Glutamatergic drive along the septo-temporal axis of hippocampus boosts prelimbic oscillations in the neonatal mouse

PubMed Central

Ahlbeck, Joachim; Song, Lingzhen; Chini, Mattia; Bitzenhofer, Sebastian H

2018-01-01

The long-range coupling within prefrontal-hippocampal networks that account for cognitive performance emerges early in life. The discontinuous hippocampal theta bursts have been proposed to drive the generation of neonatal prefrontal oscillations, yet the cellular substrate of these early interactions is still unresolved. Here, we selectively target optogenetic manipulation of glutamatergic projection neurons in the CA1 area of either dorsal or intermediate/ventral hippocampus at neonatal age to elucidate their contribution to the emergence of prefrontal oscillatory entrainment. We show that despite stronger theta and ripples power in dorsal hippocampus, the prefrontal cortex is mainly coupled with intermediate/ventral hippocampus by phase-locking of neuronal firing via dense direct axonal projections. Theta band-confined activation by light of pyramidal neurons in intermediate/ventral but not dorsal CA1 that were transfected by in utero electroporation with high-efficiency channelrhodopsin boosts prefrontal oscillations. Our data causally elucidate the cellular origin of the long-range coupling in the developing brain. PMID:29631696

Structure of the Shroom-Rho Kinase Complex Reveals a Binding Interface with Monomeric Shroom That Regulates Cell Morphology and Stimulates Kinase Activity

DOE PAGES

Zalewski, Jenna K.; Mo, Joshua H.; Heber, Simone; ...

2016-10-10

Shroom-mediated remodeling of the actomyosin cytoskeleton is a critical driver of cellular shape and tissue morphology that underlies the development of many tissues including the neural tube, eye, intestines, and vasculature. Shroom uses a conserved SD2 domain to direct the subcellular localization of Rho-associated kinase (Rock), which in turn drives changes in the cytoskeleton and cellular morphology through its ability to phosphorylate and activate non-muscle myosin II. Here in this paper, we present the structure of the human Shroom-Rock binding module, revealing an unexpected stoichiometry for Shroom in which two Shroom SD2 domains bind independent surfaces on Rock. Mutation ofmore » interfacial residues impaired Shroom-Rock binding in vitro and resulted in altered remodeling of the cytoskeleton and loss of Shroom-mediated changes in cellular morphology. In addition, we provide the first direct evidence that Shroom can function as a Rock activator. These data provide molecular insight into the Shroom-Rock interface and demonstrate that Shroom directly participates in regulating cytoskeletal dynamics, adding to its known role in Rock localization.« less

Cell migration, intercalation and growth regulate mammalian cochlear extension.

PubMed

Driver, Elizabeth Carroll; Northrop, Amy; Kelley, Matthew W

2017-10-15

Developmental remodeling of the sensory epithelium of the cochlea is required for the formation of an elongated, tonotopically organized auditory organ, but the cellular processes that mediate these events are largely unknown. We used both morphological assessments of cellular rearrangements and time-lapse imaging to visualize cochlear remodeling in mouse. Analysis of cell redistribution showed that the cochlea extends through a combination of radial intercalation and cell growth. Live imaging demonstrated that concomitant cellular intercalation results in a brief period of epithelial convergence, although subsequent changes in cell size lead to medial-lateral spreading. Supporting cells, which retain contact with the basement membrane, exhibit biased protrusive activity and directed movement along the axis of extension. By contrast, hair cells lose contact with the basement membrane, but contribute to continued outgrowth through increased cell size. Regulation of cellular protrusions, movement and intercalation within the cochlea all require myosin II. These results establish, for the first time, many of the cellular processes that drive the distribution of sensory cells along the tonotopic axis of the cochlea. © 2017. Published by The Company of Biologists Ltd.

Driven to distraction: dual-Task studies of simulated driving and conversing on a cellular telephone.

PubMed

Strayer, D L; Johnston, W A

2001-11-01

Dual-task studies assessed the effects of cellular-phone conversations on performance of a simulated driving task. Performance was not disrupted by listening to radio broadcasts or listening to a book on tape. Nor was it disrupted by a continuous shadowing task using a handheld phone, ruling out, in this case, dual-task interpretations associated with holding the phone, listening, or speaking, However significant interference was observed in a word-generation variant of the shadowing task, and this deficit increased with the difficulty of driving. Moreover unconstrained conversations using either a handheld or a hands-free cell phone resulted in a twofold increase in the failure to detect simulated traffic signals and slower reactions to those signals that were detected. We suggest that cellular-phone use disrupts performance by diverting attention to an engaging cognitive context other than the one immediately associated with driving.

The Die Is Cast: Precision Electrophilic Modifications Contribute to Cellular Decision Making

PubMed Central

2016-01-01

This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins. The latest interrogations into these on-target electrophilic responses set forth a new horizon in the molecular mechanism of redox signal propagation wherein direct low-occupancy electrophilic modifications on a single sensor target are biologically sufficient to drive functional redox responses with precision timing. We detail how the various mechanisms through which redox signals function could contribute to their interesting phenotypic responses, including hormesis. PMID:27617777

The Die Is Cast: Precision Electrophilic Modifications Contribute to Cellular Decision Making.

PubMed

Long, Marcus J C; Aye, Yimon

2016-10-02

This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins. The latest interrogations into these on-target electrophilic responses set forth a new horizon in the molecular mechanism of redox signal propagation wherein direct low-occupancy electrophilic modifications on a single sensor target are biologically sufficient to drive functional redox responses with precision timing. We detail how the various mechanisms through which redox signals function could contribute to their interesting phenotypic responses, including hormesis.

Safety Solutions and Differences in Motor Vehicle Drivers Who Use Cellular Telephones

ERIC Educational Resources Information Center

Eidelman, James Andrew

2013-01-01

The purpose of the proposed study was to determine whether there is a correlation between attitudes toward the use of handheld cellular telephone devices while driving and the use of such devices while driving, with particular interest in the role of gender, age, marital status, parental status, age of children, having a disability, level of…

A propagating ATPase gradient drives transport of surface-confined cellular cargo

NASA Astrophysics Data System (ADS)

Vecchiarelli, Anthony; Neuman, Keir; Mizuuchi, Kiyoshi

2014-03-01

The process of DNA segregation is of central importance for all organisms. Although eukaryotic mitosis is relatively well established, the most common mechanism employed for bacterial DNA segregation has been unclear. ParA ATPases form dynamic patterns on the bacterial nucleoid, to spatially organize plasmids, chromosomes and other large cellular cargo, but the force generating mechanism has been a source of controversy and debate. A dominant view proposes that ParA-mediated transport and cargo positioning occurs via a filament-based mechanism that resembles eukaryotic mitosis. Here we present direct evidence against such models. Our cell-free reconstitution supports a non-filament-based mode of transport that may be as widely found in nature as actin filaments and microtubules.

Mechanisms of DNA Damage Response to Targeted Irradiation in Organotypic 3D Skin Cultures

PubMed Central

Acheva, Anna; Ghita, Mihaela; Patel, Gaurang; Prise, Kevin M.; Schettino, Giuseppe

2014-01-01

DNA damage (caused by direct cellular exposure and bystander signaling) and the complex pathways involved in its repair are critical events underpinning cellular and tissue response following radiation exposures. There are limited data addressing the dynamics of DNA damage induction and repair in the skin particularly in areas not directly exposed. Here we investigate the mechanisms regulating DNA damage, repair, intracellular signalling and their impact on premature differentiation and development of inflammatory-like response in the irradiated and surrounding areas of a 3D organotypic skin model. Following localized low-LET irradiation (225 kVp X-rays), low levels of 53BP1 foci were observed in the 3D model (3.8±0.28 foci/Gy/cell) with foci persisting and increasing in size up to 48 h post irradiation. In contrast, in cell monolayers 14.2±0.6 foci/Gy/cell and biphasic repair kinetics with repair completed before 24 h was observed. These differences are linked to differences in cellular status with variable level of p21 driving apoptotic signalling in 2D and accelerated differentiation in both the directly irradiated and bystander areas of the 3D model. The signalling pathways utilized by irradiated keratinocytes to induce DNA damage in non-exposed areas of the skin involved the NF-κB transcription factor and its downstream target COX-2. PMID:24505255

Current knowledge on psoriasis and autoimmune diseases

PubMed Central

Ayala-Fontánez, Nilmarie; Soler, David C; McCormick, Thomas S

2016-01-01

Psoriasis is a prevalent, chronic inflammatory disease of the skin, mediated by crosstalk between epidermal keratinocytes, dermal vascular cells, and immunocytes such as antigen presenting cells (APCs) and T cells. Exclusive cellular “responsibility” for the induction and maintenance of psoriatic plaques has not been clearly defined. Increased proliferation of keratinocytes and endothelial cells in conjunction with APC/T cell/monocyte/macrophage inflammation leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin. Despite the identification of numerous susceptibility loci, no single genetic determinant has been identified as responsible for the induction of psoriasis. Thus, numerous other triggers of disease, such as environmental, microbial and complex cellular interactions must also be considered as participants in the development of this multifactorial disease. Recent advances in therapeutics, especially systemic so-called “biologics” have provided new hope for identifying the critical cellular targets that drive psoriasis pathogenesis. Recent recognition of the numerous co-morbidities and other autoimmune disorders associated with psoriasis, including inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus suggest common signaling elements and cellular mediators may direct disease pathogenesis. In this review, we discuss common cellular pathways and participants that mediate psoriasis and other autoimmune disorders that share these cellular signaling pathways. PMID:29387591

Effects of practice on interference from an auditory task while driving : a simulation study

DOT National Transportation Integrated Search

2004-12-01

Experimental research on the effects of cellular phone conversations on driving indicates that the phone task interferes with many driving-related functions, especially with older drivers. Limitations of past research have been that (1) the dual task...

HPV integration hijacks and multimerizes a cellular enhancer to generate a viral-cellular super-enhancer that drives high viral oncogene expression

PubMed Central

Redmond, Catherine J.; Dooley, Katharine E.; Fu, Haiqing; Gillison, Maura L.; Akagi, Keiko; Symer, David E.; Aladjem, Mirit I.

2018-01-01

Integration of human papillomavirus (HPV) genomes into cellular chromatin is common in HPV-associated cancers. Integration is random, and each site is unique depending on how and where the virus integrates. We recently showed that tandemly integrated HPV16 could result in the formation of a super-enhancer-like element that drives transcription of the viral oncogenes. Here, we characterize the chromatin landscape and genomic architecture of this integration locus to elucidate the mechanisms that promoted de novo super-enhancer formation. Using next-generation sequencing and molecular combing/fiber-FISH, we show that ~26 copies of HPV16 are integrated into an intergenic region of chromosome 2p23.2, interspersed with 25 kb of amplified, flanking cellular DNA. This interspersed, co-amplified viral-host pattern is frequent in HPV-associated cancers and here we designate it as Type III integration. An abundant viral-cellular fusion transcript encoding the viral E6/E7 oncogenes is expressed from the integration locus and the chromatin encompassing both the viral enhancer and a region in the adjacent amplified cellular sequences is strongly enriched in the super-enhancer markers H3K27ac and Brd4. Notably, the peak in the amplified cellular sequence corresponds to an epithelial-cell-type specific enhancer. Thus, HPV16 integration generated a super-enhancer-like element composed of tandem interspersed copies of the viral upstream regulatory region and a cellular enhancer, to drive high levels of oncogene expression. PMID:29364907

Modeling the effect of microscopic driving behaviors on Kerner's time-delayed traffic breakdown at traffic signal using cellular automata

NASA Astrophysics Data System (ADS)

Wang, Yang; Chen, Yan-Yan

2016-12-01

The signalized traffic is considerably complex due to the fact that various driving behaviors have emerged to respond to traffic signals. However, the existing cellular automaton models take the signal-vehicle interactions into account inadequately, resulting in a potential risk that vehicular traffic flow dynamics may not be completely explored. To remedy this defect, this paper proposes a more realistic cellular automaton model by incorporating a number of the driving behaviors typically observed when the vehicles are approaching a traffic light. In particular, the anticipatory behavior proposed in this paper is realized with a perception factor designed by considering the vehicle speed implicitly and the gap to its preceding vehicle explicitly. Numerical simulations have been performed based on a signal controlled road which is partitioned into three sections according to the different reactions of drivers. The effects of microscopic driving behaviors on Kerner's time-delayed traffic breakdown at signal (Kerner 2011, 2013) have been investigated with the assistance of spatiotemporal pattern and trajectory analysis. Furthermore, the contributions of the driving behaviors on the traffic breakdown have been statistically examined. Finally, with the activation of the anticipatory behavior, the influences of the other driving behaviors on the formation of platoon have been investigated in terms of the number of platoons, the averaged platoon size, and the averaged flow rate.

A Method for the Direct Identification of Differentiating Muscle Cells by a Fluorescent Mitochondrial Dye

PubMed Central

Miyake, Tetsuaki; McDermott, John C.; Gramolini, Anthony O.

2011-01-01

Identification of differentiating muscle cells generally requires fixation, antibodies directed against muscle specific proteins, and lengthy staining processes or, alternatively, transfection of muscle specific reporter genes driving GFP expression. In this study, we examined the possibility of using the robust mitochondrial network seen in maturing muscle cells as a marker of cellular differentiation. The mitochondrial fluorescent tracking dye, MitoTracker, which is a cell-permeable, low toxicity, fluorescent dye, allowed us to distinguish and track living differentiating muscle cells visually by epi-fluorescence microscopy. MitoTracker staining provides a robust and simple detection strategy for living differentiating cells in culture without the need for fixation or biochemical processing. PMID:22174849

Cellular and Molecular Mechanisms of REM Sleep Homeostatic Drive: A Plausible Component for Behavioral Plasticity

PubMed Central

Datta, Subimal; Oliver, Michael D.

2017-01-01

Homeostatic regulation of REM sleep drive, as measured by an increase in the number of REM sleep transitions, plays a key role in neuronal and behavioral plasticity (i.e., learning and memory). Deficits in REM sleep homeostatic drive (RSHD) are implicated in the development of many neuropsychiatric disorders. Yet, the cellular and molecular mechanisms underlying this RSHD remain to be incomplete. To further our understanding of this mechanism, the current study was performed on freely moving rats to test a hypothesis that a positive interaction between extracellular-signal-regulated kinase 1 and 2 (ERK1/2) activity and brain-derived neurotrophic factor (BDNF) signaling in the pedunculopontine tegmentum (PPT) is a causal factor for the development of RSHD. Behavioral results of this study demonstrated that a short period (<90 min) of selective REM sleep restriction (RSR) exhibited a strong RSHD. Molecular analyses revealed that this increased RSHD increased phosphorylation and activation of ERK1/2 and BDNF expression in the PPT. Additionally, pharmacological results demonstrated that the application of the ERK1/2 activation inhibitor U0126 into the PPT prevented RSHD and suppressed BDNF expression in the PPT. These results, for the first time, suggest that the positive interaction between ERK1/2 and BDNF in the PPT is a casual factor for the development of RSHD. These findings provide a novel direction in understanding how RSHD-associated specific molecular changes can facilitate neuronal plasticity and memory processing. PMID:28959190

Direct in vivo inflammatory cell-induced corrosion of CoCrMo alloy orthopedic implant surfaces.

PubMed

Gilbert, Jeremy L; Sivan, Shiril; Liu, Yangping; Kocagöz, Sevi B; Arnholt, Christina M; Kurtz, Steven M

2015-01-01

Cobalt-chromium-molybdenum (CoCrMo) alloy, used for over five decades in orthopedic implants, may corrode and release wear debris into the body during use. These degradation products may stimulate immune and inflammatory responses in vivo. We report here on evidence of direct inflammatory cell-induced corrosion of human implanted and retrieved CoCrMo implant surfaces. Corrosion morphology on CoCrMo implant surfaces, in unique and characteristic patterns, and the presence of cellular remnants and biological materials intimately entwined with the corrosion indicates direct cellular attack under the cell membrane region of adhered and/or migrating inflammatory cells. Evidence supports a Fenton-like reaction mechanism driving corrosion in which reactive oxygen species are the major driver of corrosion. Using in vitro tests, large increases in corrosion susceptibility of CoCrMo were seen (40-100 fold) when immersed in phosphate buffered saline solutions modified with hydrogen peroxide and hydrochloric acid to represent the chemistry under inflammatory cells. This discovery raises significant new questions about the clinical consequences of such corrosion interactions, the role of patient inflammatory reactions, and the detailed mechanisms at play. © 2014 Wiley Periodicals, Inc.

Direct In Vivo Inflammatory Cell-Induced Corrosion of CoCrMo Alloy Orthopedic Implant Surfaces

PubMed Central

Gilbert, Jeremy L.; Sivan, Shiril; Liu, Yangping; Kocagöz, Sevi; Arnholt, Christina; Kurtz, Steven M.

2014-01-01

Cobalt-chromium-molybdenum alloy, used for over four decades in orthopedic implants, may corrode and release wear debris into the body during use. These degradation products may stimulate immune and inflammatory responses in vivo. We report here on evidence of direct inflammatory cell-induced corrosion of human implanted and retrieved CoCrMo implant surfaces. Corrosion morphology on CoCrMo implant surfaces, in unique and characteristic patterns, and the presence of cellular remnants and biological materials intimately entwined with the corrosion indicates direct cellular attack under the cell membrane region of adhered and/or migrating inflammatory cells. Evidence supports a Fenton-like reaction mechanism driving corrosion in which reactive oxygen species are the major driver of corrosion. Using in vitro tests, large increases in corrosion susceptibility of CoCrMo were seen (40 to 100 fold) when immersed in phosphate buffered saline solutions modified with hydrogen peroxide and HCl to represent the chemistry under inflammatory cells. This discovery raises significant new questions about the clinical consequences of such corrosion interactions, the role of patient inflammatory reactions, and the detailed mechanisms at play. PMID:24619511

Safety evaluation of driver cognitive failures and driving errors on right-turn filtering movement at signalized road intersections based on Fuzzy Cellular Automata (FCA) model.

PubMed

Chai, Chen; Wong, Yiik Diew; Wang, Xuesong

2017-07-01

This paper proposes a simulation-based approach to estimate safety impact of driver cognitive failures and driving errors. Fuzzy Logic, which involves linguistic terms and uncertainty, is incorporated with Cellular Automata model to simulate decision-making process of right-turn filtering movement at signalized intersections. Simulation experiments are conducted to estimate the relationships between cognitive failures and driving errors with safety performance. Simulation results show Different types of cognitive failures are found to have varied relationship with driving errors and safety performance. For right-turn filtering movement, cognitive failures are more likely to result in driving errors with denser conflicting traffic stream. Moreover, different driving errors are found to have different safety impacts. The study serves to provide a novel approach to linguistically assess cognitions and replicate decision-making procedures of the individual driver. Compare to crash analysis, the proposed FCA model allows quantitative estimation of particular cognitive failures, and the impact of cognitions on driving errors and safety performance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Induction of CD4 T cell memory by local cellular collectivity.

PubMed

Polonsky, Michal; Rimer, Jacob; Kern-Perets, Amos; Zaretsky, Irina; Miller, Stav; Bornstein, Chamutal; David, Eyal; Kopelman, Naama Meira; Stelzer, Gil; Porat, Ziv; Chain, Benjamin; Friedman, Nir

2018-06-15

Cell differentiation is directed by signals driving progenitors into specialized cell types. This process can involve collective decision-making, when differentiating cells determine their lineage choice by interacting with each other. We used live-cell imaging in microwell arrays to study collective processes affecting differentiation of naïve CD4 + T cells into memory precursors. We found that differentiation of precursor memory T cells sharply increases above a threshold number of locally interacting cells. These homotypic interactions involve the cytokines interleukin-2 (IL-2) and IL-6, which affect memory differentiation orthogonal to their effect on proliferation and survival. Mathematical modeling suggests that the differentiation rate is continuously modulated by the instantaneous number of locally interacting cells. This cellular collectivity can prioritize allocation of immune memory to stronger responses. Copyright © 2018, American Association for the Advancement of Science.

The Relationship between Cellular Phone Use, Performance, and Reaction Time among College Students: Implications for Cellular Phone Use while Driving

ERIC Educational Resources Information Center

Szyfman, Adam; Wanner, Gregory; Spencer, Leslie

2003-01-01

Two studies were performed to determine the relationship between cellular phone use and either reaction time or performance among college students. In the first study 60 undergraduates completed a computerized reaction time test. Mean reaction times were significantly higher when participants were talking on a cellular phone, either handheld or on…

Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development.

PubMed

Viringipurampeer, Ishaq A; Ferreira, Todd; DeMaria, Shannon; Yoon, Jookyung J; Shan, Xianghong; Moosajee, Mariya; Gregory-Evans, Kevin; Ngai, John; Gregory-Evans, Cheryl Y

2012-05-15

Tissue fusion is an essential morphogenetic mechanism in development, playing a fundamental role in developing neural tube, palate and the optic fissure. Disruption of genes associated with the tissue fusion can lead to congenital malformations, such as spina bifida, cleft lip/palate and ocular coloboma. For instance, the Pax2 transcription factor is required for optic fissure closure, although the mechanism of Pax2 action leading to tissue fusion remains elusive. This lack of information defining how transcription factors drive tissue morphogenesis at the cellular level is hampering new treatments options. Through loss- and gain-of-function analysis, we now establish that pax2 in combination with vax2 directly regulate the fas-associated death domain (fadd) gene. In the presence of fadd, cell proliferation is restricted in the developing eye through a caspase-dependent pathway. However, the loss of fadd results in a proliferation defect and concomitant activation of the necroptosis pathway through RIP1/RIP3 activity, leading to an abnormal open fissure. Inhibition of RIP1 with the small molecule drug necrostatin-1 rescues the pax2 eye fusion defect, thereby overcoming the underlying genetic defect. Thus, fadd has an essential physiological function in protecting the developing optic fissure neuroepithelium from RIP3-dependent necroptosis. This study demonstrates the molecular hierarchies that regulate a cellular switch between proliferation and the apoptotic and necroptotic cell death pathways, which in combination drive tissue morphogenesis. Furthermore, our data suggest that future therapeutic strategies may be based on small molecule drugs that can bypass the gene defects causing common congenital tissue fusion defects.

Driving mechanisms of passive and active transport across cellular membranes as the mechanisms of cell metabolism and development as well as the mechanisms of cellular distance reactions on hormonal expression and the immune response.

PubMed

Ponisovskiy, M R

2011-01-01

The article presents mechanisms of cell metabolism, cell development, cell activity, and maintenance of cellular stability. The literature is reviewed from the point of view of these concepts. The balance between anabolic and catabolic processes induces chemical potentials in the extracellular and intracellular media. The chemical potentials of these media are defined as the driving forces of both passive and active transport of substances across cellular membranes. The driving forces of substance transport across cellular membranes as in cellular metabolism and in immune responses and hormonal expressions are considered in the biochemical and biophysical models, reflecting the mechanisms for maintenance of stability of the internal medium and internal energy of an organism. The interactions of passive transport and active transport of substances across cellular walls promote cell proliferation, as well as the mechanism of cellular capacitors, promoting remote reactions across distance for hormonal expression and immune responses. The offered concept of cellular capacitors has given the possibility to explain the mechanism of remote responses of cells to new situations, resulting in the appearance of additional agents. The biophysical model develops an explanation of some cellular functions: cellular membrane action have been identified with capacitor action, based on the similarity of the structures and as well as on similarity of biophysical properties of electric data that confirm the action of the compound-specific interactions of cells within an organism, promoting hormonal expressions and immune responses to stabilize the thermodynamic system of an organism. Comparison of a cellular membrane action to a capacitor has given the possibility for the explanations of exocytosis and endocytosis mechanisms, internalization of the receptor-ligand complex, selection as a receptor reaction to a ligand by immune responses or hormonal effects, reflecting cellular distance reactions on the hormonal expressions, immune responses, and specificity of the mechanisms of immune reactions. Reviewing current research of cell activity, explanations are presented of mechanisms of apoptosis, autophagy, hormonal expression, and immune responses from the point of view of described cellular mechanisms. Thermodynamic laws are used to confirm the importance of the actions of these mechanisms for maintenance of stability of the internal medium and internal energy of an organism.

Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain.

PubMed

Martin, David A; Nichols, Charles D

2016-09-01

There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT 2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT 2A -expressing excitatory neurons is directly activated by psychedelics and subsequently recruits other select cell types including subpopulations of inhibitory somatostatin and parvalbumin GABAergic interneurons, as well as astrocytes, to produce distinct and regional responses. To gather data regarding the response of specific neuronal populations, we developed methodology for fluorescence-activated cell sorting (FACS) to segregate and enrich specific cellular subtypes in the brain. These methods allow for robust neuronal sorting based on cytoplasmic epitopes followed by downstream nucleic acid analysis, expanding the utility of FACS in neuroscience research. Copyright © 2016 Forschungsgesellschaft für Arbeitsphysiologie und Arbeitschutz e.V. Published by Elsevier B.V. All rights reserved.

Clay energetics in chemical evolution

NASA Technical Reports Server (NTRS)

Coyne, L. M.

1986-01-01

Clays have been implicated in the origin of terrestrial life since the 1950's. Originally they were considered agents which aid in selecting, concentrating and promoting oligomerization of the organic monomeric substituents of cellular life forms. However, more recently, it has been suggested that minerals, with particular emphasis on clays, may have played a yet more fundamental role. It has been suggested that clays are prototypic life forms in themselves and that they served as a template which directed the self-assembly of cellular life. If the clay-life theory is to have other than conceptual credibility, clays must be shown by experiment to execute the operations of cellular life, not only individually, but also in a sufficiently concerted manner as to produce some semblance of the functional attributes of living cells. Current studies are focussed on the ability of clays to absorb, store and transfer energy under plausible prebiotic conditions and to use this energy to drive chemistry of prebiotic relevance. Conclusions of the work are applicable to the role of clays either as substrates for organic chemistry, or in fueling their own life-mimetic processes.

ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia.

PubMed

Thirant, Cécile; Ignacimouttou, Cathy; Lopez, Cécile K; Diop, M'Boyba; Le Mouël, Lou; Thiollier, Clarisse; Siret, Aurélie; Dessen, Phillipe; Aid, Zakia; Rivière, Julie; Rameau, Philippe; Lefebvre, Céline; Khaled, Mehdi; Leverger, Guy; Ballerini, Paola; Petit, Arnaud; Raslova, Hana; Carmichael, Catherine L; Kile, Benjamin T; Soler, Eric; Crispino, John D; Wichmann, Christian; Pflumio, Françoise; Schwaller, Jürg; Vainchenker, William; Lobry, Camille; Droin, Nathalie; Bernard, Olivier A; Malinge, Sébastien; Mercher, Thomas

2017-03-13

Chimeric transcription factors are a hallmark of human leukemia, but the molecular mechanisms by which they block differentiation and promote aberrant self-renewal remain unclear. Here, we demonstrate that the ETO2-GLIS2 fusion oncoprotein, which is found in aggressive acute megakaryoblastic leukemia, confers megakaryocytic identity via the GLIS2 moiety while both ETO2 and GLIS2 domains are required to drive increased self-renewal properties. ETO2-GLIS2 directly binds DNA to control transcription of associated genes by upregulation of expression and interaction with the ETS-related ERG protein at enhancer elements. Importantly, specific interference with ETO2-GLIS2 oligomerization reverses the transcriptional activation at enhancers and promotes megakaryocytic differentiation, providing a relevant interface to target in this poor-prognosis pediatric leukemia. Copyright © 2017 Elsevier Inc. All rights reserved.

The body electric 2.0: recent advances in developmental bioelectricity for regenerative and synthetic bioengineering.

PubMed

Mathews, Juanita; Levin, Michael

2018-04-20

Breakthroughs in biomedicine and synthetic bioengineering require predictive, rational control over anatomical structure and function. Recent successes in manipulating cellular and molecular hardware have not been matched by progress in understanding the patterning software implemented during embryogenesis and regeneration. A fundamental capability gap is driving desired changes in growth and form to address birth defects and traumatic injury. Here we review new tools, results, and conceptual advances in an exciting emerging field: endogenous non-neural bioelectric signaling, which enables cellular collectives to make global decisions and implement large-scale pattern homeostasis. Spatially distributed electric circuits regulate gene expression, organ morphogenesis, and body-wide axial patterning. Developmental bioelectricity facilitates the interface to organ-level modular control points that direct patterning in vivo. Cracking the bioelectric code will enable transformative progress in bioengineering and regenerative medicine. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structured Post-IQ Domain Governs Selectivity of Myosin X for Fascin-Actin Bundles*

PubMed Central

Nagy, Stanislav; Rock, Ronald S.

2010-01-01

Without guidance cues, cytoskeletal motors would traffic components to the wrong destination with disastrous consequences for the cell. Recently, we identified a motor protein, myosin X, that identifies bundled actin filaments for transport. These bundles direct myosin X to a unique destination, the tips of cellular filopodia. Because the structural and kinetic features that drive bundle selection are unknown, we employed a domain-swapping approach with the nonselective myosin V to identify the selectivity module of myosin X. We found a surprising role of the myosin X tail region (post-IQ) in supporting long runs on bundles. Moreover, the myosin X head is adapted for initiating processive runs on bundles. We found that the tail is structured and biases the orientation of the two myosin X heads because a targeted insertion that introduces flexibility in the tail abolishes selectivity. Together, these results suggest how myosin motors may manage to read cellular addresses. PMID:20538587

Mitofusin 2 as a driver that controls energy metabolism and insulin signaling.

PubMed

Zorzano, Antonio; Hernández-Alvarez, María Isabel; Sebastián, David; Muñoz, Juan Pablo

2015-04-20

Mitochondrial dynamics is a complex process that impacts on mitochondrial biology. Recent evidence indicates that proteins participating in mitochondrial dynamics have additional cellular roles. Mitofusin 2 (Mfn2) is a potent modulator of mitochondrial metabolism with an impact on energy metabolism in muscle, liver, and hypothalamic neurons. In addition, Mfn2 is subjected to tight regulation. Hence, factors such as proinflammatory cytokines, lipid availability, or glucocorticoids block its expression, whereas exercise and increased energy expenditure promote its upregulation. Importantly, Mfn2 controls cell metabolism and insulin signaling by limiting reactive oxygen species production and by modulation of endoplasmic reticulum stress. In this connection, it is critical to understand precisely the molecular mechanisms involved in the global actions of Mfn2. Future directions should concentrate into the analysis of those mechanisms, and to fully demonstrate that Mfn2 represents a cellular hub that senses the metabolic and hormonal milieu and drives the control of metabolic homeostasis.

Phosphoinositide function in cytokinesis.

PubMed

Brill, Julie A; Wong, Raymond; Wilde, Andrew

2011-11-22

In systems as diverse as yeast, slime mold and animal cells, the levels and distribution of phosphatidylinositol phosphates (PIPs) must be strictly regulated for successful cell cleavage. The precise mechanism by which PIPs function in this process remains unknown. Recent experiments are beginning to shed light on the cellular pathways in which PIPs make key contributions during cytokinesis. In particular, PIPs promote proper actin cytoskeletal organization and direct membrane trafficking in dividing cells. Future research will uncover temporal and spatial regulation of the different PIPs, thus elucidating their role in cytoskeletal and membrane events that drive cell cleavage. Copyright © 2011 Elsevier Ltd. All rights reserved.

A decrease in brain activation associated with driving when listening to someone speak

DOT National Transportation Integrated Search

2008-02-01

Behavioral studies have shown that engaging in a secondary task, such as talking on a cellular : telephone, disrupts driving performance. This study used functional magnetic resonance : imaging (fMRI) to investigate the impact of concurrent auditory ...

CUL4B impedes stress-induced cellular senescence by dampening a p53-reactive oxygen species positive feedback loop.

PubMed

Wei, Zhao; Guo, Haiyang; Liu, Zhaojian; Zhang, Xiyu; Liu, Qiao; Qian, Yanyan; Gong, Yaoqin; Shao, Changshun

2015-02-01

Tumor suppressor p53 is known to regulate the level of intracellular reactive oxygen species (ROS). It can either alleviate oxidative stress under physiological and mildly stressed conditions or exacerbate oxidative stress under highly stressed conditions. We here report that a p53-ROS positive feedback loop drives a senescence program in normal human fibroblasts (NHFs) and this senescence-driving loop is negatively regulated by CUL4B. CUL4B, which can assemble various ubiquitin E3 ligases, was found to be downregulated in stress-induced senescent cells, but not in replicative senescent cells. We observed that p53-dependent ROS production was significantly augmented and stress-induced senescence was greatly enhanced when CUL4B was absent or depleted. Ectopic expression of CUL4B, on the other hand, blunted p53 activation, reduced ROS production, and attenuated cellular senescence in cells treated with H2O2. CUL4B was shown to promote p53 ubiquitination and proteosomal degradation in NHFs exposed to oxidative stress, thus dampening the p53-dependent cellular senescence. Together, our results established a critical role of CUL4B in negatively regulating the p53-ROS positive feedback loop that drives cellular senescence. Copyright © 2014 Elsevier Inc. All rights reserved.

TULIPs: tunable, light-controlled interacting protein tags for cell biology.

PubMed

Strickland, Devin; Lin, Yuan; Wagner, Elizabeth; Hope, C Matthew; Zayner, Josiah; Antoniou, Chloe; Sosnick, Tobin R; Weiss, Eric L; Glotzer, Michael

2012-03-04

Naturally photoswitchable proteins offer a means of directly manipulating the formation of protein complexes that drive a diversity of cellular processes. We developed tunable light-inducible dimerization tags (TULIPs) based on a synthetic interaction between the LOV2 domain of Avena sativa phototropin 1 (AsLOV2) and an engineered PDZ domain (ePDZ). TULIPs can recruit proteins to diverse structures in living yeast and mammalian cells, either globally or with precise spatial control using a steerable laser. The equilibrium binding and kinetic parameters of the interaction are tunable by mutation, making TULIPs readily adaptable to signaling pathways with varying sensitivities and response times. We demonstrate the utility of TULIPs by conferring light sensitivity to functionally distinct components of the yeast mating pathway and by directing the site of cell polarization.

Cell phone use while driving in North Carolina : 2002 update report

DOT National Transportation Integrated Search

2002-12-01

As a follow-on to an earlier study funded by the North Carolina Governor's Highway Safety Program, the current study was carried out to further understanding regarding the safety implications of cellular telephone use while driving. The study involve...

Polyphenols and the human brain: plant “secondary metabolite” ecologic roles and endogenous signaling functions drive benefits.

PubMed

Kennedy, David O

2014-09-01

Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfill a range of ecologic roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet, and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related variables, including those related to cardiovascular and brain function. Over recent years, the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and toward their modulation of cellular signal transduction pathways. To date, little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. Therefore, this review summarizes the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecologic roles and potential endogenous signaling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of “cross-kingdom” signaling predicated on the many conserved similarities in plant, microbial, and human cellular signal transduction pathways.

A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues

PubMed Central

Anderson, Matthew Z.; Porman, Allison M.; Wang, Na; Mancera, Eugenio; Bennett, Richard J.

2016-01-01

Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming. PMID:27711197

Polyphenols and the Human Brain: Plant “Secondary Metabolite” Ecologic Roles and Endogenous Signaling Functions Drive Benefits12

PubMed Central

Kennedy, David O.

2014-01-01

Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfill a range of ecologic roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet, and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related variables, including those related to cardiovascular and brain function. Over recent years, the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and toward their modulation of cellular signal transduction pathways. To date, little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. Therefore, this review summarizes the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecologic roles and potential endogenous signaling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of “cross-kingdom” signaling predicated on the many conserved similarities in plant, microbial, and human cellular signal transduction pathways. PMID:25469384

Physiology and Evolution of Voltage-Gated Calcium Channels in Early Diverging Animal Phyla: Cnidaria, Placozoa, Porifera and Ctenophora

PubMed Central

Senatore, Adriano; Raiss, Hamad; Le, Phuong

2016-01-01

Voltage-gated calcium (Cav) channels serve dual roles in the cell, where they can both depolarize the membrane potential for electrical excitability, and activate transient cytoplasmic Ca2+ signals. In animals, Cav channels play crucial roles including driving muscle contraction (excitation-contraction coupling), gene expression (excitation-transcription coupling), pre-synaptic and neuroendocrine exocytosis (excitation-secretion coupling), regulation of flagellar/ciliary beating, and regulation of cellular excitability, either directly or through modulation of other Ca2+-sensitive ion channels. In recent years, genome sequencing has provided significant insights into the molecular evolution of Cav channels. Furthermore, expanded gene datasets have permitted improved inference of the species phylogeny at the base of Metazoa, providing clearer insights into the evolution of complex animal traits which involve Cav channels, including the nervous system. For the various types of metazoan Cav channels, key properties that determine their cellular contribution include: Ion selectivity, pore gating, and, importantly, cytoplasmic protein-protein interactions that direct sub-cellular localization and functional complexing. It is unclear when these defining features, many of which are essential for nervous system function, evolved. In this review, we highlight some experimental observations that implicate Cav channels in the physiology and behavior of the most early-diverging animals from the phyla Cnidaria, Placozoa, Porifera, and Ctenophora. Given our limited understanding of the molecular biology of Cav channels in these basal animal lineages, we infer insights from better-studied vertebrate and invertebrate animals. We also highlight some apparently conserved cellular functions of Cav channels, which might have emerged very early on during metazoan evolution, or perhaps predated it. PMID:27867359

A 3D scanning laser endoscope architecture utilizing a circular piezoelectric membrane

NASA Astrophysics Data System (ADS)

Khayatzadeh, Ramin; Çivitci, Fehmi; Ferhanoğlu, Onur

2017-12-01

A piezo-scanning fiber endoscopic device architecture is proposed for 3D imaging or ablation. The endoscopic device consists of a piezoelectric membrane that is placed perpendicular to the optical axis, a fiber optic cable that extends out from and actuated by the piezoelectric membrane, and one or multiple lenses for beam delivery and collection. Unlike its counterparts that utilize piezoelectric cylinders for fiber actuation, the proposed architecture offers quasi-static actuation in the axial direction along with resonant actuation in the lateral directions forming a 3D scanning pattern, allowing adjustment of the focus plane. The actuation of the four-quadrant piezoelectric membrane involves driving of two orthogonal electrodes with AC signals for lateral scanning, while simultaneously driving all electrodes for axial scanning and focus adjustment. We have characterized piezoelectric membranes (5 -15mm diameter) with varying sizes to monitor axial displacement behavior with respect to applied DC voltage. We also demonstrate simultaneous lateral and axial actuation on a resolution target, and observe the change of lateral resolution on a selected plane through performing 1D cross-sectional images, as an indicator of focal shift through axial actuation. Based on experimental results, we identify the optical and geometrical parameters for optimal 3D imaging of tissue samples. Our findings reveal that a simple piezoelectric membrane, having comparable dimensions and drive voltage requirement with off-the-shelf MEMS scanner chips, offers tissue epithelial imaging with sub-cellular resolution.

Proteomics in Heart Failure: Top-down or Bottom-up?

PubMed Central

Gregorich, Zachery R.; Chang, Ying-Hua; Ge, Ying

2014-01-01

Summary The pathophysiology of heart failure (HF) is diverse, owing to multiple etiologies and aberrations in a number of cellular processes. Therefore, it is essential to understand how defects in the molecular pathways that mediate cellular responses to internal and external stressors function as a system to drive the HF phenotype. Mass spectrometry (MS)-based proteomics strategies have great potential for advancing our understanding of disease mechanisms at the systems level because proteins are the effector molecules for all cell functions and, thus, are directly responsible for determining cell phenotype. Two MS-based proteomics strategies exist: peptide-based bottom-up and protein-based top-down proteomics—each with its own unique strengths and weaknesses for interrogating the proteome. In this review, we will discuss the advantages and disadvantages of bottom-up and top-down MS for protein identification, quantification, and the analysis of post-translational modifications, as well as highlight how both of these strategies have contributed to our understanding of the molecular and cellular mechanisms underlying HF. Additionally, the challenges associated with both proteomics approaches will be discussed and insights will be offered regarding the future of MS-based proteomics in HF research. PMID:24619480

An Adenosine-Mediated Glial-Neuronal Circuit for Homeostatic Sleep.

PubMed

Bjorness, Theresa E; Dale, Nicholas; Mettlach, Gabriel; Sonneborn, Alex; Sahin, Bogachan; Fienberg, Allen A; Yanagisawa, Masashi; Bibb, James A; Greene, Robert W

2016-03-30

Sleep homeostasis reflects a centrally mediated drive for sleep, which increases during waking and resolves during subsequent sleep. Here we demonstrate that mice deficient for glial adenosine kinase (AdK), the primary metabolizing enzyme for adenosine (Ado), exhibit enhanced expression of this homeostatic drive by three independent measures: (1) increased rebound of slow-wave activity; (2) increased consolidation of slow-wave sleep; and (3) increased time constant of slow-wave activity decay during an average slow-wave sleep episode, proposed and validated here as a new index for homeostatic sleep drive. Conversely, mice deficient for the neuronal adenosine A1 receptor exhibit significantly decreased sleep drive as judged by these same indices. Neuronal knock-out of AdK did not influence homeostatic sleep need. Together, these findings implicate a glial-neuronal circuit mediated by intercellular Ado, controlling expression of homeostatic sleep drive. Because AdK is tightly regulated by glial metabolic state, our findings suggest a functional link between cellular metabolism and sleep homeostasis. The work presented here provides evidence for an adenosine-mediated regulation of sleep in response to waking (i.e., homeostatic sleep need), requiring activation of neuronal adenosine A1 receptors and controlled by glial adenosine kinase. Adenosine kinase acts as a highly sensitive and important metabolic sensor of the glial ATP/ADP and AMP ratio directly controlling intracellular adenosine concentration. Glial equilibrative adenosine transporters reflect the intracellular concentration to the extracellular milieu to activate neuronal adenosine receptors. Thus, adenosine mediates a glial-neuronal circuit linking glial metabolic state to neural-expressed sleep homeostasis. This indicates a metabolically related function(s) for this glial-neuronal circuit in the buildup and resolution of our need to sleep and suggests potential therapeutic targets more directly related to sleep function. Copyright © 2016 the authors 0270-6474/16/363709-13$15.00/0.

Measuring a conceptual model of the relationship between compulsive cell phone use, in-vehicle cell phone use, and motor vehicle crash.

PubMed

O'Connor, Stephen S; Shain, Lindsey M; Whitehill, Jennifer M; Ebel, Beth E

2017-02-01

Previous research suggests that anticipation of incoming phone calls or messages and impulsivity are significantly associated with motor vehicle crash. We took a more explanative approach to investigate a conceptual model regarding the direct and indirect effect of compulsive cell phone use and impulsive personality traits on crash risk. We recruited a sample of 307 undergraduate college students to complete an online survey that included measures of cell phone use, impulsivity, and history of motor vehicle crash. Using a structural equation model, we examined the direct and indirect relationships between factors of the Cell Phone Overuse Scale-II (CPOS-II), impulsivity, in-vehicle phone use, and severity and frequency of previous motor vehicle crash. Self-reported miles driven per week and year in college were included as covariates in the model. Our findings suggest that anticipation of incoming communication has a direct association with greater in-vehicle phone use, but was not directly or indirectly associated with increasing risk of previous motor vehicle crash. Of the three latent factors comprising the CPOS-II, only anticipation was significantly associated with elevated cell phone use while driving. Greater impulsivity and use of in-vehicle cell phone use while driving were directly and significantly associated with greater risk of motor vehicle crash. Anticipation of incoming cellular contacts (calls or texts) is associated with greater in-vehicle phone use, while greater in-vehicle cell phone use and impulsive traits are associated with elevated risk of motor vehicle crashes. Copyright © 2017 Elsevier Ltd. All rights reserved.

A new cellular automaton for signal controlled traffic flow based on driving behaviors

NASA Astrophysics Data System (ADS)

Wang, Yang; Chen, Yan-Yan

2015-03-01

The complexity of signal controlled traffic largely stems from the various driving behaviors developed in response to the traffic signal. However, the existing models take a few driving behaviors into account and consequently the traffic dynamics has not been completely explored. Therefore, a new cellular automaton model, which incorporates the driving behaviors typically manifesting during the different stages when the vehicles are moving toward a traffic light, is proposed in this paper. Numerical simulations have demonstrated that the proposed model can produce the spontaneous traffic breakdown and the dissolution of the over-saturated traffic phenomena. Furthermore, the simulation results indicate that the slow-to-start behavior and the inch-forward behavior can foster the traffic breakdown. Particularly, it has been discovered that the over-saturated traffic can be revised to be an under-saturated state when the slow-down behavior is activated after the spontaneous breakdown. Finally, the contributions of the driving behaviors on the traffic breakdown have been examined. Project supported by the National Basic Research Program of China (Grand No. 2012CB723303) and the Beijing Committee of Science and Technology, China (Grand No. Z1211000003120100).

Redistribution of Adhesive Forces through Src/FAK Drives Contact Inhibition of Locomotion in Neural Crest.

PubMed

Roycroft, Alice; Szabó, András; Bahm, Isabel; Daly, Liam; Charras, Guillaume; Parsons, Maddy; Mayor, Roberto

2018-06-04

Contact inhibition of locomotion is defined as the behavior of cells to cease migrating in their former direction after colliding with another cell. It has been implicated in multiple developmental processes and its absence has been linked to cancer invasion. Cellular forces are thought to govern this process; however, the exact role of traction through cell-matrix adhesions and tension through cell-cell adhesions during contact inhibition of locomotion remains unknown. Here we use neural crest cells to address this and show that cell-matrix adhesions are rapidly disassembled at the contact between two cells upon collision. This disassembly is dependent upon the formation of N-cadherin-based cell-cell adhesions and driven by Src and FAK activity. We demonstrate that the loss of cell-matrix adhesions near the contact leads to a buildup of tension across the cell-cell contact, a step that is essential to drive cell-cell separation after collision. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.

PubMed

Rai, Ashim; Pathak, Divya; Thakur, Shreyasi; Singh, Shampa; Dubey, Alok Kumar; Mallik, Roop

2016-02-11

Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule. This results in rapid directed transport of the phagosome toward microtubule minus ends, likely promoting phagolysosome fusion and pathogen degradation. We show that lipophosphoglycan, the major molecule implicated in immune evasion of Leishmania donovani, inhibits phagosome motion by disrupting the clustering and therefore the cooperative force generation of dynein. These findings appear relevant to several pathogens that prevent phagosome-lysosome fusion by targeting lipid microdomains on phagosomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

75 FR 59579 - Restrictions on Railroad Operating Employees' Use of Cellular Telephones and Other Electronic...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... using personal laptop computers and discussing airline crew scheduling procedures. Using personal laptop.... Distracted Driving Impacts All Transportation Modes 1. Aviation 2. Rail 3. Motorcoach G. Studies 1. FRA Study 1. National Motor Vehicle Crash Causation Survey (NMVCCS) 2. 100-Car Naturalistic Driving Study 3...

Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis

PubMed Central

Ivanov, Alexander V.; Valuev-Elliston, Vladimir T.; Tyurina, Daria A.; Ivanova, Olga N.; Kochetkov, Sergey N.; Bartosch, Birke; Isaguliants, Maria G.

2017-01-01

Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review. PMID:27965466

Using exploratory regression to identify optimal driving factors for cellular automaton modeling of land use change.

PubMed

Feng, Yongjiu; Tong, Xiaohua

2017-09-22

Defining transition rules is an important issue in cellular automaton (CA)-based land use modeling because these models incorporate highly correlated driving factors. Multicollinearity among correlated driving factors may produce negative effects that must be eliminated from the modeling. Using exploratory regression under pre-defined criteria, we identified all possible combinations of factors from the candidate factors affecting land use change. Three combinations that incorporate five driving factors meeting pre-defined criteria were assessed. With the selected combinations of factors, three logistic regression-based CA models were built to simulate dynamic land use change in Shanghai, China, from 2000 to 2015. For comparative purposes, a CA model with all candidate factors was also applied to simulate the land use change. Simulations using three CA models with multicollinearity eliminated performed better (with accuracy improvements about 3.6%) than the model incorporating all candidate factors. Our results showed that not all candidate factors are necessary for accurate CA modeling and the simulations were not sensitive to changes in statistically non-significant driving factors. We conclude that exploratory regression is an effective method to search for the optimal combinations of driving factors, leading to better land use change models that are devoid of multicollinearity. We suggest identification of dominant factors and elimination of multicollinearity before building land change models, making it possible to simulate more realistic outcomes.

Cellular responses to endogenous electrochemical gradients in morphological development

NASA Technical Reports Server (NTRS)

Desrosiers, M. F.

1996-01-01

Endogenous electric fields give vectorial direction to morphological development in Zea mays (sweet corn) in response to gravity. Endogenous electrical fields are important because of their ability to influence: (1) intercellular organization and development through their effects on the membrane potential, (2) direct effects such as electrophoresis of membrane components, and (3) both intracellular and extracellular transport of charged compounds. Their primary influence is in providing a vectorial dimension to the progression of one physiological state to another. Gravity perception and transduction in the mesocotyl of vascular plants is a complex interplay of electrical and chemical gradients which ultimately provide the driving force for the resulting growth curvature called gravitropism. Among the earliest events in gravitropism are changes in impedance, voltage, and conductance between the vascular stele and the growth tissues, the cortex, in the mesocotyl of corn shoots. In response to gravistimulation: (1) a potential develops which is vectorial and of sufficient magnitude to be a driving force for transport between the vascular stele and cortex, (2) the ionic conductance changes within seconds showing altered transport between the tissues, and (3) the impedance shows a transient biphasic response which indicates that the mobility of charges is altered following gravistimulation and is possibly the triggering event for the cascade of actions which leads to growth curvature.

Th17 Cells and Activated Dendritic Cells Are Increased in Vitiligo Lesions

PubMed Central

Fuentes-Duculan, Judilyn; Moussai, Dariush; Gulati, Nicholas; Sullivan-Whalen, Mary; Gilleaudeau, Patricia; Cohen, Jules A.; Krueger, James G.

2011-01-01

Background Vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. The exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis. Methodology/Principal Findings In this study, we characterized T cell and inflammation-related dermal dendritic cell (DC) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. By immunohistochemistry staining, we observed enhanced populations of CD11c+ myeloid dermal DCs and CD207+ Langerhans cells in leading edge vitiligo biopsies. DC-LAMP+ and CD1c+ sub-populations of dermal DCs expanded significantly in leading edge and lesional vitiligo skin. We also detected elevated tissue mRNA levels of IL-17A in leading edge skin biopsies of vitiligo patients, as well as IL-17A positive T cells by immunohistochemistry and immunofluorescence. Langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased IL-1ß mRNA, which suggest the potential of Langerhans cells to drive Th17 activation in vitiligo. Conclusions/Significance These studies provided direct tissue evidence that implicates active Th17 cells in vitiligo skin lesions. We characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses. PMID:21541348

Fine tuning of Rac1 and RhoA alters cuspal shapes by remolding the cellular geometry

PubMed Central

Li, Liwen; Tang, Qinghuang; Nakamura, Takashi; Suh, Jun-Gyo; Ohshima, Hayato; Jung, Han-Sung

2016-01-01

The anatomic and functional combinations of cusps and lophs (ridges) define the tooth shape of rodent molars, which distinguishes species. The species-specific cusp patterns result from the spatiotemporal induction of enamel knots (EKs), which require precisely controlled cellular behavior to control the epithelial invagination. Despite the well-defined roles of EK in cusp patterning, the determinants of the ultimate cuspal shapes and involvement of epithelial cellular geometry are unknown. Using two typical tooth patterns, the lophodont in gerbils and the bunodont in mice, we showed that the cuspal shape is determined by the dental epithelium at the cap stage, whereas the cellular geometry in the inner dental epithelium (IDE) is correlated with the cuspal shape. Intriguingly, fine tuning Rac1 and RhoA interconvert cuspal shapes between two species by remolding the cellular geometry. Either inhibition of Rac1 or ectopic expression of RhoA could region-distinctively change the columnar shape of IDE cells in gerbils to drive invagination to produce cusps. Conversely, RhoA reduction in mice inhibited invagination and developed lophs. Furthermore, we found that Rac1 and RhoA modulate the choices of cuspal shape by coordinating adhesion junctions, actin distribution, and fibronectin localization to drive IDE invagination. PMID:27892530

The Science of Stroke: Mechanisms in Search of Treatments

PubMed Central

Moskowitz, Michael A.; Lo, Eng H.; Iadecola, Costantino

2010-01-01

Summary This review focuses on mechanisms and emerging concepts that drive the science of stroke in a therapeutic direction. Once considered exclusively a disorder of blood vessels, growing evidence has led to the realization that the biological processes underlying stroke are driven by the interaction of neurons, glia, vascular cells and matrix components, which actively participate in mechanisms of tissue injury and repair. As new targets are identified, new opportunities emerge that build on an appreciation of acute cellular events acting in a broader context of ongoing destructive, protective and reparative processes. The burden of disease is great and its magnitude widens as a role for blood vessels and stroke in vascular and non-vascular dementias becomes more clearly established. This review then poses a number of fundamental questions, the answers to which may generate new directions for research and possibly new treatments that could reduce the impact of this enormous economic and societal burden. PMID:20670828

Redox cofactor engineering in industrial microorganisms: strategies, recent applications and future directions.

PubMed

Liu, Jiaheng; Li, Huiling; Zhao, Guangrong; Caiyin, Qinggele; Qiao, Jianjun

2018-05-01

NAD and NADP, a pivotal class of cofactors, which function as essential electron donors or acceptors in all biological organisms, drive considerable catabolic and anabolic reactions. Furthermore, they play critical roles in maintaining intracellular redox homeostasis. However, many metabolic engineering efforts in industrial microorganisms towards modification or introduction of metabolic pathways, especially those involving consumption, generation or transformation of NAD/NADP, often induce fluctuations in redox state, which dramatically impede cellular metabolism, resulting in decreased growth performance and biosynthetic capacity. Here, we comprehensively review the cofactor engineering strategies for solving the problematic redox imbalance in metabolism modification, as well as their features, suitabilities and recent applications. Some representative examples of in vitro biocatalysis are also described. In addition, we briefly discuss how tools and methods from the field of synthetic biology can be applied for cofactor engineering. Finally, future directions and challenges for development of cofactor redox engineering are presented.

How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes

PubMed Central

MacGrogan, Donal; Luxán, Guillermo; Driessen-Mol, Anita; Bouten, Carlijn; Baaijens, Frank; de la Pompa, José Luis

2014-01-01

Cardiac valve disease is a significant cause of ill health and death worldwide, and valve replacement remains one of the most common cardiac interventions in high-income economies. Despite major advances in surgical treatment, long-term therapy remains inadequate because none of the current valve substitutes have the potential for remodeling, regeneration, and growth of native structures. Valve development is coordinated by a complex interplay of signaling pathways and environmental cues that cause disease when perturbed. Cardiac valves develop from endocardial cushions that become populated by valve precursor mesenchyme formed by an epithelial–mesenchymal transition (EMT). The mesenchymal precursors, subsequently, undergo directed growth, characterized by cellular compartmentalization and layering of a structured extracellular matrix (ECM). Knowledge gained from research into the development of cardiac valves is driving exploration into valve biomechanics and tissue engineering directed at creating novel valve substitutes endowed with native form and function. PMID:25368013

Imaging Cell Shape Change in Living Drosophila Embryos

PubMed Central

Figard, Lauren; Sokac, Anna Marie

2011-01-01

The developing Drosophila melanogaster embryo undergoes a number of cell shape changes that are highly amenable to live confocal imaging. Cell shape changes in the fly are analogous to those in higher organisms, and they drive tissue morphogenesis. So, in many cases, their study has direct implications for understanding human disease (Table 1)1-5. On the sub-cellular scale, these cell shape changes are the product of activities ranging from gene expression to signal transduction, cell polarity, cytoskeletal remodeling and membrane trafficking. Thus, the Drosophila embryo provides not only the context to evaluate cell shape changes as they relate to tissue morphogenesis, but also offers a completely physiological environment to study the sub-cellular activities that shape cells. The protocol described here is designed to image a specific cell shape change called cellularization. Cellularization is a process of dramatic plasma membrane growth, and it ultimately converts the syncytial embryo into the cellular blastoderm. That is, at interphase of mitotic cycle 14, the plasma membrane simultaneously invaginates around each of ~6000 cortically anchored nuclei to generate a sheet of primary epithelial cells. Counter to previous suggestions, cellularization is not driven by Myosin-2 contractility6, but is instead fueled largely by exocytosis of membrane from internal stores7. Thus, cellularization is an excellent system for studying membrane trafficking during cell shape changes that require plasma membrane invagination or expansion, such as cytokinesis or transverse-tubule (T-tubule) morphogenesis in muscle. Note that this protocol is easily applied to the imaging of other cell shape changes in the fly embryo, and only requires slight adaptations such as changing the stage of embryo collection, or using "embryo glue" to mount the embryo in a specific orientation (Table 1)8-19. In all cases, the workflow is basically the same (Figure 1). Standard methods for cloning and Drosophila transgenesis are used to prepare stable fly stocks that express a protein of interest, fused to Green Fluorescent Protein (GFP) or its variants, and these flies provide a renewable source of embryos. Alternatively, fluorescent proteins/probes are directly introduced into fly embryos via straightforward micro-injection techniques9-10. Then, depending on the developmental event and cell shape change to be imaged, embryos are collected and staged by morphology on a dissecting microscope, and finally positioned and mounted for time-lapse imaging on a confocal microscope. PMID:21490577

Heavy vehicle driver workload assessment. Task 7B, in-cab text message system and cellular phone use by heavy vehicle drivers in a part-task driving simulator

DOT National Transportation Integrated Search

This report contains the results of a simulator study conducted to serve as a supplement to a National Highway Traffic Safety Administration (NHTSA) heavy vehicle driver workload field study. Its purpose was the evaluation of effects of cellular phon...

Adenomatous polyposis coli nucleates actin assembly to drive cell migration and microtubule-induced focal adhesion turnover

PubMed Central

Eskin, Julian A.; Jaiswal, Richa

2017-01-01

Cell motility depends on tight coordination between the microtubule (MT) and actin cytoskeletons, but the mechanisms underlying this MT–actin cross talk have remained poorly understood. Here, we show that the tumor suppressor protein adenomatous polyposis coli (APC), which is a known MT-associated protein, directly nucleates actin assembly to promote directed cell migration. By changing only two residues in APC, we generated a separation-of-function mutant, APC (m4), that abolishes actin nucleation activity without affecting MT interactions. Expression of full-length APC carrying the m4 mutation (APC (m4)) rescued cellular defects in MT organization, MT dynamics, and mitochondrial distribution caused by depletion of endogenous APC but failed to restore cell migration. Wild-type APC and APC (m4) localized to focal adhesions (FAs), and APC (m4) was defective in promoting actin assembly at FAs to facilitate MT-induced FA turnover. These results provide the first direct evidence for APC-mediated actin assembly in vivo and establish a role for APC in coordinating MTs and actin at FAs to direct cell migration. PMID:28663347

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

PubMed Central

Tilstra, Jeremy S.; Robinson, Andria R.; Wang, Jin; Gregg, Siobhán Q.; Clauson, Cheryl L.; Reay, Daniel P.; Nasto, Luigi A.; St Croix, Claudette M.; Usas, Arvydas; Vo, Nam; Huard, Johnny; Clemens, Paula R.; Stolz, Donna B.; Guttridge, Denis C.; Watkins, Simon C.; Garinis, George A.; Wang, Yinsheng; Niedernhofer, Laura J.; Robbins, Paul D.

2012-01-01

The accumulation of cellular damage, including DNA damage, is thought to contribute to aging-related degenerative changes, but how damage drives aging is unknown. XFE progeroid syndrome is a disease of accelerated aging caused by a defect in DNA repair. NF-κB, a transcription factor activated by cellular damage and stress, has increased activity with aging and aging-related chronic diseases. To determine whether NF-κB drives aging in response to the accumulation of spontaneous, endogenous DNA damage, we measured the activation of NF-κB in WT and progeroid model mice. As both WT and progeroid mice aged, NF-κB was activated stochastically in a variety of cell types. Genetic depletion of one allele of the p65 subunit of NF-κB or treatment with a pharmacological inhibitor of the NF-κB–activating kinase, IKK, delayed the age-related symptoms and pathologies of progeroid mice. Additionally, inhibition of NF-κB reduced oxidative DNA damage and stress and delayed cellular senescence. These results indicate that the mechanism by which DNA damage drives aging is due in part to NF-κB activation. IKK/NF-κB inhibitors are sufficient to attenuate this damage and could provide clinical benefit for degenerative changes associated with accelerated aging disorders and normal aging. PMID:22706308

Histone-Targeted Nucleic Acid Delivery for Tissue Regenerative Applications

NASA Astrophysics Data System (ADS)

Munsell, Erik V.

Nucleic acid delivery has garnered significant attention as an innovative therapeutic approach for treating a wide variety of diseases. However, the design of non-viral delivery systems that negotiate efficient intracellular trafficking and nuclear entry represents a significant challenge. Overcoming these hurdles requires a combination of well-controlled materials approaches with techniques to understand and direct cellular delivery. Recent investigations have highlighted the roles histone tail sequences play in directing nuclear delivery and retention, as well as activating DNA transcription. We established the ability to recapitulate these natural histone tail activities within non-viral gene nanocarriers, driving gene transfer/expression by enabling effective navigation to the nucleus via retrograde vesicular trafficking. A unique finding of this histone-targeted approach was that nanocarriers gained enhanced access to the nucleus during mitosis. The work described in this dissertation builds off of these fundamental insights to facilitate the translation of this histone-targeted delivery approach toward regenerative medicine applications. During native tissue repair, actively proliferating mesenchymal stem cells (MSCs) respond to a complex series of growth factor signals that direct their differentiation. Accordingly, the investigations in this work focused on utilizing the histone-targeted nanocarriers to enhance osteogenic growth factor gene transfer in dividing MSCs leading to augmented MSC chondrogenic differentiation, an essential first step in skeletal tissue repair. Concurrently, additional studies focused on optimizing the histone-targeted nanocarrier design strategy to enable improved plasmid DNA (pDNA) binding stability and tunable harnessing of native cellular processing pathways for enhanced gene transfer. Overall, the work presented herein demonstrated substantial increases in growth factor expression following histone-targeted gene transfer. This enhanced expression enabled more robust levels of chondrogenesis in MSCs than treatments with equivalent amounts of recombinant growth factor protein. Additionally, nanocarrier design optimization provided effective pDNA condensation and controllable interactions with native histone effectors. Importantly, these optimized nanocarriers conferred stable nanoplex formation and maintained transfection efficiency under physiologically relevant conditions. Taken together, these advances may help drive the clinical translation of histone-targeted nucleic acid delivery strategies for the regeneration of damaged tissue following traumatic injury.

The National Direct-Drive Program: OMEGA to the National Ignition Facility

DOE PAGES

Regan, S. P.; Goncharov, V. N.; Sangster, T. C.; ...

