The sex differences in nature of vascular endothelial stress: nitrergic mechanisms

NASA Astrophysics Data System (ADS)

Sindeev, Sergey; Gekaluyk, Artem; Ulanova, Maria; Agranovich, Ilana; Sharref, Ali Esmat; Semyachkina-Glushkovskaya, Oxana

2016-04-01

Here we studied the role of nitric oxide in cardiovascular regulation in male and female hypertensive rats under normal and stress conditions. We found that the severity of hypertension in females was lower than in males. Hypertensive females demonstrated more favorable pattern of cardiovascular responses to stress. Nitric oxide blockade by NG-nitro-L-arginine methyl ester (L-NAME) increased the mean arterial pressure and decreased the heart rate more effectively in females than in males. During stress, L-NAME modified the stress-induced cardiovascular responses more significantly in female compared with male groups. Our data show that hypertensive females demonstrated the more effective nitric oxide control of cardiovascular activity under normal and especially stress conditions than male groups. This sex differences may be important mechanism underlying greater in females vs. males stress-resistance of cardiovascular system and hypertension formation.

Autonomic consequences of arousal from sleep: mechanisms and implications.

PubMed

Horner, R L

1996-12-01

Normal spontaneous arousals from sleep are associated with transient increases in blood pressure, heart rate, and ventilation caused by large transient changes in autonomic output. These autonomic changes are out of proportion to obvious physiological need and are in excess of those observed in later periods of quiet wakefulness. This paper discusses some of the mechanisms underlying the cardio-respiratory consequences of arousal from sleep, and discusses why the normal onset of wakefulness may be associated with such large changes in autonomic output.

Effect of tibial plateau leveling osteotomy on femorotibial contact mechanics and stifle kinematics.

PubMed

Kim, Stanley E; Pozzi, Antonio; Banks, Scott A; Conrad, Bryan P; Lewis, Daniel D

2009-01-01

To evaluate the effects of tibial plateau leveling osteotomy (TPLO) on femorotibial contact mechanics and 3-dimensional (3D) kinematics in cranial cruciate ligament (CrCL)-deficient stifles of dogs. In vitro biomechanical study. Unpaired pelvic limbs from 8 dogs, weighing 28-35 kg. Digital pressure sensors placed subjacent to the menisci were used to measure femorotibial contact force, contact area, peak and mean contact pressure, and peak pressure location with the limb under an axial load of 30% body weight and a stifle angle of 135 degrees. Three-dimensional static poses of the stifle were obtained using a Microscribe digitizing arm. Each specimen was tested under normal, CrCL-deficient, and TPLO-treated conditions. Repeated measures analysis of variance with a Tukey post hoc test (P<.05) was used for statistical comparison. Significant disturbances to all measured contact mechanical variables were evident after CrCL transection, which corresponded to marked cranial tibial subluxation and increased internal tibial rotation in the CrCL-deficient stifle. No significant differences in 3D femorotibial alignment were observed between normal and TPLO-treated stifles; however, femorotibial contact area remained significantly smaller and peak contact pressures in both medial and lateral stifle compartments were positioned more caudally on the tibial plateau, when compared with normal. Whereas TPLO eliminates craniocaudal stifle instability during simulated weight bearing, the procedure fails to concurrently restore femorotibial contact mechanics to normal. Progression of stifle osteoarthritis in dogs treated with TPLO may be partly the result of abnormal stifle contact mechanics induced by altering the orientation of the proximal tibial articulating surface.

Is the normal heart rate ``chaotic'' due to respiration?

