories that utilize classical homogenization schemes in the course of calculating microscopic and macroscopic field quantities, in the present approach the actual microstructural details are explicitly coupled with the macrostructure of the composite. Examples are offered that illustrate limitations of the classical homogenization approach in predicting the response of thin-walled metal matrix composites with large-diameter fibers when subjected to thermal gradients. These examples include composites with a finite number of fibers in the thickness direction that may be uniformly or nonuniformly spaced, thus admitting so-called functionally gradient composites. The results illustrate that the classical approach of decoupling micromechanical and macromechanical analyses in the presence of a finite number of large-diameter fibers, finite dimensions of the composite, and temperature gradient may produce excessively conservative estimates for macroscopic field quantities, while both underestimating and overestimating the local fluctuations of the microscopic quantities in different regions of the composite. Also demonstrated is the usefulness of the present approach in generating favorable stress distributions in the presence of thermal gradients by appropriately tailoring the internal microstructure details of the composite.

Distinguishing graded and ultrasensitive signalling cascade kinetics by the shape of morphogen gradients in Drosophila.

PubMed

MacNamara, Shev; Baker, Ruth E; Maini, Philip K

2011-09-21

Recently, signalling gradients in cascades of two-state reaction-diffusion systems were described as a model for understanding key biochemical mechanisms that underlie development and differentiation processes in the Drosophila embryo. Diffusion-trapping at the exterior of the cell membrane triggers the mitogen-activated protein kinase (MAPK) cascade to relay an appropriate signal from the membrane to the inner part of the cytosol, whereupon another diffusion-trapping mechanism involving the nucleus reads out this signal to trigger appropriate changes in gene expression. Proposed mathematical models exhibit equilibrium distributions consistent with experimental measurements of key spatial gradients in these processes. A significant property of the formulation is that the signal is assumed to be relayed from one system to the next in a linear fashion. However, the MAPK cascade often exhibits nonlinear dose-response properties and the final remark of Berezhkovskii et al. (2009) is that this assumption remains an important property to be tested experimentally, perhaps via a new quantitative assay across multiple genetic backgrounds. In anticipation of the need to be able to sensibly interpret data from such experiments, here we provide a complementary analysis that recovers existing formulae as a special case but is also capable of handling nonlinear functional forms. Predictions of linear and nonlinear signal relays and, in particular, graded and ultrasensitive MAPK kinetics, are compared. Copyright © 2011 Elsevier Ltd. All rights reserved.

The sensitivity of Turing self-organization to biological feedback delays: 2D models of fish pigmentation.

PubMed

Gaffney, E A; Lee, S Seirin

2015-03-01

Turing morphogen models have been extensively explored in the context of large-scale self-organization in multicellular biological systems. However, reconciling the detailed biology of morphogen dynamics, while accounting for time delays associated with gene expression, reveals aberrant behaviours that are not consistent with early developmental self-organization, especially the requirement for exquisite temporal control. Attempts to reconcile the interpretation of Turing's ideas with an increasing understanding of the mechanisms driving zebrafish pigmentation suggests that one should reconsider Turing's model in terms of pigment cells rather than morphogens (Nakamasu et al., 2009, PNAS, 106: , 8429-8434; Yamaguchi et al., 2007, PNAS, 104: , 4790-4793). Here the dynamics of pigment cells is subject to response delays implicit in the cell cycle and apoptosis. Hence we explore simulations of fish skin patterning, focussing on the dynamical influence of gene expression delays in morphogen-based Turing models and response delays for cell-based Turing models. We find that reconciling the mechanisms driving the behaviour of Turing systems with observations of fish skin patterning remains a fundamental challenge. © The Authors 2013. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Hybrid Quantum-Classical Approach to Quantum Optimal Control.

PubMed

Li, Jun; Yang, Xiaodong; Peng, Xinhua; Sun, Chang-Pu

2017-04-14

A central challenge in quantum computing is to identify more computational problems for which utilization of quantum resources can offer significant speedup. Here, we propose a hybrid quantum-classical scheme to tackle the quantum optimal control problem. We show that the most computationally demanding part of gradient-based algorithms, namely, computing the fitness function and its gradient for a control input, can be accomplished by the process of evolution and measurement on a quantum simulator. By posing queries to and receiving answers from the quantum simulator, classical computing devices update the control parameters until an optimal control solution is found. To demonstrate the quantum-classical scheme in experiment, we use a seven-qubit nuclear magnetic resonance system, on which we have succeeded in optimizing state preparation without involving classical computation of the large Hilbert space evolution.

Preclinical and clinical studies on the use of growth factors for bone repair: a systematic review.

PubMed

Fisher, Daniel Mark; Wong, James Min-Leong; Crowley, Conor; Khan, Wasim S

2013-05-01

Bone healing is a complex process. Whilst the majority of fractures heal with conventional treatment, open fractures, large bone defects and non unions still provide great challenges to Orthopaedic Surgeons. Whilst autologous bone graft is seen as the gold standard, the use of growth factors is a growing area of research to find an effective alternative with lower side effects such as donor site morbidity and the finite amount available. This systematic review aims to summarize the pre clinical in-vivo studies and examine the clinical studies on the use of growth factors in bone healing. Databases: PubMed, Medline, OVID, and Cochrane library. The following key words and search terms were used: Growth Factors, Bone Healing, Bone Morphogenic Protein, Transforming Growth Factor Beta, Insulin Like Growth Factor, Platelet Derived Growth Factor, Fracture. All articles were screened based on title with abstracts and full text articles reviewed as appropriate. Reference lists were reviewed from relevant articles to ensure comprehensive and systematic review. Three tables of studies were constructed focussing on Bone Morphogenic Proteins, Platelet Rich Plasma and Growth Factors and Tissue Engineering. Bone Morphogenic Proteins and Platelet Rich Plasma, which contains multiple growth factors, have been shown in preclinical and clinical trials to be an effective alternative to autologous bone graft. Bone Morphogenic Proteins have been shown to be effective in fracture non union, and in open tibial fractures. Platelet Rich Plasma has shown promise in preclinical trials and some small clinical trials, however numbers are limited. Bone Morphogenic Proteins have been shown to be superior to Platelet Rich Protein in one trial. Combining these growth factors with tissue engineering techniques is the focus of ongoing research, and through further clinical trials the most effective techniques for enhancing bone healing will be revealed.

Morphogen and community effects determine cell fates in response to BMP4 signaling in human embryonic stem cells.

PubMed

Nemashkalo, Anastasiia; Ruzo, Albert; Heemskerk, Idse; Warmflash, Aryeh

2017-09-01

Paracrine signals maintain developmental states and create cell fate patterns in vivo and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ('µColonies') to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in µColonies and standard culture conditions and find that in µColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems. Under standard culture conditions BMP4 acts as a morphogen but this requires secondary signals and particular cell densities. We find that a 'community effect' enforces a common fate within µColonies, both in the state of pluripotency and when cells are differentiated, and that this effect allows a more precise response to external signals. Using live cell imaging to correlate signaling histories with cell fates, we demonstrate that interactions between neighbors result in sustained, homogenous signaling necessary for differentiation. © 2017. Published by The Company of Biologists Ltd.

Low-gradient aortic stenosis

PubMed Central

Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

2016-01-01

Abstract An important proportion of patients with aortic stenosis (AS) have a ‘low-gradient’ AS, i.e. a small aortic valve area (AVA <1.0 cm2) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA—low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. PMID:27190103

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.

A unified design space of synthetic stripe-forming networks

PubMed Central

Schaerli, Yolanda; Munteanu, Andreea; Gili, Magüi; Cotterell, James; Sharpe, James; Isalan, Mark

2014-01-01

Synthetic biology is a promising tool to study the function and properties of gene regulatory networks. Gene circuits with predefined behaviours have been successfully built and modelled, but largely on a case-by-case basis. Here we go beyond individual networks and explore both computationally and synthetically the design space of possible dynamical mechanisms for 3-node stripe-forming networks. First, we computationally test every possible 3-node network for stripe formation in a morphogen gradient. We discover four different dynamical mechanisms to form a stripe and identify the minimal network of each group. Next, with the help of newly established engineering criteria we build these four networks synthetically and show that they indeed operate with four fundamentally distinct mechanisms. Finally, this close match between theory and experiment allows us to infer and subsequently build a 2-node network that represents the archetype of the explored design space. PMID:25247316

Spatial patterns of correlated scale size and scale color in relation to color pattern elements in butterfly wings.

PubMed

Iwata, Masaki; Otaki, Joji M

2016-02-01

Complex butterfly wing color patterns are coordinated throughout a wing by unknown mechanisms that provide undifferentiated immature scale cells with positional information for scale color. Because there is a reasonable level of correspondence between the color pattern element and scale size at least in Junonia orithya and Junonia oenone, a single morphogenic signal may contain positional information for both color and size. However, this color-size relationship has not been demonstrated in other species of the family Nymphalidae. Here, we investigated the distribution patterns of scale size in relation to color pattern elements on the hindwings of the peacock pansy butterfly Junonia almana, together with other nymphalid butterflies, Vanessa indica and Danaus chrysippus. In these species, we observed a general decrease in scale size from the basal to the distal areas, although the size gradient was small in D. chrysippus. Scales of dark color in color pattern elements, including eyespot black rings, parafocal elements, and submarginal bands, were larger than those of their surroundings. Within an eyespot, the largest scales were found at the focal white area, although there were exceptional cases. Similarly, ectopic eyespots that were induced by physical damage on the J. almana background area had larger scales than in the surrounding area. These results are consistent with the previous finding that scale color and size coordinate to form color pattern elements. We propose a ploidy hypothesis to explain the color-size relationship in which the putative morphogenic signal induces the polyploidization (genome amplification) of immature scale cells and that the degrees of ploidy (gene dosage) determine scale color and scale size simultaneously in butterfly wings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Uncovering a Dynamic Feature of the Transcriptional Regulatory Network for Anterior-Posterior Patterning in the Drosophila Embryo

PubMed Central

Liu, Junbo; Ma, Jun

2013-01-01

Anterior-posterior (AP) patterning in the Drosophila embryo is dependent on the Bicoid (Bcd) morphogen gradient. However, most target genes of Bcd also require additional inputs to establish their expression domains, reflective of the operation of a cross-regulatory network and contributions of other maternal signals. This is in contrast to hunchback (hb), which has an anterior expression domain driven by an enhancer that appears to respond primarily to the Bcd input. To gain a better understanding of the regulatory logic of the AP patterning network, we perform quantitative studies that specifically investigate the dynamics of hb transcription during development. We show that Bcd-dependent hb transcription, monitored by the intron-containing nascent transcripts near the P2 promoter, is turned off quickly–on the order of a few minutes–upon entering the interphase of nuclear cycle 14A. This shutdown contrasts with earlier cycles during which active hb transcription can persist until the moment when the nucleus enters mitosis. The shutdown takes place at a time when the nuclear Bcd gradient profile in the embryo remains largely intact, suggesting that this is a process likely subject to control of a currently unknown regulatory mechanism. We suggest that this dynamic feature offers a window of opportunity for hb to faithfully interpret, and directly benefit from, Bcd gradient properties, including its scaling properties, to help craft a robust AP patterning outcome. PMID:23646132

Efficient spectral computation of the stationary states of rotating Bose-Einstein condensates by preconditioned nonlinear conjugate gradient methods

NASA Astrophysics Data System (ADS)

Antoine, Xavier; Levitt, Antoine; Tang, Qinglin

2017-08-01

We propose a preconditioned nonlinear conjugate gradient method coupled with a spectral spatial discretization scheme for computing the ground states (GS) of rotating Bose-Einstein condensates (BEC), modeled by the Gross-Pitaevskii Equation (GPE). We first start by reviewing the classical gradient flow (also known as imaginary time (IMT)) method which considers the problem from the PDE standpoint, leading to numerically solve a dissipative equation. Based on this IMT equation, we analyze the forward Euler (FE), Crank-Nicolson (CN) and the classical backward Euler (BE) schemes for linear problems and recognize classical power iterations, allowing us to derive convergence rates. By considering the alternative point of view of minimization problems, we propose the preconditioned steepest descent (PSD) and conjugate gradient (PCG) methods for the GS computation of the GPE. We investigate the choice of the preconditioner, which plays a key role in the acceleration of the convergence process. The performance of the new algorithms is tested in 1D, 2D and 3D. We conclude that the PCG method outperforms all the previous methods, most particularly for 2D and 3D fast rotating BECs, while being simple to implement.

SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

PubMed

Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

2013-04-30

The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

Low-gradient aortic stenosis.

PubMed

Clavel, Marie-Annick; Magne, Julien; Pibarot, Philippe

2016-09-07

An important proportion of patients with aortic stenosis (AS) have a 'low-gradient' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Periodontal tissue regeneration by combined applications of recombinant human osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma baboons (Papio ursinus).

PubMed

Ripamonti, U; Crooks, J; Petit, J C; Rueger, D C

2001-08-01

Native and recombinant human bone morphogenetic/osteogenic proteins (BMPs/ OPs) singly initiate bone induction in vivo. The finding of synchronous but spatially different BMPs/OPs expression during periodontal tissue morphogenesis suggests novel therapeutic approaches using morphogen combinations based on recapitulation of embryonic development. Twelve furcation defects prepared in the first and second mandibular molars of three adult baboons (Papio ursinus) were used to assess whether qualitative histological aspects of periodontal tissue regeneration could be enhanced and tissue morphogenesis modified by combined or single applications of recombinant hOP-1 and hBMP-2. Doses of BMPs/OPs were 100 microg of each protein per 1 g of insoluble collagenous bone matrix as carrier. Approximately 200 mg of carrier matrix was used per furcation defect. Undecalcified sections cut for histological analysis 60 d after healing of hOP-1-treated specimens showed substantial cementogenesis with scattered remnants of the collagenous carrier. hBMP-2 applied alone induced greater amounts of mineralized bone and osteoid when compared to hOP-1 alone or to combined morphogen applications. Combined applications of hOP-1 and hBMP-2 did not enhance alveolar bone regeneration or new attachment formation over and above the single applications of the morphogens. The results of this study, which is the first to attempt to address the structure-activity relationship amongst BMP/OP family members, indicate that tissue morphogenesis induced by hOP-1 and hBMP-2 is qualitatively different when the morphogens are applied singly, with hOP-1 inducing substantial cementogenesis. hBMP-2 treated defects, on the other hand, showed limited cementum formation but a temporal enhancement of alveolar bone regeneration and remodelling. The demonstration of therapeutic mosaicism in periodontal regeneration will require extensive testing of ratios and doses of recombinant morphogen combinations for optimal tissue engineering in clinical contexts.

Gradient-based Optimization for Poroelastic and Viscoelastic MR Elastography

PubMed Central

Tan, Likun; McGarry, Matthew D.J.; Van Houten, Elijah E.W.; Ji, Ming; Solamen, Ligin; Weaver, John B.

2017-01-01

We describe an efficient gradient computation for solving inverse problems arising in magnetic resonance elastography (MRE). The algorithm can be considered as a generalized ‘adjoint method’ based on a Lagrangian formulation. One requirement for the classic adjoint method is assurance of the self-adjoint property of the stiffness matrix in the elasticity problem. In this paper, we show this property is no longer a necessary condition in our algorithm, but the computational performance can be as efficient as the classic method, which involves only two forward solutions and is independent of the number of parameters to be estimated. The algorithm is developed and implemented in material property reconstructions using poroelastic and viscoelastic modeling. Various gradient- and Hessian-based optimization techniques have been tested on simulation, phantom and in vivo brain data. The numerical results show the feasibility and the efficiency of the proposed scheme for gradient calculation. PMID:27608454

Drosophila S2 cells secrete wingless on exosome-like vesicles but the wingless gradient forms independently of exosomes.

PubMed

Beckett, Karen; Monier, Solange; Palmer, Lucy; Alexandre, Cyrille; Green, Hannah; Bonneil, Eric; Raposo, Graca; Thibault, Pierre; Le Borgne, Roland; Vincent, Jean-Paul

2013-01-01

Wingless acts as a morphogen in Drosophila wing discs, where it specifies cell fates and controls growth several cell diameters away from its site of expression. Thus, despite being acylated and membrane associated, Wingless spreads in the extracellular space. Recent studies have focussed on identifying the route that Wingless follows in the secretory pathway and determining how it is packaged for release. We have found that, in medium conditioned by Wingless-expressing Drosophila S2 cells, Wingless is present on exosome-like vesicles and that this fraction activates signal transduction. Proteomic analysis shows that Wingless-containing exosome-like structures contain many Drosophila proteins that are homologous to mammalian exosome proteins. In addition, Evi, a multipass transmembrane protein, is also present on exosome-like vesicles. Using these exosome markers and a cell-based RNAi assay, we found that the small GTPase Rab11 contributes significantly to exosome production. This finding allows us to conclude from in vivo Rab11 knockdown experiments, that exosomes are unlikely to contribute to Wingless secretion and gradient formation in wing discs. Consistent with this conclusion, extracellularly tagged Evi expressed from a Bacterial Artificial Chromosome is not released from imaginal disc Wingless-expressing cells. © 2012 John Wiley & Sons A/S.

Dpp Signaling Activity Requires Pentagone to Scale with Tissue Size in the Growing Drosophila Wing Imaginal Disc

PubMed Central

Pyrowolakis, George; Bergmann, Sven; Affolter, Markus

2011-01-01

The wing of the fruit fly, Drosophila melanogaster, with its simple, two-dimensional structure, is a model organ well suited for a systems biology approach. The wing arises from an epithelial sac referred to as the wing imaginal disc, which undergoes a phase of massive growth and concomitant patterning during larval stages. The Decapentaplegic (Dpp) morphogen plays a central role in wing formation with its ability to co-coordinately regulate patterning and growth. Here, we asked whether the Dpp signaling activity scales, i.e. expands proportionally, with the growing wing imaginal disc. Using new methods for spatial and temporal quantification of Dpp activity and its scaling properties, we found that the Dpp response scales with the size of the growing tissue. Notably, scaling is not perfect at all positions in the field and the scaling of target gene domains is ensured specifically where they define vein positions. We also found that the target gene domains are not defined at constant concentration thresholds of the downstream Dpp activity gradients P-Mad and Brinker. Most interestingly, Pentagone, an important secreted feedback regulator of the pathway, plays a central role in scaling and acts as an expander of the Dpp gradient during disc growth. PMID:22039350

Haematopoietic stem and progenitor cells from human pluripotent stem cells

PubMed Central

Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.

2018-01-01

A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into haematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. Our combined approach of morphogen-driven differentiation and transcription-factor-mediated cell fate conversion produces haematopoietic stem and progenitor cells from pluripotent stem cells and holds promise for modelling haematopoietic disease in humanized mice and for therapeutic strategies in genetic blood disorders. PMID:28514439

[Role of G-protein alpha sub-units in the morphogenic processes of filamentous Ascomycota fungi].

PubMed

García-Rico, Ramón O; Fierro, Francisco

The phylum Ascomycota comprises about 75% of all the fungal species described, and includes species of medical, phytosanitary, agricultural, and biotechnological importance. The ability to spread, explore, and colonise new substrates is a feature of critical importance for this group of organisms. In this regard, basic processes such as conidial germination, the extension of hyphae and sporulation, make up the backbone of development in most filamentous fungi. These processes require specialised morphogenic machinery, coordinated and regulated by mechanisms that are still being elucidated. In recent years, substantial progress has been made in understanding the role of the signalling pathway mediated by heterotrimericG proteins in basic biological processes of many filamentous fungi. This review focuses on the role of the alpha subunits of heterotrimericG proteins in the morphogenic processes of filamentous Ascomycota. Copyright © 2016 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Crk synergizes with epidermal growth factor for epithelial invasion and morphogenesis and is required for the met morphogenic program.

PubMed

Lamorte, Louie; Rodrigues, Sonia; Naujokas, Monica; Park, Morag

2002-10-04

Activation of the Met receptor tyrosine kinase through its ligand, hepatocyte growth factor, stimulates cell spreading, cell dispersal, and the inherent morphogenic program of various epithelial cell lines. Although both hepatocyte growth factor and epidermal growth factor (EGF) can activate downstream signaling pathways in Madin-Darby canine kidney epithelial cells, EGF fails to promote the breakdown of cell-cell junctional complexes and initiate an invasive morphogenic program. We have undertaken a strategy to identify signals that synergize with EGF in this process. We provide evidence that the overexpression of the CrkII adapter protein complements EGF-stimulated pathways to induce cell dispersal in two-dimensional cultures and cell invasion and branching morphogenesis in three-dimensional collagen gels. This finding correlates with the ability of CrkII to promote the breakdown of adherens junctions in stable cell lines and the ability of EGF to stimulate enhanced Rac activity in cells overexpressing CrkII. We have previously shown that the Gab1-docking protein is required for branching morphogenesis downstream of the Met receptor. Consistent with a role for CrkII in promoting EGF-dependent branching morphogenesis, the binding of Gab1 to CrkII is required for the branching morphogenic program downstream of Met. Together, our data support a role for the CrkII adapter protein in epithelial invasion and morphogenesis and underscores the importance of considering the synergistic actions of signaling pathways in cancer progression.

Transcriptional response of Hoxb genes to retinoid signalling is regionally restricted along the neural tube rostrocaudal axis.

PubMed

Carucci, Nicoletta; Cacci, Emanuele; Nisi, Paola S; Licursi, Valerio; Paul, Yu-Lee; Biagioni, Stefano; Negri, Rodolfo; Rugg-Gunn, Peter J; Lupo, Giuseppe

2017-04-01

During vertebrate neural development, positional information is largely specified by extracellular morphogens. Their distribution, however, is very dynamic due to the multiple roles played by the same signals in the developing and adult neural tissue. This suggests that neural progenitors are able to modify their competence to respond to morphogen signalling and autonomously maintain positional identities after their initial specification. In this work, we take advantage of in vitro culture systems of mouse neural stem/progenitor cells (NSPCs) to show that NSPCs isolated from rostral or caudal regions of the mouse neural tube are differentially responsive to retinoic acid (RA), a pivotal morphogen for the specification of posterior neural fates. Hoxb genes are among the best known RA direct targets in the neural tissue, yet we found that RA could promote their transcription only in caudal but not in rostral NSPCs. Correlating with these effects, key RA-responsive regulatory regions in the Hoxb cluster displayed opposite enrichment of activating or repressing histone marks in rostral and caudal NSPCs. Finally, RA was able to strengthen Hoxb chromatin activation in caudal NSPCs, but was ineffective on the repressed Hoxb chromatin of rostral NSPCs. These results suggest that the response of NSPCs to morphogen signalling across the rostrocaudal axis of the neural tube may be gated by the epigenetic configuration of target patterning genes, allowing long-term maintenance of intrinsic positional values in spite of continuously changing extrinsic signals.

Medical image registration by combining global and local information: a chain-type diffeomorphic demons algorithm.

PubMed

Liu, Xiaozheng; Yuan, Zhenming; Zhu, Junming; Xu, Dongrong

2013-12-07

The demons algorithm is a popular algorithm for non-rigid image registration because of its computational efficiency and simple implementation. The deformation forces of the classic demons algorithm were derived from image gradients by considering the deformation to decrease the intensity dissimilarity between images. However, the methods using the difference of image intensity for medical image registration are easily affected by image artifacts, such as image noise, non-uniform imaging and partial volume effects. The gradient magnitude image is constructed from the local information of an image, so the difference in a gradient magnitude image can be regarded as more reliable and robust for these artifacts. Then, registering medical images by considering the differences in both image intensity and gradient magnitude is a straightforward selection. In this paper, based on a diffeomorphic demons algorithm, we propose a chain-type diffeomorphic demons algorithm by combining the differences in both image intensity and gradient magnitude for medical image registration. Previous work had shown that the classic demons algorithm can be considered as an approximation of a second order gradient descent on the sum of the squared intensity differences. By optimizing the new dissimilarity criteria, we also present a set of new demons forces which were derived from the gradients of the image and gradient magnitude image. We show that, in controlled experiments, this advantage is confirmed, and yields a fast convergence.

Meropenem/colistin synergy testing for multidrug-resistant Acinetobacter baumannii strains by a two-dimensional gradient technique applicable in routine microbiology.

PubMed

van Belkum, Alex; Halimi, Diane; Bonetti, Eve-Julie; Renzi, Gesuele; Cherkaoui, Abdessalam; Sauvonnet, Véronique; Martelin, Roland; Durand, Géraldine; Chatellier, Sonia; Zambardi, Gilles; Engelhardt, Anette; Karlsson, Åsa; Schrenzel, Jacques

2015-01-01

Precise assessment of potential therapeutic synergy, antagonism or indifference between antimicrobial agents currently depends on time-consuming and hard-to-standardize in vitro chequerboard titration methods. We here present a method based on a novel two-dimensional antibiotic gradient technique named Xact™. We used a test comprising a combination of perpendicular gradients of meropenem and colistin in a single quadrant. We compared test outcomes with those obtained with classical chequerboard microbroth dilution testing in a study involving 27 unique strains of multidrug-resistant Acinetobacter baumannii from diverse origins. We were able to demonstrate 92% concordance between the new technology and classical chequerboard titration using the A. baumannii collection. Two strains could not be analysed by Xact™ due to their out-of-range MIC of meropenem (>128 mg/L). The new test was shown to be diagnostically useful, easy to implement and less labour intensive than the classical method. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A quantum-classical theory with nonlinear and stochastic dynamics

NASA Astrophysics Data System (ADS)

Burić, N.; Popović, D. B.; Radonjić, M.; Prvanović, S.

2014-12-01

The method of constrained dynamical systems on the quantum-classical phase space is utilized to develop a theory of quantum-classical hybrid systems. Effects of the classical degrees of freedom on the quantum part are modeled using an appropriate constraint, and the interaction also includes the effects of neglected degrees of freedom. Dynamical law of the theory is given in terms of nonlinear stochastic differential equations with Hamiltonian and gradient terms. The theory provides a successful dynamical description of the collapse during quantum measurement.

Membrane Targeting of Grb2-associated Binder-1 (Gab1) Scaffolding Protein through Src Myristoylation Sequence Substitutes for Gab1 Pleckstrin Homology Domain and Switches an Epidermal Growth Factor Response to an Invasive Morphogenic Program

PubMed Central

Maroun, Christiane R.; Naujokas, Monica A.; Park, Morag

2003-01-01

The hepatocyte growth factor receptor tyrosine kinase Met promotes cell dissociation and the inherent morphogenic program of epithelial cells. In a search for substrates downstream from Met, we have previously identified the Grb2-associated binder-1 (Gab1) as critical for the morphogenic program. Gab1 is a scaffold protein that acts to diversify the signal downstream from the Met receptor through its ability to couple with multiple signal transduction pathways. Gab1 contains a pleckstrin homology (PH) domain with specificity for phosphatidylinositol 3,4,5-trisphosphate. The phospholipid binding capacity of the Gab1 PH domain is required for the localization of Gab1 at sites of cell-cell contact in colonies of epithelial cells and for epithelial morphogenesis, suggesting that PH domain-dependent subcellular localization of Gab1 is a prerequisite for function. We have investigated the requirement for membrane localization of Gab1 for biological activity. We show that substitution of the Gab1 PH domain with the myristoylation signal from the c-Src protein is sufficient to replace the Gab1 PH domain for epithelial morphogenesis. The membrane targeting of Gab1 enhances Rac activity in the absence of stimulation and switches a nonmorphogenic noninvasive response to epidermal growth factor to a morphogenic invasive program. These results suggest that the subcellular localization of Gab1 is a critical determinant for epithelial morphogenesis and invasiveness. PMID:12686619

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.

PubMed

Davis, Hayley; Irshad, Shazia; Bansal, Mukesh; Rafferty, Hannah; Boitsova, Tatjana; Bardella, Chiara; Jaeger, Emma; Lewis, Annabelle; Freeman-Mills, Luke; Giner, Francesc Castro; Rodenas-Cuadrado, Pedro; Mallappa, Sreelakshmi; Clark, Susan; Thomas, Huw; Jeffery, Rosemary; Poulsom, Richard; Rodriguez-Justo, Manuel; Novelli, Marco; Chetty, Runjan; Silver, Andrew; Sansom, Owen James; Greten, Florian R; Wang, Lai Mun; East, James Edward; Tomlinson, Ian; Leedham, Simon John

2015-01-01

Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.

Decoding the phosphorylation code in Hedgehog signal transduction

PubMed Central

Chen, Yongbin; Jiang, Jin

2013-01-01

Hedgehog (Hh) signaling plays pivotal roles in embryonic development and adult tissue homeostasis, and its deregulation leads to numerous human disorders including cancer. Binding of Hh to Patched (Ptc), a twelve-transmembrane protein, alleviates its inhibition of Smoothened (Smo), a seven-transmembrane protein related to G-protein-coupled receptors (GPCRs), leading to Smo phosphorylation and activation. Smo acts through intracellular signaling complexes to convert the latent transcription factor Cubitus interruptus (Ci)/Gli from a truncated repressor to a full-length activator, leading to derepression/activation of Hh target genes. Increasing evidence suggests that phosphorylation participates in almost every step in the signal relay from Smo to Ci/Gli, and that differential phosphorylation of several key pathway components may be crucial for translating the Hh morphogen gradient into graded pathway activities. In this review, we focus on the multifaceted roles that phosphorylation plays in Hh signal transduction, and discuss the conservation and difference between Drosophila and mammalian Hh signaling mechanisms. PMID:23337587

Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C. elegans.

PubMed

Mentink, Remco A; Middelkoop, Teije C; Rella, Lorenzo; Ji, Ni; Tang, Chung Yin; Betist, Marco C; van Oudenaarden, Alexander; Korswagen, Hendrik C

2014-10-27

Members of the Wnt family of secreted signaling proteins are key regulators of cell migration and axon guidance. In the nematode C. elegans, the migration of the QR neuroblast descendants requires multiple Wnt ligands and receptors. We found that the migration of the QR descendants is divided into three sequential phases that are each mediated by a distinct Wnt signaling mechanism. Importantly, the transition from the first to the second phase, which is the main determinant of the final position of the QR descendants along the anteroposterior body axis, is mediated through a cell-autonomous process in which the time-dependent expression of a Wnt receptor turns on the canonical Wnt/β-catenin signaling response that is required to terminate long-range anterior migration. Our results show that, in addition to direct guidance of cell migration by Wnt morphogenic gradients, cell migration can also be controlled indirectly through cell-intrinsic modulation of Wnt signaling responses.

Signaling networks in joint development

PubMed Central

Salva, Joanna E.; Merrill, Amy E.

2016-01-01

Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the fluid-filled synovial space between the bones, are found in high-mobility regions and are the most common type of joint. Cartilaginous joints unite adjacent bones through either a hyaline cartilage or fibrocartilage intermediate. Fibrous joints, which include the cranial sutures, form a direct union between bones through fibrous connective tissue. We describe how the distinct morphologic and histogenic characteristics of these joint classes are established during embryonic development. Collectively, these studies reveal that despite the heterogeneity of joint strength and mobility, joint development throughout the skeleton utilizes common signaling networks via long-range morphogen gradients and direct cell-cell contact. This suggests that different joint types represent specialized variants of homologous developmental modules. Identifying the unifying aspects of the signaling networks between joint classes allows a more complete understanding of the signaling code for joint formation, which is critical to improving strategies for joint regeneration and repair. PMID:27859991

Modelling Spatially Regulated β-Catenin Dynamics and Invasion in Intestinal Crypts

PubMed Central

Murray, Philip J.; Kang, Jun-Won; Mirams, Gary R.; Shin, Sung-Young; Byrne, Helen M.; Maini, Philip K.; Cho, Kwang-Hyun

2010-01-01

Experimental data (e.g., genetic lineage and cell population studies) on intestinal crypts reveal that regulatory features of crypt behavior, such as control via morphogen gradients, are remarkably well conserved among numerous organisms (e.g., from mouse and rat to human) and throughout the different regions of the small and large intestines. In this article, we construct a partial differential equation model of a single colonic crypt that describes the spatial distribution of Wnt pathway proteins along the crypt axis. The novelty of our continuum model is that it is based upon assumptions that can be directly related to processes at the cellular and subcellular scales. We use the model to predict how the distributions of Wnt pathway proteins are affected by mutations. The model is then extended to investigate how mutant cell populations can invade neighboring crypts. The model simulations suggest that cell crowding caused by increased proliferation and decreased cell loss may be sufficient for a mutant cell population to colonize a neighboring healthy crypt. PMID:20682248

An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling

PubMed Central

Sciammas, Roger; Li, Ying; Warmflash, Aryeh; Song, Yiqiang; Dinner, Aaron R; Singh, Harinder

2011-01-01

The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks (GRNs) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation (SHM) and/or class switch DNA recombination (CSR) before differentiating into antibody-secreting plasma cells. We construct a mathematical model for a GRN underlying this developmental dynamic. The intensity of signaling through the Ig receptor is shown to control the bimodal expression of a pivotal transcription factor, IRF-4, which dictates B cell fate outcomes. Computational modeling coupled with experimental analysis supports a model of ‘kinetic control', in which B cell developmental trajectories pass through an obligate transient state of variable duration that promotes diversification of the antibody repertoire by SHM/CSR in direct response to antigens. More generally, this network motif could be used to translate a morphogen gradient into developmental inductive events of varying time, thereby enabling the specification of distinct cell fates. PMID:21613984

Collective chemotaxis and segregation of active bacterial colonies

NASA Astrophysics Data System (ADS)

Amar, M. Ben

2016-02-01

Still recently, bacterial fluid suspensions have motivated a lot of works, both experimental and theoretical, with the objective to understand their collective dynamics from universal and simple rules. Since some species are active, most of these works concern the strong interactions that these bacteria exert on a forced flow leading to instabilities, chaos and turbulence. Here, we investigate the self-organization of expanding bacterial colonies under chemotaxis, proliferation and eventually active-reaction. We propose a simple model to understand and quantify the physical properties of these living organisms which either give cohesion or on the contrary dispersion to the colony. Taking into account the diffusion and capture of morphogens complicates the model since it induces a bacterial density gradient coupled to bacterial density fluctuations and dynamics. Nevertheless under some specific conditions, it is possible to investigate the pattern formation as a usual viscous fingering instability. This explains the similarity and differences of patterns according to the physical bacterial suspension properties and explain the factors which favor compactness or branching.

Patterned Cell Alignment in Response to Macroscale Curvature

NASA Astrophysics Data System (ADS)

Bade, Nathan; Kamien, Randall; Assoian, Richard; Stebe, Kathleen

The formation of spatial behavior patterns in tissues is a long-standing problem in biology. Decades of research have focused on understanding how biochemical signaling and morphogen gradients establish cell patterns during development and tissue morphogenesis. Here, we show that geometry and physical cues can drive organization and pattern formation. We find that mouse embryonic fibroblasts and human vascular smooth muscle cells sense curvature differently when in monolayers than when isolated on surfaces with various amounts of Gaussian curvature. While the long, apical stress fibers within these cells align in the direction of minimum curvature on cylindrical substrates, a subpopulation of stress fibers beneath the nucleus aligns in the circumferential direction and is bent maximally. We find dramatic reorganization of the actin cytoskeleton upon activation of RhoA, which is associated with increased contractility of the fibers. Thus, stress fiber alignment is likely a result of a complex balance between energy penalties associated with stress fiber bending, contractility, and the dynamics of F-actin assembly.

A role for NRAGE in NF-κB activation through the non-canonical BMP pathway

PubMed Central

2010-01-01

Background Previous studies have linked neurotrophin receptor-interacting MAGE protein to the bone morphogenic protein signaling pathway and its effect on p38 mediated apoptosis of neural progenitor cells via the XIAP-Tak1-Tab1 complex. Its effect on NF-κB has yet to be explored. Results Herein we report that NRAGE, via the same XIAP-Tak1-Tab1 complex, is required for the phosphorylation of IKK -α/β and subsequent transcriptional activation of the p65 subunit of NF-κB. Ablation of endogenous NRAGE by siRNA inhibited NF-κB pathway activation, while ablation of Tak1 and Tab1 by morpholino inhibited overexpression of NRAGE from activating NF-κB. Finally, cytokine profiling of an NRAGE over-expressing stable line revealed the expression of macrophage migration inhibitory factor. Conclusion Modulation of NRAGE expression revealed novel roles in regulating NF-κB activity in the non-canonical bone morphogenic protein signaling pathway. The expression of macrophage migration inhibitory factor by bone morphogenic protein -4 reveals novel crosstalk between an immune cytokine and a developmental pathway. PMID:20100315

Structural analysis of eyespots: dynamics of morphogenic signals that govern elemental positions in butterfly wings

PubMed Central

2012-01-01

Background To explain eyespot colour-pattern determination in butterfly wings, the induction model has been discussed based on colour-pattern analyses of various butterfly eyespots. However, a detailed structural analysis of eyespots that can serve as a foundation for future studies is still lacking. In this study, fundamental structural rules related to butterfly eyespots are proposed, and the induction model is elaborated in terms of the possible dynamics of morphogenic signals involved in the development of eyespots and parafocal elements (PFEs) based on colour-pattern analysis of the nymphalid butterfly Junonia almana. Results In a well-developed eyespot, the inner black core ring is much wider than the outer black ring; this is termed the inside-wide rule. It appears that signals are wider near the focus of the eyespot and become narrower as they expand. Although fundamental signal dynamics are likely to be based on a reaction-diffusion mechanism, they were described well mathematically as a type of simple uniformly decelerated motion in which signals associated with the outer and inner black rings of eyespots and PFEs are released at different time points, durations, intervals, and initial velocities into a two-dimensional field of fundamentally uniform or graded resistance; this produces eyespots and PFEs that are diverse in size and structure. The inside-wide rule, eyespot distortion, structural differences between small and large eyespots, and structural changes in eyespots and PFEs in response to physiological treatments were explained well using mathematical simulations. Natural colour patterns and previous experimental findings that are not easily explained by the conventional gradient model were also explained reasonably well by the formal mathematical simulations performed in this study. Conclusions In a mode free from speculative molecular interactions, the present study clarifies fundamental structural rules related to butterfly eyespots, delineates a theoretical basis for the induction model, and proposes a mathematically simple mode of long-range signalling that may reflect developmental mechanisms associated with butterfly eyespots. PMID:22409965

An intermediate level of BMP signaling directly specifies cranial neural crest progenitor cells in zebrafish.

PubMed

Schumacher, Jennifer A; Hashiguchi, Megumi; Nguyen, Vu H; Mullins, Mary C

2011-01-01

The specification of the neural crest progenitor cell (NCPC) population in the early vertebrate embryo requires an elaborate network of signaling pathways, one of which is the Bone Morphogenetic Protein (BMP) pathway. Based on alterations in neural crest gene expression in zebrafish BMP pathway component mutants, we previously proposed a model in which the gastrula BMP morphogen gradient establishes an intermediate level of BMP activity establishing the future NCPC domain. Here, we tested this model and show that an intermediate level of BMP signaling acts directly to specify the NCPC. We quantified the effects of reducing BMP signaling on the number of neural crest cells and show that neural crest cells are significantly increased when BMP signaling is reduced and that this increase is not due to an increase in cell proliferation. In contrast, when BMP signaling is eliminated, NCPC fail to be specified. We modulated BMP signaling levels in BMP pathway mutants with expanded or no NCPCs to demonstrate that an intermediate level of BMP signaling specifies the NCPC. We further investigated the ability of Smad5 to act in a graded fashion by injecting smad5 antisense morpholinos and show that increasing doses first expand the NCPCs and then cause a loss of NCPCs, consistent with Smad5 acting directly in neural crest progenitor specification. Using Western blot analysis, we show that P-Smad5 levels are dose-dependently reduced in smad5 morphants, consistent with an intermediate level of BMP signaling acting through Smad5 to specify the neural crest progenitors. Finally, we performed chimeric analysis to demonstrate for the first time that BMP signal reception is required directly by NCPCs for their specification. Together these results add substantial evidence to a model in which graded BMP signaling acts as a morphogen to pattern the ectoderm, with an intermediate level acting in neural crest specification.

Structural analysis of eyespots: dynamics of morphogenic signals that govern elemental positions in butterfly wings.

PubMed

Otaki, Joji M

2012-03-13

To explain eyespot colour-pattern determination in butterfly wings, the induction model has been discussed based on colour-pattern analyses of various butterfly eyespots. However, a detailed structural analysis of eyespots that can serve as a foundation for future studies is still lacking. In this study, fundamental structural rules related to butterfly eyespots are proposed, and the induction model is elaborated in terms of the possible dynamics of morphogenic signals involved in the development of eyespots and parafocal elements (PFEs) based on colour-pattern analysis of the nymphalid butterfly Junonia almana. In a well-developed eyespot, the inner black core ring is much wider than the outer black ring; this is termed the inside-wide rule. It appears that signals are wider near the focus of the eyespot and become narrower as they expand. Although fundamental signal dynamics are likely to be based on a reaction-diffusion mechanism, they were described well mathematically as a type of simple uniformly decelerated motion in which signals associated with the outer and inner black rings of eyespots and PFEs are released at different time points, durations, intervals, and initial velocities into a two-dimensional field of fundamentally uniform or graded resistance; this produces eyespots and PFEs that are diverse in size and structure. The inside-wide rule, eyespot distortion, structural differences between small and large eyespots, and structural changes in eyespots and PFEs in response to physiological treatments were explained well using mathematical simulations. Natural colour patterns and previous experimental findings that are not easily explained by the conventional gradient model were also explained reasonably well by the formal mathematical simulations performed in this study. In a mode free from speculative molecular interactions, the present study clarifies fundamental structural rules related to butterfly eyespots, delineates a theoretical basis for the induction model, and proposes a mathematically simple mode of long-range signalling that may reflect developmental mechanisms associated with butterfly eyespots.

Optimal trajectories for aeroassisted orbital transfer

NASA Technical Reports Server (NTRS)

Miele, A.; Venkataraman, P.

1983-01-01

Consideration is given to classical and minimax problems involved in aeroassisted transfer from high earth orbit (HEO) to low earth orbit (LEO). The transfer is restricted to coplanar operation, with trajectory control effected by means of lift modulation. The performance of the maneuver is indexed to the energy expenditure or, alternatively, the time integral of the heating rate. Firist-order optimality conditions are defined for the classical approach, as are a sequential gradient-restoration algorithm and a combined gradient-restoration algorithm. Minimization techniques are presented for the aeroassisted transfer energy consumption and time-delay integral of the heating rate, as well as minimization of the pressure. It is shown that the eigenvalues of the Jacobian matrix of the differential system is both stiff and unstable, implying that the sequential gradient restoration algorithm in its present version is unsuitable. A new method, involving a multipoint approach to the two-poing boundary value problem, is recommended.

Flow regimes in a shallow rotating cylindrical annulus with temperature gradients imposed on the horizontal boundaries

NASA Technical Reports Server (NTRS)

Hathaway, D. H.; Fowlis, W. W.

1986-01-01

Experimental flow regime diagrams are determined for a new rotating cylindrical annulus configuration which permits a measure of control over the internal vertical temperature gradient. The new annulus has radial temperature gradients imposed on plane horizontal thermally conducting endwalls (with the cylindrical sidewalls as insulators) and is considered to be more relevant to atmospheric dynamics studies than the classical cylindrical annulus. Observations have revealed that, in addition to the axisymmetric flow and nonaxisymmetric baroclinic wave flow which occur in the classical annulus, two additional nonaxisymmetric flow types occur in the new annulus: boundary-layer thermal convection and deep thermal convection. Flow regime diagrams for three different values of the imposed vertical temperature difference are presented, and explanations for the flow transitions are offered. The new annulus provides scientific backup for the proposed Atmospheric General Circulation Experiment for Spacelab. The apparatus diagram is included.

Validity of the toposequence approach along a rainfall gradient at a desert fringe

NASA Astrophysics Data System (ADS)

Yair, Aaron

2017-04-01

According to the "classic" toposequence approach soil's properties are closely related to the position of a soil along a slope. The positional differences in soil properties are usually attributed to spatial differences in runoff; erosion and deposition processes. These processes reflect long term effects of the spatial redistribution of water, solids and soluble materials, which are of great importance in respect of nutrient cycling on the landscape scale, and the structuring of natural ecosystems. The "classic" toposequence approach has been seriously questioned by Sommer and Schlichting (1997). They were followed by many scientists of various disciplines (hydrology, ecology, paleopedology, paleoclimate etc). The present study covers three topo-sequences, located in southern Israel, along an average annual rainfall gradient of 90-300 mm. The classic toposequence approach does not apply to none of them, and the controlling factors vary from one site to another.

Local pharmacological effects of tungstate on the color-pattern determination of butterfly wings: a possible relationship between the eyespot and parafocal element.

PubMed

Dhungel, Bidur; Otaki, Joji M

2009-11-01

Butterfly wing color patterns can be changed by the application of a temperature shock or pharmacological agents such as tungstate, producing a distinctive type of elemental modification called the TS (temperature shock) type. Heterochronic uncoupling between the signaling and reception steps during the color-pattern determination process has been proposed as a mechanism for TS-type changes. As an extension of this hypothesis, both the parafocal element (PFE) and the eyespot in the same wing compartment are considered to be determined by morphogenic signal(s) emitted from the same eyespot focus. However, these models need to be examined with additional experimental data. Furthermore, there is controversy as to whether the action of tungstate on wing color patterns is direct or Indirect. Using a species of nymphalid butterfly (Junonia orithya), we have devised a simple method for the local application of pharmacological agents directly on developing wings of pupae. Local tungstate application resulted in reduced eyespots and circular dislocated PFEs in the eyespot-less compartments only on the treated wing, demonstrating that tungstate directly induces color-pattern changes on wings. We further examined the eyespot-PFE relationship in normal and cold-shocked Individuals, showing that an eyespot can be superimposed on a PFE and vice versa, probably depending on the timing of their fate determination. Taken together, we propose a two-morphogen model for the normal color-pattern determination, in which the morphogenic signals for the eyespot and PFE are different from each other despite their Identical origin. This two-morphogen model is compatible with the heterochronic uncoupling model for TS-type changes.

Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

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

Yang Dongren; Howard, Angela; Bruun, Donald

2008-04-01

A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrationsmore » that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE{sup -/-}) versus wild type (AChE{sup +/+}) mice indicated that while these OPs inhibited axonal growth in AChE{sup +/+} DRG neurons, they had no effect on axonal growth in AChE{sup -/-} DRG neurons. However, transfection of AChE{sup -/-} DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.« less

Quantitative analysis of Hedgehog gradient formation using an inducible expression system

PubMed Central

Su, Vivian F; Jones, Kelly A; Brodsky, Michael; The, Inge

2007-01-01

Background The Hedgehog (Hh) family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh. Results We have used an inducible, cell type-specific expression system to characterize the three-dimensional distribution of newly synthesized, GFP-tagged Hh in the developing Drosophila wing. Following induction of Hh-GFP expression in posterior producing cells, punctate structures containing Hh-GFP were observed in the anterior target cells. The distance of these particles from the expressing cells was quantified to determine the shape of the Hh gradient at different time points following induction. The majority of cholesterol-modified Hh-GFP was found associated with cells near the anterior/posterior (A/P) boundary, which express high levels of Hh target genes. Without cholesterol, the Hh gradient was flatter, with a lower percentage of particles near the source and a greater maximum distance. Inhibition of Dynamin-dependent endocytosis blocked formation of intracellular Hh particles, but did not prevent movement of newly synthesized Hh to the apical or basolateral surfaces of target cells. In the absence of both cholesterol and endocytosis, Hh particles accumulated in the extracellular space. Staining for the Hh receptor Ptc revealed four categories of Hh particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Interestingly, mainly cholesterol-modified Hh is detected in the cytoplasmic particles lacking Ptc. Conclusion We have developed a system to quantitatively analyze Hh distribution during gradient formation. We directly demonstrate that inhibition of Dynamin-dependent endocytosis is not required for movement of Hh across target cells, indicating that transcytosis is not required for Hh gradient formation. The localization of Hh in these cells suggests that Hh normally moves across both apical and basolateral regions of the target cells. We also conclude that cholesterol modification is required for formation of a specific subset of Hh particles that are both cytoplasmic and not associated with the receptor Ptc. PMID:17484784

Quantitative analysis of Hedgehog gradient formation using an inducible expression system.

PubMed

Su, Vivian F; Jones, Kelly A; Brodsky, Michael; The, Inge

2007-05-07

The Hedgehog (Hh) family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh. We have used an inducible, cell type-specific expression system to characterize the three-dimensional distribution of newly synthesized, GFP-tagged Hh in the developing Drosophila wing. Following induction of Hh-GFP expression in posterior producing cells, punctate structures containing Hh-GFP were observed in the anterior target cells. The distance of these particles from the expressing cells was quantified to determine the shape of the Hh gradient at different time points following induction. The majority of cholesterol-modified Hh-GFP was found associated with cells near the anterior/posterior (A/P) boundary, which express high levels of Hh target genes. Without cholesterol, the Hh gradient was flatter, with a lower percentage of particles near the source and a greater maximum distance. Inhibition of Dynamin-dependent endocytosis blocked formation of intracellular Hh particles, but did not prevent movement of newly synthesized Hh to the apical or basolateral surfaces of target cells. In the absence of both cholesterol and endocytosis, Hh particles accumulated in the extracellular space. Staining for the Hh receptor Ptc revealed four categories of Hh particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Interestingly, mainly cholesterol-modified Hh is detected in the cytoplasmic particles lacking Ptc. We have developed a system to quantitatively analyze Hh distribution during gradient formation. We directly demonstrate that inhibition of Dynamin-dependent endocytosis is not required for movement of Hh across target cells, indicating that transcytosis is not required for Hh gradient formation. The localization of Hh in these cells suggests that Hh normally moves across both apical and basolateral regions of the target cells. We also conclude that cholesterol modification is required for formation of a specific subset of Hh particles that are both cytoplasmic and not associated with the receptor Ptc.

Development of 3D in vitro platform technology to engineer mesenchymal stem cells.

PubMed

Hosseinkhani, Hossein; Hong, Po-Da; Yu, Dah-Shyong; Chen, Yi-Ru; Ickowicz, Diana; Farber, Ira-Yudovin; Domb, Abraham J

2012-01-01

This study aims to develop a three-dimensional in vitro culture system to genetically engineer mesenchymal stem cells (MSC) to express bone morphogenic protein-2. We employed nanofabrication technologies borrowed from the spinning industry, such as electrospinning, to mass-produce identical building blocks in a variety of shapes and sizes to fabricate electrospun nanofiber sheets comprised of composites of poly (glycolic acid) and collagen. Homogenous nanoparticles of cationic biodegradable natural polymer were formed by simple mixing of an aqueous solution of plasmid DNA encoded bone morphogenic protein-2 with the same volume of cationic polysaccharide, dextran-spermine. Rat bone marrow MSC were cultured on electrospun nanofiber sheets comprised of composites of poly (glycolic acid) and collagen prior to the incorporation of the nanoparticles into the nanofiber sheets. Bone morphogenic protein-2 was significantly detected in MSC cultured on nanofiber sheets incorporated with nanoparticles after 2 days compared with MSC cultured on nanofiber sheets incorporated with naked plasmid DNA. We conclude that the incorporation of nanoparticles into nanofiber sheets is a very promising strategy to genetically engineer MSC and can be used for further applications in regenerative medicine therapy.

Cell death and morphogenesis during early mouse development: Are they interconnected?

PubMed Central

Bedzhov, Ivan; Zernicka-Goetz, Magdalena

2015-01-01

Shortly after implantation the embryonic lineage transforms from a coherent ball of cells into polarized cup shaped epithelium. Recently we elucidated a previously unknown apoptosis-independent morphogenic event that reorganizes the pluripotent lineage. Polarization cues from the surrounding basement membrane rearrange the epiblast into a polarized rosette-like structure, where subsequently a central lumen is established. Thus, we provided a new model revising the current concept of apoptosis-dependent epiblast morphogenesis. Cell death however has to be tightly regulated during embryogenesis to ensure developmental success. Here, we follow the stages of early mouse development and take a glimpse at the critical signaling and morphogenic events that determine cells destiny and reshape the embryonic lineage. PMID:25640415

Classical continuum theory limits to determine the size-dependency of mechanical properties of GaN NWs

NASA Astrophysics Data System (ADS)

Zamani Kouhpanji, Mohammad Reza; Behzadirad, Mahmoud; Busani, Tito

2017-12-01

We used the stable strain gradient theory including acceleration gradients to investigate the classical and nonclassical mechanical properties of gallium nitride (GaN) nanowires (NWs). We predicted the static length scales, Young's modulus, and shear modulus of the GaN NWs from the experimental data. Combining these results with atomic simulations, we also found the dynamic length scale of the GaN NWs. Young's modulus, shear modulus, static, and dynamic length scales were found to be 318 GPa, 131 GPa, 8 nm, and 8.9 nm, respectively, usable for demonstrating the static and dynamic behaviors of GaN NWs having diameters from a few nm to bulk dimensions. Furthermore, the experimental data were analyzed with classical continuum theory (CCT) and compared with the available literature to illustrate the size-dependency of the mechanical properties of GaN NWs. This practice resolves the previous published discrepancies that happened due to the limitations of CCT used for determining the mechanical properties of GaN NWs and their size-dependency.

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside of the crypt base stem cell niche

PubMed Central

Bansal, Mukesh; Rafferty, Hannah; Boitsova, Tatjana; Bardella, Chiara; Jaeger, Emma; Lewis, Annabelle; Freeman-Mills, Luke; Giner, Francesc Castro; Rodenas-Cuadrado, Pedro; Mallappa, Sreelakshmi; Clark, Susan; Thomas, Huw; Jeffery, Rosemary; Poulsom, Richard; Rodriguez-Justo, Manuel; Novelli, Marco; Chetty, Runjan; Silver, Andrew; Sansom, Owen James; Greten, Florian R; Wang, Lai Mun; East, James Edward; Tomlinson, Ian; Leedham, Simon John

2015-01-01

Hereditary mixed polyposis syndrome (HMPS) is characterised by the development of mixed morphology colorectal tumours and is caused by a 40 kb duplication that results in aberrant epithelial expression of the mesenchymal Bone Morphogenetic Protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell-fate, that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem-cell properties in Lgr5 negative (non-expressing) progenitor cells that have exited the stem-cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem-cell is not the sole cell-of-origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic pre-malignant lesions with a hitherto unknown pathogenesis and these lesions can be considered the sporadic equivalents of HMPS polyps. PMID:25419707

Modelling spatially regulated beta-catenin dynamics and invasion in intestinal crypts.

PubMed

Murray, Philip J; Kang, Jun-Won; Mirams, Gary R; Shin, Sung-Young; Byrne, Helen M; Maini, Philip K; Cho, Kwang-Hyun

2010-08-04

Experimental data (e.g., genetic lineage and cell population studies) on intestinal crypts reveal that regulatory features of crypt behavior, such as control via morphogen gradients, are remarkably well conserved among numerous organisms (e.g., from mouse and rat to human) and throughout the different regions of the small and large intestines. In this article, we construct a partial differential equation model of a single colonic crypt that describes the spatial distribution of Wnt pathway proteins along the crypt axis. The novelty of our continuum model is that it is based upon assumptions that can be directly related to processes at the cellular and subcellular scales. We use the model to predict how the distributions of Wnt pathway proteins are affected by mutations. The model is then extended to investigate how mutant cell populations can invade neighboring crypts. The model simulations suggest that cell crowding caused by increased proliferation and decreased cell loss may be sufficient for a mutant cell population to colonize a neighboring healthy crypt. 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

FGF signaling refines Wnt gradients to regulate the patterning of taste papillae.

PubMed

Prochazkova, Michaela; Häkkinen, Teemu J; Prochazka, Jan; Spoutil, Frantisek; Jheon, Andrew H; Ahn, Youngwook; Krumlauf, Robb; Jernvall, Jukka; Klein, Ophir D

2017-06-15

The patterning of repeated structures is a major theme in developmental biology, and the inter-relationship between spacing and size of such structures is an unresolved issue. Fungiform papillae are repeated epithelial structures that house taste buds on the anterior tongue. Here, we report that FGF signaling is a crucial regulator of fungiform papillae development. We found that mesenchymal FGF10 controls the size of the papillary area, while overall patterning remains unchanged. Our results show that FGF signaling negatively affects the extent of canonical Wnt signaling, which is the main activation pathway during fungiform papillae development; however, this effect does not occur at the level of gene transcription. Rather, our experimental data, together with computational modeling, indicate that FGF10 modulates the range of Wnt effects, likely via induction of Sostdc1 expression. We suggest that modification of the reach of Wnt signaling could be due to local changes in morphogen diffusion, representing a novel mechanism in this tissue context, and we propose that this phenomenon might be involved in a broader array of mammalian developmental processes. © 2017. Published by The Company of Biologists Ltd.

The disruption of a novel limb cis-regulatory element of SHH is associated with autosomal dominant preaxial polydactyly-hypertrichosis

PubMed Central

Petit, Florence; Jourdain, Anne-Sophie; Holder-Espinasse, Muriel; Keren, Boris; Andrieux, Joris; Duterque-Coquillaud, Martine; Porchet, Nicole; Manouvrier-Hanu, Sylvie; Escande, Fabienne

2016-01-01

The expression gradient of the morphogen Sonic Hedgehog (SHH) is crucial in establishing the number and the identity of the digits during anteroposterior patterning of the limb. Its anterior ectopic expression is responsible for preaxial polydactyly (PPD). Most of these malformations are due to the gain-of-function of the Zone of Polarizing Activity Regulatory Sequence, the only limb-specific enhancer of SHH known to date. We report a family affected with a novel condition associating PPD and hypertrichosis of the upper back, following an autosomal dominant mode of inheritance. This phenotype is consistent with deregulation of SHH expression during limb and follicle development. In affected members, we identified a 2 kb deletion located ~240 kb upstream from the SHH promoter. The deleted sequence is capable of repressing the transcriptional activity of the SHH promoter in vitro, consistent with a silencer activity. We hypothesize that the deletion of this silencer could be responsible for SHH deregulation during development, leading to a PPD-hypertrichosis phenotype. PMID:25782671

Organogenic nodule formation in hop: a tool to study morphogenesis in plants with biotechnological and medicinal applications.

PubMed

Fortes, Ana M; Santos, Filipa; Pais, Maria S

2010-01-01

The usage of Humulus lupulus for brewing increased the demand for high-quality plant material. Simultaneously, hop has been used in traditional medicine and recently recognized with anticancer and anti-infective properties. Tissue culture techniques have been reported for a wide range of species, and open the prospect for propagation of disease-free, genetically uniform and massive amounts of plants in vitro. Moreover, the development of large-scale culture methods using bioreactors enables the industrial production of secondary metabolites. Reliable and efficient tissue culture protocol for shoot regeneration through organogenic nodule formation was established for hop. The present review describes the histological, and biochemical changes occurring during this morphogenic process, together with an analysis of transcriptional and metabolic profiles. We also discuss the existence of common molecular factors among three different morphogenic processes: organogenic nodules and somatic embryogenesis, which strictly speaking depend exclusively on intrinsic developmental reprogramming, and legume nitrogen-fixing root nodules, which arises in response to symbiosis. The review of the key factors that participate in hop nodule organogenesis and the comparison with other morphogenic processes may have merit as a study presenting recent advances in complex molecular networks occurring during morphogenesis and together, these provide a rich framework for biotechnology applications.

Sonic Hedgehog promotes the survival of neural crest cells by limiting apoptosis induced by the dependence receptor CDON during branchial arch development.

PubMed

Delloye-Bourgeois, Céline; Rama, Nicolas; Brito, José; Le Douarin, Nicole; Mehlen, Patrick

2014-09-26

Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO or CDON) was identified as a receptor for the classic morphogen Sonic Hedgehog (SHH). It has been shown that, in cell culture, CDO also behaves as a SHH dependence receptor: CDO actively triggers apoptosis in absence of SHH via a proteolytic cleavage in CDO intracellular domain. We present evidence that CDO is also pro-apoptotic in the developing neural tube where SHH is known to act as a survival factor. SHH, produced by the ventral foregut endoderm, was shown to promote survival of facial neural crest cells (NCCs) that colonize the first branchial arch (BA1). We show here that the survival activity of SHH on neural crest cells is due to SHH-mediated inhibition of CDO pro-apoptotic activity. Silencing of CDO rescued NCCs from apoptosis observed upon SHH inhibition in the ventral foregut endoderm. Thus, the pair SHH/dependence receptor CDO may play an important role in neural crest cell survival during the formation of the first branchial arch. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantum generalisation of feedforward neural networks

NASA Astrophysics Data System (ADS)

Wan, Kwok Ho; Dahlsten, Oscar; Kristjánsson, Hlér; Gardner, Robert; Kim, M. S.