2017-12-28

The goal of the National Direct-Drive Program is to demonstrate and understand the physics of laser direct drive (LDD). Efforts are underway on OMEGA for the 100-Gbar Campaign to demonstrate and understand the physics for hot-spot conditions and formation relevant for ignition at the 1-MJ scale, and at the National Ignition Facility to develop an understanding of the direct-drive physics at long scale lengths for the MJ Direct-Drive Campaign. For this paper the strategy of the National Direct-Drive Program is described; the requirements for the DT cryogenic fill-tube target being developed for OMEGA are presented; and preliminary LDD implosion measurementsmore » of hydrodynamic mixing seeded by laser imprint, the target-mounting stalk, and microscopic surface debris are reported.« less

The National Direct-Drive Program: OMEGA to the National Ignition Facility

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

Regan, S. P.; Goncharov, V. N.; Sangster, T. C.

The goal of the National Direct-Drive Program is to demonstrate and understand the physics of laser direct drive (LDD). Efforts are underway on OMEGA for the 100-Gbar Campaign to demonstrate and understand the physics for hot-spot conditions and formation relevant for ignition at the 1-MJ scale, and at the National Ignition Facility to develop an understanding of the direct-drive physics at long scale lengths for the MJ Direct-Drive Campaign. For this paper the strategy of the National Direct-Drive Program is described; the requirements for the DT cryogenic fill-tube target being developed for OMEGA are presented; and preliminary LDD implosion measurementsmore » of hydrodynamic mixing seeded by laser imprint, the target-mounting stalk, and microscopic surface debris are reported.« less

A murine monoclonal antibody directed against the carboxyl-terminal domain of GRP78 suppresses melanoma growth in mice.

PubMed

de Ridder, Gustaaf G; Ray, Rupa; Pizzo, Salvatore V

2012-06-01

The HSP70 family member GRP78 is a selective tumor marker upregulated on the surface of many tumor cell types, including melanoma, where it acts as a growth factor receptor-like protein. Receptor-recognized forms of the proteinase inhibitor α2-macroglobulin (α2M*) are the best-characterized ligands for GRP78, but in melanoma and other cancer patients, autoantibodies arise against the NH2-terminal domain of GRP78 that react with tumor cell-surface GRP78. This causes the activation of signaling cascades that are proproliferative and antiapoptotic. Antibodies directed against the COOH-terminal domain of GRP78, however, upregulate p53-mediated proapoptotic signaling, leading to cell death. Here, we describe the binding characteristics, cell signaling properties, and downstream cellular effects of three novel murine monoclonal antibodies. The NH2-terminal domain-reactive antibody, N88, mimics α2M* as a ligand and drives PI 3-kinase-dependent activation of Akt and the subsequent stimulation of cellular proliferation in vitro. The COOH-terminal domain-reactive antibody, C38, acts as an antagonist of both α2M* and N88, whereas another, C107, directly induces apoptosis in vitro. In a murine B16F1 melanoma flank tumor model, we demonstrate the acceleration of tumor growth by treatment with N88, whereas C107 significantly slowed tumor growth whether administered before (P<0.005) or after (P<0.05) tumor implantation.

A decrease in brain activation associated with driving when listening to someone speak.

PubMed

Just, Marcel Adam; Keller, Timothy A; Cynkar, Jacquelyn

2008-04-18

Behavioral studies have shown that engaging in a secondary task, such as talking on a cellular telephone, disrupts driving performance. This study used functional magnetic resonance imaging (fMRI) to investigate the impact of concurrent auditory language comprehension on the brain activity associated with a simulated driving task. Participants steered a vehicle along a curving virtual road, either undisturbed or while listening to spoken sentences that they judged as true or false. The dual-task condition produced a significant deterioration in driving accuracy caused by the processing of the auditory sentences. At the same time, the parietal lobe activation associated with spatial processing in the undisturbed driving task decreased by 37% when participants concurrently listened to sentences. The findings show that language comprehension performed concurrently with driving draws mental resources away from the driving and produces deterioration in driving performance, even when it does not require holding or dialing a phone.

A Decrease in Brain Activation Associated with Driving When Listening to Someone Speak

PubMed Central

Just, Marcel Adam; Keller, Timothy A.; Cynkar, Jacquelyn

2009-01-01

Behavioral studies have shown that engaging in a secondary task, such as talking on a cellular telephone, disrupts driving performance. This study used functional magnetic resonance imaging (fMRI) to investigate the impact of concurrent auditory language comprehension on the brain activity associated with a simulated driving task. Participants steered a vehicle along a curving virtual road, either undisturbed or while listening to spoken sentences that they judged as true or false. The dual task condition produced a significant deterioration in driving accuracy caused by the processing of the auditory sentences. At the same time, the parietal lobe activation associated with spatial processing in the undisturbed driving task decreased by 37% when participants concurrently listened to sentences. The findings show that language comprehension performed concurrently with driving draws mental resources away from the driving and produces deterioration in driving performance, even when it does not require holding or dialing a phone. PMID:18353285

Laser-direct-drive program: Promise, challenge, and path forward

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

Campbell, E. M.; Goncharov, V. N.; Sangster, T. C.

Along with laser-indirect (x-ray)-drive and magnetic-drive target concepts, laser direct drive is a viable approach to achieving ignition and gain with inertial confinement fusion. In the United States, a national program has been established to demonstrate and understand the physics of laser direct drive. The program utilizes the Omega Laser Facility to conduct implosion and coupling physics at the nominally 30-kJ scale and laser–plasma interaction and coupling physics at the MJ scale at the National Ignition Facility. This paper will discuss the motivation and challenges for laser direct drive and the broad-based program presently underway in the United States.

Laser-direct-drive program: Promise, challenge, and path forward

DOE PAGES

Campbell, E. M.; Goncharov, V. N.; Sangster, T. C.; ...

2017-03-19

Along with laser-indirect (x-ray)-drive and magnetic-drive target concepts, laser direct drive is a viable approach to achieving ignition and gain with inertial confinement fusion. In the United States, a national program has been established to demonstrate and understand the physics of laser direct drive. The program utilizes the Omega Laser Facility to conduct implosion and coupling physics at the nominally 30-kJ scale and laser–plasma interaction and coupling physics at the MJ scale at the National Ignition Facility. This paper will discuss the motivation and challenges for laser direct drive and the broad-based program presently underway in the United States.

Analysis of Peristaltic Waves & their Role in Migrating Physarum Plasmodia

NASA Astrophysics Data System (ADS)

Lewis, Owen; Guy, Robert

2017-11-01

The true slime mold Physarum polycephalum exhibits a vast array of sophisticated manipulations of its intracellular cytoplasm. Growing microplasmodia of physarum have been observed to adopt an elongated tadpole shape, then contract in a rhythmic, traveling wave pattern that resembles peristaltic pumping. This contraction drives a fast flow of non-gelated cytoplasm along the cell longitudinal axis. It has been hypothesized that this flow of cytoplasm is a driving factor in generating motility of the plasmodium. In this work, we use two different mathematical models to investigate how peristaltic pumping within physarum may be used to drive cellular motility. We compare the relative phase of flow and deformation waves predicted by both models to similar phase data collected from in vivo experiments using physarum plasmodia. Both models suggest that a mechanical asymmetry in the cell is required to reproduce the experimental observations. Such a mechanical asymmetry is also shown to increase the potential for cellular migration, as measured by both stress generation and migration velocity.

Circadian actin dynamics drive rhythmic fibroblast mobilisation during wound healing

PubMed Central

Hoyle, Nathaniel P.; Seinkmane, Estere; Putker, Marrit; Feeney, Kevin A.; Krogager, Toke P.; Chesham, Johanna E.; Bray, Liam K.; Thomas, Justyn M.; Dunn, Ken; Blaikley, John; O’Neill, John S.

2017-01-01

Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping which imparts a ~24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically expressed proteins. We observed temporal coordination of actin regulators that drives cell-intrinsic rhythms in actin dynamics. In consequence the cellular clock modulates the efficiency of actin-dependent processes such as cell migration and adhesion, which ultimately impact the efficacy of wound healing. Accordingly, skin wounds incurred during a mouse’s active phase exhibited increased fibroblast invasion in vivo and ex vivo, as well as in cultured fibroblasts and keratinocytes. Our experimental results correlate with the observation that the time of injury significantly affects healing after burns in humans, with daytime wounds healing ~60% faster than night-time wounds. We suggest that circadian regulation of the cytoskeleton influences wound healing efficacy from the cellular to the organismal scale. PMID:29118260

Useful field of view in simulated driving: Reaction times and eye movements of drivers

PubMed Central

Seya, Yasuhiro; Nakayasu, Hidetoshi; Yagi, Tadasu

2013-01-01

To examine the spatial distribution of a useful field of view (UFOV) in driving, reaction times (RTs) and eye movements were measured in simulated driving. In the experiment, a normal or mirror-reversed letter “E” was presented on driving images with different eccentricities and directions from the current gaze position. The results showed significantly slower RTs in the upper and upper left directions than in the other directions. The RTs were significantly slower in the left directions than in the right directions. These results suggest that the UFOV in driving may be asymmetrical among the meridians in the visual field. PMID:24349688

Influence of wheelchair front caster wheel on reverse directional stability.

PubMed

Guo, Songfeng; Cooper, Rory A; Corfman, Tom; Ding, Dan; Grindle, Garrett

2003-01-01

The purpose of this research was to study directional stability during reversing of rear-wheel drive, electric powered wheelchairs (EPW) under different initial front caster orientations. Specifically, the weight distribution differences caused by certain initial caster orientations were examined as a possible mechanism for causing directional instability that could lead to accidents. Directional stability was quantified by measuring the drive direction error of the EPW by a motion analysis system. The ground reaction forces were collected to determine the load on the front casters, as well as back-emf data to attain the speed of the motors. The drive direction error was found to be different for various initial caster orientations. Drive direction error was greatest when both casters were oriented 90 degrees to the left or right, and least when both casters were oriented forward. The results show that drive direction error corresponds to the loading difference on the casters. The data indicates that loading differences may cause asymmetric drag on the casters, which in turn causes unbalanced torque load on the motors. This leads to a difference in motor speed and drive direction error.

Design and simulation of the direct drive servo system

NASA Astrophysics Data System (ADS)

Ren, Changzhi; Liu, Zhao; Song, Libin; Yi, Qiang; Chen, Ken; Zhang, Zhenchao

2010-07-01

As direct drive technology is finding their way into telescope drive designs for its many advantages, it would push to more reliable and cheaper solutions for future telescope complex motion system. However, the telescope drive system based on the direct drive technology is one high integrated electromechanical system, which one complex electromechanical design method is adopted to improve the efficiency, reliability and quality of the system during the design and manufacture circle. The telescope is one ultra-exact, ultra-speed, high precision and huge inertial instrument, which the direct torque motor adopted by the telescope drive system is different from traditional motor. This paper explores the design process and some simulation results are discussed.

Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate

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

Hudson, William H.; Pickard, Mark R.; de Vera, Ian Mitchelle S.

2014-12-23

The majority of the eukaryotic genome is transcribed, generating a significant number of long intergenic noncoding RNAs (lincRNAs). Although lincRNAs represent the most poorly understood product of transcription, recent work has shown lincRNAs fulfill important cellular functions. In addition to low sequence conservation, poor understanding of structural mechanisms driving lincRNA biology hinders systematic prediction of their function. Here we report the molecular requirements for the recognition of steroid receptors (SRs) by the lincRNA growth arrest-specific 5 (Gas5), which regulates steroid-mediated transcriptional regulation, growth arrest and apoptosis. We identify the functional Gas5-SR interface and generate point mutations that ablate the SR-Gas5more » lincRNA interaction, altering Gas5-driven apoptosis in cancer cell lines. Further, we find that the Gas5 SR-recognition sequence is conserved among haplorhines, with its evolutionary origin as a splice acceptor site. This study demonstrates that lincRNAs can recognize protein targets in a conserved, sequence-specific manner in order to affect critical cell functions.« less

Direct-drive inertial confinement fusion research at the Laboratory for Laser Energetics: charting the path to thermonuclear ignition

NASA Astrophysics Data System (ADS)

McCrory, R. L.; Regan, S. P.; Loucks, S. J.; Meyerhofer, D. D.; Skupsky, S.; Betti, R.; Boehly, T. R.; Craxton, R. S.; Collins, T. J. B.; Delettrez, J. A.; Edgell, D.; Epstein, R.; Fletcher, K. A.; Freeman, C.; Frenje, J. A.; Glebov, V. Yu.; Goncharov, V. N.; Harding, D. R.; Igumenshchev, I. V.; Keck, R. L.; Kilkenny, J. D.; Knauer, J. P.; Li, C. K.; Marciante, J.; Marozas, J. A.; Marshall, F. J.; Maximov, A. V.; McKenty, P. W.; Myatt, J.; Padalino, S.; Petrasso, R. D.; Radha, P. B.; Sangster, T. C.; Séguin, F. H.; Seka, W.; Smalyuk, V. A.; Soures, J. M.; Stoeckl, C.; Yaakobi, B.; Zuegel, J. D.

2005-10-01

Significant theoretical and experimental progress continues to be made at the University of Rochester's Laboratory for Laser Energetics (LLE), charting the path to direct-drive inertial confinement fusion (ICF) ignition. Direct drive offers the potential for higher-gain implosions than x-ray drive and is a leading candidate for an inertial fusion energy power plant. LLE's direct-drive ICF ignition target designs for the National Ignition Facility (NIF) are based on hot-spot ignition. A cryogenic target with a spherical DT-ice layer, within or without a foam matrix, enclosed by a thin plastic shell, will be directly irradiated with ~1.5 MJ of laser energy. Cryogenic and plastic/foam (surrogate-cryogenic) targets that are hydrodynamically scaled from these ignition target designs are imploded on the 60-beam, 30 kJ, UV OMEGA laser system to validate the key target physics issues, including energy coupling, hydrodynamic instabilities and implosion symmetry. Prospects for direct-drive ignition on the NIF are extremely favourable, even while it is in its x-ray-drive irradiation configuration, with the development of the polar-direct-drive concept. A high-energy petawatt capability is being constructed at LLE next to the existing 60-beam OMEGA compression facility. This OMEGA EP (extended performance) laser will add two short-pulse, 2.6 kJ beams to the OMEGA laser system to backlight direct-drive ICF implosions and study fast-ignition physics with focused intensities up to 6 × 1020 W cm-2.

Modulation of Enhancer Looping and Differential Gene Targeting by Epstein-Barr Virus Transcription Factors Directs Cellular Reprogramming

PubMed Central

McClellan, Michael J.; Wood, C. David; Ojeniyi, Opeoluwa; Cooper, Tim J.; Kanhere, Aditi; Arvey, Aaron; Webb, Helen M.; Palermo, Richard D.; Harth-Hertle, Marie L.; Kempkes, Bettina; Jenner, Richard G.; West, Michelle J.

2013-01-01

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors. PMID:24068937

Assembly of high-density lipoprotein.

PubMed

Yokoyama, Shinji

2006-01-01

Mammalian somatic cells do not catabolize cholesterol and need to export it for its homeostasis at the levels of cells and whole bodies. This reaction may reduce intracellularly accumulated cholesterol in excess and would contribute to prevention or regression of the initial stage of atherosclerosis. High-density lipoprotein (HDL) is thought to play a main role in this reaction, and 2 independent mechanisms are proposed for this reaction. First, cholesterol is exchanged in a nonspecific physicochemical manner between cell surface and extracellular lipoproteins, and cholesterol esterification on HDL provides a driving force for net removal of cell cholesterol. Second, apolipoproteins directly interact with cells and generate HDL by removing cellular phospholipid and cholesterol. This reaction is a major source of plasma HDL and is mediated by a membrane protein, ABCA1. Lipid-free or lipid-poor helical apolipoproteins primarily recruit cellular phospholipid to assemble HDL particles, and cholesterol enrichment in these particles is regulated independently. ABCA1 is a rate-limiting factor of the HDL assembly and is regulated by transcriptional factors and posttranscriptional factors. Posttranscriptional regulation of ABCA1 includes modulation of its calpain-mediated degradation.

EPHRIN-B1 Mosaicism Drives Cell Segregation in Craniofrontonasal Syndrome hiPSC-Derived Neuroepithelial Cells.

PubMed

Niethamer, Terren K; Larson, Andrew R; O'Neill, Audrey K; Bershteyn, Marina; Hsiao, Edward C; Klein, Ophir D; Pomerantz, Jason H; Bush, Jeffrey O

2017-03-14

Although human induced pluripotent stem cells (hiPSCs) hold great potential for the study of human diseases affecting disparate cell types, they have been underutilized in seeking mechanistic insights into the pathogenesis of congenital craniofacial disorders. Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder caused by mutations in EFNB1 and characterized by craniofacial, skeletal, and neurological anomalies. Heterozygous females are more severely affected than hemizygous males, a phenomenon termed cellular interference that involves mosaicism for EPHRIN-B1 function. Although the mechanistic basis for cellular interference in CFNS has been hypothesized to involve Eph/ephrin-mediated cell segregation, no direct evidence for this has been demonstrated. Here, by generating hiPSCs from CFNS patients, we demonstrate that mosaicism for EPHRIN-B1 expression induced by random X inactivation in heterozygous females results in robust cell segregation in human neuroepithelial cells, thus supplying experimental evidence that Eph/ephrin-mediated cell segregation is relevant to pathogenesis in human CFNS patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

State-of-the-art on viral microRNAs in HPV infection and cancer development.

PubMed

Poltronieri, Palmiro; Sun, Binlian; Huang, Kai-Yao; Chang, Tzu-Hao; Lee, Tzong-Yi

2018-03-27

high-risk HPV subtypes are driving forces for human cancer development: HPV-16 and HPV-18 are responsible for most HPV-caused cancers. This review describes the present knowledge on HR-HPV genomes coding potential for viral miRNAs. HPV subtypes miRNA database, VIRmiRtar, has been constructed applying bioinformatics and a computational method, ViralMir, exploiting structural features, presence of hairpins, and validation by comparison with RNA sequencing datasets. Several miRNA candidates have been localised in the genomes of high-risk HPV subtypes. Among these, HPV-16 miR-1, miR-2 and miR-3. The database contains a list of host candidate gene targets that may be responsible for the oncogenesis in the various cellular environments. miRNA silencing therapies, based on specific cellular uptake of miRNA mimics and antagomiRs, directed towards HPV encoded miRNAs and/or microRNAs deregulated in the host cells, could be a valuable approach to support pharmaceutical interventions in the treatment of HPV dependent cancers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Driving error and anxiety related to iPod mp3 player use in a simulated driving experience.

PubMed

Harvey, Ashley R; Carden, Randy L

2009-08-01

Driver distraction due to cellular phone usage has repeatedly been shown to increase the risk of vehicular accidents; however, the literature regarding the use of other personal electronic devices while driving is relatively sparse. It was hypothesized that the usage of an mp3 player would result in an increase in not only driving error while operating a driving simulator, but driver anxiety scores as well. It was also hypothesized that anxiety scores would be positively related to driving errors when using an mp3 player. 32 participants drove through a set course in a driving simulator twice, once with and once without an iPod mp3 player, with the order counterbalanced. Number of driving errors per course, such as leaving the road, impacts with stationary objects, loss of vehicular control, etc., and anxiety were significantly higher when an iPod was in use. Anxiety scores were unrelated to number of driving errors.

Molecular Processes that Drive Cigarette Smoke–Induced Epithelial Cell Fate of the Lung

PubMed Central

Nyunoya, Toru; Mebratu, Yohannes; Contreras, Amelia; Delgado, Monica; Chand, Hitendra S.

2014-01-01

Cigarette smoke contains numerous chemical compounds, including abundant reactive oxygen/nitrogen species and aldehydes, and many other carcinogens. Long-term cigarette smoking significantly increases the risk of various lung diseases, including chronic obstructive pulmonary disease and lung cancer, and contributes to premature death. Many in vitro and in vivo studies have elucidated mechanisms involved in cigarette smoke–induced inflammation, DNA damage, and autophagy, and the subsequent cell fates, including cell death, cellular senescence, and transformation. In this Translational Review, we summarize the known pathways underlying these processes in airway epithelial cells to help reveal future challenges and describe possible directions of research that could lead to better management and treatment of these diseases. PMID:24111585

Drive Direction Image by Opportunity After Surpassing 20 Miles

NASA Image and Video Library

2011-07-19

NASA Mars Exploration Rover Opportunity used its navigation camera to record this view in the eastward driving direction after completing a drive on July 17, 2011, that took the rover total driving distance on Mars beyond 20 miles.

Effect of a concurrent auditory task on visual search performance in a driving-related image-flicker task.

PubMed

Richard, Christian M; Wright, Richard D; Ee, Cheryl; Prime, Steven L; Shimizu, Yujiro; Vavrik, John

2002-01-01

The effect of a concurrent auditory task on visual search was investigated using an image-flicker technique. Participants were undergraduate university students with normal or corrected-to-normal vision who searched for changes in images of driving scenes that involved either driving-related (e.g., traffic light) or driving-unrelated (e.g., mailbox) scene elements. The results indicated that response times were significantly slower if the search was accompanied by a concurrent auditory task. In addition, slower overall responses to scenes involving driving-unrelated changes suggest that the underlying process affected by the concurrent auditory task is strategic in nature. These results were interpreted in terms of their implications for using a cellular telephone while driving. Actual or potential applications of this research include the development of safer in-vehicle communication devices.

The Role of Spatially Controlled Cell Proliferation in Limb Bud Morphogenesis

PubMed Central

Boehm, Bernd; Westerberg, Henrik; Lesnicar-Pucko, Gaja; Raja, Sahdia; Rautschka, Michael; Cotterell, James; Swoger, Jim; Sharpe, James

2010-01-01

Although the vertebrate limb bud has been studied for decades as a model system for spatial pattern formation and cell specification, the cellular basis of its distally oriented elongation has been a relatively neglected topic by comparison. The conventional view is that a gradient of isotropic proliferation exists along the limb, with high proliferation rates at the distal tip and lower rates towards the body, and that this gradient is the driving force behind outgrowth. Here we test this hypothesis by combining quantitative empirical data sets with computer modelling to assess the potential role of spatially controlled proliferation rates in the process of directional limb bud outgrowth. In particular, we generate two new empirical data sets for the mouse hind limb—a numerical description of shape change and a quantitative 3D map of cell cycle times—and combine these with a new 3D finite element model of tissue growth. By developing a parameter optimization approach (which explores spatial patterns of tissue growth) our computer simulations reveal that the observed distribution of proliferation rates plays no significant role in controlling the distally extending limb shape, and suggests that directional cell activities are likely to be the driving force behind limb bud outgrowth. This theoretical prediction prompted us to search for evidence of directional cell orientations in the limb bud mesenchyme, and we thus discovered a striking highly branched and extended cell shape composed of dynamically extending and retracting filopodia, a distally oriented bias in Golgi position, and also a bias in the orientation of cell division. We therefore provide both theoretical and empirical evidence that limb bud elongation is achieved by directional cell activities, rather than a PD gradient of proliferation rates. PMID:20644711

Progress in the Science and Technology of Direct Drive Laser Fusion with the KrF Laser

DTIC Science & Technology

2010-12-01

important parameters KrF technology leads) Direct Laser Drive is a better choice for Energy Indirect Drive (initial path for NIF ) Laser Beams x-rays Hohlraum...Pellet Direct Drive (IFE) Laser Beams Pellet .. • ID Ignition being explored on NIF • Providing high enough gain for pure fusion energy is...challenging. • DD Ignition physics can be explored on NIF . • More efficient use of laser light, and greater flexibility in applying drive provides potential for

Krüppel-like Factor 3 (KLF3/BKLF) Is Required for Widespread Repression of the Inflammatory Modulator Galectin-3 (Lgals3)*

PubMed Central

Knights, Alexander J.; Yik, Jinfen J.; Mat Jusoh, Hanapi; Norton, Laura J.; Funnell, Alister P. W.; Pearson, Richard C. M.; Bell-Anderson, Kim S.; Crossley, Merlin; Quinlan, Kate G. R.

2016-01-01

The Lgals3 gene encodes a multifunctional β-galactoside-binding protein, galectin-3. Galectin-3 has been implicated in a broad range of biological processes from chemotaxis and inflammation to fibrosis and apoptosis. The role of galectin-3 as a modulator of inflammation has been studied intensively, and recent evidence suggests that it may serve as a protective factor in obesity and other metabolic disorders. Despite considerable interest in galectin-3, little is known about its physiological regulation at the transcriptional level. Here, using knockout mice, chromatin immunoprecipitations, and cellular and molecular analyses, we show that the zinc finger transcription factor Krüppel-like factor 3 (KLF3) directly represses galectin-3 transcription. We find that galectin-3 is broadly up-regulated in KLF3-deficient mouse tissues, that KLF3 occupies regulatory regions of the Lgals3 gene, and that KLF3 directly binds its cognate elements (CACCC boxes) in the galectin-3 promoter and represses its activation in cellular assays. We also provide mechanistic insights into the regulation of Lgals3, demonstrating that C-terminal binding protein (CtBP) is required to drive optimal KLF3-mediated silencing. These findings help to enhance our understanding of how expression of the inflammatory modulator galectin-3 is controlled, opening up avenues for potential therapeutic interventions in the future. PMID:27226561

Cellular automata in photonic cavity arrays.

PubMed

Li, Jing; Liew, T C H

2016-10-31

We propose theoretically a photonic Turing machine based on cellular automata in arrays of nonlinear cavities coupled with artificial gauge fields. The state of the system is recorded making use of the bistability of driven cavities, in which losses are fully compensated by an external continuous drive. The sequential update of the automaton layers is achieved automatically, by the local switching of bistable states, without requiring any additional synchronization or temporal control.

Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.

PubMed

Veri, Amanda O; Miao, Zhengqiang; Shapiro, Rebecca S; Tebbji, Faiza; O'Meara, Teresa R; Kim, Sang Hu; Colazo, Juan; Tan, Kaeling; Vyas, Valmik K; Whiteway, Malcolm; Robbins, Nicole; Wong, Koon Ho; Cowen, Leah E

2018-03-01

The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition.

Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space

PubMed Central

Miao, Zhengqiang; Tan, Kaeling; Vyas, Valmik K.; Whiteway, Malcolm; Robbins, Nicole; Wong, Koon Ho; Cowen, Leah E.

2018-01-01

The capacity to respond to temperature fluctuations is critical for microorganisms to survive within mammalian hosts, and temperature modulates virulence traits of diverse pathogens. One key temperature-dependent virulence trait of the fungal pathogen Candida albicans is its ability to transition from yeast to filamentous growth, which is induced by environmental cues at host physiological temperature. A key regulator of temperature-dependent morphogenesis is the molecular chaperone Hsp90, which has complex functional relationships with the transcription factor Hsf1. Although Hsf1 controls global transcriptional remodeling in response to heat shock, its impact on morphogenesis remains unknown. Here, we establish an intriguing paradigm whereby overexpression or depletion of C. albicans HSF1 induces morphogenesis in the absence of external cues. HSF1 depletion compromises Hsp90 function, thereby driving filamentation. HSF1 overexpression does not impact Hsp90 function, but rather induces a dose-dependent expansion of Hsf1 direct targets that drives overexpression of positive regulators of filamentation, including Brg1 and Ume6, thereby bypassing the requirement for elevated temperature during morphogenesis. This work provides new insight into Hsf1-mediated environmentally contingent transcriptional control, implicates Hsf1 in regulation of a key virulence trait, and highlights fascinating biology whereby either overexpression or depletion of a single cellular regulator induces a profound developmental transition. PMID:29590106

Roles for FGF in lamprey pharyngeal pouch formation and skeletogenesis highlight ancestral functions in the vertebrate head.

PubMed

Jandzik, David; Hawkins, M Brent; Cattell, Maria V; Cerny, Robert; Square, Tyler A; Medeiros, Daniel M

2014-02-01

A defining feature of vertebrates (craniates) is a pronounced head supported and protected by a cellularized endoskeleton. In jawed vertebrates (gnathostomes), the head skeleton is made of rigid three-dimensional elements connected by joints. By contrast, the head skeleton of modern jawless vertebrates (agnathans) consists of thin rods of flexible cellular cartilage, a condition thought to reflect the ancestral vertebrate state. To better understand the origin and evolution of the gnathostome head skeleton, we have been analyzing head skeleton development in the agnathan, lamprey. The fibroblast growth factors FGF3 and FGF8 have various roles during head development in jawed vertebrates, including pharyngeal pouch morphogenesis, patterning of the oral skeleton and chondrogenesis. We isolated lamprey homologs of FGF3, FGF8 and FGF receptors and asked whether these functions are ancestral features of vertebrate development or gnathostome novelties. Using gene expression and pharmacological agents, we found that proper formation of the lamprey head skeleton requires two phases of FGF signaling: an early phase during which FGFs drive pharyngeal pouch formation, and a later phase when they directly regulate skeletal differentiation and patterning. In the context of gene expression and functional studies in gnathostomes, our results suggest that these roles for FGFs arose in the first vertebrates and that the evolution of the jaw and gnathostome cellular cartilage was driven by changes developmentally downstream from pharyngeal FGF signaling.

Paramyxovirus activation and inhibition of innate immune responses.

PubMed

Parks, Griffith D; Alexander-Miller, Martha A

2013-12-13

Paramyxoviruses represent a remarkably diverse family of enveloped nonsegmented negative-strand RNA viruses, some of which are the most ubiquitous disease-causing viruses of humans and animals. This review focuses on paramyxovirus activation of innate immune pathways, the mechanisms by which these RNA viruses counteract these pathways, and the innate response to paramyxovirus infection of dendritic cells (DC). Paramyxoviruses are potent activators of extracellular complement pathways, a first line of defense that viruses must face during natural infections. We discuss mechanisms by which these viruses activate and combat complement to delay neutralization. Once cells are infected, virus replication drives type I interferon (IFN) synthesis that has the potential to induce a large number of antiviral genes. Here we describe four approaches by which paramyxoviruses limit IFN induction: by limiting synthesis of IFN-inducing aberrant viral RNAs, through targeted inhibition of RNA sensors, by providing viral decoy substrates for cellular kinase complexes, and through direct blocking of the IFN promoter. In addition, paramyxoviruses have evolved diverse mechanisms to disrupt IFN signaling pathways. We describe three general mechanisms, including targeted proteolysis of signaling factors, sequestering cellular factors, and upregulation of cellular inhibitors. DC are exceptional cells with the capacity to generate adaptive immunity through the coupling of innate immune signals and T cell activation. We discuss the importance of innate responses in DC following paramyxovirus infection and their consequences for the ability to mount and maintain antiviral T cells. © 2013.

Paramyxovirus Activation and Inhibition of Innate Immune Responses

PubMed Central

Parks, Griffith D.; Alexander-Miller, Martha A.

2014-01-01

Paramyxoviruses represent a remarkably diverse family of enveloped nonsegmented negative-strand RNA viruses, some of which are the most ubiquitous disease-causing viruses of humans and animals. This review focuses on paramyxovirus activation of innate immune pathways, the mechanisms by which these RNA viruses counteract these pathways, and the innate response to paramyxovirus infection of dendritic cells (DC). Paramyxoviruses are potent activators of extracellular complement pathways, a first line of defense that viruses must face during natural infections. We discuss mechanisms by which these viruses activate and combat complement to delay neutralization. Once cells are infected, virus replication drives type I interferon (IFN) synthesis that has the potential to induce a large number of antiviral genes. Here we describe four approaches by which paramyxoviruses limit IFN induction: by limiting synthesis of IFN-inducing aberrant viral RNAs, through targeted inhibition of RNA sensors, by providing viral decoy substrates for cellular kinase complexes, and through direct blocking of the IFN promoter. In addition, paramyxoviruses have evolved diverse mechanisms to disrupt IFN signaling pathways. We describe three general mechanisms, including targeted proteolysis of signaling factors, sequestering cellular factors, and upregulation of cellular inhibitors. DC are exceptional cells with the capacity to generate adaptive immunity through the coupling of innate immune signals and T cell activation. We discuss the importance of innate responses in DC following paramyxovirus infection and their consequences for the ability to mount and maintain antiviral T cells. PMID:24056173

Cellular automata models for diffusion of information and highway traffic flow

NASA Astrophysics Data System (ADS)

Fuks, Henryk

In the first part of this work we study a family of deterministic models for highway traffic flow which generalize cellular automaton rule 184. This family is parameterized by the speed limit m and another parameter k that represents degree of 'anticipatory driving'. We compare two driving strategies with identical maximum throughput: 'conservative' driving with high speed limit and 'anticipatory' driving with low speed limit. Those two strategies are evaluated in terms of accident probability. We also discuss fundamental diagrams of generalized traffic rules and examine limitations of maximum achievable throughput. Possible modifications of the model are considered. For rule 184, we present exact calculations of the order parameter in a transition from the moving phase to the jammed phase using the method of preimage counting, and use this result to construct a solution to the density classification problem. In the second part we propose a probabilistic cellular automaton model for the spread of innovations, rumors, news, etc., in a social system. We start from simple deterministic models, for which exact expressions for the density of adopters are derived. For a more realistic model, based on probabilistic cellular automata, we study the influence of a range of interaction R on the shape of the adoption curve. When the probability of adoption is proportional to the local density of adopters, and individuals can drop the innovation with some probability p, the system exhibits a second order phase transition. Critical line separating regions of parameter space in which asymptotic density of adopters is positive from the region where it is equal to zero converges toward the mean-field line when the range of the interaction increases. In a region between R=1 critical line and the mean-field line asymptotic density of adopters depends on R, becoming zero if R is too small (smaller than some critical value). This result demonstrates the importance of connectivity in diffusion of information. We also define a new class of automata networks which incorporates non-local interactions, and discuss its applicability in modeling of diffusion of innovations.

The anatomy of microbial cell state transitions in response to oxygen.

PubMed

Schmid, Amy K; Reiss, David J; Kaur, Amardeep; Pan, Min; King, Nichole; Van, Phu T; Hohmann, Laura; Martin, Daniel B; Baliga, Nitin S

2007-10-01

Adjustment of physiology in response to changes in oxygen availability is critical for the survival of all organisms. However, the chronology of events and the regulatory processes that determine how and when changes in environmental oxygen tension result in an appropriate cellular response is not well understood at a systems level. Therefore, transcriptome, proteome, ATP, and growth changes were analyzed in a halophilic archaeon to generate a temporal model that describes the cellular events that drive the transition between the organism's two opposing cell states of anoxic quiescence and aerobic growth. According to this model, upon oxygen influx, an initial burst of protein synthesis precedes ATP and transcription induction, rapidly driving the cell out of anoxic quiescence, culminating in the resumption of growth. This model also suggests that quiescent cells appear to remain actively poised for energy production from a variety of different sources. Dynamic temporal analysis of relationships between transcription and translation of key genes suggests several important mechanisms for cellular sustenance under anoxia as well as specific instances of post-transcriptional regulation.

The anatomy of microbial cell state transitions in response to oxygen

PubMed Central

Schmid, Amy K.; Reiss, David J.; Kaur, Amardeep; Pan, Min; King, Nichole; Van, Phu T.; Hohmann, Laura; Martin, Daniel B.; Baliga, Nitin S.

2007-01-01

Adjustment of physiology in response to changes in oxygen availability is critical for the survival of all organisms. However, the chronology of events and the regulatory processes that determine how and when changes in environmental oxygen tension result in an appropriate cellular response is not well understood at a systems level. Therefore, transcriptome, proteome, ATP, and growth changes were analyzed in a halophilic archaeon to generate a temporal model that describes the cellular events that drive the transition between the organism’s two opposing cell states of anoxic quiescence and aerobic growth. According to this model, upon oxygen influx, an initial burst of protein synthesis precedes ATP and transcription induction, rapidly driving the cell out of anoxic quiescence, culminating in the resumption of growth. This model also suggests that quiescent cells appear to remain actively poised for energy production from a variety of different sources. Dynamic temporal analysis of relationships between transcription and translation of key genes suggests several important mechanisms for cellular sustenance under anoxia as well as specific instances of post-transcriptional regulation. PMID:17785531

MYCN Promotes the Expansion of Phox2B-Positive Neuronal Progenitors to Drive Neuroblastoma Development

PubMed Central

Alam, Goleeta; Cui, Hongjuan; Shi, Huilin; Yang, Liqun; Ding, Jane; Mao, Ling; Maltese, William A.; Ding, Han-Fei

2009-01-01

Amplification of the oncogene MYCN is a tumorigenic event in the development of a subset of neuroblastomas that commonly consist of undifferentiated or poorly differentiated neuroblasts with unfavorable clinical outcome. The cellular origin of these neuroblasts is unknown. Additionally, the cellular functions and target cells of MYCN in neuroblastoma development remain undefined. Here we examine the cell types that drive neuroblastoma development in TH-MYCN transgenic mice, an animal model of the human disease. Neuroblastoma development in these mice begins with hyperplastic lesions in early postnatal sympathetic ganglia. We show that both hyperplasia and primary tumors are composed predominantly of highly proliferative Phox2B+ neuronal progenitors. MYCN induces the expansion of these progenitors by both promoting their proliferation and preventing their differentiation. We further identify a minor population of undifferentiated nestin+ cells in both hyperplastic lesions and primary tumors that may serve as precursors of Phox2B+ neuronal progenitors. These findings establish the identity of neuroblasts that characterize the tumor phenotype and suggest a cellular pathway by which MYCN can promote neuroblastoma development. PMID:19608868

The 3-dimensional cellular automata for HIV infection

NASA Astrophysics Data System (ADS)

Mo, Youbin; Ren, Bin; Yang, Wencao; Shuai, Jianwei

2014-04-01

The HIV infection dynamics is discussed in detail with a 3-dimensional cellular automata model in this paper. The model can reproduce the three-phase development, i.e., the acute period, the asymptotic period and the AIDS period, observed in the HIV-infected patients in a clinic. We show that the 3D HIV model performs a better robustness on the model parameters than the 2D cellular automata. Furthermore, we reveal that the occurrence of a perpetual source to successively generate infectious waves to spread to the whole system drives the model from the asymptotic state to the AIDS state.

CRISPR-Cas9 therapeutics in cancer: promising strategies and present challenges.

PubMed

Yi, Lang; Li, Jinming

2016-12-01

Cancer is characterized by multiple genetic and epigenetic alterations that drive malignant cell proliferation and confer chemoresistance. The ability to correct or ablate such mutations holds immense promise for combating cancer. Recently, because of its high efficiency and accuracy, the CRISPR-Cas9 genome editing technique has been widely used in cancer therapeutic explorations. Several studies used CRISPR-Cas9 to directly target cancer cell genomic DNA in cellular and animal cancer models which have shown therapeutic potential in expanding our anticancer protocols. Moreover, CRISPR-Cas9 can also be employed to fight oncogenic infections, explore anticancer drugs, and engineer immune cells and oncolytic viruses for cancer immunotherapeutic applications. Here, we summarize these preclinical CRISPR-Cas9-based therapeutic strategies against cancer, and discuss the challenges and improvements in translating therapeutic CRISPR-Cas9 into clinical use, which will facilitate better application of this technique in cancer research. Further, we propose potential directions of the CRISPR-Cas9 system in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Traction forces during collective cell motion.

PubMed

Gov, N S

2009-08-01

Collective motion of cell cultures is a process of great interest, as it occurs during morphogenesis, wound healing, and tumor metastasis. During these processes cell cultures move due to the traction forces induced by the individual cells on the surrounding matrix. A recent study [Trepat, et al. (2009). Nat. Phys. 5, 426-430] measured for the first time the traction forces driving collective cell migration and found that they arise throughout the cell culture. The leading 5-10 rows of cell do play a major role in directing the motion of the rest of the culture by having a distinct outwards traction. Fluctuations in the traction forces are an order of magnitude larger than the resultant directional traction at the culture edge and, furthermore, have an exponential distribution. Such exponential distributions are observed for the sizes of adhesion domains within cells, the traction forces produced by single cells, and even in nonbiological nonequilibrium systems, such as sheared granular materials. We discuss these observations and their implications for our understanding of cellular flows within a continuous culture.

Higher-order looping and nuclear organization of antigen receptor loci facilitate targeted RAG cleavage and regulated rearrangement in recombination centers

PubMed Central

Chaumeil, Julie; Micsinai, Mariann; Ntziachristos, Panagiotis; Deriano, Ludovic; Wang, Joy M-H; Ji, Yanhong; Nora, Elphege P.; Rodesch, Matthew J.; Jeddeloh, Jeffrey A.; Aifantis, Iannis; Kluger, Yuval; Schatz, David G.; Skok, Jane A.

2013-01-01

SUMMARY V(D)J recombination is essential for generating a diverse array of B and T cell receptors that can recognize and combat foreign antigen. As with any recombination event, tight control is essential to prevent the occurrence of genetic anomalies that drive cellular transformation. One important aspect of regulation is directed targeting of the RAG recombinase. Indeed, RAG accumulates at the 3’ end of individual antigen receptor loci poised for rearrangement, however, it is not known whether focal binding is involved in regulating cleavage, and what mechanisms lead to enrichment of RAG in this region. Here we show that mono-allelic looping out of the 3’ end of Tcra, coupled with transcription and increased chromatin/nuclear accessibility, are linked to focal RAG binding and ATM-mediated regulated mono-allelic cleavage on looped out 3’ regions. Our data identify higher order loop formation as a key determinant of directed RAG targeting and the maintenance of genome stability. PMID:23416051

Tensiometer, drive probe for use with environmental testing equipment, and methods of inserting environmental testing equipment into a sample

DOEpatents

Hubbell, Joel M.; Sisson, James B.

2005-07-26

A method of inserting a tensiometer into a sample, comprises providing a drive probe configured to be engaged by direct push equipment; supporting a porous member from the drive probe; and driving the drive probe into the sample using a cone penetrometer. A tensiometer comprises a drive probe configured to be engaged by direct push equipment or a cone penetrometer; a porous member supported by the drive probe; and a pressure sensor in pressure sensing relation to the porous member.

The role of personality traits and driving experience in self-reported risky driving behaviors and accident risk among Chinese drivers.

PubMed

Tao, Da; Zhang, Rui; Qu, Xingda

2017-02-01

The purpose of this study was to explore the role of personality traits and driving experience in the prediction of risky driving behaviors and accident risk among Chinese population. A convenience sample of drivers (n=511; mean (SD) age=34.2 (8.8) years) completed a self-report questionnaire that was designed based on validated scales for measuring personality traits, risky driving behaviors and self-reported accident risk. Results from structural equation modeling analysis demonstrated that the data fit well with our theoretical model. While showing no direct effects on accident risk, personality traits had direct effects on risky driving behaviors, and yielded indirect effects on accident risk mediated by risky driving behaviors. Both driving experience and risky driving behaviors directly predicted accident risk and accounted for 15% of its variance. There was little gender difference in personality traits, risky driving behaviors and accident risk. The findings emphasized the importance of personality traits and driving experience in the understanding of risky driving behaviors and accident risk among Chinese drivers and provided new insight into the design of evidence-based driving education and accident prevention interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Friction forces position the neural anlage

PubMed Central

Smutny, Michael; Ákos, Zsuzsa; Grigolon, Silvia; Shamipour, Shayan; Ruprecht, Verena; Čapek, Daniel; Behrndt, Martin; Papusheva, Ekaterina; Tada, Masazumi; Hof, Björn; Vicsek, Tamás; Salbreux, Guillaume; Heisenberg, Carl-Philipp

2017-01-01

During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo. PMID:28346437

N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

PubMed

Lee, John K; Phillips, John W; Smith, Bryan A; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M; Shokat, Kevan M; Gustafson, W Clay; Huang, Jiaoti; Witte, Owen N

2016-04-11

MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Friction forces position the neural anlage.

PubMed

Smutny, Michael; Ákos, Zsuzsa; Grigolon, Silvia; Shamipour, Shayan; Ruprecht, Verena; Čapek, Daniel; Behrndt, Martin; Papusheva, Ekaterina; Tada, Masazumi; Hof, Björn; Vicsek, Tamás; Salbreux, Guillaume; Heisenberg, Carl-Philipp

2017-04-01

During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo.

Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.

PubMed

Hinder, Lucy M; Park, Meeyoung; Rumora, Amy E; Hur, Junguk; Eichinger, Felix; Pennathur, Subramaniam; Kretzler, Matthias; Brosius, Frank C; Feldman, Eva L

2017-09-01

Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self-organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self-organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue-specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a 'one size fits all' approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Shapiro spikes and negative mobility for skyrmion motion on quasi-one-dimensional periodic substrates

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

Reichhardt, Charles; Olson Reichhardt, Cynthia Jane

2017-01-12

Using a simple numerical model of skyrmions in a two-dimensional system interacting with a quasi-one-dimensional periodic substrate under combined dc and ac drives where the dc drive is applied perpendicular to the substrate periodicity, we show that a rich variety of novel phase-locking dynamics can occur due to the influence of the Magnus term on the skyrmion dynamics. Instead of Shapiro steps, the velocity response in the direction of the dc drive exhibits a series of spikes, including extended dc drive intervals over which the skyrmions move in the direction opposite to the dc drive, producing negative mobility. Also, theremore » are specific dc drive values at which the skyrmions move exactly perpendicular to the dc drive direction, giving a condition of absolute transverse mobility.« less

Cellular Imaging | Center for Cancer Research

Cancer.gov

Innovative imaging methods developed and refined within CCR revealed atomic-level structures of biological molecules and unveiled dynamic views of a cell’s interior that are driving the design of new treatments and diagnostics for cancer.

Effects of fuel-capsule shimming and drive asymmetry on inertial-confinement-fusion symmetry and yield

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

Séguin, F. H.; Li, C. K.; DeCiantis, J. L.

Three orthogonal proton emission imaging cameras were used to study the 3D effects of low-mode drive asymmetries and target asymmetries on nuclear burn symmetry and yield in direct-drive, inertial-confinement-fusion experiments. The fusion yield decreased quickly as the burn region became asymmetric due to either drive or capsule asymmetry. Measurements and analytic scaling are used to predict how intentionally asymmetric capsule shells could improve performance by compensating for drive asymmetry when it cannot be avoided (such as with indirect drive or with polar direct drive).

Effects of fuel-capsule shimming and drive asymmetry on inertial-confinement-fusion symmetry and yield

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

Seguin, F. H.; Li, C. K.; DeCiantis, J. L.

Three orthogonal proton emission imaging cameras were used to study the 3D effects of low-mode drive asymmetries and target asymmetries on nuclear burn symmetry and yield in direct-drive, inertial-confinement-fusion experiments. The fusion yield decreased quickly as the burn region became asymmetric due to either drive or capsule asymmetry. Furthermore, measurements and analytic scaling are used to predict how intentionally asymmetric capsule shells could improve performance by compensating for drive asymmetry when it cannot be avoided (such as with indirect drive or with polar direct drive).

Effects of fuel-capsule shimming and drive asymmetry on inertial-confinement-fusion symmetry and yield

DOE PAGES

Seguin, F. H.; Li, C. K.; DeCiantis, J. L.; ...

2016-03-22

Three orthogonal proton emission imaging cameras were used to study the 3D effects of low-mode drive asymmetries and target asymmetries on nuclear burn symmetry and yield in direct-drive, inertial-confinement-fusion experiments. The fusion yield decreased quickly as the burn region became asymmetric due to either drive or capsule asymmetry. Furthermore, measurements and analytic scaling are used to predict how intentionally asymmetric capsule shells could improve performance by compensating for drive asymmetry when it cannot be avoided (such as with indirect drive or with polar direct drive).

Active Listening Delays Attentional Disengagement and Saccadic Eye Movements.

PubMed

Lester, Benjamin D; Vecera, Shaun P

2018-06-01

Successful goal-directed visual behavior depends on efficient disengagement of attention. Attention must be withdrawn from its current focus before being redeployed to a new object or internal process. Previous research has demonstrated that occupying cognitive processes with a secondary cellular phone conversation impairs attentional functioning and driving behavior. For example, attentional processing is significantly impacted by concurrent cell phone use, resulting in decreased explicit memory for on-road information. Here, we examined the impact of a critical component of cell-phone use-active listening-on the effectiveness of attentional disengagement. In the gap task-a saccadic manipulation of attentional disengagement-we measured saccade latencies while participants performed a secondary active listening task. Saccadic latencies significantly increased under an active listening load only when attention needed to be disengaged, indicating that active listening delays a disengagement operation. Simple dual-task interference did not account for the observed results. Rather, active cognitive engagement is required for measurable disengagement slowing to be observed. These results have implications for investigations of attention, gaze behavior, and distracted driving. Secondary tasks such as active listening or cell-phone conversations can have wide-ranging impacts on cognitive functioning, potentially impairing relatively elementary operations of attentional function, including disengagement.

Lethal factor unfolding is the most force-dependent step of anthrax toxin translocation

PubMed Central

Thoren, Katie L.; Worden, Evan J.; Yassif, Jaime M.; Krantz, Bryan A.

2009-01-01

Cellular compartmentalization requires machinery capable of translocating polypeptides across membranes. In many cases, transported proteins must first be unfolded by means of the proton motive force and/or ATP hydrolysis. Anthrax toxin, which is composed of a channel-forming protein and two substrate proteins, is an attractive model system to study translocation-coupled unfolding, because the applied driving force can be externally controlled and translocation can be monitored directly by using electrophysiology. By controlling the driving force and introducing destabilizing point mutations in the substrate, we identified the barriers in the transport pathway, determined which barrier corresponds to protein unfolding, and mapped how the substrate protein unfolds during translocation. In contrast to previous studies, we find that the protein's structure next to the signal tag is not rate-limiting to unfolding. Instead, a more extensive part of the structure, the amino-terminal β-sheet subdomain, must disassemble to cross the unfolding barrier. We also find that unfolding is catalyzed by the channel's phenylalanine-clamp active site. We propose a broad molecular mechanism for translocation-coupled unfolding, which is applicable to both soluble and membrane-embedded unfolding machines. PMID:19926859

Inflammasome mediated autoinflammatory disorders

PubMed Central

Wilson, Shruti P.; Cassel, Suzanne L.

2013-01-01

The nucleotide-binding domain leucine-rich repeat containing (NLR) family of receptors are members of the innate immune system with a critical role in host defense. These molecules are key to driving inflammatory responses to abnormal cellular conditions. A number of the NLRs serve this role upon activation by forming a multi-protein complex called an inflammasome. The inflammasome drives the processing and release of cytokines such as the pro-inflammatory cytokines interleukin (IL)-1β and IL-18. The important function of NLR molecules in autoinflammatory disorders has recently been recognized in part through the identification of the role of IL-1β in pathogenesis of several autoinflammatory diseases. Cryopyrin-associated periodic syndromes (CAPS) were the first autoinflammatory disorders found to be directly mediated by dysfunctional inflammasome activation. This finding has subsequently led to studies in both murine models and humans that have revealed several other inflammatory conditions associated with activation of NLR containing inflammasomes. Understanding of the molecular pathophysiology of these autoinflammatory disorders has further guided the successful development of targeted therapy against IL-1. In this review, we will provide an overview of the inflammasomes and describe the important role they play in the development and manifestations of autoinflammatory diseases. PMID:20861596

Rab GTPases and Membrane Trafficking in Neurodegeneration

PubMed Central

Kiral, Ferdi Ridvan; Kohrs, Friederike Elisabeth; Jin, Eugene Jennifer; Hiesinger, Peter Robin

2018-01-01

Defects in membrane trafficking are hallmarks of neurodegeneration. Rab GTPases are key regulators of membrane trafficking. Alterations of Rab GTPases, or the membrane compartments they regulate, are associated with virtually all neuronal activities in health and disease. The observation that many Rab GTPases are associated with neurodegeneration has proven a challenge in the quest for cause and effect. Neurodegeneration can be a direct consequence of a defect in membrane trafficking. Alternatively, changes in membrane trafficking may be secondary consequences or cellular responses. The secondary consequences and cellular responses, in turn, may protect, represent inconsequential correlates or function as drivers of pathology. Here, we attempt to disentangle the different roles of membrane trafficking in neurodegeneration by focusing on selected associations with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and selected neuropathies. We provide an overview of current knowledge on Rab GTPase functions in neurons and review the associations of Rab GTPases with neurodegeneration with respect to the following classifications: primary cause, secondary cause driving pathology or secondary correlate. This analysis is devised to aid the interpretation of frequently observed membrane trafficking defects in neurodegeneration and facilitate the identification of true causes of pathology. PMID:29689231

A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation

PubMed Central

Neufeld, Thomas P.

2017-01-01

Autophagy plays an essential role in the cellular homeostasis of neurons, facilitating the clearance of cellular debris. This clearance process is orchestrated through the assembly, transport, and fusion of autophagosomes with lysosomes for degradation. The motor protein dynein drives autophagosome motility from distal sites of assembly to sites of lysosomal fusion. In this study, we identify the scaffold protein CKA (connector of kinase to AP-1) as essential for autophagosome transport in neurons. Together with other core components of the striatin-interacting phosphatase and kinase (STRIPAK) complex, we show that CKA associates with dynein and directly binds Atg8a, an autophagosomal protein. CKA is a regulatory subunit of PP2A, a component of the STRIPAK complex. We propose that the STRIPAK complex modulates dynein activity. Consistent with this hypothesis, we provide evidence that CKA facilitates axonal transport of dense core vesicles and autophagosomes in a PP2A-dependent fashion. In addition, CKA-deficient flies exhibit PP2A-dependent motor coordination defects. CKA function within the STRIPAK complex is crucial to prevent transport defects that may contribute to neurodegeneration. PMID:28100687

Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia.

PubMed

Hattori, Ayuna; Tsunoda, Makoto; Konuma, Takaaki; Kobayashi, Masayuki; Nagy, Tamas; Glushka, John; Tayyari, Fariba; McSkimming, Daniel; Kannan, Natarajan; Tojo, Arinobu; Edison, Arthur S; Ito, Takahiro

2017-05-25

Reprogrammed cellular metabolism is a common characteristic observed in various cancers. However, whether metabolic changes directly regulate cancer development and progression remains poorly understood. Here we show that BCAT1, a cytosolic aminotransferase for branched-chain amino acids (BCAAs), is aberrantly activated and functionally required for chronic myeloid leukaemia (CML) in humans and in mouse models of CML. BCAT1 is upregulated during progression of CML and promotes BCAA production in leukaemia cells by aminating the branched-chain keto acids. Blocking BCAT1 gene expression or enzymatic activity induces cellular differentiation and impairs the propagation of blast crisis CML both in vitro and in vivo. Stable-isotope tracer experiments combined with nuclear magnetic resonance-based metabolic analysis demonstrate the intracellular production of BCAAs by BCAT1. Direct supplementation with BCAAs ameliorates the defects caused by BCAT1 knockdown, indicating that BCAT1 exerts its oncogenic function through BCAA production in blast crisis CML cells. Importantly, BCAT1 expression not only is activated in human blast crisis CML and de novo acute myeloid leukaemia, but also predicts disease outcome in patients. As an upstream regulator of BCAT1 expression, we identified Musashi2 (MSI2), an oncogenic RNA binding protein that is required for blast crisis CML. MSI2 is physically associated with the BCAT1 transcript and positively regulates its protein expression in leukaemia. Taken together, this work reveals that altered BCAA metabolism activated through the MSI2-BCAT1 axis drives cancer progression in myeloid leukaemia.

Crowd-Sourcing Management Activity Data to Drive GHG Emission Inventories in the Land Use Sector

NASA Astrophysics Data System (ADS)

Paustian, K.; Herrick, J.

2015-12-01

Greenhouse gas (GHG) emissions from the land use sector constitute the largest source category for many countries in Africa. Enhancing C sequestration and reducing GHG emissions on managed lands in Africa has to potential to attract C financing to support adoption of more sustainable land management practices that, in addition to GHG mitigation, can provide co-benefits of more productive and climate-resilient agroecosystems. However, robust systems to measure and monitor C sequestration/GHG reductions are currently a significant barrier to attracting more C financing to land use-related mitigation efforts.Anthropogenic GHG emissions are driven by a variety of environmental factors, including climate and soil attributes, as well as human-activities in the form of land use and management practices. GHG emission inventories typically use empirical or process-based models of emission rates that are driven by environmental and management variables. While a lack of field-based flux and C stock measurements are a limiting factor for GHG estimation, we argue that an even greater limitation may be availabiity of data on the management activities that influence flux rates, particularly in developing countries in Africa. In most developed countries there is a well-developed infrastructure of agricultural statistics and practice surveys that can be used to drive model-based GHG emission estimations. However, this infrastructure is largely lacking in developing countries in Africa. While some activity data (e.g. land cover change) can be derived from remote sensing, many key data (e.g., N fertilizer practices, residue management, manuring) require input from the farmers themselves. The explosive growth in cellular technology, even in many of the poorest parts of Africa, suggests the potential for a new crowd-sourcing approach and direct engagement with farmers to 'leap-frog' the land resource information model of developed countries. Among the many benefits of this approach would be high resolution management data to support GHG inventories at multiple scales. We present an overall conceptual model for this approach and examples from on-going projects in Africa employing direct farmer engagement, cellular technology and apps to develop this information resource.

Aeroallergens Induce Reactive Oxygen Species Production and DNA Damage and Dampen Antioxidant Responses in Bronchial Epithelial Cells.

PubMed

Chan, Tze Khee; Tan, W S Daniel; Peh, Hong Yong; Wong, W S Fred

2017-07-01

Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX. HDM stimulated cellular reactive oxygen species production, increased mitochondrial oxidative stress, and promoted nitrosative stress. Notably, expression of nuclear factor erythroid 2-related factor 2-dependent antioxidant genes was reduced immediately after HDM exposure, suggesting that HDM altered antioxidant responses. HDM exposure also reduced cell proliferation and induced cell death. Importantly, HDM-induced DNA damage can be prevented by the antioxidants glutathione and catalase, suggesting that HDM-induced reactive oxygen and nitrogen species can be neutralized by antioxidants. Mechanistic studies revealed that HDM-induced cellular injury is NADPH oxidase (NOX)-dependent, and apocynin, a NOX inhibitor, protected cells from double-strand breaks induced by HDM. Our results show that direct exposure of bronchial epithelial cells to HDM leads to the production of reactive oxygen and nitrogen species that damage DNA and induce cytotoxicity. Antioxidants and NOX inhibitors can prevent HDM-induced DNA damage, revealing a novel role for antioxidants and NOX inhibitors in mitigating allergic airway disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Teen driver cell phone blocker.

DOT National Transportation Integrated Search

2012-02-01

This study was a randomized control intervention to measure the effectiveness of a cellular phone control device : that communicates with the vehicles of teen drivers to deny them access to their phone while driving for the : purpose of reducing dist...

HIF Transcription Factors, Inflammation, and Immunity

PubMed Central

Palazon, Asis; Goldrath, Ananda; Nizet, Victor

2015-01-01

The hypoxic response in cells and tissues is mediated by the family of hypoxia-inducible factor (HIF) transcription factors that play an integral role in the metabolic changes that drive cellular adaptation to low oxygen availability. HIF expression and stabilization in immune cells can be triggered by hypoxia, but also by other factors associated with pathological stress: e.g., inflammation, infectious microorganisms, and cancer. HIF induces a number of aspects of host immune function, from boosting phagocyte microbicidal capacity to driving T cell differentiation and cytotoxic activity. Cellular metabolism is emerging as a key regulator of immunity, and it constitutes another layer of fine-tuned immune control by HIF that can dictate myeloid cell and lymphocyte development, fate, and function. Here we discuss how oxygen sensing in the immune microenvironment shapes immunological response and examine how HIF and the hypoxia pathway control innate and adaptive immunity. PMID:25367569

HIF transcription factors, inflammation, and immunity.

PubMed

Palazon, Asis; Goldrath, Ananda W; Nizet, Victor; Johnson, Randall S

2014-10-16

The hypoxic response in cells and tissues is mediated by the family of hypoxia-inducible factor (HIF) transcription factors; these play an integral role in the metabolic changes that drive cellular adaptation to low oxygen availability. HIF expression and stabilization in immune cells can be triggered by hypoxia, but also by other factors associated with pathological stress: e.g., inflammation, infectious microorganisms, and cancer. HIF induces a number of aspects of host immune function, from boosting phagocyte microbicidal capacity to driving T cell differentiation and cytotoxic activity. Cellular metabolism is emerging as a key regulator of immunity, and it constitutes another layer of fine-tuned immune control by HIF that can dictate myeloid cell and lymphocyte development, fate, and function. Here we discuss how oxygen sensing in the immune microenvironment shapes immunological response and examine how HIF and the hypoxia pathway control innate and adaptive immunity.

Dynamic interactions between 14-3-3 proteins and phosphoproteins regulate diverse cellular processes

PubMed Central

2004-01-01

14-3-3 proteins exert an extraordinarily widespread influence on cellular processes in all eukaryotes. They operate by binding to specific phosphorylated sites on diverse target proteins, thereby forcing conformational changes or influencing interactions between their targets and other molecules. In these ways, 14-3-3s ‘finish the job’ when phosphorylation alone lacks the power to drive changes in the activities of intracellular proteins. By interacting dynamically with phosphorylated proteins, 14-3-3s often trigger events that promote cell survival – in situations from preventing metabolic imbalances caused by sudden darkness in leaves to mammalian cell-survival responses to growth factors. Recent work linking specific 14-3-3 isoforms to genetic disorders and cancers, and the cellular effects of 14-3-3 agonists and antagonists, indicate that the cellular complement of 14-3-3 proteins may integrate the specificity and strength of signalling through to different cellular responses. PMID:15167810

Pollen tube energetics: respiration, fermentation and the race to the ovule

PubMed Central

Rounds, Caleb M.; Winship, Lawrence J.; Hepler, Peter K.

2011-01-01

Background Pollen tubes grow by transferring chemical energy from stored cellular starch and newly assimilated sugars into ATP. This drives myriad processes essential for cell elongation, directly or through the creation of ion gradients. Respiration plays a central role in generating and regulating this energy flow and thus in the success of plant reproduction. Pollen tubes are easily grown in vitro and have become an excellent model for investigating the contributions of respiration to plant cellular growth and morphogenesis at the molecular, biochemical and physiological levels. Scope In recent decades, pollen tube research has become increasingly focused on the molecular mechanisms involved in cellular processes. Yet, effective growth and development requires an intact, integrated set of cellular processes, all supplied with a constant flow of energy. Here we bring together information from the current and historical literature concerning respiration, fermentation and mitochondrial physiology in pollen tubes, and assess the significance of more recent molecular and genetic investigations in a physiological context. Conclusions The rapid growth of the pollen tube down the style has led to the evolution of high rates of pollen tube respiration. Respiration rates in lily predict a total energy turnover of 40–50 fmol ATP s−1 per pollen grain. Within this context we examine the energetic requirements of cell wall synthesis, osmoregulation, actin dynamics and cyclosis. At present, we can only estimate the amount of energy required, because data from growing pollen tubes are not available. In addition to respiration, we discuss fermentation and mitochondrial localization. We argue that the molecular pathways need to be examined within the physiological context to understand better the mechanisms that control tip growth in pollen tubes. PMID:22476489

Drosophila Neuronal Injury Follows a Temporal Sequence of Cellular Events Leading to Degeneration at the Neuromuscular Junction

PubMed Central

Lincoln, Barron L.; Alabsi, Sahar H.; Frendo, Nicholas; Freund, Robert; Keller, Lani C.