NASA Astrophysics Data System (ADS)

Wessel, Niels; Riedl, Maik; Kurths, Jürgen

2009-06-01

The incidence of cardiovascular diseases increases with the growth of the human population and an aging society, leading to very high expenses in the public health system. Therefore, it is challenging to develop sophisticated methods in order to improve medical diagnostics. The question whether the normal heart rate is chaotic or not is an attempt to elucidate the underlying mechanisms of cardiovascular dynamics and therefore a highly controversial topical challenge. In this contribution we demonstrate that linear and nonlinear parameters allow us to separate completely the data sets of the three groups provided for this controversial topic in nonlinear dynamics. The question whether these time series are chaotic or not cannot be answered satisfactorily without investigating the underlying mechanisms leading to them. We give an example of the dominant influence of respiration on heart beat dynamics, which shows that observed fluctuations can be mostly explained by respiratory modulations of heart rate and blood pressure (coefficient of determination: 96%). Therefore, we recommend reformulating the following initial question: "Is the normal heart rate chaotic?" We rather ask the following: "Is the normal heart rate `chaotic' due to respiration?"

A transparent bending-insensitive pressure sensor

NASA Astrophysics Data System (ADS)

Lee, Sungwon; Reuveny, Amir; Reeder, Jonathan; Lee, Sunghoon; Jin, Hanbit; Liu, Qihan; Yokota, Tomoyuki; Sekitani, Tsuyoshi; Isoyama, Takashi; Abe, Yusuke; Suo, Zhigang; Someya, Takao

2016-05-01

Measuring small normal pressures is essential to accurately evaluate external stimuli in curvilinear and dynamic surfaces such as natural tissues. Usually, sensitive and spatially accurate pressure sensors are achieved through conformal contact with the surface; however, this also makes them sensitive to mechanical deformation (bending). Indeed, when a soft object is pressed by another soft object, the normal pressure cannot be measured independently from the mechanical stress. Here, we show a pressure sensor that measures only the normal pressure, even under extreme bending conditions. To reduce the bending sensitivity, we use composite nanofibres of carbon nanotubes and graphene. Our simulations show that these fibres change their relative alignment to accommodate bending deformation, thus reducing the strain in individual fibres. Pressure sensitivity is maintained down to a bending radius of 80 μm. To test the suitability of our sensor for soft robotics and medical applications, we fabricated an integrated sensor matrix that is only 2 μm thick. We show real-time (response time of ∼20 ms), large-area, normal pressure monitoring under different, complex bending conditions.

Used Nuclear Fuel Loading and Structural Performance Under Normal Conditions of Transport- Demonstration of Approach and Results on Used Fuel Performance Characterization

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

Adkins, Harold; Geelhood, Ken; Koeppel, Brian

2013-09-30

This document addresses Oak Ridge National Laboratory milestone M2FT-13OR0822015 Demonstration of Approach and Results on Used Nuclear Fuel Performance Characterization. This report provides results of the initial demonstration of the modeling capability developed to perform preliminary deterministic evaluations of moderate-to-high burnup used nuclear fuel (UNF) mechanical performance under normal conditions of storage (NCS) and normal conditions of transport (NCT) conditions. This report also provides results from the sensitivity studies that have been performed. Finally, discussion on the long-term goals and objectives of this initiative are provided.

Gravitational force modulates G2/M phase exit in mechanically unloaded myoblasts

PubMed Central

Benavides Damm, Tatiana; Franco-Obregón, Alfredo; Egli, Marcel

2013-01-01

Prolonged spaceflight gives rise to muscle loss and reduced strength, a condition commonly referred to as space atrophy. During exposure to microgravity, skeletal muscle myoblasts are mechanically unloaded and respond with attenuated cell proliferation, slowed cell cycle progression, and modified protein expression. To elucidate the underlying mechanisms by which muscle mass declines in response to prolonged microgravity exposure, we grew C2C12 mouse muscle cells under conditions of simulated microgravity (SM) and analyzed their proliferative capacity, cell cycle progression, and cyclin B and D expression. We demonstrated that the retarded cell growth observed in SM was correlated with an approximate 16 h delay in G2/M phase progression, where cells accumulated specifically between the G2 checkpoint and the onset of anaphase, concomitantly with a positive expression for cyclin B. The effect was specific for gravitational mechanical unloading as cells grown under conditions of hypergravity (HG, 4 g) for similar durations of time exhibited normal proliferation and normal cell cycle progression. Our results show that SM and HG exert phenomenological distinct responses over cell cycle progression. The deficits of SM can be restored by terrestrial gravitational force, whereas the effects of HG are indistinguishable from the 1 g control. This suggests that the mechanotransduction apparatus of cells responds differently to mechanical unloading and loading. PMID:23974110

Laser Absorption by Over-Critical Plasmas

NASA Astrophysics Data System (ADS)

May, J.; Tonge, J.; Fiuza, F.; Fonseca, R. A.; Silva, L. O.; Mori, W. B.

