Sample records for responses locomotion cell

  1. Analysis of fuel cell hybrid locomotives

    Miller, Arnold R. [Vehicle Projects LLC, 621, 17th Street, Suite 2131, Denver, CO 80293 (United States); Peters, John; Smith, Brian E. [Transportation Technology Center Inc., 55500 DOT Road, Pueblo, CO 81007 (United States); Velev, Omourtag A. [AeroVironment Inc., 232 West Maple Avenue, Monrovia, CA 91016 (United States)


    Led by Vehicle Projects LLC, an international industry-government consortium is developing a 109t, 1.2MW road-switcher locomotive for commercial and military railway applications. As part of the feasibility and conceptual-design analysis, a study has been made of the potential benefits of a hybrid power plant in which fuel cells comprise the prime mover and a battery or flywheel provides auxiliary power. The potential benefits of a hybrid power plant are: (i) enhancement of transient power and hence tractive effort; (ii) regenerative braking; (iii) reduction of capital cost. Generally, the tractive effort of a locomotive at low speed is limited by wheel adhesion and not by available power. Enhanced transient power is therefore unlikely to benefit a switcher locomotive, but could assist applications that require high acceleration, e.g. subway trains with all axles powered. In most cases, the value of regeneration in locomotives is minimal. For low-speed applications such as switchers, the available kinetic energy and the effectiveness of traction motors as generators are both minimal. For high-speed heavy applications such as freight, the ability of the auxiliary power device to absorb a significant portion of the available kinetic energy is low. Moreover, the hybrid power plant suffers a double efficiency penalty, namely, losses occur in both absorbing and then releasing energy from the auxiliary device, which result in a net storage efficiency of no more than 50% for present battery technology. Capital cost in some applications may be reduced. Based on an observed locomotive duty cycle, a cost model shows that a hybrid power plant for a switcher may indeed reduce capital cost. Offsetting this potential benefit are the increased complexity, weight and volume of the power plant, as well as 20-40% increased fuel consumption that results from lower efficiency. Based on this analysis, the consortium has decided to develop a pure fuel cell road-switcher locomotive, that

  2. Locomotion

    Kiehn, Ole; Dougherty, Kimberly


    Locomotion is a complex motor behavior needed by animals and humans to move through the environment. All forms of locomotion, including swimming, flying, walking, running, and hopping, are repetitive motor activities that require the activation of the limb and body muscles in an organized rhythm ...

  3. System design of a large fuel cell hybrid locomotive

    Miller, A. R.; Hess, K. S.; Barnes, D. L.; Erickson, T. L.

    Fuel cell power for locomotives combines the environmental benefits of a catenary-electric locomotive with the higher overall energy efficiency and lower infrastructure costs of a diesel-electric. A North American consortium, a public-private partnership, is developing a prototype hydrogen-fueled fuel cell-battery hybrid switcher locomotive for urban and military-base rail applications. Switcher locomotives are used in rail yards for assembling and disassembling trains and moving trains from one point to another. At 127 tonnes (280,000 lb), continuous power of 250 kW from its (proton exchange membrane) PEM fuel cell prime mover, and transient power well in excess of 1 MW, the hybrid locomotive will be the heaviest and most powerful fuel cell land vehicle yet. This fast-paced project calls for completion of the vehicle itself near the end of 2007. Several technical challenges not found in the development of smaller vehicles arise when designing and developing such a large fuel cell vehicle. Weight, center of gravity, packaging, and safety were design factors leading to, among other features, the roof location of the lightweight 350 bar compressed hydrogen storage system. Harsh operating conditions, especially shock loads during coupling to railcars, require component mounting systems capable of absorbing high energy. Vehicle scale-up by increasing mass, density, or power presents new challenges primarily related to issues of system layout, hydrogen storage, heat transfer, and shock loads.

  4. Contact enhancement of locomotion in spreading cell colonies

    D'Alessandro, Joseph; Solon, Alexandre P.; Hayakawa, Yoshinori; Anjard, Christophe; Detcheverry, François; Rieu, Jean-Paul; Rivière, Charlotte


    The dispersal of cells from an initially constrained location is a crucial aspect of many physiological phenomena, ranging from morphogenesis to tumour spreading. In such processes, cell-cell interactions may deeply alter the motion of single cells, and in turn the collective dynamics. While contact phenomena like contact inhibition of locomotion are known to come into play at high densities, here we focus on the little explored case of non-cohesive cells at moderate densities. We fully characterize the spreading of micropatterned colonies of Dictyostelium discoideum cells from the complete set of individual trajectories. From data analysis and simulation of an elementary model, we demonstrate that contact interactions act to speed up the early population spreading by promoting individual cells to a state of higher persistence, which constitutes an as-yet unreported contact enhancement of locomotion. Our findings also suggest that the current modelling paradigm of memoryless active particles may need to be extended to account for the history-dependent internal state of motile cells.

  5. Segregation of Visual Response Properties in the Mouse Superior Colliculus and Their Modulation during Locomotion


    The superior colliculus (SC) receives direct input from the retina and integrates it with information about sound, touch, and state of the animal that is relayed from other parts of the brain to initiate specific behavioral outcomes. The superficial SC layers (sSC) contain cells that respond to visual stimuli, whereas the deep SC layers (dSC) contain cells that also respond to auditory and somatosensory stimuli. Here, we used a large-scale silicon probe recording system to examine the visual response properties of SC cells of head-fixed and alert male mice. We found cells with diverse response properties including: (1) orientation/direction-selective (OS/DS) cells with a firing rate that is suppressed by drifting sinusoidal gratings (negative OS/DS cells); (2) suppressed-by-contrast cells; (3) cells with complex-like spatial summation nonlinearity; and (4) cells with Y-like spatial summation nonlinearity. We also found specific response properties that are enriched in different depths of the SC. The sSC is enriched with cells with small RFs, high evoked firing rates (FRs), and sustained temporal responses, whereas the dSC is enriched with the negative OS/DS cells and with cells with large RFs, low evoked FRs, and transient temporal responses. Locomotion modulates the activity of the SC cells both additively and multiplicatively and changes the preferred spatial frequency of some SC cells. These results provide the first description of the negative OS/DS cells and demonstrate that the SC segregates cells with different response properties and that the behavioral state of a mouse affects SC activity. SIGNIFICANCE STATEMENT The superior colliculus (SC) receives visual input from the retina in its superficial layers (sSC) and induces eye/head-orientating movements and innate defensive responses in its deeper layers (dSC). Despite their importance, very little is known about the visual response properties of dSC neurons. Using high-density electrode recordings and novel

  6. Role of contact inhibition of locomotion and junctional mechanics in epithelial collective responses to injury

    Coburn, Luke; Lopez, Hender; Schouwenaar, Irin-Maya; Yap, Alpha S.; Lobaskin, Vladimir; Gomez, Guillermo A.


    Epithelial tissues form physically integrated barriers against the external environment protecting organs from infection and invasion. Within each tissue, epithelial cells respond to different challenges that can potentially compromise tissue integrity. In particular, cells collectively respond to injuries by reorganizing their cell-cell junctions and migrating directionally towards the sites of damage. Notwithstanding, the mechanisms that drive collective responses in epithelial aggregates remain poorly understood. In this work, we develop a minimal mechanistic model that is able to capture the essential features of epithelial collective responses to injuries. We show that a model that integrates the mechanics of cells at the cell-cell and cell-substrate interfaces as well as contact inhibition of locomotion (CIL) correctly predicts two key properties of epithelial response to injury as: (1) local relaxation of the tissue and (2) collective reorganization involving the extension of cryptic lamellipodia that extend, on average, up to 3 cell diameters from the site of injury and morphometric changes in the basal regions. Our model also suggests that active responses (like the actomyosin purse string and softening of cell-cell junctions) are needed to drive morphometric changes in the apical region. Therefore, our results highlight the importance of the crosstalk between junctional biomechanics, cell substrate adhesion, and CIL, as well as active responses, in guiding the collective rearrangements that are required to preserve the epithelial barrier in response to injury.

  7. Simulating spinal border cells and cerebellar granule cells under locomotion--a case study of spinocerebellar information processing.

    Anton Spanne

    Full Text Available The spinocerebellar systems are essential for the brain in the performance of coordinated movements, but our knowledge about the spinocerebellar interactions is very limited. Recently, several crucial pieces of information have been acquired for the spinal border cell (SBC component of the ventral spinocerebellar tract (VSCT, as well as the effects of SBC mossy fiber activation in granule cells of the cerebellar cortex. SBCs receive monosynaptic input from the reticulospinal tract (RST, which is an important driving system under locomotion, and disynaptic inhibition from Ib muscle afferents. The patterns of activity of RST neurons and Ib afferents under locomotion are known. The activity of VSCT neurons under fictive locomotion, i.e. without sensory feedback, is also known, but there is little information on how these neurons behave under actual locomotion and for cerebellar granule cells receiving SBC input this is completely unknown. But the available information makes it possible to simulate the interactions between the spinal and cerebellar neuronal circuitries with a relatively large set of biological constraints. Using a model of the various neuronal elements and the network they compose, we simulated the modulation of the SBCs and their target granule cells under locomotion and hence generated testable predictions of their general pattern of modulation under this condition. This particular system offers a unique opportunity to simulate these interactions with a limited number of assumptions, which helps making the model biologically plausible. Similar principles of information processing may be expected to apply to all spinocerebellar systems.

  8. Locomotion response of airborne, ambulatory and aquatic insects to thermal stimulation using piezoceramic microheaters

    Visvanathan, Karthik; Gianchandani, Yogesh B.


    This paper reports the locomotion response of airborne, ambulatory and aquatic insects to thermal stimulation. A finite element model has been developed to predict the variation of insect-stimulator interface temperature with input power. Piezothermal stimulators have been fabricated from lead zirconate titanate (PZT) using a batch mode micro ultrasonic machining process. Typical sizes range from 200 µm to 3.2 mm. For PZT stimulators, the temperature and thermal efficiency reach the maximum value around the resonance frequency which is typically in the range of 650 kHz to 47 MHz. Experiments have been conducted on green June beetles (GJBs), Madagascar hissing roaches and green diving beetles (GDBs) in order to show the versatility of the proposed technique. The stimulators have been implanted near the antennae of the GJBs and on either side of the thorax of the Madagascar hissing roaches and GDBs, respectively. In all cases, the insects move away from the direction of the actuated stimulator. The left and right turns are statistically similar. Thermal stimulation achieves an overall success rate of 78.7%, 92.8% and 61.6% in GJBs, roaches and GDBs, respectively. On average, thermal stimulation results in an angle turn of about 13.7°-16.2° on GJBs, 30°-45° on the roaches and 30°-50° on GDBs. The corresponding average input power is 360, 330 and 100 mW for GJBs, roach and GDBs, respectively. Scaling limits of the PZT stimulators for operating these stimulators are also discussed.

  9. Physiologic Responses to Motorized and Non-Motorized Locomotion Utilizing the International Space Station Treadmill

    Smith, Cassie; Lee, Stuart MC; Laughlin, Mitzi; Loehr, James; Norcross, Jason; DeWitt, John; Hagan, R. D.


    Treadmill locomotion is used onboard the International Space Station (ISS) as a countermeasure to the effects of prolonged weightlessness. The treadmill operates in two modes: motorized (T-M) and non-motorized (T-NM). Little is known about the potential physiologic differences between modes which may affect countermeasure exercise prescription. PURPOSE: To quantify heart rate (HR), oxygen consumption (VO2), perceived exertion (RPE), and blood lactate (BLa) during T-M and T-NM locomotion at 2 and 4 mph in normal ambulatory subjects. METHODS: Twenty subjects (10 men, 10 women; 31+/-5 yr, 172+/-10 cm, 68+/-13 kg, mean SD) with a treadmill peakVO2 of 45.5+/-5.4 ml/kg/min (mean+/-SD) exercised on the ground-based ISS treadmill. Following a familiarization session in each mode, subjects completed two data collection sessions, T-M and T-NM in random order, at 2 and 4 mph. Subjects attempted to complete 5 min of exercise at each speed; if they could not maintain the speed, the trial was discontinued. At least 5 minutes of rest separated each speed trial, and at least 48 hrs separated each session. VO2 was measured continuously (metabolic gas analysis), while HR (HR monitor) and RPE (Borg Chart, 6-20 scale) were recorded each min. Not all subjects completed 5 min during each condition, therefore the mean of the min 3 and 4 was taken as representative of steady-state. BLa was measured (finger stick) within 2 min post-exercise. Paired t-tests were used to test for differences (p<0.05) between treadmill modes within the same speed. RESULTS: All twenty subjects completed at least 4 min of exercise during all conditions, except T-NM 4 mph when only 11 subjects completed the minimum exercise duration. VO2, HR, RPE and BLa were significantly higher during T-NM locomotion at both speeds.

  10. L1cam is crucial for cell locomotion and terminal translocation of the Soma in radial migration during murine corticogenesis.

    Madoka Tonosaki

    Full Text Available L1cam (L1 is a cell adhesion molecule associated with a spectrum of human neurological diseases, the most well-known being X-linked hydrocephalus. Although we recently demonstrated that L1 plays an important role in neuronal migration during cortical histogenesis, the mechanisms of delayed migration have still not been clarified. In this study, we found that cell locomotion in the intermediate zone and terminal translocation in the primitive cortical zone (PCZ were affected by L1-knockdown (L1-KD. Time-lapse analyses revealed that L1-KD neurons produced by in utero electroporation of shRNA targeting L1 (L1-shRNAs molecules showed decreased locomotion velocity in the intermediate zone, compared with control neurons. Furthermore, L1-KD neurons showed longer and more undulated leading processes during translocation through the primitive cortical zone. The curvature index, a quantitative index for curvilinearity, as well as the length of the leading process, were increased, whereas the somal movement was decreased in L1-KD neurons during terminal translocation in the PCZ. These results suggest that L1 has a role in radial migration of cortical neurons.

  11. Dynamically Stable Legged Locomotion


    length during overground locomotion: task-specific modulation of the locomotor synergy. Journal of Experimental Psychology, 15(3). Raibert, M. I. conversions that intermediates between combus- tion of a fluid fuel such as gasoline , and the controlled delivery of force and power to the...question of this study: Can the extremely high energy density and rapid response of combustible fluid fuels such as gasoline be harnessed to produce

  12. Mutant human torsinA, responsible for early-onset dystonia, dominantly suppresses GTPCH expression, dopamine levels and locomotion in Drosophila melanogaster

    Noriko Wakabayashi-Ito


    Full Text Available Dystonia represents the third most common movement disorder in humans with over 20 genetic loci identified. TOR1A (DYT1, the gene responsible for the most common primary hereditary dystonia, encodes torsinA, an AAA ATPase family protein. Most cases of DYT1 dystonia are caused by a 3 bp (ΔGAG deletion that results in the loss of a glutamic acid residue (ΔE302/303 in the carboxyl terminal region of torsinA. This torsinAΔE mutant protein has been speculated to act in a dominant-negative manner to decrease activity of wild type torsinA. Drosophila melanogaster has a single torsin-related gene, dtorsin. Null mutants of dtorsin exhibited locomotion defects in third instar larvae. Levels of dopamine and GTP cyclohydrolase (GTPCH proteins were severely reduced in dtorsin-null brains. Further, the locomotion defect was rescued by the expression of human torsinA or feeding with dopamine. Here, we demonstrate that human torsinAΔE dominantly inhibited locomotion in larvae and adults when expressed in neurons using a pan-neuronal promoter Elav. Dopamine and tetrahydrobiopterin (BH4 levels were significantly reduced in larval brains and the expression level of GTPCH protein was severely impaired in adult and larval brains. When human torsinA and torsinAΔE were co-expressed in neurons in dtorsin-null larvae and adults, the locomotion rates and the expression levels of GTPCH protein were severely reduced. These results support the hypothesis that torsinAΔE inhibits wild type torsinA activity. Similarly, neuronal expression of a Drosophila DtorsinΔE equivalent mutation dominantly inhibited larval locomotion and GTPCH protein expression. These results indicate that both torsinAΔE and DtorsinΔE act in a dominant-negative manner. We also demonstrate that Dtorsin regulates GTPCH expression at the post-transcriptional level. This Drosophila model of DYT1 dystonia provides an important tool for studying the differences in the molecular function between the

  13. 40 CFR 201.27 - Procedures for: (1) Determining applicability of the locomotive load cell test stand standard and...


    ... localizing its apparent source(s). If the observer is clearly convinced by this localization process that the... is observed to change by 10 dB, coincident with evidence of a change in operation of the locomotive... microphone position on a diagram of the particular railroad facility, and the distances between the...

  14. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

    Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald


    Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

  15. Cell response to surgery.

    Ni Choileain, Niamh


    OBJECTIVES: To describe the profound alterations in host immunity that are produced by major surgery as demonstrated by experimental and clinical studies, and to evaluate the benefits of therapeutic strategies aimed at attenuating perioperative immune dysfunction. DATA SOURCES: A review of the English-language literature was conducted, incorporating searches of the MEDLINE, EMBASE, and Cochrane collaboration databases to identify laboratory and clinical studies investigating the cellular response to surgery. STUDY SELECTION: Original articles and case reports describing immune dysfunction secondary to surgical trauma were included. DATA EXTRACTION: The results were compiled to show outcomes of different studies and were compared. DATA SYNTHESIS: Current evidence indicates that the early systemic inflammatory response syndrome observed after major surgery that is characterized by proinflammatory cytokine release, microcirculatory disturbance, and cell-mediated immune dysfunction is followed by a compensatory anti-inflammatory response syndrome, which predisposes the patient to opportunistic infection, multiple organ dysfunction syndrome, and death. Because there are currently no effective treatment options for multiple organ dysfunction syndrome, measures to prevent its onset should be initiated at an early stage. Accumulating experimental evidence suggests that targeted therapeutic strategies involving immunomodulatory agents such as interferon gamma, granulocyte colony-stimulating factor, the prostaglandin E(2) antagonist, indomethacin, and pentoxifylline may be used for the treatment of systemic inflammatory response syndrome to prevent the onset of multiple organ dysfunction syndrome. CONCLUSIONS: Surgical trauma produces profound immunological dysfunction. Therapeutic strategies directed at restoring immune homeostasis should aim to redress the physiological proinflammatory-anti-inflammatory cell imbalance associated with major surgery.

  16. Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia.

    Calcagno, B; Eyles, D; van Alphen, B; van Swinderen, B


    It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.

  17. Locomotion through Morphosis

    Larsen, Jørgen Christian

    , this is still not the case. One of the reasons for this is that science does still not fully understand the principles of dynamic locomotion which is a requirement for them to move around in our environment with stairs, obstacles etc. In this thesis the focus will be on the creation of the modular robotic...... it have been build. This will hopefully help to identify which parameters that are affecting the locomotive abilities of a legged robot the most. Experiments shows that the system in its current state is able for form legged robots of various kinds, and perform walking gaits where phenomenon’s also seen...

  18. Changes in ventilation and locomotion of Gammarus pulex (Crustacea, Amphipoda) in response to low concentrations of pharmaceuticals

    Lange, de H.J.; Peeters, E.T.H.M.; Lürling, M.F.L.L.W.


    Exposure to contaminants below lethal concentrations may affect the performance of organisms, resulting in measurable differences in behavior. We measured the response of the benthic invertebrate Gammarus pulex (Crustacea, Amphipoda) to sublethal concentrations of three pharmaceuticals, fluoxetine,

  19. Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity

    Sundaresan, Alamelu; Risin, Diana; Pellis, Neal R.; McIntire, L. V. (Principal Investigator)


    Inflammatory adherence to, and locomotion through the interstitium is an important component of the immune response. Conditions such as microgravity and modeled microgravity (MMG) severely inhibit lymphocyte locomotion in vitro through gelled type I collagen. We used the NASA rotating wall vessel bioreactor or slow-turning lateral vessel as a prototype for MMG in ground-based experiments. Previous experiments from our laboratory revealed that when lymphocytes (human peripheral blood mononuclear cells [PBMCs]) were first activated with phytohemaglutinin followed by exposure to MMG, locomotory capacity was not affected. In the present study, MMG inhibits lymphocyte locomotion in a manner similar to that observed in microgravity. Phorbol myristate acetate (PMA) treatment of PBMCs restored lost locomotory capacity by a maximum of 87%. Augmentation of cellular calcium flux with ionomycin had no restorative effect. Treatment of lymphocytes with mitomycin C prior to exposure to MMG, followed by PMA, restored locomotion to the same extent as when nonmitomycin C-treated lymphocytes were exposed to MMG (80-87%), suggesting that deoxyribonucleic acid replication is not essential for the restoration of locomotion. Thus, direct activation of protein kinase C (PKC) with PMA was effective in restoring locomotion in MMG comparable to the normal levels seen in Ig cultures. Therefore, in MMG, lymphocyte calcium signaling pathways were functional, with defects occurring at either the level of PKC or upstream of PKC.

  20. NKT Cell Responses to B Cell Lymphoma.

    Li, Junxin; Sun, Wenji; Subrahmanyam, Priyanka B; Page, Carly; Younger, Kenisha M; Tiper, Irina V; Frieman, Matthew; Kimball, Amy S; Webb, Tonya J


    Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma.

  1. Developmental lead exposure induces opposite effects on ethanol intake and locomotion in response to central vs. systemic cyanamide administration.

    Mattalloni, Mara Soledad; Deza-Ponzio, Romina; Albrecht, Paula Alejandra; Cancela, Liliana Marina; Virgolini, Miriam Beatriz


    Lead (Pb) is a developmental neurotoxicant that elicits differential responses to drugs of abuse. Particularly, ethanol consumption has been demonstrated to be increased as a consequence of environmental Pb exposure, with catalase (CAT) and brain acetaldehyde (ACD, the first metabolite of ethanol) playing a role. The present study sought to interfere with ethanol metabolism by inhibiting ALDH2 (mitochondrial aldehyde dehydrogenase) activity in both liver and brain from control and Pb-exposed rats as a strategy to accumulate ACD, a substance that plays a major role in the drug's reinforcing and/or aversive effects. To evaluate the impact on a 2-h chronic voluntary ethanol intake test, developmentally Pb-exposed and control rats were administered with cyanamide (CY, an ALDH inhibitor) either systemically or intracerebroventricularly (i.c.v.) on the last 4 sessions of the experiment. Furthermore, on the last session and after locomotor activity was assessed, all animals were sacrificed to obtain brain and liver samples for ALDH2 and CAT activity determination. Systemic CY administration reduced the elevated ethanol intake already reported in the Pb-exposed animals (but not in the controls) accompanied by liver (but not brain) ALDH2 inactivation. On the other hand, a 0.3 mg i.c.v. CY administration enhanced both ethanol intake and locomotor activity accompanied by brain ALDH2 inactivation in control animals, while an increase in ethanol consumption was also observed in the Pb-exposed group, although in the absence of brain ALDH2 blockade. No changes were observed in CAT activity as a consequence of CY administration. These results support the participation of liver and brain ACD in ethanol intake and locomotor activity, responses that are modulated by developmental Pb exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Development of human locomotion.

    Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka


    Neural control of locomotion in human adults involves the generation of a small set of basic patterned commands directed to the leg muscles. The commands are generated sequentially in time during each step by neural networks located in the spinal cord, called Central Pattern Generators. This review outlines recent advances in understanding how motor commands are expressed at different stages of human development. Similar commands are found in several other vertebrates, indicating that locomotion development follows common principles of organization of the control networks. Movements show a high degree of flexibility at all stages of development, which is instrumental for learning and exploration of variable interactions with the environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Advanced robot locomotion.

    Neely, Jason C.; Sturgis, Beverly Rainwater; Byrne, Raymond Harry; Feddema, John Todd; Spletzer, Barry Louis; Rose, Scott E.; Novick, David Keith; Wilson, David Gerald; Buerger, Stephen P.


    This report contains the results of a research effort on advanced robot locomotion. The majority of this work focuses on walking robots. Walking robot applications include delivery of special payloads to unique locations that require human locomotion to exo-skeleton human assistance applications. A walking robot could step over obstacles and move through narrow openings that a wheeled or tracked vehicle could not overcome. It could pick up and manipulate objects in ways that a standard robot gripper could not. Most importantly, a walking robot would be able to rapidly perform these tasks through an intuitive user interface that mimics natural human motion. The largest obstacle arises in emulating stability and balance control naturally present in humans but needed for bipedal locomotion in a robot. A tracked robot is bulky and limited, but a wide wheel base assures passive stability. Human bipedal motion is so common that it is taken for granted, but bipedal motion requires active balance and stability control for which the analysis is non-trivial. This report contains an extensive literature study on the state-of-the-art of legged robotics, and it additionally provides the analysis, simulation, and hardware verification of two variants of a proto-type leg design.

  4. Pharmacological blockade of either cannabinoid CB1 or CB2 receptors prevents both cocaine-induced conditioned locomotion and cocaine-induced reduction of cell proliferation in the hippocampus of adult male rat

    Blanco-Calvo, Eduardo; Rivera, Patricia; Arrabal, Sergio; Vargas, Antonio; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Galeano, Pablo; Rubio, Leticia; Suárez, Juan; Rodriguez de Fonseca, Fernando


    Addiction to major drugs of abuse, such as cocaine, has recently been linked to alterations in adult neurogenesis in the hippocampus. The endogenous cannabinoid system modulates this proliferative response as demonstrated by the finding that pharmacological activation/blockade of cannabinoid CB1 and CB2 receptors not only modulates neurogenesis but also modulates cell death in the brain. In the present study, we evaluated whether the endogenous cannabinoid system affects cocaine-induced alterations in cell proliferation. To this end, we examined whether pharmacological blockade of either CB1 (Rimonabant, 3 mg/kg) or CB2 receptors (AM630, 3 mg/kg) would affect cell proliferation [the cells were labeled with 5-bromo-2′-deoxyuridine (BrdU)] in the subventricular zone (SVZ) of the lateral ventricle and the dentate subgranular zone (SGZ). Additionally, we measured cell apoptosis (as monitored by the expression of cleaved caspase-3) and glial activation [by analyzing the expression of glial fibrillary acidic protein (GFAP) and Iba-1] in the striatum and hippocampus during acute and repeated (4 days) cocaine administration (20 mg/kg). The results showed that acute cocaine exposure decreased the number of BrdU-immunoreactive (ir) cells in the SVZ and SGZ. In contrast, repeated cocaine exposure reduced the number of BrdU-ir cells only in the SVZ. Both acute and repeated cocaine exposure increased the number of cleaved caspase-3-, GFAP- and Iba1-ir cells in the hippocampus, and this effect was counteracted by AM630 or Rimonabant, which increased the number of BrdU-, GFAP-, and Iba1-ir cells in the hippocampus. These results indicate that the changes in neurogenic, apoptotic and gliotic processes that were produced by repeated cocaine administration were normalized by pharmacological blockade of CB1 and CB2. The restorative effects of cannabinoid receptor blockade on hippocampal cell proliferation were associated with the prevention of the induction of conditioned

  5. Locomotive energy savings possibilities

    Leonas Povilas LINGAITIS


    Full Text Available Economic indicators of electrodynamic braking have not been properly estimated. Vehicles with alternative power trains are transitional stage between development of pollution- free vehicles. According to these aspects the investigation on conventional hybrids drives and their control system is carried out in the article. The equation that allows evaluating effectiveness of regenerative braking for different variants of hybrid drive are given. Presenting different types of locomotive energy savings power systems, which are using regenerative braking energy any form of hybrid traction vehicles systems, circuit diagrams, electrical parameters curves.

  6. Steam Locomotives: a forgotten era

    The boiler was not armoured as the idea was that it was bullet proof. The locomotives were arranged into groups of five and for each group there was an engine as standby. As far as can be ascertained, locomotive No 537 was never armoured, but did work draw trains and freight trains during the Anglo-Boer War too.

  7. Neurobiology of Caenorhabditis elegans Locomotion: Where Do We Stand?

    Gjorgjieva, Julijana; Biron, David; Haspel, Gal


    Animals use a nervous system for locomotion in some stage of their life cycle. The nematode Caenorhabditis elegans, a major animal model for almost all fields of experimental biology, has long been used for detailed studies of genetic and physiological locomotion mechanisms. Of its 959 somatic cells, 302 are neurons that are identifiable by lineage, location, morphology, and neurochemistry in every adult hermaphrodite. Of those, 75 motoneurons innervate body wall muscles that provide the thru...

  8. Distribution of spinal neuronal networks controlling forward and backward locomotion.

    Merkulyeva, Natalia; Veshchitskii, Aleksandr; Gorsky, Oleg; Pavlova, Natalia; Zelenin, Pavel V; Gerasimenko, Yury; Deliagina, Tatiana G; Musienko, Pavel


    Higher vertebrates, including humans, are capable not only of forward (FW) locomotion but also of walking in other directions relative to the body axis [backward (BW), sideways, etc.]. While the neural mechanisms responsible for controlling FW locomotion have been studied in considerable detail, the mechanisms controlling steps in other directions are mostly unknown. The aim of the present study was to investigate the distribution of spinal neuronal networks controlling FW and BW locomotion. First, we applied electrical epidural stimulation (ES) to different segments of the spinal cord from L2 to S2 to reveal zones triggering FW and BW locomotion in decerebrate cats of either sex. Second, to determine the location of spinal neurons activated during FW and BW locomotion, we used c-fos immunostaining. We found that the neuronal networks responsible for FW locomotion were distributed broadly in the lumbosacral spinal cord and could be activated by ES of any segment from L3 to S2. By contrast, networks generating BW locomotion were activated by ES of a limited zone from the caudal part of L5 to the caudal part of L7. In the intermediate part of the gray matter within this zone, a significantly higher number of c- fos -positive interneurons was revealed in BW-stepping cats compared with FW-stepping cats. We suggest that this region of the spinal cord contains the network that determines the BW direction of locomotion. Significance Statement Sequential and single steps in various directions relative to the body axis [forward (FW), backward (BW), sideways, etc.] are used during locomotion and to correct for perturbations, respectively. The mechanisms controlling step direction are unknown. In the present study, for the first time we compared the distributions of spinal neuronal networks controlling FW and BW locomotion. Using a marker to visualize active neurons, we demonstrated that in the intermediate part of the gray matter within L6 and L7 spinal segments

  9. Synthesis of digital locomotive receiver of automatic locomotive signaling

    K. V. Goncharov


    Full Text Available Purpose. Automatic locomotive signaling of continuous type with a numeric coding (ALSN has several disadvantages: a small number of signal indications, low noise stability, high inertia and low functional flexibility. Search for new and more advanced methods of signal processing for automatic locomotive signaling, synthesis of the noise proof digital locomotive receiver are essential. Methodology. The proposed algorithm of detection and identification locomotive signaling codes is based on the definition of mutual correlations of received oscillation and reference signals. For selecting threshold levels of decision element the following criterion has been formulated: the locomotive receiver should maximum set the correct solution for a given probability of dangerous errors. Findings. It has been found that the random nature of the ALSN signal amplitude does not affect the detection algorithm. However, the distribution law and numeric characteristics of signal amplitude affect the probability of errors, and should be considered when selecting a threshold levels According to obtained algorithm of detection and identification ALSN signals the digital locomotive receiver has been synthesized. It contains band pass filter, peak limiter, normalizing amplifier with automatic gain control circuit, analog to digital converter and digital signal processor. Originality. The ALSN system is improved by the way of the transfer of technical means to modern microelectronic element base, more perfect methods of detection and identification codes of locomotive signaling are applied. Practical value. Use of digital technology in the construction of the locomotive receiver ALSN will expand its functionality, will increase the noise immunity and operation stability of the locomotive signal system in conditions of various destabilizing factors.

  10. Artificial locomotion control

    Azevedo, Christine; Poignet, Philippe; Espiau, Bernard


    of postural and walking control; use of evolutive optimization objectives; on-line event handling and environment adaptation and anticipation. This leads to the synthesis of an original control scheme based on non-linear model predictive control: Trajectory Free NMPC. The movement is specified implicitly......This paper concerns the simultaneous synthesis and control of walking gaits for biped robots. The goal is to propose an adaptable and reactive control law for two-legged machines. The problem is addressed with human locomotion as a reference. The starting point of our work is an analysis of human...... walking from descriptive (biomechanics) as well as explicative (neuroscience and physiology) points of view, the objective being to stress the relevant elements for the approach of robot control. The adopted principles are then: no joint trajectory tracking; explicit distinction and integration...

  11. Using entropy measures to characterize human locomotion.

    Leverick, Graham; Szturm, Tony; Wu, Christine Q


    Entropy measures have been widely used to quantify the complexity of theoretical and experimental dynamical systems. In this paper, the value of using entropy measures to characterize human locomotion is demonstrated based on their construct validity, predictive validity in a simple model of human walking and convergent validity in an experimental study. Results show that four of the five considered entropy measures increase meaningfully with the increased probability of falling in a simple passive bipedal walker model. The same four entropy measures also experienced statistically significant increases in response to increasing age and gait impairment caused by cognitive interference in an experimental study. Of the considered entropy measures, the proposed quantized dynamical entropy (QDE) and quantization-based approximation of sample entropy (QASE) offered the best combination of sensitivity to changes in gait dynamics and computational efficiency. Based on these results, entropy appears to be a viable candidate for assessing the stability of human locomotion.

  12. Animal Locomotion in Different Mediums

    IAS Admin

    examine only self-powered animal locomotion. ... At different phases of their life cycle both animals and plants are highly mobile but their ... wind driven transport (Figure C). ..... fins which serve the function of rudimentary limbs, particularly.

  13. Locomotion of bluefish.

    DuBois, A B; Cavagna, G A; Fox, R S


    1. Pressure previously measured on the body surface of swimming bluefish were resolved into their backward vectorial components to allow calculation of profile drag. It was 0.18 kg at a speed of 1.8 m/sec. Tangential drag was calculated as if for a thin plate of an area equal to that of the fish. It was 0.08 kg at 1.8 m/sec. Net drag, 0.26 kg, was the sum of profile and tangential drag. 2. Thrust and drag also were calculated from the changes of acceleration measured during steady swimming, assuming that thrust took place only during the acceleration phase, whereas drag occurred during both acceleration and deceleration. This drag was 0.08 kg at a speed of 1.1 m/sec. It is compatible with the drag of 0.26 at 1.8 m/sec calculated from profile and tangential drag provided drag varies as the square of velocity. 3. The force required to produced maximal acceleration was measured during a scare. It was calculated to be 6.9 kg at a peak acceleration of 3 g. 4. The compression strength of th vertebrae was found to be approximately 20 kg per cm2, or roughly three times the force encountered during maximal acceleration. This safety factor of 3 would be reduced when the back was curved, or if opposing groups of muscles were under tension. 5. The finding that a bluefish can accelerate at 3 g and that the vertebral column is strongg enough to withstand this force indicates that the muscles and body structure of a bluefish would be able to withstand the force of gravity if the fish were otherwise equipped for terrestrial life. This fish may have evolved these strengths simultaneously with land animals. It is speculated that other fish may have evolved some degree of strength to overcome inertia and drag during aquatic locomotion, and this evolution may have been a prelude to terrestrial locomotion.

  14. Fundamentals of soft robot locomotion

    Calisti, M.; Picardi, G.; Laschi, C.


    Soft robotics and its related technologies enable robot abilities in several robotics domains including, but not exclusively related to, manipulation, manufacturing, human���robot interaction and locomotion. Although field applications have emerged for soft manipulation and human���robot interaction, mobile soft robots appear to remain in the research stage, involving the somehow conflictual goals of having a deformable body and exerting forces on the environment to achieve locomotion. This p...

  15. Frequency response of electrochemical cells

    Thomas, Daniel L.


    The main objective was to examine the feasibility of using frequency response techniques (1) as a tool in destructive physical analysis of batteries, particularly for estimating electrode structural parameters such as specific area, porosity, and tortuosity and (2) as a non-destructive testing technique for obtaining information such as state of charge and acceptability for space flight. The phenomena that contribute to the frequency response of an electrode include: (1) double layer capacitance; (2) Faradaic reaction resistance; (3) mass transfer of Warburg impedance; and (4) ohmic solution resistance. Nickel cadmium cells were investigated in solutions of KOH. A significant amount of data was acquired. Quantitative data analysis, using the developed software, is planned for the future.

  16. Advanced underground Vehicle Power and Control: The locomotive Research Platform

    Vehicle Projects LLC


    to the project) a new motor controller capable of operating the higher rpm motor and different power characteristics of the fuelcells. In early August 2002, CANMET, with the technical assistance of Nuvera Fuel Cells and Battery Electric, installed the new PLC software, installed the new motor controller, and installed the new fuelcell stacks. After minor adjustments, the fuelcell locomotive pulled its first fully loaded ore cars on a surface track. The fuelcell-powered locomotive easily matched the battery powered equivalent in its ability to pull tonnage and equaled the battery-powered locomotive in acceleration. The final task of Phase 2, testing the locomotive underground in a production environment, occurred in early October 2002 in a gold mine. All regulatory requirements to allow the locomotive underground were completed and signed off by Hatch Associates prior to going underground. During the production tests, the locomotive performed flawlessly with no failures or downtime. The actual tests occurred during a 2-week period and involved moving both gold ore and waste rock over a 1,000 meter track. Refueling, or recharging, of the metal-hydride storage took place on the surface. After each shift, the metal-hydride storage module was removed from the locomotive, transported to surface, and filled with hydrogen from high-pressure tanks. The beginning of each shift started with taking the fully recharged metal-hydride storage module down into the mine and re-installing it onto the locomotive. Each 8 hour shift consumed approximately one half to two thirds of the onboard hydrogen. This indicates that the fuelcell-powered locomotive can work longer than a similar battery-powered locomotive, which operates about 6 hours, before needing a recharge.

  17. Coupling of cytoskeleton functions for fibroblast locomotion

    Couchman, J R; Lenn, M; Rees, D A


    caused visible protrusions in projected positions at the leading edge. We conclude that fibroblast locomotion may be driven coordinately by a common set of motility mechanisms and that this coordination may be lost as a result of physical or pharmacological disturbance. Taking our evidence with results...... from other Laboratories, we propose the following cytoskeleton functions. (i) Protrusive activity, probably based on solation--gelation cycles of the actin based cytoskeleton and membrane recycling which provides cellular and membrane components for streaming through the cell body to the leading edge...

  18. Fundamentals of soft robot locomotion.

    Calisti, M; Picardi, G; Laschi, C


    Soft robotics and its related technologies enable robot abilities in several robotics domains including, but not exclusively related to, manipulation, manufacturing, human-robot interaction and locomotion. Although field applications have emerged for soft manipulation and human-robot interaction, mobile soft robots appear to remain in the research stage, involving the somehow conflictual goals of having a deformable body and exerting forces on the environment to achieve locomotion. This paper aims to provide a reference guide for researchers approaching mobile soft robotics, to describe the underlying principles of soft robot locomotion with its pros and cons, and to envisage applications and further developments for mobile soft robotics. © 2017 The Author(s).

  19. The mechanics of slithering locomotion.

    Hu, David L; Nirody, Jasmine; Scott, Terri; Shelley, Michael J


    In this experimental and theoretical study, we investigate the slithering of snakes on flat surfaces. Previous studies of slithering have rested on the assumption that snakes slither by pushing laterally against rocks and branches. In this study, we develop a theoretical model for slithering locomotion by observing snake motion kinematics and experimentally measuring the friction coefficients of snakeskin. Our predictions of body speed show good agreement with observations, demonstrating that snake propulsion on flat ground, and possibly in general, relies critically on the frictional anisotropy of their scales. We have also highlighted the importance of weight distribution in lateral undulation, previously difficult to visualize and hence assumed uniform. The ability to redistribute weight, clearly of importance when appendages are airborne in limbed locomotion, has a much broader generality, as shown by its role in improving limbless locomotion.

  20. Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion.

    Lee, A Moses; Hoy, Jennifer L; Bonci, Antonello; Wilbrecht, Linda; Stryker, Michael P; Niell, Cristopher M


    Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Relation between observed locomotion traits and locomotion score in dairy cows

    Schlageter Tello, A.A.; Bokkers, E.A.M.; Groot Koerkamp, P.W.G.; Hertem, van T.; Viazzi, S.; Lokhorst, Kees


    Lameness is still an important problem in modern dairy farming. Human observation of locomotion, by looking at different traits in one go, is used in practice to assess locomotion. The objectives of this article were to determine which individual locomotion traits are most related to locomotion

  2. Human regulatory B cells control the TFH cell response.

    Achour, Achouak; Simon, Quentin; Mohr, Audrey; Séité, Jean-François; Youinou, Pierre; Bendaoud, Boutahar; Ghedira, Ibtissem; Pers, Jacques-Olivier; Jamin, Christophe


    Follicular helper T (T FH ) cells support terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses, but their control of T FH cell-dependent humoral immune responses is unknown. We sought to assess the role of Breg cells on T FH cell development and function. Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate T FH cells. They were cocultured with B cells to induce their terminal differentiation. Breg cells were included in these cultures, and their effects were evaluated by using flow cytometry and ELISA. B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed cell death protein 1 (PD-1) expressions increased on stimulated human T cells, characterizing T FH cell maturation. In cocultures they differentiated B cells into CD138 + plasma and IgD - CD27 + memory cells and triggered immunoglobulin secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B cells prevented T FH cell development. Added to T FH cell and B-cell cocultures, they inhibited B-cell differentiation, impeded immunoglobulin secretions, and expanded Foxp3 + CXCR5 + PD-1 + follicular regulatory T cells. Breg cells modulated IL-21 receptor expressions on T FH cells and B cells, and their suppressive activities involved CD40, CD80, CD86, and intercellular adhesion molecule interactions and required production of IL-10 and TGF-β. Human Breg cells control T FH cell maturation, expand follicular regulatory T cells, and inhibit the T FH cell-mediated antibody secretion. These novel observations demonstrate a role for the Breg cell in germinal center reactions and suggest that deficient activities might impair the T FH cell-dependent control of humoral immunity and might lead to the development of aberrant autoimmune responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. In Pipe Robot with Hybrid Locomotion System

    Cristian Miclauş


    Full Text Available The first part of the paper covers aspects concerning in pipe robots and their components, such as hybrid locomotion systems and the adapting mechanisms used. The second part describes the inspection robot that was developed, which combines tracked and wheeled locomotion (hybrid locomotion. The end of the paper presents the advantages and disadvantages of the proposed robot.

  4. Locomotive monitoring system using wireless sensor networks

    Croucamp, PL


    Full Text Available Theft of cables used for powering a locomotive not only stops the train from functioning but also paralyzes the signalling and monitoring system. This means that information on certain locomotive's cannot be passed onto other locomotives which may...

  5. A Specific Population of Reticulospinal Neurons Controls the Termination of Locomotion.

    Juvin, Laurent; Grätsch, Swantje; Trillaud-Doppia, Emilie; Gariépy, Jean-François; Büschges, Ansgar; Dubuc, Réjean


    Locomotion requires the proper sequencing of neural activity to start, maintain, and stop it. Recently, brainstem neurons were shown to specifically stop locomotion in mammals. However, the cellular properties of these neurons and their activity during locomotion are still unknown. Here, we took advantage of the lamprey model to characterize the activity of a cell population that we now show to be involved in stopping locomotion. We find that these neurons display a burst of spikes that coincides with the end of swimming activity. Their pharmacological activation ends ongoing swimming, whereas the inactivation of these neurons dramatically impairs the rapid termination of swimming. These neurons are henceforth referred to as stop cells, because they play a crucial role in the termination of locomotion. Our findings contribute to the fundamental understanding of motor control and provide important details about the cellular mechanisms involved in locomotor termination. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Two-fluid model for locomotion under self-confinement

    Reigh, Shang Yik; Lauga, Eric


    The bacterium Helicobacter pylori causes ulcers in the stomach of humans by invading mucus layers protecting epithelial cells. It does so by chemically changing the rheological properties of the mucus from a high-viscosity gel to a low-viscosity solution in which it may self-propel. We develop a two-fluid model for this process of swimming under self-generated confinement. We solve exactly for the flow and the locomotion speed of a spherical swimmer located in a spherically symmetric system of two Newtonian fluids whose boundary moves with the swimmer. We also treat separately the special case of an immobile outer fluid. In all cases, we characterize the flow fields, their spatial decay, and the impact of both the viscosity ratio and the degree of confinement on the locomotion speed of the model swimmer. The spatial decay of the flow retains the same power-law decay as for locomotion in a single fluid but with a decreased magnitude. Independent of the assumption chosen to characterize the impact of confinement on the actuation applied by the swimmer, its locomotion speed always decreases with an increase in the degree of confinement. Our modeling results suggest that a low-viscosity region of at least six times the effective swimmer size is required to lead to swimming with speeds similar to locomotion in an infinite fluid, corresponding to a region of size above ≈25 μ m for Helicobacter pylori.

  7. Regulation of T cell responses in atherosclerosis

    Puijvelde, Gijsbrecht Henricus Maria van


    One of the most important characteristics of atherosclerosis is the chronic inflammatory response in which T cells and NKT cells are very important. In this thesis several methods to modulate the activity of these T and NKT cells in atherosclerosis are described. The induction of regulatory T cells

  8. Locomotion of Mexican jumping beans

    West, Daniel M; K Lal, Ishan; Leamy, Michael J; Hu, David L


    The Mexican jumping bean, Laspeyresia saltitans, consists of a hollow seed housing a moth larva. Heating by the sun induces movements by the larva which appear as rolls, jumps and flips by the bean. In this combined experimental, numerical and robotic study, we investigate this unique means of rolling locomotion. Time-lapse videography is used to record bean trajectories across a series of terrain types, including one-dimensional channels and planar surfaces of varying inclination. We find that the shell encumbers the larva's locomotion, decreasing its speed on flat surfaces by threefold. We also observe that the two-dimensional search algorithm of the bean resembles the run-and-tumble search of bacteria. We test this search algorithm using both an agent-based simulation and a wheeled Scribbler robot. The algorithm succeeds in propelling the robot away from regions of high temperature and may have application in biomimetic micro-scale navigation systems. (paper)

  9. Emotion through Locomotion: Gender Impact

    Kr?ger, Samuel; Sokolov, Alexander N.; Enck, Paul; Kr?geloh-Mann, Ingeborg; Pavlova, Marina A.


    Body language reading is of significance for daily life social cognition and successful social interaction, and constitutes a core component of social competence. Yet it is unclear whether our ability for body language reading is gender specific. In the present work, female and male observers had to visually recognize emotions through point-light human locomotion performed by female and male actors with different emotional expressions. For subtle emotional expressions only, males surpass fema...

  10. Emotion through locomotion: gender impact.

    Samuel Krüger

    Full Text Available Body language reading is of significance for daily life social cognition and successful social interaction, and constitutes a core component of social competence. Yet it is unclear whether our ability for body language reading is gender specific. In the present work, female and male observers had to visually recognize emotions through point-light human locomotion performed by female and male actors with different emotional expressions. For subtle emotional expressions only, males surpass females in recognition accuracy and readiness to respond to happy walking portrayed by female actors, whereas females exhibit a tendency to be better in recognition of hostile angry locomotion expressed by male actors. In contrast to widespread beliefs about female superiority in social cognition, the findings suggest that gender effects in recognition of emotions from human locomotion are modulated by emotional content of actions and opposite actor gender. In a nutshell, the study makes a further step in elucidation of gender impact on body language reading and on neurodevelopmental and psychiatric deficits in visual social cognition.

  11. The role of nucleotides in augmentation of lymphocyte locomotion: Adaptional countermeasure development in microgravity analog environments

    Sundaresan, Alamelu; Kulkarni, Anil D.; Yamauchi, Keiko; Pellis, Neal R.


    Space travel and long-term space residence such as envisaged in the exploration era implicates burdens on the immune system. An optimal immune response is required to countered and with-stand exposure to pathogens. Countermeasure development is an important avenue in space research especially for long-term space exploration. Microgravity exposure causes detrimental effects in lymphocyte functions which may impair immune response. Impaired lymphocyte function can be remedied by bypassing cell membrane events. This is done by using compounds such as Phorbol Myristate Acetate (PMA). Since activation in mouse splenocytes was augmented using nucleotides, it was essential to observe their effects on human lymphocyte locomotion. A nucleotide/nucleoside (NT/NT) mixture from Otsuka Pharmaceuticals (Naruto, Japan) was used at recommended doses. In lymphocytes cultured in modeled microgravity, the NT/NT mixture used orchestrated locomotion recovery by more than 87%, similar to the response documented with PMA in lymphocytes. Both 12µM and 120µM doses worked similarly. These are preliminary results leading to the possible use of the NT/NT mixture to mitigate immune suppression in micro-gravity. More studies in this direction are required to delineate the role of NT/NT on the immune response in microgravity.

  12. The noise factor in railway locomotives.

    Rotter, T


    This article concerns the problem of acoustic work conditions on railway locomotives. The objective results of sonometric surveys in locomotive cabins are compared with subject data received from locomotive crews obtained by means of a specific questionnaire 'The Subjective Estimation of Noise'. The analysis touched 9 type of locomotives; steam, diesel and electric engines. We asked drivers of different age groups and with varying lengths of professional service for their opinions The aim of the investigation was to determine the following points: 1. to analyse the drivers' subjective estimation of the noise in the locomotive cabins; 2. to define length of time for which the driver remains under the influence of the noise after finishing work; 3. to investigate the question of perception and understanding of sounds and vocal signals used in the locomotive. These problems are a small part of the general plan to improve work conditions on the Polish National Railways.

  13. Responses of Cells to Flow in Vitro

    Shigehiro Hashimoto


    Full Text Available The response of cells to a flow has been studied in vitro. The response of cells was examined in two types of flow channels: a circumnutating flow in a donut-shaped open channel in a culture dish, and a one-way flow in a parallelepiped rhombus flow channel. Variation was made on the material of the parallelepiped channel to study on adhesion of cells to the plates: glass and polydimethylsiloxane. Behavior of cells on the plate was observed under a flow of a medium with an inverted phase-contrast-microscope. The shear stress on the plate is calculated with an estimated parabolic distribution of the velocity between the parallel plates. The adhesion of cells was evaluated with the cumulated shear, which is a product of the shear stress and the exposure time. The experimental results show that cells are responsive to the flow, which governs orientation, exfoliation, and differentiation. The response depends on the kinds of cells: endothelial cells orient along the stream line, although myocytes orient perpendicular to the stream line. The adhesion depends on the combination between scaffold and cell: myocytes are more adhesive to glass than cartilage cells, and fibroblasts are more adhesive to oxygenated polydimethylsiloxane than glass.

  14. Railroad and locomotive technology roadmap.

    Stodolsky, F.; Gaines, L.; Energy Systems


    Railroads are important to the U.S. economy. They transport freight efficiently, requiring less energy and emitting fewer pollutants than other modes of surface transportation. While the railroad industry has steadily improved its fuel efficiency--by 16% over the last decade--more can, and needs to, be done. The ability of locomotive manufacturers to conduct research into fuel efficiency and emissions reduction is limited by the small number of locomotives manufactured annually. Each year for the last five years, the two North American locomotive manufacturers--General Electric Transportation Systems and the Electro-Motive Division of General Motors--have together sold about 800 locomotives in the United States. With such a small number of units over which research costs can be spread, outside help is needed to investigate all possible ways to reduce fuel usage and emissions. Because fuel costs represent a significant portion of the total operating costs of a railroad, fuel efficiency has always been an important factor in the design of locomotives and in the operations of a railroad. However, fuel efficiency has recently become even more critical with the introduction of strict emission standards by the U.S. Environmental Protection Agency, to be implemented in stages (Tiers 0, 1, and 2) between 2000 and 2005. Some of the technologies that could be employed to meet the emission standards may negatively affect fuel economy--by as much as 10-15% when emissions are reduced to Tier 1 levels. Lowering fuel economy by that magnitude would have a serious impact on the cost to the consumer of goods shipped by rail, on the competitiveness of the railroad industry, and on this country's dependence on foreign oil. Clearly, a joint government/industry R&D program is needed to help catalyze the development of advanced technologies that will substantially reduce locomotive engine emissions while also improving train system energy efficiency. DOE convened an industry

  15. Slipping slender bodies and enhanced flagellar locomotion

    Man, Yi; Lauga, Eric


    In the biological world, many cells exploit slender appendages to swim, include numerous species of bacteria, algae and spermatozoa. A classical method to describe the flow field around such appendages is slender-body theory (SBT), which is often used to study flagellar motility in Newtonian fluids. However, biology environments are often rheologically complex due to the presence of polymers. These polymers generically phase-separate near rigid boundaries where low-viscosity fluid layers lead to effective slip on the surface. In this talk, we present an analytical derivation of SBT in the case where the no-slip boundary condition on the appendage is replaced by a Navier slip boundary condition. Our results demonstrate in particular a systematic reduction of the resistance coefficient of the slender filaments in their tangential direction, which leads to enhanced flagellar locomotion.

  16. Small-scale soft-bodied robot with multimodal locomotion

    Hu, Wenqi; Lum, Guo Zhan; Mastrangeli, Massimo; Sitti, Metin


    Untethered small-scale (from several millimetres down to a few micrometres in all dimensions) robots that can non-invasively access confined, enclosed spaces may enable applications in microfactories such as the construction of tissue scaffolds by robotic assembly, in bioengineering such as single-cell manipulation and biosensing, and in healthcare such as targeted drug delivery and minimally invasive surgery. Existing small-scale robots, however, have very limited mobility because they are unable to negotiate obstacles and changes in texture or material in unstructured environments. Of these small-scale robots, soft robots have greater potential to realize high mobility via multimodal locomotion, because such machines have higher degrees of freedom than their rigid counterparts. Here we demonstrate magneto-elastic soft millimetre-scale robots that can swim inside and on the surface of liquids, climb liquid menisci, roll and walk on solid surfaces, jump over obstacles, and crawl within narrow tunnels. These robots can transit reversibly between different liquid and solid terrains, as well as switch between locomotive modes. They can additionally execute pick-and-place and cargo-release tasks. We also present theoretical models to explain how the robots move. Like the large-scale robots that can be used to study locomotion, these soft small-scale robots could be used to study soft-bodied locomotion produced by small organisms.

  17. Locomotion and basicranial anatomy in primates and marsupials.

    Villamil, Catalina I


    There is ongoing debate in paleoanthropology about whether and how the anatomy of the cranium, and especially the cranial base, is evolving in response to locomotor and postural changes. However, the majority of studies focus on two-dimensional data, which fails to capture the complexity of cranial anatomy. This study tests whether three-dimensional cranial base anatomy is linked to locomotion or to other factors in primates (n = 473) and marsupials (n = 231). Results indicate that although there is a small effect of locomotion on cranial base anatomy in primates, this is not the case in marsupials. Instead, facial anatomy likely drives variation in cranial base anatomy in both primates and marsupials, with additional roles for body size and brain size. Although some changes to foramen magnum position and orientation are phylogenetically useful among the hominoids, they do not necessarily reflect locomotion or positional behavior. The interplay between locomotion, posture, and facial anatomy in primates requires further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. T-cell response in human leishmaniasis

    Kharazmi, A; Kemp, K; Ismail, A


    In the present communication we provide evidence for the existence of a Th1/Th2 dichotomy in the T-cell response to Leishmania antigens in human leishmaniasis. Our data suggest that the pattern of IL-4 and IFN-gamma response is polarised in these patients. Lymphocytes from individuals recovered...... from cutaneous leishmaniasis (CL) responded by IFN-gamma production following stimulation with Leishmania antigens whereas cells from patients recovered from visceral leishmaniasis (VL) showed a mixed pattern of IFN-gamma and IL-4 responses. The cells producing these cytokines were predominantly CD4......+. Furthermore, IL-10 plays an important role in the development of post kala azar dermal leishmaniasis (PKDL) from VL. The balance between the parasitic-specific T-cell response plays an important regulatory role in determining the outcome of Leishmania infections in humans....

  19. Blunt impact tests of retired passenger locomotive fuel tanks


    The Transportation Technology Center, Inc. conducted impact tests on three locomotive fuel tanks as part of the Federal Railroad Administrations locomotive fuel tank crashworthiness improvement program. Three fuel tanks, two from EMD F40PH locomot...

  20. Collective cell migration during inflammatory response

    Wu, Di; Stroka, Kimberly; Aranda-Espinoza, Helim


    Wound scratch healing assays of endothelial cell monolayers is a simple model to study collective cell migration as a function of biological signals. A signal of particular interest is the immune response, which after initial wounding in vivo causes the release of various inflammatory factors such as tumor necrosis alpha (TNF-α). TNF-α is an innate inflammatory cytokine that can induce cell growth, cell necrosis, and change cell morphology. We studied the effects of TNF-α on collective cell migration using the wound healing assays and measured several migration metrics, such as rate of scratch closure, velocities of leading edge and bulk cells, closure index, and velocity correlation functions between migrating cells. We observed that TNF-α alters all migratory metrics as a function of the size of the scratch and TNF-α content. The changes observed in migration correlate with actin reorganization upon TNF-α exposure.

  1. Le Shuttle, the locomotive from Eurotunnel

    Gabriel MOISA


    This paper present some performances of locomotive ‘Le Shuttle’, so-called locomotive from ‘Eurotunnel’, techniques characteristics of traction motors 6 FHA 7079 and converters witch use it, the principal electric scheme and its function principle and no at last rind the principle scheme of command-control equipment MICAS-S2 with detailed description of its operation mode.

  2. Locomotive Crash Energy Management Coupling Tests


    This paper describes the results of the CEM equipped locomotive coupling tests. In this set of tests, a moving CEM locomotive was coupled to a standing cab car. The primary objective was to demonstrate the robustness of the PBC design and determine t...

  3. The investigation of the locomotive boiler material

    Tucholski, Z.; Wasiak, J.; Bilous, W.; Hajewska, E.


    In the paper, the history of narrow-gauge railway system is described. The other information about the steam locomotive construction, as well as the technical regulations of its construction and exploitation are also done. The results of the studies of the locomotive boiler material are presented. (authors)

  4. 77 FR 21311 - Locomotive Safety Standards


    ... preparedness, alcohol and drug testing, locomotive engineer certification, and workplace safety. In 1980, FRA... Association (ATDA) Amtrak AAR Association of Railway Museums (ARM) Association of State Rail Safety Managers... Administration 49 CFR Parts 229 and 238 Locomotive Safety Standards; Final Rule #0;#0;Federal Register / Vol. 77...

  5. 76 FR 2199 - Locomotive Safety Standards


    ..., alcohol and drug testing, locomotive engineer certification, and workplace safety. In 1980, FRA issued the...) Association of State Rail Safety Managers (ASRSM) Brotherhood of Locomotive Engineers and Trainmen (BLET... desirable to minimize the health and safety effects of temperature extremes. Depending upon the workplace...

  6. Experimental investigation into the mechanism of the polygonal wear of electric locomotive wheels

    Tao, Gongquan; Wang, Linfeng; Wen, Zefeng; Guan, Qinghua; Jin, Xuesong


    Experiments were conducted at field sites to investigate the mechanism of the polygonal wear of electric locomotive wheels. The polygonal wear rule of electric locomotive wheels was obtained. Moreover, two on-track tests have been carried out to investigate the vibration characteristics of the electric locomotive's key components. The measurement results of wheels out-of-round show that most electric locomotive wheels exhibit polygonal wear. The main centre wavelength in the 1/3 octave bands is 200 mm and/or 160 mm. The test results of vibration characteristics indicate that the dominating frequency of the vertical acceleration measured on the axle box is approximately equal to the passing frequency of a polygonal wheel, and does not vary with the locomotive speed during the acceleration course. The wheelset modal analysis using the finite element method (FEM) indicates that the first bending resonant frequency of the wheelset is quite close to the main vibration frequency of the axle box. The FEM results are verified by the experimental modal analysis of the wheelset. Moreover, different plans were designed to verify whether the braking system and the locomotive's adhesion control have significant influence on the wheel polygon or not. The test results indicate that they are not responsible for the initiation of the wheel polygon. The first bending resonance of the wheelset is easy to be excited in the locomotive operation and it is the root cause of wheel polygon with centre wavelength of 200 mm in the 1/3 octave bands.

