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Sample records for cellular mechanisms leading

  1. Molecular and cellular mechanisms that lead to Candida biofilm formation

    NARCIS (Netherlands)

    J.M. ten Cate; F.M. Klis; T. Pereira-Cenci; W. Crielaard; P.W.J. de Groot

    2009-01-01

    Fungal infections in the oral cavity are mainly caused by C. albicans, but other Candida species are also frequently identified. They are increasing in prevalence, especially in denture-wearers and aging people, and may lead to invasive infections, which have a high mortality rate. Attachment to muc

  2. Cellular mechanics and motility

    Science.gov (United States)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  3. Cellular mechanisms during vascular development

    OpenAIRE

    Blum, Yannick

    2012-01-01

    The vascular system is an essential organ in vertebrate animals and provides the organism with enough oxygen and nutrients. It is composed of an interconnected network of blood vessels, which form using a number of different morphogenetic mechanisms. Angiogenesis describes the formation of new blood vessels from preexisting vessels. A number of molecular pathways have been shown to be essential during angiogenesis. However, cellular architecture of blood vessels as well as cellular mechanisms...

  4. Cellular mechanisms that control mistranslation

    DEFF Research Database (Denmark)

    Reynolds, Noah M; Lazazzera, Beth A; Ibba, Michael

    2010-01-01

    Mistranslation broadly encompasses the introduction of errors during any step of protein synthesis, leading to the incorporation of an amino acid that is different from the one encoded by the gene. Recent research has vastly enhanced our understanding of the mechanisms that control mistranslation...

  5. Mechanisms of cellular transformation by carcinogenic agents

    International Nuclear Information System (INIS)

    This book contains 14 chapters. Some of the chapter titles are: DNA Modification by Chemical Carcinogens; Role of DNA Lesions and Repair in the Transformation of Human Cells; The Induction and Regulation of Radiogenic Transformation In Vitro: Cellular and Molecular Mechanisms; Cellular Transformation by Adenoviruses; and The fos Gene

  6. Mechanisms of cellular transformation by carcinogenic agents

    Energy Technology Data Exchange (ETDEWEB)

    Grunberger, D.; Goff, S.P.

    1987-01-01

    This book contains 14 chapters. Some of the chapter titles are: DNA Modification by Chemical Carcinogens; Role of DNA Lesions and Repair in the Transformation of Human Cells; The Induction and Regulation of Radiogenic Transformation In Vitro: Cellular and Molecular Mechanisms; Cellular Transformation by Adenoviruses; and The fos Gene.

  7. Cellular and molecular mechanisms in kidney fibrosis

    Science.gov (United States)

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution. PMID:24892703

  8. Mechanism of cellular phospholipid efflux.

    Science.gov (United States)

    Kozar, R A; McKeone, B J; Pownall, H J

    1993-11-01

    Plasma phospholipid binding to cell-derived cholesterol is important in reverse cholesterol transport, a key step in the regression of atherosclerosis. However, the mechanism by which phospholipids are transferred from cells to plasma remains unclear. [3H]Choline-labeled phospholipid efflux from fibroblasts has been studied using plasma and its components as acceptors. The kinetics were resolved into a fast component (k1 = 0.119 +/- 0.23 min-1) that corresponded to high-affinity binding of high-density lipoproteins (HDL) to the cell surface and a slow component (k2 = 0.0047 +/- 0.0009 min-1) due to protein-mediated desorption (n = 3). Altering the donor charge with heparinase or the acceptor charge by acetylation abolished the fast component, while the slow phase was unchanged. Only HDL displayed biexponential kinetics, comparable to whole plasma. Half-lives for low-density lipoprotein and very-low-density lipoprotein were t1/2 = 278 +/- 22 min and t1/2 = 1003 +/- 147 min, respectively. In the absence of transfer factor, HDL alone significantly reduced phospholipid efflux (t1/2 = 663 min). Phospholipid transfer protein restored biexponential kinetics. We conclude that cell membranes are a potentially important source of plasma phospholipids and that protein-mediated transfer to HDL is the major route for cell-to-plasma transfer. This step represents a locus for anti-atherosclerotic intervention. PMID:8231174

  9. Cellular and molecular mechanisms in kidney fibrosis

    OpenAIRE

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progressi...

  10. Cellular pressure and volume regulation and implications for cell mechanics.

    Science.gov (United States)

    Jiang, Hongyuan; Sun, Sean X

    2013-08-01

    In eukaryotic cells, small changes in cell volume can serve as important signals for cell proliferation, death, and migration. Volume and shape regulation also directly impacts the mechanics of cells and tissues. Here, we develop a mathematical model of cellular volume and pressure regulation, incorporating essential elements such as water permeation, mechanosensitive channels, active ion pumps, and active stresses in the cortex. The model can fully explain recent experimental data, and it predicts cellular volume and pressure for several models of cell cortical mechanics. Moreover, we show that when cells are subjected to an externally applied load, such as in an atomic force microscopy indentation experiment, active regulation of volume and pressure leads to a complex cellular response. Instead of the passive mechanics of the cortex, the observed cell stiffness depends on several factors working together. This provides a mathematical explanation of rate-dependent response of cells under force. PMID:23931309

  11. Cellular mechanisms of nociception in the frog

    Czech Academy of Sciences Publication Activity Database

    Kuffler, D. P.; Lyfenko, Alla; Vyklický st., Ladislav; Vlachová, Viktorie

    2002-01-01

    Roč. 88, č. 4 (2002), s. 1843-1850. ISSN 0022-3077 R&D Projects: GA ČR GA305/00/1639; GA MŠk LN00B122 Grant ostatní: NATO(XX) Grant 977062 Institutional research plan: CEZ:AV0Z5011922 Keywords : cellular mechanisms of nociception * frog Subject RIV: FH - Neurology Impact factor: 3.743, year: 2002

  12. Molecular and cellular mechanisms of cadmium carcinogenesis

    International Nuclear Information System (INIS)

    Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

  13. Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome.

    Science.gov (United States)

    Chumpitazi, Bruno P; Shulman, Robert J

    2016-12-01

    Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability, gut microbiota, psychosocial distress, gut inflammation, bile acids, food intolerance, colonic bacterial fermentation, and genetics. The molecular and cellular mechanisms of these factors are being actively investigated. In this mini-review, we present updates of these mechanisms and, where possible, relate the findings to childhood IBS. Mechanistic elucidation may lead to the identification of biomarkers as well as personalized childhood IBS therapies. PMID:26883355

  14. Cellular and molecular mechanisms underlying radiation carcinogenesis

    International Nuclear Information System (INIS)

    When considering and analyzing experimental material concerning cellular aspects of the problem of radiation carcinogenesis, the following conclusions can be made: neoplastic transformation of cells in a culture is caused already by small radiation doses, under the effect of which the level of DNA injury is quite insignificant; the frequency of cell transformation depends on the type of radiation, it is particularly pronounced under the effect of radiations with a high linear energy transfer; a correlation between the processes of postradiation recovery and radiogenic transformation of cells is detected, nonrepairable injures of DNA playing the most important role in radiation carcinogenesis; tumour promoters and anticarcinogenic agens produce a modifying effect on the transformation of irradiated cells. Molecular mechanisms of oncogene activation are thoroughly studied using the model of virus carcinogenesis, the problem of the nature of chemical and, in particular, radiation cell transformation remains scantily investigated

  15. Molecular and cellular mechanisms of adipogenesis

    Directory of Open Access Journals (Sweden)

    Aleksander Dmitrievich Egorov

    2015-03-01

    Full Text Available The main components of metabolic syndrome include insulin resistance, hypertriglyceridemia and arterial hypertension. Obesity is the cause of metabolic syndrome, mainly as a consequence of the endocrine function of adipose tissue. The volume of adipose tissue depends on the size of individual adipocytes and on their number. The number of adipocytes increases as a result of enhanced adipocyte differentiation. The transcriptional cascade that regulates this differentiation has been well studied. The major adipogenic transcription factor peroxisome proliferator-activated receptor gamma is a ligand-activated nuclear receptor with essential roles in adipogenesis. Its ligands are used to treat metabolic syndrome and type 2 diabetes mellitus. The present article describes the basic molecular and cellular mechanisms of adipogenesis and discusses the impact of insulin, glucocorticoids, cyclic adenosine monophosphate-activating agents, nuclear receptors and transcription factors on the process of adipogenesis. New regulatory regions of the genome that are capable of binding multiple transcription factors are described, and the most promising drug targets for the treatment of metabolic syndrome and obesity, including the homeodomain proteins Pbx1 and Prep1, are discussed.

  16. Mechanisms involved in cellular ceramide homeostasis

    Directory of Open Access Journals (Sweden)

    Hussain M

    2012-07-01

    Full Text Available Abstract Sphingolipids are ubiquitous and critical components of biological membranes. Their biosynthesis starts with soluble precursors in the endoplasmic reticulum and culminates in the Golgi complex and plasma membrane. Ceramides are important intermediates in the biosynthesis of sphingolipids, such as sphingomyelin, and their overload in the membranes is injurious to cells. The major product of ceramide metabolism is sphingomyelin. We observed that sphingomyelin synthase (SMS 1 or SMS2 deficiencies significantly decreased plasma and liver sphingomyelin levels. However, SMS2 but not SMS1 deficiency increased plasma ceramides. Surprisingly, SMS1 deficiency significantly increased glucosylceramide and ganglioside GM3, but SMS2 deficiency did not. To explain these unexpected findings about modest to no significant changes in ceramides and increases in other sphingolipids after the ablation of SMS1, we hypothesize that cells have evolved several organelle specific mechanisms to maintain ceramide homeostasis. First, ceramides in the endoplasmic reticulum membranes are controlled by its export to Golgi by protein mediated transfer. Second, in the Golgi, ceramide levels are modulated by their enzymatic conversion to different sphingolipids such as sphingomyelin, and glucosylceramides. Additionally, these sphingolipids can become part of triglyceride-rich apolipoprotein B-containing lipoproteins and be secreted. Third, in the plasma membrane ceramide levels are maintained by ceramide/sphingomyelin cycle, delivery to lysosomes, and efflux to extracellular plasma acceptors. All these pathways might have evolved to ensure steady cellular ceramide levels.

  17. Cellular and molecular mechanisms in liver fibrogenesis.

    Science.gov (United States)

    Novo, Erica; Cannito, Stefania; Paternostro, Claudia; Bocca, Claudia; Miglietta, Antonella; Parola, Maurizio

    2014-04-15

    Liver fibrogenesis is a dynamic and highly integrated molecular, tissue and cellular process, potentially reversible, that drives the progression of chronic liver diseases (CLD) towards liver cirrhosis and hepatic failure. Hepatic myofibroblasts (MFs), the pro-fibrogenic effector cells, originate mainly from activation of hepatic stellate cells and portal fibroblasts being characterized by a proliferative and survival attitude. MFs also contract in response to vasoactive agents, sustain angiogenesis and recruit and modulate activity of cells of innate or adaptive immunity. Chronic activation of wound healing and oxidative stress as well as derangement of epithelial-mesenchymal interactions are "major" pro-fibrogenic mechanisms, whatever the etiology. However, literature has outlined a complex network of pro-fibrogenic factors and mediators proposed to modulate CLD progression, with some of them being at present highly debated in the field, including the role of epithelial to mesenchymal transition and Hedgehog signaling pathways. Hypoxia and angiogenesis as well as inflammasomes are recently emerged as ubiquitous pro-inflammatory and pro-fibrogenic determinants whereas adipokines are mostly involved in CLD related to metabolic disturbances (metabolic syndrome and/or obesity and type 2 diabetes). Finally, autophagy as well as natural killer and natural killer-T cells have been recently proposed to significantly affect fibrogenic CLD progression. PMID:24631571

  18. Neural and cellular mechanisms of fear and extinction memory formation.

    Science.gov (United States)

    Orsini, Caitlin A; Maren, Stephen

    2012-08-01

    Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last 30 years, neuroscientists and psychologists alike have attempted to understand the mechanisms by which the brain encodes and maintains these aversive memories. Of equal interest, though, is the neurobiology of extinction memory formation as this may shape current therapeutic techniques. Here we review the extant literature on the neurobiology of fear and extinction memory formation, with a strong focus on the cellular and molecular mechanisms underlying these processes. PMID:22230704

  19. Relationship between cellular response models and biochemical mechanisms

    International Nuclear Information System (INIS)

    In most cellular response experiments, survival reflects the kinetics of a variety of damage and repair processes. Unfortunately, biochemical studies of molecular repair deal with mechanisms which cannot be readily correlated with these kinetic observations. The difference in these approaches sometimes leads to confusion over terms such as potentially-lethal and sublethal damage. These terms were introduced with operation definitions, derived from kinetic studies of cell survival, but some researchers have since attempted to associate them with specific biochemical mechanisms. Consequently, the terms are often used in totally different ways be different investigators. The use of carefully constructed models originating either out of assumptions based on mechanisms, or on kinetics, can be used to design experiments to eliminate some alternative kinetic schemes. In turn, some mechanisms may also be eliminated, resulting in a reduction in the number of mechanisms which must be investigated biochemically. One must take advantage of a wide range of specialized radiation procedures in order to accomplish this. Examples of the use of such specialized experimental designs, which have led to a more detailed understanding of the kinetics of both algal and mammalian cell responses, are discussed

  20. Propagation Mechanism of Cylindrical Cellular Detonation

    Science.gov (United States)

    Han, Wen-Hu; Wang, Cheng; Ning, Jian-Guo

    2012-10-01

    We investigate the evolution of cylindrical cellular detonation with different instabilities. The numerical results show that with decreasing initial temperature, detonation becomes more unstable and the cells of the cylindrical detonation tend to be irregular. For stable detonation, a divergence of cylindrical detonation cells is formed eventually due to detonation instability resulting from a curved detonation front. For mildly unstable detonation, local overdriven detonation occurs. The detonation cell diverges and its size decreases. For highly unstable detonation, locally driven detonation is more obvious and the front is highly wrinkled. As a result, the diverging cylindrical detonation cell becomes highly irregular.

  1. Linking Cellular and Mechanical Processes in Articular Cartilage Lesion Formation: A Mathematical Model

    OpenAIRE

    Kapitanov, Georgi I.; Wang, Xiayi; Ayati, Bruce P; Brouillette, Marc J.; Martin, James A.

    2016-01-01

    A severe application of stress on articular cartilage can initiate a cascade of biochemical reactions that can lead to the development of osteoarthritis. We constructed a multiscale mathematical model of the process with three components: cellular, chemical, and mechanical. The cellular component describes the different chondrocyte states according to the chemicals these cells release. The chemical component models the change in concentrations of those chemicals. The mechanical component cont...

  2. Computer Studies on the Mechanisms Controlling Cellular Proliferation

    International Nuclear Information System (INIS)

    A model of the autoregulation of mitotic and functional activity of the cells is used (R. Tsanev and B. Sendov, J. theoret. Biol. 12 (1966) 327) to study by means of a digital computer the reaction of different cellular systems (a synchronous cellular population, liver and epidermis) to injuring agents disturbing the steady state of the system. The reaction of the cellular models to different kinds of injury was found to imitate adequately some particular features of the real regenerative processes. The model may also be useful to check different hypotheses concerning the mechanisms by which irradiation affects cellular proliferation. (author)

  3. Symposium on molecular and cellular mechanisms of mutagenesis

    International Nuclear Information System (INIS)

    These proceedings contain abstracts only of the 21 papers presented at the Sympsoium. The papers dealt with molecular mechanisms of mutagenesis and cellular responses to chemical and physical mutagenic agents

  4. Mechanical oscillations at the cellular scale

    CERN Document Server

    Jülicher, F

    2001-01-01

    Active phenomena which involve force generation and motion play a key role in a number of phenomena in living cells such as cell motility, muscle contraction and the active transport of material and organelles. Here we discuss mechanical oscillations generated by active systems in cells. Examples are oscillatory regimes in muscles, the periodic beating of axonemal cilia and flagella and spontaneous oscillations of auditory hair cells which play a role in active amplification of weak sounds in hearing. As a prototype system for oscillation generation by proteins, we discuss a general mechanism by which many coupled active elements such as motor molecules can generate oscillations.

  5. Material and mechanical factors:new strategy in cellular neurogenesis

    Institute of Scientific and Technical Information of China (English)

    Hillary Stoll; Il Keun Kwon; Jung Yul Lim

    2014-01-01

    Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharma-cological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material (chemical patterning, micro/nano-topography, carbon nanotube, graphene) and mechanical (static cue from substrate stiffness, dynamic cue from stretch and lfow shear) stimulations of cellular neuro-genesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering.

  6. Cellular and molecular mechanisms of muscle atrophy

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo

    2013-01-01

    Full Text Available Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.

  7. Plant regeneration: cellular origins and molecular mechanisms.

    Science.gov (United States)

    Ikeuchi, Momoko; Ogawa, Yoichi; Iwase, Akira; Sugimoto, Keiko

    2016-05-01

    Compared with animals, plants generally possess a high degree of developmental plasticity and display various types of tissue or organ regeneration. This regenerative capacity can be enhanced by exogenously supplied plant hormones in vitro, wherein the balance between auxin and cytokinin determines the developmental fate of regenerating organs. Accumulating evidence suggests that some forms of plant regeneration involve reprogramming of differentiated somatic cells, whereas others are induced through the activation of relatively undifferentiated cells in somatic tissues. We summarize the current understanding of how plants control various types of regeneration and discuss how developmental and environmental constraints influence these regulatory mechanisms. PMID:27143753

  8. Detection and cellular localization of lead by electron probe analysis in the diagnosis of suspected lead poisoning in rhesus monkeys

    International Nuclear Information System (INIS)

    Lead poisoning of unknown source was diagnosed histologically in 2 rhesus monkeys (Macaca mulatta) by finding acid-fast intranuclear inclusion bodies in the epithelial cells of renal cortical tubules. The presence of lead in the inclusions was determined by scanning electron microscopy/energy dispersive x-ray analysis using sections from paraffin embedded tissues. This observation indicates the usefulness of this technique for the detection and cellular localization of lead in tissues, even from archival material

  9. Lead free solder mechanics and reliability

    CERN Document Server

    Pang, John Hock Lye

    2012-01-01

    Lead-free solders are used extensively as interconnection materials in electronic assemblies and play a critical role in the global semiconductor packaging and electronics manufacturing industry. Electronic products such as smart phones, notebooks and high performance computers rely on lead-free solder joints to connect IC chip components to printed circuit boards. Lead Free Solder: Mechanics and Reliability provides in-depth design knowledge on lead-free solder elastic-plastic-creep and strain-rate dependent deformation behavior and its application in failure assessment of solder joint reliability. It includes coverage of advanced mechanics of materials theory and experiments, mechanical properties of solder and solder joint specimens, constitutive models for solder deformation behavior; numerical modeling and simulation of solder joint failure subject to thermal cycling, mechanical bending fatigue, vibration fatigue and board-level drop impact tests. This book also: Discusses the mechanical prope...

  10. Cellular Mechanisms of Ciliary Length Control

    Directory of Open Access Journals (Sweden)

    Jacob Keeling

    2016-01-01

    Full Text Available Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule-based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated with multiple human disorders called ciliopathies. These diseases affect diverse tissues, including, but not limited to the eyes, kidneys, brain, and lungs. Many processes must be coordinated simultaneously in order to initiate ciliogenesis. These include cell cycle, vesicular trafficking, and axonemal extension. Centrioles play a central role in both cell cycle progression and ciliogenesis, making the transition between basal bodies and mitotic spindle organizers integral to both processes. The maturation of centrioles involves a functional shift from cell division toward cilium nucleation which takes place concurrently with its migration and fusion to the plasma membrane. Several proteinaceous structures of the distal appendages in mother centrioles are required for this docking process. Ciliary assembly and maintenance requires a precise balance between two indispensable processes; so called assembly and disassembly. The interplay between them determines the length of the resulting cilia. These processes require a highly conserved transport system to provide the necessary substances at the tips of the cilia and to recycle ciliary turnover products to the base using a based microtubule intraflagellar transport (IFT system. In this review; we discuss the stages of ciliogenesis as well as mechanisms controlling the lengths of assembled cilia.

  11. Cellular and molecular mechanisms of chemical synaptic transmission.

    Science.gov (United States)

    Millhorn, D E; Bayliss, D A; Erickson, J T; Gallman, E A; Szymeczek, C L; Czyzyk-Krzeska, M; Dean, J B

    1989-12-01

    During the last decade much progress has been made in understanding the cellular and molecular mechanisms by which nerve cells communicate with each other and nonneural (e.g., muscle) target tissue. This review is intended to provide the reader with an account of this work. We begin with an historical overview of research on cell-to-cell communication and then discuss recent developments that, in some instances, have led to dramatic changes in the concept of synaptic transmission. For instance, the finding that single neurons often contain multiple messengers (i.e., neurotransmitters) invalidated the long-held theory (i.e., Dale's Law) that individual neurons contain and release one and only one type of neurotransmitter. Moreover, the last decade witnessed the inclusion of an entire group of compounds, the neuropeptides, as messenger molecules. Enormous progress has also been made in elucidating postsynaptic receptor complexes and biochemical intermediaries involved in synaptic transmission. Here the development of recombinant DNA technology has made it possible to clone and determine the molecular structure for a number of receptors. This information has been used to gain insight into how these receptors function either as a ligand-gated channel or as a G protein-linked ligand recognition molecule. Perhaps the most progress made during this era was in understanding the molecular linkage of G protein-linked receptors to intramembranous and cytoplasmic macromolecules involved in signal amplification and transduction. We conclude with a brief discussion of how synaptic transmission leads to immediate alterations in the electrical activity and, in some cases, to a change in phenotype by altering gene expression. These alterations in cellular behavior are believed to be mediated by phosphoproteins, the final biochemical product of signal transduction. PMID:2575357

  12. Molecular and cellular mechanisms of aldosterone producing adenoma development

    Directory of Open Access Journals (Sweden)

    Sheerazed eBoulkroun

    2015-06-01

    Full Text Available Primary aldosteronism (PA is the most common form of secondary hypertension with an estimated prevalence of ~10% in referred patients. PA occurs as a result of a dysregulation of the normal mechanisms controlling adrenal aldosterone production. It is characterized by hypertension with low plasma renin and elevated aldosterone and often associated with hypokalemia. The two major causes of PA are unilateral aldosterone producing adenoma (APA and bilateral adrenal hyperplasia, accounting together for ~95% of cases. In addition to the well-characterized effect of excess mineralocorticoids on blood pressure, high levels of aldosterone also have cardiovascular, renal and metabolic consequences. Hence, long-term consequences of PA include increased risk of coronary artery disease, myocardial infarction, heart failure and atrial fibrillation. Despite recent progress in the management of patients with PA, critical issues related to diagnosis, subtype differentiation and treatment of non-surgically correctable forms still persist. A better understanding of the pathogenic mechanisms of the disease should lead to the identification of more reliable diagnostic and prognostic biomarkers for a more sensitive and specific screening and new therapeutic options. In this review we will summarize our current knowledge on the molecular and cellular mechanisms of APA development. On one hand, we will discuss how various animal models have improved our understanding of the pathophysiology of excess aldosterone production. On the other hand, we will summarize the major advances made during the last few years in the genetics of APA due to transcriptomic studies and whole exome sequencing. The identification of recurrent and somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D and ATPases (ATP1A1 and ATP2B3 allowed highlighting the central role of calcium signaling in autonomous aldosterone production by the adrenal.

  13. Mechanism resulting in chemical imbalance due to cellular damage associated with mechanoporation: A molecular dynamics study

    Science.gov (United States)

    Sliozberg, Yelena R.; Chantawansri, Tanya L.

    2016-05-01

    To elucidate the mechanism of ion transport through a transmembrane pore, all-atom molecular dynamics simulations were employed. A model membrane where a pore connects the intra- and extra-cellular compartment was considered. Pores with radii of 1.5 nm or less exhibited resealing over the course of 135 ns simulations, and ionic disturbance is minimal. Ion transport through a larger pore (2 nm radius) leads to a substantial change in the intra- and extra-cellular ionic concentrations. The influx of Na+ and Cl- ions down their concentration gradients is greater than the efflux of K+ leading to an osmotic influx of water.

  14. Cellular Mechanisms of L-arginine Induced Experimental Acute Pancreatitis

    OpenAIRE

    Masood, Omar

    2013-01-01

    AbstractThe University Of ManchesterOmar MasoodMD Thesis 2013Cellular Mechanisms of L-arginine Induced Experimental Acute Pancreatitis. IntroductionImpairment of cytosolic calcium ([Ca2+]i) signaling and in particular calcium overload has emerged as a possible unifying mechanism for precipitating acute pancreatitis (AP.)In the L-arginine (L-arg) experimental model of AP, nitric oxide (NO) has been implicated however the disease progression is largely unaffected by nitric oxide synthase (NOS) ...

  15. Porosity and Mechanical Strength of an Autoclaved Clayey Cellular Concrete

    Directory of Open Access Journals (Sweden)

    P. O. Guglielmi

    2010-01-01

    Full Text Available This paper investigates the porosity and the mechanical strength of an Autoclaved Clayey Cellular Concrete (ACCC with the binder produced with 75 wt% kaolinite clay and 25 wt% Portland cement. Aluminum powder was used as foaming agent, from 0.2 wt% to 0.8 wt%, producing specimens with different porosities. The results show that the specimens with higher content of aluminum presented pore coalescence, which can explain the lower porosity of these samples. The porosities obtained with the aluminum contents used in the study were high (approximately 80%, what accounts for the low mechanical strength of the investigated cellular concretes (maximum of 0.62 MPa. Nevertheless, comparing the results obtained in this study to the ones for low temperature clayey aerated concrete with similar compositions, it can be observed that autoclaving is effective for increasing the material mechanical strength.

  16. Cellular and molecular mechanisms of repair in acute and chronic wound healing

    OpenAIRE

    Martin, P.; Nunan, R

    2015-01-01

    Summary A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to ...

  17. Composite alginate gels for tunable cellular microenvironment mechanics

    Science.gov (United States)

    Khavari, Adele; Nydén, Magnus; Weitz, David A.; Ehrlicher, Allen J.

    2016-01-01

    The mechanics of the cellular microenvironment can be as critical as biochemistry in directing cell behavior. Many commonly utilized materials derived from extra-cellular-matrix create excellent scaffolds for cell growth, however, evaluating the relative mechanical and biochemical effects independently in 3D environments has been difficult in frequently used biopolymer matrices. Here we present 3D sodium alginate hydrogel microenvironments over a physiological range of stiffness (E = 1.85 to 5.29 kPa), with and without RGD binding sites or collagen fibers. We use confocal microscopy to measure the growth of multi-cellular aggregates (MCAs), of increasing metastatic potential in different elastic moduli of hydrogels, with and without binding factors. We find that the hydrogel stiffness regulates the growth and morphology of these cell clusters; MCAs grow larger and faster in the more rigid environments similar to cancerous breast tissue (E = 4–12 kPa) as compared to healthy tissue (E = 0.4–2 kpa). Adding binding factors from collagen and RGD peptides increases growth rates, and change maximum MCA sizes. These findings demonstrate the utility of these independently tunable mechanical/biochemistry gels, and that mechanical confinement in stiffer microenvironments may increase cell proliferation. PMID:27484403

  18. Composite alginate gels for tunable cellular microenvironment mechanics

    Science.gov (United States)

    Khavari, Adele; Nydén, Magnus; Weitz, David A.; Ehrlicher, Allen J.

    2016-08-01

    The mechanics of the cellular microenvironment can be as critical as biochemistry in directing cell behavior. Many commonly utilized materials derived from extra-cellular-matrix create excellent scaffolds for cell growth, however, evaluating the relative mechanical and biochemical effects independently in 3D environments has been difficult in frequently used biopolymer matrices. Here we present 3D sodium alginate hydrogel microenvironments over a physiological range of stiffness (E = 1.85 to 5.29 kPa), with and without RGD binding sites or collagen fibers. We use confocal microscopy to measure the growth of multi-cellular aggregates (MCAs), of increasing metastatic potential in different elastic moduli of hydrogels, with and without binding factors. We find that the hydrogel stiffness regulates the growth and morphology of these cell clusters; MCAs grow larger and faster in the more rigid environments similar to cancerous breast tissue (E = 4–12 kPa) as compared to healthy tissue (E = 0.4–2 kpa). Adding binding factors from collagen and RGD peptides increases growth rates, and change maximum MCA sizes. These findings demonstrate the utility of these independently tunable mechanical/biochemistry gels, and that mechanical confinement in stiffer microenvironments may increase cell proliferation.

  19. Cellular Pressure and Volume Regulation and Implications for Cell Mechanics

    OpenAIRE

    Jiang, Hongyuan; Sun, Sean X.

    2013-01-01

    In eukaryotic cells, small changes in cell volume can serve as important signals for cell proliferation, death, and migration. Volume and shape regulation also directly impacts the mechanics of cells and tissues. Here, we develop a mathematical model of cellular volume and pressure regulation, incorporating essential elements such as water permeation, mechanosensitive channels, active ion pumps, and active stresses in the cortex. The model can fully explain recent experimental data, and it pr...

  20. Cellular Transport Mechanisms of Cytotoxic Metallodrugs: An Overview beyond Cisplatin

    Directory of Open Access Journals (Sweden)

    Sarah Spreckelmeyer

    2014-09-01

    Full Text Available The field of medicinal inorganic chemistry has grown consistently during the past 50 years; however, metal-containing coordination compounds represent only a minor proportion of drugs currently on the market, indicating that research in this area has not yet been thoroughly realized. Although platinum-based drugs as cancer chemotherapeutic agents have been widely studied, exact knowledge of the mechanisms governing their accumulation in cells is still lacking. However, evidence suggests active uptake and efflux mechanisms are involved; this may be involved also in other experimental metal coordination and organometallic compounds with promising antitumor activities in vitro and in vivo, such as ruthenium and gold compounds. Such knowledge would be necessary to elucidate the balance between activity and toxicity profiles of metal compounds. In this review, we present an overview of the information available on the cellular accumulation of Pt compounds from in vitro, in vivo and clinical studies, as well as a summary of reports on the possible accumulation mechanisms for different families of experimental anticancer metal complexes (e.g., Ru Au and Ir. Finally, we discuss the need for rationalization of the investigational approaches available to study metallodrug cellular transport.

  1. Composition, structure and mechanical properties of several natural cellular materials

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The stem piths of sunflower, kaoliang and corn are natural cellular materials. In this paper, the contents of the compositions of these piths are determined and their cell shapes and structures are examined through scanning electron microscope (SEM) and optical microscope. Further research is conducted in the effects of the compositions and structures of the piths on the mechanical properties after testing the partial mechanical properties. The results show that the total cellulose, hemicelluloses and lignin content of each sample approaches 75% of the dry mass of its primary cell walls. With the fall of R value, a parameter relative to the contents of the main compositions, the flexibilities of the cellular piths descend while their stresses and rigidities increase. The basic cell shape making up the sunflower pith is approximately a tetrakaidehedron. The stem piths of kaoliang and corn are made up of cells close to hexangular prisms and a few tubular ones which can observably reinforce their mechanical properties in the axial directions.

  2. Cellular Mechanisms of High Mobility Group 1 (HMGB-1) Protein Action in the Diabetic Retinopathy

    OpenAIRE

    Santos, Andrea Rachelle C.; Dvoriantchikova, Galina; Li, Yiwen; Mohammad, Ghulam; Abu El-Asrar, Ahmed M.; Wen, Rong; Ivanov, Dmitry

    2014-01-01

    Diabetic retinopathy is one of the main microvascular complications of diabetes and remains one of the leading causes of blindness worldwide. Recent studies have revealed an important role of inflammatory and proangiogenic high mobility group 1 (HMGB-1) cytokine in diabetic retinopathy. To elucidate cellular mechanisms of HMGB-1 activity in the retina, we performed this study. The histological features of diabetic retinopathy include loss of blood-vessel pericytes and endothelial cells, as we...

  3. Cellular mechanisms of cadmium-induced toxicity: a review.

    Science.gov (United States)

    Rani, Anju; Kumar, Anuj; Lal, Ankita; Pant, Manu

    2014-08-01

    Cadmium is a widespread toxic pollutant of occupational and environmental concern because of its diverse toxic effects: extremely protracted biological half-life (approximately 20-30 years in humans), low rate of excretion from the body and storage predominantly in soft tissues (primarily, liver and kidneys). It is an extremely toxic element of continuing concern because environmental levels have risen steadily due to continued worldwide anthropogenic mobilization. Cadmium is absorbed in significant quantities from cigarette smoke, food, water and air contamination and is known to have numerous undesirable effects in both humans and animals. Cadmium has a diversity of toxic effects including nephrotoxicity, carcinogenicity, teratogenicity and endocrine and reproductive toxicities. At the cellular level, cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Current evidence suggests that exposure to cadmium induces genomic instability through complex and multifactorial mechanisms. Most important seems to be cadmium interaction with DNA repair mechanism, generation of reactive oxygen species and induction of apoptosis. In this article, we have reviewed recent developments and findings on cadmium toxicology. PMID:24117228

  4. Mechanism of cellular uptake of genotoxic silica nanoparticles

    Directory of Open Access Journals (Sweden)

    Mu Qingshan

    2012-07-01

    Full Text Available Abstract Mechanisms for cellular uptake of nanoparticles have important implications for nanoparticulate drug delivery and toxicity. We have explored the mechanism of uptake of amorphous silica nanoparticles of 14 nm diameter, which agglomerate in culture medium to hydrodynamic diameters around 500 nm. In HT29, HaCat and A549 cells, cytotoxicity was observed at nanoparticle concentrations ≥ 1 μg/ml, but DNA damage was evident at 0.1 μg/ml and above. Transmission electron microscopy (TEM combined with energy-dispersive X-ray spectroscopy confirmed entry of the silica particles into A549 cells exposed to 10 μg/ml of nanoparticles. The particles were observed in the cytoplasm but not within membrane bound vesicles or in the nucleus. TEM of cells exposed to nanoparticles at 4°C for 30 minutes showed particles enter cells when activity is low, suggesting a passive mode of entry. Plasma lipid membrane models identified physical interactions between the membrane and the silica NPs. Quartz crystal microbalance experiments on tethered bilayer lipid membrane systems show that the nanoparticles strongly bind to lipid membranes, forming an adherent monolayer on the membrane. Leakage assays on large unilamellar vesicles (400 nm diameter indicate that binding of the silica NPs transiently disrupts the vesicles which rapidly self-seal. We suggest that an adhesive interaction between silica nanoparticles and lipid membranes could cause passive cellular uptake of the particles.

  5. Cellular mechanisms underlying eosinophilic and neutrophilic airway inflammation in asthma.

    Science.gov (United States)

    Pelaia, Girolamo; Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa; Maselli, Rosario

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments. PMID:25878402

  6. Cellular Mechanisms Underlying Eosinophilic and Neutrophilic Airway Inflammation in Asthma

    Directory of Open Access Journals (Sweden)

    Girolamo Pelaia

    2015-01-01

    Full Text Available Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments.

  7. Cardiovascular effects of cocaine: cellular, ionic and molecular mechanisms.

    Science.gov (United States)

    Turillazzi, E; Bello, S; Neri, M; Pomara, C; Riezzo, I; Fineschi, V

    2012-01-01

    Cocaine is a widely abused drug responsible for the majority of deaths ascribed to drug overdose. Many mechanisms have been proposed in order to explain the various cocaine associated cardiovascular complications. Conventionally, cocaine cardiotoxicity has been thought to be mediated indirectly through its sympathomimetic effect, i.e., by inhibiting the reuptake and thus increasing the levels of neuronal catecholamines at work on adrenoceptors. Increased oxidative stress, reactive oxygen species, and cocaine-induced apoptosis in the heart muscle have suggested a new way to understand the cardiotoxic effects of cocaine. More recent studies have led the attention to the interaction of cocaine and some metabolites with cardiac sodium, calcium and potassium channels. The current paper is aimed to investigate the molecular mechanisms of cocaine cardiotoxicity which have a specific clinical and forensic interest. From a clinical point of view the full knowledge of the exact mechanisms by which cocaine exerts cardio - vascular damage is essential to identify potential therapeutic targets and improve novel strategies for cocaine related cardiovascular diseases. From a forensic point of view, it is to be underlined that cocaine use is often associated to sudden death in young, otherwise healthy individuals. While such events are widely reported, the relationship between cardiac morphological alterations and molecular/cellular mechanisms is still controversial. In conclusion, the study of cocaine cardiovascular toxicity needs a strict collaboration between clinicians and pathologists which may be very effective in further dissecting the mechanisms underlying cocaine cardiotoxicity and understanding the cardiac cocaine connection. PMID:22856657

  8. Tensegrity, cellular biophysics, and the mechanics of living systems

    Science.gov (United States)

    Ingber, Donald E.; Wang, Ning; Stamenović, Dimitrije

    2014-01-01

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life — from individual molecules to whole living organisms — to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level. PMID:24695087

  9. Tensegrity, cellular biophysics, and the mechanics of living systems

    Science.gov (United States)

    Ingber, Donald E.; Wang, Ning; Stamenović, Dimitrije

    2014-04-01

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life—from individual molecules to whole living organisms—to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level.

  10. Tensegrity, cellular biophysics, and the mechanics of living systems

    International Nuclear Information System (INIS)

    The recent convergence between physics and biology has led many physicists to enter the fields of cell and developmental biology. One of the most exciting areas of interest has been the emerging field of mechanobiology that centers on how cells control their mechanical properties, and how physical forces regulate cellular biochemical responses, a process that is known as mechanotransduction. In this article, we review the central role that tensegrity (tensional integrity) architecture, which depends on tensile prestress for its mechanical stability, plays in biology. We describe how tensional prestress is a critical governor of cell mechanics and function, and how use of tensegrity by cells contributes to mechanotransduction. Theoretical tensegrity models are also described that predict both quantitative and qualitative behaviors of living cells, and these theoretical descriptions are placed in context of other physical models of the cell. In addition, we describe how tensegrity is used at multiple size scales in the hierarchy of life—from individual molecules to whole living organisms—to both stabilize three-dimensional form and to channel forces from the macroscale to the nanoscale, thereby facilitating mechanochemical conversion at the molecular level. (review article)

  11. Intermittent hypoxia leads to functional reorganization of mitochondria and affects cellular bioenergetics in marine molluscs.

    Science.gov (United States)

    Ivanina, Anna V; Nesmelova, Irina; Leamy, Larry; Sokolov, Eugene P; Sokolova, Inna M

    2016-06-01

    Fluctuations in oxygen (O2) concentrations represent a major challenge to aerobic organisms and can be extremely damaging to their mitochondria. Marine intertidal molluscs are well-adapted to frequent O2 fluctuations, yet it remains unknown how their mitochondrial functions are regulated to sustain energy metabolism and prevent cellular damage during hypoxia and reoxygenation (H/R). We used metabolic control analysis to investigate the mechanisms of mitochondrial responses to H/R stress (18 h at recovery, combined with the ability to suppress ATP-demanding cellular functions during hypoxia, may contribute to high resilience of clams to H/R stress and help maintain energy homeostasis during frequent H/R cycles in the intertidal zone. PMID:27252455

  12. Cellular and Humoral Mechanisms Involved in the Control of Tuberculosis

    Directory of Open Access Journals (Sweden)

    Joaquin Zuñiga

    2012-01-01

    Full Text Available Mycobacterium tuberculosis (Mtb infection is a major international public health problem. One-third of the world's population is thought to have latent tuberculosis, a condition where individuals are infected by the intracellular bacteria without active disease but are at risk for reactivation, if their immune system fails. Here, we discuss the role of nonspecific inflammatory responses mediated by cytokines and chemokines induced by interaction of innate receptors expressed in macrophages and dendritic cells (DCs. We also review current information regarding the importance of several cytokines including IL-17/IL-23 in the development of protective cellular and antibody-mediated protective responses against Mtb and their influence in containment of the infection. Finally, in this paper, emphasis is placed on the mechanisms of failure of Mtb control, including the immune dysregulation induced by the treatment with biological drugs in different autoimmune diseases. Further functional studies, focused on the mechanisms involved in the early host-Mtb interactions and the interplay between host innate and acquired immunity against Mtb, may be helpful to improve the understanding of protective responses in the lung and in the development of novel therapeutic and prophylactic tools in TB.

  13. Mitochondrial and cellular mechanisms for managing lipid excess

    Directory of Open Access Journals (Sweden)

    Miguel A Aon

    2014-07-01

    Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

  14. Embryonic exposure to lead: comparison of immune and cellular responses in unchallenged and virally stressed chickens

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji-Eun; Kao, Elizabeth; Dietert, Rodney R. [Institute for Comparative and Environmental Toxicology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States); Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States); Naqi, Syed A. [Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States)

    2002-01-01

    Lead, a ubiquitous environmental contaminant, has been shown to modulate various functions of the immune system and decrease host resistance to infectious disease. However, limited information is available concerning the direct effects of lead on the host immune response to an infectious agent after developmental exposure. The current study utilized chickens to examine the effect of embryonic lead exposure on immune and cellular responses during viral challenge. Sublethal doses of lead were introduced into fertilized Cornell K Strain White Leghorn chicken eggs via the air sac at day 5 or day 12 of embryonic development (designated as E5 and E12, respectively). Four-week-old female chickens were inoculated with infectious bronchitis virus (IBV) strain M41. Antibody titer to IBV, delayed-type hypersensitivity (DTH) response against bovine serum albumin (BSA), the absolute number and percentage of leukocyte subpopulations, and interferon-{gamma} (IFN-{gamma})-like cytokine production by splenocytes were evaluated at 5-6 weeks of age. While antibody response to IBV in juvenile chicks was unaffected by the in ovo lead exposure, IFN-{gamma}-like cytokine production by splenocytes was significantly depressed following lead exposure at both developmental stages. In contrast with this pattern, the DTH response against BSA was unaffected following E5 exposure, but was significantly decreased after E12 exposure to lead. These changes were similar to those previously reported in chickens not exposed to IBV. While lead exposure at E5 induced significant changes in the percentage of circulating heterophils at 1 day postinfection (dpi), lead did not cause any change in relative leukocyte counts after E12 exposure. At 7 dpi, E5 lead exposure resulted in decreased absolute number and percentage of circulating lymphocytes, while total leukocyte counts, and the absolute number and percentage of circulating monocytes and heterophils were significantly reduced in E12 lead

  15. Cellular mechanisms underlying the interaction between cannabinoid and opioid system.

    Science.gov (United States)

    Parolaro, D; Rubino, T; Viganò, D; Massi, P; Guidali, C; Realini, N

    2010-04-01

    Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to modulate immune system and emotions) and the combined use of the two drugs by drug abusers is becoming largely diffuse, only few papers focused on cellular and molecular mechanisms underlying this interaction. This review updates the biochemical and molecular underpinnings of opioid and cannabinoid interaction, both within the central nervous system and periphery. The most convincing theory for the explanation of this reciprocal interaction involves (i) the release of opioid peptides by cannabinoids or endocannabinoids by opioids, (ii) the existence of a direct receptor-receptor interaction when the receptors are co-expressed in the same cells, and (iii) the interaction of their intracellular pathways. Finally, the cannabinoid/opioid interaction might be different in the brain rewarding networks and in those accounting for other pharmacological effects (antinociception, modulation of emotionality and cognitive behavior), as well as between the central nervous system and periphery. Further insights about the cannabinoid/opioid interaction could pave the way for new and promising therapeutic approaches. PMID:20017730

  16. Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy.

    Science.gov (United States)

    Tradtrantip, Lukmanee; Ko, Eun-A; Verkman, Alan S

    2014-02-01

    Screening of herbal remedies for Cl(-) channel inhibition identified Krisanaklan, a herbal extract used in Thailand for treatment of diarrhea, as an effective antidiarrheal in mouse models of secretory diarrheas with inhibition activity against three Cl(-) channel targets. Krisanaklan fully inhibited cholera toxin-induced intestinal fluid secretion in a closed-loop mouse model with ∼50% inhibition at a 1 ∶ 50 dilution of the extract. Orally administered Krisanaklan (5 µL/g) prevented rotavirus-induced diarrhea in neonatal mice. Short-circuit current measurements showed full inhibition of cAMP and Ca(2+) agonist-induced Cl(-) conductance in human colonic epithelial T84 cells, with ∼ 50% inhibition at a 1 ∶ 5,000 dilution of the extract. Krisanaklan also strongly inhibited intestinal smooth muscle contraction in an ex vivo preparation. Together with measurements using specific inhibitors, we conclude that the antidiarrheal actions of Krisanaklan include inhibition of luminal CFTR and Ca(2+)-activated Cl(-) channels in enterocytes. HPLC fractionation indicated that the three Cl(-) inhibition actions of Krisanaklan are produced by different components in the herbal extract. Testing of individual herbs comprising Krisanaklan indicated that agarwood and clove extracts as primarily responsible for Cl(-) channel inhibition. The low cost, broad antidiarrheal efficacy, and defined cellular mechanisms of Krisanaklan suggests its potential application for antisecretory therapy of cholera and other enterotoxin-mediated secretory diarrheas in developing countries. PMID:24551253

  17. Antidiarrheal efficacy and cellular mechanisms of a Thai herbal remedy.

    Directory of Open Access Journals (Sweden)

    Lukmanee Tradtrantip

    2014-02-01

    Full Text Available Screening of herbal remedies for Cl(- channel inhibition identified Krisanaklan, a herbal extract used in Thailand for treatment of diarrhea, as an effective antidiarrheal in mouse models of secretory diarrheas with inhibition activity against three Cl(- channel targets. Krisanaklan fully inhibited cholera toxin-induced intestinal fluid secretion in a closed-loop mouse model with ∼50% inhibition at a 1 ∶ 50 dilution of the extract. Orally administered Krisanaklan (5 µL/g prevented rotavirus-induced diarrhea in neonatal mice. Short-circuit current measurements showed full inhibition of cAMP and Ca(2+ agonist-induced Cl(- conductance in human colonic epithelial T84 cells, with ∼ 50% inhibition at a 1 ∶ 5,000 dilution of the extract. Krisanaklan also strongly inhibited intestinal smooth muscle contraction in an ex vivo preparation. Together with measurements using specific inhibitors, we conclude that the antidiarrheal actions of Krisanaklan include inhibition of luminal CFTR and Ca(2+-activated Cl(- channels in enterocytes. HPLC fractionation indicated that the three Cl(- inhibition actions of Krisanaklan are produced by different components in the herbal extract. Testing of individual herbs comprising Krisanaklan indicated that agarwood and clove extracts as primarily responsible for Cl(- channel inhibition. The low cost, broad antidiarrheal efficacy, and defined cellular mechanisms of Krisanaklan suggests its potential application for antisecretory therapy of cholera and other enterotoxin-mediated secretory diarrheas in developing countries.

  18. Unraveling the cellular and molecular mechanisms of repetitive magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Florian Müller-Dahlhaus

    2013-12-01

    Full Text Available Despite numerous clinical studies, which have investigated the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS in various brain diseases, our knowledge of the cellular and molecular mechanisms underlying rTMS-based therapies remains limited. Thus, a deeper understanding of rTMS-induced neural plasticity is required to optimize current treatment protocols. Studies in small animals or appropriate in vitro preparations (including models of brain diseases provide highly useful experimental approaches in this context. State-of-the-art electrophysiological and live-cell imaging techniques that are well established in basic neuroscience can help answering some of the major questions in the field, such as (i which neural structures are activated during TMS, (ii how does rTMS induce Hebbian plasticity, and (iii are other forms of plasticity (e.g., metaplasticity, structural plasticity induced by rTMS? We argue that data gained from these studies will support the development of more effective and specific applications of rTMS in clinical practice.

  19. Cellular mechanisms of skin repair in humans and other mammals.

    Science.gov (United States)

    Rittié, Laure

    2016-06-01

    The increased incidence of non-healing skin wounds in developed societies has prompted tremendous research efforts on the complex process known as "wound healing". Unfortunately, the weak relevance of modern wound healing research to human health continues to be a matter of concern. This review summarizes the current knowledge of the cellular mechanisms that mediate wound closure in the skin of humans and laboratory animals. The author highlights the anatomical singularities of human skin vs. the skin of other mammals commonly used for wound healing research (i.e. as mice, rats, rabbits, and pigs), and discusses the roles of stem cells, myofibroblasts, and the matrix environment in the repair process. The majority of this review focuses on reepithelialization and wound closure. Other aspects of wound healing (e.g. inflammation, fibrous healing) are referred to when relevant to the main topic. This review aims at providing the reader with a clear understanding of the similarities and differences that have been reported over the past 100 years between the healing of human wounds and that of other mammals. PMID:27170326

  20. Molecular and Cellular Mechanisms Elucidating Neurocognitive Basis of Functional Impairments Associated with Intellectual Disability in Down Syndrome

    Science.gov (United States)

    Rachidi, Mohammed; Lopes, Carmela

    2010-01-01

    Down syndrome, the most common genetic cause of intellectual disability, is associated with brain disorders due to chromosome 21 gene overdosage. Molecular and cellular mechanisms involved in the neuromorphological alterations and cognitive impairments are reported herein in a global model. Recent advances in Down syndrome research have lead to…

  1. [Glycotoxins and cellular dysfunction. A new mechanism for understanding the preventive effects of lifestyle modifications].

    Science.gov (United States)

    Michalsen, A; Bierhaus, A; Nawroth, P P; Dobos, G J

    2006-08-01

    Recently the AGE-RAGE interaction was identified as a potential mechanism underlying chronic and inflammatory diseases like atherosclerosis, diabetes mellitus and kidney disease. Advanced glycation end products (AGEs) are the derivatives of glucose-protein or glucose-lipid reactions and are mainly generated from the diet (depending on intensity of heating, cooking time and oxygenation). Binding of AGEs or other ligands to the AGE receptor (RAGE) results in cellular activation, i.e. increased expression of inflammatory mediators and oxidative stress. Diet-derived AGEs thus induce deleterious effects on tissues and the cardiovascular system. Recent research also found that other lifestyle factors are associated with pronounced inflammatory activation, e.g. psychosocial stress and smoking. In addition, each intake of meals is associated with proinflammatory cellular changes. The AGE-RAGE model and investigations of the underlying cellular mechanisms thus may lead to a better understanding of the health benefits of diets (Mediterranean diet, uncooked vegetarian diets), caloric restriction and intermittent fasting. The clinical impact of low-AGE diets and fasting and the interaction between stress and food intake should be further investigated in controlled trials. PMID:16897151

  2. The cytotoxicity of lead and uranium on rat osteoblastic cells is highly dependent on chemical speciation and cellular accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Milgram, S.; Carriere, M.; Thiebault, C.; Gouget, B. [CEA Saclay, CNRS - UMR9956, Lab Pierre Sue, F-91198 Gif Sur Yvette, (France); Malval, L. [INSERM, E366, Lab Biol Tissue Osseux, St Etienne, (France)

    2007-07-01

    Complete text of publication follows: Uranium (U) and lead (Pb), as other heavy metals, present a strong chemical toxicity. After blood contamination, U and Pb, complexed with proteins or inorganic molecules are conveyed to target organs, the skeleton being the major long-term storage site. Once in bones, both metals are incorporated in the hydroxyapatite matrix by substitution with calcium. They can thus be released during re-modelling, which explains in part their toxicity. Although the clinical effects of these metals are well known, the cellular mechanisms of their action are not well understood. To investigate the biological effects of U and Pb acute exposure on osteoblasts, ROS17/2.8 cells were exposed to Pb or U [0-1 mM] for 24 h. The most relevant chemical and physical states, namely the most likely forms (species) of the toxics in contact with cells after blood contamination were selected for cell exposure. For each metal species, Pb and U toxicity were assessed through cell viability assay. The results show that whatever the speciation, U chemical toxicity to bone cells is far lower than Pb toxicity. Pb appears to be cytotoxic when left free in the exposure medium or when it is complexed with bicarbonate, cysteine or citrate, but not with albumin or phosphate (an insoluble form of Pb). In order to explain these differences in sensitivity between different metals and metal chemical species, time-course and dose-response curves of cellular accumulation at lethal or sub-lethal doses were drawn by direct elemental analysis of metal concentrations in digested cell pellets, using Inductive Coupling Plasma Mass Spectroscopy. These showed a clear correlation between toxicity and cellular accumulation. Also, Pb induces an inhibition of ALP activity after 24 h exposure to sub-lethal doses, which is speciation-dependent and again correlates with cellular accumulation. Phenotypic effects of U are under investigation. In addition, electron-microscopic observation of

  3. Mood disorders in Huntington’s disease: from behavior to cellular and molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Patrick Pla

    2014-04-01

    Full Text Available Huntington’s disease (HD is a neurodegenerative disorder that is best known for its effect on motor control. Mood disturbances such as depression, anxiety, and irritability also have a high prevalence in patients with HD, and often start before the onset of motor symptoms. Various rodent models of HD recapitulate the anxiety/depressive behavior seen in patients. HD is caused by an expanded polyglutamine stretch in the N-terminal part of a 350 kDa protein called huntingtin (HTT. HTT is ubiquitously expressed and is implicated in several cellular functions including control of transcription, vesicular trafficking, ciliogenesis, and mitosis. This review summarizes progress in efforts to understand the cellular and molecular mechanisms underlying behavioral disorders in patients with HD. Dysfunctional HTT affects cellular pathways that are involved in mood disorders or in the response to antidepressants, including BDNF/TrkB and serotonergic signaling. Moreover, HTT affects adult hippocampal neurogenesis, a physiological phenomenon that is implicated in some of the behavioral effects of antidepressants and is linked to the control of anxiety. These findings are consistent with the emerging role of wild-type HTT as a crucial component of neuronal development and physiology. Thus, the pathogenic polyQ expansion in HTT could lead to mood disorders not only by the gain of a new toxic function but also by the perturbation of its normal function.

  4. Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

    International Nuclear Information System (INIS)

    Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

  5. Nonlinear dose-response relationships and inducible cellular defence mechanisms

    International Nuclear Information System (INIS)

    With the inclusion of inducible radioprotective mechanisms in a radiobiological state-vector model it was possible to explain plateaus in dose-response relationships for neoplastic transformation produced by in vitro irradiation of different cell lines with low-LET irradiation at high dose rates. The current study repeated the simulation of one data set that contains a plateau at mid doses. In contrast to earlier studies, the new one did not model the repair of double-strand breaks (DSBs) located in bulk DNA (likely via non-homologous end joining) as being inducible. Repair of specific DSBs located in actively transcribed genes was assumed to occur via homologous recombination and was considered to be inducible. This reduced the number of parameters that have to be determined by fitting the model to data. In addition, all types of radical scavengers were formerly considered to be inducible by radiation. This was redefined in the current work and the effectiveness of scavengers was implemented in a refined way. The current work investigated whether these and other model adjustments lead to an improved fit of the data set. (author)

  6. A sub-cellular viscoelastic model for cell population mechanics.

    Directory of Open Access Journals (Sweden)

    Yousef Jamali

    Full Text Available Understanding the biomechanical properties and the effect of biomechanical force on epithelial cells is key to understanding how epithelial cells form uniquely shaped structures in two or three-dimensional space. Nevertheless, with the limitations and challenges posed by biological experiments at this scale, it becomes advantageous to use mathematical and 'in silico' (computational models as an alternate solution. This paper introduces a single-cell-based model representing the cross section of a typical tissue. Each cell in this model is an individual unit containing several sub-cellular elements, such as the elastic plasma membrane, enclosed viscoelastic elements that play the role of cytoskeleton, and the viscoelastic elements of the cell nucleus. The cell membrane is divided into segments where each segment (or point incorporates the cell's interaction and communication with other cells and its environment. The model is capable of simulating how cells cooperate and contribute to the overall structure and function of a particular tissue; it mimics many aspects of cellular behavior such as cell growth, division, apoptosis and polarization. The model allows for investigation of the biomechanical properties of cells, cell-cell interactions, effect of environment on cellular clusters, and how individual cells work together and contribute to the structure and function of a particular tissue. To evaluate the current approach in modeling different topologies of growing tissues in distinct biochemical conditions of the surrounding media, we model several key cellular phenomena, namely monolayer cell culture, effects of adhesion intensity, growth of epithelial cell through interaction with extra-cellular matrix (ECM, effects of a gap in the ECM, tensegrity and tissue morphogenesis and formation of hollow epithelial acini. The proposed computational model enables one to isolate the effects of biomechanical properties of individual cells and the

  7. Mediated coalescence: a possible mechanism for tumor cellular heterogeneity

    Science.gov (United States)

    Ambrose, Joseph; Livitz, Michelle; Wessels, Deborah; Kuhl, Spencer; Lusche, Daniel F; Scherer, Amanda; Voss, Edward; Soll, David R

    2015-01-01

    Recently, we demonstrated that tumorigenic cell lines and fresh tumor cells seeded in a 3D Matrigel model, first grow as clonal islands (primary aggregates), then coalesce through the formation and contraction of cellular cables. Non-tumorigenic cell lines and cells from normal tissue form clonal islands, but do not form cables or coalesce. Here we show that as little as 5% tumorigenic cells will actively mediate coalescence between primary aggregates of majority non-tumorigenic or non-cancerous cells, by forming cellular cables between them. We suggest that this newly discovered, specialized characteristic of tumorigenic cells may explain, at least in part, why tumors contain primarily non-tumorigenic cells. PMID:26807328

  8. Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs

    OpenAIRE

    Adams, Drew J.; Dai, Mingji; Pellegrino, Giovanni; Wagner, Bridget K.; Stern, Andrew M.; Shamji, Alykhan F.; Schreiber, Stuart L.

    2012-01-01

    Piperlongumine is a naturally occurring small molecule recently identified to be toxic selectively to cancer cells in vitro and in vivo. This compound was found to elevate cellular levels of reactive oxygen species (ROS) selectively in cancer cell lines. The synthesis of 80 piperlongumine analogs has revealed structural modifications that retain, enhance, and ablate key piperlongumine-associated effects on cells, including elevation of ROS, cancer cell death, and selectivity for cancer cells ...

  9. Cellular solid behaviour of liquid crystal colloids. 2. Mechanical properties

    OpenAIRE

    Anderson, V.J.; Terentjev, E. M.

    2000-01-01

    This paper presents the results of a rheological study of thermotropic nematic colloids aggregated into cellular structures. Small sterically stabilised PMMA particles dispersed in a liquid crystal matrix densely pack on cell interfaces, but reversibly mix with the matrix when the system is heated above Tni. We obtain a remarkably high elastic modulus, G'~10^5 Pa, which is a nearly linear function of particle concentration. A characteristic yield stress is required to disrupt the continuity o...

  10. Engineered mutations in fibrillin-1 leading to Marfan syndrome act at the protein, cellular and organismal levels.

    Science.gov (United States)

    Zeyer, Karina A; Reinhardt, Dieter P

    2015-01-01

    Fibrillins are the major components of microfibrils in the extracellular matrix of elastic and non-elastic tissues. They are multi-domain proteins, containing primarily calcium binding epidermal growth factor-like (cbEGF) domains and 8-cysteine/transforming growth factor-beta binding protein-like (TB) domains. Mutations in the fibrillin-1 gene give rise to Marfan syndrome, a connective tissue disorder with clinical complications in the cardiovascular, skeletal, ocular and other organ systems. Here, we review the consequences of engineered Marfan syndrome mutations in fibrillin-1 at the protein, cellular and organismal levels. Representative point mutations associated with Marfan syndrome in affected individuals have been introduced and analyzed in recombinant fibrillin-1 fragments. Those mutations affect fibrillin-1 on a structural and functional level. Mutations which impair folding of cbEGF domains can affect protein trafficking. Protein folding disrupted by some mutations can lead to defective secretion in mutant fibrillin-1 fragments, whereas fragments with other Marfan mutations are secreted normally. Many Marfan mutations render fibrillin-1 more susceptible to proteolysis. There is also evidence that some mutations affect heparin binding. Few mutations have been further analyzed in mouse models. An extensively studied mouse model of Marfan syndrome expresses mouse fibrillin-1 with a missense mutation (p.C1039G). The mice display similar characteristics to human patients with Marfan syndrome. Overall, the analyses of engineered mutations leading to Marfan syndrome provide important insights into the pathogenic molecular mechanisms exerted by mutated fibrillin-1. PMID:26281765

  11. Mechanically stable insoluble titanium-lead anodes for sulfate electrolytes

    Directory of Open Access Journals (Sweden)

    Chmiola J.

    2003-01-01

    Full Text Available Different formulations of a new material to be used as an insoluble anode for copper electrowinning, a Ti-Pb composite, were investigated for both mechanical and electrochemical properties. Mechanical and metallographic characteristic tests, as well as short-term deposition tests were used to study the effect of the Ti/Pb ratio on anode performance. Yield strength and elastic modulus, obtained through tensile testing, significantly exceed that of lead. Metallographic procedures were used to assess the uniformity of lead distribution in the material, as well as porosity, which would be decreased below 1 % for most of the compositions under study. Short-term deposition tests were used to determine power consumption, deposit quality current efficiency and weight loss characteristics of the new anode material. The material with only 30 vol.% lead shows approximately the same electrochemical performance as a pure lead anode, but has much higher mechanical properties which prevent warping and extend the lifetime of the anode.

  12. Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism.