2015-01-01

Neurodegenerative diseases affect millions of people worldwide, and as the global population ages, there is a critical need to improve our understanding of the molecular and cellular mechanisms that drive neurodegeneration. At the molecular level, neurodegeneration involves the activation of complex signaling pathways that drive the active destruction of neurons and their intracellular components. Here, we use an in vivo motor neuron injury assay to acutely induce neurodegeneration in order to follow the temporal order of events that occur following injury in Drosophila melanogaster. We find that sites of injury can be rapidly identified based on structural defects to the neuronal cytoskeleton that result in disrupted axonal transport. Additionally, the neuromuscular junction accumulates ubiquitinated proteins prior to the neurodegenerative events, occurring at 24 hours post injury. Our data provide insights into the early molecular events that occur during axonal and neuromuscular degeneration in a genetically tractable model organism. Importantly, the mechanisms that mediate neurodegeneration in flies are conserved in humans. Thus, these studies have implications for our understanding of the cellular and molecular events that occur in humans and will facilitate the identification of biomedically relevant targets for future treatments. PMID:26512206

Phospholipid Chain Interactions with Cholesterol Drive Domain Formation in Lipid Membranes.

PubMed

Bennett, W F Drew; Shea, Joan-Emma; Tieleman, D Peter

2018-06-05

Cholesterol is a key component of eukaryotic membranes, but its role in cellular biology in general and in lipid rafts in particular remains controversial. Model membranes are used extensively to determine the phase behavior of ternary mixtures of cholesterol, a saturated lipid, and an unsaturated lipid with liquid-ordered and liquid-disordered phase coexistence. Despite many different experiments that determine lipid-phase diagrams, we lack an understanding of the molecular-level driving forces for liquid phase coexistence in bilayers with cholesterol. Here, we use atomistic molecular dynamics computer simulations to address the driving forces for phase coexistence in ternary lipid mixtures. Domain formation is directly observed in a long-timescale simulation of a mixture of 1,2-distearoyl-sn-glycero-3-phosphocholine, unsaturated 1,2-dilinoleoyl-sn-glycero-3-phosphocholine, and cholesterol. Free-energy calculations for the exchange of the saturated and unsaturated lipids between the ordered and disordered phases give insight into the mixing behavior. We show that a large energetic contribution to domain formation is favorable enthalpic interactions of the saturated lipid in the ordered phase. This favorable energy for forming an ordered, cholesterol-rich phase is opposed by a large unfavorable entropy. Martini coarse-grained simulations capture the unfavorable free energy of mixing but do not reproduce the entropic contribution because of the reduced representation of the phospholipid tails. Phospholipid tails and their degree of unsaturation are key energetic contributors to lipid phase separation. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

S-nitrosylation drives cell senescence and aging in mammals by controlling mitochondrial dynamics and mitophagy.

PubMed

Rizza, Salvatore; Cardaci, Simone; Montagna, Costanza; Di Giacomo, Giuseppina; De Zio, Daniela; Bordi, Matteo; Maiani, Emiliano; Campello, Silvia; Borreca, Antonella; Puca, Annibale A; Stamler, Jonathan S; Cecconi, Francesco; Filomeni, Giuseppe

2018-04-10

S -nitrosylation, a prototypic redox-based posttranslational modification, is frequently dysregulated in disease. S -nitrosoglutathione reductase (GSNOR) regulates protein S -nitrosylation by functioning as a protein denitrosylase. Deficiency of GSNOR results in tumorigenesis and disrupts cellular homeostasis broadly, including metabolic, cardiovascular, and immune function. Here, we demonstrate that GSNOR expression decreases in primary cells undergoing senescence, as well as in mice and humans during their life span. In stark contrast, exceptionally long-lived individuals maintain GSNOR levels. We also show that GSNOR deficiency promotes mitochondrial nitrosative stress, including excessive S -nitrosylation of Drp1 and Parkin, thereby impairing mitochondrial dynamics and mitophagy. Our findings implicate GSNOR in mammalian longevity, suggest a molecular link between protein S -nitrosylation and mitochondria quality control in aging, and provide a redox-based perspective on aging with direct therapeutic implications.

Re-criticizing RNA-mediated cell evolution: a radical perspective

NASA Astrophysics Data System (ADS)

Kotakis, Christos

2016-01-01

Genetic inter-communication of the nucleic-organellar dual in eukaryotes is dominated by DNA-directed phenomena. RNA regulatory circuits have also been observed in artificial laboratory prototypes where gene transfer events are reconstructed, but they are excluded from the primary norm due to their rarity. Recent technical advances in organellar biotechnology, genome engineering and single-molecule tracking give novel experimental insights on RNA metabolism not only at cellular level, but also on organismal survival. Here, I put forward a hypothesis for RNA's involvement in gene piece transfer, taken together the current knowledge on the primitive RNA character as a biochemical modulator with model organisms from peculiar natural habitats. It is proposed that RNA molecules of special structural signature and functional identity can drive evolution, integrating the ecological pressure of environmental oscillations into genome imprinting by buffering-out epigenetic aberrancies.

Wavelength-detuning cross-beam energy transfer mitigation scheme for direct drive: Modeling and evidence from National Ignition Facility implosions

NASA Astrophysics Data System (ADS)

Marozas, J. A.; Hohenberger, M.; Rosenberg, M. J.; Turnbull, D.; Collins, T. J. B.; Radha, P. B.; McKenty, P. W.; Zuegel, J. D.; Marshall, F. J.; Regan, S. P.; Sangster, T. C.; Seka, W.; Campbell, E. M.; Goncharov, V. N.; Bowers, M. W.; Di Nicola, J.-M. G.; Erbert, G.; MacGowan, B. J.; Pelz, L. J.; Moody, J.; Yang, S. T.

2018-05-01

Cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces laser-energy absorption for direct-drive inertial confinement fusion. Consequently, ablation pressure and implosion velocity suffer from the decreased absorption, reducing target performance in both symmetric and polar direct drive. Additionally, CBET alters the time-resolved scattered-light spectra and redistributes absorbed and scattered-light-changing shell morphology and low-mode drive symmetry. Mitigating CBET is demonstrated in inertial confinement implosions at the National Ignition Facility by detuning the laser-source wavelengths (±2.3 Å UV) of the interacting beams. In polar direct drive, wavelength detuning was shown to increase the equatorial region velocity experimentally by 16% and to alter the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation-hydrodynamic simulations that indicate a 10% increase in the average ablation pressure. These results indicate that wavelength detuning successfully mitigates CBET. Simulations predict that optimized phase plates and wavelength-detuning CBET mitigation utilizing the three-legged beam layout of the OMEGA Laser System significantly increase absorption and achieve >100-Gbar hot-spot pressures in symmetric direct drive.

Finite driving rate and anisotropy effects in landslide modeling

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

Piegari, E.; Cataudella, V.; Di Maio, R.

2006-02-15

In order to characterize landslide frequency-size distributions and individuate hazard scenarios and their possible precursors, we investigate a cellular automaton where the effects of a finite driving rate and the anisotropy are taken into account. The model is able to reproduce observed features of landslide events, such as power-law distributions, as experimentally reported. We analyze the key role of the driving rate and show that, as it is increased, a crossover from power-law to non-power-law behaviors occurs. Finally, a systematic investigation of the model on varying its anisotropy factors is performed and the full diagram of its dynamical behaviors ismore » presented.« less

The influence of parental and peer drinking behaviors on underage drinking and driving by young men.

PubMed

Zhang, Lening; Wieczorek, William F; Welte, John W

2012-01-01

Studies have consistently found that parental and peer drinking behaviors significantly influence adolescent drinking behavior and that adolescent drinking has a significant effect on their drinking-and-driving behavior. Building upon these studies, the present article assesses whether parental and peer drinking behaviors have direct and indirect effects on adolescent drinking and driving as well as whether they moderate the effect of adolescent drinking on their drinking-and-driving behavior. The assessment is conducted using data collected from the Buffalo Longitudinal Survey of Young Men (BLSYM) with Ordinary Least Squares (OLS) regression analyses. The data reveal that peer drinking has direct and indirect effects on adolescent drinking-and-driving behavior when adolescent drinking behavior is controlled. It also moderates the effect of adolescent drinking behavior on their drinking and driving. However, parental drinking does not have these direct and interactive effects, although it may have an indirect effect on adolescent drinking and driving via adolescent drinking behavior. These findings imply that peer drinking behavior should be considered seriously in prevention and intervention for reducing the risk of adolescent drinking-and-driving behavior.

Do aggressive driving and negative emotional driving mediate the link between impulsiveness and risky driving among young Italian drivers?

PubMed

Smorti, Martina; Guarnieri, Silvia

2016-01-01

The present study examined the contribution of impulsiveness and aggressive and negative emotional driving to the prediction of traffic violations and accidents taking into account potential mediation effects. Three hundred and four young drivers completed self-report measures assessing impulsiveness, aggressive and negative emotional driving, driving violations, and accidents. Structural equation modeling was used to assess the direct and indirect effects of impulsiveness on violations and accidents among young drivers through aggressive and negative emotional driving. Impulsiveness only indirectly influenced drivers' violations on the road via both the behavioral and emotional states of the driver. On the contrary, impulsiveness was neither directly nor indirectly associated with traffic accidents. Therefore, impulsiveness modulates young drivers' behavioral and emotional states while driving, which in turn influences risky driving.

Bidirectional drive and brake mechanism

NASA Technical Reports Server (NTRS)

Swan, Scott A. (Inventor)

1991-01-01

A space transport vehicle is disclosed as including a body which is arranged to be movably mounted on an elongated guide member disposed in outer space and driven therealong. A drive wheel is mounted on a drive shaft and arranged to be positioned in rolling engagement with the elongated guide carrying the vehicle. A brake member is arranged on the drive shaft for movement into and out of engagement with an adjacent surface of the drive wheel. An actuator is mounted on the body to be manually moved back and forth between spaced positions in an arc of movement. A ratchet-and-pawl mechanism is arranged to operate upon movements of the actuator in one direction between first and second positions for coupling the actuator to the drive wheel to incrementally rotate the wheel in one rotational direction and to operate upon movements of the actuator in the opposite direction for uncoupling the actuator from the wheel. The brake member is threadedly coupled to the drive shaft in order that the brake member will be operated only when the actuator is moved on beyond its first and second positions for shifting the brake member along the drive shaft and into frictional engagement with the adjacent surface on the drive wheel.

The critical protein interactions and structures that elicit growth deregulation in cancer and viral replication

PubMed Central

Ou, Horng D.; May, Andrew P.

2010-01-01

One of the greatest challenges in biomedicine is to define the critical targets and network interactions that are subverted to elicit growth deregulation in human cells. Understanding and developing rational treatments for cancer requires a definition of the key molecular targets and how they interact to elicit the complex growth deregulation phenotype. Viral proteins provide discerning and powerful probes to understand both how cells work and how they can be manipulated using a minimal number of components. The small DNA viruses have evolved to target inherent weaknesses in cellular protein interaction networks to hijack the cellular DNA and protein replication machinery. In the battle to escape the inevitability of senescence and programmed cell death, cancers have converged on similar mechanisms, through the acquisition and selection of somatic mutations that drive unchecked cellular replication in tumors. Understanding the dynamic mechanisms through which a minimal number of viral proteins promote host cells to undergo unscheduled and pathological replication is a powerful strategy to identify critical targets that are also disrupted in cancer. Viruses can therefore be used as tools to probe the system-wide protein-protein interactions and structures that drive growth deregulation in human cells. Ultimately this can provide a path for developing system context-dependent therapeutics. This review will describe ongoing experimental approaches using viruses to study pathways deregulated in cancer, with a particular focus on viral cellular protein-protein interactions and structures. PMID:21061422

Optimized Ion Energy Profiles for Heavy Ion Direct Drive Targets

NASA Astrophysics Data System (ADS)

Hay, Michael J.; Barnard, John J.; Perkins, L. John; Logan, B. Grant

2009-11-01

Recent 1-D implosion calculations [1] have characterized pure-DT targets delivering gains of 50-90 with less than 0.5 MJ of heavy ion direct drive. With a payload fraction of 1/3, these low-aspect ratio targets operate near the peak of rocket efficiency and achieve ˜10% overall coupling efficiencies (vs. the 15-20% efficiencies analytically predicted for less stable, higher-aspect ratio targets). In Ref. 1, the ion energy is ramped directly from a 50 MeV foot pulse to a 500 MeV main pulse. In this paper, we instead tune the ion energy throughout the drive to closely match the beam deposition with the inward progress of the ablation front. We will present the ion energy and intensity time histories that maximize drive efficiency and gain for a single target at constant integrated drive energy. [1] L. J. Perkins, B. G. Logan, J. J. Barnard, and M. J. Hay. ``High Efficiency High Gain Heavy Ion Direct Drive Targets,'' Bulletin of the American Physical Society, vol. 54: DPP, Nov. 2009.

Direct Drive Hall Thruster System Development

NASA Technical Reports Server (NTRS)

Hoskins, W. Andrew; Homiak, Daniel; Cassady, R. Joseph; Kerslake, Tom; Peterson, Todd; Ferguson, Dale; Snyder, Dave; Mikellides, Ioannis; Jongeward, Gary; Schneider, Todd

2003-01-01

The sta:us of development of a Direct Drive Ha!! Thruster System is presented. 13 the first part. a s:udy of the impacts to spacecraft systems and mass benefits of a direct-drive architecture is reviewed. The study initially examines four cases of SPT-100 and BPT-4000 Hall thrusters used for north-south station keeping on an EXPRESS-like geosynchronous spacecraft and for primary propulsion for a Deep Space- 1 based science spacecraft. The study is also extended the impact of direct drive on orbit raising for higher power geosynchronous spacecraft and on other deep space missions as a function of power and delta velocity. The major system considerations for accommodating a direct drive Hall thruster are discussed, including array regulation, system grounding, distribution of power to the spacecraft bus, and interactions between current-voltage characteristics for the arrays and thrusters. The mass benefit analysis shows that, for the initial cases, up to 42 kg of dry mass savings is attributable directly to changes in the propulsion hardware. When projected mass impacts of operating the arrays and the electric power system at 300V are included, up to 63 kg is saved for the four initial cases. Adoption of high voltage lithium ion battery technology is projected to further improve these savings. Orbit raising of higher powered geosynchronous spacecraft, is the mission for which direct drive provides the most benefit, allowing higher efficiency electric orbit raising to be accomplished in a limited period of time, as well as nearly eliminating significant power processing heat rejection mass. The total increase in useful payload to orbit ranges up to 278 kg for a 25 kW spacecraft, launched from an Atlas IIA. For deep space missions, direct drive is found to be most applicable to higher power missions with delta velocities up to several km/s , typical of several Discovery-class missions. In the second part, the status of development of direct drive propulsion power electronics is presented. The core of this hardware is the heater-keeper-magnet supply being qualified for the BPT-4000 by Aerojet. A breadboard propulsion power unit is in fabrication and is scheduled for delivery late in 2003.

Nucleotide-induced asymmetry within ATPase activator ring drives σ54-RNAP interaction and ATP hydrolysis

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

Sysoeva, Tatyana A.; Chowdhury, Saikat; Guo, Liang

2013-12-10

It is largely unknown how the typical homomeric ring geometry of ATPases associated with various cellular activities enables them to perform mechanical work. Small-angle solution X-ray scattering, crystallography, and electron microscopy (EM) reconstructions revealed that partial ATP occupancy caused the heptameric closed ring of the bacterial enhancer-binding protein (bEBP) NtrC1 to rearrange into a hexameric split ring of striking asymmetry. The highly conserved and functionally crucial GAFTGA loops responsible for interacting with σ54–RNA polymerase formed a spiral staircase. We propose that splitting of the ensemble directs ATP hydrolysis within the oligomer, and the ring's asymmetry guides interaction between ATPase andmore » the complex of σ54 and promoter DNA. Similarity between the structure of the transcriptional activator NtrC1 and those of distantly related helicases Rho and E1 reveals a general mechanism in homomeric ATPases whereby complex allostery within the ring geometry forms asymmetric functional states that allow these biological motors to exert directional forces on their target macromolecules.« less

Utilizing Fibronectin Integrin-Binding Specificity to Control Cellular Responses

PubMed Central

Bachman, Haylee; Nicosia, John; Dysart, Marilyn; Barker, Thomas H.

2015-01-01

Significance: Cells communicate with the extracellular matrix (ECM) protein fibronectin (Fn) through integrin receptors on the cell surface. Controlling integrin–Fn interactions offers a promising approach to directing cell behavior, such as adhesion, migration, and differentiation, as well as coordinated tissue behaviors such as morphogenesis and wound healing. Recent Advances: Several different groups have developed recombinant fragments of Fn that can control epithelial to mesenchymal transition, sequester growth factors, and promote bone and wound healing. It is thought that these physiological responses are, in part, due to specific integrin engagement. Furthermore, it has been postulated that the integrin-binding domain of Fn is a mechanically sensitive switch that drives binding of one integrin heterodimer over another. Critical Issues: Although computational simulations have predicted the mechano-switch hypothesis and recent evidence supports the existence of varying strain states of Fn in vivo, experimental evidence of the Fn integrin switch is still lacking. Future Directions: Evidence of the integrin mechano-switch will enable the development of new Fn-based peptides in tissue engineering and wound healing, as well as deepen our understanding of ECM pathologies, such as fibrosis. PMID:26244106

Crash risk and aberrant driving behaviors among bus drivers: the role of personality and attitudes towards traffic safety.

PubMed

Mallia, Luca; Lazuras, Lambros; Violani, Cristiano; Lucidi, Fabio

2015-06-01

Several studies have shown that personality traits and attitudes toward traffic safety predict aberrant driving behaviors and crash involvement. However, this process has not been adequately investigated in professional drivers, such as bus drivers. The present study used a personality-attitudes model to assess whether personality traits predicted aberrant self-reported driving behaviors (driving violations, lapses, and errors) both directly and indirectly, through the effects of attitudes towards traffic safety in a large sample of bus drivers. Additionally, the relationship between aberrant self-reported driving behaviors and crash risk was also assessed. Three hundred and one bus drivers (mean age=39.1, SD=10.7 years) completed a structured and anonymous questionnaire measuring personality traits, attitudes toward traffic safety, self-reported aberrant driving behaviors (i.e., errors, lapses, and traffic violations), and accident risk in the last 12 months. Structural equation modeling analysis revealed that personality traits were associated to aberrant driving behaviors both directly and indirectly. In particular altruism, excitement seeking, and normlessness directly predicted bus drivers' attitudes toward traffic safety which, in turn, were negatively associated with the three types of self-reported aberrant driving behaviors. Personality traits relevant to emotionality directly predicted bus drivers' aberrant driving behaviors, without any mediation of attitudes. Finally, only self-reported violations were related to bus drivers' accident risk. The present findings suggest that the hypothesized personality-attitudes model accounts for aberrant driving behaviors in bus drivers, and provide the empirical basis for evidence-based road safety interventions in the context of public transport. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of modified driver circuit and capacitor-transfer circuit in longitudinally excited N2 laser.

PubMed

Uno, Kazuyuki; Akitsu, Tetsuya; Nakamura, Kenshi; Jitsuno, Takahisa

2013-04-01

We developed a modified driver circuit composed of a capacitance and a spark gap, called a direct-drive circuit, for a longitudinally excited gas laser. The direct-drive circuit uses a large discharge impedance caused by a long discharge length of the longitudinal excitation scheme and eliminates the buffer capacitance used in the traditional capacitor-transfer circuit. We compared the direct-drive circuit and the capacitor-transfer circuit in a longitudinally excited N2 laser (wavelength: 337 nm). Producing high output energy with the capacitor-transfer circuit requires a large storage capacitance and a discharge tube with optimum dimensions (an inner diameter of 4 mm and a length of 10 cm in this work); in contrast, the direct-drive circuit requires a high breakdown voltage, achieved with a small storage capacitance and a large discharge tube. Additionally, for the same input energy of 792 mJ, the maximum output energy of the capacitor-transfer circuit was 174.2 μJ, and that of the direct-drive circuit was 344.7 μJ.

MULTIPLE DIFFERENTIAL ROTARY MECHANICAL DRIVE

DOEpatents

Smits, R.G.

1964-01-28

This patent relates to a mechanism suitable for such applications as driving two spaced-apart spools which carry a roll film strip under conditions where the film movement must be rapidly started, stopped, and reversed while maintaining a constant tension on the film. The basic drive is provided by a variable speed, reversible rnotor coupled to both spools through a first differential mechanism and driving both spools in the same direction. A second motor, providing a constant torque, is connected to the two spools through a second differential mechanism and is coupled to impart torque to one spool in a first direction anid to the other spool in the reverse direction thus applying a constant tension to the film passing over the two spools irrespective of the speed or direction of rotation thereof. (AEC)

Wavelength-detuning cross-beam energy transfer mitigation scheme for direct drive: Modeling and evidence from National Ignition Facility implosions

DOE PAGES

Marozas, J. A.; Hohenberger, M.; Rosenberg, M. J.; ...

2018-05-25

Here, cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces laser-energy absorption for direct-drive inertial confinement fusion. Consequently, ablation pressure and implosion velocity suffer from the decreased absorption, reducing target performance in both symmetric and polar direct drive. Additionally, CBET alters the time-resolved scattered-light spectra and redistributes absorbed and scattered-light–changing shell morphology and low-mode drive symmetry. Mitigating CBET is demonstrated in inertial confinement implosions at the National Ignition Facility by detuning the laser-source wavelengths (±2.3 Å UV) of the interacting beams. In polar direct drive, wavelength detuning was shown to increase themore » equatorial region velocity experimentally by 16% and to alter the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation–hydrodynamic simulations that indicate a 10% increase in the average ablation pressure. These results indicate that wavelength detuning successfully mitigates CBET. Simulations predict that optimized phase plates and wavelength-detuning CBET mitigation utilizing the three-legged beam layout of the OMEGA Laser System significantly increase absorption and achieve >100-Gbar hot-spot pressures in symmetric direct drive.« less

Wavelength-detuning cross-beam energy transfer mitigation scheme for direct drive: Modeling and evidence from National Ignition Facility implosions

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

Marozas, J. A.; Hohenberger, M.; Rosenberg, M. J.

Here, cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces laser-energy absorption for direct-drive inertial confinement fusion. Consequently, ablation pressure and implosion velocity suffer from the decreased absorption, reducing target performance in both symmetric and polar direct drive. Additionally, CBET alters the time-resolved scattered-light spectra and redistributes absorbed and scattered-light–changing shell morphology and low-mode drive symmetry. Mitigating CBET is demonstrated in inertial confinement implosions at the National Ignition Facility by detuning the laser-source wavelengths (±2.3 Å UV) of the interacting beams. In polar direct drive, wavelength detuning was shown to increase themore » equatorial region velocity experimentally by 16% and to alter the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation–hydrodynamic simulations that indicate a 10% increase in the average ablation pressure. These results indicate that wavelength detuning successfully mitigates CBET. Simulations predict that optimized phase plates and wavelength-detuning CBET mitigation utilizing the three-legged beam layout of the OMEGA Laser System significantly increase absorption and achieve >100-Gbar hot-spot pressures in symmetric direct drive.« less

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

PubMed Central

2010-01-01

Background The difficulty of directly measuring cellular dose is a significant obstacle to application of target tissue dosimetry for nanoparticle and microparticle toxicity assessment, particularly for in vitro systems. As a consequence, the target tissue paradigm for dosimetry and hazard assessment of nanoparticles has largely been ignored in favor of using metrics of exposure (e.g. μg particle/mL culture medium, particle surface area/mL, particle number/mL). We have developed a computational model of solution particokinetics (sedimentation, diffusion) and dosimetry for non-interacting spherical particles and their agglomerates in monolayer cell culture systems. Particle transport to cells is calculated by simultaneous solution of Stokes Law (sedimentation) and the Stokes-Einstein equation (diffusion). Results The In vitro Sedimentation, Diffusion and Dosimetry model (ISDD) was tested against measured transport rates or cellular doses for multiple sizes of polystyrene spheres (20-1100 nm), 35 nm amorphous silica, and large agglomerates of 30 nm iron oxide particles. Overall, without adjusting any parameters, model predicted cellular doses were in close agreement with the experimental data, differing from as little as 5% to as much as three-fold, but in most cases approximately two-fold, within the limits of the accuracy of the measurement systems. Applying the model, we generalize the effects of particle size, particle density, agglomeration state and agglomerate characteristics on target cell dosimetry in vitro. Conclusions Our results confirm our hypothesis that for liquid-based in vitro systems, the dose-rates and target cell doses for all particles are not equal; they can vary significantly, in direct contrast to the assumption of dose-equivalency implicit in the use of mass-based media concentrations as metrics of exposure for dose-response assessment. The difference between equivalent nominal media concentration exposures on a μg/mL basis and target cell doses on a particle surface area or number basis can be as high as three to six orders of magnitude. As a consequence, in vitro hazard assessments utilizing mass-based exposure metrics have inherently high errors where particle number or surface areas target cells doses are believed to drive response. The gold standard for particle dosimetry for in vitro nanotoxicology studies should be direct experimental measurement of the cellular content of the studied particle. However, where such measurements are impractical, unfeasible, and before such measurements become common, particle dosimetry models such as ISDD provide a valuable, immediately useful alternative, and eventually, an adjunct to such measurements. PMID:21118529

Design and development of a solar array drive. [a direct drive solar array pointing mechanism

NASA Technical Reports Server (NTRS)

Rees, T.; Standing, J. M.

1977-01-01

The design and development of a dry lubricated direct drive solar array pointing mechanism is discussed for use on the Orbital Test Satellite (OTS), MAROTS, European Communication Satellite (ECS), and others. Results of life testing the original prototype and the OTS mechanism are presented together with an appraisal of expected future development.

Origami interleaved tube cellular materials

NASA Astrophysics Data System (ADS)

Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

2014-09-01

A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

Networking Omic Data to Envisage Systems Biological Regulation.

PubMed

Kalapanulak, Saowalak; Saithong, Treenut; Thammarongtham, Chinae

To understand how biological processes work, it is necessary to explore the systematic regulation governing the behaviour of the processes. Not only driving the normal behavior of organisms, the systematic regulation evidently underlies the temporal responses to surrounding environments (dynamics) and long-term phenotypic adaptation (evolution). The systematic regulation is, in effect, formulated from the regulatory components which collaboratively work together as a network. In the drive to decipher such a code of lives, a spectrum of technologies has continuously been developed in the post-genomic era. With current advances, high-throughput sequencing technologies are tremendously powerful for facilitating genomics and systems biology studies in the attempt to understand system regulation inside the cells. The ability to explore relevant regulatory components which infer transcriptional and signaling regulation, driving core cellular processes, is thus enhanced. This chapter reviews high-throughput sequencing technologies, including second and third generation sequencing technologies, which support the investigation of genomics and transcriptomics data. Utilization of this high-throughput data to form the virtual network of systems regulation is explained, particularly transcriptional regulatory networks. Analysis of the resulting regulatory networks could lead to an understanding of cellular systems regulation at the mechanistic and dynamics levels. The great contribution of the biological networking approach to envisage systems regulation is finally demonstrated by a broad range of examples.

Institutional profile. The International Society for Cellular Therapy: evolving to meet the demands of the regenerative medicine industry.

PubMed

Maziarz, Richard T; Arthurs, Jane; Horwitz, Edwin

2011-03-01

The International Society for Cellular Therapy is a global association driving the translation of scientific research to deliver innovative cellular therapies to patients. Established in 1992, its membership and leadership comprises world-class scientists, clinicians, technologists, biotech/pharma and regulatory professionals from 40 countries focused on preclinical and translational aspects of developing cell therapy products. The International Society for Cellular Therapy has evolved in alignment with the maturation of the field of cell therapy and regenerative medicine to create forums for discussion of shared concerns for commercialization of cell therapies and of development of consensus standards, recognizing that true commercialization depends upon the translational scientific community, the regional regulatory and policy institutions, and the technology support and capital investment from industry. It exists to facilitate the international work of many, to spawn new initiatives, and to synergize with other stakeholders to create the best outcome for the many patients across the world depending on the answers and improved health that cellular therapeutics will provide them.

The Development of a Novel High Throughput Computational Tool for Studying Individual and Collective Cellular Migration

PubMed Central

Chapnick, Douglas A.; Jacobsen, Jeremy; Liu, Xuedong

2013-01-01

Understanding how cells migrate individually and collectively during development and cancer metastasis can be significantly aided by a computation tool to accurately measure not only cellular migration speed, but also migration direction and changes in migration direction in a temporal and spatial manner. We have developed such a tool for cell migration researchers, named Pathfinder, which is capable of simultaneously measuring the migration speed, migration direction, and changes in migration directions of thousands of cells both instantaneously and over long periods of time from fluorescence microscopy data. Additionally, we demonstrate how the Pathfinder software can be used to quantify collective cell migration. The novel capability of the Pathfinder software to measure the changes in migration direction of large populations of cells in a spatiotemporal manner will aid cellular migration research by providing a robust method for determining the mechanisms of cellular guidance during individual and collective cell migration. PMID:24386097

Isoquinoline alkaloids and their binding with DNA: calorimetry and thermal analysis applications.

PubMed

Bhadra, Kakali; Kumar, Gopinatha Suresh

2010-11-01

Alkaloids are a group of natural products with unmatched chemical diversity and biological relevance forming potential quality pools in drug screening. The molecular aspects of their interaction with many cellular macromolecules like DNA, RNA and proteins are being currently investigated in order to evolve the structure activity relationship. Isoquinolines constitute an important group of alkaloids. They have extensive utility in cancer therapy and a large volume of data is now emerging in the literature on their mode, mechanism and specificity of binding to DNA. Thermodynamic characterization of the binding of these alkaloids to DNA may offer key insights into the molecular aspects that drive complex formation and these data can provide valuable information about the balance of driving forces. Various thermal techniques have been conveniently used for this purpose and modern calorimetric instrumentation provides direct and quick estimation of thermodynamic parameters. Thermal melting studies and calorimetric techniques like isothermal titration calorimetry and differential scanning calorimetry have further advanced the field by providing authentic, reliable and sensitive data on various aspects of temperature dependent structural analysis of the interaction. In this review we present the application of various thermal techniques, viz. isothermal titration calorimetry, differential scanning calorimetry and optical melting studies in the characterization of drug-DNA interactions with particular emphasis on isoquinoline alkaloid-DNA interaction.

A transgenic model of transactivation by the Tax protein of HTLV-I.

PubMed

Bieberich, C J; King, C M; Tinkle, B T; Jay, G

1993-09-01

The human T-lymphotropic virus type I (HTLV-I) Tax protein is a transcriptional regulatory protein that has been suggested to play a causal role in the development of several HTLV-I-associated diseases. Tax regulates expression of its own LTR and of certain cellular promoters perhaps by usurping the function of the host transcriptional machinery. We have established a transgenic mouse model system to define the spectrum of tissues in vivo that are capable of supporting Tax-mediated transcriptional transactivation. Transgenic mice carrying the HTLV-I LTR driving expression of the Escherichia coli beta-galactosidase (beta gal) gene were generated, and this LTR-beta gal gene was transcriptionally inactive in all tissues. When LTR-beta gal mice were mated to transgenic mice carrying the same LTR driving expression of the HTLV-I tax gene, mice that carried both transgenes showed restricted expression of the beta gal reporter gene in several tissues including muscle, bone, salivary glands, skin, and nerve. In addition, a dramatic increase in the number of beta gal-expressing cells was seen in response to wounding. These observations provide direct evidence for viral transactivation in vivo, delimit the tissues capable of supporting that transactivation, and provide a model system to study the mechanism of gene regulation by Tax.

Innate Immune Cytokines, Fibroblast Phenotypes, and Regulation of Extracellular Matrix in Lung.

PubMed

Richards, Carl D

2017-02-01

Chronic inflammation can be caused by adaptive immune responses in autoimmune and allergic conditions, driven by a T lymphocyte subset balance (TH1, TH2, Th17, Th22, and/or Treg) and skewed cellular profiles in an antigen-specific manner. However, several chronic inflammatory diseases have no clearly defined adaptive immune mechanisms that drive chronicity. These conditions include those that affect the lung such as nonatopic asthma or idiopathic pulmonary fibrosis comprising significant health problems. The remodeling of extracellular matrix (ECM) causes organ dysfunction, and it is largely generated by fibroblasts as the major cell controlling net ECM. As such, these are potential targets of treatment approaches in the context of ECM pathology. Fibroblast phenotypes contribute to ECM and inflammatory cell accumulation, and they are integrated into chronic disease mechanisms including cancer. Evidence suggests that innate cytokine responses may be critical in nonallergic/nonautoimmune disease, and they enable environmental agent exposure mechanisms that are independent of adaptive immunity. Innate immune cytokines derived from macrophage subsets (M1/M2) and innate lymphoid cell (ILC) subsets can directly regulate fibroblast function. We also suggest that STAT3-activating gp130 cytokines can sensitize fibroblasts to the innate cytokine milieu to drive phenotypes and exacerbate existing adaptive responses. Here, we review evidence exploring innate cytokine regulation of fibroblast behavior.

The Influence of Parental and Peer Drinking Behaviors on Underage Drinking and Driving by Young Men*

PubMed Central

Zhang, Lening; Wieczorek, William F.; Welte, John W.

2013-01-01

Background Studies have consistently found that parental and peer drinking behaviors significantly influence adolescent drinking behavior and that adolescent drinking has a significant effect on their drinking-and-driving behavior. Building upon these studies, the present article assesses whether parental and peer drinking behaviors have direct and indirect effects on adolescent drinking and driving as well as whether they moderate the effect of adolescent drinking on their drinking-and-driving behavior. Methods The assessment is conducted using data collected from the Buffalo Longitudinal Survey of Young Men (BLSYM) with Ordinary Least Squares (OLS) regression analyses. Results The data reveal that peer drinking has direct and indirect effects on adolescent drinking-and-driving behavior when adolescent drinking behavior is controlled. It also moderates the effect of adolescent drinking behavior on their drinking and driving. However, parental drinking does not have these direct and interactive effects, although it may have an indirect effect on adolescent drinking and driving via adolescent drinking behavior. Conclusions These findings imply that peer drinking behavior should be considered seriously in prevention and intervention for reducing the risk of adolescent drinking-and-driving behavior. PMID:23705513

Fuzzy Inference Based Obstacle Avoidance Control of Electric Powered Wheelchair Considering Driving Risk

NASA Astrophysics Data System (ADS)

Kiso, Atsushi; Murakami, Hiroki; Seki, Hirokazu

This paper describes a novel obstacle avoidance control scheme of electric powered wheelchairs for realizing the safe driving in various environments. The “electric powered wheelchair” which generates the driving force by electric motors is expected to be widely used as a mobility support system for elderly people and disabled people; however, the driving performance must be further improved because the number of driving accidents caused by elderly operator's narrow sight and joystick operation errors is increasing. This paper proposes a novel obstacle avoidance control scheme based on fuzzy algorithm to prevent driving accidents. The proposed control system determines the driving direction by fuzzy algorithm based on the information of the joystick operation and distance to obstacles measured by ultrasonic sensors. Fuzzy rules to determine the driving direction are designed surely to avoid passers-by and walls considering the human's intent and driving environments. Some driving experiments on the practical situations show the effectiveness of the proposed control system.

Sex Chromosome Drive

PubMed Central

Helleu, Quentin; Gérard, Pierre R.; Montchamp-Moreau, Catherine

2015-01-01

Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species. PMID:25524548

Two-lane traffic-flow model with an exact steady-state solution.

PubMed

Kanai, Masahiro

2010-12-01

We propose a stochastic cellular-automaton model for two-lane traffic flow based on the misanthrope process in one dimension. The misanthrope process is a stochastic process allowing for an exact steady-state solution; hence, we have an exact flow-density diagram for two-lane traffic. In addition, we introduce two parameters that indicate, respectively, driver's driving-lane preference and passing-lane priority. Due to the additional parameters, the model shows a deviation of the density ratio for driving-lane use and a biased lane efficiency in flow. Then, a mean-field approach explicitly describes the asymmetric flow by the hop rates, the driving-lane preference, and the passing-lane priority. Meanwhile, the simulation results are in good agreement with an observational data, and we thus estimate these parameters. We conclude that the proposed model successfully produces two-lane traffic flow particularly with the driving-lane preference and the passing-lane priority.

Two inositol hexakisphosphate kinases drive inositol pyrophosphate synthesis in plants

USDA-ARS?s Scientific Manuscript database

Inositol pyrophosphates are novel cellular signaling molecules with newly discovered roles in energy sensing and metabolic control. Studies in eukaryotes have revealed that these compounds turn over rapidly, and thus only small amounts accumulate. Inositol pyrophosphates have not been the subject of...

Developing improved durum wheat germplasm by altering the cytoplasmic genome

USDA-ARS?s Scientific Manuscript database

In eukaryotic organisms, nuclear and cytoplasmic genomes interact to drive cellular functions. These genomes have co-evolved to form specific nuclear-cytoplasmic interactions that are essential to the origin, success, and evolution of diploid and polyploid species. Hundreds of genetic diseases in h...

On the biophysics of cathodal galvanotaxis in rat prostate cancer cells: Poisson-Nernst-Planck equation approach.

PubMed

Borys, Przemysław

2012-06-01

Rat prostate cancer cells have been previously investigated using two cell lines: a highly metastatic one (Mat-Ly-Lu) and a nonmetastatic one (AT-2). It turns out that the highly metastatic Mat-Ly-Lu cells exhibit a phenomenon of cathodal galvanotaxis in an electric field which can be blocked by interrupting the voltage-gated sodium channel (VGSC) activity. The VGSC activity is postulated to be characteristic for metastatic cells and seems to be a reasonable driving force for motile behavior. However, the classical theory of cellular motion depends on calcium ions rather than sodium ions. The current research provides a theoretical connection between cellular sodium inflow and cathodal galvanotaxis of Mat-Ly-Lu cells. Electrical repulsion of intracellular calcium ions by entering sodium ions is proposed after depolarization starting from the cathodal side. The disturbance in the calcium distribution may then drive actin polymerization and myosin contraction. The presented modeling is done within a continuous one-dimensional Poisson-Nernst-Planck equation framework.

Commandeering Channel Voltage Sensors for Secretion, Cell Turgor, and Volume Control.

PubMed

Karnik, Rucha; Waghmare, Sakharam; Zhang, Ben; Larson, Emily; Lefoulon, Cécile; Gonzalez, Wendy; Blatt, Michael R

2017-01-01

Control of cell volume and osmolarity is central to cellular homeostasis in all eukaryotes. It lies at the heart of the century-old problem of how plants regulate turgor, mineral and water transport. Plants use strongly electrogenic H + -ATPases, and the substantial membrane voltages they foster, to drive solute accumulation and generate turgor pressure for cell expansion. Vesicle traffic adds membrane surface and contributes to wall remodelling as the cell grows. Although a balance between vesicle traffic and ion transport is essential for cell turgor and volume control, the mechanisms coordinating these processes have remained obscure. Recent discoveries have now uncovered interactions between conserved subsets of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that drive the final steps in secretory vesicle traffic and ion channels that mediate in inorganic solute uptake. These findings establish the core of molecular links, previously unanticipated, that coordinate cellular homeostasis and cell expansion. Copyright © 2016 Elsevier Ltd. All rights reserved.

Update on the Mechanisms of Liver Regeneration.

PubMed

Preziosi, Morgan E; Monga, Satdarshan P

2017-05-01

Liver possesses many critical functions such as synthesis, detoxification, and metabolism. It continually receives nutrient-rich blood from gut, which incidentally is also toxin-rich. That may be why liver is uniquely bestowed with a capacity to regenerate. A commonly studied procedure to understand the cellular and molecular basis of liver regeneration is that of surgical resection. Removal of two-thirds of the liver in rodents or patients instigates alterations in hepatic homeostasis, which are sensed by the deficient organ to drive the restoration process. Although the exact mechanisms that initiate regeneration are unknown, alterations in hemodynamics and metabolism have been suspected as important effectors. Key signaling pathways are activated that drive cell proliferation in various hepatic cell types through autocrine and paracrine mechanisms. Once the prehepatectomy mass is regained, the process of regeneration is adequately terminated. This review highlights recent discoveries in the cellular and molecular basis of liver regeneration. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A semi-symmetric image encryption scheme based on the function projective synchronization of two hyperchaotic systems

PubMed Central

Li, Jinqing; Qi, Hui; Cong, Ligang; Yang, Huamin

2017-01-01

Both symmetric and asymmetric color image encryption have advantages and disadvantages. In order to combine their advantages and try to overcome their disadvantages, chaos synchronization is used to avoid the key transmission for the proposed semi-symmetric image encryption scheme. Our scheme is a hybrid chaotic encryption algorithm, and it consists of a scrambling stage and a diffusion stage. The control law and the update rule of function projective synchronization between the 3-cell quantum cellular neural networks (QCNN) response system and the 6th-order cellular neural network (CNN) drive system are formulated. Since the function projective synchronization is used to synchronize the response system and drive system, Alice and Bob got the key by two different chaotic systems independently and avoid the key transmission by some extra security links, which prevents security key leakage during the transmission. Both numerical simulations and security analyses such as information entropy analysis, differential attack are conducted to verify the feasibility, security, and efficiency of the proposed scheme. PMID:28910349

Mitochondrial oxidative stress caused by Sod2 deficiency promotes cellular senescence and aging phenotypes in the skin

PubMed Central

Velarde, Michael C.; Flynn, James M.; Day, Nicholas U.; Melov, Simon; Campisi, Judith

2012-01-01

Cellular senescence arrests the proliferation of mammalian cells at risk for neoplastic transformation, and is also associated with aging. However, the factors that cause cellular senescence during aging are unclear. Excessive reactive oxygen species (ROS) have been shown to cause cellular senescence in culture, and accumulated molecular damage due to mitochondrial ROS has long been thought to drive aging phenotypes in vivo. Here, we test the hypothesis that mitochondrial oxidative stress can promote cellular senescence in vivo and contribute to aging phenotypes in vivo, specifically in the skin. We show that the number of senescent cells, as well as impaired mitochondrial (complex II) activity increase in naturally aged mouse skin. Using a mouse model of genetic Sod2 deficiency, we show that failure to express this important mitochondrial anti-oxidant enzyme also impairs mitochondrial complex II activity, causes nuclear DNA damage, and induces cellular senescence but not apoptosis in the epidermis. Sod2 deficiency also reduced the number of cells and thickness of the epidermis, while increasing terminal differentiation. Our results support the idea that mitochondrial oxidative stress and cellular senescence contribute to aging skin phenotypes in vivo. PMID:22278880

A Tissue Engineered Model of Aging: Interdependence and Cooperative Effects in Failing Tissues.

PubMed

Acun, A; Vural, D C; Zorlutuna, P

2017-07-11

Aging remains a fundamental open problem in modern biology. Although there exist a number of theories on aging on the cellular scale, nearly nothing is known about how microscopic failures cascade to macroscopic failures of tissues, organs and ultimately the organism. The goal of this work is to bridge microscopic cell failure to macroscopic manifestations of aging. We use tissue engineered constructs to control the cellular-level damage and cell-cell distance in individual tissues to establish the role of complex interdependence and interactions between cells in aging tissues. We found that while microscopic mechanisms drive aging, the interdependency between cells plays a major role in tissue death, providing evidence on how cellular aging is connected to its higher systemic consequences.

Traffic dynamics of an on-ramp system with a cellular automaton model

NASA Astrophysics Data System (ADS)

Li, Xin-Gang; Gao, Zi-You; Jia, Bin; Jiang, Rui

2010-06-01

This paper uses the cellular automaton model to study the dynamics of traffic flow around an on-ramp with an acceleration lane. It adopts a parameter, which can reflect different lane-changing behaviour, to represent the diversity of driving behaviour. The refined cellular automaton model is used to describe the lower acceleration rate of a vehicle. The phase diagram and the capacity of the on-ramp system are investigated. The simulation results show that in the single cell model, the capacity of the on-ramp system will stay at the highest flow of a one lane system when the driver is moderate and careful; it will be reduced when the driver is aggressive. In the refined cellular automaton model, the capacity is always reduced even when the driver is careful. It proposes that the capacity drop of the on-ramp system is caused by aggressive lane-changing behaviour and lower acceleration rate.

Actin dynamics, architecture, and mechanics in cell motility.

PubMed

Blanchoin, Laurent; Boujemaa-Paterski, Rajaa; Sykes, Cécile; Plastino, Julie

2014-01-01

Tight coupling between biochemical and mechanical properties of the actin cytoskeleton drives a large range of cellular processes including polarity establishment, morphogenesis, and motility. This is possible because actin filaments are semi-flexible polymers that, in conjunction with the molecular motor myosin, can act as biological active springs or "dashpots" (in laymen's terms, shock absorbers or fluidizers) able to exert or resist against force in a cellular environment. To modulate their mechanical properties, actin filaments can organize into a variety of architectures generating a diversity of cellular organizations including branched or crosslinked networks in the lamellipodium, parallel bundles in filopodia, and antiparallel structures in contractile fibers. In this review we describe the feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro, then we integrate this knowledge into our current understanding of cellular actin organization and its physiological roles.

Senescence in chronic liver disease: Is the future in aging?

PubMed

Aravinthan, Aloysious D; Alexander, Graeme J M

2016-10-01

Cellular senescence is a fundamental, complex mechanism with an important protective role present from embryogenesis to late life across all species. It limits the proliferative potential of damaged cells thus protecting against malignant change, but at the expense of substantial alterations to the microenvironment and tissue homeostasis, driving inflammation, fibrosis and paradoxically, malignant disease if the process is sustained. Cellular senescence has attracted considerable recent interest with recognition of pathways linking aging, malignancy and insulin resistance and the current focus on therapeutic interventions to extend health-span. There are major implications for hepatology in the field of fibrosis and cancer, where cellular senescence of hepatocytes, cholangiocytes, stellate cells and immune cells has been implicated in chronic liver disease progression. This review focuses on cellular senescence in chronic liver disease and explores therapeutic opportunities. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Genome plasticity in filamentous plant pathogens contributes to the emergence of novel effectors and their cellular processes in the host.

PubMed

Dong, Yanhan; Li, Ying; Qi, Zhongqiang; Zheng, Xiaobo; Zhang, Zhengguang

2016-02-01

Plant diseases cause extensive yield loss of crops worldwide, and secretory 'warfare' occurs between plants and pathogenic organisms all the time. Filamentous plant pathogens have evolved the ability to manipulate host processes and facilitate colonization through secreting effectors inside plant cells. The stresses from hosts and environment can drive the genome dynamics of plant pathogens. Remarkable advances in plant pathology have been made owing to these adaptable genome regions of several lineages of filamentous phytopathogens. Characterization new effectors and interaction analyses between pathogens and plants have provided molecular insights into the plant pathways perturbed during the infection process. In this mini-review, we highlight promising approaches of identifying novel effectors based on the genome plasticity. We also discuss the interaction mechanisms between plants and their filamentous pathogens and outline the possibilities of effector gene expression under epigenetic control that will be future directions for research.

Convergence and Extrusion Are Required for Normal Fusion of the Mammalian Secondary Palate

PubMed Central

Kim, Seungil; Lewis, Ace E.; Singh, Vivek; Ma, Xuefei; Adelstein, Robert; Bush, Jeffrey O.

2015-01-01

The fusion of two distinct prominences into one continuous structure is common during development and typically requires integration of two epithelia and subsequent removal of that intervening epithelium. Using confocal live imaging, we directly observed the cellular processes underlying tissue fusion, using the secondary palatal shelves as a model. We find that convergence of a multi-layered epithelium into a single-layer epithelium is an essential early step, driven by cell intercalation, and is concurrent to orthogonal cell displacement and epithelial cell extrusion. Functional studies in mice indicate that this process requires an actomyosin contractility pathway involving Rho kinase (ROCK) and myosin light chain kinase (MLCK), culminating in the activation of non-muscle myosin IIA (NMIIA). Together, these data indicate that actomyosin contractility drives cell intercalation and cell extrusion during palate fusion and suggest a general mechanism for tissue fusion in development. PMID:25848986

Mechanisms of bacterial DNA replication restart

PubMed Central

Windgassen, Tricia A; Wessel, Sarah R; Bhattacharyya, Basudeb

2018-01-01

Abstract Multi-protein DNA replication complexes called replisomes perform the essential process of copying cellular genetic information prior to cell division. Under ideal conditions, replisomes dissociate only after the entire genome has been duplicated. However, DNA replication rarely occurs without interruptions that can dislodge replisomes from DNA. Such events produce incompletely replicated chromosomes that, if left unrepaired, prevent the segregation of full genomes to daughter cells. To mitigate this threat, cells have evolved ‘DNA replication restart’ pathways that have been best defined in bacteria. Replication restart requires recognition and remodeling of abandoned replication forks by DNA replication restart proteins followed by reloading of the replicative DNA helicase, which subsequently directs assembly of the remaining replisome subunits. This review summarizes our current understanding of the mechanisms underlying replication restart and the proteins that drive the process in Escherichia coli (PriA, PriB, PriC and DnaT). PMID:29202195

Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision

PubMed Central

Ecker, Jennifer L.; Dumitrescu, Olivia N.; Wong, Kwoon Y.; Alam, Nazia M.; Chen, Shih-Kuo; LeGates, Tara; Renna, Jordan M.; Prusky, Glen T.; Berson, David M.; Hattar, Samer

2010-01-01

Using the photopigment melanopsin, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light to drive circadian clock resetting and pupillary constriction. We now report that ipRGCs are more abundant and diverse than previously appreciated, project more widely within the brain, and can support spatial visual perception. A Cre-based melanopsin reporter mouse line revealed at least five subtypes of ipRGCs with distinct morphological and physiological characteristics. Collectively, these cells project beyond the known brain targets of ipRGCs to heavily innervate the superior colliculus and dorsal lateral geniculate nucleus, retinotopically-organized nuclei mediating object localization and discrimination. Mice lacking classical rod-cone photoreception, and thus entirely dependent on melanopsin for light detection, were able to discriminate grating stimuli from equiluminant gray, and had measurable visual acuity. Thus, non-classical retinal photoreception occurs within diverse cell types, and influences circuits and functions encompassing luminance as well as spatial information. PMID:20624591

Matched and Mismatched Metabolic Fuels in Lymphocyte Function

PubMed Central

Caro-Maldonado, Alfredo; Gerriets, Valerie A.; Rathmell, Jeffrey C.

2012-01-01

Immunological function requires metabolic support to suit the needs of lymphocytes at a variety of distinct differentiation and activation states. It is now evident that the signaling pathways that drive lymphocyte survival and activity can directly control cellular metabolism. This linkage provides a mechanism by which activation and specific signaling pathways provide a supply of appropriate and required nutrients to support cell functions in a pro-active supply rather than consumption-based metabolic model. In this way, the metabolism and fuel choices of lymphocytes are guided to specifically match the anticipated needs. If the fuel choice or metabolic pathways of lymphocytes are dysregulated, however, metabolic checkpoints can become activated to disrupt immunological function. These changes are now shown in several immunological diseases and may open new opportunities to selectively enhance or suppress specific immune functions through targeting of glucose, lipid, or amino acid metabolism. PMID:23290889

Analyzing Protein Clusters on the Plasma Membrane: Application of Spatial Statistical Analysis Methods on Super-Resolution Microscopy Images.

PubMed

Paparelli, Laura; Corthout, Nikky; Pavie, Benjamin; Annaert, Wim; Munck, Sebastian

2016-01-01

The spatial distribution of proteins within the cell affects their capability to interact with other molecules and directly influences cellular processes and signaling. At the plasma membrane, multiple factors drive protein compartmentalization into specialized functional domains, leading to the formation of clusters in which intermolecule interactions are facilitated. Therefore, quantifying protein distributions is a necessity for understanding their regulation and function. The recent advent of super-resolution microscopy has opened up the possibility of imaging protein distributions at the nanometer scale. In parallel, new spatial analysis methods have been developed to quantify distribution patterns in super-resolution images. In this chapter, we provide an overview of super-resolution microscopy and summarize the factors influencing protein arrangements on the plasma membrane. Finally, we highlight methods for analyzing clusterization of plasma membrane proteins, including examples of their applications.

Longevity extension by phytochemicals.

PubMed

Leonov, Anna; Arlia-Ciommo, Anthony; Piano, Amanda; Svistkova, Veronika; Lutchman, Vicky; Medkour, Younes; Titorenko, Vladimir I

2015-04-13

Phytochemicals are structurally diverse secondary metabolites synthesized by plants and also by non-pathogenic endophytic microorganisms living within plants. Phytochemicals help plants to survive environmental stresses, protect plants from microbial infections and environmental pollutants, provide them with a defense from herbivorous organisms and attract natural predators of such organisms, as well as lure pollinators and other symbiotes of these plants. In addition, many phytochemicals can extend longevity in heterotrophic organisms across phyla via evolutionarily conserved mechanisms. In this review, we discuss such mechanisms. We outline how structurally diverse phytochemicals modulate a complex network of signaling pathways that orchestrate a distinct set of longevity-defining cellular processes. This review also reflects on how the release of phytochemicals by plants into a natural ecosystem may create selective forces that drive the evolution of longevity regulation mechanisms in heterotrophic organisms inhabiting this ecosystem. We outline the most important unanswered questions and directions for future research in this vibrant and rapidly evolving field.

Older adult opinions of "advance driving directives".

PubMed

Betz, Marian E; Lowenstein, Steven R; Schwartz, Robert

2013-01-01

Discussions about driving cessation are difficult. "Advance driving directives" (ADDs), like advance directives for end-of-life care, would allow drivers to designate someone to help make driving decisions for them in the future. It is not known if older drivers support the concept of ADDs. Cross-sectional study of a convenience sample of English-speaking drivers (55+ years) at 2 independent living facilities and 2 community centers who completed anonymous surveys. Of 168 participants, 80% were female; the median age was 76.5 years (range = 56-93 years). Most (74%) drove daily or almost daily, and 7% reported a crash in the past year. Few had spoken with someone about driving safety (5%) or their wishes when driving skills decline (21%). Of the few who had discussed this topic, 83% had spoken with a family member; only 17% had spoken with a health care provider. However, participants were open to driving discussions, and 54% said they would be willing to complete an ADD if recommended. Of these, 79% said it was "likely" or "very likely" they would comply with the directive in the future. Most (73%) supported mandatory, age-based retesting; the median recommended testing age suggested was 80 years. More participants thought the driver (71%), a family member (61%), or a physician (59%) should determine license revocation for an unsafe driver, rather than the department of motor vehicles (32%). Many older drivers may be open to discussing their driving plans with physicians and family members. ADDs may facilitate these discussions in the present and help define driving-related wishes in the future.

Direct drive wind turbine

DOEpatents

Bywaters, Garrett Lee; Danforth, William; Bevington, Christopher; Stowell, Jesse; Costin, Daniel

2006-09-19

A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

Direct drive wind turbine

DOEpatents

Bywaters, Garrett; Danforth, William; Bevington, Christopher; Jesse, Stowell; Costin, Daniel

2006-10-10

A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

Direct drive wind turbine

DOEpatents

Bywaters, Garrett; Danforth, William; Bevington, Christopher; Stowell, Jesse; Costin, Daniel

2006-07-11

A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

Direct drive wind turbine

DOEpatents

Bywaters, Garrett; Danforth, William; Bevington, Christopher; Jesse, Stowell; Costin, Daniel

2007-02-27

A wind turbine is provided that minimizes the size of the drive train and nacelle while maintaining the power electronics and transformer at the top of the tower. The turbine includes a direct drive generator having an integrated disk brake positioned radially inside the stator while minimizing the potential for contamination. The turbine further includes a means for mounting a transformer below the nacelle within the tower.

A Lever Coupling Mechanism in Dual-Mass Micro-Gyroscopes for Improving the Shock Resistance along the Driving Direction.

PubMed

Gao, Yang; Li, Hongsheng; Huang, Libin; Sun, Hui

2017-04-30

This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope's modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity.

Acceleration of planar foils by the indirect-direct drive scheme

NASA Astrophysics Data System (ADS)

Honrubia, J. J.; Martínez-Val, J. M.; Bocher, J. L.; Faucheux, G.

1996-05-01

We have investigated the hydrodynamic response of plastic and aluminum foils accelerated by a pulse formed by an x-ray prepulse followed by the main laser pulse. This illumination scheme, so-called indirect-direct drive scheme, has been proposed as an alternative to the direct and indirect drive. The advantages of such a scheme are that it can contribute to solve the problem of uniformity of the direct drive and, at the same time, it can be much more efficient and use simpler targets than the indirect-drive. Experiments about this hybrid drive scheme have been performed at Limeil with the PHEBUS facility and the standard experimental set-up and diagnostics. The agreement between experiments and simulations is good for quantities such as the energy of the laser converted into x-rays and the burnthrough time of the converter foil. To simulate the full hydrodynamic evolution of the converter and target foils separated a distance of 1 mm, 2-D effects should be taken into account. The basic goals have been to check the simulation codes developed by the Institute of Nuclear Fusion and to determine the hydrodynamic response of the target foil to the hybrid pulse. These goals have been fulfilled.

The plausibility of a role for mercury in the etiology of autism: a cellular perspective

PubMed Central

Garrecht, Matthew; Austin, David W.

2011-01-01

Autism is defined by a behavioral set of stereotypic and repetitious behavioral patterns in combination with social and communication deficits. There is emerging evidence supporting the hypothesis that autism may result from a combination of genetic susceptibility and exposure to environmental toxins at critical moments in development. Mercury (Hg) is recognized as a ubiquitous environmental neurotoxin and there is mounting evidence linking it to neurodevelopmental disorders, including autism. Of course, the evidence is not derived from experimental trials with humans but rather from methods focusing on biomarkers of Hg damage, measurements of Hg exposure, epidemiological data, and animal studies. For ethical reasons, controlled Hg exposure in humans will never be conducted. Therefore, to properly evaluate the Hg-autism etiological hypothesis, it is essential to first establish the biological plausibility of the hypothesis. This review examines the plausibility of Hg as the primary etiological agent driving the cellular mechanisms by which Hg-induced neurotoxicity may result in the physiological attributes of autism. Key areas of focus include: (1) route and cellular mechanisms of Hg exposure in autism; (2) current research and examples of possible genetic variables that are linked to both Hg sensitivity and autism; (3) the role Hg may play as an environmental toxin fueling the oxidative stress found in autism; (4) role of mitochondrial dysfunction; and (5) possible role of Hg in abnormal neuroexcitory and excitotoxity that may play a role in the immune dysregulation found in autism. Future research directions that would assist in addressing the gaps in our knowledge are proposed. PMID:22163375

Transfer system

DOEpatents

Kurosawa, Kanji; Koga, Bunichiro; Ito, Hideki; Kiriyama, Shigeru; Higuchi, Shizuo

2003-05-20

A transport system includes a traveling rail (1) which constitutes a transport route and a transport body (3) which is capable of traveling on the traveling rail in the longitudinal direction of the traveling rail. Flexible drive tubes (5) are arranged on the traveling rail in the longitudinal direction of the traveling rail. The transport body includes a traveling wheel (4) which is capable of rolling on the traveling rail and drive wheels (2) which are capable of rolling on the drive tubes upon receiving the rotational drive power generated by pressure of a pressure medium supplied to the drive tubes while depressing the drive tubes. The traveling rail includes a plurality of transport sections and the transport body is capable of receiving a rotational drive force from the drive tubes at every transport sections. If necessary, a transport route changeover switch which changes over the transport route can be provided between the transport sections.

Direct drive options for electric propulsion systems

NASA Technical Reports Server (NTRS)

Hamley, John A.

1995-01-01

Power processing units (PPU's) in an electric propulsion system provide many challenging integration issues. The PPU must provide power to the electric thruster while maintaining compatibility with all of the spacecraft power and data systems. Inefficiencies in the power processor produce heat, which must be radiated to the environment in order to ensure reliable operation. Although PPU efficiencies are generally greater than 0.9, heat loads are often substantial. This heat must be rejected by thermal control systems which generally have specific masses of 15-30 kg/kW. PPU's also represent a large fraction of the electric propulsion system dry mass. Simplification or elimination of power processing in a propulsion system would reduce the electric propulsion system specific mass and improve the overall reliability and performance. A direct drive system would eliminate all or some of the power supplies required to operate a thruster by directly connecting the various thruster loads to the solar array. The development of concentrator solar arrays has enabled power bus voltages in excess of 300 V which is high enough for direct drive applications for Hall thrusters such as the Stationary Plasma Thruster (SPT). The option of solar array direct drive for SPT's is explored to provide a comparison between conventional and direct drive system mass.

Direct cellular vs. indirect pager communication during orthopaedic surgical procedures: a prospective study.

PubMed

Ortega, Gil R; Taksali, Sudeep; Smart, Ryan; Baumgaertner, Michael R

2009-01-01

Cellular phone use within the hospital setting has increased as physicians, nurses, and ancillary staff incorporate wireless technologies in improving efficiencies, cost, and maintaining patient safety and high quality healthcare [11]. Through the use of wireless, cellular communication, an overall improvement in communication accuracy and efficiency between intraoperative orthopaedic surgeons and floor nurses may be achieved. Both communication types occurred while the surgeon was scrubbed in the operating room (OR). Indirect communication occurred when the pager call was answered by the OR circulating nurse with communication between the surgeon, circulating nurse, and floor nurse. Direct communication consisted of cell phone and Jabra Bluetooth BT200 wireless ear piece used by the surgeon. The surgeon answered the floor nurse's cellular call by phone ring-activated automatic answering. The study was conducted during scheduled orthopaedic procedures. An independent observer measured time variables with a stop-watch while orthopaedic nurses randomly called via pager or cell phone. The nurses asked for patient caregiver confirmation and answers to 30 different patient-care questions. Sixty trials were performed with 30 cell and 30 page communications. Direct cellular communication showed a better response rate than indirect page (Cell 100%, Page 73%). Indirect page communication allowed a 27% and 33% error rate with patient problem and surgeon solution communications, respectively. There were no reported communication errors while using direct wireless, cellular communication. When compared to page communications, cellular communications showed statistically significant improvements in mean time intervals in response time (Cell = 11s, Page = 211s), correct patient identification (Cell = 5s, Page = 172s), patient problem and solution time (Cell = 13s, Page = 189s), and total communication time (Cell = 32s, Page = 250s) (s = seconds, all P < 0.001). Floor nurse satisfaction ratings (dependent on communication times and/or difficulties) were improved with direct cellular communication (Cell = 29 excellent, Page = 11 excellent). Intraoperative case interruptions (defined as delaying surgical progress) were more frequent with indirect page communication (10 page v. 0 cell). Our study demonstrates that direct wireless communication may be used to improve intraoperative communication and enhance patient safety. Direct wireless, cellular intraoperative communication improves communication times, communication accuracy, communication satisfaction, and minimizes intraoperative case interruption. As a result of this study, we hope to maintain our transition to direct wireless, cellular intraoperative orthopaedic communication to reduce medical errors, improve patient care, and enhance both orthopaedic surgeon and nursing efficiencies.