  7. Metabolomic Responses of Guard Cells and Mesophyll Cells to Bicarbonate

    Misra, Biswapriya B.; de Armas, Evaldo; Tong, Zhaohui; Chen, Sixue


    Anthropogenic CO2 presently at 400 ppm is expected to reach 550 ppm in 2050, an increment expected to affect plant growth and productivity. Paired stomatal guard cells (GCs) are the gate-way for water, CO2, and pathogen, while mesophyll cells (MCs) represent the bulk cell-type of green leaves mainly for photosynthesis. We used the two different cell types, i.e., GCs and MCs from canola (Brassica napus) to profile metabolomic changes upon increased CO2 through supplementation with bicarbonate (HCO3 -). Two metabolomics platforms enabled quantification of 268 metabolites in a time-course study to reveal short-term responses. The HCO3 - responsive metabolomes of the cell types differed in their responsiveness. The MCs demonstrated increased amino acids, phenylpropanoids, redox metabolites, auxins and cytokinins, all of which were decreased in GCs in response to HCO3 -. In addition, the GCs showed differential increases of primary C-metabolites, N-metabolites (e.g., purines and amino acids), and defense-responsive pathways (e.g., alkaloids, phenolics, and flavonoids) as compared to the MCs, indicating differential C/N homeostasis in the cell-types. The metabolomics results provide insights into plant responses and crop productivity under future climatic changes where elevated CO2 conditions are to take center-stage. PMID:26641455

  8. Prioritizing blood flow: cardiovascular performance in response to the competing demands of locomotion and digestion for the Burmese python, Python molurus.

    Secor, Stephen M; White, Scott E


    Individually, the metabolic demands of digestion or movement can be fully supported by elevations in cardiovascular performance, but when occurring simultaneously, vascular perfusion may have to be prioritized to either the gut or skeletal muscles. Burmese pythons (Python molurus) experience similar increases in metabolic rate during the digestion of a meal as they do while crawling, hence each would have an equal demand for vascular supply when these two actions are combined. To determine, for the Burmese python, whether blood flow is prioritized when snakes are digesting and moving, we examined changes in cardiac performance and blood flow in response to digestion, movement, and the combination of digestion and movement. We used perivascular blood flow probes to measure blood flow through the left carotid artery, dorsal aorta, superior mesenteric artery and hepatic portal vein, and to calculate cardiac output, heart rate and stroke volume. Fasted pythons while crawling experienced a 2.7- and 3.3-fold increase, respectively, in heart rate and cardiac output, and a 66% decrease in superior mesenteric flow. During the digestion of a rodent meal equaling in mass to 24.7% of the snake's body mass, heart rate and cardiac output increased by 3.3- and 4.4-fold, respectively. Digestion also resulted in respective 11.6- and 14.1-fold increases in superior mesenteric and hepatic portal flow. When crawling while digesting, cardiac output and dorsal aorta flow increased by only 21% and 9%, respectively, a modest increase compared with that when they start to crawl on an empty stomach. Crawling did triggered a significant reduction in blood flow to the digesting gut, decreasing superior mesenteric and hepatic portal flow by 81% and 47%, respectively. When faced with the dual demands of digestion and crawling, Burmese pythons prioritize blood flow, apparently diverting visceral supply to the axial muscles.

  9. Nonlinear control methods for planar carangiform robot fish locomotion

    Morgansen, Kristi A.; Duindam, Vincent; Mason, Richard J.; Burdick, Joel W.; Murray, Richard M.


    Considers the design of motion control algorithms for robot fish. We present modeling, control design, and experimental trajectory tracking results for an experimental planar robotic fish system that is propelled using carangiform-like locomotion. Our model for the fish's propulsion is based on quasi-steady fluid flow. Using this model, we propose gaits for forward and turning trajectories and analyze system response under such control strategies. Our models and predictions are verified by ex...

  10. Continuum limbed robots for locomotion

    Mutlu, Alper

    This thesis focuses on continuum robots based on pneumatic muscle technology. We introduce a novel approach to use these muscles as limbs of lightweight legged robots. The flexibility of the continuum legs of these robots offers the potential to perform some duties that are not possible with classical rigid-link robots. Potential applications are as space robots in low gravity, and as cave explorer robots. The thesis covers the fabrication process of continuum pneumatic muscles and limbs. It also provides some new experimental data on this technology. Afterwards, the designs of two different novel continuum robots - one tripod, one quadruped - are introduced. Experimental data from tests using the robots is provided. The experimental results are the first published example of locomotion with tripod and quadruped continuum legged robots. Finally, discussion of the results and how far this technology can go forward is presented.

  11. Unifying Rules for Aquatic Locomotion

    Saadat, Mehdi; Domel, August; di Santo, Valentina; Lauder, George; Haj-Hariri, Hossein


    Strouhal number, St (=fA/U) , a scaling parameter that relates speed, U, to the tail-beat frequency, f, and tail-beat amplitude, A, has been used many times to describe animal locomotion. It has been observed that swimming animals cruise at 0.2 fish-like swimmer, we show that when cruising at minimum hydrodynamic input power, St is predetermined, and is only a function of the shape, i.e. drag coefficient and area. The narrow range for St, 0.2-0.4, has been previously associated with optimal propulsive efficiency. However, St alone is insufficient for deciding optimal motion. We show that hydrodynamic input power (energy usage to propel over a unit distance) in fish locomotion is minimized at all cruising speeds when A* (= A/L), a scaling parameter that relates tail-beat amplitude, A, to the length of the swimmer, L, is constrained to a narrow range of 0.15-0.25. Our analysis proposes a constraint on A*, in addition to the previously found constraint on St, to fully describe the optimal swimming gait for fast swimmers. A survey of kinematics for dolphin, as well as new data for trout, show that the range of St and A* for fast swimmers indeed are constrained to 0.2-0.4 and 0.15-0.25, respectively. Our findings provide physical explanation as to why fast aquatic swimmers cruise with relatively constant tail-beat amplitude at approximately 20 percent of body length, while their swimming speed is linearly correlated with their tail-beat frequency.

  12. T-cell responses in malaria

    Hviid, L; Jakobsen, P H; Abu-Zeid, Y A


    Malaria is caused by infection with protozoan parasites of the genus Plasmodium. It remains one of the most severe health problems in tropical regions of the world, and the rapid spread of resistance to drugs and insecticides has stimulated intensive research aimed at the development of a malaria...... vaccine. Despite this, no efficient operative vaccine is currently available. A large amount of information on T-cell responses to malaria antigens has been accumulated, concerning antigens derived from all stages of the parasite life cycle. The present review summarizes some of that information......, and discusses factors affecting the responses of T cells to malaria antigens....

  13. Locomotive Assignment Problem with Heterogeneous Vehicle Fleet and Hiring External Locomotives

    Dušan Teichmann


    Full Text Available This paper focuses on solving the problem of how to assign locomotives to assembled trains optimally. To solve the problem, linear programming is applied. The situation we model in the paper occurs in the conditions of a transport operator that provides rail transport in the Czech Republic. In the paper, an extended locomotive assignment problem is modeled; the transport operator can use different classes of the locomotives to serve individual connections, some connections must be served by a predefined locomotive class, and the locomotives can be allocated to several depots at the beginning. The proposed model also takes into consideration the fact that some connections can be served by the locomotives of external transport companies or operators. The presented model is applied to a real example in order to test its functionality.

  14. 49 CFR 229.121 - Locomotive cab noise.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Locomotive cab noise. 229.121 Section 229.121... § 229.121 Locomotive cab noise. (a) Performance standards for locomotives. (1) When tested for static noise in accordance with paragraph (a)(3) of this section, all locomotives of each design or model that...

  15. 49 CFR 238.223 - Locomotive fuel tanks.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Locomotive fuel tanks. 238.223 Section 238.223... Equipment § 238.223 Locomotive fuel tanks. Locomotive fuel tanks shall comply with either the following or....21: (a) External fuel tanks. External locomotive fuel tanks shall comply with the requirements...

  16. Atypical radiation response of SCID cells

    Chawapun, Nisa

    Murine SCID (severe combined immune deficiency) cells are well known for their defect in DNA double-strand break repair and in variable(diversity)joining [V(D)J] recombination due to a mutation in a catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). As a consequence, scid cells are hypersensitive to ionizing radiation. The present study showed that asynchronous populations of scid cells were about two-fold more sensitive than Balb/c with respect to cell killing and the defect in scid cells was corrected by complementation with human chromosome 8. Analysis of the survival of synchronized populations as a function of the cell cycle revealed that while scid cells were hypersensitive in all cell cycle phases compared to wild-type cells, this hypersensitivity is even more pronounced in G1 phase. The hypersensitivity reduced as the cells progressed into S phase suggested that homologous recombination repair plays a role. The results imply that there are at least two pathways for the repair of DSB DNA, consistent with a model previously proposed by others. The scid cells were also more sensitive to UVC light (254 nm) killing as compared to wild type cells by clonogenic survival. Using a host cell reactivation (HCR) assay to study the nucleotide excision repair (NER) which is the major repair pathway for UV-photoproducts, the results showed that NER in scid cells was not as efficient as CB- 17. This suggests that DNA-PK is involved in NER as well as non-homologous end-joining (NHEJ) DSB repair which is responsible for ionizing radiation sensitivity in scid cells. Repair in scid cells was not totally absent as shown by low dose rate sparing of cell killing after exposure to 137Cs γ-rays at dose rate of 0.6 cGy/h, 1.36 cGy/h, 6 cGy/h as compared to high dose rate at 171 cGy/min, although this phenomenon could be explained partly by proliferation. However, for radiation induced transformation, no significant dose rate effect was seen. A plot of transformation

  17. Modeling limbless locomotion using ADAMS software

    National Aeronautics and Space Administration — Until now, the methods used by probes or humans for locomotion on planetary surfaces have typically been restricted to variations of wheeled motion. As human...

  18. Le Shuttle, the locomotive from Eurotunnel

    Gabriel MOISA


    Full Text Available This paper present some performances of locomotive ‘Le Shuttle’, so-called locomotive from ‘Eurotunnel’, techniques characteristics of traction motors 6 FHA 7079 and converters witch use it, the principal electric scheme and its function principle and no at last rind the principle scheme of command-control equipment MICAS-S2 with detailed description of its operation mode.

  19. PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration.

    Bahm, Isabel; Barriga, Elias H; Frolov, Antonina; Theveneau, Eric; Frankel, Paul; Mayor, Roberto


    A fundamental property of neural crest (NC) migration is contact inhibition of locomotion (CIL), a process by which cells change their direction of migration upon cell contact. CIL has been proven to be essential for NC migration in amphibians and zebrafish by controlling cell polarity in a cell contact-dependent manner. Cell contact during CIL requires the participation of the cell adhesion molecule N-cadherin, which starts to be expressed by NC cells as a consequence of the switch between E- and N-cadherins during epithelial-to-mesenchymal transition (EMT). However, the mechanism that controls the upregulation of N-cadherin remains unknown. Here, we show that platelet-derived growth factor receptor alpha (PDGFRα) and its ligand platelet-derived growth factor A (PDGF-A) are co-expressed in migrating cranial NC. Inhibition of PDGF-A/PDGFRα blocks NC migration by inhibiting N-cadherin and, consequently, impairing CIL. Moreover, we identify phosphatidylinositol-3-kinase (PI3K)/AKT as a downstream effector of the PDGFRα cellular response during CIL. Our results lead us to propose PDGF-A/PDGFRα signalling as a tissue-autonomous regulator of CIL by controlling N-cadherin upregulation during EMT. Finally, we show that once NC cells have undergone EMT, the same PDGF-A/PDGFRα works as an NC chemoattractant, guiding their directional migration. © 2017. Published by The Company of Biologists Ltd.

  20. The PS locomotive runs again


    Over forty years ago, the PS train entered service to steer the magnets of the accelerator into place... ... a service that was resumed last Tuesday. Left to right: Raymond Brown (CERN), Claude Tholomier (D.B.S.), Marcel Genolin (CERN), Gérard Saumade (D.B.S.), Ingo Ruehl (CERN), Olivier Carlier (D.B.S.), Patrick Poisot (D.B.S.), Christian Recour (D.B.S.). It is more than ten years since people at CERN heard the rumbling of the old PS train's steel wheels. Last Tuesday, the locomotive came back into service to be tested. It is nothing like the monstrous steel engines still running on conventional railways -just a small electric battery-driven vehicle employed on installing the magnets for the PS accelerator more than 40 years ago. To do so, it used the tracks that run round the accelerator. In fact, it is the grandfather of the LEP monorail. After PS was commissioned in 1959, the little train was used more and more rarely. This is because magnets never break down, or hardly ever! In fact, the loc...

  1. Patterned control of human locomotion

    Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka


    There is much experimental evidence for the existence of biomechanical constraints which simplify the problem of control of multi-segment movements. In addition, it has been hypothesized that movements are controlled using a small set of basic temporal components or activation patterns, shared by several different muscles and reflecting global kinematic and kinetic goals. Here we review recent studies on human locomotion showing that muscle activity is accounted for by a combination of few basic patterns, each one timed at a different phase of the gait cycle. Similar patterns are involved in walking and running at different speeds, walking forwards or backwards, and walking under different loading conditions. The corresponding weights of distribution to different muscles may change as a function of the condition, allowing highly flexible control. Biomechanical correlates of each activation pattern have been described, leading to the hypothesis that the co-ordination of limb and body segments arises from the coupling of neural oscillators between each other and with limb mechanical oscillators. Muscle activations need only intervene during limited time epochs to force intrinsic oscillations of the system when energy is lost. PMID:22411012

  2. Patterned control of human locomotion.

    Lacquaniti, Francesco; Ivanenko, Yuri P; Zago, Myrka


    There is much experimental evidence for the existence of biomechanical constraints which simplify the problem of control of multi-segment movements. In addition, it has been hypothesized that movements are controlled using a small set of basic temporal components or activation patterns, shared by several different muscles and reflecting global kinematic and kinetic goals. Here we review recent studies on human locomotion showing that muscle activity is accounted for by a combination of few basic patterns, each one timed at a different phase of the gait cycle. Similar patterns are involved in walking and running at different speeds, walking forwards or backwards, and walking under different loading conditions. The corresponding weights of distribution to different muscles may change as a function of the condition, allowing highly flexible control. Biomechanical correlates of each activation pattern have been described, leading to the hypothesis that the co-ordination of limb and body segments arises from the coupling of neural oscillators between each other and with limb mechanical oscillators. Muscle activations need only intervene during limited time epochs to force intrinsic oscillations of the system when energy is lost.

  3. Inferring Characteristics of Sensorimotor Behavior by Quantifying Dynamics of Animal Locomotion

    Leung, KaWai

    Locomotion is one of the most well-studied topics in animal behavioral studies. Many fundamental and clinical research make use of the locomotion of an animal model to explore various aspects in sensorimotor behavior. In the past, most of these studies focused on population average of a specific trait due to limitation of data collection and processing power. With recent advance in computer vision and statistical modeling techniques, it is now possible to track and analyze large amounts of behavioral data. In this thesis, I present two projects that aim to infer the characteristics of sensorimotor behavior by quantifying the dynamics of locomotion of nematode Caenorhabditis elegans and fruit fly Drosophila melanogaster, shedding light on statistical dependence between sensing and behavior. In the first project, I investigate the possibility of inferring noxious sensory information from the behavior of Caenorhabditis elegans. I develop a statistical model to infer the heat stimulus level perceived by individual animals from their stereotyped escape responses after stimulation by an IR laser. The model allows quantification of analgesic-like effects of chemical agents or genetic mutations in the worm. At the same time, the method is able to differentiate perturbations of locomotion behavior that are beyond affecting the sensory system. With this model I propose experimental designs that allows statistically significant identification of analgesic-like effects. In the second project, I investigate the relationship of energy budget and stability of locomotion in determining the walking speed distribution of Drosophila melanogaster during aging. The locomotion stability at different age groups is estimated from video recordings using Floquet theory. I calculate the power consumption of different locomotion speed using a biomechanics model. In conclusion, the power consumption, not stability, predicts the locomotion speed distribution at different ages.

  4. 40 CFR 92.707 - Notification to locomotive or locomotive engine owners.


    ... the nonconformity of any such locomotives or locomotive engines which have been, if required by the... affected by the remedy and a general statement of the measures to be taken to correct the nonconformity. (5) A description of the adverse effects, if any, that an uncorrected nonconformity would have on the...

  5. Locomotive fuel tank structural safety testing program : passenger locomotive fuel tank jackknife derailment load test.


    This report presents the results of a passenger locomotive fuel tank load test simulating jackknife derailment (JD) load. The test is based on FRA requirements for locomotive fuel tanks in the Title 49, Code of Federal Regulations (CFR), Part 238, Ap...

  6. The Human Central Pattern Generator for Locomotion.

    Minassian, Karen; Hofstoetter, Ursula S; Dzeladini, Florin; Guertin, Pierre A; Ijspeert, Auke


    The ability of dedicated spinal circuits, referred to as central pattern generators (CPGs), to produce the basic rhythm and neural activation patterns underlying locomotion can be demonstrated under specific experimental conditions in reduced animal preparations. The existence of CPGs in humans is a matter of debate. Equally elusive is the contribution of CPGs to normal bipedal locomotion. To address these points, we focus on human studies that utilized spinal cord stimulation or pharmacological neuromodulation to generate rhythmic activity in individuals with spinal cord injury, and on neuromechanical modeling of human locomotion. In the absence of volitional motor control and step-specific sensory feedback, the human lumbar spinal cord can produce rhythmic muscle activation patterns that closely resemble CPG-induced neural activity of the isolated animal spinal cord. In this sense, CPGs in humans can be defined by the activity they produce. During normal locomotion, CPGs could contribute to the activation patterns during specific phases of the step cycle and simplify supraspinal control of step cycle frequency as a feedforward component to achieve a targeted speed. Determining how the human CPGs operate will be essential to advance the theory of neural control of locomotion and develop new locomotor neurorehabilitation paradigms.

  7. On the Role of the Pedunculopontine Nucleus and Mesencephalic Reticular Formation in Locomotion in Nonhuman Primates.

    Goetz, Laurent; Piallat, Brigitte; Bhattacharjee, Manik; Mathieu, Hervé; David, Olivier; Chabardès, Stéphan


    The mesencephalic reticular formation (MRF) is formed by the pedunculopontine and cuneiform nuclei, two neuronal structures thought to be key elements in the supraspinal control of locomotion, muscle tone, waking, and REM sleep. The role of MRF has also been advocated in modulation of state of arousal leading to transition from wakefulness to sleep and it is further considered to be a main player in the pathophysiology of gait disorders seen in Parkinson's disease. However, the existence of a mesencephalic locomotor region and of an arousal center has not yet been demonstrated in primates. Here, we provide the first extensive electrophysiological mapping of the MRF using extracellular recordings at rest and during locomotion in a nonhuman primate (NHP) (Macaca fascicularis) model of bipedal locomotion. We found different neuronal populations that discharged according to a phasic or a tonic mode in response to locomotion, supporting the existence of a locomotor neuronal circuit within these MRF in behaving primates. Altogether, these data constitute the first electrophysiological characterization of a locomotor neuronal system present within the MRF in behaving NHPs under normal conditions, in accordance with several studies done in different experimental animal models. We provide the first extensive electrophysiological mapping of the two major components of the mesencephalic reticular formation (MRF), namely the pedunculopontine and cuneiform nuclei. We exploited a nonhuman primate (NHP) model of bipedal locomotion with extracellular recordings in behaving NHPs at rest and during locomotion. Different MRF neuronal groups were found to respond to locomotion, with phasic or tonic patterns of response. These data constitute the first electrophysiological evidences of a locomotor neuronal system within the MRF in behaving NHPs. Copyright © 2016 the authors 0270-6474/16/364917-13$15.00/0.

  8. Passive appendages aid locomotion through symmetry breaking

    Bagheri, Shervin; Lacis, Ugis; Mazzino, Andrea; Kellay, Hamid; Brosse, Nicolas; Lundell, Fredrik; Ingremeau, Francois


    Plants and animals use plumes, barbs, tails, feathers, hairs, fins, and other types of appendages to aid locomotion. Despite their enormous variation, passive appendages may contribute to locomotion by exploiting the same physical mechanism. We present a new mechanism that applies to body appendages surrounded by a separated flow, which often develops behind moving bodies larger than a few millimeters. We use theory, experiments, and numerical simulations to show that bodies with protrusions turn and drift by exploiting a symmetry-breaking instability similar to the instability of an inverted pendulum. Our model explains why the straight position of an appendage in flowing fluid is unstable and how it stabilizes either to the left or right of the incoming fluid flow direction. The discovery suggests a new mechanism of locomotion that may be relevant for certain organisms; for example, how plumed seeds may drift without wind and how motile animals may passively reorient themselves.

  9. Operating a locomotive on liquid methane fuel

    Stolz, J.L.


    This paper reports that several years ago, Burlington Northern Railroad looked into the feasibility of operating a diesel railroad locomotive to also run on compressed natural gas in a dual-fuel mode. Recognizing the large volume of on-board storage required and other limitations of CNG in the application, a program was begun to fuel a locomotive with liquefied natural gas. Because natural gas composition can vary with source and processing, it was considered desirable to use essentially pure liquid methane as the engine fuel. Initial testing results show the locomotive system achieved full diesel-rated power when operating on liquid methane and with equivalent fuel efficiency. Extended testing, including an American Association of Railroad 500-hour durability test, was undertaken to obtain information on engine life, wear rate and lubrication oil life

  10. Numerical simulation of human biped locomotion

    Ishiguro, Misako; Fujisaki, Masahide


    This report describes the numerical simulation of the motion of human-like robot which is one of the research theme of human acts simulation program (HASP) begun at the Computing Center of JAERI in 1987. The purpose of the theme is to model the human motion using robotics kinematic/kinetic equations and to get the joint angles as the solution. As the first trial, we treat the biped locomotion (walking) which is the most fundamental human motion. We implemented a computer program on FACOM M-780 computer, where the program is originated from the book of M. Vukobratovic in Yugoslavia, and made a graphic program to draw a walking shot sequence. Mainly described here are the mathematical model of the biped locomotion, implementation method of the computer program, input data for basic walking pattern, computed results and its validation, and graphic representation of human walking image. Literature survey on robotics equation and biped locomotion is also included. (author)

  11. Muscle Coordination and Locomotion in Humans.

    Sylos-Labini, Francesca; Zago, Myrka; Guertin, Pierre A; Lacquaniti, Francesco; Ivanenko, Yury P


    Locomotion is a semi-automatic daily task. Several studies show that muscle activity is fairly stereotyped during normal walking. Nevertheless, each human leg contains over 50 muscles and locomotion requires flexibility in order to adapt to different conditions as, for instance, different speeds, gaits, turning, obstacle avoidance, altered gravity levels, etc. Therefore, locomotor control has to deal with a certain level of flexibility and non-linearity. In this review, we describe and discuss different findings dealing with both simplicity and variability of the muscular control, as well as with its maturation during development. Despite complexity and redundancy, muscle activity patterns and spatiotemporal maps of spinal motoneuron output during human locomotion show both stereotypical features as well as functional re-organization. Flexibility and different solutions to adjust motor patterns should be considered when considering new rehabilitation strategies to treat disorders involving deficits in gait. Copyright© Bentham Science Publishers; For any queries, please email at

  12. Biomimetic materials for controlling bone cell responses.

    Drevelle, Olivier; Faucheux, Nathalie


    Bone defects that cannot "heal spontaneously during life" will become an ever greater health problem as populations age. Harvesting autografts has several drawbacks, such as pain and morbidity at both donor and acceptor sites, the limited quantity of material available, and frequently its inappropriate shape. Researchers have therefore developed alternative strategies that involve biomaterials to fill bone defects. These biomaterials must be biocompatible and interact with the surrounding bone tissue to allow their colonization by bone cells and blood vessels. The latest generation biomaterials are not inert; they control cell responses like adhesion, proliferation and differentiation. These biomaterials are called biomimetic materials. This review focuses on the development of third generation materials. We first briefly describe the bone tissue with its cells and matrix, and then how bone cells interact with the extracellular matrix. The next section covers the materials currently used to repair bone defects. Finally, we describe the strategies employed to modify the surface of materials, such as coating with hydroxyapatite and grafting biomolecules.

  13. CNP-1 (ARRD-17), a novel substrate of calcineurin, is critical for modulation of egg-laying and locomotion in response to food and lysine sensation in Caenorhabditis elegans.

    Jee, Changhoon; Choi, Tae-Woo; Kalichamy, Karunambigai; Yee, Jong Zin; Song, Hyun-Ok; Ji, Yon Ju; Lee, Jungsoo; Lee, Jin Il; L'Etoile, Noelle D; Ahnn, Joohong; Lee, Sun-Kyung


    Calcineurin is a Ca(2+)/calmodulin-dependent protein phosphatase involved in calcium signaling pathways. In Caenorhabditis elegans, the loss of calcineurin activity causes pleiotropic defects including hyperadaptation of sensory neurons, hypersensation to thermal difference and hyper-egg-laying when worms are refed after starvation. In this study, we report on arrd-17 as calcineurin-interacting protein-1 (cnp-1), which is a novel molecular target of calcineurin. CNP-1 interacts with the catalytic domain of the C. elegans calcineurin A subunit, TAX-6, in a yeast two-hybrid assay and is dephosphorylated by TAX-6 in vitro. cnp-1 is expressed in ASK, ADL, ASH and ASJ sensory neurons as TAX-6. It acts downstream of tax-6 in regulation of locomotion and egg-laying after starvation, ASH sensory neuron adaptation and lysine chemotaxis, that is known to be mediated by ASK neurons. Altogether, our biochemical and genetic evidence indicates that CNP-1 is a direct target of calcineurin and required in stimulated egg-laying and locomotion after starvation, adaptation to hyperosmolarity and attraction to lysine, which is modulated by calcineurin. We suggest that the phosphorylation status of CNP-1 plays an important role in regulation of refed stimulating behaviors after starvation and attraction to amino acid, which provides valuable nutritious information. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Regulatory T Cells in Radiotherapeutic Responses

    Schaue, Dörthe; Xie, Michael W.; Ratikan, Josephine A.; McBride, William H.


    Radiation therapy (RT) can extend its influence in cancer therapy beyond what can be attributed to in-field cytotoxicity by modulating the immune system. While complex, these systemic effects can help tip the therapeutic balance in favor of treatment success or failure. Engagement of the immune system is generally through recognition of damage-associated molecules expressed or released as a result of tumor and normal tissue radiation damage. This system has evolved to discriminate pathological from physiological forms of cell death by signaling “danger.” The multiple mechanisms that can be evoked include a shift toward a pro-inflammatory, pro-oxidant microenvironment that can promote maturation of dendritic cells and, in cancer treatment, the development of effector T cell responses to tumor-associated antigens. Control over these processes is exerted by regulatory T cells (Tregs), suppressor macrophages, and immunosuppressive cytokines that act in consort to maintain tolerance to self, limit tissue damage, and re-establish tissue homeostasis. Unfortunately, by the time RT for cancer is initiated the tumor-host relationship has already been sculpted in favor of tumor growth and against immune-mediated mechanisms for tumor regression. Reversing this situation is a major challenge. However, recent data show that removal of Tregs can tip the balance in favor of the generation of radiation-induced anti-tumor immunity. The clinical challenge is to do so without excessive depletion that might precipitate serious autoimmune reactions and increase the likelihood of normal tissue complications. The selective modulation of Treg biology to maintain immune tolerance and control of normal tissue damage, while releasing the “brakes” on anti-tumor immune responses, is a worthy aim with promise for enhancing the therapeutic benefit of RT for cancer.

  15. Regulatory T cells in radiotherapeutic responses

    Dörthe eSchaue


    Full Text Available Radiation therapy (RT can extend its influence in cancer therapy beyond what can be attributed to in-field cytotoxicity by modulating the immune system. While complex, these systemic effects can help tip the therapeutic balance in favor of treatment success or failure. Engagement of the immune system is generally through recognition of damage-associated molecules expressed or released as a result of tumor and normal tissue radiation damage. This system has evolved to discriminate pathological from physiological forms of cell death by signaling danger. The multiple mechanisms that can be evoked include a shift towards a pro-inflammatory, pro-oxidant microenvironment that can promote maturation of dendritic cells and, in cancer treatment, the development of effector T cell responses to tumor-associated antigens. Control over these processes is exerted by regulatory T cells (Tregs, suppressor macrophages and immunosuppressive cytokines that act in consort to maintain tolerance to self, limit tissue damage, and re-establish tissue homeostasis. Unfortunately, by the time RT for cancer is initiated the tumor-host relationship has already been sculpted in favor of tumor growth and against immune-mediated mechanisms for tumor regression. Reversing this situation is a major challenge. However, recent data show that removal of Tregs can tip the balance in favor of the generation of radiation-induced anti-tumor immunity. The clinical challenge is to do so without excessive depletion that might precipitate serious autoimmune reactions and increase the likelihood of normal tissue complications. The selective modulation of Treg biology to maintain immune tolerance and control of normal tissue damage, while releasing the brakes on anti-tumor immune responses, is a worthy aim with promise for enhancing the therapeutic benefit of RT for cancer.


    S. V. Myamlin


    Full Text Available Purpose. To determine the dynamic qualities of the mainline freight locomotives characterizing the safe motion in tangent and curved track sections at all operational speeds, one needs a whole set of studies, which includes a selection of the design scheme, development of the corresponding mathematical model of the locomotive spatial fluctuations, construction of the computer calculation program, conducting of the theoretical and then experimental studies of the new designs. In this case, one should compare the results with existing designs. One of the necessary conditions for the qualitative improvement of the traction rolling stock is to define the parameters of its running gears. Among the issues related to this problem, an important place is occupied by the task of determining the locomotive dynamic properties on the stage of projection, taking into account the selected technical solutions in the running gear design. Methodology. The mathematical modeling studies are carried out by the numerical integration method of the dynamic loading for the mainline locomotive using the software package «Dynamics of Rail Vehicles » («DYNRAIL». Findings. As a result of research for the improvement of locomotive running gear design it can be seen that the creation of the modern locomotive requires from engineers and scientists the realization of scientific and technical solutions. The solutions enhancing design speed with simultaneous improvement of the traction, braking and dynamic qualities to provide a simple and reliable design, especially the running gear, reducing the costs for maintenance and repair, low initial cost and operating costs for the whole service life, high traction force when starting, which is as close as possible to the ultimate force of adhesion, the ability to work in multiple traction mode and sufficient design speed. Practical Value. The generalization of theoretical, scientific and methodological, experimental studies aimed

  17. Locomotion of Paramecium in patterned environments

    Park, Eun-Jik; Eddins, Aja; Kim, Junil; Yang, Sung; Jana, Saikat; Jung, Sunghwan


    Ciliary organisms like Paramecium Multimicronucleatum locomote by synchronized beating of cilia that produce metachronal waves over their body. In their natural environments they navigate through a variety of environments especially surfaces with different topology. We study the effects of wavy surfaces patterned on the PDMS channels on the locomotive abilities of Paramecium by characterizing different quantities like velocity amplitude and wavelength of the trajectories traced. We compare this result with the swimming characteristics in straight channels and draw conclusions about the effects of various patterned surfaces.

  18. Neural Control of Startle-Induced Locomotion by the Mushroom Bodies and Associated Neurons in Drosophila

    Jun Sun


    Full Text Available Startle-induced locomotion is commonly used in Drosophila research to monitor locomotor reactivity and its progressive decline with age or under various neuropathological conditions. A widely used paradigm is startle-induced negative geotaxis (SING, in which flies entrapped in a narrow column react to a gentle mechanical shock by climbing rapidly upwards. Here we combined in vivo manipulation of neuronal activity and splitGFP reconstitution across cells to search for brain neurons and putative circuits that regulate this behavior. We show that the activity of specific clusters of dopaminergic neurons (DANs afferent to the mushroom bodies (MBs modulates SING, and that DAN-mediated SING regulation requires expression of the DA receptor Dop1R1/Dumb, but not Dop1R2/Damb, in intrinsic MB Kenyon cells (KCs. We confirmed our previous observation that activating the MB α'β', but not αβ, KCs decreased the SING response, and we identified further MB neurons implicated in SING control, including KCs of the γ lobe and two subtypes of MB output neurons (MBONs. We also observed that co-activating the αβ KCs antagonizes α'β' and γ KC-mediated SING modulation, suggesting the existence of subtle regulation mechanisms between the different MB lobes in locomotion control. Overall, this study contributes to an emerging picture of the brain circuits modulating locomotor reactivity in Drosophila that appear both to overlap and differ from those underlying associative learning and memory, sleep/wake state and stress-induced hyperactivity.

  19. Cell Culture Assay for Human Noroviruses [response

    Straub, Tim M.; Honer Zu Bentrup, Kerstin; Orosz Coghlan, Patricia; Dohnalkova, Alice; Mayer, Brooke K.; Bartholomew, Rachel A.; Valdez, Catherine O.; Bruckner-Lea, Cindy J.; Gerba, Charles P.; Abbaszadegan, Morteza A.; Nickerson, Cheryl A.


    We appreciate the comments provided by Leung et al., in response to our recently published article “In Vitro Cell Culture Infectivity Assay for Human Noroviruses” by Straub et al. (1). The specific aim of our project was to develop an in vitro cell culture infectivity assay for human noroviruses (hNoV) to enhance risk assessments when they are detected in water supplies. Reverse transcription (RT) qualitative or quantitative PCR are the primary assays for waterborne NoV monitoring. However, these assays cannot distinguish between infectious vs. non-infectious virions. When hNoV is detected in water supplies, information provided by our infectivity assay will significantly improve risk assessment models and protect human health, regardless of whether we are propagating NoV. Indeed, in vitro cell culture infectivity assays for the waterborne pathogen Cryptosporidium parvum that supplement approved fluorescent microscopy assays, do not result in amplification of the environmentally resistant hard-walled oocysts (2). However, identification of life cycle stages in cell culture provides evidence of infectious oocysts in a water supply. Nonetheless, Leung et al.’s assertion regarding the suitability of our method for the in vitro propagation of high titers of NoV is valid for the medical research community. In this case, well-characterized challenge pools of virus would be useful for developing and testing diagnostics, therapeutics, and vaccines. As further validation of our published findings, we have now optimized RT quantitative PCR to assess the level of viral production in cell culture, where we are indeed finding significant increases in viral titer. The magnitude and time course of these increases is dependent on both virus strain and multiplicity of infection. We are currently preparing a manuscript that will discuss these findings in greater detail, and the implications this may have for creating viral challenge pools

  20. Plant Cell Adaptive Responses to Microgravity

    Kordyum, Elizabeth; Kozeko, Liudmyla; Talalaev, Alexandr

    simulated microgravity and temperature elevation have different effects on the small HSP genes belonging to subfamilies with different subcellular localization: cytosol/nucleus - PsHSP17.1-CII and PsHSP18.1-CI, cloroplasts - PsHSP26.2-Cl, endoplasmatic reticulum - PsHSP22.7-ER and mitochondria - PsHSP22.9-M: unlike high temperature, clinorotation does not cause denaturation of cell proteins, that confirms the sHSP chaperone function. Dynamics of investigated gene expression in pea seedlings growing 5 days after seed germination under clinorotation was similar to that in the stationary control. Similar patterns in dynamics of sHSP gene expression in the stationary control and under clinorotation may be one of mechanisms providing plant adaptation to simulated microgravity. It is pointed that plant cell responses in microgravity and under clinorotation vary according to growth phase, physiological state, and taxonomic position of the object. At the same time, the responses have, to some degree, a similar character reflecting the changes in cell organelle functional load. Thus, next certain changes in the structure and function of plant cells may be considered as adaptive: 1) an increase in the unsaturated fatty acid content in the plasmalemma, 2) rearrangements of organelle ultrastructure and an increase in their functional load, 3) an increase in cortical F-actin under destabilization of tubulin microtubules, 4) the level of gene expression and synthesis of heat shock proteins, 5) alterations of the enzyme and antioxidant system activity. The dynamics of these patterns demonstrated that the adaptation occurs on the principle of self-regulating systems in the limits of physiological norm reaction. The very importance of changed expression of genes involved in different cellular processes, especially HSP genes, in cell adaptation to altered gravity is discussed.

  1. Boldness and intermittent locomotion in the bluegill sunfish, Lepomis macrochirus

    Alexander D.M. Wilson; Jean-Guy J. Godin


    Intermittent locomotion, characterized by moves interspersed with pauses, is a common pattern of locomotion in animals, but its ecological and evolutionary significance relative to continuous locomotion remains poorly understood. Although many studies have examined individual differences in both intermittent locomotion and boldness separately, to our knowledge, no study to date has investigated the relationship between these 2 traits. Characterizing and understanding this relationship is impo...

  2. Bioinspired template-based control of legged locomotion

    Ahmad Sharbafi, Maziar


    cient and robust locomotion is a crucial condition for the more extensive use of legged robots in real world applications. In that respect, robots can learn from animals, if the principles underlying locomotion in biological legged systems can be transferred to their artificial counterparts. However, legged locomotion in biological systems is a complex and not fully understood problem. A great progress to simplify understanding locomotion dynamics and control was made by introducing simple mo...

  3. 49 CFR 230.101 - Steam locomotive driving journal boxes.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotive driving journal boxes. 230.101... Locomotives and Tenders Running Gear § 230.101 Steam locomotive driving journal boxes. (a) Driving journal boxes. Driving journal boxes shall be maintained in a safe and suitable condition for service. Not more...

  4. Lizard locomotion in heterogeneous granular media

    Schiebel, Perrin; Goldman, Daniel


    Locomotion strategies in heterogeneous granular environments (common substrates in deserts), are relatively unexplored. The zebra-tailed lizard (C. draconoides) is a useful model organism for such studies owing to its exceptional ability to navigate a variety of desert habitats at impressive speed (up to 50 body-lengths per second) using both quadrapedal and bidepal gaits. In laboratory experiments, we challenge the lizards to run across a field of boulders (2.54 cm diameter glass spheres or 3.8 cm 3D printed spheres) placed in a lattice pattern and embedded in a loosely packed granular medium of 0.3 mm diameter glass particles. Locomotion kinematics of the lizard are recorded using high speed cameras, with and without the scatterers. The data reveals that unlike the lizard's typical quadrupedal locomotion using a diagonal gait, when scatterers are present the lizard is most successful when using a bipedal gait, with a raised center of mass (CoM). We propose that the kinematics of bipedal running in conjunction with the lizard's long toes and compliant hind foot are the keys to this lizard's successful locomotion in the presence of such obstacles. NSF PoLS

  5. 49 CFR 229.129 - Locomotive horn.


    .... The locomotive shall be positioned on straight, level track. (6) Measurements shall be taken only when... between 20 percent and 95 percent inclusively; wind velocity is not more than 12 miles per hour and there..., at an angle no greater than 20 degrees from the center line of the track, and oriented with respect...

  6. 77 FR 75045 - Locomotive Safety Standards


    ...; and, locomotive diesel exhaust. In addition to the issues raised in the petitions, FRA has determined... flow method (AFM) indicator calibration date on the Form 6180-49A; the duration of the remote control... in the context of its use. For example, fuel injectors might possibly be considered as providing...

  7. Morphological self stabilization of locomotion gaits: illustration on a few examples from bio-inspired locomotion

    Chevallereau , Christine; Boyer , Frédéric; Porez , Mathieu; Mauny , Johan; Aoustin , Yannick


    International audience; — To a large extent, robotics locomotion can be viewed as cyclic motions, named gaits. Due to the high complexity of the locomotion dynamics, to find the control laws that ensure an expected gait and its stability with respect to external perturbations, is a challenging issue for feedback control. To address this issue, a promising way is to take inspiration from animals that intensively exploit the interactions of the passive degrees of freedom of their body with thei...

  8. Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

    The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

  9. 49 CFR 210.9 - Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of a noise defective locomotive, rail car, or consist of a locomotive and rail cars. 210.9 Section 210.9 Transportation Other Regulations... locomotive, rail car, or consist of a locomotive and rail cars. A locomotive, rail car, or consist of a...

  10. Metabolic features of the cell danger response.

    Naviaux, Robert K


    The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental

  11. Locomotive Schedule Optimization for Da-qin Heavy Haul Railway

    Ruiye Su


    Full Text Available The main difference between locomotive schedule of heavy haul railways and that of regular rail transportation is the number of locomotives utilized for one train. One heavy-loaded train usually has more than one locomotive, but a regular train only has one. This paper develops an optimization model for the multilocomotive scheduling problem (MLSP through analyzing the current locomotive schedule of Da-qin Railway. The objective function of our paper is to minimize the total number of utilized locomotives. The MLSP is nondeterministic polynomial (NP hard. Therefore, we convert the multilocomotive traction problem into a single-locomotive traction problem. Then, the single-locomotive traction problem (SLTP can be converted into an assignment problem. The Hungarian algorithm is applied to solve the model and obtain the optimal locomotive schedule. We use the variance of detention time of locomotives at stations to evaluate the stability of locomotive schedule. In order to evaluate the effectiveness of the proposed optimization model, case studies for 20 kt and 30 kt heavy-loaded combined trains on Da-qin Railway are both conducted. Compared to the current schedules, the optimal schedules from the proposed models can save 62 and 47 locomotives for 20 kt and 30 kt heavy-loaded combined trains, respectively. Therefore, the effectiveness of the proposed model and its solution algorithm are both valid.

  12. Development of a Novel Locomotion Algorithm for Snake Robot

    Khan, Raisuddin; Billah, Md Masum; Watanabe, Mitsuru; Shafie, A A


    A novel algorithm for snake robot locomotion is developed and analyzed in this paper. Serpentine is one of the renowned locomotion for snake robot in disaster recovery mission to overcome narrow space navigation. Several locomotion for snake navigation, such as concertina or rectilinear may be suitable for narrow spaces, but is highly inefficient if the same type of locomotion is used even in open spaces resulting friction reduction which make difficulties for snake movement. A novel locomotion algorithm has been proposed based on the modification of the multi-link snake robot, the modifications include alterations to the snake segments as well elements that mimic scales on the underside of the snake body. Snake robot can be able to navigate in the narrow space using this developed locomotion algorithm. The developed algorithm surmount the others locomotion limitation in narrow space navigation

  13. Muscarinic responses of gastric parietal cells

    Wilkes, J.M.; Kajimura, M.; Scott, D.R.; Hersey, S.J.; Sachs, G.


    Isolated rabbit gastric glands were used to study the nature of the muscarinic cholinergic responses of parietal cells. Carbachol stimulation of acid secretion, as measured by the accumulation of aminopyrine, was inhibited by the M1 antagonist, pirenzepine, with an IC50 of 13 microM; by the M2 antagonist, 11,2-(diethylamino)methyl-1 piperidinyl acetyl-5,11-dihydro-6H-pyrido 2,3-b 1,4 benzodiazepin-6-one (AF-DX 116), with an IC50 of 110 microM; and by the M1/M3 antagonist, diphenyl-acetoxy-4-methylpiperidinemethiodide, with an IC50 of 35 nM. The three antagonists displayed equivalent IC50 values for the inhibition of carbachol-stimulated production of 14CO2 from radiolabeled glucose, which is a measure of the turnover of the H,K-ATPase, the final step of acid secretion. Intracellular calcium levels were measured in gastric glands loaded with FURA 2. Carbachol was shown to both release calcium from an intracellular pool and to promote calcium entry across the plasma membrane. The calcium entry was inhibitable by 20 microM La3+. The relative potency of the three muscarinic antagonists for inhibition of calcium entry was essentially the same as for inhibition of acid secretion or pump related glucose oxidation. Image analysis of the glands showed the effects of carbachol, and of the antagonists, on intracellular calcium were occurring largely in the parietal cell. The rise in cell calcium due to release of calcium from intracellular stores was inhibited by 4-DAMP with an IC50 of 1.7 nM, suggesting that the release pathway was regulated by a low affinity M3 muscarinic receptor or state; Ca entry and acid secretion are regulated by a high affinity M3 muscarinic receptor or state, inhibited by higher 4-DAMP concentrations, suggesting that it is the steady-state elevation of Ca that is related to parietal cell function rather than the [Ca]i transient

  14. [Job stress in locomotive attendants in a locomotive depot and related influencing factors].

    Kang, L; Jia, X C; Lu, F; Zhou, W H; Chen, R


    Objective: To investigate the current status of job stress in locomotive attendants in a locomotive depot and related influencing factors. Methods: From 2012 to 2013, cluster sampling was used to select 1500 locomotive attendants in a locomotive depot in Zhengzhou Railway Bureau as respondents.The contents of the investigation included general data and occupational information.A job satisfaction questionnaire was used to investigate the degree of satisfaction, a depression scale was used to investigate the frequency of symptoms, and a daily stress scale was used to investigate the frequency of fatigue and stress. Results: There was a significant difference in depression score between locomotive attendants with different ages, working years, degrees of education, working situations of spouse, total monthly family incomes, numbers of times of attendanceat night, monthly numbers of times of attendance,ormonthly attendance times( P job satisfaction score between locomotive attendants with different ages,working years, degrees of education, working situations of spouse, total monthly family incomes, numbers of times of attendance at night, monthly attendance times,or ways to work( P job satisfaction( β =1.546)and monthly number of times of attendance,working years,attendance time at night,and degree of education were negatively correlated with job satisfaction( β =-0.185,-0.097,-0.020,and -1.106); monthly number of times of attendance andcommute time were positively correlated with depression( β =0.243 and 0.029); attendance time at night,working situation of spouse,commute time,monthly number of times of attendance,degree of education,and working years were positively correlated with daily stress( β =0.006,0.473,0.010,0.043,0.585, and 0.028). Conclusion: Number of times of attendance, attendance time,working years,and spouse are influencing factors for job stress in locomotive attendants. Improvement in work process and care for their personal life help to reduce

  15. Exotendons for assistance of human locomotion

    van den Bogert Antonie J


    Full Text Available Abstract Background Powered robotic exoskeletons for assistance of human locomotion are currently under development for military and medical applications. The energy requirements for such devices are excessive, and this has become a major obstacle for practical applications. Legged locomotion in many animals, however, is very energy efficient. We propose that poly-articular elastic mechanisms are a major contributor to the economy of locomotion in such specialized animals. Consequently, it should be possible to design unpowered assistive devices that make effective use of similar mechanisms. Methods A passive assistive technology is presented, based on long elastic cords attached to an exoskeleton and guided by pulleys placed at the joints. A general optimization procedure is described for finding the best geometrical arrangement of such "exotendons" for assisting a specific movement. Optimality is defined either as minimal residual joint moment or as minimal residual joint power. Four specific exotendon systems with increasing complexity are considered. Representative human gait data were used to optimize each of these four systems to achieve maximal assistance for normal walking. Results The most complex exotendon system, with twelve pulleys per limb, was able to reduce the joint moments required for normal walking by 71% and joint power by 74%. A simpler system, with only three pulleys per limb, could reduce joint moments by 46% and joint power by 47%. Conclusion It is concluded that unpowered passive elastic devices can substantially reduce the muscle forces and the metabolic energy needed for walking, without requiring a change in movement. When optimally designed, such devices may allow independent locomotion in patients with large deficits in muscle function.

  16. Cardio–Pulmonary Response Of Patients With Sickle Cell Anaemia ...

    Cardio–Pulmonary Response Of Patients With Sickle Cell Anaemia ... any risk of adverse cardio-respiratory response during the course of physical rehabilitation. A total of 70 subjects participated in the study; 30 of these had Haemoglobin ...

  17. Normalization of cell responses in cat striate cortex

    Heeger, D. J.


    Simple cells in the striate cortex have been depicted as half-wave-rectified linear operators. Complex cells have been depicted as energy mechanisms, constructed from the squared sum of the outputs of quadrature pairs of linear operators. However, the linear/energy model falls short of a complete explanation of striate cell responses. In this paper, a modified version of the linear/energy model is presented in which striate cells mutually inhibit one another, effectively normalizing their responses with respect to stimulus contrast. This paper reviews experimental measurements of striate cell responses, and shows that the new model explains a significantly larger body of physiological data.

  18. Chaotic exploration and learning of locomotion behaviors.

    Shim, Yoonsik; Husbands, Phil


    We present a general and fully dynamic neural system, which exploits intrinsic chaotic dynamics, for the real-time goal-directed exploration and learning of the possible locomotion patterns of an articulated robot of an arbitrary morphology in an unknown environment. The controller is modeled as a network of neural oscillators that are initially coupled only through physical embodiment, and goal-directed exploration of coordinated motor patterns is achieved by chaotic search using adaptive bifurcation. The phase space of the indirectly coupled neural-body-environment system contains multiple transient or permanent self-organized dynamics, each of which is a candidate for a locomotion behavior. The adaptive bifurcation enables the system orbit to wander through various phase-coordinated states, using its intrinsic chaotic dynamics as a driving force, and stabilizes on to one of the states matching the given goal criteria. In order to improve the sustainability of useful transient patterns, sensory homeostasis has been introduced, which results in an increased diversity of motor outputs, thus achieving multiscale exploration. A rhythmic pattern discovered by this process is memorized and sustained by changing the wiring between initially disconnected oscillators using an adaptive synchronization method. Our results show that the novel neurorobotic system is able to create and learn multiple locomotion behaviors for a wide range of body configurations and physical environments and can readapt in realtime after sustaining damage.

  19. On the rules for aquatic locomotion

    Saadat, M.; Fish, F. E.; Domel, A. G.; Di Santo, V.; Lauder, G. V.; Haj-Hariri, H.


    We present unifying rules governing the efficient locomotion of swimming fish and marine mammals. Using scaling and dimensional analysis, supported by new experimental data, we show that efficient locomotion occurs when the values of the Strouhal (St) number St (=f A /U ) and A*(=A /L ) , two nondimensional numbers that relate forward speed U , tail-beat amplitude A , tail-beat frequency f , and the length of the swimmer L are bound to the tight ranges of 0.2-0.4 and 0.1-0.3, respectively. The tight range of 0.2-0.4 for the St number has previously been associated with optimal thrust generation. We show that the St number alone is insufficient to achieve optimal aquatic locomotion, and an additional condition on A* is needed. More importantly, we show that when swimming at minimal power consumption, the Strouhal number of a cruising swimmer is predetermined solely by the shape and drag characteristics of the swimmer. We show that diverse species of fish and cetaceans cruise indeed with the St number and A* predicted by our theory. Our findings provide a physical explanation as to why fast aquatic swimmers cruise with a relatively constant tail-beat amplitude of approximately 20% of the body length, and their swimming speed is nearly proportional to their tail-beat frequency.

  20. B Cells Promote Th1- Skewed NKT Cell Response by CD1d-TCR Interaction

    Shin, Jung Hoon; Park, Se-Ho


    CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although ?-galactosylceramide (?-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-? by NKT cells, concomitant with a d...

  1. Damages and resource of locomotive wheels used under the north operating conditions

    A. V. Grigorev


    Full Text Available In operating railway equipment, in particular the elements, such as a wheel and a rail there is damage accumulation of any kind, causing a premature equipment failure. Thus, an analysis of the mechanisms and modeling of damage accumulation and fracture both on the surface and in the bulk material remain a challenge.Data on the defective wheel sets to be subjected to facing has been collected and analyzed to assess the locomotive wheel sets damage of the locomotive fleet company of AK «Yakutia Railways», city of Aldan, The Republic of Sakha (Yakutia. For this purpose, three main locomotives have been examined.The object of research carried out in this paper, is a locomotive wheels tire, which is subjected to cyclic impact (dynamic loads during operation. In this regard, the need arises to determine both the strength of material in response to such shock loads and the quantitative calculation of damage accumulated therein.The accumulated fatigue damage has been attributed to one radial cross section of the wheel coming into contact with the rail once per revolution of the wheel. Consequently, in one revolution a wheel is under one loading cycle. As stated, the average mileage of locomotives to have the unacceptable damages formed on the tread surface is 12 thousand km.Test results establish that along with the high-cycle loading the shock-contact action on rail joints significantly affects the accumulation of damage in the locomotive wheels tire. The number of cycles to failure due to the formation of unacceptable damage in the locomotive wheels tire is N = 2,4×106 and 6×105 cycles, respectively, for fatigue and shock-contact loading.In general, we can say that the problem of higher intensity to form the surface damage is directly related to the operation of the locomotive wheel tire under abnormally low climatic temperatures. With decreasing ambient temperature, this element material rapidly looses its plastic properties, thereby accelerating

  2. B Cells Promote Th1- Skewed NKT Cell Response by CD1d-TCR Interaction.

    Shin, Jung Hoon; Park, Se-Ho


    CD1d expressing dendritic cells (DCs) are good glyco-lipid antigen presenting cells for NKT cells. However, resting B cells are very weak stimulators for NKT cells. Although α-galactosylceramide (α-GalCer) loaded B cells can activate NKT cells, it is not well defined whether B cells interfere NKT cell stimulating activity of DCs. Unexpectedly, we found in this study that B cells can promote Th1-skewed NKT cell response, which means a increased level of IFN-γ by NKT cells, concomitant with a decreased level of IL-4, in the circumstance of co-culture of DCs and B Cells. Remarkably, the response promoted by B cells was dependent on CD1d expression of B cells.

  3. Axial dynamics during locomotion in vertebrates: lesson from the salamander

    GOSSARD, JEAN-PIERRE; DUBUC, RÉJEAN; KOLTA, ARLETTE; Cabelguen, Jean-Marie; Ijspeert, Auke; Lamarque, Stéphanie; Ryczko, Dimitri


    Much of what we know about the flexibility of the locomotor networks in vertebrates is derived from studies examining the adaptation of limb movements during stepping in various conditions. However, the body movements play important roles during locomotion: they produce the thrust during undulatory locomotion and they help to increase the stride length during legged locomotion. In this chapter, we review our current knowledge about the flexibility in the neuronal circuits controlling the body...

  4. The Need for Speed in Rodent Locomotion Analyses

    Batka, Richard J.; Brown, Todd J.; Mcmillan, Kathryn P.; Meadows, Rena M.; Jones, Kathryn J.; Haulcomb, Melissa M.


    Locomotion analysis is now widely used across many animal species to understand the motor defects in disease, functional recovery following neural injury, and the effectiveness of various treatments. More recently, rodent locomotion analysis has become an increasingly popular method in a diverse range of research. Speed is an inseparable aspect of locomotion that is still not fully understood, and its effects are often not properly incorporated while analyzing data. In this hybrid manuscript,...

  5. Advanced aftertreatment systems for locomotive applications; Moderne Abgasnachbehandlungssysteme fuer Lokomotiven

    Park, Paul [Caterpillar Inc., Peoria, IL (United States); Bruestle, Claus [Emitec Inc., Rochester Hill, MI (United States)


    Tier 4 legislation for locomotives, starting in 2015, will require significant reductions in particulate matter and nitrogen oxide tail pipe emissions. To reduce nitrogen oxide emissions of line-haul locomotives at least to the level of Tier 4, Caterpillar has developed an aftertreatment system. Here, for the first time an SCR system was used for diesel locomotive engines with an urea dosing system. (orig.)

  6. Nanomaterials for Engineering Stem Cell Responses.

    Kerativitayanan, Punyavee; Carrow, James K; Gaharwar, Akhilesh K


    Recent progress in nanotechnology has stimulated the development of multifunctional biomaterials for tissue engineering applications. Synergistic interactions between nanomaterials and stem cell engineering offer numerous possibilities to address some of the daunting challenges in regenerative medicine, such as controlling trigger differentiation, immune reactions, limited supply of stem cells, and engineering complex tissue structures. Specifically, the interactions between stem cells and their microenvironment play key roles in controlling stem cell fate, which underlines therapeutic success. However, the interactions between nanomaterials and stem cells are not well understood, and the effects of the nanomaterials shape, surface morphology, and chemical functionality on cellular processes need critical evaluation. In this Review, focus is put on recent development in nanomaterial-stem cell interactions, with specific emphasis on their application in regenerative medicine. Further, the emerging technologies based on nanomaterials developed over the past decade for stem cell engineering are reviewed, as well as the potential applications of these nanomaterials in tissue regeneration, stem cell isolation, and drug/gene delivery. It is anticipated that the enhanced understanding of nanomaterial-stem cell interactions will facilitate improved biomaterial design for a range of biomedical and biotechnological applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. The Need for Speed in Rodent Locomotion Analyses

    Batka, Richard J.; Brown, Todd J.; Mcmillan, Kathryn P.; Meadows, Rena M.; Jones, Kathryn J.; Haulcomb, Melissa M.


    Locomotion analysis is now widely used across many animal species to understand the motor defects in disease, functional recovery following neural injury, and the effectiveness of various treatments. More recently, rodent locomotion analysis has become an increasingly popular method in a diverse range of research. Speed is an inseparable aspect of locomotion that is still not fully understood, and its effects are often not properly incorporated while analyzing data. In this hybrid manuscript, we accomplish three things: (1) review the interaction between speed and locomotion variables in rodent studies, (2) comprehensively analyze the relationship between speed and 162 locomotion variables in a group of 16 wild-type mice using the CatWalk gait analysis system, and (3) develop and test a statistical method in which locomotion variables are analyzed and reported in the context of speed. Notable results include the following: (1) over 90% of variables, reported by CatWalk, were dependent on speed with an average R2 value of 0.624, (2) most variables were related to speed in a nonlinear manner, (3) current methods of controlling for speed are insufficient, and (4) the linear mixed model is an appropriate and effective statistical method for locomotion analyses that is inclusive of speed-dependent relationships. Given the pervasive dependency of locomotion variables on speed, we maintain that valid conclusions from locomotion analyses cannot be made unless they are analyzed and reported within the context of speed. PMID:24890845

  8. Combining Bio-inspired Sensing with Bio-inspired Locomotion

    Shaikh, Danish; Hallam, John; Christensen-Dalsgaard, Jakob

    In this paper we present a preliminary Braitenberg vehicle–like approach to combine bio-inspired audition with bio-inspired quadruped locomotion in simulation. Locomotion gaits of the salamander–like robot Salamandra robotica are modified by a lizard’s peripheral auditory system model that modula......In this paper we present a preliminary Braitenberg vehicle–like approach to combine bio-inspired audition with bio-inspired quadruped locomotion in simulation. Locomotion gaits of the salamander–like robot Salamandra robotica are modified by a lizard’s peripheral auditory system model...

  9. Investigation of the response of low-dose irradiated cells. Pt. 2. Radio-adaptive response of human embryonic cells is related to cell-to-cell communication

    Ishii, Keiichiro; Watanabe, Masami.


    To clarify the radio-adaptive response of normal cells to low-dose radiation, we irradiated human embryonic cells and HeLa cells with low-dose X-ray and examined the changes in sensitivity to subsequent high-dose X-irradiation. The results obtained were as follows; (1) When HE cells were irradiated by a high-dose of 200 cGy, the growth ratio of the living cells five days after the irradiation decreased to 37% of that of the cells which received no X-irradiation. When the cells received a preliminary irradiation of 10 to 20 cGy four hours before the irradiation of 200 cGy, the relative growth ratios increased significantly to 45-53%. (2) This preliminary irradiation effect was not observed in HeLa cells, being cancer cells. (3) When the HE cells suspended in a Ca 2+ iron-free medium or TPA added medium while receiving the preliminary irradiation of 13 cGy, the effect of the preliminary irradiation in increasing the relative growth ratio of living cells was not observed. (4) This indicates that normal cells shows an adaptive response to low-dose radiation and become more radioresistant. This phenomenon is considered to involve cell-to-cell communication maintained in normal cells and intracellular signal transduction in which Ca 2+ ion plays a role. (author)

  10. Stem Cells Matter in Response to Fasting

    Badi Sri Sailaja


    Full Text Available The molecular processes underlying intestinal adaptation to fasting and re-feeding remain largely uncharacterized. In this issue of Cell Reports, Richmond et al. report that dormant intestinal stem cells are regulated by PTEN and nutritional status.

  11. Dynamic investigation of a locomotive with effect of gear transmissions under tractive conditions

    Chen, Zaigang; Zhai, Wanming; Wang, Kaiyun


    Locomotive is used to drag trailers to move or supply the braking forces to slow the running speed of a train. The electromagnetic torque of the motor is always transmitted by the gear transmission system to the wheelset for generation of the tractive or braking forces at the wheel-rail contact interface. Consequently, gear transmission system is significant for power delivery of a locomotive. This paper develops a comprehensive locomotive-track vertical-longitudinal coupled dynamics model with dynamic effect of gear transmissions. This dynamics model enables considering the coupling interactions between the gear transmission motion, the vertical and the longitudinal motions of the vehicle, and the vertical vibration of the track structure. In this study, some complicated dynamic excitations, such as the gear time-varying mesh stiffness, nonlinear gear tooth backlash, the nonlinear wheel-rail normal contact force and creep force, and the rail vertical geometrical irregularity, are considered. Then, the dynamic responses of the locomotive under the tractive conditions are demonstrated by numerical simulations based on the established dynamics model and by experimental test. The developed dynamics model is validated by the good agreement between the experimental and the theoretical results. The calculated results reveal that the gear transmission system has strong dynamic interactions with the wheel-rail contact interface including both the vertical and the longitudinal motions, and it has negligible effect on the vibrations of the bogie frame and carbody.