    Science.gov (United States)

    Masri, Selma; Rigor, Paul; Cervantes, Marlene; Ceglia, Nicholas; Sebastian, Carlos; Xiao, Cuiying; Roqueta-Rivera, Manuel; Deng, Chuxia; Osborne, Timothy F; Mostoslavsky, Raul; Baldi, Pierre; Sassone-Corsi, Paolo

    2014-07-31

    Circadian rhythms are intimately linked to cellular metabolism. Specifically, the NAD(+)-dependent deacetylase SIRT1, the founding member of the sirtuin family, contributes to clock function. Whereas SIRT1 exhibits diversity in deacetylation targets and subcellular localization, SIRT6 is the only constitutively chromatin-associated sirtuin and is prominently present at transcriptionally active genomic loci. Comparison of the hepatic circadian transcriptomes reveals that SIRT6 and SIRT1 separately control transcriptional specificity and therefore define distinctly partitioned classes of circadian genes. SIRT6 interacts with CLOCK:BMAL1 and, differently from SIRT1, governs their chromatin recruitment to circadian gene promoters. Moreover, SIRT6 controls circadian chromatin recruitment of SREBP-1, resulting in the cyclic regulation of genes implicated in fatty acid and cholesterol metabolism. This mechanism parallels a phenotypic disruption in fatty acid metabolism in SIRT6 null mice as revealed by circadian metabolome analyses. Thus, genomic partitioning by two independent sirtuins contributes to differential control of circadian metabolism. PMID:25083875

  13. Cytotoxic and phenotypic effects of uranium and lead on osteoblastic cellular models

    International Nuclear Information System (INIS)

    This study is involved in the evaluation of bio-hazard associated with the use of uranium in nuclear activities and industrial research. The uranium, known in the literature as potentially carcinogenic or toxic for reproduction, can become a public health problem with the views of the various possibilities of human infections (military of the Gulf War, Finnish populations exposed to drinking water contaminated by example). The skeleton represents the organ of long-term storage of uranium and can be a target of its toxicity. Lead sharing this way of fixing in the bone matrix and have the same adverse effects on bone formation. The osteoblasts, cells responsible in bone formation, are specific targets of these two metals. The aim of this study was to evaluate the effects of acute toxicity of speciation controlled uranium and lead on osteoblasts culture. The intracellular accumulation, distribution and speciation were then studied to explain the observed toxicity. A cell death and phenotypic disorder were highlighted. The speciation is seen as crucial in biological effects of these metals. The most toxic species of both metals have been identified. The accumulation or cell distribution could not alone explain the impact of speciation on the toxicity observed. However, a phenomenon of intracellular precipitation of uranium and lead has been stressed and could be involved in a detoxification mechanism. (author)

  14. Lead telluride with increased mechanical stability for cylindrical thermoelectric generators

    International Nuclear Information System (INIS)

    The aim of this work is to improve the mechanical stability of lead telluride (PbTe), trying to vary its mechanical properties independently from its thermoelectric properties. Thus the influence of material preparation as well as different dopants on the mechanical and thermoelectric properties of lead telluride is being analysed. When using appropriately set process parameters, milling and sintering of lead telluride increases the material's hardness. With sintering temperatures exceeding 300 C stable material of high relative density can be achieved. Milling lead telluride generates lattice defects leading to a reduction of the material's charge carrier density. These defects can be reduced by increased sintering temperatures. Contamination of the powder due to the milling process leads to bloating during thermal cycling and thus reduced density of the sintered material. In addition to that, evaporation of tellurium at elevated temperatures causes instability of the material's thermoelectric properties. Based on the experimental results obtained in this work, the best thermoelectric and mechanical properties can be obtained by sintering coarse powders at around 400 C. Within this work a concept was developed to vary the mechanical properties of lead telluride via synthesis of PbTe with electrically nondoping elements, which thus may keep the thermoelectric properties unchanged. Therefore, the mechanical and thermoelectric properties of Pb1-xCaxTe were investigated. Doping pure PbTe with calcium causes a significant increase of the material's hardness while only slightly decreasing the charge carrier density and thus keeping the thermoelectric properties apart from a slight reduction of the electrical conductivity nearly unchanged. The abovementioned concept is proven using sodium doped lead telluride, as it is used for thermoelectric generators: The additional doping with calcium again increases the material's hardness while its thermoelectric properties remain

  15. Molecular and Cellular Evidence for the Alternative Lengthening of Telomeres (ALT) Mechanism in Chicken

    OpenAIRE

    O'Hare, T.H.; Delany, M. E.

    2011-01-01

    Telomere maintenance is an important genetic mechanism controlling cellular proliferation. Normally, telomeres are maintained by telomerase which is downregulated upon cellular differentiation in most somatic cell lineages. Telomerase activity is upregulated in immortalized cells and cancers to support an infinite lifespan and uncontrolled cell growth; however, some immortalized and transformed cells lack telomerase activity. Telomerase-negative tumors and immortalized cells utilize an altern...

  16. Effects of lead on the killing mechanisms of polymorphonuclear leukocytes

    International Nuclear Information System (INIS)

    The effects of lead on the killing mechanisms of rat polymorphonuclear leukocytes (PMN) were investigated, using male Long-Evans rats exposed to 1% lead acetate in the drinking water for varying periods of time to achieve blood lead levels ranging from 20-200 μg/dl. Studies of PMN bacterial and fungal killing activity, chemotaxis and phagocytosis demonstrated that: 1) bactericidal activity of PMN from rats exposed to lead was not altered; 2) chemotactic activity remained within normal limits; 3) the phagocytic ability of the PMN also remained unaltered. In addition to these normal findings, one major abnormality was demonstrated: a significant decrease in the ability of PMN from rats exposed to lead to kill Candida albicans. This defect was not related to age or to length of exposure. It could not be produced by addition of lead to the test system in vitro. Further investigation revealed significant decreases in PMN glucose-6-phosphate dehydrogenase, catalase, and myeloperoxidase activities. These data support two possible mechanisms for the abnormal fungicidal activity of PMN from lead-exposed rats: decrease in ability to reduce oxygen to active metabolites, or reduction in myeloperoxidase activity due to diminshed synthesis of the heme moiety required for its function

  17. Modeling mechanical behaviors of composites with various ratios of matrixeinclusion properties using movable cellular automaton method

    Institute of Scientific and Technical Information of China (English)

    A.Yu. SMOLIN; E.V. SHILKO; S.V. ASTAFUROV; I.S. KONOVALENKO; S.P. BUYAKOVA; S.G. PSAKHIE

    2015-01-01

    Two classes of composite materials are considered: classical metaleceramic composites with reinforcing hard inclusions as well as hard ceramics matrix with soft gel inclusions. Movable cellular automaton method is used for modeling the mechanical behaviors of such different heterogeneous materials. The method is based on particle approach and may be considered as a kind of discrete element method. The main feature of the method is the use of many-body forces of inter-element interaction within the formalism of simply deformable element approximation. It was shown that the strength of reinforcing particles and the width of particle-binder interphase boundaries had determining influence on the service characteristics of metaleceramic composite. In particular, the increasing of strength of carbide inclusions may lead to significant increase in the strength and ultimate strain of composite material. On the example of porous zirconia ceramics it was shown that the change in the mechanical properties of pore surface leads to the corresponding change in effective elastic modulus and strength limit of the ceramic sample. The less is the pore size, the more is this effect. The increase in the elastic properties of pore surface of ceramics may reduce its fracture energy.

  18. Mechanobiology and the microcirculation: cellular, nuclear and fluid mechanics

    OpenAIRE

    Dahl, Kris Noel; Kalinowski, Agnieszka; Pekkan, Kerem

    2010-01-01

    Endothelial cells are stimulated by shear stress throughout the vasculature and respond with changes in gene expression and by morphological reorganization. Mechanical sensors of the cell are varied and include cell surface sensors that activate intracellular chemical signaling pathways. Here, possible mechanical sensors of the cell including reorganization of the cytoskeleton and the nucleus are discussed in relation to shear flow. A mutation in the nuclear structural protein lamin A, relate...

  19. Molecular and cellular mechanisms of vomeronasal signaling in mammals

    OpenAIRE

    Cichy, Annika

    2013-01-01

    The mouse vomeronasal organ plays a critical role in chemosensory communication and regulates diverse social and sexual behaviors. However, many physiological mechanisms underlying vomeronasal chemosensory signaling remain elusive. Therefore, the overall aim of my thesis was to gain a deeper understanding of the basic mechanisms that control VNO physiology. Specifically, my research focused on HCN channel-mediated vomeronasal proton-sensing and its potential role in sensory gain control of so...

  20. Predicting bulk mechanical properties of cellularized collagen gels using multiphoton microscopy

    OpenAIRE

    Raub, CB; Putnam, AJ; Tromberg, BJ; George, SC

    2010-01-01

    Cellularized collagen gels are a common model in tissue engineering, but the relationship between the microstructure and bulk mechanical properties is only partially understood. Multiphoton microscopy (MPM) is an ideal non-invasive tool to examine collagen microstructure, cellularity and crosslink content in these gels. In order to identify robust image parameters that characterize microstructural determinants of the bulk elastic modulus, we performed serial MPM and mechanical tests on acellu...

  1. Cellular electron transfer and radical mechanisms for drug metabolism

    International Nuclear Information System (INIS)

    Aerobic and anaerobic reductions of various nitroaromatic compounds by mammalian cells result in the production of reactive intermediates. Drug reduction is dependent upon glucose, nonprotein thiols, endogenous enzyme levels, and drug electron affinity. Drugs with electron affinities approaching that of oxygen are reduced, in the presence of oxygen, beyond a one-electron radical anion. Nitroaromatic radical anion inactivation occurs by reaction with cellular ferricytochrome c, endogenous thiols, and with oxygen. In the latter case the reaction results in the production of peroxide. Drugs that are substrates for the enzyme glutathione-S-transferase remove endogeneous thiols and demonstrate peroxide production without prior thiol removal. Less electron affinic drugs such as misonidazole require thiol removal as well as the presence of cyanide or azide for maximal peroxide production. Under anaerobic conditions radical anion and nitroso intermediates are reactive with glutathione. Removal of endogenous thiols by hypoxic preincubation with misonidazole may be related to the enhanced radiation response and cytotoxicity of this drug. Reduction of nitro compounds in the presence of DNA and chemicals such as dithionite, zinc dust, or polarographic techniques causes binding to macromolecules and DNA breaks. Chemical-reduction of nitro compounds by ascorbate in the presence of cells enhances drug cytotoxic effects

  2. Cellular Magnesium Matrix Foam Composites for Mechanical Damping Applications

    Science.gov (United States)

    Shunmugasamy, Vasanth Chakravarthy; Mansoor, Bilal; Gupta, Nikhil

    2016-01-01

    The damping characteristics of metal alloys and metal matrix composites are relevant to the automotive, aerospace, and marine structures. Use of lightweight materials can help in increasing payload capacity and in decreasing fuel consumption. Lightweight composite materials possessing high damping capabilities that can be designed as structural members can greatly benefit in addressing these needs. In this context, the damping properties of lightweight metals such as aluminum and magnesium and their respective composites have been studied in the existing literature. This review focuses on analyzing the damping properties of aluminum and magnesium alloys and their cellular composites. The damping properties of various lightweight alloys and composites are compared on the basis of their density to understand the potential for weight saving in structural applications. Magnesium alloys are observed to possess better damping properties in comparison to aluminum. However, aluminum matrix syntactic foams reinforced with silicon carbide hollow particles possess a damping capacity and density comparable to magnesium alloy. By using the data presented in the study, composites with specific compositions and properties can be selected for a given application. In addition, the comparison of the results helps in identifying the areas where attention needs to be focused to address the future needs.

  3. Lipoprotein(a: Cellular Effects and Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Kirsten Riches

    2012-01-01

    Full Text Available Lipoprotein(a (Lp(a is an independent risk factor for the development of cardiovascular disease (CVD. Indeed, individuals with plasma concentrations >20 mg/dL carry a 2-fold increased risk of developing CVD, accounting for ~25% of the population. Circulating levels of Lp(a are remarkably resistant to common lipid lowering therapies, and there are currently no robust treatments available for reduction of Lp(a apart from plasma apheresis, which is costly and labour intensive. The Lp(a molecule is composed of two parts, an LDL/apoB-100 core and a unique glycoprotein, apolipoprotein(a (apo(a, both of which can interact with components of the coagulation cascade, inflammatory pathways, and cells of the blood vessel wall (smooth muscle cells (SMC and endothelial cells (EC. Therefore, it is of key importance to determine the molecular pathways by which Lp(a exerts its influence on the vascular system in order to design therapeutics to target its cellular effects. This paper will summarise the role of Lp(a in modulating cell behaviour in all aspects of the vascular system including platelets, monocytes, SMC, and EC.

  4. Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

    OpenAIRE

    Orsini, Caitlin A.; Maren, Stephen

    2012-01-01

    Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last thirty years, n...

  5. Mechanics of Cellular Adhesion to Artificial Artery Templates

    OpenAIRE

    Knöner, Gregor; Rolfe, Barbara E.; Campbell, Julie H.; Parkin, Simon J.; Heckenberg, Norman R.; Rubinsztein-Dunlop, Halina

    2006-01-01

    We are using polymer templates to grow artificial artery grafts in vivo for the replacement of diseased blood vessels. We have previously shown that adhesion of macrophages to the template starts the graft formation. We present a study of the mechanics of macrophage adhesion to these templates on a single cell and single bond level with optical tweezers. For whole cells, in vitro cell adhesion densities decreased significantly from polymer templates polyethylene to silicone to Tygon (167, 135...

  6. Antidiabetic properties of dietary flavonoids: a cellular mechanism review

    OpenAIRE

    Vinayagam, Ramachandran; Xu, Baojun

    2015-01-01

    Background Natural food products have been used for combating human diseases for thousands of years. Naturally occurring flavonoids including flavones, flavonols, flavanones, flavonols, isoflavones and anthocyanidins have been proposed as effective supplements for management and prevention of diabetes and its long-term complications based on in vitro and animal models. Aim To summarize the roles of dietary flavonoids in diabetes management and their molecular mechanisms. Findings Tremendous s...

  7. Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage

    Directory of Open Access Journals (Sweden)

    Peter Belenky

    2015-11-01

    Full Text Available Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (β-lactams, aminoglycosides, quinolones. These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products.

  8. Active Cellular Mechanics and Information Processing in the Living Cell

    Science.gov (United States)

    Rao, M.

    2014-07-01

    I will present our recent work on the organization of signaling molecules on the surface of living cells. Using novel experimental and theoretical approaches we have found that many cell surface receptors are organized as dynamic clusters driven by active currents and stresses generated by the cortical cytoskeleton adjoining the cell surface. We have shown that this organization is optimal for both information processing and computation. In connecting active mechanics in the cell with information processing and computation, we bring together two of the seminal works of Alan Turing.

  9. Mechanisms by which circadian rhythm disruption may lead to cancer

    Directory of Open Access Journals (Sweden)

    L. C. Roden

    2010-02-01

    Full Text Available Humans have evolved in a rhythmic environment and display daily (circadian rhythms in physiology, metabolism and behaviour that are in synchrony with the solar day. Modern lifestyles have compromised the exposure to bright light during the day and dark nights, resulting in the desynchronisation of endogenously generated circadian rhythms from the external environment and loss of coordination between rhythms within the body. This has detrimental effects on physical and mental health, due to the misregulation and uncoupling of important cellular and physiological processes. Long-term shift workers who are exposed to bright light at night experience the greatest disruption of their circadian rhythms. Studies have shown an association between exposure to light at night, circadian rhythm disruption and an increased risk of cancer. Previous reviews have explored the relevance of light and melatonin in cancer, but here we explore the correlation of circadian rhythm disruption and cancer in terms of molecular mechanisms affecting circadian gene expression and melatonin secretion.

  10. Leading research on artificial techniques controlling cellular function; Saibo zoshoku seigyo gijutsu no sendo kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    Advanced research and its applicability were surveyed to apply the advanced functional cells to industry. The basic target was set to develop, produce, control and utilize the functional cells, such as intelligent materials and self-regulation bioreactors. The regulation factors regarding apotosis, which is a process of cell suicide programmed within the cell itself of multicellular organisms, cell cycle and aging/ageless were investigated. Furthermore, the function of regulatory factors was investigated at the protein level. Injection of factors regulating cellular function and tissue engineering required for the regulation of cell proliferation were investigated. Tissue engineering is considered to be the intracellular regulation by gene transduction and the extracellular regulation by culture methods, such as coculture. Analysis methods for cell proliferation and function of living cells were investigated using the probes recognizing molecular structure. Novel biomaterials, artificial organ systems, cellular therapy and useful materials were investigated for utilizing the regulation techniques of cell proliferation. 425 refs., 85 figs., 9 tabs.

  11. From Stealing Fire to Cellular Reprogramming: A Scientific History Leading to the 2012 Nobel Prize

    Science.gov (United States)

    Lensch, M. William; Mummery, Christine L.

    2013-01-01

    Cellular reprogramming was recently “crowned” with the award of the Nobel Prize to two of its groundbreaking researchers, Sir John Gurdon and Shinya Yamanaka. The recent link between reprogramming and stem cells makes this appear almost a new field of research, but its historical roots have actually spanned more than a century. Here, the Nobel Prize in Physiology or Medicine 2012 is placed in its historical context. PMID:24052937

  12. Use of Computational Modeling to Evaluate Hypotheses About the Molecular and Cellular Mechanisms of Bystander Effects

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yuchao; Conolly, Rory B; Andersen, Melvin E.

    2006-11-21

    This report describes the development of a computational systems biology approach to evaluate the hypotheses of molecular and cellular mechanisms of adaptive response to low dose ionizing radiation. Our concept is that computational models of signaling pathways can be developed and linked to biologically based dose response models to evaluate the underlying molecular mechanisms which lead to adaptive response. For development of quantitatively accurate, predictive models, it will be necessary to describe tissues consisting of multiple cell types where the different types each contribute in their own way to the overall function of the tissue. Such a model will probably need to incorporate not only cell type-specific data but also spatial information on the architecture of the tissue and on intercellular signaling. The scope of the current model was more limited. Data obtained in a number of different biological systems were synthesized to describe a chimeric, “average” population cell. Biochemical signaling pathways involved in sensing of DNA damage and in the activation of cell cycle checkpoint controls and the apoptotic path were also included. As with any computational modeling effort, it was necessary to develop these simplified initial descriptions (models) that can be iteratively refined. This preliminary model is a starting point which, with time, can evolve to a level of refinement where large amounts of detailed biological information are synthesized and a capability for robust predictions of dose- and time-response behaviors is obtained.

  13. Action principle for cellular automata and the linearity of quantum mechanics

    CERN Document Server

    Elze, Hans-Thomas

    2014-01-01

    We introduce an action principle for a class of integer valued cellular automata and obtain Hamiltonian equations of motion. Employing sampling theory, these discrete deterministic equations are invertibly mapped on continuum equations for a set of bandwidth limited harmonic oscillators, which encode the Schr\\"odinger equation. Thus, the linearity of quantum mechanics is related to the action principle of such cellular automata and its conservation laws to discrete ones.

  14. Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes.

    Science.gov (United States)

    Shah, Manasi S; Brownlee, Michael

    2016-05-27

    The clinical correlations linking diabetes mellitus with accelerated atherosclerosis, cardiomyopathy, and increased post-myocardial infarction fatality rates are increasingly understood in mechanistic terms. The multiple mechanisms discussed in this review seem to share a common element: prolonged increases in reactive oxygen species (ROS) production in diabetic cardiovascular cells. Intracellular hyperglycemia causes excessive ROS production. This activates nuclear poly(ADP-ribose) polymerase, which inhibits GAPDH, shunting early glycolytic intermediates into pathogenic signaling pathways. ROS and poly(ADP-ribose) polymerase also reduce sirtuin, PGC-1α, and AMP-activated protein kinase activity. These changes cause decreased mitochondrial biogenesis, increased ROS production, and disturbed circadian clock synchronization of glucose and lipid metabolism. Excessive ROS production also facilitates nuclear transport of proatherogenic transcription factors, increases transcription of the neutrophil enzyme initiating NETosis, peptidylarginine deiminase 4, and activates the NOD-like receptor family, pyrin domain-containing 3 inflammasome. Insulin resistance causes excessive cardiomyocyte ROS production by increasing fatty acid flux and oxidation. This stimulates overexpression of the nuclear receptor PPARα and nuclear translocation of forkhead box O 1, which cause cardiomyopathy. ROS also shift the balance between mitochondrial fusion and fission in favor of increased fission, reducing the metabolic capacity and efficiency of the mitochondrial electron transport chain and ATP synthesis. Mitochondrial oxidative stress also plays a central role in angiotensin II-induced gap junction remodeling and arrhythmogenesis. ROS contribute to sudden death in diabetics after myocardial infarction by increasing post-translational protein modifications, which cause increased ryanodine receptor phosphorylation and downregulation of sarco-endoplasmic reticulum Ca

  15. Cellular Mechanisms of Calcium-Mediated Triggered Activity

    Science.gov (United States)

    Song, Zhen

    Life-threatening cardiac arrhythmias continue to pose a major health problem. Ventricular fibrillation, which is a complex form of electrical wave turbulence in the lower chambers of the heart, stops the heart from pumping and is the largest cause of natural death in the United States. Atrial fibrillation, a related form of wave turbulence in the upper heart chambers, is in turn the most common arrhythmia diagnosed in clinical practice. Despite extensive research to date, mechanisms of cardiac arrhythmias remain poorly understood. It is well established that both spatial disorder of the refractory period of heart cells and triggered activity (TA) jointly contribute to the initiation and maintenance of arrhythmias. TA broadly refers to the abnormal generation of a single or a sequence of abnormal excitation waves from a small submillimeter region of the heart in the interval of time between two normal waves generated by the heart's natural pacemaker (the sinoatrial node). TA has been widely investigated experimentally and occurs in several pathological conditions where the intracellular concentration of free Ca2+ ions in heart cells becomes elevated. Under such conditions, Ca2+ can be spontaneously released from intracellular stores, thereby driving an electrogenic current that exchanges 3Na+ ions for one Ca2+ ion across the cell membrane. This current in turn depolarizes the membrane of heart cells after a normal excitation. If this calcium-mediated "delayed after depolarization'' (DAD) is sufficiently large, it can generate an action potential. While the arrhythmogenic importance of spontaneous Ca2+ release and DADs is well appreciated, the conditions under which they occur in heart pathologies remain poorly understood. Calcium overload is only one factor among several other factors that can promote DADs, including sympathetic nerve stimulation, different expression levels of membrane ion channels and calcium handling proteins, and different mutations of those

  16. Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells

    International Nuclear Information System (INIS)

    Highlights: → Depletion of cellular PABP level arrests mRNA translation in HeLa cells. → PABP knock down leads to apoptotic cell death. → PABP depletion does not affect transcription. → PABP depletion does not lead to nuclear accumulation of mRNA. -- Abstract: The cytoplasmic poly (A) binding protein (PABP) is important in mRNA translation and stability. In yeast, depletion of PABP leads to translation arrest. Similarly, the PABP gene in Drosophila is important for proper development. It is however uncertain, whether mammalian PABP is essential for mRNA translation. Here we showed the effect of PABP depletion on mRNA metabolism in HeLa cells by using a small interfering RNA. Our results suggest that depletion of PABP prevents protein synthesis and consequently leads to cell death through apoptosis. Interestingly, no detectable effect of PABP depletion on transcription, transport and stability of mRNA was observed.

  17. Depletion of cellular poly (A) binding protein prevents protein synthesis and leads to apoptosis in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Thangima Zannat, Mst.; Bhattacharjee, Rumpa B. [Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G2W1 (Canada); Bag, Jnanankur, E-mail: jbag@uoguelph.ca [Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G2W1 (Canada)

    2011-05-13

    Highlights: {yields} Depletion of cellular PABP level arrests mRNA translation in HeLa cells. {yields} PABP knock down leads to apoptotic cell death. {yields} PABP depletion does not affect transcription. {yields} PABP depletion does not lead to nuclear accumulation of mRNA. -- Abstract: The cytoplasmic poly (A) binding protein (PABP) is important in mRNA translation and stability. In yeast, depletion of PABP leads to translation arrest. Similarly, the PABP gene in Drosophila is important for proper development. It is however uncertain, whether mammalian PABP is essential for mRNA translation. Here we showed the effect of PABP depletion on mRNA metabolism in HeLa cells by using a small interfering RNA. Our results suggest that depletion of PABP prevents protein synthesis and consequently leads to cell death through apoptosis. Interestingly, no detectable effect of PABP depletion on transcription, transport and stability of mRNA was observed.

  18. Freely Suspended Cellular “Backpacks” Lead to Cell Aggregate Self-Assembly

    OpenAIRE

    Swiston, Albert J., Jr.; Gilbert, Jonathan B.; Irvine, Darrell J.; Cohen, Robert E; Rubner, Michael F.

    2010-01-01

    Cellular “backpacks” are a new type of anisotropic, nanoscale thickness microparticle that may be attached to the surface of living cells creating a “bio-hybrid” material. Previous work has shown that these backpacks do not impair cell viability or native functions such as migration in a B and T cell line, respectively. In the current work, we show that backpacks, when added to a cell suspension, assemble cells into aggregates of reproducible size. We investigate the efficiency of backpack−ce...

  19. Tuning of the electro-mechanical behavior of the cellular carbon nanotube structures with nanoparticle dispersions

    International Nuclear Information System (INIS)

    The mechanical and electrical characteristics of cellular network of the carbon nanotubes (CNT) impregnated with metallic and nonmetallic nanoparticles were examined simultaneously by employing the nanoindentation technique. Experimental results show that the nanoparticle dispersion not only enhances the mechanical strength of the cellular CNT by two orders of magnitude but also imparts variable nonlinear electrical characteristics; the latter depends on the contact resistance between nanoparticles and CNT, which is shown to depend on the applied load while indentation. Impregnation with silver nanoparticles enhances the electrical conductance, the dispersion with copper oxide and zinc oxide nanoparticles reduces the conductance of CNT network. In all cases, a power law behavior with suppression in the differential conductivity at zero bias was noted, indicating electron tunneling through the channels formed at the CNT-nanoparticle interfaces. These results open avenues for designing cellular CNT foams with desired electro-mechanical properties and coupling

  20. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function

    Directory of Open Access Journals (Sweden)

    Aarti eNagayach

    2014-10-01

    Full Text Available Behavioural impairments are the most empirical consequence of diabetes mellitus documented in both humans and animal models, but the underlying causes are still poorly understood. As the cerebellum plays a major role in coordination and execution of the motor functions, we investigated the possible involvement of glial activation, cellular degeneration and glutamate transportation in the cerebellum of rats, rendered diabetic by a single injection of streptozotocin (STZ; 45mg/ kg body weight; intraperitoneally. Motor function alterations were studied using Rotarod test (motor coordination and grip strength (muscle activity at 2nd, 4th, 6th, 8th, 10th and 12th week post diabetic confirmation. Scenario of glial (astroglia and microglia activation, cell death and glutamate transportation was gauged using immunohistochemistry, histological study and image analysis. Cellular degeneration was clearly demarcated in the diabetic cerebellum. Glial cells were showing sequential and marked activation following diabetes in terms of both morphology and cell number. Bergmann glial cells were hypertrophied and distorted. Active caspase-3 positive apoptotic cells were profoundly present in all three cerebellar layers. Reduced co-labelling of GLT-1 and GFAP revealed the altered glutamate transportation in cerebellum following diabetes. These results, exclusively derived from histology, immunohistochemistry and cellular quantification, provide first insight over the associative reciprocity between the glial activation, cellular degeneration and reduced glutamate transportation, which presumably lead to the behavioural alterations following STZ-induced diabetes.

  1. Creatine transporter deficiency leads to increased whole body and cellular metabolism.

    Science.gov (United States)

    Perna, Marla K; Kokenge, Amanda N; Miles, Keila N; Udobi, Kenea C; Clark, Joseph F; Pyne-Geithman, Gail J; Khuchua, Zaza; Skelton, Matthew R

    2016-08-01

    Creatine (Cr) is a guanidino compound required for rapid replenishment of ATP in cells with a high-energy demand. In humans, mutations in the Cr transporter (CRT;SLC6A8) prevent Cr entry into tissue and result in a significant intellectual impairment, epilepsy, and aphasia. The lack of Cr on both the whole body and cellular metabolism was evaluated in Crt knockout (Crt (-/y) ) mice, a high-fidelity model of human CRT deficiency. Crt (-/y) mice have reduced body mass and, however, show a twofold increase in body fat. There was increased energy expenditure in a home cage environment and during treadmill running in Crt (-/y) mice. Consistent with the increases in the whole-body metabolic function, Crt (-/y) mice show increased cellular metabolism as well. Mitochondrial respiration increased in skeletal muscle fibers and hippocampal lysates from Crt (-/y) mice. In addition, Crt (-/y) mice had increased citrate synthase activity, suggesting a higher number of mitochondria instead of an increase in mitochondrial activity. To determine if the increase in respiration was due to increased mitochondrial numbers, we measured oxygen consumption in an equal number of mitochondria from Crt (+/y) and Crt (-/y) mice. There were no changes in mitochondrial respiration when normalized to mitochondrial number, suggesting that the increase in respiration observed could be to higher mitochondrial content in Crt (-/y) mice. PMID:27401086

  2. Diffractive Excitation of Heavy Flavors: Leading Twist Mechanisms

    CERN Document Server

    Kopeliovich, B Z; Schmidt, I; Tarasov, A V

    2007-01-01

    Diffractive production of heavy flavors is calculated within the light-cone dipole approach. Novel leading twist mechanisms are proposed, which involve both short and long transverse distances inside the incoming hadron. Nevertheless, the diffractive cross section turns out to be sensitive to the primordial transverse momenta of projectile gluons, rather than to the hadronic size. Our calculations agree with the available data for diffractive production of charm and beauty, and with the observed weak variation of the diffraction-to-inclusive cross section ratios as function of the hard scale.

  3. Mechanism of instabilities in turbulent combustion leading to flashback

    Science.gov (United States)

    Keller, J. O.; Vaneveld, L.; Ghoniem, A. F.; Daily, J. W.; Oppenheim, A. K.; Korschelt, D.; Hubbard, G. L.

    1981-01-01

    High-speed schlieren cinematography, combined with synchronized pressure transducer records, was used to investigate the mechanism of combustion instabilities leading to flashback. The combustion chamber had an oblong rectangular cross-section to model the essential features of planar flow, and was provided with a rearward facing step acting as a flameholder. As the rich limit was approached, three instability modes were observed: (1) humming - a significant increase in the amplitude of the vortex pattern; (2) buzzing - a large-scale oscillation of the flame; and (3) chucking - a cyclic reformation of the flame, which results in flashback. The mechanism of these phenomena is ascribed to the action of vortices in the recirculation zone and their interactions with the trailing vortex pattern of the turbulent mixing layer behind the step.

  4. Freely suspended cellular "backpacks" lead to cell aggregate self-assembly.

    Science.gov (United States)

    Swiston, Albert J; Gilbert, Jonathan B; Irvine, Darrell J; Cohen, Robert E; Rubner, Michael F

    2010-07-12

    Cellular "backpacks" are a new type of anisotropic, nanoscale thickness microparticle that may be attached to the surface of living cells creating a "bio-hybrid" material. Previous work has shown that these backpacks do not impair cell viability or native functions such as migration in a B and T cell line, respectively. In the current work, we show that backpacks, when added to a cell suspension, assemble cells into aggregates of reproducible size. We investigate the efficiency of backpack-cell binding using flow cytometry and laser diffraction, examine the influence of backpack diameter on aggregate size, and show that even when cell-backpack complexes are forced through small pores, backpacks are not removed from the surfaces of cells. PMID:20527876

  5. Computational up-scaling of anisotropic swelling and mechanical behavior of hierarchical cellular material

    CERN Document Server

    Rafsanjani, Ahmad; Wittel, Falk K; Carmeliet, Jan

    2015-01-01

    The hygro-mechanical behavior of a hierarchical cellular material, i.e. growth rings of softwood is investigated using a two-scale micro-mechanics model based on a computational homogenization technique. The lower scale considers the individual wood cells of varying geometry and dimensions. Honeycomb unit cells with periodic boundary conditions are utilized to calculate the mechanical properties and swelling coefficients of wood cells. Using the cellular scale results, the anisotropy in mechanical and swelling behavior of a growth ring in transverse directions is investigated. Predicted results are found to be comparable to experimental data. It is found that the orthotropic swelling properties of the cell wall in thin-walled earlywood cells produce anisotropic swelling behavior while, in thick latewood cells, this anisotropy vanishes. The proposed approach provides the ability to consider the complex microstructure when predicting the effective mechanical and swelling properties of softwood.

  6. The linearity of quantum mechanics from the perspective of Hamiltonian cellular automata

    CERN Document Server

    Elze, Hans-Thomas

    2014-01-01

    We discuss the action principle and resulting Hamiltonian equations of motion for a class of integer-valued cellular automata introduced recently [1]. Employing sampling theory, these deterministic finite-difference equations are mapped reversibly on continuum equations describing a set of bandwidth limited harmonic oscillators. They represent the Schroedinger equation. However, modifications reflecting the bandwidth limit are incorporated, i.e., the presence of a time (or length) scale. When this discreteness scale is taken to zero, the usual results are obtained. Thus, the linearity of quantum mechanics can be traced to the postulated action principle of such cellular automata and its conservation laws to discrete ones. The cellular automaton conservation laws are in one-to-one correspondence with those of the related quantum mechanical model, while admissible symmetries are not.

  7. The linearity of quantum mechanics from the perspective of Hamiltonian cellular automata

    International Nuclear Information System (INIS)

    We discuss the action principle and resulting Hamiltonian equations of motion for a class of integer-valued cellular automata introduced recently [1]. Employing sampling theory, these deterministic finite-difference equations are mapped reversibly on continuum equations describing a set of bandwidth limited harmonic oscillators. They represent the Schrödinger equation. However, modifications reflecting the bandwidth limit are incorporated, i.e., the presence of a time (or length) scale. When this discreteness scale is taken to zero, the usual results are obtained. Thus, the linearity of quantum mechanics can be traced to the postulated action principle of such cellular automata and its conservation laws to discrete ones. The cellular automaton conservation laws are in one-to-one correspondence with those of the related quantum mechanical model, while admissible symmetries are not.

  8. Cellular and molecular mechanisms of osteoporosis: current concepts and future direction treatment

    OpenAIRE

    A. T. Dolzhenko; S. Sagalovsky

    2016-01-01

    The article presents review of literature dedicated to the contemporary view on the cellular-molecular mechanisms of the bone remodeling and pathogenesis of the osteoporosis. The discovery of the cytokine RANKL-RANK-OPG system and significant role of the cathepsin K in process bone remodeling has made progress in understanding the mechanisms development disease and possible to development drugs of the new generation – denosumab, a fully human RANKL monoclonal antibody and inhibitor cathepsin ...

  9. The role of focal adhesion kinase in the regulation of cellular mechanical properties

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-12-01

    The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation.

  10. The role of focal adhesion kinase in the regulation of cellular mechanical properties

    International Nuclear Information System (INIS)

    The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation. (paper)

  11. Lead tolerance and cellular distribution in Elsholtzia splendens using synchrotron radiation micro-X-ray fluorescence

    International Nuclear Information System (INIS)

    Highlights: ► Elsholtzia splendens had a good ability of lead tolerance and accumulation. ► Pb was mostly restricted to the vascular bundles and epidermis tissues. ► Pb and Ca shared most similar distribution patterns in E. splendens. - Abstract: Hydroponic experiments were conducted to investigate the tolerance and spatial distribution of lead (Pb) in Elsholtzia splendens—a copper (Cu) accumulator plant using synchrotron-based micro-X-ray fluorescence. According to chlorophyll concentration and chlorophyll fluorescence parameters, E. splendens displayed certain tolerance at 100 μM Pb treatment. Lead concentration in roots, stems and leaves of E. splendens reached 45,183.6, 1657.6, and 380.9 mg kg−1, respectively. Pb was mostly accumulated in the roots, and there were also high concentrations of Pb been transported into stems and leaves. Micro-XRF analysis of the stem and leaf cross section revealed that Pb was mostly restricted in the vascular bundles and epidermis tissues of both stem and leaf of E. splendens. The correlation between distribution of K, Ca, Zn and Pb were analyzed. There were significant positive correlations (P < 0.01) among Pb and Ca, K, Zn distribution both in stem and leaf of E. splendens. However, among the three elements, Ca shared the most similar distribution pattern and the highest correlation coefficients with Pb in both stem and leaf cross section of E. splendens. This suggests that Ca may play an important role in Pb accumulation in stem and leaf of E. splendens.

  12. Lead tolerance and cellular distribution in Elsholtzia splendens using synchrotron radiation micro-X-ray fluorescence

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jie [MOE Key Laboratory of Environment Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Tian, Shengke [MOE Key Laboratory of Environment Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); University of Florida, Institute of Food and Agricultural Science, Indian River Research and Education Center, Fort Pierce, FL 34945 (United States); Lu, Lingli; Shohag, M.J.I.; Liao, Haibing [MOE Key Laboratory of Environment Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Yang, Xiaoe, E-mail: xyang@zju.edu.cn [MOE Key Laboratory of Environment Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer Elsholtzia splendens had a good ability of lead tolerance and accumulation. Black-Right-Pointing-Pointer Pb was mostly restricted to the vascular bundles and epidermis tissues. Black-Right-Pointing-Pointer Pb and Ca shared most similar distribution patterns in E. splendens. - Abstract: Hydroponic experiments were conducted to investigate the tolerance and spatial distribution of lead (Pb) in Elsholtzia splendens-a copper (Cu) accumulator plant using synchrotron-based micro-X-ray fluorescence. According to chlorophyll concentration and chlorophyll fluorescence parameters, E. splendens displayed certain tolerance at 100 {mu}M Pb treatment. Lead concentration in roots, stems and leaves of E. splendens reached 45,183.6, 1657.6, and 380.9 mg kg{sup -1}, respectively. Pb was mostly accumulated in the roots, and there were also high concentrations of Pb been transported into stems and leaves. Micro-XRF analysis of the stem and leaf cross section revealed that Pb was mostly restricted in the vascular bundles and epidermis tissues of both stem and leaf of E. splendens. The correlation between distribution of K, Ca, Zn and Pb were analyzed. There were significant positive correlations (P < 0.01) among Pb and Ca, K, Zn distribution both in stem and leaf of E. splendens. However, among the three elements, Ca shared the most similar distribution pattern and the highest correlation coefficients with Pb in both stem and leaf cross section of E. splendens. This suggests that Ca may play an important role in Pb accumulation in stem and leaf of E. splendens.

  13. Experimental evaluation of mechanical property for lead rubber bearing

    International Nuclear Information System (INIS)

    In these days, the basic isolation system is often used to improve the seismic capacity of the structures instead of conventional techniques of strengthening the structural members. The purpose of this study is to evaluate dynamic properties and mechanical characteristics of the 10 tonf-LRB(Lead-Rubber Bearing). Experimental studies were performed to obtain the hysteretic behavior, effective shear stiffness (Keff), equivalent damping (Heq), capacity of energy dissipation (WD) of six 10tons-LRB. Especially, in this study, the response of the LRB for high loading frequency(0.5Hz∼3.0Hz) was estimated. The effective shear stiffness of the LRB decrease and the capacity of energy dissipation increases as the shear strain amplitude increase. But the shear behavior of the LRB is not affected sensitivity by loading frequency

  14. Cellular and circuit mechanisms maintain low spike co-variability and enhance population coding in somatosensory cortex

    Directory of Open Access Journals (Sweden)

    Cheng eLy

    2012-03-01

    Full Text Available The responses of cortical neurons are highly variable across repeated presentations of a stimulus. Understanding this variability is critical for theories of both sensory and motor processing, since response variance affects the accuracy of neural codes. Despite this influence, the cellular and circuit mechanisms that shape the trial-to-trial variability of population responses remain poorly understood. We used a combination of experimental and computational techniques to uncover the mechanisms underlying response variability of populations of pyramidal (E cells in layer 2/3 of rat whisker barrel cortex. Spike trains recorded from pairs of E-cells during either spontaneous activity or whisker deflected responses show similarly low levels of spiking co-variability, despite large differences in network activation between the two states. We developed network models that show how spike threshold nonlinearities dilutes E-cell spiking co-variability during spontaneous activity and low velocity whisker deflections. In contrast, during high velocity whisker deflections, cancelation mechanisms mediated by feedforward inhibition maintain low E-cell pairwise co-variability. Thus, the combination of these two mechanisms ensure low E-cell population variability over a wide range of whisker deflection velocities. Finally, we show how this active decorrelation of population variability leads to a drastic increase in the population information about whisker velocity. The canonical cellular and circuit components of our study suggest that low network variability over a broad range of neural states may generalize across the nervous system.

  15. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. PMID:27178343

  16. Research of Toxic Mechanism on Anaerobic Digestion by Lead

    Institute of Scientific and Technical Information of China (English)

    Han Jianhong; Wang Zhe; Zhang Lianke; Han Jintao

    2008-01-01

    The paper analyzes the influence of lead toxicity by anaerobic granule sludge inhibition and recovering experiments.The result shows that there are different inhibition types at differ ent lead contents.Higher lead content leads to more inhibition granular sludge,and at the same time,the time of gas recovery is different.Lower lead content per microorganism results in sooner sludge recovery.Microorganisms have a good ability to resist lead toxicity.

  17. Interleukin-13 Activates Distinct Cellular Pathways Leading to Ductular Reaction, Steatosis, and Fibrosis.

    Science.gov (United States)

    Gieseck, Richard L; Ramalingam, Thirumalai R; Hart, Kevin M; Vannella, Kevin M; Cantu, David A; Lu, Wei-Yu; Ferreira-González, Sofía; Forbes, Stuart J; Vallier, Ludovic; Wynn, Thomas A

    2016-07-19

    Fibroproliferative diseases are driven by dysregulated tissue repair responses and are a major cause of morbidity and mortality because they affect nearly every organ system. Type 2 cytokine responses are critically involved in tissue repair; however, the mechanisms that regulate beneficial regeneration versus pathological fibrosis are not well understood. Here, we have shown that the type 2 effector cytokine interleukin-13 simultaneously, yet independently, directed hepatic fibrosis and the compensatory proliferation of hepatocytes and biliary cells in progressive models of liver disease induced by interleukin-13 overexpression or after infection with Schistosoma mansoni. Using transgenic mice with interleukin-13 signaling genetically disrupted in hepatocytes, cholangiocytes, or resident tissue fibroblasts, we have revealed direct and distinct roles for interleukin-13 in fibrosis, steatosis, cholestasis, and ductular reaction. Together, these studies show that these mechanisms are simultaneously controlled but distinctly regulated by interleukin-13 signaling. Thus, it may be possible to promote interleukin-13-dependent hepatobiliary expansion without generating pathological fibrosis. VIDEO ABSTRACT. PMID:27421703

  18. Diverse pathomechanisms leading to the breakdown of cellular estrogen surveillance and breast cancer development: new therapeutic strategies

    OpenAIRE

    Suba Z

    2014-01-01

    Zsuzsanna SubaNational Institute of Oncology, Budapest, HungaryAbstract: Recognition of the two main pathologic mechanisms equally leading to breast cancer development may provide explanations for the apparently controversial results obtained by sexual hormone measurements in breast cancer cases. Either insulin resistance or estrogen receptor (ER) defect is the initiator of pathologic processes and both of them may lead to breast cancer development. Primary insulin resistance induces hyperand...

  19. Cellular mechanisms of arrhythmias: from rate-dependent APD variations to heterocellular coupling

    OpenAIRE

    Salvarani, Nicolò

    2008-01-01

    It is well established that a variety of pathological conditions induces structural and electrical remodeling of the heart which can lead to heart failure and cardiac arrhythmias. Clinically, structural remodeling is characterized by changes in the shape, size and function of the heart. These changes are based on diverse and complex cellular reactions to injury and involve both cardiomyocytes and non-cardiomyocytes. Histopathologically, remodeling typically involves cardiomyocyte hypertrophy,...

  20. Cellular and molecular mechanisms of sexual differentiation in the mammalian nervous system.

    Science.gov (United States)

    Forger, Nancy G; Strahan, J Alex; Castillo-Ruiz, Alexandra

    2016-01-01

    Neuroscientists are likely to discover new sex differences in the coming years, spurred by the National Institutes of Health initiative to include both sexes in preclinical studies. This review summarizes the current state of knowledge of the cellular and molecular mechanisms underlying sex differences in the mammalian nervous system, based primarily on work in rodents. Cellular mechanisms examined include neurogenesis, migration, the differentiation of neurochemical and morphological cell phenotype, and cell death. At the molecular level we discuss evolving roles for epigenetics, sex chromosome complement, the immune system, and newly identified cell signaling pathways. We review recent findings on the role of the environment, as well as genome-wide studies with some surprising results, causing us to re-think often-used models of sexual differentiation. We end by pointing to future directions, including an increased awareness of the important contributions of tissues outside of the nervous system to sexual differentiation of the brain. PMID:26790970

  1. Investigation of the Cellular and Molecular Mechanisms of Radiation-induced Bystander Effects

    OpenAIRE

    Furlong, Hayley

    2014-01-01

    The overall aim of this study was to investigate the cellular and molecular mechanisms involved in radiation-induced bystander effects in HaCaT cells, predominantly at low-doses of irradiation. They do not follow the original dose-response theory and exhibit a unique cascade of signalling events, which are under intense investigation for radiation risk purposes. An in vitro system was first used to observe the bystander effect, comparing two cell viability assays while measuring apoptotic cel...

  2. Identification of the cellular mechanisms undelying the contribution of stress and glucocorticoids to Alzheimer's disease pathology

    OpenAIRE

    Sotiropoulos, Ioannis

    2006-01-01

    Clinical evidence suggests the involvement of stress and glucocorticoids (GC) in the etiopathogenesis of Alzheimer’s disease (AD), a disease marked by severe memory impairments as well as alterations in mood and emotional state. The experiments described in this dissertation represent an attempt to establish the cellular mechanisms through which stress and GC may impact on the development of AD. These studies focused on the hippocampus and prefrontal cortex (PFC), brain areas that are severel...

  3. Optimization of the diabetic nephropathy treatment with attention to the special features of cellular inflammation mechanisms

    OpenAIRE

    Щербань, Тетяна Дмитрівна

    2016-01-01

    Aim. Optimization of the diabetic nephropathy (DN) treatment in association with hypertonic disease (HD) based on the study of neutrophil chain of pathogenic cellular mechanisms of these diseases development and the special features of its clinical course.Materials and methods. There were complexly examined 86 patients with HD associated with DN and 30 patients with isolated HD. The control group was formed by 30 practically healthy persons. The activity of NO-synthases in neutrophils was det...

  4. Regional differences in cellular mechanisms of adipose tissue gain with overfeeding

    OpenAIRE

    Tchoukalova, Yourka D.; Votruba, Susanne B; Tchkonia, Tamara; Giorgadze, Nino; Kirkland, James L.; Jensen, Michael D.

    2010-01-01

    Body fat distribution is an important predictor of the metabolic consequences of obesity, but the cellular mechanisms regulating regional fat accumulation are unknown. We assessed the changes in adipocyte size (photomicrographs) and number in response to overfeeding in upper- and lower-body s.c. fat depots of 28 healthy, normal weight adults (15 men) age 29 ± 2 y. We analyzed how these changes relate to regional fat gain (dual energy X-ray absorptiometry and computed tomography) and baseline ...

  5. Cellular and Molecular Mechanisms of Novel Therapies to Ameliorate Liver Sinusoidal Dysfunction in Cirrhotic Portal Hypertension

    OpenAIRE

    Marrone, Giusi

    2014-01-01

    Increased intrahepatic vascular resistance (IHVR), mainly due to elevated vascular tone together with the maturation of hepatic fibrosis and the drop of the hepatic endothelial function, is the main factor in the development of portal hypertension (PH) in cirrhosis. This PhD thesis investigates the cellular and molecular mechanisms necessary for the identification of new therapeutic targets and evaluates the possible cross- talk between the hepatic cells in static and physiological conditions...

  6. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms

    OpenAIRE

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-01-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially c...

  7. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    Directory of Open Access Journals (Sweden)

    Ana-Maria Florea

    2011-03-01

    Full Text Available Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs and might provide new therapeutic strategies and reduce side effects.

  8. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    Energy Technology Data Exchange (ETDEWEB)

    Florea, Ana-Maria [Department of Neuropathology, Heinrich-Heine University, Düsseldorf (Germany); Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weil Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha (Qatar)

    2011-03-15

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects.

  9. Cellular and molecular mechanisms of osteoporosis: current concepts and future direction treatment

    Directory of Open Access Journals (Sweden)

    A. T. Dolzhenko

    2016-01-01

    Full Text Available The article presents review of literature dedicated to the contemporary view on the cellular-molecular mechanisms of the bone remodeling and pathogenesis of the osteoporosis. The discovery of the cytokine RANKL-RANK-OPG system and significant role of the cathepsin K in process bone remodeling has made progress in understanding the mechanisms development disease and possible to development drugs of the new generation – denosumab, a fully human RANKL monoclonal antibody and inhibitor cathepsin K odanacatib that inhibits of the bone resorption.

  10. Mechanical models of the cellular cytoskeletal network for the analysis of intracellular mechanical properties and force distributions: a review.

    Science.gov (United States)

    Chen, Ting-Jung; Wu, Chia-Ching; Su, Fong-Chin

    2012-12-01

    The cytoskeleton, which is the major mechanical component of cells, supports the cell body and regulates the cellular motility to assist the cell in performing its biological functions. Several cytoskeletal network models have been proposed to investigate the mechanical properties of cells. This review paper summarizes these models with a focus on the prestressed cable network, the semi-flexible chain network, the open-cell foam, the tensegrity, and the granular models. The components, material parameters, types of connection joints, tension conditions, and the advantages and disadvantages of each model are evaluated from a structural and biological point of view. The underlying mechanisms that are associated with the morphological changes of spreading cells are expected to be simulated using a cytoskeletal model; however, it is still paid less attention most likely due to the lack of a suitable cytoskeletal model that can accurately model the spreading process. In this review article, the established cytoskeletal models are hoped to provide useful information for the development of future cytoskeletal models with different degrees of cell attachment for the study of the mechanical mechanisms underlying the cellular behaviors in response to external stimulations. PMID:23062682

  11. The anthocyanidin delphinidin mobilizes endogenous copper ions from human lymphocytes leading to oxidative degradation of cellular DNA

    International Nuclear Information System (INIS)

    Epidemiological and experimental evidence exists to suggest that pomegranate and its juice possess chemopreventive and anticancer properties. The anthocyanidin delphinidin is a major polyphenol present in pomegranates and has been shown to be responsible for these effects. Plant polyphenols are recognized as naturally occurring antioxidants but also catalyze oxidative DNA degradation of cellular DNA either alone or in the presence of transition metal ions such as copper. In this paper we show that similar to various other classes of polyphenols, delphinidin is also capable of causing oxidative degradation of cellular DNA. Lymphocytes were exposed to various concentrations of delphinidin (10, 20, 50 μM) for 1 h and the DNA breakage was assessed using single cell alkaline gel electrophoresis (Comet assay). Inhibition of DNA breakage by several scavengers of reactive oxygen species (ROS) indicated that it is caused by the formation of ROS. Incubation of lymphocytes with neocuproine (a cell membrane permeable Cu(I) chelator) inhibited DNA degradation in intact lymphocytes in a dose dependent manner. Bathocuproine, which is unable to permeate through the cell membrane, did not cause such inhibition. We have further shown that delphinidin is able to degrade DNA in cell nuclei and that such DNA degradation is also inhibited by neocuproine suggesting that nuclear copper is mobilized in this reaction. These results indicate that the generation of ROS possibly occurs through mobilization of endogenous copper ions. The results are in support of our hypothesis that the prooxidant activity of plant polyphenols may be an important mechanism for their anticancer properties

  12. Relative Contributions of Various Cellular Mechanisms to Loss of Algae during Cnidarian Bleaching

    Science.gov (United States)

    Bieri, Tamaki; Onishi, Masayuki; Xiang, Tingting; Grossman, Arthur R.; Pringle, John R

    2016-01-01

    When exposed to stress such as high seawater temperature, corals and other cnidarians can bleach due to loss of symbiotic algae from the host tissue and/or loss of pigments from the algae. Although the environmental conditions that trigger bleaching are reasonably well known, its cellular and molecular mechanisms are not well understood. Previous studies have reported the occurrence of at least four different cellular mechanisms for the loss of symbiotic algae from the host tissue: in situ degradation of algae, exocytic release of algae from the host, detachment of host cells containing algae, and death of host cells containing algae. The relative contributions of these several mechanisms to bleaching remain unclear, and it is also not known whether these relative contributions change in animals subjected to different types and/or durations of stresses. In this study, we used a clonal population of the small sea anemone Aiptasia, exposed individuals to various precisely controlled stress conditions, and quantitatively assessed the several possible bleaching mechanisms in parallel. Under all stress conditions tested, except for acute cold shock at 4°C, expulsion of intact algae from the host cells appeared to be by far the predominant mechanism of bleaching. During acute cold shock, in situ degradation of algae and host-cell detachment also became quantitatively significant, and the algae released under these conditions appeared to be severely damaged. PMID:27119147

  13. Diesel exhaust: current knowledge of adverse effects and underlying cellular mechanisms.

    Science.gov (United States)

    Steiner, Sandro; Bisig, Christoph; Petri-Fink, Alke; Rothen-Rutishauser, Barbara

    2016-07-01

    Diesel engine emissions are among the most prevalent anthropogenic pollutants worldwide, and with the growing popularity of diesel-fueled engines in the private transportation sector, they are becoming increasingly widespread in densely populated urban regions. However, a large number of toxicological studies clearly show that diesel engine emissions profoundly affect human health. Thus the interest in the molecular and cellular mechanisms underlying these effects is large, especially concerning the nature of the components of diesel exhaust responsible for the effects and how they could be eliminated from the exhaust. This review describes the fundamental properties of diesel exhaust as well as the human respiratory tract and concludes that adverse health effects of diesel exhaust not only emerge from its chemical composition, but also from the interplay between its physical properties, the physiological and cellular properties, and function of the human respiratory tract. Furthermore, the primary molecular and cellular mechanisms triggered by diesel exhaust exposure, as well as the fundamentals of the methods for toxicological testing of diesel exhaust toxicity, are described. The key aspects of adverse effects induced by diesel exhaust exposure described herein will be important for regulators to support or ban certain technologies or to legitimate incentives for the development of promising new technologies such as catalytic diesel particle filters. PMID:27165416

  14. Cellular accumulation and distribution of uranium and lead in osteoblastic cells as a function of their speciation

    International Nuclear Information System (INIS)

    Uranium (U) and lead (Pb) are accumulated and fixed for long periods in bone, impairing remodeling processes. Their toxicity to osteoblasts, the cells responsible for bone formation, is poorly documented. It has been previously shown that cytotoxicity and phenotypic effects of both metals on osteoblasts are highly influenced by metal speciation. Differences in sensitivity between cell types have been underlined as well. In this paper, cellular accumulation of U and Pb in cultured and primary osteoblastic cells was assessed by trace element analysis. Distribution of different species at the cell scale was investigated by electron microscopy. Internalization of both metals was shown to be correlated to cytotoxicity and population growth recovery after exposure. For each metal, the amount of metal uptake leading to 50% cell death was shown to be speciation-dependent. Scanning and transmission electron microscopy showed the formation of precipitates with phosphate in lysosomes for both metals, whose role in toxicity or cell defence remains to be clarified. Although a clear link was established between cytotoxicity and accumulation, differences in sensitivity observed in terms of speciation could not be fully explained and other studies seem necessary

  15. Patterns and Cellular Mechanisms of Arm Regeneration in Adult Starfish Asterias rollestoni Bell

    Institute of Scientific and Technical Information of China (English)

    FAN Tingjun; FAN Xianyuan; DU Yutang; SUN Wenjie; ZHANG Shaofeng; LI Jiaxin

    2011-01-01

    To understand the mechanisms of starfish regeneration,the arms of adult starfish Asterias rollestoni Bell were amputated and their regeneration pattems and cellular mechanisms were studied.It was found that cells in the outer epidermis and inner parietal peritoneum near the end of the stump began to dedifferentiate 4d after amputation.The dedifferentiated cells in the outer epidermis proliferated,migrated to the wound site and formed a thickened pre-epidermis which would then re-differentiate gradually into mature epidermis.The new parietal peritoneum formed on the coelomic side of wound might be from the curvely elongated parietal peritoneum,resulting from the dedifferentiated and proliferated cells by extension.Afterwards,the proliferated cells made the outer epidermis and inner parietal peritoneum invaginate into the interior dermis and formed blastema-like structures together with induced dedifferentiated dermal cells.Most interestingly,the arm regeneration in A.rollestoni was achieved synchronously by de novo arm-bud formation and growth,and arm-stump elongation.The crucial aspects of arm-bud formation included cell dedifferentiation,proliferation and migration,while those of arm-stump elongation included cell dedifferentiation,proliferation,invagination,and arm-wall-across blastema-like structure formation.The unique pattern and cellular mechanisms of amputated arm regeneration make it easier to understand the rapid regeneration process of adult starfish.This study may lay solid foundations for the research into molecular mechanisms of echinoderm regeneration.

  16. Mechanisms of abnormal brain development leading to transsexualism (review

    Directory of Open Access Journals (Sweden)

    L. F. Kurilo

    2014-11-01

    Full Text Available Overview of national and world literature on sexual autoidentification is analyzed. Prenatal brain development abnormalities leading to transsexualism are discussed. Results of own cytogenetic analysis, ооgenesis and spermatоgenesis examination are reported.

  17. Mechanisms of abnormal brain development leading to transsexualism (review)

    OpenAIRE

    L. F. Kurilo; S. Sh. Khayat; S. Yu. Kalinchenko; B. Yu. Slonimskiy; T. M. Sorokina

    2014-01-01

    Overview of national and world literature on sexual autoidentification is analyzed. Prenatal brain development abnormalities leading to transsexualism are discussed. Results of own cytogenetic analysis, ооgenesis and spermatоgenesis examination are reported.

  18. Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia.

    Directory of Open Access Journals (Sweden)

    Nathalie Boone

    Full Text Available BACKGROUND: Familial dysautonomia (FD is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and modelize the molecular mechanisms of IKBKAP mRNA splicing, we collected human olfactory ecto-mesenchymal stem cells (hOE-MSC from FD patients. hOE-MSCs have a pluripotent ability to differentiate into various cell lineages, including neurons and glial cells. METHODOLOGY/PRINCIPAL FINDINGS: We confirmed IKBKAP mRNA alternative splicing in FD hOE-MSCs and identified 2 novel spliced isoforms also present in control cells. We observed a significant lower expression of both IKBKAP transcript and IKAP/hELP1 protein in FD cells resulting from the degradation of the transcript isoform skipping exon 20. We localized IKAP/hELP1 in different cell compartments, including the nucleus, which supports multiple roles for that protein. We also investigated cellular pathways altered in FD, at the genome-wide level, and confirmed that cell migration and cytoskeleton reorganization were among the processes altered in FD. Indeed, FD hOE-MSCs exhibit impaired migration compared to control cells. Moreover, we showed that kinetin improved exon 20 inclusion and restores a normal level of IKAP/hELP1 in FD hOE-MSCs. Furthermore, we were able to modify the IKBKAP splicing ratio in FD hOE-MSCs, increasing or reducing the WT (exon 20 inclusion:MU (exon 20 skipping ratio respectively, either by producing free-floating spheres, or by inducing cells into neural differentiation. CONCLUSIONS/SIGNIFICANCE: hOE-MSCs isolated from FD patients represent a new approach for modeling FD to better

  19. DMPD: Anti-inflammatory actions of PPAR ligands: new insights on cellular andmolecular mechanisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17981503 Anti-inflammatory actions of PPAR ligands: new insights on cellular andmol...) (.html) (.csml) Show Anti-inflammatory actions of PPAR ligands: new insights on cellular andmolecular mech...anisms. PubmedID 17981503 Title Anti-inflammatory actions of PPAR ligands: new in

  20. Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness

    International Nuclear Information System (INIS)

    The evolutionary-conserved interactions between KASH and SUN domain-containing proteins within the perinuclear space establish physical connections, called LINC complexes, between the nucleus and the cytoskeleton. Here, we show that the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2. These constructs disrupt endogenous LINC complexes as indicated by the displacement of endogenous Nesprins from the nuclear envelope. We also provide evidence that KASH domains most probably fit a pocket provided by SUN domains and that post-translational modifications are dispensable for that interaction. We demonstrate that the disruption of endogenous LINC complexes affect cellular mechanical stiffness to an extent that compares to the loss of mechanical stiffness previously reported in embryonic fibroblasts derived from mouse lacking A-type lamins, a mouse model of muscular dystrophies and cardiomyopathies. These findings support a model whereby physical connections between the nucleus and the cytoskeleton are mediated by interactions between diverse combinations of Sun proteins and Nesprins through their respective evolutionary-conserved domains. Furthermore, they emphasize, for the first time, the relevance of LINC complexes in cellular mechanical stiffness suggesting a possible involvement of their disruption in various laminopathies, a group of human diseases linked to mutations of A-type lamins

  1. Cellular and molecular investigations of the adhesion and mechanics of Listeria monocytogenes

    Science.gov (United States)

    Eskhan, Asma Omar

    Atomic force microscopy has been used to quantify the adherence and mechanical properties of an array of L. monocytogenes strains and their surface biopolymers. First, eight L. monocytogenes strains that represented the two major lineages of the species were compared for their adherence and mechanics at cellular and molecular levels. Our results indicated that strains of lineage' II were characterized by higher adhesion and Young's moduli, longer and more rigid surface biopolymers and lower specific and nonspecific forces when compared to lineage' I strains. Additionally, adherence and mechanical properties of eight L. monocytogenes epidemic and environmental strains were probed. Our results pointed to that environmental and epidemic strains representative of a given lineage were similar in their adherence and mechanical properties when investigated at a cellular level. However, when the molecular properties of the strains were considered, epidemic strains were characterized by higher specific and nonspecific forces, shorter, denser and more flexible biopolymers compared to environmental strains. Second, the role of environmental pH conditions of growth on the adhesion and mechanics of a pathogenic L. monocytogenes EGDe was investigated. Our results pointed to a transition in the adhesion energies for cells cultured at pH 7. In addition, when the types of molecular forces that govern the adhesion were quantified using Poisson statistical approach and using a new proposed method, specific hydrogen-bond energies dominated the bacterial adhesion process. Such a finding is instrumental to researchers designing methods to control bacterial adhesion. Similarly, bacterial cells underwent a transition in their mechanical properties. We have shown that cells cultured at pH 7 were the most rigid compared to those cultured in lower or higher pH conditions of growth. Due to transitions observed in adherence and mechanics when cells were cultured at pH 7, we hypothesized that

  2. In vitro kinetic studies on the mechanism of oxygen-dependent cellular uptake of copper radiopharmaceuticals

    International Nuclear Information System (INIS)

    The development of hypoxia-selective radiopharmaceuticals for use as therapeutic and/or imaging agents is of vital importance for both early identification and treatment of cancer and in the design of new drugs. Radiotracers based on copper for use in positron emission tomography have received great attention due to the successful application of copper(II) bis(thiosemicarbazonato) complexes, such as [60/62/64Cu(II)ATSM] and [60/62/64Cu(II)PTSM], as markers for tumour hypoxia and blood perfusion, respectively. Recent work has led to the proposal of a revised mechanism of hypoxia-selective cellular uptake and retention of [Cu(II)ATSM]. The work presented here describes non-steady-state kinetic simulations in which the reported pO2-dependent in vitro cellular uptake and retention of [64Cu(II)ATSM] in EMT6 murine carcinoma cells has been modelled by using the revised mechanistic scheme. Non-steady-state (NSS) kinetic analysis reveals that the model is in very good agreement with the reported experimental data with a root-mean-squared error of less than 6% between the simulated and experimental cellular uptake profiles. Estimated rate constants are derived for the cellular uptake and washout (k1 = 9.8 ± 0.59 x 10-4 s-1 and k2 = 2.9 ± 0.17 x 10-3 s-1), intracellular reduction (k3 = 5.2 ± 0.31 x 10-2 s-1), reoxidation (k4 = 2.2 ± 0.13 mol-1 dm3 s-1) and proton-mediated ligand dissociation (k5 = 9.0 ± 0.54 x 10-5 s-1). Previous mechanisms focused on the reduction and reoxidation steps. However, the data suggest that the origins of hypoxia-selective retention may reside with the stability of the copper(I) anion with respect to protonation and ligand dissociation. In vitro kinetic studies using the nicotimamide adenine dinucleotide (NADH)-dependent ferredoxin reductase enzyme PuR isolated from the bacterium Rhodopseudomonas palustris have also been conducted. NADH turnover frequencies are found to be dependent on the structure of the ligand and the results confirm that

  3. Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo.