Cellular-dendritic transition in directionally solidified binary alloys

NASA Technical Reports Server (NTRS)

Tewari, S. N.; Laxmanan, V.

1987-01-01

The microstructural development of binary alloys during directional solidification is studied. Cellular growth data for the Al-Cu and Pb-Sn binary alloy systems are analyzed in order evaluate the criteria of Kurz and Fisher (1981) and Trivedi (1984) for cellular-dendritic transition. It is observed that the experimental growth values do not correlate with the Kurz and Fisher or Trivedi data.

Quantized transport for a skyrmion moving on a two-dimensional periodic substrate

NASA Astrophysics Data System (ADS)

Reichhardt, C.; Ray, D.; Reichhardt, C. J. Olson

2015-03-01

We examine the dynamics of a skyrmion moving over a two-dimensional periodic substrate utilizing simulations of a particle-based skyrmion model. We specifically examine the role of the nondissipative Magnus term on the driven motion and the resulting skyrmion velocity-force curves. In the overdamped limit, there is a depinning transition into a sliding state in which the skyrmion moves in the same direction as the external drive. When there is a finite Magnus component in the equation of motion, a skyrmion in the absence of a substrate moves at an angle with respect to the direction of the external driving force. When a periodic substrate is added, the direction of motion or Hall angle of the skyrmion is dependent on the amplitude of the external drive, only approaching the substrate-free limit for higher drives. Due to the underlying symmetry of the substrate the direction of skyrmion motion does not change continuously as a function of drive, but rather forms a series of discrete steps corresponding to integer or rational ratios of the velocity components perpendicular ( ) and parallel ( ) to the external drive direction: / =n /m , where n and m are integers. The skyrmion passes through a series of directional locking phases in which the motion is locked to certain symmetry directions of the substrate for fixed intervals of the drive amplitude. Within a given directionally locked phase, the Hall angle remains constant and the skyrmion moves in an orderly fashion through the sample. Signatures of the transitions into and out of these locked phases take the form of pronounced cusps in the skyrmion velocity versus force curves, as well as regions of negative differential mobility in which the net skyrmion velocity decreases with increasing external driving force. The number of steps in the transport curve increases when the relative strength of the Magnus term is increased. We also observe an overshoot phenomena in the directional locking, where the skyrmion motion can lock to a Hall angle greater than the clean limit value and then jump back to the lower value at higher drives. The skyrmion-substrate interactions can also produce a skyrmion acceleration effect in which, due to the nondissipative dynamics, the skyrmion velocity exceeds the value expected to be produced by the external drive. We find that these effects are robust for different types of periodic substrates. Using a simple model for a skyrmion interacting with a single pinning site, we can capture the behavior of the change in the Hall angle with increasing external drive. When the skyrmion moves through the pinning site, its trajectory exhibits a side step phenomenon since the Magnus term induces a curvature in the skyrmion orbit. As the drive increases, this curvature is reduced and the side step effect is also reduced. Increasing the strength of the Magnus term reduces the range of impact parameters over which the skyrmion can be captured by a pinning site, which is one of the reasons that strong Magnus force effects reduce the pinning in skyrmion systems.

Life without double-headed non-muscle myosin II motor proteins

PubMed Central

Betapudi, Venkaiah

2014-01-01

Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC) belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients' life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life. PMID:25072053

Life without double-headed non-muscle myosin II motor proteins

NASA Astrophysics Data System (ADS)

Betapudi, Venkaiah

2014-07-01

Non-muscle myosin II motor proteins (myosin IIA, myosin IIB, and myosin IIC) belong to a class of molecular motor proteins that are known to transduce cellular free-energy into biological work more efficiently than man-made combustion engines. Nature has given a single myosin II motor protein for lower eukaryotes and multiple for mammals but none for plants in order to provide impetus for their life. These specialized nanomachines drive cellular activities necessary for embryogenesis, organogenesis, and immunity. However, these multifunctional myosin II motor proteins are believed to go awry due to unknown reasons and contribute for the onset and progression of many autosomal-dominant disorders, cataract, deafness, infertility, cancer, kidney, neuronal, and inflammatory diseases. Many pathogens like HIV, Dengue, hepatitis C, and Lymphoma viruses as well as Salmonella and Mycobacteria are now known to take hostage of these dedicated myosin II motor proteins for their efficient pathogenesis. Even after four decades since their discovery, we still have a limited knowledge of how these motor proteins drive cell migration and cytokinesis. We need to enrich our current knowledge on these fundamental cellular processes and develop novel therapeutic strategies to fix mutated myosin II motor proteins in pathological conditions. This is the time to think how to relieve the hijacked myosins from pathogens in order to provide a renewed impetus for patients’ life. Understanding how to steer these molecular motors in proliferating and differentiating stem cells will improve stem cell based-therapeutics development. Given the plethora of cellular activities non-muscle myosin motor proteins are involved in, their importance is apparent for human life.

The Belief and Attitude of the Drivers Toward the Usage of Cellphone while Driving; A Population-Based Survey

PubMed Central

Sedaghati Shokri, Batoul; Davoodi, Seyed Rasoul; Azimmohseni, Majid; Khoshfar, Gholamreza

2017-01-01

Objective: To presents a survey investigating differences between drivers' beliefs regarding utilizing cellphone when driving. Methods: In this population-based survey, the participants who were studied in the North of Iran, Gorgan, were categorized as main urban and rural areas. A sample of 400 drivers, 92 women and 308 men, filled out the four sections questionnaire which was based on the Theory of Planned Behavior (TPB) used for measuring the differences between the drivers' opinions (attitudinal beliefs, normative beliefs, and perceived control behavioral beliefs) about utilizing a cell phone when driving along with their age and driving purpose. Data were collected by distributing the 68- query questionnaire between the drivers. Results: The MANOVA analysis showed that important discrepancies were found between the normative, control and behavioral beliefs of cellular phone users while driving. As expected, frequent business and younger users with sturdy intention expressed more benefits of further concentration on family members and fewer obstacles that would prevent them from utilizing cellphone when driving than older and frequently personal users. Conclusion: These results indicated that the benefits of utilizing cellphone while driving are greater than its dangers. To reduce cellphone utilization when driving and increase road safety, more effort is required to lower the perceived advantages of the behavior and to outstand the risks of this hazardous driving act. PMID:29177176

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA

NASA Astrophysics Data System (ADS)

Regan, S. P.; Goncharov, V. N.; Igumenshchev, I. V.; Sangster, T. C.; Betti, R.; Bose, A.; Boehly, T. R.; Bonino, M. J.; Campbell, E. M.; Cao, D.; Collins, T. J. B.; Craxton, R. S.; Davis, A. K.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Forrest, C. J.; Frenje, J. A.; Froula, D. H.; Gatu Johnson, M.; Glebov, V. Yu.; Harding, D. R.; Hohenberger, M.; Hu, S. X.; Jacobs-Perkins, D.; Janezic, R.; Karasik, M.; Keck, R. L.; Kelly, J. H.; Kessler, T. J.; Knauer, J. P.; Kosc, T. Z.; Loucks, S. J.; Marozas, J. A.; Marshall, F. J.; McCrory, R. L.; McKenty, P. W.; Meyerhofer, D. D.; Michel, D. T.; Myatt, J. F.; Obenschain, S. P.; Petrasso, R. D.; Radha, P. B.; Rice, B.; Rosenberg, M. J.; Schmitt, A. J.; Schmitt, M. J.; Seka, W.; Shmayda, W. T.; Shoup, M. J.; Shvydky, A.; Skupsky, S.; Solodov, A. A.; Stoeckl, C.; Theobald, W.; Ulreich, J.; Wittman, M. D.; Woo, K. M.; Yaakobi, B.; Zuegel, J. D.

2016-07-01

A record fuel hot-spot pressure Phs=56 ±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ˜60 % of the value required for ignition [A. Bose et al., Phys. Rev. E 93, LM15119ER (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

Demonstration of fuel hot-spot pressure in excess of 50 Gbar for direct-drive, layered deuterium-tritium implosions on OMEGA

DOE PAGES

Regan, S. P.; Goncharov, V. N.; Igumenshchev, I. V.; ...

2016-07-07

A record fuel hot-spot pressure P hs = 56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium–tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility (NIF), these implosions achieved a Lawson parameter ~60% of the value required for ignition [A. Bose et al., Phys. Rev. E (in press)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure ismore » ~40% lower. Furthermore, three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.« less

Demonstration of fuel hot-spot pressure in excess of 50 Gbar for direct-drive, layered deuterium-tritium implosions on OMEGA

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

Regan, S. P.; Goncharov, V. N.; Igumenshchev, I. V.

A record fuel hot-spot pressure P hs = 56±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium–tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility (NIF), these implosions achieved a Lawson parameter ~60% of the value required for ignition [A. Bose et al., Phys. Rev. E (in press)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure ismore » ~40% lower. Furthermore, three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.« less

Variation of Extreme and Fatigue Design Loads on the Main Bearing of a Front Mounted Direct Drive System

NASA Astrophysics Data System (ADS)

Abrahamsen, Asger Bech; Natarajan, Anand

2016-09-01

The drivetrain of a 10 MW wind turbine has been designed as a direct drive transmission with a superconducting generator mounted in front of the hub and connected to the main frame through a King-pin stiff assembly by DNV-GL. The aeroelastic design loads of such an arrangement are evaluated based on the thrust and bending moments at the main bearing, both for ultimate design and in fatigue. It is found that the initial superconductor generator weight of 363 tons must be reduced by 25% in order not to result in higher extreme loads on main and yaw bearing than the reference10 MW geared reference drive train. A weight reduction of 50% is needed in order to maintain main bearing fatigue damage equivalent to the reference drive train. Thus a target mass of front mounted superconducting direct drive generators is found to be between 183-272 tons.

Friction phenomena and phase transition in the underdamped two-dimensional Frenkel-Kontorova model

NASA Astrophysics Data System (ADS)

Yang, Yang; Duan, Wen-Shan; Chen, Jian-Min; Yang, Lei; Tekić, Jasmina; Shao, Zhi-Gang; Wang, Cang-Long

2010-11-01

Locked-to-sliding phase transition has been studied in the driven two-dimensional Frenkel-Kontorova model with the square symmetric substrate potential. It is found that as the driving force increases, the system transfers from the locked state to the sliding state where the motion of particles is in the direction different from that of driving force. With the further increase in driving force, at some critical value, the particles start to move in the direction of driving force. These two critical forces, the static friction or depinning force, and the kinetic friction force for which particles move in the direction of driving force have been analyzed for different system parameters. Different scenarios of phase transitions have been examined and dynamical phases are classified. In the case of zero misfit angle, the analytical expressions for static and kinetic friction force have been obtained.

EEG-based decoding of error-related brain activity in a real-world driving task

NASA Astrophysics Data System (ADS)

Zhang, H.; Chavarriaga, R.; Khaliliardali, Z.; Gheorghe, L.; Iturrate, I.; Millán, J. d. R.

2015-12-01

Objectives. Recent studies have started to explore the implementation of brain-computer interfaces (BCI) as part of driving assistant systems. The current study presents an EEG-based BCI that decodes error-related brain activity. Such information can be used, e.g., to predict driver’s intended turning direction before reaching road intersections. Approach. We executed experiments in a car simulator (N = 22) and a real car (N = 8). While subject was driving, a directional cue was shown before reaching an intersection, and we classified the presence or not of an error-related potentials from EEG to infer whether the cued direction coincided with the subject’s intention. In this protocol, the directional cue can correspond to an estimation of the driving direction provided by a driving assistance system. We analyzed ERPs elicited during normal driving and evaluated the classification performance in both offline and online tests. Results. An average classification accuracy of 0.698 ± 0.065 was obtained in offline experiments in the car simulator, while tests in the real car yielded a performance of 0.682 ± 0.059. The results were significantly higher than chance level for all cases. Online experiments led to equivalent performances in both simulated and real car driving experiments. These results support the feasibility of decoding these signals to help estimating whether the driver’s intention coincides with the advice provided by the driving assistant in a real car. Significance. The study demonstrates a BCI system in real-world driving, extending the work from previous simulated studies. As far as we know, this is the first online study in real car decoding driver’s error-related brain activity. Given the encouraging results, the paradigm could be further improved by using more sophisticated machine learning approaches and possibly be combined with applications in intelligent vehicles.

A telephoto camera system with shooting direction control by gaze detection

NASA Astrophysics Data System (ADS)

Teraya, Daiki; Hachisu, Takumi; Yendo, Tomohiro

2015-05-01

For safe driving, it is important for driver to check traffic conditions such as traffic lights, or traffic signs as early as soon. If on-vehicle camera takes image of important objects to understand traffic conditions from long distance and shows these to driver, driver can understand traffic conditions earlier. To take image of long distance objects clearly, the focal length of camera must be long. When the focal length is long, on-vehicle camera doesn't have enough field of view to check traffic conditions. Therefore, in order to get necessary images from long distance, camera must have long-focal length and controllability of shooting direction. In previous study, driver indicates shooting direction on displayed image taken by a wide-angle camera, a direction controllable camera takes telescopic image, and displays these to driver. However, driver uses a touch panel to indicate the shooting direction in previous study. It is cause of disturb driving. So, we propose a telephoto camera system for driving support whose shooting direction is controlled by driver's gaze to avoid disturbing drive. This proposed system is composed of a gaze detector and an active telephoto camera whose shooting direction is controlled. We adopt non-wear detecting method to avoid hindrance to drive. The gaze detector measures driver's gaze by image processing. The shooting direction of the active telephoto camera is controlled by galvanometer scanners and the direction can be switched within a few milliseconds. We confirmed that the proposed system takes images of gazing straight ahead of subject by experiments.

Advanced Direct-Drive Generator for Improved Availability of Oscillating Wave Surge Converter Power Generation Systems Final Technical Report

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

Englebretson, Steven; Ouyang, Wen; Tschida, Colin

This report summarizes the activities conducted under the DOE-EERE funded project DE-EE0006400, where ABB Inc. (ABB), in collaboration with Texas A&M’s Advanced Electric Machines & Power Electronics (EMPE) Lab and Resolute Marine Energy (RME) designed, derisked, developed, and demonstrated a novel magnetically geared electrical generator for direct-drive, low-speed, high torque MHK applications The project objective was to investigate a novel and compact direct-drive electric generator and its system aspects that would enable elimination of hydraulic components in the Power Take-Off (PTO) of a Marine and Hydrokinetic (MHK) system with an oscillating wave surge converter (OWSC), thereby improving the availability ofmore » the MHK system. The scope of this project was limited to the development and dry lab demonstration of a low speed generator to enable future direct drive MHK systems.« less

High reduction transaxle for electric vehicle

DOEpatents

Kalns, Ilmars

1987-01-01

A drivetrain (12) includes a transaxle assembly (16) for driving ground engaging wheels of a land vehicle powered by an AC motor. The transaxle includes a ratio change section having planetary gear sets (24, 26) and brake assemblies (28, 30). Sun gears (60, 62) of the gear sets are directly and continuously connected to an input drive shaft (38) driven by the motor. A first drive (78a) directly and continuously connects a planetary gear carrier (78) of gear sets (24) with a ring gear (68) of gear set (26). A second drive (80a) directly and continuously connects a planetary gear carrier (80) of gear set (26) with a sun gear (64) of a final speed reduction gear set (34) having a planetary gear carrier directly and continuously connected to a differential (22). Brakes (28, 30) are selectively engageable to respectively ground a ring gear 66 of gear set 24 and ring gear 68 of gear set 26.

A Comprehensive Review of Permanent Magnet Transverse Flux Machines for Direct Drive Applications

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

Muljadi, Eduard; Husain, Tausif; Hasan, Iftekhar

The use of direct drive machines in renewable and industrial applications are increasing at a rapid rate. Transverse flux machines (TFM) are ideally suited for direct drive applications due to their high torque density. In this paper, a comprehensive review of the permanent magnet (PM) TFMs for direct drive applications is presented. The paper introduces TFMs and their operating principle and then reviews the different type of TFMs proposed in the literature. The TFMs are categorized according to the number of stator sides, types of stator cores and magnet arrangement in the rotor. The review covers different design topologies, materialsmore » used for manufacturing, structural and thermal analysis, modeling and design optimization and cogging torque minimization in TFMs. The paper also reviews various applications and comparisons for TFMs that have been presented in the literature.« less

Position measurement of the direct drive motor of Large Aperture Telescope

NASA Astrophysics Data System (ADS)

Li, Ying; Wang, Daxing

2010-07-01

Along with the development of space and astronomy science, production of large aperture telescope and super large aperture telescope will definitely become the trend. It's one of methods to solve precise drive of large aperture telescope using direct drive technology unified designed of electricity and magnetism structure. A direct drive precise rotary table with diameter of 2.5 meters researched and produced by us is a typical mechanical & electrical integration design. This paper mainly introduces position measurement control system of direct drive motor. In design of this motor, position measurement control system requires having high resolution, and precisely aligning the position of rotor shaft and making measurement, meanwhile transferring position information to position reversing information corresponding to needed motor pole number. This system has chosen high precision metal band coder and absolute type coder, processing information of coders, and has sent 32-bit RISC CPU making software processing, and gained high resolution composite coder. The paper gives relevant laboratory test results at the end, indicating the position measurement can apply to large aperture telescope control system. This project is subsidized by Chinese National Natural Science Funds (10833004).

Development of a bi-directional standing wave linear piezoelectric actuator with four driving feet.

PubMed

Liu, Yingxiang; Shi, Shengjun; Li, Chunhong; Chen, Weishan; Wang, Liang; Liu, Junkao

2018-03-01

A bi-directional standing wave linear piezoelectric ultrasonic actuator with four driving feet is proposed in this work. Two sandwich type transducers operated in longitudinal-bending hybrid modes are set parallelly. The working mode of the transducer is not simple hybrid vibrations of a longitudinal one and a bending one, but a special coupling vibration mode contained both longitudinal and bending components. Two transducers with the same structure and unsymmetrical boundary conditions are set parallelly to accomplish the bi-directional driving: the first transducer can push the runner forward, while the other one produces the backward driving. In the experiments, two voltages with different amplitudes are applied on the two transducers, respectively: the one with higher voltage serves as the actuator, whereas the other one applied with lower voltage is used to reduce the frictional force. The prototype achieves maximum no-load speed and thrust force of 244 mm/s and 9.8 N. This work gives a new idea for the construction of standing wave piezoelectric ultrasonic actuator with bi-directional driving ability. Copyright © 2017 Elsevier B.V. All rights reserved.

Programs across the United States that aid motorists in the reporting of impaired drivers to law enforcement

DOT National Transportation Integrated Search

2007-03-01

The objective of this project was to identify States that use a statewide cellular drunk driving reporting program which provides free airtime and allows motorists with cell phones to dial a special number (such as *DUI) to report suspected drunk dri...

Sex chromosome drive.

PubMed

Helleu, Quentin; Gérard, Pierre R; Montchamp-Moreau, Catherine

2014-12-18

Sex chromosome drivers are selfish elements that subvert Mendel's first law of segregation and therefore are overrepresented among the products of meiosis. The sex-biased progeny produced then fuels an extended genetic conflict between the driver and the rest of the genome. Many examples of sex chromosome drive are known, but the occurrence of this phenomenon is probably largely underestimated because of the difficulty to detect it. Remarkably, nearly all sex chromosome drivers are found in two clades, Rodentia and Diptera. Although very little is known about the molecular and cellular mechanisms of drive, epigenetic processes such as chromatin regulation could be involved in many instances. Yet, its evolutionary consequences are far-reaching, from the evolution of mating systems and sex determination to the emergence of new species. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

3. DETAIL VIEW OF DIRECT DRIVE STERLING 'DOLPHIN T' MODEL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. DETAIL VIEW OF DIRECT DRIVE STERLING 'DOLPHIN T' MODEL 4 CYLINDER, GASOLINE TRACTOR-TYPE ENGINE WITH FALKBIBBY FLEXIBLE COUPLING - Central Railroad of New Jersey, Newark Bay Lift Bridge, Spanning Newark Bay, Newark, Essex County, NJ

A Lever Coupling Mechanism in Dual-Mass Micro-Gyroscopes for Improving the Shock Resistance along the Driving Direction

PubMed Central

Gao, Yang; Li, Hongsheng; Huang, Libin; Sun, Hui

2017-01-01

This paper presents the design and application of a lever coupling mechanism to improve the shock resistance of a dual-mass silicon micro-gyroscope with drive mode coupled along the driving direction without sacrificing the mechanical sensitivity. Firstly, the mechanical sensitivity and the shock response of the micro-gyroscope are theoretically analyzed. In the mechanical design, a novel lever coupling mechanism is proposed to change the modal order and to improve the frequency separation. The micro-gyroscope with the lever coupling mechanism optimizes the drive mode order, increasing the in-phase mode frequency to be much larger than the anti-phase one. Shock analysis results show that the micro-gyroscope structure with the designed lever coupling mechanism can notably reduce the magnitudes of the shock response and cut down the stress produced in the shock process compared with the traditional elastic coupled one. Simulations reveal that the shock resistance along the drive direction is greatly increased. Consequently, the lever coupling mechanism can change the gyroscope’s modal order and improve the frequency separation by structurally offering a higher stiffness difference ratio. The shock resistance along the driving direction is tremendously enhanced without loss of the mechanical sensitivity. PMID:28468288

Risky Teen Driving in a Rural Southern State.

PubMed

Monroe, Kathy; Hardwick, William; Lawson, Victoria; Nichols, Elizabeth; Nichols, Michele; King, William D

2017-05-01

Alabama is one of the five US states with the highest teen driving mortality. We recruited teen drivers to participate in a questionnaire regarding high-risk driving behaviors. Teens were recruited from a large county school system to participate in a voluntary anonymous survey. Questions were taken in part from the National Youth Risk Behavior Survey. Descriptive statistics and odds ratios with 95% confidence intervals were calculated. A total of 1023 teen drivers participated (46% boys, 47% African American, 39% white, 6% Latino, and 7% other). In all, 526 students (52%) reported inconsistent seat belt use. Half of the teens surveyed reported using a cellular telephone while driving within the past 30 days (51%); 10% admitted to driving after drinking alcoholic beverages in the past 30 days, with 23% saying they had ridden with a driver who had been drinking. High-risk teen driving behaviors were reported by many of the participants in our study. The majority of teens surveyed do not routinely wear seatbelts. Common misperceptions still exist regarding seatbelts and should be a focus of future education. Future research should focus on parental behaviors and correcting misperceptions of young drivers.

A 1-D Study of the Ignition Space for Magnetic Indirect (X-ray) Drive Targets

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

Cobble, James Allen; Sinars, Daniel Brian

The ICF program today is investigating three approaches to achieving multi-MJ fusion yields and ignition: (1) laser indirect (x-ray) drive on the National Ignition Facility (NIF), (2) laser direct drive (primarily on the Omega laser facility at the University of Rochester), and (3) magnetic direct drive on the Z pulsed power facility. In this white paper we briefly consider a fourth approach, magnetic indirect drive, in which pulsedpower- driven x-ray sources are used in place of laser driven sources. We first look at some of the x-ray sources studied on Z prior to 2007 before the pulsed power ICF programmore » shifted to magnetic direct drive. We then show results from a series of 1D Helios calculations of double-shell capsules that suggest that these sources, scaled to higher temperatures, could be a promising path to achieving multi-MJ fusion yields and ignition. We advocate here that more detailed design calculations with widely accepted 2D/3D ICF codes should be conducted for a better assessment of the prospects.« less

Engineering cellular fibers for musculoskeletal soft tissues using directed self-assembly.

PubMed

Schiele, Nathan R; Koppes, Ryan A; Chrisey, Douglas B; Corr, David T

2013-05-01

Engineering strategies guided by developmental biology may enhance and accelerate in vitro tissue formation for tissue engineering and regenerative medicine applications. In this study, we looked toward embryonic tendon development as a model system to guide our soft tissue engineering approach. To direct cellular self-assembly, we utilized laser micromachined, differentially adherent growth channels lined with fibronectin. The micromachined growth channels directed human dermal fibroblast cells to form single cellular fibers, without the need for a provisional three-dimensional extracellular matrix or scaffold to establish a fiber structure. Therefore, the resulting tissue structure and mechanical characteristics were determined solely by the cells. Due to the self-assembly nature of this approach, the growing fibers exhibit some key aspects of embryonic tendon development, such as high cellularity, the rapid formation (within 24 h) of a highly organized and aligned cellular structure, and the expression of cadherin-11 (indicating direct cell-to-cell adhesions). To provide a dynamic mechanical environment, we have also developed and characterized a method to apply precise cyclic tensile strain to the cellular fibers as they develop. After an initial period of cellular fiber formation (24 h postseeding), cyclic strain was applied for 48 h, in 8-h intervals, with tensile strain increasing from 0.7% to 1.0%, and at a frequency of 0.5 Hz. Dynamic loading dramatically increased cellular fiber mechanical properties with a nearly twofold increase in both the linear region stiffness and maximum load at failure, thereby demonstrating a mechanism for enhancing cellular fiber formation and mechanical properties. Tissue engineering strategies, designed to capture key aspects of embryonic development, may provide unique insight into accelerated maturation of engineered replacement tissue, and offer significant advances for regenerative medicine applications in tendon, ligament, and other fibrous soft tissues.

The life story of hydrogen peroxide II: a periodic pH and thermochemical drive for the RNA world

PubMed Central

Ball, Rowena; Brindley, John

2015-01-01

It is now accepted that primordial non-cellular RNA communities must have been subject to a periodic drive in order to replicate and prosper. We have proposed the oxidation of thiosulfate by hydrogen peroxide as this drive. This reaction system behaves as (i) a thermochemical and (ii) a pH oscillator, and in this work, we unify (i) and (ii) for the first time. We report thermally self-consistent, dynamical simulations in which the system transitions smoothly from nearly isothermal pH to fully developed thermo-pH oscillatory regimes. We use this oscillator to drive simulated replication of a 39-bp RNA species. Production of replicated duplex under thermo-pH drive was significantly enhanced compared with that under purely thermochemical drive, effectively allowing longer strands to replicate. Longer strands are fitter, with more potential to evolve enzyme activity and resist degradation. We affirm that concern over the alleged toxicity of hydrogen peroxide to life is largely misplaced in the current context, we survey its occurrence in the solar system to motivate its inclusion as a biosignature in the search for life on other worlds and highlight that pH oscillations in a spatially extended, bounded system manifest as the fundamental driving force of life: a proton gradient. PMID:26202683

Galectin-3 in autoimmunity and autoimmune diseases

PubMed Central

de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo

2015-01-01

Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell–cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte–macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. PMID:26142116

Possible roles of mechanical cell elimination intrinsic to growing tissues from the perspective of tissue growth efficiency and homeostasis.

PubMed

Lee, Sang-Woo; Morishita, Yoshihiro

2017-07-01

Cell competition is a phenomenon originally described as the competition between cell populations with different genetic backgrounds; losing cells with lower fitness are eliminated. With the progress in identification of related molecules, some reports described the relevance of cell mechanics during elimination. Furthermore, recent live imaging studies have shown that even in tissues composed of genetically identical cells, a non-negligible number of cells are eliminated during growth. Thus, mechanical cell elimination (MCE) as a consequence of mechanical cellular interactions is an unavoidable event in growing tissues and a commonly observed phenomenon. Here, we studied MCE in a genetically-homogeneous tissue from the perspective of tissue growth efficiency and homeostasis. First, we propose two quantitative measures, cell and tissue fitness, to evaluate cellular competitiveness and tissue growth efficiency, respectively. By mechanical tissue simulation in a pure population where all cells have the same mechanical traits, we clarified the dependence of cell elimination rate or cell fitness on different mechanical/growth parameters. In particular, we found that geometrical (specifically, cell size) and mechanical (stress magnitude) heterogeneities are common determinants of the elimination rate. Based on these results, we propose possible mechanical feedback mechanisms that could improve tissue growth efficiency and density/stress homeostasis. Moreover, when cells with different mechanical traits are mixed (e.g., in the presence of phenotypic variation), we show that MCE could drive a drastic shift in cell trait distribution, thereby improving tissue growth efficiency through the selection of cellular traits, i.e. intra-tissue "evolution". Along with the improvement of growth efficiency, cell density, stress state, and phenotype (mechanical traits) were also shown to be homogenized through growth. More theoretically, we propose a mathematical model that approximates cell competition dynamics, by which the time evolution of tissue fitness and cellular trait distribution can be predicted without directly simulating a cell-based mechanical model.

Possible roles of mechanical cell elimination intrinsic to growing tissues from the perspective of tissue growth efficiency and homeostasis

PubMed Central

2017-01-01

Cell competition is a phenomenon originally described as the competition between cell populations with different genetic backgrounds; losing cells with lower fitness are eliminated. With the progress in identification of related molecules, some reports described the relevance of cell mechanics during elimination. Furthermore, recent live imaging studies have shown that even in tissues composed of genetically identical cells, a non-negligible number of cells are eliminated during growth. Thus, mechanical cell elimination (MCE) as a consequence of mechanical cellular interactions is an unavoidable event in growing tissues and a commonly observed phenomenon. Here, we studied MCE in a genetically-homogeneous tissue from the perspective of tissue growth efficiency and homeostasis. First, we propose two quantitative measures, cell and tissue fitness, to evaluate cellular competitiveness and tissue growth efficiency, respectively. By mechanical tissue simulation in a pure population where all cells have the same mechanical traits, we clarified the dependence of cell elimination rate or cell fitness on different mechanical/growth parameters. In particular, we found that geometrical (specifically, cell size) and mechanical (stress magnitude) heterogeneities are common determinants of the elimination rate. Based on these results, we propose possible mechanical feedback mechanisms that could improve tissue growth efficiency and density/stress homeostasis. Moreover, when cells with different mechanical traits are mixed (e.g., in the presence of phenotypic variation), we show that MCE could drive a drastic shift in cell trait distribution, thereby improving tissue growth efficiency through the selection of cellular traits, i.e. intra-tissue “evolution”. Along with the improvement of growth efficiency, cell density, stress state, and phenotype (mechanical traits) were also shown to be homogenized through growth. More theoretically, we propose a mathematical model that approximates cell competition dynamics, by which the time evolution of tissue fitness and cellular trait distribution can be predicted without directly simulating a cell-based mechanical model. PMID:28704373

Differing types of cellular phone conversations and dangerous driving.

PubMed

Dula, Chris S; Martin, Benjamin A; Fox, Russell T; Leonard, Robin L

2011-01-01

This study sought to investigate the relationship between cell phone conversation type and dangerous driving behaviors. It was hypothesized that more emotional phone conversations engaged in while driving would produce greater frequencies of dangerous driving behaviors in a simulated environment than more mundane conversation or no phone conversation at all. Participants were semi-randomly assigned to one of three conditions: (1) no call, (2) mundane call, and, (3) emotional call. While driving in a simulated environment, participants in the experimental groups received a phone call from a research confederate who either engaged them in innocuous conversation (mundane call) or arguing the opposite position of a deeply held belief of the participant (emotional call). Participants in the no call and mundane call groups differed significantly only on percent time spent speeding and center line crossings, though the mundane call group consistently engaged in more of all dangerous driving behaviors than did the no call participants. Participants in the emotional call group engaged in significantly more dangerous driving behaviors than participants in both the no call and mundane call groups, with the exception of traffic light infractions, where there were no significant group differences. Though there is need for replication, the authors concluded that whereas talking on a cell phone while driving is risky to begin with, having emotionally intense conversations is considerably more dangerous. Copyright © 2010 Elsevier Ltd. All rights reserved.

Journey of oocyte from metaphase-I to metaphase-II stage in mammals.

PubMed

Sharma, Alka; Tiwari, Meenakshi; Gupta, Anumegha; Pandey, Ashutosh N; Yadav, Pramod K; Chaube, Shail K

2018-08-01

In mammals, journey from metaphase-I (M-I) to metaphase-II (M-II) is important since oocyte extrude first polar body (PB-I) and gets converted into haploid gamete. The molecular and cellular changes associated with meiotic cell cycle progression from M-I to M-II stage and extrusion of PB-I remain ill understood. Several factors drive oocyte meiosis from M-I to M-II stage. The mitogen-activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases act through various pathways to drive cell cycle progression from M-I to M-II stage. The down regulation of MOS/MEK/MAPK3/1 pathway results in the activation of anaphase-promoting complex/cyclosome (APC/C). The active APC/C destabilizes maturation promoting factor (MPF) and induces meiotic resumption. Several signal molecules such as, c-Jun N-terminal kinase (JNK2), SENP3, mitotic kinesin-like protein 2 (MKlp2), regulator of G-protein signaling (RGS2), Epsin2, polo-like kinase 1 (Plk1) are directly or indirectly involved in chromosomal segregation. Rho family GTPase is another enzyme that along with cell division cycle (Cdc42) to form actomyosin contractile ring required for chromosomal segregation. In the presence of origin recognition complex (ORC4), eccentrically localized haploid set of chromosomes trigger cortex differentiation and determine the division site for polar body formation. The actomyosin contractile activity at the site of division plane helps to form cytokinetic furrow that results in the formation and extrusion of PB-I. Indeed, oocyte journey from M-I to M-II stage is coordinated by several factors and pathways that enable oocyte to extrude PB-I. Quality of oocyte directly impact fertilization rate, early embryonic development, and reproductive outcome in mammals. © 2018 Wiley Periodicals, Inc.

Accelerated geroncogenesis in hereditary breast-ovarian cancer syndrome

PubMed Central

Menendez, Javier A.; Folguera-Blasco, Núria; Cuyàs, Elisabet; Fernández-Arroyo, Salvador; Joven, Jorge; Alarcón, Tomás

2016-01-01

The geroncogenesis hypothesis postulates that the decline in metabolic cellular health that occurs naturally with aging drives a “field effect” predisposing normal tissues for cancer development. We propose that mutations in the cancer susceptibility genes BRCA1/2 might trigger “accelerated geroncogenesis” in breast and ovarian epithelia. By speeding up the rate at which the metabolic threshold becomes “permissive” with survival and expansion of genomically unstable pre-tumoral epithelial cells, BRCA haploinsufficiency-driven metabolic reprogramming would operate as a bona fide oncogenic event enabling malignant transformation and tumor formation in BRCA carriers. The metabolic facet of BRCA1 one-hit might involve tissue-specific alterations in acetyl-CoA, α-ketoglutarate, NAD+, FAD, or S-adenosylmethionine, critical factors for de/methylation or de/acetylation dynamics in the nuclear epigenome. This in turn might induce faulty epigenetic reprogramming at the “install phase” that directs cell-specific differentiation of breast/ovarian epithelial cells, which can ultimately determine the penetrance of BRCA defects during developmental windows of susceptibility. This model offers a framework to study whether metabolic drugs that prevent or revert metabolic reprogramming induced by BRCA haploinsufficiency might displace the “geroncogenic risk” of BRCA carriers to the age typical for those without the mutation. The identification of the key nodes that directly communicate changes in cellular metabolism to the chromatin in BRCA haploinsufficient cells may allow the epigenetic targeting of genomic instability using exclusively metabolic means. The validation of accelerated geroncogenesis as an inherited “one-hit” metabolic “field effect” might offer new strategies to therapeutically revisit the apparently irreversible genetic-hereditary fate of women with hereditary breast-ovarian cancer syndrome. PMID:26943589

Single Event Resolution of Plant Plasma Membrane Protein Endocytosis by TIRF Microscopy.

PubMed

Johnson, Alexander; Vert, Grégory

2017-01-01

Endocytosis is a key process in the internalization of extracellular materials and plasma membrane proteins, such as receptors and transporters, thereby controlling many aspects of cell signaling and cellular homeostasis. Endocytosis in plants has an essential role not only for basic cellular functions but also for growth and development, nutrient delivery, toxin avoidance, and pathogen defense. The precise mechanisms of endocytosis in plants remain quite elusive. The lack of direct visualization and examination of single events of endocytosis has greatly hampered our ability to precisely monitor the cell surface lifetime and the recruitment profile of proteins driving endocytosis or endocytosed cargos in plants. Here, we discuss the necessity to systematically implement total internal reflection fluorescence microcopy (TIRF) in the Plant Cell Biology community and present reliable protocols for high spatial and temporal imaging of endocytosis in plants using clathrin-mediated endocytosis as a test case, since it represents the major route for internalization of cell-surface proteins in plants. We developed a robust method to directly visualize cell surface proteins using TIRF microscopy combined to a high throughput, automated and unbiased analysis pipeline to determine the temporal recruitment profile of proteins to single sites of endocytosis, using the departure of clathrin as a physiological reference for scission. Using this 'departure assay', we assessed the recruitment of two different AP-2 subunits, alpha and mu, to the sites of endocytosis and found that AP2A1 was recruited in concert with clathrin, while AP2M was not. This validated approach therefore offers a powerful solution to better characterize the plant endocytic machinery and the dynamics of one's favorite cargo protein.

Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

PubMed Central

Baer, Matthew L.; Henderson, Scott C.; Colello, Raymond J.

2015-01-01

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair. PMID:26562295

Novel AC Servo Rotating and Linear Composite Driving Device for Plastic Forming Equipment

NASA Astrophysics Data System (ADS)

Liang, Jin-Tao; Zhao, Sheng-Dun; Li, Yong-Yi; Zhu, Mu-Zhi

2017-07-01

The existing plastic forming equipment are mostly driven by traditional AC motors with long transmission chains, low efficiency, large size, low precision and poor dynamic response are the common disadvantages. In order to realize high performance forming processes, the driving device should be improved, especially for complicated processing motions. Based on electric servo direct drive technology, a novel AC servo rotating and linear composite driving device is proposed, which features implementing both spindle rotation and feed motion without transmission, so that compact structure and precise control can be achieved. Flux switching topology is employed in the rotating drive component for strong robustness, and fractional slot is employed in the linear direct drive component for large force capability. Then the mechanical structure for compositing rotation and linear motion is designed. A device prototype is manufactured, machining of each component and the whole assembly are presented respectively. Commercial servo amplifiers are utilized to construct the control system of the proposed device. To validate the effectiveness of the proposed composite driving device, experimental study on the dynamic test benches are conducted. The results indicate that the output torque can attain to 420 N·m and the dynamic tracking errors are less than about 0.3 rad in the rotating drive. the dynamic tracking errors are less than about 1.6 mm in the linear feed. The proposed research provides a method to construct high efficiency and accuracy direct driving device in plastic forming equipment.

Design and simulation of bi-directional microfluid driving systems

NASA Astrophysics Data System (ADS)

Jen, Chun-Ping; Lin, Yu-Cheng

2002-03-01

Micro total analysis systems (μTAS) have been developed to perform a number of analytical processes involving chemical reactions, separation and sensing on a single chip. In medical and biomedical applications, μTAS must be designed considering special transport mechanisms to move samples and reagents through the microchannels in the system. For conventional micropumps, however, complicated relationships exist between the pumping mechanisms, the conditions under which the devices operate and the behavior of the multi-component fluids transported in these channels. A bi-directional microfluid driving system has been developed in this paper. This pneumatic system is an on-chip planar structure with no moving parts and does not require microfabricated heaters or electrodes. The pumping actuation is introduced to the microchannel fabricated in the chip by blowing an airflow through this device. The bi-directional driving module combines two individual components for suction and exclusion. The driving system provides a stable and flexible bi-directional microfluid driving control. The tunable parameters for adjusting the exclusion/suction ratios, such as the location of the inlet channel and the velocities of the airflow, have been observed in the numerical study. The optimal exclusion/suction ratio for the specific purpose of the driving system can be selected by changing the location of the microchannel to the reaction area for the sample/reagent. The velocity at the microchannel can be adjusted by varying the inlet velocities for the suction and exclusion components. For the presented design, no air conduit was employed to connect the servo-system to the driving system; therefore the packaging difficulty and leakage problem, which may arise in conventional systems, can be eliminated. The final airflow outlet was fixed in one direction so that it can prevent cross-contamination between the servo-system and the chip. The driving system is therefore particularly suited to microdevices for biochemical analysis.

78 FR 17359 - Takes of Marine Mammals Incidental to Specified Activities; Marine Geophysical Survey in the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... BRG-6 diesel engines which drive two propellers directly. Each propeller has four blades and the shaft... 930 kW and drives one propeller directly. The propeller has five blades, and the shaft typically...

Cellular Microcultures: Programming Mechanical and Physicochemical Properties of 3D Hydrogel Cellular Microcultures via Direct Ink Writing (Adv. Healthcare Mater. 9/2016).

PubMed

McCracken, Joselle M; Badea, Adina; Kandel, Mikhail E; Gladman, A Sydney; Wetzel, David J; Popescu, Gabriel; Lewis, Jennifer A; Nuzzo, Ralph G

2016-05-01

R. Nuzzo and co-workers show on page 1025 how compositional differences in hydrogels are used to tune their cellular compliance by controlling their polymer mesh properties and subsequent uptake of the protein poly-l-lysine (green spheres in circled inset). The cover image shows pyramid micro-scaffolds prepared using direct ink writing (DIW) that differentially direct fibroblast and preosteoblast growth in 3D, depending on cell motility and surface treatment. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Shapiro steps for skyrmion motion on a washboard potential with longitudinal and transverse ac drives

DOE PAGES

Reichhardt, Charles; Reichhardt, Cynthia Jane

2015-12-28

In this work, we numerically study the behavior of two-dimensional skyrmions in the presence of a quasi-one-dimensional sinusoidal substrate under the influence of externally applied dc and ac drives. In the overdamped limit, when both dc and ac drives are aligned in the longitudinal direction parallel to the direction of the substrate modulation, the velocity-force curves exhibit classic Shapiro step features when the frequency of the ac drive matches the washboard frequency that is dynamically generated by the motion of the skyrmions over the substrate, similar to previous observations in superconducting vortex systems. In the case of skyrmions, the additionalmore » contribution to the skyrmion motion from a nondissipative Magnus force shifts the location of the locking steps to higher dc drives, and we find that the skyrmions move at an angle with respect to the direction of the dc drive. For a longitudinal dc drive and a perpendicular or transverse ac drive, the overdamped system exhibits no Shapiro steps; however, when a finite Magnus force is present, we find pronounced transverse Shapiro steps along with complex two-dimensional periodic orbits of the skyrmions in the phase-locked regimes. Both the longitudinal and transverse ac drives produce locking steps whose widths oscillate with increasing ac drive amplitude. We examine the role of collective skyrmion interactions and find that additional fractional locking steps occur for both longitudinal and transverse ac drives. Finally, at higher skyrmion densities, the system undergoes a series of dynamical order-disorder transitions, with the skyrmions forming a moving solid on the phase locking steps and a fluctuating dynamical liquid in regimes between the steps.« less

Perceived social pressures and the internalization of the mesomorphic ideal: The role of drive for muscularity and autonomy in physically active men.

PubMed

Edwards, Christian; Tod, David; Molnar, Gyozo; Markland, David

2016-03-01

We examined if there were both direct and indirect relationships (via the drive for muscularity) between the perceived pressure to be muscular and internalization of the mesomorphic ideal, and if autonomy moderates these relationships in physically active men. A sample of 330 men, who were undergraduate students studying sport, completed the Behavioral Regulation in Exercise Questionnaire-2, the Mesomorphic Ideal Internalization subscale of the revised male version Sociocultural Attitudes Toward Appearance Questionnaire, the Perceived Sociocultural Pressure Scale-Modified, and the Drive for Muscularity Scale Attitudes subscale. Perceived pressure predicted internalization directly, and indirectly through the drive for muscularity. The direct relationship between pressure and internalization was weaker under higher levels of autonomy. The indirect path, via drive for muscularity, was stronger under higher levels of autonomy. These results provide insights into why men vary in the degree to which they internalize pressure to develop a mesomorphic ideal, supporting further examination of autonomy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

PubMed

Regan, S P; Goncharov, V N; Igumenshchev, I V; Sangster, T C; Betti, R; Bose, A; Boehly, T R; Bonino, M J; Campbell, E M; Cao, D; Collins, T J B; Craxton, R S; Davis, A K; Delettrez, J A; Edgell, D H; Epstein, R; Forrest, C J; Frenje, J A; Froula, D H; Gatu Johnson, M; Glebov, V Yu; Harding, D R; Hohenberger, M; Hu, S X; Jacobs-Perkins, D; Janezic, R; Karasik, M; Keck, R L; Kelly, J H; Kessler, T J; Knauer, J P; Kosc, T Z; Loucks, S J; Marozas, J A; Marshall, F J; McCrory, R L; McKenty, P W; Meyerhofer, D D; Michel, D T; Myatt, J F; Obenschain, S P; Petrasso, R D; Radha, P B; Rice, B; Rosenberg, M J; Schmitt, A J; Schmitt, M J; Seka, W; Shmayda, W T; Shoup, M J; Shvydky, A; Skupsky, S; Solodov, A A; Stoeckl, C; Theobald, W; Ulreich, J; Wittman, M D; Woo, K M; Yaakobi, B; Zuegel, J D

2016-07-08

A record fuel hot-spot pressure P_{hs}=56±7  Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

Folliculin directs the formation of a Rab34-RILP complex to control the nutrient-dependent dynamic distribution of lysosomes.

PubMed

Starling, Georgina P; Yip, Yan Y; Sanger, Anneri; Morton, Penny E; Eden, Emily R; Dodding, Mark P

2016-06-01

The spatial distribution of lysosomes is important for their function and is, in part, controlled by cellular nutrient status. Here, we show that the lysosome associated Birt-Hoge-Dubé (BHD) syndrome renal tumour suppressor folliculin (FLCN) regulates this process. FLCN promotes the peri-nuclear clustering of lysosomes following serum and amino acid withdrawal and is supported by the predominantly Golgi-associated small GTPase Rab34. Rab34-positive peri-nuclear membranes contact lysosomes and cause a reduction in lysosome motility and knockdown of FLCN inhibits Rab34-induced peri-nuclear lysosome clustering. FLCN interacts directly via its C-terminal DENN domain with the Rab34 effector RILP Using purified recombinant proteins, we show that the FLCN-DENN domain does not act as a GEF for Rab34, but rather, loads active Rab34 onto RILP We propose a model whereby starvation-induced FLCN association with lysosomes drives the formation of contact sites between lysosomes and Rab34-positive peri-nuclear membranes that restrict lysosome motility and thus promote their retention in this region of the cell. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Direct Visualisation of the Structural Transformation between the Lyotropic Liquid Crystalline Lamellar and Bicontinuous Cubic Mesophase.

PubMed

Tran, Nhiem; Zhai, Jiali; Conn, Charlotte E; Mulet, Xavier; Waddington, Lynne J; Drummond, Calum J

2018-05-29

The transition between the lyotropic liquid crystalline lamellar and the bicontinuous cubic mesophase drives multiple fundamental cellular processes involving changes in cell membrane topology including endocytosis and membrane budding. While several theoretical models have been proposed to explain this dynamic transformation, experimental validation of these models has been challenging due to the short lived nature of the intermediates present during the phase transition. Herein, we report the direct observation of a lamellar to bicontinuous cubic phase transition in nanoscale dispersions using a combination of cryogenic transmission electron microscopy and static small angle X-ray scattering. The results represent the first experimental confirmation of a theoretical model which proposed that the bicontinuous cubic phase originates from the centre of a lamellar vesicle, then propagates outward via the formation of inter-lamellar attachments and stalks. The observation was possible due to the precise control of the lipid composition to place the dispersion systems at the phase boundary of a lamellar and a cubic phase, allowing for the creation of long-lived structural intermediates. By surveying the nanoparticles using cryogenic transmission electron microscopy, a complete phase transition sequence was established.

Epithelial control of gut-associated lymphoid tissue formation through p38α-dependent restraint of NF-κB signaling

PubMed Central

Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

2015-01-01

The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. Here we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a non-cell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. PMID:26792803

Near-field acoustic microbead trapping as remote anchor for single particle manipulation

NASA Astrophysics Data System (ADS)

Hwang, Jae Youn; Cheon, Dong Young; Shin, Hyunjune; Kim, Hyun Bin; Lee, Jungwoo

2015-05-01

We recently proposed an analytical model of a two-dimensional acoustic trapping of polystyrene beads in the ray acoustics regime, where a bead diameter is larger than the wavelength used. As its experimental validation, this paper demonstrates the transverse (or lateral) trapping of individual polystyrene beads in the near field of focused ultrasound. A 100 μm bead is immobilized on the central beam axis by a focused sound beam from a 30 MHz single element lithium niobate transducer, after being laterally displaced through hundreds of micrometers. Maximum displacement, a longest lateral distance at which a trapped bead can be directed towards the central axis, is thus measured over a discrete frequency range from 24 MHz to 36 MHz. The displacement data are found to be between 323.7 μm and 470.2 μm, depending on the transducer's driving frequency and input voltage amplitude. The experimental results are compared with their corresponding model values, and their relative errors lie between 0.9% and 3.9%. The results suggest that this remote maneuvering technique may be employed to manipulate individual cells through solid microbeads, provoking certain cellular reactions to localized mechanical disturbance without direct contact.

Reactive oxygen species are required for driving efficient and sustained aerobic glycolysis during CD4+ T cell activation.

PubMed

Previte, Dana M; O'Connor, Erin C; Novak, Elizabeth A; Martins, Christina P; Mollen, Kevin P; Piganelli, Jon D

2017-01-01

The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive immune cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors to the immunopathology in T1D, and in order to drive optimal T cell activation, third signal reactive oxygen species (ROS) must be present. However, the role ROS play in mediating this process remains to be further understood. Recently, cellular metabolic programs have been shown to dictate the function and fate of immune cells, including CD4+ T cells. During activation, CD4+ T cells must transition metabolically from oxidative phosphorylation to aerobic glycolysis to support proliferation and effector function. As ROS are capable of modulating cellular metabolism in other models, we sought to understand if blocking ROS also regulates CD4+ T cell activation and effector function by modulating T cell metabolism. To do so, we utilized an ROS scavenging and potent antioxidant manganese metalloporphyrin (MnP). Our results demonstrate that redox modulation during activation regulates the mTOR/AMPK axis by maintaining AMPK activation, resulting in diminished mTOR activation and reduced transition to aerobic glycolysis in diabetogenic splenocytes. These results correlated with decreased Myc and Glut1 upregulation, reduced glucose uptake, and diminished lactate production. In an adoptive transfer model of T1D, animals treated with MnP demonstrated delayed diabetes progression, concurrent with reduced CD4+ T cell activation. Our results demonstrate that ROS are required for driving and sustaining T cell activation-induced metabolic reprogramming, and further support ROS as a target to minimize aberrant immune responses in autoimmunity.

Broadening the functionality of a J-protein/Hsp70 molecular chaperone system.

PubMed

Schilke, Brenda A; Ciesielski, Szymon J; Ziegelhoffer, Thomas; Kamiya, Erina; Tonelli, Marco; Lee, Woonghee; Cornilescu, Gabriel; Hines, Justin K; Markley, John L; Craig, Elizabeth A

2017-10-01

By binding to a multitude of polypeptide substrates, Hsp70-based molecular chaperone systems perform a range of cellular functions. All J-protein co-chaperones play the essential role, via action of their J-domains, of stimulating the ATPase activity of Hsp70, thereby stabilizing its interaction with substrate. In addition, J-proteins drive the functional diversity of Hsp70 chaperone systems through action of regions outside their J-domains. Targeting to specific locations within a cellular compartment and binding of specific substrates for delivery to Hsp70 have been identified as modes of J-protein specialization. To better understand J-protein specialization, we concentrated on Saccharomyces cerevisiae SIS1, which encodes an essential J-protein of the cytosol/nucleus. We selected suppressors that allowed cells lacking SIS1 to form colonies. Substitutions changing single residues in Ydj1, a J-protein, which, like Sis1, partners with Hsp70 Ssa1, were isolated. These gain-of-function substitutions were located at the end of the J-domain, suggesting that suppression was connected to interaction with its partner Hsp70, rather than substrate binding or subcellular localization. Reasoning that, if YDJ1 suppressors affect Ssa1 function, substitutions in Hsp70 itself might also be able to overcome the cellular requirement for Sis1, we carried out a selection for SSA1 suppressor mutations. Suppressing substitutions were isolated that altered sites in Ssa1 affecting the cycle of substrate interaction. Together, our results point to a third, additional means by which J-proteins can drive Hsp70's ability to function in a wide range of cellular processes-modulating the Hsp70-substrate interaction cycle.

Glutamine drives glutathione synthesis and contributes to radiation sensitivity of A549 and H460 lung cancer cell lines

PubMed Central

Sappington, Daniel R.; Siegel, Eric R.; Hiatt, Gloria; Desai, Abhishek; Penney, Rosalind B.; Jamshidi-Parsian, Azemat; Griffin, Robert J.; Boysen, Gunnar

2016-01-01

Background Increased glutamine uptake is known to drive cancer cell proliferation, making tumor cells glutamine-dependent. Glutamine provides additional carbon and nitrogen sources for cell growth. The first step in glutamine utilization is its conversion to glutamate by glutaminase (GLS). Glutamate is a precursor for glutathione synthesis, and we investigated the hypothesis that glutamine drives glutathione synthesis and thereby contributes to cellular defense systems. Methods The importance of glutamine for glutathione synthesis was studied in H460 and A549 lung cancer cell lines using glutamine-free medium and Bis-2-(5-phenyl-acetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) a GLS inhibitor. Metabolic activities were determined by targeted mass spectrometry. Results A significant correlation between glutamine consumption and glutathione excretion was demonstrated in H460 and A549 tumor cells. Culturing in the presence of [13C5]glutamine demonstrated that by 12 hrs >50% of excreted glutathione is derived from glutamine. Culturing in glutamine-free medium or treatment with BPTES, a glutaminase (GLS)-specific inhibitor, reduced cell proliferation and viability, and abolished glutathione excretion. Treatment with glutathione-ester prevented BPTES induced cytotoxicity. Inhibition of GLS markedly radiosensitized the lung tumor cell lines, suggesting an important role of glutamine-derived glutathione in determining radiation sensitivity. Conclusions We demonstrate here for the first time that a significant amount of extracellular glutathione is directly derived from glutamine. This finding adds yet another important function to the already known glutamine dependence of tumor cells and probably tumors as well. General significance Glutamine is essential for synthesis and excretion of glutathione to promote cell growth and viability. PMID:26825773

Fusomorphogenesis: cell fusion in organ formation.

PubMed

Shemer, G; Podbilewicz, B

2000-05-01

Cell fusion is a universal process that occurs during fertilization and in the formation of organs such as muscles, placenta, and bones. Very little is known about the molecular and cellular mechanisms of cell fusion during pattern formation. Here we review the dynamic anatomy of all cell fusions during embryonic and postembryonic development in an organism. Nearly all the cell fates and cell lineages are invariant in the nematode C. elegans and one third of the cells that are born fuse to form 44 syncytia in a reproducible and stereotyped way. To explain the function of cell fusion in organ formation we propose the fusomorphogenetic model as a simple cellular mechanism to efficiently redistribute membranes using a combination of cell fusion and polarized membrane recycling during morphogenesis. Thus, regulated intercellular and intracellular membrane fusion processes may drive elongation of the embryo as well as postembryonic organ formation in C. elegans. Finally, we use the fusomorphogenetic hypothesis to explain the role of cell fusion in the formation of organs like muscles, bones, and placenta in mammals and other species and to speculate on how the intracellular machinery that drive fusomorphogenesis may have evolved.

The effects of gear reduction on robot dynamics

NASA Technical Reports Server (NTRS)

Chen, J.

1989-01-01

The effect of the joint drive system with gear reduction for a generic two-link system is studied. It is done by comparing the kinetic energy of such a system with that of a direct drive two-link system. The only difference are two terms involving the inertia of the motor rotor and gear ratio. Modifications of the equations of motion from a direct drive system are then developed and generalized to various cases encountered in robot manipulators.

Structure and function of CrACA1, the major PM-type Ca2+-ATPase, expressed at the peak of the gravity-directed trans-cell calcium current in spores of the fern Ceratopteris richardii.

PubMed

Bushart, T J; Cannon, A; Clark, G; Roux, S J

2014-01-01

Spores of the fern Ceratopteris richardii have proven to be a valuable single-cell system for studying gravity responses. The earliest cellular change directed by gravity in these cells is a trans-cell calcium current, which peaks near 10 h after the spores are induced to germinate. This current is needed for gravity-directed axis alignment, and its peak is coincident with the time period when gravity polarises the direction of subsequent nuclear migration and rhizoid growth. Transcriptomic analysis of genes expressed at the 10-h time point revealed several that encode proteins likely to be key components that either drive the current or regulate it. Notable among these is a plasma membrane (PM)-type Ca(2+) ATPase, CrACA1, whose activity pumping Ca(2+) out of cells is regulated by gravity. This report provides an initial characterisation of the structure and expression of this protein, and demonstrates its heterologous function complementing the K616 mutant of yeast, which is deficient in PM-type Ca(2+) pump activity. Gravity-induced changes in the trans-cell Ca(2+) current occur within seconds, a result consistent with the hypothesis that the force of gravity can rapidly alter the post-translational state of the channels and pumps that drive this current across spore cells. This report identifies a transporter likely to be a key driver of the current, CrACA1, and characterises the role of this protein in early germination and gravity-driven polarity fixation through analysis of expression levels, functional complementation and pharmacological treatments. These data, along with newly available transcriptomic data obtained at the 10-h time point, indicate that CrACA1 is present, functional and likely a major contributing component of the trans-cell Ca(2+) efflux. CrACA1 is not necessary for polar axis alignment, but pharmacological perturbations of it disrupt rhizoid development. These data support and help refine the post-translational modification model for gravity responses. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

The emergence of ECM mechanics and cytoskeletal tension as important regulators of cell function.

PubMed

Peyton, Shelly R; Ghajar, Cyrus M; Khatiwala, Chirag B; Putnam, Andrew J

2007-01-01

The ability to harvest and maintain viable cells from mammalian tissues represented a critical advance in biomedical research, enabling individual cells to be cultured and studied in molecular detail. However, in these traditional cultures, cells are grown on rigid glass or polystyrene substrates, the mechanical properties of which often do not match those of the in vivo tissue from which the cells were originally derived. This mechanical mismatch likely contributes to abrupt changes in cellular phenotype. In fact, it has been proposed that mechanical changes in the cellular microenvironment may alone be responsible for driving specific cellular behaviors. Recent multidisciplinary efforts from basic scientists and engineers have begun to address this hypothesis more explicitly by probing the effects of ECM mechanics on cell and tissue function. Understanding the consequences of such mechanical changes is physiologically relevant in the context of a number of tissues in which altered mechanics may either correlate with or play an important role in the onset of pathology. Examples include changes in the compliance of blood vessels associated with atherosclerosis and intimal hyperplasia, as well as changes in the mechanical properties of developing tumors. Compelling evidence from 2-D in vitro model systems has shown that substrate mechanical properties induce changes in cell shape, migration, proliferation, and differentiation, but it remains to be seen whether or not these same effects translate to 3-D systems or in vivo. Furthermore, the molecular "mechanotransduction" mechanisms by which cells respond to changes in ECM mechanics remain unclear. Here, we provide some historical context for this emerging area of research, and discuss recent evidence that regulation of cytoskeletal tension by changes in ECM mechanics (either directly or indirectly) may provide a critical switch that controls cell function.

Tribbles pseudokinases: novel targets for chemical biology and drug discovery?

PubMed

Foulkes, Daniel M; Byrne, Dominic P; Bailey, Fiona P; Eyers, Patrick A

2015-10-01

Tribbles (TRIB) proteins are pseudokinase mediators of eukaryotic signalling that have evolved important roles in lipoprotein metabolism, immune function and cellular differentiation and proliferation. In addition, an evolutionary-conserved modulation of PI3K/AKT signalling pathways highlights them as novel and rather unusual pharmaceutical targets. The three human TRIB family members are uniquely defined by an acidic pseudokinase domain containing a 'broken' α C-helix and a MEK (MAPK/ERK)-binding site at the end of the putative C-lobe and a distinct C-terminal peptide motif that interacts directly with a small subset of cellular E3 ubiquitin ligases. This latter interaction drives proteasomal-dependent degradation of networks of transcription factors, whose rate of turnover determines the biological attributes of individual TRIB family members. Defining the function of individual Tribs has been made possible through evaluation of individual TRIB knockout mice, siRNA/overexpression approaches and genetic screening in flies, where the single TRIB gene was originally described 15 years ago. The rapidly maturing TRIB field is primed to exploit chemical biology approaches to evaluate endogenous TRIB signalling events in intact cells. This will help define how TRIB-driven protein-protein interactions and the atypical TRIB ATP-binding site, fit into cellular signalling modules in experimental scenarios where TRIB-signalling complexes remain unperturbed. In this mini-review, we discuss how small molecules can reveal rate-limiting signalling outputs and functions of Tribs in cells and intact organisms, perhaps serving as guides for the development of new drugs. We predict that appropriate small molecule TRIB ligands will further accelerate the transition of TRIB pseudokinase analysis into the mainstream of cell signalling. © 2015 Authors; published by Portland Press Limited.

A Novel Role of Proline Oxidase in HIV-1 Envelope Glycoprotein-induced Neuronal Autophagy*

PubMed Central

Pandhare, Jui; Dash, Sabyasachi; Jones, Bobby; Villalta, Fernando; Dash, Chandravanu

2015-01-01

Proline oxidase (POX) catalytically converts proline to pyrroline-5-carboxylate. This catabolic conversion generates reactive oxygen species (ROS) that triggers cellular signaling cascades including autophagy and apoptosis. This study for the first time demonstrates a role of POX in HIV-1 envelope glycoprotein (gp120)-induced neuronal autophagy. HIV-1 gp120 is a neurotoxic factor and is involved in HIV-1-associated neurological disorders. However, the mechanism of gp120-mediated neurotoxicity remains unclear. Using SH-SY5Y neuroblastoma cells as a model, this study demonstrates that gp120 treatment induced POX expression and catalytic activity. Concurrently, gp120 also increased intracellular ROS levels. However, increased ROS had a minimal effect on neuronal apoptosis. Further investigation indicated that the immediate cellular response to increased ROS paralleled with induction of autophagy markers, beclin-1 and LC3-II. These data lead to the hypothesis that neuronal autophagy is activated as a cellular protective response to the toxic effects of gp120. A direct and functional role of POX in gp120-mediated neuronal autophagy was examined by inhibition and overexpression studies. Inhibition of POX activity by a competitive inhibitor “dehydroproline” decreased ROS levels concomitant with reduced neuronal autophagy. Conversely, overexpression of POX in neuronal cells increased ROS levels and activated ROS-dependent autophagy. Mechanistic studies suggest that gp120 induces POX by targeting p53. Luciferase reporter assays confirm that p53 drives POX transcription. Furthermore, data demonstrate that gp120 induces p53 via binding to the CXCR4 co-receptor. Collectively, these results demonstrate a novel role of POX as a stress response metabolic regulator in HIV-1 gp120-associated neuronal autophagy. PMID:26330555

Interleukin-6 increases matrix metalloproteinase-14 (MMP-14) levels via down-regulation of p53 to drive cancer progression.