  12. Morphological self stabilization of locomotion gaits: illustration on a few examples from bio-inspired locomotion.

    Chevallereau, Christine; Boyer, Frédéric; Porez, Mathieu; Mauny, Johan; Aoustin, Yannick


    To a large extent, robotics locomotion can be viewed as cyclic motions, named gaits. Due to the high complexity of the locomotion dynamics, to find the control laws that ensure an expected gait and its stability with respect to external perturbations, is a challenging issue for feedback control. To address this issue, a promising way is to take inspiration from animals that intensively exploit the interactions of the passive degrees of freedom of their body with their physical surroundings, to outsource the high-level exteroceptive feedback control to low-level proprioceptive ones. In this case, passive interactions can ensure most of the expected control goals. In this article, we propose a methodological framework to study the role of morphology in the design of locomotion gaits and their stability. This framework ranges from modelling to control aspects, and is illustrated through three examples from bio-inspired locomotion: a three-dimensional micro air vehicle in hovering flight, a pendular planar climber and a bipedal planar walker. In these three cases, we will see how simple considerations based on the morphology of the body can ensure the existence of passive stable gaits without requiring any high-level control.

  13. Performance requirements for locomotive braking systems

    Vermaak, P


    Full Text Available operated “Neutral Brake”. This brake may become active immediately or after a certain time delay when the controller is placed in the neutral position or moved into the neutral position by the “dead-man’s device”. Because this brake will interfere... in testing emergency brake systems due to the inherent braking action of the service brakes and/or locomotive controllers; • Potential problems limitations to braking effort associated with the prime movers and/or hydraulic systems on hydrostatically...

  14. The slow cell death response when screening chemotherapeutic agents.

    Blois, Joseph; Smith, Adam; Josephson, Lee


    To examine the correlation between cell death and a common surrogate of death used in screening assays, we compared cell death responses to those obtained with the sulforhodamine B (SRB) cell protein-based "cytotoxicity" assay. With the SRB assay, the Hill equation was used to obtain an IC50 and final cell mass, or cell mass present at infinite agent concentrations, with eight adherent cell lines and four agents (32 agent/cell combinations). Cells were treated with high agent concentrations (well above the SRB IC50) and the death response determined as the time-dependent decrease in cells failing to bind both annexin V and vital fluorochromes by flow cytometry. Death kinetics were categorized as fast (5/32) (similar to the reference nonadherent Jurkat line), slow (17/32), or none (10/32), despite positive responses in the SRB assay in all cases. With slow cell death, a single exposure to a chemotherapeutic agent caused a slow, progressive increase in dead (necrotic) and dying (apoptotic) cells for at least 72 h. Cell death (defined by annexin and/or fluorochrome binding) did not correlate with the standard SRB "cytotoxicity" assay. With the slow cell death response, a single exposure to an agent caused a slow conversion from vital to apoptotic and necrotic cells over at least 72 h (the longest time point examined). Here, increasing the time of exposure to agent concentrations modestly above the SRB IC50 provides a method of maximizing cell kill. If tumors respond similarly, sustained low doses of chemotherapeutic agents, rather than a log-kill, maximum tolerated dose strategy may be an optimal strategy of maximizing tumor cell death.

  15. System-wide Analysis of the T Cell Response

    Ruxandra Covacu


    Full Text Available The T cell receptor (TCR controls the cellular adaptive immune response to antigens, but our understanding of TCR repertoire diversity and response to challenge is still incomplete. For example, TCR clones shared by different individuals with minimal alteration to germline gene sequences (public clones are detectable in all vertebrates, but their significance is unknown. Although small in size, the zebrafish TCR repertoire is controlled by processes similar to those operating in mammals. Thus, we studied the zebrafish TCR repertoire and its response to stimulation with self and foreign antigens. We found that cross-reactive public TCRs dominate the T cell response, endowing a limited TCR repertoire with the ability to cope with diverse antigenic challenges. These features of vertebrate public TCRs might provide a mechanism for the rapid generation of protective T cell immunity, allowing a short temporal window for the development of more specific private T cell responses.

  16. Mesenchymal stem cells induce dermal fibroblast responses to injury

    Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.


    Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.

  17. The radiation response of cells recovering after chronic hypoxia

    Kwok, T.T.; Sutherland, R.M.


    Experiments were performed to study the influence of hypoxic pretreatment on the radiation response of A431 human squamous carcinoma cells. Reaeration for 10 min after chronic hypoxia (greater than 2 h) was found to enhance the radiosensitivity of A431 cells, and the maximal effect was seen for those cells reaerated after 12 h of hypoxia. The radiosensitivity enhancement for reaerated cells after 12 h of hypoxia was maximized by 5 min after the return to aerobic conditions and reached the control level by 12 h of reaeration. This enhanced radiosensitive state was characterized by a reduced shoulder region and increased slope of the radiation dose-response curve for cells in both the exponential and plateau phases of growth. There was a slight increase in the number of G1 and decrease in the number of S and G2 + M cells for both exponential- and plateau-phase cultures following 12 h hypoxic treatment. Although growth inhibition induced by 12 h of hypoxia was seen for cells in the exponential phase, there was no cell number change in the plateau-phase culture after hypoxia. Plating efficiency (PE) of cells in both growth phases was reduced by 30% after hypoxia. Furthermore, in the exponential-phase culture, the extent of reduction in PE after hypoxia was similar among cells in different phases of the cell cycle. Although S-phase cells in exponentially growing cultures were relatively more resistant to radiation than G1 and G2 + M cells, the cell age-response pattern was the same whether the cells had been aerobic or hypoxic before reaeration and irradiation. Furthermore, the enhancement ratio associated with reaeration after 12 h of hypoxia for these three subpopulations of cells was 1.3. Our results indicate that the increase in radiosensitivity due to reaeration after chronic hypoxia is unlikely to be related to the changes of cell cycle stage and growth phase during hypoxic treatment

  18. The intersection between DNA damage response and cell death pathways.

    Nowsheen, S; Yang, E S


    Apoptosis is a finely regulated process that serves to determine the fate of cells in response to various stresses. One such stress is DNA damage, which not only can signal repair processes but is also intimately involved in regulating cell fate. In this review we examine the relationship between the DNA damage/repair response in cell survival and apoptosis following insults to the DNA. Elucidating these pathways and the crosstalk between them is of great importance, as they eventually contribute to the etiology of human disease such as cancer and may play key roles in determining therapeutic response. This article is part of a Special Issue entitled "Apoptosis: Four Decades Later".

  19. Proprioceptive Actuation Design for Dynamic Legged locomotion

    Kim, Sangbae; Wensing, Patrick; Biomimetic Robotics Lab Team

    Designing an actuator system for highly-dynamic legged locomotion exhibited by animals has been one of the grand challenges in robotics research. Conventional actuators designed for manufacturing applications have difficulty satisfying challenging requirements for high-speed locomotion, such as the need for high torque density and the ability to manage dynamic physical interactions. It is critical to introduce a new actuator design paradigm and provide guidelines for its incorporation in future mobile robots for research and industry. To this end, we suggest a paradigm called proprioceptive actuation, which enables highly- dynamic operation in legged machines. Proprioceptive actuation uses collocated force control at the joints to effectively control contact interactions at the feet under dynamic conditions. In the realm of legged machines, this paradigm provides a unique combination of high torque density, high-bandwidth force control, and the ability to mitigate impacts through backdrivability. Results show that the proposed design provides an impact mitigation factor that is comparable to other quadruped designs with series springs to handle impact. The paradigm is shown to enable the MIT Cheetah to manage the application of contact forces during dynamic bounding, with results given down to contact times of 85ms and peak forces over 450N. As a result, the MIT Cheetah achieves high-speed 3D running up to 13mph and jumping over an 18-inch high obstacle. The project is sponsored by DARPA M3 program.

  20. Epidermal stem cells response to radiative genotoxic stress

    Marie, Melanie


    Human skin is the first organ exposed to various environmental stresses, which requires the development by skin stem cells of specific mechanisms to protect themselves and to ensure tissue homeostasis. As stem cells are responsible for the maintenance of epidermis during individual lifetime, the preservation of genomic integrity in these cells is essential. My PhD aimed at exploring the mechanisms set up by epidermal stem cells in order to protect themselves from two genotoxic stresses, ionizing radiation (Gamma Rays) and ultraviolet radiation (UVB). To begin my PhD, I have taken part of the demonstration of protective mechanisms used by keratinocyte stem cells after ionizing radiation. It has been shown that these cells are able to rapidly repair most types of radiation-induced DNA damage. Furthermore, we demonstrated that this repair is activated by the fibroblast growth factor 2 (FGF2). In order to know if this protective mechanism is also operating in cutaneous carcinoma stem cells, we investigated the response to gamma Rays of carcinoma stem cells isolated from a human carcinoma cell line. As in normal keratinocyte stem cells, we demonstrated that cancer stem cells could rapidly repair radio-induced DNA damage. Furthermore, fibroblast growth factor 2 also mediates this repair, notably thanks to its nuclear isoforms. The second project of my PhD was to study human epidermal stem cells and progenitors responses to UVB radiation. Once cytometry and irradiation conditions were set up, the toxicity of UVB radiation has been evaluate in the primary cell model. We then characterized UVB photons effects on cell viability, proliferation and repair of DNA damage. This study allowed us to bring out that responses of stem cells and their progeny to UVB are different, notably at the level of part of their repair activity of DNA damage. Moreover, progenitors and stem cells transcriptomic responses after UVB irradiation have been study in order to analyze the global

  1. Undulatory locomotion of finite filaments: lessons from Caenorhabditis elegans

    Berman, R S; Kenneth, O; Sznitman, J; Leshansky, A M


    Undulatory swimming is a widespread propulsion strategy adopted by many small-scale organisms including various single-cell eukaryotes and nematodes. In this work, we report a comprehensive study of undulatory locomotion of a finite filament using (i) approximate resistive force theory (RFT) assuming a local nature of hydrodynamic interaction between the filament and the surrounding viscous liquid and (ii) particle-based numerical computations taking into account the intra-filament hydrodynamic interaction. Using the ubiquitous model of a propagating sinusoidal waveform, we identify the limit of applicability of the RFT and determine the optimal propulsion gait in terms of (i) swimming distance per period of undulation and (ii) hydrodynamic propulsion efficiency. The occurrence of the optimal swimming gait maximizing hydrodynamic efficiency at finite wavelength in particle-based computations diverges from the prediction of the RFT. To compare the model swimmer powered by sine wave undulations to biological undulatory swimmers, we apply the particle-based approach to study locomotion of the model organism nematode Caenorhabditis elegans using the swimming gait extracted from experiments. The analysis reveals that even though the amplitude and the wavenumber of undulations are similar to those determined for the best performing sinusoidal swimmer, C. elegans overperforms the latter in terms of both displacement and hydrodynamic efficiency. Further comparison with other undulatory microorganisms reveals that many adopt waveforms with characteristics similar to the optimal model swimmer, yet real swimmers still manage to beat the best performing sine-wave swimmer in terms of distance covered per period. Overall our results underline the importance of further waveform optimization, as periodic undulations adopted by C. elegans and other organisms deviate considerably from a simple sine wave. (paper)

  2. [Skin cell response after jellyfish sting].

    Adamicová, Katarína; Výbohová, Desanka; Fetisovová, Želmíra; Nováková, Elena; Mellová, Yvetta


    Jellyfish burning is not commonly part of the professional finding in the central Europe health care laboratory. Holiday seaside tourism includes different and unusual presentations of diseases for our worklplaces. Sea water-sports and leisure is commonly connected with jellyfish burning and changes in the skin, that are not precisely described. Authors focused their research on detection of morphological and quantitative changes of some inflammatory cells in the skin biopsy of a 59-years-old woman ten days after a jellyfish stinging. Because of a comparison of findings the biopsy was performed in the skin with lesional and nonlesional skin. Both excisions of the skin were tested by imunohistochemical methods to detect CD68, CD163, CD30, CD4, CD3, CD8, CD20 a CD1a, to detect histiocytes, as well as several clones of lymphocytes and Langerhans cells (antigen presenting cells of skin), CD 117, toluidin blue and chloracetase esterase to detect mastocytes and neutrophils. Material was tested by immunofluorescent methods to detect IgA, IgM, IgG, C3, C4, albumin and fibrinogen. Representative view-fields were documented by microscope photocamera Leica DFC 420 C. Registered photos from both samples of the skin were processed by morphometrical analysis by the Vision Assistant software. A student t-test was used for statistical analysis of reached results. Mean values of individual found cells in the sample with lesion and without lesion were as follows: CD117 -2.64/0.37, CD68-6.86/1.63, CD163-3.13/2.23, CD30-1.36/0.02, CD4-3.51/0.32, CD8-8.22/0.50, CD3-10.69/0.66, CD20-0.56/0.66, CD1a-7.97/0.47 respectively. Generally mild elevation of eosinofils in lesional skin was detected. Increased values of tested cells seen in excision from lesional skin when compared with nonlesional ones were statistically significant in eight case at the level p = 0.033 to 0.001. A not statistically significant difference was found only in the group of CD163+ histiocytes. Authors detected numbers

  3. 49 CFR 232.105 - General requirements for locomotives.


    ... locomotives. (a) The air brake equipment on a locomotive shall be in safe and suitable condition for service... set pressure at any service application with the brakes control valve in the freight position. If such... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION BRAKE SYSTEM SAFETY STANDARDS FOR FREIGHT AND OTHER NON-PASSENGER...

  4. 49 CFR 230.106 - Steam locomotive frame.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotive frame. 230.106 Section 230.106... Tenders Trucks, Frames and Equalizing System § 230.106 Steam locomotive frame. (a) Maintenance and inspection. Frames, decks, plates, tailpieces, pedestals, and braces shall be maintained in a safe and...

  5. Locomotive emissions measurements for various blends of biodiesel fuel.


    The objective of this project was to assess the effects of various blends of biodiesel on locomotive engine exhaust emissions. The : emission tests were conducted on two locomotive models, a Tier 2 EMD SD70ACe and a Tier 1 Plus GE Dash9-44CW, using t...


    S. V. Pylypenko


    Full Text Available In the article the results of dynamic running and traction-energy tests of the electric locomotive VL40U are presented. In accordance with the test results a conclusion about the suitability of electric locomotive of such a type for operation with trains containing up to 15 passenger coaches inclusive is made.

  7. Architectures of soft robotic locomotion enabled by simple mechanical principles.

    Zhu, Liangliang; Cao, Yunteng; Liu, Yilun; Yang, Zhe; Chen, Xi


    In nature, a variety of limbless locomotion patterns flourish, from the small or basic life forms (Escherichia coli, amoebae, etc.) to the large or intelligent creatures (e.g., slugs, starfishes, earthworms, octopuses, jellyfishes, and snakes). Many bioinspired soft robots based on locomotion have been developed in the past few decades. In this work, based on the kinematics and dynamics of two representative locomotion modes (i.e., worm-like crawling and snake-like slithering), we propose a broad set of innovative designs for soft mobile robots through simple mechanical principles. Inspired by and going beyond the existing biological systems, these designs include 1-D (dimensional), 2-D, and 3-D robotic locomotion patterns enabled by the simple actuation of continuous beams. We report herein over 20 locomotion modes achieving various locomotion functions, including crawling, rising, running, creeping, squirming, slithering, swimming, jumping, turning, turning over, helix rolling, wheeling, etc. Some are able to reach high speed, high efficiency, and overcome obstacles. All these locomotion strategies and functions can be integrated into a simple beam model. The proposed simple and robust models are adaptive for severe and complex environments. These elegant designs for diverse robotic locomotion patterns are expected to underpin future deployments of soft robots and to inspire a series of advanced designs.

  8. Modular control of limb movements during human locomotion

    Ivanenko, Yuri P; Cappellini, Germana; Dominici, Nadia; Poppele, Richard E; Lacquaniti, Francesco


    The idea that the CNS may control complex interactions by modular decomposition has received considerable attention. We explored this idea for human locomotion by examining limb kinematics. The coordination of limb segments during human locomotion has been shown to follow a planar law for walking at

  9. The Determination of the Asynchronous Traction Motor Characteristics of Locomotive

    Pavel Grigorievich Kolpakhchyan


    Full Text Available The article deals with the problem of the locomotive asynchronous traction motor control with the AC diesel-electric transmission. The limitations of the torque of the traction motor when powered by the inverter are determined. The recommendations to improve the use of asynchronous traction motor of locomotives with the AC diesel-electric transmission are given.


    T. V. Butko


    Full Text Available Purpose. The efficiency and safety of locomotive control improving is important and relevant scientific and practical problem. Every driver during the trains-handling bases on his experience and knowledge, that is why the compilation and detection the most efficient ways to control the locomotive-handling is one of the stages of measures development to reduce transportation costs. The purpose of this paper is a formalization process description of locomotive-handling and quality parameters determination of this process. Methodology. In order to achieve this goal the theory of fuzzy probabilistic graphs was used. Vertices of the graph correspond to the events start and end operations at train-handling. The graph arcs describe operations on train-handling. Graph consists of thirteen peaks corresponding to the main control actions of the engine-driver. The weighting factors of transitions between vertices are assigned by fuzzy numbers. Their values were obtained by expert estimates. Fuzzy probabilities and transition time are presented as numbers with trapezoidal membership function. Findings. Using successive merging of parallel arcs, loops and vertices elimination, the equivalent fuzzy graph of train-handling and the corresponding L-matrix were obtained. Equivalent graph takes into account separately activity of the driver during normal operation and during emergency situations. Originality. The theoretical foundations of describing process formalization in driver’s locomotive-handling activity were developed using the fuzzy probabilistic graph. The parameters characterizing the decision-making process of engineer were obtained. Practical value. With the resulting model it is possible to estimate the available reserves for the quality improvement of locomotive-handling. Reduction in the time for decision-making will lead to the approximation the current mode of control to the rational one and decrease costs of hauling operations. And reduction

  11. Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat.

    Baev, K V; Esipenko, V B; Shimansky YuP


    Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high-intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just

  12. iNKT cells suppress the CD8+ T cell response to a murine Burkitt's-like B cell lymphoma.

    Ryan L Bjordahl

    Full Text Available The T cell response to B cell lymphomas differs from the majority of solid tumors in that the malignant cells themselves are derived from B lymphocytes, key players in immune response. B cell lymphomas are therefore well situated to manipulate their surrounding microenvironment to enhance tumor growth and minimize anti-tumor T cell responses. We analyzed the effect of T cells on the growth of a transplantable B cell lymphoma and found that iNKT cells suppressed the anti-tumor CD8(+ T cell response. Lymphoma cells transplanted into syngeneic wild type (WT mice or Jalpha18(-/- mice that specifically lack iNKT cells grew initially at the same rate, but only the mice lacking iNKT cells were able to reject the lymphoma. This effect was due to the enhanced activity of tumor-specific CD8(+ T cells in the absence of iNKT cells, and could be partially reversed by reconstitution of iNKT cells in Jalpha 18(-/- mice. Treatment of tumor-bearing WT mice with alpha -galactosyl ceramide, an activating ligand for iNKT cells, reduced the number of tumor-specific CD8(+ T cells. In contrast, lymphoma growth in CD1d1(-/- mice that lack both iNKT and type II NKT cells was similar to that in WT mice, suggesting that type II NKT cells are required for full activation of the anti-tumor immune response. This study reveals a tumor-promoting role for iNKT cells and suggests their capacity to inhibit the CD8(+ T cell response to B cell lymphoma by opposing the effects of type II NKT cells.

  13. Locomotion Gait Planning of Climber Snake-Like Robot

    Mohammad Nezaminia


    Full Text Available In this article a novel breed of snake-like climber robots has been introduced. Structure and operation of the first generation of snake-like climber robot "Marak I" has been discussed. The gait planning for two dimensional locomotion of a novel snake-like climber robot "Marak I" is presented. The types of locomotion investigated were rectilinear and wheeling gaits. The gaits of locomotion were experimented and their suitability for various applications has been mentioned. Some encountered practical problems plus solutions were addressed. Finally we found out that: the vertical motion was producing more fault than horizontal locomotion, and notably the fastest gait of locomotion was the wheeling gait

  14. Nonlinear dynamics analysis of the spur gear system for railway locomotive

    Wang, Junguo; He, Guangyue; Zhang, Jie; Zhao, Yongxiang; Yao, Yuan


    Considering the factors such as the nonlinearity backlash, static transmission error and time-varying meshing stiffness, a three-degree-of-freedom torsional vibration model of spur gear transmission system for a typical locomotive is developed, in which the wheel/rail adhesion torque is considered as uncertain but bounded parameter. Meantime, the Ishikawa method is used for analysis and calculation of the time-varying mesh stiffness of the gear pair in meshing process. With the help of bifurcation diagrams, phase plane diagrams, Poincaré maps, time domain response diagrams and amplitude-frequency spectrums, the effects of the pinion speed and stiffness on the dynamic behavior of gear transmission system for locomotive are investigated in detail by using the numerical integration method. Numerical examples reveal various types of nonlinear phenomena and dynamic evolution mechanism involving one-period responses, multi-periodic responses, bifurcation and chaotic responses. Some research results present useful information to dynamic design and vibration control of the gear transmission system for railway locomotive.

  15. Phenomenon of adaptive response of cells in radiobiology

    Fillipovich, I.V.


    Consideration is given to various adaptive reactions to low-level radiation, their association with an absorbed dose, dose rate, radiation quality and time-interval between exposures, as well as with a cell cycle phase. Possible mechanisms of the adaptive response and the character and role of DNA damages, that can induce gene expression of the adaptive response, are discussed. The data on the influence of a preliminary long-term exposure to low-level radiation on the radiosensitivity of biological objects are analyzed with due regard for the adaptive cell response. It is concluded that the adaptive response of cells to ionizing radiation is a particular case of the phenomenon of cell adaptation of the effect of genotoxic factors of the environment

  16. Dynamics of NKT-Cell Responses to Chlamydial Infection.

    Shekhar, Sudhanshu; Joyee, Antony George; Yang, Xi


    Natural killer T (NKT) cells have gained great attention owing to their critical functional roles in immunity to various pathogens. In this review, we provide an overview of the current knowledge on the role of NKT cells in host defense against and pathogenesis due to Chlamydia, which is an intracellular bacterial pathogen that poses a threat to the public health worldwide. Accumulating evidence has demonstrated that NKT cells, particularly invariant NKT (iNKT) cells, play a crucial role in host defense against chlamydial infections, especially in C. pneumoniae infection. iNKT cells can promote type-1 protective responses to C. pneumoniae by inducing enhanced production of IL-12 by dendritic cells (DCs), in particular CD8α+ DCs, which promote the differentiation of naive T cells into protective IFN-γ-producing Th1/Tc1 type CD4+/CD8+ T cells. This iNKT-cell-mediated modulation of DC function is largely dependent upon CD40-CD40L interaction, IFN-γ production, and cell-to-cell contact. In addition, iNKT cells modulate the function of natural killer cells. NKT cells may be also involved in the pathogenesis of some chlamydial diseases by inducing different patterns of cytokine production. A better understanding of NKT-cell biology will enable us to rationally design prophylactic and therapeutic tools to combat infectious diseases.

  17. 40 CFR 1033.515 - Discrete-mode steady-state emission tests of locomotives and locomotive engines.


    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Discrete-mode steady-state emission... Procedures § 1033.515 Discrete-mode steady-state emission tests of locomotives and locomotive engines. This... a warm-up followed by a sequence of nominally steady-state discrete test modes, as described in...

  18. Suppression of pro-inflammatory T-cell responses by human mesothelial cells.

    Lin, Chan-Yu; Kift-Morgan, Ann; Moser, Bernhard; Topley, Nicholas; Eberl, Matthias


    Human γδ T cells reactive to the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) contribute to acute inflammatory responses. We have previously shown that peritoneal dialysis (PD)-associated infections with HMB-PP producing bacteria are characterized by locally elevated γδ T-cell frequencies and poorer clinical outcome compared with HMB-PP negative infections, implying that γδ T cells may be of diagnostic, prognostic and therapeutic value in acute disease. The regulation by local tissue cells of these potentially detrimental γδ T-cell responses remains to be investigated. Freshly isolated γδ or αβ T cells were cultured with primary mesothelial cells derived from omental tissue, or with mesothelial cell-conditioned medium. Stimulation of cytokine production and proliferation by peripheral T cells in response to HMB-PP or CD3/CD28 beads was assessed by flow cytometry. Resting mesothelial cells were potent suppressors of pro-inflammatory γδ T cells as well as CD4+ and CD8+ αβ T cells. The suppression of γδ T-cell responses was mediated through soluble factors released by primary mesothelial cells and could be counteracted by SB-431542, a selective inhibitor of TGF-β and activin signalling. Recombinant TGF-β1 but not activin-A mimicked the mesothelial cell-mediated suppression of γδ T-cell responses to HMB-PP. The present findings indicate an important regulatory function of mesothelial cells in the peritoneal cavity by dampening pro-inflammatory T-cell responses, which may help preserve the tissue integrity of the peritoneal membrane in the steady state and possibly during the resolution of acute inflammation.

  19. Responses of fibroblasts and glial cells to nanostructured platinum surfaces

    Pennisi, C P; Sevcencu, C; Yoshida, K [Center for Sensory-Motor Interaction (SMI), Aalborg University, Aalborg (Denmark); Dolatshahi-Pirouz, A; Foss, M; Larsen, A Nylandsted; Besenbacher, F [Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus (Denmark); Hansen, J Lundsgaard [Department of Physics and Astronomy, Aarhus University, Aarhus (Denmark); Zachar, V, E-mail: cpennisi@hst.aau.d [Laboratory for Stem Cell Research, Aalborg University (Denmark)


    The chronic performance of implantable neural prostheses is affected by the growth of encapsulation tissue onto the stimulation electrodes. Encapsulation is associated with activation of connective tissue cells at the electrode's metallic contacts, usually made of platinum. Since surface nanotopography can modulate the cellular responses to materials, the aim of the present work was to evaluate the 'in vitro' responses of connective tissue cells to platinum strictly by modulating its surface nanoroughness. Using molecular beam epitaxy combined with sputtering, we produced platinum nanostructured substrates consisting of irregularly distributed nanopyramids and investigated their effect on the proliferation, cytoskeletal organization and cellular morphology of primary fibroblasts and transformed glial cells. Cells were cultured on these substrates and their responses to surface roughness were studied. After one day in culture, the fibroblasts were more elongated and their cytoskeleton less mature when cultured on rough substrates. This effect increased as the roughness of the surface increased and was associated with reduced cell proliferation throughout the observation period (4 days). Morphological changes also occurred in glial cells, but they were triggered by a different roughness scale and did not affect cellular proliferation. In conclusion, surface nanotopography modulates the responses of fibroblasts and glial cells to platinum, which may be an important factor in optimizing the tissue response to implanted neural electrodes.

  20. Cytokines and the Inception of CD8 T Cell Responses

    Cox, Maureen A.; Harrington, Laurie E.; Zajac, Allan J.


    The activation and differentiation of CD8 T cells is a necessary first step that endows these cells with the phenotypic and functional properties required for the control of intracellular pathogens. The induction of the CD8 T cell responses typically results in the development of a massive overall population of effector cells, comprised of both highly functional but short-lived terminally differentiated cells, as well as a smaller subset of precursors that are predisposed to survive and transition into the memory T cell pool. In this article we discuss how inflammatory cytokines and IL-2 bias the initial response towards short-lived effector generation and also highlight the potential counterbalancing role of IL-21. PMID:21371940

  1. Radiation response of haematopoietic cell lines of human origin

    Lehnert, S.; Rybka, W.B.; Suissa, S.; Giambattisto, D.


    Six human haematopoietic cell lines, five of leukaemic origin, including cells with myeloid, lymphoid and undifferentiated phenotype have been studied with respect to radiation response. The intrinsic radio-sensitivity of the cells varied widely, the D 0 s ranging from 0.53 to 1.39 Gy. Five of the cell lines showed some capacity to accumulate sublethal damage; in three of these, enhanced survival was demonstrated in split-dose experiments. One cell line (HL-60) was anomalous in that although little accumulation of sublethal damage was demonstrable, survival was enhanced by fractionation of the dose. Five of the six cell lines studied were of leukaemic origin. The results support the belief that, in contrast to the almost constant radiosensitivity of normal haematopoietic cell progenitors, leukaemic cell progenitors may show a wide range of radiosensitivities. (author)

  2. Tissue specific heterogeneity in effector immune cell response

    Saba eTufail


    Full Text Available Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct ‘homing codes’ (adhesion molecules and chemokine receptors during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A and sunlight (vitamin D3 prime dendritic cells, imprinting them to play centrestage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues alongwith giving an overview of tissue tropism in B cells.

  3. Cyperus scariosus Chloroform Fraction Inhibits T cell Responses in ...


    CSC did not significantly (p < 0.01) suppress Th2 (IL-4) system. Conclusion: The findings from this investigation reveal that C. scariosus causes immunosuppression by inhibiting Th1 cytokines. Keywords: Cyperus scariosus; Immunosuppression; Humoral antibody titre; Cell-mediated immune response; CD 4+ T- helper cells ...

  4. T Cell Responses: Naive to Memory and Everything in Between

    Pennock, Nathan D.; White, Jason T.; Cross, Eric W.; Cheney, Elizabeth E.; Tamburini, Beth A.; Kedl, Ross M.


    The authors describe the actions that take place in T cells because of their amazing capacity to proliferate and adopt functional roles aimed at clearing a host of an infectious agent. There is a drastic decline in the T cell population once the primary response is over and the infection is terminated. What remains afterward is a population of T…

  5. A response calculus for immobilized T cell receptor ligands

    Andersen, P S; Menné, C; Mariuzza, R A


    determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated...

  6. Radiation adaptive response for the growth of cultured glial cells

    Suzuki, S.; Miura, Y.; Kano, M.; Toda, T.; Urano, S.


    Full text: To examine the molecular mechanism of radiation adaptive response (RAR) for the growth of cultured glial cells and to investigate the influence of aging on the response, glial cells were cultured from young and aged rats (1 month and 24 months old). RAR for the growth of glial cells conditioned with a low dose of X-rays and subsequently exposed to a high dose of X-rays was examined for cell number and BrdU incorporation. Involvement of the subcellular signaling pathway factors in RAR was investigated using their inhibitors, activators and mutated glial cells. RAR was observed in cells cultured from young rats, but was not in cells from aged rats. The inhibitors of protein kinase C (PKC) and DNA-dependent protein kinase (DNA-PK) or phosphatidylinositol 3-kinase (PI3K) suppressed RAR. The activators of PKC instead of low dose irradiation also caused RAR. Moreover, glial cells cultured from severe combined immunodeficiency (scid) mice (CB-17 scid) and ataxia-telangiectasia (AT) cells from AT patients showed no RAR. These results indicated that PKC, ATM, DNAPK and/or PI3K were involved in RAR for growth and BrdU incorporation of cultured glial cells and RAR decreased with aging. Proteomics data of glial cells exposed to severe stress of H 2 O 2 or X-rays also will be presented in the conference since little or no difference has not been observed with slight stress yet

  7. Temporal Analyses of the Response of Intervertebral Disc Cells and Mesenchymal Stem Cells to Nutrient Deprivation

    Sarah A. Turner


    Full Text Available Much emphasis has been placed recently on the repair of degenerate discs using implanted cells, such as disc cells or bone marrow derived mesenchymal stem cells (MSCs. This study examines the temporal response of bovine and human nucleus pulposus (NP cells and MSCs cultured in monolayer following exposure to altered levels of glucose (0, 3.15, and 4.5 g/L and foetal bovine serum (0, 10, and 20% using an automated time-lapse imaging system. NP cells were also exposed to the cell death inducers, hydrogen peroxide and staurosporine, in comparison to serum starvation. We have demonstrated that human NP cells show an initial “shock” response to reduced nutrition (glucose. However, as time progresses, NP cells supplemented with serum recover with minimal evidence of cell death. Human NP cells show no evidence of proliferation in response to nutrient supplementation, whereas MSCs showed greater response to increased nutrition. When specifically inducing NP cell death with hydrogen peroxide and staurosporine, as expected, the cell number declined. These results support the concept that implanted NP cells or MSCs may be capable of survival in the nutrient-poor environment of the degenerate human disc, which has important clinical implications for the development of IVD cell therapies.

  8. Regulatory T Cells and Host Anti-CML Responses

    Wong, Jr, K. K


    CD4+CD25+FoxP-3+ regulatory T-cells (Tregs) suppress immune responses to "self" antigens, but also have been shown to suppress host anti-tumor responses in several human malignancies, including breast, gastrointestinal, and ovarian cancer...

  9. Cerebellar contribution to feedforward control of locomotion.

    Pisotta, Iolanda; Molinari, Marco


    The cerebellum is an important contributor to feedforward control mechanisms of the central nervous system, and sequencing-the process that allows spatial and temporal relationships between events to be recognized-has been implicated as the fundamental cerebellar mode of operation. By adopting such a mode and because cerebellar activity patterns are sensitive to a variety of sensorimotor-related tasks, the cerebellum is believed to support motor and cognitive functions that are encoded in the frontal and parietal lobes of the cerebral cortex. In this model, the cerebellum is hypothesized to make predictions about the consequences of a motor or cognitive command that originates from the cortex to prepare the entire system to cope with ongoing changes. In this framework, cerebellar predictive mechanisms for locomotion are addressed, focusing on sensorial and motoric sequencing. The hypothesis that sequence recognition is the mechanism by which the cerebellum functions in gait control is presented and discussed.

  10. Natural killer cells promote early CD8 T cell responses against cytomegalovirus.

    Scott H Robbins


    Full Text Available Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs for cytokine production, preserves the conventional dendritic cell (cDC compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate

  11. Modulation of immune response by alloactivated suppressor T cells

    Bernstein, A.; Sopori, M.L.; Gose, J.E.; Sondel, P.M.


    These studies show that there may be several different kinds of suppressor cells, each activated by different pathways and able to suppress different parts of the immune response either specifically or nonspecifically. As such, the physiology of one type of suppressor cell need not necessarily apply to that of another type of suppressor. Thus we emphasize the trap that the suppressor cell option provides: that is, virtually any previously inexplicable in vitro and in vivo immune phenomenon can always be adequately accounted for by evoking a suppressor mechanism, either by suppressing the response or suppressing the suppressor

  12. Phagocytic response of astrocytes to damaged neighboring cells.

    Nicole M Wakida

    Full Text Available This study aims to understand the phagocytic response of astrocytes to the injury of neurons or other astrocytes at the single cell level. Laser nanosurgery was used to damage individual cells in both primary mouse cortical astrocytes and an established astrocyte cell line. In both cases, the release of material/substances from laser-irradiated astrocytes or neurons induced a phagocytic response in near-by astrocytes. Propidium iodide stained DNA originating from irradiated cells was visible in vesicles of neighboring cells, confirming phagocytosis of material from damaged cortical cells. In the presence of an intracellular pH indicator dye, newly formed vesicles correspond to acidic pH fluorescence, thus suggesting lysosome bound degradation of cellular debris. Cells with shared membrane connections prior to laser damage had a significantly higher frequency of induced phagocytosis compared to isolated cells with no shared membrane. The increase in phagocytic response of cells with a shared membrane occurred regardless of the extent of shared membrane (a thin filopodial connection vs. a cell cluster with significant shared membrane. In addition to the presence (or lack of a membrane connection, variation in phagocytic ability was also observed with differences in injury location within the cell and distance separating isolated astrocytes. These results demonstrate the ability of an astrocyte to respond to the damage of a single cell, be it another astrocyte, or a neuron. This single-cell level of analysis results in a better understanding of the role of astrocytes to maintain homeostasis in the CNS, particularly in the sensing and removal of debris in damaged or pathologic nervous tissue.

  13. Dynamic legged locomotion in robots and animals

    Raibert, Marc; Playter, Robert; Ringrose, Robert; Bailey, Dave; Leeser, Karl


    This report documents our study of active legged systems that balance actively and move dynamically. The purpose of this research is to build a foundation of knowledge that can lead both to the construction of useful legged vehicles and to a better understanding of how animal locomotion works. In this report we provide an update on progress during the past year. Here are the topics covered in this report: (1) Is cockroach locomotion dynamic? To address this question we created three models of cockroaches, each abstracted at a different level. We provided each model with a control system and computer simulation. One set of results suggests that 'Groucho Running,' a type of dynamic walking, seems feasible at cockroach scale. (2) How do bipeds shift weight between the legs? We built a simple planar biped robot specifically to explore this question. It shifts its weight from one curved foot to the other, using a toe-off and toe-on strategy, in conjunction with dynamic tipping. (3) 3D biped gymnastics: The 3D biped robot has done front somersaults in the laboratory. The robot changes its leg length in flight to control rotation rate. This in turn provides a mechanism for controlling the landing attitude of the robot once airborne. (4) Passively stabilized layout somersault: We have found that the passive structure of a gymnast, the configuration of masses and compliances, can stabilize inherently unstable maneuvers. This means that body biomechanics could play a larger role in controlling behavior than is generally thought. We used a physical 'doll' model and computer simulation to illustrate the point. (5) Twisting: Some gymnastic maneuvers require twisting. We are studying how to couple the biomechanics of the system to its control to produce efficient, stable twisting maneuvers.

  14. Studies on adaptive responses in Chinese hamster cells

    Michelin, S.C.; Perez, M.R. Del; Dubner, D.; Gisone, P.A.


    For many years the possibility has been considered of low doses of radiation inducing adaptive responses in cells and organisms against the mutagenic effects of radiation. Currently, a number of experimental data appraise the existence of an adaptive response that is characterized by a decrease of radiation induced genetic damages. The understanding of the molecular mechanism involved in this phenomenon permits to estimate the effects and risks of low dose exposure. In this work, preliminary results of studies on the induction of adaptive response in cells subjected to different doses of ionizing radiation are presented

  15. Antitumor Responses of Invariant Natural Killer T Cells

    Jennie B. Altman


    Full Text Available Natural killer T (NKT cells are innate-like lymphocytes that were first described in the late 1980s. Since their initial description, numerous studies have collectively shed light on their development and effector function. These studies have highlighted the unique requirements for the activation of these lymphocytes and the functional responses that distinguish these cells from other effector lymphocyte populations such as conventional T cells and NK cells. This body of literature suggests that NKT cells play diverse nonredundant roles in a number of disease processes, including the initiation and propagation of airway hyperreactivity, protection against a variety of pathogens, development of autoimmunity, and mediation of allograft responses. In this review, however, we focus on the role of a specific lineage of NKT cells in antitumor immunity. Specifically, we describe the development of invariant NKT (iNKT cells and the factors that are critical for their acquisition of effector function. Next, we delineate the mechanisms by which iNKT cells influence and modulate the activity of other immune cells to directly or indirectly affect tumor growth. Finally, we review the successes and failures of clinical trials employing iNKT cell-based immunotherapies and explore the future prospects for the use of such strategies.

  16. Healthy human T-Cell Responses to Aspergillus fumigatus antigens.

    Neelkamal Chaudhary


    Full Text Available Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (T(H1-T(H17 and destructive allergic (T(H2 immunity. How Aspergillus allergens (Asp f proteins participate in the development of allergic sensitization is unknown.To determine whether Asp f proteins are strictly associated with T(H2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-gamma, IL-4 or IL-17 to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-gamma more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 T(H1-responses to Asp f3 (a putative peroxismal membrane protein, Asp f9/16 (cell wall glucanase, Asp f11 (cyclophilin type peptidyl-prolyl isomerase and Asp f22 (enolase. Strong IFN-gamma responses were reproduced in most subjects tested over 6 month intervals.Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.

  17. Nanosecond electric pulses trigger actin responses in plant cells

    Berghoefer, Thomas; Eing, Christian; Flickinger, Bianca; Hohenberger, Petra; Wegner, Lars H.; Frey, Wolfgang; Nick, Peter


    We have analyzed the cellular effects of nanosecond pulsed electrical fields on plant cells using fluorescently tagged marker lines in the tobacco cell line BY-2 and confocal laser scanning microscopy. We observe a disintegration of the cytoskeleton in the cell cortex, followed by contraction of actin filaments towards the nucleus, and disintegration of the nuclear envelope. These responses are accompanied by irreversible permeabilization of the plasma membrane manifest as uptake of Trypan Blue. By pretreatment with the actin-stabilizing drug phalloidin, the detachment of transvacuolar actin from the cell periphery can be suppressed, and this treatment can also suppress the irreversible perforation of the plasma membrane. We discuss these findings in terms of a model, where nanosecond pulsed electric fields trigger actin responses that are key events in the plant-specific form of programmed cell death.

  18. The coordination between mechanical and chemical subsystems initiates locomotion of Physarum plasmodial fragments

    Zhang, Shun; Guy, Robert; Del Alamo, Juan Carlos


    Physarum polycephalum is a multinucleated slime mold whose endoplasm flows periodically driven by the contraction of its ectoplasm, a dense shell of F-actin cross-linked by myosin molecular motors and attached to the cell membrane. We find that physarum fragments smaller than 100 microns remain round and stay in place. However, larger fragments break symmetry leading to sustained forward locomotion, in process that is reminiscent of an interfacial instability that seems to settle around two different limit cycles (traveling waves and standing waves). We use both theory and experiments to study how coordination emerges between the different mechanical and chemical subsystems of the fragment to initiate locomotion. The role of many involved factors, such as fragment size, substratum adhesiveness, rheological properties, actin polymerization and traction stresses are investigated, and we find they agree well with our predictive model.

  19. Immunotherapeutic strategies targeting Natural killer T cell responses in cancer

    Shissler, Susannah C.; Bollino, Dominique R.; Tiper, Irina V.; Bates, Joshua; Derakhshandeh, Roshanak; Webb, Tonya J.


    Natural killer T (NKT) cells are a unique subset of lymphocytes that bridge the innate and adaptive immune system. NKT cells possess a classic αβ T-cell receptor (TCR) that is able to recognize self and foreign glycolipid antigens presented by the nonclassical class I major histocompatibility complex (MHC) molecule, CD1d. Type I NKT cells (referred to as invariant NKT cells) express a semi-invariant Vα14Jα18 TCR in mice and Vα24Jα18 TCR in humans. Type II NKT cells are CD1d-restricted T cells that express a more diverse set of TCR α chains. The two types of NKT cells often exert opposing effects especially in tumor immunity, where Type II cells generally suppress tumor immunity while Type I NKT cells can enhance antitumor immune responses. In this review, we focus on the role of NKT cells in cancer. We discuss their effector and suppressive functions, as well as describe preclinical and clinical studies utilizing therapeutic strategies focused on harnessing their potent anti-tumor effector functions, and conclude with a discussion on potential next steps for the utilization of NKT cell targeted therapies for the treatment of cancer. PMID:27393665

  20. T-cell proliferative responses following sepsis in neonatal rats.

    Dallal, Ousama; Ravindranath, Thyyar M; Choudhry, Mashkoor A; Kohn, Annamarie; Muraskas, Jonathan K; Namak, Shahla Y; Alattar, Mohammad H; Sayeed, Mohammed M


    Both experimental and clinical evidence suggest a suppression of T-cell function in burn and sepsis. The objective of the present study was to evaluate splenocyte and purified T-cell proliferative response and IL-2 production in septic neonatal rats. We also examined if alterations in T-cell proliferation and IL-2 production in neonatal sepsis is due to elevation in PGE2. PGE2 is known to play a significant role in T-cell suppression during sepsis in adults. Sepsis was induced in 15-day-old neonatal Sprague-Dawley rats by implanting 0.1 cm3 of fecal pellet impregnated with Escherichia coli (50 CFU) and Bacteroides fragilis (10(3) CFU). Animals receiving fecal pellets without the bacteria were designated as sterile. A group of septic and sterile rats were treated with PGE2 synthesis inhibitors, NS398 and resveratrol. These treatments of animals allowed us to evaluate the role of PGE2 in T-cell suppression during neonatal sepsis. Splenocytes as well as purified T cells were prepared and then proliferative response and IL-2 productive capacities were measured. A significant suppression of splenocyte proliferation and IL-2 production was noticed in both sterile and septic animals compared to the T cells from unoperated control rats. In contrast, the proliferation and IL-2 production by nylon wool purified T cells in sterile rats was not significantly different from control rats, whereas, a significant suppression in Con A-mediated T-cell proliferation and IL-2 production noticed in septic rat T cells compared to the sterile and control rat T cells. Such decrease in T-cell proliferation and IL-2 production was accompanied with 20-25% deaths in neonates implanted with septic pellets. No mortality was noted in sterile-implanted neonates. Treatment of animals with COX-1 inhibitor had no effect on T-cell proliferation response in both septic and sterile groups, whereas COX-2 inhibitor abrogated the decrease in T-cell proliferative response in the septic group. The treatment

  1. Cell-cycle distributions and radiation responses of Chinese hamster cells cultured continuously under hypoxic conditions

    Tokita, N.; Carpenter, S.G.; Raju, M.R.


    Cell-cycle distributions were measured by flow cytometry for Chinese hamster (CHO) cells cultured continuously under hypoxic conditions. DNA histograms showed an accumulation of cells in the early S phase followed by a traverse delay through the S phase, and a G 2 block. During hypoxic culturing, cell viability decreased rapidly to less than 0.1% at 120 h. Radiation responses for cells cultured under these conditions showed an extreme radioresistance at 72 h. Results suggest that hypoxia induces a condition similar to cell synchrony which itself changes the radioresistance of hypoxic cells. (author)

  2. A survey report for the turning of biped locomotion robot

    Kato, Ichiro; Takanishi, Atsuo; Kume, Etsuo.


    A mechanical design study of biped locomotion robots is going on at JAERI within the scope of the Human Acts Simulation Program (HASP). The design study at JAERI is of an arbitrarily mobile robot for inspection of nuclear facilities. A survey has been performed for collecting useful information from already existing biped locomotion robots. This is a survey report for the turning of biped locomotion robot: the WL-10R designed and developed at Waseda University. This report includes the control method of turning, machine model and control system. (author)

  3. T-cell activation and early gene response in dogs.

    Sally-Anne Mortlock

    Full Text Available T-cells play a crucial role in canine immunoregulation and defence against invading pathogens. Proliferation is fundamental to T-cell differentiation, homeostasis and immune response. Initiation of proliferation following receptor mediated stimuli requires a temporally programmed gene response that can be identified as immediate-early, mid- and late phases. The immediate-early response genes in T-cell activation engage the cell cycle machinery and promote subsequent gene activation events. Genes involved in this immediate-early response in dogs are yet to be identified. The present study was undertaken to characterise the early T-cell gene response in dogs to improve understanding of the genetic mechanisms regulating immune function. Gene expression profiles were characterised using canine gene expression microarrays and quantitative reverse transcription PCR (qRT-PCR, and paired samples from eleven dogs. Significant functional annotation clusters were identified following stimulation with phytohemagluttinin (PHA (5μg/ml, including the Toll-like receptor signaling pathway and phosphorylation pathways. Using strict statistical criteria, 13 individual genes were found to be differentially expressed, nine of which have ontologies that relate to proliferation and cell cycle control. These included, prostaglandin-endoperoxide synthase 2 (PTGS2/COX2, early growth response 1 (EGR1, growth arrest and DNA damage-inducible gene (GADD45B, phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, V-FOS FBJ murine osteosarcoma viral oncogene homolog (FOS, early growth response 2 (EGR2, hemogen (HEMGN, polo-like kinase 2 (PLK2 and polo-like kinase 3 (PLK3. Differential gene expression was re-examined using qRT-PCR, which confirmed that EGR1, EGR2, PMAIP1, PTGS2, FOS and GADD45B were significantly upregulated in stimulated cells and ALAS2 downregulated. PTGS2 and EGR1 showed the highest levels of response in these dogs. Both of these genes are involved in

  4. Rolling towards a cleaner future: the development of Canadian locomotive emissions regulations


    In 2006, the Government of Canada published a notice of intent that it would develop regulations aimed at reducing anthropogenic criteria air contaminants and greenhouse gas emissions. The Government now intends to develop railway emissions regulations for criteria air contaminants under the Railway Safety Act. The Railway Safety Act not only provides the legislative basis for developing regulations governing railways, it also gives the authority for developing the rules governing federally regulated railroads to the Minister of Transport. For the future, Transport Canada will be responsible for developing regulations governing the rail sector. The transportation sector is a substantial emitter of criteria air contaminants, so rail transportation is a key element of the current work. This paper seeks to give a framework for consultations with stakeholders and facilitate dialogue. It collects feedback from stakeholders on the design of a Canadian regulatory regime for locomotive-generated criteria air contaminant emissions. Canadian railways have managed locomotive air contaminant emissions since 1995.

  5. Stem cell responses to plasma surface modified electrospun polyurethane scaffolds.

    Zandén, Carl; Hellström Erkenstam, Nina; Padel, Thomas; Wittgenstein, Julia; Liu, Johan; Kuhn, H Georg


    The topographical effects from functional materials on stem cell behavior are currently of interest in tissue engineering and regenerative medicine. Here we investigate the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell (hESC) and rat postnatal neural stem cell (NSC) responses. The plasma gases were found to induce three combinations of fiber surface functionalities and roughness textures. On randomly oriented fibers, plasma treatments lead to substantially increased hESC attachment and proliferation as compared to native fibers. Argon plasma was found to induce the most optimal combination of surface functionality and roughness for cell expansion. Contact guided migration of cells and alignment of cell processes were observed on aligned fibers. Neuronal differentiation around 5% was found for all samples and was not significantly affected by the induced variations of surface functional group distribution or individual fiber topography. In this study the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell and rat postnatal neural stem cell (NSC) responses is studied with the goal of clarifying the potential effects of functional materials on stem cell behavior, a topic of substantial interest in tissue engineering and regenerative medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. 49 CFR 230.90 - Draw gear between steam locomotive and tender.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Draw gear between steam locomotive and tender. 230... Steam Locomotives and Tenders Draw Gear and Draft Systems § 230.90 Draw gear between steam locomotive and tender. (a) Maintenance and testing. The draw gear between the steam locomotive and tender...

  7. 49 CFR 230.108 - Steam locomotive leading and trailing trucks.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotive leading and trailing trucks. 230... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION STEAM LOCOMOTIVE INSPECTION AND MAINTENANCE STANDARDS Steam Locomotives and Tenders Trucks, Frames and Equalizing System § 230.108 Steam locomotive leading...

  8. Relation between radio-adaptive response and cell to cell communication

    Keiichiro Ishii


    Ionizing radiation has been considered to cause severe damages to DNA and do harm to cells in proportion to the dose, however low it might be. In 1984, Wolff et al. showed that human peripheral lymphocytes adapted to the low-dose radiation from 3 H-TdR added in culture medium and became resistant to the subsequent irradiation with high-doses of X-rays. This response, which is called radio-adaptive response, is also induced by X-rays and gamma-rays in human lymphocytes and Chinese hamster V79 cells. However, the mechanisms of and conditions for adaptive responses to radiation have not been clarified. With an objective of clarifying the conditions for adaptive responses of cells to radiation, we examined how the cell to cell communication is involved in the adaptive responses. We irradiated normal human embryo-derived (HE) cells and cancer cells (HeLa) in culture at high density with low-dose X-ray and examined their radio-adaptive responses by measuring the changes in sensitivity to subsequent high-dose X-ray irradiation using the Trypan Blue dye-exclusion test method. We also conducted experiments to examine the effects of Ca 2+ ions and Phorbol 12-Myristate 13-Acetate (TPA) which are supposed to be involved in cell to cell communication. (author)

  9. DNA damage responses in human induced pluripotent stem cells and embryonic stem cells.

    Olga Momcilovic


    Full Text Available Induced pluripotent stem (iPS cells have the capability to undergo self-renewal and differentiation into all somatic cell types. Since they can be produced through somatic cell reprogramming, which uses a defined set of transcription factors, iPS cells represent important sources of patient-specific cells for clinical applications. However, before these cells can be used in therapeutic designs, it is essential to understand their genetic stability.Here, we describe DNA damage responses in human iPS cells. We observe hypersensitivity to DNA damaging agents resulting in rapid induction of apoptosis after γ-irradiation. Expression of pluripotency factors does not appear to be diminished after irradiation in iPS cells. Following irradiation, iPS cells activate checkpoint signaling, evidenced by phosphorylation of ATM, NBS1, CHEK2, and TP53, localization of ATM to the double strand breaks (DSB, and localization of TP53 to the nucleus of NANOG-positive cells. We demonstrate that iPS cells temporary arrest cell cycle progression in the G(2 phase of the cell cycle, displaying a lack of the G(1/S cell cycle arrest similar to human embryonic stem (ES cells. Furthermore, both cell types remove DSB within six hours of γ-irradiation, form RAD51 foci and exhibit sister chromatid exchanges suggesting homologous recombination repair. Finally, we report elevated expression of genes involved in DNA damage signaling, checkpoint function, and repair of various types of DNA lesions in ES and iPS cells relative to their differentiated counterparts.High degrees of similarity in DNA damage responses between ES and iPS cells were found. Even though reprogramming did not alter checkpoint signaling following DNA damage, dramatic changes in cell cycle structure, including a high percentage of cells in the S phase, increased radiosensitivity and loss of DNA damage-induced G(1/S cell cycle arrest, were observed in stem cells generated by induced pluripotency.

  10. Regulation of T Cell Homeostasis and Responses by Pten

    Ryan H. Newton


    Full Text Available The generation of lipid products catalyzed by PI3K is critical for normal T cell homeostasis and a productive immune response. PI3K can be activated in response to antigen receptor, costimulatory, cytokine and chemokine signals. Moreover, dysregulation of this pathway frequently occurs in T cell lymphomas and is implicated in lymphoproliferative autoimmune disease. Akt acts as a central mediator of PI3K signals, downstream of which is the mTOR pathway, controlling cell growth and metabolism. Members of the Foxo family of transcription factors are also regulated by Akt, thus linking control over homing and migration of T cells, as well cell cycle entry, apoptosis, and DNA damage and oxidative stress responses, to PI3K signaling. PTEN, first identified as a tumor suppressor gene, encodes a lipid phosphatase that, by catalyzing the reverse of the PI3K reaction, directly opposes PI3K signaling. However, PTEN may have other functions as well, and recent reports have suggested roles for PTEN as a tumor suppressor independent of its effects on PI3K signaling. Through the use of models in which Pten is deleted specifically in T cells, it is becoming increasingly clear that control over autoimmunity and lymphomagenesis by PTEN involves multi-faceted functions of this molecule at multiple stages of T cell development.

  11. Radiation response of spermatogonial stem cells in the mouse

    Bootsma, A.L.


    Spermatogonial stem cells are able to repopulate the testis by forming clones that elongate along the walls of the seminiferous tubules depleted of spermatogenetic cells as a result of an irradiation. The surviving number of stem cells after irradiation was estimated by determining the fraction of repopulated tubules in cross-sections of the testis 11 weeks after irradiation. This fraction, called the 'repopulation index', is assumed to be directly proportional to the number of surviving stem cells. The response of spermatogonial stem cells in the CBA mouse to 1-MeV fission neutrons was investigated. Radioresistant, colony forming stem cells in the mouse testis move into a much more radiosensitive phase of their cell cycle shortly after irradiation. This is demonstrated in publication II in experiments in which total doses of 300 rad of neutrons and 1200 rad of X-rays were split into two equal fractions. The radiation response of spermatogonial stem cells in the mouse which survived various doses of fission neutrons 24 hours before was studied in publication III. Twenty four hours after a dose of 150 rad of fission neutrons all first-dose survivors have moved from a radioresistant (D 0 89+-4 rad in this study) towards a radiosensitive phase of their cell cycle. Spermatogonial stem cells which survive a neutron dose of 150 rad all belong to a radioresistant stem cell population in the seminiferous epithelium. The data in publication IV show that during the first 26 days after a dose of 150 rad of neutrons the stem cell population first increases and then slowly decreases its radiosensitivity, to stay fixed at a relatively high level. (Auth.)

  12. The Inflammation Response to DEHP through PPARγ in Endometrial Cells

    Qiansheng Huang


    Full Text Available Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa were recruited to investigate the effects of di-(2-ethylhexyl phthalate (DEHP at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction.

  13. Dynamic Locomotion With Four and Six-Legged Robots

    Buehler, M; Saranli, U; Papadopoulos, D; Koditschek, D


    .... The Scout II quadruped runs on flat ground in a bounding gait, and was motivated by an effort to understand the minimal mechanical design and control complexity for dynamically stable locomotion...

  14. Hybrid Locomotive for Energy Savings and Reduced Emissions


    Norfolk Southern Corporation (NS) and Pennsylvania State University tested several different battery systems in hybrid locomotives. Advanced lithium-ion battery technology was the only kind that displayed the capacity to perform in heavy switching or...

  15. Test requirements of locomotive fuel tank blunt impact tests


    The Federal Railroad Administrations Office of Research : and Development is conducting research into passenger : locomotive fuel tank crashworthiness. A series of impact tests : are planned to measure fuel tank deformation under two types : of dy...

  16. Review of codes, standards, and regulations for natural gas locomotives.


    This report identified, collected, and summarized relevant international codes, standards, and regulations with potential : applicability to the use of natural gas as a locomotive fuel. Few international or country-specific codes, standards, and regu...

  17. Th17 cell-mediated immune responses promote mast cell proliferation by triggering stem cell factor in keratinocytes

    Cho, Kyung-Ah; Park, Minhwa; Kim, Yu-Hee; Woo, So-Youn


    Although mast cells are traditionally thought to function as effector cells in allergic responses, they have increasingly been recognized as important regulators of various immune responses. Mast cells mature locally; thus, tissue-specific influences are important for promoting mast cell accumulation and survival in the skin and the gastrointestinal tract. In this study, we determined the effects of keratinocytes on mast cell accumulation during Th17-mediated skin inflammation. We observed increases in dermal mast cells in imiquimod-induced psoriatic dermatitis in mice accompanied by the expression of epidermal stem cell factor (SCF), a critical mast cell growth factor. Similar to mouse epidermal keratinocytes, SCF was highly expressed in the human HaCaT keratinocyte cell line following stimulation with IL−17. Further, keratinocytes promoted mast cell proliferation following stimulation with IL−17 in vitro. However, the effects of keratinocytes on mast cells were significantly diminished in the presence of anti−CD117 (stem cell factor receptor) blocking antibodies. Taken together, our results revealed that the Th17-mediated inflammatory environment promotes mast cell accumulation through keratinocyte-derived SCF. - Highlights: • Psoriasis-like skin inflammation increase dermal mast cells. • Keratinocyte produce stem cell factor in psoriasis-like skin inflammation. • Keratinocyte promote mast cell proliferation by stem cell factor dependent manner

  18. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

    King Nicholas JC


    Full Text Available Abstract Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM. We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. Methods HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. Results RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. Conclusion This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.

  19. Spectral response of a polycrystalline silicon solar cell

    Ba, B.; Kane, M.


    A theoretical study of the spectral response of a polycrystalline silicon n-p junction solar cell is presented. The case of a fibrously oriented grain structure, involving grain boundary recombination velocity and grain size effects is discussed. The contribution of the base region on the internal quantum efficiency Q int is computed for different grain sizes and grain boundary recombination velocities in order to examine their influence. Suggestions are also made for the determination of base diffusion length in polycrystalline silicon solar cells using the spectral response method. (author). 15 refs, 4 figs

  20. Expression of emotion in the kinematics of locomotion.

    Barliya, Avi; Omlor, Lars; Giese, Martin A; Berthoz, Alain; Flash, Tamar


    Here, we examine how different emotions-happiness, fear, sadness and anger-affect the kinematics of locomotion. We focus on a compact representation of locomotion properties using the intersegmental law of coordination (Borghese et al. in J Physiol 494(3):863-879, 1996), which states that, during the gait cycle of human locomotion, the elevation angles of the thigh, shank and foot do not evolve independently of each other but form a planar pattern of co-variation. This phenomenon is highly robust and has been extensively studied. The orientation of the plane has been correlated with changes in the speed of locomotion and with reduction in energy expenditure as speed increases. An analytical model explaining the conditions underlying the emergence of this plane and predicting its orientation reveals that it suffices to examine the amplitudes of the elevation angles of the different segments along with the phase shifts between them (Barliya et al. in Exp Brain Res 193:371-385, 2009). We thus investigated the influence of different emotions on the parameters directly determining the orientation of the intersegmental plane and on the angular rotation profiles of the leg segments, examining both the effect of changes in walking speed and effects independent of speed. Subjects were professional actors and naïve subjects with no training in acting. As expected, emotions were found to strongly affect the kinematics of locomotion, particularly walking speed. The intersegmental coordination patterns revealed that emotional expression caused additional modifications to the locomotion patterns that could not be explained solely by a change in speed. For all emotions except sadness, the amplitude of thigh elevation angles changed from those in neutral locomotion. The intersegmental plane was also differently oriented, especially during anger. We suggest that, while speed is the dominant variable allowing discrimination between different emotional gaits, emotion can be

  1. Fluid Mechanics of Aquatic Locomotion at Large Reynolds Numbers

    Govardhan, RN; Arakeri, JH


    Abstract | There exist a huge range of fish species besides other aquatic organisms like squids and salps that locomote in water at large Reynolds numbers, a regime of flow where inertial forces dominate viscous forces. In the present review, we discuss the fluid mechanics governing the locomotion of such organisms. Most fishes propel themselves by periodic undulatory motions of the body and tail, and the typical classification of their swimming modes is based on the fraction of their body...