    Science.gov (United States)

    Herwig, Lukas; Blum, Yannick; Krudewig, Alice; Ellertsdottir, Elin; Lenard, Anna; Belting, Heinz-Georg; Affolter, Markus

    2011-11-22

    Although many of the cellular and molecular mechanisms of angiogenesis have been intensely studied [1], little is known about the processes that underlie vascular anastomosis. We have generated transgenic fish lines expressing an EGFP-tagged version of the junctional protein zona occludens 1 (ZO1) to visualize individual cell behaviors that occur during vessel fusion and lumen formation in vivo. These life observations show that endothelial cells (ECs) use two distinct morphogenetic mechanisms, cell membrane invagination and cord hollowing to generate different types of vascular tubes. During initial steps of anastomosis, cell junctions that have formed at the initial site of cell contacts expand into rings, generating a cellular interface of apical membrane compartments, as defined by the localization of the apical marker podocalyxin-2 (Pdxl2). During the cord hollowing process, these apical membrane compartments are brought together via cell rearrangements and extensive junctional remodeling, resulting in lumen coalescence and formation of a multicellular tube. Vessel fusion by membrane invagination occurs adjacent to a preexisting lumen in a proximal to distal direction and is blood-flow dependent. Here, the invaginating inner cell membrane undergoes concomitant apicobasal polarization and the vascular lumen is formed by the extension of a transcellular lumen through the EC, which forms a unicellular or seamless tube. PMID:22079115

  4. The biocompatibility of fluorescent nanodiamonds and their mechanism of cellular uptake

    Science.gov (United States)

    Vaijayanthimala, Vairakkannu; Tzeng, Yan-Kai; Chang, Huan-Cheng; Li, Chung-Leung

    2009-10-01

    The labeling of cells with fluorescent nanoparticles is promising for various biomedical applications. The objective of this study is to evaluate the biocompatibility and the mechanism of the cellular uptake of fluorescent nanodiamonds (FNDs) in cancer cells (HeLa) and pre-adipocytes (3T3-L1). With flow cytometry and the use of a battery of metabolic and cytoskeletal inhibitors, we found that the mechanism of the FND uptake in both cells is by energy-dependent clathrin-mediated endocytosis. In addition, the surface charge of FND influences its cellular uptake, as the uptake of poly-L-lysine-coated FNDs is better than that of oxidative-acid-purified FNDs at the same concentration in regular medium with or without serum. We also confirm that the proliferative potential of FND-treated and untreated cells does not exhibit any significant differences when measured at bulk cultures, and more stringently at clonal cell density. Further biocompatibility studies indicate that the in vitro differentiation of 3T3-L1 pre-adipocytes and 489-2 osteoprogenitors is not affected by the FND treatment. Our results show that FNDs are biocompatible and ideal candidates for potential applications in human stem cell research.

  5. The mechanics of cellular compartmentalization as a model for tumor spreading

    Science.gov (United States)

    Fritsch, Anatol; Pawlizak, Steve; Zink, Mareike; Kaes, Josef A.

    2012-02-01

    Based on a recently developed surgical method of Michael H"ockel, which makes use of cellular confinement to compartments in the human body, we study the mechanics of the process of cell segregation. Compartmentalization is a fundamental process of cellular organization and occurs during embryonic development. A simple model system can demonstrate the process of compartmentalization: When two populations of suspended cells are mixed, this mixture will eventually segregate into two phases, whereas mixtures of the same cell type will not. In the 1960s, Malcolm S. Steinberg formulated the so-called differential adhesion hypothesis which explains the segregation in the model system and the process of compartmentalization by differences in surface tension and adhesiveness of the interacting cells. We are interested in to which extend the same physical principles affect tumor growth and spreading between compartments. For our studies, we use healthy and cancerous breast cell lines of different malignancy as well as primary cells from human cervix carcinoma. We apply a set of techniques to study their mechanical properties and interactions. The Optical Stretcher is used for whole cell rheology, while Cell-cell-adhesion forces are directly measured with a modified AFM. In combination with 3D segregation experiments in droplet cultures we try to clarify the role of surface tension in tumor spreading.

  6. Resonance and decay phenomena lead to quantum mechanical time asymmetry

    International Nuclear Information System (INIS)

    The states (Schrödinger picture) and observables (Heisenberg picture) in the standard quantum theory evolve symmetrically in time, given by the unitary group with time extending over −∞ 0 ≤ t 0, where t0 is the ensemble of time at which each individual system has been prepared. The Hardy space axiom also leads to the new prediction: the width Γ and the lifetime τ are exactly related by τ = h/Γ.

  7. Microscopic mechanism of low thermal conductivity in lead-telluride

    OpenAIRE

    Shiga, Takuma; Shiomi, Junichiro; Ma, Jie; Delaire, Olivier; Radzynski, Tomasz; Lusakowski, Andrzej; Esfarjani, Keivan; Chen, Gang

    2012-01-01

    The microscopic physics behind low lattice thermal conductivity of single crystal rocksalt lead telluride (PbTe) is investigated. Mode-dependent phonon (normal and umklapp) scattering rates and their impact on thermal conductivity were quantified by the first-principles-based anharmonic lattice dynamics calculations that accurately reproduce thermal conductivity in a wide temperature range. The low thermal conductivity of PbTe is attributed to the scattering of longitudinal acoustic phonons b...

  8. On the effects of geometry, defects, and material asymmetry on the mechanical response of shape memory alloy cellular lattice structures

    Science.gov (United States)

    Karamooz Ravari, M. R.; Nasr Esfahani, S.; Taheri Andani, M.; Kadkhodaei, M.; Ghaei, A.; Karaca, H.; Elahinia, M.

    2016-02-01

    Shape memory alloy (such as NiTi) cellular lattice structures are a new class of advanced materials with many potential applications. The cost of fabrication of these structures however is high. It is therefore necessary to develop modeling methods to predict the functional behavior of these alloys before fabrication. The main aim of the present study is to assess the effects of geometry, microstructural imperfections and material asymmetric response of dense shape memory alloys on the mechanical response of cellular structures. To this end, several cellular and dense NiTi samples are fabricated using a selective laser melting process. Both cellular and dense specimens were tested in compression in order to obtain their stress-strain response. For modeling purposes, a three -dimensional (3D) constitutive model based on microplane theory which is able to describe the material asymmetry was employed. Five finite element models based on unit cell and multi-cell methods were generated to predict the mechanical response of cellular lattices. The results show the considerable effects of the microstructural imperfections on the mechanical response of the cellular lattice structures. The asymmetric material response of the bulk material also affects the mechanical response of the corresponding cellular structure.

  9. Early Passage Dependence of Mesenchymal Stem Cell Mechanics Influences Cellular Invasion and Migration.

    Science.gov (United States)

    Spagnol, Stephen T; Lin, Wei-Chun; Booth, Elizabeth A; Ladoux, Benoit; Lazarus, Hillard M; Dahl, Kris Noel

    2016-07-01

    The cellular structures and mechanical properties of human mesenchymal stem cells (hMSCs) vary significantly during culture and with differentiation. Previously, studies to measure mechanics have provided divergent results using different quantitative parameters and mechanical models of deformation. Here, we examine hMSCs prepared for clinical use and subject them to mechanical testing conducive to the relevant deformability associated with clinical injection procedures. Micropipette aspiration of hMSCs shows deformation as a viscoelastic fluid, with little variation from cell to cell within a population. After two passages, hMSCs deform as viscoelastic solids. Further, for clinical applicability during stem cell migration in vivo, we investigated the ability of hMSCs to invade into micropillar arrays of increasing confinement from 12 to 8 μm spacing between adjacent micropillars. We find that hMSC samples with reduced deformability and cells that are more solid-like with passage are more easily able to enter the micropillar arrays. Increased cell fluidity is an advantage for injection procedures and optimization of cell selection based on mechanical properties may enhance efficacy of injected hMSC populations. However, the ability to invade and migrate within tight interstitial spaces appears to be increased with a more solidified cytoskeleton, likely from increased force generation and contractility. Thus, there may be a balance between optimal injection survival and in situ tissue invasion. PMID:26581348

  10. Finite element analysis of the mechanical properties of cellular aluminium based on micro-computed tomography

    International Nuclear Information System (INIS)

    Research highlights: → Elastic and plastic anisotropy is observed for both materials → Both show qualitatively similar characteristics with quantitative differences → Distinctly higher mechanical properties for closed-cell foam → The 'big' and 'small' models show good agreement for the closed-cell foam. - Abstract: In the present paper, the macroscopic mechanical properties of open-cell M-Pore sponge (porosity of 91-93%) and closed-cell Alporas foam (porosity of 80-86%) are investigated. The complex geometry of these cellular materials is scanned by micro-computed tomography and used in finite element (FE) analysis. The mechanical properties are determined by uni-axial compression simulations in three perpendicular directions (x-, y- and z-direction). M-Pore and Alporas exhibit the same qualitative mechanical characteristics but with quantitative differences. In both cases, strong anisotropy is observed for Young's modulus and the 0.002 offset yield stress. Furthermore, for the investigated relative density range a linear dependence between relative density and mechanical properties is found. Finally, a distinctly higher Young's modulus and 0.002 offset yield stress is observed for Alporas.

  11. A Comparative Study of Lead Oxide Modified Graphite Paste Electrodes and Solid Graphite Electrodes with Mechanically Immobilized Lead Oxides

    OpenAIRE

    Zakharchuk, Nina; Meyer, Stefan; Lange, Britta; Scholz, Fritz

    2000-01-01

    The cyclic voltammetry of red PbO, α-PbO2, β-PbO2 and BaPbO3 was studied with two different types of electrodes in acidic and alkaline media. In one case, microcrystalline particles of lead oxides were mechanically immobilized on the surface of paraffin-impregnated graphite rod electrodes (PIGE), while in the other case, lead oxides were added to a paste of graphite and silicone oil. The overall behaviour of lead oxides in both electrodes is very similar to the well-known behaviour...

  12. Mechanisms by which stress can lead to coronary heart disease.

    OpenAIRE

    Henry, J. P.

    1986-01-01

    Much stress is of psychological origin and due to emotional arousal. The mechanisms by which anger, helplessness, or a sense of control and serenity exert their various neuroendocrine effects are discussed. Primacy is given to three systems; to the catecholamines, to testosterone and to cortisol. Evidence that they interact to accelerate the arteriosclerotic process is cited. The protective aspects of intimacy are discussed together with evidence that certain personality types promote it in t...

  13. Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging.

    Science.gov (United States)

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

    2015-08-01

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

  14. Lead

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-31

    This is one of a series of reports made on industrial pollutants by the Expert Panel on Air Quality Standards to advise the United Kingdom Government on air quality standards. It describes the main sources of lead exposure, including the relative contribution of lead in the air and lead in the diet, and the methods by which it is measured in air. The Panel also considers the airborne concentrations recorded to date in the United Kingdom, ways in which lead is handled in by the body, and its toxic effects on people. The dominant source of airborne lead is petrol combustion. Other source include coal combustion, the production of non-ferrous metals and waste treatment and disposal. The justification of an air quality standard for lead is set down. The Panel recommends an air quality standard for lead in the United Kingdom of 0.25 {mu}g/m{sup 3} measured as an annual average. This is intended to protect young children, the group most vulnerable to impairment of brain function. 17 refs., 3 figs., 2 tabs.

  15. Calcitriol-copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma.

    Science.gov (United States)

    Rizvi, Asim; Farhan, Mohd; Naseem, Imrana; Hadi, S M

    2016-09-01

    Calcitriol is the metabolically active form of Vitamin D and is known to kill cancer cells. Using the rat model of DEN induced hepatocellular carcinoma we show that there is a marked increase in cellular levels of copper in hepatocellular carcinoma and that calcitriol-copper interaction leads to reactive oxygen species mediated DNA breakage selectively in hepatocellular carcinoma cells. In vivo studies show that calcitriol selectively induces severe fluctuations in cellular enzymatic and non enzymatic scavengers of reactive oxygen species in the malignant tissue. Lipid peroxidation, a well established marker of oxidative stress, was found to increase, and substantial cellular DNA breakage was observed. We propose that calcitriol is a proxidant in the cellular milieu of hepatocellular carcinoma cells, and this copper mediated prooxidant action of calcitriol causes selective DNA breakage in malignant cells, while sparing normal (non malignant) cells. PMID:27343126

  16. Mechanisms and Regulation of Intestinal Absorption of Water-soluble Vitamins: Cellular and Molecular Aspects

    DEFF Research Database (Denmark)

    Nexø, Ebba; Said, Hamid M

    2012-01-01

    The water-soluble vitamins represent a group of structurally and functionally unrelated compounds that share the common feature of being essential for normal cellular functions, growth, and development. With the exception of some endogenous production of niacin, human cells cannot synthesize thes...... deficiency. An impaired absorptive function occurs in a variety of conditions including congenital defects in the digestive or absorptive processes, intestinal diseases, drug interaction, and chronic alcohol use....... micronutrients, and thus, must obtain them from exogenous sources via intestinal absorption. The intestine, therefore, plays a critical role in maintaining and regulating normal body homeostasis of these essential nutrients, and interference with its normal absorptive function could lead to suboptimal states or...

  17. Mechanisms leading to work related Musculoskeletal Disorders in Dental Professionals

    Directory of Open Access Journals (Sweden)

    Waqar M. Naqvi

    2008-12-01

    Full Text Available Dentists commonly experience musculoskeletal pain during the course of their careers. While the occasional backache or neck-ache is not a cause for alarm, if regularly occurring pain or discomfort is ignored, the cumulative physiological damage can lead to an injuryor a career-ending disability. The musculoskeletal health of dental professionals has been the subject of numerous studies worldwide, and their focus has been on the pain experienced by the practitioner. Biller[1]found that 65% of dentists complained of back pain.Even after the evolution to seated four-handed dentistry and ergonomic equipment, studies found back, neck, and shoulder or arm pain present in up to 81% of dentists[2-6].

  18. Robust mechanisms of ventral furrow invagination require the combination of cellular shape changes

    International Nuclear Information System (INIS)

    Ventral furrow formation in Drosophila is the first large-scale morphogenetic movement during the life of the embryo, and is driven by co-ordinated changes in the shape of individual epithelial cells within the cellular blastoderm. Although many of the genes involved have been identified, the details of the mechanical processes that convert local changes in gene expression into whole-scale changes in embryonic form remain to be fully understood. Biologists have identified two main cell deformation modes responsible for ventral furrow invagination: constriction of the apical ends of the cells (apical wedging) and deformation along their apical–basal axes (radial lengthening/shortening). In this work, we used a computer 2D finite element model of ventral furrow formation to investigate the ability of different combinations of three plausible elementary active cell shape changes to bring about epithelial invagination: ectodermal apical–basal shortening, mesodermal apical–basal lengthening/shortening and mesodermal apical constriction. We undertook a systems analysis of the biomechanical system, which revealed many different combinations of active forces (invagination mechanisms) were able to generate a ventral furrow. Two important general features were revealed. First that combinations of shape changes are the most robust to environmental and mutational perturbation, in particular those combining ectodermal pushing and mesodermal wedging. Second, that ectodermal pushing plays a big part in all of the robust mechanisms (mesodermal forces alone do not close the furrow), and this provides evidence that it may be an important element in the mechanics of invagination in Drosophila

  19. Effects of Mechanical Properties on Tumor Invasion: Insights from a Cellular Model

    KAUST Repository

    Li, YZ

    2014-08-01

    Understanding the regulating mechanism of tumor invasion is of crucial importance for both fundamental cancer research and clinical applications. Previous in vivo experiments have shown that invasive cancer cells dissociate from the primary tumor and invade into the stroma, forming an irregular invasive morphology. Although cell movements involved in tumor invasion are ultimately driven by mechanical forces of cell-cell interactions and tumor-host interactions, how these mechanical properties affect tumor invasion is still poorly understood. In this study, we use a recently developed two-dimensional cellular model to study the effects of mechanical properties on tumor invasion. We study the effects of cell-cell adhesions as well as the degree of degradation and stiffness of extracellular matrix (ECM). Our simulation results show that cell-cell adhesion relationship must be satisfied for tumor invasion. Increased adhesion to ECM and decreased adhesion among tumor cells result in invasive tumor behaviors. When this invasive behavior occurs, ECM plays an important role for both tumor morphology and the shape of invasive cancer cells. Increased stiffness and stronger degree of degradation of ECM promote tumor invasion, generating more aggressive tumor invasive morphologies. It can also generate irregular shape of invasive cancer cells, protruding towards ECM. The capability of our model suggests it a useful tool to study tumor invasion and might be used to propose optimal treatment in clinical applications.

  20. Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death.

    Science.gov (United States)

    Narayanan, Kannan Badri; Ali, Manaf; Barclay, Barry J; Cheng, Qiang Shawn; D'Abronzo, Leandro; Dornetshuber-Fleiss, Rita; Ghosh, Paramita M; Gonzalez Guzman, Michael J; Lee, Tae-Jin; Leung, Po Sing; Li, Lin; Luanpitpong, Suidjit; Ratovitski, Edward; Rojanasakul, Yon; Romano, Maria Fiammetta; Romano, Simona; Sinha, Ranjeet K; Yedjou, Clement; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Brown, Dustin G; Ryan, Elizabeth P; Colacci, Annamaria; Hamid, Roslida A; Mondello, Chiara; Raju, Jayadev; Salem, Hosni K; Woodrick, Jordan; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Kim, Seo Yun; Bisson, William H; Lowe, Leroy; Park, Hyun Ho

    2015-06-01

    Cell death is a process of dying within biological cells that are ceasing to function. This process is essential in regulating organism development, tissue homeostasis, and to eliminate cells in the body that are irreparably damaged. In general, dysfunction in normal cellular death is tightly linked to cancer progression. Specifically, the up-regulation of pro-survival factors, including oncogenic factors and antiapoptotic signaling pathways, and the down-regulation of pro-apoptotic factors, including tumor suppressive factors, confers resistance to cell death in tumor cells, which supports the emergence of a fully immortalized cellular phenotype. This review considers the potential relevance of ubiquitous environmental chemical exposures that have been shown to disrupt key pathways and mechanisms associated with this sort of dysfunction. Specifically, bisphenol A, chlorothalonil, dibutyl phthalate, dichlorvos, lindane, linuron, methoxychlor and oxyfluorfen are discussed as prototypical chemical disruptors; as their effects relate to resistance to cell death, as constituents within environmental mixtures and as potential contributors to environmental carcinogenesis. PMID:26106145

  1. Mechanism of cellular uptake and impact of ferucarbotran on macrophage physiology.

    Directory of Open Access Journals (Sweden)

    Chung-Yi Yang

    Full Text Available Superparamagnetic iron oxide (SPIO nanoparticles are contrast agents used for magnetic resonance imaging. Ferucarbotran is a clinically approved SPIO-coated carboxydextran with a diameter of about 45-60 nm. We investigated the mechanism of cellular uptake of Ferucarbotran with a cell model using the murine macrophage cell line Raw 264.7. We observed a dose-dependent uptake of these SPIO particles by spectrophotometer analysis and also a dose-dependent increase in the granularity of the macrophages as determined by flow cytometry. There was a linear correlation between the side scattering mean value and iron content (P<0.001, R(2 = 0. 8048. For evaluation of the endocytotic pathway of these ingested SPIO particles, different inhibitors of the endocytotic pathways were employed. There was a significant decrease of side scattering counts in the cells and a less significant change in signal intensity based on magnetic resonance in the phenylarsine oxide-treated macrophages. After labeling with SPIO particles, the macrophages showed an increase in the production of reactive oxygen species at 2, 24, and 48 h; a decrease in mitochondrial membrane potential at 24 h; and an increase in cell proliferation at 24 h. We concluded that Ferucarbotran was internalized into macrophages via the clathrin-mediated pathway and can change the cellular behavior of these cells after labeling.

  2. Mechanisms by which stress can lead to coronary heart disease.

    Science.gov (United States)

    Henry, J P

    1986-07-01

    Much stress is of psychological origin and due to emotional arousal. The mechanisms by which anger, helplessness, or a sense of control and serenity exert their various neuroendocrine effects are discussed. Primacy is given to three systems; to the catecholamines, to testosterone and to cortisol. Evidence that they interact to accelerate the arteriosclerotic process is cited. The protective aspects of intimacy are discussed together with evidence that certain personality types promote it in the marital situation while others do not. It is suggested that the post-traumatic stress syndrome may relate to the coronary-prone personality for it involves an alexithymic disturbance of the emotional competence required for successful intimacy. PMID:3748938

  3. A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Qin; Ya-Nan Wang

    2012-01-01

    A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper.The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model.Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model),but also predict the realtime development pattern of BMC and BFE,as well as the dynamics of osteoblasts (OBA),osteoclasts (OCA),nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme,which can hardly be monitored through experiment.In conclusion,the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass.More importantly,this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated.The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies.Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

  4. Cellular origin and developmental mechanisms during the formation of skin melanocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ernfors, Patrik, E-mail: patrik.ernfors@ki.se [Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm (Sweden)

    2010-05-01

    Melanocytes are derived from the neural crest (NC), which are transient multipotent cells arising by delamination from the developing dorsal neural tube. During recent years, signaling systems and molecular mechanisms of melanocyte development have been studied in detail, but the exact diversification of the NC into melanocytes and how they migrate, expand and disperse in the skin have not been fully understood. The recent finding that Schwann cell precursors (SCPs) of the growing nerve represents a stem cell niche from which various cell types, including Schwann cells, endoneural fibroblasts and melanocytes arise has exposed new knowledge on the cellular basis for melanocyte development. This opens for the identification of new factors and reinterpretation of old data on cell fate instructive, proliferative, survival and cell homing factors participating in melanocyte development.

  5. Understanding the mechanisms of ATPase beta family genes for cellular thermotolerance in crossbred bulls

    Science.gov (United States)

    Deb, Rajib; Sajjanar, Basavaraj; Singh, Umesh; Alex, Rani; Raja, T. V.; Alyethodi, Rafeeque R.; Kumar, Sushil; Sengar, Gyanendra; Sharma, Sheetal; Singh, Rani; Prakash, B.

    2015-12-01

    Na+/K+-ATPase is an integral membrane protein composed of a large catalytic subunit (alpha), a smaller glycoprotein subunit (beta), and gamma subunit. The beta subunit is essential for ion recognition as well as maintenance of the membrane integrity. Present study was aimed to analyze the expression pattern of ATPase beta subunit genes (ATPase B1, ATPase B2, and ATPase B3) among the crossbred bulls under different ambient temperatures (20-44 °C). The present study was also aimed to look into the relationship of HSP70 with the ATPase beta family genes. Our results demonstrated that among beta family genes, transcript abundance of ATPase B1 and ATPase B2 is significantly ( P P mechanisms of ATPase beta family genes for cellular thermotolerance in cattle.

  6. Cellular and molecular mechanisms of HGF/Met in the cardiovascular system.

    Science.gov (United States)

    Gallo, Simona; Sala, Valentina; Gatti, Stefano; Crepaldi, Tiziana

    2015-12-01

    Met tyrosine kinase receptor, also known as c-Met, is the HGF (hepatocyte growth factor) receptor. The HGF/Met pathway has a prominent role in cardiovascular remodelling after tissue injury. The present review provides a synopsis of the cellular and molecular mechanisms underlying the effects of HGF/Met in the heart and blood vessels. In vivo, HGF/Met function is particularly important for the protection of the heart in response to both acute and chronic insults, including ischaemic injury and doxorubicin-induced cardiotoxicity. Accordingly, conditional deletion of Met in cardiomyocytes results in impaired organ defence against oxidative stress. After ischaemic injury, activation of Met provides strong anti-apoptotic stimuli for cardiomyocytes through PI3K (phosphoinositide 3-kinase)/Akt and MAPK (mitogen-activated protein kinase) cascades. Recently, we found that HGF/Met is also important for autophagy regulation in cardiomyocytes via the mTOR (mammalian target of rapamycin) pathway. HGF/Met induces proliferation and migration of endothelial cells through Rac1 (Ras-related C3 botulinum toxin substrate 1) activation. In fibroblasts, HGF/Met antagonizes the actions of TGFβ1 (transforming growth factor β1) and AngII (angiotensin II), thus preventing fibrosis. Moreover, HGF/Met influences the inflammatory response of macrophages and the immune response of dendritic cells, indicating its protective function against atherosclerotic and autoimmune diseases. The HGF/Met axis also plays an important role in regulating self-renewal and myocardial regeneration through the enhancement of cardiac progenitor cells. HGF/Met has beneficial effects against myocardial infarction and endothelial dysfunction: the cellular and molecular mechanisms underlying repair function in the heart and blood vessels are common and include pro-angiogenic, anti-inflammatory and anti-fibrotic actions. Thus administration of HGF or HGF mimetics may represent a promising therapeutic agent for the

  7. Mechanism of electric fatigue crack growth in lead zirconate titanate

    International Nuclear Information System (INIS)

    A series of experiments was performed with through-thickness cracks in ferroelectric double cantilever beam (DCB) specimens. Cyclic electric fields of different amplitudes were applied which resulted in cyclic crack propagation perpendicular to the electric field direction. Crack propagation was observed optically and three regimes were identified: a pop-in from a notch, steady-state crack growth and a decrease of the crack growth rate with increasing cycle number. Crack growth only occurred if the applied field exceeded the coercive field strength of the material. Furthermore, the crack extended during each field reversal and the crack growth rate increased with increasing field. Based on the experimental observations, a mechanistic understanding was developed and contrasted with a nonlinear finite element analysis which quantified the stress intensity in the DCB specimens. The driving forces for crack formation at the notch and subsequent fatigue crack growth were computed based on the distribution of residual stresses due to ferroelectric switching. The finite element results are in good agreement with the experimental observations and support the proposed mechanism

  8. Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate.

    Science.gov (United States)

    Kondoh, Hisato; Takada, Shinji; Takemoto, Tatsuya

    2016-06-01

    The transcription factor gene Sox2, centrally involved in neural primordial regulation, is activated by many enhancers. During the early stages of embryonic development, Sox2 is regulated by the enhancers N2 and N1 in the anterior neural plate (ANP) and posterior neural plate (PNP), respectively. This differential use of the enhancers reflects distinct regulatory mechanisms underlying the genesis of ANP and PNP. The ANP develops directly from the epiblast, triggered by nodal signal inhibition, and via the combined action of TFs SOX2, OTX2, POU3F1, and ZIC2, which promotes the the ANP development and inhibits other cell lineages. In contrast, the PNP is derived from neuromesodermal bipotential axial stem cells that develop into the neural plate when Sox2 is activated by the N1 enhancer, whereas they develop into the paraxial mesoderm when the N1 enhancer is repressed by the action of TBX6. The axial stem cells are maintained by the activity of WNT3a and T (Brachyury). However, at axial levels more anterior to the 8th somites (cervical levels), the development of both the neural plate and somite proceeds in the absence of WNT3a, T, or TBX6. These observations indicate that distinct molecular and cellular mechanisms determine neural plate genesis based on the axial level, and contradict the classical concept of the term "neural induction," which assumes a pan-neural plate mechanism. PMID:27279156

  9. Cellular and deafness mechanisms underlying connexin mutation induced hearing loss – A common hereditary deafness

    Directory of Open Access Journals (Sweden)

    Hong-Bo Zhao

    2015-05-01

    Full Text Available Hearing loss due to mutations in the connexin gene family which encodes gap junctional proteins is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2 mutations are responsible for ~50% of nonsyndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential (EP reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Additionally, there is no clear relationship between specific changes in connexin (channel functions and the phenotypes of mutation-induced hearing loss. Cx30, Cx29, Cx31, and Cx43 mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes and pathogeneses of specific-mutation induced hearing loss remain unclear. Finally, little information is available for humans. Further studies to address these deficiencies are urgently required.

  10. Electrospun PCL/Gelatin composite fibrous scaffolds: mechanical properties and cellular responses.

    Science.gov (United States)

    Yao, Ruijuan; He, Jing; Meng, Guolong; Jiang, Bo; Wu, Fang

    2016-06-01

    Electrospinning of hybrid polymer has gained widespread interest by taking advantages of the biological property of the natural polymer and the mechanical property of the synthetic polymer. However, the effect of the blend ratio on the above two properties has been less reported despite the importance to balance these two properties in various tissue engineering applications. To this aim, we investigated the electrospun PCL/Gelatin composite fibrous scaffolds with different blend ratios of 4:1, 2:1, 1:1, 1:2, 1:4, respectively. The morphology of the electrospun samples was observed by SEM and the result showed that the fiber diameter distribution became more uniform with the increase of the gelatin content. The mechanical testing results indicated that the 2:1 PCL/Gelatin sample had both the highest tensile strength of 3.7 MPa and the highest elongation rate of about 90%. Surprisingly, the 2:1 PCL/Gelatin sample also showed the best mesenchymal stem cell responses in terms of attachment, spreading, and cytoskeleton organization. Such correlation might be partly due to the fact that the enhanced mechanical property, an integral part of the physical microenvironment, likely played an important role in regulating the cellular functions. Overall, our results indicated that the PCL/Gelatin sample with the blend ratio of 2:1 was a superior candidate for scaffolds for tissue engineering applications. PMID:27044505

  11. The asymmetric self-assembly mechanism of adherens junctions: a cellular push–pull unit

    International Nuclear Information System (INIS)

    To form adherens junctions (AJ), cells first establish contact by sending out lamellipodia onto neighboring cells. We investigated the role of contacting cells in AJ assembly by studying an asymmetric AJ motif: finger-like AJ extending across the cell–cell interface. Using a cytoskeleton replica and immunofluorescence, we observed that actin bundles embedded in the lamellipodia are co-localized with stress fibers in the neighboring cell at the AJ. This suggests that donor lamellipodia present actin fingers, which are stabilized by acceptor lamellae via acto-myosin contractility. Indeed, we show that changes in actin network geometry promoted by Rac overexpression lead to corresponding changes in AJ morphology. Moreover, contractility inhibition and enhancement (via drugs or local traction) lead respectively to the disappearance and further growth of AJ fingers. Thus, we propose that receiving lamellae exert a local pull on AJ, promoting further polymerization of the donor actin bundles. In spite of different compositions, AJ and focal contacts both act as cellular mechanosensors

  12. Cellular Mechanism of Inner Ear Genetic Disease, roles of Kv7.1 (KCNQ1) Channel

    Science.gov (United States)

    Mousavi Nik, Atefeh

    Potassium channels are the most diverse and widely distributed membrane protein in all living organisms. They have various roles in the body such as controlling membrane potential, cell volume, and cell migration. Many studies have shown that mutation in these channels is associated with different diseases for example: Hearing Defect, Cardiac Arrhythmia, Episodic Ataxia, Seizure and Neuromyotonia. One of the most important diseases associated with K+ channel mutations is called Jervell and Lange-Nielsen syndrome (JLNS). This disease causes bilateral congenital deafness and the patients also suffer from Long QT and they usually experience syncopal episodes in their life and eventually die as a result of cardiac arrest. The gene KCNQ1 encodes the Kv7.1 voltage gated potassium channel. This channel expresses in apical membrane of marginal cell in stria vasularis of cochlea and secret K+ ion to endolymp to keep the endocochlear potential stable, which is necessary for the inner ear to function properly. Kv7.1 channel also expresses in cardiac myocytes and mutation in this gene is associated with another syndrome called Romano-Ward syndrome (RWS). Although Romano-Ward patients have mutation in KCNQ1, similar to Jervell and Lange-Nielsen patients, they only suffer from cardiac defect, and their hearing is completely normal. Several studies identified that mutations in Kv7.1 gene is associated with JLNS and RWS, but the biophysical and cellular mechanisms of these mutations are still unknown. To determine the cellular mechanisms of JLNS and RWS, and to provide mechanistic insight on the functional outputs of JLNS versus RWS mutations, we generated several mutant forms of the human Kv7.1 ( KCNQ1) clone, using site-directed mutagenesis to define their sub-cellular localization and examined their electrophysiological properties. We identified JLNS and RWS mutations at the S4-S5-linker, the pore loop (P-loop) and the C-terminus of hKv7.1 which have been found to control

  13. Structural-mechanical model of wax crystal networks—a mesoscale cellular solid approach

    International Nuclear Information System (INIS)

    Mineral waxes are widely used materials in industrial applications; however, the relationship between structure and mechanical properties is poorly understood. In this work, mineral wax-oil networks were characterized as closed-cell cellular solids, and differences in their mechanical response predicted from structural data. The systems studied included straight-chain paraffin wax (SW)-oil mixtures and polyethylene wax (PW)-oil mixtures. Analysis of cryogenic-SEM images of wax-oil networks allowed for the determination of the length (l) and thickness (t) of the wax cell walls as a function of wax mass fraction (Φ). A linear relationship between t/l and Φ (t/l ∼ Φ 0.89) suggested that wax-oil networks were cellular solids of the closed-cell type. However, the scaling behavior of the elastic modulus with the volume fraction of solids did not agree with theoretical predictions, yielding the same scaling exponent, μ = 0.84, for both waxes. This scaling exponent obtained from mechanical measurements could be predicted from the scaling behavior of the effective wax cell size as a function of wax mass fraction in oil obtained by cryogenic scanning electron microscopy. Microscopy studies allowed us to propose that wax-oil networks are structured as an ensemble of close-packed spherical cells filled with oil, and that it is the links between cells that yield under simple uniaxial compression. Thus, the Young’s moduli for the links between cells in SW and PW wax systems could be estimated as E L(SW) = 2.76 × 109 Pa and E L(PW) = 1.64 × 109 Pa, respectively. The structural parameter responsible for the observed differences in the mechanical strength between the two wax-oil systems is the size of the cells. Polyethylene wax has much smaller cell sizes than the straight chain wax and thus displays a higher Young’s modulus and yield stress. (papers)

  14. MECANISMOS CELULARES EN RESPUESTA AL ESTRÉS:: SIRTUINAS Cellular mechanisms in response to stress: sirtuin

    Directory of Open Access Journals (Sweden)

    Nancy Paola Echeverri-Ruíz

    2010-07-01

    Full Text Available Desde hace algún tiempo se conoce el papel de la restricción calórica sobre la longevidad y la prevención de enfermedades crónicas, pero hasta hace poco los mecanismos celulares involucrados comienzan a ser elucidados. El estrés celular se podría definir como el estado en el que la célula no presenta las condiciones óptimas de supervivencia, siendo el oxidativo un tipo de estrés en el que se generan radicales libres nocivos para las estructuras celulares. La restricción calórica podría incrementar la resistencia celular a diferentes formas de estrés. Las sirtuinas, proteínas deacetilasas de histonas tipo III, están involucradas en la relación entre balance energético y transcripción génica, permitiendo que la célula responda a la restricción calórica y sobreviva a situaciones de estrés oxidativo. En esta relación las sirtuinas regulan genes de la familia FOXO, cMYC, hTERT, p53, entre otros. La activación o silenciamiento de estos genes es importante en los procesos de apoptosis, reparación y muerte celular.The role of caloric restriction on longevity and prevention of chronic diseases has been known for some time; recently, cellular mechanisms involved are beginning to be elucidated. Cellular stress could be defined as the state in which the cell does not present optimal survival conditions; oxidative stress is a type of stress in which free radicals harmful cell structures. Caloric restriction might increase cellular resistance to various forms of stress. Sirtuins, histone deacetylases type III proteins are involved in the relationship between energy balance and gene transcription, allowing cell to respond to caloric restriction and to survive to oxidative stress. In this relationship, sirtuins regulate FOXO family genes, cMYC, hTERT, p53, among others. Activation or silencing of those genes is important in the process of apoptosis, repair and cell death

  15. Cellular mechanisms of tissue fibrosis. 6. Purinergic signaling and response in fibroblasts and tissue fibrosis.

    Science.gov (United States)

    Lu, David; Insel, Paul A

    2014-05-01

    Tissue fibrosis occurs as a result of the dysregulation of extracellular matrix (ECM) synthesis. Tissue fibroblasts, resident cells responsible for the synthesis and turnover of ECM, are regulated via numerous hormonal and mechanical signals. The release of intracellular nucleotides and their resultant autocrine/paracrine signaling have been shown to play key roles in the homeostatic maintenance of tissue remodeling and in fibrotic response post-injury. Extracellular nucleotides signal through P2 nucleotide and P1 adenosine receptors to activate signaling networks that regulate the proliferation and activity of fibroblasts, which, in turn, influence tissue structure and pathologic remodeling. An important component in the signaling and functional responses of fibroblasts to extracellular ATP and adenosine is the expression and activity of ectonucleotideases that attenuate nucleotide-mediated signaling, and thereby integrate P2 receptor- and subsequent adenosine receptor-initiated responses. Results of studies of the mechanisms of cellular nucleotide release and the effects of this autocrine/paracrine signaling axis on fibroblast-to-myofibroblast conversion and the fibrotic phenotype have advanced understanding of tissue remodeling and fibrosis. This review summarizes recent findings related to purinergic signaling in the regulation of fibroblasts and the development of tissue fibrosis in the heart, lungs, liver, and kidney. PMID:24352335

  16. Mechanism of acute cadmium toxicity in the testis of the rat: a cellular and molecular inquiry

    International Nuclear Information System (INIS)

    The more sensitive Sertoli cells were chosen as a model to investigate a molecular mechanism of toxicity. Primary rat Sertoli cells were exposed to sublethal concentrations of cadmium and the changes in [32P]-orthophosphate-labelled phosphoproteins using two-dimensional polyacrylamide gel electrophoresis were examined. Resultant autoradiograms showed a delayed dose- and time-dependent increase in intensity of two acidic proteins having identical molecular weights. These changes were most probably a result of increased synthesis of the proteins. Pretreatment of the cells with zinc, a cadmium antagonist, partially reduced the effect of cadmium. This research concludes that Sertoli cells are relatively more sensitive to the effects of cadmium than interstitial cells. A time- and dose dependent increase in [32P]-associated activity to two small Sertoli cell phosphoproteins was consistently seen after cadmium exposure, whereas no effect could be seen using essential, non-toxic metals. This response may be an early indicator in the disruption of cellular homeostasis by cadmium, and will hopefully contribute positive evidence in the search for a molecular mechanism of cadmium toxicity

  17. Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs.

    Science.gov (United States)

    Cunha-Oliveira, Teresa; Rego, Ana Cristina; Oliveira, Catarina R

    2008-06-01

    Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been developed. Drug addiction is now considered a brain disease, because the abuse of drugs affects several brain functions. Neurological impairments observed in drug addicts may reflect drug-induced neuronal dysfunction and neurotoxicity. The drugs of abuse directly or indirectly affect neurotransmitter systems, particularly dopaminergic and glutamatergic neurons. This review explores the literature reporting cellular and molecular alterations reflecting the cytotoxicity induced by amphetamines, cocaine and opiates in neuronal systems. The neurotoxic effects of drugs of abuse are often associated with oxidative stress, mitochondrial dysfunction, apoptosis and inhibition of neurogenesis, among other mechanisms. Understanding the mechanisms that underlie brain dysfunction observed in drug-addicted individuals may contribute to improve the treatment of drug addiction, which may have social and economic consequences. PMID:18440072

  18. Interconnection of thermal parameters, microstructure and mechanical properties in directionally solidified Sn–Sb lead-free solder alloys

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Marcelino; Costa, Thiago [Department of Manufacturing and Materials Engineering, University of Campinas — UNICAMP, 13083-860 Campinas, SP (Brazil); Rocha, Otávio [Federal Institute of Education, Science and Technology of Pará — IFPA, 66093-020 Belém, PA (Brazil); Spinelli, José E. [Department of Materials Engineering, Federal University of São Carlos — UFSCar, 13565-905 São Carlos, SP (Brazil); Cheung, Noé, E-mail: cheung@fem.unicamp.br [Department of Manufacturing and Materials Engineering, University of Campinas — UNICAMP, 13083-860 Campinas, SP (Brazil); Garcia, Amauri [Department of Manufacturing and Materials Engineering, University of Campinas — UNICAMP, 13083-860 Campinas, SP (Brazil)

    2015-08-15

    Considerable effort is being made to develop lead-free solders for assembling in environmental-conscious electronics, due to the inherent toxicity of Pb. The search for substitute alloys of Pb–Sn solders has increased in order to comply with different soldering purposes. The solder must not only meet the expected levels of electrical performance but may also have appropriate mechanical strength, with the absence of cracks in the solder joints. The Sn–Sb alloy system has a range of compositions that can be potentially included in the class of high temperature solders. This study aims to establish interrelations of solidification thermal parameters, microstructure and mechanical properties of Sn–Sb alloys (2 wt.%Sb and 5.5 wt.%Sb) samples, which were directionally solidified under cooling rates similar to those of reflow procedures in industrial practice. A complete high-cooling rate cellular growth is shown to be associated with the Sn–2.0 wt.%Sb alloy and a reverse dendrite-to-cell transition is observed for the Sn–5.5 wt.%Sb alloy. Strength and ductility of the Sn–2.0 wt.%Sb alloy are shown not to be affected by the cellular spacing. On the other hand, a considerable variation in these properties is associated with the cellular region of the Sn–5.5 wt.%Sb alloy casting. - Graphical abstract: Display Omitted - Highlights: • The microstructure of the Sn–2 wt.%Sb alloy is characterized by high-cooling rates cells. • Reverse dendrite > cell transition occurs for Sn–5.5 wt.%Sb alloy: cells prevail for cooling rates > 1.2 K/s. • Sn–5.5 wt.%Sb alloy: the dendritic region occurs for cooling rates < 0.9 K/s. • Sn–5.5 wt.%Sb alloy: tensile properties are improved with decreasing cellular spacing.

  19. Interconnection of thermal parameters, microstructure and mechanical properties in directionally solidified Sn–Sb lead-free solder alloys

    International Nuclear Information System (INIS)

    Considerable effort is being made to develop lead-free solders for assembling in environmental-conscious electronics, due to the inherent toxicity of Pb. The search for substitute alloys of Pb–Sn solders has increased in order to comply with different soldering purposes. The solder must not only meet the expected levels of electrical performance but may also have appropriate mechanical strength, with the absence of cracks in the solder joints. The Sn–Sb alloy system has a range of compositions that can be potentially included in the class of high temperature solders. This study aims to establish interrelations of solidification thermal parameters, microstructure and mechanical properties of Sn–Sb alloys (2 wt.%Sb and 5.5 wt.%Sb) samples, which were directionally solidified under cooling rates similar to those of reflow procedures in industrial practice. A complete high-cooling rate cellular growth is shown to be associated with the Sn–2.0 wt.%Sb alloy and a reverse dendrite-to-cell transition is observed for the Sn–5.5 wt.%Sb alloy. Strength and ductility of the Sn–2.0 wt.%Sb alloy are shown not to be affected by the cellular spacing. On the other hand, a considerable variation in these properties is associated with the cellular region of the Sn–5.5 wt.%Sb alloy casting. - Graphical abstract: Display Omitted - Highlights: • The microstructure of the Sn–2 wt.%Sb alloy is characterized by high-cooling rates cells. • Reverse dendrite > cell transition occurs for Sn–5.5 wt.%Sb alloy: cells prevail for cooling rates > 1.2 K/s. • Sn–5.5 wt.%Sb alloy: the dendritic region occurs for cooling rates < 0.9 K/s. • Sn–5.5 wt.%Sb alloy: tensile properties are improved with decreasing cellular spacing

  20. Cellular mechanisms of activity-dependent BDNF expression in primary sensory neurons.

    Science.gov (United States)

    Vermehren-Schmaedick, A; Khanjian, R A; Balkowiec, A

    2015-12-01

    Brain-derived neurotrophic factor (BDNF) is abundantly expressed by both developing and adult rat visceral sensory neurons from the nodose ganglion (NG) in vivo and in vitro. We have previously shown that BDNF is released from neonatal NG neurons by activity and regulates dendritic development in their postsynaptic targets in the brainstem. The current study was carried out to examine the cellular and molecular mechanisms of activity-dependent BDNF expression in neonatal rat NG neurons, using our established in vitro model of neuronal activation by electrical field stimulation with patterns that mimic neuronal activity in vivo. We show that BDNF mRNA (transcript 4) increases over threefold in response to a 4-h tonic or bursting pattern delivered at the frequency of 6 Hz, which corresponds to the normal heart rate of a newborn rat. No significant increase in BDNF expression was observed following stimulation at 1 Hz. The latter effect suggests a frequency-dependent mechanism of regulated BDNF expression. In addition to BDNF transcript 4, which is known to be regulated by activity, transcript 1 also showed significant upregulation. The increases in BDNF mRNA were followed by BDNF protein upregulation of a similar magnitude after 24h of stimulation at 6 Hz. Electrical stimulation-evoked BDNF expression was inhibited by pretreating neurons with the blocker of voltage-gated sodium channels tetrodotoxin and by removing extracellular calcium. Moreover, our data show that repetitive stimulation-evoked BDNF expression requires calcium influx through N-, but not L-type, channels. Together, our study reveals novel mechanisms through which electrical activity stimulates de novo synthesis of BDNF in sensory neurons, and points to the role of N-type calcium channels in regulating BDNF expression in sensory neurons in response to repetitive stimulation. PMID:26459016

  1. The Physical Mechanism for Retinal Discrete Dark Noise: Thermal Activation or Cellular Ultraweak Photon Emission?

    Science.gov (United States)

    Salari, Vahid; Scholkmann, Felix; Bokkon, Istvan; Shahbazi, Farhad; Tuszynski, Jack

    2016-01-01

    For several decades the physical mechanism underlying discrete dark noise of photoreceptors in the eye has remained highly controversial and poorly understood. It is known that the Arrhenius equation, which is based on the Boltzmann distribution for thermal activation, can model only a part (e.g. half of the activation energy) of the retinal dark noise experimentally observed for vertebrate rod and cone pigments. Using the Hinshelwood distribution instead of the Boltzmann distribution in the Arrhenius equation has been proposed as a solution to the problem. Here, we show that the using the Hinshelwood distribution does not solve the problem completely. As the discrete components of noise are indistinguishable in shape and duration from those produced by real photon induced photo-isomerization, the retinal discrete dark noise is most likely due to ‘internal photons’ inside cells and not due to thermal activation of visual pigments. Indeed, all living cells exhibit spontaneous ultraweak photon emission (UPE), mainly in the optical wavelength range, i.e., 350–700 nm. We show here that the retinal discrete dark noise has a similar rate as UPE and therefore dark noise is most likely due to spontaneous cellular UPE and not due to thermal activation. PMID:26950936

  2. Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2013-01-01

    Full Text Available Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

  3. Fundamental molecular mechanism for the cellular uptake of guanidinium-rich molecules.

    Science.gov (United States)

    Herce, Henry D; Garcia, Angel E; Cardoso, M Cristina

    2014-12-17

    Guanidinium-rich molecules, such as cell-penetrating peptides, efficiently enter living cells in a non-endocytic energy-independent manner and transport a wide range of cargos, including drugs and biomarkers. The mechanism by which these highly cationic molecules efficiently cross the hydrophobic barrier imposed by the plasma membrane remains a fundamental open question. Here, a combination of computational results and in vitro and live-cell experimental evidence reveals an efficient energy-independent translocation mechanism for arginine-rich molecules. This mechanism unveils the essential role of guanidinium groups and two universal cell components: fatty acids and the cell membrane pH gradient. Deprotonated fatty acids in contact with the cell exterior interact with guanidinium groups, leading to a transient membrane channel that facilitates the transport of arginine-rich peptides toward the cell interior. On the cytosolic side, the fatty acids become protonated, releasing the peptides and resealing the channel. This fundamental mechanism appears to be universal across cells from different species and kingdoms. PMID:25405895

  4. Lead tolerance mechanism in Conyza canadensis: subcellular distribution, ultrastructure, antioxidative defense system, and phytochelatins.

    Science.gov (United States)

    Li, Ying; Zhou, Chuifan; Huang, Meiying; Luo, Jiewen; Hou, Xiaolong; Wu, Pengfei; Ma, Xiangqing

    2016-03-01

    We used hydroponic experiments to examine the effects of different concentrations of lead (Pb) on the performance of the Pb-tolerable plant Conyza canadensis. In these experiments, most of the Pb was accumulated in the roots; there was very little Pb accumulated in stems and leaves. C. canadensis is able to take up significant amounts of Pb whilst greatly restricting its transportation to specific parts of the aboveground biomass. High Pb concentrations inhibited plant growth, increased membrane permeability, elevated antioxidant enzyme activity in roots, and caused a significant increase in root H2O2 and malondialdehyde content. Analysis of Pb content at the subcellular level showed that most Pb was associated with the cell wall fraction, followed by the nucleus-rich fraction, and with a minority present in the mitochondrial and soluble fractions. Furthermore, transmission electron microscopy and energy dispersive X-ray analysis of root cells revealed that the cell wall and intercellular space in C. canadensis roots are the main locations of Pb accumulation. Additionally, high Pb concentrations adversely affected the cellular structure of C. canadensis roots. The increased enzyme activity suggests that the antioxidant system may play an important role in eliminating or alleviating Pb toxicity in C. canadensis roots. However, the levels of non-protein sulfhydryl compounds, glutathione, and phytochelatin did not significantly change in either the roots or leaves under Pb-contaminated treatments. Our results provide strong evidence that cell walls restrict Pb uptake into the root and act as an important barrier protecting root cells, while demonstrating that antioxidant enzyme levels are correlated with Pb exposure. These findings demonstrate the roles played by these detoxification mechanisms in supporting Pb tolerance in C. canadensis. PMID:26733305

  5. Cellular polarization: Interaction between extrinsic bounded noises and the wave-pinning mechanism

    Science.gov (United States)

    de Franciscis, Sebastiano; d'Onofrio, Alberto

    2013-09-01

    Cell polarization (cued or uncued) is a fundamental mechanism in cell biology. As an alternative to the classical Turing bifurcation, it has been proposed that the onset of cell polarity might arise by means of the well-known phenomenon of wave-pinning [Gamba , Proc. Natl. Acad. Sci. USAPNASA60027-842410.1073/pnas.0503974102 102, 16927 (2005)]. A particularly simple and elegant deterministic model of cell polarization based on the wave-pinning mechanism has been proposed by Edelstein-Keshet and coworkers [Biophys. J.BIOJAU0006-349510.1529/biophysj.107.120824 94, 3684 (2008)]. This model consists of a small biomolecular network where an active membrane-bound factor interconverts into its inactive form that freely diffuses in the cell cytosol. However, biomolecular networks do communicate with other networks as well as with the external world. Thus, their dynamics must be considered as perturbed by extrinsic noises. These noises may have both a spatial and a temporal correlation, and in any case they must be bounded to preserve the biological meaningfulness of the perturbed parameters. Here we numerically show that the inclusion of external spatiotemporal bounded parametric perturbations in the above wave-pinning-based model of cellular polarization may sometimes destroy the polarized state. The polarization loss depends on both the extent of temporal and spatial correlations and on the kind of noise employed. For example, an increase of the spatial correlation of the noise induces an increase of the probability of cell polarization. However, if the noise is spatially homogeneous then the polarization is lost in the majority of cases. These phenomena are independent of the type of noise. Conversely, an increase of the temporal autocorrelation of the noise induces an effect that depends on the model of noise.

  6. Phytoplankton calcification as an effective mechanism to alleviate cellular calcium poisoning

    Science.gov (United States)

    Müller, M. N.; Ramos, J. Barcelos e.; Schulz, K. G.; Riebesell, U.; Kaźmierczak, J.; Gallo, F.; Mackinder, L.; Li, Y.; Nesterenko, P. N.; Trull, T. W.; Hallegraeff, G. M.

    2015-11-01

    Marine phytoplankton have developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L-1 in the presence of seawater Ca2+ concentrations of 10 mmol L-1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, phytoplankton taxonomic groups appear to have evolved different strategies, which may affect their ability to cope with changes in seawater Ca2+ concentrations in their environment on geological timescales. For example, the Cretaceous (145 to 66 Ma), an era known for the high abundance of coccolithophores and the production of enormous calcium carbonate deposits, exhibited seawater calcium concentrations up to 4 times present-day levels. We show that calcifying coccolithophore species (Emiliania huxleyi, Gephyrocapsa oceanica and Coccolithus braarudii) are able to maintain their relative fitness (in terms of growth rate and photosynthesis) at simulated Cretaceous seawater calcium concentrations, whereas these rates are severely reduced under these conditions in some non-calcareous phytoplankton species (Chaetoceros sp., Ceratoneis closterium and Heterosigma akashiwo). Most notably, this also applies to a non-calcifying strain of E. huxleyi which displays a calcium sensitivity similar to the non-calcareous species. We hypothesize that the process of calcification in coccolithophores provides an efficient mechanism to alleviate cellular calcium poisoning and thereby offered a potential key evolutionary advantage, responsible for the proliferation of coccolithophores during times of high seawater calcium concentrations. The exact function of calcification and the reason behind the highly ornate physical structures of coccoliths remain elusive.

  7. A computational framework for 3D mechanical modeling of plant morphogenesis with cellular resolution.

    Directory of Open Access Journals (Sweden)

    Frédéric Boudon

    2015-01-01

    Full Text Available The link between genetic regulation and the definition of form and size during morphogenesis remains largely an open question in both plant and animal biology. This is partially due to the complexity of the process, involving extensive molecular networks, multiple feedbacks between different scales of organization and physical forces operating at multiple levels. Here we present a conceptual and modeling framework aimed at generating an integrated understanding of morphogenesis in plants. This framework is based on the biophysical properties of plant cells, which are under high internal turgor pressure, and are prevented from bursting because of the presence of a rigid cell wall. To control cell growth, the underlying molecular networks must interfere locally with the elastic and/or plastic extensibility of this cell wall. We present a model in the form of a three dimensional (3D virtual tissue, where growth depends on the local modulation of wall mechanical properties and turgor pressure. The model shows how forces generated by turgor-pressure can act both cell autonomously and non-cell autonomously to drive growth in different directions. We use simulations to explore lateral organ formation at the shoot apical meristem. Although different scenarios lead to similar shape changes, they are not equivalent and lead to different, testable predictions regarding the mechanical and geometrical properties of the growing lateral organs. Using flower development as an example, we further show how a limited number of gene activities can explain the complex shape changes that accompany organ outgrowth.

  8. PHYSIOLOGY AND ENDOCRINOLOGY SYMPOSIUM: Cellular and molecular mechanisms of heat stress related to bovine ovarian function.

    Science.gov (United States)

    Roth, Z

    2015-05-01

    In light of the intensive genetic selection for high milk production and the onset of global warming, it seems that the reduced fertility of lactating cows during the summer will worsen in coming years. Although not entirely clear, the mechanism appears to be multifactorial in nature. It includes alterations in follicular development, depression of follicular dominance, and impairment of steroidogenesis and gonadotropin secretion. Heat-induced perturbations in the physiology of the follicle-enclosed oocyte have also been documented, expressed by impaired cleavage rate and reduced developmental competence. With respect to the oocyte, alterations include an increase in PUFA in the membrane, reactive oxygen species, ceramide formation and caspase activity, and induction of apoptosis via the sphingomyelin and/or mitochondrial pathways. New insight into cellular and molecular alterations has revealed that heat induces perturbations in both nuclear and cytoplasmic maturation events, such as resumption of meiosis, metaphase II plate formation, cytoskeleton rearrangement, and translocation of cortical granules. Alterations in mitochondrial distribution (i.e., low proportion of category I mitochondria) and function (i.e., low membrane potential) have recently been reported for oocytes collected during the summer. These were associated with impaired expression of both nuclear (succinate dehydrogenase subunit [SDHD], adenosine triphosphate [ATP] synthase subunit beta [ATP5B]), mitochondrially NADH dehydrogenase subunit 2 (ND2), and mitochondiral (cytochrome c oxidase subunit II [MT-CO2] and cytochrome b [MT-CYB]) genes that are crucial in the mitochondrial respiratory chain. In addition, season-induced alteration in the stored maternal mRNA has been documented, expressed by reduced transcript levels (oocyte maturation factor MOS [C-MOS], growth differentiation factor 9 [GDF9], POU domain class 5 transcription factor 1 [POU5F1], and glyceraldehyde-3-phosphate dehydrogenase

  9. Involvement of the Wnt/β-catenin signaling pathway in the cellular and molecular mechanisms of fibrosis in endometriosis.

    Directory of Open Access Journals (Sweden)

    Sachiko Matsuzaki

    Full Text Available BACKGROUND: During the development and progression of endometriotic lesions, excess fibrosis may lead to scarring, chronic pain, and altered tissue function. However, the cellular and molecular mechanisms of fibrosis in endometriosis remain to be clarified. OBJECTIVES: The objective of the present study was to investigate whether the Wnt/β-catenin signaling pathway was involved in regulating the cellular and molecular mechanisms of fibrosis in endometriosis in vitro and to evaluate whether fibrosis could be prevented by targeting the Wnt/β-catenin pathway in a xenograft model of endometriosis in immunodeficient nude mice. METHODS: Seventy patients (40 with and 30 without endometriosis with normal menstrual cycles were recruited. In vitro effects of small-molecule antagonists of the Tcf/β-catenin complex (PKF 115-584 and CGP049090 on fibrotic markers (alpha smooth muscle actin, type I collagen, connective tissue growth factor, fibronectin and collagen gel contraction were evaluated in endometrial and endometriotic stromal cells from patients with endometriosis. In vitro effects of activation of the Wnt/β-catenin signaling pathway by treatment with recombinant Wnt3a on profibrotic responses were evaluated in endometrial stromal cells of patients without endometriosis. The effects of CGP049090 treatment on the fibrosis of endometriotic implants were evaluated in a xenograft model of endometriosis in immunodeficient nude mice. RESULTS: Treatment with PKF 115-584 and CGP049090 significantly decreased the expression of alpha smooth muscle actin, type I collagen, connective tissue growth factor and fibronectin mRNAs in both endometriotic and endometrial stromal cells with or without transforming growth factor-β1 stimulation. Both endometriotic and endometrial stromal cell-mediated contraction of collagen gels was significantly decreased by treatment with PKF 115-584 and CGP049090 as compared to that of untreated cells. The animal experiments

  10. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

    Science.gov (United States)

    Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

    2016-01-01

    IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain

  11. Kinematic Accuracy Analysis of Lead Screw W Insertion Mechanism with Flexibility

    Science.gov (United States)

    He, Hu; Zhang, Lei; Kong, Jiayuan

    According to the actual requirements of w insertion, a set of variable lead screw w mechanism was designed, motion characteristics of the mechanism were analyzed and kinematics simulation was carried out with MATLAB. Mechanism precision was analyzed with the analytical method and the error coefficient curve of each component in the mechanism was obtained. Dynamics simulation for rigid mechanism and mechanism with flexibility in different speed was conducted with ADAMS, furthermore, real-time elastic deformation of the flexible Connecting rod was obtained. In consideration of the influences of the elastic connecting rod, the outputs motion error and elastic deformation of components were increased with the speed of the loom.

  12. Zinc, cadmium and lead resistance mechanisms in bacteria and their contribution to biosensing

    OpenAIRE

    Hynninen, Anu

    2010-01-01

    In bacteria resistance to heavy metals is mainly achieved through active efflux, but also sequestration with proteins or as insoluble compounds is used. Although numerous studies have dealt with zinc, cadmium and lead resistance mechanisms in bacteria, it has still remained unclear how different transporters are integrated into an effective homeostasis/resistance network and whether specific mechanisms for lead sequestration exist. Furthermore, since metals are toxic not only to bacteria but ...

  13. Microstructures, mechanical behavior, cellular response, and hemocompatibility of bulk ultrafine-grained pure tantalum.