PubMed

Cathcart, Jillian M; Banach, Anna; Liu, Alice; Chen, Jun; Goligorsky, Michael; Cao, Jian

2016-09-20

Matrix metalloproteinases (MMPs) play critical roles in cancer invasion and metastasis by digesting basement membrane and extracellular matrix (ECM). Much attention has focused on the enzymatic activities of MMPs; however, the regulatory mechanism of MMP expression remains elusive. By employing bioinformatics analysis, we identified a potential p53 response element within the MMP-14 promoter. Experimentally, we found that p53 can repress MMP-14 promoter activity, whereas deletion of this p53 response element abrogated this effect. Furthermore, we found that p53 expression decreases MMP-14 mRNA and protein levels and attenuates MMP-14-mediated cellular functions. Additional promoter analysis and chromatin immunoprecipitation studies identified a mechanism of regulation of MMP-14 expression by which p53 and transcription factor Sp1 competitively bind to the promoter. As the correlation between inflammation and cancer aggressiveness is well described, we next sought to evaluate if inflammatory cytokines could differentially affect p53 and MMP-14 levels. We demonstrate that interleukin-6 (IL-6) down-regulates p53 protein levels and thus results in a concomitant increase in MMP-14 expression, leading to enhanced cancer cell invasion and metastasis. Our data collectively indicate a novel mechanism of regulation of MMP-14 by a cascade of IL-6 and p53, demonstrating that the tumor microenvironment directly stimulates molecular changes in cancer cells to drive an invasive phenotype.

BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon

PubMed Central

Farías, Ginny G.; Guardia, Carlos M.; De Pace, Raffaella; Britt, Dylan J.; Bonifacino, Juan S.

2017-01-01

The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes. PMID:28320970

BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon.

PubMed

Farías, Ginny G; Guardia, Carlos M; De Pace, Raffaella; Britt, Dylan J; Bonifacino, Juan S

2017-04-04

The ability of lysosomes to move within the cytoplasm is important for many cellular functions. This ability is particularly critical in neurons, which comprise vast, highly differentiated domains such as the axon and dendrites. The mechanisms that control lysosome movement in these domains, however, remain poorly understood. Here we show that an ensemble of BORC, Arl8, SKIP, and kinesin-1, previously shown to mediate centrifugal transport of lysosomes in nonneuronal cells, specifically drives lysosome transport into the axon, and not the dendrites, in cultured rat hippocampal neurons. This transport is essential for maintenance of axonal growth-cone dynamics and autophagosome turnover. Our findings illustrate how a general mechanism for lysosome dispersal in nonneuronal cells is adapted to drive polarized transport in neurons, and emphasize the importance of this mechanism for critical axonal processes.

In Vivo Biochemistry: Single-Cell Dynamics of Cyclic Di-GMP in Escherichia coli in Response to Zinc Overload.

PubMed

Yeo, Jongchan; Dippel, Andrew B; Wang, Xin C; Hammond, Ming C

2018-01-09

Intracellular signaling enzymes drive critical changes in cellular physiology and gene expression, but their endogenous activities in vivo remain highly challenging to study in real time and for individual cells. Here we show that flow cytometry can be performed in complex media to monitor single-cell population distributions and dynamics of cyclic di-GMP signaling, which controls the bacterial colonization program. These in vivo biochemistry experiments are enabled by our second-generation RNA-based fluorescent (RBF) biosensors, which exhibit high fluorescence turn-on in response to cyclic di-GMP. Specifically, we demonstrate that intracellular levels of cyclic di-GMP in Escherichia coli are repressed with excess zinc, but not with other divalent metals. Furthermore, in both flow cytometry and fluorescence microscopy setups, we monitor the dynamic increase in cellular cyclic di-GMP levels upon zinc depletion and show that this response is due to de-repression of the endogenous diguanylate cyclase DgcZ. In the presence of zinc, cells exhibit enhanced cell motility and increased sensitivity to antibiotics due to inhibited biofilm formation. Taken together, these results showcase the application of RBF biosensors in visualizing single-cell dynamic changes in cyclic di-GMP signaling in direct response to environmental cues such as zinc and highlight our ability to assess whether observed phenotypes are related to specific signaling enzymes and pathways.

Cell chirality: its origin and roles in left–right asymmetric development

PubMed Central

Inaki, Mikiko; Liu, Jingyang

2016-01-01

An item is chiral if it cannot be superimposed on its mirror image. Most biological molecules are chiral. The homochirality of amino acids ensures that proteins are chiral, which is essential for their functions. Chirality also occurs at the whole-cell level, which was first studied mostly in ciliates, single-celled protozoans. Ciliates show chirality in their cortical structures, which is not determined by genetics, but by ‘cortical inheritance’. These studies suggested that molecular chirality directs whole-cell chirality. Intriguingly, chirality in cellular structures and functions is also found in metazoans. In Drosophila, intrinsic cell chirality is observed in various left–right (LR) asymmetric tissues, and appears to be responsible for their LR asymmetric morphogenesis. In other invertebrates, such as snails and Caenorhabditis elegans, blastomere chirality is responsible for subsequent LR asymmetric development. Various cultured cells of vertebrates also show intrinsic chirality in their cellular behaviours and intracellular structural dynamics. Thus, cell chirality may be a general property of eukaryotic cells. In Drosophila, cell chirality drives the LR asymmetric development of individual organs, without establishing the LR axis of the whole embryo. Considering that organ-intrinsic LR asymmetry is also reported in vertebrates, this mechanism may contribute to LR asymmetric development across phyla. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821533

Cell chirality: its origin and roles in left-right asymmetric development.

PubMed

Inaki, Mikiko; Liu, Jingyang; Matsuno, Kenji

2016-12-19

An item is chiral if it cannot be superimposed on its mirror image. Most biological molecules are chiral. The homochirality of amino acids ensures that proteins are chiral, which is essential for their functions. Chirality also occurs at the whole-cell level, which was first studied mostly in ciliates, single-celled protozoans. Ciliates show chirality in their cortical structures, which is not determined by genetics, but by 'cortical inheritance'. These studies suggested that molecular chirality directs whole-cell chirality. Intriguingly, chirality in cellular structures and functions is also found in metazoans. In Drosophila, intrinsic cell chirality is observed in various left-right (LR) asymmetric tissues, and appears to be responsible for their LR asymmetric morphogenesis. In other invertebrates, such as snails and Caenorhabditis elegans, blastomere chirality is responsible for subsequent LR asymmetric development. Various cultured cells of vertebrates also show intrinsic chirality in their cellular behaviours and intracellular structural dynamics. Thus, cell chirality may be a general property of eukaryotic cells. In Drosophila, cell chirality drives the LR asymmetric development of individual organs, without establishing the LR axis of the whole embryo. Considering that organ-intrinsic LR asymmetry is also reported in vertebrates, this mechanism may contribute to LR asymmetric development across phyla.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Authors.

A multidimensional intergenerational model of young males' driving styles.

PubMed

Gil, Shani; Taubman-Ben-Ari, Orit; Toledo, Tomer

2016-12-01

This study examines the associations between fathers' driving styles, the family's general and driving-related atmosphere, and the young drivers' motivations, on one hand, and young males' driving styles, on the other. The 242 father and son pairs that participated in the study independently completed several self-report questionnaires at different points in time within the first year after licensure of the young drivers. A structural equation model (SEM) was developed, in which the contribution of fathers' driving style and their sons' perceptions of the general family relations, the family climate for road safety (FCRS), and costs and benefits of driving, to the driving styles of the young male drivers was examined. The SEM estimation results show direct as well as indirect significant effects between the various dimensions. The FCRS factors of non-commitment and messages, and the cost of thrill, were found to be the strongest mediators between the fathers' driving style and the family cohesion, on one hand, and the driving style of the young driver, on the other. These results may be useful in pointing out directions for the development of interventions that could assist in reducing the involvement of youngsters in risky driving and car crashes, and encourage safe and considerate driving. Copyright © 2016 Elsevier Ltd. All rights reserved.

Redox Regulation of Mitochondrial Function

PubMed Central

Handy, Diane E.

2012-01-01

Abstract Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323–1367. PMID:22146081

Pump impeller

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

Wickoren, D.R.

1990-02-27

This patent describes an impeller for pumping highly viscous liquids. It comprises: a substantially circular drive plate having first and second sides, a geometric center, and a marginal edge. The drive plate being adapted for rotation within a pump housing; a plurality of symmetrical, evenly spaced blades extending radially outwardly to present a tip. Each of the blades being connected only to the drive plate and extending substantially normal thereto to present a sharpened top edge opposite the drive plate. Each of the blades including a leading face corresponding to the direction of rotation of the impeller during operation andmore » a trailing face oriented away from a direction of rotation of the impeller during operation thereof. Each of the blades including winglet means secured to the leading face thereof and located intermediate aid top edge and the drive plate and positioned more proximate to the top edge than to the drive plate.« less

Comparison on driving fatigue related hemodynamics activated by auditory and visual stimulus

NASA Astrophysics Data System (ADS)

Deng, Zishan; Gao, Yuan; Li, Ting

2018-02-01

As one of the main causes of traffic accidents, driving fatigue deserves researchers' attention and its detection and monitoring during long-term driving require a new technique to realize. Since functional near-infrared spectroscopy (fNIRS) can be applied to detect cerebral hemodynamic responses, we can promisingly expect its application in fatigue level detection. Here, we performed three different kinds of experiments on a driver and recorded his cerebral hemodynamic responses when driving for long hours utilizing our device based on fNIRS. Each experiment lasted for 7 hours and one of the three specific experimental tests, detecting the driver's response to sounds, traffic lights and direction signs respectively, was done every hour. The results showed that visual stimulus was easier to cause fatigue compared with auditory stimulus and visual stimulus induced by traffic lights scenes was easier to cause fatigue compared with visual stimulus induced by direction signs in the first few hours. We also found that fatigue related hemodynamics caused by auditory stimulus increased fastest, then traffic lights scenes, and direction signs scenes slowest. Our study successfully compared audio, visual color, and visual character stimulus in sensitivity to cause driving fatigue, which is meaningful for driving safety management.

Progress in Direct-Drive Inertial Confinement Fusion

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

McCrory, R.L.; Meyerhofer, D.D.; Betti, R.

Significant progress in direct-drive inertial confinement fusion (ICF) research has been made since the completion of the 60-beam, 30-kJ UV OMEGA Laser System [T. R. Boehly, Opt. Commun. 133, 495 (1997)] in 1995. A theory of ignition requirements, applicable to any ICF concept, has been developed. Detailed understanding of laser-plasma coupling, electron thermal transport, and hot-electron preheating has lead to the measurement of neutron-averaged areal densities of ~200 mg/cm^2 in cryogenic target implosions. These correspond to an estimated peak fuel density in excess of 100 g/cm^3 and are in good agreement with hydrodynamic simulations. The implosions were performed using anmore » 18-kJ drive pulse designed to put the converging fuel on an adiabat of two. The polar-drive concept will allow direct-drive-ignition research on the National Ignition Facility while it is configured for indirect drive. Advanced ICF ignition concepts—fast ignition [Tabak et al., Phys. Plasmas 1, 1626 (1994)] and shock ignition [R. Betti et al., Phys. Rev. Lett. 98, 155001 (2007)]—have the potential to significantly reduce ignition driver energies and/or provide higher target gain.« less

Progress in direct-drive inertial confinement fusion

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

McCrory, R. L.; Meyerhofer, D. D.; Betti, R.

Significant progress in direct-drive inertial confinement fusion (ICF) research has been made since the completion of the 60-beam, 30-kJ{sub UV} OMEGA Laser System [Boehly, Opt. Commun. 133, 495 (1997)] in 1995. A theory of ignition requirements, applicable to any ICF concept, has been developed. Detailed understanding of laser-plasma coupling, electron thermal transport, and hot-electron preheating has lead to the measurement of neutron-averaged areal densities of {approx}200 mg/cm{sup 2} in cryogenic target implosions. These correspond to an estimated peak fuel density in excess of 100 g/cm{sup 3} and are in good agreement with hydrodynamic simulations. The implosions were performed using anmore » 18-kJ drive pulse designed to put the converging fuel on an adiabat of two. The polar-drive concept will allow direct-drive-ignition research on the National Ignition Facility while it is configured for indirect drive. Advanced ICF ignition concepts - fast ignition [Tabak et al., Phys. Plasmas 1, 1626 (1994)] and shock ignition [Betti et al., Phys. Rev. Lett. 98, 155001 (2007)] - have the potential to significantly reduce ignition driver energies and/or provide higher target gain.« less

Tilt assembly for tracking solar collector assembly

DOEpatents

Almy, Charles; Peurach, John; Sandler, Reuben

2012-01-24

A tilt assembly is used with a solar collector assembly of the type comprising a frame, supporting a solar collector, for movement about a tilt axis by pivoting a drive element between first and second orientations. The tilt assembly comprises a drive element coupler connected to the drive element and a driver, the driver comprising a drive frame, a drive arm and a drive arm driver. The drive arm is mounted to the drive frame for pivotal movement about a drive arm axis. Movement on the drive arm mimics movement of the drive element. Drive element couplers can extend in opposite directions from the outer portion of the drive arm, whereby the assembly can be used between adjacent solar collector assemblies in a row of solar collector assemblies.

Single-cell epigenomics: techniques and emerging applications.

PubMed

Schwartzman, Omer; Tanay, Amos

2015-12-01

Epigenomics is the study of the physical modifications, associations and conformations of genomic DNA sequences, with the aim of linking these with epigenetic memory, cellular identity and tissue-specific functions. While current techniques in the field are characterizing the average epigenomic features across large cell ensembles, the increasing interest in the epigenetics within complex and heterogeneous tissues is driving the development of single-cell epigenomics. We review emerging single-cell methods for capturing DNA methylation, chromatin accessibility, histone modifications, chromosome conformation and replication dynamics. Together, these techniques are rapidly becoming a powerful tool in studies of cellular plasticity and diversity, as seen in stem cells and cancer.

GENERAL: A modified weighted probabilistic cellular automaton traffic flow model

NASA Astrophysics Data System (ADS)

Zhuang, Qian; Jia, Bin; Li, Xin-Gang

2009-08-01

This paper modifies the weighted probabilistic cellular automaton model (Li X L, Kuang H, Song T, et al 2008 Chin. Phys. B 17 2366) which considered a diversity of traffic behaviors under real traffic situations induced by various driving characters and habits. In the new model, the effects of the velocity at the last time step and drivers' desire for acceleration are taken into account. The fundamental diagram, spatial-temporal diagram, and the time series of one-minute data are analyzed. The results show that this model reproduces synchronized flow. Finally, it simulates the on-ramp system with the proposed model. Some characteristics including the phase diagram are studied.

Alcohol & drug use among drivers : British Columbia roadside survey 2008

DOT National Transportation Integrated Search

2009-01-01

Following two decades of progress dealing with alcoholimpaired : driving, greater attention is now being : directed toward the issue of driving while impaired by : drugs. Currently, there is far less information related to drug-impaired : driving tha...

Magnus-induced dynamics of driven skyrmions on a quasi-one-dimensional periodic substrate

DOE PAGES

Reichhardt, Charles; Reichhardt, Cynthia Jane

2016-09-13

Here we numerically examine driven skyrmions interacting with a periodic quasi-one-dimensional substrate where the driving force is applied either parallel or perpendicular to the substrate periodicity direction. For perpendicular driving, the particles in a purely overdamped system simply slide along the substrate minima; however, for skyrmions where the Magnus force is relevant, we find that a rich variety of dynamics can arise. In the single skyrmion limit, the skyrmion motion is locked along the driving or longitudinal direction for low drives, while at higher drives a transition occurs to a state in which the skyrmion moves both transverse and longitudinalmore » to the driving direction. Within the longitudinally locked phase we find a pronounced speedup effect that occurs when the Magnus force aligns with the external driving force, while at the transition to transverse and longitudinal motion, the skyrmion velocity drops, producing negative differential conductivity. For collectively interacting skyrmion assemblies, the speedup effect is still present and we observe a number of distinct dynamical phases, including a sliding smectic phase, a disordered or moving liquid phase, a moving hexatic phase, and a moving crystal phase. The transitions between the dynamic phases produce distinct features in the structure of the skyrmion lattice and in the velocity-force curves. Lastly, we map these different phases as a function of the ratio of the Magnus term to the dissipative term, the substrate strength, the commensurability ratio, and the magnitude of the driving force.« less

Magnus-induced dynamics of driven skyrmions on a quasi-one-dimensional periodic substrate

NASA Astrophysics Data System (ADS)

Reichhardt, C.; Reichhardt, C. J. Olson

2016-09-01

We numerically examine driven skyrmions interacting with a periodic quasi-one-dimensional substrate where the driving force is applied either parallel or perpendicular to the substrate periodicity direction. For perpendicular driving, the particles in a purely overdamped system simply slide along the substrate minima; however, for skyrmions where the Magnus force is relevant, we find that a rich variety of dynamics can arise. In the single skyrmion limit, the skyrmion motion is locked along the driving or longitudinal direction for low drives, while at higher drives a transition occurs to a state in which the skyrmion moves both transverse and longitudinal to the driving direction. Within the longitudinally locked phase we find a pronounced speedup effect that occurs when the Magnus force aligns with the external driving force, while at the transition to transverse and longitudinal motion, the skyrmion velocity drops, producing negative differential conductivity. For collectively interacting skyrmion assemblies, the speedup effect is still present and we observe a number of distinct dynamical phases, including a sliding smectic phase, a disordered or moving liquid phase, a moving hexatic phase, and a moving crystal phase. The transitions between the dynamic phases produce distinct features in the structure of the skyrmion lattice and in the velocity-force curves. We map these different phases as a function of the ratio of the Magnus term to the dissipative term, the substrate strength, the commensurability ratio, and the magnitude of the driving force.

Transparent metal model study of the use of a cellular growth front to form aligned monotectic composite materials

NASA Technical Reports Server (NTRS)

Kaukler, William F.

1988-01-01

The purpose of this work was to resolve a scientific controversy in the understanding of how second phase particles become aligned during unidirectional growth of a monotectic alloy. A second aspect was to make the first systematic observations of the solidification behavior of a monotectic alloy during cellular growth in-situ. This research provides the first systematic transparent model study of cellular solidification. An interface stability diagram was developed for the planar to cellular transition of the succinonitrile glycerol (SNG) system. A method was developed utilizing Fourier Transform Infrared Spectroscopy which allows quantitative compositional analysis of directionally solidified SNG along the growth axis. To determine the influence of cellular growth front on alignment for directionally solidified monotectic alloys, the planar and cellular growth morphology was observed in-situ for SNG between 8 and 17 percent glycerol and for a range of over two orders of magnitude G/R.

Sensorless optimal sinusoidal brushless direct current for hard disk drives

NASA Astrophysics Data System (ADS)

Soh, C. S.; Bi, C.

2009-04-01

Initiated by the availability of digital signal processors and emergence of new applications, market demands for permanent magnet synchronous motors have been surging. As its back-emf is sinusoidal, the drive current should also be sinusoidal for reducing the torque ripple. However, in applications like hard disk drives, brushless direct current (BLDC) drive is adopted instead of sinusoidal drive for simplification. The adoption, however, comes at the expense of increased harmonics, losses, torque pulsations, and acoustics. In this paper, we propose a sensorless optimal sinusoidal BLDC drive. First and foremost, the derivation for an optimal sinusoidal drive is presented, and a power angle control scheme is proposed to achieve an optimal sinusoidal BLDC. The scheme maintains linear relationship between the motor speed and drive voltage. In an attempt to execute the sensorless drive, an innovative power angle measurement scheme is devised, which takes advantage of the freewheeling diodes and measures the power angle through the detection of diode voltage drops. The objectives as laid out will be presented and discussed in this paper, supported by derivations, simulations, and experimental results. The proposed scheme is straightforward, brings about the benefits of sensorless sinusoidal drive, negates the need for current sensors by utilizing the freewheeling diodes, and does not incur additional cost.

Hybrid indirect-drive/direct-drive target for inertial confinement fusion

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

Perkins, Lindsay John

A hybrid indirect-drive/direct drive for inertial confinement fusion utilizing laser beams from a first direction and laser beams from a second direction including a central fusion fuel component; a first portion of a shell surrounding said central fusion fuel component, said first portion of a shell having a first thickness; a second portion of a shell surrounding said fusion fuel component, said second portion of a shell having a second thickness that is greater than said thickness of said first portion of a shell; and a hohlraum containing at least a portion of said fusion fuel component and at leastmore » a portion of said first portion of a shell; wherein said hohlraum is in a position relative to said first laser beam and to receive said first laser beam and produce X-rays that are directed to said first portion of a shell and said fusion fuel component; and wherein said fusion fuel component and said second portion of a shell are in a position relative to said second laser beam such that said second portion of a shell and said fusion fuel component receive said second laser beam.« less

Exposure to Movie Reckless Driving in Early Adolescence Predicts Reckless, but Not Inattentive Driving.

PubMed

Kostermans, Evelien; Stoolmiller, Mike; de Leeuw, Rebecca N H; Engels, Rutger C M E; Sargent, James D

2014-01-01

We examine the association between exposure to depictions of reckless driving in movies and unsafe driving, modeling inattentive and reckless driving as separate outcomes. Data were obtained by telephone from 1,630 US adolescents aged 10 to 14 years at baseline who were drivers at a survey 6 years later. Exposure to movie reckless driving was measured based on movies seen from a randomly selected list of 50 movie titles that had been content coded for reckless driving among characters. Associations were tested with inattentive and reckless driving behaviors in the subsequent survey-controlling for baseline age, sex, socioeconomic status, parental education, school performance, extracurricular activities, daily television and video/computer game exposure, number of movies watched per week, self-regulation and sensation seeking. Exposure to movie reckless driving was common, with approximately 10% of movie characters having driven recklessly. Confirmatory factor analysis revealed a significant distinction between items tapping reckless and inattentive driving at the 6th wave. Age and exposure to movie reckless driving at baseline were directly associated with wave-6 reckless (but not inattentive) driving. Additionally, growth in sensation seeking mediated a prospective relation between the total number of movies watched per week at baseline and reckless driving, independent of exposure to movie reckless driving. Males and high sensation seekers reported lower seatbelt usage and more reckless driving, whereas lower self-regulation predicted inattentive driving. In this study, exposure to movie reckless driving during early adolescence predicted adolescents' reckless driving, suggesting a direct modeling effect. Other aspects of movies were also associated with reckless driving, with that association mediated through growth in sensation seeking. Predictors of reckless driving were different from predictors of inattentive driving, with lower self-regulation associated with the latter outcome. Making a clear distinction between interventions for reckless or inattentive driving seems crucial for accident prevention.

Exposure to Movie Reckless Driving in Early Adolescence Predicts Reckless, but Not Inattentive Driving

PubMed Central

Kostermans, Evelien; Stoolmiller, Mike; de Leeuw, Rebecca N. H.; Engels, Rutger C. M. E.; Sargent, James D.

2014-01-01

Objective We examine the association between exposure to depictions of reckless driving in movies and unsafe driving, modeling inattentive and reckless driving as separate outcomes. Methods Data were obtained by telephone from 1,630 US adolescents aged 10 to 14 years at baseline who were drivers at a survey 6 years later. Exposure to movie reckless driving was measured based on movies seen from a randomly selected list of 50 movie titles that had been content coded for reckless driving among characters. Associations were tested with inattentive and reckless driving behaviors in the subsequent survey–controlling for baseline age, sex, socioeconomic status, parental education, school performance, extracurricular activities, daily television and video/computer game exposure, number of movies watched per week, self-regulation and sensation seeking. Results Exposure to movie reckless driving was common, with approximately 10% of movie characters having driven recklessly. Confirmatory factor analysis revealed a significant distinction between items tapping reckless and inattentive driving at the 6th wave. Age and exposure to movie reckless driving at baseline were directly associated with wave-6 reckless (but not inattentive) driving. Additionally, growth in sensation seeking mediated a prospective relation between the total number of movies watched per week at baseline and reckless driving, independent of exposure to movie reckless driving. Males and high sensation seekers reported lower seatbelt usage and more reckless driving, whereas lower self-regulation predicted inattentive driving. Discussion In this study, exposure to movie reckless driving during early adolescence predicted adolescents’ reckless driving, suggesting a direct modeling effect. Other aspects of movies were also associated with reckless driving, with that association mediated through growth in sensation seeking. Predictors of reckless driving were different from predictors of inattentive driving, with lower self-regulation associated with the latter outcome. Making a clear distinction between interventions for reckless or inattentive driving seems crucial for accident prevention. PMID:25493323

Altered Cellular Metabolism Drives Trained Immunity.

PubMed

Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

2018-04-04

Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

75 FR 27672 - Restrictions on Railroad Operating Employees' Use of Cellular Telephones and Other Electronic...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... by any of the following methods: Federal eRulemaking Portal: Go to http://www.Regulations.gov... while driving. In addition to hosting the Summit, DOT has reviewed recent research and has decided to... conclusions with respect to the involvement of driver distraction in causing a crash. A 2008 research paper...

Embryonic ring closure: Actomyosin rings do the two-step

PubMed Central

2016-01-01

Actomyosin rings drive numerous closure processes, but the mechanisms by which they contract are still poorly understood. In this issue, Xue and Sokac (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201608025) show that actomyosin ring closure during Drosophila melanogaster cellularization uses two steps, only one of which involves Myosin-2. PMID:27799371

Effect of the temperature-rate parameters of directional solidification on the structure formation in high-temperature materials

NASA Astrophysics Data System (ADS)

Svetlov, I. L.; Neiman, A. V.

2017-03-01

The effect of the temperature gradient and the crystal growth rate on the structure formation in nickel and niobium superalloys is studied under the conditions of the flat, cellular, dendritic, or dendritic-cellular configuration of a solidification front during directional solidification.

Texting while driving: the development and validation of the distracted driving survey and risk score among young adults.

PubMed

Bergmark, Regan W; Gliklich, Emily; Guo, Rong; Gliklich, Richard E

Texting while driving and other cell-phone reading and writing activities are high-risk activities associated with motor vehicle collisions and mortality. This paper describes the development and preliminary evaluation of the Distracted Driving Survey (DDS) and score. Survey questions were developed by a research team using semi-structured interviews, pilot-tested, and evaluated in young drivers for validity and reliability. Questions focused on texting while driving and use of email, social media, and maps on cellular phones with specific questions about the driving speeds at which these activities are performed. In 228 drivers 18-24 years old, the DDS showed excellent internal consistency (Cronbach's alpha = 0.93) and correlations with reported 12-month crash rates. The score is reported on a 0-44 scale with 44 being highest risk behaviors. For every 1 unit increase of the DDS score, the odds of reporting a car crash increases 7 %. The survey can be completed in two minutes, or less than five minutes if demographic and background information is included. Text messaging was common; 59.2 and 71.5 % of respondents said they wrote and read text messages, respectively, while driving in the last 30 days. The DDS is an 11-item scale that measures cell phone-related distracted driving risk and includes reading/viewing and writing subscores. The scale demonstrated strong validity and reliability in drivers age 24 and younger. The DDS may be useful for measuring rates of cell-phone related distracted driving and for evaluating public health interventions focused on reducing such behaviors.

Texting while driving: the development and validation of the distracted driving survey and risk score among young adults.

PubMed

Bergmark, Regan W; Gliklich, Emily; Guo, Rong; Gliklich, Richard E

2016-12-01

Texting while driving and other cell-phone reading and writing activities are high-risk activities associated with motor vehicle collisions and mortality. This paper describes the development and preliminary evaluation of the Distracted Driving Survey (DDS) and score. Survey questions were developed by a research team using semi-structured interviews, pilot-tested, and evaluated in young drivers for validity and reliability. Questions focused on texting while driving and use of email, social media, and maps on cellular phones with specific questions about the driving speeds at which these activities are performed. In 228 drivers 18-24 years old, the DDS showed excellent internal consistency (Cronbach's alpha = 0.93) and correlations with reported 12-month crash rates. The score is reported on a 0-44 scale with 44 being highest risk behaviors. For every 1 unit increase of the DDS score, the odds of reporting a car crash increases 7 %. The survey can be completed in two minutes, or less than five minutes if demographic and background information is included. Text messaging was common; 59.2 and 71.5 % of respondents said they wrote and read text messages, respectively, while driving in the last 30 days. The DDS is an 11-item scale that measures cell phone-related distracted driving risk and includes reading/viewing and writing subscores. The scale demonstrated strong validity and reliability in drivers age 24 and younger. The DDS may be useful for measuring rates of cell-phone related distracted driving and for evaluating public health interventions focused on reducing such behaviors.

Analysis of the effect of older drivers’ driving behaviors on traffic flow based on a modified CA model

NASA Astrophysics Data System (ADS)

Jian, Mei-Ying; Shi, Jing; Liu, Yang

2016-09-01

As the global population ages, there are more and more older drivers on the road. The decline in driving performance of older drivers may influence the properties of traffic flow and safety. The purpose of this paper is to investigate the effect of older drivers’ driving behaviors on traffic flow. A modified cellular automaton (CA) model which takes driving behaviors of older drivers into account is proposed. The simulation results indicate that older drivers’ driving behaviors induce a reduction in traffic flow especially when the density is higher than 15 vehicles per km per lane and an increase in Lane-changing frequency. The analysis of stability shows that a number of disturbances could frequently emerge, be propagated and eventually dissipate in this modified model. The results also reflect that with the increase of older drivers on the road, the probability of the occurrence of rear-end collisions increases greatly and obviously. Furthermore, the value of acceleration influences the traffic flow and safety significantly. These results provide the theoretical basis and reference for the traffic management departments to develop traffic management measure in the aging society.

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors.

PubMed

Trigos, Anna S; Pearson, Richard B; Papenfuss, Anthony T; Goode, David L

2017-06-13

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

PubMed Central

Trigos, Anna S.; Pearson, Richard B.; Papenfuss, Anthony T.; Goode, David L.

2017-01-01

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer. PMID:28484005

Robust spherical direct-drive design for NI

NASA Astrophysics Data System (ADS)

Masse, Laurent; Hurricane, O.; Michel, P.; Nora, R.; Tabak, M.; Lawrence Livermore Natl Lab Team

2016-10-01

Achieving ignition in a direct-drive or indirect-drive cryogenic implosion is a tremendous challenge. Both approaches need to deal with physic and technologic issues. During the past years, the indirect drive effort on the National Ignition Facility (NIF) has revealed unpredicted lost of performances that force to think to more robust designs and to dig into detailed physics aspects. Encouraging results have been obtained using a strong first shock during the implosion of CH ablator ignition capsules. These ``high-foot'' implosion results in a significantly lower ablation Rayleigh-Taylor instability growth than that of the NIC point design capsule. The trade-off with this design is a higher fuel adiabat that limits both fuel compression and theoretical capsule yield. The purpose of designing this capsule is to recover a more ideal one-dimensional implosion that is in closer agreement to simulation predictions. In the same spirit of spending energy on margin, at the coast of decreased performance, we are presenting here a study on ``robust'' spherical direct drive design for NIF. This 2-Shock direct drive pulse shape results in a high adiabat (>3) and low convergence (<17) implosion designed to produce a near 1D-like implosion. We take a particular attention to design a robust implosion with respect to long-wavelength non uniformity seeded by power imbalance and target offset. This work was performed under the auspices of the Lawrence Livermore National Security, LLC, (LLNS) under Contract No. DE-AC52-07NA27344.

Laser-plasma interactions in direct-drive ignition plasmas

NASA Astrophysics Data System (ADS)

Froula, D. H.; Michel, D. T.; Igumenshchev, I. V.; Hu, S. X.; Yaakobi, B.; Myatt, J. F.; Edgell, D. H.; Follett, R.; Glebov, V. Yu; Goncharov, V. N.; Kessler, T. J.; Maximov, A. V.; Radha, P. B.; Sangster, T. C.; Seka, W.; Short, R. W.; Solodov, A. A.; Sorce, C.; Stoeckl, C.

2012-12-01

Direct-drive ignition is most susceptible to multiple-beam laser-plasma instabilities, as the single-beam intensities are low (Is ˜ 1014 W cm-2) and the electron temperature in the underdense plasma is high (Te ≃ 3.5 keV). Cross-beam energy transfer is driven by multiple laser beams and can significantly reduce the hydrodynamic efficiency in direct-drive experiments on OMEGA (Boehly et al 1997 Opt. Commun. 133 495). Reducing the radii of the laser beams significantly increases the hydrodynamic efficiency at the cost of an increase in the low-mode modulations. Initial 2D hydrodynamic simulations indicate that zooming, transitioning the laser-beam radius prior to the main drive, does not increase low-mode nonuniformities. The combination of zooming and dynamic bandwidth reduction will provide a 30% effective increase in the drive energy on OMEGA direct-drive implosions. It was shown that two-plasmon decay (TPD) can be driven by multiple laser beams and both planar and spherical experiments were performed to study the hot electrons generated by TPD. The fraction of laser energy converted to hot electrons scales with the hot-electron temperature for all geometries and over a wide range of intensities. At ignition-relevant intensities, the fraction of laser energy converted to hot electrons is measured to decrease by an order of magnitude when the ablator material is changed from carbon-hydrogen to aluminum. The TPD results are compared with a multiple-beam linear theory and a nonlinear Zakharov model.

TFT-Directed Electroplating of RGB Luminescent Films without a Vacuum or Mask toward a Full-Color AMOLED Pixel Matrix.

PubMed

Wang, Rong; Zhang, Donglian; Xiong, You; Zhou, Xuehong; Liu, Cao; Chen, Weifeng; Wu, Weijing; Zhou, Lei; Xu, Miao; Wang, Lei; Liu, Linlin; Peng, Junbiao; Ma, Yuguang; Cao, Yong

2018-05-30

The thin-film transistor (TFT) driving circuit is a separate electronic component embedded within the panel itself to switch the current for each pixel in active-matrix organic light-emitting diode displays. We reported a TFT-directed dye electroplating method to fabricate pixels; this would be a new method to deposit films on prepatterned electrode for organic full-color display, where TFT driving circuit provide a switching current signal to drive and direct dye depositing on selected RGB pixels. A prototype patterned color pixel matrix was achieved, as high-quality light-emitting films with uniform morphology, pure RGB chromaticity, and stable output.

Hydrodynamic simulations of long-scale-length plasmas for two-plasmon-decay planar-target experiments on the NIF

NASA Astrophysics Data System (ADS)

Solodov, A. A.; Rosenberg, M. J.; Myatt, J. F.; Epstein, R.; Regan, S. P.; Seka, W.; Shaw, J.; Hohenberger, M.; Bates, J. W.; Moody, J. D.; Ralph, J. E.; Turnbull, D. P.; Barrios, M. A.

2016-05-01

The two-plasmon-decay (TPD) instability can be detrimental for direct-drive inertial confinement fusion because it generates high-energy electrons that can preheat the target, thereby reducing target performance. Hydrodynamic simulations to design a new experimental platform to investigate TPD and other laser-plasma instabilities relevant to direct-drive-ignition implosions at the National Ignition Facility are presented. The proposed experiments utilize planar plastic targets with an embedded Mo layer to characterize generation of hot electrons through Mo Kα fluorescence and hard x-ray emission. Different laser-irradiation geometries approximate conditions near both the equator and the pole of a polar-direct-drive implosion.

TAL Performance and Mission Analysis in a CDL Capacitor Powered Direct-Drive Configuration

NASA Technical Reports Server (NTRS)

Hrbud, Ivana; Rose, M. Frank; Oleson, Steve R.; Jenkins, Rhonald M.

1999-01-01

The goals of this research are (1) to prove the concept feasibility of a direct-drive electric propulsion system, and (2) to evaluate the performance and characteristics of a Russian TAL (Thruster with Anode Layer) operating in a long-pulse mode, powered by a capacitor-based power source developed at Space Power Institute. The TAL, designated D-55, is characterized by an external acceleration zone and is powered by a unique chemical double layer (CDL) capacitor bank with a capacitance of 4 F at a charge voltage of 400 V. Performance testing of this power supply on the TAL was conducted at NASA Lewis Research Center in Cleveland, OH. Direct thrust measurements of the TAL were obtained at CDL power levels ranging from 450 to 1750 W. The specific impulse encompassed a range from 1150 s to 2200 s, yielding thruster system efficiencies between 50 and 60%. Preliminary mission analysis of the CDL direct-drive concept and other electric propulsion options was performed for the ORACLE spacecraft in 6am/6pm and 12am/12pm, 300 km sun-synchronous orbits. The direct-drive option was competitive with the other systems by increasing available net mass between 5 and 42% and reducing two-year system wet mass between 18 and 63%. Overall, the electric propulsion power requirements for the satellite solar array were reduced between 57 and 91% depending oil the orbit evaluated The direct-drive, CDL capacitor-based concept in electric propulsion thus promises to be a highly-efficient, viable alternative for satellite operations in specific near-Earth missions.

CellNet: Network Biology Applied to Stem Cell Engineering

PubMed Central

Cahan, Patrick; Li, Hu; Morris, Samantha A.; da Rocha, Edroaldo Lummertz; Daley, George Q.; Collins, James J.

2014-01-01

SUMMARY Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population, and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. PMID:25126793

Signal transduction in a covalent post-assembly modification cascade

NASA Astrophysics Data System (ADS)

Pilgrim, Ben S.; Roberts, Derrick A.; Lohr, Thorsten G.; Ronson, Tanya K.; Nitschke, Jonathan R.

2017-12-01

Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels-Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels-Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes.

Vpr Promotes Macrophage-Dependent HIV-1 Infection of CD4+ T Lymphocytes

PubMed Central

Collins, David R.; Lubow, Jay; Lukic, Zana; Mashiba, Michael; Collins, Kathleen L.

2015-01-01

Vpr is a conserved primate lentiviral protein that promotes infection of T lymphocytes in vivo by an unknown mechanism. Here we demonstrate that Vpr and its cellular co-factor, DCAF1, are necessary for efficient cell-to-cell spread of HIV-1 from macrophages to CD4+ T lymphocytes when there is inadequate cell-free virus to support direct T lymphocyte infection. Remarkably, Vpr functioned to counteract a macrophage-specific intrinsic antiviral pathway that targeted Env-containing virions to LAMP1+ lysosomal compartments. This restriction of Env also impaired virological synapses formed through interactions between HIV-1 Env on infected macrophages and CD4 on T lymphocytes. Treatment of infected macrophages with exogenous interferon-alpha induced virion degradation and blocked synapse formation, overcoming the effects of Vpr. These results provide a mechanism that helps explain the in vivo requirement for Vpr and suggests that a macrophage-dependent stage of HIV-1 infection drives the evolutionary conservation of Vpr. PMID:26186441

Entropic forces drive contraction of cytoskeletal networks.

PubMed

Braun, Marcus; Lansky, Zdenek; Hilitski, Feodor; Dogic, Zvonimir; Diez, Stefan

2016-05-01

The cytoskeleton is a network of interconnected protein filaments, which provide a three-dimensional scaffold for cells. Remodeling of the cytoskeleton is important for key cellular processes, such as cell motility, division, or morphogenesis. This remodeling is traditionally considered to be driven exclusively by processes consuming chemical energy, such as the dynamics of the filaments or the action of molecular motors. Here, we review two mechanisms of cytoskeletal network remodeling that are independent of the consumption of chemical energy. In both cases directed motion of overlapping filaments is driven by entropic forces, which arise from harnessing thermal energy present in solution. Entropic forces are induced either by macromolecular crowding agents or by diffusible crosslinkers confined to the regions where filaments overlap. Both mechanisms increase filament overlap length and lead to the contraction of filament networks. These force-generating mechanisms, together with the chemical energy-dependent mechanisms, need to be considered for the comprehensive quantitative picture of the remodeling of cytoskeletal networks in cells. © 2016 WILEY Periodicals, Inc.

Long-term evolution of viruses: A Janus-faced balance.

PubMed

Nasir, Arshan; Kim, Kyung Mo; Caetano-Anollés, Gustavo

2017-08-01

The popular textbook image of viruses as noxious and selfish genetic parasites greatly underestimates the beneficial contributions of viruses to the biosphere. Given the crucial dependency of viruses to reproduce in an intracellular environment, viruses that engage in excessive killing (lysis) can drive their cellular hosts to extinction and will not survive. The lytic mode of virus propagation must, therefore, be tempered and balanced by non-lytic modes of virus latency and symbiosis. Here, we review recent bioinformatics and metagenomic studies to argue that viral endogenization and domestication may be more frequent mechanisms of virus persistence than lysis. We use a triangle diagram to explain the three major virus persistence strategies that explain the global scope of virus-cell interactions including lysis, latency and virus-cell symbiosis. This paradigm can help identify novel directions in virology research where scientists could artificially gain control over switching lytic and beneficial viral lifestyles. Also see the Video Abstract: http://youtu.be/GwXWz4N8o8. © 2017 WILEY Periodicals, Inc.

Myosin-II controls cellular branching morphogenesis and migration in 3D by minimizing cell surface curvature

PubMed Central

Elliott, Hunter; Fischer, Robert A.; Myers, Kenneth A.; Desai, Ravi A.; Gao, Lin; Chen, Christopher S.; Adelstein, Robert; Waterman, Clare M.; Danuser, Gaudenz

2014-01-01

In many cases cell function is intimately linked to cell shape control. We utilized endothelial cell branching morphogenesis as a model to understand the role of myosin-II in shape control of invasive cells migrating in 3D collagen gels. We applied principles of differential geometry and mathematical morphology to 3D image sets to parameterize cell branch structure and local cell surface curvature. We find that Rho/ROCK-stimulated myosin-II contractility minimizes cell-scale branching by recognizing and minimizing local cell surface curvature. Utilizing micro-fabrication to constrain cell shape identifies a positive feedback mechanism in which low curvature stabilizes myosin-II cortical association, where it acts to maintain minimal curvature. The feedback between myosin-II regulation by and control of curvature drives cycles of localized cortical myosin-II assembly and disassembly. These cycles in turn mediate alternating phases of directionally biased branch initiation and retraction to guide 3D cell migration. PMID:25621949

Towards artificial tissue models: past, present, and future of 3D bioprinting.

PubMed

Arslan-Yildiz, Ahu; El Assal, Rami; Chen, Pu; Guven, Sinan; Inci, Fatih; Demirci, Utkan

2016-03-01

Regenerative medicine and tissue engineering have seen unprecedented growth in the past decade, driving the field of artificial tissue models towards a revolution in future medicine. Major progress has been achieved through the development of innovative biomanufacturing strategies to pattern and assemble cells and extracellular matrix (ECM) in three-dimensions (3D) to create functional tissue constructs. Bioprinting has emerged as a promising 3D biomanufacturing technology, enabling precise control over spatial and temporal distribution of cells and ECM. Bioprinting technology can be used to engineer artificial tissues and organs by producing scaffolds with controlled spatial heterogeneity of physical properties, cellular composition, and ECM organization. This innovative approach is increasingly utilized in biomedicine, and has potential to create artificial functional constructs for drug screening and toxicology research, as well as tissue and organ transplantation. Herein, we review the recent advances in bioprinting technologies and discuss current markets, approaches, and biomedical applications. We also present current challenges and provide future directions for bioprinting research.

Reverse transduction measured in the living cochlea by low-coherence heterodyne interferometry.

PubMed

Ren, Tianying; He, Wenxuan; Barr-Gillespie, Peter G

2016-01-06

It is generally believed that the remarkable sensitivity and frequency selectivity of mammalian hearing depend on outer hair cell-generated force, which amplifies sound-induced vibrations inside the cochlea. This 'reverse transduction' force production has never been demonstrated experimentally, however, in the living ear. Here by directly measuring microstructure vibrations inside the cochlear partition using a custom-built interferometer, we demonstrate that electrical stimulation can evoke both fast broadband and slow sharply tuned responses of the reticular lamina, but only a slow tuned response of the basilar membrane. Our results indicate that outer hair cells can generate sufficient force to drive the reticular lamina over all audible frequencies in living cochleae. Contrary to expectations, the cellular force causes a travelling wave rather than an immediate local vibration of the basilar membrane; this travelling wave vibrates in phase with the reticular lamina at the best frequency, and results in maximal vibration at the apical ends of outer hair cells.

Colloidal inverse bicontinuous cubic membranes of block copolymers with tunable surface functional groups

NASA Astrophysics Data System (ADS)

La, Yunju; Park, Chiyoung; Shin, Tae Joo; Joo, Sang Hoon; Kang, Sebyung; Kim, Kyoung Taek

2014-06-01

Analogous to the complex membranes found in cellular organelles, such as the endoplasmic reticulum, the inverse cubic mesophases of lipids and their colloidal forms (cubosomes) possess internal networks of water channels arranged in crystalline order, which provide a unique nanospace for membrane-protein crystallization and guest encapsulation. Polymeric analogues of cubosomes formed by the direct self-assembly of block copolymers in solution could provide new polymeric mesoporous materials with a three-dimensionally organized internal maze of large water channels. Here we report the self-assembly of amphiphilic dendritic-linear block copolymers into polymer cubosomes in aqueous solution. The presence of precisely defined bulky dendritic blocks drives the block copolymers to form spontaneously highly curved bilayers in aqueous solution. This results in the formation of colloidal inverse bicontinuous cubic mesophases. The internal networks of water channels provide a high surface area with tunable surface functional groups that can serve as anchoring points for large guests such as proteins and enzymes.

Systems Chronobiology: Global Analysis of Gene Regulation in a 24-Hour Periodic World.

PubMed

Mermet, Jérôme; Yeung, Jake; Naef, Felix

2017-03-01

Mammals have evolved an internal timing system, the circadian clock, which synchronizes physiology and behavior to the daily light and dark cycles of the Earth. The master clock, located in the suprachiasmatic nucleus (SCN) of the brain, takes fluctuating light input from the retina and synchronizes other tissues to the same internal rhythm. The molecular clocks that drive these circadian rhythms are ticking in nearly all cells in the body. Efforts in systems chronobiology are now being directed at understanding, on a comprehensive scale, how the circadian clock controls different layers of gene regulation to provide robust timing cues at the cellular and tissue level. In this review, we introduce some basic concepts underlying periodicity of gene regulation, and then highlight recent genome-wide investigations on the propagation of rhythms across multiple regulatory layers in mammals, all the way from chromatin conformation to protein accumulation. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Effects of electromagnetic radiation of mobile phones on the central nervous system.

PubMed

Hossmann, K-A; Hermann, D M

2003-01-01

With the increasing use of mobile communication, concerns have been expressed about the possible interactions of electromagnetic radiation with the human organism and, in particular, the brain. The effects on neuronal electrical activity, energy metabolism, genomic responses, neurotransmitter balance, blood-brain barrier permeability, cognitive function, sleep, and various brain diseases including brain tumors are reviewed. Most of the reported effects are small as long as the radiation intensity remains in the nonthermal range, and none of the research reviewed gives an indication of the mechanisms involved at this range. However, health risks may evolve from indirect consequences of mobile telephony, such as the sharply increased incidence rate of traffic accidents caused by telephony during driving, and possibly also by stress reactions which annoyed bystanders may experience when cellular phones are used in public places. These indirect health effects presumably outweigh the direct biological perturbations and should be investigated in more detail in the future. Copyright 2002 Wiley-Liss, Inc.

Real-time intravital microscopy of individual nanoparticle dynamics in liver and tumors of live mice

PubMed Central

van de Ven, Anne L; Kim, Pilhan; Ferrari, Mauro; Yun, Seok Hyun

2013-01-01

Intravital microscopy is emerging as an important experimental tool for the research and development of multi-functional therapeutic nanoconstructs. The direct visualization of nanoparticle dynamics within live animals provides invaluable insights into the mechanisms that regulate nanotherapeutics transport and cell-particle interactions. Here we present a protocol to image the dynamics of nanoparticles within the liver and tumors of live mice immediately following systemic injection using a high-speed (30-400 fps) confocal or multi-photon laser-scanning fluorescence microscope. Techniques for quantifying the real-time accumulation and cellular association of individual particles with a size ranging from several tens of nanometers to micrometers are described, as well as an experimental strategy for labeling Kupffer cells in the liver in vivo. Experimental design considerations and controls are provided, as well as minimum equipment requirements. The entire protocol takes approximately 4-8 hours and yields quantitative information. These techniques can serve to study a wide range of kinetic parameters that drive nanotherapeutics delivery, uptake, and treatment response. PMID:25383179

Evaluation of Wavelength Detuning to Mitigate Cross-Beam Energy Transfer Using the Nike Laser

NASA Astrophysics Data System (ADS)

McKenty, P. W.; Marozas, J. A.; Weaver, J.; Obenschain, S. P.; Schmitt, A. J.

2015-11-01

Cross-beam energy transfer (CBET) has become a serious threat to the overall success of direct-drive experiments, and especially for polar-direct-drive (PDD) ignition experiments. CBET redirects incident laser light before it can be absorbed into the target, thereby degrading overall target performance. CBET is particularly detrimental over the equator of the target, which is hydrodynamically very sensitive to such losses in the PDD configuration. A promising solution uses laser wavelength detuning between beams to shift the resonance, thereby reducing the interaction cross section between them. Testing this process for direct drive is now underway at the Nike laser at the Naval Research Laboratory. Calculations evaluating the effect CBET has on the scattered-light signals indicate such an experiment will demonstrate the benefits of wavelength detuning for direct-drive implosions. Two-dimensional simulation results will be presented, predicting the effect for both spherical and cylindrical experiments. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

Direct comparison of fatty acid ratios in single cellular lipid droplets as determined by Raman spectroscopy and gas chromatography

USDA-ARS?s Scientific Manuscript database

Cellular lipid droplets are the least studied and least understood cellular organelles in eukaryotic and prokaryotic cells. Despite a broad research trying to understand lipid droplets it has not been possible to determine the composition of individual cellular lipid droplets. In this paper we prese...

Reversible ratchet effects for vortices in conformal pinning arrays

DOE PAGES

Reichhardt, Charles; Ray, Dipanjan; Reichhardt, Cynthia Jane Olson

2015-05-04

A conformal transformation of a uniform triangular pinning array produces a structure called a conformal crystal which preserves the sixfold ordering of the original lattice but contains a gradient in the pinning density. Here we use numerical simulations to show that vortices in type-II superconductors driven with an ac drive over gradient pinning arrays produce the most pronounced ratchet effect over a wide range of parameters for a conformal array, while square gradient or random gradient arrays with equivalent pinning densities give reduced ratchet effects. In the conformal array, the larger spacing of the pinning sites in the direction transversemore » to the ac drive permits easy funneling of interstitial vortices for one driving direction, producing the enhanced ratchet effect. In the square array, the transverse spacing between pinning sites is uniform, giving no asymmetry in the funneling of the vortices as the driving direction switches, while in the random array, there are numerous easy-flow channels present for either direction of drive. We find multiple ratchet reversals in the conformal arrays as a function of vortex density and ac amplitude, and correlate the features with a reversal in the vortex ordering, which is greater for motion in the ratchet direction. In conclusion, the enhanced conformal pinning ratchet effect can also be realized for colloidal particles moving over a conformal array, indicating the general usefulness of conformal structures for controlling the motion of particles.« less

Two-motor direct drive control for elevation axis of telescope

NASA Astrophysics Data System (ADS)

Tang, T.; Tan, Y.; Ren, G.

2014-07-01

Two-motor application has become a very attractive filed in important field which high performance is permitted to achieve of position, speed, and acceleration. In the elevation axis of telescope control system, two-motor direct drive is proposed to enhance the high performance of tracking control system. Although there are several dominant strengths such as low size of motors and high torsional structural dynamics, the synchronization control of two motors is a very difficult and important. In this paper, a multi-loop control technique base master-slave current control is used to synchronize two motors, including current control loop, speed control loop and position control loop. First, the direct drive function of two motors is modeled. Compared of single motor direct control system, the resonance frequency of two motor control systems is same; while the anti-resonance frequency of two motors control system is 1.414 times than those of sing motor system. Because of rigid coupling for direct drive, the speed of two motor of the system is same, and the synchronization of torque for motors is critical. The current master-slave control technique is effective to synchronize the torque, which the current loop of the master motors is tracked the other slave motor. The speed feedback into the input of current loop of the master motors. The experiments test the performance of the two motors drive system. The random tracking error is 0.0119" for the line trajectory of 0.01°/s.

New Frontiers and Challenges for Single-Cell Electrochemical Analysis.

PubMed

Zhang, Jingjing; Zhou, Junyu; Pan, Rongrong; Jiang, Dechen; Burgess, James D; Chen, Hong-Yuan

2018-02-23

Previous measurements of cell populations might obscure many important cellular differences, and new strategies for single-cell analyses are urgently needed to re-examine these fundamental biological principles for better diagnosis and treatment of diseases. Electrochemistry is a robust technique for the analysis of single living cells that has the advantages of minor interruption of cellular activity and provides the capability of high spatiotemporal resolution. The achievements of the past 30 years have revealed significant information about the exocytotic events of single cells to elucidate the mechanisms of cellular activity. Currently, the rapid developments of micro/nanofabrication and optoelectronic technologies drive the development of multifunctional electrodes and novel electrochemical approaches with higher resolution for single cells. In this Perspective, three new frontiers in this field, namely, electrochemical microscopy, intracellular analysis, and single-cell analysis in a biological system (i.e., neocortex and retina), are reviewed. The unique features and remaining challenges of these techniques are discussed.

Lifesavers and Samaritans: emergency use of cellular (mobile) phones in Australia.

PubMed

Chapman, S; Schofield, W N

1998-11-01

There has been highly publicised concern about possible radiation health effects from mobile phones and towers, but scant attention has been paid to the use of mobile phones in reducing notification times in emergencies. National random telephone survey of Australian mobile phone users (n = 720) and extrapolation to national user population (n = 5.1 million). Using a cellular phone, 1 in 8 users have reported a traffic accident; 1 in 4 a dangerous situation; 1 in 16 a non-road medical emergency; 1 in 20 a crime; and 1 in 45 being lost in the bush or being in difficulty at sea. Any debate about the net health impact of mobile phone proliferation must balance possible negative effects (cancer, driving incidents) with the benefits from what appears to be their widespread use in rapidly reporting emergencies and in numerous acts of often health-relevant 'cellular Samaritanism'.

Asymmetric spermatocyte division as a mechanism for controlling sex ratios

PubMed Central

Shakes, Diane C.; Neva, Bryan J.; Huynh, Henry; Chaudhuri, Jyotiska; Pires-daSilva, Andre

2016-01-01

Although Mendel's first law predicts that crosses between XY (or XO) males and XX females should yield equal numbers of males and females, individuals in a wide variety of metazoans transmit their sex chromosomes unequally and produce broods with highly skewed sex ratios. Here we report two modifications to the cellular program of spermatogenesis which, in combination, help explain why males of the free-living nematode species Rhabditis sp. SB347 sire less than 5% male progeny. First, the spermatogenesis program involves a modified meiosis in which chromatids of the unpaired X chromosome separate prematurely, in meiosis I. Second, during anaphase II, cellular components essential for sperm motility are partitioned almost exclusively to the X-bearing sperm. Our studies reveal a novel cellular mechanism for the differential transmission of X-bearing sperm and suggest R. sp. SB347 as a useful model for studying sex chromosome drive and the evolution of new mating systems. PMID:21245838

Asymmetric spermatocyte division as a mechanism for controlling sex ratios.

PubMed

Shakes, Diane C; Neva, Bryan J; Huynh, Henry; Chaudhuri, Jyotiska; Pires-Dasilva, Andre

2011-01-18

Although Mendel's first law predicts that crosses between XY (or XO) males and XX females should yield equal numbers of males and females, individuals in a wide variety of metazoans transmit their sex chromosomes unequally and produce broods with highly skewed sex ratios. Here, we report two modifications to the cellular programme of spermatogenesis, which, in combination, help to explain why males of the free-living nematode species Rhabditis sp. SB347 sire <5% male progeny. First, the spermatogenesis programme involves a modified meiosis in which chromatids of the unpaired X chromosome separate prematurely, in meiosis I. Second, during anaphase II, cellular components essential for sperm motility are partitioned almost exclusively to the X-bearing sperm. Our studies reveal a novel cellular mechanism for the differential transmission of X-bearing sperm and suggest Rhabditis sp. SB347 as a useful model for studying sex chromosome drive and the evolution of new mating systems.

Low backlash direct drive actuator

DOEpatents

Kuklo, Thomas C.

1994-01-01

A low backlash direct drive actuator is described which comprises a motor such as a stepper motor having at least 200 steps per revolution; a two part hub assembly comprising a drive hub coaxially attached to the shaft of the motor and having a plurality of drive pins; a driven hub having a plurality of bores in one end thereof in alignment with the drive pins in the drive hub and a threaded shaft coaxially mounted in an opposite end of the driven hub; and a housing having a central bore therein into which are fitted the drive hub and driven hub, the housing having a motor mount on one end thereof to which is mounted the stepper motor, and a closed end portion with a threaded opening therein coaxial with the central bore in the housing and receiving therein the threaded shaft attached to the driven hub. Limit switches mounted to the housing cooperate with an enlarged lip on the driven hub to limit the lateral travel of the driven hub in the housing, which also acts to limit the lateral travel of the threaded shaft which functions as a lead screw.

Clogging and transport of driven particles in asymmetric funnel arrays

NASA Astrophysics Data System (ADS)

Reichhardt, C. J. O.; Reichhardt, C.

2018-06-01

We numerically examine the flow and clogging of particles driven through asymmetric funnel arrays when the commensurability ratio of the number of particles per plaquette is varied. The particle–particle interactions are modeled with a soft repulsive potential that could represent vortex flow in type-II superconductors or driven charged colloids. The velocity-force curves for driving in the easy flow direction of the funnels exhibit a single depinning threshold; however, for driving in the hard flow direction, we find that there can be both negative mobility where the velocity decreases with increasing driving force as well as a reentrant pinning effect in which the particles flow at low drives but become pinned at intermediate drives. This reentrant pinning is associated with a transition from smooth 1D flow at low drives to a clogged state at higher drives that occurs when the particles cluster in a small number of plaquettes and block the flow. When the drive is further increased, particle rearrangements occur that cause the clog to break apart. We map out the regimes in which the pinned, flowing, and clogged states appear as a function of plaquette filling and drive. The clogged states remain robust at finite temperatures but develop intermittent bursts of flow in which a clog temporarily breaks apart but quickly reforms.

Bringing MapReduce Closer To Data With Active Drives

NASA Astrophysics Data System (ADS)

Golpayegani, N.; Prathapan, S.; Warmka, R.; Wyatt, B.; Halem, M.; Trantham, J. D.; Markey, C. A.

2017-12-01

Moving computation closer to the data location has been a much theorized improvement to computation for decades. The increase in processor performance, the decrease in processor size and power requirement combined with the increase in data intensive computing has created a push to move computation as close to data as possible. We will show the next logical step in this evolution in computing: moving computation directly to storage. Hypothetical systems, known as Active Drives, have been proposed as early as 1998. These Active Drives would have a general-purpose CPU on each disk allowing for computations to be performed on them without the need to transfer the data to the computer over the system bus or via a network. We will utilize Seagate's Active Drives to perform general purpose parallel computing using the MapReduce programming model directly on each drive. We will detail how the MapReduce programming model can be adapted to the Active Drive compute model to perform general purpose computing with comparable results to traditional MapReduce computations performed via Hadoop. We will show how an Active Drive based approach significantly reduces the amount of data leaving the drive when performing several common algorithms: subsetting and gridding. We will show that an Active Drive based design significantly improves data transfer speeds into and out of drives compared to Hadoop's HDFS while at the same time keeping comparable compute speeds as Hadoop.

Effects of fatigue on driving performance under different roadway geometries: a simulator study.

PubMed

Du, Hongji; Zhao, Xiaohua; Zhang, Xingjian; Zhang, Yunlong; Rong, Jian

2015-01-01

This article examines the effects of fatigue on driving performance under different roadway geometries using a driving simulator. Twenty-four participants each completed a driving scenario twice: while alert and while experiencing fatigue. The driving scenario was composed of straight road segments and curves; there were 6 curves with 3 radius values (i.e., 200, 500, and 800 m) and 2 turning directions (i.e., left and right). Analysis was conducted on driving performance measures such as longitudinal speed, steering wheel movements, and lateral position. RESULTS confirmed that decremental changes in driving performance due to fatigue varied among road conditions. On straight segments, drivers' abilities to steer and maintain lane position were impaired, whereas on curves we found decremental changes in the quality of longitudinal speed as well as steering control and keeping the vehicle in the lane. Moreover, the effects of fatigue on driving performance were relative to the radius and direction of the curve. Fatigue impaired drivers' abilities to control the steering wheel, and the impairment proved more obvious on curves. The degree varied significantly as the curve radius changed. Drivers tended to drive closer to the right side due to fatigue, and the impairment in maintaining lane position became more obvious as the right-turn curve radius decreased. Driver fatigue has detrimental effects on driving performance, and the effects differ under different roadway geometries.

An Examination of Four Successes in the Coast Guard’s Innovation Program and Implications for Innovation within Homeland Security

DTIC Science & Technology

2008-03-01

patterns, determine positive directions, and rapidly drive process improvements. This thesis examines literature related to leadership, strategic...an effective mechanism to sense emerging patterns, determine positive directions, and rapidly drive process improvements. This thesis examines...VESSEL SIGHTING APPLICATION - MISLE LITE .............................42 B. RUGGEDIZED TABLET COMPUTER

First Observation of Cross-Beam Energy Transfer Mitigation for Direct-Drive Inertial Confinement Fusion Implosions Using Wavelength Detuning at the National Ignition Facility.

PubMed

Marozas, J A; Hohenberger, M; Rosenberg, M J; Turnbull, D; Collins, T J B; Radha, P B; McKenty, P W; Zuegel, J D; Marshall, F J; Regan, S P; Sangster, T C; Seka, W; Campbell, E M; Goncharov, V N; Bowers, M W; Di Nicola, J-M G; Erbert, G; MacGowan, B J; Pelz, L J; Yang, S T

2018-02-23

Cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces ablation pressure and implosion velocity in direct-drive inertial confinement fusion. Mitigating CBET is demonstrated for the first time in inertial-confinement implosions at the National Ignition Facility by detuning the laser-source wavelengths (±2.3  Å UV) of the interacting beams. We show that, in polar direct-drive, wavelength detuning increases the equatorial region velocity experimentally by 16% and alters the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation-hydrodynamic simulations that indicate a 10% increase in the average ablation pressure.

First Observation of Cross-Beam Energy Transfer Mitigation for Direct-Drive Inertial Confinement Fusion Implosions Using Wavelength Detuning at the National Ignition Facility

NASA Astrophysics Data System (ADS)

Marozas, J. A.; Hohenberger, M.; Rosenberg, M. J.; Turnbull, D.; Collins, T. J. B.; Radha, P. B.; McKenty, P. W.; Zuegel, J. D.; Marshall, F. J.; Regan, S. P.; Sangster, T. C.; Seka, W.; Campbell, E. M.; Goncharov, V. N.; Bowers, M. W.; Di Nicola, J.-M. G.; Erbert, G.; MacGowan, B. J.; Pelz, L. J.; Yang, S. T.