  2. Cell Wall Metabolism in Response to Abiotic Stress

    Gall, Hyacinthe Le; Philippe, Florian; Domon, Jean-Marc; Gillet, Françoise; Pelloux, Jérôme; Rayon, Catherine


    This review focuses on the responses of the plant cell wall to several abiotic stresses including drought, flooding, heat, cold, salt, heavy metals, light, and air pollutants. The effects of stress on cell wall metabolism are discussed at the physiological (morphogenic), transcriptomic, proteomic and biochemical levels. The analysis of a large set of data shows that the plant response is highly complex. The overall effects of most abiotic stress are often dependent on the plant species, the genotype, the age of the plant, the timing of the stress application, and the intensity of this stress. This shows the difficulty of identifying a common pattern of stress response in cell wall architecture that could enable adaptation and/or resistance to abiotic stress. However, in most cases, two main mechanisms can be highlighted: (i) an increased level in xyloglucan endotransglucosylase/hydrolase (XTH) and expansin proteins, associated with an increase in the degree of rhamnogalacturonan I branching that maintains cell wall plasticity and (ii) an increased cell wall thickening by reinforcement of the secondary wall with hemicellulose and lignin deposition. Taken together, these results show the need to undertake large-scale analyses, using multidisciplinary approaches, to unravel the consequences of stress on the cell wall. This will help identify the key components that could be targeted to improve biomass production under stress conditions. PMID:27135320

  3. The response of human and rodent cells to hyperthermia

    Roizin-Towle, L.; Pirro, J.P.


    Inherent cellular radiosensitivity in vitro has been shown to be a good predictor of human tumor response in vivo. In contrast, the importance of the intrinsic thermosensitivity of normal and neoplastic human cells as a factor in the responsiveness of human tumors to adjuvant hyperthermia has never been analyzed systematically. A comparison of thermal sensitivity and thermo-radiosensitization in four rodent and eight human-derived cell lines was made in vitro. Arrhenius plots indicated that the rodent cells were more sensitive to heat killing than the human, and the break-point was 0.5 degrees C higher for the human than rodent cells. The relationship between thermal sensitivity and the interaction of heat with X rays at low doses was documented by thermal enhancement ratios (TER's). Cells received either a 1 hr exposure to 43 degrees C or a 20 minute treatment at 45 degrees C before exposure to 300 kVp X rays. Thermal enhancement ratios ranged from 1.0 to 2.7 for human cells heated at 43 degrees C and from 2.1 to 5.3 for heat exposures at 45 degrees C. Thermal enhancement ratios for rodent cells were generally 2 to 3 times higher than for human cells, because of the fact that the greater thermosensitivity of rodent cells results in a greater enhancement of radiation damage. Intrinsic thermosensitivity of human cells has relevance to the concept of thermal dose; intrinsic thermo-radiosensitization of a range of different tumor cells is useful in documenting the interactive effects of radiation combined with heat


    B. E. Bodnar


    Full Text Available Purpose. In difficult economic conditions, cost reduction of electricity consumption for the needs of production is an urgent task for the country’s industrial enterprises. Technical specifications of enterprises, which repair diesel locomotive hydraulic transmission, recommend conducting a certain amount of evaluation and regulatory tests to monitor their condition after repair. Experience shows that a significant portion of hydraulic transmission defects is revealed by bench tests. The advantages of bench tests include the ability to detect defects after repair, ease of maintenance of the hydraulic transmission and relatively low labour intensity for eliminating defects. The quality of these tests results in the transmission resource and its efficiency. Improvement of the technology of plant post-repairs hydraulic tests in order to reduce electricity consumption while testing. Methodology. The possible options for hydraulic transmission test bench improvement were analysed. There was proposed an energy efficiency method for diesel locomotive hydraulic transmission testing in locomotive repair plant environment. This is achieved by installing additional drive motor which receives power from the load generator. Findings. Based on the conducted analysis the necessity of improving the plant stand testing of hydraulic transmission was proved. The variants of the stand modernization were examined. The test stand modernization analysis was conducted. Originality. The possibility of using electric power load generator to power the stand electric drive motor or the additional drive motor was theoretically substantiated. Practical value. A variant of hydraulic transmission test stand based on the mutual load method was proposed. Using this method increases the hydraulic transmission load range and power consumption by stand remains unchanged. The additional drive motor will increase the speed of the input shaft that in its turn wil allow testing in

  5. Biological response of cancer cells to radiation treatment

    Rajamanickam eBaskar


    Full Text Available Cancer is a class of diseases characterized by uncontrolled cell growth and has the ability to spread or metastasize throughout the body. In recent years, remarkable progress has been made towards the understanding of proposed hallmarks of cancer development, care and treatment modalities. Radiation therapy or radiotherapy is an important and integral component of cancer management, mostly conferring a survival benefit. Radiation therapy destroys cancer by depositing high-energy radiation on the cancer tissues. Over the years, radiation therapy has been driven by constant technological advances and approximately 50% of all patients with localized malignant tumors are treated with radiation at some point in the course of their disease. In radiation oncology, research and development in the last three decades has led to considerable improvement in our understanding of the differential responses of normal and cancer cells. The biological effectiveness of radiation depends on the linear energy transfer (LET, total dose, number of fractions and radiosensitivity of the targeted cells or tissues. Radiation can either directly or indirectly (by producing free radicals damages the genome of the cell. This has been challenged in recent years by a newly identified phenomenon known as radiation induced bystander effect (RIBE. In RIBE, the non-irradiated cells adjacent to or located far from the irradiated cells/tissues demonstrate similar responses to that of the directly irradiated cells. Understanding the cancer cell responses during the fractions or after the course of irradiation will lead to improvements in therapeutic efficacy and potentially, benefitting a significant proportion of cancer patients. In this review, the clinical implications of radiation induced direct and bystander effects on the cancer cell are discussed.

  6. How animals move: comparative lessons on animal locomotion.

    Schaeffer, Paul J; Lindstedt, Stan L


    Comparative physiology often provides unique insights in animal structure and function. It is specifically through this lens that we discuss the fundamental properties of skeletal muscle and animal locomotion, incorporating variation in body size and evolved difference among species. For example, muscle frequencies in vivo are highly constrained by body size, which apparently tunes muscle use to maximize recovery of elastic recoil potential energy. Secondary to this constraint, there is an expected linking of skeletal muscle structural and functional properties. Muscle is relatively simple structurally, but by changing proportions of the few muscle components, a diverse range of functional outputs is possible. Thus, there is a consistent and predictable relation between muscle function and myocyte composition that illuminates animal locomotion. When animals move, the mechanical properties of muscle diverge from the static textbook force-velocity relations described by A. V. Hill, as recovery of elastic potential energy together with force and power enhancement with activation during stretch combine to modulate performance. These relations are best understood through the tool of work loops. Also, when animals move, locomotion is often conveniently categorized energetically. Burst locomotion is typified by high-power outputs and short durations while sustained, cyclic, locomotion engages a smaller fraction of the muscle tissue, yielding lower force and power. However, closer examination reveals that rather than a dichotomy, energetics of locomotion is a continuum. There is a remarkably predictable relationship between duration of activity and peak sustainable performance.

  7. Multi-modal locomotion: from animal to application

    Lock, R J; Burgess, S C; Vaidyanathan, R


    The majority of robotic vehicles that can be found today are bound to operations within a single media (i.e. land, air or water). This is very rarely the case when considering locomotive capabilities in natural systems. Utility for small robots often reflects the exact same problem domain as small animals, hence providing numerous avenues for biological inspiration. This paper begins to investigate the various modes of locomotion adopted by different genus groups in multiple media as an initial attempt to determine the compromise in ability adopted by the animals when achieving multi-modal locomotion. A review of current biologically inspired multi-modal robots is also presented. The primary aim of this research is to lay the foundation for a generation of vehicles capable of multi-modal locomotion, allowing ambulatory abilities in more than one media, surpassing current capabilities. By identifying and understanding when natural systems use specific locomotion mechanisms, when they opt for disparate mechanisms for each mode of locomotion rather than using a synergized singular mechanism, and how this affects their capability in each medium, similar combinations can be used as inspiration for future multi-modal biologically inspired robotic platforms. (topical review)

  8. Responses of macaque ganglion cells to far violet lights

    De Monasterio, F.M.; Gouras, P.


    In a sample of 487 colour-opponent ganglion cells recorded in the central retina of the rhesus and cynomolgus monkeys, 9% of these neurones were found to have responses with the same sign at both ends of the visible spectrum mediated by red-sensitive cones and mid-spectral responses of opposite sign mediated by green-sensitive cones. Selective chromatic adaptation showed that the responses to far violet lights (400 to 420 nm) were due to input from red- and not blue-sensitive cones. These responses were enhanced by backgrounds depressing the sensitivity of blue- and green-sensitive cones and they were depressed by backgrounds depressing the sensitivity of red-sensitive cones; the sensitivity of these responses was yoked to that of responses to far red lights. The relative incidence of these ganglion cells was maximal at the foveal region and decreased towards the peripheral retina. The properties of these cells are consistent with some psychophysical observations of human vision at the short wave-lengths. (author)

  9. Cellullar insights into cerebral cortical development: focusing on the locomotion mode of neuronal migration

    Takeshi eKawauchi


    Full Text Available The mammalian brain consists of numerous compartments that are closely connected with each other via neural networks, comprising the basis of higher order brain functions. The highly specialized structure originates from simple pseudostratified neuroepithelium-derived neural progenitors located near the ventricle. A long journey by neurons from the ventricular side is essential for the formation of a sophisticated brain structure, including a mammalian-specific six-layered cerebral cortex. Neuronal migration consists of several contiguous steps, but the locomotion mode comprises a large part of the migration. The locomoting neurons exhibit unique features; a radial glial fiber-dependent migration requiring the endocytic recycling of N-cadherin and a neuron-specific migration mode with dilation/swelling formation that requires the actin and microtubule organization possibly regulated by cyclin-dependent kinase 5 (Cdk5, Dcx, p27kip1, Rac1 and POSH. Here I will introduce the roles of various cellular events, such as cytoskeletal organization, cell adhesion and membrane trafficking, in the regulation of the neuronal migration, with particular focus on the locomotion mode.

  10. Sensory modulation of movement, posture and locomotion.

    Saradjian, A H


    During voluntary movement, there exists a well known functional sensory attenuation of afferent inputs, which allows us to discriminate between information related to our own movements and those arising from the external environment. This attenuation or 'gating' prevents some signals from interfering with movement elaboration and production. However, there are situations in which certain task-relevant sensory inputs may not be gated. This review begins by identifying the prevalent findings in the literature with specific regard to the somatosensory modality, and reviews the many cases of classical sensory gating phenomenon accompanying voluntary movement and their neural basis. This review also focuses on the newer axes of research that demonstrate that task-specific sensory information may be disinhibited or even facilitated during engagement in voluntary actions. Finally, a particular emphasis will be placed on postural and/or locomotor tasks involving strong somatosensory demands, especially for the setting of the anticipatory postural adjustments observed prior the initiation of locomotion. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Linking pedestrian flow characteristics with stepping locomotion

    Wang, Jiayue; Boltes, Maik; Seyfried, Armin; Zhang, Jun; Ziemer, Verena; Weng, Wenguo


    While properties of human traffic flow are described by speed, density and flow, the locomotion of pedestrian is based on steps. To relate characteristics of human locomotor system with properties of human traffic flow, this paper aims to connect gait characteristics like step length, step frequency, swaying amplitude and synchronization with speed and density and thus to build a ground for advanced pedestrian models. For this aim, observational and experimental study on the single-file movement of pedestrians at different densities is conducted. Methods to measure step length, step frequency, swaying amplitude and step synchronization are proposed by means of trajectories of the head. Mathematical models for the relations of step length or frequency and speed are evaluated. The problem how step length and step duration are influenced by factors like body height and density is investigated. It is shown that the effect of body height on step length and step duration changes with density. Furthermore, two different types of step in-phase synchronization between two successive pedestrians are observed and the influence of step synchronization on step length is examined.

  12. Semiallogenic fusions of MSI+ tumor cells and activated B cells induce MSI-specific T cell responses

    Garbe, Yvette; Klier, Ulrike; Linnebacher, Michael


    Various strategies have been developed to transfer tumor-specific antigens into antigen presenting cells in order to induce cytotoxic T cell responses against tumor cells. One approach uses cellular vaccines based on fusions of autologous antigen presenting cells and allogeneic tumor cells. The fusion cells combine antigenicity of the tumor cell with optimal immunostimulatory capacity of the antigen presenting cells. Microsatellite instability caused by mutational inactivation of DNA mismatch repair genes results in translational frameshifts when affecting coding regions. It has been shown by us and others that these mutant proteins lead to the presentation of immunogenic frameshift peptides that are - in principle - recognized by a multiplicity of effector T cells. We chose microsatellite instability-induced frameshift antigens as ideal to test for induction of tumor specific T cell responses by semiallogenic fusions of microsatellite instable carcinoma cells with CD40-activated B cells. Two fusion clones of HCT116 with activated B cells were selected for stimulation of T cells autologous to the B cell fusion partner. Outgrowing T cells were phenotyped and tested in functional assays. The fusion clones expressed frameshift antigens as well as high amounts of MHC and costimulatory molecules. Autologous T cells stimulated with these fusions were predominantly CD4 + , activated, and reacted specifically against the fusion clones and also against the tumor cell fusion partner. Interestingly, a response toward 6 frameshift-derived peptides (of 14 tested) could be observed. Cellular fusions of MSI + carcinoma cells and activated B cells combine the antigen-presenting capacity of the B cell with the antigenic repertoire of the carcinoma cell. They present frameshift-derived peptides and can induce specific and fully functional T cells recognizing not only fusion cells but also the carcinoma cells. These hybrid cells may have great potential for cellular immunotherapy and

  13. Rapid assay for cell age response to radiation by electronic volume flow cell sorting

    Freyer, J.P.; Wilder, M.E.; Raju, M.R.


    A new technique is described for measuring cell survival as a function of cell cycle position using flow cytometric cell sorting on the basis of electronic volume signals. Sorting of cells into different cell age compartments is demonstrated for three different cell lines commonly used in radiobiological research. Using flow cytometric DNA content analysis and [ 3 H]thymidine autoradiography of the sorted cell populations, it is demonstrated that resolution of the age compartment separation is as good as or better than that reported for other cell synchronizing techniques. Variation in cell survival as a function of position in the cell cycle after a single dose of radiation as measured by volume cell sorting is similar to that determined by other cell synchrony techniques. Advantages of this method include: (1) no treatment of the cells is required, thus, this method is noncytotoxic; (2) no cell cycle progression is needed to obtain different cell age compartments; (3) the cell population can be held in complete growth medium at any desired temperature during sorting; (4) a complete radiation age - response assay can be plated in 2 h. Applications of this method are discussed, along with some technical limitations. (author)

  14. Cell responses to FGFR3 signalling: growth, differentiation and apoptosis

    L'Hote, Corine G.M.; Knowles, Margaret A.


    FGFR3 is a receptor tyrosine kinase (RTK) of the FGF receptor family, known to have a negative regulatory effect on long bone growth. Fgfr3 knockout mice display longer bones and, accordingly, most germline-activating mutations in man are associated with dwarfism. Somatically, some of the same activating mutations are associated with the human cancers multiple myeloma, cervical carcinoma and carcinoma of the bladder. How signalling through FGFR3 can lead to either chondrocyte apoptosis or cancer cell proliferation is not fully understood. Although FGFR3 can be expressed as two main splice isoforms (IIIb or IIIc), there is no apparent link with specific cell responses, which may rather be associated with the cell type or its differentiation status. Depending on cell type, differential activation of STAT proteins has been observed. STAT1 phosphorylation seems to be involved in inhibition of chondrocyte proliferation while activation of the ERK pathway inhibits chondrocyte differentiation and B-cell proliferation (as in multiple myeloma). The role of FGFR3 in epithelial cancers (bladder and cervix) is not known. Some of the cell specificity may arise via modulation of signalling by crosstalk with other signalling pathways. Recently, inhibition of the ERK pathway in achondroplastic mice has provided hope for an approach to the treatment of dwarfism. Further understanding of the ability of FGFR3 to trigger different responses depending on cell type and cellular context may lead to treatments for both skeletal dysplasias and cancer

  15. Lysophosphatidic acid mediates pleiotropic responses in skeletal muscle cells

    Jean-Baptiste, Gael; Yang Zhao; Khoury, Chamel; Greenwood, Michael T.


    Lysophosphatidic acid (LPA) is a potent modulator of growth, cell survival, and apoptosis. Although all four LPA receptors are expressed in skeletal muscle, very little is known regarding the role they play in this tissue. We used RT-PCR to demonstrate that cultured skeletal muscle C2C12 cells endogenously express multiple LPA receptor subtypes. The demonstration that LPA mediates the activation of ERK1/2 MAP kinase and Akt/PKB in C2C12 cells is consistent with the widely observed mitogenic properties of LPA. In spite of these observations, LPA did not induce proliferation in C2C12 cells. Paradoxically, we found that prolonged treatment of C2C12 cells with LPA led to caspase 3 and PARP cleavage as well as the activation of stress-associated MAP kinases JNK and p38. In spite of these typically pro-apoptotic responses, LPA did not induce cell death. Blocking ERK1/2 and Akt/PKB activation with specific pharmacological inhibitors, nevertheless, stimulated LPA-mediated apoptosis. Taken together, these results suggest that both mitogenic and apoptotic responses serve to counterbalance the effects of LPA in cultured C2C12 cells

  16. An Arabidopsis kinase cascade influences auxin-responsive cell expansion.

    Enders, Tara A; Frick, Elizabeth M; Strader, Lucia C


    Mitogen-activated protein kinase (MPK) cascades are conserved mechanisms of signal transduction across eukaryotes. Despite the importance of MPK proteins in signaling events, specific roles for many Arabidopsis MPK proteins remain unknown. Multiple studies have suggested roles for MPK signaling in a variety of auxin-related processes. To identify MPK proteins with roles in auxin response, we screened mpk insertional alleles and identified mpk1-1 as a mutant that displays hypersensitivity in auxin-responsive cell expansion assays. Further, mutants defective in the upstream MAP kinase kinase MKK3 also display hypersensitivity in auxin-responsive cell expansion assays, suggesting that this MPK cascade affects auxin-influenced cell expansion. We found that MPK1 interacts with and phosphorylates ROP BINDING PROTEIN KINASE 1 (RBK1), a protein kinase that interacts with members of the Rho-like GTPases from Plants (ROP) small GTPase family. Similar to mpk1-1 and mkk3-1 mutants, rbk1 insertional mutants display auxin hypersensitivity, consistent with a possible role for RBK1 downstream of MPK1 in influencing auxin-responsive cell expansion. We found that RBK1 directly phosphorylates ROP4 and ROP6, supporting the possibility that RBK1 effects on auxin-responsive cell expansion are mediated through phosphorylation-dependent modulation of ROP activity. Our data suggest a MKK3 • MPK1 • RBK1 phosphorylation cascade that may provide a dynamic module for altering cell expansion. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  17. Directional Cell Migration in Response to Repeated Substratum Stretching

    Okimura, Chika; Iwadate, Yoshiaki


    Crawling migration plays an essential role in a variety of biological phenomena, including development, wound healing, and immune system function. Migration properties such as anterior-posterior polarity, directionality, and velocity are regulated not only by the reception of a chemoattractant but also by sensing mechanical inputs from the external environment. In this review, we describe the mechanical response of migrating cells, particularly under repeated stretching of the elastic substratum, highlighting the fact that there appear to be two independent mechanosensing systems that generate the polarity needed for migration. Cells that have no stress fibers, such as Dictyostelium cells and neutrophil-like differentiated HL-60 cells, migrate perpendicular to the stretching direction via myosin II localization. Cells that do possess stress fibers, however, such as fish keratocytes, migrate parallel to the stretching via a stress-fiber-dependent process.

  18. The islet beta-cell: fuel responsive and vulnerable.

    Nolan, Christopher J; Prentki, Marc


    The pancreatic beta-cell senses blood nutrient levels and is modulated by neurohormonal signals so that it secretes insulin according to the need of the organism. Nutrient sensing involves marked metabolic activation, resulting in the production of coupling signals that promote insulin biosynthesis and secretion. The beta-cell's high capacity for nutrient sensing, however, necessitates reduced protection to nutrient toxicity. This potentially explains why in susceptible individuals, chronic fuel surfeit results in beta-cell failure and type 2 diabetes. Here we discuss recent insights into first, the biochemical basis of beta-cell signaling in response to glucose, amino acids and fatty acids, and second, beta-cell nutrient detoxification. We emphasize the emerging role of glycerolipid/fatty acid cycling in these processes.

  19. Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells.

    Ly, Tony; Endo, Aki; Lamond, Angus I


    Previously, we analyzed protein abundance changes across a 'minimally perturbed' cell cycle by using centrifugal elutriation to differentially enrich distinct cell cycle phases in human NB4 cells (Ly et al., 2014). In this study, we compare data from elutriated cells with NB4 cells arrested at comparable phases using serum starvation, hydroxyurea, or RO-3306. While elutriated and arrested cells have similar patterns of DNA content and cyclin expression, a large fraction of the proteome changes detected in arrested cells are found to reflect arrest-specific responses (i.e., starvation, DNA damage, CDK1 inhibition), rather than physiological cell cycle regulation. For example, we show most cells arrested in G2 by CDK1 inhibition express abnormally high levels of replication and origin licensing factors and are likely poised for genome re-replication. The protein data are available in the Encyclopedia of Proteome Dynamics (

  20. Morphological responses of dissociated sponge cells to different organic substrata.

    Gaino, E; Magnino, G; Burlando, B; Sara', M


    To study interactions between sponge cells and components of the extracellular matrix (ECM), cells of the calcareous sponge Clathrina cerebrum were investigated in vitro by scanning electron microscopy. Cells were settled on glass coverslips, used as controls, and on coverslips coated with various ECM components (laminin, collagens and fibronectin), and with an adhesive substance (polylysine). Cells tended to conserve a rounded shape, producing thin, stiff processes (scleropodia) and lamellipodia, whose shape and extension varied according to the substrata. Spreading was observed only on polylysine, inducing cells to assume a fibroblast-like aspect. On laminin, cell adhesion was assured only by scleropodia. On fibronectin, scleropodia and lamellipodia were present, but reduced in size and length. On collagens, laminar processes occurred among prevailing scleropodia. Measurements of cell area and perimeter allowed statistical comparison of substrata, on the basis of their induction of cell flattening and protuberance formation. In summary, sponge cells were found to modulate their morphology in response to the external environment, expressing features for dynamic activities most fully in the presence of substances close to their natural ECM constituents. These results are discussed in the context of tissue rearrangement as a basic adaptation occurring throughout the life span of these organisms.

  1. Caterpillar locomotion-inspired valveless pneumatic micropump using a single teardrop-shaped elastomeric membrane

    So, Hongyun; Pisano, Albert P.; Seo, Young Ho


    This paper presents a microfluidic pump operated by an asymmetrically deformed membrane, which was inspired by caterpillar locomotion. Almost all mechanical micropumps consist of two major components of fluid halting and fluid pushing parts, whereas the proposed caterpillar locomotion-inspired micropump has only a single, bilaterally symmetric membrane-like teardrop shape. A teardrop-shaped elastomeric membrane was asymmetrically deformed and then consecutively touched down to the bottom of the chamber in response to pneumatic pressure, thus achieving fluid pushing. Consecutive touchdown motions of the teardrop-shaped membrane mimicked the propagation of a caterpillar's hump during its locomotory gait. The initial touchdown motion of the teardrop-shaped membrane at the centroid worked as a valve that blocked the inlet channel, and then, the consecutive touchdown motions pushed fluid in the chamber toward the tail of the chamber connected to the outlet channel. The propagation of the touchdown motion of the teardrop-shaped membrane was investigated using computational analysis as well as experimental studies. This caterpillar locomotion-inspired micropump composed of only a single membrane can provide new opportunities for simple integration of microfluidic systems. © the Partner Organisations 2014.

  2. Caterpillar locomotion-inspired valveless pneumatic micropump using a single teardrop-shaped elastomeric membrane

    So, Hongyun


    This paper presents a microfluidic pump operated by an asymmetrically deformed membrane, which was inspired by caterpillar locomotion. Almost all mechanical micropumps consist of two major components of fluid halting and fluid pushing parts, whereas the proposed caterpillar locomotion-inspired micropump has only a single, bilaterally symmetric membrane-like teardrop shape. A teardrop-shaped elastomeric membrane was asymmetrically deformed and then consecutively touched down to the bottom of the chamber in response to pneumatic pressure, thus achieving fluid pushing. Consecutive touchdown motions of the teardrop-shaped membrane mimicked the propagation of a caterpillar\\'s hump during its locomotory gait. The initial touchdown motion of the teardrop-shaped membrane at the centroid worked as a valve that blocked the inlet channel, and then, the consecutive touchdown motions pushed fluid in the chamber toward the tail of the chamber connected to the outlet channel. The propagation of the touchdown motion of the teardrop-shaped membrane was investigated using computational analysis as well as experimental studies. This caterpillar locomotion-inspired micropump composed of only a single membrane can provide new opportunities for simple integration of microfluidic systems. © the Partner Organisations 2014.

  3. Vestibular-Somatosensory Convergence in Head Movement Control During Locomotion after Long-Duration Space Flight

    Mulavara, Ajitkumar; Ruttley, Tara; Cohen, Helen; Peters, Brian; Miller, Chris; Brady, Rachel; Merkle, Lauren; Bloomberg, Jacob


    Exposure to the microgravity conditions of space flight induces adaptive modification in the control of vestibular-mediated reflexive head movement during locomotion after space flight. Space flight causes astronauts to be exposed to somatosensory adaptation in both the vestibular and body load-sensing (BLS) systems. The goal of these studies was to examine the contributions of vestibular and BLS-mediated somatosensory influences on head movement control during locomotion after long-duration space flight. Subjects were asked to walk on a treadmill driven at 1.8 m/s while performing a visual acuity task. Data were collected using the same testing protocol from three independent subject groups; 1) normal subjects before and after exposure to 30 minutes of 40% bodyweight unloaded treadmill walking, 2) bilateral labyrinthine deficient (LD) patients and 3) astronauts who performed the protocol before and after long duration space flight. Motion data from head and trunk segmental motion data were obtained to calculate the angular head pitch (HP) movements during walking trials while subjects performed the visual task, to estimate the contributions of vestibular reflexive mechanisms in HP movements. Results showed that exposure to unloaded locomotion caused a significant increase in HP movements, whereas in the LD patients the HP movements were significantly decreased. Astronaut subjects results showed a heterogeneous response of both increases and decreases in the amplitude of HP movement. We infer that BLS-mediated somatosensory input centrally modulates vestibular input and can adaptively modify head-movement control during locomotion. Thus, space flight may cause a central adaptation mediated by the converging vestibular and body load-sensing somatosensory systems.

  4. CD83 Antibody Inhibits Human B Cell Responses to Antigen as well as Dendritic Cell-Mediated CD4 T Cell Responses.

    Wong, Kuan Y; Baron, Rebecca; Seldon, Therese A; Jones, Martina L; Rice, Alison M; Munster, David J


    Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83 + human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment. This inhibition occurred without depletion of all human B cells because anti-CD83 lysed activated CD83 + B cells by Ab-dependent cellular cytotoxicity and spared resting (CD83 - ) B cells. In cultured human PBMC, anti-CD83 inhibited tetanus toxoid-stimulated B cell proliferation and concomitant dendritic cell-mediated CD4 T cell proliferation and expression of IFN-γ and IL-17A, with minimal losses of B cells (80% of B cells but had no effect on CD4 T cell proliferation and cytokine expression. By virtue of the ability of anti-CD83 to selectively deplete activated, but not resting, B cells and dendritic cells, with the latter reducing CD4 T cell responses, anti-CD83 may be clinically useful in autoimmunity and transplantation. Advantages might include inhibited expansion of autoantigen- or alloantigen-specific B cells and CD4 T cells, thus preventing further production of pathogenic Abs and inflammatory cytokines while preserving protective memory and regulatory cells. Copyright © 2018 by The American Association of Immunologists, Inc.

  5. Modeling posture-dependent leg actuation in sagittal plane locomotion

    Schmitt, J; Clark, J


    The spring loaded inverted pendulum template has been shown to accurately model the steady locomotion dynamics of a variety of running animals, and has served as the inspiration for an entire class of dynamic running robots. While the template models the leg dynamics by an energy-conserving spring, insects and animals have structures that dissipate, store and produce energy during a stance phase. Recent investigations into the spring-like properties of limbs, as well as animal response to drop-step perturbations, suggest that animals use their legs to manage energy storage and dissipation, and that this management is important for gait stability. In this paper, we extend our previous analysis of control of the spring loaded inverted pendulum template via changes in the leg touch-down angle to include energy variations during the stance phase. Energy variations are incorporated through leg actuation that varies the force-free leg length during the stance phase, yet maintains qualitatively correct force and velocity profiles. In contrast to the partially asymptotically stable gaits identified in previous analyses, incorporating energy and leg angle variations in this manner produces complete asymptotic stability. Drop-step perturbation simulations reveal that the control strategy is rather robust, with gaits recovering from drops of up to 30% of the nominal hip height.

  6. Touching force response of the piezoelectric Braille cell.

    Smithmaitrie, Pruittikorn; Kanjantoe, Jinda; Tandayya, Pichaya


    The objective of this research is to investigate dynamic responses of the piezoelectric Braille cell when it is subjected to both electrical signal and touching force. Physical behavior of the piezoelectric actuator inside the piezoelectric Braille cell is analyzed. The mathematical model of the piezoelectric Braille system is presented. Then, data of visually impaired people using a Braille Note is studied as design information and a reference input for calculation of the piezoelectric Braille response under the touching force. The results show dynamic responses of the piezoelectric Braille cell. The designed piezoelectric bimorph has a settling time of 0.15 second. The relationship between the Braille dot height and applied voltage is linear. The behavior of the piezoelectric Braille dot when it is touched during operation shows that the dot height is decreased as the force increases. The result provides understanding of the piezoelectric Braille cell behavior under both touching force and electrical excitation simultaneously. This is the important issue for the design and development of piezoelectric Braille cells in senses of controlling Braille dot displacement or force-feedback in the future.

  7. Unraveling the response of plant cells to cytotoxic saponins

    Balestrazzi, Alma; Macovei, Anca; Tava, Aldo; Avato, Pinarosa; Raimondi, Elena


    A wide range of pharmacological properties are ascribed to natural saponins, in addition to their biological activities against herbivores, plant soil-borne pathogens and pests. As for animal cells, the cytotoxicity and the chemopreventive role of saponins are mediated by a complex network of signal transduction pathways which include reactive oxygen species (ROS) and nitric oxide (NO). The involvement of other relevant components of the saponin-related signaling routes, such as the Tumor Necrosis Factor (TNF)α, the interleukin (IL)-6 and the Nuclear Transcription FactorκB (NFκB), has been highlighted in animal cells. By contrast, information concerning the response of plant cells to saponins and the related signal transduction pathways is almost missing. To date, there are only a few common features which link plant and animal cells in their response to saponins, such as the early burst in ROS and NO production and the induction of metallothioneins (MTs), small cysteine-rich, metal-binding proteins. This aspect is discussed in the present paper in view of the recent hypothesis that MTs and NO are part of a novel signal transduction pathway participating in the cell response to oxidative stress. PMID:21673512

  8. The Role of the Immune Response in Merkel Cell Carcinoma

    Triozzi, Pierre L.; Fernandez, Anthony P.


    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies

  9. The Role of the Immune Response in Merkel Cell Carcinoma

    Triozzi, Pierre L., E-mail: [Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Fernandez, Anthony P. [Departments of Dermatology and Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States)


    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

  10. Problems of locomotive wheel wear in fleet replacement

    L.P. Lingaytis


    Full Text Available Purpose. To conduct a research and find out the causes of defects appearing on the wheel thread of freight locomotives 2М62 and SIEMENS ER20CF. Methodology. To find the ways to solve this problem comparing the locomotive designs and their operating conditions. Findings. After examining the nature of the wheel wear the main difference was found: in locomotives of the 2M62 line wears the wheel flange, and in the locomotives SIEMENS ER20CF – the tread surface. After installation on the 2M62 locomotive the lubrication system of flanges their wear rate significantly decreased. On the new freight locomotives SIEMENS ER20CF the flange lubrication systems of the wheel set have been already installed at the factory, however the wheel thread is wearing. As for locomotives 2M62, and on locomotives SIEMENS ER20CF most wear profile skating wheels of the first wheel set. On both locomotive lines the 2М62 and the SIEMENS ER20CF the tread profile of the first wheel set most of all is subject to the wear. After reaching the 170 000 km run, the tread surface of some wheels begins to crumble. There was a suspicion that the reason for crumb formation of the wheel surface may be insufficient or excessive wheel hardness or its chemical composition. In order to confirm or deny this suspicion the following studies were conducted: the examination of the rim surface, the study of the wheel metal hardness and the document analysis of the wheel production and their comparison with the results of wheel hardness measurement. Practical value. The technical condition of locomotives is one of the bases of safety and reliability of the rolling stock. The reduction of the wheel wear significantly reduces the operating costs of railway transport. After study completion it was found that there was no evidence to suggest that the ratio of the wheel-rail hardness could be the cause of the wheel surface crumbling.


    S. V. Myamlin


    Full Text Available Purpose. The paper is devoted to dynamic characteristics evaluation of the locomotive with prospective design and determination the feasibility of its use on the Ukrainian railways. Methodology. The methods of mathematical and computer modeling of the dynamics of railway vehicles, as well as methods for the numerical integration of systems of ordinary nonlinear differential equations were used to solve the problem. Findings. The calculated diagram of a locomotive on three-axle bogies was built to solve the problem, and it is a system of rigid bodies connected by various elements of rheology. The mathematical model of the locomotive movement, allowing studying its spatial vibrations at driving on straight and curved sections of the track with random irregularities in plan and profile was developed with use of this calculated diagram. At compiling the mathematical model took into account both geometric (nonlinearity profile of the wheel roll surface and physical nonlinearity of the system (the work forces of dry friction, nonlinearity characteristics of interaction forces between wheels and rails. The multivariate calculations, which allowed assessing the dynamic qualities of the locomotive at its movement along straight and curved sections of the track, were realized with the use of computer modeling. The smoothness movement indicators of the locomotive in horizontal and vertical planes, frame strength, coefficients of vertical dynamics in the first and second stages of the suspension, the load factor of resistance against the derailment of the wheel from the rail were determined at the period of research. In addition, a comparison of the obtained results with similar characteristics is widely used on the Ukrainian railways in six-axle locomotive TE 116. The influence of speed and technical state of the track on the locomotive traffic safety was determined.Originality. A mathematical model of the spatial movement of a six-axle locomotive with


    I. V. Zhukovytskyy


    Full Text Available Purpose. The article describes the process of developing the information-measuring test system of diesel locomotives hydraulic transmission, which gives the possibility to obtain baseline data to conduct further studies for the determination of the technical condition of diesel locomotives hydraulic transmission. The improvement of factory technology of post-repair tests of hydraulic transmissions by automating the existing hydraulic transmission test stands according to the specifications of the diesel locomotive repair enterprises was analyzed. It is achieved based on a detailed review of existing foreign information-measuring test systems for hydraulic transmission of diesel locomotives, BelAZ earthmover, aircraft tug, slag car, truck, BelAZ wheel dozer, some brands of tractors, etc. The problem for creation the information-measuring test systems for diesel locomotive hydraulic transmission is being solved, starting in the first place from the possibility of automation of the existing test stand of diesel locomotives hydraulic transmission at Dnipropetrovsk Diesel Locomotive Repair Plant "Promteplovoz". Methodology. In the work the researchers proposed the method to create a microprocessor automated system of diesel locomotives hydraulic transmission stand testing in the locomotive plant conditions. It acts by justifying the selection of the necessary sensors, as well as the application of the necessary hardware and software for information-measuring systems. Findings. Based on the conducted analysis there was grounded the necessity of improvement the plant hydraulic transmission stand testing by creating a microprocessor testing system, supported by the experience of developing such systems abroad. Further research should be aimed to improve the accuracy and frequency of data collection by adopting the more modern and reliable sensors in tandem with the use of filtering software for electromagnetic and other interference. Originality. The

  13. Responses to recipient and donor B cells by genetically donor T cells from human haploidentical chimeras

    Schiff, S.; Sampson, H.; Buckley, R.


    Following administration of haploidentical stem cells to infants with severe combined immunodeficiency (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-versus-host disease. To investigate the effect of the host environment on the responsiveness of these genetically donor T cells, blood B and T lymphocytes from 6 SCID recipients, their parental donors and unrelated controls were purified by double SRBC rosetting. T cells were stimulated by irradiated B cells at a 1:1 ratio in 6 day cultures. Engrafted T cells of donor karyotype gave much smaller responses to irradiated genetically recipient B cells than did fresh donor T cells. Moreover, engrafted T cells of donor karyotype from two of the three SCIDs who are longest post-transplantation responded more vigorously (14,685 and 31,623 cpm) than fresh donor T cells (5141 and 22,709 cpm) to donor B cells. These data indicate that T lymphocytes which have matured from donor stem cells in the recipient microenvironment behave differently from those that have matured in the donor

  14. Molecular mechanisms of radioadaptive responses in human lymphoblastoid cells

    Kakimoto, Ayana; Taki, Keiko; Nakajima, Tetsuo


    Radioadaptive response is a biodefensive response observed in a variety of mammalian cells and animals where exposure to low dose radiation induces resistance against the subsequent high dose radiation. Elucidation of its mechanisms is important for risk estimation of low dose radiation because the radioadaptive response implies that low dose radiation affects cells/individuals in a different manner from high dose radiation. In the present study, we explored the molecular mechanisms of the radioadaptive response in human lymphoblastoid cells AHH-1 in terms of mutation at the hypoxanthine phosphoribosyltransferase (HPRT) gene locus. First we observed that preexposure to the priming dose in the range from 0.02 Gy to 0.2 Gy significantly reduced mutation frequency at HPRT gene locus after irradiation with 3 Gy of X rays. As no significant adaptive response was observed with the priming dose of 0.005 Gy, it was indicated that the lower limit of the priming dose to induce radioadaptive response may be between 0.005 Gy and 0.02 Gy. Second, we examined the effect of 3-amino-benzamide (3AB), an inhibitor of poly(ADP-ribose)polymerase1, which has been reported to inhibit the radioadaptive response in terms of chromosome aberration. However we could observe significant radioadaptive responses in terms of mutation even in the presence of 3AB. These findings suggested that molecular mechanisms of the radioadaptive response in terms of mutation may be different from that for radioadaptive responses in terms of chromosomal aberration, although we could not exclude a possibility that the differential effects of 3AB was due to cell type difference. Finally, by performing a comprehensive analysis of alterations in gene expression using high coverage expression profiling (HiCEP), we could identify 17 genes whose expressions were significantly altered 6 h after irradiation with 0.02 Gy. We also found 17 and 20 genes, the expressions of which were different with or without priming

  15. Epigenetics of peripheral B cell differentiation and the antibody response

    Hong eZan


    Full Text Available Epigenetic modifications, such as histone post-translational modifications, DNA methylation, and alteration of gene expression by non-coding RNAs, including microRNAs (miRNAs and long non-coding RNAs (lncRNAs, are heritable changes that are independent from the genomic DNA sequence. These regulate gene activities and, therefore, cellular functions. Epigenetic modifications act in concert with transcription factors and play critical roles in B cell development and differentiation, thereby modulating antibody responses to foreign- and self-antigens. Upon antigen encounter by mature B cells in the periphery, alterations of these lymphocytes epigenetic landscape are induced by the same stimuli that drive the antibody response. Such alterations instruct B cells to undergo immunoglobulin class switch DNA recombination (CSR and somatic hypermutation (SHM, as well as differentiation to memory B cells or long-lived plasma cells for the immune memory. Inducible histone modifications, together with DNA methylation and miRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase (AID, which is essential for CSR and SHM, and factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1 (Blimp-1. These inducible B cell-intrinsic epigenetic marks guide the maturation of antibody responses. Combinatorial histone modifications also function as histone codes to target CSR and, possibly, SHM machinery to the Ig loci by recruiting specific adaptors that can stabilize CSR/SHM factors. In addition, lncRNAs, such as recently reported lncRNA-CSR and an lncRNA generated through transcription of the S region that form G-quadruplex structures, are also important for CSR targeting. Epigenetic dysregulation in B cells, including the aberrant expression of non-coding RNAs and alterations of histone modifications and DNA methylation, can result in aberrant antibody responses to foreign antigens

  16. Cell response to quasi-monochromatic light with different coherence

    Budagovsky, A V; Solovykh, N V [I.V.Michurin All-Russian Recearch Institute of Fruit Crops Genetics and Breeding (Russian Federation); Budagovskaya, O N [I.V.Michurin All-Russia Research and Development Institute of Gardening, Michurinsk, Tambov region (Russian Federation); Budagovsky, I A [P N Lebedev Physics Institute, Russian Academy of Sciences, Moscow (Russian Federation)


    The problem of the light coherence effect on the magnitude of the photoinduced cell response is discussed. The origins of ambiguous interpretation of the known experimental results are considered. Using the biological models, essentially differing in anatomy, morphology and biological functions (acrospires of radish, blackberry microsprouts cultivated in vitro, plum pollen), the effect of statistical properties of quasi-monochromatic light (λ{sub max} = 633 nm) on the magnitude of the photoinduced cell response is shown. It is found that for relatively low spatial coherence, the cell functional activity changes insignificantly. The maximal enhancement of growing processes (stimulating effect) is observed when the coherence length L{sub coh} and the correlation radius r{sub cor} are greater than the cell size, i.e., the entire cell fits into the field coherence volume. In this case, the representative indicators (germination of seeds and pollen, the spears length) exceeds those of non-irradiated objects by 1.7 – 3.9 times. For more correct assessment of the effect of light statistical properties on photocontrol processes, it is proposed to replace the qualitative description (coherent – incoherent) with the quantitative one, using the determination of spatial and temporal correlation functions and comparing them with the characteristic dimensions of the biological structures, e.g., the cell size. (biophotonics)

  17. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai


    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  18. Heterogeneous response of isolated adult rat heart cells to insulin

    Haworth, R.A.; Hunter, D.R.; Berkoff, H.A.


    3-O-Methylglucose uptake by Ca2+-resistant adult rat heart cells in suspension was measured, free of artifactual inhibitor-insensitive uptake, and with an accuracy of +/- 1.9% pellet water. (Ca2+-resistant cells are cells which retain their original rod-shaped morphology in the presence of physiological levels of Ca2+.) High levels of insulin (10(-6) M) stimulated the rate of 3-O-methylglucose uptake approximately 10-fold. In the presence of low levels of insulin (3 X 10(-11) M, 10(-10) M) uptake was biphasic; it could not be described by a single exponential function within experimental error, but required the sum of two exponentials. Deviation from a single exponential function was not so great with high levels of insulin (10(-6) M) or no insulin. Cell sugar uptake was also investigated using autoradiography of cells which had accumulated [2-14C]deoxyglucose under similar conditions. This showed considerable heterogeneity of 2-deoxyglucose uptake by cells treated with low levels of insulin, but significantly less heterogeneity of 2-deoxyglucose uptake by cells treated with high levels of insulin. It is concluded that the deviation of 3-O-methylglucose uptake from a single exponential observed at low insulin levels can be accounted for in terms of a heterogeneous response of cells to insulin

  19. Marrow fat cell: response to x-ray induced aplasia

    Bathija, A.; Ohanian, M.; Davis, S.; Trubowitz, S.


    Adipose tissue is an integral structural component of normal rabbit marrow and is believed to behave primarily as a cushion in response to hemopoietic proliferation, accommodating to changes in hemopoiesis by change in either size or number or both of the fat cells in order to maintain constancy of the marrow volume. To test this hypothesis, aplasia of the right femur of New Zealand white rabbits was induced by x irradiation with 8000 rads; the left unirradiated limb served as control. Twenty-four hours before sacrifice 50 μCi of palmitate-114C was administered intravenously and the marrow of both femurs removed. Samples of perinephric fat were taken for comparison. Fat cell volume, C14 palmitate turnover and fatty acid composition were determined. The total number of fat cells in the entire marrow of both femurs was calculated. The measurements showed no difference in size or fatty acid turnover of the fat cells in the irradiated aplastic marrow from the cells of the control marrow. The number of fat cells in both the irradiated and the unirradiated control femurs was essentially the same. These findings do not support the view that marrow fat cells respond to diminished hematopoiesis by either increase in their volume or number. In addition, the findings suggest that both marrow and subcutaneous fat cells are fairly resistant to high doses of x-ray irradiation

  20. Human neuronal cell protein responses to Nipah virus infection

    Hassan Sharifah


    Full Text Available Abstract Background Nipah virus (NiV, a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches. Results Method for separation of the NiV-infected human neuronal cell proteins using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE was established. At least 800 protein spots were resolved of which seven were unique, six were significantly up-regulated and eight were significantly down-regulated. Six of these altered proteins were identified using mass spectrometry (MS and confirmed using MS/MS. The heterogenous nuclear ribonucleoprotein (hnRNP F, guanine nucleotide binding protein (G protein, voltage-dependent anion channel 2 (VDAC2 and cytochrome bc1 were present in abundance in the NiV-infected SK-N-MC cells in contrast to hnRNPs H and H2 that were significantly down-regulated. Conclusion Several human neuronal cell proteins that are differentially expressed following NiV infection are identified. The proteins are associated with various cellular functions and their abundance reflects their significance in the cytopathologic responses to the infection and the regulation of NiV replication. The potential importance of the ratio of hnRNP F, and hnRNPs H and H2 in regulation of NiV replication, the association of the mitochondrial protein with the cytopathologic responses to the infection and induction of apoptosis are highlighted.

  1. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

    Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo


    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. Human Locomotion in Hypogravity: From Basic Research to Clinical Applications

    Francesco Lacquaniti


    Full Text Available We have considerable knowledge about the mechanisms underlying compensation of Earth gravity during locomotion, a knowledge obtained from physiological, biomechanical, modeling, developmental, comparative, and paleoanthropological studies. By contrast, we know much less about locomotion and movement in general under sustained hypogravity. This lack of information poses a serious problem for human space exploration. In a near future humans will walk again on the Moon and for the first time on Mars. It would be important to predict how they will move around, since we know that locomotion and mobility in general may be jeopardized in hypogravity, especially when landing after a prolonged weightlessness of the space flight. The combination of muscle weakness, of wearing a cumbersome spacesuit, and of maladaptive patterns of locomotion in hypogravity significantly increase the risk of falls and injuries. Much of what we currently know about locomotion in hypogravity derives from the video archives of the Apollo missions on the Moon, the experiments performed with parabolic flight or with body weight support on Earth, and the theoretical models. These are the topics of our review, along with the issue of the application of simulated hypogravity in rehabilitation to help patients with deambulation problems. We consider several issues that are common to the field of space science and clinical rehabilitation: the general principles governing locomotion in hypogravity, the methods used to reduce gravity effects on locomotion, the extent to which the resulting behavior is comparable across different methods, the important non-linearities of several locomotor parameters as a function of the gravity reduction, the need to use multiple methods to obtain reliable results, and the need to tailor the methods individually based on the physiology and medical history of each person.

  3. Hybrid Locomotion Evaluation for a Novel Amphibious Spherical Robot

    Huiming Xing


    Full Text Available We describe the novel, multiply gaited, vectored water-jet, hybrid locomotion-capable, amphibious spherical robot III (termed ASR-III featuring a wheel-legged, water-jet composite driving system incorporating a lifting and supporting wheel mechanism (LSWM and mechanical legs with a water-jet thruster. The LSWM allows the ASR-III to support the body and slide flexibly on smooth (flat terrain. The composite driving system facilitates two on-land locomotion modes (sliding and walking and underwater locomotion mode with vectored thrusters, improving adaptability to the amphibious environment. Sliding locomotion improves the stability and maneuverability of ASR-III on smooth flat terrain, whereas walking locomotion allows ASR-III to conquer rough terrain. We used both forward and reverse kinematic models to evaluate the walking and sliding gait efficiency. The robot can also realize underwater locomotion with four vectored water-jet thrusters, and is capable of forward motion, heading angle control and depth control. We evaluated LSWM efficiency and the sliding velocities associated with varying extensions of the LSWM. To explore gait stability and mobility, we performed on-land experiments on smooth flat terrain to define the optimal stride length and frequency. We also evaluated the efficacy of waypoint tracking when the sliding gait was employed, using a closed-loop proportional-integral-derivative (PID control mechanism. Moreover, experiments of forward locomotion, heading angle control and depth control were conducted to verify the underwater performance of ASR-III. Comparison of the previous robot and ASR-III demonstrated the ASR-III had better amphibious motion performance.

  4. Human Locomotion in Hypogravity: From Basic Research to Clinical Applications.

    Lacquaniti, Francesco; Ivanenko, Yury P; Sylos-Labini, Francesca; La Scaleia, Valentina; La Scaleia, Barbara; Willems, Patrick A; Zago, Myrka


    We have considerable knowledge about the mechanisms underlying compensation of Earth gravity during locomotion, a knowledge obtained from physiological, biomechanical, modeling, developmental, comparative, and paleoanthropological studies. By contrast, we know much less about locomotion and movement in general under sustained hypogravity. This lack of information poses a serious problem for human space exploration. In a near future humans will walk again on the Moon and for the first time on Mars. It would be important to predict how they will move around, since we know that locomotion and mobility in general may be jeopardized in hypogravity, especially when landing after a prolonged weightlessness of the space flight. The combination of muscle weakness, of wearing a cumbersome spacesuit, and of maladaptive patterns of locomotion in hypogravity significantly increase the risk of falls and injuries. Much of what we currently know about locomotion in hypogravity derives from the video archives of the Apollo missions on the Moon, the experiments performed with parabolic flight or with body weight support on Earth, and the theoretical models. These are the topics of our review, along with the issue of the application of simulated hypogravity in rehabilitation to help patients with deambulation problems. We consider several issues that are common to the field of space science and clinical rehabilitation: the general principles governing locomotion in hypogravity, the methods used to reduce gravity effects on locomotion, the extent to which the resulting behavior is comparable across different methods, the important non-linearities of several locomotor parameters as a function of the gravity reduction, the need to use multiple methods to obtain reliable results, and the need to tailor the methods individually based on the physiology and medical history of each person.

  5. Mitochondrial respiration controls lysosomal function during inflammatory T cell responses

    Baixauli, Francesc; Acín-Pérez, Rebeca; Villarroya-Beltrí, Carolina; Mazzeo, Carla; Nuñez-Andrade, Norman; Gabandé-Rodriguez, Enrique; Dolores Ledesma, Maria; Blázquez, Alberto; Martin, Miguel Angel; Falcón-Pérez, Juan Manuel; Redondo, Juan Miguel; Enríquez, Jose Antonio; Mittelbrunn, Maria


    Summary The endolysosomal system is critical for the maintenance of cellular homeostasis. However, how endolysosomal compartment is regulated by mitochondrial function is largely unknown. We have generated a mouse model with defective mitochondrial function in CD4+ T lymphocytes by genetic deletion of the mitochondrial transcription factor A (Tfam). Mitochondrial respiration-deficiency impairs lysosome function, promotes p62 and sphingomyelin accumulation and disrupts endolysosomal trafficking pathways and autophagy, thus linking a primary mitochondrial dysfunction to a lysosomal storage disorder. The impaired lysosome function in Tfam-deficient cells subverts T cell differentiation toward pro-inflammatory subsets and exacerbates the in vivo inflammatory response. Restoration of NAD+ levels improves lysosome function and corrects the inflammatory defects in Tfam-deficient T cells. Our results uncover a mechanism by which mitochondria regulate lysosome function to preserve T cell differentiation and effector functions, and identify novel strategies for intervention in mitochondrial-related diseases. PMID:26299452

  6. Effects of rubber flooring during the first 2 lactations on production, locomotion, hoof health, immune functions, and stress.

    Eicher, S D; Lay, D C; Arthington, J D; Schutz, M M


    Some housing systems on dairy farms can result in long-term chronic pain. The effects of acute pain on immunity have been explored, but chronic pain's influence on immune responses is still poorly understood. Therefore, the objective of this research was to determine chronic effects of flooring on immune responses and production in freestall housing for dairy cows. Thirty heifers were studied from before calving as first-calf heifers until d 180 of their second lactation. Treatments were rubber (Kraiburg; Agromatic Inc., Fond du Lac, WI) flooring or concrete with diamond grooves in a freestall barn, each in 2 quadrants of the barn. Heifers entered the treatments after calving, so the system was dynamic and each cow was considered an experimental unit. At the end of the first lactation, cows were housed in a bedded pack barn with pasture access until calving was imminent. At that time, they returned to their assigned treatment, but not necessarily into the same quadrant. Production, reproduction, cortisol, acute-phase proteins, and health data were recorded throughout lactation 1, locomotion was scored weekly, and hoof scoring and care was conducted on d 60 and 180 of lactations 1 and 2, and quantitative real-time-PCR of blood leukocytes was analyzed in mid lactation of lactation 1. Mature-equivalent milk fat, milk protein, and protein percentages during the first lactation were greater for cows on the rubber flooring. Hoof and leg therapy treatments per cow were fewer for rubber floor-housed cows. Locomotion scores were less for cows housed on rubber during the second lactation. White blood cell counts were less for cows housed on rubber, and caused by greater lymphocyte counts for cows housed on concrete. The possibility of chronic inflammation was substantiated by less IL-1β and more IL-1 receptor antagonists for cows housed on rubber at d 150 in the second lactation. Cortisol and acute-phase proteins did not differ between the treatments. Interferon-γ, IL-12

  7. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.


    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  8. Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies

    Erika Meroni


    Full Text Available The ketogenic diet (KD is a high-fat, low-carbohydrate diet based on the induction of the synthesis of ketone bodies (KB. Despite its widespread use, the systemic impact of KD is not completely understood. The purpose of this study was to evaluate the effects of physiological levels of KB on HMEC-1 endothelial cells. To this aim, DNA oxidative damage and the activation of Nrf2, a known transcriptional factor involved in cell responses to oxidative stress, were assessed. The exposure of cells to KB exerted a moderate genotoxic effect, measured by a significant increase in DNA oxidative damage. However, cells pre-treated with KB for 48 h and subjected to a secondary oxidative insult (H2O2, significantly decreased DNA damage compared to control oxidized cells. This protection occurred by the activation of Nrf2 pathway. In KB-treated cells, we found increased levels of Nrf2 in nuclear extracts and higher gene expression of HO-1, a target gene of Nrf2, compared to control cells. These results suggest that KB, by inducing moderate oxidative stress, activate the transcription factor Nrf2, which induces the transcription of target genes involved in the cellular antioxidant defense system.

  9. Protective immunization with B16 melanoma induces antibody response and not cytotoxic T cell response

    Sarzotti, M.; Sriyuktasuth, P.; Klimpel, G.R.; Cerny, J.


    C57BL/6 mice immunized with three intraperitoneal injections of syngeneic, irradiated B16 melanoma cells, became resistant to B16 tumor challenge. Immunized mice had high levels of serum antibody against a membrane antigen of B16 cells. The B16 antigen recognized by the anti-B16 sera formed a major band of 90 KD in gel electrophoresis. The anti-B16 antibody was partially protective when mixed with B16 cells and injected into normal recipient mice. Surprisingly, B16 resistance mice were incapable of generating cytotoxic T cells (CTL) specific for the B16 tumor. Both spleen and lymph node cell populations from immunized mice did not generate B16-specific CTL. Allogeneic mice (DBA/2 or C3H) were also unable to generate B16-specific CTL: however, alloreactive CTL produced in these strains of mice by immunization with C57BL/6 lymphocytes, did kill B16 target cells. Interestingly, spleen cells from syngeneic mice immunized with B16 tumor produced 6-fold more interleukin-2 (IL-2) than normal spleen cells, in vitro. These data suggest that immunization with B16 tumor activates a helper subset of T cells (for antibody and IL-2 production) but not the effector CTL response

  10. An unexpected antibody response to an engineered influenza virus modifies CD8+ T cell responses.

    Thomas, Paul G; Brown, Scott A; Yue, Wen; So, Jenny; Webby, Richard J; Doherty, Peter C


    The ovalbumin(323-339) peptide that binds H2I-A(b) was engineered into the globular heads of hemagglutinin (H) molecules from serologically non-cross-reactive H1N1 and H3N2 influenza A viruses, the aim being to analyze recall CD4+ T cell responses in a virus-induced respiratory disease. Prime/challenge experiments with these H1ova and H3ova viruses in H2(b) mice gave the predicted, ovalbumin-specific CD4+ T cell response but showed an unexpectedly enhanced, early expansion of viral epitope-specific CD8+ T cells in spleen and a greatly diminished inflammatory process in the virus-infected respiratory tract. At the same time, the primary antibody response to the H3N2 challenge virus was significantly reduced, an effect that has been associated with preexisting neutralizing antibody in other experimental systems. Analysis of serum from the H1ova-primed mice showed low-level binding to H3ova but not to the wild-type H3N2 virus. Experiments with CD4+ T cell-depleted and Ig-/- mice indicated that this cross-reactive Ig is indeed responsible for the modified pathogenesis after respiratory challenge. Furthermore, the effect does not seem to be virus-dose related, although it does require infection. These findings suggest intriguing possibilities for vaccination and, at the same time, emphasize that engineered modifications in viruses may have unintended immunological consequences.

  11. Cells responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers

    Reizenstein, P.; Ogier, C.; Blomgren, H.; Petrini, B.; Wasserman, J.


    Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). 154 references

  12. Extracellular Alkalinization as a Defense Response in Potato Cells.

    Moroz, Natalia; Fritch, Karen R; Marcec, Matthew J; Tripathi, Diwaker; Smertenko, Andrei; Tanaka, Kiwamu


    A quantitative and robust bioassay to assess plant defense response is important for studies of disease resistance and also for the early identification of disease during pre- or non-symptomatic phases. An increase in extracellular pH is known to be an early defense response in plants. In this study, we demonstrate extracellular alkalinization as a defense response in potatoes. Using potato suspension cell cultures, we observed an alkalinization response against various pathogen- and plant-derived elicitors in a dose- and time-dependent manner. We also assessed the defense response against a variety of potato pathogens, such as protists ( Phytophthora infestans and Spongospora subterranea ) and fungi ( Verticillium dahliae and Colletotrichum coccodes ). Our results show that extracellular pH increases within 30 min in proportion to the number of pathogen spores added. Consistently with the alkalinization effect, the higher transcription level of several defense-related genes and production of reactive oxygen species was observed. Our results demonstrate that the alkalinization response is an effective marker to study early stages of defense response in potatoes.

  13. Respiratory epithelial cell responses to cigarette smoke: the unfolded protein response.

    Kelsen, Steven G


    Cigarette smoking exposes the respiratory epithelium to highly toxic, reactive oxygen nitrogen species which damage lung proteins in the endoplasmic reticulum (ER), the cell organelle in which all secreted and membrane proteins are processed. Accumulation of damaged or misfolded proteins in the ER, a condition termed ER stress, activates a complex cellular process termed the unfolded protein responses (UPR). The UPR acts to restore cellular protein homeostasis by regulating all aspects of protein metabolism including: protein translation and syntheses; protein folding; and protein degradation. However, activation of the UPR may also induce signaling pathways which induce inflammation and cell apoptosis. This review discusses the role of UPR in the respiratory epithelial cell response to cigarette smoke and the pathogenesis of lung diseases like COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun [Division of heavy ion clinical research, Korea University, Seoul (Korea, Republic of); Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)


    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy.

  15. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun; Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook


    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy

  16. Curcumin prevents human dendritic cell response to immune stimulants

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.