    Science.gov (United States)

    Nie, F L; Zheng, Y F; Wang, Y; Wang, J T

    2014-02-01

    Bulk ultrafine-grained (UFG) pure Ta had been successfully prepared by equal channel angular pressing (ECAP) technique till eight passes. The 1st, 2nd, 4th, and 8th ECAPed Ta samples were investigated in the current study, with the 0th ECAPed Ta sample as the microcrystalline counterpart control. The microstructure and grain size distribution were characterized by X-ray diffractometer patterns, scanning electron microscopy, and transmission electron microscopy analysis by means of histogram. Although the mechanical behavior of all the experimental samples were analyzed through uniaxial tensile measurement and microhardness test, in vitro biological interactions onto the substrates such as protein adsorption, cellular responses derived from different types of cell lines, and the activity of erythrocyte and platelets were further evaluated and specifically assessed by bicinchoninic acid assay, enzyme-linked immunosorbent assay, and the method of colorimetric reading. A superior percentage of protein adsorption can be observed on the substrate of the UFG 8th ECAPed Ta (around 90%), even above those on the tissue culture plate (control) and the other ECAPed Ta samples. Furthermore, the UFG 8th ECAPed Ta shows no cytotoxic within 4 days culture when incubated with the murine fibroblast cell lines (L929). In addition, a priority order in the growth of endothelial cells (ECV304) other than vascular smooth muscle cells was observed in the case of the UFG 8th ECAPed Ta. In terms of hemolysis rate and adhered platelets (both the amount and the individual morphology), an evolutionary outcome of preferentially enhanced hemocompatibility can be concluded for the case of the UFG 8th ECAPed Ta. PMID:23908098

  14. Molecular, Cellular, and Structural Mechanisms of Cocaine Addiction: A Key Role for MicroRNAs

    Science.gov (United States)

    Jonkman, Sietse; Kenny, Paul J

    2013-01-01

    The rewarding properties of cocaine play a key role in establishing and maintaining the drug-taking habit. However, as exposure to cocaine increases, drug use can transition from controlled to compulsive. Importantly, very little is known about the neurobiological mechanisms that control this switch in drug use that defines addiction. MicroRNAs (miRNAs) are small non-protein coding RNA transcripts that can regulate the expression of messenger RNAs that code for proteins. Because of their highly pleiotropic nature, each miRNA has the potential to regulate hundreds or even thousands of protein-coding RNA transcripts. This property of miRNAs has generated considerable interest in their potential involvement in complex psychiatric disorders such as addiction, as each miRNA could potentially influence the many different molecular and cellular adaptations that arise in response to drug use that are hypothesized to drive the emergence of addiction. Here, we review recent evidence supporting a key role for miRNAs in the ventral striatum in regulating the rewarding and reinforcing properties of cocaine in animals with limited exposure to the drug. Moreover, we discuss evidence suggesting that miRNAs in the dorsal striatum control the escalation of drug intake in rats with extended cocaine access. These findings highlight the central role for miRNAs in drug-induced neuroplasticity in brain reward systems that drive the emergence of compulsive-like drug use in animals, and suggest that a better understanding of how miRNAs control drug intake will provide new insights into the neurobiology of drug addiction. PMID:22968819

  15. Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment

    Directory of Open Access Journals (Sweden)

    Gaurav eSinghal

    2014-04-01

    Full Text Available Recent studies on environmental enrichment (EE have shown cytokines, cellular immune components (e.g. T lymphocytes, NK cells and glial cells in causal relationship to EE in bringing out changes to neurobiology and behavior. The purpose of this review is to evaluate these neuroimmune mechanisms associated with neurobiological and behavioral changes in response to different EE methods. We systematically reviewed common research databases. After applying all inclusion and exclusion criteria, 328 articles remained for this review. Physical exercise, a form of EE, elicits anti-inflammatory and neuromodulatory effects through interaction with several immune pathways including IL-6 secretion from muscle fibers, reduced expression of TLR’s on monocytes and macrophages, reduced secretion of adipokines, modulation of hippocampal T cells, priming of microglia and upregulation of MKP-1 in CNS. In contrast, immunomodulatory roles of other enrichment methods are not studied extensively. Nonetheless, studies showing reduction in the expression of IL-1β and TNF-α in response to enrichment with novel objects and accessories suggest anti-inflammatory effects of novel environment. Likewise, social enrichment, though considered a necessity for healthy behavior, results in immunosuppression in socially defeated animals. This has been attributed to reduction in T lymphocytes, NK cells and IL-10 in subordinate animals. EE through sensory stimuli has been investigated to a lesser extent and the effect on immune factors has not been evaluated yet. Discovery of this multidimensional relationship between immune system, brain functioning and EE has paved a way towards formulating environ-immuno therapies for treating psychiatric illnesses with minimal use of pharmacotherapy. While the immuno-modulatory role of physical exercise has been evaluated extensively, more research is required to investigate neuroimmune changes associated with other enrichment methods.

  16. Adaptation of the black yeast Wangiella dermatitidis to ionizing radiation: molecular and cellular mechanisms.

    Directory of Open Access Journals (Sweden)

    Kelly L Robertson

    Full Text Available Observations of enhanced growth of melanized fungi under low-dose ionizing radiation in the laboratory and in the damaged Chernobyl nuclear reactor suggest they have adapted the ability to survive or even benefit from exposure to ionizing radiation. However, the cellular and molecular mechanism of fungal responses to such radiation remains poorly understood. Using the black yeast Wangiella dermatitidis as a model, we confirmed that ionizing radiation enhanced cell growth by increasing cell division and cell size. Using RNA-seq technology, we compared the transcriptomic profiles of the wild type and the melanin-deficient wdpks1 mutant under irradiation and non-irradiation conditions. It was found that more than 3000 genes were differentially expressed when these two strains were constantly exposed to a low dose of ionizing radiation and that half were regulated at least two fold in either direction. Functional analysis indicated that many genes for amino acid and carbohydrate metabolism and cell cycle progression were down-regulated and that a number of antioxidant genes and genes affecting membrane fluidity were up-regulated in both irradiated strains. However, the expression of ribosomal biogenesis genes was significantly up-regulated in the irradiated wild-type strain but not in the irradiated wdpks1 mutant, implying that melanin might help to contribute radiation energy for protein translation. Furthermore, we demonstrated that long-term exposure to low doses of radiation significantly increased survivability of both the wild-type and the wdpks1 mutant, which was correlated with reduced levels of reactive oxygen species (ROS, increased production of carotenoid and induced expression of genes encoding translesion DNA synthesis. Our results represent the first functional genomic study of how melanized fungal cells respond to low dose ionizing radiation and provide clues for the identification of biological processes, molecular pathways and

  17. A computational model of cellular mechanisms of temporal coding in the medial geniculate body (MGB.

    Directory of Open Access Journals (Sweden)

    Cal F Rabang

    Full Text Available Acoustic stimuli are often represented in the early auditory pathway as patterns of neural activity synchronized to time-varying features. This phase-locking predominates until the level of the medial geniculate body (MGB, where previous studies have identified two main, largely segregated response types: Stimulus-synchronized responses faithfully preserve the temporal coding from its afferent inputs, and Non-synchronized responses, which are not phase locked to the inputs, represent changes in temporal modulation by a rate code. The cellular mechanisms underlying this transformation from phase-locked to rate code are not well understood. We use a computational model of a MGB thalamocortical neuron to test the hypothesis that these response classes arise from inferior colliculus (IC excitatory afferents with divergent properties similar to those observed in brain slice studies. Large-conductance inputs exhibiting synaptic depression preserved input synchrony as short as 12.5 ms interclick intervals, while maintaining low firing rates and low-pass filtering responses. By contrast, small-conductance inputs with Mixed plasticity (depression of AMPA-receptor component and facilitation of NMDA-receptor component desynchronized afferent inputs, generated a click-rate dependent increase in firing rate, and high-pass filtered the inputs. Synaptic inputs with facilitation often permitted band-pass synchrony along with band-pass rate tuning. These responses could be tuned by changes in membrane potential, strength of the NMDA component, and characteristics of synaptic plasticity. These results demonstrate how the same synchronized input spike trains from the inferior colliculus can be transformed into different representations of temporal modulation by divergent synaptic properties.

  18. Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Xuanbin Wang

    2014-01-01

    Full Text Available Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and Methods. Chinese medicines (including Chinese medicinal herbs, animal parts, and minerals were used in the study. The key words including “cancer”, “cell death”, “apoptosis”, “autophagy,” “necrosis,” and “Chinese medicine” were used in retrieval of related information from PubMed and other databases. Results. The cell death induced by Chinese medicines is described as apoptotic, autophagic, or necrotic cell death and other types with an emphasis on their mechanisms of anticancer action. The relationship among different types of cell death induced by Chinese medicines is critically reviewed and discussed. Conclusions. This review summarizes that CMs treatment could induce multiple pathways leading to cancer cell death, in which apoptosis is the dominant type. To apply these preclinical researches to clinic application will be a key issue in the future.

  19. A Postulated Mechanism That Leads to Materialization and Dematerialization of Matter and to Antigravity.

    Science.gov (United States)

    Bearden, Thomas E.

    This document presents a discussion of the postulated mechanism that leads to the materialization and dematerialization of matter and to antigravity. The mechanism also explains why an orbital electron does not radiate energy, in contradiction to classical electromagnetic theory. One of the paradoxes of special relativity is explained. A new model…

  20. Elucidating the cellular uptake mechanism of aptamer-functionalized graphene-isolated-Au-nanocrystals with dual-modal imaging.

    Science.gov (United States)

    Wang, Shanshan; Liu, Zhangkun; Zou, Yuxiu; Lai, Xiaofang; Ding, Ding; Chen, Long; Zhang, Liqin; Wu, Yuan; Chen, Zhuo; Tan, Weihong

    2016-05-23

    Elucidating the endocytosis and metabolism of nanoparticles in cells could improve the diagnostic sensitivity and therapeutic efficiency. In this work, we explore the cellular uptake mechanism of a biocompatible nanocrystal nanostructure, graphene-isolated-Au-nanocrystals (GIANs), by monitoring the intrinsic Raman and two-photon luminescence signals of GIANs in live cells. Aptamers functionalized on the GIAN nanostructure through simple, but strong, π-π interactions entered the cells through a clathrin-dependent pathway, while unmodified GIANs mainly entered the cells through a caveolae-mediated endocytosis pathway. Thus, it can be concluded that the mechanism of cellular uptake in these graphene-isolated-Au-nanocrystal nanostructures is determined by the presence or absence of aptamer modification. PMID:27111129

  1. RNase-L control of cellular mRNAs: roles in biologic functions and mechanisms of substrate targeting.

    Science.gov (United States)

    Brennan-Laun, Sarah E; Ezelle, Heather J; Li, Xiao-Ling; Hassel, Bret A

    2014-04-01

    RNase-L is a mediator of type 1 interferon-induced antiviral activity that has diverse and critical cellular roles, including the regulation of cell proliferation, differentiation, senescence and apoptosis, tumorigenesis, and the control of the innate immune response. Although RNase-L was originally shown to mediate the endonucleolytic cleavage of both viral and ribosomal RNAs in response to infection, more recent evidence indicates that RNase-L also functions in the regulation of cellular mRNAs as an important mechanism by which it exerts its diverse biological functions. Despite this growing body of work, many questions remain regarding the roles of mRNAs as RNase-L substrates. This review will survey known and putative mRNA substrates of RNase-L, propose mechanisms by which it may selectively cleave these transcripts, and postulate future clinical applications. PMID:24697205

  2. Profiling human protein degradome delineates cellular responses to proteasomal inhibition and reveals a feedback mechanism in regulating proteasome homeostasis

    OpenAIRE

    Yu, Tao; Tao, Yonghui; Yang, Meiqiang; Chen, Peng; Gao, XiaoBo; Zhang, Yanbo; Zhang,Tao; Chen, Zi; Hou, Jian; Zhang, Yan; Ruan, Kangcheng; Wang, Hongyan; Hu, Ronggui

    2014-01-01

    Global change in protein turnover (protein degradome) constitutes a central part of cellular responses to intrinsic or extrinsic stimuli. However, profiling protein degradome remains technically challenging. Recently, inhibition of the proteasome, e.g., by using bortezomib (BTZ), has emerged as a major chemotherapeutic strategy for treating multiple myeloma and other human malignancies, but systematic understanding of the mechanisms for BTZ drug action and tumor drug resistance is yet to be a...

  3. Regulation of hTERT transcription: a target of cellular and viral mechanisms for immortalization and carcinogenesis

    OpenAIRE

    Horikawa, Izumi; Michishita, Eriko; Barrett, J. Carl

    2004-01-01

    A hallmark of human cancer cells is immortal cell growth, which is associated with telomere maintenance by telomerase. The transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene is a major mechanism that negatively and positively controls telomerase activity in normal and cancer cells, respectively. A growing body of data suggests that various cellular and viral factors and pathways involved in cell senescence, immortalization and carcinogenesis act on the hTERT...

  4. Complex I Disorders: Causes, Mechanisms, and Development of Treatment Strategies at the Cellular Level

    Science.gov (United States)

    Valsecchi, Federica; Koopman, Werner J. H.; Manjeri, Ganesh R.; Rodenburg, Richard J.; Smeitink, Jan A. M.; Willems, Peter H. G. M.

    2010-01-01

    Mitochondrial oxidative phosphorylation (OXPHOS) represents the final step in the conversion of nutrients into cellular energy. Genetic defects in the OXPHOS system have an incidence between 1:5,000 and 1:10,000 live births. Inherited isolated deficiency of the first complex (CI) of this system, a multisubunit assembly of 45 different proteins,…

  5. Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on Targeted Therapy.

    Science.gov (United States)

    Gill, Harinder; Leung, Anskar Y H; Kwong, Yok-Lam

    2016-01-01

    Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal hematopoietic stem cell disorders characterized by cytopenia, ineffective hematopoiesis, and progression to secondary acute myeloid leukemia in high-risk cases. Conventional prognostication relies on clinicopathological parameters supplemented by cytogenetic information. However, recent studies have shown that genetic aberrations also have critical impacts on treatment outcome. Moreover, these genetic alterations may themselves be a target for treatment. The mutation landscape in MDS is shaped by gene aberrations involved in DNA methylation (TET2, DNMT3A, IDH1/2), histone modification (ASXL1, EZH2), the RNA splicing machinery (SF3B1, SRSF2, ZRSR2, U2AF1/2), transcription (RUNX1, TP53, BCOR, PHF6, NCOR, CEBPA, GATA2), tyrosine kinase receptor signaling (JAK2, MPL, FLT3, GNAS, KIT), RAS pathways (KRAS, NRAS, CBL, NF1, PTPN11), DNA repair (ATM, BRCC3, DLRE1C, FANCL), and cohesion complexes (STAG2, CTCF, SMC1A, RAD21). A detailed understanding of the pathogenetic mechanisms leading to transformation is critical for designing single-agent or combinatorial approaches in target therapy of MDS. PMID:27023522

  6. Mechanical performances of lead-free solder joint connections with applications in the aerospace domain

    Directory of Open Access Journals (Sweden)

    Georgiana PADURARU

    2016-03-01

    Full Text Available The paper presents some theoretical and experimental aspects regarding the tribological performances of lead-free solder joint connections, with application in the aerospace domain. In order to highlight the mechanical and tribological properties of solder joint in correlation with different pad finishes, there were made some mechanical determinations using a dedicated Share Test System. The theoretical model highlights the link between the experimental results and the influence of gravitational acceleration on the mechanical and functional integrity of the electronic assemblies that works in vibration environment. The paper novelty is provided by the interdisciplinary experiment that offers results that can be used in the mechanical, tribological, electronical and aerospace domains.

  7. Thermal protection mechanism of heat pipe in leading edge under hypersonic conditions

    OpenAIRE

    Peng Wengen; He Yurong; Wang Xinzhi; Zhu Jiaqi; Han Jiecai

    2015-01-01

    Sharp local structure, like the leading edge of hypersonic aircraft, confronts a severe aerodynamic heating environment at a Mach number greater than 5. To eliminate the danger of a material failure, a semi-active thermal protection system is proposed by integrating a metallic heat pipe into the structure of the leading edge. An analytical heat-balance model is established from traditional aerodynamic theories, and then thermal and mechanical characteristics of the structure are studied at Ma...

  8. Numerical study of mechanical behavior of ceramic composites under compression loading in the framework of movable cellular automaton method

    Energy Technology Data Exchange (ETDEWEB)

    Konovalenko, Igor S., E-mail: igkon@ispms.tsc.ru; Smolin, Alexey Yu., E-mail: igkon@ispms.tsc.ru; Konovalenko, Ivan S., E-mail: igkon@ispms.tsc.ru [Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation); Promakhov, Vladimir V. [Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055, Russia and National Research Tomsk State University, Tomsk, 634050 (Russian Federation); Psakhie, Sergey G. [Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation); National Research Tomsk State University, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2014-11-14

    Movable cellular automaton method was used for investigating the mechanical behavior of ceramic composites under uniaxial compression. A 2D numerical model of ceramic composites based on oxides of zirconium and aluminum with different structural parameters was developed using the SEM images of micro-sections of a real composite. The influence of such structural parameters as the geometrical dimensions of layers, inclusions, and their spatial distribution in the sample, the volume content of the composite components and their mechanical properties (as well as the amount of zirconium dioxide that underwent the phase transformation) on the fracture, strength, deformation and dissipative properties was investigated.

  9. An evaluation of the mechanism of ABCA7 on cellular lipid release in ABCA7-HEC293 cell

    Institute of Scientific and Technical Information of China (English)

    WU Cheng-ai; WANG Na; ZHAO Dan-hui

    2013-01-01

    Background ABCA7 is a member of the ABCA subfamily that shows a high degree of homology to ABCA1 and,like ABCA1,mediates cellular cholesterol and phospholipid release by apolipoproteins when transfected in vitro.However,expression of ABCA7 has been shown to be downregulated by increased cellular cholesterol while ABCA1 was upregulated.Methods The underlying mechanism for this effect was examined in ABCA1 or ABCA7-transfected HEC293.Lipid content in the medium and cells was determined by enzymatic assays.Gene expression was quantitated by real time PCR,and protein content was determined by Western blotting.Results While ABCA7 mRNA was decreased by 25-hydroxycholesterol treatment,ABCA1 was apparently increased.Treatment with the synthetic LXR agonist T0901317 (T09) upregulated ABCA1 expression and apoAI-mediated cellular lipid release in ABCA1-transfected HEC293 cells,but ABCA7 expression and cellular lipid release in ABCA7-transfected HEC293 cells showed no obvious changes.Conclusion The ABCA7 gene is regulated by sterol in a direction opposite to that of ABCA1.

  10. A postulated mechanism that leads to materialization and dematerialization of matter and to antigravity. Technical report

    Energy Technology Data Exchange (ETDEWEB)

    Bearden, T.E.

    1975-10-08

    This report presents a discussion of the postulated mechanism that leads to the materialization and dematerialization of matter and to antigravity. The mechanism also explains why an orbital electron does not radiate energy, in contradiction to classical electromagnetic theory. One of the paradoxes of special relativity is explained. A new model of a photon is advanced. The relativistic increase of mass with velocity is explained. (GRA)

  11. Fracture Mechanics Analyses of the Slip-Side Joggle Regions of Wing-Leading-Edge Panels

    Science.gov (United States)

    Raju, Ivatury S.; Knight, Norman F., Jr.; Song, Kyongchan; Phillips, Dawn R.

    2011-01-01

    The Space Shuttle wing-leading edge consists of panels that are made of reinforced carbon-carbon. Coating spallation was observed near the slip-side region of the panels that experience extreme heating. To understand this phenomenon, a root-cause investigation was conducted. As part of that investigation, fracture mechanics analyses of the slip-side joggle regions of the hot panels were conducted. This paper presents an overview of the fracture mechanics analyses.

  12. Fracture mechanics analyses of the slip-side joggle regions of wing-leading-edge panels

    Directory of Open Access Journals (Sweden)

    Kyongchan Song

    2011-01-01

    Full Text Available The Space Shuttle wing-leading edge consists of panels that are made of reinforced carbon-carbon. Coating spallation was observed near the slip-side region of the panels that experience extreme heating. To understand this phenomenon, a root-cause investigation was conducted. As part of that investigation, fracture mechanics analyses of the slip-side joggle regions of the hot panels were conducted. This paper presents an overview of the fracture mechanics analyses.

  13. Cellular origins and differentiation control mechanisms during periodontal development and wound healing.

    Science.gov (United States)

    Pitaru, S; McCulloch, C A; Narayanan, S A

    1994-03-01

    In the context of cellular origins, odontogenic epithelium and oral epithelium are the sources for junctional epithelium during development and during wound healing respectively. In contrast, both odontogenic and non-odontogenic mesenchyme contain the progenitors for gingival fibroblasts in developing tissues while in wounded tissues, gingival fibroblasts are derived from gingival connective tissues and comprise a heterogeneous population of cells with diverse properties and functions. Periodontal ligament, bone and cementum cell populations apparently originate from dental follicle progenitor cells during development, but during wound healing derive from ancestral cells in periodontal ligament and bone. Cellular differentiation in developing periodontium is governed in part by epithelial-mesenchymal interactions that generate specific signals which regulate selective cell populations in time and space. On the other hand, differentiation during wound healing and regeneration is regulated by a vast array of extracellular matrix informational molecules and by cytokines that induce both selective and non-selective responses in the different cell lineages and their precursors. Further, several important signalling systems are irretrievably lost after development is complete. Thus, in the context of cellular origins and differentiation, developing and wounded periodontal tissues exhibit fundamental differences. Future prospects for improved healing and regeneration of periodontal tissues may derive from identification and isolation of informational molecules that are stored in connective tissue matrices. These molecules and elucidation of their functions may open new perspectives in our understanding of the biology of periodontal wound healing and may provide novel approaches to periodontal regeneration. PMID:8158503

  14. Incorporation of Ortho- and Meta-Tyrosine Into Cellular Proteins Leads to Erythropoietin-Resistance in an Erythroid Cell Line

    Directory of Open Access Journals (Sweden)

    Esztella Mikolás

    2014-04-01

    Full Text Available Background/Aims: Erythropoietin-resistance is an unsolved concern in the treatment of renal anaemia. We aimed to investigate the possible role of ortho- and meta-tyrosine - the hydroxyl free radical products of L-phenylalanine - in the development of erythropoietin-resistance. Methods: TF-1 erythroblast cell line was used. Cell concentration was determined on day 1; 2 and 3 by two independent observers simultaneously in Bürker cell counting chambers. Protein concentration was determined with colorimetric method. Para-, ortho- and meta-tyrosine levels were measured using reverse phase-HPLC with fluorescence detection. Using Western blot method activating phosphorylation of STAT5 and ERK1/2 were investigated. Results: We found a time- and concentration-dependent decrease of erythropoietin-induced proliferative activity in case of ortho- and meta-tyrosine treated TF-1 erythroblasts, compared to the para-tyrosine cultured cells. Decreased erythropoietin-response could be regained with a competitive dose of para-tyrosine. Proteins of erythroblasts treated by ortho- or meta-tyrosine had lower para-tyrosine and higher ortho- or meta-tyrosine content. Activating phosphorylation of ERK and STAT5 due to erythropoietin was practically prevented by ortho- or meta-tyrosine treatment. Conclusion: According to this study elevated ortho- and meta-tyrosine content of erythroblasts may lead to the dysfunction of intracellular signaling, resulting in erythropoietin-hyporesponsiveness.

  15. Investigation of mechanical properties for open cellular structure CoCrMo alloy fabricated by selective laser melting process

    Science.gov (United States)

    Azidin, A.; Taib, Z. A. M.; Harun, W. S. W.; Che Ghani, S. A.; Faisae, M. F.; Omar, M. A.; Ramli, H.

    2015-12-01

    Orthodontic implants have been a major focus through mechanical and biological performance in advance to fabricate shape of complex anatomical. Designing the part with a complex mechanism is one of the challenging process and addition to achieve the balance and desired mechanical performance brought to the right manufacture technique to fabricate. Metal additive manufacturing (MAM) is brought forward to the newest fabrication technology in this field. In this study, selective laser melting (SLM) process was utilized on a medical grade cobalt-chrome molybdenum (CoCrMo) alloy. The work has focused on mechanical properties of the CoCrMo open cellular structures samples with 60%, 70%, and 80% designed volume porosity that could potentially emulate the properties of human bone. It was observed that hardness values decreased as the soaking time increases except for bottom face. For compression test, 60% designed volume porosity demonstrated highest ultimate compressive strength compared to 70% and 80%.

  16. Thermo-mechanical tests on W7-X current lead flanges

    Energy Technology Data Exchange (ETDEWEB)

    Dhard, Chandra Prakash, E-mail: dhard@ipp.mpg.de; Rummel, Thomas; Zacharias, Daniel; Bykov, Victor; Moennich, Thomas; Buscher, Klaus-Peter

    2013-10-15

    Highlights: • There are significant mechanical loads on the cryostat and radial flanges for W7-X current leads. • These are due to evacuation of W7-X cryostat, cool-down of cold mass, electro-magnetic forces and self weight of leads. • The actual mechanical loads were reduced to simplify the experimental set-up. • The tests were carried out on mock-up flanges test assembly at ambient temperature and at 77 K. • The thermo-mechanical tests on W7-X current lead flanges validate the design and joints of these flanges to the leads. -- Abstract: Fourteen pieces of high temperature superconducting current leads (CL) arranged in seven pairs, will be installed on the outer vessel of Wendelstein 7-X (W7-X) stellarator. In order to support the CL, it is provided with two glass fiber reinforce plastic (GFRP) flanges, namely, the lower cryostat flange (CF) remaining at room temperature and upper radial flange (RF) at about 5 K. Both the flanges i.e. CF and RF experience high mechanical loads with respect to the CL, due to the evacuation of W7-X cryostat, cool-down of cold mass including the CL, electro-magnetic forces due to current and plasma operations and self weight of CL. In order to check the integrity of these flanges for such mechanical loads, thermo-mechanical tests were carried out on these flanges at room temperatures and at liquid nitrogen (LN2) temperatures. The details of test set-up, results and modeling are described in the paper.

  17. Thermo-mechanical tests on W7-X current lead flanges

    International Nuclear Information System (INIS)

    Highlights: • There are significant mechanical loads on the cryostat and radial flanges for W7-X current leads. • These are due to evacuation of W7-X cryostat, cool-down of cold mass, electro-magnetic forces and self weight of leads. • The actual mechanical loads were reduced to simplify the experimental set-up. • The tests were carried out on mock-up flanges test assembly at ambient temperature and at 77 K. • The thermo-mechanical tests on W7-X current lead flanges validate the design and joints of these flanges to the leads. -- Abstract: Fourteen pieces of high temperature superconducting current leads (CL) arranged in seven pairs, will be installed on the outer vessel of Wendelstein 7-X (W7-X) stellarator. In order to support the CL, it is provided with two glass fiber reinforce plastic (GFRP) flanges, namely, the lower cryostat flange (CF) remaining at room temperature and upper radial flange (RF) at about 5 K. Both the flanges i.e. CF and RF experience high mechanical loads with respect to the CL, due to the evacuation of W7-X cryostat, cool-down of cold mass including the CL, electro-magnetic forces due to current and plasma operations and self weight of CL. In order to check the integrity of these flanges for such mechanical loads, thermo-mechanical tests were carried out on these flanges at room temperatures and at liquid nitrogen (LN2) temperatures. The details of test set-up, results and modeling are described in the paper

  18. Cellular Homeostasis and Aging.

    Science.gov (United States)

    Hartl, F Ulrich

    2016-06-01

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans. PMID:27050288

  19. Behavioural evidence for separate mechanisms of audiovisual temporal binding as a function of leading sensory modality.

    Science.gov (United States)

    Cecere, Roberto; Gross, Joachim; Thut, Gregor

    2016-06-01

    The ability to integrate auditory and visual information is critical for effective perception and interaction with the environment, and is thought to be abnormal in some clinical populations. Several studies have investigated the time window over which audiovisual events are integrated, also called the temporal binding window, and revealed asymmetries depending on the order of audiovisual input (i.e. the leading sense). When judging audiovisual simultaneity, the binding window appears narrower and non-malleable for auditory-leading stimulus pairs and wider and trainable for visual-leading pairs. Here we specifically examined the level of independence of binding mechanisms when auditory-before-visual vs. visual-before-auditory input is bound. Three groups of healthy participants practiced audiovisual simultaneity detection with feedback, selectively training on auditory-leading stimulus pairs (group 1), visual-leading stimulus pairs (group 2) or both (group 3). Subsequently, we tested for learning transfer (crossover) from trained stimulus pairs to non-trained pairs with opposite audiovisual input. Our data confirmed the known asymmetry in size and trainability for auditory-visual vs. visual-auditory binding windows. More importantly, practicing one type of audiovisual integration (e.g. auditory-visual) did not affect the other type (e.g. visual-auditory), even if trainable by within-condition practice. Together, these results provide crucial evidence that audiovisual temporal binding for auditory-leading vs. visual-leading stimulus pairs are independent, possibly tapping into different circuits for audiovisual integration due to engagement of different multisensory sampling mechanisms depending on leading sense. Our results have implications for informing the study of multisensory interactions in healthy participants and clinical populations with dysfunctional multisensory integration. PMID:27003546

  20. Urban gardens: Lead exposure, recontamination mechanisms, and implications for remediation design

    International Nuclear Information System (INIS)

    Environmental lead contamination is prevalent in urban areas where soil represents a significant sink and pathway of exposure. This study characterizes the speciation of lead that is relevant to local recontamination and to human exposure in the backyard gardens of Roxbury and Dorchester, MA, USA. One hundred forty-one backyard gardens were tested by X-ray fluorescence, and 81% of gardens have lead levels above the US EPA action limit of 400 μg/g. Raised gardening beds are the in situ exposure reduction method used in the communities to promote urban gardening. Raised beds were tested for lead and the results showed that the lead concentration increased from an initial range of 150±40 μg/g to an average of 336 μg/g over 4 years. The percent distribution of lead in the fine grain soil (<100 μm) and the trace metal signature of the raised beds support the conclusion that the mechanism of recontamination is wind-transported particles. Scanning electron microscopy and sequential extraction were used to characterize the speciation of lead, and the trace metal signature of the fine grain soil in both gardens and raised gardening beds is characteristic of lead-based paint. This study demonstrates that raised beds are a limited exposure reduction method and require maintenance to achieve exposure reduction goals. An exposure model was developed based on a suite of parameters that combine relevant values from the literature with site-specific quantification of exposure pathways. This model suggests that consumption of homegrown produce accounts for only 3% of children's daily exposure of lead while ingestion of fine grained soil (<100 μm) accounts for 82% of the daily exposure. This study indicates that urban lead remediation on a yard-by-yard scale requires constant maintenance and that remediation may need to occur on a neighborhood-wide scale

  1. Helicobacter pylori eradication to prevent gastric cancer:underlying molecular and cellular mechanisms

    Institute of Scientific and Technical Information of China (English)

    Shingo Tsuji; Norio Hayashi; Masahiko Tsujii; Hiroaki Murata; Tsutomu Nishida; Masato Komori; Masakazu Yasumaru; Shuji Ishii; Yoshiaki Sasayama; Sunao Kawano

    2006-01-01

    Numerous cellular and molecular events have been described in development of gastric cancer. In this article,we overviewed roles of Helicobacter pylori(H pylori) infection on some of the important events in gastric carcinogenesis and discussed whether these cellular and molecular events are reversible after cure of the infection. There are several bacterial components affecting gastric epithelial kinetics and promotion of gastric carcinogenesis. The bacterium also increases risks of genetic instability and mutations due to NO and other reactive oxygen species. Epigenetic silencing of tumor suppressor genes such as RUNX3 may alter the frequency of phenotype change of gastric glands to those with intestinal metaplasia. Host factors such as increased expression of growth factors, cytokines and COX-2 have been also reported in non-cancerous tissue in H pylori-positive subjects. It is noteworthy that most of the above phenomena are reversed after the cure of the infection. However,some of them including overexpression of COX-2 continue to exist and may increase risks for carcinogenesis in metaplastic or dysplastic mucosa even after successful H pylori eradication. Thus, H pylori eradication may not completely abolish the risk for gastric carcinogenesis. Efficiency of the cure of the infection in suppressing gastric cancer depends on the timing and the target population,and warrant further investigation.

  2. Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation

    Science.gov (United States)

    Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

    2016-01-01

    The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm−3) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability. PMID:27174450

  3. Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation.

    Science.gov (United States)

    Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

    2016-01-01

    The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density <3 mg cm(-3)) yet mechanically resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability. PMID:27174450

  4. Leaching Mechanism of Complicated Antimony-Lead Concentrate and Sulfur Formation in Slurry Electrolysis

    Institute of Scientific and Technical Information of China (English)

    WangChengyan; QiuDingfan; JiangPeihai

    2004-01-01

    Anodic reaction mechanism of complicated antimony-lead concentrate in slurry electrolysis was investigated by the anodic polarization curves determined under various conditions. The main reactions on the anode are the oxidations of FeCln(2-n) . Though the oxidation of jamesonite particle on the anode can occur during the whole process, it is less. With the help of mineralogy studies and relevant tests, the leaching reaction mechanism of jameson[to and gudmundite during slurry electrolysis was ascertained. Because of the oxidation reaction of FeCl3 produced by antimony-lead concentrate itself, the non-oxidation complex acid dissolution of jameson[re, the oxidation complex acid dissolution of gudmundite, and the oxidation of air carried by stirring, the leaching ratio of antimony reaches about 35% when HCl-NH4Cl solution is used to leach antimony-lead concentrate directly. So when the theoretical electric quantity is given to oxidation of antimony in slurry electrolysis, all of antimony, lead and iron containing in antimony-lead concentrate, are leached. The formation of sulfur is through the directly redox reaction of Fe3+ and jameson[re. The S2- in jamesonite is oxidized into S0 , and forms the crystals of sulfur again on the spot. The redox reaction of Fe3+ and H2S formed by non-oxidative acid dissolution of jamesonite is less.

  5. Cellular and molecular mechanism study of declined intestinal transit function in the cholesterol gallstone formation process of the guinea pig

    OpenAIRE

    Fan, Ying; Wu, Shuodong; YIN, ZHENHUA; Fu, Bei-Bei

    2014-01-01

    The aim of this study was to investigate the cellular and molecular mechanisms of declined intestinal transit (IT) function in the cholesterol gallstone (CG) formation process. Forty guinea pigs were divided into an experimental group (EG) and a control group (CoG), and the reverse transcription-polymerase chain reaction (RT-PCR) was performed for the analysis of c-kit and stem cell factor (scf) mRNA expression in the small bowel. In addition, immunofluorescence staining and confocal laser mi...

  6. MECHANISMS OF DAMAGING EFFECT OF MANGENESE IN TOXIC CONCENTRATIONS ON CELLULAR AND SUBCELLULAR LEVELS

    Directory of Open Access Journals (Sweden)

    Goncharenko A. V.

    2012-11-01

    Full Text Available Influence of subtoxic concentration of manganese chloride in dose equal to LD 50 on condition of plasmatic membranes (model: erythrocytes and functional activity of cell power (model: the isolated liver mitochondrion of rats was studied. It was established that manganese chloride in fixed concentration caused authentic augmentation of sorption capacity of erythrocytes towards alcian blue, influenced increasing of their spontaneous haemolysis and activation of peroxide oxidation of lipids. In experiment on the isolated mitochondrion it was proved that manganese chloride caused dissociation of an oxidizing phosphorusling and complete inhibition of respiration in concentrations of 3 and 4,5mM. These dependences testify that subtoxic concentration of manganese can damage the cell energy. Thus, this pilot research indicated damaging effect of manganese on cellular (erythrocytes and subcellular (mitochondrion levels which are realized through external functioning of membrane structures and deprived them from restoration.

  7. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Soo Mi Kim

    2016-07-01

    Full Text Available Studies in humans have shown that 3,3′-diindolylmethane (DIM, which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers.

  8. An intrinsic poperty of memory of the Cellular automaton infrastructure of Nature leading to the organization of the physical world as an Internet o things; TOE = IOT

    Science.gov (United States)

    Berkovich, Simon

    2015-04-01

    The undamental advantage of a Cellular automaton construction foris that it can be viewed as an undetectable absolute frame o reference, in accordance with Lorentz-Poincare's interpretation.. The cellular automaton model for physical poblems comes upon two basic hurdles: (1) How to find the Elemental Rule that, and how to get non-locality from local transformations. Both problems are resolved considering the transfomation rule of mutual distributed synchronization Actually any information proessing device starts with a clocking system. and it turns out that ``All physical phenomena are different aspects of the high-level description of distributed mutual synchronization in a network of digital clocks''. Non-locality comes from two hugely different time-scales of signaling.. The universe is acombinines information and matter processes, These fast spreading diffusion wave solutions create the mechanism of the Holographic Universe. And thirdly Disengaged from synchronization, circular counters can perform memory functions by retaining phases of their oscillations, an idea of Von Neumann'. Thus, the suggested model generates the necessary constructs for the physical world as an Internet of Things. Life emerges due to the specifics of macromolecules that serve as communication means, with the holographic memory...

  9. Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling

    Science.gov (United States)

    Gibson, Daniel; Chang, Frederick; Gnad, Florian; Gunawardena, Jeremy

    2016-01-01

    The molecular complexity within a cell may be seen as an evolutionary response to the external complexity of the cell’s environment. This suggests that the external environment may be harnessed to interrogate the cell’s internal molecular architecture. Cells, however, are not only nonlinear and non-stationary, but also exhibit heterogeneous responses within a clonal, isogenic population. In effect, each cell undertakes its own experiment. Here, we develop a method of cellular interrogation using programmable microfluidic devices which exploits the additional information present in cell-to-cell variation, without requiring model parameters to be fitted to data. We focussed on Ca2+ signalling in response to hormone stimulation, which exhibits oscillatory spiking in many cell types and chose eight models of Ca2+ signalling networks which exhibit similar behaviour in simulation. We developed a nonlinear frequency analysis for non-stationary responses, which could classify models into groups under parameter variation, but found that this question alone was unable to distinguish critical feedback loops. We further developed a nonlinear amplitude analysis and found that the combination of both questions ruled out six of the models as inconsistent with the experimentally-observed dynamics and heterogeneity. The two models that survived the double interrogation were mathematically different but schematically identical and yielded the same unexpected predictions that we confirmed experimentally. Further analysis showed that subtle mathematical details can markedly influence non-stationary responses under parameter variation, emphasising the difficulty of finding a “correct” model. By developing questions for the pathway being studied, and designing more versatile microfluidics, cellular interrogation holds promise as a systematic strategy that can complement direct intervention by genetics or pharmacology. PMID:27367445

  10. Comparisons of Mechanical Properties of sub-mm Lead Based and Lead Free Based Solder Using in Manufacturing of Printed Circuits

    OpenAIRE

    Alaa Hasan Ali

    2014-01-01

    This study investigates the mechanical compression properties of tin-lead and lead-free alloy spherical balls, using more than 500 samples to identify statistical variability in the properties in each alloy. Isothermal aging was done to study and compare the aging effect on the microstructure and properties. The results showed significant elastic and plastic anisotropy of tin phase in lead-free tin based solder and that was compared with simulation using a Crystal Plasticity Finite Element (C...

  11. Presynaptic Mechanisms of Lead Neurotoxicity: Effects on Vesicular Release, Vesicle Clustering and Mitochondria Number

    OpenAIRE

    Zhang, Xiao-Lei; Sara R Guariglia; McGlothan, Jennifer L.; Stansfield, Kirstie H.; Stanton, Patric K.; Guilarte, Tomás R.

    2015-01-01

    Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+...

  12. Microwave emission from lead zirconate titanate induced by impulsive mechanical load

    International Nuclear Information System (INIS)

    This paper focuses on microwave emission from Lead zirconate titanate Pb [ZrxTi1−x] O3 (PZT) induced by mechanical stressing. The mechanical stress was initiated by impact of a sharp tungsten indenter on the upper surface of PZT ceramic. The sequences of microwave and current impulses, which flew from indenter to electric ground, were detected simultaneously. The voltage between the upper and lower surface of ceramic was measured to obtain the behavior of mechanical force acting on ceramic during the impact. It was found that the amplitude, form, and frequency of measured microwave impulses were different by compression and restitution phase of impact. Two different mechanisms of electron emission, responsible for microwave impulse generation, were proposed based on the dissimilar impulse behavior. The field emission from tungsten indenter is dominant during compression, whereas ferroemission dominates during restitution phase. Indeed, it was observed that the direction of the current flow, i.e., sign of current impulses is changed by transitions from compression to restitution phase of impact. The observed dissimilar behavior of microwave impulses, caused by increasing and decreasing applied force, can be used to calculate the contact time and behavior of mechanical force during mechanical impact on ceramic surface. It is shown that the generation of microwave impulses exhibits high reproducibility, impulse intensity, a low damping factor, and high mechanical failure resistance. Based on these microwave emission properties of PZT, the development of new type of stress sensor with spatial resolution of few microns becomes possible

  13. Inter-cellular nanovesicle mediated microRNA transfer: a mechanism of environmental modulation of hepatocellular cancer cell growth

    Science.gov (United States)

    Kogure, Takayuki; Lin, Wen-Lang; Yan, Irene K.; Braconi, Chiara; Patel, Tushar

    2011-01-01

    Hepatocellular carcinoma (HCC) is characterized by a propensity for multifocality, growth by local spread, and dysregulation of multiple signaling pathways. These features may be determined by the tumoral microenvironment. The potential of tumor cells to modulate HCC growth and behavior by secreted proteins has been extensively studied. In contrast the potential for genetic modulation is poorly understood. We investigated the role and involvement of tumor derived nanovesicles capable of altering gene expression, and characterized their ability to modulate cell signaling and biological effects in other cells. We show that HCC cells can produce nanovesicles, exosomes, that differ in both RNA and protein content from their cells of origin. These can be taken up and internalized by other cells, and can transmit a functional transgene. The microRNA content of these exosomes was examined, and a subset that is highly enriched within exosomes was identified. A combinatorial approach to identify potential targets identified transforming growth factor β activated kinase-1 (TAK1) as the most likely candidate pathway that could be modulated by these miRNA. Loss of TAK1 has been implicated in hepatocarcinogenesis and is a biologically plausible target for inter-cellular modulation. We showed that HCC cell derived exosomes can modulate TAK1 expression and associated signaling and enhance transformed cell growth in recipient cells. Conclusion: Exosome mediated miRNA transfer is an important mechanism of inter-cellular communication in HCC cells. These observations identify a unique inter-cellular mechanism that could potentially contribute to local spread, intrahepatic metastases or multifocal growth in HCC. PMID:21721029

  14. Mechanism of Laser/light beam interaction at cellular and tissue level and study of the influential factors for the application of low level laser therapy

    OpenAIRE

    Khalid, Muhammad Zeeshan

    2016-01-01

    After the discovery of laser therapy it was realized it has useful application of wound healing and reduce pain, but due to the poor understanding of the mechanism and dose response this technique remained to be controversial for therapeutic applications. In order to understand the working and effectiveness different experiments were performed to determine the laser beam effect at the cellular and tissue level. This article discusses the mechanism of beam interaction at tissues and cellular l...

  15. Cellular graphene aerogel combines ultralow weight and high mechanical strength: A highly efficient reactor for catalytic hydrogenation

    Science.gov (United States)

    Zhang, Bingxing; Zhang, Jianling; Sang, Xinxin; Liu, Chengcheng; Luo, Tian; Peng, Li; Han, Buxing; Tan, Xiuniang; Ma, Xue; Wang, Dong; Zhao, Ning

    2016-05-01

    The construction of three-dimensional graphene aerogels (GAs) is of great importance owing to their outstanding properties for various applications. Up to now, the combination of ultralow weight and super mechanical strength for GA remains a great challenge. Here we demonstrate the fabrication of cellular GAs by a facile, easily controlled and versatile route, i.e. the chemical reduction of graphene oxide assemblies at oil-water interface under a mild condition (70 °C). The GA is ultralight (with density resilient because the walls of the cell closely pack in a highly ordered manner to maximize mechanical strength. The GA has been utilized as an appealing reactor for catalytic hydrogenation, which exhibited great advantages such as large oil absorption capability, exceptional catalytic activity, ease of product separation and high stability.

  16. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response.

    Science.gov (United States)

    Maiti, A; Small, W; Lewicki, J P; Weisgraber, T H; Duoss, E B; Chinn, S C; Pearson, M A; Spadaccini, C M; Maxwell, R S; Wilson, T S

    2016-01-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter's improved long-term stability and mechanical performance. PMID:27117858

  17. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    Science.gov (United States)

    Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-04-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance.

  18. 3D printed cellular solid outperforms traditional stochastic foam in long-term mechanical response

    Science.gov (United States)

    Maiti, A.; Small, W.; Lewicki, J. P.; Weisgraber, T. H.; Duoss, E. B.; Chinn, S. C.; Pearson, M. A.; Spadaccini, C. M.; Maxwell, R. S.; Wilson, T. S.

    2016-01-01

    3D printing of polymeric foams by direct-ink-write is a recent technological breakthrough that enables the creation of versatile compressible solids with programmable microstructure, customizable shapes, and tunable mechanical response including negative elastic modulus. However, in many applications the success of these 3D printed materials as a viable replacement for traditional stochastic foams critically depends on their mechanical performance and micro-architectural stability while deployed under long-term mechanical strain. To predict the long-term performance of the two types of foams we employed multi-year-long accelerated aging studies under compressive strain followed by a time-temperature-superposition analysis using a minimum-arc-length-based algorithm. The resulting master curves predict superior long-term performance of the 3D printed foam in terms of two different metrics, i.e., compression set and load retention. To gain deeper understanding, we imaged the microstructure of both foams using X-ray computed tomography, and performed finite-element analysis of the mechanical response within these microstructures. This indicates a wider stress variation in the stochastic foam with points of more extreme local stress as compared to the 3D printed material, which might explain the latter’s improved long-term stability and mechanical performance. PMID:27117858

  19. Life under Climate Change Scenarios: Sea Urchins’ Cellular Mechanisms for Reproductive Success

    Directory of Open Access Journals (Sweden)

    Desislava Bögner

    2016-03-01

    Full Text Available Ocean Acidification (OA represents a major field of research and increased efforts are being made to elucidate its repercussions on biota. Species survival is ensured by successful reproduction, which may be threatened under detrimental environmental conditions, such as OA acting in synergy with other climate change related stressors. Achieving successful gametogenesis, fertilization, and the development of larvae into healthy juveniles and adults is crucial for the perpetuation of species and, thus, ecosystems’ functionality. The considerable vulnerability of the abovementioned developmental stages to the adverse conditions that future OA may impose has been shown in many species, including sea urchins which are commonly used due to the feasibility of their maintenance in captivity and the great amount of gametes that a mature adult is able to produce. In the present review, the latest knowledge about the impact of OA on various stages of the life cycle of sea urchins is summarized with remarks on the possible impact of other stressors. The cellular physiology of the gametes before, at fertilization and, at early development, is extensively described with a focus on the complex enzymatic machinery and the intracellular pH (pHi and Ca2+ homeostasis for their vulnerability when facing adverse conditions such as acidification, temperature variations, or hypoxia.

  20. [Changes of the neuronal membrane excitability as cellular mechanisms of learning and memory].

    Science.gov (United States)

    Gaĭnutdinov, Kh L; Andrianov, V V; Gaĭnutdinova, T Kh

    2011-01-01

    In the presented review given literature and results of own studies of dynamics of electrical characteristics of neurons, which change are included in processes both an elaboration of learning, and retention of the long-term memory. Literary datas and our results allow to conclusion, that long-term retention of behavioural reactions during learning is accompanied not only by changing efficiency of synaptic transmission, as well as increasing of excitability of command neurons of the defensive reflex. This means, that in the process of learning are involved long-term changes of the characteristics a membrane of certain elements of neuronal network, dependent from the metabolism of the cells. see text). Thou phenomena possible mark as cellular (electrophysiological) correlates of long-term plastic modifications of the behaviour. The analyses of having results demonstrates an important role of membrane characteristics of neurons (their excitability) and parameters an synaptic transmission not only in initial stage of learning, as well as in long-term modifications of the behaviour (long-term memory). PMID:21442956

  1. Mechanical and Numerical Analysis Concerning Compressive Properties of Tin-Lead Open-Cell Foams

    Science.gov (United States)

    Belhadj, Abd-Elmouneïm; Gavrus, Adinel; Bernard, Fabrice; Azzaz, Mohammed

    2015-10-01

    The design of new or innovative materials has to meet two essential criteria: increased mechanical performance and minimization of the mass. This dual requirement leads to interest in the study of various classes of metallic foams. The actual research is focused on open-cell Tin-Lead foams manufactured by replication process using NaCl preform. A mechanical press equipped with a load cell and a local extensometer with a controlled deformation rate is used. Experimental tests were carried out in order to study the influences of both the cell size and of the relative density on the mechanical behavior during a compression deformation and to analyze the obtained properties variation within a new framework. This study has three main sections which start with the manufacturing description and mechanical characterization of the proposed metallic foams followed by the understanding and modeling of their response to a compression load via a Gibson-Ashby model, a Féret law, a proposed simple Avrami model, and a generalized Avrami model. Finally, an exposition of a numerical simulation analyzing the compression of the Sn-Pb foams concerning the variation of the relative densities with respect to the plastic strain is proposed.

  2. Olfactory Stem Cells, a New Cellular Model for Studying Molecular Mechanisms Underlying Familial Dysautonomia

    OpenAIRE

    Nathalie Boone; Béatrice Loriod; Aurélie Bergon; Oualid Sbai; Christine Formisano-Tréziny; Jean Gabert; Michel Khrestchatisky; Catherine Nguyen; François Féron; Axelrod, Felicia B.; El Chérif Ibrahim

    2010-01-01

    BACKGROUND: Familial dysautonomia (FD) is a hereditary neuropathy caused by mutations in the IKBKAP gene, the most common of which results in variable tissue-specific mRNA splicing with skipping of exon 20. Defective splicing is especially severe in nervous tissue, leading to incomplete development and progressive degeneration of sensory and autonomic neurons. The specificity of neuron loss in FD is poorly understood due to the lack of an appropriate model system. To better understand and mod...

  3. Removal Mechanism of Aqueous Lead by a Novel Eco-material:Carbonate Hydroxyapatite

    Institute of Scientific and Technical Information of China (English)

    Huanyan XU; Lei YANG; Peng WANG; Yu LIU; Mingsheng PENG

    2007-01-01

    Kinetics and mechanisms on the removal of aqueous lead ion by carbonate hydroxyapatite (CHap) are investigated in the present work. Experimental results show that, in the whole pH range, the lead removal percentage increases with decreasing pH values and reaches a maximum at pH=2-3. Under some conditions,the lead residual concentration is below national integrated wastewater discharge standard, even drinking water standard. The removal behavior is a complicated non-homogeneous solid/liquid reaction, which can be described by two stages from kinetic point of view. At the earlier stage, reaction rate is so fast that its kinetic course is intricate, which requires further study. At the latter stage, the rate of reaction becomes slow and the process of reaction accords with one order reaction kinetic equation. Experimental results show that the relationship between reaction rate constant k1 and temperature T accords to Arrhenius Equation, and the activation energy of sorption (Ea) is 11.93 k J/mol and frequency factor (A) is 2.51 s-1. X-ray diffraction (XRD), scanning electron microscopy with an energy dispersive X-ray fluoresence spectrometer (SEM-EDS) and toxicity characteristic leaching procedure (TCLP) test were conducted in this work. It is indicated that the main mechanism is dissolution-precipitation, accompanying with superficial sorption.

  4. 'Effective inefficiency': cellular control of protein trafficking as a mechanism of post-translational regulation.

    Science.gov (United States)

    Conn, P Michael; Janovick, Jo Ann; Brothers, Shaun P; Knollman, Paul E

    2006-07-01

    The great writer and polyglot, W Somerset Maugham said, 'I'll give you my opinion of the human race in a nutshell...their heart's in the right place, but their head is a thoroughly inefficient organ.' If his words are applied to trafficking of the human pituitary gonadotropin-releasing hormone receptor, it turns out that he was more right than he knew. Paradoxically, the inefficiency of receptor trafficking to the plasma membrane can bring regulatory advantages to cells. Understanding the mechanism by which cells recognize correctly folded proteins in health and disease opens doors to new therapeutic approaches and provides a more accurate view of mechanisms of normal cell function than is presently available. PMID:16837606

  5. Cellular Mechanisms of Tissue Fibrosis. 6. Purinergic signaling and response in fibroblasts and tissue fibrosis

    OpenAIRE

    Lu, David; Insel, Paul A.

    2013-01-01

    Tissue fibrosis occurs as a result of the dysregulation of extracellular matrix (ECM) synthesis. Tissue fibroblasts, resident cells responsible for the synthesis and turnover of ECM, are regulated via numerous hormonal and mechanical signals. The release of intracellular nucleotides and their resultant autocrine/paracrine signaling have been shown to play key roles in the homeostatic maintenance of tissue remodeling and in fibrotic response post-injury. Extracellular nucleotides signal throug...

  6. Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

    OpenAIRE

    Xuanbin Wang; Yibin Feng; Ning Wang; Fan Cheung; Hor Yue Tan; Sen Zhong; Charlie Li; Seiichi Kobayashi

    2014-01-01

    Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and...

  7. Molecular, Cellular, and Structural Mechanisms of Cocaine Addiction: A Key Role for MicroRNAs

    OpenAIRE

    Jonkman, Sietse; Kenny, Paul J.

    2012-01-01

    The rewarding properties of cocaine play a key role in establishing and maintaining the drug-taking habit. However, as exposure to cocaine increases, drug use can transition from controlled to compulsive. Importantly, very little is known about the neurobiological mechanisms that control this switch in drug use that defines addiction. MicroRNAs (miRNAs) are small non-protein coding RNA transcripts that can regulate the expression of messenger RNAs that code for proteins. Because of their high...

  8. Fundamental Molecular Mechanism for the Cellular Uptake of Guanidinium-Rich Molecules

    OpenAIRE

    Herce, Henry D.; Garcia, Angel E.; Cardoso, M. Cristina

    2014-01-01

    Guanidinium-rich molecules, such as cell-penetrating peptides, efficiently enter living cells in a non-endocytic energy-independent manner and transport a wide range of cargos, including drugs and biomarkers. The mechanism by which these highly cationic molecules efficiently cross the hydrophobic barrier imposed by the plasma membrane remains a fundamental open question. Here, a combination of computational results and in vitro and live-cell experimental evidence reveals an efficient energy-i...

  9. Cellular mechanisms of alpha herpesvirus egress: live cell fluorescence microscopy of pseudorabies virus exocytosis.

    OpenAIRE

    Hogue, Ian B.; Jens B Bosse; Jiun-Ruey Hu; Thiberge, Stephan Y.; Enquist, Lynn W.

    2014-01-01

    Egress of newly assembled herpesvirus particles from infected cells is a highly dynamic process involving the host secretory pathway working in concert with viral components. To elucidate the location, dynamics, and molecular mechanisms of alpha herpesvirus egress, we developed a live-cell fluorescence microscopy method to visualize the final transport and exocytosis of pseudorabies virus (PRV) particles in non-polarized epithelial cells. This method is based on total internal reflection fluo...

  10. Phytoplankton calcification as an effective mechanism to alleviate cellular calcium poisoning

    OpenAIRE

    Müller, M. N.; Barcelos e Ramos, J.; Schulz, K. G.; U. Riebesell; J. Kaźmierczak; Gallo, F.; Mackinder, L.; Li, Y; P. N. Nesterenko; T. W. Trull; Hallegraeff, G.M.

    2015-01-01

    Marine phytoplankton have developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L−1 in the presence of seawater Ca2+ concentrations of 10 mmol L−1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, ...

  11. Phytoplankton calcification as an effective mechanism to prevent cellular calcium poisoning

    OpenAIRE

    Müller, M. N.; J. Barcelos e Ramos; Schulz, K. G.; U. Riebesell; J. Kaźmierczak; Gallo, F.; Mackinder, L.; Y. Li; P. N. Nesterenko; T. W. Trull; Hallegraeff, G.M.

    2015-01-01

    Marine phytoplankton has developed the remarkable ability to tightly regulate the concentration of free calcium ions in the intracellular cytosol at a level of ~ 0.1 μmol L−1 in the presence of seawater Ca2+ concentrations of 10 mmol L−1. The low cytosolic calcium ion concentration is of utmost importance for proper cell signalling function. While the regulatory mechanisms responsible for the tight control of intracellular Ca2+ concentration are not completely understood, ...

  12. 1. Morphological Implication on Cellular Response to Mechanical Stress in Bone.

    Science.gov (United States)

    Amizuka, Norio

    2016-08-01

    In bone, there are 3 distinct cell types: an osteoblast, a bone forming cell; an osteocyte embedded in bone matrix as a consequence of being differentiated from an osteoblast; and an osteoclast, a multinucleated giant cell responsible for bone resorption. Bone is always remodeled by replacing old bone with new bone (bone remodeling), by which bone can maintain its stiffness and flexibility. However, in an osteoporotic state, the disrupted balance between bone resorption and formation results in not only markedly reduced bone mass, but also in disorganized geometry of trabecules, which can often give rise to a bone fracture. Osteocytes located in their lacunae insert their fine cytoplasmic processes into narrow passageways referred to as osteocytic canaliculi. Neighboring osteocytes connect to each other by means of a gap junction in their cytoplasmic processes. Therefore, osteocytes and their lacunae/canaliculi appear to form functional syncytium called osteocytic lacunar canalicular system (OLCS). The geometrical distribution of OLCS is poorly arranged in immature bone, while it appears well-arranged distribution in mature bone (cortical bone), in which molecular transports and sensing mechanical stress seems to be efficient, and therefore, may be able to respond to mechanical stress. In this seminar, I will introduce our recent findings on the morphology and function of OLCS which may respond to mechanical stress. PMID:27441762

  13. (Some cellular mechanisms influencing the transcription of human endogenous retrovirus, HERV-Fc1.

    Directory of Open Access Journals (Sweden)

    Magdalena Janina Laska

    Full Text Available DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome. However, the methylation of human endogenous retroviruses (HERVs is not well investigated. The aim of this study was to investigate the transcriptional potential of HERV-Fc1 proviral 5'LTR in more detail, and examined the specific influence of CpG methylation on this LTR in number of cell lines. Specifically, the role of demethylating chemicals e.g. 5-aza-2' deoxycytidine and Trichostatin-A, in inducing or reactivating expression of HERV-Fc1 specific sequences and the mechanisms were investigated. In our present study, 5-aza-dC is shown to be a powerful inducer of HERV-Fc1, and at the same time it strongly inhibits methylation of DNA. Treatment with this demethylating agent 5-aza-dC, results in significantly increased levels of HERV-Fc1 expression in cells previously not expressing HERV-Fc1, or with a very low expression level. The extent of expression of HERV-Fc1 RNAs precisely correlates with the apparent extent of demethylation of the related DNA sequences. In conclusion, the results suggest that inhibition of DNA methylation/histone deacetylase can interfere with gene silencing mechanisms affecting HERV-Fc1 expression in human cells.

  14. Energy cost and putative benefits of cellular mechanisms modulating buoyancy in aflagellate marine phytoplankton.

    Science.gov (United States)

    Lavoie, Michel; Raven, John A; Levasseur, Maurice

    2016-04-01

    Little information is available on the energetics of buoyancy modulation in aflagellate phytoplankton, which comprises the majority of autotrophic cells found in the ocean. Here, we computed for three aflagellate species of marine phytoplankton (Emiliania huxleyi, Thalassiosira pseudonana, and Ethmodiscus rex) the theoretical minimum energy cost as photons absorbed and nitrogen resource required of the key physiological mechanisms (i.e., replacement of quaternary ammonium by dimethyl-sulfoniopropionate, storage of polysaccharides, and cell wall biosynthesis) affecting the cell's vertical movement as a function of nitrogen (N) availability. These energy costs were also normalized to the capacity of each buoyancy mechanism to modulate sinking or rising rates based on Stokes' law. The three physiological mechanisms could act as ballast in the three species tested in conditions of low N availability at a low fraction (<12%) of the total photon energy cost for growth. Cell wall formation in E. huxleyi was the least costly ballast strategy, whereas in T. pseudonana, the photon energy cost of the three ballast strategies was similar. In E. rex, carbohydrate storage and mobilization appear to be energetically cheaper than modulations in organic solute synthesis to achieve vertical migration. This supports the carbohydrate-ballast strategy for vertical migration for this species, but argues against the theory of replacement of low- or high-density organic solutes. This study brings new insights into the energy cost and potential selective advantages of several strategies modulating the buoyancy of aflagellate marine phytoplankton. PMID:27037589

  15. Cellular intrinsic mechanism affecting the outcome of AML treated with Ara-C in a syngeneic mouse model.

    Directory of Open Access Journals (Sweden)

    Wenjun Zhao

    Full Text Available The mechanisms underlying acute myeloid leukemia (AML treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C.

  16. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    International Nuclear Information System (INIS)

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: ► Endothelial cells mount a stress response under conditions of low serum. ► Endothelial VEGFR levels are

  17. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    Energy Technology Data Exchange (ETDEWEB)

    Latham, Antony M.; Odell, Adam F. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Mughal, Nadeem A. [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Issitt, Theo; Ulyatt, Clare; Walker, John H. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Homer-Vanniasinkam, Shervanthi [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Ponnambalam, Sreenivasan, E-mail: s.ponnambalam@leeds.ac.uk [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2012-11-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black

  18. Thermal protection mechanism of heat pipe in leading edge under hypersonic conditions

    Directory of Open Access Journals (Sweden)

    Peng Wengen

    2015-02-01

    Full Text Available Sharp local structure, like the leading edge of hypersonic aircraft, confronts a severe aerodynamic heating environment at a Mach number greater than 5. To eliminate the danger of a material failure, a semi-active thermal protection system is proposed by integrating a metallic heat pipe into the structure of the leading edge. An analytical heat-balance model is established from traditional aerodynamic theories, and then thermal and mechanical characteristics of the structure are studied at Mach number 6–8 for three refractory alloys, Inconel 625, C-103, and T-111. The feasibility of this simple analytical method as an initial design tool for hypersonic aircraft is assessed through numerical simulations using a finite element method. The results indicate that both the isothermal and the maximum temperatures fall but the von Mises stress increases with a longer design length of the leading edge. These two temperatures and the stress rise remarkably at a higher Mach number. Under all investigated hypersonic conditions, with a 3 mm leading edge radius and a 0.15 m design length, the maximum stress exceeds the yield strength of Inconel 625 at Mach numbers greater than 6, which means a material failure. Moreover, both C-103 and T-111 meet all requirements at Mach number 6–8.