2017-09-01

We propose a quantum generalisation of a classical neural network. The classical neurons are firstly rendered reversible by adding ancillary bits. Then they are generalised to being quantum reversible, i.e., unitary (the classical networks we generalise are called feedforward, and have step-function activation functions). The quantum network can be trained efficiently using gradient descent on a cost function to perform quantum generalisations of classical tasks. We demonstrate numerically that it can: (i) compress quantum states onto a minimal number of qubits, creating a quantum autoencoder, and (ii) discover quantum communication protocols such as teleportation. Our general recipe is theoretical and implementation-independent. The quantum neuron module can naturally be implemented photonically.

Swarms, phase transitions, and collective intelligence

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

Millonas, M.M.

1992-01-01

A model of the collective behavior of a large number of locally acting organisms is proposed. The model is intended to be realistic, but turns out to fit naturally into the category of connectionist models, Like all connectionist models, its properties can be divided into the categories of structure, dynamics, and learning. The space in which the organisms move is discretized, and is modeled by a lattice of nodes, or cells. Each cell hag a specified volume, and is connected to other cells in the space in a definite way. Organisms move probabilistically between local cells in this space, butmore » with weights dependent on local morphogenic substances, or morphogens. The morphogens are in turn are effected by the passage of an organism. The evolution of the morphogens, and the corresponding constitutes of the organisms constitutes the collective behavior of the group. The generic properties of such systems are analyzed, and a number of results are obtained. The model has various types of phase transitions and self-organizing properties controlled both by the level of the noise, and other parameters. It is hoped that the present mode; might serve as a paradigmatic example of a complex cooperative system in nature. In particular this model can be used to explore the relation of phase transitions to at least three important issues encountered in artificial life. Firstly, that of emergence as complex adaptive behavior. Secondly, as an exploration of second order phase transitions in biological systems. Lastly, to derive behavioral criteria for the evolution of collective behavior in social organisms. The model is then applied to the specific case of ants moving on a lattice. The local behavior of the ants is inspired by the actual behavior observed in the laboratory, and analytic results for the collective behavior are compared to the corresponding laboratory results. Monte carlo simulations are used as illustrations.« less

Swarms, phase transitions, and collective intelligence

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

Millonas, M.M.

1992-12-31

A model of the collective behavior of a large number of locally acting organisms is proposed. The model is intended to be realistic, but turns out to fit naturally into the category of connectionist models, Like all connectionist models, its properties can be divided into the categories of structure, dynamics, and learning. The space in which the organisms move is discretized, and is modeled by a lattice of nodes, or cells. Each cell hag a specified volume, and is connected to other cells in the space in a definite way. Organisms move probabilistically between local cells in this space, butmore » with weights dependent on local morphogenic substances, or morphogens. The morphogens are in turn are effected by the passage of an organism. The evolution of the morphogens, and the corresponding constitutes of the organisms constitutes the collective behavior of the group. The generic properties of such systems are analyzed, and a number of results are obtained. The model has various types of phase transitions and self-organizing properties controlled both by the level of the noise, and other parameters. It is hoped that the present mode; might serve as a paradigmatic example of a complex cooperative system in nature. In particular this model can be used to explore the relation of phase transitions to at least three important issues encountered in artificial life. Firstly, that of emergence as complex adaptive behavior. Secondly, as an exploration of second order phase transitions in biological systems. Lastly, to derive behavioral criteria for the evolution of collective behavior in social organisms. The model is then applied to the specific case of ants moving on a lattice. The local behavior of the ants is inspired by the actual behavior observed in the laboratory, and analytic results for the collective behavior are compared to the corresponding laboratory results. Monte carlo simulations are used as illustrations.« less

Diffusion pore imaging with generalized temporal gradient profiles.

PubMed

Laun, Frederik B; Kuder, Tristan A

2013-09-01

In porous material research, one main interest of nuclear magnetic resonance diffusion (NMR) experiments is the determination of the shape of pores. While it has been a longstanding question if this is in principle achievable, it has been shown recently that it is indeed possible to perform NMR-based diffusion pore imaging. In this work we present a generalization of these previous results. We show that the specific temporal gradient profiles that were used so far are not unique as more general temporal diffusion gradient profiles may be used. These temporal gradient profiles may consist of any number of "short" gradient pulses, which fulfil the short-gradient approximation. Additionally, "long" gradient pulses of small amplitude may be present, which can be used to fulfil the rephasing condition for the complete profile. Some exceptions exist. For example, classical q-space gradients consisting of two short gradient pulses of opposite sign cannot be used as the phase information is lost due to the temporal antisymmetry of this profile. Copyright © 2013 Elsevier Inc. All rights reserved.

The stochastic thermodynamics of a rotating Brownian particle in a gradient flow

PubMed Central

Lan, Yueheng; Aurell, Erik

2015-01-01

We compute the entropy production engendered in the environment from a single Brownian particle which moves in a gradient flow, and show that it corresponds in expectation to classical near-equilibrium entropy production in the surrounding fluid with specific mesoscopic transport coefficients. With temperature gradient, extra terms are found which result from the nonlinear interaction between the particle and the non-equilibrated environment. The calculations are based on the fluctuation relations which relate entropy production to the probabilities of stochastic paths and carried out in a multi-time formalism. PMID:26194015

The canonical equation of adaptive dynamics for life histories: from fitness-returns to selection gradients and Pontryagin's maximum principle.

PubMed

Metz, Johan A Jacob; Staňková, Kateřina; Johansson, Jacob

2016-03-01

This paper should be read as addendum to Dieckmann et al. (J Theor Biol 241:370-389, 2006) and Parvinen et al. (J Math Biol 67: 509-533, 2013). Our goal is, using little more than high-school calculus, to (1) exhibit the form of the canonical equation of adaptive dynamics for classical life history problems, where the examples in Dieckmann et al. (J Theor Biol 241:370-389, 2006) and Parvinen et al. (J Math Biol 67: 509-533, 2013) are chosen such that they avoid a number of the problems that one gets in this most relevant of applications, (2) derive the fitness gradient occurring in the CE from simple fitness return arguments, (3) show explicitly that setting said fitness gradient equal to zero results in the classical marginal value principle from evolutionary ecology, (4) show that the latter in turn is equivalent to Pontryagin's maximum principle, a well known equivalence that however in the literature is given either ex cathedra or is proven with more advanced tools, (5) connect the classical optimisation arguments of life history theory a little better to real biology (Mendelian populations with separate sexes subject to an environmental feedback loop), (6) make a minor improvement to the form of the CE for the examples in Dieckmann et al. and Parvinen et al.

The small length scale effect for a non-local cantilever beam: a paradox solved.

PubMed

Challamel, N; Wang, C M

2008-08-27

Non-local continuum mechanics allows one to account for the small length scale effect that becomes significant when dealing with microstructures or nanostructures. This paper presents some simplified non-local elastic beam models, for the bending analyses of small scale rods. Integral-type or gradient non-local models abandon the classical assumption of locality, and admit that stress depends not only on the strain value at that point but also on the strain values of all points on the body. There is a paradox still unresolved at this stage: some bending solutions of integral-based non-local elastic beams have been found to be identical to the classical (local) solution, i.e. the small scale effect is not present at all. One example is the Euler-Bernoulli cantilever nanobeam model with a point load which has application in microelectromechanical systems and nanoelectromechanical systems as an actuator. In this paper, it will be shown that this paradox may be overcome with a gradient elastic model as well as an integral non-local elastic model that is based on combining the local and the non-local curvatures in the constitutive elastic relation. The latter model comprises the classical gradient model and Eringen's integral model, and its application produces small length scale terms in the non-local elastic cantilever beam solution.

Cytoneme-mediated contact-dependent transport of the Drosophila decapentaplegic signaling protein.

PubMed

Roy, Sougata; Huang, Hai; Liu, Songmei; Kornberg, Thomas B

2014-02-21

Decapentaplegic (Dpp), a Drosophila morphogen signaling protein, transfers directly at synapses made at sites of contact between cells that produce Dpp and cytonemes that extend from recipient cells. The Dpp that cytonemes receive moves together with activated receptors toward the recipient cell body in motile puncta. Genetic loss-of-function conditions for diaphanous, shibire, neuroglian, and capricious perturbed cytonemes by reducing their number or only the synapses they make with cells they target, and reduced cytoneme-mediated transport of Dpp and Dpp signaling. These experiments provide direct evidence that cells use cytonemes to exchange signaling proteins, that cytoneme-based exchange is essential for signaling and normal development, and that morphogen distribution and signaling can be contact-dependent, requiring cytoneme synapses.

Cytoneme-mediated contact-dependent transport of the Drosophila Decapentaplegic signaling protein

PubMed Central

Roy, Sougata; Huang, Hai; Liu, Songmei; Kornberg, Thomas B.

2015-01-01

Decapentaplegic (Dpp), a Drosophila morphogen signaling protein, transfers directly at synapes made at sites of contact between cells that produce Dpp and cytonemes that extend from recipient cells. The Dpp that cytonemes receive moves together with activated receptors toward the recipient cell body in motile puncta. Genetic loss-of-function conditions for diaphanous, shibire, neuroglian and capricious perturbed cytonemes by reducing their number or only the synapses they make with cells they target; and reduced cytoneme-mediated transport of Dpp and Dpp signaling. These experiments provide direct evidence that cells use cytonemes to exchange signaling proteins, that cytoneme-based exchange is essential for signaling and normal development, and that morphogen distribution and signaling can be contact-dependent, requiring cytoneme synapses. PMID:24385607

Cell death and morphogenesis during early mouse development: are they interconnected?

PubMed

Bedzhov, Ivan; Zernicka-Goetz, Magdalena

2015-04-01

Shortly after implantation the embryonic lineage transforms from a coherent ball of cells into polarized cup shaped epithelium. Recently we elucidated a previously unknown apoptosis-independent morphogenic event that reorganizes the pluripotent lineage. Polarization cues from the surrounding basement membrane rearrange the epiblast into a polarized rosette-like structure, where subsequently a central lumen is established. Thus, we provided a new model revising the current concept of apoptosis-dependent epiblast morphogenesis. Cell death however has to be tightly regulated during embryogenesis to ensure developmental success. Here, we follow the stages of early mouse development and take a glimpse at the critical signaling and morphogenic events that determine cells destiny and reshape the embryonic lineage. © 2015 The Authors. Bioessays published by WILEY Periodicals, Inc.

Determination of reversed-phase high performance liquid chromatography based octanol-water partition coefficients for neutral and ionizable compounds: Methodology evaluation.

PubMed

Liang, Chao; Qiao, Jun-Qin; Lian, Hong-Zhen

2017-12-15

Reversed-phase liquid chromatography (RPLC) based octanol-water partition coefficient (logP) or distribution coefficient (logD) determination methods were revisited and assessed comprehensively. Classic isocratic and some gradient RPLC methods were conducted and evaluated for neutral, weak acid and basic compounds. Different lipophilicity indexes in logP or logD determination were discussed in detail, including the retention factor logk w corresponding to neat water as mobile phase extrapolated via linear solvent strength (LSS) model from isocratic runs and calculated with software from gradient runs, the chromatographic hydrophobicity index (CHI), apparent gradient capacity factor (k g ') and gradient retention time (t g ). Among the lipophilicity indexes discussed, logk w from whether isocratic or gradient elution methods best correlated with logP or logD. Therefore logk w is recommended as the preferred lipophilicity index for logP or logD determination. logk w easily calculated from methanol gradient runs might be the main candidate to replace logk w calculated from classic isocratic run as the ideal lipophilicity index. These revisited RPLC methods were not applicable for strongly ionized compounds that are hardly ion-suppressed. A previously reported imperfect ion-pair RPLC method was attempted and further explored for studying distribution coefficients (logD) of sulfonic acids that totally ionized in the mobile phase. Notably, experimental logD values of sulfonic acids were given for the first time. The IP-RPLC method provided a distinct way to explore logD values of ionized compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism.

PubMed

Saunders, Timothy E; Pan, Kally Z; Angel, Andrew; Guan, Yinghua; Shah, Jagesh V; Howard, Martin; Chang, Fred

2012-03-13

Chemical gradients can generate pattern formation in biological systems. In the fission yeast Schizosaccharomyces pombe, a cortical gradient of pom1p (a DYRK-type protein kinase) functions to position sites of cytokinesis and cell polarity and to control cell length. Here, using quantitative imaging, fluorescence correlation spectroscopy, and mathematical modeling, we study how its gradient distribution is formed. Pom1p gradients exhibit large cell-to-cell variability, as well as dynamic fluctuations in each individual gradient. Our data lead to a two-state model for gradient formation in which pom1p molecules associate with the plasma membrane at cell tips and then diffuse on the membrane while aggregating into and fragmenting from clusters, before disassociating from the membrane. In contrast to a classical one-component gradient, this two-state gradient buffers against cell-to-cell variations in protein concentration. This buffering mechanism, together with time averaging to reduce intrinsic noise, allows the pom1p gradient to specify positional information in a robust manner. Copyright © 2012 Elsevier Inc. All rights reserved.

Density-Gradient Theory: A Macroscopic Approach to Quantum Confinement and Tunneling in Semiconductor Devices

DTIC Science & Technology

2011-01-01

that are attractive as luminescent biolabels, and possibly also for optoelectronic devices and solar cells . The equilibrium nature of such situations...The boundary layers as- sociated with the diffusion and Debye lengths are familiar, while that of LQ defines the layer in which the quantum in...circuits, transmission lines Diffusion -drift, density-gradient Semi-classical electron dynamics, Boltzmann transport Schrödinger, density- matrix, Wigner

Yeast Gup1(2) Proteins Are Homologues of the Hedgehog Morphogens Acyltransferases HHAT(L): Facts and Implications

PubMed Central

Lucas, Cândida; Ferreira, Célia; Cazzanelli, Giulia; Franco-Duarte, Ricardo; Tulha, Joana

2016-01-01

In multiple tissues, the Hedgehog secreted morphogen activates in the receiving cells a pathway involved in cell fate, proliferation and differentiation in the receiving cells. This pathway is particularly important during embryogenesis. The protein HHAT (Hedgehog O-acyltransferase) modifies Hh morphogens prior to their secretion, while HHATL (Hh O-acyltransferase-like) negatively regulates the pathway. HHAT and HHATL are homologous to Saccharomyces cerevisiae Gup2 and Gup1, respectively. In yeast, Gup1 is associated with a high number and diversity of biological functions, namely polarity establishment, secretory/endocytic pathway functionality, vacuole morphology and wall and membrane composition, structure and maintenance. Phenotypes underlying death, morphogenesis and differentiation are also included. Paracrine signalling, like the one promoted by the Hh pathway, has not been shown to occur in microbial communities, despite the fact that large aggregates of cells like biofilms or colonies behave as proto-tissues. Instead, these have been suggested to sense the population density through the secretion of quorum-sensing chemicals. This review focuses on Gup1/HHATL and Gup2/HHAT proteins. We review the functions and physiology associated with these proteins in yeasts and higher eukaryotes. We suggest standardisation of the presently chaotic Gup-related nomenclature, which includes KIAA117, c3orf3, RASP, Skinny, Sightless and Central Missing, in order to avoid the disclosure of otherwise unnoticed information. PMID:29615596

Solution of the Eshelby problem in gradient elasticity for multilayer spherical inclusions

NASA Astrophysics Data System (ADS)

Volkov-Bogorodskii, D. B.; Lurie, S. A.

2016-03-01

We consider gradient models of elasticity which permit taking into account the characteristic scale parameters of the material. We prove the Papkovich-Neuber theorems, which determine the general form of the gradient solution and the structure of scale effects. We derive the Eshelby integral formula for the gradient moduli of elasticity, which plays the role of the closing equation in the self-consistent three-phase method. In the gradient theory of deformations, we consider the fundamental Eshelby-Christensen problem of determining the effective elastic properties of dispersed composites with spherical inclusions; the exact solution of this problem for classical models was obtained in 1976. This paper is the first to present the exact analytical solution of the Eshelby-Christensen problem for the gradient theory, which permits estimating the influence of scale effects on the stress state and the effective properties of the dispersed composites under study.We also analyze the influence of scale factors.

Non-classical continuum theory for fluids incorporating internal and Cosserat rotation rates

NASA Astrophysics Data System (ADS)

Surana, K. S.; Joy, A. D.; Reddy, J. N.

2017-11-01

This paper presents a non-classical continuum theory for fluent continua in which the conservation and balance laws are derived by incorporating both internal rotation rates arising from the velocity gradient tensor and the rotation rates of the Cosserats. Specifically, in this non-classical continuum theory we have (1) the usual velocities (\\bar{ ±b {\\varvec{v }}}), (2) the three internal rotation rates ({}_i^t\\bar{ ±b {\\varvec{Θ }}}) about the axes of a fixed triad whose axes are parallel to the x-frame arising from the velocity gradient tensor (\\bar{ ±b {\\varvec{L }}}) that are completely defined by the antisymmetric part of the velocity gradient tensor, and (3) three additional rotation rates ({}_e^t\\bar{ ±b {\\varvec{Θ }}}) about the axes of the same triad located at each material point as additional three unknown degrees of freedom, referred to as Cosserat rotation rates. This gives rise to \\bar{ ±b {\\varvec{v }}} and {}_e^t\\bar{ ±b {\\varvec{Θ }}} as six degrees of freedom at a material point. The internal rotation rates {}_i^t\\bar{ ±b {\\varvec{Θ }}}, often neglected in classical fluid mechanics, exist in all deforming fluent continua as these are due to velocity gradient tensor. When the internal rotation rates {}_i^t\\bar{ ±b {\\varvec{Θ }}} are resisted by deforming fluent continua, conjugate moment tensor arises that together with {}_i^t\\bar{ ±b {\\varvec{Θ }}} may result in energy storage and/or dissipation, which must be considered in the conservation and balance laws. The Cosserat rotation rations {}_e^t\\bar{ ±b {\\varvec{Θ }}} also result in conjugate moment tensor that together with {}_e^t\\bar{ ±b {\\varvec{Θ }}} may also result in energy storage and/or dissipation. The main focus of this paper is a consistent derivation of conservation and balance laws for fluent continua that incorporate the aforementioned physics and associated constitutive theories for thermofluids using the conditions resulting from the entropy inequality. The material coefficients derived in the constitutive theories are clearly defined and discussed.

21 CFR 888.3080 - Intervertebral body fusion device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... devices that contain bone grafting material. The special control is the FDA guidance document entitled... devices that include any therapeutic biologic (e.g., bone morphogenic protein). Intervertebral body fusion...

21 CFR 888.3080 - Intervertebral body fusion device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... devices that contain bone grafting material. The special control is the FDA guidance document entitled... devices that include any therapeutic biologic (e.g., bone morphogenic protein). Intervertebral body fusion...

21 CFR 888.3080 - Intervertebral body fusion device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... devices that contain bone grafting material. The special control is the FDA guidance document entitled... devices that include any therapeutic biologic (e.g., bone morphogenic protein). Intervertebral body fusion...

21 CFR 888.3080 - Intervertebral body fusion device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... devices that contain bone grafting material. The special control is the FDA guidance document entitled... devices that include any therapeutic biologic (e.g., bone morphogenic protein). Intervertebral body fusion...

A Modulated-Gradient Parametrization for the Large-Eddy Simulation of the Atmospheric Boundary Layer Using the Weather Research and Forecasting Model

NASA Astrophysics Data System (ADS)

Khani, Sina; Porté-Agel, Fernando

2017-12-01

The performance of the modulated-gradient subgrid-scale (SGS) model is investigated using large-eddy simulation (LES) of the neutral atmospheric boundary layer within the weather research and forecasting model. Since the model includes a finite-difference scheme for spatial derivatives, the discretization errors may affect the simulation results. We focus here on understanding the effects of finite-difference schemes on the momentum balance and the mean velocity distribution, and the requirement (or not) of the ad hoc canopy model. We find that, unlike the Smagorinsky and turbulent kinetic energy (TKE) models, the calculated mean velocity and vertical shear using the modulated-gradient model, are in good agreement with Monin-Obukhov similarity theory, without the need for an extra near-wall canopy model. The structure of the near-wall turbulent eddies is better resolved using the modulated-gradient model in comparison with the classical Smagorinsky and TKE models, which are too dissipative and yield unrealistic smoothing of the smallest resolved scales. Moreover, the SGS fluxes obtained from the modulated-gradient model are much smaller near the wall in comparison with those obtained from the regular Smagorinsky and TKE models. The apparent inability of the LES model in reproducing the mean streamwise component of the momentum balance using the total (resolved plus SGS) stress near the surface is probably due to the effect of the discretization errors, which can be calculated a posteriori using the Taylor-series expansion of the resolved velocity field. Overall, we demonstrate that the modulated-gradient model is less dissipative and yields more accurate results in comparison with the classical Smagorinsky model, with similar computational costs.

Magneto-optic gradient effect in domain-wall images: At the crossroads of magneto-optics and micromagnetics

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

Kambersky, V.; Schaefer, R.; Leibniz Institute for Solid State and Materials Research, Helmholtzstrasse 20, 01069 Dresden

2011-07-15

An anomalous symmetry of magneto-optical images of ferromagnetic domain walls was reported by Schaefer and Hubert [Phys. Status Solidi A 118, 271 (1990)] and interpreted in terms of light amplitudes proportional to the magnetization gradient. We present analytic and numerical calculations supporting such proportionality under additional conditions implied by classical rules of micromagnetics and address some objections presented by Banno [Phys. Rev. A 77, 033818 (2008)] against such proportionality.

The role of fluctuation-induced transport in a toroidal plasma with strong radial electric fields

NASA Technical Reports Server (NTRS)

Roth, J. R.; Krawczonek, W. M.; Powers, E. J.; Hong, J. Y.; Kim, Y. C.

1981-01-01

Previous work employing digitally implemented spectral analysis techniques is extended to demonstrate that radial fluctuation-induced transport is the dominant ion transport mechanism in an electric field dominated toroidal plasma. Such transport can be made to occur against a density gradient, and hence may have a very beneficial effect on confinement in toroidal plasmas of fusion interest. It is shown that Bohm or classical diffusion down a density gradient, the collisional Pedersen-current mechanism, and the collisionless electric field gradient mechanism described by Cole (1976) all played a minor role, if any, in the radial transport of this plasma.

Functionalized scaffolds to control dental pulp stem cell fate

PubMed Central

Piva, Evandro; Silva, Adriana F.; Nör, Jacques E.

2014-01-01

Emerging understanding about interactions between stem cells, scaffolds and morphogenic factors has accelerated translational research in the field of dental pulp tissue engineering. Dental pulp stem cells constitute a sub-population of cells endowed with self-renewal and multipotency. Dental pulp stem cells seeded in biodegradable scaffolds and exposed to dentin-derived morphogenic signals give rise to a pulp-like tissue capable of generating new dentin. Notably, dentin-derived proteins are sufficient to induce dental pulp stem cell differentiation into odontoblasts. Ongoing work is focused on developing ways of mobilizing dentin-derived proteins and disinfecting the root canal of necrotic teeth without compromising the morphogenic potential of these signaling molecules. On the other hand, dentin by itself does not appear to be capable of inducing endothelial differentiation of dental pulp stem cells, despite the well known presence of angiogenic factors in dentin. This is particularly relevant in the context of dental pulp tissue engineering in full root canals, where access to blood supply is limited to the apical foramina. To address this challenge, scientists are looking at ways to use the scaffold as a controlled release device for angiogenic factors. The aim of this manuscript is to present and discuss current strategies to functionalize injectable scaffolds and customize them for dental pulp tissue engineering. The long-term goal of this work is to develop stem cell-based therapies that enable the engineering of functional dental pulps capable of generating new tubular dentin in humans. PMID:24698691

Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins

PubMed Central

Arvola, René M.

2017-01-01

ABSTRACT Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control. PMID:28318367

Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins.

PubMed

Arvola, René M; Weidmann, Chase A; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2017-11-02

Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control.

The Hippo-YAP signaling pathway and contact inhibition of growth

PubMed Central

Gumbiner, Barry M.; Kim, Nam-Gyun

2014-01-01

ABSTRACT The Hippo-YAP pathway mediates the control of cell proliferation by contact inhibition as well as other attributes of the physical state of cells in tissues. Several mechanisms sense the spatial and physical organization of cells, and function through distinct upstream modules to stimulate Hippo-YAP signaling: adherens junction or cadherin–catenin complexes, epithelial polarity and tight junction complexes, the FAT-Dachsous morphogen pathway, as well as cell shape, actomyosin or mechanotransduction. Soluble extracellular factors also regulate Hippo pathway signaling, often inhibiting its activity. Indeed, the Hippo pathway mediates a reciprocal relationship between contact inhibition and mitogenic signaling. As a result, cells at the edges of a colony, a wound in a tissue or a tumor are more sensitive to ambient levels of growth factors and more likely to proliferate, migrate or differentiate through a YAP and/or TAZ-dependent process. Thus, the Hippo-YAP pathway senses and responds to the physical organization of cells in tissues and coordinates these physical cues with classic growth-factor-mediated signaling pathways. This Commentary is focused on the biological significance of Hippo-YAP signaling and how upstream regulatory modules of the pathway interact to produce biological outcomes. PMID:24532814

Effect of modulator sorption on gradient shape in ion-exchange chromatography

NASA Technical Reports Server (NTRS)

Velayudhan, A.; Ladisch, M. R.; Mitchell, C. A. (Principal Investigator)

1995-01-01

Mobile phase additives, or modulators, are used in gradient elution chromatography to facilitate separation and reduce separation time. The modulators are usually assumed to be linearly adsorbed or unadsorbed. Here, the consequences of nonlinear modulator adsorption are examined for ion-exchange gradient elution through a series of simulations. Even when the buffer salt is identical to the modulator salt, gradient deformation is observed; the extent of deformation increases as the volume of the feed is increased. When the modulator salt is different from the buffer salt, unusual effects are observed, and the chromatograms are quite different from those predicted by classical gradient elution theory. In particular, local increases in the buffer concentration are found between feed bands, and serve to improve the separation. These effects become more pronounced as the feed volume increases, and could therefore prove valuable in preparative applications.

A study on the unsteady flow of two immiscible micropolar and Newtonian fluids through a horizontal channel: A numerical approach

NASA Astrophysics Data System (ADS)

Devakar, M.; Raje, Ankush

2018-05-01

The unsteady flow of two immiscible micropolar and Newtonian fluids through a horizontal channel is considered. In addition to the classical no-slip and hyper-stick conditions at the boundary, it is assumed that the fluid velocities and shear stresses are continuous across the fluid-fluid interface. Three cases for the applied pressure gradient are considered to study the problem: one with constant pressure gradient and the other two cases with time-dependent pressure gradients, viz. periodic and decaying pressure gradient. The Crank-Nicolson approach has been used to obtain numerical solutions for fluid velocity and microrotation for diverse sets of fluid parameters. The nature of fluid velocities and microrotation with various values of pressure gradient, Reynolds number, ratio of viscosities, micropolarity parameter and time is illustrated through graphs. It has been observed that micropolarity parameter and ratio of viscosities reduce the fluid velocities.

[Stents in iliac vascular changes].

PubMed

Gross-Fengels, W; Friedmann, G; Fischbach, R; Erasmi, H; Bulling, B

1991-01-01

The results of 79 iliac stent placements in 64 patients are reported. The technical success rate was 96%. The systolic pressure gradient dropped from 44 mmHg before to 2.8 mmHg after stent placement. This differed significantly as compared to a group treated by conventional PTA (gradient 5.8 mmHg). The cumulative patency after 18-20 months was 90%. Angiographic controls up to 19 months after "stenting" demonstrated only one secondary stent occlusion. Iliac stents therefore are a very valuable supplement to classic PTA.

Nucleation of insulin crystals in a wide continuous supersaturation gradient.

PubMed

Penkova, Anita; Dimitrov, Ivaylo; Nanev, Christo

2004-11-01

Modifying the classical double pulse technique, by using a supersaturation gradient along an insulin solution contained in a glass capillary tube, we found conditions appropriate for the direct measurement of nucleation parameters. The nucleation time lag has been measured. Data for the number of crystal nuclei versus the nucleation time were obtained for this hormone. Insulin was chosen as a model protein because of the availability of solubility data in the literature. A comparison with the results for hen-egg-white lysozyme, HEWL was performed.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

PubMed Central

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-01-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

An Autonomous BMP2 Regulatory Element in Mesenchymal Cells

PubMed Central

Kruithof, Boudewijn P.T.; Fritz, David T.; Liu, Yijun; Garsetti, Diane E.; Frank, David B.; Pregizer, Steven K.; Gaussin, Vinciane; Mortlock, Douglas P.; Rogers, Melissa B.

2014-01-01

BMP2 is a morphogen that controls mesenchymal cell differentiation and behavior. For example, BMP2 concentration controls the differentiation of mesenchymal precursors into myocytes, adipocytes, chondrocytes, and osteoblasts. Sequences within the 3′untranslated region (UTR) of the Bmp2 mRNA mediate a post-transcriptional block of protein synthesis. Interaction of cell and developmental stage-specific trans-regulatory factors with the 3′UTR is a nimble and versatile mechanism for modulating this potent morphogen in different cell types. We show here, that an ultra-conserved sequence in the 3′UTR functions independently of promoter, coding region, and 3′UTR context in primary and immortalized tissue culture cells and in transgenic mice. Our findings indicate that the ultra-conserved sequence is an autonomously functioning post-transcriptional element that may be used to modulate the level of BMP2 and other proteins while retaining tissue specific regulatory elements. PMID:21268088

Robust stochastic Turing patterns in the development of a one-dimensional cyanobacterial organism.

PubMed

Di Patti, Francesca; Lavacchi, Laura; Arbel-Goren, Rinat; Schein-Lubomirsky, Leora; Fanelli, Duccio; Stavans, Joel

2018-05-01

Under nitrogen deprivation, the one-dimensional cyanobacterial organism Anabaena sp. PCC 7120 develops patterns of single, nitrogen-fixing cells separated by nearly regular intervals of photosynthetic vegetative cells. We study a minimal, stochastic model of developmental patterns in Anabaena that includes a nondiffusing activator, two diffusing inhibitor morphogens, demographic fluctuations in the number of morphogen molecules, and filament growth. By tracking developing filaments, we provide experimental evidence for different spatiotemporal roles of the two inhibitors during pattern maintenance and for small molecular copy numbers, justifying a stochastic approach. In the deterministic limit, the model yields Turing patterns within a region of parameter space that shrinks markedly as the inhibitor diffusivities become equal. Transient, noise-driven, stochastic Turing patterns are produced outside this region, which can then be fixed by downstream genetic commitment pathways, dramatically enhancing the robustness of pattern formation, also in the biologically relevant situation in which the inhibitors' diffusivities may be comparable.

Probing the limits to positional information

PubMed Central

Gregor, Thomas; Tank, David W.; Wieschaus, Eric F.; Bialek, William

2008-01-01

The reproducibility and precision of biological patterning is limited by the accuracy with which concentration profiles of morphogen molecules can be established and read out by their targets. We consider four measures of precision for the Bicoid morphogen in the Drosophila embryo: The concentration differences that distinguish neighboring cells, the limits set by the random arrival of Bicoid molecules at their targets (which depends on absolute concentration), the noise in readout of Bicoid by the activation of Hunchback, and the reproducibility of Bicoid concentration at corresponding positions in multiple embryos. We show, through a combination of different experiments, that all of these quantities are ~10%. This agreement among different measures of accuracy indicates that the embryo is not faced with noisy input signals and readout mechanisms; rather the system exerts precise control over absolute concentrations and responds reliably to small concentration differences, approaching the limits set by basic physical principles. PMID:17632062

Slab Geometry and Segmentation on Seismogenic Subduction Zone; Insight from gravity gradients

NASA Astrophysics Data System (ADS)

Saraswati, A. T.; Mazzotti, S.; Cattin, R.; Cadio, C.

2017-12-01

Slab geometry is a key parameter to improve seismic hazard assessment in subduction zones. In many cases, information about structures beneath subduction are obtained from geophysical dedicated studies, including geodetic and seismic measurements. However, due to the lack of global information, both geometry and segmentation in seismogenic zone of many subductions remain badly-constrained. Here we propose an alternative approach based on satellite gravity observations. The GOCE (Gravity field and steady-state Ocean Circulation Explorer) mission enables to probe Earth deep mass structures from gravity gradients, which are more sensitive to spatial structure geometry and directional properties than classical gravitational data. Gravity gradients forward modeling of modeled slab is performed by using horizontal and vertical gravity gradient components to better determine slab geophysical model rather than vertical gradient only. Using polyhedron method, topography correction on gravity gradient signal is undertaken to enhance the anomaly signal of lithospheric structures. Afterward, we compare residual gravity gradients with the calculated signals associated with slab geometry. In this preliminary study, straightforward models are used to better understand the characteristic of gravity gradient signals due to deep mass sources. We pay a special attention to the delineation of slab borders and dip angle variations.

Expanding signaling-molecule wavefront model of cell polarization in the Drosophila wing primordium.

PubMed

Wortman, Juliana C; Nahmad, Marcos; Zhang, Peng Cheng; Lander, Arthur D; Yu, Clare C

2017-07-01

In developing tissues, cell polarization and proliferation are regulated by morphogens and signaling pathways. Cells throughout the Drosophila wing primordium typically show subcellular localization of the unconventional myosin Dachs on the distal side of cells (nearest the center of the disc). Dachs localization depends on the spatial distribution of bonds between the protocadherins Fat (Ft) and Dachsous (Ds), which form heterodimers between adjacent cells; and the Golgi kinase Four-jointed (Fj), which affects the binding affinities of Ft and Ds. The Fj concentration forms a linear gradient while the Ds concentration is roughly uniform throughout most of the wing pouch with a steep transition region that propagates from the center to the edge of the pouch during the third larval instar. Although the Fj gradient is an important cue for polarization, it is unclear how the polarization is affected by cell division and the expanding Ds transition region, both of which can alter the distribution of Ft-Ds heterodimers around the cell periphery. We have developed a computational model to address these questions. In our model, the binding affinity of Ft and Ds depends on phosphorylation by Fj. We assume that the asymmetry of the Ft-Ds bond distribution around the cell periphery defines the polarization, with greater asymmetry promoting cell proliferation. Our model predicts that this asymmetry is greatest in the radially-expanding transition region that leaves polarized cells in its wake. These cells naturally retain their bond distribution asymmetry after division by rapidly replenishing Ft-Ds bonds at new cell-cell interfaces. Thus we predict that the distal localization of Dachs in cells throughout the pouch requires the movement of the Ds transition region and the simple presence, rather than any specific spatial pattern, of Fj.

Mass transport in morphogenetic processes: A second gradient theory for volumetric growth and material remodeling

NASA Astrophysics Data System (ADS)

Ciarletta, P.; Ambrosi, D.; Maugin, G. A.

2012-03-01

In this work, we derive a novel thermo-mechanical theory for growth and remodeling of biological materials in morphogenetic processes. This second gradient hyperelastic theory is the first attempt to describe both volumetric growth and mass transport phenomena in a single-phase continuum model, where both stress- and shape-dependent growth regulations can be investigated. The diffusion of biochemical species (e.g. morphogens, growth factors, migration signals) inside the material is driven by configurational forces, enforced in the balance equations and in the set of constitutive relations. Mass transport is found to depend both on first- and on second-order material connections, possibly withstanding a chemotactic behavior with respect to diffusing molecules. We find that the driving forces of mass diffusion can be written in terms of covariant material derivatives reflecting, in a purely geometrical manner, the presence of a (first-order) torsion and a (second-order) curvature. Thermodynamical arguments show that the Eshelby stress and hyperstress tensors drive the rearrangement of the first- and second-order material inhomogeneities, respectively. In particular, an evolution law is proposed for the first-order transplant, extending a well-known result for inelastic materials. Moreover, we define the first stress-driven evolution law of the second-order transplant in function of the completely material Eshelby hyperstress. The theory is applied to two biomechanical examples, showing how an Eshelbian coupling can coordinate volumetric growth, mass transport and internal stress state, both in physiological and pathological conditions. Finally, possible applications of the proposed model are discussed for studying the unknown regulation mechanisms in morphogenetic processes, as well as for optimizing scaffold architecture in regenerative medicine and tissue engineering.

Generalization of the van der Pauw Method: Analyzing Longitudinal Magnetoresistance Asymmetry to Quantify Doping Gradients

NASA Astrophysics Data System (ADS)

Grayson, M.; Zhou, Wang; Yoo, Heun-Mo; Prabhu-Gaunkar, S.; Tiemann, L.; Reichl, C.; Wegscheider, W.

A longitudinal magnetoresistance asymmetry (LMA) between a positive and negative magnetic field is known to occur in both the extreme quantum limit and the classical Drude limit in samples with a nonuniform doping density. By analyzing the current stream function in van der Pauw measurement geometry, it is shown that the electron density gradient can be quantitatively deduced from this LMA in the Drude regime. Results agree with gradients interpolated from local densities calibrated across an entire wafer, establishing a generalization of the van der Pauw method to quantify density gradients. Results will be shown of various semoconductor systems where this method is applied, from bulk doped semiconductors, to exfoliated 2D materials. McCormick Catalyst Award from Northwestern University, EECS Bridge Funding, and AFOSR FA9550-15-1-0247.

A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium

PubMed Central

Ramsay, Joshua P.; Williamson, Neil R.; Spring, David R.; Salmond, George P. C.

2011-01-01

Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air–liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen. PMID:21873216

A quorum-sensing molecule acts as a morphogen controlling gas vesicle organelle biogenesis and adaptive flotation in an enterobacterium.

PubMed

Ramsay, Joshua P; Williamson, Neil R; Spring, David R; Salmond, George P C

2011-09-06

Gas vesicles are hollow intracellular proteinaceous organelles produced by aquatic Eubacteria and Archaea, including cyanobacteria and halobacteria. Gas vesicles increase buoyancy and allow taxis toward air-liquid interfaces, enabling subsequent niche colonization. Here we report a unique example of gas vesicle-mediated flotation in an enterobacterium; Serratia sp. strain ATCC39006. This strain is a member of the Enterobacteriaceae previously studied for its production of prodigiosin and carbapenem antibiotics. Genes required for gas vesicle synthesis mapped to a 16.6-kb gene cluster encoding three distinct homologs of the main structural protein, GvpA. Heterologous expression of this locus in Escherichia coli induced copious vesicle production and efficient cell buoyancy. Gas vesicle morphogenesis in Serratia enabled formation of a pellicle-like layer of highly vacuolated cells, which was dependent on oxygen limitation and the expression of ntrB/C and cheY-like regulatory genes within the gas-vesicle gene cluster. Gas vesicle biogenesis was strictly controlled by intercellular chemical signaling, through an N-acyl homoserine lactone, indicating that in this system the quorum-sensing molecule acts as a morphogen initiating organelle development. Flagella-based motility and gas vesicle morphogenesis were also oppositely regulated by the small RNA-binding protein, RsmA, suggesting environmental adaptation through physiological control of the choice between motility and flotation as alternative taxis modes. We propose that gas vesicle biogenesis in this strain represents a distinct mechanism of mobility, regulated by oxygen availability, nutritional status, the RsmA global regulatory system, and the quorum-sensing morphogen.

Precision bounds for gradient magnetometry with atomic ensembles

NASA Astrophysics Data System (ADS)

Apellaniz, Iagoba; Urizar-Lanz, Iñigo; Zimborás, Zoltán; Hyllus, Philipp; Tóth, Géza

2018-05-01

We study gradient magnetometry with an ensemble of atoms with arbitrary spin. We calculate precision bounds for estimating the gradient of the magnetic field based on the quantum Fisher information. For quantum states that are invariant under homogeneous magnetic fields, we need to measure a single observable to estimate the gradient. On the other hand, for states that are sensitive to homogeneous fields, a simultaneous measurement is needed, as the homogeneous field must also be estimated. We prove that for the cases studied in this paper, such a measurement is feasible. We present a method to calculate precision bounds for gradient estimation with a chain of atoms or with two spatially separated atomic ensembles. We also consider a single atomic ensemble with an arbitrary density profile, where the atoms cannot be addressed individually, and which is a very relevant case for experiments. Our model can take into account even correlations between particle positions. While in most of the discussion we consider an ensemble of localized particles that are classical with respect to their spatial degree of freedom, we also discuss the case of gradient metrology with a single Bose-Einstein condensate.

Spectra of turbulently advected scalars that have small Schmidt number

NASA Astrophysics Data System (ADS)

Hill, Reginald J.

2017-09-01

Exact statistical equations are derived for turbulent advection of a passive scalar having diffusivity much larger than the kinematic viscosity, i.e., small Schmidt number. The equations contain all terms needed for precise direct numerical simulation (DNS) quantification. In the appropriate limit, the equations reduce to the classical theory for which the scalar spectrum is proportional to the energy spectrum multiplied by k-4, which, in turn, results in the inertial-diffusive range power law, k-17 /3. The classical theory was derived for the case of isotropic velocity and scalar fields. The exact equations are simplified for less restrictive cases: (1) locally isotropic scalar fluctuations at dissipation scales with no restriction on symmetry of the velocity field, (2) isotropic velocity field with averaging over all wave-vector directions with no restriction on the symmetry of the scalar, motivated by that average being used for DNS, and (3) isotropic velocity field with axisymmetric scalar fluctuations, motivated by the mean-scalar-gradient-source case. The equations are applied to recently published DNSs of passive scalars for the cases of a freely decaying scalar and a mean-scalar-gradient source. New terms in the exact equations are estimated for those cases and are found to be significant; those terms cause the deviations from the classical theory found by the DNS studies. A new formula for the mean-scalar-gradient case explains the variation of the scalar spectra for the DNS of the smallest Schmidt-number cases. Expansion in Legendre polynomials reveals the effect of axisymmetry. Inertial-diffusive-range formulas for both the zero- and second-order Legendre contributions are given. Exact statistical equations reveal what must be quantified using DNS to determine what causes deviations from asymptotic relationships.

Intraspecific leaf trait variability along a boreal-to-tropical community diversity gradient

PubMed Central

Bastias, Cristina C.; Fortunel, Claire; Valladares, Fernando; Baraloto, Christopher; Benavides, Raquel; Cornwell, William; Markesteijn, Lars; de Oliveira, Alexandre A.; Sansevero, Jeronimo B. B.; Vaz, Marcel C.; Kraft, Nathan J. B.

2017-01-01

Disentangling the mechanisms that shape community assembly across diversity gradients is a central matter in ecology. While many studies have explored community assembly through species average trait values, there is a growing understanding that intraspecific trait variation (ITV) can also play a critical role in species coexistence. Classic biodiversity theory hypothesizes that higher diversity at species-rich sites can arise from narrower niches relative to species-poor sites, which would be reflected in reduced ITV as species richness increases. To explore how ITV in woody plant communities changes with species richness, we compiled leaf trait data (leaf size and specific leaf area) in a total of 521 woody plant species from 21 forest communities that differed dramatically in species richness, ranging from boreal to tropical rainforests. At each forest, we assessed ITV as an estimate of species niche breadth and we quantified the degree of trait overlap among co-occurring species as a measure of species functional similarity. We found ITV was relatively invariant across the species richness gradient. In addition, we found that species functional similarity increased with diversity. Contrary to the expectation from classic biodiversity theory, our results rather suggest that neutral processes or equalizing mechanisms can be acting as potential drivers shaping community assembly in hyperdiverse forests. PMID:28241033

The generalized Hill model: A kinematic approach towards active muscle contraction

NASA Astrophysics Data System (ADS)

Göktepe, Serdar; Menzel, Andreas; Kuhl, Ellen

2014-12-01

Excitation-contraction coupling is the physiological process of converting an electrical stimulus into a mechanical response. In muscle, the electrical stimulus is an action potential and the mechanical response is active contraction. The classical Hill model characterizes muscle contraction though one contractile element, activated by electrical excitation, and two non-linear springs, one in series and one in parallel. This rheology translates into an additive decomposition of the total stress into a passive and an active part. Here we supplement this additive decomposition of the stress by a multiplicative decomposition of the deformation gradient into a passive and an active part. We generalize the one-dimensional Hill model to the three-dimensional setting and constitutively define the passive stress as a function of the total deformation gradient and the active stress as a function of both the total deformation gradient and its active part. We show that this novel approach combines the features of both the classical stress-based Hill model and the recent active-strain models. While the notion of active stress is rather phenomenological in nature, active strain is micro-structurally motivated, physically measurable, and straightforward to calibrate. We demonstrate that our model is capable of simulating excitation-contraction coupling in cardiac muscle with its characteristic features of wall thickening, apical lift, and ventricular torsion.

The theory of the gravitational potential applied to orbit prediction

NASA Technical Reports Server (NTRS)

Kirkpatrick, J. C.

1976-01-01

A complete derivation of the geopotential function and its gradient is presented. Also included is the transformation of Laplace's equation from Cartesian to spherical coordinates. The analytic solution to Laplace's equation is obtained from the transformed version, in the classical manner of separating the variables. A cursory introduction to the method devised by Pines, using direction cosines to express the orientation of a point in space, is presented together with sample computer program listings for computing the geopotential function and the components of its gradient. The use of the geopotential function is illustrated.

Quantum mechanical expansion of variance of a particle in a weakly non-uniform electric and magnetic field

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

Chan, Poh Kam; Kosaka, Wataru; Oikawa, Shun-ichi

We have solved the Heisenberg equation of motion for the time evolution of the position and momentum operators for a non-relativistic spinless charged particle in the presence of a weakly non-uniform electric and magnetic field. It is shown that the drift velocity operator obtained in this study agrees with the classical counterpart, and that, using the time dependent operators, the variances in position and momentum grow with time. The expansion rate of variance in position and momentum are dependent on the magnetic gradient scale length, however, independent of the electric gradient scale length. In the presence of a weakly non-uniformmore » electric and magnetic field, the theoretical expansion rates of variance expansion are in good agreement with the numerical analysis. It is analytically shown that the variance in position reaches the square of the interparticle separation, which is the characteristic time much shorter than the proton collision time of plasma fusion. After this time, the wavefunctions of the neighboring particles would overlap, as a result, the conventional classical analysis may lose its validity. The broad distribution of individual particle in space means that their Coulomb interactions with other particles become weaker than that expected in classical mechanics.« less

METALLICITY GRADIENTS THROUGH DISK INSTABILITY: A SIMPLE MODEL FOR THE MILKY WAY'S BOXY BULGE

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

Martinez-Valpuesta, Inma; Gerhard, Ortwin, E-mail: imv@mpe.mpg.de, E-mail: gerhard@mpe.mpg.de

2013-03-20

Observations show a clear vertical metallicity gradient in the Galactic bulge, which is often taken as a signature of dissipative processes in the formation of a classical bulge. Various evidence shows, however, that the Milky Way is a barred galaxy with a boxy bulge representing the inner three-dimensional part of the bar. Here we show with a secular evolution N-body model that a boxy bulge formed through bar and buckling instabilities can show vertical metallicity gradients similar to the observed gradient if the initial axisymmetric disk had a comparable radial metallicity gradient. In this framework, the range of metallicities inmore » bulge fields constrains the chemical structure of the Galactic disk at early times before bar formation. Our secular evolution model was previously shown to reproduce inner Galaxy star counts and we show here that it also has cylindrical rotation. We use it to predict a full mean metallicity map across the Galactic bulge from a simple metallicity model for the initial disk. This map shows a general outward gradient on the sky as well as longitudinal perspective asymmetries. We also briefly comment on interpreting metallicity gradient observations in external boxy bulges.« less

Evolution of niche preference in Sphagnum peat mosses.

PubMed

Johnson, Matthew G; Granath, Gustaf; Tahvanainen, Teemu; Pouliot, Remy; Stenøien, Hans K; Rochefort, Line; Rydin, Håkan; Shaw, A Jonathan

2015-01-01

Peat mosses (Sphagnum) are ecosystem engineers-species in boreal peatlands simultaneously create and inhabit narrow habitat preferences along two microhabitat gradients: an ionic gradient and a hydrological hummock-hollow gradient. In this article, we demonstrate the connections between microhabitat preference and phylogeny in Sphagnum. Using a dataset of 39 species of Sphagnum, with an 18-locus DNA alignment and an ecological dataset encompassing three large published studies, we tested for phylogenetic signal and within-genus changes in evolutionary rate of eight niche descriptors and two multivariate niche gradients. We find little to no evidence for phylogenetic signal in most component descriptors of the ionic gradient, but interspecific variation along the hummock-hollow gradient shows considerable phylogenetic signal. We find support for a change in the rate of niche evolution within the genus-the hummock-forming subgenus Acutifolia has evolved along the multivariate hummock-hollow gradient faster than the hollow-inhabiting subgenus Cuspidata. Because peat mosses themselves create some of the ecological gradients constituting their own habitats, the classic microtopography of Sphagnum-dominated peatlands is maintained by evolutionary constraints and the biological properties of related Sphagnum species. The patterns of phylogenetic signal observed here will instruct future study on the role of functional traits in peatland growth and reconstruction. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

morphogen: Translation into Morphologically Rich Languages with Synthetic Phrases

DTIC Science & Technology

2013-10-01

specific trans - lation phrases. These “synthetic phrases” augment the standard translation grammars and decoding proceeds normally with a standard...Genitive case grandparent(poss) Hebrew Suffix ים ( masculine plural) parent=NNS after=NNS Prefix א (first person sing. + future) child(nsubj)=I child(aux

Cardiac Imaging for Assessing Low-Gradient Severe Aortic Stenosis.

PubMed

Clavel, Marie-Annick; Burwash, Ian G; Pibarot, Philippe

2017-02-01

Up to 40% of patients with aortic stenosis (AS) harbor discordant Doppler-echocardiographic findings, the most common of which is the presence of a small aortic valve area (≤1.0 cm 2 ) suggesting severe AS, but a low gradient (<40 mm Hg) suggesting nonsevere AS. The purpose of this paper is to present the role of multimodality imaging in the diagnostic and therapeutic management of this challenging entity referred to as low-gradient AS. Doppler-echocardiography is critical to determine the subtype of low-gradient AS: that is, classical low-flow, paradoxical low-flow, or normal-flow. Patients with low-flow, low-gradient AS generally have a worse prognosis compared with patients with high-gradient or with normal-flow, low-gradient AS. Patients with low-gradient AS and evidence of severe AS benefit from aortic valve replacement (AVR). However, confirmation of the presence of severe AS is particularly challenging in these patients and requires a multimodality imaging approach including low-dose dobutamine stress echocardiography and aortic valve calcium scoring by multidetector computed tomography. Transcatheter AVR using a transfemoral approach may be superior to surgical AVR in patients with low-flow, low-gradient AS. Further studies are needed to confirm the best valve replacement procedure and prosthetic valve for each category of low-gradient AS and to identify patients with low-gradient AS in whom AVR is likely to be futile. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Extracellular matrix control of mammary gland morphogenesis and tumorigenesis: insights from imaging

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

Ghajar, Cyrus M; Bissell, Mina J

2008-10-23

The extracellular matrix (ECM), once thought to solely provide physical support to a tissue, is a key component of a cell's microenvironment responsible for directing cell fate and maintaining tissue specificity. It stands to reason, then, that changes in the ECM itself or in how signals from the ECM are presented to or interpreted by cells can disrupt tissue organization; the latter is a necessary step for malignant progression. In this review, we elaborate on this concept using the mammary gland as an example. We describe how the ECM directs mammary gland formation and function, and discuss how a cell'smore » inability to interpret these signals - whether as a result of genetic insults or physicochemical alterations in the ECM - disorganizes the gland and promotes malignancy. By restoring context and forcing cells to properly interpret these native signals, aberrant behavior can be quelled and organization re-established. Traditional imaging approaches have been a key complement to the standard biochemical, molecular, and cell biology approaches used in these studies. Utilizing imaging modalities with enhanced spatial resolution in live tissues may uncover additional means by which the ECM regulates tissue structure, on different length scales, through its pericellular organization (short-scale) and by biasing morphogenic and morphostatic gradients (long-scale).« less

The Role of Heparan Sulfate Proteoglycans in Optic Disc and Stalk Morphogenesis

PubMed Central

Cai, Zhigang; Grobe, Kay; Zhang, Xin

2014-01-01

Background Heparan sulfate proteoglycans (HSPG) are important for embryonic development via the regulation of gradient formation and signaling of multiple growth factors and morphogens. Previous studies have shown that Bmp/Shh/Fgf signaling are required for the regionalization of the optic vesicle (OV) and for the closure of the optic fissure (OF), the disturbance of which underlie ocular anomalies such as microphthalmia, coloboma and optic nerve hypoplasia. Results To study HSPG-dependent coordination of these signaling pathways during mammalian visual system development, we have generated a series of OV-specific mutations in the heparan sulfate (HS) N-sulfotransferase genes (Ndst1 and Ndst2) and HS O-sulfotransferase genes (Hs2st, Hs6st1 and Hs6st2) in mice. Interestingly, the resulting HS undersulfation still allowed for normal retinal neurogenesis and optic fissure closure, but led to defective optic disc and stalk development. The adult mutant animals further developed optic nerve aplasia/hypoplasia and displayed retinal degeneration. We observed that MAPK/ERK signaling was down-regulated in Ndst mutants, and consistent with this, HS-related optic nerve morphogenesis defects in mutant mice could partially be rescued by constitutive Kras activation. Conclusions These results suggest that HSPGs, depending on their HS sulfation pattern, regulate multiple signaling pathways in optic disc and stalk morphogenesis. PMID:24753163

High-density human mesenchymal stem cell rings with spatiotemporally-controlled morphogen presentation as building blocks for engineering bone diaphyseal tissue

PubMed Central

Herberg, Samuel; Varghai, Daniel; Cheng, Yuxuan; Dikina, Anna D.; Dang, Phuong N.; Rolle, Marsha W.; Alsberg, Eben

2018-01-01

Emerging biomimetic tissue engineering strategies aim to partially recapitulate fundamental events that transpire during embryonic skeletal development; namely, cellular self-organization and targeted morphogenetic pathway activation. Here, we describe self-assembled, scaffold-free human mesenchymal stem cell (hMSC) rings featuring microparticle-mediated presentation of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2). We tested the hypothesis that spatiotemporally-controlled dual presentation of TGF-β1 and BMP-2 is superior in modulating in vitro endochondral ossification of high-density cellular constructs compared to single morphogen delivery. hMSC rings were engineered by seeding cells with microparticles presenting (1) TGF-β1, (2) BMP-2, or (3) TGF-β1 + BMP-2 in custom agarose wells to facilitate self-assembly within 2 d, followed by horizontal culture on glass tubes for 5 weeks. At day 2, hMSC rings across groups revealed homogenous cellular organization mimetic of early mesenchymal condensation with no evidence of new matrix or mineral deposition. Significant early chondrogenic and osteogenic priming occurred with TGF-β1 + BMP-2 presentation compared to single morphogen-loaded groups. By week 5, TGF-β1-loaded hMSC rings had undergone chondrogenesis, while presentation of BMP-2 alone or in conjunction with TGF-β1 stimulated chondrogenesis, chondrocyte hypertrophy, and osteogenesis indicative of endochondral ossification. Importantly, tissue mineralization was most compelling with TGF-β1 + BMP-2 loading. Lastly, hMSC ring 'building blocks' were shown to efficiently fuse into tubes within 6 d post self-assembly. The resulting tubular tissue units exhibited structural integrity, highlighting the translational potential of this advanced biomimetic technology for potential early implantation in long bone defects. PMID:29577017

Directed midbrain and spinal cord neurogenesis from pluripotent stem cells to model development and disease in a dish

PubMed Central

Allodi, Ilary; Hedlund, Eva

2014-01-01

Induction of specific neuronal fates is restricted in time and space in the developing CNS through integration of extrinsic morphogen signals and intrinsic determinants. Morphogens impose regional characteristics on neural progenitors and establish distinct progenitor domains. Such domains are defined by unique expression patterns of fate determining transcription factors. These processes of neuronal fate specification can be recapitulated in vitro using pluripotent stem cells. In this review, we focus on the generation of dopamine neurons and motor neurons, which are induced at ventral positions of the neural tube through Sonic hedgehog (Shh) signaling, and defined at anteroposterior positions by fibroblast growth factor (Fgf) 8, Wnt1, and retinoic acid (RA). In vitro utilization of these morphogenic signals typically results in the generation of multiple neuronal cell types, which are defined at the intersection of these signals. If the purpose of in vitro neurogenesis is to generate one cell type only, further lineage restriction can be accomplished by forced expression of specific transcription factors in a permissive environment. Alternatively, cell-sorting strategies allow for selection of neuronal progenitors or mature neurons. However, modeling development, disease and prospective therapies in a dish could benefit from structured heterogeneity, where desired neurons are appropriately synaptically connected and thus better reflect the three-dimensional structure of that region. By modulating the extrinsic environment to direct sequential generation of neural progenitors within a domain, followed by self-organization and synaptic establishment, a reductionist model of that brain region could be created. Here we review recent advances in neuronal fate induction in vitro, with a focus on the interplay between cell intrinsic and extrinsic factors, and discuss the implications for studying development and disease in a dish. PMID:24904255

Directed midbrain and spinal cord neurogenesis from pluripotent stem cells to model development and disease in a dish.

PubMed

Allodi, Ilary; Hedlund, Eva

2014-01-01

Induction of specific neuronal fates is restricted in time and space in the developing CNS through integration of extrinsic morphogen signals and intrinsic determinants. Morphogens impose regional characteristics on neural progenitors and establish distinct progenitor domains. Such domains are defined by unique expression patterns of fate determining transcription factors. These processes of neuronal fate specification can be recapitulated in vitro using pluripotent stem cells. In this review, we focus on the generation of dopamine neurons and motor neurons, which are induced at ventral positions of the neural tube through Sonic hedgehog (Shh) signaling, and defined at anteroposterior positions by fibroblast growth factor (Fgf) 8, Wnt1, and retinoic acid (RA). In vitro utilization of these morphogenic signals typically results in the generation of multiple neuronal cell types, which are defined at the intersection of these signals. If the purpose of in vitro neurogenesis is to generate one cell type only, further lineage restriction can be accomplished by forced expression of specific transcription factors in a permissive environment. Alternatively, cell-sorting strategies allow for selection of neuronal progenitors or mature neurons. However, modeling development, disease and prospective therapies in a dish could benefit from structured heterogeneity, where desired neurons are appropriately synaptically connected and thus better reflect the three-dimensional structure of that region. By modulating the extrinsic environment to direct sequential generation of neural progenitors within a domain, followed by self-organization and synaptic establishment, a reductionist model of that brain region could be created. Here we review recent advances in neuronal fate induction in vitro, with a focus on the interplay between cell intrinsic and extrinsic factors, and discuss the implications for studying development and disease in a dish.

DNA Methylation and Mutation of Small Colonic Neoplasms in Ulcerative Colitis and Crohn's Colitis: Implications for Surveillance.

PubMed

Johnson, David H; Taylor, William R; Aboelsoud, Mohammed M; Foote, Patrick H; Yab, Tracy C; Cao, Xiaoming; Smyrk, Thomas C; Loftus, Edward V; Mahoney, Douglas W; Ahlquist, David A; Kisiel, John B

2016-07-01

Stool DNA testing in patients with inflammatory bowel disease (IBD) may detect colorectal cancer and advanced precancers with high sensitivity; less is known about the presence of DNA markers in small IBD lesions, their association with metachronous neoplasia, or contribution to stool test positivity. At a single center in 2 blinded phases, we assayed methylated bone morphogenic protein 3, methylated N-Myc downstream-regulated gene 4, and mutant KRAS in DNA extracted from paraffin-embedded benign lesions, and matched control tissues of patients with IBD, who were followed for subsequent colorectal dysplasia. Stool samples from independent cases and controls with lesions <1 cm or advanced neoplasms were assayed for the same markers. Among IBD lesions (29 low-grade dysplasia, 19 serrated epithelial change, and 10 sessile serrated adenoma/polyps), the prevalence of methylation was significantly higher than in mucosae from 44 matched IBD controls (P < 0.0001 for methylated bone morphogenic protein 3 or methylated N-Myc downstream-regulated gene 4). KRAS mutations were more abundant in serrated epithelial change than all other groups (P < 0.001). Subsequent dysplasia was not associated with DNA marker levels. In stools, the sensitivity of methylated bone morphogenic protein 3 as a single marker was 60% for all lesions <1 cm, 63% for low-grade dysplasia ≥1 cm and 81% for high-grade dysplasia/colorectal cancer, all at 91% specificity (P < 0.0001). Selected DNA markers known to be present in advanced IBD neoplasia can also be detected in both tissues and stools from IBD patients with small adenomas and serrated lesions. Mutant KRAS exfoliated from serrated epithelial change lesions might raise false-positive rates. These findings have relevance to potential future applications of stool DNA testing for IBD surveillance.