    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14 + monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4 + T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant

  17. Tumor Response to Radiotherapy Regulated by Endothelial Cell Apoptosis

    Garcia-Barros, Monica; Paris, Francois; Cordon-Cardo, Carlos; Lyden, David; Rafii, Shahin; Haimovitz-Friedman, Adriana; Fuks, Zvi; Kolesnick, Richard


    About 50% of cancer patients receive radiation therapy. Here we investigated the hypothesis that tumor response to radiation is determined not only by tumor cell phenotype but also by microvascular sensitivity. MCA/129 fibrosarcomas and B16F1 melanomas grown in apoptosis-resistant acid sphingomyelinase (asmase)-deficient or Bax-deficient mice displayed markedly reduced baseline microvascular endothelial apoptosis and grew 200 to 400% faster than tumors on wild-type microvasculature. Thus, endothelial apoptosis is a homeostatic factor regulating angiogenesis-dependent tumor growth. Moreover, these tumors exhibited reduced endothelial apoptosis upon irradiation and, unlike tumors in wild-type mice, they were resistant to single-dose radiation up to 20 grays (Gy). These studies indicate that microvascular damage regulates tumor cell response to radiation at the clinically relevant dose range.

  18. Global gene expression response to telomerase in bovine adrenocortical cells

    Perrault, Steven D.; Hornsby, Peter J.; Betts, Dean H.


    The infinite proliferative capability of most immortalized cells is dependent upon the presence of the enzyme telomerase and its ability to maintain telomere length and structure. However, telomerase may be involved in a greater system than telomere length regulation, as recent evidence has shown it capable of increasing wound healing in vivo, and improving cellular proliferation rate and survival from apoptosis in vitro. Here, we describe the global gene expression response to ectopic telomerase expression in an in vitro bovine adrenocortical cell model. Telomerase-immortalized cells showed an increased ability for proliferation and survival in minimal essential medium above cells transgenic for GFP. cDNA microarray analyses revealed an altered cell state indicative of increased adrenocortical cell proliferation regulated by the IGF2 pathway and alterations in members of the TGF-B family. As well, we identified alterations in genes associated with development and wound healing that support a model that high telomerase expression induces a highly adaptable, progenitor-like state

  19. Human influenza viruses and CD8(+) T cell responses.

    Grant, Emma J; Quiñones-Parra, Sergio M; Clemens, E Bridie; Kedzierska, Katherine


    Influenza A viruses (IAVs) cause significant morbidity and mortality worldwide, despite new strain-specific vaccines being available annually. As IAV-specific CD8(+) T cells promote viral control in the absence of neutralizing antibodies, and can mediate cross-reactive immunity toward distinct IAVs to drive rapid recovery from both mild and severe influenza disease, there is great interest in developing a universal T cell vaccine. However, despite detailed studies in mouse models of influenza virus infection, there is still a paucity of data on human epitope-specific CD8(+) T cell responses to IAVs. This review focuses on our current understanding of human CD8(+) T cell immunity against distinct IAVs and discusses the possibility of achieving a CD8(+) T cell mediated-vaccine that protects against multiple, distinct IAV strains across diverse human populations. We also review the importance of CD8(+) T cell immunity in individuals highly susceptible to severe influenza infection, including those hospitalised with influenza, the elderly and Indigenous populations. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Purinergic responses of chondrogenic stem cells to dynamic loading

    Gađanski Ivana


    Full Text Available In habitually loaded tissues, dynamic loading can trigger ATP (adenosine 5’- triphosphate release to extracellular environment, and result in calcium signaling via ATP binding to purine P2 receptors1. In the current study we have compared purinergic responses (ATP release of two types of cells: bovine chondrocytes (bCHs and human mesenchymal stem cells (hMSC that were encapsulated in agarose and subjected to dynamic loading. Both cell types were cultured under chondrogenic conditions, and their responses to loading were evaluated by ATP release assay in combination with connexin (Cx-sensitive fluorescent dye (Lucifer Yellow - LY and a Cx-hemichannel blocker (Flufenamic acid - FFA. In response to dynamic loading, chondrogenic hMSCs released significantly higher amounts of ATP (5-fold in comparison to the bCHs early in culture (day 2. Triggering of LY uptake in the bCHs and hMSCs by dynamic loading implies opening of the Cx-hemichannels. However, the number of LY-positive cells in hMSC-constructs was 2.5-fold lower compared to the loaded bCH-constructs, suggesting utilization of additional mechanisms of ATP release. Cx-reactive sites were detected in both bCHs and hMSCs-constructs. FFA application led to reduced ATP release both in bCHs and hMSCs, which confirms the involvement of connexin hemichannels, with more prominent effects in bCHs than in hMSCs, further implying the existence of additional mechanism of ATP release in chondrogenic hMSCs. Taken together, these results indicate stronger purinergic response to dynamic loading of chondrogenic hMSCs than primary chondrocytes, by activation of connexin hemichannels and additional mechanisms of ATP release. [Projekat Ministrastva nauke Republike Srbije, ON174028 i br. III41007

  1. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M


    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  2. Cell response to long term mechanical interaction with nanopipettes

    Orynbayeva, Zulfiya; Singhal, Riju; Vitol, Elina; Bouchard, Michael; Azizkhan-Clifford, Jane; Layton, Bradley; Friedman, Gary; Gogotsi, Yury


    Traditional microinjection into cells is performed over a relatively short term. Pipettes are typically withdrawn following any kind of injection. On the other hand, there is growing interest in using nanopipettes for cellular and subcellular probing. This interest is partly due to new developments in nanopipette technology which employ carbon nanotubes and provide robustness, flexibility, and biocompatibility. However, as far as we know, no systematic study of physiological, biochemical, and biophysical processes associated with cell response to lengthy mechanical stimulations by nanopipette probing have been performed so far. We present a detailed investigation of a wide range of effects of long term pipette insertion into a cell. Both traditional glass micropipettes and the novel carbon nanotube-tipped probes were involved in this study. The mechanism of Ca2+ response to the mechanical stimuli introduced by the nanopipette, and the role of different organelles in this mechanism were studied. We hypothesize that the calcium response is a function of cytoskeleton integrity and the mode of coupling between the cytoskeleton and the plasma membrane domains.

  3. The Unfolded Protein Response and Cell Fate Control.

    Hetz, Claudio; Papa, Feroz R


    The secretory capacity of a cell is constantly challenged by physiological demands and pathological perturbations. To adjust and match the protein-folding capacity of the endoplasmic reticulum (ER) to changing secretory needs, cells employ a dynamic intracellular signaling pathway known as the unfolded protein response (UPR). Homeostatic activation of the UPR enforces adaptive programs that modulate and augment key aspects of the entire secretory pathway, whereas maladaptive UPR outputs trigger apoptosis. Here, we discuss recent advances into how the UPR integrates information about the intensity and duration of ER stress stimuli in order to control cell fate. These findings are timely and significant because they inform an evolving mechanistic understanding of a wide variety of human diseases, including diabetes mellitus, neurodegeneration, and cancer, thus opening up the potential for new therapeutic modalities to treat these diverse diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The CD8 T Cell Response to Respiratory Virus Infections.

    Schmidt, Megan E; Varga, Steven M


    Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection. However, the mucosal antibody response to many respiratory viruses is not long-lasting and declines with age. CD8 T cells are critical for mediating clearance following many acute viral infections in the lung. In addition, memory CD8 T cells are capable of providing protection against secondary infections. Therefore, the combined induction of virus-specific CD8 T cells and antibodies may provide optimal protective immunity. Herein, we review the current literature on CD8 T cell responses induced by respiratory virus infections. Additionally, we explore how this knowledge could be utilized in the development of future vaccines against respiratory viruses, with a special emphasis on RSV vaccination.

  5. Effective Stimulus Parameters for Directed Locomotion in Madagascar Hissing Cockroach Biobot.

    Jonathan C Erickson

    Full Text Available Swarms of insects instrumented with wireless electronic backpacks have previously been proposed for potential use in search and rescue operations. Before deploying such biobot swarms, an effective long-term neural-electric stimulus interface must be established, and the locomotion response to various stimuli quantified. To this end, we studied a variety of pulse types (mono- vs. bipolar; voltage- vs. current-controlled and shapes (amplitude, frequency, duration to parameters that are most effective for evoking locomotion along a desired path in the Madagascar hissing cockroach (G. portentosa in response to antennal and cercal stimulation. We identified bipolar, 2 V, 50 Hz, 0.5 s voltage controlled pulses as being optimal for evoking forward motion and turns in the expected contraversive direction without habituation in ≈50% of test subjects, a substantial increase over ≈10% success rates previously reported. Larger amplitudes for voltage (1-4 V and current (50-150 μA pulses generally evoked larger forward walking (15.6-25.6 cm; 3.9-5.6 cm/s but smaller concomitant turning responses (149 to 80.0 deg; 62.8 to 41.2 deg/s. Thus, the radius of curvature of the initial turn-then-run locomotor response (≈10-25 cm could be controlled in a graded manner by varying the stimulus amplitude. These findings could be used to help optimize stimulus protocols for swarms of cockroach biobots navigating unknown terrain.

  6. PKC activation induces inflammatory response and cell death in human bronchial epithelial cells.

    Hyunhee Kim

    Full Text Available A variety of airborne pathogens can induce inflammatory responses in airway epithelial cells, which is a crucial component of host defence. However, excessive inflammatory responses and chronic inflammation also contribute to different diseases of the respiratory system. We hypothesized that the activation of protein kinase C (PKC is one of the essential mechanisms of inflammatory response in airway epithelial cells. In the present study, we stimulated human bronchial lung epithelial (BEAS-2B cells with the phorbol ester Phorbol 12, 13-dibutyrate (PDBu, and examined gene expression profile using microarrays. Microarray analysis suggests that PKC activation induced dramatic changes in gene expression related to multiple cellular functions. The top two interaction networks generated from these changes were centered on NFκB and TNF-α, which are two commonly known pathways for cell death and inflammation. Subsequent tests confirmed the decrease in cell viability and an increase in the production of various cytokines. Interestingly, each of the increased cytokines was differentially regulated at mRNA and/or protein levels by different sub-classes of PKC isozymes. We conclude that pathological cell death and cytokine production in airway epithelial cells in various situations may be mediated through PKC related signaling pathways. These findings suggest that PKCs can be new targets for treatment of lung diseases.

  7. Natural Killer Cell Response to Chemotherapy-Stressed Cancer Cells: Role in Tumor Immunosurveillance

    Alessandra Zingoni


    Full Text Available Natural killer (NK cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i.e., mitotic catastrophe, senescence, and autophagy. However, it is becoming increasingly clear that they can trigger additional stress responses. Indeed, relevant immunostimulating effects of different therapeutic programs include also the activation of pathways able to promote their recognition by immune effector cells. Among stress-inducible immunostimulating proteins, changes in the expression levels of NK cell-activating and inhibitory ligands, as well as of death receptors on tumor cells, play a critical role in their detection and elimination by innate immune effectors, including NK cells. Here, we will review recent advances in chemotherapy-mediated cellular stress pathways able to stimulate NK cell effector functions. In particular, we will address how these cytotoxic lymphocytes sense and respond to different types of drug-induced stresses contributing to anticancer activity.

  8. Towards a general neural controller for quadrupedal locomotion.

    Maufroy, Christophe; Kimura, Hiroshi; Takase, Kunikatsu


    Our study aims at the design and implementation of a general controller for quadruped locomotion, allowing the robot to use the whole range of quadrupedal gaits (i.e. from low speed walking to fast running). A general legged locomotion controller must integrate both posture control and rhythmic motion control and have the ability to shift continuously from one control method to the other according to locomotion speed. We are developing such a general quadrupedal locomotion controller by using a neural model involving a CPG (Central Pattern Generator) utilizing ground reaction force sensory feedback. We used a biologically faithful musculoskeletal model with a spine and hind legs, and computationally simulated stable stepping motion at various speeds using the neuro-mechanical system combining the neural controller and the musculoskeletal model. We compared the changes of the most important locomotion characteristics (stepping period, duty ratio and support length) according to speed in our simulations with the data on real cat walking. We found similar tendencies for all of them. In particular, the swing period was approximately constant while the stance period decreased with speed, resulting in a decreasing stepping period and duty ratio. Moreover, the support length increased with speed due to the posterior extreme position that shifted progressively caudally, while the anterior extreme position was approximately constant. This indicates that we succeeded in reproducing to some extent the motion of a cat from the kinematical point of view, even though we used a 2D bipedal model. We expect that such computational models will become essential tools for legged locomotion neuroscience in the future.

  9. Gene expression in epithelial cells in response to pneumovirus infection

    Rosenberg Helene F


    Full Text Available Abstract Respiratory syncytial virus (RSV and pneumonia virus of mice (PVM are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood. Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner.

  10. Cell mediated immune response in human antirabies revaccination

    Débora Regina Veiga


    Full Text Available The occurrence of secondary cell mediated immune response (CMI in human antirabies immunization was studied. The Puenzalida & Palácios vaccine was used because it is routinely used in Brazil. CMI was evaluated by lymphoblastic transformation indices obtained in whole blood culture in the presence of rabies and control (nervous tissue antigens. Eleven volunteers submitted to revaccination constituted the group under study, while three other volunteers submitted primo vaccination were utilized as control group. A clear secondary CMI to rabies antigen was detected in all the revaccinated volunteers who showed earlier and more intense response than the control group. Response to the control antigen, however, present in all the components of the first group was not detectable in two out of the three primovaccinated and very low in the third one.

  11. Distinct gut-derived lactic acid bacteria elicit divergent dendritic cell-mediated NK cell responses

    Fink, Lisbeth Nielsen; Zeuthen, Louise Hjerrild; Christensen, Hanne


    Lactic acid bacteria (LAB) are abundant in the gastrointestinal tract where they continuously regulate the immune system. NK cells are potently activated by dendritic cells (DCs) matured by inflammatory stimuli, and NK cells are present in the gut epithelium and in mesenteric lymph nodes......, but it is not known how NK-DC interactions are affected by the predominantly non-pathogenic LAB. We demonstrate that human DCs exposed to different strains of gut-derived LAB consistently induce proliferation, cytotoxicity and activation markers in autologous NK cells. On the contrary, strains of LAB differ greatly...... in their ability to induce DC-dependent IFN-gamma production by NK cells. This suggests that DCs stimulated by gut LAB may expand the pool of NK cells and increase their cytotoxic potential. Specific LAB, inducing high levels of IL-12 in DCs, may promote amplification of a type-1 response via potent stimulation...

  12. The Role of B Cells for in Vivo T Cell Responses to a Friend Virus-Induced Leukemia

    Schultz, Kirk R.; Klarnet, Jay P.; Gieni, Randall S.; Hayglass, Kent T.; Greenberg, Philip D.


    B cells can function as antigen-presenting cells and accessory cells for T cell responses. This study evaluated the role of B cells in the induction of protective T cell immunity to a Friend murine leukemia virus (F-MuLV)-induced leukemia (FBL). B cell-deficient mice exhibited significantly reduced tumor-specific CD4^+ helper and CD8^+ cytotoxic T cell responses after priming with FBL or a recombinant vaccinia virus containing F-MuLV antigens. Moreover, these mice had diminished T cell responses to the vaccinia viral antigens. Tumor-primed T cells transferred into B cell-deficient mice effectively eradicated disseminated FBL. Thus, B cells appear necessary for efficient priming but not expression of tumor and viral T cell immunity.

  13. Economic aspects of advanced coal-fired gas turbine locomotives

    Liddle, S. G.; Bonzo, B. B.; Houser, B. C.


    Increases in the price of such conventional fuels as Diesel No. 2, as well as advancements in turbine technology, have prompted the present economic assessment of coal-fired gas turbine locomotive engines. A regenerative open cycle internal combustion gas turbine engine may be used, given the development of ceramic hot section components. Otherwise, an external combustion gas turbine engine appears attractive, since although its thermal efficiency is lower than that of a Diesel engine, its fuel is far less expensive. Attention is given to such a powerplant which will use a fluidized bed coal combustor. A life cycle cost analysis yields figures that are approximately half those typical of present locomotive engines.

  14. Intestinal Epithelial Cells Modulate Antigen-Presenting Cell Responses to Bacterial DNA

    Campeau, J. L.; Salim, S. Y.; Albert, E. J.; Hotte, N.


    Intestinal epithelial cells and antigen-presenting cells orchestrate mucosal innate immunity. This study investigated the role of bacterial DNA in modulating epithelial and bone marrow-derived antigen-presenting cells (BM-APCs) and subsequent T-lymphocyte responses. Murine MODE-K epithelial cells and BM-APCs were treated with DNA from either Bifidobacterium breve or Salmonella enterica serovar Dublin directly and under coculture conditions with CD4+ T cells. Apical stimulation of MODE-K cells with S. Dublin DNA enhanced secretion of cytokines from underlying BM-APCs and induced interleukin-17 (IL-17) and gamma interferon (IFN-γ) secretion from CD4+ T cells. Bacterial DNA isolated from either strain induced maturation and increased cytokine secretion from BM-APCs. Conditioned medium from S. Dublin-treated MODE-K cells elicited an increase in cytokine secretion similar to that seen for S. Dublin DNA. Treatment of conditioned medium from MODE-K cells with RNase and protease prevented the S. Dublin-induced increased cytokine secretion. Oral feeding of mice with B. breve DNA resulted in enhanced levels of colonic IL-10 and transforming growth factor β (TGFβ) compared with what was seen for mice treated with S. Dublin DNA. In contrast, feeding mice with S. Dublin DNA increased levels of colonic IL-17 and IL-12p70. T cells from S. Dublin DNA-treated mice secreted high levels of IL-12 and IFN-γ compared to controls and B. breve DNA-treated mice. These results demonstrate that intestinal epithelial cells are able to modulate subsequent antigen-presenting and T-cell responses to bacterial DNA with pathogenic but not commensal bacterial DNA inducing effector CD4+ T lymphocytes. PMID:22615241

  15. Dynamic processes during monorail locomotive rocking and their impact on draw gear characteristics



    Full Text Available The article discusses the motion of the suspended monorail locomotive, interrelation between the parameters of irregularities false path and lateral rocking monorail locomotive, the values of lateral deviation for the different speeds on the monorail.

  16. Dynamic processes during monorail locomotive rocking and their impact on draw gear characteristics



    The article discusses the motion of the suspended monorail locomotive, interrelation between the parameters of irregularities false path and lateral rocking monorail locomotive, the values of lateral deviation for the different speeds on the monorail.

  17. 49 CFR 236.1006 - Equipping locomotives operating in PTC territory.


    ... 31, 2015, a train controlled by a locomotive with an onboard PTC apparatus that has failed en route... III railroad, including a tourist or excursion railroad, and controlled by a locomotive not equipped...

  18. Hemopoietic cell precursor responses to erythropoietin in plasma clot cultures

    Kennedy, W.L.


    The time dependence of the response of mouse bone marrow cells to erythropoietin (Ep) in vitro was studied. Experiments include studies on the Ep response of marrow cells from normal, plethoric, or bled mice. Results with normal marrow reveal: (1) Not all erythroid precursors (CFU-E) are alike in their response to Ep. A significant number of the precursors develop to a mature erythroid colony after very short Ep exposures, but they account for only approx. 13% of the total colonies generated when Ep is active for 48 hrs. If Ep is active more than 6 hrs, a second population of erythroid colonies emerges at a nearly constant rate until the end of the culture. Full erythroid colony production requires prolonged exposure to erythropoietin. (2) The longer erythropoietin is actively present, the larger the number of erythroid colonies that reach 17 cells or more. Two distinct populations of immediate erythroid precursors are also present in marrow from plethoric mice. In these mice, total colony numbers are equal to or below those obtained from normal mice. However, the population of fast-responding CFU-E is consistently decreased to 10 to 20% of that found in normal marrow. The remaining colonies are formed from plethoric marrow at a rate equal to normal marrow. With increasing Ep exposures, the number of large colonies produced increases. From the marrow of bled mice, total erythroid colony production is equal to or above that of normal marrow. Two populations of colony-forming cells are again evident, with the fast-responding CFU-E being below normal levels. The lack of colonies from this group was compensated in bled mice by rapid colony production in the second population. A real increase in numbers of precursors present in this pool increased the rate of colony production in culture to twice that of normal marrow. The number of large colonies obtained from bled mice was again increased as the Ep exposure was lengthened. (ERB)

  19. Chronic low-dose γ-irradiation of Drosophila melanogaster larvae induces gene expression changes and enhances locomotive behavior

    Kim, Cha Soon; Lee, Byung Sub; Lee, In Kyung; Yang, Kwang Hee; Kim, Ji-Young; Nam, Seon Young; Seong, Ki Moon


    Although radiation effects have been extensively studied, the biological effects of low-dose radiation (LDR) are controversial. This study investigates LDR-induced alterations in locomotive behavior and gene expression profiles of Drosophila melanogaster. We measured locomotive behavior using larval pupation height and the rapid iterative negative geotaxis (RING) assay after exposure to 0.1 Gy γ-radiation (dose rate of 16.7 mGy/h). We also observed chronic LDR effects on development (pupation and eclosion rates) and longevity (life span). To identify chronic LDR effects on gene expression, we performed whole-genome expression analysis using gene-expression microarrays, and confirmed the results using quantitative real-time PCR. The pupation height of the LDR-treated group at the first larval instar was significantly higher (∼2-fold increase in PHI value, P < 0.05). The locomotive behavior of LDR-treated male flies (∼3 − 5 weeks of age) was significantly increased by 7.7%, 29% and 138%, respectively (P < 0.01), but pupation and eclosion rates and life spans were not significantly altered. Genome-wide expression analysis identified 344 genes that were differentially expressed in irradiated larvae compared with in control larvae. We identified several genes belonging to larval behavior functional groups such as locomotion (1.1%), oxidation reduction (8.0%), and genes involved in conventional functional groups modulated by irradiation such as defense response (4.9%), and sensory and perception (2.5%). Four candidate genes were confirmed as differentially expressed genes in irradiated larvae using qRT-PCR (>2-fold change). These data suggest that LDR stimulates locomotion-related genes, and these genes can be used as potential markers for LDR. (author)

  20. Response to various periods of mechanical stimuli in Physarum plasmodium

    Umedachi, Takuya; Ito, Kentaro; Kobayashi, Ryo; Ishiguro, Akio; Nakagaki, Toshiyuki


    Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli. (paper)

  1. Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene

    Giddings Ian


    Full Text Available Abstract Background Benzo[a]pyrene (BaP is a widespread environmental genotoxic carcinogen that damages DNA by forming adducts. This damage along with activation of the aryl hydrocarbon receptor (AHR induces complex transcriptional responses in cells. To investigate whether human cells are more susceptible to BaP in a particular phase of the cell cycle, synchronised breast carcinoma MCF-7 cells were exposed to BaP. Cell cycle progression was analysed by flow cytometry, DNA adduct formation was assessed by 32P-postlabeling analysis, microarrays of 44K human genome-wide oligos and RT-PCR were used to detect gene expression (mRNA changes and Western blotting was performed to determine the expression of some proteins, including cytochrome P450 (CYP 1A1 and CYP1B1, which are involved in BaP metabolism. Results Following BaP exposure, cells evaded G1 arrest and accumulated in S-phase. Higher levels of DNA damage occurred in S- and G2/M- compared with G0/G1-enriched cultures. Genes that were found to have altered expression included those involved in xenobiotic metabolism, apoptosis, cell cycle regulation and DNA repair. Gene ontology and pathway analysis showed the involvement of various signalling pathways in response to BaP exposure, such as the Catenin/Wnt pathway in G1, the ERK pathway in G1 and S, the Nrf2 pathway in S and G2/M and the Akt pathway in G2/M. An important finding was that higher levels of DNA damage in S- and G2/M-enriched cultures correlated with higher levels of CYP1A1 and CYP1B1 mRNA and proteins. Moreover, exposure of synchronised MCF-7 cells to BaP-7,8-diol-9,10-epoxide (BPDE, the ultimate carcinogenic metabolite of BaP, did not result in significant changes in DNA adduct levels at different phases of the cell cycle. Conclusions This study characterised the complex gene response to BaP in MCF-7 cells and revealed a strong correlation between the varying efficiency of BaP metabolism and DNA damage in different phases of the cell

  2. Innate lymphoid cells and their role in immune response regulation

    Bibiana Patricia Ruiz-Sánchez


    Full Text Available Innate lymphoid cells (ILCs are lymphocytes lacking antigen recognition receptors and become activated in response to cytokines and through microbe-associated molecular pattern (MAMP receptors. ILCs are found mainly in mucosal tissues and participate in the immune response against infections and in chronic inflammatory conditions. ILCs are divided in ILC-1, ILC-2 and ILC-3, and these cells have analogue functions to those of immune adaptive response lymphocytes Th1, Th2 and Th17. ILC-1 express T-bet, produce IFNγ, protect against infections with intracellular microorganisms and are related to inflammatory bowel disease immunopathology. ILC-2 express GATA3, produce IL-4, IL-5, IL-13 and amphiregulin, protect against parasitic infections and related to allergy and obesity immunopathology. ILC-3 express ROR(γt, produce IL-17 and IL-22, protect against fungal infections and contribute to tolerance to intestinal microbiota and intestinal repair. They are related to inflammatory bowel disease and psoriasis immunopathology. In general terms, ILCs maintain homeostasis and coadjuvate in the protection against infections.

  3. The circadian response of intrinsically photosensitive retinal ganglion cells.

    Andrew J Zele

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGC signal environmental light level to the central circadian clock and contribute to the pupil light reflex. It is unknown if ipRGC activity is subject to extrinsic (central or intrinsic (retinal network-mediated circadian modulation during light entrainment and phase shifting. Eleven younger persons (18-30 years with no ophthalmological, medical or sleep disorders participated. The activity of the inner (ipRGC and outer retina (cone photoreceptors was assessed hourly using the pupil light reflex during a 24 h period of constant environmental illumination (10 lux. Exogenous circadian cues of activity, sleep, posture, caffeine, ambient temperature, caloric intake and ambient illumination were controlled. Dim-light melatonin onset (DLMO was determined from salivary melatonin assay at hourly intervals, and participant melatonin onset values were set to 14 h to adjust clock time to circadian time. Here we demonstrate in humans that the ipRGC controlled post-illumination pupil response has a circadian rhythm independent of external light cues. This circadian variation precedes melatonin onset and the minimum ipRGC driven pupil response occurs post melatonin onset. Outer retinal photoreceptor contributions to the inner retinal ipRGC driven post-illumination pupil response also show circadian variation whereas direct outer retinal cone inputs to the pupil light reflex do not, indicating that intrinsically photosensitive (melanopsin retinal ganglion cells mediate this circadian variation.

  4. 49 CFR 230.12 - Movement of non-complying steam locomotives.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of non-complying steam locomotives. 230... General General Inspection Requirements § 230.12 Movement of non-complying steam locomotives. (a) General limitations on movement. A steam locomotive with one or more non-complying conditions may be moved only as a...

  5. 49 CFR 1242.25 - Locomotive servicing facilities (account XX-19-27).


    ... 49 Transportation 9 2010-10-01 2010-10-01 false Locomotive servicing facilities (account XX-19-27... Structures § 1242.25 Locomotive servicing facilities (account XX-19-27). Separate common expenses according to distribution of common expenses in the following accounts: Locomotive Fuel (XX-51-67 and XX-52-67...

  6. 49 CFR 223.17 - Identification of equipped locomotives, passenger cars and cabooses.


    ... cars and cabooses. 223.17 Section 223.17 Transportation Other Regulations Relating to Transportation...-LOCOMOTIVES, PASSENGER CARS AND CABOOSES Specific Requirements § 223.17 Identification of equipped locomotives, passenger cars and cabooses. Each locomotive, passenger car and caboose that is fully equipped with glazing...

  7. Induced pluripotent stem cells-derived myeloid-derived suppressor cells regulate the CD8+ T cell response

    Daniel Joyce


    Full Text Available Myeloid-derived suppressor cells (MDSCs are markedly increased in cancer patients and tumor-bearing mice and promote tumor growth and survival by inhibiting host innate and adaptive immunity. In this study, we generated and characterized MDSCs from murine-induced pluripotent stem cells (iPSCs. The iPSCs were co-cultured with OP9 cells, stimulated with GM-CSF, and became morphologically heterologous under co-culturing with hepatic stellate cells. Allogeneic and OVA-specific antigen stimulation demonstrated that iPS-MDSCs have a T-cell regulatory function. Furthermore, a popliteal lymph node assay and autoimmune hepatitis model showed that iPS-MDSCs also regulate immune responsiveness in vivo and have a therapeutic effect against hepatitis. Taken together, our results demonstrated a method of generating functional MDSCs from iPSCs and highlighted the potential of iPS-MDSCs as a key cell therapy resource for transplantation and autoimmune diseases. Keywords: Myeloid-derived suppressor cells, Induced pluripotent stem cells, T cell response

  8. Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis

    Sellebjerg, F; Hesse, D; Limborg, S


    , monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA. Methods: Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25high and CD26high cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS......Background: Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist. Objective: To study the activation of CD4+ T cells...... (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05–1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers...

  9. Human dental pulp cells exhibit bone cell-like responsiveness to fluid shear stress.

    Kraft, David Christian Evar; Bindslev, Dorth Arenholt; Melsen, Birte; Klein-Nulend, Jenneke


    For engineering bone tissue to restore, for example, maxillofacial defects, mechanosensitive cells are needed that are able to conduct bone cell-specific functions, such as bone remodelling. Mechanical loading affects local bone mass and architecture in vivo by initiating a cellular response via loading-induced flow of interstitial fluid. After surgical removal of ectopically impacted third molars, human dental pulp tissue is an easily accessible and interesting source of cells for mineralized tissue engineering. The aim of this study was to determine whether human dental pulp-derived cells (DPC) are responsive to mechanical loading by pulsating fluid flow (PFF) upon stimulation of mineralization in vitro. Human DPC were incubated with or without mineralization medium containing differentiation factors for 3 weeks. Cells were subjected to 1-h PFF (0.7 ± 0.3 Pa, 5 Hz) and the response was quantified by measuring nitric oxide (NO) and prostaglandin E₂ (PGE₂) production, and gene expression of cyclooxygenase (COX)-1 and COX-2. We found that DPC are intrinsically mechanosensitive and, like osteogenic cells, respond to PFF-induced fluid shear stress. PFF stimulated NO and PGE₂ production, and up-regulated COX-2 but not COX-1 gene expression. In DPC cultured under mineralizing conditions, the PFF-induced NO, but not PGE₂, production was significantly enhanced. These data suggest that human DPC, like osteogenic cells, acquire responsiveness to pulsating fluid shear stress in mineralizing conditions. Thus DPC might be able to perform bone-like functions during mineralized tissue remodeling in vivo, and therefore provide a promising new tool for mineralized tissue engineering to restore, for example, maxillofacial defects.

  10. The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses

    María Guadalupe Reyes García


    Full Text Available T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial “nurse cells” and retained in vacuoles, where most of them (95% are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called “regulatory cells,” which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.

  11. Leukemia-associated activating mutation of Flt3 expands dendritic cells and alters T cell responses.

    Lau, Colleen M; Nish, Simone A; Yogev, Nir; Waisman, Ari; Reiner, Steven L; Reizis, Boris


    A common genetic alteration in acute myeloid leukemia is the internal tandem duplication (ITD) in FLT3, the receptor for cytokine FLT3 ligand (FLT3L). Constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. Pre-leukemic mice with the Flt3(ITD) knock-in allele manifested an expansion of classical DCs (cDCs) and plasmacytoid DCs. The expansion originated in DC progenitors, was cell intrinsic, and was further enhanced in Flt3(ITD/ITD) mice. The mutation caused the down-regulation of Flt3 on the surface of DCs and reduced their responsiveness to Flt3L. Both canonical Batf3-dependent CD8(+) cDCs and noncanonical CD8(+) cDCs were expanded and showed specific alterations in their expression profiles. Flt3(ITD) mice showed enhanced capacity to support T cell proliferation, including a cell-extrinsic expansion of regulatory T (T reg) cells. Accordingly, these mice restricted alloreactive T cell responses during graft-versus-host reaction, but failed to control autoimmunity without T reg cells. Thus, the FLT3-ITD mutation directly affects DC development, indirectly modulating T cell homeostasis and supporting T reg cell expansion. We hypothesize that this effect of FLT3-ITD might subvert immunosurveillance and promote leukemogenesis in a cell-extrinsic manner. © 2016 Lau et al.

  12. Endoplasmic Reticulum Stress, Unfolded Protein Response, and Cancer Cell Fate

    Marco Corazzari


    Full Text Available Perturbation of endoplasmic reticulum (ER homeostasis results in a stress condition termed “ER stress” determining the activation of a finely regulated program defined as unfolded protein response (UPR and whose primary aim is to restore this organelle’s physiological activity. Several physiological and pathological stimuli deregulate normal ER activity causing UPR activation, such as hypoxia, glucose shortage, genome instability, and cytotoxic compounds administration. Some of these stimuli are frequently observed during uncontrolled proliferation of transformed cells, resulting in tumor core formation and stage progression. Therefore, it is not surprising that ER stress is usually induced during solid tumor development and stage progression, becoming an hallmark of such malignancies. Several UPR components are in fact deregulated in different tumor types, and accumulating data indicate their active involvement in tumor development/progression. However, although the UPR program is primarily a pro-survival process, sustained and/or prolonged stress may result in cell death induction. Therefore, understanding the mechanism(s regulating the cell survival/death decision under ER stress condition may be crucial in order to specifically target tumor cells and possibly circumvent or overcome tumor resistance to therapies. In this review, we discuss the role played by the UPR program in tumor initiation, progression and resistance to therapy, highlighting the recent advances that have improved our understanding of the molecular mechanisms that regulate the survival/death switch.

  13. Response of a direct methanol fuel cell to fuel change

    Leo, T.J. [Dpto de Sistemas Oceanicos y Navales- ETSI Navales, Univ. Politecnica de Madrid, Avda Arco de la Victoria s/n, 28040 Madrid (Spain); Raso, M.A.; de la Blanca, E. Sanchez [Dpto de Quimica Fisica I- Fac. CC. Quimicas, Univ. Complutense de Madrid, Avda Complutense s/n, 28040 Madrid (Spain); Navarro, E.; Villanueva, M. [Dpto de Motopropulsion y Termofluidodinamica, ETSI Aeronauticos, Univ. Politecnica de Madrid, Pza Cardenal Cisneros 3, 28040 Madrid (Spain); Moreno, B. [Instituto de Ceramica y Vidrio, Consejo Superior de Investigaciones Cientificas, C/Kelsen 5, Campus de la UAM, 28049 Cantoblanco, Madrid (Spain)


    Methanol and ethanol have recently received much attention as liquid fuels particularly as alternative 'energy-vectors' for the future. In this sense, to find a direct alcohol fuel cell that able to interchange the fuel without losing performances in an appreciable way would represent an evident advantage in the field of portable applications. In this work, the response of a in-house direct methanol fuel cell (DMFC) to the change of fuel from methanol to ethanol and its behaviour at different ambient temperature values have been investigated. A corrosion study on materials suitable to fabricate the bipolar plates has been carried out and either 316- or 2205-duplex stainless steels have proved to be adequate for using in direct alcohol fuel cells. Polarization curves have been measured at different ambient temperature values, controlled by an experimental setup devised for this purpose. Data have been fitted to a model taking into account the temperature effect. For both fuels, methanol and ethanol, a linear dependence of adjustable parameters with temperature is obtained. Fuel cell performance comparison in terms of open circuit voltage, kinetic and resistance is established. (author)

  14. The Transcriptional Coactivator Bob1 Is Associated With Pathologic B Cell Responses in Autoimmune Tissue Inflammation

    Levels, Maria J.; Van Tok, Melissa N.; Cantaert, Tineke; Canete, Juan D.; Kroese, Frans G. M.; Germar, Kristine; Spits, Hergen; Baeten, Dominique L. P.; Yeremenko, Nataliya G.

    Objective. The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. We undertook this study to identify molecular switches controlling pathologic B cell responses in rheumatoid arthritis (RA). Methods. Candidate molecules were identified by gene

  15. Energetic Extremes in Aquatic Locomotion by Coral Reef Fishes

    Fulton, Christopher J.; Johansen, Jacob L.; Steffensen, John F.


    Underwater locomotion is challenging due to the high friction and resistance imposed on a body moving through water and energy lost in the wake during undulatory propulsion. While aquatic organisms have evolved streamlined shapes to overcome such resistance, underwater locomotion has long been considered a costly exercise. Recent evidence for a range of swimming vertebrates, however, has suggested that flapping paired appendages around a rigid body may be an extremely efficient means of aquatic locomotion. Using intermittent flow-through respirometry, we found exceptional energetic performance in the Bluelined wrasse Stethojulis bandanensis, which maintains tuna-like optimum cruising speeds (up to 1 metre s−1) while using 40% less energy than expected for their body size. Displaying an exceptional aerobic scope (22-fold above resting), streamlined rigid-body posture, and wing-like fins that generate lift-based thrust, S. bandanensis literally flies underwater to efficiently maintain high optimum swimming speeds. Extreme energetic performance may be key to the colonization of highly variable environments, such as the wave-swept habitats where S. bandanensis and other wing-finned species tend to occur. Challenging preconceived notions of how best to power aquatic locomotion, biomimicry of such lift-based fin movements could yield dramatic reductions in the power needed to propel underwater vehicles at high speed. PMID:23326566

  16. Energetic extremes in aquatic locomotion by coral reef fishes.

    Christopher J Fulton

    Full Text Available Underwater locomotion is challenging due to the high friction and resistance imposed on a body moving through water and energy lost in the wake during undulatory propulsion. While aquatic organisms have evolved streamlined shapes to overcome such resistance, underwater locomotion has long been considered a costly exercise. Recent evidence for a range of swimming vertebrates, however, has suggested that flapping paired appendages around a rigid body may be an extremely efficient means of aquatic locomotion. Using intermittent flow-through respirometry, we found exceptional energetic performance in the Bluelined wrasse Stethojulis bandanensis, which maintains tuna-like optimum cruising speeds (up to 1 metre s(-1 while using 40% less energy than expected for their body size. Displaying an exceptional aerobic scope (22-fold above resting, streamlined rigid-body posture, and wing-like fins that generate lift-based thrust, S. bandanensis literally flies underwater to efficiently maintain high optimum swimming speeds. Extreme energetic performance may be key to the colonization of highly variable environments, such as the wave-swept habitats where S. bandanensis and other wing-finned species tend to occur. Challenging preconceived notions of how best to power aquatic locomotion, biomimicry of such lift-based fin movements could yield dramatic reductions in the power needed to propel underwater vehicles at high speed.

  17. Designing presence for real locomotion in immersive virtual environments

    Turchet, Luca


    This paper describes a framework for designing systems for real locomotion in virtual environments (VEs) in order to achieve an intense sense of presence. The main outcome of the present research is a list of design features that the virtual reality technology should have in order to achieve...

  18. A light-weight, yet powerful diesel locomotive from Vossloh

    Marti, Mariano [Vossloh Rail Vehicles, Albuixech/Valencia (Spain)


    The EUROLIGHT is an eight-wheeled diesel-electric locomotive developed by Vossloh Rail Vehicles for interoperable rail traffic. With its low axle load of less than 20 tonnes, it can be deployed flexibly on both main lines and secondary ones.

  19. Using Computational and Mechanical Models to Study Animal Locomotion

    Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas


    Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms’ performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locomotion that is characterized by the interactions of fluids, substrates, and structures. Despite the large body of recent work in this area, the application of mathematical and numerical methods to improve our understanding of organisms in the context of their environment and physiology has remained relatively unexplored. Nature has evolved a wide variety of fascinating mechanisms of locomotion that exploit the properties of complex materials and fluids, but only recently are the mathematical, computational, and robotic tools available to rigorously compare the relative advantages and disadvantages of different methods of locomotion in variable environments. Similarly, advances in computational physiology have only recently allowed investigators to explore how changes at the molecular, cellular, and tissue levels might lead to changes in performance at the organismal level. In this article, we highlight recent examples of how computational, mathematical, and experimental tools can be combined to ultimately answer the questions posed in one of the grand challenges in organismal biology: “Integrating living and physical systems.” PMID:22988026

  20. MTU locomotive drive systems for EU emissions stage IIIB

    Wintruff, Ingo [MTU Friedrichshafen GmbH, Friedrichshafen (Germany)


    Emissions limits for diesel locomotives within the European Union are regulated by EU Non-road Directive 97/68/EC which places restrictions on the pollutants NOx, particulate, CO and HC. MTU has developed suitable diesel engines for EU Emissions stage IIIB. (orig.)

  1. Energy Efficiency of Robot Locomotion Increases Proportional to Weight

    Larsen, Jørgen Christian; Støy, Kasper


    The task of producing steady, stable and energy efficient locomotion in legged robots with the ability to walk in un- known terrain have for many years been a big challenge in robotics. This work is focusing on how different robots build from the modular robotic system, LocoKit by Larsen et. la [3...

  2. Application of flywheel energy storage for heavy haul locomotives

    Spiryagin, Maksym; Wolfs, Peter; Szanto, Frank; Sun, Yan Quan; Cole, Colin; Nielsen, Dwayne


    Highlights: • A novel design for heavy haul locomotive equipped with a flywheel energy storage system is proposed. • The integrated intelligent traction control system was developed. • A flywheel energy storage system has been tested through a simulation process. • The developed hybrid system was verified using an existing heavy haul railway route. • Fuel efficiency analysis confirms advantages of the hybrid design. - Abstract: At the present time, trains in heavy haul operations are typically hauled by several diesel-electric locomotives coupled in a multiple unit. This paper studies the case of a typical consist of three Co–Co diesel-electric locomotives, and considers replacing one unit with an alternative version, with the same design parameters, except that the diesel-electric plant is replaced with flywheel energy storage equipment. The intelligent traction and energy control system installed in this unit is integrated into the multiple-unit control to allow redistribution of the power between all units. In order to verify the proposed design, a three-stage investigation has been performed as described in this paper. The initial stage studies a possible configuration of the flywheel energy storage system by detailed modelling of the proposed intelligent traction and energy control system. The second stage includes the investigation and estimation of possible energy flows using a longitudinal train dynamics simulation. The final stage compares the conventional and the proposed locomotive configurations considering two parameters: fuel efficiency and emissions reduction.

  3. Scaling in Theropod Dinosaurs: Femoral Bone Strength and Locomotion

    Lee, Scott


    In our first article on scaling in theropod dinosaurs, the longitudinal stress in the leg bones due to supporting the weight of the animal was studied and found not to control the dimensions of the femur. As a continuation of our study of elasticity in dinosaur bones, we now examine the transverse stress in the femur due to locomotion and find…

  4. Scaling in Theropod Dinosaurs: Femoral Bone Strength and Locomotion II

    Lee, Scott


    In the second paper of this series, the effect of transverse femoral stresses due to locomotion in theropod dinosaurs of different sizes was examined for the case of an unchanging leg geometry. Students are invariably thrilled to learn about theropod dinosaurs, and this activity applies the concepts of torque and stress to the issue of theropod…

  5. Energy Efficiency of Robot Locomotion Increases Proportional to Weight

    Larsen, J. C.; Stoy, K.


    The task of producing steady, stable and energy efficient locomotion in legged robots with the ability to walk in unknown terrain have for many years been a big challenge in robotics. This work is focusing on how different robots build from the modular robotic system, LocoKit by Larsen et al. [1...

  6. Decoding bipedal locomotion from the rat sensorimotor cortex

    Rigosa, J.; Panarese, A.; Dominici, N.; Friedli, L.; van den Brand, R.; Carpaneto, J.; DiGiovanna, J.; Courtine, G.; Micera, S.


    Objective. Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower

  7. MMP19 is essential for T cell development and T cell-mediated cutaneous immune responses

    Beck, Inken; Ruckert, R.; Brandt, K.; Mueller, M.S.; Sadowski, T.; Brauer, R.; Schirmacher, P.; Mentlein, R.; Sedláček, Radislav


    Roč. 3, č. 6 (2008), e2343-e2343 E-ISSN 1932-6203 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : matrix metalloproteinase * T cell * immune response Subject RIV: EB - Genetics ; Molecular Biology

  8. Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat.

    Hurteau, Marie-France; Thibaudier, Yann; Dambreville, Charline; Danner, Simon M; Rybak, Ilya A; Frigon, Alain


    When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response. SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the

  9. Response of hematopoietic stem cells to ionizing radiation

    Simonnet, A.


    experiment that a single TPO administration rescued the IR-impaired reconstitution capacity of HSCs early after exposure. In addition, the use of marrow cells from transgenic ubiquitous luciferase-expressing donors combined with bioluminescence imaging technology provided a valuable strategy that allowed visualizing HSC homing of TPO-treated compared to untreated irradiated donors, and enabled the identification of a preferential cellular expansion sites which were inaccessible to investigation in most studies. Finally, we observed that TPO injection right after irradiation considerably attenuates IR-induced long-term injury to the stem/progenitor compartment. Altogether, these data provide novel insights in the cellular response of HSC to IR and the beneficial effects of TPO administration to these cells. (author)

  10. Origami-based earthworm-like locomotion robots.

    Fang, Hongbin; Zhang, Yetong; Wang, K W


    Inspired by the morphology characteristics of the earthworms and the excellent deformability of origami structures, this research creates a novel earthworm-like locomotion robot through exploiting the origami techniques. In this innovation, appropriate actuation mechanisms are incorporated with origami ball structures into the earthworm-like robot 'body', and the earthworm's locomotion mechanism is mimicked to develop a gait generator as the robot 'centralized controller'. The origami ball, which is a periodic repetition of waterbomb units, could output significant bidirectional (axial and radial) deformations in an antagonistic way similar to the earthworm's body segment. Such bidirectional deformability can be strategically programmed by designing the number of constituent units. Experiments also indicate that the origami ball possesses two outstanding mechanical properties that are beneficial to robot development: one is the structural multistability in the axil direction that could contribute to the robot control implementation; and the other is the structural compliance in the radial direction that would increase the robot robustness and applicability. To validate the origami-based innovation, this research designs and constructs three robot segments based on different axial actuators: DC-motor, shape-memory-alloy springs, and pneumatic balloon. Performance evaluations reveal their merits and limitations, and to prove the concept, the DC-motor actuation is selected for building a six-segment robot prototype. Learning from earthworms' fundamental locomotion mechanism-retrograde peristalsis wave, seven gaits are automatically generated; controlled by which, the robot could achieve effective locomotion with qualitatively different modes and a wide range of average speeds. The outcomes of this research could lead to the development of origami locomotion robots with low fabrication costs, high customizability, light weight, good scalability, and excellent re-configurability.

  11. Cell specificity of the cytoplasmic Ca2+ response to tolbutamide is impaired in beta-cells from hyperglycemic mice

    Gustavsson, Natalia; Larsson-Nyrén, Gerd; Lindström, Per


    We recently reported that the timing and magnitude of the nutrient-induced Ca(2+) response are specific and reproducible for each isolated beta-cell. We have now used tolbutamide and arginine to test if the cell specificity exists also for the response to non-nutrient stimulation of beta-cells an...

  12. Human Bronchial Epithelial Cell Response to Heavy Particle Exposure

    Story, Michael; Ding, Liang-Hao; Minna, John; Park, Seong-mi; Peyton, Michael; Larsen, Jill


    A battery of non-oncogenically immortalized human bronchial epithelial cells (HBECs) are being used to examine the molecular changes that lead to lung carcinogenesis after exposure to heavy particles found in the free space environment. The goal is to ultimately identify biomarkers of radioresponse that can be used for prediction of carcinogenic risk for fatal lung cancer. Our initial studies have focused on the cell line HBEC3 KT and the isogenic variant HBEC3 KTR53, which overexpresses the RASv12 mutant and where p53 has been knocked down by shRNA, and is considered to be a more oncogenically progressed variant. We have previously described the response of HBEC3 KT at the cellular and molecular level, however, the focus here is on the rate of cellular transformation after HZE radiation exposure and the molecular changes in transformed cells. When comparing the two cell lines we find that there is a maximum rate of cellular transformation at 0.25 Gy when cells are exposed to 1 GeV Fe particles, and, for the HBEC3 KTR53 there are multiple pathways upregulated that promote anchorage independent growth including the mTOR pathway, the TGF-1 pathway, RhoA signaling and the ERK/MAPK pathway as early as 2 weeks after radiation. This does not occur in the HBEC3 KT cell line. Transformed HBEC3 KT cells do not show any morphologic or phenotypic changes when grown as cell cultures. HBEC3 KTR53 cells on the other hand show substantial changes in morphology from a cobblestone epithelial appearance to a mesenchymal appearance with a lack of contact inhibition. This epithelial to mesenchymal change in morphology is accompanied by the expression of vimentin and a reduction in the expression of E-cadherin, which are hallmarks of epithelial to mesenchymal transition. Interestingly, for HBEC3 KT transformed cells there are no mutations in the p53 gene, 2 of 15 clones were found to be heterozygous for the RASV12 mutation, and 3 of 15 clones expressed high levels of BigH3, a TGFB-responsive

  13. Hydrogenated amorphous silicon coatings may modulate gingival cell response

    Mussano, F.; Genova, T.; Laurenti, M.; Munaron, L.; Pirri, C. F.; Rivolo, P.; Carossa, S.; Mandracci, P.


    Silicon-based materials present a high potential for dental implant applications, since silicon has been proven necessary for the correct bone formation in animals and humans. Notably, the addition of silicon is effective to enhance the bioactivity of hydroxyapatite and other biomaterials. The present work aims to expand the knowledge of the role exerted by hydrogen in the biological interaction of silicon-based materials, comparing two hydrogenated amorphous silicon coatings, with different hydrogen content, as means to enhance soft tissue cell adhesion. To accomplish this task, the films were produced by plasma enhanced chemical vapor deposition (PECVD) on titanium substrates and their surface composition and hydrogen content were analyzed by means of X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectrophotometry (FTIR) respectively. The surface energy and roughness were measured through optical contact angle analysis (OCA) and high-resolution mechanical profilometry respectively. Coated surfaces showed a slightly lower roughness, compared to bare titanium samples, regardless of the hydrogen content. The early cell responses of human keratinocytes and fibroblasts were tested on the above mentioned surface modifications, in terms of cell adhesion, viability and morphometrical assessment. Films with lower hydrogen content were endowed with a surface energy comparable to the titanium surfaces. Films with higher hydrogen incorporation displayed a lower surface oxidation and a considerably lower surface energy, compared to the less hydrogenated samples. As regards mean cell area and focal adhesion density, both a-Si coatings influenced fibroblasts, but had no significant effects on keratinocytes. On the contrary, hydrogen-rich films increased manifolds the adhesion and viability of keratinocytes, but not of fibroblasts, suggesting a selective biological effect on these cells.

  14. Induction of non-responsiveness in human allergen-specific type 2 T helper cells.

    Yssel, H; Fasler, S; Lamb, J; de Vries, J E


    Activation of allergen-reactive human T helper (Th)2 cells in the absence of professional antigen-presenting cells, induces non-responsiveness or anergy in these cells in vitro. This induction of anergy is accompanied by phenotypic modulation and altered cytokine production. Furthermore, peptide-treated Th2 cells fail to provide B-cell help for IgE synthesis. Recent studies indicate that impaired signal transduction via the T-cell receptor may account for the lack of responsiveness to antigenic stimulation. Here, we review present knowledge on the cell biology of non-responsive or anergic Th2 cells.

  15. Noninvasive Multimodal Imaging to Predict Recovery of Locomotion after Extended Limb Ischemia.

    Jason S Radowsky

    Full Text Available Acute limb ischemia is a common cause of morbidity and mortality following trauma both in civilian centers and in combat related injuries. Rapid determination of tissue viability and surgical restoration of blood flow are desirable, but not always possible. We sought to characterize the response to increasing periods of hind limb ischemia in a porcine model such that we could define a period of critical ischemia (the point after which irreversible neuromuscular injury occurs, evaluate non-invasive methods for characterizing that ischemia, and establish a model by which we could predict whether or not the animal's locomotion would return to baselines levels post-operatively. Ischemia was induced by either application of a pneumatic tourniquet or vessel occlusion (performed by clamping the proximal iliac artery and vein at the level of the inguinal ligament. The limb was monitored for the duration of the procedure with both 3-charge coupled device (3CCD and infrared (IR imaging for tissue oxygenation and perfusion, respectively. The experimental arms of this model are effective at inducing histologically evident muscle injury with some evidence of expected secondary organ damage, particularly in animals with longer ischemia times. Noninvasive imaging data shows excellent correlation with post-operative functional outcomes, validating its use as a non-invasive means of viability assessment, and directly monitors post-occlusive reactive hyperemia. A classification model, based on partial-least squares discriminant analysis (PLSDA of imaging variables only, successfully classified animals as "returned to normal locomotion" or "did not return to normal locomotion" with 87.5% sensitivity and 66.7% specificity after cross-validation. PLSDA models generated from non-imaging data were not as accurate (AUC of 0.53 compared the PLSDA model generated from only imaging data (AUC of 0.76. With some modification, this limb ischemia model could also serve as a

  16. Locomotion of a bioinspired flyer powered by one pair of pitching foils

    Zhang, Xiang; He, Guowei; Wang, Shizhao; Zhang, Xing


    We numerically investigate the flight dynamics and aerodynamics of a two-dimensional model for the jellyfishlike ornithopter recently devised by Ristroph and Childress [L. Ristroph and S. Childress, J. R. Soc. Interface 11, 20130992 (2014), 10.1098/rsif.2013.0992]. This simplified model is composed of two rigid thin foils which are forced to pitch in antiphase fashion. The Navier-Stokes equations for the fluid and the dynamics equations for the flyer are solved together in the simulations. We first consider the constrained-flying condition where the flyer model is only allowed to move in the vertical direction. The influences of the control parameters on the hovering performance are studied. With the variations in parameter values, three different locomotion states, i.e., ascending, descending, and approximate hovering, are identified. The wake structures corresponding to these three locomotion states are explored. It is found that the approximate hovering state cannot persist due to the occurrence of wake symmetry breaking after long-time simulation. We then consider the free-flying condition where the motions in three degrees of freedom are allowed. We study the postural stability of a flyer, with its center of gravity located at the geometric center. The responses of the flyer at different locomotion states to physical and numerical perturbations are examined. Our results show that the ascending state is recoverable after the perturbation. The descending state is irrecoverable after the perturbation and a mixed fluttering and tumbling motion which resembles that of a falling card emerges. The approximate hovering state is also irrecoverable and it eventually transits to the ascending state after the perturbation. The research sheds light on the lift-producing mechanism and stability of the flyer and the results are helpful in guiding the design and optimization of the jellyfishlike flying machine.

  17. The effect of locomotion on the mobilization of minerals from the maternal skeleton.

    Wendy R Hood

    Full Text Available Bone is a dynamic tissue from which minerals are deposited or withdrawn according to the body's demand. During late pregnancy and lactation, female mammals mobilize mineral from bone to support the ossification of offspring skeleton(s. Conversely, in response to mechanical loading, minerals are deposited in bone enabling it to develop a stronger architecture. Despite their central importance to reproductive performance and skeletal integrity, the interactions between these potentially opposing forces remains poorly understood. It is possible that inter-individual differences in the loading imposed by different forms of locomotion may alter the amount of mineral mobilized during reproduction. Here, the impact of vertical versus horizontal locomotion on bone mobilization was examined during reproduction in the laboratory mouse. The vertical, or climbing, group had access to a 60-cm tower, increasing strain on their appendicular skeleton. The horizontal, or tunnel, group had access to a 100-cm tunnel, which encouraged movements within the horizontal plane. Form of locomotion did not impact the amount of bone females mobilized during reproduction or the amount of mineral females deposited in the litter, but maternal bone architecture differed between groups. The climbing group displayed more trabeculae than the tunnel group, whereas the tunnel group displayed greater cortical bone mineral density mid-shaft. Interestingly, pups born to mothers in the climbing group had a higher concentration of total body calcium at 16 days than pups of mothers in the tunnel group. As maternal total body calcium composition and the amount of calcium invested in the full litter were not different between groups, the difference in the relative calcium content of pups between groups is not suspected to reflect difference in mineral allocation. Future research should consider the impact of maternal activity on the efficiency of offspring skeletal ossification via

  18. Inflammatory cell response to calcium phosphate biomaterial particles: an overview.

    Velard, Frédéric; Braux, Julien; Amedee, Joëlle; Laquerriere, Patrice


    Bone is a metabolically active and highly organized tissue consisting of a mineral phase of hydroxyapatite (HA) and amorphous calcium phosphate (CaP) crystals deposited in an organic matrix. One objective of bone tissue engineering is to mimic the chemical and structural properties of this complex tissue. CaP ceramics, such as sintered HA and beta-tricalcium phosphate, are widely used as bone substitutes or prosthesis coatings because of their osteoconductive properties. These ceramic interactions with tissues induce a cell response that can be different according to the composition of the material. In this review, we discuss inflammatory cell responses to CaP materials to provide a comprehensive overview of mechanisms governing the integration or loosening of implants, which remains a major concern in tissue engineering. A focus on the effects of the functionalization of CaP biomaterials highlights potential ways to increase tissue integration and limit rejection processes. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  19. Cell wide responses to low oxygen exposure in Desulfovibriovulgaris Hildenborough

    Mukhopadhyay, A.; Redding, A.; Joachimiak, M.; Arkin, A.; Borglin, S.; Dehal, P.; Chakraborty, R.; Geller, J.; Hazen, T.; He, Q.; Joyner, D.; Martin, V.; Wall, J.; Yang, Z.; Zhou, J.; Keasling, J.


    The responses of the anaerobic, sulfate-reducing Desulfovibrio vulgaris Hildenborough to low oxygen exposure (0.1% O{sub 2}) were monitored via transcriptomics and proteomics. Exposure to 0.1% O{sub 2} caused a decrease in growth rate without affecting viability. A concerted up regulation in the predicted peroxide stress response regulon (PerR) genes was observed in response to the 0.1% O{sub 2} exposure. Several of these candidates also showed increases in protein abundance. Among the remaining small number of transcript changes was the up regulation of the predicted transmembrane tetraheme cytochrome c3 complex. Other known oxidative stress response candidates remained unchanged during this low O{sub 2} exposure. To fully understand the results of the 0.1% O{sub 2} exposure, transcriptomics and proteomics data were collected for exposure to air using a similar experimental protocol. In contrast to the 0.1% O{sub 2} exposure, air exposure was detrimental to both the growth rate and viability and caused dramatic changes at both the transcriptome and proteome levels. Interestingly, the transcripts of the predicted PerR regulon genes were down regulated during air exposure. Our results highlight the differences in the cell wide response to low and high O{sub 2} levels of in D. vulgaris and suggest that while exposure to air is highly detrimental to D. vulgaris, this bacterium can successfully cope with periodic exposure to low O{sub 2} levels in its environment.

  20. Response of thyroid follicular cells to accelerated iron ions

    Green, L.M.; Bianski, B.M.


    Full text: Suspension cultures of early and later passages thyroid follicular fisher rat thyroid cells (FRTL-5) were exposed to iron ions delivered over a dose range of 0-3 Gy and their comparative biological responses measured. Early passage FRTL-5 cultures are slow-growing, connexin32 competent whereas, later passage cultures are relatively rapidly growing and connexin32 defective. The iron-irradiated cells had sustained levels of incorporated dUTP into 3' strand breaks, reflecting DNA damage. There were no significant differences between early and later passage cultures except at 0.5 and 1 Gy, 48-hours (p 0.05). The presence of consistently medium-larger micronuclei was evidence that severe damage was introduced by exposure to iron ions. The levels of apoptosis were not linear with dose, nor was there a marked difference with time. In all cases the 3 Gy levels were less than or equal to the levels measured at 0.5 Gy. When survival characteristics were compared the most significant difference between early and later passage cultures were in the a-components of the survival curves (0.60 Gy -1 for early and 0.71 Gy-1 for the later passage cultures, p<0.014). When cell cycle phase redistribution was measured, both the early and later passage cultures displayed a significant shift toward G2 (p<0.001). In conclusion, these findings suggest that neither the presence of gap junctions, nor the differences in growth rate translated to significant differences in the biological response of thyroid follicles to iron ions

  1. Intraglomerular inhibition maintains mitral cell response contrast across input frequencies.

    Shao, Zuoyi; Puche, Adam C; Shipley, Michael T


    Odor signals are transmitted to the olfactory bulb by olfactory nerve (ON) synapses onto mitral/tufted cells (MTCs) and external tufted cells (ETCs); ETCs provide additional feed-forward excitation to MTCs. Both are strongly regulated by intraglomerular inhibition that can last up to 1 s and, when blocked, dramatically increases ON-evoked MC spiking. Intraglomerular inhibition thus limits the magnitude and duration of MC spike responses to sensory input. In vivo, sensory input is repetitive, dictated by sniffing rates from 1 to 8 Hz, potentially summing intraglomerular inhibition. To investigate this, we recorded MTC responses to 1- to 8-Hz ON stimulation in slices. Inhibitory postsynaptic current area (charge) following each ON stimulation was unchanged from 1 to 5 Hz and modestly paired-pulse attenuated at 8 Hz, suggesting there is no summation and only limited decrement at the highest input frequencies. Next, we investigated frequency independence of intraglomerular inhibition on MC spiking. MCs respond to single ON shocks with an initial spike burst followed by reduced spiking decaying to baseline. Upon repetitive ON stimulation peak spiking is identical across input frequencies but the ratio of peak-to-minimum rate before the stimulus (max-min) diminishes from 30:1 at 1 Hz to 15:1 at 8 Hz. When intraglomerular inhibition is selectively blocked, peak spike rate is unchanged but trough spiking increases markedly decreasing max-min firing ratios from 30:1 at 1 Hz to 2:1 at 8 Hz. Together, these results suggest intraglomerular inhibition is relatively frequency independent and can "sharpen" MC responses to input across the range of frequencies. This suggests that glomerular circuits can maintain "contrast" in MC encoding during sniff-sampled inputs.