2015-11-01

Absorption of high intensity laser light by matter has important applications to emerging sciences and technology, such as Fast Ignition ICF and ion acceleration. As such, understanding the underlying mechanisms of this absorption is key to developing these technologies. Critical features which distinguish the interaction of high intensity light - defined here as a laser field having a normalized vector potential greater than unity - are that the reaction of the material to the fields results in sharp high-density interfaces; and that the movement of the electrons is in general relativistic, both in a fluid and a thermal sense. The results of these features are that the absorption mechanisms are qualitatively distinct from those at lower intensities. We will review previous work, by our group and others, on the absorption mechanisms, and highlight current research. We will show that the standing wave structure of the reflected laser light is key to particle dynamics for normally incident lasers. The authors acknowledge the support of the Department of Energy under contract DE-NA 0001833 and the National Science Foundation under contract ACI 1339893.

Altered DNA methylation: a secondary mechanism involved in carcinogenesis.

PubMed

Goodman, Jay I; Watson, Rebecca E

2002-01-01

This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?

On the cellular autoimmune mechanism for eliminating erythrocytes normally and under extreme influences

NASA Technical Reports Server (NTRS)

Pukhova, Y. I.; Terskov, I. A.; Anikina, A. Y.; Shashkin, A. V.

1980-01-01

The presence of an autoimmune cellular mechanism for destroying erythrocytes on the basis of results of experiments in vivo is demonstrated in the blood and the organs. This mechanism is made up of a population of immunocompetent killer-lymphocytes which originates in the bone marrow and the thymus, and which is manifested in the local hemolysis effect.

Comparative metabolites profiles of osthole in normal and osteoporosis rats using liquid chromatography quadrupole time-of-flight mass spectrometry.

PubMed

Wang, Nani; Wang, Xuping; Zhang, Yang; Zhang, Qiaoyan; Xu, Pingcui; Xin, Hailiang; Wu, Renjie; Shou, Dan; Qin, Luping

2018-05-30

Osthole is a derivative of coumnarin, which has been used to treat several diseases, including osteoporosis. To investigate the metabolite profile of osthole in osteoporosis rats was utilized to understand its underlying mechanisms of its anti-osteoporosis effect. In this study, plasma samples were collected from normal and osteoporosis rats after oral administration of osthole and analyzed to identify the metabolites of osthole by high performance liquid chromatography quadrupole time-of-flight mass spectrometry. By comparing the molecular weight and MS fragmentation of the metabolites with those of parent drug and reference standards, a total of 36 metabolites in plasma were identified. Demethylation, hydroxylation, hydroxymethylene loss and reduction, and subsequent glucuronidation, methylation and sulfation were the major metabolic pathways of osthole in both normal and osteoporosis rats. A specific hydration metabolic pathway was found in osteoporosis rats. These results provided a meaningful basis for studying the underlying mechanism of the anti-osteoporosis effect of osthole. Copyright © 2018 Elsevier B.V. All rights reserved.