The genetics of geometry

PubMed Central

Coen, Enrico; Rolland-Lagan, Anne-Gaëlle; Matthews, Mark; Bangham, J. Andrew; Prusinkiewicz, Przemyslaw

2004-01-01

Although much progress has been made in understanding how gene expression patterns are established during development, much less is known about how these patterns are related to the growth of biological shapes. Here we describe conceptual and experimental approaches to bridging this gap, with particular reference to plant development where lack of cell movement simplifies matters. Growth and shape change in plants can be fully described with four types of regional parameter: growth rate, anisotropy, direction, and rotation. A key requirement is to understand how these parameters both influence and respond to the action of genes. This can be addressed by using mechanistic models that capture interactions among three components: regional identities, regionalizing morphogens, and polarizing morphogens. By incorporating these interactions within a growing framework, it is possible to generate shape changes and associated gene expression patterns according to particular hypotheses. The results can be compared with experimental observations of growth of normal and mutant forms, allowing further hypotheses and experiments to be formulated. We illustrate these principles with a study of snapdragon petal growth. PMID:14960734

Encoding of temporal signals by the TGF-β pathway and implications for embryonic patterning

PubMed Central

Sorre, Benoit; Warmflash, Aryeh; Brivanlou, Ali H.; Siggia, Eric D.

2014-01-01

Summary Genetics and biochemistry have defined the components and wiring of the signaling pathways that pattern the embryo. Among them, the TGF-β pathway has the potential to behave as a morphogen: invitro experiments have clearly established that it can dictate cell fate in a concentration dependent manner. How morphogens convey positional information in a developing embryo, where signal levels are changing with time, is less understood. Using integrated microfluidic cell culture and time-lapse microscopy, we demonstrate here that the speed of ligand presentation has a key and previously unexpected influence on TGF-β signaling outcomes. The response to a TGF-β concentration step is transient and adaptive, slowly increasing the ligand concentration diminishes the response and well-spaced pulses of ligand combine additively resulting in greater pathway output than with constant stimulation. Our results suggest that in an embryonic context, the speed of change of ligand concentration is an instructive signal for patterning. PMID:25065773

Context clues: the importance of stem cell-material interactions

PubMed Central

Murphy, William L.

2014-01-01

Understanding the processes by which stem cells give rise to de novo tissues is an active focus of stem cell biology and bioengineering disciplines. Instructive morphogenic cues surrounding the stem cell during morphogenesis create what is referred to as the stem cell microenvironment. An emerging paradigm in stem cell bioengineering involves “biologically driven assembly,” in which stem cells are encouraged to largely define their own morphogenesis processes. However, even in the case of biologically driven assembly, stem cells do not act alone. The properties of the surrounding microenvironment can be critical regulators of cell fate. Stem cell-material interactions are among the most well-characterized microenvironmental effectors of stem cell fate, and they establish a signaling “context” that can define the mode of influence for morphogenic cues. Here we describe illustrative examples of cell-material interactions that occur during in vitro stem cell studies, with an emphasis on how cell-material interactions create instructive contexts for stem cell differentiation and morphogenesis. PMID:24369691

The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans

PubMed Central

Liégeois, Samuel; Benedetto, Alexandre; Garnier, Jean-Marie; Schwab, Yannick; Labouesse, Michel

2006-01-01

Polarized intracellular trafficking in epithelia is critical in development, immunity, and physiology to deliver morphogens, defensins, or ion pumps to the appropriate membrane domain. The mechanisms that control apical trafficking remain poorly defined. Using Caenorhabditis elegans, we characterize a novel apical secretion pathway involving multivesicularbodies and the release of exosomes at the apical plasma membrane. By means of two different genetic approaches, we show that the membrane-bound V0 sector of the vacuolar H+-ATPase (V-ATPase) acts in this pathway, independent of its contribution to the V-ATPase proton pump activity. Specifically, we identified mutations in the V0 “a” subunit VHA-5 that affect either the V0-specific function or the V0+V1 function of the V-ATPase. These mutations allowed us to establish that the V0 sector mediates secretion of Hedgehog-related proteins. Our data raise the possibility that the V0 sector mediates exosome and morphogen release in mammals. PMID:16785323

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

PubMed

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

The zebrafish dorsal axis is apparent at the four-cell stage.

PubMed

Gore, Aniket V; Maegawa, Shingo; Cheong, Albert; Gilligan, Patrick C; Weinberg, Eric S; Sampath, Karuna

2005-12-15

A central question in the development of multicellular organisms pertains to the timing and mechanisms of specification of the embryonic axes. In many organisms, specification of the dorsoventral axis requires signalling by proteins of the Transforming growth factor-beta and Wnt families. Here we show that maternal transcripts of the zebrafish Nodal-related morphogen, Squint (Sqt), can localize to two blastomeres at the four-cell stage and predict the dorsal axis. Removal of cells containing sqt transcripts from four-to-eight-cell embryos or injection of antisense morpholino oligonucleotides targeting sqt into oocytes can cause a loss of dorsal structures. Localization of sqt transcripts is independent of maternal Wnt pathway function and requires a highly conserved sequence in the 3' untranslated region. Thus, the dorsoventral axis is apparent by early cleavage stages and may require the maternally encoded morphogen Sqt and its associated factors. Because the 3' untranslated region of the human nodal gene can also localize exogenous sequences to dorsal cells, this mechanism may be evolutionarily conserved.

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation.

PubMed

Choe, Youngshik; Siegenthaler, Julie A; Pleasure, Samuel J

2012-02-23

The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. By using mice either with meningeal overgrowth or selective loss of meninges, we have identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonize the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, which is produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. Copyright © 2012 Elsevier Inc. All rights reserved.

A cascade of morphogenic signaling initiated by the meninges controls corpus callosum formation

PubMed Central

Choe, Youngshik; Siegenthaler, Julie A.; Pleasure, Samuel J.

2012-01-01

Summary The corpus callosum is the most prominent commissural connection between the cortical hemispheres, and numerous neurodevelopmental disorders are associated with callosal agenesis. Using mice with either meningeal overgrowth or selective loss of meninges, we’ve identified a cascade of morphogenic signals initiated by the meninges that regulates corpus callosum development. The meninges produce BMP7, an inhibitor of callosal axon outgrowth. This activity is overcome by the induction of expression of Wnt3 by the callosal pathfinding neurons, which antagonizes the inhibitory effects of BMP7. Wnt3 expression in the cingulate callosal pathfinding axons is developmentally regulated by another BMP family member, GDF5, produced by the adjacent Cajal-Retzius neurons and turns on before outgrowth of the callosal axons. The effects of GDF5 are in turn under the control of a soluble GDF5 inhibitor, Dan, made by the meninges. Thus, the meninges and medial neocortex use a cascade of signals to regulate corpus callosum development. PMID:22365545

Hyperbolic Method for Dispersive PDEs: Same High-Order of Accuracy for Solution, Gradient, and Hessian

NASA Technical Reports Server (NTRS)

Mazaheri, Alireza; Ricchiuto, Mario; Nishikawa, Hiroaki

2016-01-01

In this paper, we introduce a new hyperbolic first-order system for general dispersive partial differential equations (PDEs). We then extend the proposed system to general advection-diffusion-dispersion PDEs. We apply the fourth-order RD scheme of Ref. 1 to the proposed hyperbolic system, and solve time-dependent dispersive equations, including the classical two-soliton KdV and a dispersive shock case. We demonstrate that the predicted results, including the gradient and Hessian (second derivative), are in a very good agreement with the exact solutions. We then show that the RD scheme applied to the proposed system accurately captures dispersive shocks without numerical oscillations. We also verify that the solution, gradient and Hessian are predicted with equal order of accuracy.

Young-Laplace equation for liquid crystal interfaces

NASA Astrophysics Data System (ADS)

Rey, Alejandro D.

2000-12-01

This letter uses the classical theories of liquid crystal physics to derive the Young-Laplace equation of capillary hydrostatics for interfaces between viscous isotropic (I) fluids and nematic liquid crystals (NLC's), and establishes the existence of four energy contributions to pressure jumps across these unusual anisotropic interfaces. It is shown that in addition to the usual curvature contribution, bulk and surface gradient elasticity, elastic stress, and anchoring energy contribute to pressure differentials across the interface. The magnitude of the effect is proportional to the elastic moduli of the NLC, and to the bulk and surface orientation gradients that may be present in the nematic phase. In contrast to the planar interface between isotropic fluids, flat liquid crystal interfaces support pressure jumps if elastic stresses, bulk and surface gradient energy, and/or anchoring energies are finite.

Global Solutions to Repulsive Hookean Elastodynamics

NASA Astrophysics Data System (ADS)

Hu, Xianpeng; Masmoudi, Nader

2017-01-01

The global existence of classical solutions to the three dimensional repulsive Hookean elastodynamics around an equilibrium is considered. By linearization and Hodge's decomposition, the compressible part of the velocity, the density, and the compressible part of the transpose of the deformation gradient satisfy Klein-Gordon equations with speed {√{2}}, while the incompressible parts of the velocity and of the transpose of the deformation gradient satisfy wave equations with speed one. The space-time resonance method combined with the vector field method is used in a novel way to obtain the decay of the solution and hence global existence.

Refined gradient theory of scale-dependent superthin rods

NASA Astrophysics Data System (ADS)

Lurie, S. A.; Kuznetsova, E. L.; Rabinskii, L. N.; Popova, E. I.

2015-03-01

A version of the refined nonclassical theory of thin beams whose thickness is comparable with the scale characteristic of the material structure is constructed on the basis of the gradient theory of elasticity which, in contrast to the classical theory, contains some additional physical characteristics depending on the structure scale parameters and is therefore most appropriate for modeling the strains of scale-dependent systems. The fundamental conditions for the well-posedness of the gradient theories are obtained for the first time, and it is shown that some of the known applied gradient theories do not generally satisfy the well-posedness criterion. A version of the well-posed gradient strain theory which satisfies the symmetry condition is proposed. The well-posed gradient theory is then used to implement the method of kinematic hypotheses for constructing a refined theory of scale-dependent beams. The equilibrium equations of the refined theory of scale-dependent Timoshenko and Bernoulli beams are obtained. It is shown that the scale effects are localized near the beam ends, and therefore, taking the scale effects into account does not give any correction to the bending rigidity of long beams as noted in the previously published papers dealing with the scale-dependent beams.

The Initial Flow of Classical Gluon Fields in Heavy Ion Collisions

NASA Astrophysics Data System (ADS)

Fries, Rainer J.; Chen, Guangyao

2015-03-01

Using analytic solutions of the Yang-Mills equations we calculate the initial flow of energy of the classical gluon field created in collisions of large nuclei at high energies. We find radial and elliptic flow which follows gradients in the initial energy density, similar to a simple hydrodynamic behavior. In addition we find a rapidity-odd transverse flow field which implies the presence of angular momentum and should lead to directed flow in final particle spectra. We trace those energy flow terms to transverse fields from the non-abelian generalization of Gauss' Law and Ampere's and Faraday's Laws.

Molecular mechanisms underlying the actions of dietary factors on the skeleton

USDA-ARS?s Scientific Manuscript database

This book chapter summarizes the current state of knowledge on molecular mechanisms whereby nutritional status and dietary factors found in fruits, vegetables, and grains affect bone turnover and skeletal quality. The Wnt-beta catenin and bone morphogenic protein (BMP) pathways in osteoblast bone ce...

The q-G method : A q-version of the Steepest Descent method for global optimization.

PubMed

Soterroni, Aline C; Galski, Roberto L; Scarabello, Marluce C; Ramos, Fernando M

2015-01-01

In this work, the q-Gradient (q-G) method, a q-version of the Steepest Descent method, is presented. The main idea behind the q-G method is the use of the negative of the q-gradient vector of the objective function as the search direction. The q-gradient vector, or simply the q-gradient, is a generalization of the classical gradient vector based on the concept of Jackson's derivative from the q-calculus. Its use provides the algorithm an effective mechanism for escaping from local minima. The q-G method reduces to the Steepest Descent method when the parameter q tends to 1. The algorithm has three free parameters and it is implemented so that the search process gradually shifts from global exploration in the beginning to local exploitation in the end. We evaluated the q-G method on 34 test functions, and compared its performance with 34 optimization algorithms, including derivative-free algorithms and the Steepest Descent method. Our results show that the q-G method is competitive and has a great potential for solving multimodal optimization problems.

Classical Optimal Control for Energy Minimization Based On Diffeomorphic Modulation under Observable-Response-Preserving Homotopy.

PubMed

Soley, Micheline B; Markmann, Andreas; Batista, Victor S

2018-06-12

We introduce the so-called "Classical Optimal Control Optimization" (COCO) method for global energy minimization based on the implementation of the diffeomorphic modulation under observable-response-preserving homotopy (DMORPH) gradient algorithm. A probe particle with time-dependent mass m( t;β) and dipole μ( r, t;β) is evolved classically on the potential energy surface V( r) coupled to an electric field E( t;β), as described by the time-dependent density of states represented on a grid, or otherwise as a linear combination of Gaussians generated by the k-means clustering algorithm. Control parameters β defining m( t;β), μ( r, t;β), and E( t;β) are optimized by following the gradients of the energy with respect to β, adapting them to steer the particle toward the global minimum energy configuration. We find that the resulting COCO algorithm is capable of resolving near-degenerate states separated by large energy barriers and successfully locates the global minima of golf potentials on flat and rugged surfaces, previously explored for testing quantum annealing methodologies and the quantum optimal control optimization (QuOCO) method. Preliminary results show successful energy minimization of multidimensional Lennard-Jones clusters. Beyond the analysis of energy minimization in the specific model systems investigated, we anticipate COCO should be valuable for solving minimization problems in general, including optimization of parameters in applications to machine learning and molecular structure determination.

Yeast G-proteins mediate directional sensing and polarization behaviors in response to changes in pheromone gradient direction

PubMed Central

Moore, Travis I.; Tanaka, Hiromasa; Kim, Hyung Joon; Jeon, Noo Li; Yi, Tau-Mu

2013-01-01

Yeast cells polarize by projecting up mating pheromone gradients, a classic cell polarity behavior. However, these chemical gradients may shift direction. We examine how yeast cells sense and respond to a 180o switch in the direction of microfluidically generated pheromone gradients. We identify two behaviors: at low concentrations of α-factor, the initial projection grows by bending, whereas at high concentrations, cells form a second projection toward the new source. Mutations that increase heterotrimeric G-protein activity expand the bending-growth morphology to high concentrations; mutations that increase Cdc42 activity result in second projections at low concentrations. Gradient-sensing projection bending requires interaction between Gβγ and Cdc24, whereas gradient-nonsensing projection extension is stimulated by Bem1 and hyperactivated Cdc42. Of interest, a mutation in Gα affects both bending and extension. Finally, we find a genetic perturbation that exhibits both behaviors. Overexpression of the formin Bni1, a component of the polarisome, makes both bending-growth projections and second projections at low and high α-factor concentrations, suggesting a role for Bni1 downstream of the heterotrimeric G-protein and Cdc42 during gradient sensing and response. Thus we demonstrate that G-proteins modulate in a ligand-dependent manner two fundamental cell-polarity behaviors in response to gradient directional change. PMID:23242998

Combining Classical and Molecular Approaches Elaborates on the Complexity of Mechanisms Underpinning Anterior Regeneration

PubMed Central

Evans, Deborah J.; Owlarn, Suthira; Tejada Romero, Belen; Chen, Chen; Aboobaker, A. Aziz

2011-01-01

The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then later homeostatic signals in AP axis regeneration. PMID:22125640

Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.

PubMed

Evans, Deborah J; Owlarn, Suthira; Tejada Romero, Belen; Chen, Chen; Aboobaker, A Aziz

2011-01-01

The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then later homeostatic signals in AP axis regeneration.

Singularity-free dislocation dynamics with strain gradient elasticity

NASA Astrophysics Data System (ADS)

Po, Giacomo; Lazar, Markus; Seif, Dariush; Ghoniem, Nasr

2014-08-01

The singular nature of the elastic fields produced by dislocations presents conceptual challenges and computational difficulties in the implementation of discrete dislocation-based models of plasticity. In the context of classical elasticity, attempts to regularize the elastic fields of discrete dislocations encounter intrinsic difficulties. On the other hand, in gradient elasticity, the issue of singularity can be removed at the outset and smooth elastic fields of dislocations are available. In this work we consider theoretical and numerical aspects of the non-singular theory of discrete dislocation loops in gradient elasticity of Helmholtz type, with interest in its applications to three dimensional dislocation dynamics (DD) simulations. The gradient solution is developed and compared to its singular and non-singular counterparts in classical elasticity using the unified framework of eigenstrain theory. The fundamental equations of curved dislocation theory are given as non-singular line integrals suitable for numerical implementation using fast one-dimensional quadrature. These include expressions for the interaction energy between two dislocation loops and the line integral form of the generalized solid angle associated with dislocations having a spread core. The single characteristic length scale of Helmholtz elasticity is determined from independent molecular statics (MS) calculations. The gradient solution is implemented numerically within our variational formulation of DD, with several examples illustrating the viability of the non-singular solution. The displacement field around a dislocation loop is shown to be smooth, and the loop self-energy non-divergent, as expected from atomic configurations of crystalline materials. The loop nucleation energy barrier and its dependence on the applied shear stress are computed and shown to be in good agreement with atomistic calculations. DD simulations of Lome-Cottrell junctions in Al show that the strength of the junction and its configuration are easily obtained, without ad-hoc regularization of the singular fields. Numerical convergence studies related to the implementation of the non-singular theory in DD are presented.

Trajectory description of the quantum–classical transition for wave packet interference

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

Chou, Chia-Chun, E-mail: ccchou@mx.nthu.edu.tw

2016-08-15

The quantum–classical transition for wave packet interference is investigated using a hydrodynamic description. A nonlinear quantum–classical transition equation is obtained by introducing a degree of quantumness ranging from zero to one into the classical time-dependent Schrödinger equation. This equation provides a continuous description for the transition process of physical systems from purely quantum to purely classical regimes. In this study, the transition trajectory formalism is developed to provide a hydrodynamic description for the quantum–classical transition. The flow momentum of transition trajectories is defined by the gradient of the action function in the transition wave function and these trajectories follow themore » main features of the evolving probability density. Then, the transition trajectory formalism is employed to analyze the quantum–classical transition of wave packet interference. For the collision-like wave packet interference where the propagation velocity is faster than the spreading speed of the wave packet, the interference process remains collision-like for all the degree of quantumness. However, the interference features demonstrated by transition trajectories gradually disappear when the degree of quantumness approaches zero. For the diffraction-like wave packet interference, the interference process changes continuously from a diffraction-like to collision-like case when the degree of quantumness gradually decreases. This study provides an insightful trajectory interpretation for the quantum–classical transition of wave packet interference.« less

Genetic Variants in the Bone Morphogenic Protein Gene Family Modify the Association between Residential Exposure to Traffic and Peripheral Arterial Disease

EPA Science Inventory

There is a growing literature indicating that genetic variants modify many of the associations between environmental exposures and clinical outcomes, potentially by increasing susceptibility to these exposures. However, genome-scale investigations of these interactions have been ...

Study of homogeneous bubble nucleation in liquid carbon dioxide by a hybrid approach combining molecular dynamics simulation and density gradient theory

NASA Astrophysics Data System (ADS)

Langenbach, K.; Heilig, M.; Horsch, M.; Hasse, H.

2018-03-01

A new method for predicting homogeneous bubble nucleation rates of pure compounds from vapor-liquid equilibrium (VLE) data is presented. It combines molecular dynamics simulation on the one side with density gradient theory using an equation of state (EOS) on the other. The new method is applied here to predict bubble nucleation rates in metastable liquid carbon dioxide (CO2). The molecular model of CO2 is taken from previous work of our group. PC-SAFT is used as an EOS. The consistency between the molecular model and the EOS is achieved by adjusting the PC-SAFT parameters to VLE data obtained from the molecular model. The influence parameter of density gradient theory is fitted to the surface tension of the molecular model. Massively parallel molecular dynamics simulations are performed close to the spinodal to compute bubble nucleation rates. From these simulations, the kinetic prefactor of the hybrid nucleation theory is estimated, whereas the nucleation barrier is calculated from density gradient theory. This enables the extrapolation of molecular simulation data to the whole metastable range including technically relevant densities. The results are tested against available experimental data and found to be in good agreement. The new method does not suffer from typical deficiencies of classical nucleation theory concerning the thermodynamic barrier at the spinodal and the bubble size dependence of surface tension, which is typically neglected in classical nucleation theory. In addition, the density in the center of critical bubbles and their surface tension is determined as a function of their radius. The usual linear Tolman correction to the capillarity approximation is found to be invalid.

Study of homogeneous bubble nucleation in liquid carbon dioxide by a hybrid approach combining molecular dynamics simulation and density gradient theory.

PubMed

Langenbach, K; Heilig, M; Horsch, M; Hasse, H

2018-03-28

A new method for predicting homogeneous bubble nucleation rates of pure compounds from vapor-liquid equilibrium (VLE) data is presented. It combines molecular dynamics simulation on the one side with density gradient theory using an equation of state (EOS) on the other. The new method is applied here to predict bubble nucleation rates in metastable liquid carbon dioxide (CO 2 ). The molecular model of CO 2 is taken from previous work of our group. PC-SAFT is used as an EOS. The consistency between the molecular model and the EOS is achieved by adjusting the PC-SAFT parameters to VLE data obtained from the molecular model. The influence parameter of density gradient theory is fitted to the surface tension of the molecular model. Massively parallel molecular dynamics simulations are performed close to the spinodal to compute bubble nucleation rates. From these simulations, the kinetic prefactor of the hybrid nucleation theory is estimated, whereas the nucleation barrier is calculated from density gradient theory. This enables the extrapolation of molecular simulation data to the whole metastable range including technically relevant densities. The results are tested against available experimental data and found to be in good agreement. The new method does not suffer from typical deficiencies of classical nucleation theory concerning the thermodynamic barrier at the spinodal and the bubble size dependence of surface tension, which is typically neglected in classical nucleation theory. In addition, the density in the center of critical bubbles and their surface tension is determined as a function of their radius. The usual linear Tolman correction to the capillarity approximation is found to be invalid.

A magnetic gradient induced force in NMR restricted diffusion experiments

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

Ghadirian, Bahman; Stait-Gardner, Tim; Castillo, Reynaldo

2014-03-28

We predict that the phase cancellation of a precessing magnetisation field carried by a diffusing species in a bounded geometry under certain nuclear magnetic resonance pulsed magnetic field gradient sequences results in a small force over typically micrometre length scales. Our calculations reveal that the total magnetisation energy in a pore under the influence of a pulsed gradient will be distance-dependent thus resulting in a force acting on the boundary. It is shown that this effect of the magnetisation of diffusing particles will appear as either an attractive or repulsive force depending on the geometry of the pore and magneticmore » properties of the material. A detailed analysis is performed for the case of a pulsed gradient spin-echo experiment on parallel planes. It is shown that the force decays exponentially in terms of the spin-spin relaxation. The proof is based on classical electrodynamics. An application of this effect to soft matter is suggested.« less

Direct measurements of classical and enhanced gradient-aligned cross-field ion flows in a helicon plasma source using laser-induced fluorescence

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

Siddiqui, M. Umair, E-mail: musiddiqui@mail.wvu.edu; Thompson, Derek S.; McIlvain, Julianne M.

2015-12-15

Direct laser induced fluorescence measurements are shown of cross-field ion flows normal to an absorbing boundary that is aligned parallel to the axial magnetic field in a helicon plasma. We show Langmuir and emissive probe measurements of local density and plasma potential in the same region, as well as floating probe spectra near the boundary. With these measurements, we investigate the influence of ion-neutral collisionality on radial ion transport by varying the ratio of the ion gyro-radius, ρ{sub i}, to the ion-neutral collision length, λ, over the range 0.34 ≤ ρ{sub i}λ{sup −1} ≤ 1.60. Classical drift-diffusion transport along density and potential gradients ismore » sufficient to describe flow profiles for most cases. For two parameter regimes (ρ{sub i}λ{sup −1} = 0.65 and 0.44), low-frequency electrostatic fluctuations (f < 10 kHz) and enhanced cross-field bulk ion flow to the boundary are observed.« less

Structure of the plasmapause from ISEE 1 low-energy ion and plasma wave observations

NASA Technical Reports Server (NTRS)

Nagai, T.; Horwitz, J. L.; Anderson, R. R.; Chappell, C. R.

1985-01-01

Low-energy ion pitch angle distributions are compared with plasma density profiles in the near-earth magnetosphere using ISEE 1 observations. The classical plasmapause determined by the sharp density gradient is not always observed in the dayside region, whereas there almost always exists the ion pitch angle distribution transition from cold, isotropic to warm, bidirectional, field-aligned distributions. In the nightside region the plasmapause density gradient is typically found, and it normally coincides with the ion pitch angle distribution transition. The sunward motion of the plasma is found in the outer part of the 'plasmaspheric' plasma in the dusk bulge region.

Fast gradient-based algorithm on extended landscapes for wave-front reconstruction of Earth observation satellite

NASA Astrophysics Data System (ADS)

Thiebaut, C.; Perraud, L.; Delvit, J. M.; Latry, C.

2016-07-01

We present an on-board satellite implementation of a gradient-based (optical flows) algorithm for the shifts estimation between images of a Shack-Hartmann wave-front sensor on extended landscapes. The proposed algorithm has low complexity in comparison with classical correlation methods which is a big advantage for being used on-board a satellite at high instrument data rate and in real-time. The electronic board used for this implementation is designed for space applications and is composed of radiation-hardened software and hardware. Processing times of both shift estimations and pre-processing steps are compatible of on-board real-time computation.

Infant formula promotes bone growth in neonatal piglets by enhancing osteoblastogenesis through bone morphogenic protein signaling

USDA-ARS?s Scientific Manuscript database

Relatively few studies have examined the effects of formula feeding relative to breast-feeding on bone in the neonate. Using peripheral quantitative CT scan and histomorphometric analysis, we demonstrated that neonatal piglets fed with soy-based formula (SF) and cow milk-based formula (MF) for 21 or...

Fractalkine receptor is expressed in mature ovarian teratomas and required for epidermal lineage differentiation

PubMed Central

2013-01-01

Background The goal of this study was to determine a predominant cell type expressing fractalkine receptor (CX3CR1) in mature ovarian teratomas and to establish functional significance of its expression in cell differentiation. Methods Specimens of ovarian teratoma and human fetal tissues were analyzed by immunohistochemistry for CX3CR1expression. Ovarian teratocarcinoma cell line PA-1 was used as a model for cell differentiation. Results We found that the majority of the specimens contained CX3CR1-positive cells of epidermal lineage. Skin keratinocytes in fetal tissues were also CX3CR1- positive. PA-1 cells with downregulated CX3CR1 failed to express a skin keratinocyte marker cytokeratin 14 when cultured on Matrigel in the presence of a morphogen, bone morphogenic protein 4 (BMP-4), as compared to those expressing scrambled shRNA. Conclusions Here we demonstrate that CX3CR1 is expressed in both normally (fetal skin) and abnormally (ovarian teratoma) differentiated keratinocytes and is required for cell differentiation into epidermal lineage. PMID:23958497

Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells

PubMed Central

Wang, Wei; Mariani, Francesca V.; Harland, Richard M.; Luo, Kunxin

2000-01-01

The bone morphogenic proteins (BMPs) play important roles in vertebrate development. In Xenopus, BMPs act as epidermal inducers and also as negative regulators of neurogenesis. Antagonism of BMP signaling results in neuralization. BMPs signal through the cell-surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. Here, we show that the Ski oncoprotein can block BMP signaling and the expression of BMP-responsive genes in both Xenopus and mammalian cells by directly interacting with and repressing the activity of BMP-specific Smad complexes. This ability to antagonize BMP signaling results in neuralization by Ski in the Xenopus embryo and blocking of osteoblast differentiation of murine W-20-17 cells. Thus, Ski is able to repress the activity of all receptor-associated Smads and may regulate vertebrate development by modulating the signaling activity of transforming growth factor-β family members. PMID:11121043

Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells.

PubMed

Wang, W; Mariani, F V; Harland, R M; Luo, K

2000-12-19

The bone morphogenic proteins (BMPs) play important roles in vertebrate development. In Xenopus, BMPs act as epidermal inducers and also as negative regulators of neurogenesis. Antagonism of BMP signaling results in neuralization. BMPs signal through the cell-surface receptors and downstream Smad molecules. Upon stimulation with BMP, Smad1, Smad5, and Smad8 are phosphorylated by the activated BMP receptors, form a complex with Smad4, and translocate into the nucleus, where they regulate the expression of BMP target genes. Here, we show that the Ski oncoprotein can block BMP signaling and the expression of BMP-responsive genes in both Xenopus and mammalian cells by directly interacting with and repressing the activity of BMP-specific Smad complexes. This ability to antagonize BMP signaling results in neuralization by Ski in the Xenopus embryo and blocking of osteoblast differentiation of murine W-20-17 cells. Thus, Ski is able to repress the activity of all receptor-associated Smads and may regulate vertebrate development by modulating the signaling activity of transforming growth factor-beta family members.

The bone morphogenic protein inhibitor, noggin, reduces glycemia and vascular inflammation in db/db mice

PubMed Central

Koga, Mitsuhisa; Engberding, Niels; Dikalova, Anna E.; Chang, Kyung Hwa; Seidel-Rogol, Bonnie; Long, James S.; Lassègue, Bernard; Jo, Hanjoong

2013-01-01

Vascular diseases frequently accompany diabetes mellitus. Based on the current understanding of atherosclerosis as an inflammatory disorder of the vascular wall, it has been speculated that diabetes may accelerate atherosclerosis by inducing a proinflammatory milieu in the vasculature. ANG II and bone morphogenic proteins (BMPs) have been implicated in vascular inflammation. We evaluated the effect of angiotensin receptor blockade by valsartan and BMP inhibition by noggin on markers of vascular inflammation in a mouse model of diabetes. Noggin had no effect on blood pressure but decreased serum glucose levels, whereas valsartan significantly decreased blood pressure, but not serum glucose. Both inhibitors reduced reactive oxygen species production in the aorta. Additionally, noggin and valsartan diminish gene transcription and protein expression of various inflammatory molecules in the vascular wall. These observations indicate that although both inhibitors block superoxide production and have similar effects on inflammatory gene expression, glycemia and blood pressure may represent a secondary target differentially affected by noggin and valsartan. Our data clearly identify the BMP pathway as a potentially potent therapeutic target in diabetic inflammatory vascular disease. PMID:23812391

Positional dependence of scale size and shape in butterfly wings: wing-wide phenotypic coordination of color-pattern elements and background.

PubMed

Kusaba, Kiseki; Otaki, Joji M

2009-02-01

Butterfly wing color-patterns are a phenotypically coordinated array of scales whose color is determined as cellular interpretation outputs for morphogenic signals. Here we investigated distribution patterns of scale shape and size in relation to position and coloration on the hindwings of a nymphalid butterfly Junonia orithya. Most scales had a smooth edge but scales at and near the natural and ectopic eyespot foci and in the postbasal area were jagged. Scale size decreased regularly from the postbasal to distal areas, and eyespots occasionally had larger scales than the background. Reasonable correlations were obtained between the eyespot size and focal scale size in females. Histological and real-time individual observations of the color-pattern developmental sequence showed that the background brown and blue colors expanded from the postbasal to distal areas independently from the color-pattern elements such as eyespots. These data suggest that morphogenic signals for coloration directly or indirectly influence the scale shape and size and that the blue "background" is organized by a long-range signal from an unidentified organizing center in J. orithya.

Zika Virus Can Strongly Infect and Disrupt Secondary Organizers in the Ventricular Zone of the Embryonic Chicken Brain.

PubMed

Thawani, Ankita; Sirohi, Devika; Kuhn, Richard J; Fekete, Donna M

2018-04-17

Zika virus (ZIKV) is associated with severe neurodevelopmental impairments in human fetuses, including microencephaly. Previous reports examining neural progenitor tropism of ZIKV in organoid and animal models did not address whether the virus infects all neural progenitors uniformly. To explore this, ZIKV was injected into the neural tube of 2-day-old chicken embryos, resulting in nonuniform periventricular infection 3 days later. Recurrent foci of intense infection were present at specific signaling centers that influence neuroepithelial patterning at a distance through secretion of morphogens. ZIKV infection reduced transcript levels for 3 morphogens, SHH, BMP7, and FGF8 expressed at the midbrain basal plate, hypothalamic floor plate, and isthmus, respectively. Levels of Patched1, a SHH-pathway downstream gene, were also reduced, and a SHH-dependent cell population in the ventral midbrain was shifted in position. Thus, the diminishment of signaling centers through ZIKV-mediated apoptosis may yield broader, non-cell-autonomous changes in brain patterning. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Colors of Inner Disk Classical Kuiper Belt Objects

NASA Astrophysics Data System (ADS)

Romanishin, W.; Tegler, S. C.; Consolmagno, G. J.

2010-07-01

We present new optical broadband colors, obtained with the Keck 1 and Vatican Advanced Technology telescopes, for six objects in the inner classical Kuiper Belt. Objects in the inner classical Kuiper Belt are of interest as they may represent the surviving members of the primordial Kuiper Belt that formed interior to the current position of the 3:2 resonance with Neptune, the current position of the plutinos, or, alternatively, they may be objects formed at a different heliocentric distance that were then moved to their present locations. The six new colors, combined with four previously published, show that the ten inner belt objects with known colors form a neutral clump and a reddish clump in B-R color. Nonparametric statistical tests show no significant difference between the B-R color distribution of the inner disk objects compared to the color distributions of Centaurs, plutinos, or scattered disk objects. However, the B-R color distribution of the inner classical Kuiper Belt Objects does differ significantly from the distribution of colors in the cold (low inclination) main classical Kuiper Belt. The cold main classical objects are predominately red, while the inner classical belt objects are a mixture of neutral and red. The color difference may reveal the existence of a gradient in the composition and/or surface processing history in the primordial Kuiper Belt, or indicate that the inner disk objects are not dynamically analogous to the cold main classical belt objects.

COLORS OF INNER DISK CLASSICAL KUIPER BELT OBJECTS

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

Romanishin, W.; Tegler, S. C.; Consolmagno, G. J., E-mail: wromanishin@ou.ed, E-mail: Stephen.Tegler@nau.ed, E-mail: gjc@specola.v

2010-07-15

We present new optical broadband colors, obtained with the Keck 1 and Vatican Advanced Technology telescopes, for six objects in the inner classical Kuiper Belt. Objects in the inner classical Kuiper Belt are of interest as they may represent the surviving members of the primordial Kuiper Belt that formed interior to the current position of the 3:2 resonance with Neptune, the current position of the plutinos, or, alternatively, they may be objects formed at a different heliocentric distance that were then moved to their present locations. The six new colors, combined with four previously published, show that the ten innermore » belt objects with known colors form a neutral clump and a reddish clump in B-R color. Nonparametric statistical tests show no significant difference between the B-R color distribution of the inner disk objects compared to the color distributions of Centaurs, plutinos, or scattered disk objects. However, the B-R color distribution of the inner classical Kuiper Belt Objects does differ significantly from the distribution of colors in the cold (low inclination) main classical Kuiper Belt. The cold main classical objects are predominately red, while the inner classical belt objects are a mixture of neutral and red. The color difference may reveal the existence of a gradient in the composition and/or surface processing history in the primordial Kuiper Belt, or indicate that the inner disk objects are not dynamically analogous to the cold main classical belt objects.« less

Convective flows of generalized time-nonlocal nanofluids through a vertical rectangular channel

NASA Astrophysics Data System (ADS)

Ahmed, Najma; Vieru, Dumitru; Fetecau, Constantin; Shah, Nehad Ali

2018-05-01

Time-nonlocal generalized model of the natural convection heat transfer and nanofluid flows through a rectangular vertical channel with wall conditions of the Robin type are studied. The generalized mathematical model with time-nonlocality is developed by considering the fractional constitutive equations for the shear stress and thermal flux defined with the time-fractional Caputo derivative. The Caputo power-law non-local kernel provides the damping to the velocity and temperature gradient; therefore, transport processes are influenced by the histories at all past and present times. Analytical solutions for dimensionless velocity and temperature fields are obtained by using the Laplace transform coupled with the finite sine-cosine Fourier transform which is suitable to problems with boundary conditions of the Robin type. Particularizing the fractional thermal and velocity parameters, solutions for three simplified models are obtained (classical linear momentum equation with damped thermal flux; fractional shear stress constitutive equation with classical Fourier's law for thermal flux; classical shear stress and thermal flux constitutive equations). It is found that the thermal histories strongly influence the thermal transport for small values of time t. Also, the thermal transport can be enhanced if the thermal fractional parameter decreases or by increasing the nanoparticles' volume fraction. The velocity field is influenced on the one hand by the temperature of the fluid and on the other by the damping of the velocity gradient introduced by the fractional derivative. Also, the transport motions of the channel walls influence the motion of the fluid layers located near them.

Parallel conjugate gradient algorithms for manipulator dynamic simulation

NASA Technical Reports Server (NTRS)

Fijany, Amir; Scheld, Robert E.

1989-01-01

Parallel conjugate gradient algorithms for the computation of multibody dynamics are developed for the specialized case of a robot manipulator. For an n-dimensional positive-definite linear system, the Classical Conjugate Gradient (CCG) algorithms are guaranteed to converge in n iterations, each with a computation cost of O(n); this leads to a total computational cost of O(n sq) on a serial processor. A conjugate gradient algorithms is presented that provide greater efficiency using a preconditioner, which reduces the number of iterations required, and by exploiting parallelism, which reduces the cost of each iteration. Two Preconditioned Conjugate Gradient (PCG) algorithms are proposed which respectively use a diagonal and a tridiagonal matrix, composed of the diagonal and tridiagonal elements of the mass matrix, as preconditioners. Parallel algorithms are developed to compute the preconditioners and their inversions in O(log sub 2 n) steps using n processors. A parallel algorithm is also presented which, on the same architecture, achieves the computational time of O(log sub 2 n) for each iteration. Simulation results for a seven degree-of-freedom manipulator are presented. Variants of the proposed algorithms are also developed which can be efficiently implemented on the Robot Mathematics Processor (RMP).

Size-dependent axial instability of microtubules surrounded by cytoplasm of a living cell based on nonlocal strain gradient elasticity theory.

PubMed

Sahmani, S; Aghdam, M M

2017-06-07

Microtubules including tubulin heterodimers arranging in a parallel shape of cylindrical hollow plays an important role in the mechanical stiffness of a living cell. In the present study, the nonlocal strain gradient theory of elasticity including simultaneously the both nonlocality and strain gradient size dependency is put to use within the framework of a refined orthotropic shell theory with hyperbolic distribution of shear deformation to analyze the size-dependent buckling and postbuckling characteristics of microtubules embedded in cytoplasm under axial compressive load. The non-classical governing differential equations are deduced via boundary layer theory of shell buckling incorporating the nonlinear prebuckling deformation and microtubule-cytoplasm interaction in the living cell environment. Finally, with the aid of a two-stepped perturbation solution methodology, the explicit analytical expressions for nonlocal strain gradient stability paths of axially loaded microtubules are achieved. It is illustrated that by taking the nonlocal size effect into consideration, the critical buckling load of microtubule and its maximum deflection associated with the minimum postbuckling load decreases, while the strain gradient size dependency causes to increase them. Copyright © 2017 Elsevier Ltd. All rights reserved.

A computational model for BMP movement in sea urchin embryos.

PubMed

van Heijster, Peter; Hardway, Heather; Kaper, Tasso J; Bradham, Cynthia A

2014-12-21

Bone morphogen proteins (BMPs) are distributed along a dorsal-ventral (DV) gradient in many developing embryos. The spatial distribution of this signaling ligand is critical for correct DV axis specification. In various species, BMP expression is spatially localized, and BMP gradient formation relies on BMP transport, which in turn requires interactions with the extracellular proteins Short gastrulation/Chordin (Chd) and Twisted gastrulation (Tsg). These binding interactions promote BMP movement and concomitantly inhibit BMP signaling. The protease Tolloid (Tld) cleaves Chd, which releases BMP from the complex and permits it to bind the BMP receptor and signal. In sea urchin embryos, BMP is produced in the ventral ectoderm, but signals in the dorsal ectoderm. The transport of BMP from the ventral ectoderm to the dorsal ectoderm in sea urchin embryos is not understood. Therefore, using information from a series of experiments, we adapt the mathematical model of Mizutani et al. (2005) and embed it as the reaction part of a one-dimensional reaction-diffusion model. We use it to study aspects of this transport process in sea urchin embryos. We demonstrate that the receptor-bound BMP concentration exhibits dorsally centered peaks of the same type as those observed experimentally when the ternary transport complex (Chd-Tsg-BMP) forms relatively quickly and BMP receptor binding is relatively slow. Similarly, dorsally centered peaks are created when the diffusivities of BMP, Chd, and Chd-Tsg are relatively low and that of Chd-Tsg-BMP is relatively high, and the model dynamics also suggest that Tld is a principal regulator of the system. At the end of this paper, we briefly compare the observed dynamics in the sea urchin model to a version that applies to the fly embryo, and we find that the same conditions can account for BMP transport in the two types of embryos only if Tld levels are reduced in sea urchin compared to fly. Copyright © 2014 Elsevier Ltd. All rights reserved.

A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens

PubMed Central

Wu, Jun Jie; Wu, Weiju; Tholozan, Frederique M.; Saunter, Christopher D.; Girkin, John M.; Quinlan, Roy A.

2015-01-01

We present a mathematical (ordered pull-through; OPT) model of the cell-density profile for the mammalian lens epithelium together with new experimental data. The model is based upon dimensionless parameters, an important criterion for inter-species comparisons where lens sizes can vary greatly (e.g. bovine (approx. 18 mm); mouse (approx. 2 mm)) and confirms that mammalian lenses scale with size. The validated model includes two parameters: β/α, which is the ratio of the proliferation rate in the peripheral and in the central region of the lens; and γGZ, a dimensionless pull-through parameter that accounts for the cell transition and exit from the epithelium into the lens body. Best-fit values were determined for mouse, rat, rabbit, bovine and human lens epithelia. The OPT model accounts for the peak in cell density at the periphery of the lens epithelium, a region where cell proliferation is concentrated and reaches a maximum coincident with the germinative zone. The β/α ratio correlates with the measured FGF-2 gradient, a morphogen critical to lens cell survival, proliferation and differentiation. As proliferation declines with age, the OPT model predicted age-dependent changes in cell-density profiles, which we observed in mouse and human lenses. PMID:26236824

Parallels between Global Transcriptional Programs of Polarizing Caco-2 Intestinal Epithelial Cells In Vitro and Gene Expression Programs in Normal Colon and Colon Cancer

PubMed Central

Sääf, Annika M.; Halbleib, Jennifer M.; Chen, Xin; Yuen, Siu Tsan; Leung, Suet Yi

2007-01-01

Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell–cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2. PMID:17699589

Role of ID Proteins in BMP4 Inhibition of Profibrotic Effects of TGF-β2 in Human TM Cells.

PubMed

Mody, Avani A; Wordinger, Robert J; Clark, Abbot F

2017-02-01

Increased expression of TGF-β2 in primary open-angle glaucoma (POAG) aqueous humor (AH) and trabecular meshwork (TM) causes deposition of extracellular matrix (ECM) in the TM and elevated IOP. Bone morphogenetic proteins (BMPs) regulate TGF-β2-induced ECM production. The underlying mechanism for BMP4 inhibition of TGF-β2-induced fibrosis remains undetermined. Bone morphogenic protein 4 induces inhibitor of DNA binding proteins (ID1, ID3), which suppress transcription factor activities to regulate gene expression. Our study will determine whether ID1and ID3 proteins are downstream targets of BMP4, which attenuates TGF-β2 induction of ECM proteins in TM cells. Primary human TM cells were treated with BMP4, and ID1 and ID3 mRNA, and protein expression was determined by quantitative PCR (Q-PCR) and Western immunoblotting. Intracellular ID1 and ID3 protein localization was studied by immunocytochemistry. Transformed human TM cells (GTM3 cells) were transfected with ID1 or ID3 expression vectors to determine their potential inhibitory effects on TGF-β2-induced fibronectin and plasminogen activator inhibitor-I (PAI-1) protein expression. Basal expression of ID1-3 was detected in primary human TM cells. Bone morphogenic protein 4 significantly induced early expression of ID1 and ID3 mRNA (P < 0.05) and protein in primary TM cells, and a BMP receptor inhibitor blocked this induction. Overexpression of ID1 and ID3 significantly inhibited TGF-β2-induced expression of fibronectin and PAI-1 in TM cells (P < 0.01). Bone morphogenic protein 4 induced ID1 and ID3 expression suppresses TGF-β2 profibrotic activity in human TM cells. In the future, targeting specific regulators may control the TGF-β2 profibrotic effects on the TM, leading to disease modifying IOP lowering therapies.

Correlating the internal length in strain gradient plasticity theory with the microstructure of material

NASA Astrophysics Data System (ADS)

Zhao, Jianfeng; Zhang, Xu; Konstantinidis, Avraam A.; Kang, Guozheng

2015-06-01

The internal length is the governing parameter in strain gradient theories which among other things have been used successfully to interpret size effects at the microscale. Physically, the internal length is supposed to be related with the microstructure of the material and evolves during the deformation. Based on Taylor hardening law, we propose a power-law relationship to describe the evolution of the variable internal length with strain. Then, the classical Fleck-Hutchinson strain gradient theory is extended with a strain-dependent internal length, and the generalized Fleck-Hutchinson theory is confirmed here, by comparing our model predictions to recent experimental data on tension and torsion of thin wires with varying diameter and grain size. Our work suggests that the internal length is a configuration-dependent parameter, closely related to dislocation characteristics and grain size, as well as sample geometry when this affects either the underlying microstructure or the ductility of the material.

A biconjugate gradient type algorithm on massively parallel architectures

NASA Technical Reports Server (NTRS)

Freund, Roland W.; Hochbruck, Marlis

1991-01-01

The biconjugate gradient (BCG) method is the natural generalization of the classical conjugate gradient algorithm for Hermitian positive definite matrices to general non-Hermitian linear systems. Unfortunately, the original BCG algorithm is susceptible to possible breakdowns and numerical instabilities. Recently, Freund and Nachtigal have proposed a novel BCG type approach, the quasi-minimal residual method (QMR), which overcomes the problems of BCG. Here, an implementation is presented of QMR based on an s-step version of the nonsymmetric look-ahead Lanczos algorithm. The main feature of the s-step Lanczos algorithm is that, in general, all inner products, except for one, can be computed in parallel at the end of each block; this is unlike the other standard Lanczos process where inner products are generated sequentially. The resulting implementation of QMR is particularly attractive on massively parallel SIMD architectures, such as the Connection Machine.

The lowest-order weak Galerkin finite element method for the Darcy equation on quadrilateral and hybrid meshes

NASA Astrophysics Data System (ADS)

Liu, Jiangguo; Tavener, Simon; Wang, Zhuoran

2018-04-01

This paper investigates the lowest-order weak Galerkin finite element method for solving the Darcy equation on quadrilateral and hybrid meshes consisting of quadrilaterals and triangles. In this approach, the pressure is approximated by constants in element interiors and on edges. The discrete weak gradients of these constant basis functions are specified in local Raviart-Thomas spaces, specifically RT0 for triangles and unmapped RT[0] for quadrilaterals. These discrete weak gradients are used to approximate the classical gradient when solving the Darcy equation. The method produces continuous normal fluxes and is locally mass-conservative, regardless of mesh quality, and has optimal order convergence in pressure, velocity, and normal flux, when the quadrilaterals are asymptotically parallelograms. Implementation is straightforward and results in symmetric positive-definite discrete linear systems. We present numerical experiments and comparisons with other existing methods.

Cyp15F1: A novel cytochrome P450 gene linked to juvenile hormone-dependent caste differention in the termite R. flavipes

USDA-ARS?s Scientific Manuscript database

Termites are eusocial insects that perform social interactions that facilitate chemical signaling. Previous research identified two cytochrome P450s that have homology to other insect p450s responsible for the production of juvenile hormone. Juvenile hormone is an important morphogenic hormone tha...

The Green's functions for peridynamic non-local diffusion.

PubMed

Wang, L J; Xu, J F; Wang, J X

2016-09-01

In this work, we develop the Green's function method for the solution of the peridynamic non-local diffusion model in which the spatial gradient of the generalized potential in the classical theory is replaced by an integral of a generalized response function in a horizon. We first show that the general solutions of the peridynamic non-local diffusion model can be expressed as functionals of the corresponding Green's functions for point sources, along with volume constraints for non-local diffusion. Then, we obtain the Green's functions by the Fourier transform method for unsteady and steady diffusions in infinite domains. We also demonstrate that the peridynamic non-local solutions converge to the classical differential solutions when the non-local length approaches zero. Finally, the peridynamic analytical solutions are applied to an infinite plate heated by a Gauss source, and the predicted variations of temperature are compared with the classical local solutions. The peridynamic non-local diffusion model predicts a lower rate of variation of the field quantities than that of the classical theory, which is consistent with experimental observations. The developed method is applicable to general diffusion-type problems.

Smooth particle hydrodynamics: theory and application to the origin of the moon

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

Benz, W.

1986-01-01

The origin of the moon is modeled by the so-called smooth particle hydrodynamics (SPH) method (Lucy, 1977, Monaghan 1985) which substitutes to the fluid a finite set of extended particles, the hydrodynamics equations reduce to the equation of motion of individual particles. These equations of motion differ only from the standard gravitational N-body problem insofar that pressure gradients and viscosity terms have to be added to the gradient of the potential to derive the forces between the particles. The numerical tools developed for ''classical'' N-body problems can therefore be readily applied to solve 3 dimensional hydroynamical problems. 12 refs., 1more » fig.« less

Convex Optimization over Classes of Multiparticle Entanglement

NASA Astrophysics Data System (ADS)

Shang, Jiangwei; Gühne, Otfried

2018-02-01

A well-known strategy to characterize multiparticle entanglement utilizes the notion of stochastic local operations and classical communication (SLOCC), but characterizing the resulting entanglement classes is difficult. Given a multiparticle quantum state, we first show that Gilbert's algorithm can be adapted to prove separability or membership in a certain entanglement class. We then present two algorithms for convex optimization over SLOCC classes. The first algorithm uses a simple gradient approach, while the other one employs the accelerated projected-gradient method. For demonstration, the algorithms are applied to the likelihood-ratio test using experimental data on bound entanglement of a noisy four-photon Smolin state [Phys. Rev. Lett. 105, 130501 (2010), 10.1103/PhysRevLett.105.130501].

A new nonlinear conjugate gradient coefficient under strong Wolfe-Powell line search

NASA Astrophysics Data System (ADS)

Mohamed, Nur Syarafina; Mamat, Mustafa; Rivaie, Mohd

2017-08-01

A nonlinear conjugate gradient method (CG) plays an important role in solving a large-scale unconstrained optimization problem. This method is widely used due to its simplicity. The method is known to possess sufficient descend condition and global convergence properties. In this paper, a new nonlinear of CG coefficient βk is presented by employing the Strong Wolfe-Powell inexact line search. The new βk performance is tested based on number of iterations and central processing unit (CPU) time by using MATLAB software with Intel Core i7-3470 CPU processor. Numerical experimental results show that the new βk converge rapidly compared to other classical CG method.

QMR: A Quasi-Minimal Residual method for non-Hermitian linear systems

NASA Technical Reports Server (NTRS)

Freund, Roland W.; Nachtigal, Noel M.

1990-01-01

The biconjugate gradient (BCG) method is the natural generalization of the classical conjugate gradient algorithm for Hermitian positive definite matrices to general non-Hermitian linear systems. Unfortunately, the original BCG algorithm is susceptible to possible breakdowns and numerical instabilities. A novel BCG like approach is presented called the quasi-minimal residual (QMR) method, which overcomes the problems of BCG. An implementation of QMR based on a look-ahead version of the nonsymmetric Lanczos algorithm is proposed. It is shown how BCG iterates can be recovered stably from the QMR process. Some further properties of the QMR approach are given and an error bound is presented. Finally, numerical experiments are reported.

New approaches with two cyano columns to the separation of acetaminophen, phenylephrine, chlorpheniramine and related compounds.

PubMed

Olmo, B; García, A; Marín, A; Barbas, C

2005-03-25

The development of new pharmaceutical forms with classical active compounds generates new analytical problems. That is the case of sugar-free sachets of cough-cold products containing acetaminophen, phenylephrine hydrochloride and chlorpheniramine maleate. Two cyanopropyl stationary phases have been employed to tackle the problem. The Discovery cyanopropyl (SUPELCO) column permitted the separation of the three actives, maleate and excipients (mainly saccharine and orange flavour) with a constant proportion of aqueous/ organic solvent (95:5, v/v) and a pH gradient from 7.5 to 2. The run lasted 14 min. This technique avoids many problems related to baseline shifts with classical organic solvent gradients and opens great possibilities to modify selectivity not generally used in reversed phase HPLC. On the other hand, the Agilent Zorbax SB-CN column with a different retention profile permitted us to separate not only the three actives and the excipients but also the three known related compounds: 4-aminophenol, 4-chloracetanilide and 4-nitrophenol in an isocratic method with a run time under 30 min. This method was validated following ICH guidelines and validation parameters showed that it could be employed as stability-indicating method for this pharmaceutical form.

Remote sensing-based measurement of Living Environment Deprivation: Improving classical approaches with machine learning

PubMed Central

2017-01-01

This paper provides evidence on the usefulness of very high spatial resolution (VHR) imagery in gathering socioeconomic information in urban settlements. We use land cover, spectral, structure and texture features extracted from a Google Earth image of Liverpool (UK) to evaluate their potential to predict Living Environment Deprivation at a small statistical area level. We also contribute to the methodological literature on the estimation of socioeconomic indices with remote-sensing data by introducing elements from modern machine learning. In addition to classical approaches such as Ordinary Least Squares (OLS) regression and a spatial lag model, we explore the potential of the Gradient Boost Regressor and Random Forests to improve predictive performance and accuracy. In addition to novel predicting methods, we also introduce tools for model interpretation and evaluation such as feature importance and partial dependence plots, or cross-validation. Our results show that Random Forest proved to be the best model with an R2 of around 0.54, followed by Gradient Boost Regressor with 0.5. Both the spatial lag model and the OLS fall behind with significantly lower performances of 0.43 and 0.3, respectively. PMID:28464010

Remote sensing-based measurement of Living Environment Deprivation: Improving classical approaches with machine learning.

PubMed

Arribas-Bel, Daniel; Patino, Jorge E; Duque, Juan C

2017-01-01

This paper provides evidence on the usefulness of very high spatial resolution (VHR) imagery in gathering socioeconomic information in urban settlements. We use land cover, spectral, structure and texture features extracted from a Google Earth image of Liverpool (UK) to evaluate their potential to predict Living Environment Deprivation at a small statistical area level. We also contribute to the methodological literature on the estimation of socioeconomic indices with remote-sensing data by introducing elements from modern machine learning. In addition to classical approaches such as Ordinary Least Squares (OLS) regression and a spatial lag model, we explore the potential of the Gradient Boost Regressor and Random Forests to improve predictive performance and accuracy. In addition to novel predicting methods, we also introduce tools for model interpretation and evaluation such as feature importance and partial dependence plots, or cross-validation. Our results show that Random Forest proved to be the best model with an R2 of around 0.54, followed by Gradient Boost Regressor with 0.5. Both the spatial lag model and the OLS fall behind with significantly lower performances of 0.43 and 0.3, respectively.

Stereo particle image velocimetry of nonequilibrium turbulence relaxation in a supersonic boundary layer

NASA Astrophysics Data System (ADS)

Lapsa, Andrew P.; Dahm, Werner J. A.

2011-01-01

Measurements using stereo particle image velocimetry are presented for a developing turbulent boundary layer in a wind tunnel with a Mach 2.75 free stream. As the boundary layer exits from the tunnel nozzle and moves through the wave-free test section, small initial departures from equilibrium turbulence relax, and the boundary layer develops toward the equilibrium zero-pressure-gradient form. This relaxation process is quantified by comparison of first and second order mean, fluctuation, and gradient statistics to classical inner and outer layer scalings. Simultaneous measurement of all three instantaneous velocity components enables direct assessment of the complete turbulence anisotropy tensor. Profiles of the turbulence Mach number show that, despite the M = 2.75 free stream, the incompressibility relation among spatial gradients in the velocity fluctuations applies. This result is used in constructing various estimates of the measured-dissipation rate, comparisons among which show only remarkably small differences over most of the boundary layer. The resulting measured-dissipation profiles, together with measured profiles of the turbulence kinetic energy and mean-flow gradients, enable an assessment of how the turbulence anisotropy relaxes toward its equilibrium zero-pressure-gradient state. The results suggest that the relaxation of the initially disturbed turbulence anisotropy profile toward its equilibrium zero-pressure-gradient form begins near the upper edge of the boundary layer and propagates downward through the defect layer.

A study on Rayleigh wave dispersion in bone according to Mindlin's Form II gradient elasticity.

PubMed

Vavva, Maria G; Gergidis, Leonidas N; Protopappas, Vasilios C; Charalambopoulos, Antonios; Polyzos, Demosthenes; Fotiadis, Dimitrios I

2014-05-01

The classical elasticity cannot effectively describe bone's mechanical behavior since only homogeneous media and local stresses are assumed. Additionally, it cannot predict the dispersive nature of the Rayleigh wave which has been reported in experimental studies and was also demonstrated in a previous computational study by adopting Mindlin's Form II gradient elasticity. In this work Mindlin's theory is employed to analytically determine the dispersion of Rayleigh waves in a strain gradient elastic half-space. An isotropic semi-infinite space is considered with properties equal to those of bone and dynamic behavior suffering from microstructural effects. Microstructural effects are considered by incorporating four intrinsic parameters in the stress analysis. The results are presented in the form of group and phase velocity dispersion curves and compared with existing computational results and semi-analytical curves calculated for a simpler case of Rayleigh waves in dipolar gradient elastic half-spaces. Comparisons are also performed with the velocity of the first-order antisymmetric mode propagating in a dipolar plate so as to observe the Rayleigh asymptotic behavior. It is shown that Mindlin's Form II gradient elasticity can effectively describe the dispersive nature of Rayleigh waves. This study could be regarded as a step toward the ultrasonic characterization of bone.

Biodiversity patterns along ecological gradients: unifying β-diversity indices.

PubMed

Szava-Kovats, Robert C; Pärtel, Meelis

2014-01-01

Ecologists have developed an abundance of conceptions and mathematical expressions to define β-diversity, the link between local (α) and regional-scale (γ) richness, in order to characterize patterns of biodiversity along ecological (i.e., spatial and environmental) gradients. These patterns are often realized by regression of β-diversity indices against one or more ecological gradients. This practice, however, is subject to two shortcomings that can undermine the validity of the biodiversity patterns. First, many β-diversity indices are constrained to range between fixed lower and upper limits. As such, regression analysis of β-diversity indices against ecological gradients can result in regression curves that extend beyond these mathematical constraints, thus creating an interpretational dilemma. Second, despite being a function of the same measured α- and γ-diversity, the resultant biodiversity pattern depends on the choice of β-diversity index. We propose a simple logistic transformation that rids beta-diversity indices of their mathematical constraints, thus eliminating the possibility of an uninterpretable regression curve. Moreover, this transformation results in identical biodiversity patterns for three commonly used classical beta-diversity indices. As a result, this transformation eliminates the difficulties of both shortcomings, while allowing the researcher to use whichever beta-diversity index deemed most appropriate. We believe this method can help unify the study of biodiversity patterns along ecological gradients.

Biodiversity Patterns along Ecological Gradients: Unifying β-Diversity Indices

PubMed Central

Szava-Kovats, Robert C.; Pärtel, Meelis

2014-01-01

Ecologists have developed an abundance of conceptions and mathematical expressions to define β-diversity, the link between local (α) and regional-scale (γ) richness, in order to characterize patterns of biodiversity along ecological (i.e., spatial and environmental) gradients. These patterns are often realized by regression of β-diversity indices against one or more ecological gradients. This practice, however, is subject to two shortcomings that can undermine the validity of the biodiversity patterns. First, many β-diversity indices are constrained to range between fixed lower and upper limits. As such, regression analysis of β-diversity indices against ecological gradients can result in regression curves that extend beyond these mathematical constraints, thus creating an interpretational dilemma. Second, despite being a function of the same measured α- and γ-diversity, the resultant biodiversity pattern depends on the choice of β-diversity index. We propose a simple logistic transformation that rids beta-diversity indices of their mathematical constraints, thus eliminating the possibility of an uninterpretable regression curve. Moreover, this transformation results in identical biodiversity patterns for three commonly used classical beta-diversity indices. As a result, this transformation eliminates the difficulties of both shortcomings, while allowing the researcher to use whichever beta-diversity index deemed most appropriate. We believe this method can help unify the study of biodiversity patterns along ecological gradients. PMID:25330181

Energy harvesting from vibration of Timoshenko nanobeam under base excitation considering flexoelectric and elastic strain gradient effects

NASA Astrophysics Data System (ADS)

Managheb, S. A. M.; Ziaei-Rad, S.; Tikani, R.