  19. Thermal protection mechanism of heat pipe in leading edge under hypersonic conditions

    Institute of Scientific and Technical Information of China (English)

    Peng Wengen; He Yurong; Wang Xinzhi; Zhu Jiaqi; Han Jiecai

    2015-01-01

    Sharp local structure, like the leading edge of hypersonic aircraft, confronts a severe aerodynamic heating environment at a Mach number greater than 5. To eliminate the danger of a material failure, a semi-active thermal protection system is proposed by integrating a metallic heat pipe into the structure of the leading edge. An analytical heat-balance model is established from tra-ditional aerodynamic theories, and then thermal and mechanical characteristics of the structure are studied at Mach number 6–8 for three refractory alloys, Inconel 625, C-103, and T-111. The feasi-bility of this simple analytical method as an initial design tool for hypersonic aircraft is assessed through numerical simulations using a finite element method. The results indicate that both the iso-thermal and the maximum temperatures fall but the von Mises stress increases with a longer design length of the leading edge. These two temperatures and the stress rise remarkably at a higher Mach number. Under all investigated hypersonic conditions, with a 3 mm leading edge radius and a 0.15 m design length, the maximum stress exceeds the yield strength of Inconel 625 at Mach num-bers greater than 6, which means a material failure. Moreover, both C-103 and T-111 meet all requirements at Mach number 6–8.

  20. Characterization of Wave Dispersion in Viscoelastic Cellular Assemblies by Doublet Mechanics

    Institute of Scientific and Technical Information of China (English)

    JIN Yan-Fang; XIONG Chun-Yang; FANG Jing; FERRARI Mauro

    2009-01-01

    Using the Voigt model, we analyze wave propagation in viscoelastic granular media with a monatomic lattice, planar simple cubic package and cubical-tetrahedral assembly within the context of doublet mechanics. Microstrains of elongation between the doublet particles are considered in the models. Wave dispersive relations are derived from dynamic equations of the particles involved in the media, and phase velocities and attenuations of the dispersive waves are obtained for the different assemblies. Variations in these dispersion characteristics are analyzed with the changes of cell interval, modulus, and wave frequency. The relations between micro-constants and macro-parameters are presented under the condition of non-scale continuity of the media.

  1. Cellular Mechanism of Newly Synthesized Indoledione Derivative-induced Immunological Death of Tumor Cell

    OpenAIRE

    Oh, Su-Jin; Ryu, Chung-Kyu; Baek, So-Young; Lee, Hyunah

    2011-01-01

    Background EY-6 is one of the newly synthesized indoledione derivatives to induce tumor cell-specific cell death. In this study, we investigated the mechanism of immunological death induced by EY-6 at mouse colon cancer cell as well as at the normal immune cell represented by dendritic cell. Methods C57BL/6 mouse syngeneic colon cancer cell MC38 was treated with EY-6, and analyzed by MTT for viability test, flow cytometry for confirming surface expressing molecules and ELISA for detection of ...

  2. The Effect of Structural Design on Mechanical Properties and Cellular Response of Additive Manufactured Titanium Scaffolds

    Directory of Open Access Journals (Sweden)

    Jan Wieding

    2012-08-01

    Full Text Available Restoration of segmental defects in long bones remains a challenging task in orthopedic surgery. Although autologous bone is still the ‘Gold Standard’ because of its high biocompatibility, it has nevertheless been associated with several disadvantages. Consequently, artificial materials, such as calcium phosphate and titanium, have been considered for the treatment of bone defects. In the present study, the mechanical properties of three different scaffold designs were investigated. The scaffolds were made of titanium alloy (Ti6Al4V, fabricated by means of an additive manufacturing process with defined pore geometry and porosities of approximately 70%. Two scaffolds exhibited rectangular struts, orientated in the direction of loading. The struts for the third scaffold were orientated diagonal to the load direction, and featured a circular cross-section. Material properties were calculated from stress-strain relationships under axial compression testing. In vitro cell testing was undertaken with human osteoblasts on scaffolds fabricated using the same manufacturing process. Although the scaffolds exhibited different strut geometry, the mechanical properties of ultimate compressive strength were similar (145–164 MPa and in the range of human cortical bone. Test results for elastic modulus revealed values between 3.7 and 6.7 GPa. In vitro testing demonstrated proliferation and spreading of bone cells on the scaffold surface.

  3. The cytotoxicity of polycationic iron oxide nanoparticles: Common endpoint assays and alternative approaches for improved understanding of cellular response mechanism

    Directory of Open Access Journals (Sweden)

    Hoskins Clare

    2012-04-01

    Our findings indicate that common in vitro cell endpoint assays do not give detailed and complete information on cellular state and it is essential to explore novel approaches and carry out more in-depth studies to elucidate cellular response mechanism to magnetic nanoparticles.

  4. Structural and mechanical characteristics of some lead-free Cu-Sn based solder alloys

    OpenAIRE

    Mitovski Aleksandra M.; Balanović Ljubiša T.; Živković Dragana T.; Marjanović Šaša R.; Marjanović Bata R.; Novaković Slađana O.

    2008-01-01

    The results of structural and mechanical characteristics of lead-free Cu-Sn based solder alloys, produced in Company "11. mart" AD Srebrenica (Republic of Srpska), are presented in this paper. The results of investigation of samples - alloys CuSnl4, CuSnlFelAlO.5, CuSnlOFelAllMnO.5 and CuA110Fe3Mn produced by different processing methods, include the data obtained by optical microscopy and measurements of hardness, micro hardness and electroconductivity, in order to characterize mentioned all...

  5. Elucidation of lead-induced oxidative stress in Talinum triangulare roots by analysis of antioxidant responses and DNA damage at cellular level.

    Science.gov (United States)

    Kumar, Abhay; Prasad, M N V; Mohan Murali Achary, V; Panda, Brahma B

    2013-07-01

    Hydroponic experiments were performed with Talinum triangulare (Jacq.) Willd. focusing the root cellular biochemistry with special emphasis on DNA damage, structural, and elemental analyses in Pb(NO3)2 exposed with 0, 0.25, 0.5, 0.75, 1.0, and 1.25 mM for 7 days. Lead (Pb) increased reactive oxygen species production, lipid peroxidation, protein oxidation, cell death, and DNA damage and decreased the protein content in a dose-dependent manner. Likewise, a dose-dependent induction of antioxidative enzymes superoxide dismutase and catalase by Pb was evident. Ascorbate peroxidase on the other hand responded biphasically to Pb treatments by showing induction at low (0.25 and 0.50) and repression at high (0.75-1.25 mM) concentrations. The estimation of proline content also indicated a similar biphasic trend. Scanning electron microscope and energy-dispersive X-ray spectroscopy analysis showed that 1.25 mM Pb treatment resulted in ultrastructural modifications in roots and stem tissue that was marked by the change in the elemental profile. The findings pointed to the role of oxidative stress in the underlying Pb phytotoxicity and genotoxicity in T. triangulare. PMID:23263755

  6. Natural killer cell cytotoxicity of breast cancer targets is enhanced by two distinct mechanisms of antibody-dependent cellular cytotoxicity against LFA-3 and HER2/neu.

    Science.gov (United States)

    Cooley, S; Burns, L J; Repka, T; Miller, J S

    1999-10-01

    Treatment of advanced breast cancer with autologous stem cell transplantation is limited by a high probability of disease relapse. In clinical trials, interleukin 2 (IL-2) alone can expand natural killer (NK) cells in vivo and increase their cytotoxic activity against breast cancer cell lines, but this increase is modest. Understanding the mechanisms that mediate NK cell lysis of breast cancer targets may lead to improvements of current immunotherapy strategies. NK cells from normal donors or patients receiving subcutaneous IL-2 were tested in cytotoxicity assays against five breast cancer cell lines. The role of adhesion molecules and antibodies that interact through Fc receptors on NK cells was explored. NK cell lysis of breast cancer targets is variable and is partially dependent on recognition through ICAM-1 and CD18. While blocking CD2 slightly decreased cytotoxicity, contrary to expectations, an antibody against CD58 (the ligand for CD2), failed to block killing and instead mediated an increased cytotoxicity that correlated with target density of CD58. The CD58 antibody-enhanced killing was dependent not only on FcRgammaIII but also on CD2 and ICAM-1/CD18. To further elucidate the mechanism of this CD58 antibody-dependent cellular cytotoxicity (ADCC), another antibody was tested. Trastuzumab (Herceptin), a humanized antibody against HER2/neu, mediated potent ADCC against all the HER2/neu positive breast cancer targets. Unlike CD58 antibody-mediated ADCC, Herceptin ADCC was minimally affected by blocking antibodies to CD2 or ICAM-1/CD18, which suggests a different mechanism of action. This study shows that multiple mechanisms are involved in NK cell lysis of breast cancer targets, that none of the targets are inherently resistant to killing, and that two distinct mechanisms of ADCC can target immunotherapy to breast cancer cells. PMID:10517495

  7. Fuel rod mechanical deformation during the PBF/LOFT lead rod loss-of-coolant experiments

    International Nuclear Information System (INIS)

    Results of four PBF/LOFT Lead Rod (LLR) sequential blowdown tests conducted in the Power Burst Facility (PBF) are presented. Each test employed four separately shrouded fuel rods. The primary objective of the test series was to evaluate the extent of mechanical deformation that would be expected to occur to low pressure (0.1 MPa), light water reactor design fuel rods when subjected to a series of double ended cold leg break loss-of-coolant accident (LOCA) tests, and to determine whether subjecting these deformed fuel rods to subsequent testing would result in rod failure. The extent of mechanical deformation (buckling, collapse, or waisting of the cladding) was evaluated by comparison of cladding temperature and system pressure measurements with out-of-pile experimental data, and by posttest visual examinations and cladding diametral measurements

  8. Morphogenesis of the lymphatic vasculature: A focus on new progenitors and cellular mechanisms important for constructing lymphatic vessels.

    Science.gov (United States)

    Kazenwadel, Jan; Harvey, Natasha L

    2016-03-01

    Lymphatic vessels serve crucial roles in the regulation of tissue fluid homeostasis, dietary lipid absorption and immune cell trafficking. Defects in lymphatic vessel morphogenesis and function have been associated with lymphedema, obesity, hypertension and tumour metastasis. Morphogenetic events important for construction of the lymphatic vasculature during development include the specification and emergence of lymphatic endothelial progenitor cells, their differentiation and assembly into interconnected vessels and vascular remodeling, ultimately giving rise to a functional vascular network. Despite the embryonic origins of lymphatic endothelial progenitor cells being long debated, work performed over the last decade had overwhelmingly supported at least a great majority of progenitor cells arising from the venous vasculature. Here, we review the most recent advances in the field of lymphatic vessel morphogenesis, with a focus on studies that have identified novel sources of embryonic lymphatic endothelial progenitor cells, together with the cellular mechanisms by which lymphatic vessels are initially assembled. PMID:26228815

  9. Mechanical Properties of 3-D Printed Cellular Foams with triangular cells

    Science.gov (United States)

    Bunga, Pratap Kumar

    In the present work, poly lactic acid (PLA) is used as a model system to investigate the mechanical behavior of 3-D printed foams with triangular cells. Solid PLA tension and compression specimens and foams made of PLA were fabricated using fused deposition 3-D printing technique. The solid PLA tension specimens were characterized for their densities and found to be about 10% lower in density as compared to their bulk counter parts. The triangular foams had a relative density of about 64%. The relationships between the structure of the foams and its deformation behavior under compression along two in-plane directions were characterized. Furthermore, simple finite element models were developed to understand the observed deformation behavior of triangular foams.

  10. Auxin apical control of the auxin polar transport and its oscillation - a suggested cellular transduction mechanism

    Directory of Open Access Journals (Sweden)

    Tomasz J. Wodzicki

    2014-02-01

    Full Text Available The proposed hypothesis concerns the transduction of auxin molecular signals arriving from the apoplast at the plasma membrane or recognized by the proteineous receptors of the responding cell, to the concentration gradients oscillating in the supracellular space, associated usually with the specific plant growth and differentiation. Acting as an agonist from outside the target cell auxin stimulates in this cell: (1 the liberation of auxin from the cytosolic pool of its conjugates directly into the basipetal efflux; (2 the synthesis of new auxin which restores the cytosolic reserve of auxin conjugates. The functioning of such a system may be effective in a series of processes initiated by the changing concentration of cytosolic calcium. The hypothesis suggests a molecular mechanism for the development and effective operation of the morphogenetic field in the supracellular space of the plant body, such as the field resulting from auxin waves discovered in cambium.

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

    Science.gov (United States)

    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. PMID:27166616

  12. Cellular uptake of the antitumor agent Dp44mT occurs via a carrier/receptor-mediated mechanism.

    Science.gov (United States)

    Merlot, Angelica M; Pantarat, Namfon; Menezes, Sharleen V; Sahni, Sumit; Richardson, Des R; Kalinowski, Danuta S

    2013-12-01

    The chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) shows potent and selective anticancer and antimetastatic activity. However, the mechanism by which it is initially transported into cells to induce cytotoxicity is unknown. Hence, the current investigation examined the cellular uptake of ¹⁴C-Dp44mT relative to two structurally related ligands, namely the aroylhydrazone ¹⁴C-pyridoxal isonicotinoyl hydrazone (¹⁴C-PIH) and the thiosemicarbazone (¹⁴C-2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (¹⁴C-Bp4eT). In marked contrast to the cellular uptake of ¹⁴C-PIH and ¹⁴C-Bp4eT, which were linear as a function of concentration, ¹⁴C-Dp44mT uptake was saturable using SK-N-MC neuroepithelioma cells (Bmax, 4.28 × 10⁷ molecules of chelator/cell; and Kd, 2.45 μM). Together with the fact that ¹⁴C-Dp44mT uptake was temperature-dependent and significantly (P complex [Fe(¹⁴C-Dp44mT)₂] was not saturable as a function of concentration and was much greater than the ligand alone, indicating an alternate mode of transport. Studies examining the tissue distribution of ¹⁴C-Dp44mT injected intravenously into a mouse tumor model demonstrated the ¹⁴C label was primarily identified in the excretory system. Collectively, these findings examining the mechanism of Dp44mT uptake and its distribution and excretion have clinical implications for its bioavailability and uptake in vivo. PMID:24085840

  13. Fracture Mechanics Analyses of Reinforced Carbon-Carbon Wing-Leading-Edge Panels

    Science.gov (United States)

    Raju, Ivatury S.; Phillips, Dawn R.; Knight, Norman F., Jr.; Song, Kyongchan

    2010-01-01

    Fracture mechanics analyses of subsurface defects within the joggle regions of the Space Shuttle wing-leading-edge RCC panels are performed. A 2D plane strain idealized joggle finite element model is developed to study the fracture behavior of the panels for three distinct loading conditions - lift-off and ascent, on-orbit, and entry. For lift-off and ascent, an estimated bounding aerodynamic pressure load is used for the analyses, while for on-orbit and entry, thermo-mechanical analyses are performed using the extreme cold and hot temperatures experienced by the panels. In addition, a best estimate for the material stress-free temperature is used in the thermo-mechanical analyses. In the finite element models, the substrate and coating are modeled separately as two distinct materials. Subsurface defects are introduced at the coating-substrate interface and within the substrate. The objective of the fracture mechanics analyses is to evaluate the defect driving forces, which are characterized by the strain energy release rates, and determine if defects can become unstable for each of the loading conditions.

  14. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low

    Energy Technology Data Exchange (ETDEWEB)

    Kadhim, Munira A

    2012-08-22

    The above studies will provide fundamental mechanistic information relating genetic predisposition to important low dose phenomena, and will aid in the development of Department of Energy policy, as well as radiation risk policy for the public and the workplace. We believe the proposed studies accurately reflect the goals of the DOE low dose program. To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e. less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these "non-targeted responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate non-targeted effects of ionizing radiation with a focus on the induction of genomic instability (GI) in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/CaH and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition in these models on genomic instability. We will specifically focus on the effects of low doses of low LET radiation, down to the dose of 10mGy (0.01Gy) X-rays. Using conventional X-ray and we will be able to assess the role of genetic variation under various conditions at a range of doses down to the very low dose of 0.01Gy. Irradiations will be carried out using facilities in routine operation for such studies. Mechanistic studies of instability in different cell

  15. Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

    Directory of Open Access Journals (Sweden)

    Michael E. Hasselmo

    2008-01-01

    Full Text Available The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.

  16. Application of cellular mechanisms to growth and development of food producing animals.

    Science.gov (United States)

    Chung, K Y; Johnson, B J

    2008-04-01

    Postnatal skeletal muscle growth is a result of hypertrophy of existing skeletal muscle fibers in food producing animals. Accumulation of additional nuclei, as a source of DNA, to the multinucleated skeletal muscle fiber aids in fiber hypertrophy during periods of rapid skeletal muscle growth. Muscle satellite cells are recognized as the source of nuclei to support muscle hypertrophy. Exogenous growth-enhancing compounds have been used to modulate growth rate and efficiency in meat animals for over a half century. In cattle, these compounds enhance efficiency of growth by preferentially stimulating skeletal muscle growth compared with adipose tissue. There are 2 main classes of compounds approved for use in cattle in the United States, anabolic steroids and beta-adrenergic agonists (beta-AA). Administration of both trenbolone acetate and estradiol-17beta, as implants, increased carcass protein accumulation 8 to 10% in yearling steers. Muscle satellite cells isolated from steers implanted with trenbolone acetate/ estradiol-17beta had a shorter lag phase in culture compared with satellite cells isolated from control steers. Collectively, these data indicate that activation, increased proliferation, and subsequent fusion of satellite cells in muscles of implanted cattle may be an important mechanism by which anabolic steroids enhance muscle hypertrophy. Oral administration of beta-AA to ruminants does not alter DNA accumulation in skeletal muscle over a typical feeding period (28 to 42 d). Enhanced muscle hypertrophy observed due to beta-AA feeding occurs by direct, receptor-mediated changes in protein synthesis and degradation rates of skeletal muscle tissue. Proper timing of anabolic steroid administration when coupled with beta-AA feeding could result in a synergistic response in skeletal muscle growth due to the effects of anabolic steroids at increasing satellite cell activity, which then can support the rapid hypertrophic changes of the muscle fiber when exposed

  17. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Han Wern; Lim, Hwee Ying [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore); Wong, Kim Ping, E-mail: bchsitkp@nus.edu.sg [Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260 (Singapore)

    2009-11-06

    Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F{sub 0}F{sub 1}-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 {mu}M, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F{sub 0}F{sub 1}-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

  18. Molecular and cellular mechanisms for the regulation of ovarian follicular function in cows.

    Science.gov (United States)

    Shimizu, Takashi

    2016-08-25

    Ovary is an important organ that houses the oocytes (reproductive cell). Oocyte growth depends on the function of follicular cells such as the granulosa and theca cells. Two-cell two gonadotropin systems are associated with oocyte growth and follicular cell functions. In addition to these systems, it is also known that several growth factors regulate oocyte growth and follicular cell functions. Vascular endothelial growth factor (VEGF) is involved in thecal vasculature during follicular development and the suppression of granulosa cell apoptosis. Metabolic factors such as insulin, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) also play critical roles in the process of follicular development and growth. These factors are associated not only with follicular development, but also with follicular cell function. Steroid hormones (estrogens, androgens, and progestins) that are secreted from follicular cells influence the function of the female genital tract and its affect the susceptibility to bacterial infection. This review covers our current understanding of the mechanisms by which gonadotrophins and/or steroid hormones regulate the growth factors in the follicular cells of the bovine ovary. In addition, this review describes the effect of endotoxin on the function of follicular cells. PMID:27097851

  19. Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action

    International Nuclear Information System (INIS)

    Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F0F1-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F0F1-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

  20. Study on the Cellular Molecular Mechanism of Intrauterine Transmission of Hepatitis B Virus

    Institute of Scientific and Technical Information of China (English)

    王健; 孙琳

    2003-01-01

    Objective: To study intrauterine transmission of HBV and its celbular molecular mechanism and influence on the fetus. Methods: A total of 46 cases of Fegnant uxnnen who suffered from HBV were divided into HBeAg (+) and HBeAg (-) groups. HBV-DNA in serum and peripheral blood mononuclear cells ( PBMC ) of 46 cases of pregnant women before delivery urns detected by polymerase chain reaction ( PCR). After placenta being delivery, HBV-DNA in serum and cord blood mononuclear cells ( CBMC) was also detected by PCR. Results: The total of positive rates of HBV-DNA in serum and PBMC of pregnant women with hepatitis B were 69.57% (32/46) and 41.30% (19/46). The positive rates of HBV-DNA in serum of cord blood and CBMC were 56.52%(26/46) and 21.74% (10/46) respectively. Among them, the positive rates of HBV-DNA inserum and PBMC of pregnant women with HBeAg (+) were 100. 00% (25/25) and 60.00% (15/25) respectively. The positive rates of HBV-DNA in serum of cord blood and CBMC were 88.00% (22/25) and 32. 00% (8/25) respectively. The positive rates of HBV-DNA in serum and PBMC of pregnant women with HBeAg (-) were 33.33%(7/21) and 19.05%(4/21) respectively. The positive rates of HBV-DNA in serum of card blood and CBMC were 19.05%(4/21) and 9.52%(2/21) resspectively. The positive rates of HBV-DNA in serum of card blood and CBMC of newborns were higher in the group of pregnant women with HBeAg (+) than those in the group of pregnant women with HBeAg (--) (P<0. O1 and P<0. 05). There was no HBV-DNA in serum, PBMC and CBMC of normal pregnant women and normal neorwles. Conclusion : The intrauterine transmission of HBV can be existent and its transmission way not only can be induced by serum but also can be induced by PBMC. The way of intrauterine transmission of HBV in-duced by PBMC was concealed. The dangerous possibility of intrauterine transmission is higher in thepregnant women with HBeAg (+) than that in the group of pregnant women with HBeAg (-).

  1. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  2. Powder processing and mechanical properties of Silver0.86Lead19Antimony telluride20 (LAST) and Lead0.95Tin0.05Tellurium - Lead sulfide 8% (Lead telluride -Lead sulfide) thermoelectric materials

    Science.gov (United States)

    Ni, Jennifer Elisabeth

    Thermoelectric (TE) materials convert between thermal and electrical energy and when used with existing processes will increase the efficiency via waste heat recovery. Ag0.86Pb19SbTe20 (LAST) and Pb0.95Sn0.05Te - PbS 8% (PbTe-PbS) materials exhibit good thermoelectric (TE) properties and have potential applications as thermoelectric generators in waste heat recovery. However, to fully characterize the thermo-mechanical behavior of LAST and PbTe-PbS materials under in-service conditions, knowledge is needed of the mechanical and thermal properties at room and high temperature. As fracture strength is inversely proportional to the square root of grain size, cast ingots were powder processed to reduce powder particle size. Three different powder processing methods were used (1) dry milling only, (2) wet milling only, or (3) dry milling and wet milling The specimens were fabricated using hot pressing or pulsed electric current sintering (PECS) from planetary ball milled powders. In this study, elastic moduli, including Young's modulus, shear modulus, and Poisson's ratio, were measured dynamically using resonant ultrasound spectroscopy (RUS) at room temperature and as a function of temperature up to 663 K. The room temperature porosity dependence for Young's modulus followed the empirical exponential relationships common for brittle materials, with a material dependent constant bPE of 3.5 and 1.3 for LAST and PbTe-PbS, respectively. The room temperature Young's modulus for a theoretically dense specimen was 58.4 +/- 0.6 GPa and 56.2 +/- 0.4 GPa for for LAST and PbTe-PbS, respectively. For hot pressed PbTe-PbS specimens, the Vickers indentations mean hardness and fracture toughness was 1.18 + 0.09 GPa and 0.35 +/- 0.04 MPa·m 1/2. The coefficient of thermal expansion is important for understanding the mechanical response of a material to a thermal gradient or a thermal transient. For PbTe-PbS the coefficient of thermal expansion measured using dilatometry and high

  3. Optimal Ordering Policy and Coordination Mechanism of a Supply Chain with Controllable Lead-Time-Dependent Demand Forecast

    OpenAIRE

    Jian-Qiang Luo; Hui Yang; Hua-Ming Song

    2011-01-01

    This paper investigates the ordering decisions and coordination mechanism for a distributed short-life-cycle supply chain. The objective is to maximize the whole supply chain's expected profit and meanwhile make the supply chain participants achieve a Pareto improvement. We treat lead time as a controllable variable, thus the demand forecast is dependent on lead time: the shorter lead time, the better forecast. Moreover, optimal decision-making models for lead time and order quantity are form...

  4. Epilepsy-Related Slack Channel Mutants Lead to Channel Over-Activity by Two Different Mechanisms.

    Science.gov (United States)

    Tang, Qiong-Yao; Zhang, Fei-Fei; Xu, Jie; Wang, Ran; Chen, Jian; Logothetis, Diomedes E; Zhang, Zhe

    2016-01-01

    Twelve sodium-activated potassium channel (KCNT1, Slack) genetic mutants have been identified from severe early-onset epilepsy patients. The changes in biophysical properties of these mutants and the underlying mechanisms causing disease remain elusive. Here, we report that seven of the 12 mutations increase, whereas one mutation decreases, the channel's sodium sensitivity. Two of the mutants exhibit channel over-activity only when the intracellular Na(+) ([Na(+)]i) concentration is ∼80 mM. In contrast, single-channel data reveal that all 12 mutants increase the maximal open probability (Po). We conclude that these mutant channels lead to channel over-activity predominantly by increasing the ability of sodium binding to activate the channel, which is indicated by its maximal Po. The sodium sensitivity of these epilepsy causing mutants probably determines the [Na(+)]i concentration at which these mutants exert their pathological effects. PMID:26725113

  5. Apoptotic regulation of epithelial cellular extrusion

    OpenAIRE

    De Andrade, Daniel,; Rosenblatt, Jody

    2011-01-01

    Cellular extrusion is a mechanism that removes dying cells from epithelial tissues to prevent compromising their barrier function. Extrusion occurs in all observed epithelia in vivo and can be modeled in vitro by inducing apoptosis in cultured epithelial monolayers. We established that actin and myosin form a ring that contracts in the surrounding cells that drives cellular extrusion. It is not clear, however, if all apoptotic pathways lead to extrusion and how apoptosis and extrusion are mol...

  6. Fracture Mechanics Analyses of the Slip-Side Joggle Regions of Wing-Leading Edge Panels

    Science.gov (United States)

    Raju, Ivatury S.; Knight, Norman F., Jr.; Song, Kyongchan; Phillips, Dawn R.

    2010-01-01

    The Space Shuttle Orbiter wing comprises of 22 leading edge panels on each side of the wing. These panels are part of the thermal protection system that protects the Orbiter wings from extreme heating that take place on the reentry in to the earth atmosphere. On some panels that experience extreme heating, liberation of silicon carbon (SiC) coating was observed on the slip side regions of the panels. Global structural and local fracture mechanics analyses were performed on these panels as a part of the root cause investigation of this coating liberation anomaly. The wing-leading-edge reinforced carbon-carbon (RCC) panels, Panel 9, T-seal 10, and Panel 10, are shown in Figure 1 and the progression of the stress analysis models is presented in Figure 2. The global structural analyses showed minimal interaction between adjacent panels and the T-seal that bridges the gap between the panels. A bounding uniform temperature is applied to a representative panel and the resulting stress distribution is examined. For this loading condition, the interlaminar normal stresses showed negligible variation in the chord direction and increased values in the vicinity of the slip-side joggle shoulder. As such, a representative span wise slice on the panel can be taken and the cross section can be analyzed using plane strain analysis.

  7. Mechanism of Laser/light beam interaction at cellular and tissue level and study of the influential factors for the application of low level laser therapy

    CERN Document Server

    Khalid, Muhammad Zeeshan

    2016-01-01

    After the discovery of laser therapy it was realized it has useful application of wound healing and reduce pain, but due to the poor understanding of the mechanism and dose response this technique remained to be controversial for therapeutic applications. In order to understand the working and effectiveness different experiments were performed to determine the laser beam effect at the cellular and tissue level. This article discusses the mechanism of beam interaction at tissues and cellular level with different light sources and dosimetry principles for clinical application of low level laser therapy. Different application techniques and methods currently in use for clinical treatment has also been reviewed.

  8. Selective peptide inhibitors of antiapoptotic cellular and viral Bcl-2 proteins lead to cytochrome c release during latent Kaposi’s sarcoma-associated herpesvirus infection

    OpenAIRE

    Burrer, Christine M.; Foight, Glenna W.; Keating, Amy E.; Chan, Gary C.

    2015-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with B-cell lymphomas including primary effusion lymphoma and multicentric Castleman’s disease. KSHV establishes latency within B cells by modulating or mimicking the antiapoptotic Bcl-2 family of proteins to promote cell survival. Our previous BH3 profiling analysis, a functional assay that assesses the contribution of Bcl-2 proteins towards cellular survival, identified two Bcl-2 proteins, cellular Mcl-1 and viral KsBcl-2, as pote...

  9. Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

    Science.gov (United States)

    Zhang, Xiao-Lei; Guariglia, Sara R; McGlothan, Jennifer L; Stansfield, Kirstie H; Stanton, Patric K; Guilarte, Tomás R

    2015-01-01

    Childhood lead (Pb2+) intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development. PMID:26011056

  10. Presynaptic mechanisms of lead neurotoxicity: effects on vesicular release, vesicle clustering and mitochondria number.

    Directory of Open Access Journals (Sweden)

    Xiao-Lei Zhang

    Full Text Available Childhood lead (Pb2+ intoxication is a global public health problem and accounts for 0.6% of the global burden of disease associated with intellectual disabilities. Despite the recognition that childhood Pb2+ intoxication contributes significantly to intellectual disabilities, there is a fundamental lack of knowledge on presynaptic mechanisms by which Pb2+ disrupts synaptic function. In this study, using a well-characterized rodent model of developmental Pb2+ neurotoxicity, we show that Pb2+ exposure markedly inhibits presynaptic vesicular release in hippocampal Schaffer collateral-CA1 synapses in young adult rats. This effect was associated with ultrastructural changes which revealed a reduction in vesicle number in the readily releasable/docked vesicle pool, disperse vesicle clusters in the resting pool, and a reduced number of presynaptic terminals with multiple mitochondria with no change in presynaptic calcium influx. These studies provide fundamental knowledge on mechanisms by which Pb2+ produces profound inhibition of presynaptic vesicular release that contribute to deficits in synaptic plasticity and intellectual development.

  11. Mechanical properties of the steel T91 in contact with lead

    Energy Technology Data Exchange (ETDEWEB)

    Klecka, Jakub, E-mail: jakub.klecka@cvrez.cz; Di Gabriele, Fosca; Hojna, Anna

    2015-03-15

    Highlights: • Tensile specimens of T91 steel were tested in liquid lead at 350 °C and 400 °C. • Several different fluxes were tested to promote wetting. • Liquid metal embrittlement occurred for notched however not for smooth specimens. - Abstract: Interaction of the steel T91 with the liquid Pb, issue of main concern for LFR, has been studied. The experimental cell CALLISTO was designed and manufactured in the aim of carrying out mechanical testing of materials immersed in the liquid metal to study sensitivity to Liquid Metal Embrittlement, LME. Several tensile tests were carried out in CALLISTO, with Pb. Experimental variables considered were the surface state and the temperature. When testing notched specimens and inducing wetting, it was observed that loaded specimens showed the typical features of the embrittlement induced by LM in their fracture surfaces. Results are discussed in terms of effect of the environment on the mechanical properties of the steel T91 and the brittle features observed in the fracture surface.

  12. Induction of multixenobiotic defense mechanisms in resistant Daphnia magna clones as a general cellular response to stress.

    Science.gov (United States)

    Jordão, Rita; Campos, Bruno; Lemos, Marco F L; Soares, Amadeu M V M; Tauler, Romà; Barata, Carlos

    2016-06-01

    Multixenobiotic resistance mechanisms (MXR) were recently identified in Daphnia magna. Previous results characterized gene transcripts of genes encoding and efflux activities of four putative ABCB1 and ABCC transporters that were chemically induced but showed low specificity against model transporter substrates and inhibitors, thus preventing us from distinguishing between activities of different efflux transporter types. In this study we report on the specificity of induction of ABC transporters and of the stress protein hsp70 in clones selected to be genetically resistant to ABCB1 chemical substrates. Clones resistant to mitoxantrone, ivermectin and pentachlorophenol showed distinctive transcriptional responses of transporter protein coding genes and of putative transporter dye activities. Expression of hsp70 proteins also varied across resistant clones. Clones resistant to mitoxantrone and pentachlorophenol showed high constitutive levels of hsp70. Transcriptional levels of the abcb1 gene transporter and of putative dye transporter activity were also induced to a greater extent in the pentachlorophenol resistant clone. Observed higher dye transporter activities in individuals from clones resistant to mitoxantrone and ivermectin were unrelated with transcriptional levels of the studied four abcc and abcb1 transporter genes. These findings suggest that Abcb1 induction in D. magna may be a part of a general cellular stress response. PMID:27039215

  13. Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius

    Directory of Open Access Journals (Sweden)

    M.C. Andresen

    2004-04-01

    Full Text Available Visceral afferents send information via cranial nerves to the nucleus tractus solitarius (NTS. The NTS is the initial step of information processing that culminates in homeostatic reflex responses. Recent evidence suggests that strong afferent synaptic responses in the NTS are most often modulated by depression and this forms a basic principle of central integration of these autonomic pathways. The visceral afferent synapse is uncommonly powerful at the NTS with large unitary response amplitudes and depression rather than facilitation at moderate to high frequencies of activation. Substantial signal depression occurs through multiple mechanisms at this very first brainstem synapse onto second order NTS neurons. This review highlights new approaches to the study of these basic processes featuring patch clamp recordings in NTS brain slices and optical techniques with fluorescent tracers. The vanilloid receptor agonist, capsaicin, distinguishes two classes of second order neurons (capsaicin sensitive or capsaicin resistant that appear to reflect unmyelinated and myelinated afferent pathways. The differences in cellular properties of these two classes of NTS neurons indicate clear functional differentiation at both the pre- and postsynaptic portions of these first synapses. By virtue of their position at the earliest stage of these pathways, such mechanistic differences probably impart important differentiation in the performance over the entire reflex pathways.

  14. Suppression of cellular immunity by head and neck irradiation. Precipitating factors and reparative mechanisms in an experimental model

    International Nuclear Information System (INIS)

    A model was developed in C3H mice to investigate the immunosuppressive effects of head and neck irradiation and to explore mechanisms for repair of the defects. Mice receiving 1200 rad (12 Gy) of head and neck irradiation showed significant depression of delayed-type hypersensitivity, peripheral blood lymphocyte counts, spleen cell counts, and spleen cell production of interleukin-2. Treatment with optimal dosages of thymosin alpha 1 (T alpha-1) produced significant increases in all of these values, in some instances to levels higher than in the nonirradiated controls. In identical experiments with mice irradiated to a portal limited to the pelvic region, T alpha-1 induced only partial remission of the abnormalities. The dose response of T alpha-1 with head and neck irradiation showed a relatively limited dose range for immune restoration, a finding that warrants similar determinations in clinical trials with immunomodulating agents. The results suggest a potential clinical usefulness of T alpha-1 and also interleukin-2 in restoring cellular immunity after irradiation for head and neck cancers. The model appears to be useful for investigating immunomodulating agents before they are clinically evaluated as adjuvants with head and neck irradiation regimens

  15. Cellular Cell Bifurcation of Cylindrical Detonations

    Institute of Scientific and Technical Information of China (English)

    HAN Gui-Lai; JIANG Zong-Lin; WANG Chun; ZHANG Fan

    2008-01-01

    Cellular cell pattern evolution of cylindrically-diverging detonations is numerically simulated successfully by solving two-dimensional Euler equations implemented with an improved two-step chemical kinetic model. From the simulation, three cell bifurcation modes are observed during the evolution and referred to as concave front focusing, kinked and wrinkled wave front instability, and self-merging of cellular cells. Numerical research demonstrates that the wave front expansion resulted from detonation front diverging plays a major role in the cellular cell bifurcation, which can disturb the nonlinearly self-sustained mechanism of detonations and finally lead to cell bifurcations.

  16. Ionoregulatory disruption as the acute toxic mechanism for lead in the rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    The mechanism for acute toxicity of lead (Pb) in rainbow trout (Oncorhynchus mykiss) was investigated at Pb concentrations close to the 96 h LC50 of 1.0 mg dissolved Pb l-1 (0.8-1.4, 95% C.I.) determined in dechlorinated Hamilton city tap water (from Lake Ontario, hardness=140 mg l-1 CaCO3). Tissue Pb accumulation associated with death was highest in the gill, followed by kidney and liver. Significant ionoregulatory impacts were observed in adult rainbow trout (200-300 g) fitted with indwelling dorsal aortic catheters and exposed to 1.1±0.04 mg dissolved Pb l-1. Decreased plasma [Ca2+], [Na+] and [Cl-] occurred after 48 h of exposure through to 120 h, with increases in plasma [Mg2+], ammonia, and cortisol. No marked changes in PaO2, PaCO2, pH, glucose, or hematological parameters were evident. Branchial Na+/K+ ATPase activity in juvenile trout exposed to concentrations close to the 96 h LC50 was inhibited by approximately 40% after 48 h of Pb exposure. Calcium ion flux measurements using 45Ca as a radiotracer showed 65% inhibition of Ca2+ influx after 0, 12, 24 or 48 h exposure to the 96 h LC50 concentration of Pb. There was also significant inhibition (40-50%) of both Na+ and Cl- uptake, measured with 22Na and 36Cl simultaneously. We conclude that the mechanism of acute toxicity for Pb in rainbow trout occurs by ionoregulatory disruption rather than respiratory or acid/base distress at Pb concentrations close to the 96 h LC50 in moderately hard water

  17. Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes

    OpenAIRE

    Saeed, Mohammad F.; Kolokoltsov, Andrey A.; Albrecht, Thomas; Davey, Robert A.

    2010-01-01

    Zaire ebolavirus (ZEBOV), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing o...

  18. Dual strain mechanisms in a lead-free morphotropic phase boundary ferroelectric

    Science.gov (United States)

    Walker, Julian; Simons, Hugh; Alikin, Denis O.; Turygin, Anton P.; Shur, Vladimir Y.; Kholkin, Andrei L.; Ursic, Hana; Bencan, Andreja; Malic, Barbara; Nagarajan, Valanoor; Rojac, Tadej

    2016-01-01

    Electromechanical properties such as d33 and strain are significantly enhanced at morphotropic phase boundaries (MPBs) between two or more different crystal structures. Many actuators, sensors and MEMS devices are therefore systems with MPBs, usually between polar phases in lead (Pb)-based ferroelectric ceramics. In the search for Pb-free alternatives, systems with MPBs between polar and non-polar phases have recently been theorized as having great promise. While such an MPB was identified in rare-earth (RE) modified bismuth ferrite (BFO) thin films, synthesis challenges have prevented its realization in ceramics. Overcoming these, we demonstrate a comparable electromechanical response to Pb-based materials at the polar-to-non-polar MPB in Sm modified BFO. This arises from ‘dual’ strain mechanisms: ferroelectric/ferroelastic switching and a previously unreported electric-field induced transition of an anti-polar intermediate phase. We show that intermediate phases play an important role in the macroscopic strain response, and may have potential to enhance electromechanical properties at polar-to-non-polar MPBs.

  19. Dual strain mechanisms in a lead-free morphotropic phase boundary ferroelectric

    Science.gov (United States)

    Walker, Julian; Simons, Hugh; Alikin, Denis O.; Turygin, Anton P.; Shur, Vladimir Y.; Kholkin, Andrei L.; Ursic, Hana; Bencan, Andreja; Malic, Barbara; Nagarajan, Valanoor; Rojac, Tadej

    2016-01-01

    Electromechanical properties such as d33 and strain are significantly enhanced at morphotropic phase boundaries (MPBs) between two or more different crystal structures. Many actuators, sensors and MEMS devices are therefore systems with MPBs, usually between polar phases in lead (Pb)-based ferroelectric ceramics. In the search for Pb-free alternatives, systems with MPBs between polar and non-polar phases have recently been theorized as having great promise. While such an MPB was identified in rare-earth (RE) modified bismuth ferrite (BFO) thin films, synthesis challenges have prevented its realization in ceramics. Overcoming these, we demonstrate a comparable electromechanical response to Pb-based materials at the polar-to-non-polar MPB in Sm modified BFO. This arises from ‘dual’ strain mechanisms: ferroelectric/ferroelastic switching and a previously unreported electric-field induced transition of an anti-polar intermediate phase. We show that intermediate phases play an important role in the macroscopic strain response, and may have potential to enhance electromechanical properties at polar-to-non-polar MPBs. PMID:26791098

  20. Mechanism of Water Droplet Breakup Near the Leading Edge of an Airfoil

    Science.gov (United States)

    Vargas, Mario; Sor, Suthyvann; Magarino, Adelaida, Garcia

    2012-01-01

    This work presents results of an experimental study on droplet deformation and breakup near the leading edge of an airfoil. The experiment was conducted in the rotating rig test cell at the Instituto Nacional de Tecnica Aeroespacial (INTA) in Madrid, Spain. The airfoil model was placed at the end of the rotating arm and a monosize droplet generator produced droplets that fell from above, perpendicular to the path of the airfoil. The interaction between the droplets and the airfoil was captured with high speed imaging and allowed observation of droplet deformation and breakup as the droplet approached the airfoil near the stagnation line. Image processing software was used to measure the position of the droplet centroid, equivalent diameter, perimeter, area, and the major and minor axes of an ellipse superimposed over the deforming droplet. The horizontal and vertical displacement of each droplet against time was also measured, and the velocity, acceleration, Weber number, Bond number, Reynolds number, and the drag coefficients were calculated along the path of the droplet to the beginning of breakup. Droplet deformation is defined and studied against main parameters. The high speed imaging allowed observation of the actual mechanism of breakup and identification of the sequence of configurations from the initiation of the breakup to the disintegration of the droplet. Results and comparisons are presented for droplets of diameters in the range of 500 to 1800 microns, and airfoil velocities of 70 and 90 m/sec.

  1. Study and understanding of the ageing mechanisms in lead-calcium alloys

    International Nuclear Information System (INIS)

    The data available in the literature about ageing and over-ageing of lead-calcium alloys are often incomplete and inconsistent. It is undoubtedly due to the experimental difficulties encountered to observe the structure transformations which are numerous. As a result there is a certain confusion among the results of the different authors. Moreover, small variations in the process parameters and chemical composition may have some influence on the alloy behaviour. This work enabled us to obtain a set of TTT diagrams, more realistic and accurate than the ones available in the literature. Experimental techniques developed (particularly the preservation of the cold chain with is essential for the guaranty of the results repeatability), enabled particularly the study of the first transformations and better control the five stages of ageing and over-ageing. Our work have enabled to determine precisely the kinetics and the mechanisms of the transformations. This work constitutes a thorough analysis of the ageing and over-ageing of theses alloys. (author)

  2. Mechanisms of shrub encroachment into Northern Chihuahuan Desert grasslands and impacts of climate change investigated using a cellular automata model

    Science.gov (United States)

    Caracciolo, Domenico; Istanbulluoglu, Erkan; Noto, Leonardo Valerio; Collins, Scott L.

    2016-05-01

    Arid and semiarid grasslands of southwestern North America have changed dramatically over the last 150 years as a result of woody plant encroachment. Overgrazing, reduced fire frequency, and climate change are known drivers of woody plant encroachment into grasslands. In this study, relatively simple algorithms for encroachment factors (i.e., grazing, grassland fires, and seed dispersal by grazers) are proposed and implemented in the ecohydrological Cellular-Automata Tree Grass Shrub Simulator (CATGraSS). CATGraSS is used in a 7.3 km2 rectangular domain located in central New Mexico along a zone of grassland to shrubland transition, where shrub encroachment is currently active. CATGraSS is calibrated and used to investigate the relative contributions of grazing, fire frequency, seed dispersal by herbivores and climate change on shrub abundance over a 150-year period of historical shrub encroachment. The impact of future climate change is examined using a model output that realistically represents current vegetation cover as initial condition, in a series of stochastic CATGraSS future climate simulations. Model simulations are found to be highly sensitive to the initial distribution of shrub cover. Encroachment factors more actively lead to shrub propagation within the domain when the model starts with randomly distributed individual shrubs. However, when shrubs are naturally evolved into clusters, the model response to encroachment factors is muted unless the effect of seed dispersal by herbivores is amplified. The relative contribution of different drivers on modeled shrub encroachment varied based on the initial shrub cover condition used in the model. When historical weather data is used, CATGraSS predicted loss of shrub and grass cover during the 1950 s drought. While future climate change is found to amplify shrub encroachment (∼13% more shrub cover by 2100), grazing remains the dominant factor promoting shrub encroachment. When we modeled future climate

  3. RNase-L Control of Cellular mRNAs: Roles in Biologic Functions and Mechanisms of Substrate Targeting

    OpenAIRE

    Brennan-Laun, Sarah E.; Ezelle, Heather J.; Li, Xiao-Ling; Hassel, Bret A.

    2014-01-01

    RNase-L is a mediator of type 1 interferon-induced antiviral activity that has diverse and critical cellular roles, including the regulation of cell proliferation, differentiation, senescence and apoptosis, tumorigenesis, and the control of the innate immune response. Although RNase-L was originally shown to mediate the endonucleolytic cleavage of both viral and ribosomal RNAs in response to infection, more recent evidence indicates that RNase-L also functions in the regulation of cellular mR...

  4. Dysregulation of apoptosis: a possible mechanism leading to chronic progressive renal histological changes in lupus nephritis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To evakuate apoptosis in lupus nephritis and the relationship between the existence of apoptotic cells in renal tissue and histopathological or clinical changes. Methods Apoptosis was detected by in situ nick-end labeling techniques (TUNEL) in renal biopsies from 25 patients with type Ⅳ lupus nephritis (LN),12 patientswith lgA nephropathy lgAN, 4 patients with idiopathic easangnioproliferative lomerulonephritis(MsPGN) and 3 patients with acute poststreptococcal gornerulonephritis (APGN).Normal renal tissue obtained at nephrectomy for hypernephroma in 4 adults wes used as control. Proliferating cells were identified by proliferating cell nuclear antigen (PCNA) in these patiants. Results Compared to other proliferative glomerulonephritis and controls, the patients with lupus nephritis had lase apoptotic cells, a higher ratio of PCNA+cells/TdT+cells (P/T) in renal tissues; and their P/T ratio in glomeruli and tubulointerstitium correlated with the chronicity index, r=0.4983 (P=0.0132), r -0.8399 (P<0.001), r=0.6614 (,P=0.0033),respactively. P/T retios in the glomerulus and tubule had a positive correlation with 24-hour urinary protein,r=0.8554(P<0.001) and r=0.7134 (P=0.001); and a negative correlation with crsetinine clearance (Ccr), r=-0.4880(P=0.0133) and r=-0.7229(P=0.001),which in tubules positively correlated with serum creatinine (Scr), r=0.4107 (P=0.0414). Conclusions Apoptosis is reduced in proliferative lupus nephritis. Intense proliferation without a commensurate increase in apoptosis is a possible mechanism that leads to chronic progressive renalhistopathological changes.

  5. Study of apoptotic mechanisms induced by all-trans retinoic acid and its 13-cis isomer on cellular lines of human hepato carcinoma Hep3B and HepG2

    International Nuclear Information System (INIS)

    Two cellular lines of liver cancer (Hep3B and HepG2) were incubated during different periods of time with some concentrations of two retinoic acid isomers (ATRA and 13-cis AR) and with 5-fu chemotherapeutic agents, cisplatin and paclitaxel. It was determined if these substances leaded cytotoxicity, apoptosis and if they modified the expression of different genes related to cellular death by apoptosis, in order to explain the hepatocellular carcinoma resistance to these drugs. HepG2 cells showed more resistance than Hep3B cells to 72 hours of treatment, as much ATRA as the 13-cis AR were toxic and produced apoptosis in two cellular lines. This type of cellular death seems to be mediated by a decrease in Bcl-xL concentration in Hep3B cells treated with both retinoids an increase in bax concentration in HepG2 cells treated with 13-cis AR. It were observed 3 and 8 proteolysis of procaspase in Hep3B cells, suggesting extrinsic via activation of the apoptosis, while cellular death in HepG2 cells seems to be independent of caspases. Cisplatin and paclitaxel leaded cytotoxicity to 48 hours of treatment, with significant differences between two cellular lines only in case of paclitaxel. Hep3B cells treated with cisplatin and HepG2 cells treated with paclytaxel suffered apoptosis. 5-FU produced toxicity only when it was used to high concentrations and the mechanism of cellular death induced by this agent seems to be primarily necrosis in Hep3B cells and apoptosis in HepG2. There was decrease in the Bcl-xL concentration in two cellular lines when it was treated with cisplatin and in HepG2 cells treated with 5-FU. Bax concentration there no was modified with no treatment. Activation of the 3 caspases seems to happen only in HepG2 cells with 5-FU and paclytaxel. These two agents, also, decreased the survivin concentration of HepG2 cells. Treatments of the three drugs produced an increase in the expression of this gen in Hep3B cells, which might explain partially the resistance

  6. Modeling mechanical restriction differences between car and heavy truck in two-lane cellular automata traffic flow model

    Science.gov (United States)

    Li, Xin; Li, Xingang; Xiao, Yao; Jia, Bin

    2016-06-01

    Real traffic is heterogeneous with car and truck. Due to mechanical restrictions, the car and the truck have different limited deceleration capabilities, which are important factors in safety driving. This paper extends the single lane safety driving (SD) model with limited deceleration capability to two-lane SD model, in which car-truck heterogeneous traffic is considered. A car has a larger limited deceleration capability while a heavy truck has a smaller limited deceleration capability as a result of loaded goods. Then the safety driving conditions are different as the types of the following and the leading vehicles vary. In order to eliminate the well-known plug in heterogeneous two-lane traffic, it is assumed that heavy truck has active deceleration behavior when the heavy truck perceives the forming plug. The lane-changing decisions are also determined by the safety driving conditions. The fundamental diagram, spatiotemporal diagram, and lane-changing frequency were investigated to show the effect of mechanical restriction on heterogeneous traffic flow. It was shown that there would be still three traffic phases in heterogeneous traffic condition; the active deceleration of the heavy truck could well eliminate the plug; the lane-changing frequency was low in synchronized flow; the flow and velocity would decrease as the proportion of heavy truck grows or the limited deceleration capability of heavy truck drops; and the flow could be improved with lane control measures.

  7. Examples of processing problematic waste and material. A-3. Processing of lead by mechanical decontamination at UKAEA Harwell

    International Nuclear Information System (INIS)

    The UKAEA and its contractor (NNC) have decontaminated lead blocks arising from the decommissioning of a metallurgical site that comprised three concrete shielded remote handling cells and 36 lead shielded enclosures. The primary decommissioning and dismantling work entailed the dismantling of the 36 lead enclosures, which were expected to yield over 1000 t of lead shielding bricks as waste. During the initial dismantling of the lead shielded enclosures, all the lead bricks were monitored for radioactive contamination; clean items were segregated and set aside for detailed clearance and assurance checks. The contaminated blocks were sent for assessment and decontamination treatment, as necessary. The decontamination process utilized a purpose built partitioned containment tent, ventilated with a HEPA filtration system, so that the receipt, decontamination and radiological monitoring of individual items could be segregated in order to minimize any cross-contamination. The dismantled lead blocks comprised a range of standard thicknesses (2, 4, 9 and 10 in, or 3, 8, 13 and 15 cm) and incorporated a variety of chevron, concave and convex shapes, which are utilized to avoid weaknesses within the assembled shielding. The primary technical issues for the mechanical processing of the contaminated lead blocks were consideration of the individual lead brick shapes (i.e. the bricks were contoured) and the individual weight of the bricks, which had a range of 10-75 kg. The preferred option was a manual dry cutting technique using a handheld rotary industrial planer (the selected planer is normally associated with the joinery trade). The dry cutting option considered the malleability of the lead, which under certain circumstances during dry cutting could give rise to localized heating effects, leading to melted lead over the cutting surface, resulting in limited effectiveness in the removal of the contaminated layer. To mitigate this effect the planer was set to take cuts

  8. Mechanisms of ALA-D inhibition by lead and of its restoration by zinc and dithiothreitol.

    OpenAIRE

    Sakai, T.; Yanagihara, S; Kunugi, Y.; Ushio, K

    1983-01-01

    To induce the inhibition of ALA-D (delta-aminolaevulinic acid dehydratase) activity by lead in vitro, it is necessary to preincubate the enzyme fraction with lead ions and the Hb fraction (factors) together. The combination of two of the three (ALA-D fraction, lead acetate, and Hb fraction) in the preincubation has only a small effect on the activity. Lead preincubated with ALA-D and Hb fractions does not alter the affinity of the enzyme for the substrate, suggesting that the substrate can bi...

  9. Lead telluride with increased mechanical stability for cylindrical thermoelectric generators; Bleitellurid mit erhoehter mechanischer Stabilitaet fuer zylindrische thermoelektrische Generatoren

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, Andreas

    2013-04-30

    The aim of this work is to improve the mechanical stability of lead telluride (PbTe), trying to vary its mechanical properties independently from its thermoelectric properties. Thus the influence of material preparation as well as different dopants on the mechanical and thermoelectric properties of lead telluride is being analysed. When using appropriately set process parameters, milling and sintering of lead telluride increases the material's hardness. With sintering temperatures exceeding 300 C stable material of high relative density can be achieved. Milling lead telluride generates lattice defects leading to a reduction of the material's charge carrier density. These defects can be reduced by increased sintering temperatures. Contamination of the powder due to the milling process leads to bloating during thermal cycling and thus reduced density of the sintered material. In addition to that, evaporation of tellurium at elevated temperatures causes instability of the material's thermoelectric properties. Based on the experimental results obtained in this work, the best thermoelectric and mechanical properties can be obtained by sintering coarse powders at around 400 C. Within this work a concept was developed to vary the mechanical properties of lead telluride via synthesis of PbTe with electrically nondoping elements, which thus may keep the thermoelectric properties unchanged. Therefore, the mechanical and thermoelectric properties of Pb{sub 1-x}Ca{sub x}Te were investigated. Doping pure PbTe with calcium causes a significant increase of the material's hardness while only slightly decreasing the charge carrier density and thus keeping the thermoelectric properties apart from a slight reduction of the electrical conductivity nearly unchanged. The abovementioned concept is proven using sodium doped lead telluride, as it is used for thermoelectric generators: The additional doping with calcium again increases the material's hardness while

  10. The ACADS gene variation spectrum in 114 patients with short-chain acyl-CoA dehydrogenase (SCAD) deficiency is dominated by missense variations leading to protein misfolding at the cellular level

    DEFF Research Database (Denmark)

    Pedersen, Christina Bak; Kølvrå, Steen; Kølvraa, Agnete;

    2008-01-01

    , 26 missense, one start codon, and two stop codon variations. In vitro import studies of variant SCAD proteins in isolated mitochondria from SCAD deficient (SCAD-/-) mice demonstrated an increased tendency of the abnormal proteins to misfold and aggregate compared to the wild-type, a phenomenon that...... often leads to gain-of-function cellular phenotypes. However, no correlation was found between the clinical phenotype and the degree of SCAD dysfunction. We propose that SCAD deficiency should be considered as a disorder of protein folding that can lead to clinical disease in combination with other...

  11. Hemerythrin-like domain within F-box and leucine-rich repeat protein 5 (FBXL5) communicates cellular iron and oxygen availability by distinct mechanisms.

    Science.gov (United States)

    Chollangi, Srinivas; Thompson, Joel W; Ruiz, Julio C; Gardner, Kevin H; Bruick, Richard K

    2012-07-01

    Iron regulatory proteins play a principal role in maintaining cellular iron homeostasis by post-transcriptionally regulating factors responsible for iron uptake, utilization, and storage. An E3 ubiquitin ligase complex containing FBXL5 targets IRP2 for proteasomal degradation under iron- and oxygen-replete conditions, whereas FBXL5 itself is degraded when iron and oxygen availability decreases. FBXL5 contains a hemerythrin-like (Hr) domain at its N terminus that mediates its own differential stability. Here, we investigated the iron- and oxygen-dependent conformational changes within FBXL5-Hr that underlie its role as a cellular sensor. As predicted, FBXL5-Hr undergoes substantive structural changes when iron becomes limiting, accounting for its switch-like behavior. However, these same changes are not observed in response to oxygen depletion, indicating that this domain accommodates two distinct sensing mechanisms. Moreover, FBXL5-Hr does not behave as a dynamic sensor that continuously samples the cellular environment, assuming conformations in equilibrium with ever-changing cellular iron levels. Instead, the isolated domain appears competent to incorporate iron only at or near the time of its own synthesis. These observations have important implications for mechanisms by which these metabolites are sensed within mammalian cells. PMID:22648410

  12. Cellular resilience.

    Science.gov (United States)

    Smirnova, Lena; Harris, Georgina; Leist, Marcel; Hartung, Thomas

    2015-01-01

    Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks. PMID:26536287

  13. Cellular effects of LRRK2 mutations

    OpenAIRE

    Cookson, Mark R.

    2012-01-01

    Mutations in leucine-rich repeat kinase 2 (LRRK2) are a relatively common cause of inherited Parkinson's disease (PD) but the mechanism(s) by which mutations lead to disease are poorly understood. Here, I will discuss what is known about LRRK2 in cellular models, focusing on specifically on assays that have been used to tease apart the effects of LRRK2 mutations on cellular phenotypes. LRRK2 expression has been suggested to cause loss of neuronal viability, although because it also has a stro...

  14. Mechanisms Leading to Co-Existence of Gas Hydrate in Ocean Sediments [Part 1 of 2

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, Steven; Juanes, Ruben

    2011-12-31

    In this project we have sought to explain the co-existence of gas and hydrate phases in sediments within the gas hydrate stability zone. We have focused on the gas/brine interface at the scale of individual grains in the sediment. The capillary forces associated with a gas/brine interface play a dominant role in many processes that occur in the pores of sediments and sedimentary rocks. The mechanical forces associated with the same interface can lead to fracture initiation and propagation in hydrate-bearing sediments. Thus the unifying theme of the research reported here is that pore scale phenomena are key to understanding large scale phenomena in hydrate-bearing sediments whenever a free gas phase is present. Our analysis of pore-scale phenomena in this project has delineated three regimes that govern processes in which the gas phase pressure is increasing: fracturing, capillary fingering and viscous fingering. These regimes are characterized by different morphology of the region invaded by the gas. On the other hand when the gas phase pressure is decreasing, the corresponding regimes are capillary fingering and compaction. In this project, we studied all these regimes except compaction. Many processes of interest in hydrate-bearing sediments can be better understood when placed in the context of the appropriate regime. For example, hydrate formation in sub-permafrost sediments falls in the capillary fingering regime, whereas gas invasion into ocean sediments is likely to fall into the fracturing regime. Our research provides insight into the mechanisms by which gas reservoirs are converted to hydrate as the base of the gas hydrate stability zone descends through the reservoir. If the reservoir was no longer being charged, then variation in grain size distribution within the reservoir explain hydrate saturation profiles such as that at Mt. Elbert, where sand-rich intervals containing little hydrate are interspersed between intervals containing large hydrate

  15. Mechanisms Leading to Co-Existence of Gas Hydrate in Ocean Sediments [Part 2 of 2

    Energy Technology Data Exchange (ETDEWEB)

    Bryant, Steven; Juanes, Ruben

    2011-12-31

    In this project we have sought to explain the co-existence of gas and hydrate phases in sediments within the gas hydrate stability zone. We have focused on the gas/brine interface at the scale of individual grains in the sediment. The capillary forces associated with a gas/brine interface play a dominant role in many processes that occur in the pores of sediments and sedimentary rocks. The mechanical forces associated with the same interface can lead to fracture initiation and propagation in hydrate-bearing sediments. Thus the unifying theme of the research reported here is that pore scale phenomena are key to understanding large scale phenomena in hydrate-bearing sediments whenever a free gas phase is present. Our analysis of pore-scale phenomena in this project has delineated three regimes that govern processes in which the gas phase pressure is increasing: fracturing, capillary fingering and viscous fingering. These regimes are characterized by different morphology of the region invaded by the gas. On the other hand when the gas phase pressure is decreasing, the corresponding regimes are capillary fingering and compaction. In this project, we studied all these regimes except compaction. Many processes of interest in hydrate-bearing sediments can be better understood when placed in the context of the appropriate regime. For example, hydrate formation in sub-permafrost sediments falls in the capillary fingering regime, whereas gas invasion into ocean sediments is likely to fall into the fracturing regime. Our research provides insight into the mechanisms by which gas reservoirs are converted to hydrate as the base of the gas hydrate stability zone descends through the reservoir. If the reservoir was no longer being charged, then variation in grain size distribution within the reservoir explain hydrate saturation profiles such as that at Mt. Elbert, where sand-rich intervals containing little hydrate are interspersed between intervals containing large hydrate

  16. 中小企业单元组织的信息结构及创新机制%SMEs’ Cellular Organizations and their Information Structures and Innovation Mechanisms

    Institute of Scientific and Technical Information of China (English)

    刘群慧; 张建林

    2012-01-01

    Information structure is an important issue of corporate governance structure.Different information structures generate different governance mechanisms,which lead to different governance efficiency.The cellular organization is an effective collaborative innovation form for small & medium enterprises(SMEs),and its information structure is closely related to innovation mechanisms.Based on the definition discussion of SMEs’ cellular organization,this paper analyzes the organizational information structure and the innovation mechanisms corresponding to the variety information structure.%信息结构是分析组织治理问题的核心,不同的信息结构会产生相应的治理机制,从而形成不同的治理效率。单元组织模式作为一种中小企业协作创新的有效组织形式,其所表现出来的信息结构与组织的创新机制密切相关。从探讨中小企业单元组织内涵入手,分析单元组织内部成员企业间存在的主要信息结构,能够揭示基于不同信息结构的创新机制。

  17. A knock-in model of human epilepsy in Drosophila reveals a novel cellular mechanism associated with heat-induced seizure

    OpenAIRE

    Sun, Lei; Gilligan, Jeff; Staber, Cynthia; Schutte, Ryan J; Nguyen, Vivian; O'Dowd, Diane K.; Reenan, Robert

    2012-01-01

    Over 40 missense mutations in the human SCN1A sodium channel gene are linked to an epilepsy syndrome termed genetic epilepsy with febrile seizures plus (GEFS+). Inheritance of GEFS+ is dominant but the underlying cellular mechanisms remain poorly understood. Here we report knock-in of a GEFS+ SCN1A mutation (K1270T) into the Drosophila sodium channel gene, para, causes a semi-dominant temperature-induced seizure phenotype. Electrophysiological studies of GABAergic interneurons in the brains o...