2018-02-01

Cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces ablation pressure and implosion velocity in direct-drive inertial confinement fusion. Mitigating CBET is demonstrated for the first time in inertial-confinement implosions at the National Ignition Facility by detuning the laser-source wavelengths (±2.3 Å UV) of the interacting beams. We show that, in polar direct-drive, wavelength detuning increases the equatorial region velocity experimentally by 16% and alters the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation-hydrodynamic simulations that indicate a 10% increase in the average ablation pressure.

Hypothesis: solid tumours behave as systemic metabolic dictators.

PubMed

Lee, Yang-Ming; Chang, Wei-Chun; Ma, Wen-Lung

2016-06-01

Current knowledge regarding mechanisms of carcinogenesis in human beings centres around the accumulation of genetic instability, amplified cellular signalling, disturbed cellular energy metabolism and microenvironmental regulation governed by complicated cell-cell interactions. In this article, we provide an alternative view of cancer biology. We propose that cancer behaves as a systemic dictator that interacts with tissues throughout the body to control their metabolism and eventually homeostasis. The mechanism of development of this endocrine organ-like tumour (EOLT) tissue might be the driving force for cancer progression. Here, we review the literature that led to the development of this hypothesis. The EOLT phenotype can be defined as a tumour that alters systemic homeostasis. The literature indicates that the EOLT phenotype is present throughout cancer progression. The feedback mechanism that governs the interaction between tumours and various organs is unknown. We believe that investigating the mechanism of EOLT development may advance the current knowledge of regulation within the tumour macroenvironment and consequently lead to new diagnostic methods and therapy. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Microdialysis Sampling Techniques Applied to Studies of the Foreign Body Reaction

PubMed Central

Sides, Cynthia R.; Stenken, Julie A.

2014-01-01

Implanted materials including drug delivery devices and chemical sensors undergo what is termed the foreign body reaction (FBR). Depending on the device and its intended application, the FBR can have differing consequences. An extensive scientific research effort has been devoted to elucidating the cellular and molecular mechanisms that drive the FBR. Important, yet relatively unexplored, research includes the localized tissue biochemistry and the chemical signaling events that occur throughout the FBR. This review provides an overview of the mechanisms of the FBR, describes how the FBR affects different implanted devices, and illustrates the role that microdialysis sampling can play in further elucidating the chemical communication processes that drive FBR outcomes. PMID:24269987

Drink-driving and the alcohol beverage industry: will reducing per capita consumption solve the problem in the United Kingdom?

PubMed

Riley, D

1987-12-01

The impact of drinking and driving is one focus of the mounting concern in the West over the widespread incidence of alcohol-related problems. Conventional wisdom, in the United Kingdom as well as in other countries, suggests that reducing average consumption levels will diminish the impact of the negative effects of alcohol including drinking and driving. But whether policies designed to achieve changes in per capita consumption by increasing alcohol taxes across the board constitute the most effective strategy to reduce drinking and driving is called into question. A number of competing interventions directed at the alcohol beverage industry are analysed and new directions for producers and policymakers are proposed.

Extracellular matrix motion and early morphogenesis

PubMed Central

Loganathan, Rajprasad; Rongish, Brenda J.; Smith, Christopher M.; Filla, Michael B.; Czirok, Andras; Bénazéraf, Bertrand

2016-01-01

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale ‘total’ cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. PMID:27302396

Water wave energy transducer

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

Lamberti, J.

1983-06-28

A water wave energy transducer comprises a boat having pivoted arms projecting out over the water, a float being mounted on the outboard end of each arm so that the arms are oscillated by wave action on the floats. Drive sprockets fixed on the arms coaxially with their pivots are connected by drive chains with two driven sprockets coaxial, respectively, with two gears which mesh with one another and one of which meshes with an output gear. The driven sprockets are coupled with the coaxial gears by one-way clutches which are oppositely arranged so that one drives when the sprocketsmore » turn in one direction and the other drives when the sprockets turn in the opposite direction. Hence, the output gear is driven in the same direction by both upward and downward movement of the floats. The output gear is connected by a speed increasing gear train with an electric generator which can supply current to a motor for propelling the boat, or through a cable to the shore when the boat is anchored.« less

Mid-sized omnidirectional robot with hydraulic drive and steering

NASA Astrophysics Data System (ADS)

Wood, Carl G.; Perry, Trent; Cook, Douglas; Maxfield, Russell; Davidson, Morgan E.

2003-09-01

Through funding from the US Army-Tank-Automotive and Armaments Command's (TACOM) Intelligent Mobility Program, Utah State University's (USU) Center for Self-Organizing and Intelligent Systems (CSOIS) has developed the T-series of omni-directional robots based on the USU omni-directional vehicle (ODV) technology. The ODV provides independent computer control of steering and drive in a single wheel assembly. By putting multiple omni-directional (OD) wheels on a chassis, a vehicle is capable of uncoupled translational and rotational motion. Previous robots in the series, the T1, T2, T3, ODIS, ODIS-T, and ODIS-S have all used OD wheels based on electric motors. The T4 weighs approximately 1400 lbs and features a 4-wheel drive wheel configuration. Each wheel assembly consists of a hydraulic drive motor and a hydraulic steering motor. A gasoline engine is used to power both the hydraulic and electrical systems. The paper presents an overview of the mechanical design of the vehicle as well as potential uses of this technology in fielded systems.

Design and analysis of a new high frequency double-servo direct drive rotary valve

NASA Astrophysics Data System (ADS)

Zhu, Muzhi; Zhao, Shengdun; Li, Jingxiang

2016-12-01

Researchers have investigated direct drive valve for many years to solve problems, such as fluid force imbalance and switching frequency. The structure of the rotary valve has received considerable research interest because of its favorable dynamic properties and simple structure. This paper studied the high frequency doubleservo direct drive rotary valve (DDRV), and proposed a novel structure and drive method satisfying high reversing frequency and adequate quantity of flow. Servo motors are integrated into the valve by the innovative structure, which is designed to equilibrate the unbalanced radial fluid force with the symmetric distributed oil ports. Aside from the fast reversing function of the valve, the DDRV presented high performance in linearity of the flow quantity and valve opening as a result of the fan-shaped flow ports. In addition, a computational fluid dynamics (CFD) method based on Fluent was conducted to verify the flux regulation effect of the height change of the adjustable boss.

Traffic signs recognition for driving assistance

NASA Astrophysics Data System (ADS)

Sai Sangram Reddy, Yatham; Karthik, Devareddy; Rana, Nikunj; Jasmine Pemeena Priyadarsini, M.; Rajini, G. K.; Naseera, Shaik

2017-11-01

In the current circumstances with the innovative headway, we must be able to provide assistance to the driving in recognising the traffic signs on the roads. At present time, many reviews are being directed moving in the direction of the usage of a keen Traffic Systems. One field of this exploration is driving support systems, and many reviews are being directed to create frameworks which distinguish and perceive street signs in front of the vehicle, and afterward utilize the data to advise the driver or to even control the vehicle by implementing this system on self-driving vehicles. In this paper we propose a method to detect the traffic sign board in a frame using HAAR cascading and then identifying the sign on it. The output may be either given out in voice or can be displayed as per the driver’s convenience. Each of the Traffic Sign is recognised using a database of images of symbols used to train the KNN classifier using open CV libraries.

Dromosagnosia, or why some people lose their sense of direction while driving.

PubMed

Tseng, Wei-Shih; Tzeng, Nian-Sheng

2013-11-01

We coined a new word, "dromosagnosia", from the Greek words, dromos ("way, road")+agnosia, to describe the loss of direction while driving, an orientation disorder similar to but different from pure topographic disorientation. Historically, human beings have moved more quickly, from using domesticated animals to high speed vehicles, and this may be beyond the brain's ability to react. Without the benefit of an automatic navigation system, automobiles are associated with more problems of dromosagnosia than are fast-moving aircraft or ships. Previous studies have noted that some areas of the brain are associated with spatial orientation, spatial memory, and even emotion, and abnormalities there could exacerbate the loss of sense of direction. We hypothesize that some people are especially disadvantaged from these brain differences and emotional disturbances when driving their cars. Functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) studies combined with a virtual reality driving simulation might be used to find the areas of the brain related to dromosagnosia. Future applications: some people with dromosagnosia might benefit from special remedial training and a driving safety support system to avoid potential problems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of cellular influences of platinum nanoparticles by stable medium dispersion.

PubMed

Horie, Masanori; Kato, Haruhisa; Endoh, Shigehisa; Fujita, Katsuhide; Nishio, Keiko; Komaba, Lilian Kaede; Fukui, Hiroko; Nakamura, Ayako; Miyauchi, Arisa; Nakazato, Tetsuya; Kinugasa, Shinichi; Yoshida, Yasukazu; Hagihara, Yoshihisa; Morimoto, Yasuo; Iwahashi, Hitoshi

2011-11-01

Platinum nanoparticles have industrial application, for example in catalysis, and are used in consumer products such as cosmetics and supplements. Therefore, among the many nanoparticles, platinum is one of the more accessible nanoparticles for consumers. Most platinum nanoparticles that are used in cosmetics and supplements which have an anti-oxidant activity are modified particles. However, the cellular influences of pristine platinum nanoparticles are still unclear, although it has been reported that platinum nanoparticles induce oxidative stress. In this study, we investigated the cellular influences induced by pure pristine platinum nanoparticles. Platinum nanoparticles of 100% purity were dispersed in a cell culture medium and stable medium dispersion was obtained. The platinum nanoparticle medium dispersion was applied to two kinds of cultured cells, A549 and HaCaT cells, and the cellular influences were examined. Cell viability (MTT assay), cell proliferation (clonogenic assay), apoptosis induction (caspase-3 activity), intracellular ROS level (DCFH assay), and lipid peroxidation level (DPPP assay) were measured as markers of cellular influences. Transmission electron microscope observation showed cellular uptake of platinum nanoparticles. However, the platinum nanoparticles did not drive any markers. It is known that some metal oxide nanoparticles such as NiO and CuO show severe cytotoxicity via metal ion release. Compared with these toxic nanoparticles, the platinum nanoparticles used in this study did not release platinum ions into the culture media. These results suggest that the physically and chemically inactive cellular influences of platinum nanoparticles are small.

Gaps and Pathways Project: driving pathways by diagnosis sheets.

PubMed

Touchinsky, Susan; Chew, Felicia; Davis, Elin Schold

2014-04-01

This paper describes the development and use of information sheets for occupational therapy practitioners to use as guides for evaluation and intervention planning to address their client's driving and community mobility needs. Called Driving Pathways by Diagnosis Sheets, the information assists therapists with direction to connect impairment to driving risk and incorporate intervention to client goals and priorities related to driving and community mobility. An example of one of the sheets for the diagnosis of arthritis is highlighted and implications for use are discussed.

The traffic climate in China: The mediating effect of traffic safety climate between personality and dangerous driving behavior.

PubMed

Zhang, Qian; Ge, Yan; Qu, Weina; Zhang, Kan; Sun, Xianghong

2018-04-01

Traffic safety climate is defined as road users' attitudes and perceptions of traffic in a specific context at a given point in time. The current study aimed to validate the Chinese version of the Traffic Climate Scale (TCS) and to explore its relation to drivers' personality and dangerous driving behavior. A sample of 413 drivers completed the Big Five Inventory (BFI), the Chinese version of the TCS, the Dula Dangerous Driving Index (DDDI) and a demographic questionnaire. Exploratory factor analysis and confirmatory factor analysis were performed to confirm a three-factor (external affective demands, internal requirements and functionality) solution of the TCS. The reliability and validity of the Chinese version of TCS were verified. More importantly, the results showed that the effect of personality on dangerous driving behavior was mediated by traffic climate. Specifically, the functionality of the TCS mediated the effect of neuroticism on negative cognitive/emotional driving and drunk driving, while openness had an indirect impact on aggressive driving, risky driving and drunk driving based on the internal requirements of the TCS. Additionally, agreeableness had a negative direct impact on four factors of the DDDI, while neuroticism had a positive direct impact on negative cognitive/emotional driving, drunk driving and risky driving. In conclusion, the Chinese version of the TCS will be useful to evaluate drivers' attitudes towards and perceptions of the requirements of traffic environment in which they participate and will also be valuable for comparing traffic cultures and environments in different countries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Shape selection criterion for cellular array during constrained growth of binary alloys - Need for low gravity experiment

NASA Technical Reports Server (NTRS)

Tewari, Surendra N.; Trivedi, Rohit

1991-01-01

Development of steady-state periodic cellular array is one of the critical problems in the study of nonlinear pattern formation during directional solidification of binary alloys. The criterion which establishes the values of cell tip radius and spacing under given growth condition is not known. Theoretical models, such as marginal stability and microscopic solvability, have been developed for purely diffusive regime. However, the experimental conditions where cellular structures are stable are precisely the ones where the convection effects are predominant. Thus, the critical data for meaningful evaluation of cellular array growth models can only be obtained by partial directional solidification and quenching experiments carried out in the low gravity environment of space.

Matrix remodeling between cells and cellular interactions with collagen bundle

NASA Astrophysics Data System (ADS)

Kim, Jihan; Sun, Bo

When cells are surrounded by complex environment, they continuously probe and interact with it by applying cellular traction forces. As cells apply traction forces, they can sense rigidity of their local environment and remodel the matrix microstructure simultaneously. Previous study shows that single human carcinoma cell (MDA-MB-231) remodeled its surrounding extracellular matrix (ECM) and the matrix remodeling was reversible. In this study we examined the matrix microstructure between cells and cellular interaction between them using quantitative confocal microscopy. The result shows that the matrix microstructure is the most significantly remodeled between cells consisting of aligned, and densified collagen fibers (collagen bundle)., the result shows that collagen bundle is irreversible and significantly change micromechanics of ECM around the bundle. We further examined cellular interaction with collagen bundle by analyzing dynamics of actin and talin formation along with the direction of bundle. Lastly, we analyzed dynamics of cellular protrusion and migrating direction of cells along the bundle.

Fluorescence-based detection and quantification of features of cellular senescence.

PubMed

Cho, Sohee; Hwang, Eun Seong

2011-01-01

Cellular senescence is a spontaneous organismal defense mechanism against tumor progression which is raised upon the activation of oncoproteins or other cellular environmental stresses that must be circumvented for tumorigenesis to occur. It involves growth-arrest state of normal cells after a number of active divisions. There are multiple experimental routes that can drive cells into a state of senescence. Normal somatic cells and cancer cells enter a state of senescence upon overexpression of oncogenic Ras or Raf protein or by imposing certain kinds of stress such as cellular tumor suppressor function. Both flow cytometry and confocal imaging analysis techniques are very useful in quantitative analysis of cellular senescence phenomenon. They allow quantitative estimates of multiple different phenotypes expressed in multiple cell populations simultaneously. Here we review the various types of fluorescence methodologies including confocal imaging and flow cytometry that are frequently utilized to study a variety of senescence. First, we discuss key cell biological changes occurring during senescence and review the current understanding on the mechanisms of these changes with the goal of improving existing protocols and further developing new ones. Next, we list specific senescence phenotypes associated with each cellular trait along with the principles of their assay methods and the significance of the assay outcomes. We conclude by selecting appropriate references that demonstrate a typical example of each method. Copyright © 2011 Elsevier Inc. All rights reserved.

Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets

PubMed Central

Vinayagam, Arunachalam; Gibson, Travis E.; Lee, Ho-Joon; Yilmazel, Bahar; Roesel, Charles; Hu, Yanhui; Kwon, Young; Sharma, Amitabh; Liu, Yang-Yu; Perrimon, Norbert; Barabási, Albert-László

2016-01-01

The protein–protein interaction (PPI) network is crucial for cellular information processing and decision-making. With suitable inputs, PPI networks drive the cells to diverse functional outcomes such as cell proliferation or cell death. Here, we characterize the structural controllability of a large directed human PPI network comprising 6,339 proteins and 34,813 interactions. This network allows us to classify proteins as “indispensable,” “neutral,” or “dispensable,” which correlates to increasing, no effect, or decreasing the number of driver nodes in the network upon removal of that protein. We find that 21% of the proteins in the PPI network are indispensable. Interestingly, these indispensable proteins are the primary targets of disease-causing mutations, human viruses, and drugs, suggesting that altering a network’s control property is critical for the transition between healthy and disease states. Furthermore, analyzing copy number alterations data from 1,547 cancer patients reveals that 56 genes that are frequently amplified or deleted in nine different cancers are indispensable. Among the 56 genes, 46 of them have not been previously associated with cancer. This suggests that controllability analysis is very useful in identifying novel disease genes and potential drug targets. PMID:27091990

Epithelial Control of Gut-Associated Lymphoid Tissue Formation through p38α-Dependent Restraint of NF-κB Signaling.

PubMed

Caballero-Franco, Celia; Guma, Monica; Choo, Min-Kyung; Sano, Yasuyo; Enzler, Thomas; Karin, Michael; Mizoguchi, Atsushi; Park, Jin Mo

2016-03-01

The protein kinase p38α mediates cellular responses to environmental and endogenous cues that direct tissue homeostasis and immune responses. Studies of mice lacking p38α in several different cell types have demonstrated that p38α signaling is essential to maintaining the proliferation-differentiation balance in developing and steady-state tissues. The mechanisms underlying these roles involve cell-autonomous control of signaling and gene expression by p38α. In this study, we show that p38α regulates gut-associated lymphoid tissue (GALT) formation in a noncell-autonomous manner. From an investigation of mice with intestinal epithelial cell-specific deletion of the p38α gene, we find that p38α serves to limit NF-κB signaling and thereby attenuate GALT-promoting chemokine expression in the intestinal epithelium. Loss of this regulation results in GALT hyperplasia and, in some animals, mucosa-associated B cell lymphoma. These anomalies occur independently of luminal microbial stimuli and are most likely driven by direct epithelial-lymphoid interactions. Our study illustrates a novel p38α-dependent mechanism preventing excessive generation of epithelial-derived signals that drive lymphoid tissue overgrowth and malignancy. Copyright © 2016 by The American Association of Immunologists, Inc.

Quantitative analysis of mechanical force required for cell extrusion in zebrafish embryonic epithelia.

PubMed

Yamada, Sohei; Iino, Takanori; Bessho, Yasumasa; Hosokawa, Yoichiroh; Matsui, Takaaki

2017-10-15

When cells in epithelial sheets are damaged by intrinsic or extrinsic causes, they are eliminated by extrusion from the sheet. Cell extrusion, which is required for maintenance of tissue integrity, is the consequence of contraction of actomyosin rings, as demonstrated by both molecular/cellular biological experimentation and numerical simulation. However, quantitative evaluation of actomyosin contraction has not been performed because of the lack of a suitable direct measurement system. In this study, we developed a new method using a femtosecond laser to quantify the contraction force of the actomyosin ring during cell extrusion in zebrafish embryonic epithelia. In this system, an epithelial cell in zebrafish embryo is first damaged by direct femtosecond laser irradiation. Next, a femtosecond laser-induced impulsive force is loaded onto the actomyosin ring, and the contraction force is quantified to be on the order of kPa as a unit of pressure. We found that cell extrusion was delayed when the contraction force was slightly attenuated, suggesting that a relatively small force is sufficient to drive cell extrusion. Thus, our method is suitable for the relative quantitative evaluation of mechanical dynamics in the process of cell extrusion, and in principle the method is applicable to similar phenomena in different tissues and organs of various species. © 2017. Published by The Company of Biologists Ltd.

Interleukin-6 increases matrix metalloproteinase-14 (MMP-14) levels via down-regulation of p53 to drive cancer progression

PubMed Central

Cathcart, Jillian M.; Banach, Anna; Liu, Alice; Chen, Jun; Goligorsky, Michael; Cao, Jian

2016-01-01

Matrix metalloproteinases (MMPs) play critical roles in cancer invasion and metastasis by digesting basement membrane and extracellular matrix (ECM). Much attention has focused on the enzymatic activities of MMPs; however, the regulatory mechanism of MMP expression remains elusive. By employing bioinformatics analysis, we identified a potential p53 response element within the MMP-14 promoter. Experimentally, we found that p53 can repress MMP-14 promoter activity, whereas deletion of this p53 response element abrogated this effect. Furthermore, we found that p53 expression decreases MMP-14 mRNA and protein levels and attenuates MMP-14-mediated cellular functions. Additional promoter analysis and chromatin immunoprecipitation studies identified a mechanism of regulation of MMP-14 expression by which p53 and transcription factor Sp1 competitively bind to the promoter. As the correlation between inflammation and cancer aggressiveness is well described, we next sought to evaluate if inflammatory cytokines could differentially affect p53 and MMP-14 levels. We demonstrate that interleukin-6 (IL-6) down-regulates p53 protein levels and thus results in a concomitant increase in MMP-14 expression, leading to enhanced cancer cell invasion and metastasis. Our data collectively indicate a novel mechanism of regulation of MMP-14 by a cascade of IL-6 and p53, demonstrating that the tumor microenvironment directly stimulates molecular changes in cancer cells to drive an invasive phenotype. PMID:27531896

Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the Future

PubMed Central

van de Stolpe, Anja; den Toonder, Jaap M. J.

2014-01-01

Knowledge on cellular signal transduction pathways as drivers of cancer growth and metastasis has fuelled development of “targeted therapy” which “targets” aberrant oncogenic signal transduction pathways. These drugs require nearly invariably companion diagnostic tests to identify the tumor-driving pathway and the cause of the abnormal pathway activity in a tumor sample, both for therapy response prediction as well as for monitoring of therapy response and emerging secondary drug resistance. Obtaining sufficient tumor material for this analysis in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may provide an attractive alternative to biopsy on the premise that they can be captured from blood and the companion diagnostic test results are correctly interpreted. We discuss novel companion diagnostic directions, including the challenges, to identify the tumor driving pathway in CTCs, which in combination with a digital pathology platform and algorithms to quantitatively interpret complex CTC diagnostic results may enable optimized therapy response prediction and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration is envisioned to be largely replaced by cell free tumor DNA measurements in blood for therapy response and recurrence monitoring. The recent emergence of novel in vitro human model systems in the form of cancer-on-a-chip may enable elucidation of some of the so far elusive characteristics of CTCs, and is expected to contribute to more efficient CTC capture and CTC-based diagnostics. PMID:24879438

β-Hydroxy-β-methylbutyrate as a countermeasure for cancer cachexia: a cellular and molecular rationale.

PubMed

Kim, Jeong-Su; Khamoui, Andy V; Jo, Edward; Park, Bong-Sup; Lee, Won Jun

2013-10-01

Cancer cachexia is a life-threatening condition characterized by involuntary body weight loss and skeletal muscle wasting. In addition to being associated with poor prognosis and reduced survival, patients with cachexia exhibit a critical loss of physical function that impinges upon their ability to perform basic activities of daily living. Consequently, there is a loss of independence and a drastically reduced quality of life. Despite being a major unmet medical need of patients, very few treatment options exist. Maintaining muscle mass represents an important objective in the cancer patient trajectory not only because it relates to one's capacity to perform activities of daily living, but also because muscle preservation may be a critical determinant of survival while in a tumor-bearing state. In this regard, research has been directed towards identifying countermeasures effective in preserving muscle. With respect to nutritional approaches, administration of the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) could be a viable component in multi-modal therapies targeting cancer cachexia. Evidence suggests that HMB treatment promotes regenerative events (i.e. myogenic program), suppresses protein degradation, and activates signaling pathways preceding protein synthesis and skeletal muscle growth. HMB therefore, could conceivably act on key regulatory events driving cancer cachexia, thereby favoring muscle growth/preservation. In this review, we take a mechanistic approach in making a case for the use of HMB provision as a possible therapeutic strategy for cancer cachexia by highlighting the cellular and molecular aspects of HMB function.

Epstein–Barr Virus: Diseases Linked to Infection and Transformation

PubMed Central

Jha, Hem C.; Pei, Yonggang; Robertson, Erle S.

2016-01-01

Epstein–Barr virus (EBV) was first discovered in 1964, and was the first known human tumor virus now shown to be associated with a vast number of human diseases. Numerous studies have been conducted to understand infection, propagation, and transformation in various cell types linked to human diseases. However, a comprehensive lens through which virus infection, reactivation and transformation of infected host cells can be visualized is yet to be formally established and will need much further investigation. Several human cell types infected by EBV have been linked to associated diseases. However, whether these are a direct result of EBV infection or indirectly due to contributions by additional infectious agents will need to be fully investigated. Therefore, a thorough examination of infection, reactivation, and cell transformation induced by EBV will provide a more detailed view of its contributions that drive pathogenesis. This undoubtedly expand our knowledge of the biology of EBV infection and the signaling activities of targeted cellular factors dysregulated on infection. Furthermore, these insights may lead to identification of therapeutic targets and agents for clinical interventions. Here, we review the spectrum of EBV-associated diseases, the role of the encoded latent antigens, and the switch to latency or lytic replication which occurs in EBV infected cells. Furthermore, we describe the cellular processes and critical factors which contribute to cell transformation. We also describe the fate of B-cells and epithelial cells after EBV infection and the expected consequences which contribute to establishment of viral-associated pathologies. PMID:27826287

CellNet: network biology applied to stem cell engineering.

PubMed

Cahan, Patrick; Li, Hu; Morris, Samantha A; Lummertz da Rocha, Edroaldo; Daley, George Q; Collins, James J

2014-08-14

Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

Laser-Plasma Interaction Experiments at Direct-Drive Ignition-Relevant Plasma Conditions at the National Ignition Facility

NASA Astrophysics Data System (ADS)

Solodov, A. A.; Rosenberg, M. J.; Myatt, J. F.; Shaw, J. G.; Seka, W.; Epstein, R.; Short, R. W.; Follett, R. K.; Regan, S. P.; Froula, D. H.; Radha, P. B.; Michel, P.; Chapman, T.; Hohenberger, M.

2017-10-01

Laser-plasma interaction (LPI) instabilities, such as stimulated Raman scattering (SRS) and two-plasmon decay, can be detrimental for direct-drive inertial confinement fusion because of target preheat by the high-energy electrons they generate. The radiation-hydrodynamic code DRACO was used to design planar-target experiments at the National Ignition Facility that generated plasma and interaction conditions relevant to ignition direct-drive designs (IL 1015W/cm2 , Te > 3 keV, density gradient scale lengths of Ln 600 μm). Laser-energy conversion efficiency to hot electrons of 0.5% to 2.5% with temperature of 45 to 60 keV was inferred from the experiment when the laser intensity at the quarter-critical surface increased from 6 to 15 ×1014W/cm2 . LPI was dominated by SRS, as indicated by the measured scattered-light spectra. Simulations of SRS using the LPI code LPSE have been performed and compared with predictions of theoretical models. Implications for ignition-scale direct-drive experiments will be discussed. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

Long-duration planar direct-drive hydrodynamics experiments on the NIF

NASA Astrophysics Data System (ADS)

Casner, A.; Mailliet, C.; Khan, S. F.; Martinez, D.; Izumi, N.; Kalantar, D.; Di Nicola, P.; Di Nicola, J. M.; Le Bel, E.; Igumenshchev, I.; Tikhonchuk, V. T.; Remington, B. A.; Masse, L.; Smalyuk, V. A.

2018-01-01

The advent of high-power lasers facilities such as the National Ignition Facility (NIF) and the laser megajoule provide unique platforms to study the physics of turbulent mixing flows in high energy density plasmas. We report here on the commissioning of a novel planar direct-drive platform on the NIF, which allows the acceleration of targets during 30 ns. Planar plastic samples were directly irradiated by 300-450 kJ of UV laser light (351 nm) and a very good planarity of the laser drive is demonstrated. No detrimental effect of imprint is observed in the case of these thick plastic targets (300 μm), which is beneficial for future academic experiments requesting similar irradiation conditions. The long-duration direct-drive (DD) platform is thereafter harnessed to study the ablative Rayleigh-Taylor instability (RTI) in DD. The growth of two-dimensional pre-imposed perturbations is quantified through time-resolved face-on x-ray radiography and used as a benchmark for radiative hydrocode simulations. The ablative RTI is then quantified in its highly nonlinear stage starting from intentionally large 3D imprinted broadband modulations. Two generations of bubble mergers is observed for the first time in DD, as a result of the unprecedented long laser acceleration.

Modeling Laser-Plasma Interactions at Direct-Drive Ignition-Relevant Plasma Conditions at the National Ignition Facility

NASA Astrophysics Data System (ADS)

Solodov, A. A.; Rosenberg, M. J.; Myatt, J. F.; Epstein, R.; Seka, W.; Hohenberger, M.; Short, R. W.; Shaw, J. G.; Regan, S. P.; Froula, D. H.; Radha, P. B.; Bates, J. W.; Schmitt, A. J.; Michel, P.; Moody, J. D.; Ralph, J. E.; Turnbull, D. P.; Barrios, M. A.

2016-10-01

Laser-plasma interaction instabilities, such as two-plasmon decay (TPD) and stimulated Raman scattering (SRS), can be detrimental for direct-drive inertial confinement fusion because of target preheat by generated high-energy electrons. The radiation-hydrodynamics code DRACO has been used to design planar-target experiments that generate plasma and interaction conditions relevant to direct-drive-ignition designs (IL 1015 W / cm 2 , Te > 3 KeV density gradient scale lengths of Ln 600 μm) . The hot-electron temperature of 40to50keV and the fraction of laser energy converted to hot electrons of 0.5to were inferred based on comparing the simulated and experimentally observed x-ray emission when the laser intensity at the quarter-critical surface increased from 6 to 15 ×1014 W / cm 2 . The measured SRS energy was sufficient to explain the observed total energy in hot electrons. Implications for ignition-scale direct-drive experiments and hot-electron preheat mitigation using mid- Z ablators will be discussed. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

Direct-drive inertial confinement fusion: A review

NASA Astrophysics Data System (ADS)

Craxton, R. S.; Anderson, K. S.; Boehly, T. R.; Goncharov, V. N.; Harding, D. R.; Knauer, J. P.; McCrory, R. L.; McKenty, P. W.; Meyerhofer, D. D.; Myatt, J. F.; Schmitt, A. J.; Sethian, J. D.; Short, R. W.; Skupsky, S.; Theobald, W.; Kruer, W. L.; Tanaka, K.; Betti, R.; Collins, T. J. B.; Delettrez, J. A.; Hu, S. X.; Marozas, J. A.; Maximov, A. V.; Michel, D. T.; Radha, P. B.; Regan, S. P.; Sangster, T. C.; Seka, W.; Solodov, A. A.; Soures, J. M.; Stoeckl, C.; Zuegel, J. D.

2015-11-01

The direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser-plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. The problem of suprathermal electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 μm—the third harmonic of the Nd:glass laser—and 0.248 μm (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon-decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be nonlocal in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive-ignition experiments to be performed on the National Ignition Facility [Haynam et al., Appl. Opt. 46(16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.

Clogging and transport of driven particles in asymmetric funnel arrays

DOE PAGES

Olson Reichhardt, Cynthia J.; Reichhardt, Charles

2018-05-03

In this paper, we numerically examine the flow and clogging of particles driven through asymmetric funnel arrays when the commensurability ratio of the number of particles per plaquette is varied. The particle-particle interactions are modeled with a soft repulsive potential that could represent vortex flow in type-II superconductors or driven charged colloids. The velocity-force curves for driving in the easy flow direction of the funnels exhibit a single depinning threshold; however, for driving in the hard flow direction, we find that there can be both negative mobility where the velocity decreases with increasing driving force as well as a reentrantmore » pinning effect in which the particles flow at low drives but become pinned at intermediate drives. This reentrant pinning is associated with a transition from smooth one-dimensional flow at low drives to a clogged state at higher drives that occurs when the particles cluster in a small number of plaquettes and block the flow. When the drive is further increased, particle rearrangements occur that cause the clog to break apart. We map out the regimes in which the pinned, flowing, and clogged states appear as a function of plaquette filling and drive. Finally, the clogged states remain robust at finite temperatures but develop intermittent bursts of flow in which a clog temporarily breaks apart but quickly reforms.« less

Clogging and transport of driven particles in asymmetric funnel arrays

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

Olson Reichhardt, Cynthia J.; Reichhardt, Charles

In this paper, we numerically examine the flow and clogging of particles driven through asymmetric funnel arrays when the commensurability ratio of the number of particles per plaquette is varied. The particle-particle interactions are modeled with a soft repulsive potential that could represent vortex flow in type-II superconductors or driven charged colloids. The velocity-force curves for driving in the easy flow direction of the funnels exhibit a single depinning threshold; however, for driving in the hard flow direction, we find that there can be both negative mobility where the velocity decreases with increasing driving force as well as a reentrantmore » pinning effect in which the particles flow at low drives but become pinned at intermediate drives. This reentrant pinning is associated with a transition from smooth one-dimensional flow at low drives to a clogged state at higher drives that occurs when the particles cluster in a small number of plaquettes and block the flow. When the drive is further increased, particle rearrangements occur that cause the clog to break apart. We map out the regimes in which the pinned, flowing, and clogged states appear as a function of plaquette filling and drive. Finally, the clogged states remain robust at finite temperatures but develop intermittent bursts of flow in which a clog temporarily breaks apart but quickly reforms.« less

Low backlash direct drive actuator

DOEpatents

Kuklo, T.C.

1994-10-25

A low backlash direct drive actuator is described which comprises a motor such as a stepper motor having at least 200 steps per revolution; a two part hub assembly comprising a drive hub coaxially attached to the shaft of the motor and having a plurality of drive pins; a driven hub having a plurality of bores in one end thereof in alignment with the drive pins in the drive hub and a threaded shaft coaxially mounted in an opposite end of the driven hub; and a housing having a central bore therein into which are fitted the drive hub and driven hub, the housing having a motor mount on one end thereof to which is mounted the stepper motor, and a closed end portion with a threaded opening therein coaxial with the central bore in the housing and receiving therein the threaded shaft attached to the driven hub. Limit switches mounted to the housing cooperate with an enlarged lip on the driven hub to limit the lateral travel of the driven hub in the housing, which also acts to limit the lateral travel of the threaded shaft which functions as a lead screw. 10 figs.

DriveWise: an interdisciplinary hospital-based driving assessment program.

PubMed

O'Connor, Margaret G; Kapust, Lissa R; Hollis, Ann M

2008-01-01

Health care professionals working with the elderly have opportunities through research and clinical practice to shape public policy affecting the older driver. This article describes DriveWise, an interdisciplinary hospital-based driving assessment program developed in response to clinical concerns about the driving safety of individuals with medical conditions. DriveWise clinicians use evidence-based, functional assessments to determine driving competence. In addition, the program was designed to meet the emotional needs of individuals whose driving safety has been called into question. To date, approximately 380 participants have been assessed through DriveWise. The following report details the DriveWise mission, DriveWise team members, and road test results. We continue to refine the assessment process to promote safety and support the dignity and independence of all participants. The DriveWise interdisciplinary approach to practice is a concrete example of how gerontological education across professions can have direct benefits to the older adult.

First Observation of Cross-Beam Energy Transfer Mitigation for Direct-Drive Inertial Confinement Fusion Implosions Using Wavelength Detuning at the National Ignition Facility

DOE PAGES

Marozas, J. A.; Hohenberger, M.; Rosenberg, M. J.; ...

2018-02-22

Cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces ablation pressure and implosion velocity in direct-drive inertial confinement fusion. Direct-drive implosions at the National Ignition Facility were conducted to reduce CBET by detuning the laser-source wavelengths (±2.3 Å UV) of the interacting beams over the equatorial region of the target. For the first time, wavelength detuning was shown to increase the equatorial region velocity experimentally by 16% and to alter the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation–hydrodynamic simulations that indicate a 10% increase in themore » average ablation pressure.« less

First Observation of Cross-Beam Energy Transfer Mitigation for Direct-Drive Inertial Confinement Fusion Implosions Using Wavelength Detuning at the National Ignition Facility

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

Marozas, J. A.; Hohenberger, M.; Rosenberg, M. J.

Cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces ablation pressure and implosion velocity in direct-drive inertial confinement fusion. Direct-drive implosions at the National Ignition Facility were conducted to reduce CBET by detuning the laser-source wavelengths (±2.3 Å UV) of the interacting beams over the equatorial region of the target. For the first time, wavelength detuning was shown to increase the equatorial region velocity experimentally by 16% and to alter the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation–hydrodynamic simulations that indicate a 10% increase in themore » average ablation pressure.« less

The BMP pathway acts to directly regulate Tbx20 in the developing heart

PubMed Central

Mandel, Elizabeth M.; Kaltenbrun, Erin; Callis, Thomas E.; Zeng, Xin-Xin I.; Marques, Sara R.; Yelon, Deborah; Wang, Da-Zhi; Conlon, Frank L.

2010-01-01

TBX20 has been shown to be essential for vertebrate heart development. Mutations within the TBX20 coding region are associated with human congenital heart disease, and the loss of Tbx20 in a wide variety of model systems leads to cardiac defects and eventually heart failure. Despite the crucial role of TBX20 in a range of cardiac cellular processes, the signal transduction pathways that act upstream of Tbx20 remain unknown. Here, we have identified and characterized a conserved 334 bp Tbx20 cardiac regulatory element that is directly activated by the BMP/SMAD1 signaling pathway. We demonstrate that this element is both necessary and sufficient to drive cardiac-specific expression of Tbx20 in Xenopus, and that blocking SMAD1 signaling in vivo specifically abolishes transcription of Tbx20, but not that of other cardiac factors, such as Tbx5 and MHC, in the developing heart. We further demonstrate that activation of Tbx20 by SMAD1 is mediated by a set of novel, non-canonical, high-affinity SMAD-binding sites located within this regulatory element and that phospho-SMAD1 directly binds a non-canonical SMAD1 site in vivo. Finally, we show that these non-canonical sites are necessary and sufficient for Tbx20 expression in Xenopus, and that reporter constructs containing these sites are expressed in a cardiac-specific manner in zebrafish and mouse. Collectively, our findings define Tbx20 as a direct transcriptional target of the BMP/SMAD1 signaling pathway during cardiac maturation. PMID:20460370

Mechanisms of Regulating Tissue Elongation in Drosophila Wing: Impact of Oriented Cell Divisions, Oriented Mechanical Forces, and Reduced Cell Size

PubMed Central

Li, Yingzi; Naveed, Hammad; Kachalo, Sema; Xu, Lisa X.; Liang, Jie

2014-01-01

Regulation of cell growth and cell division plays fundamental roles in tissue morphogenesis. However, the mechanisms of regulating tissue elongation through cell growth and cell division are still not well understood. The wing imaginal disc of Drosophila provides a model system that has been widely used to study tissue morphogenesis. Here we use a recently developed two-dimensional cellular model to study the mechanisms of regulating tissue elongation in Drosophila wing. We simulate the effects of directional cues on tissue elongation. We also computationally analyze the role of reduced cell size. Our simulation results indicate that oriented cell divisions, oriented mechanical forces, and reduced cell size can all mediate tissue elongation, but they function differently. We show that oriented cell divisions and oriented mechanical forces act as directional cues during tissue elongation. Between these two directional cues, oriented mechanical forces have a stronger influence than oriented cell divisions. In addition, we raise the novel hypothesis that reduced cell size may significantly promote tissue elongation. We find that reduced cell size alone cannot drive tissue elongation. However, when combined with directional cues, such as oriented cell divisions or oriented mechanical forces, reduced cell size can significantly enhance tissue elongation in Drosophila wing. Furthermore, our simulation results suggest that reduced cell size has a short-term effect on cell topology by decreasing the frequency of hexagonal cells, which is consistent with experimental observations. Our simulation results suggest that cell divisions without cell growth play essential roles in tissue elongation. PMID:24504016

O-linked β-N-acetylglucosamine transferase directs cell proliferation in idiopathic pulmonary arterial hypertension.

PubMed

Barnes, Jarrod W; Tian, Liping; Heresi, Gustavo A; Farver, Carol F; Asosingh, Kewal; Comhair, Suzy A A; Aulak, Kulwant S; Dweik, Raed A

2015-04-07

Idiopathic pulmonary arterial hypertension (IPAH) is a cardiopulmonary disease characterized by cellular proliferation and vascular remodeling. A more recently recognized characteristic of the disease is the dysregulation of glucose metabolism. The primary link between altered glucose metabolism and cell proliferation in IPAH has not been elucidated. We aimed to determine the relationship between glucose metabolism and smooth muscle cell proliferation in IPAH. Human IPAH and control patient lung tissues and pulmonary artery smooth muscle cells (PASMCs) were used to analyze a specific pathway of glucose metabolism, the hexosamine biosynthetic pathway. We measured the levels of O-linked β-N-acetylglucosamine modification, O-linked β-N-acetylglucosamine transferase (OGT), and O-linked β-N-acetylglucosamine hydrolase in control and IPAH cells and tissues. Our data suggest that the activation of the hexosamine biosynthetic pathway directly increased OGT levels and activity, triggering changes in glycosylation and PASMC proliferation. Partial knockdown of OGT in IPAH PASMCs resulted in reduced global O-linked β-N-acetylglucosamine modification levels and abrogated PASMC proliferation. The increased proliferation observed in IPAH PASMCs was directly impacted by proteolytic activation of the cell cycle regulator, host cell factor-1. Our data demonstrate that hexosamine biosynthetic pathway flux is increased in IPAH and drives OGT-facilitated PASMC proliferation through specific proteolysis and direct activation of host cell factor-1. These findings establish a novel regulatory role for OGT in IPAH, shed a new light on our understanding of the disease pathobiology, and provide opportunities to design novel therapeutic strategies for IPAH. © 2015 American Heart Association, Inc.

Comparing spatially static and dynamic vibrotactile take-over requests in the driver seat.

PubMed

Petermeijer, S M; Cieler, S; de Winter, J C F

2017-02-01

Vibrotactile stimuli can be effective as warning signals, but their effectiveness as directional take-over requests in automated driving is yet unknown. This study aimed to investigate the correct response rate, reaction times, and eye and head orientation for static versus dynamic directional take-over requests presented via vibrating motors in the driver seat. In a driving simulator, eighteen participants performed three sessions: 1) a session involving no driving (Baseline), 2) driving a highly automated car without additional task (HAD), and 3) driving a highly automated car while performing a mentally demanding task (N-Back). Per session, participants received four directional static (in the left or right part of the seat) and four dynamic (moving from one side towards the opposite left or right of the seat) take-over requests via two 6×4 motor matrices embedded in the seat back and bottom. In the Baseline condition, participants reported whether the cue was left or right, and in the HAD and N-Back conditions participants had to change lanes to the left or to the right according to the directional cue. The correct response rate was operationalized as the accuracy of the self-reported direction (Baseline session) and the accuracy of the lane change direction (HAD & N-Back sessions). The results showed that the correct response rate ranged between 94% for static patterns in the Baseline session and 74% for dynamic patterns in the N-Back session, although these effects were not statistically significant. Steering wheel touch and steering input reaction times were approximately 200ms faster for static patterns than for dynamic ones. Eye tracking results revealed a correspondence between head/eye-gaze direction and lane change direction, and showed that head and eye-gaze movements where initiated faster for static vibrations than for dynamic ones. In conclusion, vibrotactile stimuli presented via the driver seat are effective as warnings, but their effectiveness as directional take-over requests may be limited. The present study may encourage further investigation into how to get drivers safely back into the loop. Copyright © 2016 Elsevier Ltd. All rights reserved.

Laser direct writing of combinatorial libraries of idealized cellular constructs: Biomedical applications

NASA Astrophysics Data System (ADS)

Schiele, Nathan R.; Koppes, Ryan A.; Corr, David T.; Ellison, Karen S.; Thompson, Deanna M.; Ligon, Lee A.; Lippert, Thomas K. M.; Chrisey, Douglas B.

2009-03-01

The ability to control cell placement and to produce idealized cellular constructs is essential for understanding and controlling intercellular processes and ultimately for producing engineered tissue replacements. We have utilized a novel intra-cavity variable aperture excimer laser operated at 193 nm to reproducibly direct write mammalian cells with micrometer resolution to form a combinatorial array of idealized cellular constructs. We deposited patterns of human dermal fibroblasts, mouse myoblasts, rat neural stem cells, human breast cancer cells, and bovine pulmonary artery endothelial cells to study aspects of collagen network formation, breast cancer progression, and neural stem cell proliferation, respectively. Mammalian cells were deposited by matrix assisted pulsed laser evaporation direct write from ribbons comprised of a UV transparent quartz coated with either a thin layer of extracellular matrix or triazene as a dynamic release layer using CAD/CAM control. We demonstrate that through optical imaging and incorporation of a machine vision algorithm, specific cells on the ribbon can be laser deposited in spatial coherence with respect to geometrical arrays and existing cells on the receiving substrate. Having the ability to direct write cells into idealized cellular constructs can help to answer many biomedical questions and advance tissue engineering and cancer research.

Research on traffic flow characteristics at signal intersection

NASA Astrophysics Data System (ADS)

Zeng, Jun-Wei; Yu, Sen-Bin; Qian, Yong-Sheng; Wei, Xu-Ting; Feng, Xiao; Wang, Hui

2017-09-01

Based on the cautious driving behavior and the principle of the vehicles at left-side having priority to pass in the intersection, a two-dimensional cellular automata model for planar signalized intersection (NS-STCA) is established. The different turning vehicles are regarded as the research objects and the effect of the left-turn probability, signal cycle, vehicle flow density on traffic flow at the intersection is investigated.

Toward Pride and Professionalism: Increasing Personal Responsibility. Facilitator Guide.

DTIC Science & Technology

1985-05-22

Stress Intervention. Richmond, CA: New Harbinger, 1981. 6. Medical Device Corporation, 1555 Bellefontaine, North Drive, Indianapolis, Indiana, 46202. (317...impair one’s cellular building and repair, as well as immune responses, making him or her less able to withstand bacterial and viral infection. Cancer ...facilitator should begin a collection of ads--perhaps those from medical magazines, treatment magazines, or other professional sources not ordinarily

Voltage directive drive with claw pole motor and control without rotor position indicator

NASA Astrophysics Data System (ADS)

Stroenisch, Volker Ewald

Design and testing of a voltage directive drive for synchronous variable speed claw pole motor and control without rotor position indicator is described. Economic analysis of the designed regulation is performed. Computations of stationary and dynamic behavior are given and experimental operational behavior is determined. The motors can be used for electric transportation vehicles, diesel motors, and electric railway engines.

Measuring listening effort: driving simulator vs. simple dual-task paradigm

PubMed Central

Wu, Yu-Hsiang; Aksan, Nazan; Rizzo, Matthew; Stangl, Elizabeth; Zhang, Xuyang; Bentler, Ruth

2014-01-01

Objectives The dual-task paradigm has been widely used to measure listening effort. The primary objectives of the study were to (1) investigate the effect of hearing aid amplification and a hearing aid directional technology on listening effort measured by a complicated, more real world dual-task paradigm, and (2) compare the results obtained with this paradigm to a simpler laboratory-style dual-task paradigm. Design The listening effort of adults with hearing impairment was measured using two dual-task paradigms, wherein participants performed a speech recognition task simultaneously with either a driving task in a simulator or a visual reaction-time task in a sound-treated booth. The speech materials and road noises for the speech recognition task were recorded in a van traveling on the highway in three hearing aid conditions: unaided, aided with omni directional processing (OMNI), and aided with directional processing (DIR). The change in the driving task or the visual reaction-time task performance across the conditions quantified the change in listening effort. Results Compared to the driving-only condition, driving performance declined significantly with the addition of the speech recognition task. Although the speech recognition score was higher in the OMNI and DIR conditions than in the unaided condition, driving performance was similar across these three conditions, suggesting that listening effort was not affected by amplification and directional processing. Results from the simple dual-task paradigm showed a similar trend: hearing aid technologies improved speech recognition performance, but did not affect performance in the visual reaction-time task (i.e., reduce listening effort). The correlation between listening effort measured using the driving paradigm and the visual reaction-time task paradigm was significant. The finding showing that our older (56 to 85 years old) participants’ better speech recognition performance did not result in reduced listening effort was not consistent with literature that evaluated younger (approximately 20 years old), normal hearing adults. Because of this, a follow-up study was conducted. In the follow-up study, the visual reaction-time dual-task experiment using the same speech materials and road noises was repeated on younger adults with normal hearing. Contrary to findings with older participants, the results indicated that the directional technology significantly improved performance in both speech recognition and visual reaction-time tasks. Conclusions Adding a speech listening task to driving undermined driving performance. Hearing aid technologies significantly improved speech recognition while driving, but did not significantly reduce listening effort. Listening effort measured by dual-task experiments using a simulated real-world driving task and a conventional laboratory-style task was generally consistent. For a given listening environment, the benefit of hearing aid technologies on listening effort measured from younger adults with normal hearing may not be fully translated to older listeners with hearing impairment. PMID:25083599

Linking microbial and ecosystem ecology using ecological stoichiometry: a synthesis of conceptual and empirical approaches

USGS Publications Warehouse

Hall, E.K.; Maixner, F.; Franklin, O.; Daims, H.; Richter, A.; Battin, T.

2011-01-01

Currently, one of the biggest challenges in microbial and ecosystem ecology is to develop conceptual models that organize the growing body of information on environmental microbiology into a clear mechanistic framework with a direct link to ecosystem processes. Doing so will enable development of testable hypotheses to better direct future research and increase understanding of key constraints on biogeochemical networks. Although the understanding of phenotypic and genotypic diversity of microorganisms in the environment is rapidly accumulating, how controls on microbial physiology ultimately affect biogeochemical fluxes remains poorly understood. We propose that insight into constraints on biogeochemical cycles can be achieved by a more rigorous evaluation of microbial community biomass composition within the context of ecological stoichiometry. Multiple recent studies have pointed to microbial biomass stoichiometry as an important determinant of when microorganisms retain or recycle mineral nutrients. We identify the relevant cellular components that most likely drive changes in microbial biomass stoichiometry by defining a conceptual model rooted in ecological stoichiometry. More importantly, we show how X-ray microanalysis (XRMA), nanoscale secondary ion mass spectroscopy (NanoSIMS), Raman microspectroscopy, and in situ hybridization techniques (for example, FISH) can be applied in concert to allow for direct empirical evaluation of the proposed conceptual framework. This approach links an important piece of the ecological literature, ecological stoichiometry, with the molecular front of the microbial revolution, in an attempt to provide new insight into how microbial physiology could constrain ecosystem processes.

Electrical motor/generator drive apparatus and method

DOEpatents

Su, Gui Jia

2013-02-12

The present disclosure includes electrical motor/generator drive systems and methods that significantly reduce inverter direct-current (DC) bus ripple currents and thus the volume and cost of a capacitor. The drive methodology is based on a segmented drive system that does not add switches or passive components but involves reconfiguring inverter switches and motor stator winding connections in a way that allows the formation of multiple, independent drive units and the use of simple alternated switching and optimized Pulse Width Modulation (PWM) schemes to eliminate or significantly reduce the capacitor ripple current.

Platelets: No longer bystanders in liver disease

PubMed Central

Adams, David H.; Watson, Steve P.; Lalor, Patricia F.

2016-01-01

Growing lines of evidence recognize that platelets play a central role in liver homeostasis and pathobiology. Platelets have important roles at every stage during the continuum of liver injury and healing. These cells contribute to the initiation of liver inflammation by promoting leukocyte recruitment through sinusoidal endothelium. They can activate effector cells, thus amplifying liver damage, and by modifying the hepatic cellular and cytokine milieu drive both hepatoprotective and hepatotoxic processes. Conclusion: In this review we summarize how platelets drive such pleiotropic actions and attempt to reconcile the paradox of platelets being both deleterious and beneficial to liver function; with increasingly novel methods of manipulating platelet function at our disposal, we highlight avenues for future therapeutic intervention in liver disease. (Hepatology 2016;64:1774‐1784) PMID:26934463

Mechano-adaptation of the stem cell nucleus.

PubMed

Heo, Su-Jin; Cosgrove, Brian D; Dai, Eric N; Mauck, Robert L

2018-01-01

Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this "mechano-adaptation" are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation.

Mechano-adaptation of the stem cell nucleus

PubMed Central

Heo, Su-Jin; Cosgrove, Brian D.; Dai, Eric N.; Mauck, Robert L.

2018-01-01

ABSTRACT Exogenous mechanical forces are transmitted through the cell and to the nucleus, initiating mechanotransductive signaling cascades with profound effects on cellular function and stem cell fate. A growing body of evidence has shown that the force sensing and force-responsive elements of the nucleus adapt to these mechanotransductive events, tuning their response to future mechanical input. The mechanisms underlying this “mechano-adaptation” are only just beginning to be elucidated, and it remains poorly understood how these components act and adapt in tandem to drive stem cell differentiation. Here, we review the evidence on how the stem cell nucleus responds and adapts to physical forces, and provide a perspective on how this mechano-adaptation may function to drive and enforce stem cell differentiation. PMID:29099288

The Position Control of the Surface Motor with the Poles Distribution of Triangular Lattice

NASA Astrophysics Data System (ADS)

Watada, Masaya; Katsuyama, Norikazu; Ebihara, Daiki

Recently, as for the machine tools or industrial robots, high performance, accuracy, etc. are demanded. Generally, when drive of many degrees of freedom is required in the machine tools or industrial robots, it has realized by using two or more motors. For example, two-dimensional positioning stages such as the X-Y plotter or the X-Y stage are enabling the two-dimensional drive by using each one motor in the direction of x, y. In order to use plural motors, these, however, have problems that equipment becomes large and complicate control system. From such problems, the Surface Motor (SFM) that can drive two directions by only one motor is researched. Authors have proposed SFM that considered wide range movement and the application to a curved surface. In this paper, the characteristics of the micro step drive by the open loop control are showed. Introduction of closed loop control for highly accurate positioning, moreover, is examined. The drive characteristics by each control are compared.

Signaling by STATs.

PubMed

Ivashkiv, Lionel B; Hu, Xiaoyu

2004-01-01

A variety of cytokines and growth factors use the Janus kinase (Jak)-STAT signaling pathway to transmit extracellular signals to the nucleus. STATs (signal transducers and activators of transcription) are latent cytoplasmic transcription factors. There are seven mammalian STATs and they have critical, nonredundant roles in mediating cellular transcriptional responses to cytokines. The physiological roles of STATs have been elucidated by analysis of mice rendered deficient in STAT genes. STAT activation is regulated and can be modulated in a positive or negative fashion; it can be reprogrammed to drive different cellular responses. Several auto-regulatory and signaling crosstalk mechanisms for regulating Jak-STAT signaling have been described. Understanding and manipulation of the function of STATs will help in the development of therapeutic strategies for diseases that are regulated by cytokines.

Characterizing emergent properties of immunological systems with multi-cellular rule-based computational modeling.

PubMed

Chavali, Arvind K; Gianchandani, Erwin P; Tung, Kenneth S; Lawrence, Michael B; Peirce, Shayn M; Papin, Jason A

2008-12-01

The immune system is comprised of numerous components that interact with one another to give rise to phenotypic behaviors that are sometimes unexpected. Agent-based modeling (ABM) and cellular automata (CA) belong to a class of discrete mathematical approaches in which autonomous entities detect local information and act over time according to logical rules. The power of this approach lies in the emergence of behavior that arises from interactions between agents, which would otherwise be impossible to know a priori. Recent work exploring the immune system with ABM and CA has revealed novel insights into immunological processes. Here, we summarize these applications to immunology and, particularly, how ABM can help formulate hypotheses that might drive further experimental investigations of disease mechanisms.

Extracellular matrix motion and early morphogenesis.

PubMed

Loganathan, Rajprasad; Rongish, Brenda J; Smith, Christopher M; Filla, Michael B; Czirok, Andras; Bénazéraf, Bertrand; Little, Charles D

2016-06-15

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale 'total' cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. © 2016. Published by The Company of Biologists Ltd.

Traffic ticket fixing and driving behaviours in a large French working population.

PubMed

Lagarde, E; Chiron, M; Lafont, S

2004-07-01

The use of connections who have the authority to cancel penalties related to traffic violations seems to be very frequent in France. This study aimed at describing risk taking driving behaviours associated in France with using connections to have traffic tickets cancelled (ticket fixing). Retrospective study on driving behaviour and road safety conducted between March and December 2001 within a cohort of French employees. France. Employees of the French national utility company who have been followed up since 1989. The sample comprises 10 594 men aged 53-63 years and 3258 women aged 48-63 in 2001. One third of the men and one fifth of the women reported that they had had a ticket fixed at some time. Those who reported having tickets fixed were more likely than the others to report high driving speeds (adjusted odds ratios (aOR) were 1.24, 1.52, and 1.66 in built up areas, on rural roads, and on motorways respectively), to report driving while under the influence (aOR = 1.39), and to report risky use of cellular phone while driving (aOR = 1.83). In addition, participants who reported having tickets fixed were more likely to have had at least one serious road traffic accident in the past 11 years (aOR = 1.21). Indulgence and the use of connections are common practices in France. These results suggest that it is to confer a feeling of impunity that jeopardises efforts to combat unsafe driving. Abolition of these traditions is essential to ensure the credibility of preventive and repressive measures.

Schistosome egg antigens, including the glycoprotein IPSE/alpha-1, trigger the development of regulatory B cells

PubMed Central

Veninga, Henrike; van der Vlugt, Luciën E. P. M.; Voskamp, Astrid; Boon, Louis; Westerhof, Lotte B.; Smits, Hermelijn H.

2017-01-01

Infection with the helminth Schistosoma (S.) mansoni drives the development of interleukin (IL)-10-producing regulatory B (Breg) cells in mice and man, which have the capacity to reduce experimental allergic airway inflammation and are thus of high therapeutic interest. However, both the involved antigen and cellular mechanisms that drive Breg cell development remain to be elucidated. Therefore, we investigated whether S. mansoni soluble egg antigens (SEA) directly interact with B cells to enhance their regulatory potential, or act indirectly on B cells via SEA-modulated macrophage subsets. Intraperitoneal injections of S. mansoni eggs or SEA significantly upregulated IL-10 and CD86 expression by marginal zone B cells. Both B cells as well as macrophages of the splenic marginal zone efficiently bound SEA in vivo, but macrophages were dispensable for Breg cell induction as shown by macrophage depletion with clodronate liposomes. SEA was internalized into acidic cell compartments of B cells and induced a 3-fold increase of IL-10, which was dependent on endosomal acidification and was further enhanced by CD40 ligation. IPSE/alpha-1, one of the major antigens in SEA, was also capable of inducing IL-10 in naïve B cells, which was reproduced by tobacco plant-derived recombinant IPSE. Other major schistosomal antigens, omega-1 and kappa-5, had no effect. SEA depleted of IPSE/alpha-1 was still able to induce Breg cells indicating that SEA contains more Breg cell-inducing components. Importantly, SEA- and IPSE-induced Breg cells triggered regulatory T cell development in vitro. SEA and recombinant IPSE/alpha-1 also induced IL-10 production in human CD1d+ B cells. In conclusion, the mechanism of S. mansoni-induced Breg cell development involves a direct targeting of B cells by SEA components such as the secretory glycoprotein IPSE/alpha-1. PMID:28753651

Force loading explains spatial sensing of ligands by cells

NASA Astrophysics Data System (ADS)

Oria, Roger; Wiegand, Tina; Escribano, Jorge; Elosegui-Artola, Alberto; Uriarte, Juan Jose; Moreno-Pulido, Cristian; Platzman, Ilia; Delcanale, Pietro; Albertazzi, Lorenzo; Navajas, Daniel; Trepat, Xavier; García-Aznar, José Manuel; Cavalcanti-Adam, Elisabetta Ada; Roca-Cusachs, Pere

2017-12-01

Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin-ligand bonds are separated by more than a few tens of nanometres. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model, in which individual integrin-ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds support our model. Our results provide a general framework for how cells sense spatial and physical information at the nanoscale, precisely tuning the range of conditions at which they form adhesions and activate transcriptional regulation.

Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

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

Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu

Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, andmore » chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.« less

Polar-Direct-Drive Defect Implosions at OMEGA inPreparation for Experiments at NIF

NASA Astrophysics Data System (ADS)

Cobble, J. A.; Schmitt, M. J.; Murphy, T. J.; Tregillis, I. L.; Wysocki, F. J.; Obrey, K. D.; Magelssen, G. R.; Glebov, V.; Bradley, P. A.; Hsu, S. C.; Krasheninnikova, N. V.; Batha, S. H.

2011-10-01

The Defect-Implosion (DIME) campaign involves compressing perturbed spherical capsules with polar direct drive (PDD). For direct-drive implosions at NIF, PDD will be used. We have done simulations and experiments at OMEGA to test our modeling capability for equatorial-plane defects in fusion capsules and for PDD at NIF. Since PDD is anisotropic, we show the results of 0th hydrodynamics of implosions and perturbation-driven features near stagnation. Later presentations discuss defect-induced mix and neutronics, and laser pointing for NIF experiments. Prototype OMEGA shots used 865- μm diameter CH shells filled with 5 atm of D2. Machined channels 30- μm wide and up to 9- μm deep formed the defects. This work has been performed under the auspices of the US DOE, contract number DE-AC52-06NA25396.

First measurements of deuterium-tritium and deuterium-deuterium fusion reaction yields in ignition-scalable direct-drive implosions

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

Forrest, C. J.; Radha, P. B.; Knauer, J. P.

In this study, the deuterium-tritium (D-T) and deuterium-deuterium neutron yield ratio in cryogenic inertial confinement fusion (ICF) experiments is used to examine multifluid effects, traditionally not included in ICF modeling. This ratio has been measured for ignition-scalable direct-drive cryogenic DT implosions at the Omega Laser Facility using a high-dynamic-range neutron time-of-flight spectrometer. The experimentally inferred yield ratio is consistent with both the calculated values of the nuclear reaction rates and the measured preshot target-fuel composition. These observations indicate that the physical mechanisms that have been proposed to alter the fuel composition, such as species separation of the hydrogen isotopes, aremore » not significant during the period of peak neutron production in ignition-scalable cryogenic direct-drive DT implosions.« less

First measurements of deuterium-tritium and deuterium-deuterium fusion reaction yields in ignition-scalable direct-drive implosions

DOE PAGES

Forrest, C. J.; Radha, P. B.; Knauer, J. P.; ...

2017-03-03

In this study, the deuterium-tritium (D-T) and deuterium-deuterium neutron yield ratio in cryogenic inertial confinement fusion (ICF) experiments is used to examine multifluid effects, traditionally not included in ICF modeling. This ratio has been measured for ignition-scalable direct-drive cryogenic DT implosions at the Omega Laser Facility using a high-dynamic-range neutron time-of-flight spectrometer. The experimentally inferred yield ratio is consistent with both the calculated values of the nuclear reaction rates and the measured preshot target-fuel composition. These observations indicate that the physical mechanisms that have been proposed to alter the fuel composition, such as species separation of the hydrogen isotopes, aremore » not significant during the period of peak neutron production in ignition-scalable cryogenic direct-drive DT implosions.« less

Relative Advantages of Direct and Indirect Drive for an Inertial Fusion Energy Power Plant Driven by a Diode-Pumped Solid-State Laser

NASA Astrophysics Data System (ADS)

Orth, C. D.