2018-05-01

The coupling between polarization and strain gradients is called flexoelectricity. This phenomenon exists in all dielectrics with any symmetry. In this paper, energy harvesting from a Timoshenko beam is studied by considering the flexoelectric and strain gradient effects. General governing equations and related boundary conditions are derived using Hamilton's principle. The flexoelectric effects are defined by gradients of normal and shear strains which lead to a more general model. The developed model also covers the classical Timoshenko beam theory by ignoring the flexoelectric effect. Based on the developed model, flexoelectricity effect on dielectric beams and energy harvesting from cantilever beam under harmonic base excitation is investigated. A parametric study was conducted to evaluate the effects of flexoelectric coefficients, strain gradient constants, base acceleration and the attaching tip mass on the energy harvested from a cantilever Timoshenko beam. Results show that the flexoelectricity has a significant effect on the energy harvester performance, especially in submicron and nano scales. In addition, this effect makes the beam to behave softer than before and also it changes the harvester first resonance frequency. The present study provides guidance for flexoelectric nano-beam analysis and a method to evaluate the performance of energy harvester in nano-dielectric devices.

Understanding the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions

NASA Astrophysics Data System (ADS)

Dahms, Rainer N.

2016-04-01

A generalized framework for multi-component liquid injections is presented to understand and predict the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions. The analysis focuses on the thermodynamic structure and the immiscibility state of representative gas-liquid interfaces. The most modern form of Helmholtz energy mixture state equation is utilized which exhibits a unique and physically consistent behavior over the entire two-phase regime of fluid densities. It is combined with generalized models for non-linear gradient theory and for liquid injections to quantify multi-component two-phase interface structures in global thermal equilibrium. Then, the Helmholtz free energy is minimized which determines the interfacial species distribution as a consequence. This minimal free energy state is demonstrated to validate the underlying assumptions of classic two-phase theory and spray atomization. However, under certain engine-relevant conditions for which corroborating experimental data are presented, this requirement for interfacial thermal equilibrium becomes unsustainable. A rigorously derived probability density function quantifies the ability of the interface to develop internal spatial temperature gradients in the presence of significant temperature differences between injected liquid and ambient gas. Then, the interface can no longer be viewed as an isolated system at minimal free energy. Instead, the interfacial dynamics become intimately connected to those of the separated homogeneous phases. Hence, the interface transitions toward a state in local equilibrium whereupon it becomes a dense-fluid mixing layer. A new conceptual view of a transitional liquid injection process emerges from a transition time scale analysis. Close to the nozzle exit, the two-phase interface still remains largely intact and more classic two-phase processes prevail as a consequence. Further downstream, however, the transition to dense-fluid mixing generally occurs before the liquid length is reached. The significance of the presented modeling expressions is established by a direct comparison to a reduced model, which utilizes widely applied approximations but fundamentally fails to capture the physical complexity discussed in this paper.

Thick-tissue bioreactor as a platform for long-term organotypic culture and drug delivery.

PubMed

Markov, Dmitry A; Lu, Jenny Q; Samson, Philip C; Wikswo, John P; McCawley, Lisa J

2012-11-07

We have developed a novel, portable, gravity-fed, microfluidics-based platform suitable for optical interrogation of long-term organotypic cell culture. This system is designed to provide convenient control of cell maintenance, nutrients, and experimental reagent delivery to tissue-like cell densities housed in a transparent, low-volume microenvironment. To demonstrate the ability of our Thick-Tissue Bioreactor (TTB) to provide stable, long-term maintenance of high-density cellular arrays, we observed the morphogenic growth of human mammary epithelial cell lines, MCF-10A and their invasive variants, cultured under three-dimensional (3D) conditions inside our system. Over the course of 21 days, these cells typically develop into hollow "mammospheres" if cultured in standard 3D Matrigel. This complex morphogenic process requires alterations in a variety of cellular functions, including degradation of extracellular matrix that is regulated by cell-produced matrix proteinases. For our "drug" delivery testing and validation experiments we have introduced proteinase inhibitors into the fluid supply system, and we observed both reduced proteinase activity and inhibited cellular morphogenesis. The size inhibition results correlated well with the overall proteinase activities of the tested cells.

Morphogenic Protein RodZ Interacts with Sporulation Specific SpoIIE in Bacillus subtilis.

PubMed

Muchová, Katarína; Chromiková, Zuzana; Bradshaw, Niels; Wilkinson, Anthony J; Barák, Imrich

2016-01-01

The first landmark in sporulation of Bacillus subtilis is the formation of an asymmetric septum followed by selective activation of the transcription factor σF in the resulting smaller cell. How the morphological transformations that occur during sporulation are coupled to cell-specific activation of transcription is largely unknown. The membrane protein SpoIIE is a constituent of the asymmetric sporulation septum and is a crucial determinant of σF activation. Here we report that the morphogenic protein, RodZ, which is essential for cell shape determination, is additionally required for asymmetric septum formation and sporulation. In cells depleted of RodZ, formation of asymmetric septa is disturbed and σF activation is perturbed. During sporulation, we found that SpoIIE recruits RodZ to the asymmetric septum. Moreover, we detected a direct interaction between SpoIIE and RodZ in vitro and in vivo, indicating that SpoIIE-RodZ may form a complex to coordinate asymmetric septum formation and σF activation. We propose that RodZ could provide a link between the cell shape machinery and the coordinated morphological and developmental transitions required to form a resistant spore.

Effects of Bone Morphogenic Proteins on Engineered Cartilage

NASA Technical Reports Server (NTRS)

Gooch, Keith, J.; Blunk, Torsten; Courter, Donald L.; Sieminski, Alisha; Vunjak-Novakovic, Gordana; Freed, Lisa E.

2007-01-01

A report describes experiments on the effects of bone morphogenic proteins (BMPs) on engineered cartilage grown in vitro. In the experiments, bovine calf articular chondrocytes were seeded onto biodegradable polyglycolic acid scaffolds and cultured in, variously, a control medium or a medium supplemented with BMP-2, BMP-12, or BMP-13 in various concentrations. Under all conditions investigated, cell-polymer constructs cultivated for 4 weeks macroscopically and histologically resembled native cartilage. At a concentration of 100 ng/mL, BMP-2, BMP-12, or BMP-13 caused (1) total masses of the constructs to exceed those of the controls by 121, 80, or 62 percent, respectively; (2) weight percentages of glycosaminoglycans in the constructs to increase by 27, 18, or 15, respectively; and (3) total collagen contents of the constructs to decrease to 63, 89, or 83 percent of the control values, respectively. BMP-2, but not BMP-12 or BMP-13, promoted chondrocyte hypertrophy. These observations were interpreted as suggesting that the three BMPs increase the growth rates and modulate the compositions of engineered cartilage. It was also concluded that in vitro engineered cartilage is a suitable system for studying effects of BMPs on chondrogenesis in a well-defined environment.

Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response

NASA Technical Reports Server (NTRS)

Sorescu, George P.; Sykes, Michelle; Weiss, Daiana; Platt, Manu O.; Saha, Aniket; Hwang, Jinah; Boyd, Nolan; Boo, Yong C.; Vega, J. David; Taylor, W. Robert;

Studies on callose and cutin during the expression of competence and determination for organogenic nodule formation from internodes of Humulus lupulus var. Nugget.

PubMed

Fortes, Ana M; Testillano, Pilar S; Del Carmen Risueño, Maria; Pais, Maria S

2002-09-01

Callose and cutin deposition were followed by staining with Aniline Blue and Nile Red and by immunolocalization using antibodies raised against callose. Along with morphogenesis induction from internodes of Humulus lupulus var. Nugget, a temporal and spatial differential deposition of callose and cutin was observed. A cutin layer showing bright yellow autofluorescence appears, surrounding cells or groups of cells committed to express morphogenic competence. This cutin layer that evolves to a randomly organized network appeared underneath a callose layer and may create a specific cellular environment with altered permeability and altered receptors providing conditions for entering the cell cycle. The incipient callose accumulation in control explants cultured on basal medium suggests the involvement of callose in the initiation of the morphogenic programme leading to nodule formation. A scanning electron microscopic study during the organogenic process showed that before shoot bud regeneration, the cutin layer increases in thickness and acquires a smooth texture. This cutin layer is specific to nodular organogenic regions and disappeared with plantlet regeneration. This layer may control permeability to water and solute transfer throughout plantlet regeneration.

Complications Associated With the Use of Recombinant Human Bone Morphogenic Protein-2 in Ridge Augmentation: A Case Report.

PubMed

Dragonas, Panagiotis; Palin, Charles; Khan, Saba; Gajendrareddy, Praveen K; Weiner, Whitney D

2017-10-01

This case report aims to describe in detail a complication associated with resorption of regenerated bone following implant placement and ridge augmentation using recombinant human bone morphogenic protein-2 (rhBMP-2) in combination with allograft and xenograft. Bilateral maxillary sinus and ridge augmentation procedures were completed using rhBMP-2 combined with allograft and xenograft. Five months later, significant bone augmentation was achieved, which allowed for the placement of 4 implants. Upon stage 2 surgery, significant dehiscence was noted in all implants. Treatment steps to address this complication included implant removal, guided bone regeneration with xenograft only, and placement of new implants followed by soft-tissue grafting. At the time of publication, this patient is status 1½ years post case completion with maintenance of therapy outcomes. Off-label use of rhBMP-2 has gained significant acceptance in implant dentistry. However, there is limited evidence regarding the bone maturation process when rhBMP-2 is combined with other biomaterials. More research may be needed regarding the timing and process of bone healing in the presence of rhBMP-2, in an effort to avoid surgical complications.

Morphogenic designer--an efficient tool to digitally design tooth forms.

PubMed

Hajtó, J; Marinescu, C; Silva, N R F A

2014-01-01

Different digital software tools are available today for the purpose of designing anatomically correct anterior and posterior restorations. The current concepts present weaknesses, which can be potentially addressed by more advanced modeling tools, such as the ones already available in professional CAD (Computer Aided Design) graphical software. This study describes the morphogenic designer (MGD) as an efficient and easy method for digitally designing tooth forms for the anterior and posterior dentition. Anterior and posterior tooth forms were selected from a collection of digitalized natural teeth and subjectively assessed as "average". The models in the form of STL files were filtered, cleaned, idealized, and re-meshed to match the specifications of the software used. The shapes were then imported as wavefront ".obj" model into Modo 701, software built for modeling, texturing, visualization, and animation. In order to create a parametric design system, intentional interactive deformations were performed on the average tooth shapes and then further defined as morph targets. By combining various such parameters, several tooth shapes were formed virtually and their images presented. MGD proved to be a versatile and powerful tool for the purpose of esthetic and functional digital crown designs.

Morphogen-based simulation model of ray growth and joint patterning during fin development and regeneration.

PubMed

Rolland-Lagan, Anne-Gaëlle; Paquette, Mathieu; Tweedle, Valerie; Akimenko, Marie-Andrée

2012-03-01

The fact that some organisms are able to regenerate organs of the correct shape and size following amputation is particularly fascinating, but the mechanism by which this occurs remains poorly understood. The zebrafish (Danio rerio) caudal fin has emerged as a model system for the study of bone development and regeneration. The fin comprises 16 to 18 bony rays, each containing multiple joints along its proximodistal axis that give rise to segments. Experimental observations on fin ray growth, regeneration and joint formation have been described, but no unified theory has yet been put forward to explain how growth and joint patterns are controlled. We present a model for the control of fin ray growth during development and regeneration, integrated with a model for joint pattern formation, which is in agreement with published, as well as new, experimental data. We propose that fin ray growth and joint patterning are coordinated through the interaction of three morphogens. When the model is extended to incorporate multiple rays across the fin, it also accounts for how the caudal fin acquires its shape during development, and regains its correct size and shape following amputation.

A new computational growth model for sea urchin skeletons.

PubMed

Zachos, Louis G

2009-08-07

A new computational model has been developed to simulate growth of regular sea urchin skeletons. The model incorporates the processes of plate addition and individual plate growth into a composite model of whole-body (somatic) growth. A simple developmental model based on hypothetical morphogens underlies the assumptions used to define the simulated growth processes. The data model is based on a Delaunay triangulation of plate growth center points, using the dual Voronoi polygons to define plate topologies. A spherical frame of reference is used for growth calculations, with affine deformation of the sphere (based on a Young-Laplace membrane model) to result in an urchin-like three-dimensional form. The model verifies that the patterns of coronal plates in general meet the criteria of Voronoi polygonalization, that a morphogen/threshold inhibition model for plate addition results in the alternating plate addition pattern characteristic of sea urchins, and that application of the Bertalanffy growth model to individual plates results in simulated somatic growth that approximates that seen in living urchins. The model suggests avenues of research that could explain some of the distinctions between modern sea urchins and the much more disparate groups of forms that characterized the Paleozoic Era.

Eddy-driven stratification initiates North Atlantic spring phytoplankton blooms.

PubMed

Mahadevan, Amala; D'Asaro, Eric; Lee, Craig; Perry, Mary Jane

2012-07-06

Springtime phytoplankton blooms photosynthetically fix carbon and export it from the surface ocean at globally important rates. These blooms are triggered by increased light exposure of the phytoplankton due to both seasonal light increase and the development of a near-surface vertical density gradient (stratification) that inhibits vertical mixing of the phytoplankton. Classically and in current climate models, that stratification is ascribed to a springtime warming of the sea surface. Here, using observations from the subpolar North Atlantic and a three-dimensional biophysical model, we show that the initial stratification and resulting bloom are instead caused by eddy-driven slumping of the basin-scale north-south density gradient, resulting in a patchy bloom beginning 20 to 30 days earlier than would occur by warming.

A conjugate gradient method for solving the non-LTE line radiation transfer problem

NASA Astrophysics Data System (ADS)

Paletou, F.; Anterrieu, E.

2009-12-01

This study concerns the fast and accurate solution of the line radiation transfer problem, under non-LTE conditions. We propose and evaluate an alternative iterative scheme to the classical ALI-Jacobi method, and to the more recently proposed Gauss-Seidel and successive over-relaxation (GS/SOR) schemes. Our study is indeed based on applying a preconditioned bi-conjugate gradient method (BiCG-P). Standard tests, in 1D plane parallel geometry and in the frame of the two-level atom model with monochromatic scattering are discussed. Rates of convergence between the previously mentioned iterative schemes are compared, as are their respective timing properties. The smoothing capability of the BiCG-P method is also demonstrated.

Time-resolved lateral spin-caloric transport of optically generated spin packets in n-GaAs

NASA Astrophysics Data System (ADS)

Göbbels, Stefan; Güntherodt, Gernot; Beschoten, Bernd

2018-05-01

We report on lateral spin-caloric transport (LSCT) of electron spin packets which are optically generated by ps laser pulses in the non-magnetic semiconductor n-GaAs at K. LSCT is driven by a local temperature gradient induced by an additional cw heating laser. The spatio-temporal evolution of the spin packets is probed using time-resolved Faraday rotation. We demonstrate that the local temperature-gradient induced spin diffusion is solely driven by a non-equilibrium hot spin distribution, i.e. without involvement of phonon drag effects. Additional electric field-driven spin drift experiments are used to verify directly the validity of the non-classical Einstein relation for moderately doped semiconductors at low temperatures for near band-gap excitation.

Modeling and simulation of protein elution in linear pH and salt gradients on weak, strong and mixed cation exchange resins applying an extended Donnan ion exchange model.

PubMed

Wittkopp, Felix; Peeck, Lars; Hafner, Mathias; Frech, Christian

2018-04-13

Process development and characterization based on mathematic modeling provides several advantages and has been applied more frequently over the last few years. In this work, a Donnan equilibrium ion exchange (DIX) model is applied for modelling and simulation of ion exchange chromatography of a monoclonal antibody in linear chromatography. Four different cation exchange resin prototypes consisting of weak, strong and mixed ligands are characterized using pH and salt gradient elution experiments applying the extended DIX model. The modelling results are compared with the results using a classic stoichiometric displacement model. The Donnan equilibrium model is able to describe all four prototype resins while the stoichiometric displacement model fails for the weak and mixed weak/strong ligands. Finally, in silico chromatogram simulations of pH and pH/salt dual gradients are performed to verify the results and to show the consistency of the developed model. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional diversity of benthic ciliate communities in response to environmental gradients in a wetland of Yangtze Estuary, China.

PubMed

Xu, Yuan; Fan, Xinpeng; Warren, Alan; Zhang, Liquan; Xu, Henglong

2018-02-01

Researches on the functional diversity of benthic ecosystems have mainly focused on macrofauna, and studies on functional structure of ciliate communities have been based only on trophic- or size-groups. Current research was carried out on the changing patterns of classical and functional diversity of benthic ciliates in response to environmental gradients at three sites in a wetland in Yangtze Estuary. The results showed that changes of environmental factors (e.g. salinity, sediment grain size and hydrodynamic conditions) in the Yangtze Estuary induce variability in species composition and functional trait distribution. Furthermore, increased species richness and diversity did not lead to significant changes in functional diversity due to functional redundancy. However, salt water intrusion of Yangtze Estuary during the dry season could cause reduced functional diversity of ciliate communities. Current study provides the first insight into the functional diversity of ciliate communities in response to environmental gradients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Experimental viscous fingering in a tapered radial Hele-Shaw cell

NASA Astrophysics Data System (ADS)

Bongrand, Gregoire; Tsai, Peichun Amy; Complex Fludis Group Team

2017-11-01

The fluid-fluid displacement in porous media is a common process that finds direct applications in various fields, such as enhanced oil recovery and geological CO2 sequestration. In this work, we experimentally investigate the influence of converging cells on viscous fingering instabilities using a radially-tapered cell. For air displacing oil, in contrast to the classical Saffman-Taylor fingering, our results show that a converging gradient in a radial propagation can provide a stabilizing effect and hinder fingering. For a fixed gap gradient and thickness, with increasing injection rates we find a stable displacement under small flow rates, whereas unstable fingering occurs above a certain threshold. We further investigate this critical flow rate delineating the stable and unstable regimes for different gap gradients. These results reveal that the displacement efficiency not only depends on the fluid properties but also on the interfacial velocity and channel structure. The latter factors provide a useful and convenient control to either trigger or inhibit fingering instability. NSERC Discovery, Accelerator, and CRC programs.

Quantification of the effect of temperature gradients in soils on subsurface radon signal

NASA Astrophysics Data System (ADS)

Haquin, Gustavo; Ilzycer, Danielle; Kamai, Tamir; Zafrir, Hovav; Weisbrod, Noam

2017-04-01

Temperature gradients that develop in soils due to atmospheric temperature cycles are factors of primary importance in determining the rates and directions of subsurface gas flow. Models including mechanisms of thermal convection and thermal diffusion partially explain the impact of temperature gradients on subsurface radon transport. However, the overall impact of temperature gradients on subsurface radon transport is still not well understood. A laboratory setup was designed and built to experimentally investigate the influence of temperature gradients on radon transport under well controlled conditions. A 60 cm diameter and 120 cm tall column was thermally insulated except from the atmosphere-soil interface, such that it was constructed to simulate field conditions where temperature gradients in soils are developed following atmospheric temperature cycles. The column was filled with fine grinded phosphate rock which provided the porous media with radon source. Radon in soil-air was continuously monitored using NaI gamma detectors positioned at different heights along the column. Soil temperature, differential pressure, and relative humidity were monitored along the column. Experiments based on steep and gradual stepwise changes in ambient temperature were conducted. Absolute changes on radon levels in the order of 10-30% were measured at temperature gradients of up to ±20oC/m. Results showed a non-linear correlation between the temperature gradient and the subsurface radon concentration. An asymmetric relationship between the radon concentration and the temperature gradients for ΔT>0 and ΔT<0 was also observed. Laboratory simulations of the time- and depth-dependent temperature wave functions with frequencies ranged from a daily cycle to few days were performed. In response to the harmonic temperature behaviour radon oscillations at similar frequencies were detected correspondingly. In this work a quantitative relationship between radon and temperature gradients will be presented for cases beyond the classical conditions for thermal convection and thermal diffusion.

Density-functional theory simulation of large quantum dots

NASA Astrophysics Data System (ADS)

Jiang, Hong; Baranger, Harold U.; Yang, Weitao

2003-10-01

Kohn-Sham spin-density functional theory provides an efficient and accurate model to study electron-electron interaction effects in quantum dots, but its application to large systems is a challenge. Here an efficient method for the simulation of quantum dots using density-function theory is developed; it includes the particle-in-the-box representation of the Kohn-Sham orbitals, an efficient conjugate-gradient method to directly minimize the total energy, a Fourier convolution approach for the calculation of the Hartree potential, and a simplified multigrid technique to accelerate the convergence. We test the methodology in a two-dimensional model system and show that numerical studies of large quantum dots with several hundred electrons become computationally affordable. In the noninteracting limit, the classical dynamics of the system we study can be continuously varied from integrable to fully chaotic. The qualitative difference in the noninteracting classical dynamics has an effect on the quantum properties of the interacting system: integrable classical dynamics leads to higher-spin states and a broader distribution of spacing between Coulomb blockade peaks.

Classical Heat-Flux Measurements in Coronal Plasmas from Collective Thomson-Scattering Spectra

NASA Astrophysics Data System (ADS)

Henchen, R. J.; Hu, S. X.; Katz, J.; Froula, D. H.; Rozmus, W.

2016-10-01

Collective Thomson scattering was used to measure heat flux in coronal plasmas. The relative amplitude of the Thomson-scattered power into the up- and downshifted electron plasma wave features was used to determine the flux of electrons moving along the temperature gradient at three to four times the electron thermal velocity. Simultaneously, the ion-acoustic wave features were measured. Their relative amplitude was used to measure the flux of the return-current electrons. The frequencies of these ion-acoustic and electron plasma wave features provide local measurements of the electron temperature and density. These spectra were obtained at five locations along the temperature gradient in a laser-produced blowoff plasma. These measurements of plasma parameters are used to infer the Spitzer-Härm flux (qSH = - κ∇Te ) and are in good agreement with the values of the heat flux measured from the scattering-feature asymmetries. Additional experiments probed plasma waves perpendicular to the temperature gradient. The data show small effects resulting from heat flux compared to probing waves along the temperature gradient. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

Adaptive two-regime method: Application to front propagation

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

Robinson, Martin, E-mail: martin.robinson@maths.ox.ac.uk; Erban, Radek, E-mail: erban@maths.ox.ac.uk; Flegg, Mark, E-mail: mark.flegg@monash.edu

2014-03-28

The Adaptive Two-Regime Method (ATRM) is developed for hybrid (multiscale) stochastic simulation of reaction-diffusion problems. It efficiently couples detailed Brownian dynamics simulations with coarser lattice-based models. The ATRM is a generalization of the previously developed Two-Regime Method [Flegg et al., J. R. Soc., Interface 9, 859 (2012)] to multiscale problems which require a dynamic selection of regions where detailed Brownian dynamics simulation is used. Typical applications include a front propagation or spatio-temporal oscillations. In this paper, the ATRM is used for an in-depth study of front propagation in a stochastic reaction-diffusion system which has its mean-field model given in termsmore » of the Fisher equation [R. Fisher, Ann. Eugen. 7, 355 (1937)]. It exhibits a travelling reaction front which is sensitive to stochastic fluctuations at the leading edge of the wavefront. Previous studies into stochastic effects on the Fisher wave propagation speed have focused on lattice-based models, but there has been limited progress using off-lattice (Brownian dynamics) models, which suffer due to their high computational cost, particularly at the high molecular numbers that are necessary to approach the Fisher mean-field model. By modelling only the wavefront itself with the off-lattice model, it is shown that the ATRM leads to the same Fisher wave results as purely off-lattice models, but at a fraction of the computational cost. The error analysis of the ATRM is also presented for a morphogen gradient model.« less

Microsphere-Based Scaffolds Encapsulating Tricalcium Phosphate And Hydroxyapatite For Bone Regeneration

PubMed Central

Gupta, Vineet; Lyne, Dina V.; Barragan, Marilyn; Berkland, Cory J.; Detamore, Michael S.

2016-01-01

Bioceramic mixtures of tricalcium phosphate (TCP) and hydroxyapatite (HAp) are widely used for bone regeneration because of their excellent cytocompatibility, osteoconduction, and osteoinduction. Therefore, we hypothesized that incorporation of a mixture of TCP and HAp in microsphere-based scaffolds would enhance osteogenesis of rat bone marrow stromal cells (rBMSCs) compared to a positive control of scaffolds with encapsulated bone-morphogenic protein-2 (BMP-2). Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds encapsulating TCP and HAp mixtures in two different ratios (7:3 and 1:1) were fabricated with the same net ceramic content (30 wt%) to evaluate how incorporation of these ceramic mixtures would affect the osteogenesis in rBMSCs. Encapsulation of TCP/HAp mixtures impacted microsphere morphologies and the compressive moduli of the scaffolds. Additionally, TCP/HAp mixtures enhanced the end-point secretion of extracellular matrix (ECM) components relevant to bone tissue compared to the “blank” (PLGA-only) microsphere-based scaffolds as evidenced by the biochemical, gene expression, histology, and immunohistochemical characterization. Moreover, the TCP/HAp mixture groups even surpassed the BMP-2 positive control group in some instances in terms of matrix synthesis and gene expression. Lastly, gene expression data suggested that the rBMSCs responded differently to different TCP/HAp ratios presented to them. Altogether, it can be concluded that TCP/HAp mixtures stimulated the differentiation of rBMSCs toward an osteoblastic phenotype, and therefore may be beneficial in gradient microsphere-based scaffolds for osteochondral regeneration. PMID:27272903

The ECM moves during primitive streak formation--computation of ECM versus cellular motion.

PubMed

Zamir, Evan A; Rongish, Brenda J; Little, Charles D

2008-10-14

Galileo described the concept of motion relativity--motion with respect to a reference frame--in 1632. He noted that a person below deck would be unable to discern whether the boat was moving. Embryologists, while recognizing that embryonic tissues undergo large-scale deformations, have failed to account for relative motion when analyzing cell motility data. A century of scientific articles has advanced the concept that embryonic cells move ("migrate") in an autonomous fashion such that, as time progresses, the cells and their progeny assemble an embryo. In sharp contrast, the motion of the surrounding extracellular matrix scaffold has been largely ignored/overlooked. We developed computational/optical methods that measure the extent embryonic cells move relative to the extracellular matrix. Our time-lapse data show that epiblastic cells largely move in concert with a sub-epiblastic extracellular matrix during stages 2 and 3 in primitive streak quail embryos. In other words, there is little cellular motion relative to the extracellular matrix scaffold--both components move together as a tissue. The extracellular matrix displacements exhibit bilateral vortical motion, convergence to the midline, and extension along the presumptive vertebral axis--all patterns previously attributed solely to cellular "migration." Our time-resolved data pose new challenges for understanding how extracellular chemical (morphogen) gradients, widely hypothesized to guide cellular trajectories at early gastrulation stages, are maintained in this dynamic extracellular environment. We conclude that models describing primitive streak cellular guidance mechanisms must be able to account for sub-epiblastic extracellular matrix displacements.

The Green’s functions for peridynamic non-local diffusion

PubMed Central

Wang, L. J.; Xu, J. F.

2016-01-01

In this work, we develop the Green’s function method for the solution of the peridynamic non-local diffusion model in which the spatial gradient of the generalized potential in the classical theory is replaced by an integral of a generalized response function in a horizon. We first show that the general solutions of the peridynamic non-local diffusion model can be expressed as functionals of the corresponding Green’s functions for point sources, along with volume constraints for non-local diffusion. Then, we obtain the Green’s functions by the Fourier transform method for unsteady and steady diffusions in infinite domains. We also demonstrate that the peridynamic non-local solutions converge to the classical differential solutions when the non-local length approaches zero. Finally, the peridynamic analytical solutions are applied to an infinite plate heated by a Gauss source, and the predicted variations of temperature are compared with the classical local solutions. The peridynamic non-local diffusion model predicts a lower rate of variation of the field quantities than that of the classical theory, which is consistent with experimental observations. The developed method is applicable to general diffusion-type problems. PMID:27713658

Analysis of Morphogenic Effect of hDAB2IP on Prostate Cancer and its Disease Correlation

DTIC Science & Technology

2007-02-01

variety of or- gans and cell lines. By determining the promoter sequence from the 5’- flanking region of the mDab2ip gene in mouse prosta - tic epithelial...patient with de novo acute myeloid leukemia. Genes Chromo- somes Cancer 39, 324 –334. WANG, Z., TSENG, C.P., PONG, R.C., CHEN, H., MCCONNELL, J.D

The biochemistry of hematopoietic stem cell development.

PubMed

Kaimakis, P; Crisan, M; Dzierzak, E

2013-02-01

The cornerstone of the adult hematopoietic system and clinical treatments for blood-related disease is the cohort of hematopoietic stem cells (HSC) that is harbored in the adult bone marrow microenvironment. Interestingly, this cohort of HSCs is generated only during a short window of developmental time. In mammalian embryos, hematopoietic progenitor and HSC generation occurs within several extra- and intraembryonic microenvironments, most notably from 'hemogenic' endothelial cells lining the major vasculature. HSCs are made through a remarkable transdifferentiation of endothelial cells to a hematopoietic fate that is long-lived and self-renewable. Recent studies are beginning to provide an understanding of the biochemical signaling pathways and transcription factors/complexes that promote their generation. The focus of this review is on the biochemistry behind the generation of these potent long-lived self-renewing stem cells of the blood system. Both the intrinsic (master transcription factors) and extrinsic regulators (morphogens and growth factors) that affect the generation, maintenance and expansion of HSCs in the embryo will be discussed. The generation of HSCs is a stepwise process involving many developmental signaling pathways, morphogens and cytokines. Pivotal hematopoietic transcription factors are required for their generation. Interestingly, whereas these factors are necessary for HSC generation, their expression in adult bone marrow HSCs is oftentimes not required. Thus, the biochemistry and molecular regulation of HSC development in the embryo are overlapping, but differ significantly from the regulation of HSCs in the adult. HSC numbers for clinical use are limiting, and despite much research into the molecular basis of HSC regulation in the adult bone marrow, no panel of growth factors, interleukins and/or morphogens has been found to sufficiently increase the number of these important stem cells. An understanding of the biochemistry of HSC generation in the developing embryo provides important new knowledge on how these complex stem cells are made, sustained and expanded in the embryo to give rise to the complete adult hematopoietic system, thus stimulating novel strategies for producing increased numbers of clinically useful HSCs. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

S6K is a morphogenic protein with a mechanism involving Filamin-A phosphorylation and phosphatidic acid binding.

PubMed

Henkels, Karen M; Mallets, Elizabeth R; Dennis, Patrick B; Gomez-Cambronero, Julian

2015-04-01

Change of cell shape in vivo plays many roles that are central to life itself, such as embryonic development, inflammation, wound healing, and pathologic processes such as cancer metastasis. Nonetheless, the spatiotemporal mechanisms that control the concerted regulation of cell shape remain understudied. Here, we show that ribosomal S6K, which is normally considered a protein involved in protein translation, is a morphogenic protein. Its presence in cells alters the overall organization of the cell surface and cell circularity [(4π × area)/(perimeter)(2)] from 0.47 ± 0.06 units in mock-treated cells to 0.09 ± 0.03 units in S6K-overexpressing macrophages causing stellation and arborization of cell shape. This effect was partially reversed in cells expressing a kinase-inactive S6K mutant and was fully reversed in cells silenced with small interference RNA. Equally important is that S6K is itself regulated by phospholipids, specifically phosphatidic acid, whereby 300 nM 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), but not the control 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), binds directly to S6K and causes an ∼ 2.9-fold increase in S6K catalytic activity. This was followed by an increase in Filamin A (FLNA) functionality as measured by phospho-FLNA (S(2152)) expression and by a subsequent elevation of actin nucleation. This reliance of S6K on phosphatidic acid (PA), a curvature-inducing phospholipid, explained the extra-large perimeter of cells that overexpressed S6K. Furthermore, the diversity of the response to S6K in several unrelated cell types (fibroblasts, leukocytes, and invasive cancer cells) that we report here indicates the existence of an underlying common mechanism in mammalian cells. This new signaling set, PA-S6K-FLNA-actin, sheds light for the first time into the morphogenic pathway of cytoskeletal structures that are crucial for adhesion and cell locomotion during inflammation and metastasis. © FASEB.

Spontaneous In Vivo Chondrogenesis of Bone Marrow-Derived Mesenchymal Progenitor Cells by Blocking Vascular Endothelial Growth Factor Signaling.

PubMed

Marsano, Anna; Medeiros da Cunha, Carolina M; Ghanaati, Shahram; Gueven, Sinan; Centola, Matteo; Tsaryk, Roman; Barbeck, Mike; Stuedle, Chiara; Barbero, Andrea; Helmrich, Uta; Schaeren, Stefan; Kirkpatrick, James C; Banfi, Andrea; Martin, Ivan

2016-12-01

: Chondrogenic differentiation of bone marrow-derived mesenchymal stromal/stem cells (MSCs) can be induced by presenting morphogenetic factors or soluble signals but typically suffers from limited efficiency, reproducibility across primary batches, and maintenance of phenotypic stability. Considering the avascular and hypoxic milieu of articular cartilage, we hypothesized that sole inhibition of angiogenesis can provide physiological cues to direct in vivo differentiation of uncommitted MSCs to stable cartilage formation. Human MSCs were retrovirally transduced to express a decoy soluble vascular endothelial growth factor (VEGF) receptor-2 (sFlk1), which efficiently sequesters endogenous VEGF in vivo, seeded on collagen sponges and immediately implanted ectopically in nude mice. Although naïve cells formed vascularized fibrous tissue, sFlk1-MSCs abolished vascular ingrowth into engineered constructs, which efficiently and reproducibly developed into hyaline cartilage. The generated cartilage was phenotypically stable and showed no sign of hypertrophic evolution up to 12 weeks. In vitro analyses indicated that spontaneous chondrogenic differentiation by blockade of angiogenesis was related to the generation of a hypoxic environment, in turn activating the transforming growth factor-β pathway. These findings suggest that VEGF blockade is a robust strategy to enhance cartilage repair by endogenous or grafted mesenchymal progenitors. This article outlines the general paradigm of controlling the fate of implanted stem/progenitor cells by engineering their ability to establish specific microenvironmental conditions rather than directly providing individual morphogenic cues. Chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs) is typically targeted by morphogen delivery, which is often associated with limited efficiency, stability, and robustness. This article proposes a strategy to engineer MSCs with the capacity to establish specific microenvironmental conditions, supporting their own targeted differentiation program. Sole blockade of angiogenesis mediated by transduction for sFlk-1, without delivery of additional morphogens, is sufficient for inducing MSC chondrogenic differentiation. The findings represent a relevant step forward in the field because the method allowed reducing interdonor variability in MSC differentiation efficiency and, importantly, onset of a stable, nonhypertrophic chondrocyte phenotype. ©AlphaMed Press.

A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas

PubMed Central

Deel, Michael D.; Li, Jenny J.; Crose, Lisa E. S.; Linardic, Corinne M.

2015-01-01

The Hippo signaling pathway is an evolutionarily conserved developmental network vital for the regulation of organ size, tissue homeostasis, repair and regeneration, and cell fate. The Hippo pathway has also been shown to have tumor suppressor properties. Hippo transduction involves a series of kinases and scaffolding proteins that are intricately connected to proteins in developmental cascades and in the tissue microenvironment. This network governs the downstream Hippo transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs, as well as other transcription factors responsible for cellular proliferation, self-renewal, differentiation, and survival. Surprisingly, there are few oncogenic mutations within the core components of the Hippo pathway. Instead, dysregulated Hippo signaling is a versatile accomplice to commonly mutated cancer pathways. For example, YAP and TAZ can be activated by oncogenic signaling from other pathways, or serve as co-activators for classical oncogenes. Emerging evidence suggests that Hippo signaling couples cell density and cytoskeletal structural changes to morphogenic signals and conveys a mesenchymal phenotype. While much of Hippo biology has been described in epithelial cell systems, it is clear that dysregulated Hippo signaling also contributes to malignancies of mesenchymal origin. This review will summarize the known molecular alterations within the Hippo pathway in sarcomas and highlight how several pharmacologic compounds have shown activity in modulating Hippo components, providing proof-of-principle that Hippo signaling may be harnessed for therapeutic application in sarcomas. PMID:26389076

A Review: Molecular Aberrations within Hippo Signaling in Bone and Soft-Tissue Sarcomas.

PubMed

Deel, Michael D; Li, Jenny J; Crose, Lisa E S; Linardic, Corinne M

2015-01-01

The Hippo signaling pathway is an evolutionarily conserved developmental network vital for the regulation of organ size, tissue homeostasis, repair and regeneration, and cell fate. The Hippo pathway has also been shown to have tumor suppressor properties. Hippo transduction involves a series of kinases and scaffolding proteins that are intricately connected to proteins in developmental cascades and in the tissue microenvironment. This network governs the downstream Hippo transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs, as well as other transcription factors responsible for cellular proliferation, self-renewal, differentiation, and survival. Surprisingly, there are few oncogenic mutations within the core components of the Hippo pathway. Instead, dysregulated Hippo signaling is a versatile accomplice to commonly mutated cancer pathways. For example, YAP and TAZ can be activated by oncogenic signaling from other pathways, or serve as co-activators for classical oncogenes. Emerging evidence suggests that Hippo signaling couples cell density and cytoskeletal structural changes to morphogenic signals and conveys a mesenchymal phenotype. While much of Hippo biology has been described in epithelial cell systems, it is clear that dysregulated Hippo signaling also contributes to malignancies of mesenchymal origin. This review will summarize the known molecular alterations within the Hippo pathway in sarcomas and highlight how several pharmacologic compounds have shown activity in modulating Hippo components, providing proof-of-principle that Hippo signaling may be harnessed for therapeutic application in sarcomas.

Cadherins in cerebellar development: translation of embryonic patterning into mature functional compartmentalization.

PubMed

Redies, Christoph; Neudert, Franziska; Lin, Juntang

2011-09-01

Cadherins are cell adhesion molecules with multiple morphogenic functions in brain development, for example, in neuroblast migration and aggregation, axon navigation, neural circuit formation, and synaptogenesis. More than 100 members of the cadherin superfamily are expressed in the developing and mature brain. Most of the cadherins investigated, in particular classic cadherins and δ-protocadherins, are expressed in the cerebellum. For several cadherin subtypes, expression begins at early embryonic stages and persists until mature stages of cerebellar development. At intermediate stages, distinct Purkinje cell clusters exhibit unique rostrocaudal and mediolateral expression profiles for each cadherin. In the chicken, mouse, and other species, the Purkinje cell clusters are separated by intervening raphes of migrating granule cells. This pattern of Purkinje cell clusters/raphes is, at least in part, continuous with the parasagittal striping pattern that is apparent in the mature cerebellar cortex, for example, for zebrin II/aldolase C. Moreover, subregions of the deep cerebellar nuclei, vestibular nuclei and the olivary complex also express cadherins differentially. Neuroanatomical evidence suggests that the nuclear subregions and cortical domains that express the same cadherin subtype are connected to each other, to form neural subcircuits of the cerebellar system. Cadherins thus provide a molecular code that specifies not only embryonic structures but also functional cerebellar compartmentalization. By following the implementation of this code, it can be revealed how mature functional architecture emerges from embryonic patterning during cerebellar development. Dysfunction of some cadherins is associated with psychiatric diseases and developmental impairments and may also affect cerebellar function.

Anatomy of the Spinal Meninges.

PubMed

Sakka, Laurent; Gabrillargues, Jean; Coll, Guillaume

2016-06-01

The spinal meninges have received less attention than the cranial meninges in the literature, although several points remain debatable and poorly understood, like their phylogenesis, their development, and their interactions with the spinal cord. Their constancy among the chordates shows their crucial importance in central nervous system homeostasis and suggests a role far beyond mechanical protection of the neuraxis. This work provides an extensive study of the spinal meninges, from an overview of their phylogenesis and embryology to a descriptive and topographic anatomy with clinical implications. It examines their involvement in spinal cord development, functioning, and repair. This work is a review of the literature using PubMed as a search engine on Medline. The stages followed by the meninges along the phylogenesis could not be easily compared with their development in vertebrates for methodological aspects and convergence processes throughout evolution. The distinction between arachnoid and pia mater appeared controversial. Several points of descriptive anatomy remain debatable: the functional organization of the arterial network, and the venous and lymphatic drainages, considered differently by classical anatomic and neuroradiological approaches. Spinal meninges are involved in neurodevelopment and neurorepair producing neural stem cells and morphogens, in cerebrospinal fluid dynamics and neuraxis functioning by the synthesis of active molecules, and the elimination of waste products of central nervous system metabolism. The spinal meninges should be considered as dynamic functional formations evolving over a lifetime, with ultrastructural features and functional interactions with the neuraxis remaining not fully understood.

DNA translocation across protein channels: How does a polymer worm through a hole?

NASA Astrophysics Data System (ADS)

Muthukumar, M.

2001-03-01

Free energy barriers control the translocation of polymers through narrow channels. Based on an analogy with the classical nucleation and growth process, we have calculated the translocation time and its dependencies on the length, stiffness, and sequence of the polymer, solution conditions, and the strength of the driving electrochemical potential gradient. Our predictions will be compared with experimental results and prospects of reading polymer sequences.

Fast ion beta limit measurements by collimated neutron detection in MST plasmas

NASA Astrophysics Data System (ADS)

Capecchi, William; Anderson, Jay; Bonofiglo, Phillip; Kim, Jungha; Sears, Stephanie

2015-11-01

Fast ion orbits in the reversed field pinch (RFP) are well ordered and classically confined despite magnetic field stochasticity generated by multiple tearing modes. Classical TRANSP modeling of a 1MW tangentially injected hydrogen neutral beam in MST deuterium plasmas predicts a core-localized fast ion density that can be up to 25% of the electron density and a fast ion beta of many times the local thermal beta. However, neutral particle analysis of an NBI-driven mode (presumably driven by a fast ion pressure gradient) shows mode-induced transport of core-localized fast ions and a saturated fast ion density. The TRANSP modeling is presumed valid until the onset of the beam-driven mode and gives an initial estimate of the volume-averaged fast ion beta of 1-2% (local core value up to 10%). A collimated neutron detector for fusion product profile measurements will be used to determine the spatial distribution of fast ions, allowing for a first measurement of the critical fast-ion pressure gradient required for mode destabilization. Testing/calibration data and initial fast-ion profiles will be presented. Characterization of both the local and global fast ion beta will be done for deuterium beam injection into deuterium plasmas for comparison to TRANSP predictions. Work supported by US DOE.

Characterization of anomalous relaxation using the time-fractional Bloch equation and multiple echo T2 *-weighted magnetic resonance imaging at 7 T.

PubMed

Qin, Shanlin; Liu, Fawang; Turner, Ian W; Yu, Qiang; Yang, Qianqian; Vegh, Viktor

2017-04-01

To study the utility of fractional calculus in modeling gradient-recalled echo MRI signal decay in the normal human brain. We solved analytically the extended time-fractional Bloch equations resulting in five model parameters, namely, the amplitude, relaxation rate, order of the time-fractional derivative, frequency shift, and constant offset. Voxel-level temporal fitting of the MRI signal was performed using the classical monoexponential model, a previously developed anomalous relaxation model, and using our extended time-fractional relaxation model. Nine brain regions segmented from multiple echo gradient-recalled echo 7 Tesla MRI data acquired from five participants were then used to investigate the characteristics of the extended time-fractional model parameters. We found that the extended time-fractional model is able to fit the experimental data with smaller mean squared error than the classical monoexponential relaxation model and the anomalous relaxation model, which do not account for frequency shift. We were able to fit multiple echo time MRI data with high accuracy using the developed model. Parameters of the model likely capture information on microstructural and susceptibility-induced changes in the human brain. Magn Reson Med 77:1485-1494, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Seminal plasma removal by density-gradient centrifugation is superior for goat sperm preservation compared with classical sperm washing.

PubMed

Santiago-Moreno, J; Esteso, M C; Castaño, C; Toledano-Díaz, A; Delgadillo, J A; López-Sebastián, A

2017-06-01

Seminal plasma removal is routine in goat sperm cryopreservation protocols. The classical washing procedure designed to accomplish this usually leaves the pellet resulting from use of this procedure contaminated with dead sperm, debris, and cells other than sperm. This contamination negatively affects viability of sperm after cryopreservation. The present research was conducted to compare the effect on chilled and frozen-thawed goat sperm of the classical washing method to that of a selective washing method involving density gradient centrifugation (DGC). In the first experiment, sperm variables were measured in freshly collected sperm, and again after its washing with both methods and chilling at 5°C for 0, 3, 24, 48, 72 or 96h. The DGC-washed sperm had greater (P<0.01) straight line velocity (VSL), average path velocity (VAP) and progression ratio values at all chilling times. The amplitude of lateral head displacement (ALH) was, however, less (P<0.001) in the DGC-washed sperm at all chilling times. There was a negative correlation (P<0.05) between ALH and VSL. In the second experiment involving the freezing-thawing of sperm washed by using either method, aliquots were post-wash diluted with a Tris-citric acid/glucose/egg yolk/glycerol-based medium and frozen in liquid nitrogen for 5days. After thawing, neither the VCL, VSL nor VAP of the DGC-washed samples were affected, whereas the traditionally washed samples had less motility. In conclusion, the use of DGC was associated with enhanced sperm motility variables after chilling and freezing-thawing. This procedure would, therefore, be a useful means of removing seminal plasma from goat semen and obtaining greater quality sperm for insemination purposes. Copyright © 2017. Published by Elsevier B.V.

A Diffusion Approximation Based on Renewal Processes with Applications to Strongly Biased Run-Tumble Motion.

PubMed

Thygesen, Uffe Høgsbro

2016-03-01

We consider organisms which use a renewal strategy such as run-tumble when moving in space, for example to perform chemotaxis in chemical gradients. We derive a diffusion approximation for the motion, applying a central limit theorem due to Anscombe for renewal-reward processes; this theorem has not previously been applied in this context. Our results extend previous work, which has established the mean drift but not the diffusivity. For a classical model of tumble rates applied to chemotaxis, we find that the resulting chemotactic drift saturates to the swimming velocity of the organism when the chemical gradients grow increasingly steep. The dispersal becomes anisotropic in steep gradients, with larger dispersal across the gradient than along the gradient. In contrast to one-dimensional settings, strong bias increases dispersal. We next include Brownian rotation in the model and find that, in limit of high chemotactic sensitivity, the chemotactic drift is 64% of the swimming velocity, independent of the magnitude of the Brownian rotation. We finally derive characteristic timescales of the motion that can be used to assess whether the diffusion limit is justified in a given situation. The proposed technique for obtaining diffusion approximations is conceptually and computationally simple, and applicable also when statistics of the motion is obtained empirically or through Monte Carlo simulation of the motion.

Nuclear magnetic resonance diffusion pore imaging: Experimental phase detection by double diffusion encoding

NASA Astrophysics Data System (ADS)

Demberg, Kerstin; Laun, Frederik Bernd; Windschuh, Johannes; Umathum, Reiner; Bachert, Peter; Kuder, Tristan Anselm

2017-02-01

Diffusion pore imaging is an extension of diffusion-weighted nuclear magnetic resonance imaging enabling the direct measurement of the shape of arbitrarily formed, closed pores by probing diffusion restrictions using the motion of spin-bearing particles. Examples of such pores comprise cells in biological tissue or oil containing cavities in porous rocks. All pores contained in the measurement volume contribute to one reconstructed image, which reduces the problem of vanishing signal at increasing resolution present in conventional magnetic resonance imaging. It has been previously experimentally demonstrated that pore imaging using a combination of a long and a narrow magnetic field gradient pulse is feasible. In this work, an experimental verification is presented showing that pores can be imaged using short gradient pulses only. Experiments were carried out using hyperpolarized xenon gas in well-defined pores. The phase required for pore image reconstruction was retrieved from double diffusion encoded (DDE) measurements, while the magnitude could either be obtained from DDE signals or classical diffusion measurements with single encoding. The occurring image artifacts caused by restrictions of the gradient system, insufficient diffusion time, and by the phase reconstruction approach were investigated. Employing short gradient pulses only is advantageous compared to the initial long-narrow approach due to a more flexible sequence design when omitting the long gradient and due to faster convergence to the diffusion long-time limit, which may enable application to larger pores.

Local richness along gradients in the Siskiyou herb flora: R.H. Whittaker revisited

USGS Publications Warehouse

Grace, James B.; Harrison, Susan; Damschen, Ellen Ingman

2011-01-01

In his classic study in the Siskiyou Mountains (Oregon, USA), one of the most botanically rich forested regions in North America, R. H. Whittaker (1960) foreshadowed many modern ideas on the multivariate control of local species richness along environmental gradients related to productivity. Using a structural equation model to analyze his data, which were never previously statistically analyzed, we demonstrate that Whittaker was remarkably accurate in concluding that local herb richness in these late-seral forests is explained to a large extent by three major abiotic gradients (soils, topography, and elevation), and in turn, by the effects of these gradients on tree densities and the numbers of individual herbs. However, while Whittaker also clearly appreciated the significance of large-scale evolutionary and biogeographic influences on community composition, he did not fully articulate the more recent concept that variation in the species richness of local communities could be explained in part by variation in the sizes of regional species pools. Our model of his data is among the first to use estimates of regional species pool size to explain variation in local community richness along productivity-related gradients. We find that regional pool size, combined with a modest number of other interacting abiotic and biotic factors, explains most of the variation in local herb richness in the Siskiyou biodiversity hotspot.

Extremal edges: a powerful cue to depth perception and figure-ground organization.

PubMed

Palmer, Stephen E; Ghose, Tandra

2008-01-01

Extremal edges (EEs) are projections of viewpoint-specific horizons of self-occlusion on smooth convex surfaces. An ecological analysis of viewpoint constraints suggests that an EE surface is likely to be closer to the observer than the non-EE surface on the other side of the edge. In two experiments, one using shading gradients and the other using texture gradients, we demonstrated that EEs operate as strong cues to relative depth perception and figure-ground organization. Image regions with an EE along the shared border were overwhelmingly perceived as closer than either flat or equally convex surfaces without an EE along that border. A further demonstration suggests that EEs are more powerful than classical figure-ground cues, including even the joint effects of small size, convexity, and surroundedness.

Artificial Bee Colony Optimization of Capping Potentials for Hybrid Quantum Mechanical/Molecular Mechanical Calculations.

PubMed

Schiffmann, Christoph; Sebastiani, Daniel

2011-05-10

We present an algorithmic extension of a numerical optimization scheme for analytic capping potentials for use in mixed quantum-classical (quantum mechanical/molecular mechanical, QM/MM) ab initio calculations. Our goal is to minimize bond-cleavage-induced perturbations in the electronic structure, measured by means of a suitable penalty functional. The optimization algorithm-a variant of the artificial bee colony (ABC) algorithm, which relies on swarm intelligence-couples deterministic (downhill gradient) and stochastic elements to avoid local minimum trapping. The ABC algorithm outperforms the conventional downhill gradient approach, if the penalty hypersurface exhibits wiggles that prevent a straight minimization pathway. We characterize the optimized capping potentials by computing NMR chemical shifts. This approach will increase the accuracy of QM/MM calculations of complex biomolecules.

A New Expanded Mixed Element Method for Convection-Dominated Sobolev Equation

PubMed Central

Wang, Jinfeng; Li, Hong; Fang, Zhichao

2014-01-01

We propose and analyze a new expanded mixed element method, whose gradient belongs to the simple square integrable space instead of the classical H(div; Ω) space of Chen's expanded mixed element method. We study the new expanded mixed element method for convection-dominated Sobolev equation, prove the existence and uniqueness for finite element solution, and introduce a new expanded mixed projection. We derive the optimal a priori error estimates in L 2-norm for the scalar unknown u and a priori error estimates in (L 2)2-norm for its gradient λ and its flux σ. Moreover, we obtain the optimal a priori error estimates in H 1-norm for the scalar unknown u. Finally, we obtained some numerical results to illustrate efficiency of the new method. PMID:24701153

Multi-Dimensional Quantum Effect Simulation Using a Density-Gradient Model and Script-Level Programming Techniques

NASA Technical Reports Server (NTRS)

Rafferty, Connor S.; Biegel, Bryan A.; Yu, Zhi-Ping; Ancona, Mario G.; Bude, J.; Dutton, Robert W.; Saini, Subhash (Technical Monitor)

1998-01-01

A density-gradient (DG) model is used to calculate quantum-mechanical corrections to classical carrier transport in MOS (Metal Oxide Semiconductor) inversion/accumulation layers. The model is compared to measured data and to a fully self-consistent coupled Schrodinger and Poisson equation (SCSP) solver. Good agreement is demonstrated for MOS capacitors with gate oxide as thin as 21 A. It is then applied to study carrier distribution in ultra short MOSFETs (Metal Oxide Semiconductor Field Effect Transistor) with surface roughness. This work represents the first implementation of the DG formulation on multidimensional unstructured meshes. It was enabled by a powerful scripting approach which provides an easy-to-use and flexible framework for solving the fourth-order PDEs (Partial Differential Equation) of the DG model.

Electrokinetic Control of Viscous Fingering

NASA Astrophysics Data System (ADS)

Mirzadeh, Mohammad; Bazant, Martin Z.

2017-10-01

We present a theory of the interfacial stability of two immiscible electrolytes under the coupled action of pressure gradients and electric fields in a Hele-Shaw cell or porous medium. Mathematically, our theory describes a phenomenon of "vector Laplacian growth," in which the interface moves in response to the gradient of a vector-valued potential function through a generalized mobility tensor. Physically, we extend the classical Saffman-Taylor problem to electrolytes by incorporating electrokinetic (EK) phenomena. A surprising prediction is that viscous fingering can be controlled by varying the injection ratio of electric current to flow rate. Beyond a critical injection ratio, stability depends only upon the relative direction of flow and current, regardless of the viscosity ratio. Possible applications include porous materials processing, electrically enhanced oil recovery, and EK remediation of contaminated soils.

Application of classical models of chirality to optical rectification

NASA Astrophysics Data System (ADS)

Wang, Xiao-Ou; Gong, Li-Jing; Li, Chun-Fei

2008-08-01

Classical models of chirality are used to investigate the optical rectification effect in chiral molecular media. Calculation of the zero frequency first hyperpolarizabilities of chiral molecules with different structures is performed and applied to the derivation of a dc electric-dipole polarization. The expression of second-order nonlinear static-electric-dipole susceptibilities is obtained by theoretical derivation in the isotropic chiral thin films. The microscopic mechanism producing optical rectification is analyzed in view of this calculation. We find that optical rectification is derived from interaction between the electric field gradient (spatial dispersion) and chiral molecules in optically active liquids and solution by our calculation, which is consistent with the result given by Woźniak and Wagnière [Opt. Commun. 114, 131 (1995)]: The optical rectification depends on the fourth-order electric-dipole susceptibilities.

Using a Classical Gluon Cascade to study the Equilibration of a Gluon-Plasma

NASA Astrophysics Data System (ADS)

McConnell, Lucas

2015-10-01

Using a classical gluon cascade, we study the thermalisation of a gluon-plasma in a homogeneous box by considering the time evolution of the entropy, and in particular how the thermalisation time depends on the strong coupling αs. We then partition the volume into cells with a linearly increasing temperature gradient in one direction, and homogeneous/isotropic in the the other two directions. We allow the gluons to stream in one direction in order to study how they then evolve spatially. We examine cases with and without collisions. We study the entropy as well as the flow-velocity in the z-direction and find that the system initially has a flow which dissipates over time as the gluons become distributed homogeneously throughout the box.

Development of iterative techniques for the solution of unsteady compressible viscous flows

NASA Technical Reports Server (NTRS)

Sankar, Lakshmi N.; Hixon, Duane

1992-01-01

The development of efficient iterative solution methods for the numerical solution of two- and three-dimensional compressible Navier-Stokes equations is discussed. Iterative time marching methods have several advantages over classical multi-step explicit time marching schemes, and non-iterative implicit time marching schemes. Iterative schemes have better stability characteristics than non-iterative explicit and implicit schemes. In this work, another approach based on the classical conjugate gradient method, known as the Generalized Minimum Residual (GMRES) algorithm is investigated. The GMRES algorithm has been used in the past by a number of researchers for solving steady viscous and inviscid flow problems. Here, we investigate the suitability of this algorithm for solving the system of non-linear equations that arise in unsteady Navier-Stokes solvers at each time step.

Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

PubMed

Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

2013-11-01

Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

Inhibition of BMP signaling overcomes acquired resistance to cetuximab in oral squamous cell carcinomas.

PubMed

Yin, Jinlong; Jung, Ji-Eun; Choi, Sun Il; Kim, Sung Soo; Oh, Young Taek; Kim, Tae-Hoon; Choi, Eunji; Lee, Sun Joo; Kim, Hana; Kim, Eun Ok; Lee, Yu Sun; Chang, Hee Jin; Park, Joo Yong; Kim, Yeejeong; Yun, Tak; Heo, Kyun; Kim, Youn-Jae; Kim, Hyunggee; Kim, Yun-Hee; Park, Jong Bae; Choi, Sung Weon

2018-02-01

Despite expressing high levels of the epidermal growth factor receptor (EGFR), a majority of oral squamous cell carcinoma (OSCC) patients show limited response to cetuximab and ultimately develop drug resistance. However, mechanism underlying cetuximab resistance in OSCC is not clearly understood. Here, using a mouse orthotopic xenograft model of OSCC, we show that bone morphogenic protein-7-phosphorylated Smad-1, -5, -8 (BMP7-p-Smad1/5/8) signaling contributes to cetuximab resistance. Tumor cells isolated from the recurrent cetuximab-resistant xenograft models exhibited low EGFR expression but extremely high levels of p-Smad1/5/8. Treatment with the bone morphogenic protein receptor type 1 (BMPRI) inhibitor, DMH1 significantly reduced cetuximab-resistant OSCC tumor growth, and combined treatment of DMH1 and cetuximab remarkably reduced relapsed tumor growth in vivo. Importantly, p-Smad1/5/8 level was elevated in cetuximab-resistant patients and this correlated with poor prognosis. Collectively, our results indicate that the BMP7-p-Smad1/5/8 signaling is a key pathway to acquired cetuximab resistance, and demonstrate that combination therapy of cetuximab and a BMP signaling inhibitor as potentially a new therapeutic strategy for overcoming acquired resistance to cetuximab in OSCC. Copyright © 2017 Elsevier B.V. All rights reserved.

Bone Morphogenic Protein-2 (rhBMP2)-Loaded Silk Fibroin Scaffolds to Enhance the Osteoinductivity in Bone Tissue Engineering

NASA Astrophysics Data System (ADS)

Du, Guang-Yu; He, Sheng-Wei; Sun, Chuan-Xiu; Mi, Li-Dong

2017-10-01

There is an increasing demand for formulations of silk fibroin (SF) scaffolds in biomedical applications. SF was crosslinked via glutaraldehyde with osteoinductive recombinant human bone morphogenic protein-2 (rhBMP2) of different ratios viz. (i) 3% SF with no rhBMP2 (SF), (ii) 3% SF with equal amount of rhBMP2 (SF+BMP2), and (iii) 12% SF with 3% of rhBMP2 (4SF+BMP2), and these solutions were used in electrospinning-based fabrication of nanoscaffolds for evaluating increased osteoinductive potential of SF scaffolds with rhBMP2. Stress-strain relationship suggested there is no loss in mechanical strength of fibers with addition of rhBMP2, and mechanical strength of scaffold was improved with increase in concentration of SF. rhBMP2 association increased the water retention capacity of scaffold as evident from swelling studies. Viability of hMSCs was found to be higher in conjugated scaffolds, and scaffolds do not exhibit any cytotoxicity towards guest cells. Cells were found to have higher alkaline phosphatase activity in conjugated scaffolds under in vitro and in vivo conditions which establishes the increased osteoinductivity of the novel construct. The scaffolds were found to be effective for in vivo bone formation as well.