  18. A novel antibody-dependent cellular cytotoxicity mechanism involved in defense against malaria requires costimulation of monocytes FcgammaRII and FcgammaRIII

    DEFF Research Database (Denmark)

    Jafarshad, Ali; Dziegiel, Morten Hanefeld; Lundquist, Rasmus; Nielsen, Leif K; Singh, Subhash; Druilhe, Pierre L

    2007-01-01

    Clinical experiments have shown that the Ab-dependent cell-mediated inhibition of Plasmodium falciparum is a major mechanism controlling malaria parasitemia and thereby symptoms. In this study, we demonstrate that a single merozoite per monocyte (MN) is sufficient to trigger optimal antiparasitic......-dependent cellular cytotoxicity and implies that all MN are not equally effective. These findings have both fundamental and practical implications, particularly for vaccine discovery....

  19. Mechanisms of antibody-dependent cellular cytotoxicity: the use of effector cells from chronic granulomatous disease patients as investigative probes.

    OpenAIRE

    Katz, P.; Simone, C B; Henkart, P A; Fauci, A S

    1980-01-01

    The present study characterized the antibody-dependent cellular cytoxicity (ADCC) of leukocyte effector cells (neutrophils, lymphocytes, and monocytes) from normal subjects and from chronic granulomatous disease (CGD) patients. CGD phagocytic cells (neutrophils and monocytes) had depressed ADCC activity against antibody-coated human erythrocyte (HRBC) targets in suspension cultures indicative of abnormal intracellular postphagocytic killing. However, when phagocytosis was prevented by using a...

  20. p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Li

    Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

  1. Comparison on cellular mechanisms of iron and cadmium accumulation in rice: prospects for cultivating Fe-rich but Cd-free rice.

    Science.gov (United States)

    Gao, Lei; Chang, Jiadong; Chen, Ruijie; Li, Hubo; Lu, Hongfei; Tao, Longxing; Xiong, Jie

    2016-12-01

    Iron (Fe) is essential for rice growth and humans consuming as their staple food but is often deficient because of insoluble Fe(III) in soil for rice growth and limited assimilation for human bodies, while cadmium (Cd) is non-essential and toxic for rice growth and humans if accumulating at high levels. Over-accumulated Cd can cause damage to human bodies. Selecting and breeding Fe-rich but Cd-free rice cultivars are ambitious, challenging and meaningful tasks for researchers. Although evidences show that the mechanisms of Fe/Cd uptake and accumulation in rice are common to some extent as a result of similar entry routes within rice, an increasing number of researchers have discovered distinct mechanisms between Fe/Cd uptake and accumulation in rice. This comprehensive review systematically elaborates and compares cellular mechanisms of Fe/Cd uptake and accumulation in rice, respectively. Mechanisms for maintaining Fe homeostasis and Cd detoxicification are also elucidated. Then, effects of different fertilizer management on Fe/Cd accumulation in rice are discussed. Finally, this review enumerates various approaches for reducing grain Cd accumulation and enhancing Fe content in rice. In summary, understanding of discrepant cellular mechanisms of Fe/Cd accumulation in rice provides guidance for cultivating Fe-fortified rice and has paved the way to develop rice that are tolerant to Cd stress, aiming at breeding Fe-rich but Cd-free rice. PMID:27502932

  2. Optimal Ordering Policy and Coordination Mechanism of a Supply Chain with Controllable Lead-Time-Dependent Demand Forecast

    Directory of Open Access Journals (Sweden)

    Hua-Ming Song

    2011-01-01

    Full Text Available This paper investigates the ordering decisions and coordination mechanism for a distributed short-life-cycle supply chain. The objective is to maximize the whole supply chain's expected profit and meanwhile make the supply chain participants achieve a Pareto improvement. We treat lead time as a controllable variable, thus the demand forecast is dependent on lead time: the shorter lead time, the better forecast. Moreover, optimal decision-making models for lead time and order quantity are formulated and compared in the decentralized and centralized cases. Besides, a three-parameter contract is proposed to coordinate the supply chain and alleviate the double margin in the decentralized scenario. In addition, based on the analysis of the models, we develop an algorithmic procedure to find the optimal ordering decisions. Finally, a numerical example is also presented to illustrate the results.

  3. Keratin network modifications lead to the mechanical stiffening of the hair follicle fiber.

    Science.gov (United States)

    Bornschlögl, Thomas; Bildstein, Lucien; Thibaut, Sébastien; Santoprete, Roberto; Fiat, Françoise; Luengo, Gustavo S; Doucet, Jean; Bernard, Bruno A; Baghdadli, Nawel

    2016-05-24

    The complex mechanical properties of biomaterials such as hair, horn, skin, or bone are determined by the architecture of the underlying fibrous bionetworks. Although much is known about the influence of the cytoskeleton on the mechanics of isolated cells, this has been less studied in tridimensional tissues. We used the hair follicle as a model to link changes in the keratin network composition and architecture to the mechanical properties of the nascent hair. We show using atomic force microscopy that the soft keratinocyte matrix at the base of the follicle stiffens by a factor of ∼360, from 30 kPa to 11 MPa along the first millimeter of the follicle. The early mechanical stiffening is concomitant to an increase in diameter of the keratin macrofibrils, their continuous compaction, and increasingly parallel orientation. The related stiffening of the material follows a power law, typical of the mechanics of nonthermal bending-dominated fiber networks. In addition, we used X-ray diffraction to monitor changes in the (supra)molecular organization within the keratin fibers. At later keratinization stages, the inner mechanical properties of the macrofibrils dominate the stiffening due to the progressive setting up of the cystine network. Our findings corroborate existing models on the sequence of biological and structural events during hair keratinization. PMID:27162354

  4. Early-life Stress Impacts the Developing Hippocampus and Primes Seizure Occurrence: cellular, molecular, and epigenetic mechanisms

    Directory of Open Access Journals (Sweden)

    Li-Tung eHuang

    2014-02-01

    Full Text Available Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed.

  5. DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences

    Directory of Open Access Journals (Sweden)

    Gaëlle Lenglet

    2010-01-01

    Full Text Available DNA targeting drugs represent a large proportion of the actual anticancer drug pharmacopeia, both in terms of drug brands and prescription volumes. Small DNA-interacting molecules share the ability of certain proteins to change the DNA helix's overall organization and geometrical orientation via tilt, roll, twist, slip, and flip effects. In this ocean of DNA-interacting compounds, most stabilize both DNA strands and very few display helix-destabilizing properties. These types of DNA-destabilizing effect are observed with certain mono- or bis-intercalators and DNA alkylating agents (some of which have been or are being developed as cancer drugs. The formation of locally destabilized DNA portions could interfere with protein/DNA recognition and potentially affect several crucial cellular processes, such as DNA repair, replication, and transcription. The present paper describes the molecular basis of DNA destabilization, the cellular impact on protein recognition, and DNA repair processes and the latter's relationships with antitumour efficacy.

  6. Differential Effects of Polymer-Surface Decoration on Drug Delivery, Cellular Retention, and Action Mechanisms of Functionalized Mesoporous Silica Nanoparticles.

    Science.gov (United States)

    You, Yuanyuan; Hu, Hao; He, Lizhen; Chen, Tianfeng

    2015-12-01

    Polymer-surface decoration has been found to be an effective strategy to enhance the biological activities of nanomedicine. Herein, three different types of polymers with a cancer-targeting ligand Arg-Gly-Asp peptide (RGD) have been used to decorate mesoporous silica nanoparticles (MSNs) and the functionalized nanosystems were used as drug carriers of oxaliplatin (OXA). The results showed that polymer-surface decoration of the MSNs nanosystem by poly(ethylene glycol) (PEG) and polyethyleneimine (PEI) significantly enhanced the anticancer efficacy of OXA, which was much higher than that of chitosan (CTS). This effect was closely related to the enhancement of the cellular uptake and cellular drug retention. Moreover, PEI@MSNs-OXA possessed excellent advantages in penetrating ability and inhibitory effects on SW480 spheroids that were used to simulate the in vivo tumor environments. Therefore, this study provides useful information for the rational design of a cancer-targeted MSNs nanosystem with polymer-surface decoration. PMID:26248202

  7. Early-life Stress Impacts the Developing Hippocampus and Primes Seizure Occurrence: cellular, molecular, and epigenetic mechanisms

    OpenAIRE

    Li-Tung eHuang

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures...

  8. Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

    OpenAIRE

    Huang, Li-Tung

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures...

  9. Contributions of mass spectrometry-based proteomics to defining cellular mechanisms and diagnostic markers for systemic lupus erythematosus

    OpenAIRE

    Korte, Erik A.; Gaffney, Patrick M.; Powell, David W.

    2012-01-01

    Systematic lupus erythematosus (SLE) is a complex disease for which molecular diagnostics are limited and pathogenesis is not clearly understood. Important information is provided in this regard by identification and characterization of more specific molecular and cellular targets in SLE immune cells and target tissue and markers of early-onset and effective response to treatment of SLE complications. In recent years, advances in proteomic technologies and applications have facilitated such d...

  10. Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

    Science.gov (United States)

    Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

    2014-03-01

    Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

  11. Analysis of physical mechanisms which lead to destruction of fuel containing materials

    International Nuclear Information System (INIS)

    Analysis of physical processes that may cause the fragility and destruction of the lava-like fuel containing materials (FCM) of 4-th unit of Chernobyl nuclear plant has been carried out. The following processes are considered: 1) influence of electric fields arising in medium with incorporated radio-nuclides, 2) the role of the defect creation by irradiation of incorporated nuclides, 3) residual mechanical strains caused by their cooling from the melting temperature in the time of the accident to the ambient temperature at present. It is shown that mechanical strains of such kind might be one of the causes of degradation and destruction of fuel containing materials

  12. Combination of different molecular mechanisms leading to fluconazole resistance in a Candida lusitaniae clinical isolate.

    Science.gov (United States)

    Reboutier, David; Piednoël, Mathieu; Boisnard, Stéphanie; Conti, Audrey; Chevalier, Virginie; Florent, Martine; Gibot-Leclerc, Stéphanie; Da Silva, Bruno; Chastin, Christiane; Fallague, Karim; Favel, Anne; Noël, Thierry; Ruprich-Robert, Gwenaël; Chapeland-Leclerc, Florence; Papon, Nicolas

    2009-02-01

    We report on the underlying molecular mechanisms likely responsible for the high-level fluconazole resistance in a Candida lusitaniae clinical isolate. Fluconazole resistance correlated with overexpression of ERG11 and of several efflux pump genes, in particular, the orthologs of the Candida albicans MDR1, PDR16, CDR1, CDR2, and YOR1. PMID:19070454

  13. The involvement of selected membrane transport mechanisms in the cellular uptake of 177Lu-labeled bombesin, somatostatin and gastrin analogues

    International Nuclear Information System (INIS)

    Introduction: Radiolabeled receptor-targeting peptides are a useful tool for the diagnostic imaging and radiotherapy of some malignancies. However, the retention of radioactivity in the kidney may result in renal radiotoxic injury. This study seeks to evaluate the role of endocytic receptor megalin, renal SLC influx transporters and fluid phase endocytosis (FPE) in the cellular accumulation of radiolabeled peptides. Methods: In vitro transport cellular studies using megalin ligands (RAP, albumin), fluid phase endocytosis (FPE) inhibitor rottlerin and low temperature were employed to evaluate the transport mechanisms of the peptides. Cells transfected with hOAT1 or hOCT2 were used to analyze the role of these SLC transporters. Somatostatin (177Lu-DOTA-[Tyr3]octreotate, 177Lu-DOTA-[1-Nal3]octreotide), gastrin (177Lu-DOTA-sargastrin) and bombesin (177Lu-DOTA-[Pro1,Tyr4]bombesin, 177Lu-DOTA-[Lys3]bombesin, 177Lu-PCTA-[Lys3]bombesin) analogues were involved in the study. Results: RAP, albumin and low temperature decreased the accumulation of all the studied peptides significantly. With one exception, rottlerin caused the concentration dependent inhibition of the cellular accumulation of the radiopeptides. No significant differences in the uptake of the peptides between the control cells and those transfected with hOAT1 or hOCT2 were observed. Conclusion: The study showed that active transport mechanisms are decisive for the cellular accumulation in all tested 177Lu-labeled somatostatin, gastrin and bombesin analogues. Besides receptor-mediated endocytosis by megalin, FPE participates significantly in the uptake. The tested types of renal SLC transporters are not involved in this process

  14. Cu(II)-coumestrol interaction leads to ROS-mediated DNA damage and cell death: a putative mechanism for anticancer activity.

    Science.gov (United States)

    Zafar, Atif; Singh, Swarnendra; Naseem, Imrana

    2016-07-01

    Phytoestrogens have attracted considerable interest as natural alternatives to hormone replacement therapy and their potential as cancer therapeutic agents. Among phytoestrogens, coumestrol has shown multipharmacological properties such as antiinflammatory, neuroprotective, osteoblastic differentiation and anticancer. Though several studies have described anticancer effects of coumestrol, a clear underlying molecular mechanism has not been elucidated. Unlike normal cells, cancer cells contain elevated copper levels that play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper in cancer cells can serve as effective anticancer strategy. Using human peripheral lymphocytes, we assessed lipid peroxidation, protein carbonylation, reactive oxygen species (ROS) generation, DNA damage and apoptosis by coumestrol in the presence of exogenously added Cu(II) in cells to simulate malignancy-like condition. Results showed that Cu(II)-coumestrol interaction leads to lipid peroxidation and protein carbonylation (markers of oxidative stress), DNA fragmentation and apoptosis in treated lymphocytes. Further, incubation of lymphocytes with ROS scavengers and membrane-permeant copper chelator, neocuproine, resulted in inhibition of DNA damage and apoptosis. This suggests that coumestrol engages in redox cycling of Cu(II) to generate ROS that leads to DNA fragmentation and apoptosis. In conclusion, this is the first report showing that coumestrol targets cellular copper to induce prooxidant death in malignant cells. We believe that such a prooxidant cytotoxic mechanism better explains the anticancer activity of coumestrol. These findings will provide significant insights into the development of new chemical molecules with better copper-chelating and prooxidant properties against cancer cells. PMID:27260464

  15. Postnatal overnutrition in mice leads to impaired pulmonary mechanics in response to salbutamol.

    Science.gov (United States)

    Teixeira, Vanessa P; Cervilha, Daniela A B; Cabral, Layla D M; Oliveira, Luiz M; Incerpi, Erika K; Novaes, Rômulo D; Ionta, Marisa; Soncini, Roseli

    2016-05-01

    Obesity increases the risk of respiratory disease, which is associated with airway hyperresponsiveness. Although the molecular underpinnings of this phenomenon are not well established, lung remodeling is known as an important factor in this process and could potentially explain compromised lung functions. In the present study, the obesity was induced by postnatal overnutrition in Swiss mice and we investigated the pulmonary mechanics after aerosolization of saline, methacholine, and salbutamol. The lungs were prepared for morphometric analysis. Obese animals showed bronchoconstriction in response to methacholine, as evidenced by airway and tissue resistance, tissue elastance, and hysteresivity. Salbutamol was effective at recovering the response only for airway resistance but not for tissue mechanics. We suggest that this impaired response in obese mice is related to collapsed alveolar, to inflammatory cells, and to elevated deposition collagen fibers in parenchymal tissue. PMID:26497334

  16. The ownership structure and control mechanisms in Sweden: Case study of leading pyramidal corporations

    OpenAIRE

    Sharifi, Nazanin

    2014-01-01

    ABSTRACT: This study describes the differences between the corporate governance systems and the ownership structures around the world. It concentrates on the ownership structure of the firms in continental European countries and examined control-enhancing mechanisms that are used to increase controlling power of dominated shareholders in selected developed countries such as Germany, France, Italy and the Netherlands. By using data collected from listed companies in Stockholm stock market, thi...

  17. Effects of voids on thermal-mechanical reliability of lead-free solder joints

    OpenAIRE

    Benabou Lahouari; Le Van Nhat; Sun Zhidan; Pougnet Philippe; Etgens Victor

    2014-01-01

    Reliability of electronic packages has become a major issue, particularly in systems used in electrical or hybrid cars where severe operating conditions must be met. Many studies have shown that solder interconnects are critical elements since many failure mechanisms originate from their typical response under thermal cycles. In this study, effects of voids in solder interconnects on the electronic assembly lifetime are estimated based on finite element simulations.

  18. AFM and SEM-FEG study on fundamental mechanisms leading to fatigue crack initiation

    Czech Academy of Sciences Publication Activity Database

    Man, Jiří; Valtr, M.; Petrenec, Martin; Dluhoš, J.; Kuběna, Ivo; Obrtlík, Karel; Polák, Jaroslav

    2015-01-01

    Roč. 76, JUL (2015), s. 11-18. ISSN 0142-1123 R&D Projects: GA ČR(CZ) GAP108/10/2371; GA MŠk(CZ) ED1.1.00/02.0068; GA ČR(CZ) GA13-23652S Institutional support: RVO:68081723 Keywords : fatigue crack initiation * 316L austenitic steel * atomic force microscopy * extrusion * intrusion Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.275, year: 2014

  19. Effects of voids on thermal-mechanical reliability of lead-free solder joints

    Directory of Open Access Journals (Sweden)

    Benabou Lahouari

    2014-06-01

    Full Text Available Reliability of electronic packages has become a major issue, particularly in systems used in electrical or hybrid cars where severe operating conditions must be met. Many studies have shown that solder interconnects are critical elements since many failure mechanisms originate from their typical response under thermal cycles. In this study, effects of voids in solder interconnects on the electronic assembly lifetime are estimated based on finite element simulations.

  20. New genetic findings lead the way to a better understanding of fundamental mechanisms of drug hypersensitivity.

    Science.gov (United States)

    Pirmohamed, Munir; Ostrov, David A; Park, B Kevin

    2015-08-01

    Drug hypersensitivity reactions are an important clinical problem for both health care and industry. Recent advances in genetics have identified a number of HLA alleles associated with a range of these adverse reactions predominantly affecting the skin but also other organs, such as the liver. The associations between abacavir hypersensitivity and HLA-B*57:01 and carbamazepine-induced Stevens-Johnson syndrome and HLA-B*15:02 have been implemented in clinical practice. There are many different mechanisms proposed in the pathogenesis of drug hypersensitivity reactions, including the hapten hypothesis, direct binding to T-cell receptors (the pharmacologic interaction hypothesis), and peptide-binding displacement. A problem with all the hypotheses is that they are largely based on in vitro findings, with little direct in vivo evidence. Although most studies have focused on individual mechanisms, it is perhaps more important to consider them all as being complementary, potentially occurring at the same time with the same drug in the same patient. This might at least partly account for the heterogeneity of the immune response seen in different patients. There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention of these serious adverse reactions. PMID:26254050

  1. Failure mechanisms and assembly-process-based solution of FCBGA high lead C4 bump non-wetting

    International Nuclear Information System (INIS)

    This paper studies the typical failure modes and failure mechanisms of non-wetting in an FCBGA (flip chip ball grid array) assembly. We have identified that the residual lead and tin oxide layer on the surface of the die bumps as the primary contributor to non-wetting between die bumps and substrate bumps during the chip-attach reflow process. Experiments with bump reflow parameters revealed that an optimized reflow dwell time and H2 flow rate in the reflow oven can significantly reduce the amount of lead and tin oxides on the surface of the die bumps, thereby reducing the non-wetting failure rate by about 90%. Both failure analysis results and mass production data validate the non-wetting failure mechanisms identified by this study. As a result of the reflow process optimization, the failure rate associated with non-wetting is significantly reduced, which further saves manufacturing cost and increases capacity utilization. (semiconductor technology)

  2. Positive and negative regulatory mechanisms for fine-tuning cellularity and functions of medullary thymic epithelial cells

    Directory of Open Access Journals (Sweden)

    Taishin eAkiyama

    2015-09-01

    Full Text Available Self-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell-cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of thymic epithelial cells (TECs. Tumor necrosis factor (TNF family RANK ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid cells (ILCs, promote the differentiation and proliferation of medullary TECs (mTECs that play critical roles in the induction of immune tolerance. A recent study suggests that interleukin-22 (IL-22 produced by ILCs promotes regeneration of TECs after irradiation. Intriguingly, TGF-β and osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell generation. We will review recent insights into the molecular basis for cell-cell interactions regulating differentiation and proliferation of mTECs and also discuss about a perspective on use of mathematical models for understanding this complicated system.

  3. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  4. Effect of iron and indium on IMC formation and mechanical properties of lead-free solder

    International Nuclear Information System (INIS)

    Highlights: ► The addition of In and Ce/Fe affected the IMC morphology and increased shear strength. ► The addition of Fe resulted in increased wettability of the SAC solder. ► The melting Point of the SAC solder was decreased by the addition of In and Ce. ► The addition of Fe/In and Ce led to a decrease in the CTE. ► The addition of 0.6Fe/In and Ce resulted in a single peak in DSC, despite the addition of 0.2Fe. - Abstract: In recent years, because of environmental concerns, lead solders have been replaced by lead-free solders. One of the numerous lead-free solders developed in the past several years is the Sn–Ag–Cu (SAC) eutectic solder. This work explored the effects of adding iron and indium to the reliability of SAC solder. Four different solders have been fabricated by adding Fe or In into the solder, i.e., Sn3.6Ag0.9Cu (SAC–E), SAC–Fe02, SAC–Fe06 and SAC–InCe. DSC results showed that adding indium decreased the melting point of SAC, and the single eutectic peak was maintained in all cases. Solders were reflowed on bare Cu and electroless Ni–P-coated substrates. It was found that the SAC–E and SAC–InCe gave the highest and the lowest IMC thickness, respectively among all solders. The same pattern was observed in the wetting angle measurement. Shear strength results showed that the SAC–Fe06 and SAC–Fe02 solder displayed the highest strength, followed by SAC–InCe and the SAC–E solder had the lowest strength. Results suggest that adding small amounts of Fe and In and Ce improved the wettability and shear strength of the SAC solder. Also, the Coefficient of thermal expansion measurement showed a possible decrease in thermal expansion mismatch with the addition of In and Ce and Fe into the SAC eutectic solder.

  5. Solidification mechanism of highly undercooled metal alloys. [tin-lead and nickel-tin alloys

    Science.gov (United States)

    Shiohara, Y.; Chu, M. G.; Macisaac, D. G.; Flemings, M. C.

    1982-01-01

    Experiments were conducted on metal droplet undercooling, using Sn-25wt%Pb and Ni-34wt%Sn alloys. To achieve the high degree of undercooling, emulsification treatments were employed. Results show the fraction of supersaturated primary phase is a function of the amount of undercooling, as is the fineness of the structures. The solidification behavior of the tin-lead droplets during recalescence was analyzed using three different hypotheses; (1) solid forming throughout recalescence is of the maximum thermodynamically stable composition; (2) partitionless solidification below the T sub o temperature, and solid forming thereafter is of the maximum thermodynamically stable composition; and (3) partitionless solidification below the T sub o temperature with solid forming thereafter that is of the maximum thermodynamically metastable composition that is possible. The T sub o temperature is calculated from the equal molar free energies of the liquid solid using the regular solution approximation.

  6. Elements for the Development of a Darwinian Scheme Leading to Quantum Mechanics

    Science.gov (United States)

    Baladrón, Carlos

    2015-10-01

    A subquantum theory is examined in which a fundamental system has been characterized as the association of a particle with a continuous trajectory in real space and a classical probabilistic Turing machine defined on an informational space. The particle transfers information to the machine, and this steers the particle by means of self-interaction. In a certain sense, the associated Turing machine might be considered a generalization of the pilot wave function of Bohmian mechanics. The data processing capability entailed by the Turing machine makes the particle a generalized Darwinian system on which natural selection may operate. Darwinian evolution acting on the informational space should then drive the particle from random behaviour purportedly associated to an initial blank state to a possible evolutionarily stable strategy (ESS). Three regulating principles that plausibly encode an ESS are stated. The derivation of the postulates of quantum mechanics is discussed assuming that the behaviour of systems is governed by the three regulating principles. The theory also enables, within the generalized Darwinian framework, a natural characterization of entanglement through the local interaction between the Turing machines of the subsystems. Some possible future experimental and computational tests of the theory are outlined. The central aim of this scheme is to explore the possibility that generalized Darwinian natural selection might induce the emergence of quantum mechanics and its weird features from a real and local underlying description of particles supplemented with a Turing machine on an informational space, since those systems presenting quantum behaviour seem to be the most robust at a microscopic level.

  7. A mechanism for mitigation of blade-vortex interaction using leading edge blowing flow control

    Science.gov (United States)

    Weiland, Chris; Vlachos, Pavlos P.

    2009-09-01

    The interaction of a vortical unsteady flow with structures is often encountered in engineering applications. Such flow structure interactions (FSI) can be responsible for generating significant loads and can have many detrimental structural and acoustic side effects, such as structural fatigue, radiated noise and even catastrophic results. Amongst the different types of FSI, the parallel blade-vortex interaction (BVI) is the most common, often encountered in helicopters and propulsors. In this work, we report on the implementation of leading edge blowing (LEB) active flow control for successfully minimizing the parallel BVI. Our results show reduction of the airfoil vibrations up to 38% based on the root-mean-square of the vibration velocity amplitude. This technique is based on displacing an incident vortex using a jet issued from the leading edge of a sharp airfoil effectively increasing the stand-off distance of the vortex from the body. The effectiveness of the method was experimentally analyzed using time-resolved digital particle image velocimetry (TRDPIV) recorded at an 800 Hz rate, which is sufficient to resolve the spatio-temporal dynamics of the flow field and it was combined with simultaneous accelerometer measurements of the airfoil, which was free to oscillate in a direction perpendicular to the freestream. Analysis of the flow field spectra and a Proper Orthogonal Decomposition (POD) of the TRDPIV data of the temporally resolved planar flow fields indicate that the LEB effectively modified the flow field surrounding the airfoil and increased the convecting vortices stand-off distance for over half of the airfoil chord length. It is shown that LEB also causes a redistribution of the flow field spectral energy over a larger range of frequencies.

  8. A mechanism for mitigation of blade-vortex interaction using leading edge blowing flow control

    Energy Technology Data Exchange (ETDEWEB)

    Weiland, Chris; Vlachos, Pavlos P. [Virginia Tech, Department of Mechanical Engineering, Blacksburg, VA (United States)

    2009-09-15

    The interaction of a vortical unsteady flow with structures is often encountered in engineering applications. Such flow structure interactions (FSI) can be responsible for generating significant loads and can have many detrimental structural and acoustic side effects, such as structural fatigue, radiated noise and even catastrophic results. Amongst the different types of FSI, the parallel blade-vortex interaction (BVI) is the most common, often encountered in helicopters and propulsors. In this work, we report on the implementation of leading edge blowing (LEB) active flow control for successfully minimizing the parallel BVI. Our results show reduction of the airfoil vibrations up to 38% based on the root-mean-square of the vibration velocity amplitude. This technique is based on displacing an incident vortex using a jet issued from the leading edge of a sharp airfoil effectively increasing the stand-off distance of the vortex from the body. The effectiveness of the method was experimentally analyzed using time-resolved digital particle image velocimetry (TRDPIV) recorded at an 800 Hz rate, which is sufficient to resolve the spatio-temporal dynamics of the flow field and it was combined with simultaneous accelerometer measurements of the airfoil, which was free to oscillate in a direction perpendicular to the freestream. Analysis of the flow field spectra and a Proper Orthogonal Decomposition (POD) of the TRDPIV data of the temporally resolved planar flow fields indicate that the LEB effectively modified the flow field surrounding the airfoil and increased the convecting vortices stand-off distance for over half of the airfoil chord length. It is shown that LEB also causes a redistribution of the flow field spectral energy over a larger range of frequencies. (orig.)

  9. Dual strain mechanisms in a lead-free morphotropic phase boundary ferroelectric

    DEFF Research Database (Denmark)

    Walker, Julian; Simons, Hugh; Alikin, Denis O;

    2016-01-01

    )-based ferroelectric ceramics. In the search for Pb-free alternatives, systems with MPBs between polar and non-polar phases have recently been theorized as having great promise. While such an MPB was identified in rare-earth (RE) modified bismuth ferrite (BFO) thin films, synthesis challenges have prevented its...... realization in ceramics. Overcoming these, we demonstrate a comparable electromechanical response to Pb-based materials at the polar-to-non-polar MPB in Sm modified BFO. This arises from 'dual' strain mechanisms: ferroelectric/ferroelastic switching and a previously unreported electric-field induced...

  10. The cellular decision between apoptosis and autophagy

    Directory of Open Access Journals (Sweden)

    Yong-Jun Fan

    2013-03-01

    Full Text Available Apoptosis and autophagy are important molecular processes that maintain organismal and cellular homeostasis, respectively. While apoptosis fulfills its role through dismantling damaged or unwanted cells, autophagy maintains cellular homeostasis through recycling selective intracellular organelles and molecules. Yet in some conditions, autophagy can lead to cell death. Apoptosis and autophagy can be stimulated by the same stresses. Emerging evidence indicates an interplay between the core proteins in both pathways, which underlies the molecular mechanism of the crosstalk between apoptosis and autophagy. This review summarizes recent literature on molecules that regulate both the apoptotic and autophagic processes.

  11. Physical mechanisms leading to high currents of highly charged ions in laser-driven ion sources

    Energy Technology Data Exchange (ETDEWEB)

    Haseroth, Helmut [European Organization for Nuclear Research, Geneva (Switzerland); Hora, Heinrich [New South Wales Univ., Kensington, NSW (Australia)]|[Regensburg Inst. of Tech. (Germany). Anwenderzentrum

    1996-12-31

    Heavy ion sources for the big accelerators, for example, the LHC, require considerably more ions per pulse during a short time than the best developed classical ion source, the electron cyclotron resonance (ECR) provides; thus an alternative ion source is needed. This can be expected from laser-produced plasmas, where dramatically new types of ion generation have been observed. Experiments with rather modest lasers have confirmed operation with one million pulses of 1 Hz, and 10{sup 11} C{sup 4+} ions per pulse reached 2 GeV/u in the Dubna synchrotron. We review here the complexities of laser-plasma interactions to underline the unique and extraordinary possibilities that the laser ion source offers. The complexities are elaborated with respect to keV and MeV ion generation, nonlinear (ponderomotive) forces, self-focusing, resonances and ``hot`` electrons, parametric instabilities, double-layer effects, and the few ps stochastic pulsation (stuttering). Recent experiments with the laser ion source have been analyzed to distinguish between the ps and ns interaction, and it was discovered that one mechanism of highly charged ion generation is the electron impact ionization (EII) mechanism, similar to the ECR, but with so much higher plasma densities that the required very large number of ions per pulse are produced. (author).

  12. Rapid Disruption of Cellular Integrity of Zinc-treated Astroglia Is Regulated by p38 MAPK and Ca2+-dependent Mechanisms

    OpenAIRE

    Im, Joo-Young; Joo, Hyo-Jin; Han, Pyung-Lim

    2011-01-01

    Cultured cortical primary astroglia treated with zinc died while rapidly detached from culture plates, a distinct part of zinc-treated astroglia. In the present study, we investigated the mechanism underlying the rapid change in the morphologic integrity of zinc-treated astroglia. Among the early cellular events occurring in zinc-treated astroglia, strong activation of p38 MAPK and JNK was evident. Although inhibitors of p38 (SB203580 and SB202190) or JNK (SP600125) did not protect zinc-insul...

  13. International Legal Mechanisms Of Responsibility For The Harm To Climate Leading To Change Of The State Territory Formation

    Directory of Open Access Journals (Sweden)

    Sergey D. Belockiy

    2014-09-01

    Full Text Available In the present article author analyzed question international legal responsibility of state’s for harm done by the climatic changes caused by the emission of greenhouse gases in the course of activity in the power sphere, leading to flooding of the state territories formation. Such mechanisms are based on a number of international legal acts, from which the documents of the system UN FCCC play a key role, including both FCCC, and the Kyoto Protocol and the decisions made within the Conference of parties. At the same time there is a number of problems, unresolved within the modern international law, namely mechanisms of such responsibility realization and proof of connection existence between emissions of greenhouse gases by this state and flooding of other state territory which in principle have to lead to the responsibility occurrence. Author explains that this moment is especially important because international law doesn't forbid emissions of greenhouse gases itself. Besides, recently perspectives of climate changes began to be considered as a threat to peace and safety, what makes it possibility of implement other then UN FCCC mechanisms. Author notes that, for example, they are considered by the UN Security Council. In the conclusion author makes a statement that at this stage of development of international law we deal with a forming mechanism of the state’s international legal responsibility for the harm done by the climate changes caused by factors, including emission of greenhouse gases in the course of activity in the power sphere.

  14. Hypoxic ischemia encephalopathy leading to external hydrocephalus and the cerebral atrophy: mechanism and differential diagnosis

    International Nuclear Information System (INIS)

    Objective: It is a study of the mechanism and differential diagnosis of the infant external hydrocephalus and cerebral atrophy. Methods: In total 84 cases of neonatal hypoxic ischemia encephalopathy followed by infant external hydrocephalus were investigated, among which 26 patients gradually were found having developed cerebral atrophy in follow up. Results: Characteristic dilation of the frontal-parietal subarachnoid space and the adjacent cistern was noted on the CT images of the external hydrocephalus. CT revealed the enlarged ventricle besides the dilated subarachnoid space in the cases of cerebral atrophy, while these two entities were indistinguishable on CT in the early stage. Conclusion: Clinical manifestations make a major differential diagnosis of the external hydrocephalus and cerebral atrophy: tic and mild delayed development of locomotion over major presentation of external hydrocephalus, while cerebral atrophy is featured by remarkable dysnoesia and severe delayed development of locomotion. In addition, hemiplegia and increased muscular tension are presented in a few cases of cerebral atrophy

  15. Depletion of cellular iron by curcumin leads to alteration in histone acetylation and degradation of Sml1p in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Gajendra Kumar Azad

    Full Text Available Curcumin, a naturally occurring polyphenolic compound, is known to possess diverse pharmacological properties. There is a scarcity of literature documenting the exact mechanism by which curcumin modulates its biological effects. In the present study, we have used yeast as a model organism to dissect the mechanism underlying the action of curcumin. We found that the yeast mutants of histone proteins and chromatin modifying enzymes were sensitive to curcumin and further supplementation of iron resulted in reversal of the changes induced by curcumin. Additionally, treatment of curcumin caused the iron starvation induced expression of FET3, FRE1 genes. We also demonstrated that curcumin induces degradation of Sml1p, a ribonucleotide reductase inhibitor involved in regulating dNTPs production. The degradation of Sml1p was mediated through proteasome and vacuole dependent protein degradation pathways. Furthermore, curcumin exerts biological effect by altering global proteome profile without affecting chromatin architecture. These findings suggest that the medicinal properties of curcumin are largely contributed by its cumulative effect of iron starvation and epigenetic modifications.

  16. Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad F Saeed

    Full Text Available Zaire ebolavirus (ZEBOV, a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new

  17. Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

    Science.gov (United States)

    Saeed, Mohammad F; Kolokoltsov, Andrey A; Albrecht, Thomas; Davey, Robert A

    2010-01-01

    Zaire ebolavirus (ZEBOV), a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new therapeutics as well as

  18. The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR

    Directory of Open Access Journals (Sweden)

    Mónica Roxo-Rosa

    2015-11-01

    Full Text Available In autosomal dominant polycystic kidney disease (ADPKD, cyst inflation and continuous enlargement are associated with marked transepithelial ion and fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR. Indeed, the inhibition or degradation of CFTR prevents the fluid accumulation within cysts. The in vivo mechanisms by which the lack of Polycystin-2 leads to CFTR stimulation are an outstanding challenge in ADPKD research and may bring important biomarkers for the disease. However, hampering their study, the available ADPKD in vitro cellular models lack the three-dimensional architecture of renal cysts and the ADPKD mouse models offer limited access for live-imaging experiments in embryonic kidneys. Here, we tested the zebrafish Kupffer's vesicle (KV as an alternative model-organ. KV is a fluid-filled vesicular organ, lined by epithelial cells that express both CFTR and Polycystin-2 endogenously, being each of them easily knocked-down. Our data on the intracellular distribution of Polycystin-2 support its involvement in the KV fluid-flow induced Ca2+-signalling. Mirroring kidney cysts, the KV lumen inflation is dependent on CFTR activity and, as we clearly show, the knockdown of Polycystin-2 results in larger KV lumens through overstimulation of CFTR. In conclusion, we propose the zebrafish KV as a model organ to study the renal cyst inflation. Favouring its use, KV volume can be easily determined by in vivo imaging offering a live readout for screening compounds and genes that may prevent cyst enlargement through CFTR inhibition.

  19. Temperature effect on the corrosion mechanism of austenitic and martensitic steels in lead-bismuth

    International Nuclear Information System (INIS)

    Compatibility tests on the austenitic AISI 316L and the martensitic MANET II steels in stagnant PbBi were performed at 573, 673 and 823 K with exposures up to 5000 h. The change of the corrosion mechanism with increasing temperature has been evaluated. The results showed that at 573 and 673 K a thin oxide layer growth on the surface of both steels. By increasing the temperature to 823 K both types of steels were attacked by the liquid metal and dissolution of the steel alloying elements has been observed. The herein-reported experimental activities were performed in collaboration with the IPPE of Obninsk, where preliminary dynamic tests were performed in the experimental facility CU-2. The Russian ferritic-martensitic steel EP823 has been exposed to flowing PbBi at 623, 723 and 823 K for 700 h. After 700 h of testing, the surface of the EP823 samples showed for the three temperatures a compact oxide layer

  20. Hormesis and Cellular Quality Control: A Possible Explanation for the Molecular Mechanisms that Underlie the Benefits of Mild Stress

    OpenAIRE

    Wiegant, F.A.C.; de Poot, S A H; Boers-Trilles, V.E.; Schreij, A.M.A

    2012-01-01

    In contrast to the detrimental action of severe stress conditions, the beneficial effects of mild stress, known as hormesis, is increasingly discussed and studied. A variety of applications for hormesis in risk assessment processes, anti-ageing strategies and clinical therapies have been proposed. The molecular mechanisms underlying the phenomenon of hormesis, however, are not yet fully understood. A possible mechanism that has been proposed for hormesis, the homoeostasis overshoot hypothesis...

  1. Metal and metalloid foliar uptake by various plant species exposed to atmospheric industrial fallout: Mechanisms involved for lead

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, E., E-mail: eva.schreck@ensat.fr [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); Foucault, Y. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); STCM, Societe de Traitements Chimiques des Metaux, 30 Avenue de Fondeyre 31200 Toulouse (France); Sarret, G. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Sobanska, S. [LASIR (UMR CNRS 8516), Universite de Lille 1, Bat. C5, 59655 Villeneuve d' Ascq cedex (France); Cecillon, L. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Castrec-Rouelle, M. [Universite Pierre and Marie Curie (UPMC-Paris 6), Bioemco (Biogeochimie et Ecologie des Milieux Continentaux), Site Jussieu, Tour 56, 4 Place Jussieu, 75252 Paris cedex 05 (France); Uzu, G. [Laboratoire d' Aerologie (UMR 5560), OMP, UPS 14, Avenue Edouard Belin, 31400 Toulouse (France); GET (UMR 5563), IRD, 14, Avenue Edouard Belin, 31400 Toulouse (France); Dumat, C. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France)

    2012-06-15

    Fine and ultrafine metallic particulate matters (PMs) are emitted from metallurgic activities in peri-urban zones into the atmosphere and can be deposited in terrestrial ecosystems. The foliar transfer of metals and metalloids and their fate in plant leaves remain unclear, although this way of penetration may be a major contributor to the transfer of metals into plants. This study focused on the foliar uptake of various metals and metalloids from enriched PM (Cu, Zn, Cd, Sn, Sb, As, and especially lead (Pb)) resulting from the emissions of a battery-recycling factory. Metal and metalloid foliar uptake by various vegetable species, exhibiting different morphologies, use (food or fodder) and life-cycle (lettuce, parsley and rye-grass) were studied. The mechanisms involved in foliar metal transfer from atmospheric particulate matter fallout, using lead (Pb) as a model element was also investigated. Several complementary techniques (micro-X-ray fluorescence, scanning electron microscopy coupled with energy dispersive X-ray microanalysis and time-of-flight secondary ion mass spectrometry) were used to investigate the localization and the speciation of lead in their edible parts, i.e. leaves. The results showed lead-enriched PM on the surface of plant leaves. Biogeochemical transformations occurred on the leaf surfaces with the formation of lead secondary species (PbCO{sub 3} and organic Pb). Some compounds were internalized in their primary form (PbSO{sub 4}) underneath an organic layer. Internalization through the cuticle or penetration through stomata openings are proposed as two major mechanisms involved in foliar uptake of particulate matter. - Graphical abstract: Overall picture of performed observations and mechanisms potentially involved in lead foliar uptake. Highlights: Black-Right-Pointing-Pointer Foliar uptake of metallic particulate matter (PM) is of environmental and health concerns. Black-Right-Pointing-Pointer The leaf morphology influences the adsorption

  2. Physical mechanisms that lead to large-scale gas accumulation in a volcanic conduit

    Science.gov (United States)

    Collombet, Marielle; Burgisser, Alain

    2016-04-01

    The eruption of viscous magma at the Earth's surface often gives rise to abrupt regime changes. The transition from the gentle effusion of a lava dome to brief but powerful explosions is a common regime change. This transition is often preceded by the sealing of the shallow part of the volcanic conduit and the accumulation of volatile-rich magma underneath, a situation that collects the energy to be brutally released during the subsequent explosion. While conduit sealing is well-documented, volatile accumulation has proven harder to characterize. We use a 2D conduit flow model including gas loss within the magma and into the wallrock to find steady-state magma flow configurations in the effusive regime. Model outputs yield a strongly heterogeneous distribution of the gas volume fraction underneath a dense, impermeable magma cap. Gas accumulates in inclined structures hundredths of meters long and several meters thick. These structures probably constitute the gas pockets that accumulate explosive energy and that were intuited by previous studies. We tested the numerical robustness of our results by simulating the fragmented state of the magma contained within the pockets, by testing various fragmentation criteria, and by varying computational gird size. These gas pockets are robust features that occur regardless of wallrock permeability (from very permeable at 10-12 m2 to quasi impermeable at 10-16 m2) but that are sensitive to the volume to surface ratio of the volcanic conduit. One implication is that the formation of these large degassing structures probably plays an essential role in the triggering of violent explosions. Such large scale outgassing feature may also bring a partial answer to the long standing issue of the observed gas transfer across entire magmatic systems despite high magma viscosity and no obvious physical mechanism of transfer.

  3. Fatigue failure kinetics and structural changes in lead-free interconnects due to mechanical and thermal cycling

    Science.gov (United States)

    Fiedler, Brent Alan

    Environmental and human health concerns drove European parliament to mandate the Reduction of Hazardous Substances (RoHS) for electronics. This was enacted in July 2006 and has practically eliminated lead in solder interconnects. There is concern in the electronics packaging community because modern lead-free solder is rich in tin. Presently, near-eutectic tin-silver-copper solders are favored by industry. These solders are stiffer than the lead-tin near-eutectic alloys, have a higher melting temperature, fewer slip systems, and form intermetallic compounds (IMC) with Cu, Ni and Ag, each of which tend to have a negative effect on lifetime. In order to design more reliable interconnects, the experimental observation of cracking mechanisms is necessary for the correct application of existing theories. The goal of this research is to observe the failure modes resulting from mode II strain and to determine the damage mechanisms which describe fatigue failures in 95.5 Sn- 4.0 Ag - 0.5 Cu wt% (SAC405) lead-free solder interconnects. In this work the initiation sites and crack paths were characterized for SAC405 ball-grid array (BGA) interconnects with electroless-nickel immersion-gold (ENIG) pad-finish. The interconnects were arranged in a perimeter array and tested in fully assembled packages. Evaluation methods included monotonic and displacement controlled mechanical shear fatigue tests, and temperature cycling. The specimens were characterized using metallogaphy, including optical and electron microscopy as well as energy dispersive spectroscopy (EDS) and precise real-time electrical resistance structural health monitoring (SHM). In mechanical shear fatigue tests, strain was applied by the substrates, simulating dissimilar coefficients of thermal expansion (CTE) between the board and chip-carrier. This type of strain caused cracks to initiate in the soft Sn-rich solder and grow near the interface between the solder and intermetallic compounds (IMC). The growth near

  4. A numerical investigation into the effects of Reynolds number on the flow mechanism induced by a tubercled leading edge

    Science.gov (United States)

    Rostamzadeh, Nikan; Kelso, Richard M.; Dally, Bassam

    2016-05-01

    Leading-edge modifications based on designs inspired by the protrusions on the pectoral flippers of the humpback whale (tubercles) have been the subject of research for the past decade primarily due to their flow control potential in ameliorating stall characteristics. Previous studies have demonstrated that, in the transitional flow regime, full-span wings with tubercled leading edges outperform unmodified wings at high attack angles. The flow mechanism associated with such enhanced loading traits is, however, still being investigated. Also, the performance of full-span tubercled wings in the turbulent regime is largely unexplored. The present study aims to investigate Reynolds number effects on the flow mechanism induced by a full-span tubercled wing with the NACA-0021 cross-sectional profile in the transitional and near-turbulent regimes using computational fluid dynamics. The analysis of the flow field suggests that, with the exception of a few different flow features, the same underlying flow mechanism, involving the presence of transverse and streamwise vorticity, is at play in both cases. With regard to lift-generation characteristics, the numerical simulation results indicate that in contrast to the transitional flow regime, where the unmodified NACA-0021 undergoes a sudden loss of lift, in the turbulent regime, the baseline foil experiences gradual stall and produces more lift than the tubercled foil. This observation highlights the importance of considerations regarding the Reynolds number effects and the stall characteristics of the baseline foil, in the industrial applications of tubercled lifting bodies.

  5. Mobilization of Intracellular Copper by Gossypol and Apogossypolone Leads to Reactive Oxygen Species-Mediated Cell Death: Putative Anticancer Mechanism.

    Science.gov (United States)

    Zubair, Haseeb; Azim, Shafquat; Khan, Husain Yar; Ullah, Mohammad Fahad; Wu, Daocheng; Singh, Ajay Pratap; Hadi, Sheikh Mumtaz; Ahmad, Aamir

    2016-01-01

    There is compelling evidence that serum, tissue and intracellular levels of copper are elevated in all types of cancer. Copper has been suggested as an important co-factor for angiogenesis. It is also a major metal ion present inside the nucleus, bound to DNA bases, particularly guanine. We have earlier proposed that the interaction of phenolic-antioxidants with intracellular copper leads to the generation of reactive oxygen species (ROS) that ultimately serve as DNA cleaving agents. To further validate our hypothesis we show here that the antioxidant gossypol and its semi-synthetic derivative apogossypolone induce copper-mediated apoptosis in breast MDA-MB-231, prostate PC3 and pancreatic BxPC-3 cancer cells, through the generation of ROS. MCF10A breast epithelial cells refractory to the cytotoxic property of these compounds become sensitized to treatment against gossypol, as well as apogossypolone, when pre-incubated with copper. Our present results confirm our earlier findings and strengthen our hypothesis that plant-derived antioxidants mobilize intracellular copper instigating ROS-mediated cellular DNA breakage. As cancer cells exist under significant oxidative stress, this increase in ROS-stress to cytotoxic levels could be a successful anticancer approach. PMID:27331811

  6. Mobilization of Intracellular Copper by Gossypol and Apogossypolone Leads to Reactive Oxygen Species-Mediated Cell Death: Putative Anticancer Mechanism

    Directory of Open Access Journals (Sweden)

    Haseeb Zubair

    2016-06-01

    Full Text Available There is compelling evidence that serum, tissue and intracellular levels of copper are elevated in all types of cancer. Copper has been suggested as an important co-factor for angiogenesis. It is also a major metal ion present inside the nucleus, bound to DNA bases, particularly guanine. We have earlier proposed that the interaction of phenolic-antioxidants with intracellular copper leads to the generation of reactive oxygen species (ROS that ultimately serve as DNA cleaving agents. To further validate our hypothesis we show here that the antioxidant gossypol and its semi-synthetic derivative apogossypolone induce copper-mediated apoptosis in breast MDA-MB-231, prostate PC3 and pancreatic BxPC-3 cancer cells, through the generation of ROS. MCF10A breast epithelial cells refractory to the cytotoxic property of these compounds become sensitized to treatment against gossypol, as well as apogossypolone, when pre-incubated with copper. Our present results confirm our earlier findings and strengthen our hypothesis that plant-derived antioxidants mobilize intracellular copper instigating ROS-mediated cellular DNA breakage. As cancer cells exist under significant oxidative stress, this increase in ROS-stress to cytotoxic levels could be a successful anticancer approach.

  7. Mechanical properties and cellular response of novel electrospun nanofibers for ligament tissue engineering: Effects of orientation and geometry.

    Science.gov (United States)

    Pauly, Hannah M; Kelly, Daniel J; Popat, Ketul C; Trujillo, Nathan A; Dunne, Nicholas J; McCarthy, Helen O; Haut Donahue, Tammy L

    2016-08-01

    Electrospun nanofibers are a promising material for ligamentous tissue engineering, however weak mechanical properties of fibers to date have limited their clinical usage. The goal of this work was to modify electrospun nanofibers to create a robust structure that mimics the complex hierarchy of native tendons and ligaments. The scaffolds that were fabricated in this study consisted of either random or aligned nanofibers in flat sheets or rolled nanofiber bundles that mimic the size scale of fascicle units in primarily tensile load bearing soft musculoskeletal tissues. Altering nanofiber orientation and geometry significantly affected mechanical properties; most notably aligned nanofiber sheets had the greatest modulus; 125% higher than that of random nanofiber sheets; and 45% higher than aligned nanofiber bundles. Modifying aligned nanofiber sheets to form aligned nanofiber bundles also resulted in approximately 107% higher yield stresses and 140% higher yield strains. The mechanical properties of aligned nanofiber bundles were in the range of the mechanical properties of the native ACL: modulus=158±32MPa, yield stress=57±23MPa and yield strain=0.38±0.08. Adipose derived stem cells cultured on all surfaces remained viable and proliferated extensively over a 7 day culture period and cells elongated on nanofiber bundles. The results of the study suggest that aligned nanofiber bundles may be useful for ligament and tendon tissue engineering based on their mechanical properties and ability to support cell adhesion, proliferation, and elongation. PMID:27082129

  8. SMTCI: Secure Multi-Trial Trust Evaluation and Cost- Effective Incentive Mechanism for Multi-Hop Cellular Networks

    Directory of Open Access Journals (Sweden)

    B.Sumathi

    2013-04-01

    Full Text Available In multi-hop cellular networks, finding an optimum and trusted route in the network through intermediate node is a major issue. At MCN, or the next-generation wireless networks, can significantly improve network performance and deployment and help implement many novel applications and services. However, when compared to wired and single-hop wireless networks, MCNs are highly vulnerable to serious security threats because packets may be relayed through integrated networks and autonomous devices. Our Proposed work has been focusing on developing secure trust based protocols for securing MCNs. Specifically, we are interested in securing route establishment and data transmission processes, establishing stable routes, and preserving users’ anonymity and location privacy. In this paperwe propose a multi-trial trust evaluation scheme, trusted node based ad hoc routing using trials to establish security accomplishes establishment of trusted networks in MANETs. We apply the same idea todevelop our proposed algorithm TBARA to rate neighbor nodes using hash values for identifying the misbehaving nodes. After the successful transmission of packets from source to destination, thedestination will send acknowledgement for the corresponding packet, upon receiving of acknowledgement incentive will be generated. It reduces the number of public-key cryptographic operations and protectagainst collusion attack.

  9. Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function.

    Science.gov (United States)

    Sandlers, Yana; Mercier, Kelly; Pathmasiri, Wimal; Carlson, Jim; McRitchie, Susan; Sumner, Susan; Vernon, Hilary J

    2016-01-01

    Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects. PMID:27015085

  10. The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells.

    Science.gov (United States)

    Zhang, Jie; Liu, Dan; Zhang, Mengjun; Sun, Yuqi; Zhang, Xiaojun; Guan, Guannan; Zhao, Xiuli; Qiao, Mingxi; Chen, Dawei; Hu, Haiyang

    2016-01-01

    Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting increased research attention, but their transportation behavior in resistant cells remains unclear. In this paper, we performed a systematic analysis of the cellular uptake, intracellular transportation, and efflux of PAMAM-NH2 dendrimers in multidrug-resistant breast cancer cells (MCF-7/ADR cells) using sensitive breast cancer cells (MCF-7 cells) as the control. We found that the uptake rate of PAMAM-NH2 was much lower and exocytosis of PAMAM-NH2 was much greater in MCF-7/ADR cells than in MCF-7 cells due to the elimination of PAMAM-NH2 from P-glycoprotein and the multidrug resistance-associated protein in MCF-7/ADR cells. Macropinocytosis played a more important role in its uptake in MCF-7/ADR cells than in MCF-7 cells. PAMAM-NH2 aggregated and became more degraded in the lysosomal vesicles of the MCF-7/ADR cells than in those of the MCF-7 cells. The endoplasmic reticulum and Golgi complex were found to participate in the exocytosis rather than endocytosis process of PAMAM-NH2 in both types of cells. Our findings clearly showed the intracellular transportation process of PAMAM-NH2 in MCF-7/ADR cells and provided a guide of using PAMAM-NH2 as a drug and gene vector in resistant cells. PMID:27536106

  11. Force control for mechanoinduction of impedance variation in cellular organisms

    International Nuclear Information System (INIS)

    Constantly exposed to various forms of mechanical forces inherent in their physical environment (such as gravity, stress induced by fluid flow or cell–cell interactions, etc), cellular organisms sense such forces and convert them into biochemical signals through the processes of mechanosensing and mechanotransduction that eventually lead to biological changes. The effect of external forces on the internal structures and activities in a cellular organism may manifest in changes its physical properties, such as impedance. Studying variation in the impedance of a cellular organism induced by the application of an external mechanical force represents a meaningful endeavor (from a biosystems perspective) in exploring the complex mechanosensing and mechanotransduction mechanisms that govern the behavior of a cellular organism under the influence of external mechanical stimuli. In this paper we describe the development of an explicit force-feedback control system for exerting an indentation force on a cellular organism while simultaneously measuring its impedance. To demonstrate the effectiveness of this force-control system, we have conducted experiments using zebrafish embryos as a test model of a cellular organism. We report experimental results demonstrating that the application of a properly controlled external force leads to a significant change in the impedance of a zebrafish embryo. These results offer support for a plausible explanation that activities of pore canals in the chorion are responsible for the observed change in impedance.

  12. Effects Of Nickel On The Microstructure And The Mechanical Properties Of Sn-0.7Cu Lead-Free Solders

    Directory of Open Access Journals (Sweden)

    Gyenes A.

    2015-06-01

    Full Text Available This paper investigates the effects of small amount nickel addition (0, 200, 400, 800, 1800 ppm on the microstructure and the mechanical properties of Sn-0.7Cu lead-free solder alloys. It is known that even ppm level Ni additions have significant effects on the microstructure of Sn-Cu solder alloys. Ni suppresses the growth of β-Sn dendrites in favour of eutectic formation. As the nickel content increases, the microstructure undergoes a morphological evolution from hypoeutectic through fully eutectic to hypereutectic. Along with these transformations, the mechanical properties of the alloy also significantly change. Based on the experimental results presented in this paper, the Sn-0.7Cu solder achieves maximum strength at the addition level of 800 ppm Ni, when the microstructure becomes fully eutectic.

  13. Cellular Metabolism and Dose Reveal Carnitine-Dependent and -Independent Mechanisms of Butyrate Oxidation in Colorectal Cancer Cells.

    Science.gov (United States)

    Han, Anna; Bennett, Natalie; MacDonald, Amber; Johnstone, Megan; Whelan, Jay; Donohoe, Dallas R

    2016-08-01

    Dietary fiber has been suggested to suppress colorectal cancer development, although the mechanisms contributing to this beneficial effect remain elusive. Butyrate, a fermentation product of fiber, has been shown to have anti-proliferative and pro-apoptotic effects on colorectal cancer cells. The metabolic fate of butyrate in the cell is important in determining whether, it acts as an HDAC inhibitor or is consumed as a short-chain fatty acid. Non-cancerous colonocytes utilize butyrate as the primary energy source whereas cancerous colonocytes increase glucose utilization through the Warburg effect. In this study, we show that butyrate oxidation is decreased in cancerous colonocytes compared to non-cancerous colonocytes. We demonstrate that colorectal cancer cells utilize both a carnitine-dependent and carnitine-independent mechanism that contributes to butyrate oxidation. The carnitine-dependent mechanism is contingent on butyrate concentration. Knockdown of CPT1A in colorectal cancer cells abolishes butyrate oxidation. In terms of selectivity, the carnitine-dependent mechanism only regulated butyrate oxidation, as acetate and propionate oxidation were carnitine-independent. Carnitine decreased the action of butyrate as an HDAC inhibitor and suppressed induction of H3 acetylation by butyrate in colorectal cancer cells. Thus, diminished oxidation of butyrate is associated with decreased HDAC inhibition and histone acetylation. In relation to the mechanism, we find that dichloroacetate, which decreases phosphorylation of pyruvate dehydrogenase, increased butyrate oxidation and that this effect was carnitine-dependent. In conclusion, these data suggest that colorectal cancer cells decrease butyrate oxidation through inhibition of pyruvate dehydrogenase, which is carnitine-dependent, and provide insight into why butyrate shows selective effects toward colorectal cancer cells. J. Cell. Physiol. 231: 1804-1813, 2016. © 2015 Wiley Periodicals, Inc. PMID:26661480

  14. By Different Cellular Mechanisms, Lymphatic Vessels Sprout by Endothelial Cell Recruitment Whereas Blood Vessels Grow by Vascular Expansion

    Science.gov (United States)

    Parsons-Wingerter, Patricia; McKay, Terri L.; Leontiev, Dmitry; Condrich, Terence K.; DiCorleto, Paul E.

    2005-01-01

    The development of effective vascular therapies requires the understanding of all modes of vessel formation contributing to vasculogenesis, angiogenesis (here termed hemangiogenesis) and lymphangiogenesis. We show that lymphangiogenesis proceeds by blind-ended vessel sprouting via recruitment of isolated endothelial progenitor cells to the tips of growing vessels, whereas hemangiogenesis occurs by non-sprouting vessel expansion from the capillary network, during middevelopment in the quail chorioallantoic membrane (CAM). Blood vessels expanded out of capillaries that displayed transient expression of alpha smooth muscle actin (alphaSMA), accompanied by mural recruitment of migratory progenitor cells expressing SMA. Lymphatics and blood vessels were identified by confocal/fluorescence microscopy of vascular endothelial growth factor (VEGF) receptors VEGFR-1 and VEGFR-2, alphaSMA (expressed on CAM blood vessels but not on lymphatics), homeobox transcription factor Prox-1 (specific to CAM lymphatic endothelium), and the quail hematopoetic/vascular marker, QH-1. Expression of VEGFR-1 was highly restricted to blood vessels (primarily capillaries). VEGFR-2 was expressed intensely in isolated hematopoietic cells, lymphatic vessels and moderately in blood vessels. Prox-1 was absent from endothelial progenitor cells prior to lymphatic recruitment. Although vascular endothelial growth factor-165 (VEGF(sub 165)) is a key regulator of numerous cellular processes in hemangiogenesis and vasculogenesis, the role of VEGF(sub 165) in lymphangiogenesis is less clear. Exogenous VEGF(sub 165) increased blood vessel density without changing endogenous modes of vascular/lymphatic vessel formation or marker expression patterns. However, VEGF(sub 165) did increase the frequency of blood vascular anastomoses and strongly induced the antimaturational dissociation of lymphatics from blood vessels, with frequent formation of homogeneous lymphatic networks.

  15. Neuronal Hypoxia Induces Hsp40-Mediated Nuclear Import of Type 3 Deiodinase As an Adaptive Mechanism to Reduce Cellular Metabolism

    OpenAIRE

    Jo, S; Kallo, I.; Bardoczi, Z.; Arrojo e Drigo, R.; Zeold, A.; Liposits, Z.; Oliva, A.; Lemmon, V.P.; Bixby, J. L.; Gereben, B.; A.C. Bianco

    2012-01-01

    In neurons, the type 3 deiodinase (D3) inactivates thyroid hormone and reduces oxygen consumption, thus creating a state of cell-specific hypothyroidism. Here we show that hypoxia leads to nuclear import of D3 in neurons, without which thyroid hormone signaling and metabolism cannot be reduced. After unilateral hypoxia in the rat brain, D3 protein level is increased predominantly in the nucleus of the neurons in the pyramidal and granular ipsilateral layers, as well as in the hilus of the den...

  16. Mechanism of cellular uptake of HIV-TAT peptide & effects of TAT-SOD against ultraviolet induced skin damage

    OpenAIRE

    Chen, Xiaochao

    2013-01-01

    TAT peptide is one of the best-characterised cell penetrating peptides (CPPs) derived from the transactivator of transcription protein from the human immunodeficiency virus 1 (HIV-1). TAT peptide is able to cross the cell membrane and deliver various biomolecules into cells with low immunogenicity and no toxicity. However, the exact mechanism of internalization still remains a subject of controversy. Lamellar neutron scattering was used to determine the location of TAT pepti...