Joint Contact Stress

PubMed Central

Brand, Richard A

2005-01-01

A joint's normal mechanical history contributes to the maintenance of articular cartilage and underlying bone. Loading facilitates the flow of nutrients into cartilage and waste products away, and additionally provides the mechanical signals essential for normal cell and tissue maintenance. Deleteriously low or high contact stresses have been presumed to result in joint deterioration, and particular aspects of the mechanical environment may facilitate repair of damaged cartilage. For decades, investigators have explored static joint contact stresses (under some more or less arbitrary condition) as a surrogate of the relevant mechanical history. Contact stresses have been estimated in vitro in many joints and in a number of species, although only rarely in vivo. Despite a number of widely varying techniques (and spatial resolutions) to measure these contact stresses, reported ranges of static peak normal stresses are relatively similar from joint to joint across species, and in the range of 0.5 to 5.0 MPa. This suggests vertebrate diarthrodial joints have evolved to achieve similar mechanical design criteria. Available evidence also suggests some disorders of cartilage deterioration are associated with somewhat higher peak pressures ranging from 1-20 MPa, but overlapping the range of normal pressures. Some evidence and considerable logic suggests static contact stresses per se do not predict cartilage responses, but rather temporal aspects of the contact stress history. Static contact stresses may therefore not be a reasonable surrogate for biomechanical studies. Rather, temporal and spatial aspects of the loading history undoubtedly induce beneficial and deleterious biological responses. Finally, since all articular cartilage experiences similar stresses, the concept of a "weight-bearing" versus a "non-weight-bearing" joint seems flawed, and should be abandoned. PMID:16089079

Biomechanical mechanism of lateral trunk lean gait for knee osteoarthritis patients.

PubMed

Tokuda, Kazuki; Anan, Masaya; Takahashi, Makoto; Sawada, Tomonori; Tanimoto, Kenji; Kito, Nobuhiro; Shinkoda, Koichi

2018-01-03

The biomechanical mechanism of lateral trunk lean gait employed to reduce external knee adduction moment (KAM) for knee osteoarthritis (OA) patients is not well known. This mechanism may relate to the center of mass (COM) motion. Moreover, lateral trunk lean gait may affect motor control of the COM displacement. Uncontrolled manifold (UCM) analysis is an evaluation index used to understand motor control and variability of the motor task. Here we aimed to clarify the biomechanical mechanism to reduce KAM during lateral trunk lean gait and how motor variability controls the COM displacement. Twenty knee OA patients walked under two conditions: normal and lateral trunk lean gait conditions. UCM analysis was performed with respect to the COM displacement in the frontal plane. We also determined how the variability is structured with regards to the COM displacement as a performance variable. The peak KAM under lateral trunk lean gait was lower than that under normal gait. The reduced peak KAM observed was accompanied by medially shifted knee joint center, shortened distance of the center of pressure to knee joint center, and shortened distance of the knee-ground reaction force lever arm during the stance phase. Knee OA patients with lateral trunk lean gait could maintain kinematic synergy by utilizing greater segmental configuration variance to the performance variable. However, the COM displacement variability of lateral trunk lean gait was larger than that of normal gait. Our findings may provide clinical insights to effectively evaluate and prescribe gait modification training for knee OA patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Signatures of the Mott transition in the antiferromagnetic state of the two-dimensional Hubbard model

DOE PAGES

Fratino, L.; Sémon, P.; Charlebois, M.; ...

2017-06-06

The properties of a phase with large correlation length can be strongly influenced by the underlying normal phase. Here, we illustrate this by studying the half-filled two-dimensional Hubbard model using cellular dynamical mean-field theory with continuous-time quantum Monte Carlo. Sharp crossovers in the mechanism that favors antiferromagnetic correlations and in the corresponding local density of states are observed. We found that these crossovers occur at values of the interaction strength U and temperature T that are controlled by the underlying normal-state Mott transition.

Relating normalization to neuronal populations across cortical areas.

PubMed

Ruff, Douglas A; Alberts, Joshua J; Cohen, Marlene R

2016-09-01

Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. Copyright © 2016 the American Physiological Society.

Relating normalization to neuronal populations across cortical areas

PubMed Central

Alberts, Joshua J.; Cohen, Marlene R.