Conserved developmental expression of Fezf in chordates and Drosophila and the origin of the Zona Limitans Intrathalamica (ZLI) brain organizer

PubMed Central

2010-01-01

Background The zona limitans intrathalamica (ZLI) and the isthmus organizer (IsO) are two major secondary organizers of vertebrate brain development. These organizers are located at the interface of the expression domains of key patterning genes (Fezf-Irx and Otx-Gbx, respectively). To gain insights into the evolutionary origin of the ZLI, we studied Fezf in bilaterians. Results In this paper, we identified a conserved sequence motif (Fezf box) in all bilaterians. We report the expression pattern of Fezf in amphioxus and Drosophila and compare it with those of Gbx, Otx and Irx. We found that the relative expression patterns of these genes in vertebrates are fully conserved in amphioxus and flies, indicating that the genetic subdivisions defining the location of both secondary organizers in early vertebrate brain development were probably present in the last common ancestor of extant bilaterians. However, in contrast to vertebrates, we found that Irx-defective flies do not show an affected Fezf expression pattern. Conclusions The absence of expression of the corresponding morphogens from cells at these conserved genetic boundaries in invertebrates suggests that the organizing properties might have evolved specifically in the vertebrate lineage by the recruitment of key morphogens to these conserved genetic locations. PMID:20849572

The level of BMP4 signaling is critical for the regulation of distinct T-box gene expression domains and growth along the dorso-ventral axis of the optic cup

PubMed Central

Behesti, Hourinaz; Holt, James KL; Sowden, Jane C

2006-01-01

Background Polarised gene expression is thought to lead to the graded distribution of signaling molecules providing a patterning mechanism across the embryonic eye. Bone morphogenetic protein 4 (Bmp4) is expressed in the dorsal optic vesicle as it transforms into the optic cup. Bmp4 deletions in human and mouse result in failure of eye development, but little attempt has been made to investigate mammalian targets of BMP4 signaling. In chick, retroviral gene overexpression studies indicate that Bmp4 activates the dorsally expressed Tbx5 gene, which represses ventrally expressed cVax. It is not known whether the Tbx5 related genes, Tbx2 and Tbx3, are BMP4 targets in the mammalian retina and whether BMP4 acts at a distance from its site of expression. Although it is established that Drosophila Dpp (homologue of vertebrate Bmp4) acts as a morphogen, there is little evidence that BMP4 gradients are interpreted to create domains of BMP4 target gene expression in the mouse. Results Our data show that the level of BMP4 signaling is critical for the regulation of distinct Tbx2, Tbx3, Tbx5 and Vax2 gene expression domains along the dorso-ventral axis of the mouse optic cup. BMP4 signaling gradients were manipulated in whole mouse embryo cultures during optic cup development, by implantation of beads soaked in BMP4, or the BMP antagonist Noggin, to provide a local signaling source. Tbx2, Tbx3 and Tbx5, showed a differential response to alterations in the level of BMP4 along the entire dorso-ventral axis of the optic cup, suggesting that BMP4 acts across a distance. Increased levels of BMP4 caused expansion of Tbx2 and Tbx3, but not Tbx5, into the ventral retina and repression of the ventral marker Vax2. Conversely, Noggin abolished Tbx5 expression but only shifted Tbx2 expression dorsally. Increased levels of BMP4 signaling caused decreased proliferation, reduced retinal volume and altered the shape of the optic cup. Conclusion Our findings suggest the existence of a dorsal-high, ventral-low BMP4 signaling gradient across which distinct domains of Tbx2, Tbx3, Tbx5 and Vax2 transcription factor gene expression are set up. Furthermore we show that the correct level of BMP4 signaling is critical for normal growth of the mammalian embryonic eye. PMID:17173667

Sea-surface temperature gradients across blue whale and sea turtle foraging trajectories off the Baja California Peninsula, Mexico

NASA Astrophysics Data System (ADS)

Etnoyer, Peter; Canny, David; Mate, Bruce R.; Morgan, Lance E.; Ortega-Ortiz, Joel G.; Nichols, Wallace J.

2006-02-01

Sea-surface temperature (SST) fronts are integral to pelagic ecology in the North Pacific Ocean, so it is necessary to understand their character and distribution, and the way these features influence the behavior of endangered and highly migratory species. Here, telemetry data from sixteen satellite-tagged blue whales ( Balaenoptera musculus) and sea turtles ( Caretta caretta, Chelonia mydas, and Lepidochelys olivacea) are employed to characterize 'biologically relevant' SST fronts off Baja California Sur. High residence times are used to identify presumed foraging areas, and SST gradients are calculated across advanced very high resolution radiometer (AVHRR) images of these regions. The resulting values are compared to classic definitions of SST fronts in the oceanographic literature. We find subtle changes in surface temperature (between 0.01 and 0.10 °C/km) across the foraging trajectories, near the lowest end of the oceanographic scale (between 0.03 and 0.3 °C/km), suggesting that edge-detection algorithms using gradient thresholds >0.10 °C/km may overlook pelagic habitats in tropical waters. We use this information to sensitize our edge-detection algorithm, and to identify persistent concentrations of subtle SST fronts in the Northeast Pacific Ocean between 2002 and 2004. The lower-gradient threshold increases the number of fronts detected, revealing more potential habitats in different places than we find with a higher-gradient threshold. This is the expected result, but it confirms that pelagic habitat can be overlooked, and that the temperature gradient parameter is an important one.

Understanding the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions

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

Dahms, Rainer N.

A generalized framework for multi-component liquid injections is presented to understand and predict the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions. The analysis focuses on the thermodynamic structure and the immiscibility state of representative gas-liquid interfaces. The most modern form of Helmholtz energy mixture state equation is utilized which exhibits a unique and physically consistent behavior over the entire two-phase regime of fluid densities. It is combined with generalized models for non-linear gradient theory and for liquid injections to quantify multi-component two-phase interface structures in global thermal equilibrium. Then, the Helmholtz free energy is minimized whichmore » determines the interfacial species distribution as a consequence. This minimal free energy state is demonstrated to validate the underlying assumptions of classic two-phase theory and spray atomization. However, under certain engine-relevant conditions for which corroborating experimental data are presented, this requirement for interfacial thermal equilibrium becomes unsustainable. A rigorously derived probability density function quantifies the ability of the interface to develop internal spatial temperature gradients in the presence of significant temperature differences between injected liquid and ambient gas. Then, the interface can no longer be viewed as an isolated system at minimal free energy. Instead, the interfacial dynamics become intimately connected to those of the separated homogeneous phases. Hence, the interface transitions toward a state in local equilibrium whereupon it becomes a dense-fluid mixing layer. A new conceptual view of a transitional liquid injection process emerges from a transition time scale analysis. Close to the nozzle exit, the two-phase interface still remains largely intact and more classic two-phase processes prevail as a consequence. Further downstream, however, the transition to dense-fluid mixing generally occurs before the liquid length is reached. As a result, the significance of the presented modeling expressions is established by a direct comparison to a reduced model, which utilizes widely applied approximations but fundamentally fails to capture the physical complexity discussed in this paper.« less

Understanding the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions

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

Dahms, Rainer N., E-mail: Rndahms@sandia.gov

A generalized framework for multi-component liquid injections is presented to understand and predict the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions. The analysis focuses on the thermodynamic structure and the immiscibility state of representative gas-liquid interfaces. The most modern form of Helmholtz energy mixture state equation is utilized which exhibits a unique and physically consistent behavior over the entire two-phase regime of fluid densities. It is combined with generalized models for non-linear gradient theory and for liquid injections to quantify multi-component two-phase interface structures in global thermal equilibrium. Then, the Helmholtz free energy is minimized whichmore » determines the interfacial species distribution as a consequence. This minimal free energy state is demonstrated to validate the underlying assumptions of classic two-phase theory and spray atomization. However, under certain engine-relevant conditions for which corroborating experimental data are presented, this requirement for interfacial thermal equilibrium becomes unsustainable. A rigorously derived probability density function quantifies the ability of the interface to develop internal spatial temperature gradients in the presence of significant temperature differences between injected liquid and ambient gas. Then, the interface can no longer be viewed as an isolated system at minimal free energy. Instead, the interfacial dynamics become intimately connected to those of the separated homogeneous phases. Hence, the interface transitions toward a state in local equilibrium whereupon it becomes a dense-fluid mixing layer. A new conceptual view of a transitional liquid injection process emerges from a transition time scale analysis. Close to the nozzle exit, the two-phase interface still remains largely intact and more classic two-phase processes prevail as a consequence. Further downstream, however, the transition to dense-fluid mixing generally occurs before the liquid length is reached. The significance of the presented modeling expressions is established by a direct comparison to a reduced model, which utilizes widely applied approximations but fundamentally fails to capture the physical complexity discussed in this paper.« less

Understanding the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions

DOE PAGES

Dahms, Rainer N.

2016-04-26

A generalized framework for multi-component liquid injections is presented to understand and predict the breakdown of classic two-phase theory and spray atomization at engine-relevant conditions. The analysis focuses on the thermodynamic structure and the immiscibility state of representative gas-liquid interfaces. The most modern form of Helmholtz energy mixture state equation is utilized which exhibits a unique and physically consistent behavior over the entire two-phase regime of fluid densities. It is combined with generalized models for non-linear gradient theory and for liquid injections to quantify multi-component two-phase interface structures in global thermal equilibrium. Then, the Helmholtz free energy is minimized whichmore » determines the interfacial species distribution as a consequence. This minimal free energy state is demonstrated to validate the underlying assumptions of classic two-phase theory and spray atomization. However, under certain engine-relevant conditions for which corroborating experimental data are presented, this requirement for interfacial thermal equilibrium becomes unsustainable. A rigorously derived probability density function quantifies the ability of the interface to develop internal spatial temperature gradients in the presence of significant temperature differences between injected liquid and ambient gas. Then, the interface can no longer be viewed as an isolated system at minimal free energy. Instead, the interfacial dynamics become intimately connected to those of the separated homogeneous phases. Hence, the interface transitions toward a state in local equilibrium whereupon it becomes a dense-fluid mixing layer. A new conceptual view of a transitional liquid injection process emerges from a transition time scale analysis. Close to the nozzle exit, the two-phase interface still remains largely intact and more classic two-phase processes prevail as a consequence. Further downstream, however, the transition to dense-fluid mixing generally occurs before the liquid length is reached. As a result, the significance of the presented modeling expressions is established by a direct comparison to a reduced model, which utilizes widely applied approximations but fundamentally fails to capture the physical complexity discussed in this paper.« less

Equilibrium and initial linear stability analysis of liquid metal falling film flows in a varying spanwise magnetic field

NASA Astrophysics Data System (ADS)

Gao, D.; Morley, N. B.

2002-12-01

A 2D model for MHD free surface flow in a spanwise field is developed. The model, designed to simulate film flows of liquid metals in future thermo­nuclear fusion reactors, considers an applied spanwise magnetic field with spatial and temporal variation and an applied streamwise external current. A special case - a thin falling film flow in spanwise magnetic field with constant gradient and constant applied external streamwise current, is here investigated in depth to gain insight into the behavior of the MHD film flow. The fully developed flow solution is derived and initial linear stability analysis is performed for this special case. It is seen that the velocity profile is significantly changed due to the presence of the MHD effect, resulting in the free surface analog of the classic M-shape velocity profile seen in developing pipe flows in a field gradient. The field gradient is also seen to destabilize the film flow under most conditions. The effect of external current depends on the relative direction of the field gradient to the current direction. By controlling the magnitude of an external current, it is possible to obtain a linearly stable falling film under these magnetic field conditions. Tables 1, Figs 12, Refs 20.

Modified Whole Effluent Toxicity Test to Assess and Decouple Wastewater Effects from Environmental Gradients

PubMed Central

Sauco, Sebastián; Gómez, Julio; Barboza, Francisco R.; Lercari, Diego; Defeo, Omar

2013-01-01

Environmental gradients and wastewater discharges produce aggregated effects on marine populations, obscuring the detection of human impact. Classical assessment methods do not include environmental effects in toxicity tests designs, which could lead to incorrect conclusions. We proposed a modified Whole Effluent Toxicity test (mWET) that includes environmental gradients in addition to effluent dilutions, together with the application of Generalized Linear Mixed Models (GLMM) to assess and decouple those effects. We tested this approach, analyzing the lethal effects of wastewater on a marine sandy beach bivalve affected by an artificial canal freshwater discharge used for rice crops irrigation. To this end, we compared bivalve mortality between canal water dilutions (CWd) and salinity controls (SC: without canal water). CWd were prepared by diluting the water effluent (sampled during the pesticide application period) with artificial marine water. The salinity gradient was included in the design by achieving the same final salinities in both CWd and SC, allowing us to account for the effects of salinity by including this variable as a random factor in the GLMM. Our approach detected significantly higher mortalities in CWd, indicating potential toxic effects of the effluent discharge. mWET represents an improvement over the internationally standardized WET tests, since it considers environmental variability and uses appropriate statistical analyses. PMID:23755304

Geometry in a dynamical system without space: Hyperbolic Geometry in Kuramoto Oscillator Systems

NASA Astrophysics Data System (ADS)

Engelbrecht, Jan; Chen, Bolun; Mirollo, Renato

Kuramoto oscillator networks have the special property that their time evolution is constrained to lie on 3D orbits of the Möbius group acting on the N-fold torus TN which explains the N - 3 constants of motion discovered by Watanabe and Strogatz. The dynamics for phase models can be further reduced to 2D invariant sets in T N - 1 which have a natural geometry equivalent to the unit disk Δ with hyperbolic metric. We show that the classic Kuramoto model with order parameter Z1 (the first moment of the oscillator configuration) is a gradient flow in this metric with a unique fixed point on each generic 2D invariant set, corresponding to the hyperbolic barycenter of an oscillator configuration. This gradient property makes the dynamics especially easy to analyze. We exhibit several new families of Kuramoto oscillator models which reduce to gradient flows in this metric; some of these have a richer fixed point structure including non-hyperbolic fixed points associated with fixed point bifurcations. Work Supported by NSF DMS 1413020.

Solving ill-posed inverse problems using iterative deep neural networks

NASA Astrophysics Data System (ADS)

Adler, Jonas; Öktem, Ozan

2017-12-01

We propose a partially learned approach for the solution of ill-posed inverse problems with not necessarily linear forward operators. The method builds on ideas from classical regularisation theory and recent advances in deep learning to perform learning while making use of prior information about the inverse problem encoded in the forward operator, noise model and a regularising functional. The method results in a gradient-like iterative scheme, where the ‘gradient’ component is learned using a convolutional network that includes the gradients of the data discrepancy and regulariser as input in each iteration. We present results of such a partially learned gradient scheme on a non-linear tomographic inversion problem with simulated data from both the Sheep-Logan phantom as well as a head CT. The outcome is compared against filtered backprojection and total variation reconstruction and the proposed method provides a 5.4 dB PSNR improvement over the total variation reconstruction while being significantly faster, giving reconstructions of 512 × 512 pixel images in about 0.4 s using a single graphics processing unit (GPU).

Effective Inertial Frame in an Atom Interferometric Test of the Equivalence Principle

NASA Astrophysics Data System (ADS)

Overstreet, Chris; Asenbaum, Peter; Kovachy, Tim; Notermans, Remy; Hogan, Jason M.; Kasevich, Mark A.

2018-05-01

In an ideal test of the equivalence principle, the test masses fall in a common inertial frame. A real experiment is affected by gravity gradients, which introduce systematic errors by coupling to initial kinematic differences between the test masses. Here we demonstrate a method that reduces the sensitivity of a dual-species atom interferometer to initial kinematics by using a frequency shift of the mirror pulse to create an effective inertial frame for both atomic species. Using this method, we suppress the gravity-gradient-induced dependence of the differential phase on initial kinematic differences by 2 orders of magnitude and precisely measure these differences. We realize a relative precision of Δ g /g ≈6 ×10-11 per shot, which improves on the best previous result for a dual-species atom interferometer by more than 3 orders of magnitude. By reducing gravity gradient systematic errors to one part in 1 013 , these results pave the way for an atomic test of the equivalence principle at an accuracy comparable with state-of-the-art classical tests.

Wave propagation in strain gradient poroelastic medium with microinertia: closed-form and finite element solutions

NASA Astrophysics Data System (ADS)

Rosi, Giuseppe; Scala, Ilaria; Nguyen, Vu-Hieu; Naili, Salah

2017-06-01

This article is about ultrasonic wave propagation in microstructured porous media. The classic Biot's model is enriched using a strain gradient approach to be able to capture high-order effects when the wavelength approaches the characteristic size of the microstructure. In order to reproduce actual transmission/reflection experiments performed on poroelastic samples, and to validate the choice of the model, the computation of the time domain response is necessary, as it allows for a direct comparison with experimental results. For obtaining the time response, we use two strategies: on the one hand we compute the closed form solution by using the Laplace and Fourier transforms techniques; on the other hand we used a finite element method. The results are presented for a transmission/reflection test performed on a poroelastic sample immersed in water. The effects introduced by the strain gradient terms are visible in the time response and in agreement with experimental observations. The results can be exploited in characterization of mechanical properties of poroelastic media by enhancing the reliability of quantitative ultrasound techniques.

Antigravity Acts on Photons

NASA Astrophysics Data System (ADS)

Brynjolfsson, Ari

2002-04-01

Einstein's general theory of relativity assumes that photons don't change frequency as they move from Sun to Earth. This assumption is correct in classical physics. All experiments proving the general relativity are in the domain of classical physics. This include the tests by Pound et al. of the gravitational redshift of 14.4 keV photons; the rocket experiments by Vessot et al.; the Galileo solar redshift experiments by Krisher et al.; the gravitational deflection of light experiments by Riveros and Vucetich; and delay of echoes of radar signals passing close to Sun as observed by Shapiro et al. Bohr's correspondence principle assures that quantum mechanical theory of general relativity agrees with Einstein's classical theory when frequency and gravitational field gradient approach zero, or when photons cannot interact with the gravitational field. When we treat photons as quantum mechanical particles; we find that gravitational force on photons is reversed (antigravity). This modified theory contradicts the equivalence principle, but is consistent with all experiments. Solar lines and distant stars are redshifted in accordance with author's plasma redshift theory. These changes result in a beautiful consistent cosmology.

Coupled discrete element and finite volume solution of two classical soil mechanics problems

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

Chen, Feng; Drumm, Eric; Guiochon, Georges A

One dimensional solutions for the classic critical upward seepage gradient/quick condition and the time rate of consolidation problems are obtained using coupled routines for the finite volume method (FVM) and discrete element method (DEM), and the results compared with the analytical solutions. The two phase flow in a system composed of fluid and solid is simulated with the fluid phase modeled by solving the averaged Navier-Stokes equation using the FVM and the solid phase is modeled using the DEM. A framework is described for the coupling of two open source computer codes: YADE-OpenDEM for the discrete element method and OpenFOAMmore » for the computational fluid dynamics. The particle-fluid interaction is quantified using a semi-empirical relationship proposed by Ergun [12]. The two classical verification problems are used to explore issues encountered when using coupled flow DEM codes, namely, the appropriate time step size for both the fluid and mechanical solution processes, the choice of the viscous damping coefficient, and the number of solid particles per finite fluid volume.« less

Conditions for Aeronomic Applicability of the Classical Electron Heat Conduction Formula

NASA Technical Reports Server (NTRS)

Cole, K. D.; Hoegy, W. R.

1998-01-01

Conditions for the applicability of the classical formula for heat conduction in the electrons in ionized gas are investigated. In a fully ionised gas ( V(sub en) much greater than V(sub ei)), when the mean free path for electron-electron (or electron-ion) collisions is much larger than the characteristic thermal scale length of the observed system, the conditions for applicability break down. In the case of the Venus ionosphere this breakdown is indicated for a large fraction of the electron temperature data from altitudes greater than 180 km, for electron densities less than 10(exp 4)/cc cm. In a partially ionised gas such that V(sub en) much greater than V(sub ei) there is breakdown of the formula not only when the mean free path of electrons greatly exceeds the thermal scale length, but also when the gradient of neutral particle density exceeds the electron thermal gradient. It is shown that electron heat conduction may be neglected in estimating the temperature of joule heated electrons by observed strong 100 Hz electric fields when the conduction flux is limited by the saturation flux. The results of this paper support our earlier aeronomical arguments against the hypothesis of planetary scale whistlers for the 100 Hz electric field signal. In turn this means that data from the 100 Hz signal may not be used to support the case for lightning on Venus.

Dynamics of Reactive Microbial Hotspots in Concentration Gradient.

NASA Astrophysics Data System (ADS)

Hubert, A.; Farasin, J.; Tabuteau, H.; Dufresne, A.; Meheust, Y.; Le Borgne, T.

2017-12-01

In subsurface environments, bacteria play a major role in controlling the kinetics of a broad range of biogeochemical reactions. In such environments, nutrients fluxes and solute concentrations needed for bacteria metabolism may be highly variable in space and intermittent in time. This can lead to the formation of reactive hotspots where and when conditions are favorable to particular microorganisms, hence inducing biogeochemical reaction kinetics that differ significantly from those measured in homogeneous model environments. To investigate the impact of chemical gradients on the spatial structure and temporal dynamics of subsurface microorganism populations, we develop microfluidic cells allowing for a precise control of flow and chemical gradient conditions, as well as quantitative monitoring of the bacteria's spatial distribution and biofilm development. Using the non-motile Escherichia coli JW1908-1 strain and Gallionella capsiferriformans ES-2 as model organisms, we investigate the behavior and development of bacteria over a range of single and double concentration gradients in the concentrations of nutrients, electron donors and electron acceptors. We measure bacterial activity and population growth locally in precisely known hydrodynamic and chemical environments. This approach allows time-resolved monitoring of the location and intensity of reactive hotspots in micromodels as a function of the flow and chemical gradient conditions. We compare reactive microbial hotspot dynamics in our micromodels to classic growth laws and well-known growth parameters for the laboratory model bacteria Escherichia coli.We also discuss consequences for the formation and temporal dynamics of biofilms in the subsurface.

On Localized Vapor Pressure Gradients Governing Condensation and Frost Phenomena.

PubMed

Nath, Saurabh; Boreyko, Jonathan B

2016-08-23

Interdroplet vapor pressure gradients are the driving mechanism for several phase-change phenomena such as condensation dry zones, interdroplet ice bridging, dry zones around ice, and frost halos. Despite the fundamental nature of the underlying pressure gradients, the majority of studies on these emerging phenomena have been primarily empirical. Using classical nucleation theory and Becker-Döring embryo formation kinetics, here we calculate the pressure field for all possible modes of condensation and desublimation in order to gain fundamental insight into how pressure gradients govern the behavior of dry zones, condensation frosting, and frost halos. Our findings reveal that in a variety of phase-change systems the thermodynamically favorable mode of nucleation can switch between condensation and desublimation depending upon the temperature and wettability of the surface. The calculated pressure field is used to model the length of a dry zone around liquid or ice droplets over a broad parameter space. The long-standing question of whether the vapor pressure at the interface of growing frost is saturated or supersaturated is resolved by considering the kinetics of interdroplet ice bridging. Finally, on the basis of theoretical calculations, we propose that there exists a new mode of frost halo that is yet to be experimentally observed; a bimodal phase map is developed, demonstrating its dependence on the temperature and wettability of the underlying substrate. We hope that the model and predictions contained herein will assist future efforts to exploit localized vapor pressure gradients for the design of spatially controlled or antifrosting phase-change systems.

On-line pH modification of carbonate eluents using an electrolytic potassium hydroxide generator for ion chromatography.

PubMed

Novic, Milko; Liu, Yan; Avdalovic, Nebojsa; Pihlar, Boris

2002-05-31

Classical gradient elution, based on the application of a gradient pump used for mixing two or more prepared eluent components in pre-determined concentrations, was replaced by a chromatography system equipped with an isocratic pump and an electrolytic KOH generator. The isocratic pump delivered a constant concentration eluent composed of pure hydrogencarbonate solution. Carbonate ions, the main component of carbonate/hydrogencarbonate-based eluents, were formed by titration of hydrogencarbonate with KOH formed on-line in the electrolytic KOH generator. By changing the concentration of electrolytically-generated KOH, the eluent composition could be changed from pure hydrogencarbonate to a carbonate/hydrogencarbonate buffer, and finally to a carbonate/hydroxide-based eluent. The described system was tested to achieve pH-based changes of retention behavior of phosphate under constant inflow eluent composition conditions.

SNW 2000 Proceedings. Oxide Thickness Variation Induced Threshold Voltage Fluctuations in Decanano MOSFETs: a 3D Density Gradient Simulation Study

NASA Technical Reports Server (NTRS)

Asenov, Asen; Kaya, S.; Davies, J. H.; Saini, S.

2000-01-01

We use the density gradient (DG) simulation approach to study, in 3D, the effect of local oxide thickness fluctuations on the threshold voltage of decanano MOSFETs in a statistical manner. A description of the reconstruction procedure for the random 2D surfaces representing the 'atomistic' Si-SiO2 interface variations is presented. The procedure is based on power spectrum synthesis in the Fourier domain and can include either Gaussian or exponential spectra. The simulations show that threshold voltage variations induced by oxide thickness fluctuation become significant when the gate length of the devices become comparable to the correlation length of the fluctuations. The extent of quantum corrections in the simulations with respect to the classical case and the dependence of threshold variations on the oxide thickness are examined.

Auditory frequency generalization in the goldfish (Carassius auratus)1

PubMed Central

Fay, Richard R.

1970-01-01

Auditory frequency generalization in the goldfish was studied at five points within the best hearing range through the use of classical respiratory conditioning. Each experimental group received single-stimulus conditioning sessions at one of five stimulus frequencies (100, 200, 400, 800, and 1600 Hz), and were subsequently tested for generalization at eight neighboring frequencies. All stimuli were presented 30 db above absolute threshold. Significant generalization decrements were found for all subjects. For the subjects conditioned in the range between 100 and 800 Hz, a nearly complete failure to generalize was found at one octave above and below the training frequency. The subjects conditioned at 1600 Hz produced relatively more flat gradients between 900 and 2000 Hz. The widths of the generalization gradients, expressed in Hz, increased as a power function of frequency with a slope greater than one. PMID:16811481

Classically Stable Nonsingular Cosmological Bounces

NASA Astrophysics Data System (ADS)

Ijjas, Anna; Steinhardt, Paul J.

2016-09-01

One of the fundamental questions of theoretical cosmology is whether the Universe can undergo a nonsingular bounce, i.e., smoothly transit from a period of contraction to a period of expansion through violation of the null energy condition (NEC) at energies well below the Planck scale and at finite values of the scale factor such that the entire evolution remains classical. A common claim has been that a nonsingular bounce either leads to ghost or gradient instabilities or a cosmological singularity. In this Letter, we consider a well-motivated class of theories based on the cubic Galileon action and present a procedure for explicitly constructing examples of a nonsingular cosmological bounce without encountering any pathologies and maintaining a subluminal sound speed for comoving curvature modes throughout the NEC violating phase. We also discuss the relation between our procedure and earlier work.

A hybrid algorithm for coupling partial differential equation and compartment-based dynamics.

PubMed

Harrison, Jonathan U; Yates, Christian A

2016-09-01

Stochastic simulation methods can be applied successfully to model exact spatio-temporally resolved reaction-diffusion systems. However, in many cases, these methods can quickly become extremely computationally intensive with increasing particle numbers. An alternative description of many of these systems can be derived in the diffusive limit as a deterministic, continuum system of partial differential equations (PDEs). Although the numerical solution of such PDEs is, in general, much more efficient than the full stochastic simulation, the deterministic continuum description is generally not valid when copy numbers are low and stochastic effects dominate. Therefore, to take advantage of the benefits of both of these types of models, each of which may be appropriate in different parts of a spatial domain, we have developed an algorithm that can be used to couple these two types of model together. This hybrid coupling algorithm uses an overlap region between the two modelling regimes. By coupling fluxes at one end of the interface and using a concentration-matching condition at the other end, we ensure that mass is appropriately transferred between PDE- and compartment-based regimes. Our methodology gives notable reductions in simulation time in comparison with using a fully stochastic model, while maintaining the important stochastic features of the system and providing detail in appropriate areas of the domain. We test our hybrid methodology robustly by applying it to several biologically motivated problems including diffusion and morphogen gradient formation. Our analysis shows that the resulting error is small, unbiased and does not grow over time. © 2016 The Authors.

A hybrid algorithm for coupling partial differential equation and compartment-based dynamics

PubMed Central

Yates, Christian A.

2016-01-01

Stochastic simulation methods can be applied successfully to model exact spatio-temporally resolved reaction–diffusion systems. However, in many cases, these methods can quickly become extremely computationally intensive with increasing particle numbers. An alternative description of many of these systems can be derived in the diffusive limit as a deterministic, continuum system of partial differential equations (PDEs). Although the numerical solution of such PDEs is, in general, much more efficient than the full stochastic simulation, the deterministic continuum description is generally not valid when copy numbers are low and stochastic effects dominate. Therefore, to take advantage of the benefits of both of these types of models, each of which may be appropriate in different parts of a spatial domain, we have developed an algorithm that can be used to couple these two types of model together. This hybrid coupling algorithm uses an overlap region between the two modelling regimes. By coupling fluxes at one end of the interface and using a concentration-matching condition at the other end, we ensure that mass is appropriately transferred between PDE- and compartment-based regimes. Our methodology gives notable reductions in simulation time in comparison with using a fully stochastic model, while maintaining the important stochastic features of the system and providing detail in appropriate areas of the domain. We test our hybrid methodology robustly by applying it to several biologically motivated problems including diffusion and morphogen gradient formation. Our analysis shows that the resulting error is small, unbiased and does not grow over time. PMID:27628171

Electron-shuttling antibiotics structure bacterial communities by modulating cellular levels of c-di-GMP

PubMed Central

Okegbe, Chinweike; Fields, Blanche L.; Cole, Stephanie J.; Beierschmitt, Christopher; Morgan, Chase J.; Price-Whelan, Alexa; Stewart, Richard C.; Lee, Vincent T.; Dietrich, Lars E. P.

2017-01-01

Diverse organisms secrete redox-active antibiotics, which can be used as extracellular electron shuttles by resistant microbes. Shuttle-mediated metabolism can support survival when substrates are available not locally but rather at a distance. Such conditions arise in multicellular communities, where the formation of chemical gradients leads to resource limitation for cells at depth. In the pathogenic bacterium Pseudomonas aeruginosa PA14, antibiotics called phenazines act as oxidants to balance the intracellular redox state of cells in anoxic biofilm subzones. PA14 colony biofilms show a profound morphogenic response to phenazines resulting from electron acceptor-dependent inhibition of ECM production. This effect is reminiscent of the developmental responses of some eukaryotic systems to redox control, but for bacterial systems its mechanistic basis has not been well defined. Here, we identify the regulatory protein RmcA and show that it links redox conditions to PA14 colony morphogenesis by modulating levels of bis-(3′,5′)-cyclic-dimeric-guanosine (c-di-GMP), a second messenger that stimulates matrix production, in response to phenazine availability. RmcA contains four Per-Arnt-Sim (PAS) domains and domains with the potential to catalyze the synthesis and degradation of c-di-GMP. Our results suggest that phenazine production modulates RmcA activity such that the protein degrades c-di-GMP and thereby inhibits matrix production during oxidizing conditions. RmcA thus forms a mechanistic link between cellular redox sensing and community morphogenesis analogous to the functions performed by PAS-domain–containing regulatory proteins found in complex eukaryotes. PMID:28607054

A developmental basis for stochasticity in floral organ numbers

PubMed Central

Kitazawa, Miho S.; Fujimoto, Koichi

2014-01-01

Stochasticity ubiquitously inevitably appears at all levels from molecular traits to multicellular, morphological traits. Intrinsic stochasticity in biochemical reactions underlies the typical intercellular distributions of chemical concentrations, e.g., morphogen gradients, which can give rise to stochastic morphogenesis. While the universal statistics and mechanisms underlying the stochasticity at the biochemical level have been widely analyzed, those at the morphological level have not. Such morphological stochasticity is found in foral organ numbers. Although the floral organ number is a hallmark of floral species, it can distribute stochastically even within an individual plant. The probability distribution of the floral organ number within a population is usually asymmetric, i.e., it is more likely to increase rather than decrease from the modal value, or vice versa. We combined field observations, statistical analysis, and mathematical modeling to study the developmental basis of the variation in floral organ numbers among 50 species mainly from Ranunculaceae and several other families from core eudicots. We compared six hypothetical mechanisms and found that a modified error function reproduced much of the asymmetric variation found in eudicot floral organ numbers. The error function is derived from mathematical modeling of floral organ positioning, and its parameters represent measurable distances in the floral bud morphologies. The model predicts two developmental sources of the organ-number distributions: stochastic shifts in the expression boundaries of homeotic genes and a semi-concentric (whorled-type) organ arrangement. Other models species- or organ-specifically reproduced different types of distributions that reflect different developmental processes. The organ-number variation could be an indicator of stochasticity in organ fate determination and organ positioning. PMID:25404932

Bmp 2 and bmp 7 induce odonto- and osteogenesis of human tooth germ stem cells.

PubMed

Taşlı, P Neslihan; Aydın, Safa; Yalvaç, Mehmet Emir; Sahin, Fikrettin

2014-03-01

Bone morphogenetic proteins (BMPs) initiate, promote, and maintain odontogenesis and osteogenesis. In this study, we studied the effect of bone morphogenic protein 2 (BMP 2) and bone morphogenic protein 7 (BMP 7) as differentiation inducers in tooth and bone regeneration. We compared the effect of BMP 2 and BMP 7 on odontogenic and osteogenic differentiation of human tooth germ stem cells (hTGSCs). Third molar-derived hTGSCs were characterized with mesenchymal stem cell surface markers by flow cytometry. BMP 2 and BMP 7 were transfected into hTGSCs and the cells were seeded onto six-well plates. One day after the transfection, hTGSCs were treated with odontogenic and osteogenic mediums for 14 days. For confirmation of odontogenic and osteogenic differentiation, mRNA levels of BMP2, BMP 7, collagen type 1 (COL1A), osteocalsin (OCN), and dentin sialophosphoprotein (DSPP) genes were measured by quantitative real-time PCR. In addition to this, immunocytochemistry was performed by odontogenic and osteogenic antibodies and mineralization obtained by von Kossa staining. Our results showed that the BMP 2 and BMP 7 both promoted odontogenic and osteogenic differentiation of hTGSCs. Data indicated that BMP 2 treatment and BMP 7 treatment induce odontogenic differentiation without affecting each other, whereas they induce osteogenic differentiation by triggering expression of each other. These findings provide a feasible tool for tooth and bone tissue engineering.

Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

PubMed

Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

2015-03-01

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.

Identifying the cellular mechanisms of symbiont-induced epithelial morphogenesis in the squid-vibrio association

PubMed Central

Koropatnick, Tanya; Goodson, Michael S.; Heath-Heckman, Elizabeth A. C.; McFall-Ngai, Margaret

2014-01-01

The symbiotic association between the Hawaiian bobtail squid Euprymna scolopes and the luminous marine bacterium Vibrio fischeri provides a unique opportunity to study epithelial morphogenesis. Shortly after hatching, the squid host harvests bacteria from the seawater using currents created by two elaborate fields of ciliated epithelia on the surface of the juvenile light organ. After light organ colonization, the symbiont population signals the gradual loss of the ciliated epithelia through apoptosis of the cells, which culminates in the complete regression of these tissues. Whereas aspects of this process have been studied at the morphological, biochemical and molecular levels, no in-depth analysis of the cellular events has been reported. Here we describe the cellular structure of the epithelial field and present evidence that the symbiosis-induced regression occurs in two steps. Using confocal microscopic analyses, we observed an initial epithelial remodeling, which serves to disable the function of the harvesting apparatus, followed by a protracted regression involving actin rearrangements and epithelial cell extrusion. We identified a metal-dependent gelatinolytic activity in the symbiont-induced morphogenic epithelial fields, suggesting the involvement of Zn-dependent matrix metalloproteinase(s) (MMP) in light organ morphogenesis. These data show that the bacterial symbionts not only induce apoptosis of the field, but also change the form, function and biochemistry of the cells as part of the morphogenic program. PMID:24648207

Identifying the cellular mechanisms of symbiont-induced epithelial morphogenesis in the squid-Vibrio association.

PubMed

Koropatnick, Tanya; Goodson, Michael S; Heath-Heckman, Elizabeth A C; McFall-Ngai, Margaret

2014-02-01

The symbiotic association between the Hawaiian bobtail squid Euprymna scolopes and the luminous marine bacterium Vibrio fischeri provides a unique opportunity to study epithelial morphogenesis. Shortly after hatching, the squid host harvests bacteria from the seawater using currents created by two elaborate fields of ciliated epithelia on the surface of the juvenile light organ. After light organ colonization, the symbiont population signals the gradual loss of the ciliated epithelia through apoptosis of the cells, which culminates in the complete regression of these tissues. Whereas aspects of this process have been studied at the morphological, biochemical, and molecular levels, no in-depth analysis of the cellular events has been reported. Here we describe the cellular structure of the epithelial field and present evidence that the symbiosis-induced regression occurs in two steps. Using confocal microscopic analyses, we observed an initial epithelial remodeling, which serves to disable the function of the harvesting apparatus, followed by a protracted regression involving actin rearrangements and epithelial cell extrusion. We identified a metal-dependent gelatinolytic activity in the symbiont-induced morphogenic epithelial fields, suggesting the involvement of Zn-dependent matrix metalloproteinase(s) (MMP) in light organ morphogenesis. These data show that the bacterial symbionts not only induce apoptosis of the field, but also change the form, function, and biochemistry of the cells as part of the morphogenic program.

Dynamic load balancing algorithm for molecular dynamics based on Voronoi cells domain decompositions

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

Fattebert, J.-L.; Richards, D.F.; Glosli, J.N.

2012-12-01

We present a new algorithm for automatic parallel load balancing in classical molecular dynamics. It assumes a spatial domain decomposition of particles into Voronoi cells. It is a gradient method which attempts to minimize a cost function by displacing Voronoi sites associated with each processor/sub-domain along steepest descent directions. Excellent load balance has been obtained for quasi-2D and 3D practical applications, with up to 440·10 6 particles on 65,536 MPI tasks.

Shock wave as a probe of flux-dimited thermal transport in laser-heated solids

NASA Astrophysics Data System (ADS)

Smith, K.; Forsman, A.; Chiu, G.

1996-11-01

Laser-generated shock waves in solids result from the ablation of the target material. Where radiation transport is negligible, the ablation process is dominated by electron thermal conduction. This offers an opportunity to probe the degree of transport inhibition (compared with classical heat flow) for steep temperature gradients in a dense plasma. Using a 1-dimensional hydrodynamic code, we have examined the effect of flux-limited thermal conduction on the amplitude of the resulting shock wave.

Interpolation bias for the inverse compositional Gauss-Newton algorithm in digital image correlation

NASA Astrophysics Data System (ADS)

Su, Yong; Zhang, Qingchuan; Xu, Xiaohai; Gao, Zeren; Wu, Shangquan

2018-01-01

It is believed that the classic forward additive Newton-Raphson (FA-NR) algorithm and the recently introduced inverse compositional Gauss-Newton (IC-GN) algorithm give rise to roughly equal interpolation bias. Questioning the correctness of this statement, this paper presents a thorough analysis of interpolation bias for the IC-GN algorithm. A theoretical model is built to analytically characterize the dependence of interpolation bias upon speckle image, target image interpolation, and reference image gradient estimation. The interpolation biases of the FA-NR algorithm and the IC-GN algorithm can be significantly different, whose relative difference can exceed 80%. For the IC-GN algorithm, the gradient estimator can strongly affect the interpolation bias; the relative difference can reach 178%. Since the mean bias errors are insensitive to image noise, the theoretical model proposed remains valid in the presence of noise. To provide more implementation details, source codes are uploaded as a supplement.

Well-posedness of the free boundary problem in compressible elastodynamics

NASA Astrophysics Data System (ADS)

Trakhinin, Yuri

2018-02-01

We study the free boundary problem for the flow of a compressible isentropic inviscid elastic fluid. At the free boundary moving with the velocity of the fluid particles the columns of the deformation gradient are tangent to the boundary and the pressure vanishes outside the flow domain. We prove the local-in-time existence of a unique smooth solution of the free boundary problem provided that among three columns of the deformation gradient there are two which are non-collinear vectors at each point of the initial free boundary. If this non-collinearity condition fails, the local-in-time existence is proved under the classical Rayleigh-Taylor sign condition satisfied at the first moment. By constructing an Hadamard-type ill-posedness example for the frozen coefficients linearized problem we show that the simultaneous failure of the non-collinearity condition and the Rayleigh-Taylor sign condition leads to Rayleigh-Taylor instability.

Brownian motion and entropic torque driven motion of domain walls in antiferromagnets

NASA Astrophysics Data System (ADS)

Yan, Zhengren; Chen, Zhiyuan; Qin, Minghui; Lu, Xubing; Gao, Xingsen; Liu, Junming

2018-02-01

We study the spin dynamics in antiferromagnetic nanowire under an applied temperature gradient using micromagnetic simulations on a classical spin model with a uniaxial anisotropy. The entropic torque driven domain-wall motion and the Brownian motion are discussed in detail, and their competition determines the antiferromagnetic wall motion towards the hotter or colder region. Furthermore, the spin dynamics in an antiferromagnet can be well tuned by the anisotropy and the temperature gradient. Thus, this paper not only strengthens the main conclusions obtained in earlier works [Kim et al., Phys. Rev. B 92, 020402(R) (2015), 10.1103/PhysRevB.92.020402; Selzer et al., Phys. Rev. Lett. 117, 107201 (2016), 10.1103/PhysRevLett.117.107201], but more importantly gives the concrete conditions under which these conclusions apply, respectively. Our results may provide useful information on the antiferromagnetic spintronics for future experiments and storage device design.

Suppressed ion-scale turbulence in a hot high-β plasma

NASA Astrophysics Data System (ADS)

Schmitz, L.; Fulton, D. P.; Ruskov, E.; Lau, C.; Deng, B. H.; Tajima, T.; Binderbauer, M. W.; Holod, I.; Lin, Z.; Gota, H.; Tuszewski, M.; Dettrick, S. A.; Steinhauer, L. C.

2016-12-01

An economic magnetic fusion reactor favours a high ratio of plasma kinetic pressure to magnetic pressure in a well-confined, hot plasma with low thermal losses across the confining magnetic field. Field-reversed configuration (FRC) plasmas are potentially attractive as a reactor concept, achieving high plasma pressure in a simple axisymmetric geometry. Here, we show that FRC plasmas have unique, beneficial microstability properties that differ from typical regimes in toroidal confinement devices. Ion-scale fluctuations are found to be absent or strongly suppressed in the plasma core, mainly due to the large FRC ion orbits, resulting in near-classical thermal ion confinement. In the surrounding boundary layer plasma, ion- and electron-scale turbulence is observed once a critical pressure gradient is exceeded. The critical gradient increases in the presence of sheared plasma flow induced via electrostatic biasing, opening the prospect of active boundary and transport control in view of reactor requirements.

Nonlinear responses of chiral fluids from kinetic theory

NASA Astrophysics Data System (ADS)

Hidaka, Yoshimasa; Pu, Shi; Yang, Di-Lun

2018-01-01

The second-order nonlinear responses of inviscid chiral fluids near local equilibrium are investigated by applying the chiral kinetic theory (CKT) incorporating side-jump effects. It is shown that the local equilibrium distribution function can be nontrivially introduced in a comoving frame with respect to the fluid velocity when the quantum corrections in collisions are involved. For the study of anomalous transport, contributions from both quantum corrections in anomalous hydrodynamic equations of motion and those from the CKT and Wigner functions are considered under the relaxation-time (RT) approximation, which result in anomalous charge Hall currents propagating along the cross product of the background electric field and the temperature (or chemical-potential) gradient and of the temperature and chemical-potential gradients. On the other hand, the nonlinear quantum correction on the charge density vanishes in the classical RT approximation, which in fact satisfies the matching condition given by the anomalous equation obtained from the CKT.

Suppressed ion-scale turbulence in a hot high-β plasma

PubMed Central

Schmitz, L.; Fulton, D. P.; Ruskov, E.; Lau, C.; Deng, B. H.; Tajima, T.; Binderbauer, M. W.; Holod, I.; Lin, Z.; Gota, H.; Tuszewski, M.; Dettrick, S. A.; Steinhauer, L. C.

2016-01-01

An economic magnetic fusion reactor favours a high ratio of plasma kinetic pressure to magnetic pressure in a well-confined, hot plasma with low thermal losses across the confining magnetic field. Field-reversed configuration (FRC) plasmas are potentially attractive as a reactor concept, achieving high plasma pressure in a simple axisymmetric geometry. Here, we show that FRC plasmas have unique, beneficial microstability properties that differ from typical regimes in toroidal confinement devices. Ion-scale fluctuations are found to be absent or strongly suppressed in the plasma core, mainly due to the large FRC ion orbits, resulting in near-classical thermal ion confinement. In the surrounding boundary layer plasma, ion- and electron-scale turbulence is observed once a critical pressure gradient is exceeded. The critical gradient increases in the presence of sheared plasma flow induced via electrostatic biasing, opening the prospect of active boundary and transport control in view of reactor requirements. PMID:28000675

Exact cone beam reconstruction formulae for functions and their gradients for spherical and flat detectors

NASA Astrophysics Data System (ADS)

Louis, Alfred K.

2016-11-01

We derive unified inversion formulae for the cone beam transform similar to the Radon transform. Reinterpreting Grangeat’s formula we find a relation between the Radon transform of the gradient of the searched-for function and a quantity computable from cone beam data. This gives a uniqueness result for the cone beam transform of compactly supported functions under much weaker assumptions than the Tuy-Kirillov condition. Furthermore this relation leads to an exact formula for the direct calculation of derivatives of the density distribution; but here, similar to the classical Radon transform, complete Radon data are needed, hence the Tuy-Kirillov condition has to be imposed. Numerical experiments reported in Hahn B N et al (2013 Meas. Sci. Technol. 24 125601) indicate that these calculations are less corrupted by beam-hardening noise. Finally, we present flat detector versions for these results, which are mathematically less attractive but important for applications.

A result about scale transformation families in approximation

NASA Astrophysics Data System (ADS)

Apprato, Dominique; Gout, Christian

2000-06-01

Scale transformations are common in approximation. In surface approximation from rapidly varying data, one wants to suppress, or at least dampen the oscillations of the approximation near steep gradients implied by the data. In that case, scale transformations can be used to give some control over overshoot when the surface has large variations of its gradient. Conversely, in image analysis, scale transformations are used in preprocessing to enhance some features present on the image or to increase jumps of grey levels before segmentation of the image. In this paper, we establish the convergence of an approximation method which allows some control over the behavior of the approximation. More precisely, we study the convergence of an approximation from a data set of , while using scale transformations on the values before and after classical approximation. In addition, the construction of scale transformations is also given. The algorithm is presented with some numerical examples.

Sensitivity analysis, approximate analysis, and design optimization for internal and external viscous flows

NASA Technical Reports Server (NTRS)

Taylor, Arthur C., III; Hou, Gene W.; Korivi, Vamshi M.

1991-01-01

A gradient-based design optimization strategy for practical aerodynamic design applications is presented, which uses the 2D thin-layer Navier-Stokes equations. The strategy is based on the classic idea of constructing different modules for performing the major tasks such as function evaluation, function approximation and sensitivity analysis, mesh regeneration, and grid sensitivity analysis, all driven and controlled by a general-purpose design optimization program. The accuracy of aerodynamic shape sensitivity derivatives is validated on two viscous test problems: internal flow through a double-throat nozzle and external flow over a NACA 4-digit airfoil. A significant improvement in aerodynamic performance has been achieved in both cases. Particular attention is given to a consistent treatment of the boundary conditions in the calculation of the aerodynamic sensitivity derivatives for the classic problems of external flow over an isolated lifting airfoil on 'C' or 'O' meshes.

Quantum annealing versus classical machine learning applied to a simplified computational biology problem

PubMed Central

Li, Richard Y.; Di Felice, Rosa; Rohs, Remo; Lidar, Daniel A.

2018-01-01

Transcription factors regulate gene expression, but how these proteins recognize and specifically bind to their DNA targets is still debated. Machine learning models are effective means to reveal interaction mechanisms. Here we studied the ability of a quantum machine learning approach to predict binding specificity. Using simplified datasets of a small number of DNA sequences derived from actual binding affinity experiments, we trained a commercially available quantum annealer to classify and rank transcription factor binding. The results were compared to state-of-the-art classical approaches for the same simplified datasets, including simulated annealing, simulated quantum annealing, multiple linear regression, LASSO, and extreme gradient boosting. Despite technological limitations, we find a slight advantage in classification performance and nearly equal ranking performance using the quantum annealer for these fairly small training data sets. Thus, we propose that quantum annealing might be an effective method to implement machine learning for certain computational biology problems. PMID:29652405

Layout optimization with algebraic multigrid methods

NASA Technical Reports Server (NTRS)

Regler, Hans; Ruede, Ulrich

1993-01-01

Finding the optimal position for the individual cells (also called functional modules) on the chip surface is an important and difficult step in the design of integrated circuits. This paper deals with the problem of relative placement, that is the minimization of a quadratic functional with a large, sparse, positive definite system matrix. The basic optimization problem must be augmented by constraints to inhibit solutions where cells overlap. Besides classical iterative methods, based on conjugate gradients (CG), we show that algebraic multigrid methods (AMG) provide an interesting alternative. For moderately sized examples with about 10000 cells, AMG is already competitive with CG and is expected to be superior for larger problems. Besides the classical 'multiplicative' AMG algorithm where the levels are visited sequentially, we propose an 'additive' variant of AMG where levels may be treated in parallel and that is suitable as a preconditioner in the CG algorithm.

Unsteady Computational Tests of a Non-Equilibrium

NASA Astrophysics Data System (ADS)

Jirasek, Adam; Hamlington, Peter; Lofthouse, Andrew; Usafa Collaboration; Cu Boulder Collaboration

2017-11-01

A non-equilibrium turbulence model is assessed on simulations of three practically-relevant unsteady test cases; oscillating channel flow, transonic flow around an oscillating airfoil, and transonic flow around the Benchmark Super-Critical Wing. The first case is related to piston-driven flows while the remaining cases are relevant to unsteady aerodynamics at high angles of attack and transonic speeds. Non-equilibrium turbulence effects arise in each of these cases in the form of a lag between the mean strain rate and Reynolds stresses, resulting in reduced kinetic energy production compared to classical equilibrium turbulence models that are based on the gradient transport (or Boussinesq) hypothesis. As a result of the improved representation of unsteady flow effects, the non-equilibrium model provides substantially better agreement with available experimental data than do classical equilibrium turbulence models. This suggests that the non-equilibrium model may be ideally suited for simulations of modern high-speed, high angle of attack aerodynamics problems.

Optical imaging measurements of oxygen transport fluctuations and gradients in tumor microvascular networks

NASA Astrophysics Data System (ADS)

Sorg, Brian S.; Hardee, Matthew E.; Moeller, Benjamin J.; Dewhirst, Mark W.

2006-02-01

It is well established that hypoxia can influence tumor biology and physiology, gene expression, metastatic potential, treatment efficacy, and patient survival. Most human solid tumors have been shown to have some hypoxic regions, thus there is a strong motivation to understand the various causes of hypoxia. One key to understanding tumor hypoxia involves the study of oxygen transport to tumors, and the connection between hypoxia, tumor microvasculature, and the tumor microenvironment. Recent research has suggested that the causes of tumor hypoxia are much more complex than indicated by the classical paradigms ("chronic" and "acute" hypoxia), and several potential factors have been identified. Two such factors are temporal fluctuations in tissue pO II and longitudinal gradients in oxygen transport. Research has shown the existence of low frequency (<2 cycles per minute) fluctuations in tumor pO II without cessation of blood flow that can lead to transient hypoxia. In addition, longitudinal gradients in tumor pO II along the arteriolar afferent direction have been documented in window chamber tumors. However, the causes of the pO II temporal fluctuations and longitudinal gradients are not exactly known, and the clinical significance of these observations is not well understood. In this preliminary study, we demonstrate the potential of optical imaging measurements of hemoglobin saturation to add new information in these areas. Slow temporal fluctuations of hemoglobin saturation (HbSat) and gradients in the average HbSat were observed in some 4T1 mouse mammary carcinoma microvessels. With additional research, the mechanisms behind these phenomena and insights into their clinical significance may be revealed.

On the role of micro-inertia in enriched continuum mechanics.

PubMed

Madeo, Angela; Neff, Patrizio; Aifantis, Elias C; Barbagallo, Gabriele; d'Agostino, Marco Valerio

2017-02-01

In this paper, the role of gradient micro-inertia terms [Formula: see text] and free micro-inertia terms [Formula: see text] is investigated to unveil their respective effects on the dynamic behaviour of band-gap metamaterials. We show that the term [Formula: see text] alone is only able to disclose relatively simplified dispersive behaviour. On the other hand, the term [Formula: see text] alone describes the full complex behaviour of band-gap metamaterials. A suitable mixing of the two micro-inertia terms allows us to describe a new feature of the relaxed-micromorphic model, i.e. the description of a second band-gap occurring for higher frequencies. We also show that a split of the gradient micro-inertia [Formula: see text], in the sense of Cartan-Lie decomposition of matrices, allows us to flatten separately the longitudinal and transverse optic branches, thus giving us the possibility of a second band-gap. Finally, we investigate the effect of the gradient inertia [Formula: see text] on more classical enriched models such as the Mindlin-Eringen and the internal variable ones. We find that the addition of such a gradient micro-inertia allows for the onset of one band-gap in the Mindlin-Eringen model and three band-gaps in the internal variable model. In this last case, however, non-local effects cannot be accounted for, which is a too drastic simplification for most metamaterials. We conclude that, even when adding gradient micro-inertia terms, the relaxed micromorphic model remains the best performing one, among the considered enriched models, for the description of non-local band-gap metamaterials.

Quasi-static responses and variational principles in gradient plasticity

NASA Astrophysics Data System (ADS)

Nguyen, Quoc-Son

2016-12-01

Gradient models have been much discussed in the literature for the study of time-dependent or time-independent processes such as visco-plasticity, plasticity and damage. This paper is devoted to the theory of Standard Gradient Plasticity at small strain. A general and consistent mathematical description available for common time-independent behaviours is presented. Our attention is focussed on the derivation of general results such as the description of the governing equations for the global response and the derivation of related variational principles in terms of the energy and the dissipation potentials. It is shown that the quasi-static response under a loading path is a solution of an evolution variational inequality as in classical plasticity. The rate problem and the rate minimum principle are revisited. A time-discretization by the implicit scheme of the evolution equation leads to the increment problem. An increment of the response associated with a load increment is a solution of a variational inequality and satisfies also a minimum principle if the energy potential is convex. The increment minimum principle deals with stables solutions of the variational inequality. Some numerical methods are discussed in view of the numerical simulation of the quasi-static response.

Local structure of scalar flux in turbulent passive scalar mixing

NASA Astrophysics Data System (ADS)

Konduri, Aditya; Donzis, Diego

2012-11-01

Understanding the properties of scalar flux is important in the study of turbulent mixing. Classical theories suggest that it mainly depends on the large scale structures in the flow. Recent studies suggest that the mean scalar flux reaches an asymptotic value at high Peclet numbers, independent of molecular transport properties of the fluid. A large DNS database of isotropic turbulence with passive scalars forced with a mean scalar gradient with resolution up to 40963, is used to explore the structure of scalar flux based on the local topology of the flow. It is found that regions of small velocity gradients, where dissipation and enstrophy are small, constitute the main contribution to scalar flux. On the other hand, regions of very small scalar gradient (and scalar dissipation) become less important to the scalar flux at high Reynolds numbers. The scaling of the scalar flux spectra is also investigated. The k - 7 / 3 scaling proposed by Lumley (1964) is observed at high Reynolds numbers, but collapse is not complete. A spectral bump similar to that in the velocity spectrum is observed close to dissipative scales. A number of features, including the height of the bump, appear to reach an asymptotic value at high Schmidt number.

Renal intraspecific variation along an aridity gradient detected by new renal indices in a desert herbivorous rodent.

PubMed

Tejo Riquelme, Patricia A; Diaz Isenrath, Gabriela B; Andino, Natalia; Borghi, Carlos E

2014-07-01

Mammals that live in arid and semi-arid environments in South America present physiological mechanisms that enable them to conserve water. Body water is lost through the kidneys, lungs, skin, and intestines. Regarding renal adaptation for water conservation, several indices have been used to estimate the capacity of the kidneys to produce a maximum urine concentration. Most studies were conducted at an inter-specific level, with only few performed at the intraspecific level. In this work, we compare renal function and morphology among five populations of Southern mountain cavy, Microcavia australis, present along an aridity gradient. We hypothesized that individuals from drier zones would present morphological and functional renal modifications that imply a greater capability to conserve body water. These features were studied considering the classical indices (RMT, PMT, PMA, and RMA) and three new indices that consider area measurements; the latter showed to be more adequate to reflect intraspecific differences. Our results suggest that the morphological modifications of kidneys, that is, the greater areas of renal inner medulla, would be related to the aridity gradient where populations of Southern mountain cavy occur. © 2014 Wiley Periodicals, Inc.

Torsion of a Cosserat elastic bar with square cross section: theory and experiment

NASA Astrophysics Data System (ADS)

Drugan, W. J.; Lakes, R. S.

2018-04-01

An approximate analytical solution for the displacement and microrotation vector fields is derived for pure torsion of a prismatic bar with square cross section comprised of homogeneous, isotropic linear Cosserat elastic material. This is accomplished by analytical simplification coupled with use of the principle of minimum potential energy together with polynomial representations for the desired field components. Explicit approximate expressions are derived for cross section warp and for applied torque versus angle of twist of the bar. These show that torsional rigidity exceeds the classical elasticity value, the difference being larger for slender bars, and that cross section warp is less than the classical amount. Experimental measurements on two sets of 3D printed square cross section polymeric bars, each set having a different microstructure and four different cross section sizes, revealed size effects not captured by classical elasticity but consistent with the present analysis for physically sensible values of the Cosserat moduli. The warp can allow inference of Cosserat elastic constants independently of any sensitivity the material may have to dilatation gradients; warp also facilitates inference of Cosserat constants that are difficult to obtain via size effects.

Upper Water Structure and Mixed Layer Depth in Sub-Tropical Waters: The Seats Station in the Northern South China Sea

NASA Astrophysics Data System (ADS)

Wong, G. T. F.; Tai, J. H.

2014-12-01

702 CTD profiles were collected in the subtropical northern South China Sea at and in the vicinity of the SouthEast Asian Time-series Study (SEATS) station (18.2oN, 115.8oE) between 17.5 and 18.5oN and 115.3 and 116.3oE in 64 cruises in 1997 to 2013. The hydrographic structure of the upper water above the permanent thermocline may be classified into 4 principal types: (a) classic type (an almost isopycnic upper water); (b) stepwise type (with one or more small but significant step-increases in σθ in the upper water); (c) graded type (an approximately constant depth gradient in a monotonic increase in σθ in the upper water); and (d) mixed type (a combination of the stepwise and graded types). The 4 types of upper water were found in 75, 14, 5, and 6% of the cruises, respectively. Ten schemes were applied to these data to determine the mixed layer depth (MLD): 4 fixed temperature difference (FTD) methods (0.2, 0.5, 0.8 and 1.0oC decrease from 10 m); 1 fixed density difference (FDD) method (0.125 σθ increase from 10 m); 1 fixed temperature gradient (FTG) method (at 0.05oC/m); 3 fixed density gradient (FDG) methods (at 0.01, 0.05 and 0.1 σθ/m); and the maximum density gradient (MDG) method. MLD could not be clearly depicted in the 3 minor types of upper water. In the classical type, while similar MLD-s were found in a large majority of the cruises among all 10 methods, substantial discrepancies among methods could be found. The most consistent results, generally within ±5 m, were found among the FDG method at 0.05, 0.1 σθ/m and FTD method at 0.8 and 1.0oC. The MDG method gave consistently deeper MLD by ~8 m. If that difference was taken into account, the results were generally consistent with those from the other 4 methods. The remaining 5 methods could all yield MLD-s shallower than the first 4 methods by >10 m as they failed to capture the bottom of the mixed layer as indicated by visual inspection.

Left-right asymmetry: cilia stir up new surprises in the node.

PubMed

Babu, Deepak; Roy, Sudipto

2013-05-29

Cilia are microtubule-based hair-like organelles that project from the surface of most eukaryotic cells. They play critical roles in cellular motility, fluid transport and a variety of signal transduction pathways. While we have a good appreciation of the mechanisms of ciliary biogenesis and the details of their structure, many of their functions demand a more lucid understanding. One such function, which remains as intriguing as the time when it was first discovered, is how beating cilia in the node drive the establishment of left-right asymmetry in the vertebrate embryo. The bone of contention has been the two schools of thought that have been put forth to explain this phenomenon. While the 'morphogen hypothesis' believes that ciliary motility is responsible for the transport of a morphogen preferentially to the left side, the 'two-cilia model' posits that the motile cilia generate a leftward-directed fluid flow that is somehow sensed by the immotile sensory cilia on the periphery of the node. Recent studies with the mouse embryo argue in favour of the latter scenario. Yet this principle may not be generally conserved in other vertebrates that use nodal flow to specify their left-right axis. Work with the teleost fish medaka raises the tantalizing possibility that motility as well as sensory functions of the nodal cilia could be residing within the same organelle. In the end, how ciliary signalling is transmitted to institute asymmetric gene expression that ultimately induces asymmetric organogenesis remains unresolved.