  17. Cellular differentiation in 3D-bioprinted mesenchymal stem cell-loaded hydrogels with varying structural and mechanical properties

    OpenAIRE

    Duarte Campos, Daniela Filipa

    2016-01-01

    Hydrogels are a promising alternative to rigid biomaterials typically used in the field of bone tissue engineering for the treatment of musculoskeletal disorders. By hydrogel-based 3D-bioprinting, the native ornamentation of cells and matrix from bone tissue could be resembled. Herein, it was hypothesized the combination of polysaccharides (agarose, alginate) with biological components (collagen, fibrinogen) would increase mechanical stiffness of printed constructs as well as support the prin...

  18. Dopamine as a potent inducer of cellular glutathione and NAD(P)H:quinone oxidoreductase 1 in PC12 neuronal cells: a potential adaptive mechanism for dopaminergic neuroprotection.

    Science.gov (United States)

    Jia, Zhenquan; Zhu, Hong; Misra, Bhaba R; Li, Yunbo; Misra, Hara P

    2008-11-01

    Dopamine auto-oxidation and the consequent formation of reactive oxygen species and electrophilic quinone molecules have been implicated in dopaminergic neuronal cell death in Parkinson's disease. We reported here that in PC12 dopaminergic neuronal cells dopamine at noncytotoxic concentrations (50-150 muM) potently induced cellular glutathione (GSH) and the phase 2 enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), two critical cellular defenses in detoxification of ROS and electrophilic quinone molecules. Incubation of PC12 cells with dopamine also led to a marked increase in the mRNA levels for gamma-glutamylcysteine ligase catalytic subunit (GCLC) and NQO1. In addition, treatment of PC12 cells with dopamine resulted in a significant elevation of GSH content in the mitochondrial compartment. To determine whether treatment with dopamine at noncytotoxic concentrations, which upregulated the cellular defenses could protect the neuronal cells against subsequent lethal oxidative and electrophilic injury, PC12 cells were pretreated with dopamine (150 muM) for 24 h and then exposed to various cytotoxic concentrations of dopamine or 6-hydroxydopamine (6-OHDA). We found that pretreatment of PC12 cells with dopamine at a noncytotoxic concentration led to a remarkable protection against cytotoxicity caused by dopamine or 6-OHDA at lethal concentrations, as detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium reduction assay. In view of the critical roles of GSH and NQO1 in protecting against dopaminergic neuron degeneration, the above findings implicate that upregulation of both GSH and NQO1 by dopamine at noncytotoxic concentrations may serve as an important adaptive mechanism for dopaminergic neuroprotection. PMID:18368484

  19. Factors influencing the transfection efficiency and cellular uptake mechanisms of Pluronic P123-modified polypropyleneimine/pDNA polyplexes in multidrug resistant breast cancer cells.

    Science.gov (United States)

    Gu, Jijin; Hao, Junguo; Fang, Xiaoling; Sha, Xianyi

    2016-04-01

    Generally, the major obstacles for efficient gene delivery are cellular internalization and endosomal escape of nucleic acid such as plasmid DNA (pDNA) or small interfering RNA (siRNA). We previously developed Pluronic P123 modified polypropyleneimine (PPI)/pDNA (P123-PPI/pDNA) polyplexes as a gene delivery system. The results showed that P123-PPI/pDNA polyplexes revealed higher transfection efficiency than PPI/pDNA polyplexes in multidrug resistant breast cancer cells. As a continued effort, the present investigation on the factors influencing the transfection efficiency, cellular uptake mechanisms, and intracellular fate of P123-PPI/pDNA polyplexes is reported. The presence of P123 was the main factor influencing the transfection efficiency of P123-PPI/pDNA polyplexes in MCF-7/ADR cells, but other parameters, such as N/P ratio, FBS concentration, incubation time and temperature were important as well. The endocytic inhibitors against clathrin-mediated endocytosis (CME), caveolae-mediated endocytosis (CvME), and macropinocytosis were involved in the internalization to investigate their effects on the cellular uptake and transfection efficiency of P123-PPI/pDNA polyplexes in vitro. The data showed that the internalization of P123-PPI/pDNA polyplexes was obtained from both CME and CvME. Colocalization experiments with TRITC-transferrin (CME indicator), Alexa Fluor 555-CTB (CvME indicator), monoclonal anti-α-tubulin (microtubule indicator), and LysoTracker Green (Endosome/lysosome indicator) were carried out to confirm the internalization routes. The results showed that both CME and CvME played vital roles in the effective transfection of P123-PPI/pDNA polyplexes. Endosome/lysosome system and skeleton, including actin filament and microtubule, were necessary for the transportation after internalization. PMID:26741268

  20. Failure mechanisms and assembly-process-based solution of FCBGA high lead C4 bump non-wetting

    Institute of Scientific and Technical Information of China (English)

    Li Wenqi; Qiu Yiming; Jin Xing; Wang Lei; Wu Qidi

    2012-01-01

    This paper studies the typical failure modes and failure mechanisms of non-wetting in an FCBGA (flip chip ball grid array) assembly.We have identified that the residual lead and tin oxide layer on the surface of the die bumps as the primary contributor to non-wetting between die bumps and substrate bumps during the chipattach reflow process.Experiments with bump reflow parameters revealed that an optimized reflow dwell time and H2 flow rate in the reflow oven can significantly reduce the amount of lead and tin oxides on the surface of the die bumps,thereby reducing the non-wetting failure rate by about 90%.Both failure analysis results and mass production data validate the non-wetting failure mechanisms identified by this study.As a result of the reflow process optimization,the failure rate associated with non-wetting is significantly reduced,which further saves manufacturing cost and increases capacity utilization.

  1. Phononic Band Gaps in 2D Quadratic and 3D Cubic Cellular Structures

    Directory of Open Access Journals (Sweden)

    Franziska Warmuth

    2015-12-01

    Full Text Available The static and dynamic mechanical behaviour of cellular materials can be designed by the architecture of the underlying unit cell. In this paper, the phononic band structure of 2D and 3D cellular structures is investigated. It is shown how the geometry of the unit cell influences the band structure and eventually leads to full band gaps. The mechanism leading to full band gaps is elucidated. Based on this knowledge, a 3D cellular structure with a broad full band gap is identified. Furthermore, the dependence of the width of the gap on the geometry parameters of the unit cell is presented.

  2. Mechanical and Physical Properties of In-Zn-Ga Lead-Free Solder Alloy for Low Energy Consumption

    Science.gov (United States)

    Ervina Efzan, M. N.; Nur Faziera, M. N.; Bakri Abdullah, Mohd Mustafa Al

    2016-06-01

    Due to the demand in the use of electronics devices in industry, the usage of solder connections has increased. Concerning with the toxicity of lead in Sn-37Pb solder alloy, developing lead free solder alloy with low melting temperature is one of the most important issues in electronic industry. Previously, researchers found out that the most promising candidate of lead free solder alloy is Sn-3.0Ag-0.5Cu (SAC). However, the melting temperature of this solder alloy is 217°C, 34°C higher than Sn-37Pb. This can lead to high energy consumption in electronic industry. In this paper, In-Zn-Ga solder alloy was investigated as a potential candidate replacing SAC. This study covers on the physical and mechanical properties of the solder alloy. Differential Scanning Calorimetry (DSC) testing shows that this solder alloy gave low melting temperature as low as 141.31°C. The addition of Ga in In-Zn solder alloy lowered the melting temperature compared to SAC and Sn-37Pb. From coefficient of thermal expansion (CTE) analysis, the In-Zn-Ga solder alloy gives good expansion properties and able to avoid the mismatch between the solder and copper substrates. The density of In-Zn-Ga solder alloy is 6.801g/cm3, lower than SAC and Sn-37Pb. For the strength, single lap shear testing was conducted on the In-Zn-Ga solder alloy and the results is near to the strength of SAC.

  3. Study on mechanical properties in superconducting ceramics based on Bi-Sr-Ca-Cu-O doped with lead

    International Nuclear Information System (INIS)

    Investigations performed in superconducting ceramics based on Bi-Sr-Ca-Cu-O, doped with lead, according to the stoichiometric formulae Bi2-x Pbx SR2 Ca2 Cu3 Oy, demonstrated the insertion of lead alters the mechanical properties of the material,particularly the plasticity. When employing an Hardness Testing, it was observed that the sample with a lead concentration of x = 0.4 holds the highest Vickers microhardness. It was laos noticed, when using a mercury porosimeter, that on this concentration there was a drastic reduction of the volume of each pore, evincing the lead enhanced the sintering process, considering that the sample with a lead concentration of x = 0.4 holds the minimum interval in which 80% of the pores meet (0.19 a 0.79 μm). Through optical and electronic microscopy, one can notice the presence of two main phases: a phase presenting isolating properties and another with superconducting ones. A minor phase, with birefringent properties, was also observed showing its highest concentration in the sample x = 0.2. The increase in microhardness, reaching its top in sample x = 0.4, is due to the volume reduction of the phase with isolating properties (with a lower hardness, as it was observed in the polishing), for it reaches its minimum in the sample presenting the same concentration. Also through electronic microscopy, it was noted the highest microhardness in the sample x = 0.4 was not influenced by the diameter variance or by the crystal shape, since they all present the shape of lamelars plates. Chemical etching based on acetic acid and water, have been performed in order to verify the solubility of the present phases. It was observed that the phase showing birefringent properties were much more soluble than the others. It was also observed the features of sheet, product of the reaction between the acid and the sample, on the surfaces of the samples. The diameter of these decreased until the moment when in lead concentration x = 0.1 there was no more

  4. Effects of mechanical property variability in lead rubber bearings on the response of seismic isolation system for different ground motions

    International Nuclear Information System (INIS)

    The effects of variability of the mechanical properties of lead rubber bearings on the response of a seismic isolation system are investigated. Material variability in manufacturing, aging, and operation temperature is assumed, and two variation models of an isolation system are considered. To evaluate the effect of ground motion characteristics on the response, 27 earthquake record sets with different peak A/V ratios were selected, and three components of ground motions were used for a seismic response analysis. The response in an isolation system and a superstructure increases significantly for ground motions with low A/V ratios. The variation in the mechanical properties of isolators results in a significant influence on the shear strains of the isolators and the acceleration response of the superstructure. The variation provisions in the ASCE-4 are reasonable, but more strict variation limits should be given to isolation systems subjected to ground motions having low A/V ratios. For application of seismic isolation systems to safety-related nuclear structures, the variation in the material and mechanical properties of the isolation system should be properly controlled during the manufacturing and aging processes. In addition, special consideration should be given to minimize the accidental torsion caused by the dissimilarity in the stiffness variations of the isolators.

  5. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. V. Anamnestic cellular and humoral responses following challenge infection

    Energy Technology Data Exchange (ETDEWEB)

    Correa-Oliveira, R.; Sher, A.; James, S.L.

    1984-03-01

    Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnestic circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model.

  6. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercariae. V. Anamnestic cellular and humoral responses following challenge infection

    International Nuclear Information System (INIS)

    Mice vaccinated with radiation-attenuated cercariae display low levels of cellular and humoral immune responses toward schistosomulum antigens, as measured in vitro by lymphocyte blastogenesis and quantitation of anti-larval antibodies by indirect immunofluorescence. Both responses wane with time after vaccination. However subsequent challenge infection provokes immune responses of classical anamnestic character, being both more rapid in appearance and of greater magnitude. Antigen responsive cells appear in lymph nodes draining the challenge site within 24 hours after infection. Both circulating anti-schistosomulum surface antibodies as well as cytophilic IgE anti-worm antigen antibodies increase substantially by 1 week after challenge. All of the anamnestic circulating antibodies belong to the IgG class. Those findings support the concept that vaccine-induced resistance to Schistosoma mansoni infection involves sensitized T and B lymphocytes, and point to the possible role of post-challenge anamnestic responses in the effector mechanism of parasite killing in this model

  7. Report on NCI symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. II. Cellular and animal models

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1984-01-01

    The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could be demonstrated after exposure to low-LET radiation but not after exposure to chemical carcinogens.

  8. The influence of receptor-mediated interactions on reaction-diffusion mechanisms of cellular self-organisation.

    Science.gov (United States)

    Klika, Václav; Baker, Ruth E; Headon, Denis; Gaffney, Eamonn A

    2012-04-01

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. PMID:22072186

  9. Report on NCI symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. II. Cellular and animal models

    International Nuclear Information System (INIS)

    The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could be demonstrated after exposure to low-LET radiation but not after exposure to chemical carcinogens

  10. Inhibition of cAMP-activated intestinal chloride secretion by diclofenac: cellular mechanism and potential application in cholera.

    Directory of Open Access Journals (Sweden)

    Pawin Pongkorpsakol

    2014-09-01

    Full Text Available Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84 cells with IC50 of ∼ 20 µM. The effect required no cytochrome P450 enzyme-mediated metabolic activation. Interestingly, exposures of T84 cell monolayers to diclofenac, either in apical or basolateral solutions, produced similar degree of inhibitions. Analyses of the apical Cl- current showed that diclofenac reversibly inhibited CFTR Cl- channel activity (IC50 ∼ 10 µM via mechanisms not involving either changes in intracellular cAMP levels or CFTR channel inactivation by AMP-activated protein kinase and protein phosphatase. Of interest, diclofenac had no effect on Na(+-K(+ ATPases and Na(+-K(+-Cl- cotransporters, but inhibited cAMP-activated basolateral K(+ channels with IC50 of ∼ 3 µM. In addition, diclofenac suppressed Ca(2+-activated Cl- channels, inwardly rectifying Cl- channels, and Ca(2+-activated basolateral K(+ channels. Furthermore, diclofenac (up to 200 µM; 24 h of treatment had no effect on cell viability and barrier function in T84 cells. Importantly, cholera toxin (CT-induced Cl- secretion across T84 cell monolayers was effectively suppressed by diclofenac. Intraperitoneal administration of diclofenac (30 mg/kg reduced both CT and Vibrio cholerae-induced intestinal fluid secretion by ∼ 70% without affecting intestinal fluid absorption in mice. Collectively, our results indicate that diclofenac inhibits both cAMP-activated and Ca(2+-activated Cl- secretion by inhibiting both apical Cl- channels and basolateral K+ channels in intestinal epithelial cells. Diclofenac may be useful in the treatment of cholera and other types of secretory diarrheas resulting from intestinal

  11. A novel autosomal recessive TERT T1129P mutation in a dyskeratosis congenita family leads to cellular senescence and loss of CD34+ hematopoietic stem cells not reversible by mTOR-inhibition.

    Science.gov (United States)

    Stockklausner, Clemens; Raffel, Simon; Klermund, Julia; Bandapalli, Obul Reddy; Beier, Fabian; Brümmendorf, Tim H; Bürger, Friederike; Sauer, Sven W; Hoffmann, Georg F; Lorenz, Holger; Tagliaferri, Laura; Nowak, Daniel; Hofmann, Wolf-Karsten; Buergermeister, Rebecca; Kerber, Carolin; Rausch, Tobias; Korbel, Jan O; Luke, Brian; Trumpp, Andreas; Kulozik, Andreas E

    2015-11-01

    The TERT gene encodes for the reverse transcriptase activity of the telomerase complex and mutations in TERT can lead to dysfunctional telomerase activity resulting in diseases such as dyskeratosis congenita (DKC). Here, we describe a novel TERT mutation at position T1129P leading to DKC with progressive bone marrow (BM) failure in homozygous members of a consanguineous family. BM hematopoietic stem cells (HSCs) of an affected family member were 300-fold reduced associated with a significantly impaired colony forming capacity in vitro and impaired repopulation activity in mouse xenografts. Recent data in yeast suggested improved cellular checkpoint controls by mTOR inhibition preventing cells with short telomeres or DNA damage from dividing. To evaluate a potential therapeutic option for the patient, we treated her primary skin fibroblasts and BM HSCs with the mTOR inhibitor rapamycin. This led to prolonged survival and decreased levels of senescence in T1129P mutant fibroblasts. In contrast, the impaired HSC function could not be improved by mTOR inhibition, as colony forming capacity and multilineage engraftment potential in xenotransplanted mice remained severely impaired. Thus, rapamycin treatment did not rescue the compromised stem cell function of TERTT1129P mutant patient HSCs and outlines limitations of a potential DKC therapy based on rapamycin. PMID:26546739

  12. A Specialized Mechanism of Translation Mediated by FXR1a-Associated MicroRNP in Cellular Quiescence.

    Science.gov (United States)

    Bukhari, Syed I A; Truesdell, Samuel S; Lee, Sooncheol; Kollu, Swapna; Classon, Anthony; Boukhali, Myriam; Jain, Esha; Mortensen, Richard D; Yanagiya, Akiko; Sadreyev, Ruslan I; Haas, Wilhelm; Vasudevan, Shobha

    2016-03-01

    MicroRNAs predominantly decrease gene expression; however, specific mRNAs are translationally upregulated in quiescent (G0) mammalian cells and immature Xenopus laevis oocytes by an FXR1a-associated microRNA-protein complex (microRNP) that lacks the microRNP repressor, GW182. Their mechanism in these conditions of decreased mTOR signaling, and therefore reduced canonical (cap-and-poly(A)-tail-mediated) translation, remains undiscovered. Our data reveal that mTOR inhibition in human THP1 cells enables microRNA-mediated activation. Activation requires shortened/no poly(A)-tail targets; polyadenylated mRNAs are partially activated upon PAIP2 overexpression, which interferes with poly(A)-bound PABP, precluding PABP-enhanced microRNA-mediated inhibition and canonical translation. Consistently, inhibition of PARN deadenylase prevents activation. P97/DAP5, a homolog of canonical translation factor, eIF4G, which lacks PABP- and cap binding complex-interacting domains, is required for activation, and thereby for the oocyte immature state. P97 interacts with 3' UTR-binding FXR1a-associated microRNPs and with PARN, which binds mRNA 5' caps, forming a specialized complex to translate recruited mRNAs in these altered canonical translation conditions. PMID:26942679

  13. Cellular mechanisms of reduced sarcoplasmic reticulum Ca2+ content in L-thyroxin-induced rat ventricular hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Lai-jing SONG; Guan-lei WANG; Jie LIU; Qin-ying QIU; Jing-hua OU; Yong-yuan GUAN

    2008-01-01

    Aim:To examine how the sarcoplasmic reticulum (SR) Ca2+ content changes and the underlying mechanism in L-thyroxin-induced cardiac hypertrophy. Methods:Echocardiography was used to confirm the establishment of the cardiac hypertro-phy model. The confocal microscopy and fluorescent indicator Fluo-3 was ap-plied to examine the intracellular Ca2+ concentration ([Ca2+]I), the Ca2+ sparks, and the caffeine-induced Ca2+ transient in freshly isolated cardiac ventricular myocytes. The activity of sarcolemmal and SR Ca2+-ATPase 2a (SERCA2a) in the ventricular tissue was also measured, respectively. Results:L-thyroxin (1 mg/kg injection for 10 d) induces left ventricular cardiac hypertrophy with normal myocardial function. The decreased caffeine-induced Ca2+ transient in the Ca2+-free solution was detected. The spontaneous Ca2+ sparks in hypertrophied myocytes occurred more frequently than in normal cells, with similar duration and spatial spread, but smaller amplitude. Then the basal [Ca2+]I increase was observed in quiescent left ventricular myocytes from hyperthyroidism rats. The activity of sarcolemmal and SR Ca2+-ATPase was decreased in the hypertrophied ventricle tissue. Conclusion:The results suggested that the reduced SR Ca2+ content may be associated with an increased Ca2+ leak and reduced SERCA2a activity, contributing to abnormal intracellular Ca2+ handling during hypertrophy in hyperthyroidism rats.

  14. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    KAUST Repository

    Klika, Václav

    2011-11-10

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. © 2011 Society for Mathematical Biology.

  15. The phosphoinositide 3-kinase signaling pathway in normal and malignant B cells: activation mechanisms, regulation and impact on cellular functions.

    Science.gov (United States)

    Pauls, Samantha D; Lafarge, Sandrine T; Landego, Ivan; Zhang, Tingting; Marshall, Aaron J

    2012-01-01

    The phosphoinositide 3-kinase (PI3K) pathway is a central signal transduction axis controlling normal B cell homeostasis and activation in humoral immunity. The p110δ PI3K catalytic subunit has emerged as a critical mediator of multiple B cell functions. The activity of this pathway is regulated at multiple levels, with inositol phosphatases PTEN and SHIP both playing critical roles. When deregulated, the PI3K pathway can contribute to B cell malignancies and autoantibody production. This review summarizes current knowledge on key mechanisms that activate and regulate the PI3K pathway and influence normal B cell functional responses including the development of B cell subsets, antigen presentation, immunoglobulin isotype switch, germinal center responses, and maintenance of B cell anergy. We also discuss PI3K pathway alterations reported in select B cell malignancies and highlight studies indicating the functional significance of this pathway in malignant B cell survival and growth within tissue microenvironments. Finally, we comment on early clinical trial results, which support PI3K inhibition as a promising treatment of chronic lymphocytic leukemia. PMID:22908014

  16. Cellular Automata

    OpenAIRE

    Bagnoli, Franco

    1998-01-01

    An introduction to cellular automata (both deterministic and probabilistic) with examples. Definition of deterministic automata, dynamical properties, damage spreading and Lyapunov exponents; probabilistic automata and Markov processes, nonequilibrium phase transitions, directed percolation, diffusion; simulation techniques, mean field. Investigation themes: life, epidemics, forest fires, percolation, modeling of ecosystems and speciation. They represent my notes for the school "Dynamical Mod...

  17. Cellular mechanisms regulating activity-dependent release of native brain-derived neurotrophic factor from hippocampal neurons.

    Science.gov (United States)

    Balkowiec, Agnieszka; Katz, David M

    2002-12-01

    Brain-derived neurotrophic factor (BDNF) plays a critical role in activity-dependent modifications of neuronal connectivity and synaptic strength, including establishment of hippocampal long-term potentiation (LTP). To shed light on mechanisms underlying BDNF-dependent synaptic plasticity, the present study was undertaken to characterize release of native BDNF from newborn rat hippocampal neurons in response to physiologically relevant patterns of electrical field stimulation in culture, including tonic stimulation at 5 Hz, bursting stimulation at 25 and 100 Hz, and theta-burst stimulation (TBS). Release was measured using the ELISA in situ technique, developed in our laboratory to quantify secretion of native BDNF without the need to first overexpress the protein to nonphysiological levels. Each stimulation protocol resulted in a significant increase in BDNF release that was tetrodotoxin sensitive and occurred in the absence of glutamate receptor activation. However, 100 Hz tetanus and TBS, stimulus patterns that are most effective in inducing hippocampal LTP, were significantly more effective in releasing native BDNF than lower-frequency stimulation. For all stimulation protocols tested, removal of extracellular calcium, or blockade of N-type calcium channels, prevented BDNF release. Similarly, depletion of intracellular calcium stores with thapsigargin and treatment with dantrolene, an inhibitor of calcium release from caffeine-ryanodine-sensitive stores, markedly inhibited activity-dependent BDNF release. Our results indicate that BDNF release can encode temporal features of hippocampal neuronal activity. The dual requirement for calcium influx through N-type calcium channels and calcium mobilization from intracellular stores strongly implicates a role for calcium-induced calcium release in activity-dependent BDNF secretion. PMID:12451139

  18. Effect of rapid solidification on mechanical properties of a lead free Sn-3.5Ag solder

    International Nuclear Information System (INIS)

    The melt-spinning processes of Sn-3.5Ag, Sn-3.5Ag-2In, Sn-3.5Ag-2Bi and Sn-3.5Ag-2Zn lead free solders were investigated and analyzed. The results showed that formation of intermetallic compounds of ε-Ag3Sn, In0.2Sn0.8 and AgZn embedded in Sn matrix phase, were produced during melt-spinning technique not found under equilibrium conditions. Addition of small amount (2 wt.%) In, Bi, or Zn refines the grain size, increases Hv, delay the fracture strength and improves creep resistance. The ternary alloys exhibits mechanical properties superior to that of the binary alloy Sn-3.5Ag because it has a uniform fine dispersion of precipitates and small effective grain size. It is found that in the lead free solder has composition of Sn-3.5Ag-2In, Sn-3.5Ag-2Bi and Sn-3.5Ag-2Zn melt-spun alloys, have eutectic composition which could be attributed to the shift of eutectic point under rapid solidification. The addition of indium, bismuth and zinc to the Sn-Ag binary system lowers the melting temperature.

  19. Effect of rapid solidification on mechanical properties of a lead free Sn-3.5Ag solder

    Energy Technology Data Exchange (ETDEWEB)

    Shalaby, R.M., E-mail: rizk1969@yahoo.co.u [Metal Physics Lab., Physics Department, Faculty of Science, Mansoura University, Mansoura 35516 (Egypt)

    2010-08-27

    The melt-spinning processes of Sn-3.5Ag, Sn-3.5Ag-2In, Sn-3.5Ag-2Bi and Sn-3.5Ag-2Zn lead free solders were investigated and analyzed. The results showed that formation of intermetallic compounds of {epsilon}-Ag{sub 3}Sn, In{sub 0.2}Sn{sub 0.8} and AgZn embedded in Sn matrix phase, were produced during melt-spinning technique not found under equilibrium conditions. Addition of small amount (2 wt.%) In, Bi, or Zn refines the grain size, increases H{sub v}, delay the fracture strength and improves creep resistance. The ternary alloys exhibits mechanical properties superior to that of the binary alloy Sn-3.5Ag because it has a uniform fine dispersion of precipitates and small effective grain size. It is found that in the lead free solder has composition of Sn-3.5Ag-2In, Sn-3.5Ag-2Bi and Sn-3.5Ag-2Zn melt-spun alloys, have eutectic composition which could be attributed to the shift of eutectic point under rapid solidification. The addition of indium, bismuth and zinc to the Sn-Ag binary system lowers the melting temperature.

  20. The formation mechanism and impact of streamwise vortices on NACA 0021 airfoil's performance with undulating leading edge modification

    Science.gov (United States)

    Rostamzadeh, N.; Hansen, K. L.; Kelso, R. M.; Dally, B. B.

    2014-10-01

    Wings with tubercles have been shown to display advantageous loading behavior at high attack angles compared to their unmodified counterparts. In an earlier study by the authors, it was shown that an undulating leading-edge configuration, including but not limited to a tubercled model, induces a cyclic variation in circulation along the span that gives rise to the formation of counter-rotating streamwise vortices. While the aerodynamic benefits of full-span tubercled wings have been associated with the presence of such vortices, their formation mechanism and influence on wing performance are still in question. In the present work, experimental and numerical tests were conducted to further investigate the effect of tubercles on the flow structure over full-span modified wings based on the NACA 0021 profile, in the transitional flow regime. It is found that a skew-induced mechanism accounts for the formation of streamwise vortices whose development is accompanied by flow separation in delta-shaped regions near the trailing edge. The presence of vortices is detrimental to the performance of full-span wings pre-stall, however renders benefits post-stall as demonstrated by wind tunnel pressure measurement tests. Finally, primary and secondary vortices are identified post-stall that produce an enhanced momentum transfer effect that reduces flow separation, thus increasing the generated amount of lift.

  1. Genetic Dominance & Cellular Processes

    Science.gov (United States)

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  2. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  3. A systematic approach to identify cellular auxetic materials

    International Nuclear Information System (INIS)

    Auxetics are materials showing a negative Poisson’s ratio. This characteristic leads to unusual mechanical properties that make this an interesting class of materials. So far no systematic approach for generating auxetic cellular materials has been reported. In this contribution, we present a systematic approach to identifying auxetic cellular materials based on eigenmode analysis. The fundamental mechanism generating auxetic behavior is identified as rotation. With this knowledge, a variety of complex two-dimensional (2D) and three-dimensional (3D) auxetic structures based on simple unit cells can be identified. (paper)

  4. Never-ageing cellular senescence

    OpenAIRE

    Ogrunc, Müge; d’Adda di Fagagna, Fabrizio

    2011-01-01

    Cellular senescence was historically discovered as a form of cellular ageing of in vitro cultured cells. It has been under the spotlight following the evidence of oncogene-induced senescence in vivo and its role as a potent tumour suppressor mechanism. Presently, a PubMed search using keywords ‘cellular senescence and cancer’ reveals 8398 number of references (by April 2011) showing that while our knowledge of senescence keeps expanding, the complexity of the phenomenon keeps us – researchers...

  5. Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

    Science.gov (United States)

    Li, Taoli; Gao, Xiangqian; Yang, Liu; Shi, Yunli; Gao, Qingzhi

    2016-05-19

    Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation. PMID:27135196

  6. Preliminary treatment of chlorinated streams containing fission products: mechanisms leading to crystalline phases in molten chloride media

    International Nuclear Information System (INIS)

    The world of the nuclear power gets ready for profound modifications so that 'the atom' can aspire in conformance with long-lasting energy: it is what we call the development of generation IV nuclear systems. So, the new pyrochemical separation processes for the spent fuel reprocessing are currently being investigated. Techniques in molten chloride media generate an ultimate flow (with high chlorine content) which cannot be incorporated in conventional glass matrices. This flow is entirely water-soluble and must be conditioned in a chemical form which is compatible with a long-term disposal. This work of thesis consists in studying new ways for the management of the chlorinated streams loaded with fission products (FP). To do it, a strategy of selective FP extraction via the in situ formation of crystalline phases was retained. The possibility of extracting rare earths in the eutectic LiCl-KCl was demonstrated via the development of a new way of synthesis of rare earth phosphates (TRPO4). As regards alkaline earths, the conversion of strontium and barium chlorides to the corresponding tungstates or molybdates was studied in different solvents. Mechanisms leading to the crystalline phases in molten chloride media were studied via the coupling of NMR and XRD techniques. First of all, it has been shown that these mechanisms are dependent on the stability of the used precursors. So in the case of the formation of rare earth phosphates the solvent is chemically active. On the other hand, in the case of the formation of alkaline earth tungstates it would seem that the solvent plays the role of structuring agent which can control the ability to react of chlorides. (author)

  7. Cocaine mediated apoptosis of vascular cells as a mechanism for carotid artery dissection leading to ischemic stroke.

    Science.gov (United States)

    Dabbouseh, Noura M; Ardelt, Agnieszka

    2011-08-01

    In arterial dissection, blood may enter the arterial wall through an intimal tear, splitting the arterial wall and activating the coagulation cascade at the site of endothelial damage. Dissection of extracranial and intracranial vessels may lead to ischemic stroke through thromboembolic or hemodynamic mechanisms. Major blunt trauma or rapid acceleration-deceleration may cause dissection, but in patients with inherent arterial wall weakness, dissection can occur spontaneously or as a result of minor neck movement. Cocaine use has been associated with dissection of the aortic arch and coronary and renal arteries through cocaine-mediated hypertension. Recent preclinical studies have suggested, however, that cocaine may cause apoptosis of cells in the vascular wall. In this article, we postulate that cocaine may cause apoptosis of vascular endothelial and/or smooth muscle cells, thus weakening the vascular wall and resulting in a dissection-prone state. We review the literature and propose a biological basis for vasculopathy, vascular dissection, and ischemic stroke in the setting of cocaine use. Further research studies on vascular cells, as well as focused analysis of human pathological material, will be important in providing evidence for or against our hypotheses. PMID:21546166

  8. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  9. Injury Mechanisms and Biomarkers of Lead Toxicity to Bone%铅对骨骼的损伤机制及其生物学标志物

    Institute of Scientific and Technical Information of China (English)

    刘云忠

    2011-01-01

    When lead compounds in the environment ore absorbed into human body,they can affect bone function at the cellular and molecular levels.Lead mainly regulates blood hormones and disrupts the response of bone cells to hormones.Lead directly impairs the function of bone cells and damages skeletal cells and active macromolecules via oxidative stress.The compromise of calcium messenger system can also interfere with the physiological regulation of bone cells.Therefore, the level of bone lead rather than that of serum lead better reflects the chronic lead toxicity.%环境中各种铅的化合物被机体吸收后,可以在细胞和分子水平影响骨骼系统的功能,主要有调节血液中激素的水平,干扰骨细胞对激素的调节能力;直接影响成骨细胞的功能;通过氧化应激损伤骨骼系统中的细胞或大分子活性蛋白;影响钙信使系统,导致骨细胞生理调节功能损伤.因此,骨骼中铅的水平较血液中铅的水平更能反映慢性铅中毒对机体的损害程度.

  10. Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

    International Nuclear Information System (INIS)

    To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces

  11. Girdin/GIV is upregulated by cyclic tension, propagates mechanical signal transduction, and is required for the cellular proliferation and migration of MG-63 cells

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Jiang-Tian; Li, Yan; Yu, Bing; Gao, Guo-Jie; Zhou, Ting; Li, Song, E-mail: song_li59@126.com

    2015-08-21

    To explore how Girdin/GIV is regulated by cyclic tension and propagates downstream signals to affect cell proliferation and migration. Human osteoblast-like MG-63 cells were exposed to cyclic tension force at 4000 μstrain and 0.5 Hz for 6 h, produced by a four-point bending system. Cyclic tension force upregulated Girdin and Akt expression and phosphorylation in cultured MG-63 cells. Girdin and Akt each promoted the phosphorylation of the other under stimulated tension. In vitro MTT and transwell assays showed that Girdin and Akt are required for cell proliferation and migration during cellular quiescence. Moreover, STAT3 was determined to be essential for Girdin expression under stimulated tension force in the physiological condition, as well as for osteoblast proliferation and migration during quiescence. These findings suggest that the STAT3/Girdin/Akt pathway activates in osteoblasts in response to mechanical stimulation and may play a significant role in triggering osteoblast proliferation and migration during orthodontic treatment. - Highlights: • Tension force upregulates Girdin and Akt expression and phosphorylation. • Girdin and Akt promotes the phosphorylation of each other under tension stimulation. • Girdin and Akt are required for MG-63 cell proliferation and migration. • STAT3 is essential for Girdin expression after application of the tension forces.

  12. Cytotoxic and phenotypic effects of uranium and lead on osteoblastic cellular models; Effets cytotoxiques et phenotypiques de l'uranium et du plomb sur des modeles cellulaires osteoblastiques

    Energy Technology Data Exchange (ETDEWEB)

    Milgram, S

    2008-04-15

    This study is involved in the evaluation of bio-hazard associated with the use of uranium in nuclear activities and industrial research. The uranium, known in the literature as potentially carcinogenic or toxic for reproduction, can become a public health problem with the views of the various possibilities of human infections (military of the Gulf War, Finnish populations exposed to drinking water contaminated by example). The skeleton represents the organ of long-term storage of uranium and can be a target of its toxicity. Lead sharing this way of fixing in the bone matrix and have the same adverse effects on bone formation. The osteoblasts, cells responsible in bone formation, are specific targets of these two metals. The aim of this study was to evaluate the effects of acute toxicity of speciation controlled uranium and lead on osteoblasts culture. The intracellular accumulation, distribution and speciation were then studied to explain the observed toxicity. A cell death and phenotypic disorder were highlighted. The speciation is seen as crucial in biological effects of these metals. The most toxic species of both metals have been identified. The accumulation or cell distribution could not alone explain the impact of speciation on the toxicity observed. However, a phenomenon of intracellular precipitation of uranium and lead has been stressed and could be involved in a detoxification mechanism. (author)

  13. Biosorption behavior and mechanism of lead (II) from aqueous solution by aerobic granules (AG) and bacterial alginate (BA)

    Science.gov (United States)

    Wang, Lin; Li, Yu

    2012-12-01

    Lead (Pb) and its compounds are common pollutants in industrial wastewaters. To develop appropriate Pb2+ treatment technologies, aerobic granules (AG) and bacterial alginates (BA) were studied as alternative biosorbents to remove Pb2+ from aqueous solutions. The biosorption mechanism of AG and BA were further analyzed to determine which functional groups in AG and BA are active in Pb2+ biosorption. In this paper, the Pb2+ biosorption behavior of AG and BA was respectively investigated in batch experiments from the perspectives of the initial pH, contact time, and initial Pb2+ concentration. The results showed that biosorption of Pb2+ by AG and BA occurred within 60min at the initial Pb2+ concentrations (0-150 mg L-1). The actual saturated Pb2+ biosorption capability of AG was 101.97 mg g-1 (dry weight of aerobic granular biomass). When the initial pH was 5, the biosorption capability of AG and BA was highest at the initial Pb2+ concentrations (0-20mg L-1). During the process of Pb2+ biosorption, K+, Ca2+, and Mg2+ were released. The Ion Chromatography (IC) and Fourier Transform Infrared Spectroscopy (FTIR) further highlighted the main role of ion exchange between Ca2+ and Pb2+ and sequestration of Pb2+ with carboxyl (-COO-) of AG and BA. This analogical analysis verifies that BA is responsible for biosorption of Pb2+ by AG. At the same optimal pH, AG cultivated with different carbon source has different Pb2+ biosorption capacity. The Pb2+ biosorption by AG with sodium acetate as the sole carbon source is higher than AG with glucose as carbon source.

  14. Biosorption Behavior and Mechanism of Lead (Ⅱ) from Aqueous Solution by Aerobic Granules (AG) and Bacterial Alginate (BA)

    Institute of Scientific and Technical Information of China (English)

    WANG Lin; LI Yu

    2012-01-01

    Lead (Pb) and its compounds are common pollutants in industrial wastewaters.To develop appropriate Pb2+ treatment technologies,aerobic granules (AG) and bacterial alginates (BA) were studied as alternative biosorbents to remove Pb2+ from aqueous solutions.The biosorption mechanism of AG and BA were further analyzed to determine which functional groups in AG and BA are active in Pb2+ biosorption.In this paper,the Pb2+ biosorption behavior of AG and BA was respectively investigated in batch experiments from the perspectives of the initial pH,contact time,and initial Pb2+ concentration.The results showed that biosorption of Pb2+ by AG and BA occurred within 60min at the initial Pb2+ concentrations (0-150mg L-1).The actual saturated Pb2+ biosorption capability of AG was 101.97 mg g-1 (dry weight of aerobic granular biomass).When the initial pH was 5,the biosorption capability of AG and BA was highest at the initial Pb2+ concentrations (0-20mg L-1).During the process of Pb2+ biosorption,K+,Ca2+,and Mg2+ were released.The Ion Chromatography (IC) and Fourier Transform Infrared Spectroscopy (FTIR) further highlighted the main role of ion exchange between Ca2+ and Pb2+ and sequestration of Pb2+ with carboxyl (-COO-) of AG and BA.This analogical analysis verifies that BA is responsible for biosorption of Pb2+ by AG.At the same optimal pH,AG cultivated with different carbon source has different Pb2+ biosorption capacity.The Pb2+ biosorption by AG with sodium acetate as the sole carbon source is higher than AG with glucose as carbon source.

  15. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    International Nuclear Information System (INIS)

    analysis revealed that the order of severity of damage declines from the spino-cerebellar, ventral, and dorsal tract respectively, suggesting neuroanatomical specificity. Thus, early activation of cell death and cell survival processes may play significant role in the clinical progression and syndromic clinical feature presentation of OPIDN. -- Highlights: ► Multiple mechanisms of neurodegeneration were indicated in a study on OPIDN model. ► Altered expressions of BCL2 and GADD45 were recorded in various tissues of CNS. ► Multiple anomalous cellular (neuronal and astroglial) features were recorded. ► Anatomical specificity of the neurodegeneration was described.

  16. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    Science.gov (United States)

    Monette, M.Y.; Yada, T.; Matey, V.; McCormick, S.D.

    2010-01-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4??gl-1 Al), acid and low Al (LAl: pH 5.4, 11??gl-1 Al), acid and moderate Al (MAl: pH 5.3, 42??gl-1 Al), and acid and high Al (HAl: pH 5.4, 56??gl-1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na+/K+-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl- channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose that when smolts are

  17. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    Energy Technology Data Exchange (ETDEWEB)

    Damodaran, T.V., E-mail: tdamodar@nccu.edu [Dept of Medicine, Duke University Medical Center, Durham, NC (United States); Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States); Dept of Biology, North Carolina Central University, Durham, NC 27707 (United States); Attia, M.K. [Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States); Abou-Donia, M.B., E-mail: donia@mc.duke.edu [Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States)

    2011-11-15

    analysis revealed that the order of severity of damage declines from the spino-cerebellar, ventral, and dorsal tract respectively, suggesting neuroanatomical specificity. Thus, early activation of cell death and cell survival processes may play significant role in the clinical progression and syndromic clinical feature presentation of OPIDN. -- Highlights: Black-Right-Pointing-Pointer Multiple mechanisms of neurodegeneration were indicated in a study on OPIDN model. Black-Right-Pointing-Pointer Altered expressions of BCL2 and GADD45 were recorded in various tissues of CNS. Black-Right-Pointing-Pointer Multiple anomalous cellular (neuronal and astroglial) features were recorded. Black-Right-Pointing-Pointer Anatomical specificity of the neurodegeneration was described.

  18. Thermal optimum analyses and mechanical design of 10-kA, vapor-cooled power leads for SSC superconducting magnet tests at MTL

    International Nuclear Information System (INIS)

    The spiral-fin, 10-kA, helium vapor-cooled power leads have been designed for Superconducting Super Collider superconducting magnet tests at the Magnet Test Laboratory. In order to thermally optimize the parameters of the power leads, the lead diameters-which minimize the Carnot work for several different lengths, two different fin geometries, and two RRR values of the lead materials-were determined. The cryogenic refrigeration and liquefaction loads for supporting the leads have also been calculated. The optimum operational condition with different currents is discussed. An improved mechanical design of the 10-kA power leads was undertaken, with careful consideration of the cryogenic and mechanical performance. In the design, a new thermal barrier device to reduce heat conduction from the vacuum and gas seal area was employed. Therefore, the electric insulation assembly, which isolates the ground potential parts of the lead from the high-power parts, was moved into a warm region in order to prevent vacuum and helium leakage in the 0-ring seals due to transient cold temperature. The instrumentation for testing the power leads is also discussed

  19. Thermal optimum analyses and mechanical design of 10-kA, vapor-cooled power leads for SSC superconducting magnet tests at MTL

    International Nuclear Information System (INIS)

    The spiral-fin, 10-kA, helium vapor-cooled power leads have been designed for Superconducting Super Collider superconducting magnet tests at the Magnet Test Laboratory. In order to thermally optimize the parameters of the power leads, the lead diameters-which minimize the Carnot work for several different lengths, two different fin geometries, and two RRR values of the lead materials-were determined. The cryogenic refrigeration and liquefaction loads for supporting the leads have also been calculated. The optimum operational condition with different currents is discussed. An improved mechanical design of the 10-kA power leads was undertaken, with careful consideration of the cryogenic and mechanical performance. In the design, a new thermal barrier device to reduce heat conduction from the vacuum and gas seal area was employed. Therefore, the electric insulation assembly, which isolates the ground potential parts of the lead from the high-power parts, was moved into a warm region in order to prevent vacuum and helium leakage in the O-ring seals due to transient cold temperature. The instrumentation for testing the power leads is also discussed

  20. Klotho-Dependent Cellular Transport Regulation.

    Science.gov (United States)

    Sopjani, M; Dërmaku-Sopjani, M

    2016-01-01

    Klotho is a transmembrane protein that in humans is encoded by the hKL gene. This protein is known to have aging suppressor effects and is predominantly expressed in the distal convoluted tubule of the kidney, parathyroid glands, and choroid plexus of the brain. The Klotho protein exists in both full-length membrane form and a soluble secreted form, which exerts numerous distinct functions. The extracellular domain of Klotho can be enzymatically cleaved off and released into the systemic circulation where it functions as β-glucuronidase and a hormone. Soluble Klotho is a multifunction protein present in the biological fluids including blood, urine, and cerebrospinal fluid of mammals. Klotho deficiency leads to multiple organ failure accompanied by early appearance of multiple age-related disorders and early death, whereas overexpression of Klotho results in the opposite effects. Klotho, an enzyme and hormone, has been reported to participate in the regulation of cellular transport processes across the plasma membrane either indirectly through inhibiting calcitriol (1,25(OH)2D3) formation or other mechanism, or by directly affecting transporter proteins, including ion channels, cellular carriers, and Na(+)/K(+)-ATPase. Accordingly, Klotho protein serves as a powerful regulator of cellular transport across the plasma membrane. Importantly, Klotho-dependent cellular transport regulation implies stimulatory or inhibitory effects. Klotho has been shown to play a key role in the regulation of multiple calcium and potassium ion channels, and various cellular carriers including the Na(+)-coupled cotransporters such as NaPi-IIa, NaPi-IIb, EAAT3, and EAAT4, CreaT1 as well as Na(+)/K(+)-ATPase. These regulations are parts of the antiaging function of Klotho, which will be discussing throughout this chapter. Clearly, further experimental efforts are required to investigate the effect of Klotho on other transport proteins and underlying molecular mechanisms by which Klotho

  1. Intra-cellular Staphylococcus aureus alone causes infection in vivo

    Directory of Open Access Journals (Sweden)

    T Hamza

    2013-07-01

    Full Text Available Chronic and recurrent bone infections occur frequently but have not been explained. Staphylococcus aureus (S. aureus is often found among chronic and recurrent infections and may be responsible for such infections. One possible reason is that S. aureus can internalize and survive within host cells and by doing so, S. aureus can evade both host defense mechanisms and most conventional antibiotic treatments. In this study, we hypothesized that intra-cellular S. aureus could induce infections in vivo. Osteoblasts were infected with S. aureus and, after eliminating extra-cellular S. aureus, inoculated into an open fracture rat model. Bacterial cultures and radiographic observations at post-operative day 21 confirmed local bone infections in animals inoculated with intra-cellular S. aureus within osteoblasts alone. We present direct in vivo evidence that intra-cellular S. aureus could be sufficient to induce bone infection in animals; we found that intra-cellular S. aureus inoculation of as low as 102 colony forming units could induce severe bone infections. Our data may suggest that intra-cellular S. aureus can “hide” in host cells during symptom-free periods and, under certain conditions, they may escape and lead to infection recurrence. Intra-cellular S. aureus therefore could play an important role in the pathogenesis of S. aureus infections, especially those chronic and recurrent infections in which disease episodes may be separated by weeks, months, or even years.

  2. Increased extracellular and intracellular Ca2+ lead to adipocyte accumulation in bone marrow stromal cells by different mechanisms

    International Nuclear Information System (INIS)

    Mesenchymal stem cells found in bone marrow stromal cells (BMSCs) are the common progenitors for both adipocyte and osteoblast. An increase in marrow adipogenesis is associated with age-related osteopenia and anemia. Both extracellular and intracellular Ca2+ ([Ca2+]o and [Ca2+]i) are versatile signaling molecules that are involved in the regulation of cell functions, including proliferation and differentiation. We have recently reported that upon treatment of BMSCs with insulin and dexamethasone, both high [Ca2+]o and high [Ca2+]i enhanced adipocyte accumulation, which suggested that increases in [Ca2+]o caused by bone resorption may accelerate adipocyte accumulation in aging and diabetic patients. In this study, we used primary mouse BMSCs to investigate the mechanisms by which high [Ca2+]o and high [Ca2+]i may enhance adipocyte accumulation. In the process of adipocyte accumulation, two important keys are adipocyte differentiation and the proliferation of BMSCs, which have the potential to differentiate into adipocytes. Use of MTT assay and real-time RT-PCR revealed that high [Ca2+]i (ionomycin)-dependent adipocyte accumulation is caused by enhanced proliferation of BMSCs but not enhanced differentiation into adipocytes. Using fura-2 fluorescence-based approaches, we showed that high [Ca2+]o (addition of CaCl2) leads to increases in [Ca2+]i. Flow cytometric methods revealed that high [Ca2+]o suppressed the phosphorylation of ERK independently of intracellular Ca2+. The inhibition of ERK by U0126 and PD0325901 enhanced the differentiation of BMSCs into adipocytes. These data suggest that increased extracellular Ca2+ provides the differentiation of BMSCs into adipocytes by the suppression of ERK activity independently of increased intracellular Ca2+, which results in BMSC proliferation. - Highlights: • Both high [Ca2+]o and high [Ca2+]i enhanced adipocyte accumulation in BMSCs. • High [Ca2+]i enhanced the proliferation of BMSCs but not adipocyte differentiation

  3. Increased extracellular and intracellular Ca{sup 2+} lead to adipocyte accumulation in bone marrow stromal cells by different mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Ryota, E-mail: hryota@juntendo.ac.jp [Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Katoh, Youichi, E-mail: katoyo@juntendo-urayasu.jp [Juntendo University Faculty of International Liberal Arts, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Miyamoto, Yuki [Juntendo University Faculty of Health Care and Nursing, Takasu 2-5-1, Urayasu-shi, Chiba 279-0023 (Japan); Itoh, Seigo; Daida, Hiroyuki [Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Nakazato, Yuji [Center for Environmental Research, Department of Cardiology, Juntendo University Faculty of Medicine Urayasu Hospital, Tomioka 2-1-1, Urayasu-shi, Chiba 279-0022 (Japan); Okada, Takao [Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2015-02-20

    Mesenchymal stem cells found in bone marrow stromal cells (BMSCs) are the common progenitors for both adipocyte and osteoblast. An increase in marrow adipogenesis is associated with age-related osteopenia and anemia. Both extracellular and intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub o} and [Ca{sup 2+}]{sub i}) are versatile signaling molecules that are involved in the regulation of cell functions, including proliferation and differentiation. We have recently reported that upon treatment of BMSCs with insulin and dexamethasone, both high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} enhanced adipocyte accumulation, which suggested that increases in [Ca{sup 2+}]{sub o} caused by bone resorption may accelerate adipocyte accumulation in aging and diabetic patients. In this study, we used primary mouse BMSCs to investigate the mechanisms by which high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} may enhance adipocyte accumulation. In the process of adipocyte accumulation, two important keys are adipocyte differentiation and the proliferation of BMSCs, which have the potential to differentiate into adipocytes. Use of MTT assay and real-time RT-PCR revealed that high [Ca{sup 2+}]{sub i} (ionomycin)-dependent adipocyte accumulation is caused by enhanced proliferation of BMSCs but not enhanced differentiation into adipocytes. Using fura-2 fluorescence-based approaches, we showed that high [Ca{sup 2+}]{sub o} (addition of CaCl{sub 2}) leads to increases in [Ca{sup 2+}]{sub i}. Flow cytometric methods revealed that high [Ca{sup 2+}]{sub o} suppressed the phosphorylation of ERK independently of intracellular Ca{sup 2+}. The inhibition of ERK by U0126 and PD0325901 enhanced the differentiation of BMSCs into adipocytes. These data suggest that increased extracellular Ca{sup 2+} provides the differentiation of BMSCs into adipocytes by the suppression of ERK activity independently of increased intracellular Ca{sup 2+}, which results in BMSC proliferation. - Highlights:

  4. Pathologic Cellular Events in Smoking-Related Pancreatitis

    International Nuclear Information System (INIS)

    Pancreatitis, a debilitating inflammatory disorder, results from pancreatic injury. Alcohol abuse is the foremost cause, although cigarette smoking has recently surfaced as a distinct risk factor. The mechanisms by which cigarette smoke and its toxins initiate pathological cellular events leading to pancreatitis, have not been clearly defined. Although cigarette smoke is composed of more than 4000 compounds, it is mainly nicotine and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which have been extensively studied with respect to pancreatic diseases. This review summarizes these research findings and highlights cellular pathways which may be of relevance in initiation and progression of smoking-related pancreatitis

  5. Pathologic Cellular Events in Smoking-Related Pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Thrower, Edwin [Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520 (United States); Veterans Affairs Connecticut Healthcare, West Haven, CT 06516 (United States)

    2015-04-29

    Pancreatitis, a debilitating inflammatory disorder, results from pancreatic injury. Alcohol abuse is the foremost cause, although cigarette smoking has recently surfaced as a distinct risk factor. The mechanisms by which cigarette smoke and its toxins initiate pathological cellular events leading to pancreatitis, have not been clearly defined. Although cigarette smoke is composed of more than 4000 compounds, it is mainly nicotine and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which have been extensively studied with respect to pancreatic diseases. This review summarizes these research findings and highlights cellular pathways which may be of relevance in initiation and progression of smoking-related pancreatitis.

  6. Immune cellular response to HPV: current concepts

    Directory of Open Access Journals (Sweden)

    Maria Alice Guimarães Gonçalves

    2004-02-01

    Full Text Available Although cellular immunity is essential for the elimination of human papillomavirus (HPV, the mechanisms involved are still poorly understood. We summarize the main mechanisms involved in cellular immune response to infections caused by HPV. Immunotherapies for HPV-related cancers require the disruption of T-cell response control mechanisms, associated with the stimulation of the Th1 cytokine response.

  7. Optimized Cellular Core for Rotorcraft Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Patz Materials and Technologies proposes to develop a unique structural cellular core material to improve mechanical performance, reduce platform weight and lower...

  8. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    Energy Technology Data Exchange (ETDEWEB)

    Monette, Michelle Y., E-mail: michelle.monette@yale.edu [Organismic and Evolutionary Biology Program, University of Massachusetts, Amherst, MA 01003 (United States); USGS, Conte Anadromous Fish Research Center, Turners Falls, MA 01376 (United States); Yada, Takashi [Freshwater Fisheries Research Department, National Research Institute of Fisheries Science, Nikko (Japan); Matey, Victoria [Department of Biology, San Diego State University, San Diego, CA 92182 (United States); McCormick, Stephen D. [Organismic and Evolutionary Biology Program, University of Massachusetts, Amherst, MA 01003 (United States); USGS, Conte Anadromous Fish Research Center, Turners Falls, MA 01376 (United States)

    2010-08-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4 {mu}g l{sup -1} Al), acid and low Al (LAl: pH 5.4, 11 {mu}g l{sup -1} Al), acid and moderate Al (MAl: pH 5.3, 42 {mu}g l{sup -1} Al), and acid and high Al (HAl: pH 5.4, 56 {mu}g l{sup -1} Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24 h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na{sup +}/K{sup +}-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl{sup -} channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time

  9. Investigation of the effect of mechanical pressure on the performance of negative lead accumulator electrodes during partial state of charge operation

    Czech Academy of Sciences Publication Activity Database

    Bača, P.; Micka, Karel; Křivík, P.; Tonar, K.; Tošer, P.

    2012-01-01

    Roč. 207, JUN 1 2012 (2012), s. 37-44. ISSN 0378-7753 Institutional research plan: CEZ:AV0Z40400503 Keywords : Lead battery electrodes * Doping with carbon or titanium dioxide * Effect of mechanical pressure Subject RIV: CG - Electrochemistry Impact factor: 4.675, year: 2012

  10. Contriving new spacer grid shapes and choosing the leading candidates of the spacer grid from the mechanical/structural point of view

    International Nuclear Information System (INIS)

    Based on the fuel assembly mechanical/thermal-hydraulic design experience and scrutinizing the design features on the foreign advanced nuclear fuel and the foreign patents of the spacer grid, 13 kinds of spacer grid candidates are derived. Among, the candidates the mechanical/structural performance on the five candidates was evaluated by the screening test and the analysis. As a result of the test and the analysis, two spacer grid shapes are finally selected to be the leading candidates in order to investigate the mechanical/structural performance in detail

  11. Task Group 7B: Cellular and Molecular Mechanisms of Biological Aging: The Roles of Nature, Nurture and Chance in the Maintenance of Human Healthspan

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich; Arya, Suresh; Grant, Christine; Miller, Linda; Ono, Santa Jeremy; Patil, Chris; Shay, Jerry; Topol, Eric; Torry, Michael; Weier, Heinz-Ulrich G.; Tse, Iris; Lin, Su-Ju; Miller, Richard

    2007-11-14

    The degree to which an individual organism maintains healthspan and lifespan is a function of complex interactions between genetic inheritance ('nature'), environment, including cultural inheritance (nurture) and stochastic events ('luck' or 'chance'). This task group will focus upon the role of chance because it is so poorly understood and because it appears to be of major importance in the determination of individual variations in healthspan and lifespan within species. The major factor determining variations in healthspan and lifespan between species is genetic inheritance. Broader aspects of cellular and molecular mechanisms of biological aging will also be considered, given their importance for understanding the cellular and molecular basis of successful aging. The task force will consider the cellular and molecular basis for nature, nurture and chance in healthspan and life span determination. On the basis of comparisons between identical and non-identical twins, geneticists have estimated that genes control no more than about a quarter of the inter-individual differences in lifespan (Herskind 1996). Twin studies of very old individuals, however, show substantially greater genetic contributions to Healthspan (McClearn 2004; Reed 2003). The environment clearly plays an important role in the length and the quality of life. Tobacco smoke, for example has the potential to impact upon multiple body systems in ways that appear to accelerate the rates at which those systems age (Bernhard 2007). To document the role of chance events on aging, one must rigorously control both the genetic composition of an organism and its environment. This has been done to a remarkable degree in a species of nematodes, Caenorhabditis elegans (Vanfleteren 1998). The results confirm hundreds of previous studies with a wide range of species, especially those with inbred rodents housed under apparently identical but less well controlled environments. One

  12. Cytotoxicity and cellular mechanisms involved in the toxicity of CdS quantum dots in hemocytes and gill cells of the mussel Mytilus galloprovincialis

    International Nuclear Information System (INIS)

    Highlights: • CdS QDs were cytotoxic for mussel hemocytes and gill cells in vitro. • Ionic Cd was the most toxic form, followed by CdS QDs and bulk CdS. • CdS QDs altered oxidative balance and caused DNA damage in mussel cells. • CdS QDs caused a particle-specific immunostimulation on phagocytosis of hemocytes. • Conceptual models for cellular handling and toxicity of CdS QDs are proposed. - Abstract: CdS quantum dots (QDs) show a great promise for treatment and diagnosis of cancer and for targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. In spite of their advantages it is important to determine if CdS QDs can exert toxicity on biological systems. In the present work, cytotoxicity of CdS QDs (5 nm) at a wide range of concentrations (0.001–100 mg Cd/L) was screened using neutral red (NR) and thiazolyl blue tetrazolium bromide (MTT) assays in isolated hemocytes and gill cells of mussels (Mytilus galloprovincialis). The mechanisms of action of CdS QDs were assessed at sublethal concentrations (0.31–5 mg Cd/L) in the same cell types through a series of functional in vitro assays: production of reactive oxygen species (ROS), catalase (CAT) activity, DNA damage, lysosomal acid phosphatase (AcP) activity, multixenobiotic resistance (MXR) transport activity, Na-K-ATPase activity (only in gill cells) and phagocytic activity and damage to actin cytoskeleton (only in hemocytes). Exposures to CdS QDs lasted for 24 h and were performed in parallel with exposures to bulk CdS and ionic Cd. Ionic Cd was the most toxic form to both cell types, followed by CdS QDs and bulk CdS. ROS production, DNA damage, AcP activity and MXR transport were significantly increased in both cell types exposed to the 3 forms of Cd. CAT activity increased in hemocytes exposed to the three forms of Cd while in gill cells only in those exposed to ionic Cd. No effects were found on hemocytes cytoskeleton integrity. Effects on

  13. Cytotoxicity and cellular mechanisms involved in the toxicity of CdS quantum dots in hemocytes and gill cells of the mussel Mytilus galloprovincialis

    Energy Technology Data Exchange (ETDEWEB)

    Katsumiti, A. [CBET Research Group, Dept. Zoology and Animal Cell Biology, Faculty of Science and Technology and Research Centre for Experimental Marine Biology and Biotechnology PIE, University of the Basque Country UPV/EHU, Basque Country (Spain); Gilliland, D. [EU Commission–Joint Research Centre, Institute of Health and Consumer Protection, NSB Unit, Ispra (Italy); Arostegui, I. [Department of Applied Mathematics, Statistics and Operations Research, Faculty of Science and Technology, University of the Basque Country UPV/EHU, Leioa (Spain); Cajaraville, M.P., E-mail: mirenp.cajaraville@ehu.es [CBET Research Group, Dept. Zoology and Animal Cell Biology, Faculty of Science and Technology and Research Centre for Experimental Marine Biology and Biotechnology PIE, University of the Basque Country UPV/EHU, Basque Country (Spain)

    2014-08-15

    Highlights: • CdS QDs were cytotoxic for mussel hemocytes and gill cells in vitro. • Ionic Cd was the most toxic form, followed by CdS QDs and bulk CdS. • CdS QDs altered oxidative balance and caused DNA damage in mussel cells. • CdS QDs caused a particle-specific immunostimulation on phagocytosis of hemocytes. • Conceptual models for cellular handling and toxicity of CdS QDs are proposed. - Abstract: CdS quantum dots (QDs) show a great promise for treatment and diagnosis of cancer and for targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. In spite of their advantages it is important to determine if CdS QDs can exert toxicity on biological systems. In the present work, cytotoxicity of CdS QDs (5 nm) at a wide range of concentrations (0.001–100 mg Cd/L) was screened using neutral red (NR) and thiazolyl blue tetrazolium bromide (MTT) assays in isolated hemocytes and gill cells of mussels (Mytilus galloprovincialis). The mechanisms of action of CdS QDs were assessed at sublethal concentrations (0.31–5 mg Cd/L) in the same cell types through a series of functional in vitro assays: production of reactive oxygen species (ROS), catalase (CAT) activity, DNA damage, lysosomal acid phosphatase (AcP) activity, multixenobiotic resistance (MXR) transport activity, Na-K-ATPase activity (only in gill cells) and phagocytic activity and damage to actin cytoskeleton (only in hemocytes). Exposures to CdS QDs lasted for 24 h and were performed in parallel with exposures to bulk CdS and ionic Cd. Ionic Cd was the most toxic form to both cell types, followed by CdS QDs and bulk CdS. ROS production, DNA damage, AcP activity and MXR transport were significantly increased in both cell types exposed to the 3 forms of Cd. CAT activity increased in hemocytes exposed to the three forms of Cd while in gill cells only in those exposed to ionic Cd. No effects were found on hemocytes cytoskeleton integrity. Effects on

  14. Origami interleaved tube cellular materials

    International Nuclear Information System (INIS)

    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. (paper)

  15. The environmental agreement may lead to large losses for the oil producers. The Kyoto mechanisms are very important to Norway

    International Nuclear Information System (INIS)

    The article presents an economic model study of the implications of an climatic agreement. Two main scenarios are presented: 1) The Kyoto protocol is extended to 2020. 2) All counties ratify a climatic agreement. The conclusions are that the Kyoto protocol may have great effects on the oil and gas markets and large economic consequences for Norway. It is therefore mandatory to extensively use the Kyoto mechanisms such as trade with quotas, common implementation and the green development mechanism

  16. Actual problems of cellular cardiomyoplasty

    Directory of Open Access Journals (Sweden)

    Bulat Kaupov

    2010-04-01

    Full Text Available The paper provides review of cellular technologies used incardiology, describes types of cellular preparations depending onsources of cells and types of compounding cells. The generalmechanisms of therapies with stem cells applications are described.Use of cellular preparations for treatment of cardiovascular diseasesand is improvement of the forecast at patients with heartinsufficiency of various genesis is considered as alternative topractice with organ transplantations. Efforts of biotechnologicallaboratories are directed on search of optimum population of cellsfor application in cardiology and studying of mechanisms andfactors regulating function of cardiac stem cells.