    L. V. Ursulyak


    Full Text Available Purpose. To compare the operational characteristics of freight diesel-electric locomotives ER20CF and 2М62м, which are operated with Lithuanian Railways. Important problems on traction calculations are considered in this article. In this article the critical tasks of traction calculations are solved. It is the main computational tool in the rational functioning, planning and development of railways: determination of the estimated weight of the rolling stock, the diagrams construction of specific resultant forces of a train, the permitted speed definition of the train on the slopes, curves of train traffic construction on the section. Methodology. Using the rules and methods of traction calculations the analysis of the basic operational characteristics of the modernized freight diesel-electric locomotive 2М62m and freight passenger dual locomotive 2ER20CF was held. The maximum weight of the train set, the track structure on a high-speed ascent through the use of kinetic energy (with traction and without traction, technical speed, acceleration force and the value of the smallest radius curve are selected as controlled parameters. During the calculations it was considered that the trains were formed of a fully loaded four-axle gondola cars, model 112-119 (feature-606 with axle load of 23.5 t; the motion was carried out on the continuous welded rail track; the front of the train set is a dual locomotive 2ER20CF or two locomotive 2М62м. Longitudinal profile of the road on the route Vilnus–KlF was analyzed for the choice of theoretical rise. Inspection concerning the possibility of overcoming the high-speed rise was performed with an analytical method, based on the use of the kinetic energy accumulated by the overcoming of «light» elements of the profile. Findings. In the calculations, the maximum weight of the train set taking into account theoretical rise was analyzed. The inspection of the theoretical weight of the train set on a reliable

  3. Spatially Compact Neural Clusters in the Dorsal Striatum Encode Locomotion Relevant Information.

    Barbera, Giovanni; Liang, Bo; Zhang, Lifeng; Gerfen, Charles R; Culurciello, Eugenio; Chen, Rong; Li, Yun; Lin, Da-Ting


    An influential striatal model postulates that neural activities in the striatal direct and indirect pathways promote and inhibit movement, respectively. Normal behavior requires coordinated activity in the direct pathway to facilitate intended locomotion and indirect pathway to inhibit unwanted locomotion. In this striatal model, neuronal population activity is assumed to encode locomotion relevant information. Here, we propose a novel encoding mechanism for the dorsal striatum. We identified spatially compact neural clusters in both the direct and indirect pathways. Detailed characterization revealed similar cluster organization between the direct and indirect pathways, and cluster activities from both pathways were correlated with mouse locomotion velocities. Using machine-learning algorithms, cluster activities could be used to decode locomotion relevant behavioral states and locomotion velocity. We propose that neural clusters in the dorsal striatum encode locomotion relevant information and that coordinated activities of direct and indirect pathway neural clusters are required for normal striatal controlled behavior. VIDEO ABSTRACT. Published by Elsevier Inc.

  4. Energy-based control for a biologically inspired hexapod robot with rolling locomotion

    Takuma Nemoto


    Full Text Available This paper presents an approach to control rolling locomotion on the level ground with a biologically inspired hexapod robot. For controlling rolling locomotion, a controller which can compensate energy loss with rolling locomotion of the hexapod robot is designed based on its dynamic model. The dynamic model describes the rolling locomotion which is limited to planar one by an assumption that the hexapod robot does not fall down while rolling and influences due to collision and contact with the ground, and it is applied for computing the mechanical energy of the hexapod robot and a plant for a numerical simulation. The numerical simulation of the rolling locomotion on the level ground verifies the effectiveness of the proposed controller. The simulation results show that the hexapod robot can perform the rolling locomotion with the proposed controller. In conclusion, it is shown that the proposed control approach is effective in achieving the rolling locomotion on the level ground.

  5. Injectable, Biomolecule-Responsive Polypeptide Hydrogels for Cell Encapsulation and Facile Cell Recovery through Triggered Degradation.

    Xu, Qinghua; He, Chaoliang; Zhang, Zhen; Ren, Kaixuan; Chen, Xuesi


    Injectable hydrogels have been widely investigated in biomedical applications, and increasing demand has been proposed to achieve dynamic regulation of physiological properties of hydrogels. Herein, a new type of injectable and biomolecule-responsive hydrogel based on poly(l-glutamic acid) (PLG) grafted with disulfide bond-modified phloretic acid (denoted as PLG-g-CPA) was developed. The hydrogels formed in situ via enzymatic cross-linking under physiological conditions in the presence of horseradish peroxidase and hydrogen peroxide. The physiochemical properties of the hydrogels, including gelation time and the rheological property, were measured. Particularly, the triggered degradation of the hydrogel in response to a reductive biomolecule, glutathione (GSH), was investigated in detail. The mechanical strength and inner porous structure of the hydrogel were influenced by the addition of GSH. The polypeptide hydrogel was used as a three-dimensional (3D) platform for cell encapsulation, which could release the cells through triggered disruption of the hydrogel in response to the addition of GSH. The cells released from the hydrogel were found to maintain high viability. Moreover, after subcutaneous injection into rats, the PLG-g-CPA hydrogels with disulfide-containing cross-links exhibited a markedly faster degradation behavior in vivo compared to that of the PLG hydrogels without disulfide cross-links, implying an interesting accelerated degradation process of the disulfide-containing polypeptide hydrogels in the physiological environment in vivo. Overall, the injectable and biomolecule-responsive polypeptide hydrogels may serve as a potential platform for 3D cell culture and easy cell collection.

  6. Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses

    Andoh Y


    Full Text Available Yoshiaki Andoh,1,2 Naohiko Makino,2 Mitsunori Yamakawa11Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanBackground: It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL and CD4+CD25high regulatory T-cells (Tregs among dendritic cells (DCs fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines.Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs, were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated.Results: The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1 was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines.Conclusion: The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs

  7. Radiogenic responses of normal cells induced by fractionated irradiation -a simulation study. Pt. 2. Late responses

    Duechting, W.; Ulmer, W.; Ginsberg, T.; Kikhounga-N'Got, O.; Saile, C.


    Based on controlled theory, a computed simulation model has been constructed which describes the time course of slowly responding normal cells after irradiation exposure. Subsequently, different clinical irradiation schemes are compared in regard to their delayed radiogenic responses referred to as late effects in radiological terminology. A cybernetic model of a paraenchymal tissue consisting of dominantly resting functional cells has been developed and transferred into a computer model. The radiation effects are considered by characteristic cell parameters as well as by the linear-quadratic model. Three kinds of tissue (brain and lung parenchym of the mouse, liver parenchym of rat) have been irradiated in the model according to standard-, super-, hyperfractionation and a single high dose per week. The simulation studies indicate that the late reaction of brain parenchym to hyperfractionation (3 x 1.5 Gy per day) and of lung parenchym tissue with regard to all fractionation schemes applied is particularly severe. The behavior of liver parenchym is not unique. A comparison of the simulation results basing to the survival of cell numbers with clinical experience and practice shows that the clinical reality can qualitatively be represented by the model. This opens the door for connecting side effects to normal tissue with the corresponding tumor efficacy (discussed in previous papers). The model is open to further refinement and to discussions referring to the phenomenon of late effects. (orig.) [de

  8. Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses.

    Cruz-Adalia, Aránzazu; Ramirez-Santiago, Guillermo; Osuna-Pérez, Jesús; Torres-Torresano, Mónica; Zorita, Virgina; Martínez-Riaño, Ana; Boccasavia, Viola; Borroto, Aldo; Martínez Del Hoyo, Gloria; González-Granado, José María; Alarcón, Balbino; Sánchez-Madrid, Francisco; Veiga, Esteban


    Bacterial phagocytosis and antigen cross-presentation to activate CD8 + T cells are principal functions of professional antigen presenting cells. However, conventional CD4 + T cells also capture and kill bacteria from infected dendritic cells in a process termed transphagocytosis (also known as transinfection). Here, we show that transphagocytic T cells present bacterial antigens to naive CD8 + T cells, which proliferate and become cytotoxic in response. CD4 + T-cell-mediated antigen presentation also occurs in vivo in the course of infection, and induces the generation of central memory CD8 + T cells with low PD-1 expression. Moreover, transphagocytic CD4 + T cells induce protective anti-tumour immune responses by priming CD8 + T cells, highlighting the potential of CD4 + T cells as a tool for cancer immunotherapy.

  9. Ability of γδ T cells to modulate the Foxp3 T cell response is dependent on adenosine.

    Dongchun Liang

    Full Text Available Whether γδ T cells inhibit or enhance the Foxp3 T cell response depends upon their activation status. The critical enhancing effector in the supernatant is adenosine. Activated γδ T cells express adenosine receptors at high levels, which enables them to deprive Foxp3+ T cells of adenosine, and to inhibit their expansion. Meanwhile, cell-free supernatants of γδ T cell cultures enhance Foxp3 T cell expansion. Thus, inhibition and enhancement by γδ T cells of Foxp3 T cell response are a reflection of the balance between adenosine production and absorption by γδ T cells. Non-activated γδ T cells produce adenosine but bind little, and thus enhance the Foxp3 T cell response. Activated γδ T cells express high density of adenosine receptors and have a greatly increased ability to bind adenosine. Extracellular adenosine metabolism and expression of adenosine receptor A2ARs by γδ T cells played a major role in the outcome of γδ and Foxp3 T cell interactions. A better understanding of the functional conversion of γδ T cells could lead to γδ T cell-targeted immunotherapies for related diseases.

  10. [Conjunctival squamous cell carcinoma: paradoxical response to interferon eyedrops].

    Mata, E; Conesa, E; Castro, M; Martínez, L; de Pablo, C; González, M L


    A 67 year-old male seen for a longstanding corneal-conjunctival tumor. topical interferon α2b (IFN-α2b) 10 U/ml. A significant increase in lesion size was observed after 8 weeks. A surgical excision with cryotherapy was then performed. Pathological examination confirmed the diagnosis of squamous cell carcinoma. At this time the patient was found to have a positive HIV serology. Conjunctival intraepithelial neoplasia (CIN) is a pre-cancerous lesion of the ocular surface. Medical treatment of CIN is essentially with IFN-α2b due to its antiviral/antitumor properties. In patients with HIV, treatment response could be paradoxical. We recommend serology for HIV before treatment with topical IFN-α2b. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  11. Cell envelope stress response in cell wall-deficient L-forms of Bacillus subtilis.

    Wolf, Diana; Domínguez-Cuevas, Patricia; Daniel, Richard A; Mascher, Thorsten


    L-forms are cell wall-deficient bacteria that can grow and proliferate in osmotically stabilizing media. Recently, a strain of the Gram-positive model bacterium Bacillus subtilis was constructed that allowed controlled switching between rod-shaped wild-type cells and corresponding L-forms. Both states can be stably maintained under suitable culture conditions. Because of the absence of a cell wall, L-forms are known to be insensitive to β-lactam antibiotics, but reports on the susceptibility of L-forms to other antibiotics that interfere with membrane-anchored steps of cell wall biosynthesis are sparse, conflicting, and strongly influenced by strain background and method of L-form generation. Here we investigated the response of B. subtilis to the presence of cell envelope antibiotics, with regard to both antibiotic resistance and the induction of the known LiaRS- and BceRS-dependent cell envelope stress biosensors. Our results show that B. subtilis L-forms are resistant to antibiotics that interfere with the bactoprenol cycle, such as bacitracin, vancomycin, and mersacidin, but are hypersensitive to nisin and daptomycin, which both affect membrane integrity. Moreover, we established a lacZ-based reporter gene assay for L-forms and provide evidence that LiaRS senses its inducers indirectly (damage sensing), while the Bce module detects its inducers directly (drug sensing).

  12. Bipedal locomotion of bonnet macaques after spinal cord injury.

    Babu, Rangasamy Suresh; Anand, P; Jeraud, Mathew; Periasamy, P; Namasivayam, A


    Experimental studies concerning the analysis of locomotor behavior in spinal cord injury research are widely performed in rodent models. The purpose of this study was to quantitatively evaluate the degree of functional recovery in reflex components and bipedal locomotor behavior of bonnet macaques (Macaca radiata) after spinal contusive injury. Six monkeys were tested for various reflex components (grasping, righting, hopping, extension withdrawal) and were trained preoperatively to walk in bipedal fashion on the simple and complex locomotor runways (narrow beam, grid, inclined plane, treadmill) of this investigation. The overall performance of the animals'motor behavior and the functional status of limb movements during bipedal locomotion were graded by the Combined Behavioral Score (CBS) system. Using the simple Allen weight-drop technique, a contusive injury was produced by dropping a 13-g weight from a height of 30 cm to the exposed spinal cord at the T12-L1 vertebral level of the trained monkeys. All the monkeys showed significant impairments in every reflex activity and in walking behavior during the early part of the postoperative period. In subsequent periods, the animals displayed mild alterations in certain reflex responses, such as grasping, extension withdrawal, and placing reflexes, which persisted through a 1-year follow-up. The contused animals traversed locomotor runways--narrow beam, incline plane, and grid runways--with more steps and few errors, as evaluated with the CBS system. Eventually, the behavioral performance of all spinal-contused monkeys recovered to near-preoperative level by the fifth postoperative month. The findings of this study reveal the recovery time course of various reflex components and bipedal locomotor behavior of spinal-contused macaques on runways for a postoperative period of up to 1 year. Our spinal cord research in primates is advantageous in understanding the characteristics of hind limb functions only, which possibly

  13. Kinematically stable bipedal locomotion using ionic polymer–metal composite actuators

    Hosseinipour, Milad; Elahinia, Mohammad


    Ionic conducting polymer–metal composites (abbreviated as IPMCs) are interesting actuators that can act as artificial muscles in robotic and microelectromechanical systems. Various black or gray box models have modeled the electrochemical–mechanical behavior of these materials. In this study, the governing partial differential equation of the behavior of IPMCs is solved using finite element methods to find the critical actuation parameters, such as strain distribution, maximum strain, and response time. One-dimensional results of the FEM solution are then extended to 2D to find the tip displacement of a flap actuator and experimentally verified. A model of a seven-degree-of-freedom biped robot, actuated by IPMC flaps, is then introduced. The possibility of fast and stable bipedal locomotion using IPMC artificial muscles is the main motivation of this study. Considering the actuator limits, joint path trajectories are generated to achieve a fast and smooth motion. The stability of the proposed gait is then evaluated using the ZMP criterion and motion simulation. The fabrication parameters of each actuator, such as length, platinum plating thickness and installation angle, are then determined using the generated trajectories. A discussion on future studies on force–torque generation of IPMCs for biped locomotion concludes this paper. (paper)

  14. Fish and robots swimming together: attraction towards the robot demands biomimetic locomotion.

    Marras, Stefano; Porfiri, Maurizio


    The integration of biomimetic robots in a fish school may enable a better understanding of collective behaviour, offering a new experimental method to test group feedback in response to behavioural modulations of its 'engineered' member. Here, we analyse a robotic fish and individual golden shiners (Notemigonus crysoleucas) swimming together in a water tunnel at different flow velocities. We determine the positional preference of fish with respect to the robot, and we study the flow structure using a digital particle image velocimetry system. We find that biomimetic locomotion is a determinant of fish preference as fish are more attracted towards the robot when its tail is beating rather than when it is statically immersed in the water as a 'dummy'. At specific conditions, the fish hold station behind the robot, which may be due to the hydrodynamic advantage obtained by swimming in the robot's wake. This work makes a compelling case for the need of biomimetic locomotion in promoting robot-animal interactions and it strengthens the hypothesis that biomimetic robots can be used to study and modulate collective animal behaviour.

  15. Heart rate profiles and energy cost of locomotion during cross-country skiing races.

    Mognoni, P; Rossi, G; Gastaldelli, F; Canclini, A; Cotelli, F


    The purpose of this study was to compare heart rate responses and speed in two cross-country skiing races, which were run by seven male and seven female subjects by using classic and free style. Heart rates and skiing velocities were analyzed over flat, uphill and downhill sections, which were run from one to three times. Heart rates were higher in uphill sections than in flat sections; a steady-state heart rate was never reached in the downhill section. When the same uphill section was repeated, the heart rate tended to increase but the speed to decrease. Oxygen uptake (VO2) was calculated from heart rate:VO2 ratio, measured during uphill walking with the aid of poles. The mean (SD) energy cost of locomotion (i.e., the ratio between net VO2 and speed) was 162.1 (9.4) and 147.7 (7.1) when male subjects ran the flat section after first downhill by using classic and free style, respectively. Females had lower values for VO2 and speed, but similar energy costs. In general, the variability of the energy cost of locomotion in skiers of a similar competitive level is of the same order as that found in uphill walking on a treadmill.

  16. Harmonic analysis of electric locomotive and traction power system based on wavelet singular entropy

    Dun, Xiaohong


    With the rapid development of high-speed railway and heavy-haul transport, the locomotive and traction power system has become the main harmonic source of China's power grid. In response to this phenomenon, the system's power quality issues need timely monitoring, assessment and governance. Wavelet singular entropy is an organic combination of wavelet transform, singular value decomposition and information entropy theory, which combines the unique advantages of the three in signal processing: the time-frequency local characteristics of wavelet transform, singular value decomposition explores the basic modal characteristics of data, and information entropy quantifies the feature data. Based on the theory of singular value decomposition, the wavelet coefficient matrix after wavelet transform is decomposed into a series of singular values that can reflect the basic characteristics of the original coefficient matrix. Then the statistical properties of information entropy are used to analyze the uncertainty of the singular value set, so as to give a definite measurement of the complexity of the original signal. It can be said that wavelet entropy has a good application prospect in fault detection, classification and protection. The mat lab simulation shows that the use of wavelet singular entropy on the locomotive and traction power system harmonic analysis is effective.

  17. Changes in Postural Syntax Characterize Sensory Modulation and Natural Variation of C. elegans Locomotion.

    Roland F Schwarz


    Full Text Available Locomotion is driven by shape changes coordinated by the nervous system through time; thus, enumerating an animal's complete repertoire of shape transitions would provide a basis for a comprehensive understanding of locomotor behaviour. Here we introduce a discrete representation of behaviour in the nematode C. elegans. At each point in time, the worm's posture is approximated by its closest matching template from a set of 90 postures and locomotion is represented as sequences of postures. The frequency distribution of postural sequences is heavy-tailed with a core of frequent behaviours and a much larger set of rarely used behaviours. Responses to optogenetic and environmental stimuli can be quantified as changes in postural syntax: worms show different preferences for different sequences of postures drawn from the same set of templates. A discrete representation of behaviour will enable the use of methods developed for other kinds of discrete data in bioinformatics and language processing to be harnessed for the study of behaviour.

  18. Untethered Recyclable Tubular Actuators with Versatile Locomotion for Soft Continuum Robots.

    Qian, Xiaojie; Chen, Qiaomei; Yang, Yang; Xu, Yanshuang; Li, Zhen; Wang, Zhenhua; Wu, Yahe; Wei, Yen; Ji, Yan


    Stimuli-responsive materials offer a distinguished platform to build tether-free compact soft robots, which can combine sensing and actuation without a linked power supply. In the past, tubular soft robots have to be made by multiple components with various internal channels or complex cavities assembled together. Moreover, robust processing, complex locomotion, simple structure, and easy recyclability represent major challenges in this area. Here, it is shown that those challenges can be tackled by liquid crystalline elastomers with allyl sulfide functional groups. The light-controlled exchange reaction between allyl sulfide groups allows flexible processing of tubular soft robots/actuators, which does not need any assisting materials. Complex locomotion demonstrated here includes reversible simultaneous bending and elongation; reversible diameter expansion; and omnidirectional bending via remote infrared light control. Different modes of actuation can be programmed into the same tube without the routine assembly of multiple tubes as used in the past. In addition, the exchange reaction also makes it possible to use the same single tube repeatedly to perform different functions by erasing and reprogramming. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Assessment of locomotion behavior in adult Zebrafish after acute exposure to different pharmacological reference compounds

    Pankaj Gupta


    Full Text Available Objectives: The objective of the present study was to assess locomotor behavior of adult zebrafish after acute exposure to different pharmacological reference compounds. Materials and Methods: Adult zebrafish of 4-5-months-old were exposed to different concentrations of known reference compounds for 15 min. The test was conducted separately for each drug concentration as well as control. Locomotor activity parameters viz. distance travelled, speed, total mobile time, and total immobile time were recorded for each animal during the exposure period. Results: Out of 11 compounds tested, nine compounds showed decrease in locomotor behavior with significant changes in distance travelled, speed, total mobile time, and total immobile time. Caffeine exhibited biphasic response in locomotion behavior, while scopolamine failed to induce any significant changes. Conclusion: In view of the above findings, these results suggested that exposure of adult zebrafish with different known compounds produce the expected changes in the locomotion behavior; therefore, adult zebrafish can be used an alternative approach for the assessment of new chemical entities for their effect on locomotor behavior.

  20. Cell type-specific responses to salinity - the epidermal bladder cell transcriptome of Mesembryanthemum crystallinum.

    Oh, Dong-Ha; Barkla, Bronwyn J; Vera-Estrella, Rosario; Pantoja, Omar; Lee, Sang-Yeol; Bohnert, Hans J; Dassanayake, Maheshi


    Mesembryanthemum crystallinum (ice plant) exhibits extreme tolerance to salt. Epidermal bladder cells (EBCs), developing on the surface of aerial tissues and specialized in sodium sequestration and other protective functions, are critical for the plant's stress adaptation. We present the first transcriptome analysis of EBCs isolated from intact plants, to investigate cell type-specific responses during plant salt adaptation. We developed a de novo assembled, nonredundant EBC reference transcriptome. Using RNAseq, we compared the expression patterns of the EBC-specific transcriptome between control and salt-treated plants. The EBC reference transcriptome consists of 37 341 transcript-contigs, of which 7% showed significantly different expression between salt-treated and control samples. We identified significant changes in ion transport, metabolism related to energy generation and osmolyte accumulation, stress signalling, and organelle functions, as well as a number of lineage-specific genes of unknown function, in response to salt treatment. The salinity-induced EBC transcriptome includes active transcript clusters, refuting the view of EBCs as passive storage compartments in the whole-plant stress response. EBC transcriptomes, differing from those of whole plants or leaf tissue, exemplify the importance of cell type-specific resolution in understanding stress adaptive mechanisms. No claim to original US government works. New Phytologist © 2015 New Phytologist Trust.

  1. Stress responses in flavivirus-infected cells: activation of unfolded protein response and autophagy

    Ana-Belén eBlázquez


    Full Text Available The Flavivirus is a genus of RNA viruses that includes multiple long known human, animal and zoonotic pathogens such as Dengue virus, yellow fever virus, West Nile virus or Japanese encephalitis virus, as well as other less known viruses that represent potential threats for human and animal health such as Usutu or Zika viruses. Flavivirus replication is based on endoplasmic reticulum-derived structures. Membrane remodeling and accumulation of viral factors induce endoplasmic reticulum stress that results in activation of a cellular signaling response termed unfolded protein response (UPR, which can be modulated by the viruses for their own benefit. Concomitant with the activation of the UPR, an upregulation of the autophagic pathway in cells infected with different flaviviruses has also been described. This review addresses the current knowledge of the relationship between endoplasmic reticulum stress, UPR and autophagy in flavivirus-infected cells and the growing evidences for an involvement of these cellular pathways in the replication and pathogenesis of these viruses.

  2. The coal-fired gas turbine locomotive - A new look

    Liddle, S. G.; Bonzo, B. B.; Purohit, G. P.


    Advances in turbomachine technology and novel methods of coal combustion may have made possible the development of a competitive coal fired gas turbine locomotive engine. Of the combustor, thermodynamic cycle, and turbine combinations presently assessed, an external combustion closed cycle regenerative gas turbine with a fluidized bed coal combustor is judged to be the best suited for locomotive requirements. Some merit is also discerned in external combustion open cycle regenerative systems and internal combustion open cycle regenerative gas turbine systems employing a coal gasifier. The choice of an open or closed cycle depends on the selection of a working fluid and the relative advantages of loop pressurization, with air being the most attractive closed cycle working fluid on the basis of cost.

  3. The Perceived Naturalness of Virtual Walking Speeds during WIP Locomotion

    Nilsson, Niels Chr.; Serafin, Stefania; Nordahl, Rolf


    It is well established that individuals tend to underestimate visually presented walking speeds when relying on treadmills for virtual walking. However, prior to the present studies this perceptual distortion had not been observed in relation to Walking-in-Place (WIP) locomotion, and a number...... to how gait cycle characteristics, visual display properties, and methodological differences affect speed underestimation during treadmill and WIP locomotion. The studies suggested the following: A significant main effect was found for step frequency; both display and geometric field of view were...... inversely proportional to the degree of underestimation; varying degrees of peripheral occlusion and increased HMD weight did not yield significant main effects; and the choice of method (i.e., how the speeds were presented) had a significant effect on the upper and lower bounds of what speeds were...

  4. Helicobacter pylori impairs murine dendritic cell responses to infection.

    Ya-Hui Wang

    Full Text Available BACKGROUND: Helicobacter pylori, a human pathogen associated with chronic gastritis, peptic ulcer and gastric malignancies, is generally viewed as an extracellular microorganism. Here, we show that H. pylori replicates in murine bone marrow derived-dendritic cells (BMDCs within autophagosomes. METHODOLOGY/PRINCIPAL FINDINGS: A 10-fold increase of CFU is found between 2 h and 6 h p.i. in H. pylori-infected BMDCs. Autophagy is induced around the bacterium and participates at late time points of infection for the clearance of intracellular H. pylori. As a consequence of infection, LC3, LAMP1 and MHC class II molecules are retained within the H. pylori-containing vacuoles and export of MHC class II molecules to cell surface is blocked. However, formalin-fixed H. pylori still maintain this inhibitory activity in BMDC derived from wild type mice, but not in from either TLR4 or TLR2-deficient mice, suggesting the involvement of H. pylori-LPS in this process. TNF-alpha, IL-6 and IL-10 expression was also modulated upon infection showing a TLR2-specific dependent IL-10 secretion. No IL-12 was detected favoring the hypothesis of a down modulation of DC functions during H. pylori infection. Furthermore, antigen-specific T cells proliferation was also impaired upon infection. CONCLUSIONS/SIGNIFICANCE: H. pylori can infect and replicate in BMDCs and thereby affects DC-mediated immune responses. The implication of this new finding is discussed for the biological life cycle of H. pylori in the host.

  5. Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation.

    Ringelstein-Harlev, Shimrit; Avivi, Irit; Fanadka, Mona; Horowitz, Netanel A; Katz, Tami


    Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia. Co-culture assays were used to examine the ability of CLL cells to suppress autologous T-cell immune responses. IL-10 potency of CLL cells was assessed following stimulation with activators of the toll-like receptor 9 (TLR9) or CD40 and was correlated with the inhibitory activity of the cells. TLR9-activated CLL cells were found to increase the frequency of CD4 + CD25 hi FOXp3 + regulatory T-cells (Tregs) and to inhibit autologous CD4 + T-cell proliferation. This signaling cascade proved to control IL-10 generation in CLL cells, which in turn promoted the inhibition of T-cell proliferation by CLL cells. However, CD40 activation of CLL cells, while exhibiting a similar ability to augment Treg frequency, did not either affect IL-10 generation or T-cell proliferation. In conclusion, CLL cells demonstrate a unique clonal quality of adopting Breg properties which promote modulation of T-cell characteristics. TLR9 appears to be a potent activator of regulatory abilities in CLL cells, possibly contributing to preferential immune escape of TLR9-responsive cells.

  6. To investigate the necessity of STRA6 upregulation in T cells during T cell immune responses.

    Rafik Terra

    Full Text Available Our earlier study revealed that STRA6 (stimulated by retinoic acid gene 6 was up-regulated within 3 h of TCR stimulation. STRA6 is the high-affinity receptor for plasma retinol-binding protein (RBP and mediates cellular vitamin A uptake. We generated STRA6 knockout (KO mice to assess whether such up-regulation was critical for T-cell activation, differentiation and function. STRA6 KO mice under vitamin A sufficient conditions were fertile without apparent anomalies upon visual inspection. The size, cellularity and lymphocyte subpopulations of STRA6 KO thymus and spleen were comparable to those of their wild type (WT controls. KO and WT T cells were similar in terms of TCR-stimulated proliferation in vitro and homeostatic expansion in vivo. Naive KO CD4 cells differentiated in vitro into Th1, Th2, Th17 as well as regulatory T cells in an analogous manner as their WT counterparts. In vivo experiments revealed that anti-viral immune responses to lymphocytic choriomeningitis virus in KO mice were comparable to those of WT controls. We also demonstrated that STRA6 KO and WT mice had similar glucose tolerance. Total vitamin A levels are dramatically lower in the eyes of KO mice as compared to those of WT mice, but the levels in other organs were not significantly affected after STRA6 deletion under vitamin A sufficient conditions, indicating that the eye is the mouse organ most sensitive to the loss of STRA6. Our results demonstrate that 1 in vitamin A sufficiency, the deletion of STRA6 in T cells does no affect the T-cell immune responses so-far tested, including those depend on STAT5 signaling; 2 STRA6-independent vitamin A uptake compensated the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; 3 STRA6 is critical for vitamin A uptake in the eyes even in vitamin A sufficiency.

  7. Performance analysis of jump-gliding locomotion for miniature robotics.

    Vidyasagar, A; Zufferey, Jean-Christohphe; Floreano, Dario; Kovač, M


    Recent work suggests that jumping locomotion in combination with a gliding phase can be used as an effective mobility principle in robotics. Compared to pure jumping without a gliding phase, the potential benefits of hybrid jump-gliding locomotion includes the ability to extend the distance travelled and reduce the potentially damaging impact forces upon landing. This publication evaluates the performance of jump-gliding locomotion and provides models for the analysis of the relevant dynamics of flight. It also defines a jump-gliding envelope that encompasses the range that can be achieved with jump-gliding robots and that can be used to evaluate the performance and improvement potential of jump-gliding robots. We present first a planar dynamic model and then a simplified closed form model, which allow for quantification of the distance travelled and the impact energy on landing. In order to validate the prediction of these models, we validate the model with experiments using a novel jump-gliding robot, named the 'EPFL jump-glider'. It has a mass of 16.5 g and is able to perform jumps from elevated positions, perform steered gliding flight, land safely and traverse on the ground by repetitive jumping. The experiments indicate that the developed jump-gliding model fits very well with the measured flight data using the EPFL jump-glider, confirming the benefits of jump-gliding locomotion to mobile robotics. The jump-glide envelope considerations indicate that the EPFL jump-glider, when traversing from a 2 m height, reaches 74.3% of optimal jump-gliding distance compared to pure jumping without a gliding phase which only reaches 33.4% of the optimal jump-gliding distance. Methods of further improving flight performance based on the models and inspiration from biological systems are presented providing mechanical design pathways to future jump-gliding robot designs.

  8. Using Computational and Mechanical Models to Study Animal Locomotion

    Miller, Laura A.; Goldman, Daniel I.; Hedrick, Tyson L.; Tytell, Eric D.; Wang, Z. Jane; Yen, Jeannette; Alben, Silas


    Recent advances in computational methods have made realistic large-scale simulations of animal locomotion possible. This has resulted in numerous mathematical and computational studies of animal movement through fluids and over substrates with the purpose of better understanding organisms’ performance and improving the design of vehicles moving through air and water and on land. This work has also motivated the development of improved numerical methods and modeling techniques for animal locom...

  9. Markerless 3D motion capture for animal locomotion studies

    William Irvin Sellers; Eishi Hirasaki


    ABSTRACT Obtaining quantitative data describing the movements of animals is an essential step in understanding their locomotor biology. Outside the laboratory, measuring animal locomotion often relies on video-based approaches and analysis is hampered because of difficulties in calibration and often the limited availability of possible camera positions. It is also usually restricted to two dimensions, which is often an undesirable over-simplification given the essentially three-dimensional na...

  10. Improved Usability of Locomotion Devices Using Human-Centric Taxonomy


    the classification of interaction devices by the limbs used in the interaction rather than by arbitrary classifications, such as “ wand ”, or “glove...ABILITY REQUIREMENTS ANALYSIS USING F-JAS In Tables 5 through 8, we took the results of a sample HAR analysis done by Cockayne and Darken [13] comparing...point less than natural locomotion in all categories except for explosive strength, in which it receives 2 less points. 2. Decelerate from Walk or Jog

  11. Sustained periodic terrestrial locomotion in air-breathing fishes.

    Pace, C M; Gibb, A C


    While emergent behaviours have long been reported for air-breathing osteichthyians, only recently have researchers undertaken quantitative analyses of terrestrial locomotion. This review summarizes studies of sustained periodic terrestrial movements by air-breathing fishes and quantifies the contributions of the paired appendages and the axial body to forward propulsion. Elongate fishes with axial-based locomotion, e.g. the ropefish Erpetoichthys calabaricus, generate an anterior-to-posterior wave of undulation that travels down the axial musculoskeletal system and pushes the body against the substratum at multiple points. In contrast, appendage-based locomotors, e.g. the barred mudskipper Periophthalmus argentilineatus, produce no axial bending during sustained locomotion, but instead use repeated protraction-retraction cycles of the pectoral fins to elevate the centre of mass and propel the entire body anteriorly. Fishes that use an axial-appendage-based mechanism, e.g. walking catfishes Clarias spp., produce side-to-side, whole-body bending in co-ordination with protraction-retraction cycles of the pectoral fins. Once the body is maximally bent to one side, the tail is pressed against the substratum and drawn back through the mid-sagittal plane, which elevates the centre of mass and rotates it about a fulcrum formed by the pectoral fin and the ground. Although appendage-based terrestrial locomotion appears to be rare in osteichthyians, many different species appear to have converged upon functionally similar axial-based and axial-appendage-based movements. Based on common forms observed across divergent taxa, it appears that dorsoventral compression of the body, elongation of the axial skeleton or the presence of robust pectoral fins can facilitate effective terrestrial movement by air-breathing fishes. © 2014 The Fisheries Society of the British Isles.

  12. The role of vortices in animal locomotion in fluids

    Dvořák R.


    Full Text Available The aim of this paper is to show the significance of vortices in animal locomotion in fluids on two deliberately chosen examples. The first example concerns lift generation by bird and insect wings, the second example briefly mentiones swimming and walking on water. In all the examples, the vortices generated by the moving animal impart the necessary momentum to the surrounding fluid, the reaction to which is the force moving or lifting the animal.

  13. Equilibrium Condition during Locomotion and Gait in Broiler Chickens

    MCF Alves

    Full Text Available ABSTRACT The experiment was carried out with the objective of evaluating a methodology to estimate the angulation and equilibrium condition, relating them to gait score and the main diseases of the locomotion system in males and females of commercial broiler strains. A completely randomized experimental design in a factorial arrangement (2x2 was applied, consisting of two sexes and two genetic strains, with five replicates of 53 chickens each. The following characteristics related to broiler locomotion were studied: gait score (GS; incidence of Valgus (VAL and Varus (VAR deformities and of pododermatitis (POD; body angle relative the ground (ANG; equilibrium condition (EC; body weight (BW and breast weight (BrW; and incidence of femoral degeneration (FD, tibial dyschondroplasia (TD and spondylolisthesis (SPO. GS, and VAL and VAR were assessed inside a broiler house. Birds were then photographed to estimate ANG and EC. Birds were sacrificed at 42 days of age and analyzed for FD, TD, and SPO. Breast percentage was not influenced by sex or strain. Males showed better ANG than females, regardless of strain. Overall, the strains studied showed prostrated EC. The correlation between GS and the evaluated traits was low. There was a moderate to high association between EC and ANG both in males and females. GS showed low correlation with locomotion problems, and therefore, it is a poor indicator of skeletal diseases. On the other hand, the moderate to high correlations of ANG and EC with locomotion problems make them better indicators of bone diseases than gait score, which is possibly more related to EC and body posture than to bone pathologies.

  14. Stream biofilm responses to flow intermittency: from cells to ecosystems

    Sergi eSabater


    Full Text Available Temporary streams are characterized by the alternation of dry and wet hydrological phases, creating both a harsh environment for the biota as well as a high diversity of opportunities for adaptation. These systems are eminently microbial-based during several of these hydrological phases, and those growing on all solid substrata (biofilms accordingly change their physical structure and community composition. Biofilms experience large decreases on cell densities and biomass, both of bacteria and algae, during dryness. Algal and bacterial communities show remarkable decreases in their diversity, at least locally (at the habitat scale. Biofilms also respond with significant physiological plasticity to each of the hydrological changes. The decreasing humidity of the substrata through the drying process, and the changing quantity and quality of organic matter and nutrients available in the stream during that process, causes unequal responses on the biofilm bacteria and algae. Biofilm algae are affected faster than bacteria by the hydric stress, and as a result the ecosystem respiration resists longer than gross primary production to the increasing duration of flow intermittency. This response implies enhancing ecosystem heterotrophy, a pattern that can be exacerbated in temporary streams suffering of longer dry periods under global change.

  15. Acrolein in cigarette smoke inhibits T-cell responses.

    Lambert, Cherie; McCue, Jesica; Portas, Mary; Ouyang, Yanli; Li, JiMei; Rosano, Thomas G; Lazis, Alexander; Freed, Brian M


    Cigarette smoking inhibits T-cell responses in the lungs, but the immunosuppressive compounds have not been fully identified. Cigarette smoke extracts inhibit IL-2, IFN-gamma, and TNF-alpha production in stimulated lymphocytes obtained from peripheral blood, even when the extracts were diluted 100-fold to 1000-fold. The objective of these studies was to identify the immunosuppressive compounds found in cigarette smoke. Gas chromatography/mass spectroscopy and HPLC were used to identify and quantitate volatile compounds found in cigarette smoke extracts. Bioactivity was measured by viability and production of cytokine mRNA and protein levels in treated human lymphocytes. The vapor phase of the cigarette smoke extract inhibited cytokine production, indicating that the immunosuppressive compounds were volatile. Among the volatile compounds identified in cigarette smoke extracts, only the alpha,beta-unsaturated aldehydes, acrolein (inhibitory concentration of 50% [IC50] = 3 micromol/L) and crotonaldehyde (IC50 = 6 micromol/L), exhibited significant inhibition of cytokine production. Although the levels of aldehydes varied 10-fold between high-tar (Camel) and ultralow-tar (Carlton) extracts, even ultralow-tar cigarettes produced sufficient levels of acrolein (34 micromol/L) to suppress cytokine production by >95%. We determined that the cigarette smoke extract inhibited transcription of cytokine genes. The inhibitory effects of acrolein could be blocked with the thiol compound N-acetylcysteine. The vapor phase from cigarette smoke extracts potently suppresses cytokine production. The compound responsible for this inhibition appears to be acrolein.

  16. Fast Neutrons - LET Distributions and the Response of Mammalian Cells

    Bewley, D. K. [Medical Research Council Cyclotron Unit, Hammersmith Hospital, London (United Kingdom)


    Distributions of stopping power (LET) are given for four beams of fast neutrons, namely, neutrons of 14.6 MeV, neutrons produced by bombarding a thick beryllium target with 15 MeV deuterons, neutrons of 3 MeV, and fast neutrons produced by bombardment of a {sup 235}U converter plate with thermal neutrons. The track average LET is correlated with mean neutron energy, but the dose average is approximately constant. However, neither of these types of average is expected to have much relevance to radiobiology. Further, specification of a ''biologically effective LET'' depends on the biological test used, and is not solely a function of the radiation quality. An attempt has been made to calculate the response of T.I. kidney cells in tissue culture to these four beams of neutrons, based on their response to charged particles using the track-segment method. The calculated RBE's of the neutron beams are lower than the observed values and the calculated values of the oxygen enhancement ratio are higher. These differences seem too great to be explained by errors in dosimetry and in the calculated LET spectra. The suggestion is made that LET is not an adequate criterion of radiation quality, and that the discrepancies may be explained by more detailed consideration of the part played by delta rays and by heavy recoil tracks of short range. (author)

  17. Full-scale locomotive dynamic crash testing and correlations : locomotive consist colliding with steel coil truck at grade crossing (test 3).


    This report presents the test results and finite element correlations of a full-scale dynamic collision between a locomotive and a highway truck loaded with two heavy steel coils. The locomotive consist was moving at 58 miles per hour before it struc...

  18. Immune responses of dendritic cells after acquiring antigen from apoptotic hepatocholangioma cells caused by γ-ray

    Wu Gang; Gu Hongguang; Han Benli; Pei Xuetao


    Objective: To investigate the induction of cytotoxic T lymphocytes (CTLs) in antitumor responsiveness and therapeutic effects after dendritic cells (DCs) acquired antigen from apoptotic hepatocholangioma cells. Methods: DCs from blood mononuclear cells that maintain the characteristics of immaturity-anti-gen-capturing and-processing capacity were established in vitro by using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Then, apoptosis in hepatocholangioma cells was induced with γ-radiation. The experimental groups included (1) co-culture of DCs, and apoptotic cancer cells and T cells; (2) co-culture of DCs necrotic cancer cells and T cells; (3) co-culture of DCs-cultured cancer cell and T cells. These cells were co-cultured for 7 days. DCs and T cell were enriched separately. Finally, antitumor response test was carried out. Results: These cells had typical dendritic morphology, expressed high levels of CD1a, B7 and acquired antigen from apoptotic cells caused by γ-rays and induced an increased T cell-stimulatory capacity in MLR. Conclusions: DCs obtained from blood mononuclear cells using GM-CSF and IL-4 and DCs can efficiently present antigen driven from apoptotic cells caused by γ-rays and induce T cells increasing obviously. It can probably become an effective approach of DC transduction with antigen

  19. Differential pulmonic NK and NKT cell responses in Schistosoma japonicum-infected mice.

    Cha, Hefei; Qin, Wenjuan; Yang, Quan; Xie, Hongyan; Qu, Jiale; Wang, Mei; Chen, Daixiong; Wang, Fang; Dong, Nuo; Chen, Longhua; Huang, Jun


    Natural killer cells (NK cells) and natural killer T cells (NKT cells) play a role in anti-infection, anti-tumor, transplantation immunity, and autoimmune regulation. However, the role of NK and NKT cells during Schistosoma japonicum (S. japonicum) infection has not been widely reported, especially regarding lung infections. The aim of this study was to research the NK and NKT cell response to S. japonicum infection in the lungs of mice. Using immunofluorescent histological analysis, NK and NKT cells were found near pulmonary granulomas. Moreover, flow cytometry revealed that the percentage and number of pulmonic NK cells in S. japonicum-infected mice were significantly increased (P cell number of NKT cells were decreased compared to those of normal mice (P NKT cells was increased after infection (P NKT cells (P cells (P NKT cells significantly increased (P NKT cells (P NKT cell activation during S. japonicum infection.

  20. Control method for biped locomotion robots based on ZMP information

    Kume, Etsuo


    The Human Acts Simulation Program (HASP) started as a ten year program of Computing and Information Systems Center (CISC) at Japan Atomic Energy Research Institute (JAERI) in 1987. A mechanical design study of biped locomotion robots for patrol and inspection in nuclear facilities is being performed as an item of the research scope. One of the goals of our research is to design a biped locomotion robot for practical use in nuclear facilities. So far, we have been studying for several dynamic walking patterns. In conventional control methods for biped locomotion robots, the program control is used based on preset walking patterns, so it dose not have the robustness such as a dynamic change of walking pattern. Therefore, a real-time control method based on dynamic information of the robot states is necessary for the high performance of walking. In this study a new control method based on Zero Moment Point (ZMP) information is proposed as one of real-time control methods. The proposed method is discussed and validated based on the numerical simulation. (author)

  1. The aspect of vector control using the asynchronous traction motor in locomotives

    L. Liudvinavičius


    Full Text Available The article examines curves controlling asynchronous traction motors increasingly used in locomotive electric drives the main task of which is to create a tractive effort-speed curve of an ideal locomotive Fk = f(v, including a hyperbolic area the curve of which will create conditions showing that energy created by the diesel engine of diesel locomotives (electric locomotives and in case of electric trains, electricity taken from the contact network over the entire range of locomotive speed is turned into efficient work. Mechanical power on wheel sets is constant Pk = Fkv = const, the power of the diesel engine is fully used over the entire range of locomotive speed. Tractive effort-speed curve Fk(v shows the dependency of locomotive traction power Fk on movement speed v. The article presents theoretical and practical aspects relevant to creating the structure of locomotive electric drive and selecting optimal control that is especially relevant to creating the structure of locomotive electric drive using ATM (asynchronous traction motor that gains special popularity in traction rolling stock replacing DC traction motors having low reliability. The frequency modes of asynchronous motor speed regulation are examined. To control ATM, the authors suggest the method of vector control presenting the structural schemes of a locomotive with ATM and control algorithm.

  2. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells.

    Gornalusse, Germán G; Hirata, Roli K; Funk, Sarah E; Riolobos, Laura; Lopes, Vanda S; Manske, Gabriel; Prunkard, Donna; Colunga, Aric G; Hanafi, Laïla-Aïcha; Clegg, Dennis O; Turtle, Cameron; Russell, David W


    Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C. These HLA-engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8 + T cells, do not bind anti-HLA antibodies and are resistant to NK-mediated lysis. Our approach provides a potential source of universal donor cells for applications where the differentiated derivatives lack HLA class II expression.

  3. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells

    Gornalusse, Germán G.; Hirata, Roli K.; Funk, Sarah; Riolobos, Laura; Lopes, Vanda S.; Manske, Gabriel; Prunkard, Donna; Colunga, Aric G.; Hanafi, Laïla-Aïcha; Clegg, Dennis O.; Turtle, Cameron; Russell, David W.


    Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this ‘missing self’ response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C. These HLA-engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8+ T cells, do not bind anti-HLA antibodies, and are resistant to NK-mediated lysis. Our approach provides a potential source of universal donor cells for applications where the differentiated derivatives lack HLA class II expression. PMID:28504668

  4. Fibroblast and T cells conditioned media induce maturation dendritic cell and promote T helper immune response

    Masoumeh Asadi


    Full Text Available Dendritic cells (DCs induce pathogen-specific T cell responses. We comprehensively studied the effects of addition of maturation stimulus, fibroblasts (fibroblast conditioned medium, PHA activated T cells (T cell conditioned medium, and mixture of fibroblast & PHA activated T cells (FCM-TCCM conditioned media on maturation of DCs. Monocytes were cultured with GM-CSF and IL-4 for five days. Maturation factors included MCM and TNF-α as control group. FCM and TCCM, or FCM-TCCM supernatant were considered as the treatment group. Tumor antigens were added at day five. Matured DCs were harvested at day seven. Phenotypic and functional analyses were carried out using anti (CD14, CD80, CD86, CD83 and HLA-DR monoclonal antibodies. Phagocytic activity, mixed lymphocyte reaction (MLR and cytokine production were also evaluated. At the end of culturing period, significantly fully matured DCs with large amount cytoplasm and copious dendritic projections were found in the presence of MCM, TNF-α with or without FCM, TCCM, FCM as well as TCCM. Flow cytometric analysis revealed that expression of CD14 decreased in particular in treated DCs, at the 5th day and expression of CD80, CD86 and HLA-DR was higher when FCM, TCCM, FCM plus TCCM were added to maturation factor. This study demonstrated that DCs matured with these methods had optimum function in comparison with either factor alone.

  5. B-Cell and T-Cell Immune Responses to Experimental Helicobacter pylori Infection in Humans

    Nurgalieva, Zhannat Z.; Conner, Margaret E.; Opekun, Antone R.; Zheng, Carl Q.; Elliott, Susan N.; Ernst, Peter B.; Osato, Michael; Estes, Mary K.; Graham, David Y.


    The acute antibody and T-cell immune response to Helicobacter pylori infection in humans has not been studied systematically. Serum from H. pylori-naive volunteers challenged with H. pylori and cured after 4 or 12 weeks was tested by enzyme-linked immunosorbent assays for anti-H. pylori-specific immunoglobulin M (IgM) and IgA established using bacterial lysates from homologous (the infecting strain) and heterologous H. pylori. Proteins recognized by IgM antibody were identified by mass spectrometry of immunoreactive bands separated by two-dimensional gel electrophoresis. Mucosal T-cell subsets (CD4, CD8, CD3, and CD30 cells) were assessed by immunohistochemistry. All 18 infected volunteers developed H. pylori-specific IgM responses to both homologous or heterologous H. pylori antigens. H. pylori antigens reacted with IgM antibody at 4 weeks postinfection. IgM Western blotting showed immunoreactivity of postinfection serum samples to multiple H. pylori proteins with molecular weights ranging between 9,000 (9K) to 150K with homologous strains but only a 70K band using heterologous antigens. Two-dimensional electrophoresis demonstrated that production of H. pylori-specific IgM antibodies was elicited by H. pylori flagellins A and B, urease B, ABC transporter binding protein, heat shock protein 70 (DnaK), and alkyl hydroperoxide reductase. Mucosal CD3, CD4, and CD8 T-cell numbers increased following infection. IgM antibody responses were detected to a range of homologous H. pylori antigens 2 to 4 weeks postchallenge. The majority of H. pylori proteins were those involved in motility and colonization and may represent targets for vaccine development. PMID:15845507

  6. Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

    Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J


    To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.

  7. Distinct Responses of Stem Cells to Telomere Uncapping-A Potential Strategy to Improve the Safety of Cell Therapy.

    Liu, Chang Ching; Ma, Dong Liang; Yan, Ting-Dong; Fan, XiuBo; Poon, Zhiyong; Poon, Lai-Fong; Goh, Su-Ann; Rozen, Steve G; Hwang, William Ying Khee; Tergaonkar, Vinay; Tan, Patrick; Ghosh, Sujoy; Virshup, David M; Goh, Eyleen L K; Li, Shang


    In most human somatic cells, the lack of telomerase activity results in progressive telomere shortening during each cell division. Eventually, DNA damage responses triggered by critically short telomeres induce an irreversible cell cycle arrest termed replicative senescence. However, the cellular responses of human pluripotent stem cells to telomere uncapping remain unknown. We generated telomerase knockout human embryonic stem (ES) cells through gene targeting. Telomerase inactivation in ES cells results in progressive telomere shortening. Telomere DNA damage in ES cells and neural progenitor cells induces rapid apoptosis when telomeres are uncapped, in contrast to fibroblast cells that enter a state of replicative senescence. Significantly, telomerase inactivation limits the proliferation capacity of human ES cells without affecting their pluripotency. By targeting telomerase activity, we can functionally separate the two unique properties of human pluripotent stem cells, namely unlimited self-renewal and pluripotency. We show that the potential of ES cells to form teratomas in vivo is dictated by their telomere length. By controlling telomere length of ES cells through telomerase inactivation, we can inhibit teratoma formation and potentially improve the safety of cell therapies involving terminally differentiated cells as well as specific progenitor cells that do not require sustained cellular proliferation in vivo, and thus sustained telomerase activity. Stem Cells 2016;34:2471-2484. © 2016 AlphaMed Press.

  8. Locomotion training of legged robots using hybrid machine learning techniques

    Simon, William E.; Doerschuk, Peggy I.; Zhang, Wen-Ran; Li, Andrew L.


    In this study artificial neural networks and fuzzy logic are used to control the jumping behavior of a three-link uniped robot. The biped locomotion control problem is an increment of the uniped locomotion control. Study of legged locomotion dynamics indicates that a hierarchical controller is required to control the behavior of a legged robot. A structured control strategy is suggested which includes navigator, motion planner, biped coordinator and uniped controllers. A three-link uniped robot simulation is developed to be used as the plant. Neurocontrollers were trained both online and offline. In the case of on-line training, a reinforcement learning technique was used to train the neurocontroller to make the robot jump to a specified height. After several hundred iterations of training, the plant output achieved an accuracy of 7.4%. However, when jump distance and body angular momentum were also included in the control objectives, training time became impractically long. In the case of off-line training, a three-layered backpropagation (BP) network was first used with three inputs, three outputs and 15 to 40 hidden nodes. Pre-generated data were presented to the network with a learning rate as low as 0.003 in order to reach convergence. The low learning rate required for convergence resulted in a very slow training process which took weeks to learn 460 examples. After training, performance of the neurocontroller was rather poor. Consequently, the BP network was replaced by a Cerebeller Model Articulation Controller (CMAC) network. Subsequent experiments described in this document show that the CMAC network is more suitable to the solution of uniped locomotion control problems in terms of both learning efficiency and performance. A new approach is introduced in this report, viz., a self-organizing multiagent cerebeller model for fuzzy-neural control of uniped locomotion is suggested to improve training efficiency. This is currently being evaluated for a possible

  9. Cellular cooperation in lymphocyte activation. III. B-cell helper effect in the enhancement of T-cell response.

    Kasahara, T; Kin, K; Itoh, Y; Kawai, T; Kano, Y; Shioiri-Nakano, K


    T and B cells were purified from human tonsil and peripheral blood by the removal of phagocytic cells, followed by filtration through a nylon fiber column (NC) and E-rosette formation. Purified T and B cells contained less than 1% of other cell types. The responses of T cells to concanavalin A (Con A) and soluble protein A were greatly enhanced in the presence of autologous B cells. Participation of B cells in T-cell enhancement was confirmed by the following observations: (a) purified B copulation, which was separated further from adherent B cells, retained its enhancing activity. (b) Another adherent cell-free B-cell preparation, which was purified from the NC-passed fraction, and (c) no T lymphoid but some B lymphoid cell lines, elicited strong T-cell enhancement. It was also found that the enhancing capacity of B cells required no metabolic activity, but rather an intact cell form and direct cell-to-cell contact with responding cells. The stimulatory determinants on B cells were resistant to trypsin and neuraminidase treatment. In this paper a hypothesis will be presented that at least two signals are prerequisite for the effective activation of T cells.

  10. Ionizing radiation affects generation of MART-1-specific cytotoxic T cell responses by dendritic cells

    Liao, Y.P.; Wang, C.-C.; McBride, W.H.


    Full text: The human MART-1/Melan-A (MART-1) melanoma tumor antigen is known to be recognized by cytotoxic T lymphocytes (CTLs) and several groups are using this target for clinical immunotherapy. Most approaches use dendritic cells (DCs) that are potent antigen presentation cells for initiating CTL responses. In order for CTL recognition to occur, DCs must display 9-residue antigenic peptides on MHC class I molecules. These peptides are generated by proteasome degradation and then transported through the endoplasmic reticulum to the cell surface where they stabilize MHC class I expression. Our previous data showed that irradiation inhibits proteasome function and, therefore, we hypothesized that irradiation may inhibit antigen processing and CTL activation, as has been shown for proteasome inhibitors. To study the importance of irradiation effects on DCs, we studied the generation MART-1-specific CTL responses. Preliminary data showed that irradiation of murine bone marrow derived DCs did not affect expression of MHC class I, II, CD80, or CD86, as assessed by flow cytometric analyses 24-hour after irradiation. The effect of irradiation on MART-1 antigen processing by DCs was evaluated using DC transduced with adenovirus MART-1 (AdVMART1). C57BL/6 mice were immunized with AdVMART1 transduced DCs, with and without prior irradiation. IFN-γ production was measured by ELISPOT assays after 10-14 days of immunization. Prior radiation treatment resulted in a significant decrease in MART-1-specific T cell responses. The ability of irradiated and non-irradiated AdVMART1/DC vaccines to protect mice against growth of murine B16 tumors, which endogenously express murine MART-1, was also examined. AdVMART1/DC vaccination protected C57BL/6 mice against challenge with viable B16 melanoma cells while DCs irradiated (10 Gy) prior to AdVMART1 transduction abrogated protection. These results suggest that proteasome inhibition in DCs by irradiation may be a possible pathway in

  11. Association of Mode of Locomotion and Independence in Locomotion With Long-Term Outcomes After Spinal Cord Injury

    Krause, James; Carter, Rickey E; Brotherton, Sandra


    Background/Objective: To explore the association of mode of locomotion (ambulation vs wheelchair use) and independence in locomotion (independent vs require assistance) with health, participation, and subjective well-being (SWB) after spinal cord injury (SCI). Research Design: Secondary analysis was conducted on survey data collected from 2 rehabilitation hospitals in the Midwest and a specialty hospital in the southeastern United States. The 1,493 participants were a minimum of 18 years of age and had traumatic SCI of at least 1 year duration at enrollment. Main Outcome Measures: Three sets of outcome measures were used: SWB, participation, and health. SWB was measured by 8 scales and a measure of depressive symptoms, participation by 3 items, health by general health ratings, days in poor health, hospitalizations, and treatments. Results: Small but significant associations were observed between independence in locomotion and every outcome. Ambulation was associated with greater participation but a mixed pattern of favorable and unfavorable health and SWB outcomes. Supplemental analyses were conducted on those who ambulated but who were dependent on others to do so (n = 117), because this group reported poor outcomes in several areas. Individuals who were independent in wheelchair use reported substantially better outcomes than nonwheelchair users and those dependent on others in wheelchair use. Conclusions: Although ambulation is often a recovery goal, individuals with SCI who ambulate do not uniformly report better outcomes than wheelchair users, and those who depend on others for assistance with ambulation may experience a unique set of problems. PMID:19810625

  12. Inhibition of host cell translation elongation by Legionella pneumophila blocks the host cell unfolded protein response.

    Hempstead, Andrew D; Isberg, Ralph R


    Cells of the innate immune system recognize bacterial pathogens by detecting common microbial patterns as well as pathogen-specific activities. One system that responds to these stimuli is the IRE1 branch of the unfolded protein response (UPR), a sensor of endoplasmic reticulum (ER) stress. Activation of IRE1, in the context of Toll-like receptor (TLR) signaling, induces strong proinflammatory cytokine induction. We show here that Legionella pneumophila, an intravacuolar pathogen that replicates in an ER-associated compartment, blocks activation of the IRE1 pathway despite presenting pathogen products that stimulate this response. L. pneumophila TLR ligands induced the splicing of mRNA encoding XBP1s, the main target of IRE1 activity. L. pneumophila was able to inhibit both chemical and bacterial induction of XBP1 splicing via bacterial translocated proteins that interfere with host protein translation. A strain lacking five translocated translation elongation inhibitors was unable to block XBP1 splicing, but this could be rescued by expression of a single such inhibitor, consistent with limitation of the response by translation elongation inhibitors. Chemical inhibition of translation elongation blocked pattern recognition receptor-mediated XBP1 splicing, mimicking the effects of the bacterial translation inhibitors. In contrast, host cell-promoted inhibition of translation initiation in response to the pathogen was ineffective in blocking XBP1 splicing, demonstrating the need for the elongation inhibitors for protection from the UPR. The inhibition of host translation elongation may be a common strategy used by pathogens to limit the innate immune response by interfering with signaling via the UPR.

  13. Application of laser tweezers Raman spectroscopy techniques to the monitoring of single cell response to stimuli

    Chan, James W.; Liu, Rui; Matthews, Dennis L.


    Laser tweezers Raman spectroscopy (LTRS) combines optical trapping with micro-Raman spectroscopy to enable label-free biochemical analysis of individual cells and small biological particles in suspension. The integration of the two technologies greatly simplifies the sample preparation and handling of suspension cells for spectroscopic analysis in physiologically meaningful conditions. In our group, LTRS has been used to study the effects of external perturbations, both chemical and mechanical, on the biochemistry of the cell. Single cell dynamics can be studied by performing longitudinal studies to continuously monitor the response of the cell as it interacts with its environment. The ability to carry out these measurements in-vitro makes LTRS an attractive tool for many biomedical applications. Here, we discuss the use of LTRS to study the response of cancer cells to chemotherapeutics and bacteria cells to antibiotics and show that the life cycle and apoptosis of the cells can be detected. These results show the promise of LTRS for drug discovery/screening, antibiotic susceptibility testing, and chemotherapy response monitoring applications. In separate experiments, we study the response of red blood cells to the mechanical forces imposed on the cell by the optical tweezers. A laser power dependent deoxygenation of the red blood cell in the single beam trap is reported. Normal, sickle cell, and fetal red blood cells have a different behavior that enables the discrimination of the cell types based on this mechanochemical response. These results show the potential utility of LTRS for diagnosing and studying red blood cell diseases.