Left–right asymmetry: cilia stir up new surprises in the node

PubMed Central

Babu, Deepak; Roy, Sudipto

2013-01-01

Cilia are microtubule-based hair-like organelles that project from the surface of most eukaryotic cells. They play critical roles in cellular motility, fluid transport and a variety of signal transduction pathways. While we have a good appreciation of the mechanisms of ciliary biogenesis and the details of their structure, many of their functions demand a more lucid understanding. One such function, which remains as intriguing as the time when it was first discovered, is how beating cilia in the node drive the establishment of left–right asymmetry in the vertebrate embryo. The bone of contention has been the two schools of thought that have been put forth to explain this phenomenon. While the ‘morphogen hypothesis’ believes that ciliary motility is responsible for the transport of a morphogen preferentially to the left side, the ‘two-cilia model’ posits that the motile cilia generate a leftward-directed fluid flow that is somehow sensed by the immotile sensory cilia on the periphery of the node. Recent studies with the mouse embryo argue in favour of the latter scenario. Yet this principle may not be generally conserved in other vertebrates that use nodal flow to specify their left–right axis. Work with the teleost fish medaka raises the tantalizing possibility that motility as well as sensory functions of the nodal cilia could be residing within the same organelle. In the end, how ciliary signalling is transmitted to institute asymmetric gene expression that ultimately induces asymmetric organogenesis remains unresolved. PMID:23720541

Distinct Recruitment and Function of Gab1 and Gab2 in Met Receptor-mediated Epithelial Morphogenesis

PubMed Central

Lock, Lisa S.; Maroun, Christiane R.; Naujokas, Monica A.; Park, Morag

2002-01-01

The Gab family of docking proteins (Gab1 and Gab2) are phosphorylated in response to various cytokines and growth factors. Gab1 acts to diversify the signal downstream from the Met receptor tyrosine kinase through the recruitment of multiple signaling proteins, and is essential for epithelial morphogenesis. To determine whether Gab1 and Gab2 are functionally redundant, we have examined the role of Gab2 in epithelial cells. Both Gab1 and Gab2 are expressed in epithelial cells and localize to cell-cell junctions. However, whereas overexpression of Gab1 promotes a morphogenic response, the overexpression of Gab2 fails to induce this response. We show that Gab2 recruitment to the Met receptor is dependent on the Grb2 adapter protein. In contrast, Gab1 recruitment to Met is both Grb2 dependent and Grb2 independent. The latter requires a novel amino acid sequence present in the Met-binding domain of Gab1 but not Gab2. Mutation of these residues in Gab1 impairs both association with the Met receptor and the ability of Gab1 to promote a morphogenic response, whereas their insertion into Gab2 increases Gab2 association with Met, but does not confer on Gab2 the ability to promote epithelial morphogenesis. We propose that the Grb2-independent recruitment of Gab proteins to Met is necessary but not sufficient to promote epithelial morphogenesis. PMID:12058075

Morphogenes bolA and mreB mediate the photoregulation of cellular morphology during complementary chromatic acclimation in Fremyella diplosiphon.

PubMed

Singh, Shailendra P; Montgomery, Beronda L

2014-07-01

Photoregulation of pigmentation during complementary chromatic acclimation (CCA) is well studied in Fremyella diplosiphon; however, mechanistic insights into the CCA-associated morphological changes are still emerging. F. diplosiphon cells are rectangular under green light (GL), whereas cells are smaller and spherical under red light (RL). Here, we investigate the role of morphogenes bolA and mreB during CCA using gene expression and gene function analyses. The F. diplosiphon bolA gene is essential as its complete removal from the genome was unsuccessful. Depletion of bolA resulted in slow growth, morphological defects and the accumulation of high levels of reactive oxygen species in a partially segregated ΔbolA strain. Higher expression of bolA was observed under RL and was correlated with lower expression of mreB and mreC genes in wild type. In a ΔrcaE strain that lacks the red-/green-responsive RcaE photoreceptor, the expression of bolA and mre genes was altered under both RL and GL. Observed gene expression relationships suggest that mreB and mreC expression is controlled by RcaE-dependent photoregulation of bolA expression. Expression of F. diplosiphon bolA and mreB homologues in Escherichia coli demonstrated functional conservation of the encoded proteins. Together, these studies establish roles for bolA and mreB in RcaE-dependent regulation of cellular morphology. © 2014 John Wiley & Sons Ltd.

Directing three-dimensional multicellular morphogenesis by self-organization of vascular mesenchymal cells in hyaluronic acid hydrogels.

PubMed

Zhu, Xiaolu; Gojgini, Shiva; Chen, Ting-Hsuan; Fei, Peng; Dong, Siyan; Ho, Chih-Ming; Segura, Tatiana

2017-01-01

Physical scaffolds are useful for supporting cells to form three-dimensional (3D) tissue. However, it is non-trivial to develop a scheme that can robustly guide cells to self-organize into a tissue with the desired 3D spatial structures. To achieve this goal, the rational regulation of cellular self-organization in 3D extracellular matrix (ECM) such as hydrogel is needed. In this study, we integrated the Turing reaction-diffusion mechanism with the self-organization process of cells and produced multicellular 3D structures with the desired configurations in a rational manner. By optimizing the components of the hydrogel and applying exogenous morphogens, a variety of multicellular 3D architectures composed of multipotent vascular mesenchymal cells (VMCs) were formed inside hyaluronic acid (HA) hydrogels. These 3D architectures could mimic the features of trabecular bones and multicellular nodules. Based on the Turing reaction-diffusion instability of morphogens and cells, a theoretical model was proposed to predict the variations observed in 3D multicellular structures in response to exogenous factors. It enabled the feasibility to obtain diverse types of 3D multicellular structures by addition of Noggin and/or BMP2. The morphological consistency between the simulation prediction and experimental results probably revealed a Turing-type mechanism underlying the 3D self-organization of VMCs in HA hydrogels. Our study has provided new ways to create a variety of self-organized 3D multicellular architectures for regenerating biomaterial and tissues in a Turing mechanism-based approach.

A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

PubMed Central

Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner; Kumar, Ashok; Lidgren, Lars; Tägil, Magnus

2016-01-01

In orthopedic surgery, large amount of diseased or injured bone routinely needs to be replaced. Autografts are mainly used but their availability is limited. Commercially available bone substitutes allow bone ingrowth but lack the capacity to induce bone formation. Thus, off-the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay early resorption. In-vitro, the biphasic material released 90% of rhBMP-2 and 10% of ZA in the first week. No major changes were found in the surface structure using scanning electron microscopy (SEM) or in the mechanical properties after adding rhBMP-2 or ZA. In-vivo bone formation was studied in an abdominal muscle pouch model in rats (n = 6/group). The mineralized volume was significantly higher when the biphasic material was combined with both rhBMP-2 and ZA (21.4 ± 5.5 mm3) as compared to rhBMP-2 alone (10.9 ± 2.1 mm3) when analyzed using micro computed tomography (μ-CT) (p < 0.01). In the clinical setting, the biphasic material combined with both rhBMP-2 and ZA can potentially regenerate large volumes of bone. PMID:27189411

Microfluidic-based patterning of embryonic stem cells for in vitro development studies.

PubMed

Suri, Shalu; Singh, Ankur; Nguyen, Anh H; Bratt-Leal, Andres M; McDevitt, Todd C; Lu, Hang

2013-12-07

In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study multicellular populations in 3D configurations are limited by the inability to create complex (i.e. spatially heterogeneous) environments in a reproducible manner with high fidelity thus impeding the ability to engineer microenvironments and combinations of cells with similar complexity to that found during morphogenic processes such as development, remodelling and wound healing. Here, we develop a multicellular embryoid body (EB) fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. We describe the physical principles of the EB fusion microfluidic device design; we demonstrate that >60 conjoined EBs can be generated overnight and emulate a development process analogous to mouse gastrulation during early embryogenesis. Using temporal delivery of bone morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day 6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation in murine embryonic stem cells leading to expression of Brachyury-T-green fluorescent protein (T-GFP), an indicator of primitive streak development and mesoderm differentiation during gastrulation. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments.

Microfluidic-based patterning of embryonic stem cells for in vitro development studies

PubMed Central

Suri, Shalu; Singh, Ankur; Nguyen, Anh H.; Bratt-Leal, Andres M.; McDevitt, Todd C.

2013-01-01

In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study multicellular populations in 3D configurations are limited by the inability to create complex (i.e. spatially heterogeneous) environments in a reproducible manner with high fidelity thus impeding the ability to engineer microenvironments and combinations of cells with similar complexity to that found during morphogenic processes such as development, remodelling and wound healing. Here, we develop a multicellular embryoid body (EB) fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. We describe the physical principles of the EB fusion microfluidic device design; we demonstrate that >60 conjoined EBs can be generated overnight and emulate a development process analogous to mouse gastrulation during early embryogenesis. Using temporal delivery of bone morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day 6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation in murine embryonic stem cells leading to expression of Brachyury-T-green fluorescent protein (T-GFP), an indicator of primitive streak development and mesoderm differentiation during gastrulation. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments. PMID:24113509

Nonclassical acoustics

NASA Technical Reports Server (NTRS)

Kentzer, C. P.

1976-01-01

A statistical approach to sound propagation is considered in situations where, due to the presence of large gradients of properties of the medium, the classical (deterministic) treatment of wave motion is inadequate. Mathematical methods for wave motions not restricted to small wavelengths (analogous to known methods of quantum mechanics) are used to formulate a wave theory of sound in nonuniform flows. Nonlinear transport equations for field probabilities are derived for the limiting case of noninteracting sound waves and it is postulated that such transport equations, appropriately generalized, may be used to predict the statistical behavior of sound in arbitrary flows.

Extraction of shear viscosity in stationary states of relativistic particle systems

NASA Astrophysics Data System (ADS)

Reining, F.; Bouras, I.; El, A.; Wesp, C.; Xu, Z.; Greiner, C.

2012-02-01

Starting from a classical picture of shear viscosity we construct a stationary velocity gradient in a microscopic parton cascade. Employing the Navier-Stokes ansatz we extract the shear viscosity coefficient η. For elastic isotropic scatterings we find an excellent agreement with the analytic values. This confirms the applicability of this method. Furthermore, for both elastic and inelastic scatterings with pQCD based cross sections we extract the shear viscosity coefficient η for a pure gluonic system and find a good agreement with already published calculations.

A superlinear convergence estimate for an iterative method for the biharmonic equation

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

Horn, M.A.

In [CDH] a method for the solution of boundary value problems for the biharmonic equation using conformal mapping was investigated. The method is an implementation of the classical method of Muskhelishvili. In [CDH] it was shown, using the Hankel structure, that the linear system in [Musk] is the discretization of the identify plus a compact operator, and therefore the conjugate gradient method will converge superlinearly. The purpose of this paper is to give an estimate of the superlinear convergence in the case when the boundary curve is in a Hoelder class.

Energy repartition in the nonequilibrium steady state

NASA Astrophysics Data System (ADS)

Yan, Peng; Bauer, Gerrit E. W.; Zhang, Huaiwu

2017-01-01

The concept of temperature in nonequilibrium thermodynamics is an outstanding theoretical issue. We propose an energy repartition principle that leads to a spectral (mode-dependent) temperature in steady-state nonequilibrium systems. The general concepts are illustrated by analytic solutions of the classical Heisenberg spin chain connected to Langevin heat reservoirs with arbitrary temperature profiles. Gradients of external magnetic fields are shown to localize spin waves in a Wannier-Zeemann fashion, while magnon interactions renormalize the spectral temperature. Our generic results are applicable to other thermodynamic systems such as Newtonian liquids, elastic solids, and Josephson junctions.

Classical Model of the Electromagnetic Interaction Suitable for High Speed Semiconductor Device Simulation

DTIC Science & Technology

2006-11-01

color images. 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18 . NUMBER OF PAGES 8 19a. NAME OF...Std Z39- 18 small problem domain can require millions of solution vari- ables solved repeatedly for tens of thousands of time steps. Finally, the...terms of vector and scalar potentials, A and ψ respec- tively. E = − ( ∂A ∂t +∇ψ ) = Erot + Eirr (5) Since the curl of a gradient is always zero, ∇ψ

Baseline mathematics and geodetics for tracking operations

NASA Technical Reports Server (NTRS)

James, R.

1981-01-01

Various geodetic and mapping algorithms are analyzed as they apply to radar tracking systems and tested in extended BASIC computer language for real time computer applications. Closed-form approaches to the solution of converting Earth centered coordinates to latitude, longitude, and altitude are compared with classical approximations. A simplified approach to atmospheric refractivity called gradient refraction is compared with conventional ray tracing processes. An extremely detailed set of documentation which provides the theory, derivations, and application of algorithms used in the programs is included. Validation methods are also presented for testing the accuracy of the algorithms.

Chemotaxis migration and morphogenesis of living colonies.

PubMed

Ben Amar, Martine

2013-06-01

Development of forms in living organisms is complex and fascinating. Morphogenetic theories that investigate these shapes range from discrete to continuous models, from the variational elasticity to time-dependent fluid approach. Here a mixture model is chosen to describe the mass transport in a morphogenetic gradient: it gives a mathematical description of a mixture involving several constituents in mechanical interactions. This model, which is highly flexible can incorporate many biological processes but also complex interactions between cells as well as between cells and their environment. We use this model to derive a free-boundary problem easier to handle analytically. We solve it in the simplest geometry: an infinite linear front advancing with a constant velocity. In all the cases investigated here as the 3 D diffusion, the increase of mitotic activity at the border, nonlinear laws for the uptake of morphogens or for the mobility coefficient, a planar front exists above a critical threshold for the mobility coefficient but it becomes unstable just above the threshold at long wavelengths due to the existence of a Goldstone mode. This explains why sparsely bacteria exhibit dendritic patterns experimentally in opposition to other colonies such as biofilms and epithelia which are more compact. In the most unstable situation, where all the laws: diffusion, chemotaxis driving and chemoattractant uptake are linear, we show also that the system can recover a dynamic stability. A second threshold for the mobility exists which has a lower value as the ratio between diffusion coefficients decreases. Within the framework of this model where the biomass is treated mainly as a viscous and diffusive fluid, we show that the multiplicity of independent parameters in real biologic experimental set-up may explain varieties of observed patterns.

On the role of micro-inertia in enriched continuum mechanics

NASA Astrophysics Data System (ADS)

Madeo, Angela; Neff, Patrizio; Aifantis, Elias C.; Barbagallo, Gabriele; d'Agostino, Marco Valerio

2017-02-01

In this paper, the role of gradient micro-inertia terms η ¯ ∥ ∇ u,t∥2 and free micro-inertia terms η ∥P,t∥2 is investigated to unveil their respective effects on the dynamic behaviour of band-gap metamaterials. We show that the term η ¯ ∥ ∇ u,t∥2 alone is only able to disclose relatively simplified dispersive behaviour. On the other hand, the term η ∥P,t∥2 alone describes the full complex behaviour of band-gap metamaterials. A suitable mixing of the two micro-inertia terms allows us to describe a new feature of the relaxed-micromorphic model, i.e. the description of a second band-gap occurring for higher frequencies. We also show that a split of the gradient micro-inertia η ¯ ∥ ∇ u,t∥2, in the sense of Cartan-Lie decomposition of matrices, allows us to flatten separately the longitudinal and transverse optic branches, thus giving us the possibility of a second band-gap. Finally, we investigate the effect of the gradient inertia η ¯ ∥ ∇ u,t∥2 on more classical enriched models such as the Mindlin-Eringen and the internal variable ones. We find that the addition of such a gradient micro-inertia allows for the onset of one band-gap in the Mindlin-Eringen model and three band-gaps in the internal variable model. In this last case, however, non-local effects cannot be accounted for, which is a too drastic simplification for most metamaterials. We conclude that, even when adding gradient micro-inertia terms, the relaxed micromorphic model remains the best performing one, among the considered enriched models, for the description of non-local band-gap metamaterials.

On the role of micro-inertia in enriched continuum mechanics

PubMed Central

Neff, Patrizio; Aifantis, Elias C.; Barbagallo, Gabriele; d’Agostino, Marco Valerio

2017-01-01

In this paper, the role of gradient micro-inertia terms η¯∥ ∇u,t∥2 and free micro-inertia terms η∥P,t∥2 is investigated to unveil their respective effects on the dynamic behaviour of band-gap metamaterials. We show that the term η¯∥ ∇u,t∥2 alone is only able to disclose relatively simplified dispersive behaviour. On the other hand, the term η∥P,t∥2 alone describes the full complex behaviour of band-gap metamaterials. A suitable mixing of the two micro-inertia terms allows us to describe a new feature of the relaxed-micromorphic model, i.e. the description of a second band-gap occurring for higher frequencies. We also show that a split of the gradient micro-inertia η¯∥ ∇u,t∥2, in the sense of Cartan–Lie decomposition of matrices, allows us to flatten separately the longitudinal and transverse optic branches, thus giving us the possibility of a second band-gap. Finally, we investigate the effect of the gradient inertia η¯∥ ∇u,t∥2 on more classical enriched models such as the Mindlin–Eringen and the internal variable ones. We find that the addition of such a gradient micro-inertia allows for the onset of one band-gap in the Mindlin–Eringen model and three band-gaps in the internal variable model. In this last case, however, non-local effects cannot be accounted for, which is a too drastic simplification for most metamaterials. We conclude that, even when adding gradient micro-inertia terms, the relaxed micromorphic model remains the best performing one, among the considered enriched models, for the description of non-local band-gap metamaterials. PMID:28293136

The coupling between flame surface dynamics and species mass conservation in premixed turbulent combustion

NASA Technical Reports Server (NTRS)

Trouve, A.; Veynante, D.; Bray, K. N. C.; Mantel, T.

1994-01-01

Current flamelot models based on a description of the flame surface dynamics require the closure of two inter-related equations: a transport equation for the mean reaction progress variable, (tilde)c, and a transport equation for the flame surface density, Sigma. The coupling between these two equations is investigated using direct numerical simulations (DNS) with emphasis on the correlation between the turbulent fluxes of (tilde)c, bar(pu''c''), and Sigma, (u'')(sub S)Sigma. Two different DNS databases are used in the present work: a database developed at CTR by A. Trouve and a database developed by C. J. Rutland using a different code. Both databases correspond to statistically one-dimensional premixed flames in isotropic turbulent flow. The run parameters, however, are significantly different, and the two databases correspond to different combustion regimes. It is found that in all simulated flames, the correlation between bar(pu''c'') and (u'')(sub S)Sigma is always strong. The sign, however, of the turbulent flux of (tilde)c or Sigma with respect to the mean gradients, delta(tilde)c/delta(x) or delta(Sigma)/delta(x), is case-dependent. The CTR database is found to exhibit gradient turbulent transport of (tilde)c and Sigma, whereas the Rutland DNS features counter-gradient diffusion. The two databases are analyzed and compared using various tools (a local analysis of the flow field near the flame, a classical analysis of the conservation equation for (tilde)(u''c''), and a thin flame theoretical analysis). A mechanism is then proposed to explain the discrepancies between the two databases and a preliminary simple criterion is derived to predict the occurrence of gradient/counter-gradient turbulent diffusion.

Differences in fat and muscle mass associated with a functional human polymorphism in a post-transcriptional BMP2 gene regulatory element.

PubMed

Devaney, Joseph M; Tosi, Laura L; Fritz, David T; Gordish-Dressman, Heather A; Jiang, Shan; Orkunoglu-Suer, Funda E; Gordon, Andrew H; Harmon, Brennan T; Thompson, Paul D; Clarkson, Priscilla M; Angelopoulos, Theodore J; Gordon, Paul M; Moyna, Niall M; Pescatello, Linda S; Visich, Paul S; Zoeller, Robert F; Brandoli, Cinzia; Hoffman, Eric P; Rogers, Melissa B

2009-08-15

A classic morphogen, bone morphogenetic protein 2 (BMP2) regulates the differentiation of pluripotent mesenchymal cells. High BMP2 levels promote osteogenesis or chondrogenesis and low levels promote adipogenesis. BMP2 inhibits myogenesis. Thus, BMP2 synthesis is tightly controlled. Several hundred nucleotides within the 3' untranslated regions of BMP2 genes are conserved from mammals to fishes indicating that the region is under stringent selective pressure. Our analyses indicate that this region controls BMP2 synthesis by post-transcriptional mechanisms. A common A to C single nucleotide polymorphism (SNP) in the BMP2 gene (rs15705, +A1123C) disrupts a putative post-transcriptional regulatory motif within the human ultra-conserved sequence. In vitro studies indicate that RNAs bearing the A or C alleles have different protein binding characteristics in extracts from mesenchymal cells. Reporter genes with the C allele of the ultra-conserved sequence were differentially expressed in mesenchymal cells. Finally, we analyzed MRI data from the upper arm of 517 healthy individuals aged 18-41 years. Individuals with the C/C genotype were associated with lower baseline subcutaneous fat volumes (P = 0.0030) and an increased gain in skeletal muscle volume (P = 0.0060) following resistance training in a cohort of young males. The rs15705 SNP explained 2-4% of inter-individual variability in the measured parameters. The rs15705 variant is one of the first genetic markers that may be exploited to facilitate early diagnosis, treatment, and/or prevention of diseases associated with poor fitness. Furthermore, understanding the mechanisms by which regulatory polymorphisms influence BMP2 synthesis will reveal novel pharmaceutical targets for these disabling conditions. (c) 2009 Wiley-Liss, Inc.

Differences in Fat and Muscle Mass Associated With a Functional Human Polymorphism in a Post-Transcriptional BMP2 Gene Regulatory Element

PubMed Central

Devaney, Joseph M.; Tosi, Laura L.; Fritz, David T.; Gordish-Dressman, Heather A.; Jiang, Shan; Orkunoglu-Suer, Funda E.; Gordon, Andrew H.; Harmon, Brennan T.; Thompson, Paul D.; Clarkson, Priscilla M.; Angelopoulos, Theodore J.; Gordon, Paul M.; Moyna, Niall M.; Pescatello, Linda S.; Visich, Paul S.; Zoeller, Robert F.; Brandoli, Cinzia; Hoffman, Eric P.; Rogers, Melissa B.

2014-01-01

A classic morphogen, bone morphogenetic protein 2 (BMP2) regulates the differentiation of pluripotent mesenchymal cells. High BMP2 levels promote osteogenesis or chondrogenesis and low levels promote adipogenesis. BMP2 inhibits myogenesis. Thus, BMP2 synthesis is tightly controlled. Several hundred nucleotides within the 3′ untranslated regions of BMP2 genes are conserved from mammals to fishes indicating that the region is under stringent selective pressure. Our analyses indicate that this region controls BMP2 synthesis by post-transcriptional mechanisms. A common A to C single nucleotide polymorphism (SNP) in the BMP2 gene (rs15705, +A1123C) disrupts a putative post-transcriptional regulatory motif within the human ultra-conserved sequence. In vitro studies indicate that RNAs bearing the A or C alleles have different protein binding characteristics in extracts from mesenchymal cells. Reporter genes with the C allele of the ultra-conserved sequence were differentially expressed in mesenchymal cells. Finally, we analyzed MRI data from the upper arm of 517 healthy individuals aged 18–41 years. Individuals with the C/C genotype were associated with lower baseline subcutaneous fat volumes (P = 0.0030) and an increased gain in skeletal muscle volume (P = 0.0060) following resistance training in a cohort of young males. The rs15705 SNP explained 2–4% of inter-individual variability in the measured parameters. The rs15705 variant is one of the first genetic markers that maybe exploited to facilitate early diagnosis, treatment, and/or prevention of diseases associated with poor fitness. Furthermore, understanding the mechanisms by which regulatory polymorphisms influence BMP2 synthesis will reveal novel pharmaceutical targets for these disabling conditions. PMID:19492344

An analysis of the gradient-induced electric fields and current densities in human models when situated in a hybrid MRI-LINAC system

NASA Astrophysics Data System (ADS)

Liu, Limei; Trakic, Adnan; Sanchez-Lopez, Hector; Liu, Feng; Crozier, Stuart

2014-01-01

MRI-LINAC is a new image-guided radiotherapy treatment system that combines magnetic resonance imaging (MRI) with a linear accelerator (LINAC) in a single unit. One drawback is that the pulsing of the split gradient coils of the system induces an electric field and currents in the patient which need to be predicted and evaluated for patient safety. In this novel numerical study the in situ electric fields and associated current densities were evaluated inside tissue-accurate male and female human voxel models when a number of different split-geometry gradient coils were operated. The body models were located in the MRI-LINAC system along the axial and radial directions in three different body positions. Each model had a region of interest (ROI) suitable for image-guided radiotherapy. The simulation results show that the amplitudes and distributions of the field and current density induced by different split x-gradient coils were similar with one another in the ROI of the body model, but varied outside of the region. The fields and current densities induced by a split classic coil with the surface unconnected showed the largest deviation from those given by the conventional non-split coils. Another finding indicated that the distributions of the peak current densities varied when the body position, orientation or gender changed, while the peak electric fields mainly occurred in the skin and fat tissues.

Influence of Flow Gradients on Mach Stem Initiation of PBX-9502

NASA Astrophysics Data System (ADS)

Hull, Lawrence; Miller, Phillip; Mas, Eric; Focused Experiments Team

2017-06-01

Recent experiments and theory explore the effect of flow gradients on reaction acceleration and stability in the pressure-enhanced region between colliding sub-detonative shock waves in PBX-9502. The experiments are designed to produce divergent curved incident shock waves that interact in a convergent irregular reflection, or ``Mach stem'', configuration. Although this flow is fundamentally unsteady, such a configuration does feature particle paths having a single shock wave that increases the pressure from zero to the wave-reflected enhanced pressure. Thus, the possibility of pre-shock desensitization is precluded in this interaction region. Diagnostics record arrival wave velocity, shape, and material velocity along the angled free surface face of a large wedge. The wedge is large enough to allow observation of the wave structure for distances much larger than the run-to-detonation derived from classical ``Pop plot'' data. The explosive driver system produces the incident shocks and allows some control of the flow gradients in the collision region. Further, the incident shocks are very weak and do not transition to detonation. The experiments discussed feature incident shock waves that would be expected to cause initiation in the Mach stem, based on the Pop plot. Results show that the introduction of pressure/velocity gradients in the reaction zone strongly influences the ability of the flow to build to a steady ``CJ'' detonation. As expected, the ability of the Mach stem to stabilize or accelerate is strongly influenced by the incident shock pressure.

Exact variational nonlocal stress modeling with asymptotic higher-order strain gradients for nanobeams

NASA Astrophysics Data System (ADS)

Lim, C. W.; Wang, C. M.

2007-03-01

This article presents a complete and asymptotic representation of the one-dimensional nanobeam model with nonlocal stress via an exact variational principle approach. An asymptotic governing differential equation of infinite-order strain gradient model and the corresponding infinite number of boundary conditions are derived and discussed. For practical applications, it explores and presents a reduced higher-order solution to the asymptotic nonlocal model. It is also identified here and explained at length that most publications on this subject have inaccurately employed an excessively simplified lower-order model which furnishes intriguing solutions under certain loading and boundary conditions where the results become identical to the classical solution, i.e., without the small-scale effect at all. Various nanobeam examples are solved to demonstrate the difference between using the simplified lower-order nonlocal model and the asymptotic higher-order strain gradient nonlocal stress model. An important conclusion is the discovery of significant over- or underestimation of stress levels using the lower-order model, particularly at the vicinity of the clamped end of a cantilevered nanobeam under a tip point load. The consequence is that the design of a nanobeam based on the lower-order strain gradient model could be flawed in predicting the nonlocal stress at the clamped end where it could, depending on the magnitude of the small-scale parameter, significantly over- or underestimate the failure criteria of a nanobeam which are governed by the level of stress.

Surface-from-gradients without discrete integrability enforcement: A Gaussian kernel approach.

PubMed

Ng, Heung-Sun; Wu, Tai-Pang; Tang, Chi-Keung

2010-11-01

Representative surface reconstruction algorithms taking a gradient field as input enforce the integrability constraint in a discrete manner. While enforcing integrability allows the subsequent integration to produce surface heights, existing algorithms have one or more of the following disadvantages: They can only handle dense per-pixel gradient fields, smooth out sharp features in a partially integrable field, or produce severe surface distortion in the results. In this paper, we present a method which does not enforce discrete integrability and reconstructs a 3D continuous surface from a gradient or a height field, or a combination of both, which can be dense or sparse. The key to our approach is the use of kernel basis functions, which transfer the continuous surface reconstruction problem into high-dimensional space, where a closed-form solution exists. By using the Gaussian kernel, we can derive a straightforward implementation which is able to produce results better than traditional techniques. In general, an important advantage of our kernel-based method is that the method does not suffer discretization and finite approximation, both of which lead to surface distortion, which is typical of Fourier or wavelet bases widely adopted by previous representative approaches. We perform comparisons with classical and recent methods on benchmark as well as challenging data sets to demonstrate that our method produces accurate surface reconstruction that preserves salient and sharp features. The source code and executable of the system are available for downloading.

Non-unique turbulent boundary layer flows having a moderately large velocity defect: a rational extension of the classical asymptotic theory

NASA Astrophysics Data System (ADS)

Scheichl, B.; Kluwick, A.

2013-11-01

The classical analysis of turbulent boundary layers in the limit of large Reynolds number Re is characterised by an asymptotically small velocity defect with respect to the external irrotational flow. As an extension of the classical theory, it is shown in the present work that the defect may become moderately large and, in the most general case, independent of Re but still remain small compared to the external streamwise velocity for non-zero pressure gradient boundary layers. That wake-type flow turns out to be characterised by large values of the Rotta-Clauser parameter, serving as an appropriate measure for the defect and hence as a second perturbation parameter besides Re. Most important, it is demonstrated that also this case can be addressed by rigorous asymptotic analysis, which is essentially independent of the choice of a specific Reynolds stress closure. As a salient result of this procedure, transition from the classical small defect to a pronounced wake flow is found to be accompanied by quasi-equilibrium flow, described by a distinguished limit that involves the wall shear stress. This situation is associated with double-valued solutions of the boundary layer equations and an unconventional weak Re-dependence of the external bulk flow—a phenomenon seen to agree well with previous semi-empirical studies and early experimental observations. Numerical computations of the boundary layer flow for various values of Re reproduce these analytical findings with satisfactory agreement.

Colours of minor bodies in the outer solar system. II. A statistical analysis revisited

NASA Astrophysics Data System (ADS)

Hainaut, O. R.; Boehnhardt, H.; Protopapa, S.

2012-10-01

We present an update of the visible and near-infrared colour database of Minor Bodies in the Outer Solar System (MBOSSes), which now includes over 2000 measurement epochs of 555 objects, extracted from over 100 articles. The list is fairly complete as of December 2011. The database is now large enough to enable any dataset with a large dispersion to be safely identified and rejected from the analysis. The selection method used is quite insensitive to individual outliers. Most of the rejected datasets were observed during the early days of MBOSS photometry. The individual measurements are combined in a way that avoids possible rotational artifacts. The spectral gradient over the visible range is derived from the colours, as well as the R absolute magnitude M(1,1). The average colours, absolute magnitude, and spectral gradient are listed for each object, as well as the physico-dynamical classes using a classification adapted from Gladman and collaborators. Colour-colour diagrams, histograms, and various other plots are presented to illustrate and investigate class characteristics and trends with other parameters, whose significances are evaluated using standard statistical tests. Except for a small discrepancy for the J-H colour, the largest objects, with M(1,1) < 5, are indistinguishable from the smaller ones. The larger ones are slightly bluer than the smaller ones in J-H. Short-period comets, Plutinos and other resonant objects, hot classical disk objects, scattered disk objects and detached disk objects have similar properties in the visible, while the cold classical disk objects and the Jupiter Trojans form two separate groups of their spectral properties in the visible wavelength range. The well-known colour bimodality of Centaurs is confirmed. The hot classical disk objects with large inclinations, or large orbital excitations are found to be bluer than the others, confirming a previously known result. Additionally, the hot classical disk objects with a smaller perihelion distance are bluer than those that do not come as close to the Sun. The bluer hot classical disk objects and resonant objects have fainter absolute magnitudes than the redder ones of the same class. Finally, we discuss possible scenarios for the origin of the colour diversity observed in MBOSSes, i.e. colouration caused by evolutionary or formation processes. The colour tables and all plots are also available on the MBOSS colour web page, which will be updated when new measurements are published Full Tables 2 and 3 are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/546/A115

A current review of core decompression in the treatment of osteonecrosis of the femoral head.

PubMed

Pierce, Todd P; Jauregui, Julio J; Elmallah, Randa K; Lavernia, Carlos J; Mont, Michael A; Nace, James

2015-09-01

The review describes the following: (1) how traditional core decompression is performed, (2) adjunctive treatments, (3) multiple percutaneous drilling technique, and (4) the overall outcomes of these procedures. Core decompression has optimal outcomes when used in the earliest, precollapse disease stages. More recent studies have reported excellent outcomes with percutaneous drilling. Furthermore, adjunct treatment methods combining core decompression with growth factors, bone morphogenic proteins, stem cells, and bone grafting have demonstrated positive results; however, larger randomized trial is needed to evaluate their overall efficacy.

Spontaneous cavitation in a Lennard-Jones liquid: Molecular dynamics simulation and the van der Waals-Cahn-Hilliard gradient theory

NASA Astrophysics Data System (ADS)

Baidakov, Vladimir G.

2016-02-01

The process of bubble nucleation in a Lennard-Jones (LJ) liquid is studied by molecular dynamics (MD) simulation. The bubble nucleation rate J is determined by the mean life-time method at temperatures above that of the triple point in the region of negative pressures. The results of simulation are compared with classical nucleation theory (CNT) and modified classical nucleation theory (MCNT), in which the work of formation of a critical bubble is determined in the framework of the van der Waals-Cahn-Hilliard gradient theory (GT). It has been found that the values of J obtained in MD simulation systematically exceed the data of CNT, and this excess in the nucleation rate reaches 8-10 orders of magnitude close to the triple point temperature. The results of MCNT are in satisfactory agreement with the data of MD simulation. To describe the properties of vapor-phase nuclei in the framework of GT, an equation of state has been built up which describes stable, metastable and labile regions of LJ fluids. The surface tension of critical bubbles γ has been found from CNT and data of MD simulation as a function of the radius of curvature of the surface of tension R*. The dependence γ(R*) has also been calculated from GT. The Tolman length has been determined, which is negative and in modulus equal to ≈(0.1 - 0.2) σ. The paper discusses the applicability of the Tolman formula to the description of the properties of critical nuclei in nucleation.

Gradient Drift Turbulence from Electron Bite-Outs: Dependence on Atmospheric Parameters.

NASA Astrophysics Data System (ADS)

Young, M.; Oppenheim, M. M.; Dimant, Y. S.

2017-12-01

Electron bite-outs are regions of decreased electron density without a corresponding decrease in ion density, often caused by electron attachment to dust grains. They typically occur in the upper D-/lower E-region ionosphere and the accompanying electron gradient provides free energy to drive the gradient drift instability (GDI). The major difference between classical GDI and electron bite-out driven GDI is that the instability occurs on the top side of the bite-out region in the latter, as opposed to the bottom side in the former, in the presence of a vertical background electric field. Moreover, the mobile plasma population contains a gradient in only one species while the entire system remains quasineutral. This modified geometry presents new pathways for instabilities as the ions build up near the bite-out layer, leaving behind depletions that ascend away from the layer. Previous simulation runs showed that the presence of an electron gradient drives GDI-like turbulence even when ions and electrons start in momentum balance. Furthermore, a simulation run that replaced the electron bite-out with a layer of enhanced ion density, as though ions and electrons had filled in the bite-out region, did not lead to instability. This work examines the role of atmospheric parameters at altitudes between 80-100 km in instability formation and turbulence development, including the role of collisions in impeding instability growth as altitude decreases. Key parameters include the ambient electric field, which plays a critical role in triggering the gradient-drift instability; collision frequencies and temperature, which vary with altitude and effect the turbulent growth rate; and relative charge density of the bite-out, which increases the electron gradient strength. This work provides insight into how electron bite-out layers can produce turbulence that ground-based high frequency (HF) radars may be able to observe. The upper D-/lower E-region ionosphere is generally difficult to study in situ, making simulations of ground-based observables much more important. Assuming that electron bite-out layers result from dust charging in particular will allow the community to use the predictions of this work to study the ionospheric dust population.

Cannibalism and activity rate in larval damselflies increase along a latitudinal gradient as a consequence of time constraints.

PubMed

Sniegula, Szymon; Golab, Maria J; Johansson, Frank

2017-07-14

Predation is ubiquitous in nature. One form of predation is cannibalism, which is affected by many factors such as size structure and resource density. However, cannibalism may also be influenced by abiotic factors such as seasonal time constraints. Since time constraints are greater at high latitudes, cannibalism could be stronger at such latitudes, but we know next to nothing about latitudinal variation in cannibalism. In this study, we examined cannibalism and activity in larvae of the damselfly Lestes sponsa along a latitudinal gradient across Europe. We did this by raising larvae from the egg stage at different temperatures and photoperiods corresponding to different latitudes. We found that the more seasonally time-constrained populations in northern latitudes and individuals subjected to greater seasonal time constraints exhibited a higher level of cannibalism. We also found that activity was higher at north latitude conditions, and thus correlated with cannibalism, suggesting that this behaviour mediates higher levels of cannibalism in time-constrained animals. Our results go counter to the classical latitude-predation pattern which predicts higher predation at lower latitudes, since we found that predation was stronger at higher latitudes. The differences in cannibalism might have implications for population dynamics along the latitudinal gradients, but further experiments are needed to explore this.

High-resolution pattern of mangrove species distribution is controlled by surface elevation

NASA Astrophysics Data System (ADS)

Leong, Rick C.; Friess, Daniel A.; Crase, Beth; Lee, Wei Kit; Webb, Edward L.

2018-03-01

Mangrove vegetation species respond to multiple environmental gradients, and an enhanced understanding of how mangrove species are distributed across these gradients will facilitate conservation and management. Many environmental gradients correlate with tidal inundation; however small-scale inundation patterns resulting from microtopographical changes are difficult to capture empirically. In contrast, surface elevation is often a suitable, measurable and cost-effective proxy for inundation. This study investigated the relationships between species distribution and surface elevation in a mangrove forest in northwest Singapore. Through high-resolution land surveying, we developed a digital elevation model (DEM) and conducted a comprehensive survey of 4380 trees with a stem diameter ≥ 5 cm. A total of 15 species were encountered, and elevation envelopes were generated for 12. Species envelopes were distributed along an elevation continuum, with most species overlapping within the continuum. Spatial autocorrelation (SAC) was present for nine of the 15 species, and when taken into account, species ordering was modified across the elevation continuum. The presence of SAC strongly reinforces the need for research to control for SAC: classical spatial description of mangrove species distribution should be revised to account for ecological factors. This study suggests that (1) surface elevation applies strong controls on species distribution and (2) most mangroves at our study site have similar physiological tolerances.

An evaluation of a coupled microstructural approach for the analysis of functionally graded composites via the finite-element method

NASA Technical Reports Server (NTRS)

Pindera, Marek-Jerzy; Dunn, Patrick

1995-01-01

A comparison is presented between the predictions of the finite-element analysis and a recently developed higher-order theory for functionally graded materials subjected to a thorough-thickness temperature gradient. In contrast to existing micromechanical theories that utilize classical (i.e., uncoupled) homogenization schemes to calculate micro-level and macro-level stress and displacement fields in materials with uniform or nonuniform fiber spacing (i.e., functionally graded materials), the new theory explicitly couples the microstructural details with the macrostructure of the composite. Previous thermo-elastic analysis has demonstrated that such coupling is necessary when: the temperature gradient is large with respect to the dimension of the reinforcement; the characteristic dimension of the reinforcement is large relative to the global dimensions of the composite and the number of reinforcing fibers or inclusions is small. In these circumstances, the standard micromechanical analyses based on the concept of the representative volume element used to determine average composite properties produce questionable results. The comparison between the predictions of the finite-element method and the higher-order theory presented herein establish the theory's accuracy in predicting thermal and stress fields within composites with a finite number of fibers in the thickness direction subjected to a thorough-thickness thermal gradient.

Reproducing the nonlinear dynamic behavior of a structured beam with a generalized continuum model

NASA Astrophysics Data System (ADS)

Vila, J.; Fernández-Sáez, J.; Zaera, R.

2018-04-01

In this paper we study the coupled axial-transverse nonlinear vibrations of a kind of one dimensional structured solids by application of the so called Inertia Gradient Nonlinear continuum model. To show the accuracy of this axiomatic model, previously proposed by the authors, its predictions are compared with numeric results from a previously defined finite discrete chain of lumped masses and springs, for several number of particles. A continualization of the discrete model equations based on Taylor series allowed us to set equivalent values of the mechanical properties in both discrete and axiomatic continuum models. Contrary to the classical continuum model, the inertia gradient nonlinear continuum model used herein is able to capture scale effects, which arise for modes in which the wavelength is comparable to the characteristic distance of the structured solid. The main conclusion of the work is that the proposed generalized continuum model captures the scale effects in both linear and nonlinear regimes, reproducing the behavior of the 1D nonlinear discrete model adequately.

A New Linearized Crank-Nicolson Mixed Element Scheme for the Extended Fisher-Kolmogorov Equation

PubMed Central

Wang, Jinfeng; Li, Hong; He, Siriguleng; Gao, Wei

2013-01-01

We present a new mixed finite element method for solving the extended Fisher-Kolmogorov (EFK) equation. We first decompose the EFK equation as the two second-order equations, then deal with a second-order equation employing finite element method, and handle the other second-order equation using a new mixed finite element method. In the new mixed finite element method, the gradient ∇u belongs to the weaker (L 2(Ω))2 space taking the place of the classical H(div; Ω) space. We prove some a priori bounds for the solution for semidiscrete scheme and derive a fully discrete mixed scheme based on a linearized Crank-Nicolson method. At the same time, we get the optimal a priori error estimates in L 2 and H 1-norm for both the scalar unknown u and the diffusion term w = −Δu and a priori error estimates in (L 2)2-norm for its gradient χ = ∇u for both semi-discrete and fully discrete schemes. PMID:23864831

A new linearized Crank-Nicolson mixed element scheme for the extended Fisher-Kolmogorov equation.

PubMed

Wang, Jinfeng; Li, Hong; He, Siriguleng; Gao, Wei; Liu, Yang

2013-01-01

We present a new mixed finite element method for solving the extended Fisher-Kolmogorov (EFK) equation. We first decompose the EFK equation as the two second-order equations, then deal with a second-order equation employing finite element method, and handle the other second-order equation using a new mixed finite element method. In the new mixed finite element method, the gradient ∇u belongs to the weaker (L²(Ω))² space taking the place of the classical H(div; Ω) space. We prove some a priori bounds for the solution for semidiscrete scheme and derive a fully discrete mixed scheme based on a linearized Crank-Nicolson method. At the same time, we get the optimal a priori error estimates in L² and H¹-norm for both the scalar unknown u and the diffusion term w = -Δu and a priori error estimates in (L²)²-norm for its gradient χ = ∇u for both semi-discrete and fully discrete schemes.

Dynamical Defects in Rotating Magnetic Skyrmion Lattices

NASA Astrophysics Data System (ADS)

Pöllath, S.; Wild, J.; Heinen, L.; Meier, T. N. G.; Kronseder, M.; Tutsch, L.; Bauer, A.; Berger, H.; Pfleiderer, C.; Zweck, J.; Rosch, A.; Back, C. H.

2017-05-01

The chiral magnet Cu2 OSeO3 hosts a Skyrmion lattice that may be equivalently described as a superposition of plane waves or a lattice of particlelike topological objects. A thermal gradient may break up the Skyrmion lattice and induce rotating domains, raising the question of which of these scenarios better describes the violent dynamics at the domain boundaries. Here, we show that in an inhomogeneous temperature gradient caused by illumination in a Lorentz transmission electron microscope different parts of the Skyrmion lattice can be set into motion with different angular velocities. Tracking the time dependence, we show that the constant rearrangement of domain walls is governed by dynamic 5-7 defects arranging into lines. An analysis of the associated defect density is described by Frank's equation and agrees well with classical 2D Monte Carlo simulations. Fluctuations of boundaries show a surgelike rearrangement of Skyrmion clusters driven by defect rearrangement consistent with simulations treating Skyrmions as point particles. Our findings underline the particle character of the Skyrmion.

Tracer concentration profiles measured in central London as part of the REPARTEE campaign

NASA Astrophysics Data System (ADS)

Martin, D.; Petersson, K. F.; White, I. R.; Henshaw, S. J.; Nickless, G.; Lovelock, A.; Barlow, J. F.; Dunbar, T.; Wood, C. R.; Shallcross, D. E.

2009-11-01

There have been relatively few tracer experiments carried out that have looked at vertical plume spread in urban areas. In this paper we present results from cyclic perfluorocarbon tracer experiments carried out in 2006 and 2007 in central London centred on the BT Tower as part of the REPARTEE (Regent's Park and Tower Environmental Experiment) campaign. The height of the tower gives a unique opportunity to study dispersion over a large vertical gradient. These gradients are then compared with classical Gaussian profiles of the relevant stability classes over a range of distances as well as interpretation of data with reference to both anemometry and LIDAR measurements made. Data are then compared with an operational model and contrasted with data taken in central London as part of the DAPPLE campaign looking at dosage compared with non-dimensionalised distance from source. Such analysis illustrates the feasibility of the use of these empirical correlations over these prescribed distances in central London.

Pre-Darcy flow in tight and shale formations

NASA Astrophysics Data System (ADS)

Dejam, Morteza; Hassanzadeh, Hassan; Chen, Zhangxin

2017-11-01

There are evidences that the fluid flow in tight and shale formations does not follow Darcy law, which is identified as pre-Darcy flow. Here, the unsteady linear flow of a slightly compressible fluid under the action of pre-Darcy flow is modeled and a generalized Boltzmann transformation technique is used to solve the corresponding highly nonlinear diffusivity equation analytically. The effect of pre-Darcy flow on the pressure diffusion in a homogenous formation is studied in terms of the nonlinear exponent, m, and the threshold pressure gradient, G1. In addition, the pressure gradient, flux, and cumulative production per unit area for different m and G1 are compared with the classical solution of the diffusivity equation based on Darcy flow. Department of Petroleum Engineering in College of Engineering and Applied Science at University of Wyoming and NSERC/AI-EES(AERI)/Foundation CMG and AITF (iCORE) Chairs in Department of Chemical and Petroleum Engineering at University of Calgary.

Microfabricated Microwave-Integrated Surface Ion Trap

NASA Astrophysics Data System (ADS)

Revelle, Melissa C.; Blain, Matthew G.; Haltli, Raymond A.; Hollowell, Andrew E.; Nordquist, Christopher D.; Maunz, Peter

2017-04-01

Quantum information processing holds the key to solving computational problems that are intractable with classical computers. Trapped ions are a physical realization of a quantum information system in which qubits are encoded in hyperfine energy states. Coupling the qubit states to ion motion, as needed for two-qubit gates, is typically accomplished using Raman laser beams. Alternatively, this coupling can be achieved with strong microwave gradient fields. While microwave radiation is easier to control than a laser, it is challenging to precisely engineer the radiated microwave field. Taking advantage of Sandia's microfabrication techniques, we created a surface ion trap with integrated microwave electrodes with sub-wavelength dimensions. This multi-layered device permits co-location of the microwave antennae and the ion trap electrodes to create localized microwave gradient fields and necessary trapping fields. Here, we characterize the trap design and present simulated microwave performance with progress towards experimental results. This research was funded, in part, by the Office of the Director of National Intelligence (ODNI), Intelligence Advanced Research Projects Activity (IARPA).

Controlling heat and particle currents in nanodevices by quantum observation

NASA Astrophysics Data System (ADS)

Biele, Robert; Rodríguez-Rosario, César A.; Frauenheim, Thomas; Rubio, Angel

2017-07-01

We demonstrate that in a standard thermo-electric nanodevice the current and heat flows are not only dictated by the temperature and potential gradient, but also by the external action of a local quantum observer that controls the coherence of the device. Depending on how and where the observation takes place, the direction of heat and particle currents can be independently controlled. In fact, we show that the current and heat flow in a quantum material can go against the natural temperature and voltage gradients. Dynamical quantum observation offers new possibilities for the control of quantum transport far beyond classical thermal reservoirs. Through the concept of local projections, we illustrate how we can create and directionality control the injection of currents (electronic and heat) in nanodevices. This scheme provides novel strategies to construct quantum devices with application in thermoelectrics, spintronic injection, phononics, and sensing among others. In particular, highly efficient and selective spin injection might be achieved by local spin projection techniques.

Insufficiency of the Young’s modulus for illustrating the mechanical behavior of GaN nanowires

NASA Astrophysics Data System (ADS)

Zamani Kouhpanji, Mohammad Reza; Behzadirad, Mahmoud; Feezell, Daniel; Busani, Tito

2018-05-01

We use a non-classical modified couple stress theory including the acceleration gradients (MCST-AG), to precisely demonstrate the size dependency of the mechanical properties of gallium nitride (GaN) nanowires (NWs). The fundamental elastic constants, Young’s modulus and length scales of the GaN NWs were estimated both experimentally, using a novel experimental technique applied to atomic force microscopy, and theoretically, using atomic simulations. The Young’s modulus, static and the dynamic length scales, calculated with the MCST-AG, were found to be 323 GPa, 13 and 14.5 nm, respectively, for GaN NWs from a few nanometers radii to bulk radii. Analyzing the experimental data using the classical continuum theory shows an improvement in the experimental results by introducing smaller error. Using the length scales determined in MCST-AG, we explain the inconsistency of the Young’s moduli reported in recent literature, and we prove the insufficiency of the Young’s modulus for predicting the mechanical behavior of GaN NWs.

Swimming pattern of Pseudomonas putida - navigating with stops and reversals

NASA Astrophysics Data System (ADS)

Hintsche, Marius; Waljor, Veronika; Alirezaeizanjani, Zahra; Theves, Matthias; Beta, Carsten

Bacterial swimming strategies depend on factors such as the chemical and physical environment, as well as the flagellation pattern of a species. For some bacteria the motility pattern and the underlying flagellar dynamics are well known, such as the classical run-and-tumble behavior of E. coli. Here we study the swimming motility and chemotactic behavior of the polar, multi-flagellated soil dwelling bacterium Pseudomonas putida. Compared to E. coli, its motility pattern is more diverse. In addition to different speed levels, P. putida exhibits two types of reorientation events, stops and reversals, the occurrence of which is modulated according to the growth conditions. We also analyzed the swimming pattern in the presence of chemical gradients. Using benzoate as a chemoattractant, we measured key motility parameters in order to characterize P. putida's chemotaxis strategy and to quantify the directional bias in its random walk. Our results indicate a change in the reversal frequency depending on changes in the chemoattractant concentration consistent with the classical scenario of temporal sensing. DFG.

Sequence analysis of MHC class I α2 from sockeye salmon (Oncorhynchus nerka).

PubMed

McClelland, Erin K; Ming, Tobi J; Tabata, Amy; Miller, Kristina M

2011-09-01

Most studies assessing adaptive MHC diversity in salmon populations have focused on the classical class II DAB or DAA loci, as these have been most amenable to single PCR amplifications due to their relatively low level of sequence divergence. Herein, we report the characterization of the classical class I UBA α2 locus based on collections taken throughout the species range of sockeye salmon (Oncorhynchus nerka). Through use of multiple lineage-specific primer sets, denaturing gradient gel electrophoresis and sequencing, we identified thirty-four alleles from three highly divergent lineages. Sequence identity between lineages ranged from 30.0% to 56.8% but was relatively high within lineages. Allelic identity within the antigen recognition site (ARS) was greater than for the longer sequence. Global positive selection on UBA was seen at the sequence level (dN:dS = 1.012) with four codons under positive selection and 12 codons under negative selection. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Quantum annealing versus classical machine learning applied to a simplified computational biology problem

NASA Astrophysics Data System (ADS)

Li, Richard Y.; Di Felice, Rosa; Rohs, Remo; Lidar, Daniel A.

2018-03-01

Transcription factors regulate gene expression, but how these proteins recognize and specifically bind to their DNA targets is still debated. Machine learning models are effective means to reveal interaction mechanisms. Here we studied the ability of a quantum machine learning approach to classify and rank binding affinities. Using simplified data sets of a small number of DNA sequences derived from actual binding affinity experiments, we trained a commercially available quantum annealer to classify and rank transcription factor binding. The results were compared to state-of-the-art classical approaches for the same simplified data sets, including simulated annealing, simulated quantum annealing, multiple linear regression, LASSO, and extreme gradient boosting. Despite technological limitations, we find a slight advantage in classification performance and nearly equal ranking performance using the quantum annealer for these fairly small training data sets. Thus, we propose that quantum annealing might be an effective method to implement machine learning for certain computational biology problems.

Solving an inverse eigenvalue problem with triple constraints on eigenvalues, singular values, and diagonal elements

NASA Astrophysics Data System (ADS)

Wu, Sheng-Jhih; Chu, Moody T.

2017-08-01

An inverse eigenvalue problem usually entails two constraints, one conditioned upon the spectrum and the other on the structure. This paper investigates the problem where triple constraints of eigenvalues, singular values, and diagonal entries are imposed simultaneously. An approach combining an eclectic mix of skills from differential geometry, optimization theory, and analytic gradient flow is employed to prove the solvability of such a problem. The result generalizes the classical Mirsky, Sing-Thompson, and Weyl-Horn theorems concerning the respective majorization relationships between any two of the arrays of main diagonal entries, eigenvalues, and singular values. The existence theory fills a gap in the classical matrix theory. The problem might find applications in wireless communication and quantum information science. The technique employed can be implemented as a first-step numerical method for constructing the matrix. With slight modification, the approach might be used to explore similar types of inverse problems where the prescribed entries are at general locations.

Insufficiency of the Young's modulus for illustrating the mechanical behavior of GaN nanowires.

PubMed

Kouhpanji, Mohammad Reza Zamani; Behzadirad, Mahmoud; Feezell, Daniel; Busani, Tito

2018-05-18

We use a non-classical modified couple stress theory including the acceleration gradients (MCST-AG), to precisely demonstrate the size dependency of the mechanical properties of gallium nitride (GaN) nanowires (NWs). The fundamental elastic constants, Young's modulus and length scales of the GaN NWs were estimated both experimentally, using a novel experimental technique applied to atomic force microscopy, and theoretically, using atomic simulations. The Young's modulus, static and the dynamic length scales, calculated with the MCST-AG, were found to be 323 GPa, 13 and 14.5 nm, respectively, for GaN NWs from a few nanometers radii to bulk radii. Analyzing the experimental data using the classical continuum theory shows an improvement in the experimental results by introducing smaller error. Using the length scales determined in MCST-AG, we explain the inconsistency of the Young's moduli reported in recent literature, and we prove the insufficiency of the Young's modulus for predicting the mechanical behavior of GaN NWs.

Quantum optical effective-medium theory and transformation quantum optics for metamaterials

NASA Astrophysics Data System (ADS)

Wubs, Martijn; Amooghorban, Ehsan; Zhang, Jingjing; Mortensen, N. Asger

2016-09-01

While typically designed to manipulate classical light, metamaterials have many potential applications for quantum optics as well. We argue why a quantum optical effective-medium theory is needed. We present such a theory for layered metamaterials that is valid for light propagation in all spatial directions, thereby generalizing earlier work for one-dimensional propagation. In contrast to classical effective-medium theory there is an additional effective parameter that describes quantum noise. Our results for metamaterials are based on a rather general Lagrangian theory for the quantum electrodynamics of media with both loss and gain. In the second part of this paper, we present a new application of transformation optics whereby local spontaneous-emission rates of quantum emitters can be designed. This follows from an analysis how electromagnetic Green functions trans- form under coordinate transformations. Spontaneous-emission rates can be either enhanced or suppressed using invisibility cloaks or gradient index lenses. Furthermore, the anisotropic material profile of the cloak enables the directional control of spontaneous emission.

Outcomes of Corneal Cross-Linking Correlate With Cone-Specific Lysyl Oxidase Expression in Patients With Keratoconus.

PubMed

Shetty, Rohit; Rajiv Kumar, Nimisha; Pahuja, Natasha; Deshmukh, Rashmi; Vunnava, KrishnaPoojita; Abilash, Valsala Gopalakrishnan; Sinha Roy, Abhijit; Ghosh, Arkasubhra

2018-03-01

To evaluate the correlation of visual and keratometry outcomes after corneal cross-linking (CXL) in patients with keratoconus with cone epithelium-specific gene expression levels. Corneal epithelium was obtained from 35 eyes that underwent accelerated CXL (KXLII, 9 mW/cm for 10 min). Using corneal topography, epithelium over the cone and periphery was obtained separately from each subject. The ratio of gene expression for lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), bone morphogenic protein 7, tissue inhibitor of metalloproteinase 1, collagen, type I, alpha 1, and collagen, type IV, alpha 1 (COL IVA1) from the cone and peripheral cornea was correlated with the outcome of cross-linking surgery. Patients were assessed for visual acuity, keratometry, refraction, and corneal densitometry before and 6 months after surgery. Based on the change in corneal flattening indicated by ΔKmax, the outcomes were classified as a higher response or lower response. Reduction in keratometric indices correlated with improved spherical equivalent after CXL. Preoperative levels of cone-specific LOX expression in cases with a higher response were significant (P = 0.001). COL IVA1, bone morphogenic protein 7, and tissue inhibitor of metalloproteinase 1 gene expressions were reduced in the cones of the subjects with a lower response. MMP9 levels were relatively lower in cases with a higher response compared with those with a lower response. Our study demonstrates that preoperative levels of molecular factors such as LOX, MMP9, and COL IVA1 aid in understanding CXL outcomes at the tissue level.

Gene expression in spider appendages reveals reversal of exd/hth spatial specificity, altered leg gap gene dynamics, and suggests divergent distal morphogen signaling.

PubMed

Prpic, Nikola-Michael; Janssen, Ralf; Wigand, Barbara; Klingler, Martin; Damen, Wim G M

2003-12-01

Leg development in Drosophila has been studied in much detail. However, Drosophila limbs form in the larva as imaginal discs and not during embryogenesis as in most other arthropods. Here, we analyze appendage genes in the spider Cupiennius salei and the beetle Tribolium castaneum. Differences in decapentaplegic (dpp) expression suggest a different mode of distal morphogen signaling suitable for the specific geometry of growing limb buds. Also, expression of the proximal genes homothorax (hth) and extradenticle (exd) is significantly altered: in the spider, exd is restricted to the proximal leg and hth expression extends distally, while in insects, exd is expressed in the entire leg and hth is restricted to proximal parts. This reversal of spatial specificity demonstrates an evolutionary shift, which is nevertheless compatible with a conserved role of this gene pair as instructor of proximal fate. Different expression dynamics of dachshund and Distal-less point to modifications in the regulation of the leg gap gene system. We comment on the significance of this finding for attempts to homologize leg segments in different arthropod classes. Comparison of the expression profiles of H15 and optomotor-blind to the Drosophila patterns suggests modifications also in the dorsal-ventral patterning system of the legs. Together, our results suggest alterations in many components of the leg developmental system, namely proximal-distal and dorsal-ventral patterning, and leg segmentation. Thus, the leg developmental system exhibits a propensity to evolutionary change, which probably forms the basis for the impressive diversity of arthropod leg morphologies.

Rapid Activation of Bone Morphogenic Protein 9 by Receptor-mediated Displacement of Pro-domains*

PubMed Central

Kienast, Yvonne; Jucknischke, Ute; Scheiblich, Stefan; Thier, Martina; de Wouters, Mariana; Haas, Alexander; Lehmann, Christian; Brand, Verena; Bernicke, Dirk; Honold, Konrad; Lorenz, Stefan

2016-01-01

By non-covalent association after proteolytic cleavage, the pro-domains modulate the activities of the mature growth factor domains across the transforming growth factor-β family. In the case of bone morphogenic protein 9 (BMP9), however, the pro-domains do not inhibit the bioactivity of the growth factor, and the BMP9·pro-domain complexes have equivalent biological activities as the BMP9 mature ligand dimers. By using real-time surface plasmon resonance, we could demonstrate that either binding of pro-domain-complexed BMP9 to type I receptor activin receptor-like kinase 1 (ALK1), type II receptors, co-receptor endoglin, or to mature BMP9 domain targeting antibodies leads to immediate and complete displacement of the pro-domains from the complex. Vice versa, pro-domain binding by an anti-pro-domain antibody results in release of the mature BMP9 growth factor. Based on these findings, we adjusted ELISA assays to measure the protein levels of different BMP9 variants. Although mature BMP9 and inactive precursor BMP9 protein were directly detectable by ELISA, BMP9·pro-domain complex could only be measured indirectly as dissociated fragments due to displacement of mature growth factor and pro-domains after antibody binding. Our studies provide a model in which BMP9 can be readily activated upon getting into contact with its receptors. This increases the understanding of the underlying biology of BMP9 activation and also provides guidance for ELISA development for the detection of circulating BMP9 variants. PMID:26677222

Turing mechanism underlying a branching model for lung morphogenesis.