  17. Liver and Renal Function Tests in Artisans Occupationally Exposed to Lead in Mechanic Village in Nnewi, Nigeria

    Directory of Open Access Journals (Sweden)

    S. C. Meludu

    2004-02-01

    Full Text Available Additives in petroleum solvents have been reported to have adverse health implications. An evaluation study on some toxicological effects of occupational exposure to petroleum products (especially petrol which contains tetraethyl lead amongst twenty five occupationally exposed artisans and twenty five graduate students of College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Nigeria as controls, was carried out using the following biochemical markers: electrolytes, urea, uric acid, inorganic phosphorus, creatinine, zinc and blood lead, as well as the activities of alanine and aspartate aminotransferases, and alkaline phosphatase. The results showed that occupational exposure of human subjects to lead in petrol increases the concentrations of uric acid (357 ± 123μ mol/L and phosphate (1.5 ± 0.5m mol/L in exposed subjects compared with unexposed subjects (uric acid 228 ± 105μ mol/L, phosphate 1.2 ± 0.41m mol/L; p < 0.01 in both cases. Significantly lower activities were observed for alkaline phosphatase (66 ± 18.9 iu/L. The activities of alanine aminotransferase (11.4 ± 4.0 iu/L and aspartate aminotransferase (15.8 ± 4.4 iu/L in occupationally exposed artisans were higher compared with unexposed subjects (alkaline phosphatase = 78 ± 22.4 iu/L alanine aminotranferase = 6.8 ± 2.7 iu/L, aspartate aminotranferase = 9.6 ± 3.5i u/L; p < 0.01 in all cases. Occupational exposure of human subjects to lead significantly increased blood lead (59.6 ± 15.9 μg/dL and decreased plasma zinc (71.3 ± 14.4 μg/L in exposed compared with unexposed subjects (blood lead = 35 ± 7 μg/dL, zinc = 108.4 ± 16.9 μg/dL; p < 0.01. The results indicate that occupational exposure to lead in petrol may compromise liver and renal function.

  18. Quantum cellular automata

    Science.gov (United States)

    Porod, Wolfgang; Lent, Craig S.; Bernstein, Gary H.

    1994-06-01

    The Notre Dame group has developed a new paradigm for ultra-dense and ultra-fast information processing in nanoelectronic systems. These Quantum Cellular Automata (QCA's) are the first concrete proposal for a technology based on arrays of coupled quantum dots. The basic building block of these cellular arrays is the Notre Dame Logic Cell, as it has been called in the literature. The phenomenon of Coulomb exclusion, which is a synergistic interplay of quantum confinement and Coulomb interaction, leads to a bistable behavior of each cell which makes possible their use in large-scale cellular arrays. The physical interaction between neighboring cells has been exploited to implement logic functions. New functionality may be achieved in this fashion, and the Notre Dame group invented a versatile majority logic gate. In a series of papers, the feasibility of QCA wires, wire crossing, inverters, and Boolean logic gates was demonstrated. A major finding is that all logic functions may be integrated in a hierarchial fashion which allows the design of complicated QCA structures. The most complicated system which was simulated to date is a one-bit full adder consisting of some 200 cells. In addition to exploring these new concepts, efforts are under way to physically realize such structures both in semiconductor and metal systems. Extensive modeling work of semiconductor quantum dot structures has helped identify optimum design parameters for QCA experimental implementations.

  19. tRNA modifications regulate translation during cellular stress

    OpenAIRE

    Gu, Chen; Thomas J Begley; Peter C. Dedon

    2014-01-01

    The regulation of gene expression in response to stress is an essential cellular protection mechanism. Recent advances in tRNA modification analysis and genome-based codon bias analytics have facilitated studies that lead to a novel model for translational control, with translation elongation dynamically regulated during stress responses. Stress-induced increases in specific anticodon wobble bases are required for the optimal translation of stress response transcripts that are significantly b...

  20. Intrinsic Structural Disorder Confers Cellular Viability on Oncogenic Fusion Proteins

    OpenAIRE

    Hedi Hegyi; László Buday; Peter Tompa

    2009-01-01

    Chromosomal translocations, which often generate chimeric proteins by fusing segments of two distinct genes, represent the single major genetic aberration leading to cancer. We suggest that the unifying theme of these events is a high level of intrinsic structural disorder, enabling fusion proteins to evade cellular surveillance mechanisms that eliminate misfolded proteins. Predictions in 406 translocation-related human proteins show that they are significantly enriched in disorder (43.3% vs....

  1. Lead-Cooled Fast Reactor (LFR) Design: Safety, Neutronics, Thermal Hydraulics, Structural Mechanics, Fuel, Core, and Plant Design

    Energy Technology Data Exchange (ETDEWEB)

    Smith, C

    2010-02-22

    The idea of developing fast spectrum reactors with molten lead (or lead alloy) as a coolant is not a new one. Although initially considered in the West in the 1950s, such technology was not pursued to completion because of anticipated difficulties associated with the corrosive nature of these coolant materials. However, in the Soviet Union, such technology was actively pursued during the same time frame (1950s through the 1980s) for the specialized role of submarine propulsion. More recently, there has been a renewal of interest in the West for such technology, both for critical systems as well as for Accelerator Driven Subcritical (ADS) systems. Meanwhile, interest in the former Soviet Union, primarily Russia, has remained strong and has expanded well beyond the original limited mission of submarine propulsion. This section reviews the past and current status of LFR development.

  2. Membrane Interactions of Phytochemicals as Their Molecular Mechanism Applicable to the Discovery of Drug Leads from Plants

    Directory of Open Access Journals (Sweden)

    Hironori Tsuchiya

    2015-10-01

    Full Text Available In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and antioxidant drugs. As well as these membrane-acting drugs, bioactive plant components, phytochemicals, with amphiphilic or hydrophobic structures, are presumed to interact with biological membranes and biomimetic membranes prepared with phospholipids and cholesterol, resulting in the modification of membrane fluidity, microviscosity, order, elasticity, and permeability with the potencies being consistent with their pharmacological effects. A novel mechanistic point of view of phytochemicals would lead to a better understanding of their bioactivities, an insight into their medicinal benefits, and a strategic implication for discovering drug leads from plants. This article reviews the membrane interactions of different classes of phytochemicals by highlighting their induced changes in membrane property. The phytochemicals to be reviewed include membrane-interactive flavonoids, terpenoids, stilbenoids, capsaicinoids, phloroglucinols, naphthodianthrones, organosulfur compounds, alkaloids, anthraquinonoids, ginsenosides, pentacyclic triterpene acids, and curcuminoids. The membrane interaction’s applicability to the discovery of phytochemical drug leads is also discussed while referring to previous screening and isolating studies.

  3. Molecular mechanisms of the epithelial transport of toxic metal ions, particularly mercury, cadmium, lead, arsenic, zinc, and copper. Progress report, January 1, 1979-December 31, 1979

    International Nuclear Information System (INIS)

    The purpose of the present studies was to elucidate the mechanism of lead transport, and especially the particular similarities or dissimilarities between lead and calcium in this process. The absorption of these metals was determined in 3-week old White Leghorn cockerels, raised on a commercial diet or on a specified diet, using in vivo ligated loop procedure. The dose administered into the loop contained 0.5 μCi 203Pb (and/or 0.1 μCi 47Ca), and 0.01 mM lead acetate (and/or 1 mM CaCl2) in 0.5 ml 0.15 M NaCl,pH 6.5. It was shown that lead is rapidly taken up by the mucosal tissue, and slowly transferred into the body, whereas less calcium is retained by the tissue and the transfer of calcium is many times as effective as that for lead. They appear to respond in a similar manner to a low calcium intake and vitamin D treatment. Certain differences were, however, observed in the absorption process. Increasing luminal stable lead concentration from 0.01 to 1.00 mM Pb, significantly reduced the percentage of radiolead absorbed, but did not affect the absorption of calcium. Also, vitamin D enhanced the transfer of plasma 47Ca into the lumen but did not affect the transfer of plasma 203Pb. Intravenous administration of 1,25(OH)2CC to rachitic chicks enhanced calcium and lead absorption, but the maximal absorption of these metals occurred at slightly different times after administering this metabolite, and the effect on calcium outlasted that on lead, indicating that two different transport systems may be involved. It was concluded that lead is transported across the epithelial wall by a passive diffusion and this process is affected by vitamin D in a similar manner as this vitamin affects the diffusional component of calcium transport

  4. Microscale failure mechanisms leading to internal short circuit in Li-ion batteries under complex loading scenarios

    Science.gov (United States)

    Sahraei, Elham; Bosco, Emanuela; Dixon, Brandy; Lai, Benjamin

    2016-07-01

    One of the least understood mechanisms of Li-ion batteries is the development of internal short circuits under mechanical loads. In this study, a micro mechanical model is developed and subjected to various loading scenarios to understand the sequence of failure in the multi-layer, multi-material structure of a Li-ion battery jellyroll. The constitutive response of each component of the electrode stack is obtained by comprehensive experimental tests using uniaxial and biaxial tensile and compressive loads. The homogenized response of the model is recovered through the computational homogenization theory. The model is validated by comparing the results of a macroscale simulation against experimental data. The study focuses next on the development of a failure criterion for the electrode stack based on the microstructural observations. Results show distinct failure mechanisms when the loading is predominantly tensile versus when it is compressive or combined tensile/compressive. A failure locus is plotted from the results of the simulations as a criterion to detect the onset of short circuit under complex multi-axial loading scenarios.

  5. Cellular tolerance to pulsed heating

    Science.gov (United States)

    Simanovski, Dimitrii; Sarkar, M.; Irani, A.; O'Connell-Rodwell, C.; Contag, C.; Schwettman, H. Alan; Palanker, D.

    2005-04-01

    Many laser therapies involve significant heating of tissue with pulses varying from picoseconds to minutes in duration. In some of the applications heating is a primary goal, while in others it is an undesirable side effect. In both cases, if a hyperthermia is involved, the knowledge about the threshold temperature leading to irreversible cellular damage is critically important. We study the dependence of the threshold temperature on duration of the heat exposure in the range of 0.3 ms to 5 seconds. Thin layer of cells cultured in a Petri dish was exposed to a pulsed CO2 laser radiation. Laser beam was focused onto sample providing Gaussian intensity distribution in the focal plane with a beam diameter (2w) 2-10 mm. Surface temperature in the central part of the focal spot (1mm in diameter) was measured by thermal infrared (IR) emission from the sample, recorded with a fast IR detector. For pulses shorter than 1 s the temperature profile across the focal spot was found to closely correspond to the radial distribution of the laser beam intensity, thus allowing for accurate determination of temperature at any given distance from the center of the spot. Immediate cellular damage was assessed using vital staining with the live/dead fluorescent assay. Threshold temperatures were found to vary from 65 °C at 5 s of heating to 160 °C at pulses of 0.3 ms in duration. The shorter end of this range was limited by vaporization, which occurs during the laser pulse and results in mechanical damage to cells. Dependence of the maximal temperature on pulse duration could be approximated by Arrhenius law with activation energy being about 1 eV.

  6. Failover in cellular automata

    CERN Document Server

    Kumar, Shailesh

    2010-01-01

    A cellular automata (CA) configuration is constructed that exhibits emergent failover. The configuration is based on standard Game of Life rules. Gliders and glider-guns form the core messaging structure in the configuration. The blinker is represented as the basic computational unit, and it is shown how it can be recreated in case of a failure. Stateless failover using primary-backup mechanism is demonstrated. The details of the CA components used in the configuration and its working are described, and a simulation of the complete configuration is also presented.

  7. Cellular-scale hydrodynamics

    DEFF Research Database (Denmark)

    Abkarian, Manouk; Faivre, Magalie; Horton, Renita; Smistrup, Kristian; Best-Popescu, Catherine A; Stone, Howard A.

    2008-01-01

    Microfluidic tools are providing many new insights into the chemical, physical and physicochemical responses of cells. Both suspension-level and single-cell measurements have been studied. We review our studies of these kinds of problems for red blood cells with particular focus on the shapes of ...... mechanical effects on suspended cells can be studied systematically in small devices, and how these features can be exploited to develop methods for characterizing physicochemical responses and possibly for the diagnosis of cellular-scale changes to environmental factors....

  8. Cellular blebs: pressure-driven, axisymmetric, membrane protrusions

    KAUST Repository

    Woolley, Thomas E.

    2013-07-16

    Blebs are cellular protrusions that are used by cells for multiple purposes including locomotion. A mechanical model for the problem of pressure-driven blebs based on force and moment balances of an axisymmetric shell model is proposed. The formation of a bleb is initiated by weakening the shell over a small region, and the deformation of the cellular membrane from the cortex is obtained during inflation. However, simply weakening the shell leads to an area increase of more than 4 %, which is physically unrealistic. Thus, the model is extended to include a reconfiguration process that allows large blebs to form with small increases in area. It is observed that both geometric and biomechanical constraints are important in this process. In particular, it is shown that although blebs are driven by a pressure difference across the cellular membrane, it is not the limiting factor in determining bleb size. © 2013 Springer-Verlag Berlin Heidelberg.

  9. Mechanisms of calcium transport in small intestine. Progress report, March 1, 1976--September 30, 1977. [Chickens, rats, lead

    Energy Technology Data Exchange (ETDEWEB)

    DeLuca, H.F.

    1977-01-01

    Progress is reported on the following research projects: subcellular location of 1,25-dihydroxyvitamin D/sub 3/(1,25-(OH)/sub 2/D/sub 3/) in intestine of chickens; studies on receptor proteins in intestine for 1,25-(OH)/sub 2/D3; studies on intestinal cytosol receptors in chickens and rats; control of intestinal calcium transport; effect of calcitonin on 25-OH-D/sub 3/-1-hydroxylase; isolation and identification of the active principle of Solonum glaucophyllum, the South American plant that causes metastatic calcification and death to grazing animals; and studies on lead transport in vitro and in vivo. (HLW)

  10. Mechanical properties and microstructure of model lead-free joints for electronics made with use of nanopowders

    Czech Academy of Sciences Publication Activity Database

    Buršík, Jiří; Buršíková, V.; Pešina, Z.; Sopoušek, J.

    2012-01-01

    Roč. 106, SI (2012), s390-s392. ISSN 0009-2770. [Local Mechanical Properties 2011. Olomouc, 09.11.2011-11.11.2011] R&D Projects: GA ČR(CZ) GA106/09/0700 Institutional research plan: CEZ:AV0Z20410507 Keywords : solder * silver nanopowdwer * nanoindentation Subject RIV: JG - Metallurgy Impact factor: 0.453, year: 2012

  11. Electrical, Mechanical, and Capacity Percolation Leads to High-Performance MoS2/Nanotube Composite Lithium Ion Battery Electrodes.

    Science.gov (United States)

    Liu, Yuping; He, Xiaoyun; Hanlon, Damien; Harvey, Andrew; Khan, Umar; Li, Yanguang; Coleman, Jonathan N

    2016-06-28

    Advances in lithium ion batteries would facilitate technological developments in areas from electrical vehicles to mobile communications. While two-dimensional systems like MoS2 are promising electrode materials due to their potentially high capacity, their poor rate capability and low cycle stability are severe handicaps. Here, we study the electrical, mechanical, and lithium storage properties of solution-processed MoS2/carbon nanotube anodes. Nanotube addition gives up to 10(10)-fold and 40-fold increases in electrical conductivity and mechanical toughness, respectively. The increased conductivity results in up to a 100× capacity enhancement to ∼1200 mAh/g (∼3000 mAh/cm(3)) at 0.1 A/g, while the improved toughness significantly boosts cycle stability. Composites with 20 wt % nanotubes combine high reversible capacity with excellent cycling stability (e.g., ∼950 mAh/g after 500 cycles at 2 A/g) and high rate capability (∼600 mAh/g at 20 A/g). The conductivity, toughness, and capacity scale with nanotube content according to percolation theory, while the stability increases sharply at the mechanical percolation threshold. We believe that the improvements in conductivity and toughness obtained after addition of nanotubes can be transferred to other electrode materials, such as silicon nanoparticles. PMID:27203558

  12. Influence of polyamide-imide concentration on the cellular structure and thermo-mechanical properties of polyetherimide/polyamide-imide blend foams

    OpenAIRE

    Abbasi, Hooman; Antunes, Marcelo de Sousa Pais; Velasco Perero, José Ignacio

    2015-01-01

    The present work considers the preparation of medium-density polyetherimide (PEI)/polyamide-imide (PAI) blend foams by means of water vapor-induced phase separation (WVIPS) and their characterization. While pure polymer foams showed homogeneous cellular structures with average cell sizes of 10-12 µm, PEI/PAI blend foams presented two distinctive closed-cell structures depending on the composition of the blend. At the lowest concentration of PAI (25 wt%) foams showed a very fine homogeneous mi...

  13. Delineating cellular and molecular mechanisms of toxicity of an extract of khat (Catha edulis Forsk.) in leukemia and normal peripheral blood cells

    OpenAIRE

    Bredholt, Therese

    2010-01-01

    Plants have been used in treatment and prevention of diseases for thousands of years. In modern medicine there is a trend towards isolation and identification of bioactive molecules, whereas plant preparations continue to be used in traditional medicinal systems. However, combinations of drugs are usually administered in treatment of complex diseases like cancer and HIV, in order to target multiple deregulated cellular pathways simultaneously. Khat (Catha edulis Forsk.) has bee...

  14. Molecular mechanisms of the epithelial transport of toxic metal ions, particularly mercury, cadmium, lead, arsenic, zinc, and copper. Progress report, January 1, 1979-December 31, 1979

    International Nuclear Information System (INIS)

    The mechanism of lead transport is presented, and especially the particular similarities or dissimilarities between lead and calcium in this process. The absorption of these metals was determined cockerels, raised on a commercial diet or on a specified diet, using in vivo ligated loop procedure. The dose administered into the loop contained 0.5 μCi 203Pb (and/or 0.1 μCi 47Ca), and 0.01 mM lead acetate (and/or mM CaCl2) in 0.5 ml 0.15 M NaCl,pH 6.5. It was shown that lead is rapidly taken up by the mucosal tissue, and slowly transferred into the body, whereas less calcium is retained by the tissue and the transfer of calcium is many times as effective as that for lead. They appear to respond in a similar manner to a low calcium intake and vitamin D treatment. Increasing luminal stable lead concentration significantly reduced the percentage of radiolead significantly reduced the percentage of radiolead absorbed, but did not affect the absorption of calcium. Also, vitamin D enhanced the transfer of plasma 47Ca into the lumen but did not affect the transfer of plasma 203Pb. Intravenous administration of 1,25(OH)2CC to rachitic chicks enhanced calcium and lead absorption, but the maximal absorption of these metals occurred at slightly different times after administering this metabolite, indicating that two different transport systems may be involved. It was concluded that lead is transported across the epithelial wall by a passive diffusion and this process is affected by vitamin D in a similar manner as this vitamin affects the diffusional component of calcium transport

  15. Nongenomic Mechanisms of PTEN Regulation

    Directory of Open Access Journals (Sweden)

    Jimmie E. Fata

    2012-01-01

    Full Text Available A large amount of data supports the view that PTEN is a bona fide tumor suppressor gene. However, recent evidence suggests that derailment of cellular localization and expression levels of functional nonmutated PTEN is a determining force in inducing abnormal cellular and tissue outcomes. As the cellular mechanisms that regulate normal PTEN enzymatic activity resolve, it is evident that deregulation of these mechanisms can alter cellular processes and tissue architecture and ultimately lead to oncogenic transformation. Here we discuss PTEN ubiquitination, PTEN complex formation with components of the adherens junction, PTEN nuclear localization, and microRNA regulation of PTEN as essential regulatory mechanisms that determine PTEN function independent of gene mutations and epigenetic events.

  16. Mechanical and dielectric characterization of lead zirconate titanate(PZT)/polyurethane(PU) thin film composite for energy harvesting

    Science.gov (United States)

    Aboubakr, S.; Rguiti, M.; Hajjaji, A.; Eddiai, A.; Courtois, C.; d'Astorg, S.

    2014-04-01

    The Lead Zirconate titanate (PZT) ceramic is known by its piezoelectric feature, but also by its stiffness, the use of a composite based on a polyurethane (PU) matrix charged by a piezoelectric material, enable to generate a large deformation of the material, therefore harvesting more energy. This new material will provide a competitive alternative and low cost manufacturing technology of autonomous systems (smart clothes, car seat, boat sail, flag ...). A thin film of the PZT/PU composite was prepared using up to 80 vol. % of ceramic. Due to the dielectric nature of the PZT, inclusions of this one in a PU matrix raises the permittivity of the composite, on other hand this latter seems to decline at high frequencies.

  17. LEADING WITH LEADING INDICATORS

    International Nuclear Information System (INIS)

    This paper documents Fluor Hanford's use of Leading Indicators, management leadership, and statistical methodology in order to improve safe performance of work. By applying these methods, Fluor Hanford achieved a significant reduction in injury rates in 2003 and 2004, and the improvement continues today. The integration of data, leadership, and teamwork pays off with improved safety performance and credibility with the customer. The use of Statistical Process Control, Pareto Charts, and Systems Thinking and their effect on management decisions and employee involvement are discussed. Included are practical examples of choosing leading indicators. A statistically based color coded dashboard presentation system methodology is provided. These tools, management theories and methods, coupled with involved leadership and employee efforts, directly led to significant improvements in worker safety and health, and environmental protection and restoration at one of the nation's largest nuclear cleanup sites

  18. LEADING WITH LEADING INDICATORS

    Energy Technology Data Exchange (ETDEWEB)

    PREVETTE, S.S.

    2005-01-27

    This paper documents Fluor Hanford's use of Leading Indicators, management leadership, and statistical methodology in order to improve safe performance of work. By applying these methods, Fluor Hanford achieved a significant reduction in injury rates in 2003 and 2004, and the improvement continues today. The integration of data, leadership, and teamwork pays off with improved safety performance and credibility with the customer. The use of Statistical Process Control, Pareto Charts, and Systems Thinking and their effect on management decisions and employee involvement are discussed. Included are practical examples of choosing leading indicators. A statistically based color coded dashboard presentation system methodology is provided. These tools, management theories and methods, coupled with involved leadership and employee efforts, directly led to significant improvements in worker safety and health, and environmental protection and restoration at one of the nation's largest nuclear cleanup sites.

  19. Mechanical confinement for improved energy storage density in BNT-BT-KNN lead-free ceramic capacitors

    Directory of Open Access Journals (Sweden)

    Aditya Chauhan

    2014-08-01

    Full Text Available With the advent of modern power electronics, embedded circuits and non-conventional energy harvesting, the need for high performance capacitors is bound to become indispensible. The current state-of-art employs ferroelectric ceramics and linear dielectrics for solid state capacitance. However, lead-free ferroelectric ceramics propose to offer significant improvement in the field of electrical energy storage owing to their high discharge efficiency and energy storage density. In this regards, the authors have investigated the effects of compressive stress as a means of improving the energy storage density of lead-free ferroelectric ceramics. The energy storage density of 0.91(Bi0.5Na0.5TiO3-0.07BaTiO3-0.02(K0.5Na0.5NbO3 ferroelectric bulk ceramic was analyzed as a function of varying levels of compressive stress and operational temperature .It was observed that a peak energy density of 387 mJ.cm-3 was obtained at 100 MPa applied stress (25oC. While a maximum energy density of 568 mJ.cm-3 was obtained for the same stress at 80oC. These values are indicative of a significant, 25% and 84%, improvement in the value of stored energy compared to an unloaded material. Additionally, material's discharge efficiency has also been discussed as a function of operational parameters. The observed phenomenon has been explained on the basis of field induced structural transition and competitive domain switching theory.

  20. Adhesions due to peritoneal carcinomatosis caused by a renal carcinoma leading to mechanical gastric outlet obstruction: a case report

    Directory of Open Access Journals (Sweden)

    Gruttadauria Salvatore

    2011-07-01

    Full Text Available Abstract Introduction Gastric outlet obstruction is a clinical syndrome caused by a variety of mechanical obstructions. Peptic ulcer disease used to be responsible for most gastric outlet obstruction, but in the last 40 years the prevalence of malignant tumors has risen significantly. Adhesive disease is an infrequent and insidious cause of mechanical gastric outlet obstruction. Case presentation We report the case of a 78-year-old Caucasian man who had a clinical history of a right nephrectomy for malignancy three years earlier and who was admitted for a severe gastric outlet obstruction (score of 1 confirmed both by an upper endoscopy and by a fluoroscopic view after contrast injection. A computed tomography scan and a laparotomy, with omental biopsies, showed a peritoneal carcinomatosis with the development of abdominal adhesions that prompted an abnormal gastric rotation around the perpendicular axis of his antrum with a dislocation in the empty space of his right kidney. Symptoms disappeared after surgical bypass through a gastrojejunostomy. Conclusions Our patient experienced a very rare complication characterized by the development of adhesions due to peritoneal carcinomatosis caused by a renal carcinoma treated with nephrectomy. These adhesions prompted an abnormal dislocation of his antrum, as an internal hernia, in the empty space of his right kidney.

  1. Functional Proteomics Defines the Molecular Switch Underlying FGF Receptor Trafficking and Cellular Outputs

    DEFF Research Database (Denmark)

    Francavilla, Chiara; Rigbolt, Kristoffer T.G.; Emdal, Kristina B;

    2013-01-01

    The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferati...

  2. Study of the reaction mechanisms leading to projectile fragmentation in 40 Ar + Ag nat reactions at 30 MeV and 60 MeV per nucleon

    International Nuclear Information System (INIS)

    This work is devoted to a study of the reaction mechanisms leading to projectile fragmentation in heavy ion collisions at intermediate energy (less than 100 MeV per nucleon). In contradiction with some theoretical calculations, inclusive measurements of projectile fragments as well as correlation measurements between projectile and target fragments in the reaction 40Ar + natAg at 30 MeV and 60 MeV per nucleon do not show any evidence for a change in the reaction mechanism in this energy range. Angular, mass and velocity correlations between projectile and target fragments enable us to reject mass transfer from projectile to target as a leading mechanism in projectile fragmentations. However, a coherent description of the data can be given either in the framework of an abrasion-ablation model in which the primary fragments of the projectile and of the target are produced with very low excitation energies, or assuming a two-body reaction, reminiscent of the first steps of deeply inelastic collisions, in which the dissipated energy is shared about equally between strongly excited projectile and target. The high excitation energies deduced from the two-body analysis bring in question our description of the fragmentation process. Thus, the excitation energy of the primary fragment is a key parameter which may be used in future experiments to distinguish between different reaction mechanisms

  3. Unveiling the Mechanisms Leading to H2 Production Promoted by Water Decomposition on Epitaxial Graphene at Room Temperature.

    Science.gov (United States)

    Politano, Antonio; Cattelan, Mattia; Boukhvalov, Danil W; Campi, Davide; Cupolillo, Anna; Agnoli, Stefano; Apostol, Nicoleta G; Lacovig, Paolo; Lizzit, Silvano; Farías, Daniel; Chiarello, Gennaro; Granozzi, Gaetano; Larciprete, Rosanna

    2016-04-26

    By means of a combination of surface-science spectroscopies and theory, we investigate the mechanisms ruling the catalytic role of epitaxial graphene (Gr) grown on transition-metal substrates for the production of hydrogen from water. Water decomposition at the Gr/metal interface at room temperature provides a hydrogenated Gr sheet, which is buckled and decoupled from the metal substrate. We evaluate the performance of Gr/metal interface as a hydrogen storage medium, with a storage density in the Gr sheet comparable with state-of-the-art materials (1.42 wt %). Moreover, thermal programmed reaction experiments show that molecular hydrogen can be released upon heating the water-exposed Gr/metal interface above 400 K. The Gr hydro/dehydrogenation process might be exploited for an effective and eco-friendly device to produce (and store) hydrogen from water, i.e., starting from an almost unlimited source. PMID:27054462

  4. Leading global energy and environmental transformation: Unified ASEAN biomass-based bio-energy system incorporating the clean development mechanism

    International Nuclear Information System (INIS)

    In recent years, the ten member countries in the Association of Southeast Asia Nations (ASEAN) have experienced high economic growth and, in tandem, a substantial increment in energy usage and demand. Consequently, they are now under intense pressure to secure reliable energy supplies to keep up with their growth rate. Fossil fuels remain the primary source of energy for the ASEAN countries, due to economic and physical considerations. This situation has led to unrestrained emissions of greenhouse gases to the environment and thus effectively contributes to global climate change. The abundant supply of biomass from their tropical environmental conditions offers great potential for ASEAN countries to achieve self-reliance in energy supplies. This fact can simultaneously transform into the main driving force behind combating global climate change, which is associated with the usage of fossil fuels. This research article explores the potential and advantages for ASEAN investment in biomass-based bio-energy supply, processing and distribution network with an emphasis on regional collaborations. It also investigates the implementation and operational challenges in terms of political, economic and technical factors for the cross-border energy scheme. Reliance of ASEAN countries on the clean development mechanism (CDM) to address most of the impediments in developing the project is also under scrutiny. Unified co-operation among ASEAN countries in integrating biomass-based bio-energy systems and utilising the clean development mechanism (CDM) as the common effort could serve as the prime example for regional partnerships in achieving sustainable development for the energy and environmental sector in the future. -- Highlights: →A study that explores feasibility for ASEAN investment in biomass-based bio-energy. →Focus is given on regional supply, processing and distribution network. →Cross-border implementation and operational challenges are discussed thoroughly.

  5. Proposed chemical mechanisms leading to secondary organic aerosol in the reactions of aliphatic amines with hydroxyl and nitrate radicals

    Science.gov (United States)

    Price, Derek J.; Clark, Christopher H.; Tang, Xiaochen; Cocker, David R.; Purvis-Roberts, Kathleen L.; Silva, Philip J.

    2014-10-01

    The presence and importance of amines in the atmosphere, including aliphatic amines, continues to gain more attention. The atmospheric reaction mechanisms of these amines with key atmospheric radicals are important to predict both daytime and nighttime atmospheric chemistry. While previous studies have focused on the production of amine salts, this analysis looks at the importance of peroxy radical reactions to the formation of secondary organic aerosol. Atmospheric oxidation mechanisms are presented to explain the observed chemistry. A series of environmental chamber experiments were conducted in which aliphatic tertiary and secondary amines were reacted with either hydroxyl radical (OH) or nitrate radical (NO3). Chemical composition of the aerosol products was obtained with a High Resolution Time of Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and a Particle Into Liquid Sampler Time of Flight Mass Spectrometer (PILS-ToF-MS), while the chemical composition of the gas-phase products was obtained with a Selected Ion Flow Tube Mass Spectrometer (SIFT-MS). A number of aerosol-phase mass spectra showed highly oxidized fragments at a much higher molecular weight (MW) than the amine precursor. It is proposed that these larger compounds are oligomers formed through peroxy radical reactions with hydrogen rearrangement. Another reaction pathway observed was the formation of amine salts. The relative importance of each pathway to the overall production of aerosol is found to be dependent on the type of amine and oxidant. For example, the oligomers were observed in the tertiary methyl amines, while the formation of amine salts was more prevalent in the secondary and tertiary ethyl amines.

  6. Mechanism of Pressure-Induced Phase Transitions, Amorphization, and Absorption-Edge Shift in Photovoltaic Methylammonium Lead Iodide.

    Science.gov (United States)

    Szafrański, Marek; Katrusiak, Andrzej

    2016-09-01

    Our single-crystal X-ray diffraction study of methylammonium lead triiodide, MAPbI3, provides the first comprehensive structural information on the tetragonal phase II in the pressure range to 0.35 GPa, on the cubic phase IV stable between 0.35 and 2.5 GPa, and on the isostructural cubic phase V observed above 2.5 GPa, which undergoes a gradual amorphization. The optical absorption study confirms that up to 0.35 GPa, the absorption edge of MAPbI3 is red-shifted, allowing an extension of spectral absorption. The transitions to phases IV and V are associated with the abrupt blue shifts of the absorption edge. The strong increase of the energy gap in phase V result in a spectacular color change of the crystal from black to red around 3.5 GPa. The optical changes have been correlated with the pressure-induced strain of the MAPbI3 inorganic framework and its frustration, triggered by methylammonium cations trapped at random orientations in the squeezed voids. PMID:27538989

  7. A facile strategy for fabrication of nano-ZnO/yeast composites and their adsorption mechanism towards lead (II) ions

    Science.gov (United States)

    Zhang, Wei; Meng, Lingyin; Mu, Guiqin; Zhao, Maojun; Zou, Ping; Zhang, Yunsong

    2016-08-01

    Nano-ZnO/yeast composites were successfully fabricated by one-step alkali hydrothermal method, and their adsorption properties for Pb2+ ions were also evaluated. Various influencing parameters of nano-ZnO/yeast composites, such as initial pH, contact time and initial Pb2+ concentration were investigated, respectively. The maximum adsorption capacity of nano-ZnO/yeast composites for Pb2+ (31.72 mg g-1) is 2.03 times higher than that of pristine yeast (15.63 mg g-1). The adsorption mechanism of nano-ZnO/yeast composites was studied by a series of techniques. Scanning electron microscopy (SEM) showed that nano-ZnO is evenly deposited on yeast surface. Atomic force microscopy (AFM) analysis exhibited that the yeast surface is rougher than that of pristine yeast. Energy dispersive X-ray detector (EDX) and X-ray diffraction (XRD) indicated the existence of nano-ZnO on yeast surface. Additionally, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) measurements further illustrated that alkali hydrothermal method causes not only the generation and anchorage of nano-ZnO on yeast surface but also the exposure of more functional groups (such as amino, carboxyl groups etc.) on yeast surface, both of which could adsorb Pb2+ via synergistic effect.

  8. Mechanisms leading to oligomers and SOA through aqueous photooxidation: insights from OH radical oxidation of acetic acid

    Directory of Open Access Journals (Sweden)

    Y. Tan

    2011-06-01

    Full Text Available Previous experiments have demonstrated that the aqueous OH radical oxidation of methylglyoxal produces low volatility products including oxalate and oligomers. These products are found predominantly in the particle phase in the atmosphere, suggesting that methylglyoxal is a precursor of secondary organic aerosol (SOA. Acetic acid is an important intermediate in aqueous methylglyoxal oxidation and a ubiquitous product of gas phase photochemistry, making it a potential "aqueous" SOA precursor in its own right. Altieri et al. (2008 proposed that acetic acid was the precursor of oligoesters observed in methylglyoxal oxidation. However, the fate of acetic acid upon aqueous-phase oxidation is not well understood. In this research, acetic acid at concentrations relevant to atmospheric waters (20 μM–10 mM was oxidized by OH radical. Products were analyzed by ion chromatography (IC, electrospray ionization mass spectrometry (ESI-MS, and IC-ESI-MS. The formation of glyoxylic, glycolic, and oxalic acids were observed. In contrast to methylglyoxal oxidation, succinic acid and oligomers were not detected. Using results from these and methylglyoxal + OH radical experiments, radical mechanisms responsible for oligomer formation from methylglyoxal oxidation in clouds and wet aerosols are proposed. The importance of acetic acid/acetate as an SOA precursor is also discussed. We hypothesize that this and similar chemistry is central to the daytime formation of oligomers in wet aerosols.

  9. Mechanisms leading to oligomers and SOA through aqueous photooxidation: insights from OH radical oxidation of acetic acid and methylglyoxal

    Directory of Open Access Journals (Sweden)

    Y. Tan

    2012-01-01

    Full Text Available Previous experiments have demonstrated that the aqueous OH radical oxidation of methylglyoxal produces low volatility products including pyruvate, oxalate and oligomers. These products are found predominantly in the particle phase in the atmosphere, suggesting that methylglyoxal is a precursor of secondary organic aerosol (SOA. Acetic acid plays a central role in the aqueous oxidation of methylglyoxal and it is a ubiquitous product of gas phase photochemistry, making it a potential "aqueous" SOA precursor in its own right. However, the fate of acetic acid upon aqueous-phase oxidation is not well understood. In this research, acetic acid (20 μM–10 mM was oxidized by OH radicals, and pyruvic acid and methylglyoxal experimental samples were analyzed using new analytical methods, in order to better understand the formation of SOA from acetic acid and methylglyoxal. Glyoxylic, glycolic, and oxalic acids formed from acetic acid and OH radicals. In contrast to the aqueous OH radical oxidation of methylglyoxal, the aqueous OH radical oxidation of acetic acid did not produce succinic acid and oligomers. This suggests that the methylgloxal-derived oligomers do not form through the acid catalyzed esterification pathway proposed previously. Using results from these experiments, radical mechanisms responsible for oligomer formation from methylglyoxal oxidation in clouds and wet aerosols are proposed. The importance of acetic acid/acetate as an SOA precursor is also discussed. We hypothesize that this and similar chemistry is central to the daytime formation of oligomers in wet aerosols.

  10. The simulation of physical mechanism for HTM-free perovskite organic lead iodide planar heterojunction solar cells

    International Nuclear Information System (INIS)

    Recently, organo-metal halide perovskites have attracted much attention from the scientific community because of their successful application in the absorber layer of low-cost solar cells. For the further improvement of the performance of such cells, a thorough understanding of the influence of the material properties on the working mechanism of a device is very necessary and important. In this study, two-dimensional modeling of hole transport material free planar heterojunction solar cells was performed, in which electromagnetic simulation was directly linked to carrier transport calculations. An optimum absorber thickness of 200 nm was reproduced in the simulation at carrier diffusion length of 100 nm, in good agreement with previous experiments. This optimum thickness increased with the increase of diffusion length, and an efficiency of about 11% was obtained at 300 nm with a diffusion length of 300 nm. Finally, it was demonstrated that the relatively low efficiency of such solar cells was directly related to the low short-circuit photocurrent density (J SC) and the low open-circuit voltage (V OC) due to the insufficient absorption of the long-wavelength region and the nearly intrinsic doping concentration, respectively. (paper)

  11. Study on mechanical behavior of the deep embeded steel sheet pile cellular bulkhead. Neire no fukai hagane yaita cell shiki gogan no rikigaku teki kyodo ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Higashigawa, T.; Achiwa, F. (The Chubu Electric Power Co. Inc., Nagoya (Japan)); Matsuo, M. (Nagoya Univ., Nagoya (Japan). Faculty of Engineering); Sunami, S. (Nikken Sekkei, Osaka (Japan))

    1991-09-20

    At the Hekinan coal-burning thermal power station of Chubu Electric Power Company, there is a plan to construct its ash dump by closing the neighboring sea area with bulkheads. This bulkhead is deeply embeded steel sheet piles to be struck into a soft clay layer. Since it is necessary to improve the ground in a wide area for stabilization of soft clay, the specifications as well as the scope of improvement of the basic design plan were noticed, a qualitative study of the bulkhead was done by a numerical analysis aiming at realization of a rational and economical bulkhead and an execution plan which modified the above was prepared. In this execution plan, the reduction as much as about 9% became possible for the construction cost of about 1km long bulkheads. In order to demonstrate the adequacy of this execution plan, loading tests were conducted on full-size cellular bulkheads corresponding to the basic plan as well as the execution plan. As a result, the tested values agreed very well with the analytical results and upon comparison between them, the displacement at the tip of the cellular bulkhead and other measured values showed no meaningful difference, thereby it was confirmed that the execution plan had the same level of stability as the basic plan. 5 refs., 26 figs., 5 tabs.

  12. Mehanizmi vstopa nanodelcev v celice in njihov vpliv na dostavljanje učinkovin: Mechanisms of cellular uptake of nanoparticles and their effect on drug delivery:

    OpenAIRE

    Erdani-Kreft, Mateja; Kocbek, Petra; Kristl, Julijana; Teskač, Karmen

    2012-01-01

    In the field of diagnosis and treatment in contemporary medicine, nanoparticles (NPs) are an important novelty. They are drug delivery systems on the nanometer scale, whose uptake mechanisms and routes of internalization differ, depending on their properties. For successful treatment, it is crucially important to understand the interplay between uptake mechanisms and NP properties. In this article mechanisms of NP uptake and the subsequent intracellular events are presented. NPs can enter cel...

  13. Behaviour of rocks and mechanical model of leads on the powered supports in a fully mechanized sub-level caving face

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Y. [China Coal Research Institute (China). Beijing Research Institute of Coal Mining

    1997-06-01

    Based on the study of distribution of abutment pressure and movement of overlying rocks and main roof, the decisive effect of the weakened degree of the immediate roof (penetration of shear cracks) and width of the completely failed zone of the top coal in ground pressure manifestation period are studied. Based on which, a mechanical model for calculation of the loads on the powered supports in a sub-level caving face is established. Formulae and examples are given for calculation of loads on the supports by considering the width of the completely plastic zone in top coal in the conditions of different weakness of the immediate roof in case of a long rock beam weighting and semi-arch instability of narrow rock beam. The fracture degree of the immediate roof and the width of the failed zone in top coal are the main criteria for the control of face and in the optimal design of sub-level caving face. 2 refs., 7 figs., 2 tabs.

  14. Transcriptional adaptations following exercise in Thoroughbred horse skeletal muscle highlights molecular mechanisms that lead to muscle hypertrophy

    Directory of Open Access Journals (Sweden)

    Park Stephen DE

    2009-12-01

    . These findings suggest that protein synthesis, mechanosensation and muscle remodeling contribute to skeletal muscle adaptation towards improved integrity and hypertrophy. Conclusions This is the first study to characterize global mRNA expression profiles in equine skeletal muscle using an equine-specific microarray platform. Here we reveal novel genes and mechanisms that are temporally expressed following exercise providing new knowledge about the early and late molecular responses to exercise in the equine skeletal muscle transcriptome.

  15. Inhibition of Macrophage CD36 Expression and Cellular Oxidized Low Density Lipoprotein (oxLDL) Accumulation by Tamoxifen: A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR)γ-DEPENDENT MECHANISM.

    Science.gov (United States)

    Yu, Miao; Jiang, Meixiu; Chen, Yuanli; Zhang, Shuang; Zhang, Wenwen; Yang, Xiaoxiao; Li, Xiaoju; Li, Yan; Duan, Shengzhong; Han, Jihong; Duan, Yajun

    2016-08-12

    Macrophage CD36 binds and internalizes oxidized low density lipoprotein (oxLDL) to facilitate foam cell formation. CD36 expression is activated by peroxisome proliferator-activated receptor γ (PPARγ). Tamoxifen, an anti-breast cancer medicine, has demonstrated pleiotropic functions including cardioprotection with unfully elucidated mechanisms. In this study, we determined that treatment of ApoE-deficient mice with tamoxifen reduced atherosclerosis, which was associated with decreased CD36 and PPARγ expression in lesion areas. At the cellular level, we observed that tamoxifen inhibited CD36 protein expression in human THP-1 monocytes, THP-1/PMA macrophages, and human blood monocyte-derived macrophages. Associated with decreased CD36 protein expression, tamoxifen reduced cellular oxLDL accumulation in a CD36-dependent manner. At the transcriptional level, tamoxifen decreased CD36 mRNA expression, promoter activity, and the binding of the PPARγ response element in CD36 promoter to PPARγ protein. Tamoxifen blocked ligand-induced PPARγ nuclear translocation and CD36 expression, but it increased PPARγ phosphorylation, which was due to that tamoxifen-activated ERK1/2. Furthermore, deficiency of PPARγ expression in macrophages abolished the inhibitory effect of tamoxifen on CD36 expression or cellular oxLDL accumulation both in vitro and in vivo Taken together, our study demonstrates that tamoxifen inhibits CD36 expression and cellular oxLDL accumulation by inactivating the PPARγ signaling pathway, and the inhibition of macrophage CD36 expression can be attributed to the anti-atherogenic properties of tamoxifen. PMID:27358406

  16. Predicting Cellular Growth from Gene Expression Signatures

    OpenAIRE

    Dunham, Maitreya J.; Troyanskaya, Olga G.; Airoldi, Edoardo; Broach, James R.; Caudy, Amy A.; Gresham, David; Botstein, David; Huttenhower, Curtis; Lu, Charles

    2009-01-01

    Maintaining balanced growth in a changing environment is a fundamental systems-level challenge for cellular physiology, particularly in microorganisms. While the complete set of regulatory and functional pathways supporting growth and cellular proliferation are not yet known, portions of them are well understood. In particular, cellular proliferation is governed by mechanisms that are highly conserved from unicellular to multicellular organisms, and the disruption of these processes in metazo...

  17. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  18. A mechanism leading to q-power law distribution due to the inhomogeneity of phase space in the self-gravitational system

    International Nuclear Information System (INIS)

    One mechanism leading to the q-power law distribution has been proposed in the self-gravitational system. The friction force in the stochastic process may be nonlinearly relevant to the momentum of particle, whose friction coefficient can be expressed as the function of the kinetic energy of the particle. The correlation strength of noises is inhomogeneous in the such system, maybe due to the strength of gravitational field. This implies that the gradient of correlation strength is the function of gravitational force. With the Taylor's low order approximation, the stationary solution of the two-vector variable Fokker–Planck equation is the power law form in self-gravitational system. This Letter also verifies that the neutrino flux deviation from the theory value in the solar core is due to the same mechanism.

  19. Multiple Pathways Involved in Porcine Parvovirus Cellular Entry and Trafficking toward the Nucleus▿

    OpenAIRE

    Boisvert, Maude; Fernandes, Sandra; Tijssen, Peter

    2010-01-01

    Porcine parvovirus (PPV) is a major cause of reproductive failure in swine. The mechanisms implicated in the first steps of infection that lead to the delivery of the PPV genome to the nucleus are poorly understood. In the present work, a panel of chemical inhibitors was used to dissect the cellular mechanisms involved in establishing a PPV infection. The results demonstrated that following binding to sialic acids on cell surface glycoproteins, the virus used both clathrin-mediated endocytosi...

  20. Integrated cellular systems

    Science.gov (United States)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  1. Determining Lineage Pathways from Cellular Barcoding Experiments

    Directory of Open Access Journals (Sweden)

    Leïla Perié

    2014-02-01

    Full Text Available Cellular barcoding and other single-cell lineage-tracing strategies form experimental methodologies for analysis of in vivo cell fate that have been instrumental in several significant recent discoveries. Due to the highly nonlinear nature of proliferation and differentiation, interrogation of the resulting data for evaluation of potential lineage pathways requires a new quantitative framework complete with appropriate statistical tests. Here, we develop such a framework, illustrating its utility by analyzing data from barcoded multipotent cells of the blood system. This application demonstrates that the data require additional paths beyond those found in the classical model, which leads us to propose that hematopoietic differentiation follows a loss of potential mechanism and to suggest further experiments to test this deduction. Our quantitative framework can evaluate the compatibility of lineage trees with barcoded data from any proliferating and differentiating cell system.

  2. Mechanical Enterogenesis - A Review

    Directory of Open Access Journals (Sweden)

    Rebecca Stark

    2012-01-01

    Full Text Available Mechanical enterogenesis is a novel method of lengthening pre-existing intestine with distractive force. The application of mechanical force on small intestine aims to induce cellular proliferation and ultimately increase bowel length. This has been investigated primarily for the treatment of short bowel syndrome (SBS. Research has been ongoing for well over a decade in this arena and a multitude of advances have been made, both in the understanding of the biology behind force induced cellular proliferation and in the basic mechanics of force delivery systems. Important experimental models have been developed for studying this phenomenon and the collaboration of engineers and medical researchers has lead to the design of several devices that successfully lengthen small intestine. This has catapulted the field forward and there may soon be a device suitable for medical use in humans. This review analyses the past, present and future of mechanical enterogenesis.

  3. Mechanical properties at high strain-rate of lead core and brass jacket of a NATO 7.62 mm ball bullet

    Directory of Open Access Journals (Sweden)

    Manes A.

    2012-08-01

    Full Text Available Numerical simulations are now an actual option in order to try to reproduce and understand the mechanical response in components subjected to extreme loading conditions, like in a ballistic impact. A correct materials calibration is therefore necessary in order to extract the materials parameters. In this work the simple and widely used Johnson-Cook model was used to analyse the experimental data obtained for the characterization of the bullet materials. The bullet under investigation is a full metal jacket ball, with a lead-antimony alloy core and a brass jacket. The experimental tests cover a wide range in strain-rate, starting from quasi-static tests up to high dynamic tests performed on a standard Split Hopkinson Pressure Bar setup. In general, there is a great lack in strain-rate sensitivity and failure data. Pure lead is very soft and ductile, so antimony is used to give greater hardness and strength. The results of this study show a significant strain-rate influence for this alloy that can be associated with the presence of the lead-antimony phases and their structures. Also in case of the brass the results showed significant strain-rate sensitivity in the material response.

  4. Mechanical properties at high strain-rate of lead core and brass jacket of a NATO 7.62 mm ball bullet

    Science.gov (United States)

    Peroni, L.; Scapin, M.; Fichera, C.; Manes, A.; Giglio, M.

    2012-08-01

    Numerical simulations are now an actual option in order to try to reproduce and understand the mechanical response in components subjected to extreme loading conditions, like in a ballistic impact. A correct materials calibration is therefore necessary in order to extract the materials parameters. In this work the simple and widely used Johnson-Cook model was used to analyse the experimental data obtained for the characterization of the bullet materials. The bullet under investigation is a full metal jacket ball, with a lead-antimony alloy core and a brass jacket. The experimental tests cover a wide range in strain-rate, starting from quasi-static tests up to high dynamic tests performed on a standard Split Hopkinson Pressure Bar setup. In general, there is a great lack in strain-rate sensitivity and failure data. Pure lead is very soft and ductile, so antimony is used to give greater hardness and strength. The results of this study show a significant strain-rate influence for this alloy that can be associated with the presence of the lead-antimony phases and their structures. Also in case of the brass the results showed significant strain-rate sensitivity in the material response.

  5. Aging, cellular senescence, and cancer.

    Science.gov (United States)

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  6. Elucidation on protection mechanism of a living body from cellular obstacle due to radiation and its functional obstacle in a highly carcinogenic family

    International Nuclear Information System (INIS)

    By using a cell strain immortalized with EBV (EB-LCL), peripheral blood lymphocyte of a patient with homo-variation of ATM gene and a carrier with heterogeneous variation, cell cycle adjustment mechanism and apoptosis induction mechanism were investigated to compare them with normal human cell strain. As a distinct conclusion on relationship between ATM heterogeneous variant and generation of malignant tumor was not obtained yet, this analysis result suggests that variety in character of ATM heterogeneous variant cell can be found, and further investigation on relationship between ATM gene variation and radiation and carcinogenic sensitivity is required. (G.K.)

  7. A Mechanism to Enhance Cellular Responsivity to Hormone Action: Krüppel-Like Factor 9 Promotes Thyroid Hormone Receptor-β Autoinduction During Postembryonic Brain Development.

    Science.gov (United States)

    Hu, Fang; Knoedler, Joseph R; Denver, Robert J

    2016-04-01

    Thyroid hormone (TH) receptor (TR)-β (trb) is induced by TH (autoinduced) in Xenopus tadpoles during metamorphosis. We previously showed that Krüppel-like factor 9 (Klf9) is rapidly induced by TH in the tadpole brain, associates in chromatin with the trb upstream region in a developmental stage and TH-dependent manner, and forced expression of Klf9 in the Xenopus laevis cell line XTC-2 accelerates and enhances trb autoinduction. Here we investigated whether Klf9 can promote trb autoinduction in tadpole brain in vivo. Using electroporation-mediated gene transfer, we transfected plasmids into premetamorphic tadpole brain to express wild-type or mutant forms of Klf9. Forced expression of Klf9 increased baseline trb mRNA levels in thyroid-intact but not in goitrogen-treated tadpoles, supporting that Klf9 enhances liganded TR action. As in XTC-2 cells, forced expression of Klf9 enhanced trb autoinduction in tadpole brain in vivo and also increased TH-dependent induction of the TR target genes klf9 and thbzip. Consistent with our previous mutagenesis experiments conducted in XTC-2 cells, the actions of Klf9 in vivo required an intact N-terminal region but not a functional DNA binding domain. Forced expression of TRβ in tadpole brain by electroporation-mediated gene transfer increased baseline and TH-induced TR target gene transcription, supporting a role for trb autoinduction during metamorphosis. Our findings support that Klf9 acts as an accessory transcription factor for TR at the trb locus during tadpole metamorphosis, enhancing trb autoinduction and transcription of other TR target genes, which increases cellular responsivity to further TH action on developmental gene regulation programs. PMID:26886257

  8. Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

    Directory of Open Access Journals (Sweden)

    K.K. Sakane

    2014-01-01

    Full Text Available Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2 enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

  9. Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

    International Nuclear Information System (INIS)

    Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival

  10. Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Sakane, K.K. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Monteiro, C.J.; Silva, W.; Silva, A.R. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Santos, P.M. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Lima, K.F. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Moraes, K.C.M. [Instituto de Biociências, Departamento de Biologia, Universidade Estadual Paulista ‘‘Júlio de Mesquita Filho’’, Rio Claro, SP (Brazil)

    2013-11-29

    Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

  11. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  12. Review of cytological studies on cellular and molecular mechanisms of uniparental (maternal or paternal) inheritance of plastid and mitochondrial genomes induced by active digestion of organelle nuclei (nucleoids).

    Science.gov (United States)

    Kuroiwa, Tsuneyoshi

    2010-03-01

    In most sexual organisms, including isogamous, anisogamous and oogamous organisms, uniparental transmission is a striking and universal characteristic of the transmission of organelle (plastid and mitochondrial) genomes (DNA). Using genetic, biochemical and molecular biological techniques, mechanisms of uniparental (maternal and parental) and biparental transmission of organelle genomes have been studied and reviewed. Although to date there has been no cytological review of the transmission of organelle genomes, cytology offers advantages in terms of direct evidence and can enhance global studies of the transmission of organelle genomes. In this review, I focus on the cytological mechanism of uniparental inheritance by "active digestion of male or female organelle nuclei (nucleoids, DNA)" which is universal among isogamous, anisogamous, and oogamous organisms. The global existence of uniparental transmission since the evolution of sexual eukaryotes may imply that the cell nuclear genome continues to inhibit quantitative evolution of organelles by organelle recombination. PMID:20145972

  13. Influence of the injection-molding parameters on the cellular structure and thermo-mechanical properties of ethylene-propylene block copolymer foams

    OpenAIRE

    Gómez Gómez, Jaime Francisco; Arencón Osuna, David; Sánchez Soto, Miguel; Martínez Benasat, Antonio

    2013-01-01

    Microcellular injection-molding technology is capable of producing lightweight polymeric products. The foam morphology is determined by the injection-molding parameters, and it has been observed that depending on the parameter variations, the cell structure may exhibit substantial morphological differences through the entire section along the melt flow direction of the injected part. The effects of varying injection-molding parameters on foam morphology and thermal mechanical p...

  14. Experimental study of Americium-241 biokinetics in Homarus Gammarus lobster. Analysis of the accumulation and detoxication mechanisms at the sub-cellular level

    International Nuclear Information System (INIS)

    The Americium 241 radioelement accumulation and elimination rate and mechanisms in the lobster organism have been experimentally studied; incorporation and detoxification capacities of each organ are evaluated. The existence of various biological compartments is shown; the major role of the digestive gland in accumulation of the radioelement, its distribution towards the various organs, and its resorption is comprehensively described, with an analysis at the subcellular and molecular levels. 401 p., 65 fig., 43 tab., 428 ref

  15. Pulsed feedback defers cellular differentiation.

    Directory of Open Access Journals (Sweden)

    Joe H Levine

    2012-01-01

    Full Text Available Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle.

  16. Fracture mechanics behavior of the T91 martensitic steel in contact with liquid lead-bismuth eutectic for application in an accelerator driven system

    Energy Technology Data Exchange (ETDEWEB)

    Auger, T., E-mail: thierry.auger@ecp.fr [CNRS-MSSMAT, Ecole Centrale Paris, Grande Voie des Vignes, 92290 Chatenay-Malabry Cedex (France); Gorse, D. [CNRS-LSI, Ecole Polytechnique, Route de Saclay, 91128 Palaiseau Cedex (France); Hamouche-Hadjem, Z. [CNAM, 2 rue Conte, 75003 Paris (France); Van den Bosch, J.; Coen, G.; Almazouzi, A. [SCK-CEN (Belgian Nuclear Research Centre), Boeretang 200, 2400 Mol (Belgium); Hojna, A.; Dalikova, K.; Di Gabriele, F. [Ustav Jaderneho Vyzkumu Rez a.s., Rez 130, Husinec 25068 (Czech Republic); Serrano, M. [CIEMAT, Avda. Complutense, 22, 28040 Madrid (Spain); Gessi, A.; Agostini, P. [ENEA, CR Brasimone 40032 Camugnano, Bologna (Italy); Vogt, J.-B.; Serre, I. [CNRS-LMPGM, 59655 Villeneuved' Ascq Cedex (France)

    2011-08-31

    The fracture toughness of the T91 martensitic steel in liquid lead-bismuth eutectic has been measured at 300 deg. C in plane stress and plane strain conditions. The effect of achieving wetting at the crack tip prior starting mechanical testing is demonstrated to be the key factor for a correct evaluation of the potential effect of LBE on fracture toughness. In plane stress, one observes a serrated fracture mode associated with a reduction of fracture toughness between 20% and 30%. The toughness reduction is higher in plane strain where the cleavage fracture mode prevails. The difference between the two fracture modes is due to the higher plastic deformation level reached at final fracture in plane stress and to the higher crack growth rate in plane strain. These results will be useful for the design of future nuclear systems cooled by LBE planning to use martensitic steels as structural materials.

  17. Nanoindentation measurements and mechanical testing of as-soldered and aged Sn-0.7Cu lead-free miniature joints

    International Nuclear Information System (INIS)

    Nanoindentation testing has been used to analyze local mechanical parameter changes across interfaces formed between the solder and the Cu substrate and also in the eutectic solder, in miniature lead-free soldered joints. Effects of plastic deformation and aging were investigated. The lead-free solder alloy used in this study is commercially available and has nominal composition by weight of 99.3% Sn and 0.7% Cu. During aging, the joints were exposed to 150 deg. C for 1000 h in an inert atmosphere. Tensile testing of as-soldered miniature joints shows strong positive dependence of the plastic flow stresses on strain rate, meaning that the stresses increase with strain rate. Similar behavior was observed for aged miniature soldered joints with ∼10% decrease in the level of maximum stresses, compared to as-soldered joints. Indentation hardness and modulus were measured in soldered joint components, in the as-soldered, aged conditions, and tensile tested with strain rates in the range of 1.8 x 10-3-1.8 x 10-1 s-1. Scanning electron and optical microscopy were employed to analyze the fracture paths and microstructure of the as-soldered and aged miniature joints, as well as the location and shape of the indentations. The measured indentation hardness and modulus agreed well with previous studies on similar alloys. The tested modulus of the intermetallic phase in the eutectic area exhibited a considerable reduction as compared to the intermetallic phase at the interface between the solder and the Cu substrate. Strain rate strongly influences local mechanics: for both as-soldered and deformed miniature joints; close to the fracture face in the eutectic solder, the indentation modulus values were 53% higher and hardness more than 100% higher in joints exposed to the highest strain rate relative to the smallest rate.

  18. Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1

    Directory of Open Access Journals (Sweden)

    Koji Aoyama

    2015-05-01

    Full Text Available Reactive oxygen species (ROS are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system’s roles in maintaining redox homeostasis. Especially, glutathione (GSH is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1 plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed.

  19. Report of National Cancer Institute symposium: comparison of mechanisms of carcinogenesis by radiation and chemical agents. II. Cellular and animal models

    International Nuclear Information System (INIS)

    This segment of the report of the proceedings of the National Cancer Institute symposium is devoted to the presentations about studies with in vitro cell systems, in vitro-in vivo systems, and whole animals including humans. The NCI symposium was designed to cover many aspects of carcinogenesis so that the similarities and differences of the manner in which ionizing radiation and chemical carcinogens initiate cancer and complete its expression could be examined. The hope was that the identification of both the common and the clearly distinct features would help elucidate mechanisms and indicate areas for new research

  20. Microstructural evolution of a lead-free solder alloy Sn-Bi-Ag-Cu prepared by mechanical alloying during thermal shock and aging

    Science.gov (United States)

    Huang, M. L.; Wu, C. M. L.; Lai, J. K. L.; Chan, Y. C.

    2000-08-01

    In a previous study, a lead-free solder, Sn-6Bi-2Ag-0.5Cu, was developed by mechanical alloying. The alloy shows great potential as a lead-free solder system. In the present work, the microstructural evolution during thermal shock and aging was examined. In the as-soldered joints small bismuth (1 µm to 2 µm) and Ag3Sn (1 µm) particles were finely dispersed in a nearly pure tin matrix with a small amount of η-Cu6Sn5 phase in the bulk of solder. During thermal shock and aging microstructural evolution occurred with Cu-Sn intermetallic compound (IMC) layer growth at interface, bismuth phase coarsening and Ag3Sn phase coarsening. The microstructure of the solder appeared to be stable at high temperature. The shear strength of the present solder joint is higher than that of Sn-37Pb and Sn-3.5Ag solders. Shear failure occurred Cu-Sn IMC layer-solder interface and in the bulk of solder.