2001-03-01

This paper reviews our current understanding of the relative advantages of direct drive (DD) and indirect drive (ID) for a 1 GWe inertial fusion energy (IFE) power plant driven by a diode-pumped solid-state laser (DPSSL). This comparison is motivated by a recent study (1) that shows that the projected cost of electricity (COE) for DD is actually about the same as that for ID even though the target gain for DD can be much larger. We can therefore no longer assume that DD is the ultimate targeting scenario for IFE, and must begin a more rigorous comparison of these two drive options. The comparison begun here shows that ID may actually end up being preferred, but the uncertainties are still rather large.

Superconducting wind turbine generators

NASA Astrophysics Data System (ADS)

Abrahamsen, A. B.; Mijatovic, N.; Seiler, E.; Zirngibl, T.; Træholt, C.; Nørgård, P. B.; Pedersen, N. F.; Andersen, N. H.; Østergård, J.

2010-03-01

We have examined the potential of 10 MW superconducting direct drive generators to enter the European offshore wind power market and estimated that the production of about 1200 superconducting turbines until 2030 would correspond to 10% of the EU offshore market. The expected properties of future offshore turbines of 8 and 10 MW have been determined from an up-scaling of an existing 5 MW turbine and the necessary properties of the superconducting drive train are discussed. We have found that the absence of the gear box is the main benefit and the reduced weight and size is secondary. However, the main challenge of the superconducting direct drive technology is to prove that the reliability is superior to the alternative drive trains based on gearboxes or permanent magnets. A strategy of successive testing of superconducting direct drive trains in real wind turbines of 10 kW, 100 kW, 1 MW and 10 MW is suggested to secure the accumulation of reliability experience. Finally, the quantities of high temperature superconducting tape needed for a 10 kW and an extreme high field 10 MW generator are found to be 7.5 km and 1500 km, respectively. A more realistic estimate is 200-300 km of tape per 10 MW generator and it is concluded that the present production capacity of coated conductors must be increased by a factor of 36 by 2020, resulting in a ten times lower price of the tape in order to reach a realistic price level for the superconducting drive train.

Cellular stress induces a protective sleep-like state in C. elegans.

PubMed

Hill, Andrew J; Mansfield, Richard; Lopez, Jessie M N G; Raizen, David M; Van Buskirk, Cheryl

2014-10-20

Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Concerted action of neuroepithelial basal shrinkage and active epithelial migration ensures efficient optic cup morphogenesis

PubMed Central

Sidhaye, Jaydeep; Norden, Caren

2017-01-01

Organ formation is a multi-scale event that involves changes at the intracellular, cellular and tissue level. Organogenesis often starts with the formation of characteristically shaped organ precursors. However, the cellular mechanisms driving organ precursor formation are often not clear. Here, using zebrafish, we investigate the epithelial rearrangements responsible for the development of the hemispherical retinal neuroepithelium (RNE), a part of the optic cup. We show that in addition to basal shrinkage of RNE cells, active migration of connected epithelial cells into the RNE is a crucial player in its formation. This cellular movement is driven by progressive cell-matrix contacts and actively translocates prospective RNE cells to their correct location before they adopt neuroepithelial fate. Failure of this migration during neuroepithelium formation leads to ectopic determination of RNE cells and consequently impairs optic cup formation. Overall, this study illustrates how spatiotemporal coordination between morphogenic movements and fate determination critically influences organogenesis. DOI: http://dx.doi.org/10.7554/eLife.22689.001 PMID:28372636

Towards mechanism-based simulation of impact damage using exascale computing

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

Direct drive digital servo press with high parallel control

NASA Astrophysics Data System (ADS)

Murata, Chikara; Yabe, Jun; Endou, Junichi; Hasegawa, Kiyoshi

2013-12-01

Direct drive digital servo press has been developed as the university-industry joint research and development since 1998. On the basis of this result, 4-axes direct drive digital servo press has been developed and in the market on April of 2002. This servo press is composed of 1 slide supported by 4 ball screws and each axis has linearscale measuring the position of each axis with high accuracy less than μm order level. Each axis is controlled independently by servo motor and feedback system. This system can keep high level parallelism and high accuracy even with high eccentric load. Furthermore the 'full stroke full power' is obtained by using ball screws. Using these features, new various types of press forming and stamping have been obtained by development and production. The new stamping and forming methods are introduced and 'manufacturing' need strategy of press forming with high added value and also the future direction of press forming are also introduced.

Axial gap rotating electrical machine

DOEpatents

None

2016-02-23

Direct drive rotating electrical machines with axial air gaps are disclosed. In these machines, a rotor ring and stator ring define an axial air gap between them. Sets of gap-maintaining rolling supports bear between the rotor ring and the stator ring at their peripheries to maintain the axial air gap. Also disclosed are wind turbines using these generators, and structures and methods for mounting direct drive rotating electrical generators to the hubs of wind turbines. In particular, the rotor ring of the generator may be carried directly by the hub of a wind turbine to rotate relative to a shaft without being mounted directly to the shaft.

Novel synthetic Medea selfish genetic elements drive population replacement in Drosophila; a theoretical exploration of Medea-dependent population suppression.

PubMed

Akbari, Omar S; Chen, Chun-Hong; Marshall, John M; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A

2014-12-19

Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.

What are the driving forces for water lifting in the xylem conduit?

PubMed

Zimmermann, Ulrich; Schneider, Heike; Wegner, Lars H; Wagner, Hans-Jürgen; Szimtenings, Michael; Haase, Axel; Bentrup, Friedrich-Wilhelm

2002-03-01

After Renner had shown convincingly in 1925 that the transpirational water loss generates tensions larger than 0.1 MPa (i.e. negative pressures) in the xylem of cut leafy twigs the Cohesion Theory proposed by Böhm, Askenasy, Dixon and Joly at the end of the 19th century was immediately accepted by plant physiologists. Introduction of the pressure chamber technique by Scholander et al. in 1965 enforced the general belief that tension is the only driving force for water lifting although substantial criticism regarding the technique and/or the Cohesion Theory was published by several authors. As typical for scientific disciplines, the advent of minimal- and non-invasive techniques in the last decade as well as the development of a new, reliable method for xylem sap sampling have challenged this view. Today, xylem pressure gradients, potentials, ion concentrations and volume flows as well as cell turgor pressure gradients can be monitored online in intact transpiring higher plants, and within a given physiological context by using the pressure probe technique and high-resolution NMR imaging techniques, respectively. Application of the pressure probe technique to transpiring plants has shown that negative absolute pressures (down to - 0.6 MPa) and pressure gradients can exist temporarily in the xylem conduit, but that the magnitude and (occasionally) direction of gradients contrasts frequently the belief that tension is the only driving force. This seems to be particularly the case for plants faced with problems of height, drought, freezing and salinity as well as with cavitation of the tensile water. Reviewing the current data base shows that other forces come into operation when exclusively tension fails to lift water against gravity due to environmental conditions. Possible candidates are longitudinal cellular and xylem osmotic pressure gradients, axial potential gradients in the vessels as well as gel- and gas bubble-supported interfacial gradients. The multiforce theory overcomes the problem of the Cohesion Theory that life on earth depends on water being in a highly metastable state.

Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

PubMed Central

Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

2015-01-01

Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

Cellular instability in rapid directional solidification - Bifurcation theory

NASA Technical Reports Server (NTRS)

Braun, R. J.; Davis, S. H.

1992-01-01

Merchant and Davis performed a linear stability analysis on a model for the directional solidification of a dilute binary alloy valid for all speeds. The analysis revealed that nonequilibrium segregation effects modify the Mullins and Sekerka cellular mode, whereas attachment kinetics has no effect on these cells. In this paper, the nonlinear stability of the steady cellular mode is analyzed. A Landau equation is obtained that determines the amplitude of the cells. The Landau coefficient here depends on both nonequilibrium segregation effects and attachment kinetics. This equation gives the ranges of parameters for subcritical bifurcation (jump transition) or supercritical bifurcation (smooth transition) to cells.

Design and testing of botanical thermotropic actuator mechanisms in thermally adaptive building coverings

NASA Astrophysics Data System (ADS)

Barrett, Ronald M.; Barrett, Ronald P.; Barrett, Cassandra M.

2017-09-01

This paper lays out the inspiration, operational principles, analytical modeling and coupon testing of a new class of thermally adaptive building coverings. The fundamental driving concepts for these coverings are derived from various families of thermotropic plant structures. Certain plant cellular structures like those in Mimosa pudica (Sensitive Plant), Rhododendron leaves or Albizia julibrissin (Mimosa Tree), exhibit actuation physiology which depends on changes in cellular turgor pressures to generate motion. This form of cellular action via turgor pressure manipulation is an inspiration for a new field of thermally adaptive building coverings which use various forms of cellular foam to aid or enable actuation much like plant cells are used to move leaves. When exposed to high solar loading, the structures use the inherent actuation capability of pockets of air trapped in closed cell foam as actuators to curve plates upwards and outwards. When cold, these same structures curve back towards the building forming large convex pockets of dead air to insulate the building. This paper describes basic classical laminated plate theory models comparing theory and experiment of such coupons containing closed-cell foam actuators. The study concludes with a global description of the effectiveness of this class of thermally adaptive building coverings.

A role for G-protein coupled estrogen receptor (GPER) in estrogen-induced carcinogenesis: Dysregulated glandular homeostasis, survival and metastasis.

PubMed

Filardo, Edward J

2018-02-01

Mechanisms of carcinogenesis by estrogen center on its mitogenic and genotoxic potential on tumor target cells. These models suggest that estrogen receptor (ER) signaling promotes expansion of the transformed population and that subsequent accumulation of somatic mutations that drive cancer progression occur via metabolic activation of cathecol estrogens or by epigenetic mechanisms. Recent findings that GPER is linked to obesity, vascular pathology and immunosuppression, key events in the development of metabolic syndrome and intra-tissular estrogen synthesis, provides an alternate view of estrogen-induced carcinogenesis. Consistent with this concept, GPER is directly associated with clinicopathological indices that predict cancer progression and poor survival in breast and gynecological cancers. Moreover, GPER manifests cell biological responses and a microenvironment conducive for tumor development and cancer progression, regulating cellular responses associated with glandular homeostasis and survival, invading surrounding tissue and attracting a vascular supply. Thus, the cellular actions attributed to GPER fit well with the known molecular mechanisms of G-protein coupled receptors, GPCRs, namely, their ability to transactivate integrins and EGF receptors and alter the interaction between glandular epithelia and their extracellular environment, affecting epithelial-to-mesenchymal transition (EMT) and allowing for tumor cell survival and dissemination. This perspective reviews the molecular and cellular responses manifested by GPER and evaluates its contribution to female reproductive cancers as diseases that progress as a result of dysregulated glandular homeostasis resulting in chronic inflammation and metastasis. This review is organized in sections as follows: I) a brief synopsis of the current state of knowledge regarding estrogen-induced carcinogenesis, II) a review of evidence from clinical and animal-based studies that support a role for GPER in cancer progression, and III) a mechanistic framework describing how GPER-mediated estrogen action may influence the tumor and its microenvironment. Published by Elsevier Ltd.

T Cell LEGO: Identifying the Master Builders and What They Do.

PubMed

Li, Jasmine; Turner, Stephen J

2018-02-20

Understanding how cell fate decisions are made during cellular differentiation and the mechanisms that drive them is a holy grail of cell biology. In this issue of Immunity, Hu et al. (2018) and Johnson et al. (2018) demonstrate that key transcriptional regulators and global changes in nuclear architecture underlie differentiation decisions during T cell development. Copyright © 2018 Elsevier Inc. All rights reserved.

Collagen Matrix Density Drives the Metabolic Shift in Breast Cancer Cells.

PubMed

Morris, Brett A; Burkel, Brian; Ponik, Suzanne M; Fan, Jing; Condeelis, John S; Aguirre-Ghiso, Julio A; Castracane, James; Denu, John M; Keely, Patricia J

2016-11-01

Increased breast density attributed to collagen I deposition is associated with a 4-6 fold increased risk of developing breast cancer. Here, we assessed cellular metabolic reprogramming of mammary carcinoma cells in response to increased collagen matrix density using an in vitro 3D model. Our initial observations demonstrated changes in functional metabolism in both normal mammary epithelial cells and mammary carcinoma cells in response to changes in matrix density. Further, mammary carcinoma cells grown in high density collagen matrices displayed decreased oxygen consumption and glucose metabolism via the tricarboxylic acid (TCA) cycle compared to cells cultured in low density matrices. Despite decreased glucose entry into the TCA cycle, levels of glucose uptake, cell viability, and ROS were not different between high and low density matrices. Interestingly, under high density conditions the contribution of glutamine as a fuel source to drive the TCA cycle was significantly enhanced. These alterations in functional metabolism mirrored significant changes in the expression of metabolic genes involved in glycolysis, oxidative phosphorylation, and the serine synthesis pathway. This study highlights the broad importance of the collagen microenvironment to cellular expression profiles, and shows that changes in density of the collagen microenvironment can modulate metabolic shifts of cancer cells. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The bacterial actin MreB rotates, and rotation depends on cell-wall assembly.

PubMed

van Teeffelen, Sven; Wang, Siyuan; Furchtgott, Leon; Huang, Kerwyn Casey; Wingreen, Ned S; Shaevitz, Joshua W; Gitai, Zemer

2011-09-20

Bacterial cells possess multiple cytoskeletal proteins involved in a wide range of cellular processes. These cytoskeletal proteins are dynamic, but the driving forces and cellular functions of these dynamics remain poorly understood. Eukaryotic cytoskeletal dynamics are often driven by motor proteins, but in bacteria no motors that drive cytoskeletal motion have been identified to date. Here, we quantitatively study the dynamics of the Escherichia coli actin homolog MreB, which is essential for the maintenance of rod-like cell shape in bacteria. We find that MreB rotates around the long axis of the cell in a persistent manner. Whereas previous studies have suggested that MreB dynamics are driven by its own polymerization, we show that MreB rotation does not depend on its own polymerization but rather requires the assembly of the peptidoglycan cell wall. The cell-wall synthesis machinery thus either constitutes a novel type of extracellular motor that exerts force on cytoplasmic MreB, or is indirectly required for an as-yet-unidentified motor. Biophysical simulations suggest that one function of MreB rotation is to ensure a uniform distribution of new peptidoglycan insertion sites, a necessary condition to maintain rod shape during growth. These findings both broaden the view of cytoskeletal motors and deepen our understanding of the physical basis of bacterial morphogenesis.

Modeling and predicting urban growth pattern of the Tokyo metropolitan area based on cellular automata

NASA Astrophysics Data System (ADS)

Zhao, Yaolong; Zhao, Junsan; Murayama, Yuji

2008-10-01

The period of high economic growth in Japan which began in the latter half of the 1950s led to a massive migration of population from rural regions to the Tokyo metropolitan area. This phenomenon brought about rapid urban growth and urban structure changes in this area. Purpose of this study is to establish a constrained CA (Cellular Automata) model with GIS (Geographical Information Systems) to simulate urban growth pattern in the Tokyo metropolitan area towards predicting urban form and landscape for the near future. Urban land-use is classified into multi-categories for interpreting the effect of interaction among land-use categories in the spatial process of urban growth. Driving factors of urban growth pattern, such as land condition, railway network, land-use zoning, random perturbation, and neighborhood interaction and so forth, are explored and integrated into this model. These driving factors are calibrated based on exploratory spatial data analysis (ESDA), spatial statistics, logistic regression, and "trial and error" approach. The simulation is assessed at both macro and micro classification levels in three ways: visual approach; fractal dimension; and spatial metrics. Results indicate that this model provides an effective prototype to simulate and predict urban growth pattern of the Tokyo metropolitan area.

The RanGTP Pathway: From Nucleo-Cytoplasmic Transport to Spindle Assembly and Beyond

PubMed Central

Cavazza, Tommaso; Vernos, Isabelle

2016-01-01

The small GTPase Ran regulates the interaction of transport receptors with a number of cellular cargo proteins. The high affinity binding of the GTP-bound form of Ran to import receptors promotes cargo release, whereas its binding to export receptors stabilizes their interaction with the cargo. This basic mechanism linked to the asymmetric distribution of the two nucleotide-bound forms of Ran between the nucleus and the cytoplasm generates a switch like mechanism controlling nucleo-cytoplasmic transport. Since 1999, we have known that after nuclear envelope breakdown (NEBD) Ran and the above transport receptors also provide a local control over the activity of factors driving spindle assembly and regulating other aspects of cell division. The identification and functional characterization of RanGTP mitotic targets is providing novel insights into mechanisms essential for cell division. Here we review our current knowledge on the RanGTP system and its regulation and we focus on the recent advances made through the characterization of its mitotic targets. We then briefly review the novel functions of the pathway that were recently described. Altogether, the RanGTP system has moonlighting functions exerting a spatial control over protein interactions that drive specific functions depending on the cellular context. PMID:26793706

Cellular and Molecular Mechanisms of Action of Transcranial Direct Current Stimulation: Evidence from In Vitro and In Vivo Models

PubMed Central

Pelletier, Simon J.

2015-01-01

Transcranial direct current stimulation is a noninvasive technique that has been experimentally tested for a number of psychiatric and neurological conditions. Preliminary observations suggest that this approach can indeed influence a number of cellular and molecular pathways that may be disease relevant. However, the mechanisms of action underlying its beneficial effects are largely unknown and need to be better understood to allow this therapy to be used optimally. In this review, we summarize the physiological responses observed in vitro and in vivo, with a particular emphasis on cellular and molecular cascades associated with inflammation, angiogenesis, neurogenesis, and neuroplasticity recruited by direct current stimulation, a topic that has been largely neglected in the literature. A better understanding of the neural responses to transcranial direct current stimulation is critical if this therapy is to be used in large-scale clinical trials with a view of being routinely offered to patients suffering from various conditions affecting the central nervous system. PMID:25522391

Occupant Kinematics in Simulated Autonomous Driving Vehicle Collisions: Influence of Seating Position, Direction and Angle.

PubMed

Kitagawa, Yuichi; Hayashi, Shigeki; Yamada, Katsunori; Gotoh, Mitsuaki

2017-11-01

This two-part study analyzed occupant kinematics in simulated collisions of future automated driving vehicles in terms of seating configuration. In part one, a frontal collision was simulated with four occupants with the front seats reversed. The left front seat occupant was unbelted while the others were belted. In part two of the study, occupant restraint was examined in various seating configurations using a single seat model with a three-point seatbelt. The seat direction with respect to impact was considered as forward, rearward, and lateral facing in 45 degree increments. The effect of seat recline was also studied in the forward-facing and rear-facing cases by assuming three positions: driving position, resting position and relaxed position. Occupants were represented by human body finite element models. The results of part one showed that the front seat (rear-facing) occupants were restrained by the seatback, resulting in T1 forward displacement less than 100 mm; the rear seat occupants were restrained by the seatbelt resulting larger T1 forward displacement more than 500 mm. The results of the part two showed the directional dependence of occupant restraint. Greater T1 displacements were observed when the occupant faced lateral or front oblique. However, the seatbelt provided some restraint in all directions considered. The seatback generated contact force to the occupant when it was in the impact direction, including the lateral directions. The relaxed position allowed increased excursion compared to the driving position when the occupant faced rearward, but the magnitude of this increase was lower with lower impact speed.

Gelatin-based laser direct-write technique for the precise spatial patterning of cells.

PubMed

Schiele, Nathan R; Chrisey, Douglas B; Corr, David T

2011-03-01

Laser direct-writing provides a method to pattern living cells in vitro, to study various cell-cell interactions, and to build cellular constructs. However, the materials typically used may limit its long-term application. By utilizing gelatin coatings on the print ribbon and growth surface, we developed a new approach for laser cell printing that overcomes the limitations of Matrigel™. Gelatin is free of growth factors and extraneous matrix components that may interfere with cellular processes under investigation. Gelatin-based laser direct-write was able to successfully pattern human dermal fibroblasts with high post-transfer viability (91% ± 3%) and no observed double-strand DNA damage. As seen with atomic force microscopy, gelatin offers a unique benefit in that it is present temporarily to allow cell transfer, but melts and is removed with incubation to reveal the desired application-specific growth surface. This provides unobstructed cellular growth after printing. Monitoring cell location after transfer, we show that melting and removal of gelatin does not affect cellular placement; cells maintained registry within 5.6 ± 2.5 μm to the initial pattern. This study demonstrates the effectiveness of gelatin in laser direct-writing to create spatially precise cell patterns with the potential for applications in tissue engineering, stem cell, and cancer research.

"Smashed": A Quantitative Study on Adolescents' Attitude about Drinking and Driving after Viewing a Documentary Film

ERIC Educational Resources Information Center

Jaffe, Jana M.

2012-01-01

The use of alcohol by adolescents is a growing problem. Adolescents drinking and driving continues to be of great concern to society, as adolescent death from drinking and driving is not only untimely and unwarranted, but also preventable. Consequently, the need to find an intervention that speaks directly to adolescents about the negative effects…

Analysis of Korean Students' International Mobility by 2-D Model: Driving Force Factor and Directional Factor

ERIC Educational Resources Information Center

Park, Elisa L.

2009-01-01

The purpose of this study is to understand the dynamics of Korean students' international mobility to study abroad by using the 2-D Model. The first D, "the driving force factor," explains how and what components of the dissatisfaction with domestic higher education perceived by Korean students drives students' outward mobility to seek…

Metal band drives in spacecraft mechanisms

NASA Technical Reports Server (NTRS)

Maus, Daryl

1993-01-01

Transmitting and changing the characteristics of force and stroke is a requirement in nearly all mechanisms. Examples include changing linear to rotary motion, providing a 90 deg change in direction, and amplifying stroke or force. Requirements for size, weight, efficiency and reliability create unique problems in spacecraft mechanisms. Flexible metal band and cam drive systems provide powerful solutions to these problems. Band drives, rack and pinion gears, and bell cranks are compared for effectiveness. Band drive issues are discussed including materials, bend radius, fabrication, attachment and reliability. Numerous mechanisms are shown which illustrate practical applications of band drives.

The technology improvement and development of the new design-engineering principles of pilot bore directional drilling

NASA Astrophysics Data System (ADS)

Shadrina, A.; Saruev, L.; Vasenin, S.

2016-09-01

This paper addresses the effectiveness of impact energy use in pilot bore directional drilling at pipe driving. We establish and develop new design-engineering principles for this method. These principles are based on a drill string construction with a new nipple thread connection and a generator construction of strain waves transferred through the drill string. The experiment was conducted on a test bench. Strain measurement is used to estimate compression, tensile, shear and bending stresses in the drill string during the propagation of elastic waves. Finally, the main directions of pilot bore directional drilling improvement during pipe driving are determinated. The new engineering design, as components of the pilot bore directional drilling technology are presented.

Electric vehicle drive train with direct coupling transmission

DOEpatents

Tankersley, J.B.; Boothe, R.W.; Konrad, C.E.

1995-04-04

An electric vehicle drive train includes an electric motor and an associated speed sensor, a transmission operable in a speed reduction mode or a direct coupled mode, and a controller responsive to the speed sensor for operating the transmission in the speed reduction mode when the motor is below a predetermined value, and for operating the motor in the direct coupled mode when the motor speed is above a predetermined value. The controller reduces the speed of the motor, such as by regeneratively braking the motor, when changing from the speed reduction mode to the direct coupled mode. The motor speed may be increased when changing from the direct coupled mode to the speed reduction mode. The transmission is preferably a single stage planetary gearbox. 6 figures.

Electric vehicle drive train with direct coupling transmission

DOEpatents

Tankersley, Jerome B.; Boothe, Richard W.; Konrad, Charles E.

1995-01-01

An electric vehicle drive train includes an electric motor and an associated speed sensor, a transmission operable in a speed reduction mode or a direct coupled mode, and a controller responsive to the speed sensor for operating the transmission in the speed reduction mode when the motor is below a predetermined value, and for operating the motor in the direct coupled mode when the motor speed is above a predetermined value. The controller reduces the speed of the motor, such as by regeneratively braking the motor, when changing from the speed reduction mode to the direct coupled mode. The motor speed may be increased when changing from the direct coupled mode to the speed reduction mode. The transmission is preferably a single stage planetary gearbox.

Transposon mutagenesis identifies genes and cellular processes driving epithelial-mesenchymal transition in hepatocellular carcinoma

PubMed Central

Kodama, Takahiro; Newberg, Justin Y.; Kodama, Michiko; Rangel, Roberto; Yoshihara, Kosuke; Tien, Jean C.; Parsons, Pamela H.; Wu, Hao; Finegold, Milton J.; Copeland, Neal G.; Jenkins, Nancy A.

2016-01-01

Epithelial-mesenchymal transition (EMT) is thought to contribute to metastasis and chemoresistance in patients with hepatocellular carcinoma (HCC), leading to their poor prognosis. The genes driving EMT in HCC are not yet fully understood, however. Here, we show that mobilization of Sleeping Beauty (SB) transposons in immortalized mouse hepatoblasts induces mesenchymal liver tumors on transplantation to nude mice. These tumors show significant down-regulation of epithelial markers, along with up-regulation of mesenchymal markers and EMT-related transcription factors (EMT-TFs). Sequencing of transposon insertion sites from tumors identified 233 candidate cancer genes (CCGs) that were enriched for genes and cellular processes driving EMT. Subsequent trunk driver analysis identified 23 CCGs that are predicted to function early in tumorigenesis and whose mutation or alteration in patients with HCC is correlated with poor patient survival. Validation of the top trunk drivers identified in the screen, including MET (MET proto-oncogene, receptor tyrosine kinase), GRB2-associated binding protein 1 (GAB1), HECT, UBA, and WWE domain containing 1 (HUWE1), lysine-specific demethylase 6A (KDM6A), and protein-tyrosine phosphatase, nonreceptor-type 12 (PTPN12), showed that deregulation of these genes activates an EMT program in human HCC cells that enhances tumor cell migration. Finally, deregulation of these genes in human HCC was found to confer sorafenib resistance through apoptotic tolerance and reduced proliferation, consistent with recent studies showing that EMT contributes to the chemoresistance of tumor cells. Our unique cell-based transposon mutagenesis screen appears to be an excellent resource for discovering genes involved in EMT in human HCC and potentially for identifying new drug targets. PMID:27247392

Recent advances in understanding vitiligo.

PubMed

Manga, Prashiela; Elbuluk, Nada; Orlow, Seth J

2016-01-01

Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.

New insights into the pathways initiating and driving pancreatitis

PubMed Central

Gukovskaya, Anna S.; Pandol, Stephen J.; Gukovsky, Ilya

2016-01-01

Purpose of review In this article, we discuss recent studies that advance our understanding of molecular and cellular factors initiating and driving pancreatitis, with the emphasis on the role of acinar cell organelle disorders. Recent findings The central physiologic function of the pancreatic acinar cell – to synthesize, store, and secrete digestive enzymes – critically relies on coordinated actions of the endoplasmic reticulum (ER), the endolysosomal system, mitochondria, and autophagy. Recent studies begin to unravel the roles of these organelles’ disordering in the mechanism of pancreatitis. Mice deficient in key autophagy mediators Atg5 or Atg7, or lysosome-associated membrane protein-2, exhibit dysregulation of multiple signaling and metabolic pathways in pancreatic acinar cells and develop spontaneous pancreatitis. Mitochondrial dysfunction caused by sustained opening of the permeability transition pore is shown to mediate pancreatitis in several clinically relevant experimental models, and its inhibition by pharmacologic or genetic means greatly reduces local and systemic pathologic responses. Experimental pancreatitis is also alleviated with inhibitors of ORAI1, a key component of the plasma membrane channel mediating pathologic rise in acinar cell cytosolic Ca2+. Pancreatitis-promoting mutations are increasingly associated with the ER stress. These findings suggest novel pathways and drug targets for pancreatitis treatment. In addition, the recent studies identify new mediators (e.g., neutrophil extracellular traps) of the inflammatory and other responses of pancreatitis. Summary The recent findings illuminate a critical role of organelles regulating the autophagic, endolysosomal, mitochondrial, and ER pathways in maintaining pancreatic acinar cell homeostasis and secretory function; provide compelling evidence that organelle disordering is a key pathogenic mechanism initiating and driving pancreatitis; and identify molecular and cellular factors that could be targeted to restore organellar functions and thus alleviate or treat pancreatitis. PMID:27428704

Polar-direct-drive experiments on the National Ignition Facility

DOE PAGES

Hohenberger, M.; Radha, P. B.; Myatt, J. F.; ...

2015-05-11

To support direct-drive inertial confinement fusion experiments at the National Ignition Facility (NIF) [G. H. Miller, E. I. Moses, and C. R. Wuest, Opt. Eng. 43, 2841 (2004)] in its indirect-drive beam configuration, the polar-direct-drive (PDD) concept [S. Skupsky et al., Phys. Plasmas 11, 2763 (2004)] has been proposed. Ignition in PDD geometry requires direct-drive–specific beam smoothing, phase plates, and repointing the NIF beams toward the equator to ensure symmetric target irradiation. First experiments to study the energetics and preheat in PDD implosions at the NIF have been performed. These experiments utilize the NIF in its current configuration, including beammore » geometry, phase plates, and beam smoothing. Room-temperature, 2.2-mm-diam plastic shells filled with D₂ gas were imploded with total drive energies ranging from ~500 to 750 kJ with peak powers of 120 to 180 TW and peak on-target irradiances at the initial target radius from 8 10¹⁴ to 1.2 10¹⁵W/cm². Results from these initial experiments are presented, including measurements of shell trajectory, implosion symmetry, and the level of hot-electron preheat in plastic and Si ablators. Experiments are simulated with the 2-D hydrodynamics code DRACO including a full 3-D ray-trace to model oblique beams, and models for nonlocal electron transport and cross-beam energy transport (CBET). These simulations indicate that CBET affects the shell symmetry and leads to a loss of energy imparted onto the shell, consistent with the experimental data.« less

VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of ruptured lysosomes by autophagy.

PubMed

Papadopoulos, Chrisovalantis; Kirchner, Philipp; Bug, Monika; Grum, Daniel; Koerver, Lisa; Schulze, Nina; Poehler, Robert; Dressler, Alina; Fengler, Sven; Arhzaouy, Khalid; Lux, Vanda; Ehrmann, Michael; Weihl, Conrad C; Meyer, Hemmo

2017-01-17

Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin-directed AAA-ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. Together, they act downstream of K63-linked ubiquitination and p62 recruitment, and selectively remove K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation. Lysosomal clearance is also compromised in MEFs harboring a p97 mutation that causes inclusion body myopathy and neurodegeneration, and damaged lysosomes accumulate in affected patient tissue carrying the mutation. Moreover, we show that p97 helps clear late endosomes/lysosomes ruptured by endocytosed tau fibrils. Thus, our data reveal an important mechanism of how p97 maintains lysosomal homeostasis, and implicate the pathway as a modulator of degenerative diseases. © 2016 The Authors.

The impact of phosphatases on proliferative and survival signaling in cancer.

PubMed

Narla, Goutham; Sangodkar, Jaya; Ryder, Christopher B

2018-05-03

The dynamic and stringent coordination of kinase and phosphatase activity controls a myriad of physiologic processes. Aberrations that disrupt the balance of this interplay represent the basis of numerous diseases. For a variety of reasons, early work in this area portrayed kinases as the dominant actors in these signaling events with phosphatases playing a secondary role. In oncology, these efforts led to breakthroughs that have dramatically altered the course of certain diseases and directed vast resources toward the development of additional kinase-targeted therapies. Yet, more recent scientific efforts have demonstrated a prominent and sometimes driving role for phosphatases across numerous malignancies. This maturation of the phosphatase field has brought with it the promise of further therapeutic advances in the field of oncology. In this review, we discuss the role of phosphatases in the regulation of cellular proliferation and survival signaling using the examples of the MAPK and PI3K/AKT pathways, c-Myc and the apoptosis machinery. Emphasis is placed on instances where these signaling networks are perturbed by dysregulation of specific phosphatases to favor growth and persistence of human cancer.

Pavement cells and the topology puzzle.

PubMed

Carter, Ross; Sánchez-Corrales, Yara E; Hartley, Matthew; Grieneisen, Verônica A; Marée, Athanasius F M

2017-12-01

D'Arcy Thompson emphasised the importance of surface tension as a potential driving force in establishing cell shape and topology within tissues. Leaf epidermal pavement cells grow into jigsaw-piece shapes, highly deviating from such classical forms. We investigate the topology of developing Arabidopsis leaves composed solely of pavement cells. Image analysis of around 50,000 cells reveals a clear and unique topological signature, deviating from previously studied epidermal tissues. This topological distribution is established early during leaf development, already before the typical pavement cell shapes emerge, with topological homeostasis maintained throughout growth and unaltered between division and maturation zones. Simulating graph models, we identify a heuristic cellular division rule that reproduces the observed topology. Our parsimonious model predicts how and when cells effectively place their division plane with respect to their neighbours. We verify the predicted dynamics through in vivo tracking of 800 mitotic events, and conclude that the distinct topology is not a direct consequence of the jigsaw piece-like shape of the cells, but rather owes itself to a strongly life history-driven process, with limited impact from cell-surface mechanics. © 2017. Published by The Company of Biologists Ltd.

Selecting the Best: Evolutionary Engineering of Chemical Production in Microbes.

PubMed

Shepelin, Denis; Hansen, Anne Sofie Lærke; Lennen, Rebecca; Luo, Hao; Herrgård, Markus J

2018-05-11

Microbial cell factories have proven to be an economical means of production for many bulk, specialty, and fine chemical products. However, we still lack both a holistic understanding of organism physiology and the ability to predictively tune enzyme activities in vivo, thus slowing down rational engineering of industrially relevant strains. An alternative concept to rational engineering is to use evolution as the driving force to select for desired changes, an approach often described as evolutionary engineering. In evolutionary engineering, in vivo selections for a desired phenotype are combined with either generation of spontaneous mutations or some form of targeted or random mutagenesis. Evolutionary engineering has been used to successfully engineer easily selectable phenotypes, such as utilization of a suboptimal nutrient source or tolerance to inhibitory substrates or products. In this review, we focus primarily on a more challenging problem-the use of evolutionary engineering for improving the production of chemicals in microbes directly. We describe recent developments in evolutionary engineering strategies, in general, and discuss, in detail, case studies where production of a chemical has been successfully achieved through evolutionary engineering by coupling production to cellular growth.

Hierarchical thermoplastic rippled nanostructures regulate Schwann cell adhesion, morphology and spatial organization.

PubMed

Masciullo, Cecilia; Dell'Anna, Rossana; Tonazzini, Ilaria; Böettger, Roman; Pepponi, Giancarlo; Cecchini, Marco

2017-10-12

Periodic ripples are a variety of anisotropic nanostructures that can be realized by ion beam irradiation on a wide range of solid surfaces. Only a few authors have investigated these surfaces for tuning the response of biological systems, probably because it is challenging to directly produce them in materials that well sustain long-term cellular cultures. Here, hierarchical rippled nanotopographies with a lateral periodicity of ∼300 nm are produced from a gold-irradiated germanium mold in polyethylene terephthalate (PET), a biocompatible polymer approved by the US Food and Drug Administration for clinical applications, by a novel three-step embossing process. The effects of nano-ripples on Schwann Cells (SCs) are studied in view of their possible use for nerve-repair applications. The data demonstrate that nano-ripples can enhance short-term SC adhesion and proliferation (3-24 h after seeding), drive their actin cytoskeleton spatial organization and sustain long-term cell growth. Notably, SCs are oriented perpendicularly with respect to the nanopattern lines. These results provide information about the possible use of hierarchical nano-rippled elements for nerve-regeneration protocols.

Calcium signaling in mammalian egg activation and embryo development: Influence of subcellular localization

PubMed Central

Miao, Yi-Liang; Williams, Carmen J.

2012-01-01

Calcium (Ca2+) signals drive the fundamental events surrounding fertilization and the activation of development in all species examined to date. Initial studies of Ca2+ signaling at fertilization in marine animals were tightly linked to new discoveries of bioluminescent proteins and their use as fluorescent Ca2+ sensors. Since that time, there has been rapid progress in our understanding of the key functions for Ca2+ in many cell types and the impact of cellular localization on Ca2+ signaling pathways. In this review, which focuses on mammalian egg activation, we consider how Ca2+ is regulated and stored at different stages of oocyte development and examine the functions of molecules that serve as both regulators of Ca2+ release and effectors of Ca2+ signals. We then summarize studies exploring how Ca2+ directs downstream effectors mediating both egg activation and later signaling events required for successful preimplantation embryo development. Throughout this review, we focus attention on how localization of Ca2+ signals influences downstream signaling events, and attempt to highlight gaps in our knowledge that are ripe areas for future research. PMID:22888043

APC binds the Miro/Milton motor complex to stimulate transport of mitochondria to the plasma membrane

PubMed Central

Mills, Kate M.; Brocardo, Mariana G.; Henderson, Beric R.

2016-01-01

Mutations in adenomatous polyposis coli (APC) disrupt regulation of Wnt signaling, mitosis, and the cytoskeleton. We describe a new role for APC in the transport of mitochondria. Silencing of wild-type APC by small interfering RNA caused mitochondria to redistribute from the cell periphery to the perinuclear region. We identified novel APC interactions with the mitochondrial kinesin-motor complex Miro/Milton that were mediated by the APC C-terminus. Truncating mutations in APC abolished its ability to bind Miro/Milton and reduced formation of the Miro/Milton complex, correlating with disrupted mitochondrial distribution in colorectal cancer cells that could be recovered by reconstitution of wild-type APC. Using proximity ligation assays, we identified endogenous APC-Miro/Milton complexes at mitochondria, and live-cell imaging showed that loss of APC slowed the frequency of anterograde mitochondrial transport to the membrane. We propose that APC helps drive mitochondria to the membrane to supply energy for cellular processes such as directed cell migration, a process disrupted by cancer mutations. PMID:26658612

Listeria monocytogenes, a down-to-earth pathogen

PubMed Central

Vivant, Anne-Laure; Garmyn, Dominique; Piveteau, Pascal

2013-01-01

Listeria monocytogenes is the causative agent of the food-borne life threatening disease listeriosis. This pathogenic bacterium received much attention in the endeavor of deciphering the cellular mechanisms that underlie the onset of infection and its ability to adapt to the food processing environment. Although information is available on the presence of L. monocytogenes in many environmental niches including soil, water, plants, foodstuff and animals, understanding the ecology of L. monocytogenes in outdoor environments has received less attention. Soil is an environmental niche of pivotal importance in the transmission of this bacterium to plants and animals. Soil composition, microbial communities and macrofauna are extrinsic edaphic factors that direct the fate of L. monocytogenes in the soil environment. Moreover, farming practices may further affect its incidence. The genome of L. monocytogenes presents an extensive repertoire of genes encoding transport proteins and regulators, a characteristic of the genome of ubiquitous bacteria. Postgenomic analyses bring new insights in the process of soil adaptation. In the present paper focussing on soil, we review these extrinsic and intrinsic factors that drive environmental adaptation of L. monocytogenes. PMID:24350062

Listeria monocytogenes, a down-to-earth pathogen.

PubMed

Vivant, Anne-Laure; Garmyn, Dominique; Piveteau, Pascal

2013-01-01

Listeria monocytogenes is the causative agent of the food-borne life threatening disease listeriosis. This pathogenic bacterium received much attention in the endeavor of deciphering the cellular mechanisms that underlie the onset of infection and its ability to adapt to the food processing environment. Although information is available on the presence of L. monocytogenes in many environmental niches including soil, water, plants, foodstuff and animals, understanding the ecology of L. monocytogenes in outdoor environments has received less attention. Soil is an environmental niche of pivotal importance in the transmission of this bacterium to plants and animals. Soil composition, microbial communities and macrofauna are extrinsic edaphic factors that direct the fate of L. monocytogenes in the soil environment. Moreover, farming practices may further affect its incidence. The genome of L. monocytogenes presents an extensive repertoire of genes encoding transport proteins and regulators, a characteristic of the genome of ubiquitous bacteria. Postgenomic analyses bring new insights in the process of soil adaptation. In the present paper focussing on soil, we review these extrinsic and intrinsic factors that drive environmental adaptation of L. monocytogenes.

Pavement cells and the topology puzzle

PubMed Central

2017-01-01

D'Arcy Thompson emphasised the importance of surface tension as a potential driving force in establishing cell shape and topology within tissues. Leaf epidermal pavement cells grow into jigsaw-piece shapes, highly deviating from such classical forms. We investigate the topology of developing Arabidopsis leaves composed solely of pavement cells. Image analysis of around 50,000 cells reveals a clear and unique topological signature, deviating from previously studied epidermal tissues. This topological distribution is established early during leaf development, already before the typical pavement cell shapes emerge, with topological homeostasis maintained throughout growth and unaltered between division and maturation zones. Simulating graph models, we identify a heuristic cellular division rule that reproduces the observed topology. Our parsimonious model predicts how and when cells effectively place their division plane with respect to their neighbours. We verify the predicted dynamics through in vivo tracking of 800 mitotic events, and conclude that the distinct topology is not a direct consequence of the jigsaw piece-like shape of the cells, but rather owes itself to a strongly life history-driven process, with limited impact from cell-surface mechanics. PMID:29084800

Regulation of sGC via hsp90, Cellular Heme, sGC Agonists, and NO: New Pathways and Clinical Perspectives

PubMed Central

Ghosh, Arnab

2017-01-01

Abstract Significance: Soluble guanylate cyclase (sGC) is an intracellular enzyme that plays a primary role in sensing nitric oxide (NO) and transducing its multiple signaling effects in mammals. Recent Advances: The chaperone heat shock protein 90 (hsp90) associates with signaling proteins in cells, including sGC, where it helps to drive heme insertion into the sGC-β1 subunit. This allows sGC-β1 to associate with a partner sGC-α1 subunit and mature into an NO-responsive active form. Critical Issues: In this article, we review evidence to date regarding the mechanisms that modulate sGC activity by a pathway where binding of hsp90 or sGC agonist to heme-free sGC dictates the assembly and fate of an active sGC heterodimer, both by NO and heme-dependent or heme-independent pathways. Future Directions: We discuss some therapeutic implications of the NO-sGC-hsp90 nexus and its potential as a marker of inflammatory disease. Antioxid. Redox Signal. 26, 182–190. PMID:26983679

Comparative energetics of carbon storage molecules in green algae

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

McKie-Krisberg, Zaid M.; Laurens, Lieve M. L.; Huang, Andy

Several members of the green algae possess the ability to produce lipids and/or high value compounds in significant quantities. While for several of these green algal species induction of increased lipid production has been shown, and cultivation of species for high value molecules occurs at production scale, the molecular mechanisms governing over-accumulation of molecules synthesized from isoprenoid precursors, carotenoids, for example, have received far less attention. Here, we present a calculation of the required ATP equivalencies per carbon atom and reducing power equivalencies as NADH/NADPH (NAD(P)H) per carbon atom for the isoprenoid molecules ..beta..-carotene (C40), astaxanthin (C40), and squalene (C30).more » We compared energetic requirements of carbohydrates, triacylglycerol, and isoprenoid molecules under a gradient of conditions of cellular stress. Our calculations revealed slightly less ATP and NAD(P)H equivalency per carbon atom between triacylglycerol and the three isoprenoid molecules. Based on our results, we propose that the driving force for differences in accumulation patterns of carotenoids vs. triacylglycerols in algal cells under stress is largely dependent on the presence and regulation of bypass mechanisms at metabolic junction bottlenecks, like pyruvate dehydrogenase (PDH), within particular species. We provide a discussion of several molecular mechanisms that may influence carbon partitioning within different groups of green algae, including metabolic inhibition through accumulation of specific substrates related to ATP and reducing equivalent production (NAD(P)H) as well as cellular compartmentalization. This work contributes to the ongoing discussion of cellular homeostatic regulation during stress, as well as the potential mechanisms driving long-term carbon storage as it relates to energy and redox states within the algal cell.« less

Comparative energetics of carbon storage molecules in green algae

DOE PAGES

McKie-Krisberg, Zaid M.; Laurens, Lieve M. L.; Huang, Andy; ...

2018-02-28

Several members of the green algae possess the ability to produce lipids and/or high value compounds in significant quantities. While for several of these green algal species induction of increased lipid production has been shown, and cultivation of species for high value molecules occurs at production scale, the molecular mechanisms governing over-accumulation of molecules synthesized from isoprenoid precursors, carotenoids, for example, have received far less attention. Here, we present a calculation of the required ATP equivalencies per carbon atom and reducing power equivalencies as NADH/NADPH (NAD(P)H) per carbon atom for the isoprenoid molecules ..beta..-carotene (C40), astaxanthin (C40), and squalene (C30).more » We compared energetic requirements of carbohydrates, triacylglycerol, and isoprenoid molecules under a gradient of conditions of cellular stress. Our calculations revealed slightly less ATP and NAD(P)H equivalency per carbon atom between triacylglycerol and the three isoprenoid molecules. Based on our results, we propose that the driving force for differences in accumulation patterns of carotenoids vs. triacylglycerols in algal cells under stress is largely dependent on the presence and regulation of bypass mechanisms at metabolic junction bottlenecks, like pyruvate dehydrogenase (PDH), within particular species. We provide a discussion of several molecular mechanisms that may influence carbon partitioning within different groups of green algae, including metabolic inhibition through accumulation of specific substrates related to ATP and reducing equivalent production (NAD(P)H) as well as cellular compartmentalization. This work contributes to the ongoing discussion of cellular homeostatic regulation during stress, as well as the potential mechanisms driving long-term carbon storage as it relates to energy and redox states within the algal cell.« less

Effect of Calcium on the Oxidative Phosphorylation Cascade in Skeletal Muscle Mitochondria

PubMed Central

Glancy, Brian; Willis, Wayne T; Chess, David J; Balaban, Robert S

2014-01-01

Calcium is believed to regulate mitochondrial oxidative phosphorylation, thereby contributing to the maintenance of cellular energy homeostasis. Skeletal muscle, with an energy conversion dynamic range of up to 100-fold, is an extreme case for evaluating the cellular balance of ATP production and consumption. This study examined the role of Ca2+ on the entire oxidative phosphorylation reaction network in isolated skeletal muscle mitochondria and attempted to extrapolate these results back to the muscle, in vivo. Kinetic analysis was conducted to evaluate the dose response effect of Ca2+ on the maximum velocity of oxidative phosphorylation (VmaxO) and the ADP affinity. Force-flow analysis evaluated the interplay between energetic driving forces and flux to determine the conductance, or effective activity, of individual steps within oxidative phosphorylation. Measured driving forces (extramitochondrial phosphorylation potential (ΔGATP), membrane potential, and redox states of NADH and cytochromes bH, bL, c1, c, and a,a3) were compared with flux (oxygen consumption) at 37°C. 840 nM Ca2+ generated a ∼2 fold increase in VmaxO with no change in ADP affinity (∼43 μM). Force-flow analysis revealed that Ca2+ activation of VmaxO was distributed throughout the oxidative phosphorylation reaction sequence. Specifically, Ca2+ increased the conductance of Complex IV (2.3-fold), Complexes I+III (2.2-fold), ATP production/transport (2.4-fold), and fuel transport/dehydrogenases (1.7-fold). These data support the notion that Ca2+ activates the entire muscle oxidative phosphorylation cascade, while extrapolation of these data to the exercising muscle predicts a significant role of Ca2+ in maintaining cellular energy homeostasis. PMID:23547908

Laser-based direct-write techniques for cell printing

PubMed Central

Schiele, Nathan R; Corr, David T; Huang, Yong; Raof, Nurazhani Abdul; Xie, Yubing; Chrisey, Douglas B

2016-01-01

Fabrication of cellular constructs with spatial control of cell location (±5 μm) is essential to the advancement of a wide range of applications including tissue engineering, stem cell and cancer research. Precise cell placement, especially of multiple cell types in co- or multi-cultures and in three dimensions, can enable research possibilities otherwise impossible, such as the cell-by-cell assembly of complex cellular constructs. Laser-based direct writing, a printing technique first utilized in electronics applications, has been adapted to transfer living cells and other biological materials (e.g., enzymes, proteins and bioceramics). Many different cell types have been printed using laser-based direct writing, and this technique offers significant improvements when compared to conventional cell patterning techniques. The predominance of work to date has not been in application of the technique, but rather focused on demonstrating the ability of direct writing to pattern living cells, in a spatially precise manner, while maintaining cellular viability. This paper reviews laser-based additive direct-write techniques for cell printing, and the various cell types successfully laser direct-written that have applications in tissue engineering, stem cell and cancer research are highlighted. A particular focus is paid to process dynamics modeling and process-induced cell injury during laser-based cell direct writing. PMID:20814088

Direct Fusion Drive for a Human Mars Orbital Mission

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

Paluszek, Michael; Pajer, Gary; Razin, Yosef

2014-08-01

The Direct Fusion Drive (DFD) is a nuclear fusion engine that produces both thrust and electric power. It employs a field reversed configuration with an odd-parity rotating magnetic field heating system to heat the plasma to fusion temperatures. The engine uses deuterium and helium-3 as fuel and additional deuterium that is heated in the scrape-off layer for thrust augmentation. In this way variable exhaust velocity and thrust is obtained.

Walk and roll robot

NASA Technical Reports Server (NTRS)

Wilson, Andrew (Inventor); Punnoose, Andrew (Inventor); Strausser, Katherine (Inventor); Parikh, Neil (Inventor)

2011-01-01

A mobile robotic unit features a main body, a plurality of legs for supporting the main body on and moving the main body in forward and reverse directions about a base surface, and a drive assembly. According to an exemplary embodiment each leg includes a respective pivotal hip joint, a pivotal knee joint, and a wheeled foot adapted to roll along the base surface. Also according to an exemplary embodiments the drive assembly includes a motor operatively associated with the hip and knee joints and the wheeled foot for independently driving pivotal movement of the hip joint and the knee joint and rolling motion of the wheeled foot. The hip joint may include a ball-and-socket-type joint interconnecting top portion of the leg to the main body, such that the hip joint is adapted to pivot said leg in a direction transverse to a forward-and-reverse direction.

A fuzzy logic sliding mode controlled electronic differential for a direct wheel drive EV

NASA Astrophysics Data System (ADS)

Ozkop, Emre; Altas, Ismail H.; Okumus, H. Ibrahim; Sharaf, Adel M.

2015-11-01

In this study, a direct wheel drive electric vehicle based on an electronic differential system with a fuzzy logic sliding mode controller (FLSMC) is studied. The conventional sliding surface is modified using a fuzzy rule base to obtain fuzzy dynamic sliding surfaces by changing its slopes using the global error and its derivative in a fuzzy logic inference system. The controller is compared with proportional-integral-derivative (PID) and sliding mode controllers (SMCs), which are usually preferred to be used in industry. The proposed controller provides robustness and flexibility to direct wheel drive electric vehicles. The fuzzy logic sliding mode controller, electronic differential system and the overall electrical vehicle mechanism are modelled and digitally simulated by using the Matlab software. Simulation results show that the system with FLSMC has better efficiency and performance compared to those of PID and SMCs.

Raytracing and Direct-Drive Targets

NASA Astrophysics Data System (ADS)

Schmitt, Andrew J.; Bates, Jason; Fyfe, David; Eimerl, David

2013-10-01

Accurate simulation of the effects of laser imprinting and drive asymmetries in directly driven targets requires the ability to distinguish between raytrace noise and the intensity structure produced by the spatial and temporal incoherence of optical smoothing. We have developed and implemented a smoother raytrace algorithm for our mpi-parallel radiation hydrodynamics code, FAST3D. The underlying approach is to connect the rays into either sheets (in 2D) or volume-enclosing chunks (in 3D) so that the absorbed energy distribution continuously covers the propagation area illuminated by the laser. We will describe the status and show the different scalings encountered in 2D and 3D problems as the computational size, parallelization strategy, and number of rays is varied. Finally, we show results using the method in current NIKE experimental target simulations and in proposed symmetric and polar direct-drive target designs. Supported by US DoE/NNSA.

Research requirements for development of advanced-technology helicopter transmissions. [reduction of maintenance costs

NASA Technical Reports Server (NTRS)

Lemanski, A. J.

1976-01-01

Helicopter drive-system technology which would result in the largest benefit in direct maintenance cost when applied to civil helicopters in the 1980 timeframe was developed. A prototype baseline drive system based on 1975 technology provided the basis for comparison against the proposed advanced technology in order to determine the potential for each area recommended for improvement. A specific design example of an advanced-technology main transmission is presented to define improvements for maintainability, weight, producibility, reliability, noise, vibration, and diagnostics. Projections of the technology achievable in the 1980 timeframe are presented. Based on this data, the technologies with the highest payoff (lowest direct maintenance cost) for civil-helicopter drive systems are identified.

Magnetostrictive direct drive motors

NASA Technical Reports Server (NTRS)

Naik, Dipak; Dehoff, P. H.

1990-01-01

Developing magnetostrictive direct drive research motors to power robot joints is discussed. These type motors are expected to produce extraordinary torque density, to be able to perform microradian incremental steps and to be self-braking and safe with the power off. Several types of motor designs have been attempted using magnetostrictive materials. One of the candidate approaches (the magnetostrictive roller drive) is described. The method in which the design will function is described as is the reason why this approach is inherently superior to the other approaches. Following this, the design will be modelled and its expected performance predicted. This particular candidate design is currently undergoing detailed engineering with prototype construction and testing scheduled for mid 1991.

Modelling of piezoelectric actuator dynamics for active structural control

NASA Technical Reports Server (NTRS)

Hagood, Nesbitt W.; Chung, Walter H.; Von Flotow, Andreas

1990-01-01

The paper models the effects of dynamic coupling between a structure and an electrical network through the piezoelectric effect. The coupled equations of motion of an arbitrary elastic structure with piezoelectric elements and passive electronics are derived. State space models are developed for three important cases: direct voltage driven electrodes, direct charge driven electrodes, and an indirect drive case where the piezoelectric electrodes are connected to an arbitrary electrical circuit with embedded voltage and current sources. The equations are applied to the case of a cantilevered beam with surface mounted piezoceramics and indirect voltage and current drive. The theoretical derivations are validated experimentally on an actively controlled cantilevered beam test article with indirect voltage drive.

Numerically robust and efficient nonlocal electron transport in 2D DRACO simulations

NASA Astrophysics Data System (ADS)

Cao, Duc; Chenhall, Jeff; Moses, Greg; Delettrez, Jacques; Collins, Tim

2013-10-01

An improved implicit algorithm based on Schurtz, Nicolai and Busquet (SNB) algorithm for nonlocal electron transport is presented. Validation with direct drive shock timing experiments and verification with the Goncharov nonlocal model in 1D LILAC simulations demonstrate the viability of this efficient algorithm for producing 2D lagrangian radiation hydrodynamics direct drive simulations. Additionally, simulations provide strong incentive to further modify key parameters within the SNB theory, namely the ``mean free path.'' An example 2D polar drive simulation to study 2D effects of the nonlocal flux as well as mean free path modifications will also be presented. This research was supported by the University of Rochester Laboratory for Laser Energetics.

Temporally structured replay of neural activity in a model of entorhinal cortex, hippocampus and postsubiculum

PubMed Central

Hasselmo, Michael E.

2008-01-01

The spiking activity of hippocampal neurons during REM sleep exhibits temporally structured replay of spiking occurring during previously experienced trajectories (Louie and Wilson, 2001). Here, temporally structured replay of place cell activity during REM sleep is modeled in a large-scale network simulation of grid cells, place cells and head direction cells. During simulated waking behavior, the movement of the simulated rat drives activity of a population of head direction cells that updates the activity of a population of entorhinal grid cells. The population of grid cells drives the activity of place cells coding individual locations. Associations between location and movement direction are encoded by modification of excitatory synaptic connections from place cells to speed modulated head direction cells. During simulated REM sleep, the population of place cells coding an experienced location activates the head direction cells coding the associated movement direction. Spiking of head direction cells then causes frequency shifts within the population of entorhinal grid cells to update a phase representation of location. Spiking grid cells then activate new place cells that drive new head direction activity. In contrast to models that perform temporally compressed sequence retrieval similar to sharp wave activity, this model can simulate data on temporally structured replay of hippocampal place cell activity during REM sleep at time scales similar to those observed during waking. These mechanisms could be important for episodic memory of trajectories. PMID:18973557

Noise fluctuations and drive dependence of the skyrmion Hall effect in disordered systems

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

Reichhardt, Charles; Olson Reichhardt, Cynthia Jane

Using a particle-based simulation model, we show that quenched disorder creates a drive-dependent skyrmion Hall effect as measured by the change in the ratiomore » $$R={V}_{\\perp }/{V}_{| | }$$ of the skyrmion velocity perpendicular (V ⊥) and parallel ($${V}_{| | }$$) to an external drive. R is zero at depinning and increases linearly with increasing drive, in agreement with recent experimental observations. At sufficiently high drives where the skyrmions enter a free flow regime, R saturates to the disorder-free limit. In addition, this behavior is robust for a wide range of disorder strengths and intrinsic Hall angle values, and occurs whenever plastic flow is present. For systems with small intrinsic Hall angles, we find that the Hall angle increases linearly with external drive, as also observed in experiment. In the weak pinning regime where the skyrmion lattice depins elastically, R is nonlinear and the net direction of the skyrmion lattice motion can rotate as a function of external drive. We show that the changes in the skyrmion Hall effect correlate with changes in the power spectrum of the skyrmion velocity noise fluctuations. The plastic flow regime is associated with $1/f$ noise, while in the regime in which R has saturated, the noise is white with a weak narrow band signal, and the noise power drops by several orders of magnitude. Finally, at low drives, the velocity noise in the perpendicular and parallel directions is of the same order of magnitude, while at intermediate drives the perpendicular noise fluctuations are much larger.« less

The development of the drive object concept in Freud's work: 1905-1915.

PubMed

Compton, A

1985-01-01

In 1905 Freud established the idea of an object of an instinctual drive as the basic object concept of psychoanalysis. He also introduced the derivative concepts of object directedness, object choice, and object finding. While taking these steps he simultaneously deemphasized the importance of drive objects in sexual life, contradicted himself on whether drives are autoerotic or object-directed in infancy, and made incompatible statements about whether or not object choice occurs before puberty. Freud's clinical work, reflected especially in the major case reports and a series of papers on fantasy, led to an apparent recognition of complexity in the mental life of children far greater than had been described earlier. The increased attention to and appreciation of mental content in childhood especially augmented Freud's understanding of the role of drive objects, object directedness, and object choice in infancy. This, in turn, led him to postulate a sequence of organizations of sexual life, named according to the zonal drive source plus the mode of object directedness, a process of theory development that continued through 1924. Object choice and, to a lesser extent, object directedness are concepts derived from and dependent upon the concept of drive object. Both require, however, explanatory constructs besides drive constructs. In 1915 Freud defined the term "object" in the context of stating his drive theory. Freud used the term object with several new modifying words during this decade. No new object concept was introduced, however, in this work, although some steps in that direction appeared to be in progress.

Noise fluctuations and drive dependence of the skyrmion Hall effect in disordered systems

DOE PAGES

Reichhardt, Charles; Olson Reichhardt, Cynthia Jane

2016-09-29

Using a particle-based simulation model, we show that quenched disorder creates a drive-dependent skyrmion Hall effect as measured by the change in the ratiomore » $$R={V}_{\\perp }/{V}_{| | }$$ of the skyrmion velocity perpendicular (V ⊥) and parallel ($${V}_{| | }$$) to an external drive. R is zero at depinning and increases linearly with increasing drive, in agreement with recent experimental observations. At sufficiently high drives where the skyrmions enter a free flow regime, R saturates to the disorder-free limit. In addition, this behavior is robust for a wide range of disorder strengths and intrinsic Hall angle values, and occurs whenever plastic flow is present. For systems with small intrinsic Hall angles, we find that the Hall angle increases linearly with external drive, as also observed in experiment. In the weak pinning regime where the skyrmion lattice depins elastically, R is nonlinear and the net direction of the skyrmion lattice motion can rotate as a function of external drive. We show that the changes in the skyrmion Hall effect correlate with changes in the power spectrum of the skyrmion velocity noise fluctuations. The plastic flow regime is associated with $1/f$ noise, while in the regime in which R has saturated, the noise is white with a weak narrow band signal, and the noise power drops by several orders of magnitude. Finally, at low drives, the velocity noise in the perpendicular and parallel directions is of the same order of magnitude, while at intermediate drives the perpendicular noise fluctuations are much larger.« less

Systematic review of factors affecting driving and motor vehicle transportation among people with autism spectrum disorder.

PubMed

Lindsay, Sally

2017-05-01

This systematic review is to critically appraise the literature on factors affecting driving and motor vehicle transportation experiences of people with autism spectrum disorders (ASD) and to provide insight into future directions for research. Systematic searches of eight databases identified 22 studies meeting our inclusion criteria. These studies were analysed in terms of the characteristics of the participants, methodology, results of the study and quality of the evidence. Among the 22 studies, 2919 participants (364 individuals with ASD; 2555 parents of youth with ASD; mean age of person with ASD = 17.3) were represented, across six countries. Studies (n = 13) focused on factors affecting driving, including challenges in obtaining a licence, driving confidence, driving behaviours and strategies to improve driving skills. In regards to factors related to public and/or school transportation, nine studies explored rates of transportation use, access, cost and safety. Our findings highlight several gaps in the research and an urgent need for further transportation-related training and supports for people with ASD. Implications for rehabilitation Many people with ASD encounter challenges in obtaining a driver's licence, driving confidence and driving performance compared to those without ASD. Several strategies can be useful when teaching people with ASD to drive including direct communication, encouraging coping mechanisms, breaking down tasks and providing regular and consistent driving lessons. Clinicians and educators should advocate for further transportation-related training and supports for people with ASD. More research is needed from the perspective of people with ASD to understand their experiences and the particular challenges that they encounter in obtaining a licence and navigating public transportation.

Noise and Dynamical Pattern Selection in Solidification

NASA Technical Reports Server (NTRS)

Kurtze, Douglas A.

1997-01-01

The overall goal of this project was to understand in more detail how a pattern-forming system can adjust its spacing. "Pattern-forming systems," in this context, are nonequilibrium contina whose state is determined by experimentally adjustable control parameter. Below some critical value of the control system then has available to it a range of linearly stable, spatially periodic steady states, each characterized by a spacing which can lie anywhere within some band of values. These systems like directional solidification, where the solidification front is planar when the ratio of growth velocity to thermal gradient is below its critical value, but takes on a cellular shape above critical. They also include systems without interfaces, such as Benard convection, where it is the fluid velocity field which changes from zero to something spatially periodic as the control parameter is increased through its critical value. The basic question to be addressed was that of how the system chooses one of its myriad possible spacings when the control parameter is above critical, and in particular the role of noise in the selection process. Previous work on explosive crystallization had suggested that one spacing in the range should be preferred, in the sense that weak noise should eventually drive the system to that spacing. That work had also suggested a heuristic argument for identifying the preferred spacing. The project had three main objectives: to understand in more detail how a pattern-forming system can adjust its spacing; to investigate how noise drives a system to its preferred spacing; and to extend the heuristic argument for a preferred spacing in explosive crystallization to other pattern-forming systems.