  14. T-cell-independent immune responses do not require CXC ligand 13-mediated B1 cell migration.

    Colombo, Matthew J; Sun, Guizhi; Alugupalli, Kishore R


    The dynamic movement of B cells increases the probability of encountering specific antigen and facilitates cell-cell interactions required for mounting a rapid antibody response. B1a and B1b cells are enriched in the coelomic cavity, contribute to T-cell-independent (TI) antibody responses, and increase in number upon antigen exposure. B1 cell movement is largely governed by Cxc ligand 13 (Cxcl13), and mice deficient in this chemokine have a severe reduction in peritoneal B1 cells. In this study, we examined the role of Cxcl13-dependent B cell migration using Borrelia hermsii infection or intraperitoneal immunization with pneumococcal polysaccharide or 4-hydroxy-3-nitrophenyl-acetyl (NP)-Ficoll, all of which induce robust antibody responses from B1b cells. Surprisingly, we found that antibody responses to B. hermsii or to FhbA, an antigenic target of B1b cells, and the resolution of bacteremia were indistinguishable between wild-type and Cxcl13-/- mice. Importantly, we did not observe an expansion of peritoneal B1b cell numbers in Cxcl13-/- mice. Nonetheless, mice that had resolved infection were resistant to reinfection, indicating that the peritoneal B1b cell reservoir is not required for controlling B. hermsii. Furthermore, despite a reduced peritoneal B1b compartment, immunization with pneumococcal polysaccharide vaccine yielded comparable antigen-specific antibody responses in wild-type and Cxcl13-/- mice and conferred protection against Streptococcus pneumoniae. Likewise, immunization with NP-Ficoll elicited similar antibody responses in wild-type and Cxcl13-/- mice. These data demonstrate that homing of B1 cells into the coelomic cavity is not a requirement for generating protective TI antibody responses, even when antigen is initially localized to this anatomical compartment.

  15. Responses of crayfish photoreceptor cells following intense light adaptation.

    Cummins, D R; Goldsmith, T H


    After intense orange adapting exposures that convert 80% of the rhodopsin in the eye to metarhodopsin, rhabdoms become covered with accessory pigment and appear to lose some microvillar order. Only after a delay of hours or even days is the metarhodopsin replaced by rhodopsin (Cronin and Goldsmith 1984). After 24 h of dark adaptation, when there has been little recovery of visual pigment, the photoreceptor cells have normal resting potentials and input resistances, and the reversal potential of the light response is 10-15 mV (inside positive), unchanged from controls. The log V vs log I curve is shifted about 0.6 log units to the right on the energy axis, quantitatively consistent with the decrease in the probability of quantum catch expected from the lowered concentration of rhodopsin in the rhabdoms. Furthermore, at 24 h the photoreceptors exhibit a broader spectral sensitivity than controls, which is also expected from accumulations of metarhodopsin in the rhabdoms. In three other respects, however, the transduction process appears to be light adapted: The voltage responses are more phasic than those of control photoreceptors. The relatively larger effect (compared to controls) of low extracellular Ca++ (1 mmol/l EGTA) in potentiating the photoresponses suggests that the photoreceptors may have elevated levels of free cytoplasmic Ca++. The saturating depolarization is only about 30% as large as the maximal receptor potentials of contralateral, dark controls, and by that measure the log V-log I curve is shifted downward by 0.54 log units.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Patterns of DNA damage response in intracranial germ cell tumors versus glioblastomas reflect cell of origin rather than brain environment

    Bartkova, Jirina; Hoei-Hansen, Christina E; Krizova, Katerina


    The DNA damage response (DDR) machinery becomes commonly activated in response to oncogenes and during early stages of development of solid malignancies, with an exception of testicular germ cell tumors (TGCTs). The active DDR signaling evokes cell death or senescence but this anti-tumor barrier ...... checkpoints in intracranial tumorigenesis, with implications for the differential biological responses of diverse tumor types to endogenous stress as well as to genotoxic treatments such as ionizing radiation or chemotherapy....

  17. Evaluation of cell responses toward adhesives with different photoinitiating systems.

    Van Landuyt, Kirsten L; Krifka, Stephanie; Hiller, Karl-Anton; Bolay, Carola; Waha, Claudia; Van Meerbeek, Bart; Schmalz, Gottfried; Schweikl, Helmut


    The photoinitiator diphenyl-(2,4,6-trimethylbenzoyl)phosphine oxide (TPO) is more reactive than a camphorquinone/amine (CQ) system, and TPO-based adhesives obtained a higher degree of conversion (DC) with fewer leached monomers. The hypothesis tested here is that a TPO-based adhesive is less toxic than a CQ-based adhesive. A CQ-based adhesive (SBU-CQ) (Scotchbond Universal, 3M ESPE) and its experimental counterpart with TPO (SBU-TPO) were tested for cytotoxicity in human pulp-derived cells (tHPC). Oxidative stress was analyzed by the generation of reactive oxygen species (ROS) and by the expression of antioxidant enzymes. A dentin barrier test (DBT) was used to evaluate cell viability in simulated clinical circumstances. Unpolymerized SBU-TPO was significantly more toxic than SBU-CQ after a 24h exposure, and TPO alone (EC50=0.06mM) was more cytotoxic than CQ (EC50=0.88mM), EDMAB (EC50=0.68mM) or CQ/EDMAB (EC50=0.50mM). Cultures preincubated with BSO (l-buthionine sulfoximine), an inhibitor of glutathione synthesis, indicated a minor role of glutathione in cytotoxic responses toward the adhesives. Although the generation of ROS was not detected, a differential expression of enzymatic antioxidants revealed that cells exposed to unpolymerized SBU-TPO or SBU-CQ are subject to oxidative stress. Polymerized SBU-TPO was more cytotoxic than SBU-CQ under specific experimental conditions only, but no cytotoxicity was detected in a DBT with a 200μm dentin barrier. Not only DC and monomer-release determine the biocompatibility of adhesives, but also the cytotoxicity of the (photo-)initiator should be taken into account. Addition of TPO rendered a universal adhesive more toxic compared to CQ; however, this effect could be annulled by a thin dentin barrier. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  18. Antigen specific T-cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer.

    Hadaschik, Boris; Su, Yun; Huter, Eva; Ge, Yingzi; Hohenfellner, Markus; Beckhove, Philipp


    Immunotherapy is a promising approach in an effort to control castration resistant prostate cancer. We characterized tumor antigen reactive T cells in patients with prostate cancer and analyzed the suppression of antitumor responses by regulatory T cells. Peripheral blood samples were collected from 57 patients with histologically confirmed prostate cancer, 8 patients with benign prostatic hyperplasia and 16 healthy donors. Peripheral blood mononuclear cells were isolated and antigen specific interferon-γ secretion of isolated T cells was analyzed by enzyme-linked immunospot assay. T cells were functionally characterized and T-cell responses before and after regulatory T-cell depletion were compared. As test tumor antigens, a panel of 11 long synthetic peptides derived from a total of 8 tumor antigens was used, including prostate specific antigen and prostatic acid phosphatase. In patients with prostate cancer we noted a 74.5% effector T-cell response rate compared with only 25% in patients with benign prostatic hyperplasia and 31% in healthy donors. In most patients 2 or 3 tumor antigens were recognized. Comparing various disease stages there was a clear increase in the immune response against prostate specific antigens from intermediate to high risk tumors and castration resistant disease. Regulatory T-cell depletion led to a significant boost in effector T-cell responses against prostate specific antigen and prostatic acid phosphatase. Tumor specific effector T cells were detected in most patients with prostate cancer, especially those with castration resistant prostate cancer. Since effector T-cell responses against prostate specific antigens strongly increased after regulatory T-cell depletion, our results indicate that immunotherapy efficacy could be enhanced by decreasing regulatory T cells. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  19. Role of autophagy in disease resistance and hypersensitive response-associated cell death

    Hofius, Daniel; Munch, David; Bressendorff, Simon


    Ancient autophagy pathways are emerging as key defense modules in host eukaryotic cells against microbial pathogens. Apart from actively eliminating intracellular intruders, autophagy is also responsible for cell survival, for example by reducing the deleterious effects of endoplasmic reticulum...

  20. Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation

    Ulsh, B.A.; Miller, S.M.; Mallory, F.F.; Mitchel, R.E.J.; Morrison, D.P.; Boreham, D.R.


    In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of 60 Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment

  1. Motorneurons dedicated to either forward or backward locomotion in the nematode C. elegans

    Haspel, Gal; O'Donovan, Michael J.; Hart, Anne C.


    Multifunctional motorneurons and muscles, which are active during forward and backward locomotion and driven by common central pattern generators, are ubiquitous in animal models. However, studies in the nematode Caenorhabditis elegans suggest that some locomotor motorneurons are necessary only for forward locomotion (dorsal B-motorneurons, DB) while others (dorsal A-motorneurons, DA) are necessary only for backward locomotion. We tested this hypothesis directly by recording the activity of t...

  2. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    Doi, Keiko; Fujimoto, Takahiro; Okamura, Tadashi; Ogawa, Masahiro; Tanaka, Yoko; Mototani, Yasumasa; Goto, Motohito; Ota, Takeharu; Matsuzaki, Hiroshi; Kuroki, Masahide; Tsunoda, Toshiyuki; Sasazuki, Takehiko; Shirasawa, Senji


    Highlights: ► We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. ► Zfat-deficiency leads to reduction in the number of the peripheral T cells. ► Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. ► Decreased expression of IL-7Rα, IL-2Rα and IL-2 in Zfat-deficient peripheral T cells. ► Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7Rα and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2Rα expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  3. Antibody and B cell responses to Plasmodium sporozoites

    Johanna N Dups


    Full Text Available Antibodies are capable of blocking infection of the liver by Plasmodium sporozoites. Accordingly the induction of anti-sporozoite antibodies is a major aim of various vaccine approaches to malaria. In recent years our knowledge of the specificity and quantities of antibodies required for protection has been greatly expanded by clinical trials of various whole sporozoite and subunit vaccines. Moreover, the development of humanized mouse models and transgenic parasites have also aided our ability to assess the specificity of antibodies and their ability to block infection. Nonetheless, considerable gaps remain in our knowledge - in particular in understanding what antigens are recognized by infection blocking antibodies and in knowing how we can induce robust, long-lived antibody responses. Maintaining high levels of circulating antibodies is likely to be of primary importance, as antibodies must block infection in the short time it takes for sporozoites to reach the liver from the skin. It is clear that a better understanding of the development of protective B cell-mediated immunity will aid the development and refinement of malaria vaccines.

  4. SAP expression in invariant NKT cells is required for cognate help to support B-cell responses.

    Detre, Cynthia; Keszei, Marton; Garrido-Mesa, Natividad; Kis-Toth, Katalin; Castro, Wilson; Agyemang, Amma F; Veerapen, Natacha; Besra, Gurdyal S; Carroll, Michael C; Tsokos, George C; Wang, Ninghai; Leadbetter, Elizabeth A; Terhorst, Cox


    One of the manifestations of X-linked lymphoproliferative disease (XLP) is progressive agammaglobulinemia, caused by the absence of a functional signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) in T, invariant natural killer T (NKT) cells and NK cells. Here we report that α-galactosylceramide (αGalCer) activated NKT cells positively regulate antibody responses to haptenated protein antigens at multiple checkpoints, including germinal center formation and affinity maturation. Whereas NKT cell-dependent B cell responses were absent in SAP(-/-).B6 mice that completely lack NKT cells, the small number of SAP-deficient NKT cells in SAP(-/-).BALB/c mice adjuvated antibody production, but not the germinal center reaction. To test the hypothesis that SAP-deficient NKT cells can facilitate humoral immunity, SAP was deleted after development in SAP(fl/fl).tgCreERT2.B6 mice. We find that NKT cell intrinsic expression of SAP is dispensable for noncognate helper functions, but is critical for providing cognate help to antigen-specific B cells. These results demonstrate that SLAM-family receptor-regulated cell-cell interactions are not limited to T-B cell conjugates. We conclude that in the absence of SAP, several routes of NKT cell-mediated antibody production are still accessible. The latter suggests that residual NKT cells in XLP patients might contribute to variations in dysgammaglobulinemia.

  5. The influence of Listeria monocytogenes cells on the primary immunologic response in irradiated mice

    Borowski, J.; Jokoniuk, P.


    The influence of killed Listeria monocytogenes cells on the primary immunologic response in mice irradiated with 300 or 500 R was studied. The immunologic response of the mice to sheep red blood cells used as antigen was assessed at the cellular level (by counting PFC) and humoral level. Injection of killed Listeria monocytogenes cells before irradiation of the mice diminished the immunosuppressive effect of roentgen radiation. Injection of the cells after irradiation accelerated regeneration of immunologic reactivity in the irradiated mice. (author)

  6. The cell wall and endoplasmic reticulum stress responses are coordinately regulated in Saccharomyces cerevisiae

    Krysan, Damian J


    The unfolded protein response (UPR) is an intracellular signaling pathway that regulates the cellular response to the accumulation of misfolded proteins in eukaryotes. Our group has demonstrated that cell wall stress activates UPR in yeast through signals transmitted by the cell wall integrity (CWI) mitogen-activated protein (MAP) kinase cascade. The UPR is required to maintain cell wall integrity; mutants lacking a functional UPR have defects in cell wall biosynthesis and are hypersensitive ...

  7. Intracellular proteins produced by mammalian cells in response to environmental stress

    Goochee, Charles F.; Passini, Cheryl A.


    The nature of the response of mammalian cells to environmental stress is examined by reviewing results of studies where cultured mouse L cells and baby hamster kidney cells were exposed to heat shock and the synthesis of heat-shock proteins and stress-response proteins (including HSP70, HSC70, HSP90, ubiquitin, and GRP70) in stressed and unstressed cells was evaluated using 2D-PAGE. The intracellular roles of the individual stress response proteins are discussed together with the regulation of the stress response system.

  8. [Prediction of the molecular response to pertubations from single cell measurements].

    Remacle, Françoise; Levine, Raphael D


    The response of protein signalization networks to perturbations is analysed from single cell measurements. This experimental approach allows characterizing the fluctuations in protein expression levels from cell to cell. The analysis is based on an information theoretic approach grounded in thermodynamics leading to a quantitative version of Le Chatelier principle which allows to predict the molecular response. Two systems are investigated: human macrophages subjected to lipopolysaccharide challenge, analogous to the immune response against Gram-negative bacteria and the response of the proteins involved in the mTOR signalizing network of GBM cancer cells to changes in partial oxygen pressure. © 2014 médecine/sciences – Inserm.

  9. Lowering T Cell Activation Thresholds and Deregulating Homeostasis to Facilitate Immunotherapeutic Responses to Treat Prostate Cancer

    Kwon, Eugene D


    ... to develop immune-based therapies for prostate cancer Hence, relatively straightforward manipulations that induce specific T cell responses against prostate tumors or epithelial tissues, especially...

  10. Osteoblast cell response to surface-modified carbon nanotubes

    Zhang Faming; Weidmann, Arne; Nebe, J. Barbara; Burkel, Eberhard


    In order to investigate the interaction of cells with modified multi-walled carbon nanotubes (MWCNTs) for their potential biomedical applications, the MWCNTs were chemically modified with carboxylic acid groups (–COOH), polyvinyl alcohol (PVA) polymer and biomimetic apatite on their surfaces. Additionally, human osteoblast MG-63 cells were cultured in the presence of the surface-modified MWCNTs. The metabolic activities of osteoblastic cells, cell proliferation properties, as well as cell morphology were studied. The surface modification of MWCNTs with biomimetic apatite exhibited a significant increase in the cell viability of osteoblasts, up to 67.23%. In the proliferation phases, there were many more cells in the biomimetic apatite-modified MWCNT samples than in the MWCNTs–COOH. There were no obvious changes in cell morphology in osteoblastic MG-63 cells cultured in the presence of these chemically-modified MWCNTs. The surface modification of MWCNTs with apatite achieves an effective enhancement of their biocompatibility.

  11. On designing geometric motion planners to solve regulating and trajectory tracking problems for robotic locomotion systems

    Asnafi, Alireza; Mahzoon, Mojtaba


    Based on a geometric fiber bundle structure, a generalized method to solve both regulation and trajectory tracking problems for locomotion systems is presented. The method is especially applied to two case studies of robotic locomotion systems; a three link articulated fish-like robot as a prototype of locomotion systems with symmetry, and the snakeboard as a prototype of mixed locomotion systems. Our results show that although these motion planners have an open loop structure, due to their generalities, they can steer case studies with negligible errors for almost any complicated path.

  12. On designing geometric motion planners to solve regulating and trajectory tracking problems for robotic locomotion systems

    Asnafi, Alireza [Hydro-Aeronautical Research Center, Shiraz University, Shiraz, 71348-13668 (Iran, Islamic Republic of); Mahzoon, Mojtaba [Department of Mechanical Engineering, School of Engineering, Shiraz University, Shiraz, 71348-13668 (Iran, Islamic Republic of)


    Based on a geometric fiber bundle structure, a generalized method to solve both regulation and trajectory tracking problems for locomotion systems is presented. The method is especially applied to two case studies of robotic locomotion systems; a three link articulated fish-like robot as a prototype of locomotion systems with symmetry, and the snakeboard as a prototype of mixed locomotion systems. Our results show that although these motion planners have an open loop structure, due to their generalities, they can steer case studies with negligible errors for almost any complicated path.


    Yu. V. Zelenko


    Full Text Available Purpose.The success of the traffic on the railways of Ukraine depends on the number and the operational fleet of electric locomotives. Today, the locomotive depot exploit physically and morally outdated locomotives that have low reliability. Modernization of electric locomotives is not economically justified. The aim of this study is to improve the safety of the traction rolling stock by the frequency analysis of dynamical systems, which allows conducting the calculation of the natural (of resonant frequencies of the design and related forms of vibrations.Methodology.The study was conducted by methods of analytical mechanics and mathematical modeling of operating loads of freight locomotive when driving at different speeds on the straight and curved track sections. The theoretical value of the work is the technique of choice of constructive schemes and rational parameters of perspective electric locomotive taking into account the electric inertia ratios and stiffness coefficients of Lagrange second-order equations.Findings. The problems of theoretical research and the development of a mathematical model of the spatial electric vibrations are solved. The theoretical studies of the effect of inertia ratios and stiffness coefficients on the dynamic values and the parameter values of electric locomotive undercarriages are presented.Originality.The set of developed regulations and obtained results is a practical solution to selecting rational parameters of bogies of the freight mainline locomotive for railways of Ukraine. A concept of choice of constructive scheme and rational parameters of perspective locomotive is formulated. It is developed the method of calculation of spatial electric locomotive oscillations to determine its dynamic performance. The software complex for processing the data of experimental studies of dynamic parameters of electric locomotive and comparing the results of the theoretical calculations with the data of full

  14. Unsteady locomotion: integrating muscle function with whole body dynamics and neuromuscular control

    Biewener, Andrew A.; Daley, Monica A.


    Summary By integrating studies of muscle function with analysis of whole body and limb dynamics, broader appreciation of neuromuscular function can be achieved. Ultimately, such studies need to address non-steady locomotor behaviors relevant to animals in their natural environments. When animals move slowly they likely rely on voluntary coordination of movement involving higher brain centers. However, when moving fast, their movements depend more strongly on responses controlled at more local levels. Our focus here is on control of fast-running locomotion. A key observation emerging from studies of steady level locomotion is that simple spring-mass dynamics, which help to economize energy expenditure, also apply to stabilization of unsteady running. Spring-mass dynamics apply to conditions that involve lateral impulsive perturbations, sudden changes in terrain height, and sudden changes in substrate stiffness or damping. Experimental investigation of unsteady locomotion is challenging, however, due to the variability inherent in such behaviors. Another emerging principle is that initial conditions associated with postural changes following a perturbation define different context-dependent stabilization responses. Distinct stabilization modes following a perturbation likely result from proximo-distal differences in limb muscle architecture, function and control strategy. Proximal muscles may be less sensitive to sudden perturbations and appear to operate, in such circumstances, under feed-forward control. In contrast, multiarticular distal muscles operate, via their tendons, to distribute energy among limb joints in a manner that also depends on the initial conditions of limb contact with the ground. Intrinsic properties of these distal muscle–tendon elements, in combination with limb and body dynamics, appear to provide rapid initial stabilizing mechanisms that are often consistent with spring-mass dynamics. These intrinsic mechanisms likely help to simplify the

  15. Electroacupuncture improves gait locomotion, H-reflex and ventral root potentials of spinal compression injured rats.

    Escobar-Corona, Carlos; Torres-Castillo, Sergio; Rodríguez-Torres, Erika Elizabeth; Segura-Alegría, Bertha; Jiménez-Estrada, Ismael; Quiroz-González, Salvador


    This study explored the effect of electroacupuncture stimulation (EA) on alterations in the Hoffman reflex (H-reflex) response and gait locomotion provoked by spinal cord injury (SCI) in the rat. A compression lesion of the spinal cord was evoked by insufflating a Fogarty balloon located in the epidural space at the T8-9 spinal level of adult Wistar male rats (200-250 gr; n=60). In different groups of SCI rats, EA (frequencies: 2, 50 and 100Hz) was applied simultaneously to Huantiao (GB30), Yinmen (BL37), Jizhong (GV6) and Zhiyang (GV9) acupoints from the third post-injury day until the experimental session. At 1, 2, 3 and 4 post-injury weeks, the BBB scores of the SCI group of rats treated with EA at 50Hz showed a gradual but greater enhancement of locomotor activity than the other groups of rats. Unrestrained gait kinematic analysis of SCI rats treated with EA-50Hz stimulation showed a significant improvement in stride duration, length and speed (p<0.05), whereas a discrete recovery of gait locomotion was observed in the other groups of animals. After four post-injury weeks, the H-reflex amplitude and H-reflex/M wave amplitude ratio obtained in SCI rats had a noticeable enhancement (217%) compared to sham rats (n=10). Meanwhile, SCI rats treated with EA at 50Hz manifested a decreased facilitation of the H-reflex amplitude and H/M amplitude ratio (154%) and a reduced frequency-dependent amplitude depression of the H-reflex (66%). In addition, 50 Hz-EA treatment induced a recovery of the presynaptic depression of the Gs-VRP evoked by PBSt conditioning stimulation in the SCI rat (63.2±8.1%; n=9). In concordance with the latter, it could be suggested that 50 Hz-EA stimulation reduced the hyper-excitability of motoneurons and provokes a partial improvement of the locomotive performance and H reflex responses by a possible recovery of presynaptic mechanisms in the spinal cord of experimentally injured rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Enthesis fibrocartilage cells originate from a population of Hedgehog-responsive cells modulated by the loading environment.

    Schwartz, Andrea G; Long, Fanxin; Thomopoulos, Stavros


    Tendon attaches to bone across a specialized tissue called the enthesis. This tissue modulates the transfer of muscle forces between two materials, i.e. tendon and bone, with vastly different mechanical properties. The enthesis for many tendons consists of a mineralized graded fibrocartilage that develops postnatally, concurrent with epiphyseal mineralization. Although it is well described that the mineralization and development of functional maturity requires muscle loading, the biological factors that modulate enthesis development are poorly understood. By genetically demarcating cells expressing Gli1 in response to Hedgehog (Hh) signaling, we discovered a unique population of Hh-responsive cells in the developing murine enthesis that were distinct from tendon fibroblasts and epiphyseal chondrocytes. Lineage-tracing experiments revealed that the Gli1 lineage cells that originate in utero eventually populate the entire mature enthesis. Muscle paralysis increased the number of Hh-responsive cells in the enthesis, demonstrating that responsiveness to Hh is modulated in part by muscle loading. Ablation of the Hh-responsive cells during the first week of postnatal development resulted in a loss of mineralized fibrocartilage, with very little tissue remodeling 5 weeks after cell ablation. Conditional deletion of smoothened, a molecule necessary for responsiveness to Ihh, from the developing tendon and enthesis altered the differentiation of enthesis progenitor cells, resulting in significantly reduced fibrocartilage mineralization and decreased biomechanical function. Taken together, these results demonstrate that Hh signaling within developing enthesis fibrocartilage cells is required for enthesis formation. © 2015. Published by The Company of Biologists Ltd.

  17. Unconventional Pro-inflammatory CD4+ T Cell Response in B Cell-Deficient Mice Infected with Trypanosoma cruzi

    Melisa Gorosito Serrán


    Full Text Available Chagas disease, caused by the parasite Trypanosoma cruzi, is endemic in Latin America but has become a global public health concern by migration of infected people. It has been reported that parasite persistence as well as the intensity of the inflammatory immune response are determinants of the clinical manifestations of the disease. Even though inflammation is indispensable for host defense, when deregulated, it can contribute to tissue injury and organ dysfunction. Here, we report the importance of B cells in conditioning T cell response in T. cruzi infection. Mice deficient in mature B cells (muMT mice infected with T. cruzi exhibited an increase in plasma TNF concentration, TNF-producing CD4+ T cells, and mortality. The increase in TNF-producing CD4+ T cells was accompanied by a reduction in IFNγ+CD4+ T cells and a decrease of the frequency of regulatory Foxp3+, IL-10+, and IL17+CD4+ T cells populations. The CD4+ T cell population activated by T. cruzi infection, in absence of mature B cells, had a high frequency of Ly6C+ cells and showed a lower expression of inhibitory molecules such as CTLA-4, PD-1, and LAG3. CD4+ T cells from infected muMT mice presented a high frequency of CD62LhiCD44− cells, which is commonly associated with a naïve phenotype. Through transfer experiments we demonstrated that CD4+ T cells from infected muMT mice were able to condition the CD4+ T cells response from infected wild-type mice. Interestingly, using Blimp-flox/flox-CD23icre mice we observed that in absence of plasmablast/plasma cell T. cruzi-infected mice exhibited a higher number of TNF-producing CD4+ T cells. Our results showed that the absence of B cells during T. cruzi infection affected the T cell response at different levels and generated a favorable scenario for unconventional activation of CD4+ T cell leading to an uncontrolled effector response and inflammation. The product of B cell differentiation, the plasmablast/plasma cells, could be able

  18. Are Breast Tumor Stem Cells Responsible for Metastasis and Angiogenesis?

    Pan, Quintin


    .... The current dogma of metastasis is that most primary tumor cells have low metastatic potential, but rare cells, less than one in ten million, within large primary tumors acquire metastatic capacity...

  19. Cross-talk between cd1d-restricted nkt cells and γδ cells in t regulatory cell response

    Huber Sally A


    Full Text Available Abstract CD1d is a non-classical major histocompatibility class 1-like molecule which primarily presents either microbial or endogenous glycolipid antigens to T cells involved in innate immunity. Natural killer T (NKT cells and a subpopulation of γδ T cells expressing the Vγ4 T cell receptor (TCR recognize CD1d. NKT and Vγ4 T cells function in the innate immune response via rapid activation subsequent to infection and secrete large quantities of cytokines that both help control infection and modulate the developing adaptive immune response. T regulatory cells represent one cell population impacted by both NKT and Vγ4 T cells. This review discusses the evidence that NKT cells promote T regulatory cell activation both through direct interaction of NKT cell and dendritic cells and through NKT cell secretion of large amounts of TGFβ, IL-10 and IL-2. Recent studies have shown that CD1d-restricted Vγ4 T cells, in contrast to NKT cells, selectively kill T regulatory cells through a caspase-dependent mechanism. Vγ4 T cell elimination of the T regulatory cell population allows activation of autoimmune CD8+ effector cells leading to severe cardiac injury in a coxsackievirus B3 (CVB3 myocarditis model in mice. CD1d-restricted immunity can therefore lead to either immunosuppression or autoimmunity depending upon the type of innate effector dominating during the infection.

  20. Artifactual voltage response recorded from hair cells with patch-clamp amplifiers.

    Masetto, S; Weng, T; Valli, P; Correia, M J


    Patch-clamp amplifiers (PCAs) are commonly used to characterize voltage- and current-clamp responses in the same cell. However, the cell membrane voltage response can be severely distorted by PCAs working in the current-clamp mode. Here we compare the voltage response of pigeon semicircular canal hair cells in situ, recorded with two different PCAs, and with a classic microelectrode bridge amplifier (BA). We found that the voltage response of hair cells recorded with PCAs differed significantly from that recorded with the BA. The true hair cell membrane voltage response to positive current steps was characterized by a strongly damped oscillation, whose frequency and duration depended on hair cell location in the sensory crista ampullaris.

  1. Synergy among rat T cells in the proliferative response to alloantigen

    Wright, P.W.; Loop, S.M.; Bernstein, I.D.


    A synergistic interaction in the proliferative response to alloantigen is described for mixtures of rat thymus and lymph node cells. The optimal conditions for synergy are quantitatively defined. Regression analysis of the slope of the dose-response curve has been utilized to estimate the degree of interaction in thymus--lymph node cell mixtures. The slope of the response of cell mixtures was noted to be significantly greater than the slope for the response of lympth node cells alone. Irradiation was shown to have a differential effect on the response of thymus and lymph node cells in mixtures. Irradiated thymus cells retained the capacity for synergy in mixtures, whereas irradiated lymph node cells did not. Additional studies have demonstrated that both de novo protein synthesis and specific antigen recognition by both responding cell populations in mixtures was required for maximal synergy. These studies demonstrate that synergy cannot be explained as an artifact of altered cell density in vitro. They establish that thymus cells and lymph node cells represent distinct subsets which manifest qualitatively different functions in the proliferative response to alloantigen. Thymus cells can respond directly to alloantigen by proliferation but also have the capacity to amplify the proliferative response of lymph node cells, a capacity which is resistant to X irradiation but requires recognition of alloantigen and de novo protein synthesis. Lymph node cells may similarly respond by proliferation to alloantigen but lack the amplifier activity of thymus cells. Synergy for rat lymphoidcells, like mouse lymphoid cells, has been shown to involve an interaction of thymus-derived lymphocytes

  2. Biophysical interpretation of the response of Chinese hamster cells to 24 keV neutrons

    Holt, P.D.


    The response of V79 Chinese hamster cells to a 24 keV neutron spectrum has been compared with data for the response of V79 cells to a range of higher neutron energies (up to 15 MeV). The linear energy transfer (LET) distributions of the neutron spectra were calculated and the expected responses of the cells to the different spectra were calculated using published track-segment data on the response of V79 cells to charged particles with various LET values. The response of the cells to 24 keV neutrons was predicted satisfactorily by the LET distribution, in spite of the fact that the maximum range of the recoil protons is only 0.5 μm. The response was not correctly predicted by the microdosimetric parameter y-bar D * evaluated in a 1 μm diameter sphere. (author)

  3. Support afferentation in the posture and locomotion control system

    Grigoriev, Anatoly; Tomilovskaya, Elena; Kozlovskaya, Inesa

    Mechanisms of support afferentation contribution in posture and locomotion control, which were uncertain up to now, became the point of intensive studies recently. This became possible since the space flights era started which created the conditions for simulated microgravity experiments under conditions of dry immersion and bedrest. The results of neurophysiological studies performed under the conditions of supportlessness have shown that decline or elimination of support loads is followed by deep and fast developing alterations in postural tonic system, including development of postural muscle atonia, changes of recruitment order of motoneurons innervating the shin muscles, spinal hyperreflexia development etc. (Kozlovskaya I.B. et al., 1987). It has been also shown that application of artificial support stimulation in the regimen of natural locomotion under these conditions decreases significantly or even eliminates the development of mentioned changes. The results of these studies laid down the basis for a new hypothesis on the trigger role of support afferentation in postural tonic system and its role in organization and control of postural synergies (Grigoriev A.I. et al., 2004). According to this hypothesis the muscle reception is considered to be the leading afferent input in the control of locomotion. However the data of recent studies pointed out strongly to the participation of support afferentation in definition of cognitive strategies and motor programs of locomotor movements (Chernikova L.A. et al., 2013) and, consequently, in the processes of their initiation (Gerasimenko Yu.P. et al., 2012). The cortical locomotor reflex composes apparently the basis of these processes. The receptive field of this reflex is located in the support zones of the soles and the central part is located in the posterior parietal areas (IPL) of brain cortex. The study is supported by RFBR grant N 13-04-12091 OFI-m.

  4. Sexuality of Disabled Athletes Depending on the Form of Locomotion

    Plinta Ryszard


    Full Text Available The main purpose of this study was to determine sexuality of disabled athletes depending on the form of locomotion. The study included 170 disabled athletes, aged between 18 and 45. The entire population was divided into 3 research groups depending on the form of locomotion: moving on wheelchairs (n=52, on crutches (n=29 and unaided (n=89. The research tool was a questionnaire voluntarily and anonymously completed by the respondents of the research groups. The questionnaire was composed of a general part concerning the socio-demographic conditions, medical history, health problems, a part dedicated to physical disability as well as the Polish version of the International Index of Erectile Function (IIEF and the Female Sexual Function Index (FSFI evaluating sexual life. STATISTICA 10.0 for Windows was used in the statistical analysis. Subjects moving on crutches were significantly older than ones moving on wheelchairs and unaided (34.41 ±11.00 vs. 30.49 ±10.44 and 27.99 ±10.51 years, respectively (p=0.018. Clinically significant erectile dysfunctions were most often diagnosed in athletes moving on wheelchairs (70.27%, followed by athletes moving on crutches and moving unaided (60% and 35.42%, respectively; p=0.048. Clinical sexual dysfunctions were diagnosed on a similar level among all female athletes. It was concluded that the form of locomotion may determine sexuality of disabled men. Males on wheelchair revealed the worst sexual functioning. Female athletes moving on wheelchairs, on crutches and moving unaided were comparable in the aspect of their sexual life.

  5. Modification of surface/neuron interfaces for neural cell-type specific responses: a review

    Chen, Cen; Kong, Xiangdong; Lee, In-Seop


    Surface/neuron interfaces have played an important role in neural repair including neural prostheses and tissue engineered scaffolds. This comprehensive literature review covers recent studies on the modification of surface/neuron interfaces. These interfaces are identified in cases both where the surfaces of substrates or scaffolds were in direct contact with cells and where the surfaces were modified to facilitate cell adhesion and controlling cell-type specific responses. Different sources of cells for neural repair are described, such as pheochromocytoma neuronal-like cell, neural stem cell (NSC), embryonic stem cell (ESC), mesenchymal stem cell (MSC) and induced pluripotent stem cell (iPS). Commonly modified methods are discussed including patterned surfaces at micro- or nano-scale, surface modification with conducting coatings, and functionalized surfaces with immobilized bioactive molecules. These approaches to control cell-type specific responses have enormous potential implications in neural repair. (paper)

  6. Biomechanical Analysis of Treadmill Locomotion on the International Space Station

    De Witt, J. K.; Fincke, R. S.; Guilliams, M. E.; Ploutz-Snyder, L. L.


    Treadmill locomotion exercise is an important aspect of ISS exercise countermeasures. It is widely believed that an optimized treadmill exercise protocol could offer benefits to cardiovascular and bone health. If training heart rate is high enough, treadmill exercise is expected to lead to improvements in aerobic fitness. If impact or bone loading forces are high enough, treadmill exercise may be expected to contribute to improved bone outcomes. Ground-based research suggests that joint loads increase with increased running speed. However, it is unknown if increases in locomotion speed results in similar increases in joint loads in microgravity. Although data exist regarding the biomechanics of running and walking in microgravity, a majority were collected during parabolic flight or during investigations utilizing a microgravity analog. The Second Generation Treadmill (T2) has been in use on the International Space Station (ISS) and records the ground reaction forces (GRF) produced by crewmembers during exercise. Biomechanical analyses will aid in understanding potential differences in typical gait motion and allow for modeling of the human body to determine joint and muscle forces during exercise. By understanding these mechanisms, more appropriate exercise prescriptions can be developed that address deficiencies. The objective of this evaluation is to collect biomechanical data from crewmembers during treadmill exercise prior to and during flight. The goal is to determine if locomotive biomechanics differ between normal and microgravity environments and to determine how combinations of subject load and speed influence joint loading during in-flight treadmill exercise. Further, the data will be used to characterize any differences in specific bone and muscle loading during locomotion in these two gravitational conditions. This project maps to the HRP Integrated Research Plan risks including Risk of Bone Fracture (Gap B15), Risk of Early Onset Osteoporosis Due to

  7. Biodiesel fuel costs and environmental issues when powering railway locomotives

    Mirza, Abdul; Ziemer, Norbert; Tatara, Robert; Moraga, Reinaldo; Mirman, Clifford; Vohra, Promod


    Issues for adopting biodiesel fuel, instead of petrodiesel, to power railroad locomotives are engine performance and emissions, fuel infrastructure, and fuel cost. These are evaluated for B2 through B100 blends. Biodiesel's solvent action on fuel systems is addressed. With biodiesel, hydrocarbon, carbon monoxide, and particulate emissions are unchanged or reduced. Nitrogen oxides are elevated but it is believed that engine alterations can minimize these emissions. A Transportation Model, using data from a major railway, has demonstrated that refueling depots can be fully supplied with biodiesel at a pricing premium of 1% to 26%, depending on blend and geographical location.

  8. Human-robot interaction strategies for walker-assisted locomotion

    Cifuentes, Carlos A


    This book presents the development of a new multimodal human-robot interface for testing and validating control strategies applied to robotic walkers for assisting human mobility and gait rehabilitation. The aim is to achieve a closer interaction between the robotic device and the individual, empowering the rehabilitation potential of such devices in clinical applications. A new multimodal human-robot interface for testing and validating control strategies applied to robotic walkers for assisting human mobility and gait rehabilitation is presented. Trends and opportunities for future advances in the field of assistive locomotion via the development of hybrid solutions based on the combination of smart walkers and biomechatronic exoskeletons are also discussed. .

  9. Optimization of the Hood of Diesel Electric Locomotive

    Petr TOMEK


    Full Text Available The new construction of hood of diesel electric locomotive is analyzed in this paper. The whole construction is loaded by inertia effects caused by prescribed acceleration. The parts of the hood are subject to the standards for railway applications CSN EN 12663-1 [1]. Numerical analyses are performed by FEM computer program COSMOSWorks [2]. The original construction of hood is analyzed in first part of this paper. Structural changes are proposed in the next part of this article. Carrying capacity of the new construction of hood is verified by a numerical analysis. The results of the new construction are compared with the original construction of hood.

  10. Improvement of fuel injection system of locomotive diesel engine.

    Li, Minghai; Cui, Hongjiang; Wang, Juan; Guan, Ying


    The traditional locomotive diesels are usually designed for the performance of rated condition and much fuel will be consumed. A new plunger piston matching parts of fuel injection pump and injector nozzle matching parts were designed. The experimental results of fuel injection pump test and diesel engine show that the fuel consumption rate can be decreased a lot in the most of the working conditions. The forced lubrication is adopted for the new injector nozzle matching parts, which can reduce failure rate and increase service life. The design has been patented by Chinese State Patent Office.

  11. Bone marrow function. I. Peripheral T cells are responsible for the increased auto-antiidiotype response of older mice

    Kim, Y.T.; Goidl, E.A.; Samarut, C.; Weksler, M.E.; Thorbecke, G.J.; Siskind, G.W.


    After immunization with trinitrophenyl (TNP)-Ficoll, mice produced both anti-TNP antibodies and auto-anti-idiotype (auto-anti-Id) antibodies specific for the anti-TNP antibody. Older animals produced more auto-anti-Id than did young animals. When mice were exposed to a normally lethal dose of irradiation while their bone marrow (BM) was partially shielded, they survived and slowly (6 wk) regained immune function, as indicated by the number of nucleated cells in their spleen and the in vitro primary plaque-forming cell (PFC) response of their spleen cells to TNP-treated aminoethylated polyacrylamide beads. Recovery is presumably the result of repopulation of the peripheral lymphoid system by cells originating in the BM. By enzyme-linked immunosorbent assay (ELISA), and by hapten-augmentable PFC assay, the authors show that, after recovery from irradiation with their BM shielded, old animals produce low auto-anti-Id responses, like those of young animals. The transfer of splenic T cells into mice irradiated with their BM shielded provided evidence that the magnitude of the auto-anti-Id response is controlled by the peripheral T cells. Thus, mice that received splenic T cells from aged donors produced high levels of auto-anti-Id while those that received splenic T cells from young donors produce low levels of auto-anti-Id

  12. Lactobacilli Modulate Natural Killer Cell Responses In Vitro

    Fink, Lisbeth Nielsen; Christensen, Hanne Risager; Frøkiær, Hanne

    of certain lactic acid bacteria has been shown to increase in vivo NK cytotoxicity. Here, we investigated how human gut flora-derived lactobacilli affect NK cells in vitro, by measuring proliferation and IFN-gamma production of human NK cells upon bacterial stimulation. CD3-CD56+ NK cells were isolated from...... monocytes present, probably because cytokines, secreted by monocytes having engulfed bacteria, stimulated the NK cells. In contrast, a Lactobacillus paracasei strain caused the NK cells to proliferate only in the presence of monocytes. These results demonstrate that various strains of lactobacilli have...

  13. Radiation response characteristics of human cell in vitro

    Hall, E.J.


    Improvements in tissue culture techniques and growth media have made it possible to culture a range of cells of human origin, both normal and malignant. The most recent addition to the list are endothelial cells. Interesting results have been obtained, some of which may have implications in Radiation Therapy. (i) Repair of Potentially Lethal Damage (PLDR) has been observed in all cell lines investigated; cells of normal origin repair PLD at least as well as malignant cells, which makes clinical trials of PLDR inhibitors of doubtful usefulness. (ii) PLD in fibroblasts of human origin appears to have a component that is repaired rapidly, in a matter of minutes, as well as a slower component that takes hours to repair. (iii) Sublethal damage repair, manifest by a dose-rate effect, has also been observed in all human cell lines tested. Cells of normal tissue origin, including fibroblasts and endothelial cells, exhibit a dose-rate effect that is intermediate between that for cells from traditionally resistant tumors (melanoma and osteosarcoma) and cells from more sensitive tumors (neuroblastoma and breast). (iv) Fibroblasts from patients with Ataxia Telangectasia (AT) are much more sensitive to x-rays, with a D/sub o/ about half that for normal human fibroblasts. Nevertheless repair of both PLD and SLD can be demonstrated in these cells


    Murphy, William H.; Bullis, Cora


    Murphy, W. H. (The University of Michigan, Ann Arbor) and Cora Bullis. Effect of triiodothyronine on cells and on their response to infection by polioviruses. J. Bacteriol. 83:641–648. 1962.—An analysis was made of the effect of triiodothyronine (T3) at physiological (1 μg/ml) and maximal subliminal toxic levels (35 μg/ml) on HeLa-S3, HeLa-Gey, Chang-liver, and Maben cells, and on their response to infection by cytopathic and submoderate (noncytopathic) mutants of type 2 poliovirus. Assays of cell response to T3 alone, or in combination with the mutants of poliovirus, were made by conventional monolayer cell culture techniques, by study of the effect of T3 on plating efficiency of cells, and by study of its influence on colonies of cell variants. Cellular response to liminal doses of T3 was characterized by agglutination of cells and thickening of the cell membrane. Compact colonies of Chang-liver and Maben cells were the most sensitive to maximal subliminal amounts of T3. T3 in combination with cytopathic or submoderate (noncytopathic) mutants of poliovirus slightly increased the rate of destruction of cells susceptible to virus, but did not influence yield of virus from cell cultures. T3 at physiological or subliminal concentrations did not induce cytopathic response of cell cultures latently infected by submoderate poliovirus. Images PMID:14477441

  15. Two photon microscopy intravital study of DC-mediated anti-tumor response of NK cells

    Caccia, Michele; Gorletta, Tatiana; Sironi, Laura; Zanoni, Ivan; Salvetti, Cristina; Collini, Maddalena; Granucci, Francesca; Chirico, Giuseppe


    Recent studies have demonstrated that dendritic cells (DCs) play a crucial role in the activation of Natural Killer cells (NKs) that are responsible for anti-tumor innate immune responses. The focus of this report is on the role of pathogen associated molecular pattern (PAMP) activated-DCs in inducing NK cell-mediated anti-tumor responses. Mice transplanted sub-cute (s.c.) with AK7 cells, a mesothelioma cell line sensitive to NK cell responses, are injected with fluorescent NK cells and DC activation is then induced by s.c. injection of Lipopolysaccharide (LPS). Using 4 dimensional tracking we follow the kinetic behavior of NK cells at the Draining Lymph-Node (DLN). As control, noninflammatory conditions are also evaluated. Our data suggest that NK cells are recruited to the DLN where they can interact with activated-DCs with a peculiar kinetic behavior: short lived interactions interleaved by rarer longer ones. We also found that the changes in the NK dynamic behavior in inflammatory conditions clearly affect relevant motility parameters such as the instantaneous and average velocity and the effective diffusion coefficient. This observation suggests that NK cells and activated-DCs might efficiently interact in the DLN, where cells could be activated. Therefore the interaction between activated-DCs and NK cells in DLN is not only a reality but it may be also crucial for the start of the immune response of the NKs.

  16. Lysophosphatidic acid receptor-5 negatively regulates cellular responses in mouse fibroblast 3T3 cells

    Dong, Yan; Hirane, Miku; Araki, Mutsumi [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Tsujiuchi, Toshifumi, E-mail: [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)


    Highlights: • LPA{sub 5} inhibits the cell growth and motile activities of 3T3 cells. • LPA{sub 5} suppresses the cell motile activities stimulated by hydrogen peroxide in 3T3 cells. • Enhancement of LPA{sub 5} on the cell motile activities inhibited by LPA{sub 1} in 3T3 cells. • The expression and activation of Mmp-9 were inhibited by LPA{sub 5} in 3T3 cells. • LPA signaling via LPA{sub 5} acts as a negative regulator of cellular responses in 3T3 cells. - Abstract: Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors (LPA{sub 1}–LPA{sub 6}) mediates a variety of biological functions, including cell migration. Recently, we have reported that LPA{sub 1} inhibited the cell motile activities of mouse fibroblast 3T3 cells. In the present study, to evaluate a role of LPA{sub 5} in cellular responses, Lpar5 knockdown (3T3-L5) cells were generated from 3T3 cells. In cell proliferation assays, LPA markedly stimulated the cell proliferation activities of 3T3-L5 cells, compared with control cells. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3-L5 cells were significantly higher than those of control cells. The activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. 3T3-L5 cells stimulated the activation of Mmp-2, correlating with the expression levels of Mmp-2 gene. Moreover, to assess the co-effects of LPA{sub 1} and LPA{sub 5} on cell motile activities, Lpar5 knockdown (3T3a1-L5) cells were also established from Lpar1 over-expressing (3T3a1) cells. 3T3a1-L5 cells increased the cell motile activities of 3T3a1 cells, while the cell motile activities of 3T3a1 cells were significantly lower than those of control cells. These results suggest that LPA{sub 5} may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA{sub 1}.

  17. Lysophosphatidic acid receptor-5 negatively regulates cellular responses in mouse fibroblast 3T3 cells

    Dong, Yan; Hirane, Miku; Araki, Mutsumi; Fukushima, Nobuyuki; Tsujiuchi, Toshifumi


    Highlights: • LPA 5 inhibits the cell growth and motile activities of 3T3 cells. • LPA 5 suppresses the cell motile activities stimulated by hydrogen peroxide in 3T3 cells. • Enhancement of LPA 5 on the cell motile activities inhibited by LPA 1 in 3T3 cells. • The expression and activation of Mmp-9 were inhibited by LPA 5 in 3T3 cells. • LPA signaling via LPA 5 acts as a negative regulator of cellular responses in 3T3 cells. - Abstract: Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors (LPA 1 –LPA 6 ) mediates a variety of biological functions, including cell migration. Recently, we have reported that LPA 1 inhibited the cell motile activities of mouse fibroblast 3T3 cells. In the present study, to evaluate a role of LPA 5 in cellular responses, Lpar5 knockdown (3T3-L5) cells were generated from 3T3 cells. In cell proliferation assays, LPA markedly stimulated the cell proliferation activities of 3T3-L5 cells, compared with control cells. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3-L5 cells were significantly higher than those of control cells. The activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. 3T3-L5 cells stimulated the activation of Mmp-2, correlating with the expression levels of Mmp-2 gene. Moreover, to assess the co-effects of LPA 1 and LPA 5 on cell motile activities, Lpar5 knockdown (3T3a1-L5) cells were also established from Lpar1 over-expressing (3T3a1) cells. 3T3a1-L5 cells increased the cell motile activities of 3T3a1 cells, while the cell motile activities of 3T3a1 cells were significantly lower than those of control cells. These results suggest that LPA 5 may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA 1

  18. Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina


    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

  19. B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses

    Larimore Kevin


    Full Text Available Abstract Background The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.

  20. T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy.

    Allison S Thomas


    Full Text Available HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART, these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18. Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that

  1. Effects of spaceflight on rhesus quadrupedal locomotion after return to 1G

    Recktenwald, M. R.; Hodgson, J. A.; Roy, R. R.; Riazanski, S.; McCall, G. E.; Kozlovskaya, I.; Washburn, D. A.; Fanton, J. W.; Edgerton, V. R.; Rumbaugh, D. M. (Principal Investigator)


    Effects of spaceflight on Rhesus quadrupedal locomotion after return to 1G. Locomotor performance, activation patterns of the soleus (Sol), medial gastrocnemius (MG), vastus lateralis (VL), and tibialis anterior (TA) and MG tendon force during quadrupedal stepping were studied in adult Rhesus before and after 14 days of either spaceflight (n = 2) or flight simulation at 1G (n = 3). Flight simulation involved duplication of the spaceflight conditions and experimental protocol in a 1G environment. Postflight, but not postsimulation, electromyographic (EMG) recordings revealed clonus-like activity in all muscles. Compared with preflight, the cycle period and burst durations of the primary extensors (Sol, MG, and VL) tended to decrease postflight. These decreases were associated with shorter steps. The flexor (TA) EMG burst duration postflight was similar to preflight, whereas the burst amplitude was elevated. Consequently, the Sol:TA and MG:TA EMG amplitude ratios were lower following flight, reflecting a "flexor bias." Together, these alterations in mean EMG amplitudes reflect differential adaptations in motor-unit recruitment patterns of flexors and extensors as well as fast and slow motor pools. Shorter cycle period and burst durations persisted throughout the 20-day postflight testing period, whereas mean EMG returned to preflight levels by 17 days postflight. Compared with presimulation, the simulation group showed slight increases in the cycle period and burst durations of all muscles. Mean EMG amplitude decreased in the Sol, increased in the MG and VL, and was unchanged in the TA. Thus adaptations observed postsimulation were different from those observed postflight, indicating that there was a response unique to the microgravity environment, i.e., the modulations in the nervous system controlling locomotion cannot merely be attributed to restriction of movement but appear to be the result of changes in the interpretation of load-related proprioceptive feedback

  2. Inhibition of cathepsin X enzyme influences the immune response of THP-1 cells and dendritic cells infected with Helicobacter pylori

    Skvarc, Miha; Stubljar, David; Kopitar, Andreja Natasa; Jeverica, Samo; Tepes, Bojan; Kos, Janko; Ihan, Alojz


    The immune response to Helicobacter pylori importantly determines the outcome of infection as well as the success of eradication therapy. We demonstrate the role of a cysteine protease cathepsin X in the immune response to H. pylori infection. We analysed how the inhibition of cathepsin X influenced the immune response in experiments when THP-1 cells or dendritic cells isolated from patients were stimulated with 48 strains of H. pylori isolated from gastric biopsy samples of patients which had problems with the eradication of bacteria. The experiments, performed with the help of a flow cytometer, showed that the expression of Toll-like receptors (TLRs), especially TLR-4 molecules, on the membranes of THP-1 cells or dendritic cells was higher when we stimulated cells with H. pylori together with inhibitor of cathepsin X 2F12 compared to THP-1 cells or dendritic cells stimulated with H. pylori only, and also in comparison with negative control samples. We also demonstrated that when we inhibited the action of cathepsin X in THP-1 cells, the concentrations of pro-inflammatory cytokines were lower than when THP-1 cell were stimulated with H. pylori only. We demonstrated that inhibition of cathepsin X influences the internalization of TLR-2 and TLR-4. TLR-2 and TLR-4 redistribution to intra-cytoplasmic compartments is hampered if cathepsin X is blocked. The beginning of a successful immune response against H. pylori in the case of inhibition of cathepsin X is delayed

  3. Enhanced gamma interferon responses of mouse spleen cells following immunotherapy for tuberculosis relapse.

    Gil, Olga; Vilaplana, Cristina; Guirado, Evelyn; Díaz, Jorge; Cáceres, Neus; Singh, Mahavir; Cardona, Pere-Joan


    Gamma interferon responses of spleen cells in mice were examined during postchemotherapy relapse of intraperitoneally induced latent tuberculous infection. The mycobacterial extract RUTI, which prevented the relapse, significantly enhanced the immune responses to secreted and structural recombinant mycobacterial antigens, suggesting that RUTI-mediated protection was mediated by activated T cells.

  4. Airway responses towards allergens - from the airway epithelium to T cells

    Papazian, Dick; Hansen, Søren; Würtzen, Peter A


    -damaged, healthy epithelium lowers the DCs ability to induce inflammatory T cell responses towards allergens. The purpose of this review is to summarize the current knowledge on which signals from the airway epithelium, from first contact with inhaled allergens all the way to the ensuing Th2 cell responses...

  5. The response of high and low polyamine producing cell lines to aluminum and calcium stress

    Sridev Mohapatra; Smita Cherry; Rakesh Minocha; Rajtilak Majumdar; Palaniswamy Thangavel; Stephanie Long; Subhash C. Minocha


    The diamine putrescine (Put) has been shown to accumulate in tree leaves in response to high Al and low Ca in the soil, leading to the suggestion that this response may provide a physiological advantage to leaf cells under conditions of Al stress. The increase in Put is reversed by Ca supplementation in the soil. Using two cell lines of poplar (Populus nigra...

  6. Regulation of Cancer Cell Responsiveness to Ionizing Radiation Treatment by Cyclic AMP Response Element Binding Nuclear Transcription Factor

    Francesca D’Auria


    Full Text Available Cyclic AMP response element binding (CREB protein is a member of the CREB/activating transcription factor (ATF family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR therapy, demonstrating a relationship between IR-induced CREB family members’ activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562. On the other hand, a number of evidences highlight a proapoptotic role of CREB following IR treatment of cancer cells. Since the development of multiple mechanisms of resistance is one key problem of most malignancies, including those of hematological origin, it is highly desirable to identify biological markers of responsiveness/unresponsiveness useful to follow-up the individual response and to adjust anticancer treatments. Taking into account all these considerations, this mini-review will be focused on the involvement of CREB/ATF family members in response to IR therapy, to deepen our knowledge of this topic, and to pave the way to translation into a therapeutic context.

  7. CD8(+)NKT-like cells regulate the immune response by killing antigen-bearing DCs.

    Wang, Chao; Liu, Xi; Li, Zhengyuan; Chai, Yijie; Jiang, Yunfeng; Wang, Qian; Ji, Yewei; Zhu, Zhongli; Wan, Ying; Yuan, Zhenglong; Chang, Zhijie; Zhang, Minghui


    CD1d-dependent NKT cells have been extensively studied; however, the function of CD8(+)NKT-like cells, which are CD1d-independent T cells with NK markers, remains unknown. Here, we report that CD1d-independent CD8(+)NKT-like cells, which express both T cell markers (TCRβ and CD3) and NK cell receptors (NK1.1, CD49b and NKG2D), are activated and significantly expanded in mice immunized with GFP-expressing dendritic cells. Distinct from CD1d-dependent NKT cells, CD8(+)NKT-like cells possess a diverse repertoire of TCRs and secrete high levels of IFN-gamma but not IL-4. CD8(+)NKT-like cell development is normal in CD1d(-/-) mice, which suggests that CD8(+)NKT-like cells undergo a unique development pathway that differs from iNKT cells. Further functional analyses show that CD8(+)NKT-like cells suppress T-cell responses through elimination of dendritic cells in an antigen-specific manner. Adoptive transfer of antigen-specific CD8(+)NKT-like cells into RIP-OVA mice prevented subsequent development of diabetes in the animals induced by activated OT-I CD8 T cells. Our study suggests that CD8(+)NKT-like cells can function as antigen-specific suppressive cells to regulate the immune response through killing antigen-bearing DCs. Antigen-specific down regulation may provide an active and precise method for constraining an excessive immune response and avoiding bypass suppression of necessary immune responses to other antigens.

  8. CD8+NKT-like cells regulate the immune response by killing antigen-bearing DCs

    Wang, Chao; Liu, Xi; Li, Zhengyuan; Chai, Yijie; Jiang, Yunfeng; Wang, Qian; Ji, Yewei; Zhu, Zhongli; Wan, Ying; Yuan, Zhenglong; Chang, Zhijie; Zhang, Minghui


    CD1d-dependent NKT cells have been extensively studied; however, the function of CD8+NKT-like cells, which are CD1d-independent T cells with NK markers, remains unknown. Here, we report that CD1d-independent CD8+NKT-like cells, which express both T cell markers (TCRβ and CD3) and NK cell receptors (NK1.1, CD49b and NKG2D), are activated and significantly expanded in mice immunized with GFP-expressing dendritic cells. Distinct from CD1d-dependent NKT cells, CD8+NKT-like cells possess a diverse repertoire of TCRs and secrete high levels of IFN-gamma but not IL-4. CD8+NKT-like cell development is normal in CD1d−/− mice, which suggests that CD8+NKT-like cells undergo a unique development pathway that differs from iNKT cells. Further functional analyses show that CD8+NKT-like cells suppress T-cell responses through elimination of dendritic cells in an antigen-specific manner. Adoptive transfer of antigen-specific CD8+NKT-like cells into RIP-OVA mice prevented subsequent development of diabetes in the animals induced by activated OT-I CD8 T cells. Our study suggests that CD8+NKT-like cells can function as antigen-specific suppressive cells to regulate the immune response through killing antigen-bearing DCs. Antigen-specific down regulation may provide an active and precise method for constraining an excessive immune response and avoiding bypass suppression of necessary immune responses to other antigens. PMID:26369936

  9. Defective B cell response to T-dependent immunization in lupus-prone mice

    Niu, Haitao; Sobel, Eric S.; Morel, Laurence


    Lupus anti-nuclear Abs show the characteristics of Ag-driven T cell-dependent (TD) humoral responses. If autoAgs elicit the same response as exogenous Ags, lupus should enhance humoral responses to immunization. Blunted responses to various immunizations have, however, been reported in a significant portion of lupus patients. In this study, we show that lupus-prone B6.Sle1.Sle2.Sle3 (B6.TC) mice produce significantly less Ab in response to TD immunization than congenic controls, while producing significantly more total Ig. This blunted Ab response to TD Ag could be reconstituted with B6.TC B and CD4+ T cells. Multiple defects were found in the B6.TC response to NP-KLH as compared to total Ig, including a smaller percentage of B cells participating to the NP-response, a reduced entry into germinal centers, and highly defective production of NP-specific long-lived plasma cells in the bone marrow. B6.TC plasma cells expressed reduced levels of FcγRIIb, which suggests that reduced apoptosis in resident plasma cells prevents the establishment of newly-formed NP-specific plasma cells in bone marrow niches. Overall, these results show that lupus-prone mice responded differently to auto- and exogenous antigens and suggest that low FcγRIIb, hypergammaglobulinemia and high autoantibody production would be predictive of a poor response to immunization in lupus patients. PMID:18924209

  10. Implications of the Endothelial Cell Response in Glioblastoma to Stimulation by Mesenchymal Stem Cells and Ionizing Radiation

    Zhao, Tansy Y.

    Heightened angiogenesis is both the pathophysiologic hallmark and the potential cause of therapy resistance for glioblastoma (GBM), a deadly brain tumor. It is thought that mesenchymal stem cells (MSCs) play important roles in neovascularization and tumor progression. We postulated that MSCs protect ECs against radiotherapy, which subsequently enhances tumor angiogenesis, and promotes GBM tumor recurrence following therapy. We therefore sought to establish the in-vitro endothelial cell response to stimulation by MSC condition media and ionizing radiation (IR) treatment. We established the gene expression profiles of endothelial cells in response to IR, MSCs and the combination of both. Within the same gene profiles, we identified a unique gene signature that was highly predictive of response to Bevacizumab for GBM patients. We also demonstrated that MSC increased the viability of ECs in response to IR. Protein analysis in ECs suggested MSC-mediated cell cycle arrest as a mechanism for radio-resistance in ECs.