PubMed

Xu, Hui; Sun, Mingzhu; Zhao, Xin

2017-01-01

The mammalian lung develops through branching morphogenesis. Two primary forms of branching, which occur in order, in the lung have been identified: tip bifurcation and side branching. However, the mechanisms of lung branching morphogenesis remain to be explored. In our previous study, a biological mechanism was presented for lung branching pattern formation through a branching model. Here, we provide a mathematical mechanism underlying the branching patterns. By decoupling the branching model, we demonstrated the existence of Turing instability. We performed Turing instability analysis to reveal the mathematical mechanism of the branching patterns. Our simulation results show that the Turing patterns underlying the branching patterns are spot patterns that exhibit high local morphogen concentration. The high local morphogen concentration induces the growth of branching. Furthermore, we found that the sparse spot patterns underlie the tip bifurcation patterns, while the dense spot patterns underlies the side branching patterns. The dispersion relation analysis shows that the Turing wavelength affects the branching structure. As the wavelength decreases, the spot patterns change from sparse to dense, the rate of tip bifurcation decreases and side branching eventually occurs instead. In the process of transformation, there may exists hybrid branching that mixes tip bifurcation and side branching. Since experimental studies have reported that branching mode switching from side branching to tip bifurcation in the lung is under genetic control, our simulation results suggest that genes control the switch of the branching mode by regulating the Turing wavelength. Our results provide a novel insight into and understanding of the formation of branching patterns in the lung and other biological systems.

Characterization of Generalized Young Measures Generated by Symmetric Gradients

NASA Astrophysics Data System (ADS)

De Philippis, Guido; Rindler, Filip

2017-06-01

This work establishes a characterization theorem for (generalized) Young measures generated by symmetric derivatives of functions of bounded deformation (BD) in the spirit of the classical Kinderlehrer-Pedregal theorem. Our result places such Young measures in duality with symmetric-quasiconvex functions with linear growth. The "local" proof strategy combines blow-up arguments with the singular structure theorem in BD (the analogue of Alberti's rank-one theorem in BV), which was recently proved by the authors. As an application of our characterization theorem we show how an atomic part in a BD-Young measure can be split off in generating sequences.

Symbolic computer vector analysis

NASA Technical Reports Server (NTRS)

Stoutemyer, D. R.

1977-01-01

A MACSYMA program is described which performs symbolic vector algebra and vector calculus. The program can combine and simplify symbolic expressions including dot products and cross products, together with the gradient, divergence, curl, and Laplacian operators. The distribution of these operators over sums or products is under user control, as are various other expansions, including expansion into components in any specific orthogonal coordinate system. There is also a capability for deriving the scalar or vector potential of a vector field. Examples include derivation of the partial differential equations describing fluid flow and magnetohydrodynamics, for 12 different classic orthogonal curvilinear coordinate systems.

Flow induced crystallisation of penetrable particles

NASA Astrophysics Data System (ADS)

Scacchi, Alberto; Brader, Joseph M.

2018-03-01

For a system of Brownian particles interacting via a soft exponential potential we investigate the interaction between equilibrium crystallisation and spatially varying shear flow. For thermodynamic state points within the liquid part of the phase diagram, but close to the crystallisation phase boundary, we observe that imposing a Poiseuille flow can induce nonequilibrium crystalline ordering in regions of low shear gradient. The physical mechanism responsible for this phenomenon is shear-induced particle migration, which causes particles to drift preferentially towards the center of the flow channel, thus increasing the local density in the channel center. The method employed is classical dynamical density functional theory.

Flow induced crystallisation of penetrable particles.

PubMed

Scacchi, Alberto; Brader, Joseph M

2018-03-07

For a system of Brownian particles interacting via a soft exponential potential we investigate the interaction between equilibrium crystallisation and spatially varying shear flow. For thermodynamic state points within the liquid part of the phase diagram, but close to the crystallisation phase boundary, we observe that imposing a Poiseuille flow can induce nonequilibrium crystalline ordering in regions of low shear gradient. The physical mechanism responsible for this phenomenon is shear-induced particle migration, which causes particles to drift preferentially towards the center of the flow channel, thus increasing the local density in the channel center. The method employed is classical dynamical density functional theory.

Understanding High Temperature Gradients in the Buckman Well Field, Santa Fe County, New Mexico

NASA Astrophysics Data System (ADS)

Folsom, M.; Gulvin, C. J.; Tamakloe, F. M.; Yauk, K.; Kelley, S.; Frost, J.; Jiracek, G. R.

2014-12-01

We propose a conceptual model to explain elevated thermal gradients, localized laterally over a few 100 m, discovered during the SAGE program in 2013 and confirmed in 2014 at the Buckman water well field in the Española Basin of north central New Mexico. The anomalous gradients of temperature with depth, dT/dz, exceed 70 ºC/km and are found in three shallow (< 100 m-deep) USGS monitoring wells close to the Rio Grande. A temperature increase of only 3 - 4 ºC at ~100 m depth would elevate the regional temperature value enough to yield the anomalous dT/dz values in the upper ~100 m. The coincidence of a 25 km2 region of InSAR-confirmed subsidence with the locally anomalous dT/dz region suggests a way to achieve a higher temperature at ~ 100 m depth. The mechanism is an isothermal release of warmer water from ~ 200 m depth along a fissure or reactivated fault. A fourth well, 290 m away, has a temperature gradient of only 33ºC/km in the upper 100 m and a distinctly different geochemical profile, suggesting aquifer compartmentalization and possible faulting close to the anomaly. In 2001 a 800 m-long surface scarp with up to 0.2 m offset appeared 2 km to the east in response to over-pumping that depressed the groundwater table by over 100 m. Such drawdown is expected to have 2 - 5 m of compaction with attendant movement along faults or fissures. This could allow groundwater to be released upward isothermally until encountering an unbreached aquitard where it would establish an elevated thermal boundary. Besides the local thermal anomaly, we have temperature-logged deeper water wells in the area. These and other measurements have been used to construct cross-sections of isotherms across the Española Basin along the groundwater flow units (GFUs). This allows comparison of the local thermal anomaly with classic, regional, basin hydrological models. For example, the fully-screened Skillet well, 2.3 km from the anomaly, shows a classic concave down dT/dz form indicating upwelling water. This is consistent with the regional hydraulic head and historical accounts of artesian wells pre-dating Buckman pumping. We quantified the upwelling by Péclet number analysis to be 0.076 - 0.11 m/yr. Numerical modeling using the TOUGH2 computer code is proceeding to further understand regional and local subsurface groundwater flow patterns and dT/dz values.

Drosophila melanogaster Hedgehog cooperates with Frazzled to guide axons through a non-canonical signalling pathway.

PubMed

Ricolo, Delia; Butí, Elisenda; Araújo, Sofia J

2015-08-01

We report that the morphogen Hedgehog (Hh) is an axonal chemoattractant in the midline of Drosophila melanogaster embryos. Hh is present in the ventral nerve cord during axonal guidance and overexpression of hh in the midline causes ectopic midline crossing of FasII-positive axonal tracts. In addition, we show that Hh influences axonal guidance via a non-canonical signalling pathway dependent on Ptc. Our results reveal that the Hh pathway cooperates with the Netrin/Frazzled pathway to guide axons through the midline in invertebrates. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Xanthan gum: an economical substitute for agar in plant tissue culture media.

PubMed

Jain, R; Babbar, S B

2006-03-01

Xanthan gum, a microbial desiccation-resistant polysaccharide prepared commercially by aerobic submerged fermentation from Xanthomonas campestris, has been successfully used as a solidifying agent for plant tissue culture media. Its suitability as a substitute to agar was demonstrated for in vitro seed germination, caulogenesis and rhizogenesis of Albizzia lebbeck, androgenesis in anther cultures of Datura innoxia, and somatic embryogenesis in callus cultures of Calliandra tweedii. Culture media used for eliciting these morphogenic responses were gelled with either 1% xanthan gum or 0.9% agar. Xanthan gum, like agar, supported all these responses.

Analysis of Morphogenic Effect of hDAB2IP on Prostate Cancer and its Disease Correlation

DTIC Science & Technology

2005-02-01

Ezh2 protein became more prominent 96 hrs RESULTS after transfection. Under this condition , Profiling hDAB2IP and Ezh2 the elevated levels of hDAB2IP...Pirrotta, V., Poux, S., Melfi, R., S., Vessella, R., Lin, D. L., and Pilyugin, M. (2003) Genetica Pienta, K. J. (2001) In Vivo. 15, 117:191-197 163-168...performed using iCycler machine (Bio-Rad) and the reaction condition was as follow: 95’C (3 min) and 40 cycles amplification cycle (95 0C [30 sec], 55°C

An integrative approach to apprehend desistance.

PubMed

F-Dufour, Isabelle; Brassard, Renée; Martel, Joane

2015-05-01

The process underlying desistance is still a strong subject of debate. This article seeks to introduce several core concepts of Archer's morphogenic approach to study how people desist from crime. At first, it discusses the primary existing theories of desistance. Then, this article demonstrates the usefulness of this approach by presenting empirical evidence drawn from semistructured interviews collected with 29 men who desisted from crime in an eastern province of Canada. The study demonstrates how this alternative approach allows for the consolidation of existing knowledge on desistance. Then implication of these findings for both theory and practice are discussed. © The Author(s) 2013.

Velocity Inversion In Cylindrical Couette Gas Flows

NASA Astrophysics Data System (ADS)

Dongari, Nishanth; Barber, Robert W.; Emerson, David R.; Zhang, Yonghao; Reese, Jason M.

2012-05-01

We investigate a power-law probability distribution function to describe the mean free path of rarefied gas molecules in non-planar geometries. A new curvature-dependent model is derived by taking into account the boundary-limiting effects on the molecular mean free path for surfaces with both convex and concave curvatures. In comparison to a planar wall, we find that the mean free path for a convex surface is higher at the wall and exhibits a sharper gradient within the Knudsen layer. In contrast, a concave wall exhibits a lower mean free path near the surface and the gradients in the Knudsen layer are shallower. The Navier-Stokes constitutive relations and velocity-slip boundary conditions are modified based on a power-law scaling to describe the mean free path, in accordance with the kinetic theory of gases, i.e. transport properties can be described in terms of the mean free path. Velocity profiles for isothermal cylindrical Couette flow are obtained using the power-law model. We demonstrate that our model is more accurate than the classical slip solution, especially in the transition regime, and we are able to capture important non-linear trends associated with the non-equilibrium physics of the Knudsen layer. In addition, we establish a new criterion for the critical accommodation coefficient that leads to the non-intuitive phenomena of velocity-inversion. Our results are compared with conventional hydrodynamic models and direct simulation Monte Carlo data. The power-law model predicts that the critical accommodation coefficient is significantly lower than that calculated using the classical slip solution and is in good agreement with available DSMC data. Our proposed constitutive scaling for non-planar surfaces is based on simple physical arguments and can be readily implemented in conventional fluid dynamics codes for arbitrary geometric configurations.

A look-ahead variant of the Lanczos algorithm and its application to the quasi-minimal residual method for non-Hermitian linear systems. Ph.D. Thesis - Massachusetts Inst. of Technology, Aug. 1991

NASA Technical Reports Server (NTRS)

Nachtigal, Noel M.

1991-01-01

The Lanczos algorithm can be used both for eigenvalue problems and to solve linear systems. However, when applied to non-Hermitian matrices, the classical Lanczos algorithm is susceptible to breakdowns and potential instabilities. In addition, the biconjugate gradient (BCG) algorithm, which is the natural generalization of the conjugate gradient algorithm to non-Hermitian linear systems, has a second source of breakdowns, independent of the Lanczos breakdowns. Here, we present two new results. We propose an implementation of a look-ahead variant of the Lanczos algorithm which overcomes the breakdowns by skipping over those steps where a breakdown or a near-breakdown would occur. The new algorithm can handle look-ahead steps of any length and requires the same number of matrix-vector products and inner products per step as the classical Lanczos algorithm without look-ahead. Based on the proposed look-ahead Lanczos algorithm, we then present a novel BCG-like approach, the quasi-minimal residual (QMR) method, which avoids the second source of breakdowns in the BCG algorithm. We present details of the new method and discuss some of its properties. In particular, we discuss the relationship between QMR and BCG, showing how one can recover the BCG iterates, when they exist, from the QMR iterates. We also present convergence results for QMR, showing the connection between QMR and the generalized minimal residual (GMRES) algorithm, the optimal method in this class of methods. Finally, we give some numerical examples, both for eigenvalue computations and for non-Hermitian linear systems.

Phase unwrapping methods of corner reflector DInSAR monitoring slow ground deformation

NASA Astrophysics Data System (ADS)

Fu, Wenxue; Guo, Xiaofang; Tian, Qingjiu

2007-06-01

Difference interferometric Synthetic aperture radar (DInSAR) has turned out to be a very powerful technique for the measurement of land deformations, but it requires the observed area to be correlated, and coherence degradation will seriously affect the quality of interferogram. Corner reflector DInSAR (CRDInSAR) is a new technique in recently years, which can compensate for the limitation of the classical DInSAR. Due to the stable amplitude and phase performance of the reflector, the interferometric phase difference of the reflector can be used to monitor or measure the small and slowly ground deformation for the cases of large geometrical baseline and large time interval between acquisitions. Phase unwrapping is the process where the absolute phase is reconstructed from its principal value as accurately as possible. It is a key step in the analysis of DInSAR. The classical phase unwrapping methods are either of path following type or of minimum-norm type. However, if the coherence of the two images is very low, the both methods will get error result. In application of CRDInSAR, due to the scattered points, the phase unwrapping of corner reflectors is only dealt with on a sparse grid, so all the reflectors are connected with Delaunay triangulation firstly, which can be used to define neighboring points and elementary cycles. When the monitoring ground deformation is slow, that is unwrapped neighboring-CR phase gradients are supposed to equal their wrapped-phase counterparts, then path-following method and Phase unwrapping using Coefficient of Elevation-Phase-Relation can be used to phase unwrapping. However, in the cases of unwrapped gradients exceeding one-half cycle, minimum cost flow (MCF) method can be used to unwrap the interferogram.

Analytic non-Maxwellian electron velocity distribution function in a Hall discharge plasma

NASA Astrophysics Data System (ADS)

Shagayda, Andrey; Tarasov, Alexey

2017-10-01

The electron velocity distribution function in the low-pressure discharges with the crossed electric and magnetic fields, which occur in magnetrons, plasma accelerators, and Hall thrusters with a closed electron drift, is not Maxwellian. A deviation from equilibrium is caused by a large electron mean free path relative to the Larmor radius and the size of the discharge channel. In this study, we derived in the relaxation approximation the analytical expression of the electron velocity distribution function in a weakly ionized Lorentz plasma with the crossed electric and magnetic fields in the presence of the electron density and temperature gradients in the direction of the electric field. The solution was obtained in the stationary approximation far from boundary surfaces, when diffusion and mobility are determined by the classical effective collision frequency of electrons with ions and atoms. The moments of the distribution function including the average velocity, the stress tensor, and the heat flux were calculated and compared with the classical hydrodynamic expressions. It was shown that a kinetic correction to the drift velocity stems from a contribution of the off-diagonal component of the stress tensor. This correction becomes essential if the drift velocity in the crossed electric and magnetic fields would be comparable to the thermal velocity of electrons. The electron temperature has three different components at a nonzero effective collision frequency and two different components in the limit when the collision frequency tends to zero. It is shown that, in the presence of ionization collisions, the components of the heat flux have additives that are not related to the temperature gradient, and arise because of the electron drift.

Sweeping as a multistep enrichment process in micellar electrokinetic chromatography: the retention factor gradient effect.

PubMed

El-Awady, Mohamed; Pyell, Ute

2013-07-05

The application of a new method developed for the assessment of sweeping efficiency in MEKC under homogeneous and inhomogeneous electric field conditions is extended to the general case, in which the distribution coefficient and the electric conductivity of the analyte in the sample zone and in the separation compartment are varied. As test analytes p-hydroxybenzoates (parabens), benzamide and some aromatic amines are studied under MEKC conditions with SDS as anionic surfactant. We show that in the general case - in contrast to the classical description - the obtainable enrichment factor is not only dependent on the retention factor of the analyte in the sample zone but also dependent on the retention factor in the background electrolyte (BGE). It is shown that in the general case sweeping is inherently a multistep focusing process. We describe an additional focusing/defocusing step (the retention factor gradient effect, RFGE) quantitatively by extending the classical equation employed for the description of the sweeping process with an additional focusing/defocusing factor. The validity of this equation is demonstrated experimentally (and theoretically) under variation of the organic solvent content (in the sample and/or the BGE), the type of organic solvent (in the sample and/or the BGE), the electric conductivity (in the sample), the pH (in the sample), and the concentration of surfactant (in the BGE). It is shown that very high enrichment factors can be obtained, if the pH in the sample zone makes possible to convert the analyte into a charged species that has a high distribution coefficient with respect to an oppositely charged micellar phase, while the pH in the BGE enables separation of the neutral species under moderate retention factor conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

SegAN: Adversarial Network with Multi-scale L1 Loss for Medical Image Segmentation.

PubMed

Xue, Yuan; Xu, Tao; Zhang, Han; Long, L Rodney; Huang, Xiaolei

2018-05-03

Inspired by classic Generative Adversarial Networks (GANs), we propose a novel end-to-end adversarial neural network, called SegAN, for the task of medical image segmentation. Since image segmentation requires dense, pixel-level labeling, the single scalar real/fake output of a classic GAN's discriminator may be ineffective in producing stable and sufficient gradient feedback to the networks. Instead, we use a fully convolutional neural network as the segmentor to generate segmentation label maps, and propose a novel adversarial critic network with a multi-scale L 1 loss function to force the critic and segmentor to learn both global and local features that capture long- and short-range spatial relationships between pixels. In our SegAN framework, the segmentor and critic networks are trained in an alternating fashion in a min-max game: The critic is trained by maximizing a multi-scale loss function, while the segmentor is trained with only gradients passed along by the critic, with the aim to minimize the multi-scale loss function. We show that such a SegAN framework is more effective and stable for the segmentation task, and it leads to better performance than the state-of-the-art U-net segmentation method. We tested our SegAN method using datasets from the MICCAI BRATS brain tumor segmentation challenge. Extensive experimental results demonstrate the effectiveness of the proposed SegAN with multi-scale loss: on BRATS 2013 SegAN gives performance comparable to the state-of-the-art for whole tumor and tumor core segmentation while achieves better precision and sensitivity for Gd-enhance tumor core segmentation; on BRATS 2015 SegAN achieves better performance than the state-of-the-art in both dice score and precision.

Stationary temperature profiles in a liquid nanochannel: Comparisons between molecular-dynamics simulation and classical hydrostatics

NASA Astrophysics Data System (ADS)

Okumura, Hisashi; Heyes, David M.

2006-12-01

We compare the results of three-dimensional molecular-dynamics (MD) simulations of a Lennard-Jones (LJ) liquid with a hydrostatic (HS) solution of a high temperature liquid channel which is surrounded by a fluid at lower temperature. The maximum temperature gradient, dT/dx , between the two temperature regions ranged from ∞ (step function) to dT/dx=0.1 (in the usual LJ units). Because the systems were in stationary-nonequilibrium states with no fluid flow, both MD simulation and the HS solution gave flat profiles for the normal pressure in all temperature-gradient cases. However, the other quantities showed differences between the two methods. The MD-derived density was found to oscillate over the length of ca. 8 LJ particle diameters from the boundary plane in the system with the infinite temperature gradient, while the HS-derived density showed simply a stepwise profile. The MD simulation also showed another anomaly near the boundary in potential energy. We have found systems in which the HS treatment works well and those where the HS approach breaks down, and therefore established the minimum length scale for the HS treatment to be valid. We also compare the kinetic temperature and the configurational temperature in these systems, and show that these can differ in the transition zone between the two temperatures.

Stationary temperature profiles in a liquid nanochannel: comparisons between molecular-dynamics simulation and classical hydrostatics.

PubMed

Okumura, Hisashi; Heyes, David M

2006-12-01

We compare the results of three-dimensional molecular-dynamics (MD) simulations of a Lennard-Jones (LJ) liquid with a hydrostatic (HS) solution of a high temperature liquid channel which is surrounded by a fluid at lower temperature. The maximum temperature gradient, dT/dx , between the two temperature regions ranged from infinity (step function) to dT/dx=0.1 (in the usual LJ units). Because the systems were in stationary-nonequilibrium states with no fluid flow, both MD simulation and the HS solution gave flat profiles for the normal pressure in all temperature-gradient cases. However, the other quantities showed differences between the two methods. The MD-derived density was found to oscillate over the length of ca. 8 LJ particle diameters from the boundary plane in the system with the infinite temperature gradient, while the HS-derived density showed simply a stepwise profile. The MD simulation also showed another anomaly near the boundary in potential energy. We have found systems in which the HS treatment works well and those where the HS approach breaks down, and therefore established the minimum length scale for the HS treatment to be valid. We also compare the kinetic temperature and the configurational temperature in these systems, and show that these can differ in the transition zone between the two temperatures.

Evolution of a predator-induced, nonlinear reaction norm.

PubMed

Carter, Mauricio J; Lind, Martin I; Dennis, Stuart R; Hentley, William; Beckerman, Andrew P

2017-08-30

Inducible, anti-predator traits are a classic example of phenotypic plasticity. Their evolutionary dynamics depend on their genetic basis, the historical pattern of predation risk that populations have experienced and current selection gradients. When populations experience predators with contrasting hunting strategies and size preferences, theory suggests contrasting micro-evolutionary responses to selection. Daphnia pulex is an ideal species to explore the micro-evolutionary response of anti-predator traits because they face heterogeneous predation regimes, sometimes experiencing only invertebrate midge predators and other times experiencing vertebrate fish and invertebrate midge predators. We explored plausible patterns of adaptive evolution of a predator-induced morphological reaction norm. We combined estimates of selection gradients that characterize the various habitats that D. pulex experiences with detail on the quantitative genetic architecture of inducible morphological defences. Our data reveal a fine scale description of daphnid defensive reaction norms, and a strong covariance between the sensitivity to cues and the maximum response to cues. By analysing the response of the reaction norm to plausible, predator-specific selection gradients, we show how in the context of this covariance, micro-evolution may be more uniform than predicted from size-selective predation theory. Our results show how covariance between the sensitivity to cues and the maximum response to cues for morphological defence can shape the evolutionary trajectory of predator-induced defences in D. pulex . © 2017 The Authors.

A Comprehensive Quality Evaluation System for Complex Herbal Medicine Using PacBio Sequencing, PCR-Denaturing Gradient Gel Electrophoresis, and Several Chemical Approaches

PubMed Central

Zheng, Xiasheng; Zhang, Peng; Liao, Baosheng; Li, Jing; Liu, Xingyun; Shi, Yuhua; Cheng, Jinle; Lai, Zhitian; Xu, Jiang; Chen, Shilin

2017-01-01

Herbal medicine is a major component of complementary and alternative medicine, contributing significantly to the health of many people and communities. Quality control of herbal medicine is crucial to ensure that it is safe and sound for use. Here, we investigated a comprehensive quality evaluation system for a classic herbal medicine, Danggui Buxue Formula, by applying genetic-based and analytical chemistry approaches to authenticate and evaluate the quality of its samples. For authenticity, we successfully applied two novel technologies, third-generation sequencing and PCR-DGGE (denaturing gradient gel electrophoresis), to analyze the ingredient composition of the tested samples. For quality evaluation, we used high performance liquid chromatography assays to determine the content of chemical markers to help estimate the dosage relationship between its two raw materials, plant roots of Huangqi and Danggui. A series of surveys were then conducted against several exogenous contaminations, aiming to further access the efficacy and safety of the samples. In conclusion, the quality evaluation system demonstrated here can potentially address the authenticity, quality, and safety of herbal medicines, thus providing novel insight for enhancing their overall quality control. Highlight: We established a comprehensive quality evaluation system for herbal medicine, by combining two genetic-based approaches third-generation sequencing and DGGE (denaturing gradient gel electrophoresis) with analytical chemistry approaches to achieve the authentication and quality connotation of the samples. PMID:28955365

A Comprehensive Quality Evaluation System for Complex Herbal Medicine Using PacBio Sequencing, PCR-Denaturing Gradient Gel Electrophoresis, and Several Chemical Approaches.

PubMed

Zheng, Xiasheng; Zhang, Peng; Liao, Baosheng; Li, Jing; Liu, Xingyun; Shi, Yuhua; Cheng, Jinle; Lai, Zhitian; Xu, Jiang; Chen, Shilin

2017-01-01

Herbal medicine is a major component of complementary and alternative medicine, contributing significantly to the health of many people and communities. Quality control of herbal medicine is crucial to ensure that it is safe and sound for use. Here, we investigated a comprehensive quality evaluation system for a classic herbal medicine, Danggui Buxue Formula, by applying genetic-based and analytical chemistry approaches to authenticate and evaluate the quality of its samples. For authenticity, we successfully applied two novel technologies, third-generation sequencing and PCR-DGGE (denaturing gradient gel electrophoresis), to analyze the ingredient composition of the tested samples. For quality evaluation, we used high performance liquid chromatography assays to determine the content of chemical markers to help estimate the dosage relationship between its two raw materials, plant roots of Huangqi and Danggui. A series of surveys were then conducted against several exogenous contaminations, aiming to further access the efficacy and safety of the samples. In conclusion, the quality evaluation system demonstrated here can potentially address the authenticity, quality, and safety of herbal medicines, thus providing novel insight for enhancing their overall quality control. Highlight : We established a comprehensive quality evaluation system for herbal medicine, by combining two genetic-based approaches third-generation sequencing and DGGE (denaturing gradient gel electrophoresis) with analytical chemistry approaches to achieve the authentication and quality connotation of the samples.

Morphology dependent near-field response in atomistic plasmonic nanocavities.

PubMed

Chen, Xing; Jensen, Lasse

2018-06-21

In this work we examine how the atomistic morphologies of plasmonic dimers control the near-field response by using an atomistic electrodynamics model. At large separations, the field enhancement in the junction follows a simple inverse power law as a function of the gap separation, which agrees with classical antenna theory. However, when the separations are smaller than 0.8 nm, the so-called quantum size regime, the field enhancement is screened and thus deviates from the simple power law. Our results show that the threshold distance for the deviation depends on the specific morphology of the junction. The near field in the junction can be localized to an area of less than 1 nm2 in the presence of an atomically sharp tip, but the separation distances leading to a large confinement of near field depend strongly on the specific atomistic configuration. More importantly, the highly confined fields lead to large field gradients particularly in a tip-to-surface junction, which indicates that such a plasmonic structure favors observing strong field gradient effects in near-field spectroscopy. We find that for atomically sharp tips the field gradient becomes significant and depends strongly on the local morphology of a tip. We expect our findings to be crucial for understanding the origin of high-resolution near-field spectroscopy and for manipulating optical cavities through atomic structures in the strongly coupled plasmonic systems.

Congested Aggregation via Newtonian Interaction

NASA Astrophysics Data System (ADS)

Craig, Katy; Kim, Inwon; Yao, Yao

2018-01-01

We consider a congested aggregation model that describes the evolution of a density through the competing effects of nonlocal Newtonian attraction and a hard height constraint. This provides a counterpoint to existing literature on repulsive-attractive nonlocal interaction models, where the repulsive effects instead arise from an interaction kernel or the addition of diffusion. We formulate our model as the Wasserstein gradient flow of an interaction energy, with a penalization to enforce the constraint on the height of the density. From this perspective, the problem can be seen as a singular limit of the Keller-Segel equation with degenerate diffusion. Two key properties distinguish our problem from previous work on height constrained equations: nonconvexity of the interaction kernel (which places the model outside the scope of classical gradient flow theory) and nonlocal dependence of the velocity field on the density (which causes the problem to lack a comparison principle). To overcome these obstacles, we combine recent results on gradient flows of nonconvex energies with viscosity solution theory. We characterize the dynamics of patch solutions in terms of a Hele-Shaw type free boundary problem and, using this characterization, show that in two dimensions patch solutions converge to a characteristic function of a disk in the long-time limit, with an explicit rate on the decay of the energy. We believe that a key contribution of the present work is our blended approach, combining energy methods with viscosity solution theory.

A Dissolved Oxygen Threshold for Shifts in Bacterial Community Structure in a Seasonally Hypoxic Estuary.

PubMed

Spietz, Rachel L; Williams, Cheryl M; Rocap, Gabrielle; Horner-Devine, M Claire

2015-01-01

Pelagic ecosystems can become depleted of dissolved oxygen as a result of both natural processes and anthropogenic effects. As dissolved oxygen concentration decreases, energy shifts from macrofauna to microorganisms, which persist in these hypoxic zones. Oxygen-limited regions are rapidly expanding globally; however, patterns of microbial communities associated with dissolved oxygen gradients are not yet well understood. To assess the effects of decreasing dissolved oxygen on bacteria, we examined shifts in bacterial community structure over space and time in Hood Canal, Washington, USA-a glacial fjord-like water body that experiences seasonal low dissolved oxygen levels known to be detrimental to fish and other marine organisms. We found a strong negative association between bacterial richness and dissolved oxygen. Bacterial community composition across all samples was also strongly associated with the dissolved oxygen gradient, and significant changes in bacterial community composition occurred at a dissolved oxygen concentration between 5.18 and 7.12 mg O2 L(-1). This threshold value of dissolved oxygen is higher than classic definitions of hypoxia (<2.0 mg O2 L(-1)), suggesting that changes in bacterial communities may precede the detrimental effects on ecologically and economically important macrofauna. Furthermore, bacterial taxa responsible for driving whole community changes across the oxygen gradient are commonly detected in other oxygen-stressed ecosystems, suggesting that the patterns we uncovered in Hood Canal may be relevant in other low oxygen ecosystems.

`Surface-Layer' momentum fluxes in nocturnal slope flows over steep terrain

NASA Astrophysics Data System (ADS)

Oldroyd, H. J.; Pardyjak, E.; Higgins, C. W.; Parlange, M. B.

2017-12-01

A common working definition for the `surface layer' is the lowest 10% of the atmospheric boundary layer (ABL) where the turbulent fluxes are essentially constant. The latter part of this definition is a critical assumption that must hold for accurate flux estimations from land-surface models, wall models, similarity theory, flux-gradient relations and bulk transfer methods. We present cases from observed momentum fluxes in nocturnal slope flows over steep (35.5 degree), alpine terrain in Val Ferret, Switzerland that satisfy the classical definitions of the surface layer and other cases where no traditional surface layer is observed. These cases broadly fall into two distinct flow regimes occurring under clear-sky conditions: (1) buoyancy-driven, `katabatic flow', characterized by an elevated velocity maximum (katabatic jet peak) and (2) `downslope winds', for which larger-scale forcing prevents formation of a katabatic jet. Velocity profiles in downslope wind cases are quite similar to logarithmic profiles typically observed over horizontal and homogeneous terrain, and the corresponding momentum fluxes roughly resemble a constant-flux surface-layer. Contrastingly, velocity profiles in the katabatic regime exhibit a jet-like shape. This jet strongly modulates the corresponding momentum fluxes, which exhibit strong gradients over the shallow katabatic layer and usually change sign near the jet peak, where the velocity gradients also change sign. However, a counter-gradient momentum flux is frequently observed near the jet peak (and sometimes at higher levels), suggesting strong non-local turbulent transport within the katabatic jet layer. We compare our observations with katabatic flow theories and observational studies over shallow-angle slopes and use co-spectral analyses to better identify and understand the non-local transport dynamics. Finally, we show that because of the counter-gradient momentum fluxes, surface layer stability and even local stability can be difficult to characterize because the counter-gradient momentum flux represents a sink in the shear term of turbulence kinetic energy budget equation. These results have broad implications for stability-based modeling and general definitions and assumptions used for the ABL and so-called `surface layer' over steep terrain.

Synthetic receiver function profiles through the upper mantle and the transition zone for upwelling scenarios

NASA Astrophysics Data System (ADS)

Nagel, Thorsten; Düsterhöft, Erik; Schiffer, Christian

2017-04-01

We investigate the signature relevant mantle lithologies leave in the receiver function record for different adiabatic thermal gradients down to 800 kilometers depth. The parameter space is chosen to target the visibility of upwelling mantle (a plume). Seismic velocities for depleted mantle, primitive mantle, and three pyroxenites are extracted from thermodynamically calculated phases diagrams, which also provide the adiabatic decompression paths. Results suggest that compositional variations, i.e. the presence or absence of considerable amounts of pyroxenites in primitive mantle should produce a clear footprint while horizontal differences in thermal gradients for similar compositions might be more subtle. Peridotites best record the classic discontinuities at around 410 and 650 kilometers depth, which are associated with the olivin-wadsleyite and ringwoodite-perovskite transitions, respectively. Pyroxenites, instead, show the garnet-perovskite transition below 700 kilometers depth and SiO2-supersaturated compositions like MORB display the coesite-stishovite transition between 300 and 340 kilometers depth. The latter shows the strongest temperature-depth dependency of all significant transitions potentially allowing to infer information about the thermal state if the mantle contains a sufficient fraction of MORB-like compositions. For primitive and depleted mantle compositions, the olivin-wadsleyite transition shows a certain temperature-depth dependency reflected in slightly larger delay times for higher thermal gradients. The lower-upper-mantle discontinuity, however, is predicted to display larger delay times for higher thermal gradients although the associated assemblage transition occurs at shallower depths thus requiring a very careful depth migration if a thermal anomaly should be recognized. This counterintuitive behavior results from the downward replacement of the assemblage wadsleyite+garnet with the assemblage garnet+periclase at high temperatures. This transition causes even lower seismic velocities with greater depth (following an adiabatic gradient), the highly continuous nature of the reaction, however, should produce only a smooth negative conversion. In contrast, a small positive conversion is expected at normal thermal gradients in the same depth range between 500 and 550 kilometers because of the wadsleyite-ringwoodite-transition. Hence, the polarity of the 520 discontinuity also offers a possibility to recognize the thermal state of the upper mantle.

Fluid overpressures and strength of the sedimentary upper crust

NASA Astrophysics Data System (ADS)

Suppe, John

2014-12-01

The classic crustal strength-depth profile based on rock mechanics predicts a brittle strength σ1 -σ3 = κ(ρbar gz -Pf) that increases linearly with depth as a consequence of [1] the intrinsic brittle pressure dependence κ plus [2] an assumption of hydrostatic pore-fluid pressure, Pf = ρwgz. Many deep borehole stress data agree with a critical state of failure of this form. In contrast, fluid pressures greater than hydrostatic ρbar gz >Pf >ρw gz are normally observed in clastic continental margins and shale-rich mountain belts. Therefore we explore the predicted shapes of strength-depth profiles using data from overpressured regions, especially those dominated by the widespread disequilibrium-compaction mechanism, in which fluid pressures are hydrostatic above the fluid-retention depth zFRD and overpressured below, increasing parallel to the lithostatic gradient ρbar gz . Both brittle crustal strength and frictional fault strength below the zFRD must be constant with depth because effective stress (ρbar gz -Pf) is constant, in contrast with the classic linearly increasing profile. Borehole stress and fluid-pressure measurements in several overpressured deforming continental margins agree with this constant-strength prediction, with the same pressure-dependence κ as the overlying hydrostatic strata. The role of zFRD in critical-taper wedge mechanics and jointing is illustrated. The constant-strength approximation is more appropriate for overpressured crust than classic linearly increasing models.

TINKTEP: A fully self-consistent, mutually polarizable QM/MM approach based on the AMOEBA force field

NASA Astrophysics Data System (ADS)

Dziedzic, Jacek; Mao, Yuezhi; Shao, Yihan; Ponder, Jay; Head-Gordon, Teresa; Head-Gordon, Martin; Skylaris, Chris-Kriton

2016-09-01

We present a novel quantum mechanical/molecular mechanics (QM/MM) approach in which a quantum subsystem is coupled to a classical subsystem described by the AMOEBA polarizable force field. Our approach permits mutual polarization between the QM and MM subsystems, effected through multipolar electrostatics. Self-consistency is achieved for both the QM and MM subsystems through a total energy minimization scheme. We provide an expression for the Hamiltonian of the coupled QM/MM system, which we minimize using gradient methods. The QM subsystem is described by the onetep linear-scaling DFT approach, which makes use of strictly localized orbitals expressed in a set of periodic sinc basis functions equivalent to plane waves. The MM subsystem is described by the multipolar, polarizable force field AMOEBA, as implemented in tinker. Distributed multipole analysis is used to obtain, on the fly, a classical representation of the QM subsystem in terms of atom-centered multipoles. This auxiliary representation is used for all polarization interactions between QM and MM, allowing us to treat them on the same footing as in AMOEBA. We validate our method in tests of solute-solvent interaction energies, for neutral and charged molecules, demonstrating the simultaneous optimization of the quantum and classical degrees of freedom. Encouragingly, we find that the inclusion of explicit polarization in the MM part of QM/MM improves the agreement with fully QM calculations.

The curious incident of multi-instantons and the necessity of Lefschetz thimbles

DOE PAGES

Behtash, Alireza; Poppitz, Erich; Sulejmanpasic, Tin; ...

2015-11-25

Here, we smore » how that compatibility of supersymmetry with exact semi-classics demands that in calculating multi-instanton amplitudes, the “separation” quasi-zeromode must be complexified and the integration cycles must be found by using complex gradient flow (or Picard-Lefschetz equations.) As a non-trivial application, we study N = 2 extended supersymmetric quantum mechanics. Even though in this case supersymmetry is unbroken, the instanton-anti-instanton amplitude (naively calculated) seems to contribute to the ground state energy. We show, however, that the instanton-anti-instanton event consists of two parts: a fermion-correlated and a scalar-correlated event. Although both of these contributions are naively of the same sign and the latter is superficially higher order in the perturbative coupling, we show that the two contributions exactly cancel when they are evaluated on Lefschetz thimbles due to their relative Hidden Topological Angles (HTAs). This gives strong evidence that the semi-classical expansion using Lefschetz thimbles is not only a meaningful prescription for higher order semi-classics, but a necessary one. This deduction seems to be universal and applicable to both supersymmetric and non-supersymmetric theories. In conclusion we speculate that similar conspiracies are responsible for the non-formation of certain molecular contributions in theories where instantons have more than two fermionic zeromodes and do not contribute to the superpotential.« less

A model for one-dimensional morphoelasticity and its application to fibroblast-populated collagen lattices.

PubMed

Menon, Shakti N; Hall, Cameron L; McCue, Scott W; McElwain, D L Sean

2017-10-01

The mechanical behaviour of solid biological tissues has long been described using models based on classical continuum mechanics. However, the classical continuum theories of elasticity and viscoelasticity cannot easily capture the continual remodelling and associated structural changes in biological tissues. Furthermore, models drawn from plasticity theory are difficult to apply and interpret in this context, where there is no equivalent of a yield stress or flow rule. In this work, we describe a novel one-dimensional mathematical model of tissue remodelling based on the multiplicative decomposition of the deformation gradient. We express the mechanical effects of remodelling as an evolution equation for the effective strain, a measure of the difference between the current state and a hypothetical mechanically relaxed state of the tissue. This morphoelastic model combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. A novel feature of our model is that while most models describe growth as a continuous quantity, here we begin with discrete cells and develop a continuum representation of lattice remodelling based on an appropriate limit of the behaviour of discrete cells. To demonstrate the utility of our approach, we use this framework to capture qualitative aspects of the continual remodelling observed in fibroblast-populated collagen lattices, in particular its contraction and its subsequent sudden re-expansion when remodelling is interrupted.

Interpolating moving least-squares methods for fitting potential energy surfaces: using classical trajectories to explore configuration space.

PubMed

Dawes, Richard; Passalacqua, Alessio; Wagner, Albert F; Sewell, Thomas D; Minkoff, Michael; Thompson, Donald L

2009-04-14

We develop two approaches for growing a fitted potential energy surface (PES) by the interpolating moving least-squares (IMLS) technique using classical trajectories. We illustrate both approaches by calculating nitrous acid (HONO) cis-->trans isomerization trajectories under the control of ab initio forces from low-level HF/cc-pVDZ electronic structure calculations. In this illustrative example, as few as 300 ab initio energy/gradient calculations are required to converge the isomerization rate constant at a fixed energy to approximately 10%. Neither approach requires any preliminary electronic structure calculations or initial approximate representation of the PES (beyond information required for trajectory initial conditions). Hessians are not required. Both approaches rely on the fitting error estimation properties of IMLS fits. The first approach, called IMLS-accelerated direct dynamics, propagates individual trajectories directly with no preliminary exploratory trajectories. The PES is grown "on the fly" with the computation of new ab initio data only when a fitting error estimate exceeds a prescribed tight tolerance. The second approach, called dynamics-driven IMLS fitting, uses relatively inexpensive exploratory trajectories to both determine and fit the dynamically accessible configuration space. Once exploratory trajectories no longer find configurations with fitting error estimates higher than the designated accuracy, the IMLS fit is considered to be complete and usable in classical trajectory calculations or other applications.

Spatial and temporal functional changes in alpine summit vegetation are driven by increases in shrubs and graminoids.

PubMed

Venn, Susanna; Pickering, Catherine; Green, Ken

2014-01-01

Classical approaches to investigating temporal and spatial changes in community composition offer only partial insight into the ecology that drives species distribution, community patterns and processes, whereas a functional approach can help to determine many of the underlying mechanisms that drive such patterns. Here, we aim to bring these two approaches together to understand such drivers, using an elevation gradient of sites, a repeat species survey and species functional traits. We used data from a repeat vegetation survey on five alpine summits and measured plant height, leaf area, leaf dry matter content and specific leaf area (SLA) for every species recorded in the surveys. We combined species abundances with trait values to produce a community trait-weighted mean (CTWM) for each trait, and then combined survey results with the CTWMs. Across the gradient of summits, more favourable conditions for plant growth (warmer, longer growing season) occurred at the lower elevations. Vegetation composition changes between 2004 and 2011 (according to non-metric multi-dimensional scaling ordination) were strongly affected by the high and increasing abundance of species with high SLA at high elevations. Species life-form categories strongly affected compositional changes and functional composition, with increasing dominance of tall shrubs and graminoids at the lower-elevation summits, and an overall increase in graminoids across the gradient. The CTWM for plant height and leaf dry matter content significantly decreased with elevation, whereas for leaf area and SLA it significantly increased. The significant relationships between CTWM and elevation may suggest specific ecological processes, namely plant competition and local productivity, influencing vegetation preferentially across the elevation gradient, with the dominance of shrubs and graminoids driving the patterns in the CTWMs.

Spatial and temporal functional changes in alpine summit vegetation are driven by increases in shrubs and graminoids

PubMed Central

Venn, Susanna; Pickering, Catherine; Green, Ken

2014-01-01

Classical approaches to investigating temporal and spatial changes in community composition offer only partial insight into the ecology that drives species distribution, community patterns and processes, whereas a functional approach can help to determine many of the underlying mechanisms that drive such patterns. Here, we aim to bring these two approaches together to understand such drivers, using an elevation gradient of sites, a repeat species survey and species functional traits. We used data from a repeat vegetation survey on five alpine summits and measured plant height, leaf area, leaf dry matter content and specific leaf area (SLA) for every species recorded in the surveys. We combined species abundances with trait values to produce a community trait-weighted mean (CTWM) for each trait, and then combined survey results with the CTWMs. Across the gradient of summits, more favourable conditions for plant growth (warmer, longer growing season) occurred at the lower elevations. Vegetation composition changes between 2004 and 2011 (according to non-metric multi-dimensional scaling ordination) were strongly affected by the high and increasing abundance of species with high SLA at high elevations. Species life-form categories strongly affected compositional changes and functional composition, with increasing dominance of tall shrubs and graminoids at the lower-elevation summits, and an overall increase in graminoids across the gradient. The CTWM for plant height and leaf dry matter content significantly decreased with elevation, whereas for leaf area and SLA it significantly increased. The significant relationships between CTWM and elevation may suggest specific ecological processes, namely plant competition and local productivity, influencing vegetation preferentially across the elevation gradient, with the dominance of shrubs and graminoids driving the patterns in the CTWMs. PMID:24790129

Gradient-based multiconfiguration Shepard interpolation for generating potential energy surfaces for polyatomic reactions.

PubMed

Tishchenko, Oksana; Truhlar, Donald G

2010-02-28

This paper describes and illustrates a way to construct multidimensional representations of reactive potential energy surfaces (PESs) by a multiconfiguration Shepard interpolation (MCSI) method based only on gradient information, that is, without using any Hessian information from electronic structure calculations. MCSI, which is called multiconfiguration molecular mechanics (MCMM) in previous articles, is a semiautomated method designed for constructing full-dimensional PESs for subsequent dynamics calculations (classical trajectories, full quantum dynamics, or variational transition state theory with multidimensional tunneling). The MCSI method is based on Shepard interpolation of Taylor series expansions of the coupling term of a 2 x 2 electronically diabatic Hamiltonian matrix with the diagonal elements representing nonreactive analytical PESs for reactants and products. In contrast to the previously developed method, these expansions are truncated in the present version at the first order, and, therefore, no input of electronic structure Hessians is required. The accuracy of the interpolated energies is evaluated for two test reactions, namely, the reaction OH+H(2)-->H(2)O+H and the hydrogen atom abstraction from a model of alpha-tocopherol by methyl radical. The latter reaction involves 38 atoms and a 108-dimensional PES. The mean unsigned errors averaged over a wide range of representative nuclear configurations (corresponding to an energy range of 19.5 kcal/mol in the former case and 32 kcal/mol in the latter) are found to be within 1 kcal/mol for both reactions, based on 13 gradients in one case and 11 in the other. The gradient-based MCMM method can be applied for efficient representations of multidimensional PESs in cases where analytical electronic structure Hessians are too expensive or unavailable, and it provides new opportunities to employ high-level electronic structure calculations for dynamics at an affordable cost.

The role of boundary layer momentum advection in the mean location of the ITCZ

NASA Astrophysics Data System (ADS)

Dixit, Vishal; Srinivasan, J.

2017-08-01

The inter-tropical convergence zones (ITCZ) form closer to the equator during equinoxes while they form well away from the equator during the boreal summer. A simple three-way balance between the pressure gradients, Coriolis force and effective Rayleigh friction has been classically used to diagnose the location of maximum boundary layer convergence in the near equatorial ITCZ. If such a balance can capture the dynamics of off-equatorial convergence was not known. We used idealized aqua planet simulations with fixed, zonally symmetric sea surface temperature boundary conditions to simulate the near equatorial and off-equatorial ITCZ. As opposed to the convergence of inter-hemispheric flows in the near equatorial convergence, the off-equatorial convergence forms due to the deceleration of cross-equatorial meridional flow. The detailed momentum budget of the off-equatorial convergence zone reveals that the simple balance is not sufficient to capture the relevant dynamics. The deceleration of the meridional flow is strongly modulated by the inertial effects due to the meridional advection of zonal momentum in addition to the terms in the simple balance. The simple balance predicts a spurious near equatorial convergence and a consistent off-equatorial convergence of the meridional flow. The spurious convergence disappears when inertial effects are included in the balance. As cross equatorial meridional flow decelerates to form convergence, the inertial effects cancel the pressure gradient effects near the equator while they add away from the equator. The contribution to the off-equatorial convergence induced by the pressure gradients is significantly larger than the contribution due to the inertial effects and hence pressure gradients appear to be the primary factor in anchoring the strength and location of the off-equatorial convergence.

Finite-frequency tomography using adjoint methods-Methodology and examples using membrane surface waves

NASA Astrophysics Data System (ADS)

Tape, Carl; Liu, Qinya; Tromp, Jeroen

2007-03-01

We employ adjoint methods in a series of synthetic seismic tomography experiments to recover surface wave phase-speed models of southern California. Our approach involves computing the Fréchet derivative for tomographic inversions via the interaction between a forward wavefield, propagating from the source to the receivers, and an `adjoint' wavefield, propagating from the receivers back to the source. The forward wavefield is computed using a 2-D spectral-element method (SEM) and a phase-speed model for southern California. A `target' phase-speed model is used to generate the `data' at the receivers. We specify an objective or misfit function that defines a measure of misfit between data and synthetics. For a given receiver, the remaining differences between data and synthetics are time-reversed and used as the source of the adjoint wavefield. For each earthquake, the interaction between the regular and adjoint wavefields is used to construct finite-frequency sensitivity kernels, which we call event kernels. An event kernel may be thought of as a weighted sum of phase-specific (e.g. P) banana-doughnut kernels, with weights determined by the measurements. The overall sensitivity is simply the sum of event kernels, which defines the misfit kernel. The misfit kernel is multiplied by convenient orthonormal basis functions that are embedded in the SEM code, resulting in the gradient of the misfit function, that is, the Fréchet derivative. A non-linear conjugate gradient algorithm is used to iteratively improve the model while reducing the misfit function. We illustrate the construction of the gradient and the minimization algorithm, and consider various tomographic experiments, including source inversions, structural inversions and joint source-structure inversions. Finally, we draw connections between classical Hessian-based tomography and gradient-based adjoint tomography.

A dynamic regularized gradient model of the subgrid-scale stress tensor for large-eddy simulation

NASA Astrophysics Data System (ADS)

Vollant, A.; Balarac, G.; Corre, C.

2016-02-01

Large-eddy simulation (LES) solves only the large scales part of turbulent flows by using a scales separation based on a filtering operation. The solution of the filtered Navier-Stokes equations requires then to model the subgrid-scale (SGS) stress tensor to take into account the effect of scales smaller than the filter size. In this work, a new model is proposed for the SGS stress model. The model formulation is based on a regularization procedure of the gradient model to correct its unstable behavior. The model is developed based on a priori tests to improve the accuracy of the modeling for both structural and functional performances, i.e., the model ability to locally approximate the SGS unknown term and to reproduce enough global SGS dissipation, respectively. LES is then performed for a posteriori validation. This work is an extension to the SGS stress tensor of the regularization procedure proposed by Balarac et al. ["A dynamic regularized gradient model of the subgrid-scale scalar flux for large eddy simulations," Phys. Fluids 25(7), 075107 (2013)] to model the SGS scalar flux. A set of dynamic regularized gradient (DRG) models is thus made available for both the momentum and the scalar equations. The second objective of this work is to compare this new set of DRG models with direct numerical simulations (DNS), filtered DNS in the case of classic flows simulated with a pseudo-spectral solver and with the standard set of models based on the dynamic Smagorinsky model. Various flow configurations are considered: decaying homogeneous isotropic turbulence, turbulent plane jet, and turbulent channel flows. These tests demonstrate the stable behavior provided by the regularization procedure, along with substantial improvement for velocity and scalar statistics predictions.

Parameter estimation of extended free-burning electric arc within 1 kA

NASA Astrophysics Data System (ADS)

Sun, Qiuqin; Liu, Hao; Wang, Feng; Chen, She; Zhai, Yujia

2018-05-01

A long electric arc, as a common phenomenon in the power system, not only damages the electrical equipment but also threatens the safety of the system. In this work, a series of tests on a long electric arc in free air have been conducted. The arc voltage and current data were obtained, and the arc trajectories were captured using a high speed camera. The arc images were digitally processed by means of edge detection, and the length is formulated and achieved. Based on the experimental data, the characteristics of the long arc are discussed. It shows that the arc voltage waveform is close to the square wave with high-frequency components, whereas the current is almost sinusoidal. As the arc length elongates, the arc voltage and the resistance increase sharply. The arc takes a spiral shape with the effect of magnetic forces. The arc length will shorten briefly with the occurrence of the short-circuit phenomenon. Based on the classical Mayr model, the parameters of the long electric arc, including voltage gradient and time constant, with different lengths and current amplitudes are estimated using the linear least-square method. To reduce the computational error, segmentation interpolation is also employed. The results show that the voltage gradient of the long arc is mainly determined by the current amplitude but almost independent of the arc length. However, the time constant is jointly governed by these two variables. The voltage gradient of the arc with the current amplitude at 200-800 A is in the range of 3.9 V/cm-20 V/cm, and the voltage gradient decreases with the increase in current.

Morphogen Electrochemically Triggered Self-Construction of Polymeric Films Based on Mussel-Inspired Chemistry.

PubMed

Maerten, Clément; Garnier, Tony; Lupattelli, Paolo; Chau, Nguyet Trang Thanh; Schaaf, Pierre; Jierry, Loïc; Boulmedais, Fouzia

2015-12-15

Inspired by the strong chemical adhesion mechanism of mussels, we designed a catechol-based electrochemically triggered self-assembly of films based on ethylene glycol molecules bearing catechol groups on both sides and denoted as bis-catechol molecules. These molecules play the role of morphogens and, in contrast to previously investigated systems, they are also one of the constituents, after reaction, of the film. Unable to interact together, commercially available poly(allylamine hydrochloride) (PAH) chains and bis-catechol molecules are mixed in an aqueous solution and brought in contact with an electrode. By application of defined potential cycles, bis-catechol molecules undergo oxidation leading to molecules bearing "reactive" quinone groups which diffuse toward the solution. In this active state, the quinones react with amino groups of PAH through Michael addition and Schiff's base condensation reaction. The application of cyclic voltammetry (CV) between 0 and 500 mV (vs Ag/AgCl, scan rate of 50 mV/s) of a PAH/bis-catechol solution results in a fast self-construction of a film that reaches a thickness of 40 nm after 60 min. The films present a spiky structure which is attributed to the use of bis-functionalized molecules as one component of the films. XPS measurements show the presence of both PAH and bis-catechol cross-linked together in a covalent way. We show that the amine/catechol ratio is an important parameter which governs the film buildup. For a given amine/catechol ratio, it does exist an optimum CV scan rate leading to a maximum of the film thickness as a function of the scan rate.

Combination of Mineral Trioxide Aggregate and Platelet-rich Fibrin Promotes the Odontoblastic Differentiation and Mineralization of Human Dental Pulp Cells via BMP/Smad Signaling Pathway.

PubMed

Woo, Su-Mi; Kim, Won-Jae; Lim, Hae-Soon; Choi, Nam-Ki; Kim, Sun-Hun; Kim, Seon-Mi; Jung, Ji-Yeon

2016-01-01

Recent reports have shown that the combined use of platelet-rich fibrin (PRF), an autologous fibrin matrix, and mineral trioxide aggregate (MTA) as root filling material is beneficial for the endodontic management of an open apex. However, the potential of the combination of MTA and PRF as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro has not yet been studied. The purpose of this study was to evaluate the effect of the combination of MTA and PRF on odontoblastic maturation in HDPCs. HDPCs extracted from third molars were directly cultured with MTA and PRF extract (PRFe). Odontoblastic differentiation of HDPCs was evaluated by measuring the alkaline phosphatase (ALP) activity, and the expression of odontogenesis-related genes was detected using reverse-transcription polymerase chain reaction or Western blot. Mineralization formation was assessed by alizarin red staining. HDPCs treated with MTA and PRFe significantly up-regulated the expression of dentin sialoprotein and dentin matrix protein-1 and enhanced ALP activity and mineralization compared with those with MTA or PRFe treatment alone. In addition, the combination of MTA and PRFe induced the activation of bone morphogenic proteins (BMP)/Smad, whereas LDN193189, the bone morphogenic protein inhibitor, attenuated dentin sialophosphoprotein and dentin matrix protein-1 expression, ALP activity, and mineralization enhanced by MTA and PRFe treatment. This study shows that the combination of MTA and PRF has a synergistic effect on the stimulation of odontoblastic differentiation of HDPCs via the modulation of the BMP/Smad signaling pathway. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Morphogenetic Implications of Peristalsis-Driven Fluid Flow in the Embryonic Lung

PubMed Central

Bokka, Kishore K.; Jesudason, Edwin C.; Lozoya, Oswaldo A.; Guilak, Farshid; Warburton, David; Lubkin, Sharon R.

2015-01-01

Epithelial organs are almost universally secretory. The lung secretes mucus of extremely variable consistency. In the early prenatal period, the secretions are of largely unknown composition, consistency, and flow rates. In addition to net outflow from secretion, the embryonic lung exhibits transient reversing flows from peristalsis. Airway peristalsis (AP) begins as soon as the smooth muscle forms, and persists until birth. Since the prenatal lung is liquid-filled, smooth muscle action can transport fluid far from the immediately adjacent tissues. The sensation of internal fluid flows has been shown to have potent morphogenetic effects, as has the transport of morphogens. We hypothesize that these effects play an important role in lung morphogenesis. To test these hypotheses in a quantitative framework, we analyzed the fluid-structure interactions between embryonic tissues and lumen fluid resulting from peristaltic waves that partially occlude the airway. We found that if the airway is closed, fluid transport is minimal; by contrast, if the trachea is open, shear rates can be very high, particularly at the stenosis. We performed a parametric analysis of flow characteristics' dependence on tissue stiffnesses, smooth muscle force, geometry, and fluid viscosity, and found that most of these relationships are governed by simple ratios. We measured the viscosity of prenatal lung fluid with passive bead microrheology. This paper reports the first measurements of the viscosity of embryonic lung lumen fluid. In the range tested, lumen fluid can be considered Newtonian, with a viscosity of 0.016 ± 0.008 Pa-s. We analyzed the interaction between the internal flows and diffusion and conclude that AP has a strong effect on flow sensing away from the tip and on transport of morphogens. These effects may be the intermediate mechanisms for the enhancement of branching seen in occluded embryonic lungs. PMID:26147967

Efficient callus formation and plant regeneration of goosegrass [Eleusine indica (L.) Gaertn.].

PubMed

Yemets, A I; Klimkina, L A; Tarassenko, L V; Blume, Y B

2003-02-01

Efficient methods in totipotent callus formation, cell suspension culture establishment and whole-plant regeneration have been developed for the goosegrass [ Eleusine indica (L.) Gaertn.] and its dinitroaniline-resistant biotypes. The optimum medium for inducing morphogenic calli consisted of N6 basal salts and B5 vitamins supplemented with 1-2 mg l(-1) 2,4-dichlorophenoxyacetic acid (2,4-D), 2 mg l(-1) glycine, 100 mg l(-1) asparagine, 100 mg l(-1) casein hydrolysate, 30 g l(-1) sucrose and 0.6% agar, pH 5.7. The presence of organogenic and embryogenic structures in these calli was histologically documented. Cell suspension cultures derived from young calli were established in a liquid medium with the same composition. Morphogenic structures of direct shoots and somatic embryos were grown into rooted plantlets on medium containing MS basal salts, B5 vitamins, 1 mg l(-1) kinetin (Kn) and 0.1 mg l(-1) indole-3-acetic acid (IAA), 3% sucrose, 0.6% agar, pH 5.7. Calli derived from the R-biotype of E. indica possessed a high resistance to trifluralin (dinitroaniline herbicide) and cross-resistance to a structurally non-related herbicide, amiprophosmethyl (phosphorothioamidate herbicide), as did the original resistant plants. Embryogenic cell suspension culture was a better source of E. indica protoplasts than callus or mesophyll tissue. The enzyme solution containing 1.5% cellulase Onozuka R-10, 0.5% driselase, 1% pectolyase Y-23, 0.5% hemicellulase and N(6) mineral salts with an additional 0.2 M KCl and 0.1 M CaCl(2) (pH 5.4-5.5) was used for protoplast isolation. The purified protoplasts were cultivated in KM8p liquid medium supplemented with 2 mg l(-1) 2,4-D and 0.2 mg l(-1) Kn.

Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development

PubMed Central

Bar, Carmit; Tsai, Pai-Chi; Valdes, Victor J.; Cohen, Idan; Santoriello, Francis J.; Zhao, Dejian; Hsu, Ya-Chieh; Ezhkova, Elena

2016-01-01

An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh) signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2) in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures. PMID:27414999

Polycomb-Mediated Repression and Sonic Hedgehog Signaling Interact to Regulate Merkel Cell Specification during Skin Development.

PubMed

Perdigoto, Carolina N; Dauber, Katherine L; Bar, Carmit; Tsai, Pai-Chi; Valdes, Victor J; Cohen, Idan; Santoriello, Francis J; Zhao, Dejian; Zheng, Deyou; Hsu, Ya-Chieh; Ezhkova, Elena

2016-07-01

An increasing amount of evidence indicates that developmental programs are tightly regulated by the complex interplay between signaling pathways, as well as transcriptional and epigenetic processes. Here, we have uncovered coordination between transcriptional and morphogen cues to specify Merkel cells, poorly understood skin cells that mediate light touch sensations. In murine dorsal skin, Merkel cells are part of touch domes, which are skin structures consisting of specialized keratinocytes, Merkel cells, and afferent neurons, and are located exclusively around primary hair follicles. We show that the developing primary hair follicle functions as a niche required for Merkel cell specification. We find that intraepidermal Sonic hedgehog (Shh) signaling, initiated by the production of Shh ligand in the developing hair follicles, is required for Merkel cell specification. The importance of Shh for Merkel cell formation is further reinforced by the fact that Shh overexpression in embryonic epidermal progenitors leads to ectopic Merkel cells. Interestingly, Shh signaling is common to primary, secondary, and tertiary hair follicles, raising the possibility that there are restrictive mechanisms that regulate Merkel cell specification exclusively around primary hair follicles. Indeed, we find that loss of Polycomb repressive complex 2 (PRC2) in the epidermis results in the formation of ectopic Merkel cells that are associated with all hair types. We show that PRC2 loss expands the field of epidermal cells competent to differentiate into Merkel cells through the upregulation of key Merkel-differentiation genes, which are known PRC2 targets. Importantly, PRC2-mediated repression of the Merkel cell differentiation program requires inductive Shh signaling to form mature Merkel cells. Our study exemplifies how the interplay between epigenetic and morphogen cues regulates the complex patterning and formation of the mammalian skin structures.