Direct non-productive HIV-1 infection in a T-cell line is driven by cellular activation state and NFκB

PubMed Central

2014-01-01

Background Molecular latency allows HIV-1 to persist in resting memory CD4+ T-cells as transcriptionally silent provirus integrated into host chromosomal DNA. Multiple transcriptional regulatory mechanisms for HIV-1 latency have been described in the context of progressive epigenetic silencing and maintenance. However, our understanding of the determinants critical for the establishment of latency in newly infected cells is limited. Results In this study, we used a recently described, doubly fluorescent HIV-1 latency model to dissect the role of proviral integration sites and cellular activation state on direct non-productive infections at the single cell level. Proviral integration site mapping of infected Jurkat T-cells revealed that productively and non-productively infected cells are indistinguishable in terms of genomic landmarks, surrounding epigenetic landscapes, and proviral orientation relative to host genes. However, direct non-productive infections were inversely correlated with both cellular activation state and NFκB activity. Furthermore, modulating NFκB with either small molecules or by conditional overexpression of NFκB subunits was sufficient to alter the propensity of HIV-1 to directly enter a non-productive latent state in newly infected cells. Importantly, this modulatory effect was limited to a short time window post-infection. Conclusions Taken together, our data suggest that cellular activation state and NFκB activity during the time of infection, but not the site of proviral integration, are important regulators of direct HIV-1 non-productive infections. PMID:24502247

Cellular Scale Anisotropic Topography Guides Schwann Cell Motility

PubMed Central

Mitchel, Jennifer A.; Hoffman-Kim, Diane

2011-01-01

Directed migration of Schwann cells (SC) is critical for development and repair of the peripheral nervous system. Understanding aspects of motility specific to SC, along with SC response to engineered biomaterials, may inform strategies to enhance nerve regeneration. Rat SC were cultured on laminin-coated microgrooved poly(dimethyl siloxane) platforms that were flat or presented repeating cellular scale anisotropic topographical cues, 30 or 60 µm in width, and observed with timelapse microscopy. SC motion was directed parallel to the long axis of the topography on both the groove floor and the plateau, with accompanying differences in velocity and directional persistence in comparison to SC motion on flat substrates. In addition, feature dimension affected SC morphology, alignment, and directional persistence. Plateaus and groove floors presented distinct cues which promoted differential motility and variable interaction with the topographical features. SC on the plateau surfaces tended to have persistent interactions with the edge topography, while SC on the groove floors tended to have infrequent contact with the corners and walls. Our observations suggest the capacity of SC to be guided without continuous contact with a topographical cue. SC exhibited a range of distinct motile morphologies, characterized by their symmetry and number of extensions. Across all conditions, SC with a single extension traveled significantly faster than cells with more or no extensions. We conclude that SC motility is complex, where persistent motion requires cellular asymmetry, and that anisotropic topography with cellular scale features can direct SC motility. PMID:21949703

The scaffold protein Atg11 recruits fission machinery to drive selective mitochondria degradation by autophagy.

PubMed

Mao, Kai; Wang, Ke; Liu, Xu; Klionsky, Daniel J

2013-07-15

As the cellular power plant, mitochondria play a significant role in homeostasis. To maintain the proper quality and quantity of mitochondria requires both mitochondrial degradation and division. A selective type of autophagy, mitophagy, drives the degradation of excess or damaged mitochondria, whereas division is controlled by a specific fission complex; however, the relationship between these two processes, especially the role of mitochondrial fission during mitophagy, remains unclear. In this study, we report that mitochondrial fission is important for the progression of mitophagy. When mitophagy is induced, the fission complex is recruited to the degrading mitochondria through an interaction between Atg11 and Dnm1; interfering with this interaction severely blocks mitophagy. These data establish a paradigm for selective organelle degradation. Copyright © 2013 Elsevier Inc. All rights reserved.

Growth cone travel in space and time: the cellular ensemble of cytoskeleton, adhesion, and membrane.

PubMed

Vitriol, Eric A; Zheng, James Q

2012-03-22

Growth cones, found at the tip of axonal projections, are the sensory and motile organelles of developing neurons that enable axon pathfinding and target recognition for precise wiring of the neural circuitry. To date, many families of conserved guidance molecules and their corresponding receptors have been identified that work in space and time to ensure billions of axons to reach their targets. Research in the past two decades has also gained significant insight into the ways in which growth cones translate extracellular signals into directional migration. This review aims to examine new progress toward understanding the cellular mechanisms underlying directional motility of the growth cone and to discuss questions that remain to be addressed. Specifically, we will focus on the cellular ensemble of cytoskeleton, adhesion, and membrane and examine how the intricate interplay between these processes orchestrates the directed movement of growth cones. Copyright © 2012 Elsevier Inc. All rights reserved.

Associations between parenting styles and teen driving, safety-related behaviors and attitudes.

PubMed

Ginsburg, Kenneth R; Durbin, Dennis R; García-España, J Felipe; Kalicka, Ewa A; Winston, Flaura K

2009-10-01

The goal was to explore the association between parenting style and driving behaviors. The 2006 National Young Driver Survey gathered data on driving safety behaviors from a nationally representative sample of 5665 ninth-, 10th-, and 11th-graders. A parenting style variable was based on adolescent reports and separated parents into 4 groups, (1) authoritative (high support and high rules/monitoring), (2) authoritarian (low support and high rules/monitoring), (3) permissive (high support and low rules/monitoring), and (4) uninvolved (low support and low rules/monitoring). Associations between parenting style and driving behaviors and attitudes were assessed. One half of parents were described as authoritative, 23% as permissive, 8% as authoritarian, and 19% as uninvolved. Compared with teens with uninvolved parents, those with authoritative parents reported one half the crash risk in the past year (odds ratio [OR]: 0.47 [95% confidence interval [CI]: 0.26-0.87]), were 71% less likely to drive when intoxicated (OR: 0.29 [95% CI: 0.19-0.44]), and were less likely to use a cellular telephone while driving (OR: 0.71 [95% CI: 0.50-0.99]). Teens with authoritative or authoritarian parents reported using seat belts nearly twice as often (authoritative: OR: 1.94 [95% CI: 1.49 -2.54]; authoritarian: OR: 1.85 [95% CI: 1.08 -3.18]) and speeding one half as often (authoritative: OR: 0.47 [95% CI: 0.36-0.61]; authoritarian: OR: 0.63 [95% CI: 0.40-0.99]) as teens with uninvolved parents. No significant differences in crash risk or seat belt use were found between permissive and uninvolved parents. Clinicians should encourage parents to set rules and to monitor teens' driving behaviors, in a supportive context.

Direct drive field actuator motors

DOEpatents

Grahn, Allen R.

1998-01-01

A positive-drive field actuator motor including a stator carrying at least one field actuator which changes in dimension responsive to application of an energy field, and at least one drive shoe movable by the dimensional changes of the field actuator to contact and move a rotor element with respect to the stator. Various embodiments of the motor are disclosed, and the rotor element may be moved linearly or arcuately.

77 FR 14506 - Marine Recreational Fisheries of the United States; Southeast Data, Assessment, and Review (SEDAR...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... Manager, 4055 Faber Place Drive, Suite 201, North Charleston, SC 29405; telephone: (843) 571-4366... directed to the South Atlantic Council office (4055 Faber Place Drive, Suite 201, North Charleston, SC...

Copper and Iron Homeostasis in Plants: The Challenges of Oxidative Stress

PubMed Central

Pilon, Marinus

2013-01-01

Abstract Significance: Photosynthesis, the process that drives life on earth, relies on transition metal (e.g., Fe and Cu) containing proteins that participate in electron transfer in the chloroplast. However, the light reactions also generate high levels of reactive oxygen species (ROS), which makes metal use in plants a challenge. Recent Advances: Sophisticated regulatory networks govern Fe and Cu homeostasis in response to metal ion availability according to cellular needs and priorities. Molecular remodeling in response to Fe or Cu limitation leads to its economy to benefit photosynthesis. Fe toxicity is prevented by ferritin, a chloroplastic Fe-storage protein in plants. Recent studies on ferritin function and regulation revealed the interplay between iron homeostasis and the redox balance in the chloroplast. Critical Issues: Although the connections between metal excess and ROS in the chloroplast are established at the molecular level, the mechanistic details and physiological significance remain to be defined. The causality/effect relationship between transition metals, redox signals, and responses is difficult to establish. Future Directions: Integrated approaches have led to a comprehensive understanding of Cu homeostasis in plants. However, the biological functions of several major families of Cu proteins remain unclear. The cellular priorities for Fe use under deficiency remain largely to be determined. A number of transcription factors that function to regulate Cu and Fe homeostasis under deficiency have been characterized, but we have not identified regulators that mediate responses to excess. Importantly, details of metal sensing mechanisms and cross talk to ROS-sensing mechanisms are so far poorly documented in plants. Antioxid. Redox Signal. 19, 919–932. PMID:23199018

Environmental perfluorooctane sulfonate exposure drives T cell activation in bottlenose dolphins.

PubMed

Soloff, Adam C; Wolf, Bethany Jacobs; White, Natasha D; Muir, Derek; Courtney, Sean; Hardiman, Gary; Bossart, Gregory D; Fair, Patricia A

2017-09-01

Perfluoroalkyl acids (PFAAs) are highly stable compounds that have been associated with immunotoxicity in epidemiologic studies and experimental rodent models. Lengthy half-lives and resistance to environmental degradation result in bioaccumulation of PFAAs in humans and wildlife. Perfluorooctane sulfonate (PFOS), the most prevalent PFAA detected within the environment, is found at high levels in occupationally exposed humans. We have monitored the environmental exposure of dolphins in the Charleston, SC region for over 10 years and levels of PFAAs, and PFOS in particular, were significantly elevated. As dolphins may serve as large mammal sentinels to identify the impact of environmental chemical exposure on human disease, we sought to assess the effect of environmental PFAAs on the cellular immune system in highly exposed dolphins. Herein, we utilized a novel flow cytometry-based assay to examine T cell-specific responses to environmental PFAA exposure ex vivo and to exogenous PFOS exposure in vitro. Baseline PFOS concentrations were associated with significantly increased CD4 + and CD8 + T cell proliferation from a heterogeneous resident dolphin population. Further analysis demonstrated that in vitro exposure to environmentally relevant levels of PFOS promoted proinflammatory cytokine production and proliferation in a dose-dependent manner. Collectively, these findings indicate that PFOS is capable of inducing proinflammatory interferon-gamma, but not immunoregulatory interleukin-4 production in T cells, which may establish a state of chronic immune activation known to be associated with susceptibility to disease. These findings suggest that PFOS directly dysregulates the dolphin cellular immune system and has implications for health hazards. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Signaling by STATs

PubMed Central

Ivashkiv, Lionel B; Hu, Xiaoyu

2004-01-01

A variety of cytokines and growth factors use the Janus kinase (Jak)–STAT signaling pathway to transmit extracellular signals to the nucleus. STATs (signal transducers and activators of transcription) are latent cytoplasmic transcription factors. There are seven mammalian STATs and they have critical, nonredundant roles in mediating cellular transcriptional responses to cytokines. The physiological roles of STATs have been elucidated by analysis of mice rendered deficient in STAT genes. STAT activation is regulated and can be modulated in a positive or negative fashion; it can be reprogrammed to drive different cellular responses. Several auto-regulatory and signaling crosstalk mechanisms for regulating Jak–STAT signaling have been described. Understanding and manipulation of the function of STATs will help in the development of therapeutic strategies for diseases that are regulated by cytokines. PMID:15225360

A novel role for the condensin II complex in cellular senescence.

PubMed

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

2015-01-01

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

Effects of fresh lubricant oils on particle emissions emitted by a modern gasoline direct injection passenger car.

PubMed

Pirjola, Liisa; Karjalainen, Panu; Heikkilä, Juha; Saari, Sampo; Tzamkiozis, Theodoros; Ntziachristos, Leonidas; Kulmala, Kari; Keskinen, Jorma; Rönkkö, Topi

2015-03-17

Particle emissions from a modern turbocharged gasoline direct injection passenger car equipped with a three-way catalyst and an exhaust gas recirculation system were studied while the vehicle was running on low-sulfur gasoline and, consecutively, with five different lubrication oils. Exhaust particle number concentration, size distribution, and volatility were determined both at laboratory and on-road conditions. The results indicated that the choice of lubricant affected particle emissions both during the cold start and warm driving cycles. However, the contribution of engine oil depended on driving conditions being higher during acceleration and steady state driving than during deceleration. The highest emission factors were found with two oils that had the highest metal content. The results indicate that a 10% decrease in the Zn content of engine oils is linked with an 11-13% decrease to the nonvolatile particle number emissions in steady driving conditions and a 5% decrease over the New European Driving Cycle. The effect of lubricant on volatile particles was even higher, on the order of 20%.

Examining the influence of aggressive driving behavior on driver injury severity in traffic crashes.

PubMed

Paleti, Rajesh; Eluru, Naveen; Bhat, Chandra R

2010-11-01

In this paper, we capture the moderating effect of aggressive driving behavior while assessing the influence of a comprehensive set of variables on injury severity. In doing so, we are able to account for the indirect effects of variables on injury severity through their influence on aggressive driving behavior, as well as the direct effect of variables on injury severity. The methodology used in the paper to accommodate the moderating effect of aggressive driving behavior takes the form of two models--one for aggressive driving and another for injury severity. These are appropriately linked to obtain the indirect and direct effects of variables. The data for estimation is obtained from the National Motor Vehicle Crash Causation Study (NMVCCS). From an empirical standpoint, we consider a fine age categorization until 20 years of age when examining age effects on aggressive driving behavior and injury severity. There are several important results from the empirical analysis undertaken in the current paper based on post-crash data collection on aggressive behavior participation just prior to the crash and injury severity sustained in a crash. Young drivers (especially novice drivers between 16 and 17 years of age), drivers who are not wearing seat belt, under the influence of alcohol, not having a valid license, and driving a pick-up are found to be most likely to behave aggressively. Situational, vehicle, and roadway factors such as young drivers traveling with young passengers, young drivers driving an SUV or a pick-up truck, driving during the morning rush hour, and driving on roads with high speed limits are also found to trigger aggressive driving behavior. In terms of vehicle occupants, the safest situation from a driver injury standpoint is when there are two or more passengers in the vehicle, at least one of whom is above the age of 20 years. These and many other results are discussed, along with implications of the result for graduated driving licensing (GDL) programs. 2010 Elsevier Ltd. All rights reserved.

Training toddlers seated on mobile robots to drive indoors amidst obstacles.

PubMed

Chen, Xi; Ragonesi, Christina; Galloway, James C; Agrawal, Sunil K

2011-06-01

Mobility is a causal factor in development. Children with mobility impairments may rely upon power mobility for independence and thus require advanced driving skills to function independently. Our previous studies show that while infants can learn to drive directly to a goal using conventional joysticks in several months of training, they are unable in this timeframe to acquire the advanced skill to avoid obstacles while driving. Without adequate driving training, children are unable to explore the environment safely, the consequences of which may in turn increase their risk for developmental delay. The goal of this research therefore is to train children seated on mobile robots to purposefully and safely drive indoors. In this paper, we present results where ten typically-developing toddlers are trained to drive a robot within an obstacle course. We also report a case study with a toddler with spina-bifida who cannot independently walk. Using algorithms based on artificial potential fields to avoid obstacles, we create force field on the joystick that trains the children to navigate while avoiding obstacles. In this "assist-as-needed" approach, if the child steers the joystick outside a force tunnel centered on the desired direction, the driver experiences a bias force on the hand. Our results suggest that the use of a force-feedback joystick may yield faster learning than the use of a conventional joystick.

Benefits of Moderate-Z Ablators for Direct-Drive Inertial Confinement Fusion

NASA Astrophysics Data System (ADS)

Lafon, M.; Betti, R.; Anderson, K. S.; Collins, T. J. B.; Skupsky, S.; McKenty, P. W.

2014-10-01

Control of hydrodynamic instabilities and DT-fuel preheating by hot electrons produced by laser-plasma interaction is crucial in inertial confinement fusion. Moderate- Z ablators have been shown to reduce the laser imprinting on target and suppress the generation of hot electrons from the two-plasmon-decay instability. These results have motivated the use of ablators of higher- Z than pure plastic in direct-drive-ignition target designs for the National Ignition Facility (NIF). Two-dimensional radiation-hydrodynamic simulations assess the robustness of these ignition designs to laser imprint and capsule nonuniformities. The complex behavior of the hydrodynamic stability of mid- Z ablators is investigated through single and multimode simulations. A polar-drive configuration is developed within the NIF Laser System specifications for each ablator material. The use of multilayer ablators is also investigated to enhance the hydrodynamic stability. Results indicate that ignition target designs using mid- Z ablators exhibit good hydrodynamic properties, leading to high target gain for direct-drive implosions on the NIF. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944 and the Office of Fusion Energy Sciences Number DE-FG02-04ER54786.

Using multiple secondary fusion products to evaluate fuel ρR, electron temperature, and mix in deuterium-filled implosions at the NIF

DOE PAGES

Rinderknecht, H. G.; Rosenberg, M. J.; Zylstra, A. B.; ...

2015-08-25

In deuterium-filled inertial confinement fusion implosions, the secondary fusion processes D( 3He,p) 4He and D(T,n) 4He occur, as the primary fusion products 3He and T react in flight with thermal deuterons. In implosions with moderate fuel areal density (~ 5–100 mg/cm 2), the secondary D- 3He reaction saturates, while the D-T reaction does not, and the combined information from these secondary products is used to constrain both the areal density and either the plasma electron temperature or changes in the composition due to mix of shell material into the fuel. The underlying theory of this technique is developed and appliedmore » to three classes of implosions on the National Ignition Facility: direct-drive exploding pushers, indirect-drive 1-shock and 2-shock implosions,and polar direct-drive implosions. In the 1- and 2-shock implosions, the electron temperature is inferred to be 0.65 x and 0.33 x the burn-averaged ion temperature, respectively. The inferred mixed mass in the polar direct-drive implosions is in agreement with measurements using alternative techniques.« less

Uniform and Multi-Grid Modeling of Acoustic Wave Propagation With Cellular Automaton Techniques

DTIC Science & Technology

2013-03-01

39 Figure 26. CurrvedHillIndices fuction used to created a curved hill in the bottom...to safe passage of a submarine. Driving factors influencing SONAR improvements have alluded to the fact that primary naval missions have shifted from...CurvedHillIndices function after reaching line 12 42 Figure 26. CurrvedHillIndices fuction used to created a curved hill in the bottom of any 2D or

Global Versus Reactive Navigation for Joint UAV-UGV Missions in a Cluttered Environment

DTIC Science & Technology

2012-06-01

spaces. The vehicle uses a two- wheel 5 differential drive system with a third omnidirectional caster for balance. This uncomplicated system saves... wheels , two differential drive wheels and one omni- directional caster wheel . The vehicle changes the direction of its movement by altering the speed of...Virtual Speed Versus Time..........64  Figure 23:  Heading and Yaw Rate Versus Time................64  Figure 24:  Individual Wheel Speeds Versus Time

Enhanced direct-drive implosions with thin high-Z ablation layers.

PubMed

Mostovych, Andrew N; Colombant, Denis G; Karasik, Max; Knauer, James P; Schmitt, Andrew J; Weaver, James L

2008-02-22

New direct-drive spherical implosion experiments with deuterium filled plastic shells have demonstrated significant and absolute (2x) improvements in neutron yield when the shells are coated with a very thin layer ( approximately 200-400 A) of high-Z material such as palladium. This improvement is interpreted as resulting from increased stability of the imploding shell. These results provide for a possible path to control laser imprint and stability in laser-fusion-energy target designs.

Microfluidic device to control interstitial flow-mediated homotypic and heterotypic cellular communication.

PubMed

Alonzo, Luis F; Moya, Monica L; Shirure, Venktesh S; George, Steven C

2015-09-07

Tissue engineering can potentially recreate in vivo cellular microenvironments in vitro for an array of applications such as biological inquiry and drug discovery. However, the majority of current in vitro systems still neglect many biological, chemical, and mechanical cues that are known to impact cellular functions such as proliferation, migration, and differentiation. To address this gap, we have developed a novel microfluidic device that precisely controls the spatial and temporal interactions between adjacent three-dimensional cellular environments. The device consists of four interconnected microtissue compartments (~0.1 mm(3)) arranged in a square. The top and bottom pairs of compartments can be sequentially loaded with discrete cellularized hydrogels creating the opportunity to investigate homotypic (left to right or x-direction) and heterotypic (top to bottom or y-direction) cell-cell communication. A controlled hydrostatic pressure difference across the tissue compartments in both x and y direction induces interstitial flow and modulates communication via soluble factors. To validate the biological significance of this novel platform, we examined the role of stromal cells in the process of vasculogenesis. Our device confirms previous observations that soluble mediators derived from normal human lung fibroblasts (NHLFs) are necessary to form a vascular network derived from endothelial colony forming cell-derived endothelial cells (ECFC-ECs). We conclude that this platform could be used to study important physiological and pathological processes that rely on homotypic and heterotypic cell-cell communication.

Divided attention and driving: a pilot study using virtual reality technology.

PubMed

Lengenfelder, Jean; Schultheis, Maria T; Al-Shihabi, Talal; Mourant, Ronald; DeLuca, John

2002-02-01

Virtual reality (VR) was used to investigate the influence of divided attention (simple versus complex) on driving performance (speed control). Three individuals with traumatic brain injury (TBI) and three healthy controls (HC), matched for age, education, and gender, were examined. Preliminary results revealed no differences on driving speed between TBI and HC. In contrast, TBI subjects demonstrated a greater number of errors on a secondary task performed while driving. The findings suggest that VR may provide an innovative medium for direct evaluation of basic cognitive functions (ie, divided attention) and its impact on everyday tasks (ie, driving) not previously available through traditional neuropsychological measures.

Design of driving control strategy of torque distribution for two - wheel independent drive electric vehicle

NASA Astrophysics Data System (ADS)

Zhang, Chuanwei; Zhang, Dongsheng; Wen, Jianping

2018-02-01

In order to coordinately control the torque distribution of existing two-wheel independent drive electric vehicle, and improve the energy efficiency and control stability of the whole vehicle, the control strategies based on fuzzy control were designed which adopt the direct yaw moment control as the main line. For realizing the torque coordination simulation of the two-wheel independent drive vehicle, the vehicle model, motor model and tire model were built, including the vehicle 7 - DOF dynamics model, motion equation, torque equation. Finally, in the Carsim - Simulink joint simulation platform, the feasibility of the drive control strategy was verified.

Novel Synthetic Medea selfish genetic elements drive population replacement in Drosophila, and a theoretical exploration of Medea-dependent population suppression

PubMed Central

Akbari, Omar S.; Chen, Chun-Hong; Marshall, John M.; Huang, Haixia; Antoshechkin, Igor; Hay, Bruce A.

2013-01-01

Insects act as vectors for diseases of plants, animals and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression. PMID:23654248

The Transcription Factor EB Links Cellular Stress to the Immune Response



PubMed Central

Nabar, Neel R.; Kehrl, John H.

2017-01-01

The transcription factor EB (TFEB) is the master transcriptional regulator of autophagy and lysosome biogenesis. Recent advances have led to a paradigm shift in our understanding of lysosomes from a housekeeping cellular waste bin to a dynamically regulated pathway that is efficiently turned up or down based on cellular needs. TFEB coordinates the cellular response to nutrient deprivation and other forms of cell stress through the lysosome system, and regulates a myriad of cellular processes associated with this system including endocytosis, phagocytosis, autophagy, and lysosomal exocytosis. Autophagy and the endolysosomal system are critical to both the innate and adaptive arms of the immune system, with functions in effector cell priming and direct pathogen clearance. Recent studies have linked TFEB to the regulation of the immune response through the endolysosmal pathway and by direct transcriptional activation of immune related genes. In this review, we discuss the current understanding of TFEB’s function and the molecular mechanisms behind TFEB activation. Finally, we discuss recent advances linking TFEB to the immune response that positions lysosomal signaling as a potential target for immune modulation. PMID:28656016

Inter-Cellular Exchange of Cellular Components via VE-Cadherin-Dependent Trans-Endocytosis

PubMed Central

Sakurai, Takashi; Woolls, Melissa J.; Jin, Suk-Won

2014-01-01

Cell-cell communications typically involve receptor-mediated signaling initiated by soluble or cell-bound ligands. Here, we report a unique mode of endocytosis: proteins originating from cell-cell junctions and cytosolic cellular components from the neighboring cell are internalized, leading to direct exchange of cellular components between two adjacent endothelial cells. VE-cadherins form transcellular bridges between two endothelial cells that are the basis of adherence junctions. At such adherens junction sites, we observed the movement of the entire VE-cadherin molecule from one endothelial cell into the other with junctional and cytoplasmic components. This phenomenon, here termed trans-endocytosis, requires the establishment of a VE-cadherin homodimer in trans with internalization proceeding in a Rac1-, and actomyosin-dependent manner. Importantly, the trans-endocytosis is not dependent on any known endocytic pathway including clathrin-dependent endocytosis, macropinocytosis or phagocytosis. This novel form of cell-cell communications, leading to a direct exchange of cellular components, was observed in 2D and 3D-cultured endothelial cells as well as in the developing zebrafish vasculature. PMID:24603875

The Transcription Factor EB Links Cellular Stress to the Immune Response

.

PubMed

Nabar, Neel R; Kehrl, John H

2017-06-01

The transcription factor EB (TFEB) is the master transcriptional regulator of autophagy and lysosome biogenesis. Recent advances have led to a paradigm shift in our understanding of lysosomes from a housekeeping cellular waste bin to a dynamically regulated pathway that is efficiently turned up or down based on cellular needs. TFEB coordinates the cellular response to nutrient deprivation and other forms of cell stress through the lysosome system, and regulates a myriad of cellular processes associated with this system including endocytosis, phagocytosis, autophagy, and lysosomal exocytosis. Autophagy and the endolysosomal system are critical to both the innate and adaptive arms of the immune system, with functions in effector cell priming and direct pathogen clearance. Recent studies have linked TFEB to the regulation of the immune response through the endolysosmal pathway and by direct transcriptional activation of immune related genes. In this review, we discuss the current understanding of TFEB's function and the molecular mechanisms behind TFEB activation. Finally, we discuss recent advances linking TFEB to the immune response that positions lysosomal signaling as a potential target for immune modulation.

Adolescence, Attention Allocation, and Driving Safety

PubMed Central

Romer, Daniel; Lee, Yi-Ching; McDonald, Catherine C.; Winston, Flaura K.

2014-01-01

Motor vehicle crashes are the leading source of morbidity and mortality in adolescents in the United States and the developed world. Inadequate allocation of attention to the driving task and to driving hazards are important sources of adolescent crashes. We review major explanations for these attention failures with particular focus on the roles that brain immaturity and lack of driving experience play in causing attention problems. The review suggests that the potential for overcoming inexperience and immaturity with training to improve attention to both the driving task and hazards is substantial. Nevertheless, there are large individual differences in both attentional abilities and risky driving tendencies that pose challenges to novice driver policies. Research that can provide evidence-based direction for such policies is urgently needed. PMID:24759442

Bidirectional Drive-And-Brake Mechanism

NASA Technical Reports Server (NTRS)

Swan, Scott A.

1991-01-01

Vehicle that crawls along monorail combines features of both bicycle and railroad handcar. Bidirectional drive-and-brake mechanism includes selectable-pawl-and-ratchet overrunning clutch (drive mechanism) and mating stationary and rotating conical surfaces pressing against each other (brake mechanism). Operates similarly to bicycle drive-and-brake mechanism except limits rotation of sprocket in both directions and brakes at both limits. Conceived for use by astronaut traveling along structure in outer space, concept also applied on Earth to make very small railraod handcars or crawling vehicles for use on large structures, in pipelines under construction, or underwater.

Direct-drive inertial confinement fusion: A review

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

Craxton, R. S.; Anderson, K. S.; Boehly, T. R.

The direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser–plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. The problem of suprathermalmore » electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 μm—the third harmonic of the Nd:glass laser—and 0.248 μm (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon–decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be nonlocal in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive–ignition experiments to be performed on the National Ignition Facility [Haynam et al., Appl. Opt. 46(16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.« less

Direct-drive inertial confinement fusion: A review

DOE PAGES

Craxton, R. S.; Anderson, K. S.; Boehly, T. R.; ...

2015-11-25

In this study, the direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser–plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. Themore » problem of suprathermal electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 um—the third harmonic of the Nd:glass laser—and 0.248 um (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon–decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be non-local in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive–ignition experiments to be performed on the National Ignition Facility [C. A. Haynam et al., Appl. Opt. 46 (16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.« less

Direct-drive inertial confinement fusion: A review

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

Craxton, R. S.; Anderson, K. S.; Boehly, T. R.

In this study, the direct-drive, laser-based approach to inertial confinement fusion (ICF) is reviewed from its inception following the demonstration of the first laser to its implementation on the present generation of high-power lasers. The review focuses on the evolution of scientific understanding gained from target-physics experiments in many areas, identifying problems that were demonstrated and the solutions implemented. The review starts with the basic understanding of laser–plasma interactions that was obtained before the declassification of laser-induced compression in the early 1970s and continues with the compression experiments using infrared lasers in the late 1970s that produced thermonuclear neutrons. Themore » problem of suprathermal electrons and the target preheat that they caused, associated with the infrared laser wavelength, led to lasers being built after 1980 to operate at shorter wavelengths, especially 0.35 um—the third harmonic of the Nd:glass laser—and 0.248 um (the KrF gas laser). The main physics areas relevant to direct drive are reviewed. The primary absorption mechanism at short wavelengths is classical inverse bremsstrahlung. Nonuniformities imprinted on the target by laser irradiation have been addressed by the development of a number of beam-smoothing techniques and imprint-mitigation strategies. The effects of hydrodynamic instabilities are mitigated by a combination of imprint reduction and target designs that minimize the instability growth rates. Several coronal plasma physics processes are reviewed. The two-plasmon–decay instability, stimulated Brillouin scattering (together with cross-beam energy transfer), and (possibly) stimulated Raman scattering are identified as potential concerns, placing constraints on the laser intensities used in target designs, while other processes (self-focusing and filamentation, the parametric decay instability, and magnetic fields), once considered important, are now of lesser concern for mainline direct-drive target concepts. Filamentation is largely suppressed by beam smoothing. Thermal transport modeling, important to the interpretation of experiments and to target design, has been found to be non-local in nature. Advances in shock timing and equation-of-state measurements relevant to direct-drive ICF are reported. Room-temperature implosions have provided an increased understanding of the importance of stability and uniformity. The evolution of cryogenic implosion capabilities, leading to an extensive series carried out on the 60-beam OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)], is reviewed together with major advances in cryogenic target formation. A polar-drive concept has been developed that will enable direct-drive–ignition experiments to be performed on the National Ignition Facility [C. A. Haynam et al., Appl. Opt. 46 (16), 3276 (2007)]. The advantages offered by the alternative approaches of fast ignition and shock ignition and the issues associated with these concepts are described. The lessons learned from target-physics and implosion experiments are taken into account in ignition and high-gain target designs for laser wavelengths of 1/3 μm and 1/4 μm. Substantial advances in direct-drive inertial fusion reactor concepts are reviewed. Overall, the progress in scientific understanding over the past five decades has been enormous, to the point that inertial fusion energy using direct drive shows significant promise as a future environmentally attractive energy source.« less

Isolating and quantifying cross-beam energy transfer in direct-drive implosions on OMEGA and the National Ignition Facility

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

Davis, A. K., E-mail: adavi@lle.rochester.edu; Cao, D.; Michel, D. T.

The angularly resolved mass ablation rates and ablation-front trajectories for Si-coated CH targets were measured in direct-drive inertial confinement fusion experiments to quantify cross-beam energy transfer (CBET) while constraining the hydrodynamic coupling. A polar-direct-drive laser configuration, where the equatorial laser beams were dropped and the polar beams were repointed from a symmetric direct-drive configuration, was used to limit CBET at the pole while allowing it to persist at the equator. The combination of low- and high-CBET conditions observed in the same implosion allowed for the effects of CBET on the ablation rate and ablation pressure to be determined. Hydrodynamic simulationsmore » performed without CBET agreed with the measured ablation rate and ablation-front trajectory at the pole of the target, confirming that the CBET effects on the pole are small. The simulated mass ablation rates and ablation-front trajectories were in excellent agreement with the measurements at all angles when a CBET model based on Randall's equations [C. J. Randall et al., Phys. Fluids 24, 1474 (1981)] was included into the simulations with a multiplier on the CBET gain factor. These measurements were performed on OMEGA and at the National Ignition Facility to access a wide range of plasma conditions, laser intensities, and laser beam geometries. The presence of the CBET gain multiplier required to match the data in all of the configurations tested suggests that additional physics effects, such as intensity variations caused by diffraction, polarization effects, or shortcomings of extending the 1-D Randall model to 3-D, should be explored to explain the differences in observed and predicted drive.« less

Isolating and quantifying cross-beam energy transfer in direct-drive implosions on OMEGA and the National Ignition Facility

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

Davis, A. K.; Cao, D.; Michel, D. T.

The angularly-resolved mass ablation rates and ablation front trajectories for Si-coated CH targets were measured in direct-drive inertial confinement fusion experiments to quantify crossbeam energy transfer (CBET) while constraining the hydrodynamic coupling. A polar-direct-drive laser configuration was used, where the equatorial laser beams were dropped from a symmetric direct-drive configuration to suppress CBET at the pole, while allowing it to persist at the equator. The combination of low- and high-CBET conditions in the same implosion allowed the effects of CBET on the ablation rate and ablation pressure to be decoupled from the other physics effects that influence laser-coupling. Hydrodynamic simulationsmore » performed without CBET reproduced the measured ablation rate and ablation front trajectory at the pole of the target, verifying that the other laser-coupling physics effects are well-modeled when CBET effects are negligible. The simulated mass ablation rates and ablation front trajectories were in excellent agreement with the measurements at all angles when a CBET model based on Randall’s equations [C. J. Randall et al., Phys. Fluids 24, 1474 (1981)] was included into the simulations with an optimized multiplier on the CBET gain factor. These measurements were performed on both OMEGA and the National Ignition Facility to access a wide range of plasma conditions, laser intensities, and laser beam geometries. Furthermore, the presence of the CBET gain multiplier required to match the data in all of the configurations tested suggests that additional physics effects, such as intensity variations due to diffraction, shortcomings of extending the 1-D Randall model to 3-D, or polarization effects, should be explored to explain the differences in observed and predicted drive.« less

Isolating and quantifying cross-beam energy transfer in direct-drive implosions on OMEGA and the National Ignition Facility

DOE PAGES

Davis, A. K.; Cao, D.; Michel, D. T.; ...

2016-04-20

The angularly-resolved mass ablation rates and ablation front trajectories for Si-coated CH targets were measured in direct-drive inertial confinement fusion experiments to quantify crossbeam energy transfer (CBET) while constraining the hydrodynamic coupling. A polar-direct-drive laser configuration was used, where the equatorial laser beams were dropped from a symmetric direct-drive configuration to suppress CBET at the pole, while allowing it to persist at the equator. The combination of low- and high-CBET conditions in the same implosion allowed the effects of CBET on the ablation rate and ablation pressure to be decoupled from the other physics effects that influence laser-coupling. Hydrodynamic simulationsmore » performed without CBET reproduced the measured ablation rate and ablation front trajectory at the pole of the target, verifying that the other laser-coupling physics effects are well-modeled when CBET effects are negligible. The simulated mass ablation rates and ablation front trajectories were in excellent agreement with the measurements at all angles when a CBET model based on Randall’s equations [C. J. Randall et al., Phys. Fluids 24, 1474 (1981)] was included into the simulations with an optimized multiplier on the CBET gain factor. These measurements were performed on both OMEGA and the National Ignition Facility to access a wide range of plasma conditions, laser intensities, and laser beam geometries. Furthermore, the presence of the CBET gain multiplier required to match the data in all of the configurations tested suggests that additional physics effects, such as intensity variations due to diffraction, shortcomings of extending the 1-D Randall model to 3-D, or polarization effects, should be explored to explain the differences in observed and predicted drive.« less

Interface Pattern Selection Criterion for Cellular Structures in Directional Solidification

NASA Technical Reports Server (NTRS)

Trivedi, R.; Tewari, S. N.; Kurtze, D.

1999-01-01

The aim of this investigation is to establish key scientific concepts that govern the selection of cellular and dendritic patterns during the directional solidification of alloys. We shall first address scientific concepts that are crucial in the selection of interface patterns. Next, the results of ground-based experimental studies in the Al-4.0 wt % Cu system will be described. Both experimental studies and theoretical calculations will be presented to establish the need for microgravity experiments.

Gelatin-Based Laser Direct-Write Technique for the Precise Spatial Patterning of Cells

PubMed Central

Schiele, Nathan R.; Chrisey, Douglas B.

2011-01-01

Laser direct-writing provides a method to pattern living cells in vitro, to study various cell–cell interactions, and to build cellular constructs. However, the materials typically used may limit its long-term application. By utilizing gelatin coatings on the print ribbon and growth surface, we developed a new approach for laser cell printing that overcomes the limitations of Matrigel™. Gelatin is free of growth factors and extraneous matrix components that may interfere with cellular processes under investigation. Gelatin-based laser direct-write was able to successfully pattern human dermal fibroblasts with high post-transfer viability (91% ± 3%) and no observed double-strand DNA damage. As seen with atomic force microscopy, gelatin offers a unique benefit in that it is present temporarily to allow cell transfer, but melts and is removed with incubation to reveal the desired application-specific growth surface. This provides unobstructed cellular growth after printing. Monitoring cell location after transfer, we show that melting and removal of gelatin does not affect cellular placement; cells maintained registry within 5.6 ± 2.5 μm to the initial pattern. This study demonstrates the effectiveness of gelatin in laser direct-writing to create spatially precise cell patterns with the potential for applications in tissue engineering, stem cell, and cancer research. PMID:20849381

Reverse matrix converter control method for PMSM drives using DPC

NASA Astrophysics Data System (ADS)

Bak, Yeongsu; Lee, Kyo-Beum

2018-05-01

This paper proposes a control method for a reverse matrix converter (RMC) that drives a three-phase permanent magnet synchronous motor (PMSM). In this proposed method, direct power control (DPC) is used to control the voltage source rectifier of the RMC. The RMC is an indirect matrix converter operating in the boost mode, in which the power-flow directions of the input and output are switched. It has a minimum voltage transfer ratio of 1/0.866 in a linear-modulation region. In this paper, a control method that uses DPC as an additional control method is proposed in order to control the RMC driving a PMSM in the output stage. Simulations and experimental results verify the effectiveness of the proposed control method.

Direct-drive field actuator motors

DOEpatents

Grahn, Allen R.

1995-01-01

A high-torque, low speed, positive-drive field actuator motor including a stator carrying at least one field actuator which changes in dimension responsive to application of an energy field, and at least one drive shoe movable by the dimensional changes of the field actuator to contact and move a rotor element with respect to the stator. Various embodiments of the motor are disclosed, and the rotor element may be moved linearly or arcuately.

Characterization of an extracellular epitope antibody to the neuronal K-Cl cotransporter, KCC2.

PubMed

Gagnon, Kenneth Be; Fyffe, Robert Ew; Adragna, Norma C; Lauf, Peter K

2007-07-01

1. Ion gradients across the cell membrane are important for proper cellular communication and homeostasis. With the exception of erythrocytes, chloride (Cl), one of the most important free anions in animal cells, is not distributed at thermodynamic equilibrium across the plasma membrane. The K-Cl cotransporter (COT), consisting of at least four isoforms, utilizes the larger outwardly directed chemical driving force of K to expel Cl from the cell against its inwardly directed chemical gradient and has been implicated recently as one of the main Cl extruders in developing neurons. 2. Previous in situ hybridization studies have indicated widespread mRNA distribution of the neuronal-specific K-Cl COT isoform (KCC2) throughout the rat central nervous system (CNS). However, immunohistochemical studies have been limited owing to the availability of a more selective antibody to KCC2. The goal of the present study was to develop a new molecular tool for the immunohistochemical identification and neuronal distribution of KCC2. 3. Herein, we present evidence of immunohistochemical corroboration of the widespread KCC2 mRNA expression using a novel extracellular anti-peptide antibody directed against the second extracellular loop (ECL2) of KCC2. Immunoperoxidase and immunofluorescent labelling revealed widespread post-synaptic somatic and dendritic localization of KCC2 in multiple neuronal populations in the cerebral cortex, hippocampus, brainstem, lumbar spinal cord and cerebellum. We also demonstrate that binding of the antibody to an extracellular epitope within ECL2 does not alter cotransporter function. In essence, the present study reports on a new molecular tool for structural and functional studies of KCC2.

Methodology for functional MRI of simulated driving.

PubMed

Kan, Karen; Schweizer, Tom A; Tam, Fred; Graham, Simon J

2013-01-01

The developed world faces major socioeconomic and medical challenges associated with motor vehicle accidents caused by risky driving. Functional magnetic resonance imaging (fMRI) of individuals using virtual reality driving simulators may provide an important research tool to assess driving safety, based on brain activity and behavior. A fMRI-compatible driving simulator was developed and evaluated in the context of straight driving, turning, and stopping in 16 young healthy adults. Robust maps of brain activity were obtained, including activation of the primary motor cortex, cerebellum, visual cortex, and parietal lobe, with limited head motion (<1.5 mm deviation from mean head position in the superior∕inferior direction in all subjects) and only minor correlations between head motion, steering, or braking behavior. These results are consistent with previous literature and suggest that with care, fMRI of simulated driving is a feasible undertaking.

High-performance, polymer-based direct cellular interfaces for electrical stimulation and recording

NASA Astrophysics Data System (ADS)

Kim, Seong-Min; Kim, Nara; Kim, Youngseok; Baik, Min-Seo; Yoo, Minsu; Kim, Dongyoon; Lee, Won-June; Kang, Dong-Hee; Kim, Sohee; Lee, Kwanghee; Yoon, Myung-Han

2018-04-01

Due to the trade-off between their electrical/electrochemical performance and underwater stability, realizing polymer-based, high-performance direct cellular interfaces for electrical stimulation and recording has been very challenging. Herein, we developed transparent and conductive direct cellular interfaces based on a water-stable, high-performance poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) film via solvent-assisted crystallization. The crystallized PEDOT:PSS on a polyethylene terephthalate (PET) substrate exhibited excellent electrical/electrochemical/optical characteristics, long-term underwater stability without film dissolution/delamination, and good viability for primarily cultured cardiomyocytes and neurons over several weeks. Furthermore, the highly crystallized, nanofibrillar PEDOT:PSS networks enabled dramatically enlarged surface areas and electrochemical activities, which were successfully employed to modulate cardiomyocyte beating via direct electrical stimulation. Finally, the high-performance PEDOT:PSS layer was seamlessly incorporated into transparent microelectrode arrays for efficient, real-time recording of cardiomyocyte action potentials with a high signal fidelity. All these results demonstrate the strong potential of crystallized PEDOT:PSS as a crucial component for a variety of versatile bioelectronic interfaces.

Effect of different breath alcohol concentrations on driving performance in horizontal curves.

PubMed

Zhang, Xingjian; Zhao, Xiaohua; Du, Hongji; Ma, Jianming; Rong, Jian

2014-11-01

Driving under the influence of alcohol on curved roadway segments has a higher risk than driving on straight segments. To explore the effect of different breath alcohol concentration (BrAC) levels on driving performance in roadway curves, a driving simulation experiment was designed to collect 25 participants' driving performance parameters (i.e., speed and lane position) under the influence of 4 BrAC levels (0.00%, 0.03%, 0.06% and 0.09%) on 6 types of roadway curves (3 radii×2 turning directions). Driving performance data for 22 participants were collected successfully. Then the average and standard deviation of the two parameters were analyzed, considering the entire curve and different sections of the curve, respectively. The results show that the speed throughout curves is higher when drinking and driving than during sober driving. The significant interaction between alcohol and radius exists in the middle and tangent segments after a curve exit, indicating that a small radius can reduce speed at high BrAC levels. The significant impairment of alcohol on the stability of speed occurs mainly in the curve section between the point of curve (PC) and point of tangent (PT), with no impairment noted in tangent sections. The stability of speed is significantly worsened at higher BrAC levels. Alcohol and radius have interactive effects on the standard deviation of speed in the entry segment of curves, indicating that the small radius amplifies the instability of speed at high BrAC levels. For lateral movement, drivers tend to travel on the right side of the lane when drinking and driving, mainly in the approach and middle segments of curves. Higher BrAC levels worsen the stability of lateral movement in every segment of the curve, regardless of its radius and turning direction. The results are expected to provide reference for detecting the drinking and driving state. Copyright © 2014 Elsevier Ltd. All rights reserved.

Electric vehicle drive train with rollback detection and compensation

DOEpatents

Konrad, C.E.

1994-12-27

An electric vehicle drive train includes a controller for detecting and compensating for vehicle rollback, as when the vehicle is started upward on an incline. The vehicle includes an electric motor rotatable in opposite directions corresponding to opposite directions of vehicle movement. A gear selector permits the driver to select an intended or desired direction of vehicle movement. If a speed and rotational sensor associated with the motor indicates vehicle movement opposite to the intended direction of vehicle movement, the motor is driven to a torque output magnitude as a nonconstant function of the rollback speed to counteract the vehicle rollback. The torque function may be either a linear function of speed or a function of the speed squared. 6 figures.

Electric vehicle drive train with rollback detection and compensation

DOEpatents

Konrad, Charles E.

1994-01-01

An electric vehicle drive train includes a controller for detecting and compensating for vehicle rollback, as when the vehicle is started upward on an incline. The vehicle includes an electric motor rotatable in opposite directions corresponding to opposite directions of vehicle movement. A gear selector permits the driver to select an intended or desired direction of vehicle movement. If a speed and rotational sensor associated with the motor indicates vehicle movement opposite to the intended direction of vehicle movement, the motor is driven to a torque output magnitude as a nonconstant function of the rollback speed to counteract the vehicle rollback. The torque function may be either a linear function of speed or a function of the speed squared.

Cellular interface morphologies in directional solidification. II - The effect of grain boundaries

NASA Technical Reports Server (NTRS)

Ungar, Lyle H.; Brown, Robert A.

1984-01-01

A singular perturbation analysis valid for small grain-boundary slopes is used with the one-sided model for solidification to show that grain boundaries introduce imperfections into the symmetry of the developing cellular interfaces which rupture the junction between the family of planar shapes and the bifurcating cellular families. Undulating interfaces are shown to develop first near grain boundaries, and to evolve with decreasing temperature gradient either by a smooth transition from the almost planar family or by a sudden jump to moderate-amplitude cellular forms, depending on the growth rate.

A Model for Direction Sensing in Dictyostelium discoideum: Ras Activity and Symmetry Breaking Driven by a Gβγ-Mediated, Gα2-Ric8 -- Dependent Signal Transduction Network

PubMed Central

Cheng, Yougan; Othmer, Hans

2016-01-01

Chemotaxis is a dynamic cellular process, comprised of direction sensing, polarization and locomotion, that leads to the directed movement of eukaryotic cells along extracellular gradients. As a primary step in the response of an individual cell to a spatial stimulus, direction sensing has attracted numerous theoretical treatments aimed at explaining experimental observations in a variety of cell types. Here we propose a new model of direction sensing based on experiments using Dictyostelium discoideum (Dicty). The model is built around a reaction-diffusion-translocation system that involves three main component processes: a signal detection step based on G-protein-coupled receptors (GPCR) for cyclic AMP (cAMP), a transduction step based on a heterotrimetic G protein Gα2βγ, and an activation step of a monomeric G-protein Ras. The model can predict the experimentally-observed response of cells treated with latrunculin A, which removes feedback from downstream processes, under a variety of stimulus protocols. We show that Gα2βγ cycling modulated by Ric8, a nonreceptor guanine exchange factor for Gα2 in Dicty, drives multiple phases of Ras activation and leads to direction sensing and signal amplification in cAMP gradients. The model predicts that both Gα2 and Gβγ are essential for direction sensing, in that membrane-localized Gα2*, the activated GTP-bearing form of Gα2, leads to asymmetrical recruitment of RasGEF and Ric8, while globally-diffusing Gβγ mediates their activation. We show that the predicted response at the level of Ras activation encodes sufficient ‘memory’ to eliminate the ‘back-of-the wave’ problem, and the effects of diffusion and cell shape on direction sensing are also investigated. In contrast with existing LEGI models of chemotaxis, the results do not require a disparity between the diffusion coefficients of the Ras activator GEF and the Ras inhibitor GAP. Since the signal pathways we study are highly conserved between Dicty and mammalian leukocytes, the model can serve as a generic one for direction sensing. PMID:27152956

Efficient direct yaw moment control: tyre slip power loss minimisation for four-independent wheel drive vehicle

NASA Astrophysics Data System (ADS)

Kobayashi, Takao; Katsuyama, Etsuo; Sugiura, Hideki; Ono, Eiichi; Yamamoto, Masaki

2018-05-01

This paper proposes an efficient direct yaw moment control (DYC) capable of minimising tyre slip power loss on contact patches for a four-independent wheel drive vehicle. Simulations identified a significant power loss reduction with a direct yaw moment due to a change in steer characteristics during acceleration or deceleration while turning. Simultaneously, the vehicle motion can be stabilised. As a result, the proposed control method can ensure compatibility between vehicle dynamics performance and energy efficiency. This paper also describes the results of a full-vehicle simulation that was conducted to examine the effectiveness of the proposed DYC.

System simulation of direct-current speed regulation based on Simulink

NASA Astrophysics Data System (ADS)

Yang, Meiying

2018-06-01

Many production machines require the smooth adjustment of speed in a certain range In the process of modern industrial production, and require good steady-state and dynamic performance. Direct-current speed regulation system with wide speed regulation range, small relative speed variation, good stability, large overload capacity, can bear the frequent impact load, can realize stepless rapid starting-braking and inversion of frequency and other good dynamic performances, can meet the different kinds of special operation requirements in production process of automation system. The direct-current power drive system is almost always used in the field of drive technology of high performance for a long time.

Establishment and analysis of coupled dynamic model for dual-mass silicon micro-gyroscope

NASA Astrophysics Data System (ADS)

Wang, Zhanghui; Qiu, Anping; Shi, Qin; Zhang, Taoyuan

2017-12-01

This paper presents a coupled dynamic model for a dual-mass silicon micro-gyroscope (DMSG). It can quantitatively analyze the influence of left-right stiffness difference on the natural frequencies, modal matrix and modal coupling coefficient of the DMSG. The analytic results are verified by using the finite element method (FEM) simulation. The model shows that with the left-right stiffness difference of 1%, the modal coupling coefficient is 12% in the driving direction and 31% in the sensing direction. It also shows that in order to achieve good separation, the stiffness of base beam should be small enough in both the driving and sensing direction.

Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles

PubMed Central

Serda, Rita E.; Blanco, Elvin; Mack, Aaron; Stafford, Susan J.; Amra, Sarah; Li, Qingpo; van de Ven, Anne L.; Tanaka, Takemi; Torchilin, Vladimir P.; Wiktorowicz, John E.; Ferrari, Mauro

2014-01-01

Mass transport of drug delivery vehicles is guided by particle properties, such as shape, composition and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light chain variable region, fibrinogen, and complement component 1 compared to their anionic counterparts. The anionic-surface favored equal accumulation of microparticles in the liver and spleen, while cationic-surfaces favored preferential accumulation in the spleen. Immunohistochemistry supported macrophage internalization of both anionic and cationic silicon microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution. PMID:21303614

Advances in the cellular and molecular biology of angiogenesis.

PubMed

Egginton, Stuart; Bicknell, Roy

2011-12-01

Capillaries have been recognized for over a century as one of the most important components in regulating tissue oxygen transport, and their formation or angiogenesis a pivotal element of tissue remodelling during development and adaptation. Clinical interest stems from observations that both excessive and inadequate vascular growth plays a major role in human diseases, and novel developments in treatments for cancer and eye disease increasingly rely on anti-angiogenic therapies. Although the discovery of VEGF (vascular endothelial growth factor) provided the first clue for specificity of signalling in endothelial cell activation, understanding the integrative response that drives angiogenesis requires a much broader perspective. The Advances in the Cellular and Molecular Biology of Angiogenesis meeting brought together researchers at the forefront of this rapidly moving field to provide an update on current understanding, and the most recent insights into molecular and cellular mechanisms of vascular growth. The plenary lecture highlighted the integrative nature of the angiogenic process, whereas invited contributions from basic and clinician scientists described fundamental mechanisms and disease-associated issues of blood vessel formation, grouped under a number of themes to aid discussion. These articles will appeal to academic, clinical and pharmaceutical scientists interested in the molecular and cellular basis of angiogenesis, their modulation or dysfunction in human diseases, and application of these findings towards translational medicine.

Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis

PubMed Central

Watanabe, Miki; Muraleedharan, Ranjithmenon; Lambert, Paul F.; Lane, Andrew N.; Romick-Rosendale, Lindsey E.; Wells, Susanne I.

2017-01-01

The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth. PMID:28558019

Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis.

PubMed

Matrka, Marie C; Watanabe, Miki; Muraleedharan, Ranjithmenon; Lambert, Paul F; Lane, Andrew N; Romick-Rosendale, Lindsey E; Wells, Susanne I

2017-01-01

The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth.

Epigenetic regulation of cell fate reprogramming in aging and disease: A predictive computational model.

PubMed

Folguera-Blasco, Núria; Cuyàs, Elisabet; Menéndez, Javier A; Alarcón, Tomás

2018-03-01

Understanding the control of epigenetic regulation is key to explain and modify the aging process. Because histone-modifying enzymes are sensitive to shifts in availability of cofactors (e.g. metabolites), cellular epigenetic states may be tied to changing conditions associated with cofactor variability. The aim of this study is to analyse the relationships between cofactor fluctuations, epigenetic landscapes, and cell state transitions. Using Approximate Bayesian Computation, we generate an ensemble of epigenetic regulation (ER) systems whose heterogeneity reflects variability in cofactor pools used by histone modifiers. The heterogeneity of epigenetic metabolites, which operates as regulator of the kinetic parameters promoting/preventing histone modifications, stochastically drives phenotypic variability. The ensemble of ER configurations reveals the occurrence of distinct epi-states within the ensemble. Whereas resilient states maintain large epigenetic barriers refractory to reprogramming cellular identity, plastic states lower these barriers, and increase the sensitivity to reprogramming. Moreover, fine-tuning of cofactor levels redirects plastic epigenetic states to re-enter epigenetic resilience, and vice versa. Our ensemble model agrees with a model of metabolism-responsive loss of epigenetic resilience as a cellular aging mechanism. Our findings support the notion that cellular aging, and its reversal, might result from stochastic translation of metabolic inputs into resilient/plastic cell states via ER systems.

Alzheimer Disease Biomarkers and Driving in Clinically Normal Older Adults: Role of Spatial Navigation Abilities.

PubMed

Allison, Samantha; Babulal, Ganesh M; Stout, Sarah H; Barco, Peggy P; Carr, David B; Fagan, Anne M; Morris, John C; Roe, Catherine M; Head, Denise

2018-01-01

Older adults experience impaired driving performance, and modify their driving habits, including limiting amount and spatial extent of travel. Alzheimer disease (AD)-related pathology, as well as spatial navigation difficulties, may influence driving performance and driving behaviors in clinically normal older adults. We examined whether AD biomarkers [cerebrospinal fluid (CSF) concentrations of Aβ42, tau, and ptau181] were associated with lower self-reported spatial navigation abilities, and whether navigation abilities mediated the relationship of AD biomarkers with driving performance and extent. Clinically normal older adults (n=112; aged 65+) completed an on-road driving test, the Santa Barbara Sense of Direction scale (self-report measure of spatial navigation ability), and the Driving Habits Questionnaire for an estimate of driving extent (composite of driving exposure and driving space). All participants had a lumbar puncture to obtain CSF. CSF Aβ42, but not tau or ptau181, was associated with self-reported navigation ability. Lower self-reported navigation was associated with reduced driving extent, but not driving errors. Self-reported navigation mediated the relationship between CSF Aβ42 and driving extent. Findings suggest that cerebral amyloid deposition is associated with lower perceived ability to navigate the environment, which may lead older adults with AD pathology to limit their driving extent.

Toll-like receptor signaling in cell proliferation and survival

PubMed Central

Li, Xinyan; Jiang, Song; Tapping, Richard I.

2009-01-01

Toll-like receptors (TLRs) are important sensors of foreign microbial components as well as products of damaged or inflamed self tissues. Upon sensing these molecules, TLRs initiate a series of downstream signaling events that drive cellular responses including the production of cytokines, chemokines and other inflammatory mediators. This outcome results from the intracellular assembly of protein complexes that drive phosphorylation and other signaling cascades ultimately leading to chromatin remodeling and transcription factor activation. In addition to driving inflammatory responses, TLRs also regulate cell proliferation and survival which serves to expand useful immune cells and integrate inflammatory responses and tissue repair processes. In this context, central TLR signaling molecules, such as the mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinase (PI3K), play key roles. In addition, four major groups of transcription factors which are targets of TLR activation also control cell fate. This review focuses on the role of TLR signaling as it relates to cell proliferation and survival. This topic not only has important implications for understanding host defense and tissue repair, but also cancer which is often associated with conditions of chronic inflammation. PMID:19775907

Active mechanics in living oocytes reveal molecular-scale force kinetics

NASA Astrophysics Data System (ADS)

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

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

Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema

PubMed Central

Chiang, Chia-Wen; Wang, Yong; Sun, Peng; Lin, Tsen-Hsuan; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA), increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice. PMID:25017446

Role of resveratrol in regulation of cellular defense systems against oxidative stress.

PubMed

Truong, Van-Long; Jun, Mira; Jeong, Woo-Sik

2018-01-01

Resveratrol, a natural polyphenolic compound, is found in various kinds of fruits, plants, and their commercial products such as red wine. It has been demonstrated to exhibit a variety of health-promoting effects including prevention and/or treatment of cardiovascular diseases, inflammation, diabetes, neurodegeneration, aging, and cancer. Cellular defensive properties of resveratrol can be explained through its ability of either directly neutralizing reactive oxygen species/reactive nitrogen species (ROS/RNS) or indirectly upregulating the expression of cellular defensive genes. As a direct antioxidant agent, resveratrol scavenges diverse ROS/RNS as well as secondary organic radicals with mechanisms of hydrogen atom transfer and sequential proton loss electron transfer, thereby protecting cellular biomolecules from oxidative damage. Resveratrol also enhances the expression of various antioxidant defensive enzymes such as heme oxygenase 1, catalase, glutathione peroxidase, and superoxide dismutase as well as the induction of glutathione level responsible for maintaining the cellular redox balance. Such defenses could be achieved by regulating various signaling pathways including sirtuin 1, nuclear factor-erythroid 2-related factor 2 and nuclear factor κB. This review provides current understanding and information on the role of resveratrol in cellular defense system against oxidative stress. © 2017 BioFactors, 44(1):36-49, 2018. © 2017 International Union of Biochemistry and Molecular Biology.

Cellular phone collateral damage: A review of burns associated with lithium battery powered mobile devices.

PubMed

Mankowski, Peter J; Kanevsky, Jonathan; Bakirtzian, Parseh; Cugno, Sabrina

2016-06-01

The spontaneous destruction of lithium battery powered cellphones has raised concern about the safety of these devices. We present a case report and review of the literature of burn injuries sustained in association with cellular phone usage. A Medline search was performed to identify articles describing cellular phone associated thermal injuries using key search words including "burn," "burn injury," "cellular phone," "cellphone," "thermal injury," and "telephone." Articles were reviewed for etiology, location, severity and treatment. We also present a case of a burn to the upper thigh resulting from cellular phone battery malfunction. Six case reports were identified detailing burn injuries obtained from cellphone use. Half of these cases occurred from battery malfunction with second degree being the most common severity. All cases were managed conservatively except one case, which required excision and primary closure. Lithium powered cellular phones are susceptible to overheating and destruction from inadequate heat dissipation during thermal runaway. This process can be initiated by local short-circuiting from direct contact with a low resistance conductor such as keys or coins. We reinforce the importance of safe cell phone battery practices including avoiding overcharging and direct skin exposure to minimize thermal injury risk. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Sensitive spectrofluorometry of cellular prion protein based on the on-off interaction between fluorescent dye-labelled aptamers and multi-walled carbon nanotubes.

PubMed

Zhan, Lei; Peng, Li; Yu, Yan; Zhen, Shu Jun; Huang, Cheng Zhi

2012-11-07

The very simple and general spectrofluorometry of cellular prion protein (PrP(C)) is reported in this contribution based on the on-off noncovalent interaction of fluorescent dye-labelled PrP(C) DNA aptamers with multi-walled carbon nanotubes (MWCNTs). Due to the π-π stacking interaction between the DNA bases of the aptamer and the carbon nanotubes, the fluorescent dye and the MWCNTs are brought into close proximity, which leads to fluorescence quenching with a ratio of up to 87%. However, further addition of PrP(C), which disturbs the π-π interaction owing to the strong and specific binding of the aptamer to PrP(C), driving the aptamer away from the surface of the MWCNTs, restored the quenched fluorescence. This recovered fluorescence intensity was found to be in linear proportion to the PrP(C) concentration in the range of 8.2 to 81.7 nM, which builds the basis of the spectrofluorometry of the cellular prion protein.

Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension

PubMed Central

Lewis, Amanda H; Grandl, Jörg

2015-01-01

Piezo1 ion channels mediate the conversion of mechanical forces into electrical signals and are critical for responsiveness to touch in metazoans. The apparent mechanical sensitivity of Piezo1 varies substantially across cellular environments, stimulating methods and protocols, raising the fundamental questions of what precise physical stimulus activates the channel and how its stimulus sensitivity is regulated. Here, we measured Piezo1 currents evoked by membrane stretch in three patch configurations, while simultaneously visualizing and measuring membrane geometry. Building on this approach, we developed protocols to minimize resting membrane curvature and tension prior to probing Piezo1 activity. We find that Piezo1 responds to lateral membrane tension with exquisite sensitivity as compared to other mechanically activated channels and that resting tension can drive channel inactivation, thereby tuning overall mechanical sensitivity of Piezo1. Our results explain how Piezo1 can function efficiently and with adaptable sensitivity as a sensor of mechanical stimulation in diverse cellular contexts. DOI: http://dx.doi.org/10.7554/eLife.12088.001 PMID:26646186

De novo generation of HSCs from somatic and pluripotent stem cell sources

PubMed Central

Vo, Linda T.

2015-01-01

Generating human hematopoietic stem cells (HSCs) from autologous tissues, when coupled with genome editing technologies, is a promising approach for cellular transplantation therapy and for in vitro disease modeling, drug discovery, and toxicology studies. Human pluripotent stem cells (hPSCs) represent a potentially inexhaustible supply of autologous tissue; however, to date, directed differentiation from hPSCs has yielded hematopoietic cells that lack robust and sustained multilineage potential. Cellular reprogramming technologies represent an alternative platform for the de novo generation of HSCs via direct conversion from heterologous cell types. In this review, we discuss the latest advancements in HSC generation by directed differentiation from hPSCs or direct conversion from somatic cells, and highlight their applications in research and prospects for therapy. PMID:25762177