  11. Outer hair cell piezoelectricity: frequency response enhancement and resonance behavior.

    Weitzel, Erik K; Tasker, Ron; Brownell, William E


    Stretching or compressing an outer hair cell alters its membrane potential and, conversely, changing the electrical potential alters its length. This bi-directional energy conversion takes place in the cell's lateral wall and resembles the direct and converse piezoelectric effects both qualitatively and quantitatively. A piezoelectric model of the lateral wall has been developed that is based on the electrical and material parameters of the lateral wall. An equivalent circuit for the outer hair cell that includes piezoelectricity shows a greater admittance at high frequencies than one containing only membrane resistance and capacitance. The model also predicts resonance at ultrasonic frequencies that is inversely proportional to cell length. These features suggest all mammals use outer hair cell piezoelectricity to support the high-frequency receptor potentials that drive electromotility. It is also possible that members of some mammalian orders use outer hair cell piezoelectric resonance in detecting species-specific vocalizations.

  12. Flow cytometric quantification of radiation responses of murine peritoneal cells

    Tokita, N.; Raju, M.R.


    Methods have been developed to distinguish subpopulations of murine peritoneal cells, and these were applied to the measurement of early changes in peritoneal cells after irradiation. The ratio of the two major subpopulations in the peritoneal fluid, lymphocytes and macrophages, was measured rapidly by means of cell volume distribution analysis as well as by hypotonic propidium iodide (PI) staining. After irradiation, dose and time dependent changes were noted in the cell volume distributions: a rapid loss of peritoneal lymphocytes, and an increase in the mean cell volume of macrophages. The hypotonic PI staining characteristics of the peritoneal cells showed two or three distinctive G 1 peaks. The ratio of the areas of these peaks was also found to be dependent of the radiation dose and the time after irradiation. These results demonstrate that these two parameters may be used to monitor changes induced by irradiation (biological dosimetry), and to sort different peritoneal subpopulations

  13. Effect of radiation doses rate on SOS response induction in irradiated Escherichia coli Cells

    Cuetara Lugo, Elizabeth B.; Fuentes Lorenzo, Jorge L.; Almeida Varela, Eliseo; Prieto Miranda, Enrique F.; Sanchez Lamar, Angel; Llagostera Casal, Montserrat


    The present work is aimed to study the effect of radiation dose rate on the induction of SOS response in Escherichia coli cells. We measured the induction of sul A reporter gene in PQ-37 (SOS Chromotest) cells. Lead devises were built with different diameter and these were used for diminishing the dose rate of PX- -30M irradiator. Our results show that radiation doses rate significantly modifies the induction of SOS response. Induction factor increases proportionally to doses rate in Escherichia coli cells defective to nucleotide excision repair (uvrA), but not in wild type cells. We conclude that the dose rate affects the level of induction of SOS response

  14. Sustained CD8+ T-cell responses induced after acute parvovirus B19 infection in humans

    Norbeck, Oscar; Isa, Adiba; Pöhlmann, Christoph


    Murine models have suggested that CD8+ T-cell responses peak early in acute viral infections and are not sustained, but no evidence for humans has been available. To address this, we longitudinally analyzed the CD8+ T-cell response to human parvovirus B19 in acutely infected individuals. We...... observed striking CD8+ T-cell responses, which were sustained or even increased over many months after the resolution of acute disease, indicating that CD8+ T cells may play a prominent role in the control of parvovirus B19 and other acute viral infections of humans, including potentially those generated...

  15. Pheochromocytoma (PC12 Cell Response on Mechanobactericidal Titanium Surfaces

    Jason V. Wandiyanto


    Full Text Available Titanium is a biocompatible material that is frequently used for making implantable medical devices. Nanoengineering of the surface is the common method for increasing material biocompatibility, and while the nanostructured materials are well-known to represent attractive substrata for eukaryotic cells, very little information has been documented about the interaction between mammalian cells and bactericidal nanostructured surfaces. In this study, we investigated the effect of bactericidal titanium nanostructures on PC12 cell attachment and differentiation—a cell line which has become a widely used in vitro model to study neuronal differentiation. The effects of the nanostructures on the cells were then compared to effects observed when the cells were placed in contact with non-structured titanium. It was found that bactericidal nanostructured surfaces enhanced the attachment of neuron-like cells. In addition, the PC12 cells were able to differentiate on nanostructured surfaces, while the cells on non-structured surfaces were not able to do so. These promising results demonstrate the potential application of bactericidal nanostructured surfaces in biomedical applications such as cochlear and neuronal implants.

  16. Nitric oxide mediated bystander responses induced by microbeam targeted cells

    Shao, C.; Prise, K.M.; Folkard, M.; Michael, B.D.


    Considerable evidence has recently been accumulated in support of the existence of a 'bystander effect', which cells having received no irradiation show biological consequences from their vicinal irradiated cells. The application of microbeams is providing new insights into the radiation-induced bystander effect. The present study found that when a fraction of radioresistant human glioblastoma cells were individually targeted with a precise number of helium ions generated from the Gray Cancer Institute Charged Particle Microbeam, micronucleus (MN) induction significantly exceeded the expected value that was calculated from the number of MN observed when all of the cells were targeted assuming no bystander effect occurring. Even when only a single cell within a population was hit by one helium ion, the MN induction in the population could be increased by 16%. These results provide direct evidence of radiation-induced bystander effect. Moreover, MN was effectively induced in the unirradiated primary human fibroblasts and glioblastoma cells either co-cultured with irradiated cells or treated with the medium harvested from irradiated cells, indicating a signal molecule was produced from the irradiated cells. However, when c-PTIO, a nitric oxide (NO)-specific scavenger, was present in the medium during and after irradiation until MN analysis, the production of MN in all of the above cases was reduced to low levels. Consequently, NO plays an important role in the radiation-induced bystander effect

  17. Direct-to-consumer stem cell marketing and regulatory responses.

    Sipp, Douglas


    There is a large, poorly regulated international market of putative stem cell products, including transplants of processed autologous stem cells from various tissues, cell processing devices, cosmetics, and nutritional supplements. Despite the absence of rigorous scientific research in the form of randomized clinical trials to support the routine use of such products, the market appears to be growing and diversifying. Very few stem cell biologics have passed regulatory scrutiny, and authorities in many countries, including the United States, have begun to step up their enforcement activities to protect patients and the integrity of health care markets.

  18. Full-scale locomotive dynamic collision testing and correlations : offset collisions between a locomotive and a covered hopper car (test 4).


    This report presents the test results and finite element correlations of a full-scale dynamic collision test with rail vehicles as part of the Federal Railroad Administrations research program on improved crashworthiness of locomotive structures. ...

  19. Natural Killer Dendritic Cells Enhance Immune Responses Elicited by α-Galactosylceramide-Stimulated Natural Killer T Cells

    Sung Won Lee


    Full Text Available Natural killer dendritic cells (NKDCs possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT cells is required for the anti-tumor immune responses that are elicited by α-galactosylceramide (α-GC in mice. The rapid and strong expression of interferon-γ by NKDCs after α-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated following α-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited by α-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated by α-GC-stimulated NKT cells in vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

  20. Hybrid magnetic mechanism for active locomotion based on inchworm motion

    Kim, Sung Hoon; Hashi, Shuichiro; Ishiyama, Kazushi


    Magnetic robots have been studied in the past. Insect-type micro-robots are used in various biomedical applications; researchers have developed inchworm micro-robots for endoscopic use. A biological inchworm has a looping locomotion gait. However, most inchworm micro-robots depend on a general bending, or bellows, motion. In this paper, we introduce a new robotic mechanism using magnetic force and torque control in a rotating magnetic field for a looping gait. The proposed robot is controlled by the magnetic torque, attractive force, and body mechanisms (two stoppers, flexible body, and different frictional legs). The magnetic torque generates a general bending motion. In addition, the attractive force and body mechanisms produce the robot’s looping motion within a rotating magnetic field and without the use of an algorithm for field control. We verified the device’s performance and analyzed the motion through simulations and various experiments. The robot mechanism can be applied to active locomotion for various medical robots, such as wireless endoscopes. (technical note)

  1. Controlling legs for locomotion-insights from robotics and neurobiology.

    Buschmann, Thomas; Ewald, Alexander; von Twickel, Arndt; Büschges, Ansgar


    Walking is the most common terrestrial form of locomotion in animals. Its great versatility and flexibility has led to many attempts at building walking machines with similar capabilities. The control of walking is an active research area both in neurobiology and robotics, with a large and growing body of work. This paper gives an overview of the current knowledge on the control of legged locomotion in animals and machines and attempts to give walking control researchers from biology and robotics an overview of the current knowledge in both fields. We try to summarize the knowledge on the neurobiological basis of walking control in animals, emphasizing common principles seen in different species. In a section on walking robots, we review common approaches to walking controller design with a slight emphasis on biped walking control. We show where parallels between robotic and neurobiological walking controllers exist and how robotics and biology may benefit from each other. Finally, we discuss where research in the two fields diverges and suggest ways to bridge these gaps.

  2. Differences in gaze anticipation for locomotion with and without vision

    Authié, Colas N.; Hilt, Pauline M.; N'Guyen, Steve; Berthoz, Alain; Bennequin, Daniel


    Previous experimental studies have shown a spontaneous anticipation of locomotor trajectory by the head and gaze direction during human locomotion. This anticipatory behavior could serve several functions: an optimal selection of visual information, for instance through landmarks and optic flow, as well as trajectory planning and motor control. This would imply that anticipation remains in darkness but with different characteristics. We asked 10 participants to walk along two predefined complex trajectories (limaçon and figure eight) without any cue on the trajectory to follow. Two visual conditions were used: (i) in light and (ii) in complete darkness with eyes open. The whole body kinematics were recorded by motion capture, along with the participant's right eye movements. We showed that in darkness and in light, horizontal gaze anticipates the orientation of the head which itself anticipates the trajectory direction. However, the horizontal angular anticipation decreases by a half in darkness for both gaze and head. In both visual conditions we observed an eye nystagmus with similar properties (frequency and amplitude). The main difference comes from the fact that in light, there is a shift of the orientations of the eye nystagmus and the head in the direction of the trajectory. These results suggest that a fundamental function of gaze is to represent self motion, stabilize the perception of space during locomotion, and to simulate the future trajectory, regardless of the vision condition. PMID:26106313

  3. Locomotion and Grasping impairment in preschoolers with autism spectrum disorder

    Francesca Fulceri


    Full Text Available Objective: To investigate expressiveness of motor impairment in autism spectrum disorder (ASD and its correlation with developmental and clinical features of ASD. Method: Thirty-five male preschoolers with ASD completed the Peabody Developmental Motor Scales-2 (PDMS-2; Folio and Fewell, 2000 and underwent a multidisciplinary assessment including medical examination, standardized assessment of cognitive abilities, administration of Autism_Diagnostic_Observation_Schedule (ADOS and a parent interview about adaptive skills. Results: Results revealed a substantial impairment in locomotion and grasping skills. Both fine and gross motor skills were significantly correlated with non verbal IQ and adaptive behaviours (p<0.01 but not with chronological age or ADOS scores. Children with weaker motor skills have greater cognitive and adaptive behaviours deficits. Conclusions: Motor development in ASD can be detected at preschool age and locomotion and grasping skills are substantially the most impaired area. These findings support the need to assess motor skills in preschoolers with ASD in addition to other developmental skill areas. Along with the increasingly acknowledged importance of motor skills for subsequent social, cognitive, and communicative development our findings support the need to consider motor intervention as a key area in therapeutic program to improve outcome in preschoolers with ASD.

  4. A Reconfigurable Omnidirectional Soft Robot Based on Caterpillar Locomotion.

    Zou, Jun; Lin, Yangqiao; Ji, Chen; Yang, Huayong


    A pneumatically powered, reconfigurable omnidirectional soft robot based on caterpillar locomotion is described. The robot is composed of nine modules arranged as a three by three matrix and the length of this matrix is 154 mm. The robot propagates a traveling wave inspired by caterpillar locomotion, and it has all three degrees of freedom on a plane (X, Y, and rotation). The speed of the robot is about 18.5 m/h (two body lengths per minute) and it can rotate at a speed of 1.63°/s. The modules have neodymium-iron-boron (NdFeB) magnets embedded and can be easily replaced or combined into other configurations. Two different configurations are presented to demonstrate the possibilities of the modular structure: (1) by removing some modules, the omnidirectional robot can be reassembled into a form that can crawl in a pipe and (2) two omnidirectional robots can crawl close to each other and be assembled automatically into a bigger omnidirectional robot. Omnidirectional motion is important for soft robots to explore unstructured environments. The modular structure gives the soft robot the ability to cope with the challenges of different environments and tasks.

  5. Jumping robots: a biomimetic solution to locomotion across rough terrain.

    Armour, Rhodri; Paskins, Keith; Bowyer, Adrian; Vincent, Julian; Megill, William; Bomphrey, Richard


    This paper introduces jumping robots as a means to traverse rough terrain; such terrain can pose problems for traditional wheeled, tracked and legged designs. The diversity of jumping mechanisms found in nature is explored to support the theory that jumping is a desirable ability for a robot locomotion system to incorporate, and then the size-related constraints are determined from first principles. A series of existing jumping robots are presented and their performance summarized. The authors present two new biologically inspired jumping robots, Jollbot and Glumper, both of which incorporate additional locomotion techniques of rolling and gliding respectively. Jollbot consists of metal hoop springs forming a 300 mm diameter sphere, and when jumping it raises its centre of gravity by 0.22 m and clears a height of 0.18 m. Glumper is of octahedral shape, with four 'legs' that each comprise two 500 mm lengths of CFRP tube articulating around torsion spring 'knees'. It is able to raise its centre of gravity by 1.60 m and clears a height of 1.17 m. The jumping performance of the jumping robot designs presented is discussed and compared against some specialized jumping animals. Specific power output is thought to be the performance-limiting factor for a jumping robot, which requires the maximization of the amount of energy that can be stored together with a minimization of mass. It is demonstrated that this can be achieved through optimization and careful materials selection.

  6. Effects of wearing lower leg compression sleeves on locomotion economy.

    Kurz, Eduard; Anders, Christoph


    The purpose of this investigation was to assess the effect of compression sleeves on muscle activation cost during locomotion. Twenty-two recreationally active men (age: 25 ± 3 years) ran on a treadmill at four different speeds (ordered sequence of 2.8, 3.3, 2.2, and 3.9 m/s). The tests were performed without (control situation, CON) and while wearing specially designed lower leg compression sleeves (SL). Myoelectric activity of five lower leg muscles (tibialis anterior, fibularis longus, lateral and medial head of gastrocnemius, and soleus) was captured using Surface EMG. To assess muscle activation cost, the cumulative muscle activity per distance travelled (CMAPD) of the CON and SL situations was determined. Repeated measures analyses of variance were performed separately for each muscle. The analyses revealed a reduced lower leg muscle activation cost with respect to test situation for SL for all muscles (p  0.18). The respective significant reductions of CMAPD values during SL ranged between 4% and 16% and were largest at 2.8 m/s. The findings presented point towards an improved muscle activation cost while wearing lower leg compression sleeves during locomotion that have potential to postpone muscle fatigue.

  7. Reciprocal locomotion of dense swimmers in Stokes flow

    Gonzalez-Rodriguez, David; Lauga, Eric


    Due to the kinematic reversibility of Stokes flow, a body executing a reciprocal motion (a motion in which the sequence of body configurations remains identical under time reversal) cannot propel itself in a viscous fluid in the limit of negligible inertia; this result is known as Purcell's scallop theorem. In this limit, the Reynolds numbers based on the fluid inertia and on the body inertia are all zero. Previous studies characterized the breakdown of the scallop theorem with fluid inertia. In this paper we show that, even in the absence of fluid inertia, certain dense bodies undergoing reciprocal motion are able to swim. Using Lorentz's reciprocal theorem, we first derive the general differential equations that govern the locomotion kinematics of a dense swimmer. We demonstrate that no reciprocal swimming is possible if the body motion consists only of tangential surface deformation (squirming). We then apply our general formulation to compute the locomotion of four simple swimmers, each with a different spatial asymmetry, that perform normal surface deformations. We show that the resulting swimming speeds (or rotation rates) scale as the first power of a properly defined 'swimmer Reynolds number', demonstrating thereby a continuous breakdown of the scallop theorem with body inertia.

  8. Paper-based Pneumatic Locomotive Robot with Sticky Actuator

    Du Xiaohan


    Full Text Available Demands for small-scale and low-cost robots have witnessed a great increase in recent years [1–5]. This paper introduces the design and fabrication of a novel, simple, low-cost and designer-friendly locomotive robot. The materials and tools to build the robot originate from everyday life. The robot is pneumatically powered and manually controlled by simply pumping and vacuuming the syringe repeatedly, which realizes reliable locomotion by folding and opening of the planes. In order to realize this complicated motion, a “3D Sticky Actuator” is developed. The motion and force analysis of actuator are then modelled by the numerical method to develop the relations between design parameters. This suggests a systematic and user interactive way of manufacturing various shapes of the actuator, depending on user-defined road condition (e.g. obstacles and slopes and other constraints. One key advantage of the paper-based robot is suggested by its high feasibility.

  9. Fluid Flow Simulation and Energetic Analysis of Anomalocarididae Locomotion

    Mikel-Stites, Maxwell; Staples, Anne


    While an abundance of animal locomotion simulations have been performed modeling the motions of living arthropods and aquatic animals, little quantitative simulation and reconstruction of gait parameters has been done to model the locomotion of extinct animals, many of which bear little physical resemblance to their modern descendants. To that end, this project seeks to analyze potential swimming patterns used by the anomalocaridid family, (specifically Anomalocaris canadensis, a Cambrian Era aquatic predator), and determine the most probable modes of movement. This will serve to either verify or cast into question the current assumed movement patterns and properties of these animals and create a bridge between similar flexible-bodied swimmers and their robotic counterparts. This will be accomplished by particle-based fluid flow simulations of the flow around the fins of the animal, as well as an energy analysis of a variety of sample gaits. The energy analysis will then be compared to the extant information regarding speed/energy use curves in an attempt to determine which modes of swimming were most energy efficient for a given range of speeds. These results will provide a better understanding of how these long-extinct animals moved, possibly allowing an improved understanding of their behavioral patterns, and may also lead to a novel potential platform for bio-inspired underwater autonomous vehicles (UAVs).

  10. Progenitor cells of erythroblasts: an in vitro investigation of erythropoietin-responsive cells of guinea pig bone marrow

    Rosse, C.; Beaufait, D.W.


    The experiments were designed to therst whether erythroblast progenitor cell function could be demonstrated in a morphological cell type designated as transitional cells. Two cell fractions were obtained from the bone marrow of normal and polycythemic guinea pigs. One fraction (F1) was enriched in transitional cells and contained few other cell types which could be considered as candidates for erythropoietin responsive cells (ERC). The other fraction (F2) contained undifferentiated blast cells as well as transitional cells. The effect of human urinary erythropoiesis stimulating factors (ESF) on heme synthesis was compared in these two fractions by measuring 59 Fe incorporation into heme. ESF was more effective in stimulating heme synthesis in guinea pig bone marrow cells than homologous sera obtained from anemic or hypoxic animals. The majority of ERC sedimented in F2, but the stimulation index was comparable in the two fractions. It was confirmed by radioautography that the ESF response in F1 was due to the generation of proerythroblasts and basophilic erythroblasts that incorporated 55 Fe. The generation of these cells in F1 was dependent on the addition of ESF to the cultures, whereas 55 Fe-labeled erythroblasts were recovered from cultures of F2 not supplemented with ESF. ESF induced a proportion of transitional cells to incorporate 55 Fe in both F1 and F2. Transitional cells were the only cell type in which heme synthesis was dependent on ESF. Radioautography with 55 Fe identified a proportion of these cells as ERC in both F1 and F2 fractions of bone marrow obtained from normal and polycythemic guinea pigs. The present studies show that some transitional cells function as progenitors of erythroblasts because they respond to ESF by initiation of heme synthesis and by transformation into the earliest recognizable erythroid cells

  11. Comparison of steroid receptors from the androgen responsive DDT1 cell line and the nonresponsive HVP cell line.

    Norris, J S; Kohler, P O


    Two hamster cell lines have been isolated from androgen target tissue. The DDT1 cells derived from ductus deferens tissue exhibit a growth response to androgens, while the HVP cells derived from ventral prostate are androgen unresponsive. Both cell lines contain androgen receptors, that are similar when compared by kinetic methods, sedimentation velocity, chromatographic procedures or nuclear translocation ability. The forms of the high salt extracted nuclear receptors are indistinguishable chromatographically. Therefore, we postulate that the lesion preventing androgen induced growth in the HVP cell line is subseqent to nuclear translocation of the steroid receptor complex.

  12. A novel controller for bipedal locomotion integrating feed-forward and feedback mechanisms

    Xiong, Xiaofeng; Sartori, Massimo; Dosen, Strahinja; González-Vargas, José; Wörgötter, Florentin; Farina, Dario; Ibanez, J.; González-Vargas, J.; Azorin, J.M.; Akay, M.; Pons, J.L.


    It has been recognized that bipedal locomotion is controlled using feed-forward (e.g., patterned) and feedback (e.g., reflex) control schemes. However, most current controllers fail to integrate the two schemes to simplify speed control of bipedal locomotion. To solve this problem, we here propose a

  13. 49 CFR 230.20 - Alteration and repair report for steam locomotive boilers.


    ... boilers. 230.20 Section 230.20 Transportation Other Regulations Relating to Transportation (Continued... boilers. (a) Alterations. When an alteration is made to a steam locomotive boiler, the steam locomotive... maintained for the life of the boiler. (See appendix B of this part.) (b) Welded and riveted repairs to...

  14. 49 CFR 231.15 - Steam locomotives used in road service.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotives used in road service. 231.15 Section 231.15 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.15 Steam locomotives used...

  15. 49 CFR 229.9 - Movement of non-complying locomotives.


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Movement of non-complying locomotives. 229.9... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS General § 229.9 Movement of non... restrictions necessary for safely conducting the movement; (2)(i) The engineer in charge of the movement of the...

  16. The G6. A heavy-duty, six-wheeled shunting locomotive

    Hildebrandt, Tim [Vossloh Locomotives GmbH, Kiel (Germany). Development and Standardisation Group


    Nowadays, railway operating companies need robust, reliable and versatile locomotives. Vossloh has shown one way that future developments are likely to go with its 'G6' six-wheeled shunting locomotive, which features a central driver's cab. (orig.)

  17. 49 CFR 1242.22 - Shop buildings-locomotives (account XX-19-24).


    ... 49 Transportation 9 2010-10-01 2010-10-01 false Shop buildings-locomotives (account XX-19-24... Structures § 1242.22 Shop buildings—locomotives (account XX-19-24). Separate common expenses according to distribution of common expenses in the following accounts: Machinery Repair (XX-26-40) Locomotive—Repair and...

  18. Design and analysis of an optimal hopper for use in resonance-based locomotion

    Wanders, Ivor; Folkertsma, Gerrit Adriaan; Stramigioli, Stefano

    Quadrupedal running is an efficient form of locomotion found in nature, which serves as an inspiration for robotics. We believe that a resonance-based approach is the path towards energy-efficient legged locomotion and running robots. The first step in working towards this goal is creating an

  19. Investigations into dynamics of a draft of mine cars with two locomotives during electric braking

    Sikora-Iliew, R; Szklarski, L; Thuc, Thai Duy


    The computerized simulation of electric braking of a draft of GRANBY-5 mine cars and two locomotives (Ld2 locomotives with LDO30 electric series motors) is discussed. The following stages of simulation are analyzed: constructing a mathematical model of the draft of mine cars during electric (dynamic) braking, equations which describe dynamic states of locomotives, mine cars and electric motors during dynamic braking, equations for stability assessment of the draft during dynamic braking. The analog model for simulation of dynamic braking of the draft is given. Simulation results are shown in 10 diagrams. The WAT-1000 hybrid computer is used. Simulation shows that dynamic braking causes occurrence of maximum forces in the couplers between a locomotive and a mine car. When two locomotives are used the maximum force in couplers is lower than in a draft with one locomotive. Braking distance does not depend on position of locomotives in a draft of mine cars. Doubling draft speed causes braking distance to increase by 4 times. Optimum stability conditions of a draft of mine cars are guaranteed when one locomotive is placed at the draft head and a second is separated from the first one by one third of the draft length. 6 references

  20. 49 CFR Appendix D to Part 238 - Requirements for External Fuel Tanks on Tier I Locomotives


    ... 49 Transportation 4 2010-10-01 2010-10-01 false Requirements for External Fuel Tanks on Tier I..., App. D Appendix D to Part 238—Requirements for External Fuel Tanks on Tier I Locomotives The... properties of the locomotive fuel tank to reduce the risk of fuel spillage to acceptable levels under...

  1. 49 CFR 210.29 - Operation standards (moving locomotives and rail cars).


    ... cars). 210.29 Section 210.29 Transportation Other Regulations Relating to Transportation (Continued... REGULATIONS Inspection and Testing § 210.29 Operation standards (moving locomotives and rail cars). The operation standards for the noise emission levels of moving locomotives, rail cars, or consists of...

  2. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.


    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  3. Endogenous Tim-1 (Kim-1) promotes T-cell responses and cell-mediated injury in experimental crescentic glomerulonephritis.

    Nozaki, Yuji; Nikolic-Paterson, David J; Snelgrove, Sarah L; Akiba, Hisaya; Yagita, Hideo; Holdsworth, Stephen R; Kitching, A Richard


    The T-cell immunoglobulin mucin 1 (Tim-1) modulates CD4(+) T-cell responses and is also expressed by damaged proximal tubules in the kidney where it is known as kidney injury molecule-1 (Kim-1). We sought to define the role of endogenous Tim-1 in experimental T-cell-mediated glomerulonephritis induced by sheep anti-mouse glomerular basement membrane globulin acting as a planted foreign antigen. Tim-1 is expressed by infiltrating activated CD4(+) cells in this model, and we studied the effects of an inhibitory anti-Tim-1 antibody (RMT1-10) on immune responses and glomerular disease. Crescentic glomerulonephritis, proliferative injury, and leukocyte accumulation were attenuated following treatment with anti-Tim-1 antibodies, but interstitial foxp3(+) cell accumulation and interleukin-10 mRNA were increased. T-cell proliferation and apoptosis decreased in the immune system along with a selective reduction in Th1 and Th17 cellular responses both in the immune system and within the kidney. The urinary excretion and renal expression of Kim-1 was reduced by anti-Tim-1 antibodies reflecting diminished interstitial injury. The effects of anti-Tim-1 antibodies were not apparent in the early phase of renal injury, when the immune response to sheep globulin was developing. Thus, endogenous Tim-1 promotes Th1 and Th17 nephritogenic immune responses and its neutralization reduces renal injury while limiting inflammation in cell-mediated glomerulonephritis.

  4. Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias


    AWARD NUMBER: W81XWH-16-1-0380 TITLE: Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias PRINCIPAL...2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Enhancing Natural Killer Cell Mediated Targeting and Responses to Myeloid Leukemias 5b. GRANT NUMBER...leukemias still have poor prognosis, particularly in the elderly, and require hematopoietic cell transplants to fully kill the tumor, which is both

  5. CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization

    Routine methods for enumerating antigen-specific T-helper cells may not identify low-frequency phenotypes such as Th2 cells. We compared methods of evaluating such responses to identify tetanus toxoid- (TT) specific Th1, Th2, Th17 and IL10+ cells. Eight healthy subjects were given a TT booster vacci...

  6. Live cell microscopy of DNA damage response in Saccharomyces cerevisiae

    Pinela da Silva, Sonia Cristina; Gallina, Irene; Eckert-Boulet, Nadine Valerie


    live cell imaging allows for multiple cellular markers to be monitored over several hours. This chapter reviews useful fluorescent markers and genotoxic agents for studying the DNA damage response in living cells and provides protocols for live cell imaging, time-lapse microscopy, and for induction...

  7. Frequency response for electromotility of isolated outer hair cells of the guinea pig

    Wit, HP; vanDijk, P; Segenhout, HM


    Frequency and impulse responses were determined for isolated guinea pig outer hair cells by electrically stimulating the cells between two wire electrodes with white noise. Cells were attached to the bottom of a small culture dish at one end while the other end was freely moving. Results have the

  8. Classification of human natural killer cells based on migration behavior and cytotoxic response.

    Vanherberghen, Bruno; Olofsson, Per E; Forslund, Elin; Sternberg-Simon, Michal; Khorshidi, Mohammad Ali; Pacouret, Simon; Guldevall, Karolin; Enqvist, Monika; Malmberg, Karl-Johan; Mehr, Ramit; Önfelt, Björn


    Despite intense scrutiny of the molecular interactions between natural killer (NK) and target cells, few studies have been devoted to dissection of the basic functional heterogeneity in individual NK cell behavior. Using a microchip-based, time-lapse imaging approach allowing the entire contact history of each NK cell to be recorded, in the present study, we were able to quantify how the cytotoxic response varied between individual NK cells. Strikingly, approximately half of the NK cells did not kill any target cells at all, whereas a minority of NK cells was responsible for a majority of the target cell deaths. These dynamic cytotoxicity data allowed categorization of NK cells into 5 distinct classes. A small but particularly active subclass of NK cells killed several target cells in a consecutive fashion. These "serial killers" delivered their lytic hits faster and induced faster target cell death than other NK cells. Fast, necrotic target cell death was correlated with the amount of perforin released by the NK cells. Our data are consistent with a model in which a small fraction of NK cells drives tumor elimination and inflammation.

  9. Modeling the locomotion of the African trypanosome using multi-particle collision dynamics

    Babu, Sujin B; Stark, Holger


    The African trypanosome is a single flagellated micro-organism that causes the deadly sleeping sickness in humans and animals. We study the locomotion of a model trypanosome by modeling the spindle-shaped cell body using an elastic network of vertices with additional bending rigidity. The flagellum firmly attached to the model cell body is either straight or helical. A bending wave propagates along the flagellum and pushes the trypanosome forward in its viscous environment, which we simulate with the method of multi-particle collision dynamics. The relaxation dynamics of the model cell body due to a static bending wave reveals the sperm number from elastohydrodynamics as the relevant parameter. Characteristic cell body conformations for the helically attached flagellum resemble experimental observations. We show that the swimming velocity scales as the root of the angular frequency of the bending wave reminiscent of predictions for an actuated slender rod attached to a large viscous load. The swimming velocity for one geometry collapses on a single master curve when plotted versus the sperm number. The helically attached flagellum leads to a helical swimming path and a rotation of the model trypanosome about its long axis as observed in experiments. The simulated swimming velocity agrees with the experimental value. (paper)

  10. Acetyl CoA Carboxylase 2 Is Dispensable for CD8+ T Cell Responses.

    Jang Eun Lee

    Full Text Available Differentiation of T cells is closely associated with dynamic changes in nutrient and energy metabolism. However, the extent to which specific metabolic pathways and molecular components are determinative of CD8+ T cell fate remains unclear. It has been previously established in various tissues that acetyl CoA carboxylase 2 (ACC2 regulates fatty acid oxidation (FAO by inhibiting carnitine palmitoyltransferase 1 (CPT1, a rate-limiting enzyme of FAO in mitochondria. Here, we explore the cell-intrinsic role of ACC2 in T cell immunity in response to infections. We report here that ACC2 deficiency results in a marginal increase of cellular FAO in CD8+ T cells, but does not appear to influence antigen-specific effector and memory CD8+ T cell responses during infection with listeria or lymphocytic choriomeningitis virus. These results suggest that ACC2 is dispensable for CD8+ T cell responses.

  11. The comparison of radiation responses in MCF-7 and HeLa cells

    Kang, Mi Young; Jang, Eun Yeong; Ryu, Tae Ho; Chung, Dong-Min; Kim, Jin Hong; Kim, Jin Kyu [Advanced Radiation Technology Institute, Jeongeup (Korea, Republic of)


    Activation of this pathway temporarily arrests cells at the G1 or G2 checkpoints of cell cycle, or terminates DNA replication and cell division. The present study was carried out to identify the fate of cells to cope with DNA damage stress. Cellular responses following IR treatment were different depending on the characteristics (origin, organism and genes expressed etc.) of cell line used and extent of genomic injury. p53 expression level was increased in a dose-dependent manner in both cells. IR induced a drastic increase in expression of p21 in MCF-7 compared to that in HeLa cells. Cell cycle analysis using flow cytometry showed a significant accumulation in G2/M phase after treatment of MCF-7 with IR. This study identified that IR-induced cell fates were determined through p53-dependent activation of p21, which resulted in senescence of MCF-7 cells and autophagy of HeLa cells.


    enhances immunity by sustained HIV- viral suppression, increase in CD4+ cell count and immune restoration. ... Seventy three (70.9%) of patients still had immune depletion with low CD4+ cell counts at one year of receiving HAART. ..... homeostasis and function in advanced HIV disease. Science 1997; 277: 112- 116. 7.

  13. Dissection and manipulation of antigen-specific T cell responses

    Schepers, Koen


    T cells recognize pathogen-derived antigens and are crucial for fighting pathogens such as viruses and bacteria. In addition, T cells are able to recognize and attack certain types of tumors, in particular virally induced tumors. In this thesis we aimed 1) to obtain more insight into

  14. Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.

    Ueda, Norihiro; Uemura, Yasushi; Zhang, Rong; Kitayama, Shuichi; Iriguchi, Shoichi; Kawai, Yohei; Yasui, Yutaka; Tatsumi, Minako; Ueda, Tatsuki; Liu, Tian-Yi; Mizoro, Yasutaka; Okada, Chihiro; Watanabe, Akira; Nakanishi, Mahito; Senju, Satoru; Nishimura, Yasuharu; Kuzushima, Kiyotaka; Kiyoi, Hitoshi; Naoe, Tomoki; Kaneko, Shin


    CD4 + T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40L high iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40L high iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Targeting CD4(+) T-Helper Cells Improves the Induction of Antitumor Responses in Dendritic Cell-Based Vaccination

    Aarntzen, Erik H. J. G.; de Vries, I. Jolanda M.; Lesterhuis, W. Joost; Schuurhuis, Danita; Jacobs, Joannes F. M.; Bol, Kalijn; Schreibelt, Gerty; Mus, Roel; de Wilt, Johannes H. W.; Haanen, John B. A. G.; Schadendorf, Dirk; Croockewit, Alexandra; Blokx, Willeke A. M.; van Rossum, Michelle M.; Kwok, William W.; Adema, Gosse J.; Punt, Cornelis J. A.; Figdor, Carl G.


    To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part of effective anticancer immunotherapy, we investigated the immunologic and clinical responses to vaccination with dendritic cells (DC) pulsed with either MHC class I (MHC-I)-restricted epitopes alone or both MHC

  16. Adipose tissue-derived mesenchymal stem cells acquire bone cell-like responsiveness to fluid shear stress on osteogenic stimulation

    Knippenberg, M.; Helder, M.N.; Doulabi, B.Z.; Semeins, C.M.; Wuisman, P.I.J.M.; Klein-Nulend, J.


    To engineer bone tissue, mechanosensitive cells are needed that are able to perform bone cell-specific functions, such as (re)modeling of bone tissue. In vivo, local bone mass and architecture are affected by mechanical loading, which is thought to provoke a cellular response via loading-induced

  17. Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses.

    Kelly B McClellan


    Full Text Available B cells can use antibody-dependent mechanisms to control latent viral infections. It is unknown whether this represents the sole function of B cells during chronic viral infection. We report here that hen egg lysozyme (HEL-specific B cells can contribute to the control of murine gamma-herpesvirus 68 (gammaHV68 latency without producing anti-viral antibody. HEL-specific B cells normalized defects in T cell numbers and proliferation observed in B cell-/- mice during the early phase of gammaHV68 latency. HEL-specific B cells also reversed defects in CD8 and CD4 T cell cytokine production observed in B cell-/- mice, generating CD8 and CD4 T cells necessary for control of latency. Furthermore, HEL-specific B cells were able to present virally encoded antigen to CD8 T cells. Therefore, B cells have antibody independent functions, including antigen presentation, that are important for control of gamma-herpesvirus latency. Exploitation of this property of B cells may allow enhanced vaccine responses to chronic virus infection.

  18. Empirical evaluation of cell critical volume dose vs. cell response function for pink mutations in tradescantia

    Varma, M.N.; Bond, V.P.


    Microdosimetric spectra for 0.43, 1.8, and 14.7 MeV neutrons, and for 215 kVp x rays and 1250 keV gammas were used in conjunction with relative biological effectiveness (RBE) values for pink mutations in Tradescantia to obtain an effectiveness function (i.e., a cell critical volume dose vs. cell response function). This effectiveness function (or hit size weighting function) provides the probability of inducing a biological effect of interest (in the present study, pink mutations in Tradescantia) as a function of lineal energy density y. In a preliminary analysis the critical value of y above which pink mutations are seen was 4.5 keV/μm, and the value of y at which the probability reaches unity was 115 keV/μm. Idealized but approximate event size distributions for mono-LET particles ranging from 10 to 5000 keV/μm were generated, and these distributions were weighted by the effectiveness function to determine the pink mutation frequencies. Results are compared with measured pink mutation frequencies for 11 keV/μm ( 12 C) and 31 keV/μm ( 20 Ne) ions

  19. [The concept and definition of locomotive syndrome in a super-aged society].

    Nakamura, Kozo; Yoshimura, Noriko; Akune, Toru; Ogata, Toru; Tanaka, Sakae


    The population of elderly individuals who need nursing care is rapidly increasing in Japan. Locomotive syndrome involves a decrease in mobility due to locomotive organ dysfunction, and increases risk for dependency on nursing care service. Because gait speed and chair stand time are correlated with such risks, patients with locomotive syndrome are assessed using brief methods such as the two-step test, which involves dividing the maximum stride length by the height of the patient, and the stand-up test, which involves standing on one or both legs at different heights. One leg standing and squatting are recommended as beneficial locomotive home exercises. Locomotive syndrome has been recognized widely in Japan, and included in the National Health Promotion Movement (2013-2022).

  20. Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses.

    Webb, Tonya J; Carey, Gregory B; East, James E; Sun, Wenji; Bollino, Dominique R; Kimball, Amy S; Brutkiewicz, Randy R


    Natural killer T (NKT) cells play a critical role in the host's innate immune response. CD1d-mediated presentation of glycolipid antigens to NKT cells has been established; however, the mechanisms by which NKT cells recognize infected or cancerous cells remain unclear. 5(')-AMP activated protein kinase (AMPK) is a master regulator of lipogenic pathways. We hypothesized that activation of AMPK during infection and malignancy could alter the repertoire of antigens presented by CD1d and serve as a danger signal to NKT cells. In this study, we examined the effect of alterations in metabolism on CD1d-mediated antigen presentation to NKT cells and found that an infection with lymphocytic choriomeningitis virus rapidly increased CD1d-mediated antigen presentation. Hypoxia inducible factors (HIF) enhance T-cell effector functions during infection, therefore antigen presenting cells pretreated with pharmacological agents that inhibit glycolysis, induce HIF and activate AMPK were assessed for their ability to induce NKT-cell responses. Pretreatment with 2-deoxyglucose, cobalt chloride, AICAR and metformin significantly enhanced CD1d-mediated NKT-cell activation. In addition, NKT cells preferentially respond to malignant B cells and B-cell lymphomas express HIF-1α. These data suggest that targeting cellular metabolism may serve as a novel means of inducing innate immune responses. © FEMS 2016. All rights reserved. For permissions, please e-mail:

  1. Increased sequence diversity coverage improves detection of HIV-Specific T cell responses

    Frahm, N.; Kaufmann, D.E.; Yusim, K.


    The accurate identification of HIV-specific T cell responses is important for determining the relationship between immune response, viral control, and disease progression. HIV-specific immune responses are usually measured using peptide sets based on consensus sequences, which frequently miss res...

  2. T-helper cell-mediated proliferation and cytokine responses against recombinant Merkel cell polyomavirus-like particles.

    Arun Kumar

    Full Text Available The newly discovered Merkel Cell Polyomavirus (MCPyV resides in approximately 80% of Merkel cell carcinomas (MCC. Causal role of MCPyV for this rare and aggressive skin cancer is suggested by monoclonal integration and truncation of large T (LT viral antigen in MCC cells. The mutated MCPyV has recently been found in highly purified leukemic cells from patients with chronic lymphocytic leukemia (CLL, suggesting a pathogenic role also in CLL. About 50-80% of adults display MCPyV-specific antibodies. The humoral immunity does not protect against the development of MCC, as neutralizing MCPyV antibodies occur in higher levels among MCC patients than healthy controls. Impaired T-cell immunity has been linked with aggressive MCC behavior. Therefore, cellular immunity appears to be important in MCPyV infection surveillance. In order to elucidate the role of MCPyV-specific Th-cell immunity, peripheral blood mononuclear cells (PBMC of healthy adults were stimulated with MCPyV VP1 virus-like particles (VLPs, using human bocavirus (HBoV VLPs and Candida albicans antigen as positive controls. Proliferation, IFN-γ, IL-13 and IL-10 responses were examined in 15 MCPyV-seropositive and 15 seronegative volunteers. With the MCPyV antigen, significantly stronger Th-cell responses were found in MCPyV-seropositive than MCPyV-seronegative subjects, whereas with the control antigens, the responses were statistically similar. The most readily detectable cytokine was IFN-γ. The MCPyV antigen tended to induce stronger IFN-γ responses than HBoV VLP antigen. Taken together, MCPyV-specific Th-cells elicit vigorous IFN-γ responses. IFN-γ being a cytokine with major antiviral and tumor suppressing functions, Th-cells are suggested to be important mediators of MCPyV-specific immune surveillance.

  3. Comparison of tumour age response to radiation for cells derived from tissue culture or solid tumours

    Keng, P.C.; Siemann, D.W.; Rochester Univ., NY; Rochester Univ., NY; Wheeler, K.T.


    Direct comparison of the cell age response of 9L and KHT tumour cells derived either from tissue culture or solid tumours was achieved. Cells from dissociated KHT and 9L tumours (the latter implanted either subcutaneously or intracerebrally) and cells from tissue culture were separated into homogenous sized populations by centrifugal elutriation. In both tumour models these homogeneous sized populations correspond to populations enriched at different stages of the cell cycle. The survival of these elutriated cell populations was measured after a single dose of Cs-137 gamma rays. For cells isolated from 9L solid tumours, there was little variation in radiosensitivity throughout the cell cycle; however, a very small but significant increase in resistance was found in late G 1 cells. This lack of a large variation in radiosensitivity through the cell cycle for 9L cells from solid tumours also was seen in 9L cells growing in monolayer tissue culture. When similar experiments were performed using the KHT sarcoma tumour model, the results showed that KHT cells in vitro exhibited a fairly conventional increase in radioresistance in both mid G 1 and late S. However, the cell age response of KHT cells from solid tumours was different; particularly in the late S and G 2 + M phases. (author)


    B. Ye. Bodnar


    Full Text Available Purpose. The article describes the most common methods for determining the locomotive traction force. Solving the tasks of traction calculations involves determination of the forces influencing the train at every point of the way. When choosing a rational trajectory of the train motion and the development of operational regulations of train driving it is necessary to determine the actual value of the locomotive traction force. Considering various factors, power value of traction electric motor of locomotive may have significant differences. Advancement of the operational definition system of the locomotive traction force during the calculations by electrical parameters of traction electric motor with regard to uneven load of wheel-motor block is the purpose of the article. Methodology. The method of determining the traction force of locomotives and diesel locomotives with electric transmission, which is based on primary data acquisition of traction electric engines of direct current behavior, was proposed. Sensors and their integration into the electrical circuitry of the locomotive in order to get the data in digital form and for operational calculation of the each traction motor mode and the definition of locomotive traction force are presented. Findings. The experimental investigation of the system of locomotive traction force determination with the electric traction motor ED-105 was offered. A comparison of electrical and mechanical power of the electric motor was conducted. Originality. The system of locomotives power operational definition, which takes into account the variable electro-mechanical factors of wheel and motor blocks and increases the accuracy of the calculations, was proposed. Practical value. The system is a part of an onboard complex in definition of energy-efficient regimes for trains movement and provides the definition of accelerating and decelerating forces.

  5. Lifestyle factors are significantly associated with the locomotive syndrome: a cross-sectional study.

    Akahane, Manabu; Yoshihara, Shingo; Maeyashiki, Akie; Tanaka, Yasuhito; Imamura, Tomoaki


    The Japanese Orthopedic Association first proposed the concept of "locomotive syndrome" in 2007. It refers to circumstances in which elderly people need nursing care services or are at high risk of requiring such services within a short time. Recently, the public health burden of providing nursing care for elderly individuals has increased. Therefore, locomotive syndrome, and the means of preventing it, are a major public health focus in Japan. The purpose of this study was to investigate the relationships of lifestyle factors, such as smoking, alcohol consumption, sleep duration, and dental health, with locomotive syndrome. We conducted a cross-sectional study using an internet panel survey. The participants comprised 747 individuals aged 30-90 years. Factors related to demographics (age, sex), general health (number of teeth, presence of periodontal disease), and lifestyle (smoking, alcohol consumption, sleep duration) were assessed. We also used the 25-question Geriatric Locomotive Function Scale to determine whether each participant had locomotive syndrome. Multivariate analysis was conducted using logistic regression to investigate the independent relationships between locomotive syndrome and lifestyle factors after adjusting for sex and age. A greater proportion of women (17.7%) than men (11.2%) had locomotive syndrome (p syndrome compared with those aged syndrome, whereas sleep duration was not. The frequency of alcohol consumption, except for daily drinking, was also associated with locomotive syndrome. Our study indicates that lifestyle factors, such as smoking and number of existing teeth, may partly affect the prevalence of locomotive syndrome. Hence, lifestyle modifications, such as improving oral hygiene and promoting cessation of smoking, are important means to reduce the risk of locomotive syndrome and should be promoted by public health staff.

  6. T cell-derived Lymphotoxin is Essential for anti-HSV-1 Humoral Immune Response.

    Yang, Kaiting; Liang, Yong; Sun, Zhichen; Xue, Diyuan; Xu, Hairong; Zhu, Mingzhao; Fu, Yang-Xin; Peng, Hua


    B cell-derived lymphotoxin (LT) is required for the development of follicular dendritic cell clusters for the formation of primary and secondary lymphoid follicles, but the role of T cell-derived LT in antibody response has not been well demonstrated. We observed that lymphotoxin-β-receptor (LTβR) signaling is essential for optimal humoral immune response and protection against an acute HSV-1 infection. Blocking the LTβR pathway caused poor maintenance of germinal center B (GC-B) cells and follicular helper T (Tfh) cells. Using bone marrow chimeric mice and adoptive transplantation, we determined that T cell-derived LT played an indispensable role in the humoral immune response to HSV-1. Up-regulation of IFNγ by the LTβR-Ig blockade impairs the sustainability of Tfh-like cells, thus leading to an impaired humoral immune response. Our findings have identified a novel role of T cell-derived LT in the humoral immune response against HSV-1 infection. IMPORTANCE Immunocompromised people are susceptible for HSV-1 infection and lethal recurrence, which could be inhibited by anti-HSV-1 humoral immune response in the host. This study sought to explore the role of T cell-derived LT in the anti-HSV-1 humoral immune response using LT-LTβR signaling deficient mice and the LTβR-Ig blockade. The data indicate that the T cell-derived LT may play an essential role in sustaining Tfh-like cells and ensure Tfh-like cells' migration into primary or secondary follicles for further maturation. This study provides insights for vaccine development against infectious diseases. Copyright © 2018 American Society for Microbiology.

  7. ZFAT plays critical roles in peripheral T cell homeostasis and its T cell receptor-mediated response

    Doi, Keiko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute of Life Sciences for the Next Generation of Women Scientists, Fukuoka University, Fukuoka (Japan); Fujimoto, Takahiro [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Okamura, Tadashi [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ogawa, Masahiro [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tanaka, Yoko [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Mototani, Yasumasa; Goto, Motohito [Division of Animal Models, Department of Infectious Diseases, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Ota, Takeharu; Matsuzaki, Hiroshi [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Kuroki, Masahide [Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Tsunoda, Toshiyuki [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan); Sasazuki, Takehiko [Institute for Advanced Study, Kyushu University, Fukuoka (Japan); Shirasawa, Senji, E-mail: [Department of Cell Biology, Faculty of Medicine, Fukuoka University, Fukuoka (Japan); Central Research Institute for Advanced Molecular Medicine, Fukuoka University, Fukuoka (Japan)


    Highlights: Black-Right-Pointing-Pointer We generated Cd4-Cre-mediated T cell-specific Zfat-deficient mice. Black-Right-Pointing-Pointer Zfat-deficiency leads to reduction in the number of the peripheral T cells. Black-Right-Pointing-Pointer Impaired T cell receptor-mediated response in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Decreased expression of IL-7R{alpha}, IL-2R{alpha} and IL-2 in Zfat-deficient peripheral T cells. Black-Right-Pointing-Pointer Zfat plays critical roles in peripheral T cell homeostasis. -- Abstract: ZFAT, originally identified as a candidate susceptibility gene for autoimmune thyroid disease, has been reported to be involved in apoptosis, development and primitive hematopoiesis. Zfat is highly expressed in T- and B-cells in the lymphoid tissues, however, its physiological function in the immune system remains totally unknown. Here, we generated the T cell-specific Zfat-deficient mice and demonstrated that Zfat-deficiency leads to a remarkable reduction in the number of the peripheral T cells. Intriguingly, a reduced expression of IL-7R{alpha} and the impaired responsiveness to IL-7 for the survival were observed in the Zfat-deficient T cells. Furthermore, a severe defect in proliferation and increased apoptosis in the Zfat-deficient T cells following T cell receptor (TCR) stimulation was observed with a reduced IL-2R{alpha} expression as well as a reduced IL-2 production. Thus, our findings reveal that Zfat is a critical regulator in peripheral T cell homeostasis and its TCR-mediated response.

  8. Differential heat shock response of primary human cell cultures and established cell lines

    Richter, W W; Issinger, O G


    degrees C treatment, whereas in immortalized cell lines usually 90% of the cells were found in suspension. Enhanced expression of the major heat shock protein (hsp 70) was found in all heat-treated cells. In contrast to the primary cell cultures, established and transformed cell lines synthesized...

  9. Feasibility study for SOFC-GT hybrid locomotive power: Part I. Development of a dynamic 3.5 MW SOFC-GT FORTRAN model

    Martinez, Andrew S.; Brouwer, Jacob; Samuelsen, G. Scott


    This work presents the development of a dynamic SOFC-GT hybrid system model applied to a long-haul freight locomotive in operation. Given the expectations of the rail industry, the model is used to develop a preliminary analysis of the proposed system's operational capability on conventional diesel fuel as well as natural gas and hydrogen as potential fuels in the future. It is found that operation of the system on all three of these fuels is feasible with favorable efficiencies and reasonable dynamic response. The use of diesel fuel reformate in the SOFC presents a challenge to the electrochemistry, especially as it relates to control and optimization of the fuel utilization in the anode compartment. This is found to arise from the large amount of carbon monoxide in diesel reformate that is fed to the fuel cell, limiting the maximum fuel utilization possible. This presents an opportunity for further investigations into carbon monoxide electrochemical oxidation and/or system integration studies where the efficiency of the fuel reformer can be balanced against the needs of the SOFC.

  10. NaCl responsive taste cells in the mouse fungiform taste buds.

    Yoshida, R; Horio, N; Murata, Y; Yasumatsu, K; Shigemura, N; Ninomiya, Y


    Previous studies have demonstrated that rodents' chorda tympani (CT) nerve fibers responding to NaCl can be classified according to their sensitivities to the epithelial sodium channel (ENaC) blocker amiloride into two groups: amiloride-sensitive (AS) and -insensitive (AI). The AS fibers were shown to respond specifically to NaCl, whereas AI fibers broadly respond to various electrolytes, including NaCl. These data suggest that salt taste transduction in taste cells may be composed of at least two different systems; AS and AI ones. To further address this issue, we investigated the responses to NaCl, KCl and HCl and the amiloride sensitivity of mouse fungiform papilla taste bud cells which are innervated by the CT nerve. Comparable with the CT data, the results indicated that 56 NaCl-responsive cells tested were classified into two groups; 25 cells ( approximately 44%) narrowly responded to NaCl and their NaCl response were inhibited by amiloride (AS cells), whereas the remaining 31 cells ( approximately 56%) responded not only to NaCl, but to KCl and/or HCl and showed no amiloride inhibition of NaCl responses (AI cells). Amiloride applied to the basolateral side of taste cells had no effect on NaCl responses in the AS and AI cells. Single cell reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated that ENaC subunit mRNA was expressed in a subset of AS cells. These findings suggest that the mouse fungiform taste bud is composed of AS and AI cells that can transmit taste information differently to their corresponding types of CT fibers, and apical ENaCs may be involved in the NaCl responses of AS cells.

  11. The acquisition of cytokine responsiveness by murine B cells

    Poudrier, J; Owens, T


    chains and mRNA to levels comparable to those seen in activated T cells. Anti-mu-stimulated B cells responded to IL-2 by incorporation of [3H]thymidine and high rate immunoglobulin (Ig) secretion. Both IL-5 (at optimal concentration) and suboptimal lipopolysaccharide (LPS; 20 ng/ml) induced surface...... expression of IL-2R alpha. The level of expression induced by IL-5 was equivalent to that on anti-Ig-activated B cells. Neither stimulus induced detectable expression of IL-2R beta, and neither induced B cells to respond to IL-2. IL-2R alpha expression was strongly enhanced, and low levels of IL-2R beta...

  12. Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics.

    Gamwell, Lisa F; Gambaro, Karen; Merziotis, Maria; Crane, Colleen; Arcand, Suzanna L; Bourada, Valerie; Davis, Christopher; Squire, Jeremy A; Huntsman, David G; Tonin, Patricia N; Vanderhyden, Barbara C


    The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. Spectral karyotyping revealed a largely normal diploid karyotype (in greater than 95% of cells) with a visibly shorter chromosome 20 contig. High density SNP array analysis also revealed few genomic anomalies in BIN-67 cells, which included loss of heterozygosity of an estimated 16.7 Mb interval on chromosome 20. SNP array analyses of four SCCOHT samples also indicated a low frequency of genomic anomalies in the majority of cases. Although resistant to platinum chemotherapeutic drugs, BIN-67 cell viability in vitro was reduced by > 75% after infection with oncolytic viruses. These results show that SCCOHT differs from high-grade serous carcinomas by exhibiting few chromosomal anomalies and lacking TP53 mutations. Although BIN-67 cells are

  13. Epigenetic cell response to an influence of ionizing radiation

    Mikheev, A.N.; Gushcha, N.I.; Malinovskij, Yu.Yu.


    Importance of radiation modification of epigenetic activity in the general mechanism of radiobiological reactions is proved. Inheritable epigenetic changes induced by irradiation are one of the basic reasons of formation of the remote radiation pathology. It is noted that epigenetic inheritable changes of cells have the determined character distinguishing them mutation changes, being individual and not directed. It is underlined the ability of ionizing radiation to modify level of spontaneous genetic instability inherited in a number of cell generations on epigenetic mechanism [ru

  14. Cellular response after irradiation: Cell cycle control and apoptosis

    Siles, E.; Valenzuela, M.T.; Nunez, M.I.; Guerrero, R.; Villalobos, M.; Ruiz de Almodovar, J.M.


    The importance of apoptotic death was assessed in a set of experiments, involving eight human tumour cell lines (breast cancer, bladder carcinoma, medulloblastoma). Various aspects of the quantitative study of apoptosis and methods based on the detection of DNA fragmentation (in situ tailing and comet assay) are described and discussed. Data obtained support the hypothesis that apoptosis is not crucial for cellular radiosensitivity and that the relationship between p53 functionality or clonogenic survival and apoptosis may bee cell type specific. (author)

  15. Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

    Mansouri, Ladan; Xie, Yufen; Rappolee, Daniel A


    Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induce...

  16. Cell proliferation kinetics and radiation response in 9L tumor spheroids

    Sweigert, S.E.


    Cell kinetic parameters, including population doubling-time, cell cycle time, and growth fraction, were measured in 9L gliosarcoma spheroids. These parameters were studied as the spheroids grew from 50 to over 900 in diameter. Experiments relating the cell kinetic parameters to the radiation response of 9L spheroids were also carried out. The major findings were that the average cell cycle time (T/sub c/), is considerably longer in large spheroids than in exponentially-growing monolayers, the radiosensitivity of noncycling (but still viable) cells in spheroids is not significantly different from that of cycling spheroid cells, and the radiation-induced division delay is approximately twice as long in spheroid cells as in monolayer cells given equal radiation doses. The cell loss factor for spheroids of various sizes was calculated, by using the measured kinetic parameters in the basic equations for growth of a cell population. 157 references, 6 figures, 3 tables.

  17. Cell proliferation kinetics and radiation response in 9L tumor spheroids

    Sweigert, S.E.


    Cell kinetic parameters, including population doubling-time, cell cycle time, and growth fraction, were measured in 9L gliosarcoma spheroids. These parameters were studied as the spheroids grew from 50 μm to over 900 μm in diameter. Experiments relating the cell kinetic parameters to the radiation response of 9L spheroids were also carried out. The major findings were that the average cell cycle time (T/sub c/), is considerably longer in large spheroids than in exponentially-growing monolayers, the radiosensitivity of noncycling (but still viable) cells in spheroids is not significantly different from that of cycling spheroid cells, and the radiation-induced division delay is approximately twice as long in spheroid cells as in monolayer cells given equal radiation doses. The cell loss factor for spheroids of various sizes was calculated, by using the measured kinetic parameters in the basic equations for growth of a cell population. 157 references, 6 figures, 3 tables

  18. Response of maternal immune cells of irradiation of mouse embryos

    Nicholls, E.M.; Markovic, B.


    This work began as an attempt to explain the paradox of pregnancy - the survival and growth of the semi-allogenic embryo in an immunologically hostile environment. In 1982 and 1983 we reported the tracing of quinacrine labelled maternal leukocytes (WBC) in maternal, placental and embryonic mouse tissues by fluorescence microscopy. We found that cells in the placenta phagocytose labelled WBC, so that after 1-2 hours the labelled nuclear DNA is found as brightly fluorescing particles in the cytoplasm of the phagocytes with no evidence of it in the nuclei. Identical cells were observed in slide preparations of embryos which had been carefully separated from their placentas. We also found a small population of intact labelled lymphocytes, clearly maternal in origin, in the embryos. This seems to be another paradox - placental phagocytes are observed to be phagocytosing maternal WBC in the placenta and embryo, but there are also free maternal cells in the placenta and embryo. A theoretical explanation is that maternal lymphocytes alloreactive against the embryo will attempt to react with placental cells and in the process be phagocytosed, while other maternal cells will be able to enter the embryo where they could have a surveillance function, removing dead or mutant embryonic cells. To test this theory a series of experiments were carried out and are reported

  19. Relative contribution of "determinant selection" and "holes in the T-cell repertoire" to T-cell responses

    Schaeffer, E B; Sette, A; Johnson, D L


    -cell responses. Ia binding and Ia-restricted T-cell immunogenicity could be determined for a total of 54 peptide-MHC combinations. Only 30% of the 54 instances examined involved detectable Ia binding, but they represented almost all (12 of 13) of the immune responses found. However, binding to Ia......Using BALB/c and CBA/J mice, the I-region associated (Ia) binding capacity and T-cell immunogenicity of a panel of 14 overlapping peptides that span the entire sequence of the protein staphylococcal nuclease (Nase) was examined to evaluate major histocompatibility gene complex (MHC) control of T...... was not sufficient to ensure T-cell immunogenicity, since only 70% of the binding events were productive--i.e., were associated with an immune response. Thus, Ia molecules have the expected characteristics of a highly permissive capacity for antigen interaction that allows them to function as restriction elements...

  20. Modulation of Immune Responses by Exosomes Derived from Antigen-Presenting Cells

    Botros B. Shenoda


    Full Text Available Exosome-mediated signaling is important in mediating the inflammatory response. To exert their biological or pathophysiological functions in the recipient cells, exosomes deliver a diverse array of biomacromolecules including long and short coding and non-coding RNAs, proteins, and lipids. Exosomes secreted by antigen-presenting cells can confer therapeutic benefits by attenuating or stimulating the immune response. Exosomes play a crucial role in carrying and presenting functional major histocompatibility peptide complexes to modulate antigen-specific T cell responses. Exosomes from Dendritic Cells (DCs can activate T and B cells and have been explored for their immunostimulatory properties in cancer therapy. The immunosuppressive properties of exosomes derived from macrophages and DCs can reduce inflammation in animal models for several inflammatory disorders. This review focuses on the protective role of exosomes in attenuating inflammation or augmenting immune response, emphasizing studies on exosomes derived from DCs and macrophages.