Bone Formation in a Rat Tibial Defect Model Using Carboxymethyl Cellulose/BioC/Bone Morphogenic Protein-2 Hybrid Materials

PubMed Central

Kim, Hak-Jun; Park, Kyeongsoon; Kim, Sung Eun; Song, Hae-Ryong

2014-01-01

The objective of this study was to assess whether carboxymethyl cellulose- (CMC-) based hydrogel containing BioC (biphasic calcium phosphate (BCP); tricalcium phosphate (TCP) : hydroxyapatite (Hap) = 70 : 30) and bone morphogenic protein-2 (BMP-2) led to greater bone formation than CMC-based hydrogel containing BioC without BMP-2. In order to demonstrate bone formation at 4 and 8 weeks, plain radiographs, microcomputed tomography (micro-CT) evaluation, and histological studies were performed after implantation of all hybrid materials on an 8 mm defect of the right tibia in rats. The plain radiographs and micro-CT analyses revealed that CMC/BioC/BMP-2 (0.5 mg) led to much greater mineralization at 4 and 8 weeks than did CMC/BioC or CMC/Bio/BMP-2 (0.1 mg). Likewise, bone formation and bone remodeling studies revealed that CMC/BioC/BMP-2 (0.5 mg) led to a significantly greater amount of bone formation and bone remodeling at 4 and 8 weeks than did CMC/BioC or CMC/BioC/BMP-2 (0.1 mg). Histological studies revealed that mineralized bone tissue was present around the whole circumference of the defect site with CMC/BioC/BMP-2 (0.5 mg) but not with CMC/BioC or CMC/BioC/BMP-2 (0.1 mg) at 4 and 8 weeks. These results suggest that CMC/BioC/BMP-2 hybrid materials induced greater bone formation than CMC/BioC hybrid materials. Thus, CMC/BioC/BMP-2 hybrid materials may be used as an injectable substrate to regenerate bone defects. PMID:24804202

Modulation of the nanometer pore size improves magnesium adsorption into mesoporous titania coatings and promotes bone morphogenic protein 4 expression in adhering osteoblasts.

PubMed

Cecchinato, Francesca; Atefyekta, Saba; Wennerberg, Ann; Andersson, Martin; Jimbo, Ryo; Davies, Julia R

2016-07-01

Mesoporous (MP) titania films used as implant coatings have recently been considered as release systems for controlled administration of magnesium to enhance initial osteoblast proliferation in vitro. Tuning of the pore size in such titania films is aimed at increasing the osteogenic potential through effects on the total loading capacity and the release profile of magnesium. In this study, evaporation-induced self-assembly (EISA) was used with different structure-directing agents to form three mesoporous films with average pore sizes of 2nm (MP1), 6nm (MP2) and 7nm (MP3). Mg adsorption and release was monitored using quartz crystal microbalance with dissipation (QCM-D). The film surfaces were characterized with atomic force microscopy (AFM), scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The effect of different Mg release on osteogenesis was investigated in human fetal osteoblasts (hFOB) using pre-designed osteogenesis arrays and real-time polymerase chain reaction (RT-PCR). Results showed a sustained release from all the films investigated, with higher magnesium adsorption into MP1 and MP3 films. No significant differences were observed in the surface nanotopography of the films, either with or without the presence of magnesium. MP3 films (7nm pore size) had the greatest effect on osteogenesis, up-regulating 15 bone-related genes after 1 week of hFOB growth and significantly promoting bone morphogenic protein (BMP4) expression after 3 weeks of growth. The findings indicate that the increase in pore width on the nano scale significantly enhanced the bioactivity of the mesoporous coating, thus accelerating osteogenesis without creating differences in surface roughness. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

PubMed

Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

2014-01-01

In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, p<0.001), TGF-β1 (r=0.85, p<0.001), VEGF (r=0.46, p<0.01) and PDGF-bb (r=0.9, p<0.001). Our results demonstrate that selected growth factors are present in the platelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

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

Biver, Emmanuel, E-mail: ebiver@yahoo.fr; Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex; Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14

2012-11-02

Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exertmore » their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.« less

Desert hedgehog is a mammal-specific gene expressed during testicular and ovarian development in a marsupial.

PubMed

O'Hara, William A; Azar, Walid J; Behringer, Richard R; Renfree, Marilyn B; Pask, Andrew J

2011-12-01

Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the tammar wallaby) to determine whether DHH signalling is a conserved factor in gonadal development in all therian mammals. DHH, PTCH1 and PTCH2 were present in the marsupial genome and highly conserved with their eutherian orthologues. Phylogenetic analyses indicate that DHH has recently evolved and is a mammal-specific hedgehog orthologue. The marsupial PTCH2 receptor had an additional exon (exon 21a) not annotated in eutherian PTCH2 proteins. Interestingly we found evidence of this exon in humans and show that its translation would result in a truncated protein with functions similar to PTCH1. We also show that DHH expression was not restricted to the testes during gonadal development (as in mice), but was also expressed in the developing ovary. Expression of DHH, PTCH1 and PTCH2 in the adult tammar testis and ovary was consistent with findings in the adult mouse. These data suggest that there is a highly conserved role for DHH signalling in the differentiation and function of the mammalian testis and that DHH may be necessary for marsupial ovarian development. The receptors PTCH1 and PTCH2 are highly conserved mediators of hedgehog signalling in both the developing and adult marsupial gonads. Together these findings indicate DHH is an essential therian mammal-specific morphogen in gonadal development and gametogenesis.

Amyloid Precursor Protein 96–110 and β-Amyloid 1–42 Elicit Developmental Anomalies in Sea Urchin Embryos and Larvae that are Alleviated by Neurotransmitter Analogs for Acetylcholine, Serotonin and Cannabinoids

PubMed Central

Buznikov, Gennady A.; Nikitina, Lyudmila A.; Seidler, Frederic J.; Slotkin, Theodore A.; Bezuglov, Vladimir V.; Milošević, Ivan; Lazarević, Lidija; Rogač, Ljubica; Ruzdijić, Sabera; Rakić, Ljubiša M.

2008-01-01

Amyloid precursor protein (APP) is overexpressed in the developing brain and portions of its extracellular domain, especially amino acid residues 96–110, play an important role in neurite outgrowth and neural cell differentiation. In the current study, we evaluated the developmental abnormalities caused by administration of exogenous APP96–110 in sea urchin embryos and larvae, which, like the developing mammalian brain, utilize acetylcholine and other neurotransmitters as morphogens; effects were compared to those of β-amyloid 1–42 (Aβ42), the neurotoxic APP fragment contained within neurodegenerative plaques in Alzheimer’s Disease. Although both peptides elicited dysmorphogenesis, Aβ42 was far more potent; in addition, whereas Aβ42 produced abnormalities at developmental stages ranging from early cleavage divisions to the late pluteus, APP96–110 effects were restricted to the intermediate, mid-blastula stage. For both agents, anomalies were prevented or reduced by addition of lipid-permeable analogs of acetylcholine, serotonin or cannabinoids; physostigmine, a carbamate-derived cholinesterase inhibitor, was also effective. In contrast, agents that act on NMDA receptors (memantine) or α-adrenergic receptors (nicergoline), and that are therapeutic in Alzheimer’s Disease, were themselves embryotoxic, as was tacrine, a cholinesterase inhibitor from a different chemical class than physostigmine. Protection was also provided by agents acting downstream from receptor-mediated events: increasing cyclic AMP with caffeine or isobutylmethylxanthine, or administering the antioxidant, α-tocopherol, were all partially effective. Our findings reinforce a role for APP in development and point to specific interactions with neurotransmitter systems that act as morphogens in developing sea urchins as well as in the mammalian brain. PMID:18565728

Determination of new retention indices for quick identification of essential oils compounds.

PubMed

Hérent, Marie-France; De Bie, Véronique; Tilquin, Bernard

2007-02-19

The classical methods of chromatographic identification of compounds were based on calculation of retention indices by using different stationary phases. The aim of the work was to differentiate essential oils extracted from different plant species by identification of some of their major compounds. The method of identification was based on the calculation of new retention indices of essential oils compounds fractionated on a polar chromatographic column with temperature programming system. Similar chromatograms have been obtained on the same column for one plant family with two different temperature gradients allowing the rapid identification of essential oils of different species, sub-species or chemotypes of Citrus, Mentha and Thymus.

Phoresis in fluids.

PubMed

Brenner, Howard

2011-12-01

This paper presents a unified theory of phoretic phenomena in single-component fluids. Simple formulas are given for the phoretic velocities of small inert force-free non-Brownian particles migrating through otherwise quiescent single-component gases and liquids and animated by a gradient in the fluid's temperature (thermophoresis), pressure (barophoresis), density (pycnophoresis), or any combination thereof. The ansatz builds upon a recent paper [Phys. Rev. E 84, 046309 (2011)] concerned with slip of the fluid's mass velocity at solid surfaces--that is, with phenomena arising from violations of the classical no-slip fluid-mechanical boundary condition. Experimental and other data are cited in support of the phoretic model developed herein.

Gravity-driven soap film dynamics in subcritical regimes

NASA Astrophysics Data System (ADS)

Auliel, M. I.; Castro, F.; Sosa, R.; Artana, G.

2015-10-01

We undertake the analysis of soap-film dynamics with the classical approach of asymptotic expansions. We focus our analysis in vertical soap film tunnels operating in subcritical regimes with elastic Mach numbers Me=O(10-1) . Considering the associated set of nondimensional numbers that characterize this flow, we show that the flow behaves as a two-dimensional (2D) divergence free flow with variable mass density. When the soap film dynamics agrees with that of a 2D and almost constant mass density flow, the regions where the second invariant of the velocity gradient is non-null correspond to regions where the rate of change of film thickness is non-negligible.

Boost-phase discrimination research activities

NASA Technical Reports Server (NTRS)

Cooper, David M.; Deiwert, George S.

1989-01-01

Theoretical research in two areas was performed. The aerothermodynamics research focused on the hard-body and rocket plume flows. Analytical real gas models to describe finite rate chemistry were developed and incorporated into the three-dimensional flow codes. New numerical algorithms capable of treating multi-species reacting gas equations and treating flows with large gradients were also developed. The computational chemistry research focused on the determination of spectral radiative intensity factors, transport properties and reaction rates. Ab initio solutions to the Schrodinger equation provided potential energy curves transition moments (radiative probabilities and strengths) and potential energy surfaces. These surfaces were then coupled with classical particle reactive trajectories to compute reaction cross-sections and rates.

Frontogenesis driven by horizontally quadratic distributions of density

NASA Technical Reports Server (NTRS)

Jacqmin, David

1991-01-01

Attention is given to the quadratic density distribution in a channel, which has been established by Simpson and Linden to be the simplest case of the horizontally nonlinear distribution of fluid density required for the production of frontogenesis. The porous-media and Boussinesq flow models are examined, and their evolution equations are reduced to one-dimensional systems. While both the porous-media and the inviscid/nondiffusive Boussinesq systems exhibit classic frontogenesis behavior, the viscous Boussinesq system exhibits a more complex behavior: boundary-layer effects force frontogenesis away from the lower boundary, and at late times the steepest density gradients are close to mid-channel.

Novel self-organization mechanism in ultrathin liquid films: theory and experiment.

PubMed

Trice, Justin; Favazza, Christopher; Thomas, Dennis; Garcia, Hernando; Kalyanaraman, Ramki; Sureshkumar, Radhakrishna

2008-07-04

When an ultrathin metal film of thickness h (<20 nm) is melted by a nanosecond pulsed laser, the film temperature is a nonmonotonic function of h and achieves its maximum at a certain thickness h*. This is a consequence of the h and time dependence of energy absorption and heat flow. Linear stability analysis and nonlinear dynamical simulations that incorporate such intrinsic interfacial thermal gradients predict a characteristic pattern length scale Lambda that decreases for h>h*, in contrast to the classical spinodal dewetting behavior where Lambda increases monotonically as h2. These predictions agree well with experimental observations for Co and Fe films on SiO2.

Predicting Ga and Cu Profiles in Co-Evaporated Cu(In,Ga)Se 2 Using Modified Diffusion Equations and a Spreadsheet

DOE PAGES

Repins, Ingrid L.; Harvey, Steve; Bowers, Karen; ...

2017-05-15

Cu(In,Ga)Se 2(CIGS) photovoltaic absorbers frequently develop Ga gradients during growth. These gradients vary as a function of growth recipe, and are important to device performance. Prediction of Ga profiles using classic diffusion equations is not possible because In and Ga atoms occupy the same lattice sites and thus diffuse interdependently, and there is not yet a detailed experimental knowledge of the chemical potential as a function of composition that describes this interaction. Here, we show how diffusion equations can be modified to account for site sharing between In and Ga atoms. The analysis has been implemented in an Excel spreadsheet,more » and outputs predicted Cu, In, and Ga profiles for entered deposition recipes. A single set of diffusion coefficients and activation energies are chosen, such that simulated elemental profiles track with published data and those from this study. Extent and limits of agreement between elemental profiles predicted from the growth recipes and the spreadsheet tool are demonstrated.« less

Plant phototropic growth.

PubMed

Fankhauser, Christian; Christie, John M

2015-05-04

Plants are photoautotrophic sessile organisms that use environmental cues to optimize multiple facets of growth and development. A classic example is phototropism - in shoots this is typically positive, leading to growth towards the light, while roots frequently show negative phototropism triggering growth away from the light. Shoot phototropism optimizes light capture of leaves in low light environments and hence increases photosynthetic productivity. Phototropins are plasma-membrane-associated UV-A/blue-light activated kinases that trigger phototropic growth. Light perception liberates their protein kinase domain from the inhibitory action of the amino-terminal photosensory portion of the photoreceptor. Following a series of still poorly understood events, phototropin activation leads to the formation of a gradient of the growth hormone auxin across the photo-stimulated stem. The greater auxin concentration on the shaded compared with the lit side of the stem enables growth reorientation towards the light. In this Minireview, we briefly summarize the signaling steps starting from photoreceptor activation until the establishment of a lateral auxin gradient, ultimately leading to phototropic growth in shoots. Copyright © 2015 Elsevier Ltd. All rights reserved.

Experimental determination of pore shapes using phase retrieval from q -space NMR diffraction

NASA Astrophysics Data System (ADS)

Demberg, Kerstin; Laun, Frederik Bernd; Bertleff, Marco; Bachert, Peter; Kuder, Tristan Anselm

2018-05-01

This paper presents an approach to solving the phase problem in nuclear magnetic resonance (NMR) diffusion pore imaging, a method that allows imaging the shape of arbitrary closed pores filled with an NMR-detectable medium for investigation of the microstructure of biological tissue and porous materials. Classical q -space imaging composed of two short diffusion-encoding gradient pulses yields, analogously to diffraction experiments, the modulus squared of the Fourier transform of the pore image which entails an inversion problem: An unambiguous reconstruction of the pore image requires both magnitude and phase. Here the phase information is recovered from the Fourier modulus by applying a phase retrieval algorithm. This allows omitting experimentally challenging phase measurements using specialized temporal gradient profiles. A combination of the hybrid input-output algorithm and the error reduction algorithm was used with dynamically adapting support (shrinkwrap extension). No a priori knowledge on the pore shape was fed to the algorithm except for a finite pore extent. The phase retrieval approach proved successful for simulated data with and without noise and was validated in phantom experiments with well-defined pores using hyperpolarized xenon gas.

Smoothing of cost function leads to faster convergence of neural network learning

NASA Astrophysics Data System (ADS)

Xu, Li-Qun; Hall, Trevor J.

1994-03-01

One of the major problems in supervised learning of neural networks is the inevitable local minima inherent in the cost function f(W,D). This often makes classic gradient-descent-based learning algorithms that calculate the weight updates for each iteration according to (Delta) W(t) equals -(eta) (DOT)$DELwf(W,D) powerless. In this paper we describe a new strategy to solve this problem, which, adaptively, changes the learning rate and manipulates the gradient estimator simultaneously. The idea is to implicitly convert the local- minima-laden cost function f((DOT)) into a sequence of its smoothed versions {f(beta t)}Ttequals1, which, subject to the parameter (beta) t, bears less details at time t equals 1 and gradually more later on, the learning is actually performed on this sequence of functionals. The corresponding smoothed global minima obtained in this way, {Wt}Ttequals1, thus progressively approximate W-the desired global minimum. Experimental results on a nonconvex function minimization problem and a typical neural network learning task are given, analyses and discussions of some important issues are provided.

Non-normal dynamics and positive feedback between motion and sensation boosts run-and-tumble navigation.

NASA Astrophysics Data System (ADS)

Long, Junjiajia; Zucker, Steven W.; Emonet, Thierry

The capability to navigate environmental gradients is of critical importance for survival. Countless organisms (microbes, human cells, worms, larvae, and insects) as well as human-made robots use a run-and-tumble strategy to do so. The classical drawback of this approach is that runs in the wrong direction are wasteful. We show analytically that organisms can overcome this fundamental limitation by exploiting the non-normal dynamics and intrinsic nonlinearities inherent to the positive feedback between motion and sensation. Most importantly, this nonlinear amplification is asymmetric, elongating runs in favorable directions and abbreviating others. The result is a ``ratchet-like'' gradient climbing behavior with drift speeds that can approach half the maximum run speed of the organism. By extending the theoretical study of run-and-tumble navigation into the non-mean-field, nonlinear, and non-normal domains, our results provide a new level of understanding about this basic strategy. We thank Yale HPC, NIGMS 1R01GM106189, and the Allen Distinguished Investigator Program through The Paul G. Allen Frontiers Group for support.

Prediction of Forming Limit Diagram for Seamed Tube Hydroforming Based on Thickness Gradient Criterion

NASA Astrophysics Data System (ADS)

Chen, Xianfeng; Lin, Zhongqin; Yu, Zhongqi; Chen, Xinping; Li, Shuhui

2011-08-01

This study establishes the forming limit diagram (FLD) for QSTE340 seamed tube hydroforming by finite element method (FEM) simulation. FLD is commonly obtained from experiment, theoretical calculation and FEM simulation. But for tube hydroforming, both of the experimental and theoretical means are restricted in the application due to the equipment costs and the lack of authoritative theoretical knowledge. In this paper, a novel approach of predicting forming limit using thickness gradient criterion (TGC) is presented for seamed tube hydroforming. Firstly, tube bulge tests and uniaxial tensile tests are performed to obtain the stress-strain curve for tube three parts. Then one FE model for a classical tube free hydroforming and another FE model for a novel experimental apparatus by applying the lateral compression force and the internal pressure are constructed. After that, the forming limit strain is calculated based on TGC in the FEM simulation. Good agreement between the simulation and experimental results is indicated. By combining the TGC and FEM, an alternative way of predicting forming limit with enough accuracy and convenience is provided.

Efficient Multi-Dimensional Simulation of Quantum Confinement Effects in Advanced MOS Devices

NASA Technical Reports Server (NTRS)

Biegel, Bryan A.; Rafferty, Conor S.; Ancona, Mario G.; Yu, Zhi-Ping

2000-01-01

We investigate the density-gradient (DG) transport model for efficient multi-dimensional simulation of quantum confinement effects in advanced MOS devices. The formulation of the DG model is described as a quantum correction to the classical drift-diffusion model. Quantum confinement effects are shown to be significant in sub-100nm MOSFETs. In thin-oxide MOS capacitors, quantum effects may reduce gate capacitance by 25% or more. As a result, the inclusion or quantum effects in simulations dramatically improves the match between C-V simulations and measurements for oxide thickness down to 2 nm. Significant quantum corrections also occur in the I-V characteristics of short-channel (30 to 100 nm) n-MOSFETs, with current drive reduced by up to 70%. This effect is shown to result from reduced inversion charge due to quantum confinement of electrons in the channel. Also, subthreshold slope is degraded by 15 to 20 mV/decade with the inclusion of quantum effects via the density-gradient model, and short channel effects (in particular, drain-induced barrier lowering) are noticeably increased.

Experimental determination of pore shapes using phase retrieval from q-space NMR diffraction.

PubMed

Demberg, Kerstin; Laun, Frederik Bernd; Bertleff, Marco; Bachert, Peter; Kuder, Tristan Anselm

2018-05-01

This paper presents an approach to solving the phase problem in nuclear magnetic resonance (NMR) diffusion pore imaging, a method that allows imaging the shape of arbitrary closed pores filled with an NMR-detectable medium for investigation of the microstructure of biological tissue and porous materials. Classical q-space imaging composed of two short diffusion-encoding gradient pulses yields, analogously to diffraction experiments, the modulus squared of the Fourier transform of the pore image which entails an inversion problem: An unambiguous reconstruction of the pore image requires both magnitude and phase. Here the phase information is recovered from the Fourier modulus by applying a phase retrieval algorithm. This allows omitting experimentally challenging phase measurements using specialized temporal gradient profiles. A combination of the hybrid input-output algorithm and the error reduction algorithm was used with dynamically adapting support (shrinkwrap extension). No a priori knowledge on the pore shape was fed to the algorithm except for a finite pore extent. The phase retrieval approach proved successful for simulated data with and without noise and was validated in phantom experiments with well-defined pores using hyperpolarized xenon gas.

End-wall boundary layer measurements in a two-stage fan

NASA Technical Reports Server (NTRS)

Ball, C. L.; Reid, L.; Schmidt, J. F.

1983-01-01

Detailed flow measurements made in the casing boundary layer of a two-stage transonic fan are summarized. These measurements were taken at a station upstream of the fan, between all blade rows, and downstream of the last row. Conventional boundary layer parameters were calculated from the measured data. A classical two dimensional casing boundary layer was measured at the fan inlet and extended inward to approximately 15 percent of span. A highly three dimensional boundary layer was measured at the exit of each blade row and extended inward to approximately 10 percent of span. The steep radial gradient of axial velocity noted at the exit of the rotors was reduced substantially as the flow passed through the stators. This reduced gradient is attributed to flow mixing. The amount of flow mixing was reflected in the radial redistribution of total temperature as the flow passed through the stators. The blockage factors calculated from the measured data show an increase in blockage across the rotors and a decrease across the stators. For this fan the calculated blockages for the second stage were essentially the same as those for the first stage.

Segregation physics of a macroscale granular ratchet

NASA Astrophysics Data System (ADS)

Bhateja, Ashish; Sharma, Ishan; Singh, Jayant K.

2017-05-01

New experiments with multigrain mixtures in a laterally shaken, horizontal channel show complete axial segregation of species. The channel consists of multiple concatenated trapeziums, and superficially resembles microratchets wherein asymmetric geometries and potentials transport, and sort, randomly agitated microscopic particles. However, the physics of our macroscale granular ratchet is fundamentally different, as macroscopic segregation is gravity driven. Our observations are not explained by classical granular segregation theories either. Motivated by the experiments, extensive parallelized discrete element simulations reveal that the macroratchet differentiates grains through hierarchical bidirectional segregation over two different time scales: Grains rapidly sort vertically into horizontal bands spanning the channel's length that, subsequently, slowly separate axially, driven by strikingly gentle, average interfacial pressure gradients acting over long distances. At its maximum, the pressure gradient responsible for axial separation was due to a change in height of about two big grain diameters (d =7 mm) over a meter-long channel. The strong directional segregation achieved by the granular macroratchet has practical importance, while identifying the underlying new physics will further our understanding of granular segregation in industrial and geophysical processes.

Can phoretic particles swim in two dimensions?

NASA Astrophysics Data System (ADS)

Sondak, David; Hawley, Cory; Heng, Siyu; Vinsonhaler, Rebecca; Lauga, Eric; Thiffeault, Jean-Luc

2016-12-01

Artificial phoretic particles swim using self-generated gradients in chemical species (self-diffusiophoresis) or charges and currents (self-electrophoresis). These particles can be used to study the physics of collective motion in active matter and might have promising applications in bioengineering. In the case of self-diffusiophoresis, the classical physical model relies on a steady solution of the diffusion equation, from which chemical gradients, phoretic flows, and ultimately the swimming velocity may be derived. Motivated by disk-shaped particles in thin films and under confinement, we examine the extension to two dimensions. Because the two-dimensional diffusion equation lacks a steady state with the correct boundary conditions, Laplace transforms must be used to study the long-time behavior of the problem and determine the swimming velocity. For fixed chemical fluxes on the particle surface, we find that the swimming velocity ultimately always decays logarithmically in time. In the case of finite Péclet numbers, we solve the full advection-diffusion equation numerically and show that this decay can be avoided by the particle moving to regions of unconsumed reactant. Finite advection thus regularizes the two-dimensional phoretic problem.

Predicting Ga and Cu Profiles in Co-Evaporated Cu(In,Ga)Se 2 Using Modified Diffusion Equations and a Spreadsheet

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

Repins, Ingrid L.; Harvey, Steve; Bowers, Karen

Cu(In,Ga)Se 2(CIGS) photovoltaic absorbers frequently develop Ga gradients during growth. These gradients vary as a function of growth recipe, and are important to device performance. Prediction of Ga profiles using classic diffusion equations is not possible because In and Ga atoms occupy the same lattice sites and thus diffuse interdependently, and there is not yet a detailed experimental knowledge of the chemical potential as a function of composition that describes this interaction. Here, we show how diffusion equations can be modified to account for site sharing between In and Ga atoms. The analysis has been implemented in an Excel spreadsheet,more » and outputs predicted Cu, In, and Ga profiles for entered deposition recipes. A single set of diffusion coefficients and activation energies are chosen, such that simulated elemental profiles track with published data and those from this study. Extent and limits of agreement between elemental profiles predicted from the growth recipes and the spreadsheet tool are demonstrated.« less

Evaluating the Classical Versus an Emerging Conceptual Model of Peatland Methane Dynamics

NASA Astrophysics Data System (ADS)

Yang, Wendy H.; McNicol, Gavin; Teh, Yit Arn; Estera-Molina, Katerina; Wood, Tana E.; Silver, Whendee L.

2017-09-01

Methane (CH4) is a potent greenhouse gas that is both produced and consumed in soils by microbially mediated processes sensitive to soil redox. We evaluated the classical conceptual model of peatland CH4 dynamics—in which the water table position determines the vertical distribution of methanogenesis and methanotrophy—versus an emerging model in which methanogenesis and methanotrophy can both occur throughout the soil profile due to spatially heterogeneous redox and anaerobic CH4 oxidation. We simultaneously measured gross CH4 production and oxidation in situ across a microtopographical gradient in a drained temperate peatland and ex situ along the soil profile, giving us novel insight into the component fluxes of landscape-level net CH4 fluxes. Net CH4 fluxes varied among landforms (p < 0.001), ranging from 180.3 ± 81.2 mg C m-2 d-1 in drainage ditches to -0.7 ± 1.2 mg C m-2 d-1 in the highest landform. Contrary to prediction by the classical conceptual model, variability in methanogenesis alone drove the landscape-level net CH4 flux patterns. Consistent with the emerging model, freshly collected soils from above the water table produced CH4 within anaerobic microsites. Even in soil from beneath the water table, gross CH4 production was best predicted by the methanogenic fraction of carbon mineralization, an index of highly reducing microsites. We measured low rates of anaerobic CH4 oxidation, which may have been limited by relatively low in situ CH4 concentrations in the hummock/hollow soil profile. Our study revealed complex CH4 dynamics better represented by the emerging heterogeneous conceptual model than the classical model based on redox strata.

Adaptive synchronized switch damping on an inductor: a self-tuning switching law

NASA Astrophysics Data System (ADS)

Kelley, Christopher R.; Kauffman, Jeffrey L.

2017-03-01

Synchronized switch damping (SSD) techniques exploit low-power switching between passive circuits connected to piezoelectric material to reduce structural vibration. In the classical implementation of SSD, the piezoelectric material remains in an open circuit for the majority of the vibration cycle and switches briefly to a shunt circuit at every displacement extremum. Recent research indicates that this switch timing is only optimal for excitation exactly at resonance and points to more general optimal switch criteria based on the phase of the displacement and the system parameters. This work proposes a self-tuning approach that implements the more general optimal switch timing for synchronized switch damping on an inductor (SSDI) without needing any knowledge of the system parameters. The law involves a gradient-based search optimization that is robust to noise and uncertainties in the system. Testing of a physical implementation confirms this law successfully adapts to the frequency and parameters of the system. Overall, the adaptive SSDI controller provides better off-resonance steady-state vibration reduction than classical SSDI while matching performance at resonance.

The atmosphere, the p-factor and the bright visible circumstellar environment of the prototype of classical Cepheids δ Cep

NASA Astrophysics Data System (ADS)

Nardetto, Nicolas; Poretti, Ennio; Mérand, Antoine; Anderson, Richard I.; Fokin, Andrei; Fouqué, Pascal; Gallenne, Alexandre; Gieren, Wolfgang; Graczyk, Dariusz; Kervella, Pierre; Mathias, Philippe; Mourard, Denis; Neilson, Hilding; Pietrzynski, Grzegorz; Pilecki, Bogumil; Rainer, Monica; Storm, Jesper

2017-09-01

Even ≃ 16000 cycles after its discovery by John Goodricke in 1783, δ Cep, the prototype of classical Cepheids, is still studied intensively in order to better understand its atmospheric dynamical structure and its environment. Using HARPS-N spectroscopic measurements, we have measured the atmospheric velocity gradient of δ Cep for the first time and we confirm the decomposition of the projection factor, a subtle physical quantity limiting the Baade-Wesselink (BW) method of distance determination. This decomposition clarifies the physics behind the projection factor and will be useful to interpret the hundreds of p-factors that will come out from the next Gaia release. Besides, VEGA/CHARA interferometric observations of the star revealed a bright visible circumstellar environment contributing to about 7% to the total flux. Better understanding the physics of the pulsation and the environment of Cepheids is necessary to improve the BW method of distance determination, a robust tool to reach Cepheids in the MilkyWay, and beyond, in the Local Group.

Strong wave/mean-flow coupling in baroclinic acoustic streaming

NASA Astrophysics Data System (ADS)

Chini, Greg; Michel, Guillaume

2017-11-01

Recently, Chini et al. demonstrated the potential for large-amplitude acoustic streaming in compressible channel flows subjected to strong background cross-channel density variations. In contrast with classic Rayleigh streaming, standing acoustic waves of O (ɛ) amplitude acquire vorticity owing to baroclinic torques acting throughout the domain rather than via viscous torques acting in Stokes boundary layers. More significantly, these baroclinically-driven streaming flows have a magnitude that also is O (ɛ) , i.e. comparable to that of the sound waves. In the present study, the consequent potential for fully two-way coupling between the waves and streaming flows is investigated using a novel WKBJ analysis. The analysis confirms that the wave-driven streaming flows are sufficiently strong to modify the background density gradient, thereby modifying the leading-order acoustic wave structure. Simulations of the wave/mean-flow system enabled by the WKBJ analysis are performed to illustrate the nature of the two-way coupling, which contrasts sharply with classic Rayleigh streaming, for which the waves can first be determined and the streaming flows subsequently computed.

Correlation-based regularization and gradient operators for (joint) inversion on unstructured meshes

NASA Astrophysics Data System (ADS)

Jordi, Claudio; Doetsch, Joseph; Günther, Thomas; Schmelzbach, Cedric; Robertsson, Johan

2017-04-01

When working with unstructured meshes for geophysical inversions, special attention should be paid to the design of the operators that are used for regularizing the inverse problem and coupling of different property models in joint inversions. Regularization constraints for inversions on unstructured meshes are often defined in a rather ad-hoc manner and usually only involve the cell to which the operator is applied and its direct neighbours. Similarly, most structural coupling operators for joint inversion, such as the popular cross-gradients operator, are only defined in the direct neighbourhood of a cell. As a result, the regularization and coupling length scales and strength of these operators depend on the discretization as well as cell sizes and shape. Especially for unstructured meshes, where the cell sizes vary throughout the model domain, the dependency of the operator on the discretization may lead to artefacts. Designing operators that are based on a spatial correlation model allows to define correlation length scales over which an operator acts (called footprint), reducing the dependency on the discretization and the effects of variable cell sizes. Moreover, correlation-based operators can accommodate for expected anisotropy by using different length scales in horizontal and vertical directions. Correlation-based regularization operators also known as stochastic regularization operators have already been successfully applied to inversions on regular grids. Here, we formulate stochastic operators for unstructured meshes and apply them in 2D surface and 3D cross-well electrical resistivity tomography data inversion examples of layered media. Especially for the synthetic cross-well example, improved inversion results are achieved when stochastic regularization is used instead of a classical smoothness constraint. For the case of cross-gradients operators for joint inversion, the correlation model is used to define the footprint of the operator and weigh the contributions of the property values that are used to calculate the cross-gradients. In a first series of synthetic-data tests, we examined the mesh dependency of the cross-gradients operators. Compared to operators that are only defined in the direct neighbourhood of a cell, the dependency on the cell size of the cross-gradients calculation is markedly reduced when using operators with larger footprints. A second test with synthetic models focussed on the effect of small-scale variabilities of the parameter value on the cross-gradients calculation. Small-scale variabilities that are superimposed on a global trend of the property value can potentially degrade the cross-gradients calculation and destabilize joint inversion. We observe that the cross-gradients from operators with footprints larger than the length scale of the variabilities are less affected compared to operators with a small footprint. In joint inversions on unstructured meshes, we thus expect the correlation-based coupling operators to ensure robust coupling on a physically meaningful scale.

Gaussian processes with built-in dimensionality reduction: Applications to high-dimensional uncertainty propagation

NASA Astrophysics Data System (ADS)

Tripathy, Rohit; Bilionis, Ilias; Gonzalez, Marcial

2016-09-01

Uncertainty quantification (UQ) tasks, such as model calibration, uncertainty propagation, and optimization under uncertainty, typically require several thousand evaluations of the underlying computer codes. To cope with the cost of simulations, one replaces the real response surface with a cheap surrogate based, e.g., on polynomial chaos expansions, neural networks, support vector machines, or Gaussian processes (GP). However, the number of simulations required to learn a generic multivariate response grows exponentially as the input dimension increases. This curse of dimensionality can only be addressed, if the response exhibits some special structure that can be discovered and exploited. A wide range of physical responses exhibit a special structure known as an active subspace (AS). An AS is a linear manifold of the stochastic space characterized by maximal response variation. The idea is that one should first identify this low dimensional manifold, project the high-dimensional input onto it, and then link the projection to the output. If the dimensionality of the AS is low enough, then learning the link function is a much easier problem than the original problem of learning a high-dimensional function. The classic approach to discovering the AS requires gradient information, a fact that severely limits its applicability. Furthermore, and partly because of its reliance to gradients, it is not able to handle noisy observations. The latter is an essential trait if one wants to be able to propagate uncertainty through stochastic simulators, e.g., through molecular dynamics codes. In this work, we develop a probabilistic version of AS which is gradient-free and robust to observational noise. Our approach relies on a novel Gaussian process regression with built-in dimensionality reduction. In particular, the AS is represented as an orthogonal projection matrix that serves as yet another covariance function hyper-parameter to be estimated from the data. To train the model, we design a two-step maximum likelihood optimization procedure that ensures the orthogonality of the projection matrix by exploiting recent results on the Stiefel manifold, i.e., the manifold of matrices with orthogonal columns. The additional benefit of our probabilistic formulation, is that it allows us to select the dimensionality of the AS via the Bayesian information criterion. We validate our approach by showing that it can discover the right AS in synthetic examples without gradient information using both noiseless and noisy observations. We demonstrate that our method is able to discover the same AS as the classical approach in a challenging one-hundred-dimensional problem involving an elliptic stochastic partial differential equation with random conductivity. Finally, we use our approach to study the effect of geometric and material uncertainties in the propagation of solitary waves in a one dimensional granular system.

Gaussian processes with built-in dimensionality reduction: Applications to high-dimensional uncertainty propagation

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

Tripathy, Rohit, E-mail: rtripath@purdue.edu; Bilionis, Ilias, E-mail: ibilion@purdue.edu; Gonzalez, Marcial, E-mail: marcial-gonzalez@purdue.edu

2016-09-15

Uncertainty quantification (UQ) tasks, such as model calibration, uncertainty propagation, and optimization under uncertainty, typically require several thousand evaluations of the underlying computer codes. To cope with the cost of simulations, one replaces the real response surface with a cheap surrogate based, e.g., on polynomial chaos expansions, neural networks, support vector machines, or Gaussian processes (GP). However, the number of simulations required to learn a generic multivariate response grows exponentially as the input dimension increases. This curse of dimensionality can only be addressed, if the response exhibits some special structure that can be discovered and exploited. A wide range ofmore » physical responses exhibit a special structure known as an active subspace (AS). An AS is a linear manifold of the stochastic space characterized by maximal response variation. The idea is that one should first identify this low dimensional manifold, project the high-dimensional input onto it, and then link the projection to the output. If the dimensionality of the AS is low enough, then learning the link function is a much easier problem than the original problem of learning a high-dimensional function. The classic approach to discovering the AS requires gradient information, a fact that severely limits its applicability. Furthermore, and partly because of its reliance to gradients, it is not able to handle noisy observations. The latter is an essential trait if one wants to be able to propagate uncertainty through stochastic simulators, e.g., through molecular dynamics codes. In this work, we develop a probabilistic version of AS which is gradient-free and robust to observational noise. Our approach relies on a novel Gaussian process regression with built-in dimensionality reduction. In particular, the AS is represented as an orthogonal projection matrix that serves as yet another covariance function hyper-parameter to be estimated from the data. To train the model, we design a two-step maximum likelihood optimization procedure that ensures the orthogonality of the projection matrix by exploiting recent results on the Stiefel manifold, i.e., the manifold of matrices with orthogonal columns. The additional benefit of our probabilistic formulation, is that it allows us to select the dimensionality of the AS via the Bayesian information criterion. We validate our approach by showing that it can discover the right AS in synthetic examples without gradient information using both noiseless and noisy observations. We demonstrate that our method is able to discover the same AS as the classical approach in a challenging one-hundred-dimensional problem involving an elliptic stochastic partial differential equation with random conductivity. Finally, we use our approach to study the effect of geometric and material uncertainties in the propagation of solitary waves in a one dimensional granular system.« less

Electrophoresis in strong electric fields.

PubMed

Barany, Sandor

2009-01-01

Two kinds of non-linear electrophoresis (ef) that can be detected in strong electric fields (several hundred V/cm) are considered. The first ("classical" non-linear ef) is due to the interaction of the outer field with field-induced ionic charges in the electric double layer (EDL) under conditions, when field-induced variations of electrolyte concentration remain to be small comparatively to its equilibrium value. According to the Shilov theory, the non-linear component of the electrophoretic velocity for dielectric particles is proportional to the cubic power of the applied field strength (cubic electrophoresis) and to the second power of the particles radius; it is independent of the zeta-potential but is determined by the surface conductivity of particles. The second one, the so-called "superfast electrophoresis" is connected with the interaction of a strong outer field with a secondary diffuse layer of counterions (space charge) that is induced outside the primary (classical) diffuse EDL by the external field itself because of concentration polarization. The Dukhin-Mishchuk theory of "superfast electrophoresis" predicts quadratic dependence of the electrophoretic velocity of unipolar (ionically or electronically) conducting particles on the external field gradient and linear dependence on the particle's size in strong electric fields. These are in sharp contrast to the laws of classical electrophoresis (no dependence of V(ef) on the particle's size and linear dependence on the electric field gradient). A new method to measure the ef velocity of particles in strong electric fields is developed that is based on separation of the effects of sedimentation and electrophoresis using videoimaging and a new flowcell and use of short electric pulses. To test the "classical" non-linear electrophoresis, we have measured the ef velocity of non-conducting polystyrene, aluminium-oxide and (semiconductor) graphite particles as well as Saccharomice cerevisiae yeast cells as a function of the electric field strength, particle size, electrolyte concentration and the adsorbed polymer amount. It has been shown that the electrophoretic velocity of the particles/cells increases with field strength linearly up to about 100 and 200 V/cm (for cells) without and with adsorbed polymers both in pure water and in electrolyte solutions. In line with the theoretical predictions, in stronger fields substantial non-linear effects were recorded (V(ef)~E(3)). The ef velocity of unipolar ion-type conducting (ion-exchanger particles and fibres), electron-type conducting (magnesium and Mg/Al alloy) and semiconductor particles (graphite, activated carbon, pyrite, molybdenite) increases significantly with the electric field (V(ef)~E(2)) and the particle's size but is almost independent of the ionic strength. These trends are inconsistent with Smoluchowski's equation for dielectric particles, but are consistent with the Dukhin-Mishchuk theory of superfast electrophoresis.

Orthobiologics in Pediatric Sports Medicine.

PubMed

Bray, Christopher C; Walker, Clark M; Spence, David D

2017-07-01

Orthobiologics are biological substances that allow injured muscles, tendons, ligaments, and bone to heal more quickly. They are found naturally in the body; at higher concentrations they can aid in the healing process. These substances include autograft bone, allograft bone, demineralized bone matrix, bone morphogenic proteins, growth factors, stem cells, plasma-rich protein, and ceramic grafts. Their use in sports medicine has exploded in efforts to increase graft incorporation, stimulate healing, and get athletes back to sport with problems including anterior cruciate ligament ruptures, tendon ruptures, cartilage injuries, and fractures. This article reviews orthobiologics and their applications in pediatric sports medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural dynamics of the mitochondrial compartment.

PubMed

Thorsness, P E

1992-09-01

The metabolic activities of mitochondria have been extensively characterized. However, there is much less known about the morphogenic changes of the mitochondrial compartment during growth, development and aging of the cell and the consequences of those structural changes on cellular metabolism. There is a growing body of evidence for interactions of mitochondria with cytoskeletal components and changes of mitochondrial structure during development and in response to changing environmental conditions. Segregation and recombination of mitochondrial genomes are also processes dependent upon the dynamic nature of the mitochondrial compartment. These regulatory and structural aspects of mitochondrial compartment dynamics will play an important role in the analysis of mitochondrial function and pathology.

New activators and inhibitors in the hair cycle clock: targeting stem cells’ state of competence

PubMed Central

Plikus, Maksim V.

2014-01-01

Summary The timing mechanism of the hair cycle remains poorly understood. However, it has become increasingly clear that the telogen-to-anagen transition is controlled jointly by at least the bone morphogenic protein (BMP), WNT, fibroblast growth factor (FGF), and transforming growth factor (TGF)-β signaling pathways. New research shows that Fgf18 signaling in hair follicle stem cells synergizes BMP-mediated refractivity, whereas Tgf-β2 signaling counterbalances it. Loss of Fgf18 signaling markedly accelerates anagen initiation, whereas loss of Tgf-β2 signaling significantly delays it, supporting key roles for these pathways in hair cycle timekeeping. PMID:22499035

Tissue engineering in endodontics.

PubMed

Saber, Shehab El-Din M

2009-12-01

Tissue engineering is the science of design and manufacture of new tissues to replace impaired or damaged ones. The key ingredients for tissue engineering are stem cells, the morphogens or growth factors that regulate their differentiation, and a scaffold of extracellular matrix that constitutes the microenvironment for their growth. Recently, there has been increasing interest in applying the concept of tissue engineering to endodontics. The aim of this study was to review the body of knowledge related to dental pulp stem cells, the most common growth factors, and the scaffolds used to control their differentiation, and a clinical technique for the management of immature non-vital teeth based on this novel concept.

Barrett's esophagus: cancer and molecular biology.

PubMed

Gibson, Michael K; Dhaliwal, Arashinder S; Clemons, Nicholas J; Phillips, Wayne A; Dvorak, Katerina; Tong, Daniel; Law, Simon; Pirchi, E Daniel; Räsänen, Jari; Krasna, Mark J; Parikh, Kaushal; Krishnadath, Kausilia K; Chen, Yu; Griffiths, Leonard; Colleypriest, Benjamin J; Farrant, J Mark; Tosh, David; Das, Kiron M; Bajpai, Manisha

2013-10-01

The following paper on the molecular biology of Barrett's esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF-κB, and IL-6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the merits of minimally invasive esophagectomy versus open surgery; outcomes for patients with pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and chemoradiotherapy; animal models examining the surgical models of BE and esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and the use of in vitro BE models for chemoprevention studies. © 2013 New York Academy of Sciences.

bicoid RNA localization requires specific binding of an endosomal sorting complex

PubMed Central

Irion, Uwe; St Johnston, Daniel

2007-01-01

Summary paragraph: bicoid mRNA localises to the anterior of the Drosophila egg, where it is translated to form a morphogen gradient of Bicoid protein that patterns the head and thorax of the embryo. Although bicoid was the first identified localised cytoplasmic determinant1-4, little is known about how the mRNA is coupled to the microtubule-dependent transport pathway that targets it to the anterior, and it has been proposed that it is recognised by a complex of many redundant proteins, each of which binds to the localisation element in its 3'UTR with little or no specificity5. Indeed, the only known RNA-binding protein that co-localises with bicoid mRNA is Staufen, which binds non-specifically to dsRNA in vitro6, 7. Here we show that mutants in all subunits of the ESCRT-II complex (Vps22, Vps25 and Vps36) abolish the final Staufen-dependent step in bcd RNA localisation. ESCRT-II is a highly conserved component of the pathway that sorts ubiquitinated endosomal proteins into internal vesicles8, 9, and functions as a tumour-suppressor by removing activated receptors from the cytoplasm10, 11. However, the role of ESCRT-II in bicoid localisation appears to be independent of endosomal sorting, because mutations in ESCRT-I and III components have no effect of the targeting of bicoid mRNA. Instead, Vps36 functions by binding directly and specifically to stem-loop V of the bicoid 3'UTR through its N-terminal GLUE domain12, making it the first example of a sequence specific RNA-binding protein that recognises the bicoid localisation signal. Furthermore, Vps36 localises to the anterior of the oocyte in a bicoid mRNA-dependent manner, and is required for the subsequent recruitment of Staufen to the bicoid complex. This novel function of ESCRT-II as an RNA-binding complex is conserved in vertebrates, and may explain some of its roles that are independent of endosomal sorting. PMID:17268469

Axon and dendrite geography predict the specificity of synaptic connections in a functioning spinal cord network.

PubMed

Li, Wen-Chang; Cooke, Tom; Sautois, Bart; Soffe, Stephen R; Borisyuk, Roman; Roberts, Alan

2007-09-10

How specific are the synaptic connections formed as neuronal networks develop and can simple rules account for the formation of functioning circuits? These questions are assessed in the spinal circuits controlling swimming in hatchling frog tadpoles. This is possible because detailed information is now available on the identity and synaptic connections of the main types of neuron. The probabilities of synapses between 7 types of identified spinal neuron were measured directly by making electrical recordings from 500 pairs of neurons. For the same neuron types, the dorso-ventral distributions of axons and dendrites were measured and then used to calculate the probabilities that axons would encounter particular dendrites and so potentially form synaptic connections. Surprisingly, synapses were found between all types of neuron but contact probabilities could be predicted simply by the anatomical overlap of their axons and dendrites. These results suggested that synapse formation may not require axons to recognise specific, correct dendrites. To test the plausibility of simpler hypotheses, we first made computational models that were able to generate longitudinal axon growth paths and reproduce the axon distribution patterns and synaptic contact probabilities found in the spinal cord. To test if probabilistic rules could produce functioning spinal networks, we then made realistic computational models of spinal cord neurons, giving them established cell-specific properties and connecting them into networks using the contact probabilities we had determined. A majority of these networks produced robust swimming activity. Simple factors such as morphogen gradients controlling dorso-ventral soma, dendrite and axon positions may sufficiently constrain the synaptic connections made between different types of neuron as the spinal cord first develops and allow functional networks to form. Our analysis implies that detailed cellular recognition between spinal neuron types may not be necessary for the reliable formation of functional networks to generate early behaviour like swimming.

Discrete cilia modelling with singularity distributions: application to the embryonic node and the airway surface liquid.

PubMed

Smith, D J; Gaffney, E A; Blake, J R

2007-07-01

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous 'singularity models' is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a 'posterior tilt,' and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 mum/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system.

Tissue-Specific Gain of RTK Signalling Uncovers Selective Cell Vulnerability during Embryogenesis

PubMed Central

Audebert, Stéphane; Helmbacher, Françoise; Dono, Rosanna; Maina, Flavio

2015-01-01

The successive events that cells experience throughout development shape their intrinsic capacity to respond and integrate RTK inputs. Cellular responses to RTKs rely on different mechanisms of regulation that establish proper levels of RTK activation, define duration of RTK action, and exert quantitative/qualitative signalling outcomes. The extent to which cells are competent to deal with fluctuations in RTK signalling is incompletely understood. Here, we employ a genetic system to enhance RTK signalling in a tissue-specific manner. The chosen RTK is the hepatocyte growth factor (HGF) receptor Met, an appropriate model due to its pleiotropic requirement in distinct developmental events. Ubiquitously enhanced Met in Cre/loxP-based Rosa26 stopMet knock-in context (Del-R26 Met) reveals that most tissues are capable of buffering enhanced Met-RTK signalling thus avoiding perturbation of developmental programs. Nevertheless, this ubiquitous increase of Met does compromise selected programs such as myoblast migration. Using cell-type specific Cre drivers, we genetically showed that altered myoblast migration results from ectopic Met expression in limb mesenchyme rather than in migrating myoblasts themselves. qRT-PCR analyses show that ectopic Met in limbs causes molecular changes such as downregulation in the expression levels of Notum and Syndecan4, two known regulators of morphogen gradients. Molecular and functional studies revealed that ectopic Met expression in limb mesenchyme does not alter HGF expression patterns and levels, but impairs HGF bioavailability. Together, our findings show that myoblasts, in which Met is endogenously expressed, are capable of buffering increased RTK levels, and identify mesenchymal cells as a cell type vulnerable to ectopic Met-RTK signalling. These results illustrate that embryonic cells are sensitive to alterations in the spatial distribution of RTK action, yet resilient to fluctuations in signalling levels of an RTK when occurring in its endogenous domain of activity. PMID:26393505

Pulmonary blood flow distribution in sheep: effects of anesthesia, mechanical ventilation, and change in posture

NASA Technical Reports Server (NTRS)

Walther, S. M.; Domino, K. B.; Glenny, R. W.; Hlastala, M. P.

1997-01-01

BACKGROUND: Recent studies providing high-resolution images of pulmonary perfusion have questioned the classical zone model of pulmonary perfusion. Hence the present work was undertaken to provide detailed maps of regional pulmonary perfusion to examine the influence of anesthesia, mechanical ventilation, and posture. METHODS: Pulmonary perfusion was analyzed with intravenous fluorescent microspheres (15 microm) in six sheep studied in four conditions: prone and awake, prone with pentobarbital-anesthesia and breathing spontaneously, prone with anesthesia and mechanical ventilation, and supine with anesthesia and mechanical ventilation. Lungs were air dried at total lung capacity and sectioned into approximately 1,100 pieces (about 2 cm3) per animal. The pieces were weighed and assigned spatial coordinates. Fluorescence was read on a spectrophotometer, and signals were corrected for piece weight and normalized to mean flow. Pulmonary blood flow heterogeneity was assessed using the coefficient of variation of flow data. RESULTS: Pentobarbital anesthesia and mechanical ventilation did not influence perfusion heterogeneity, but heterogeneity increased when the animals were in the supine posture (P < 0.01). Gravitational flow gradients were absent in the prone position but present in the supine (P < 0.001 compared with zero). Pulmonary perfusion was distributed with a hilar-to-peripheral gradient in animals breathing spontaneously (P < 0.05). CONCLUSIONS: The influence of pentobarbital anesthesia and mechanical ventilation on pulmonary perfusion heterogeneity is small compared with the effect of changes in posture. Analysis of flow gradients indicate that gravity plays a small role in determining pulmonary blood flow distribution.

A Dissolved Oxygen Threshold for Shifts in Bacterial Community Structure in a Seasonally Hypoxic Estuary

PubMed Central

Spietz, Rachel L.; Williams, Cheryl M.; Rocap, Gabrielle; Horner-Devine, M. Claire

2015-01-01

Pelagic ecosystems can become depleted of dissolved oxygen as a result of both natural processes and anthropogenic effects. As dissolved oxygen concentration decreases, energy shifts from macrofauna to microorganisms, which persist in these hypoxic zones. Oxygen-limited regions are rapidly expanding globally; however, patterns of microbial communities associated with dissolved oxygen gradients are not yet well understood. To assess the effects of decreasing dissolved oxygen on bacteria, we examined shifts in bacterial community structure over space and time in Hood Canal, Washington, USA−a glacial fjord-like water body that experiences seasonal low dissolved oxygen levels known to be detrimental to fish and other marine organisms. We found a strong negative association between bacterial richness and dissolved oxygen. Bacterial community composition across all samples was also strongly associated with the dissolved oxygen gradient, and significant changes in bacterial community composition occurred at a dissolved oxygen concentration between 5.18 and 7.12 mg O2 L-1. This threshold value of dissolved oxygen is higher than classic definitions of hypoxia (<2.0 mg O2 L-1), suggesting that changes in bacterial communities may precede the detrimental effects on ecologically and economically important macrofauna. Furthermore, bacterial taxa responsible for driving whole community changes across the oxygen gradient are commonly detected in other oxygen-stressed ecosystems, suggesting that the patterns we uncovered in Hood Canal may be relevant in other low oxygen ecosystems. PMID:26270047

Temperature mapping of laser-induced hyperthermia in an ocular phantom using magnetic resonance thermography.

PubMed

Maswadi, Saher M; Dodd, Stephen J; Gao, Jia-Hong; Glickman, Randolph D

2004-01-01

Laser-induced heating in an ocular phantom is measured with magnetic resonance thermography (MRT) using temperature-dependent phase changes in proton resonance frequency. The ocular phantom contains a layer of melanosomes isolated from bovine retinal pigment epithelium. The phantom is heated by the 806-nm output of a continuous wave diode laser with an irradiance of 2.4 to 21.6 W/cm2 in a beam radius of 0.8 or 2.4 mm, depending on the experiment. MRT is performed with a 2 T magnet, and a two-turn, 6-cm-diam, circular radio frequency coil. Two-dimensional temperature gradients are measured within the plane of the melanin layer, as well as normal to it, with a temperature resolution of 1 degrees C or better. The temperature gradients extending within the melanin layer are broader than those orthogonal to the layer, consistent with the higher optical absorption and consequent heating in the melanin. The temperature gradients in the phantom measured by MRT closely approximate the predictions of a classical heat diffusion model. Three-dimensional temperature maps with a spatial resolution of 0.25 mm in all directions are also made. Although the temporal resolution is limited in the prototype system (22.9 s for a single image "slice"), improvements in future implementations are likely. These results indicate that MRT has sufficient spatial and temperature resolution to monitor target tissue temperature during transpupillary thermotherapy in the human eye.

Ghost circles in lattice Aubry-Mather theory

NASA Astrophysics Data System (ADS)

Mramor, Blaz; Rink, Bob

Monotone lattice recurrence relations such as the Frenkel-Kontorova lattice, arise in Hamiltonian lattice mechanics, as models for ferromagnetism and as discretization of elliptic PDEs. Mathematically, they are a multi-dimensional counterpart of monotone twist maps. Such recurrence relations often admit a variational structure, so that the solutions x:Z→R are the stationary points of a formal action function W(x). Given any rotation vector ω∈R, classical Aubry-Mather theory establishes the existence of a large collection of solutions of ∇W(x)=0 of rotation vector ω. For irrational ω, this is the well-known Aubry-Mather set. It consists of global minimizers and it may have gaps. In this paper, we study the parabolic gradient flow {dx}/{dt}=-∇W(x) and we will prove that every Aubry-Mather set can be interpolated by a continuous gradient-flow invariant family, the so-called 'ghost circle'. The existence of these ghost circles is known in dimension d=1, for rational rotation vectors and Morse action functions. The main technical result of this paper is therefore a compactness theorem for lattice ghost circles, based on a parabolic Harnack inequality for the gradient flow. This implies the existence of lattice ghost circles of arbitrary rotation vectors and for arbitrary actions. As a consequence, we can give a simple proof of the fact that when an Aubry-Mather set has a gap, then this gap must be filled with minimizers, or contain a non-minimizing solution.

Puzzles in modern biology. V. Why are genomes overwired?

PubMed

Frank, Steven A

2017-01-01

Many factors affect eukaryotic gene expression. Transcription factors, histone codes, DNA folding, and noncoding RNA modulate expression. Those factors interact in large, broadly connected regulatory control networks. An engineer following classical principles of control theory would design a simpler regulatory network. Why are genomes overwired? Neutrality or enhanced robustness may lead to the accumulation of additional factors that complicate network architecture. Dynamics progresses like a ratchet. New factors get added. Genomes adapt to the additional complexity. The newly added factors can no longer be removed without significant loss of fitness. Alternatively, highly wired genomes may be more malleable. In large networks, most genomic variants tend to have a relatively small effect on gene expression and trait values. Many small effects lead to a smooth gradient, in which traits may change steadily with respect to underlying regulatory changes. A smooth gradient may provide a continuous path from a starting point up to the highest peak of performance. A potential path of increasing performance promotes adaptability and learning. Genomes gain by the inductive process of natural selection, a trial and error learning algorithm that discovers general solutions for adapting to environmental challenge. Similarly, deeply and densely connected computational networks gain by various inductive trial and error learning procedures, in which the networks learn to reduce the errors in sequential trials. Overwiring alters the geometry of induction by smoothing the gradient along the inductive pathways of improving performance. Those overwiring benefits for induction apply to both natural biological networks and artificial deep learning networks.

Using Spherical-Harmonics Expansions for Optics Surface Reconstruction from Gradients.

PubMed

Solano-Altamirano, Juan Manuel; Vázquez-Otero, Alejandro; Khikhlukha, Danila; Dormido, Raquel; Duro, Natividad

2017-11-30

In this paper, we propose a new algorithm to reconstruct optics surfaces (aka wavefronts) from gradients, defined on a circular domain, by means of the Spherical Harmonics. The experimental results indicate that this algorithm renders the same accuracy, compared to the reconstruction based on classical Zernike polynomials, using a smaller number of polynomial terms, which potentially speeds up the wavefront reconstruction. Additionally, we provide an open-source C++ library, released under the terms of the GNU General Public License version 2 (GPLv2), wherein several polynomial sets are coded. Therefore, this library constitutes a robust software alternative for wavefront reconstruction in a high energy laser field, optical surface reconstruction, and, more generally, in surface reconstruction from gradients. The library is a candidate for being integrated in control systems for optical devices, or similarly to be used in ad hoc simulations. Moreover, it has been developed with flexibility in mind, and, as such, the implementation includes the following features: (i) a mock-up generator of various incident wavefronts, intended to simulate the wavefronts commonly encountered in the field of high-energy lasers production; (ii) runtime selection of the library in charge of performing the algebraic computations; (iii) a profiling mechanism to measure and compare the performance of different steps of the algorithms and/or third-party linear algebra libraries. Finally, the library can be easily extended to include additional dependencies, such as porting the algebraic operations to specific architectures, in order to exploit hardware acceleration features.

Using Spherical-Harmonics Expansions for Optics Surface Reconstruction from Gradients

PubMed Central

Solano-Altamirano, Juan Manuel; Khikhlukha, Danila

2017-01-01

In this paper, we propose a new algorithm to reconstruct optics surfaces (aka wavefronts) from gradients, defined on a circular domain, by means of the Spherical Harmonics. The experimental results indicate that this algorithm renders the same accuracy, compared to the reconstruction based on classical Zernike polynomials, using a smaller number of polynomial terms, which potentially speeds up the wavefront reconstruction. Additionally, we provide an open-source C++ library, released under the terms of the GNU General Public License version 2 (GPLv2), wherein several polynomial sets are coded. Therefore, this library constitutes a robust software alternative for wavefront reconstruction in a high energy laser field, optical surface reconstruction, and, more generally, in surface reconstruction from gradients. The library is a candidate for being integrated in control systems for optical devices, or similarly to be used in ad hoc simulations. Moreover, it has been developed with flexibility in mind, and, as such, the implementation includes the following features: (i) a mock-up generator of various incident wavefronts, intended to simulate the wavefronts commonly encountered in the field of high-energy lasers production; (ii) runtime selection of the library in charge of performing the algebraic computations; (iii) a profiling mechanism to measure and compare the performance of different steps of the algorithms and/or third-party linear algebra libraries. Finally, the library can be easily extended to include additional dependencies, such as porting the algebraic operations to specific architectures, in order to exploit hardware acceleration features. PMID:29189722