2016-01-01

Normalization, which divisively scales neuronal responses to multiple stimuli, is thought to underlie many sensory, motor, and cognitive processes. In every study where it has been investigated, neurons measured in the same brain area under identical conditions exhibit a range of normalization, ranging from suppression by nonpreferred stimuli (strong normalization) to additive responses to combinations of stimuli (no normalization). Normalization has been hypothesized to arise from interactions between neuronal populations, either in the same or different brain areas, but current models of normalization are not mechanistic and focus on trial-averaged responses. To gain insight into the mechanisms underlying normalization, we examined interactions between neurons that exhibit different degrees of normalization. We recorded from multiple neurons in three cortical areas while rhesus monkeys viewed superimposed drifting gratings. We found that neurons showing strong normalization shared less trial-to-trial variability with other neurons in the same cortical area and more variability with neurons in other cortical areas than did units with weak normalization. Furthermore, the cortical organization of normalization was not random: neurons recorded on nearby electrodes tended to exhibit similar amounts of normalization. Together, our results suggest that normalization reflects a neuron's role in its local network and that modulatory factors like normalization share the topographic organization typical of sensory tuning properties. PMID:27358313

A Digital Image-Based Discrete Fracture Network Model and Its Numerical Investigation of Direct Shear Tests

NASA Astrophysics Data System (ADS)

Wang, Peitao; Cai, Meifeng; Ren, Fenhua; Li, Changhong; Yang, Tianhong

2017-07-01

This paper develops a numerical approach to determine the mechanical behavior of discrete fractures network (DFN) models based on digital image processing technique and particle flow code (PFC2D). A series of direct shear tests of jointed rocks were numerically performed to study the effect of normal stress, friction coefficient and joint bond strength on the mechanical behavior of joint rock and evaluate the influence of micro-parameters on the shear properties of jointed rocks using the proposed approach. The complete shear stress-displacement curve of the DFN model under direct shear tests was presented to evaluate the failure processes of jointed rock. The results show that the peak and residual strength are sensitive to normal stress. A higher normal stress has a greater effect on the initiation and propagation of cracks. Additionally, an increase in the bond strength ratio results in an increase in the number of both shear and normal cracks. The friction coefficient was also found to have a significant influence on the shear strength and shear cracks. Increasing in the friction coefficient resulted in the decreasing in the initiation of normal cracks. The unique contribution of this paper is the proposed modeling technique to simulate the mechanical behavior of jointed rock mass based on particle mechanics approaches.

Effect of cranial cruciate ligament deficiency, tibial plateau leveling osteotomy, and tibial tuberosity advancement on contact mechanics and alignment of the stifle in flexion.

PubMed

Kim, Stanley E; Pozzi, Antonio; Banks, Scott A; Conrad, Bryan P; Lewis, Daniel D

2010-04-01

To assess contact mechanics and 3-dimensional (3-D) joint alignment in cranial cruciate ligament (CCL)-deficient stifles before and after tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA) with the stifle in 90 degrees of flexion. In vitro biomechanical study. Cadaveric pelvic limb pairs (n=8) from dogs weighing 28-35 kg. Contralateral limbs were assigned to receive TPLO or TTA. Digital pressure sensors were used to measure femorotibial contact area, peak and mean contact pressure, and peak pressure location with the limb under a load of 30% body weight and stifle flexion angle of 90 degrees . 3-D poses were obtained using a Microscribe digitizer. Specimens were tested under normal, CCL deficient, and treatment conditions. Significant disturbances in alignment were not observed after CCL transection, although medial contact area was 10% smaller than normal (P=.003). There were no significant differences in contact mechanics or alignment between normal and TTA conditions; TPLO induced 6 degrees varus angulation (P<.001), 26% decrease in lateral peak pressure (P=.027), and 18% increase in medial mean pressure (P=.008) when compared with normal. Cranial tibial subluxation is nominal in CCL-deficient stifles loaded in flexion. Stifle alignment and contact mechanics are not altered by TTA, whereas TPLO causes mild varus and a subsequent increase in medial compartment loading. Cranial tibial subluxation of CCL-deficient stifles may not occur during postures that load the stifle in flexion. The significance of minor changes in loading patterns after TPLO is unknown.

Ischemic Preconditioning Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat

PubMed Central

Serafín, Anna; Roselló-Catafau, Joan; Prats, Neus; Xaus, Carme; Gelpí, Emilio; Peralta, Carmen

2002-01-01

Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation. PMID:12163383

Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

PubMed Central

2015-01-01

Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent.

PubMed

Allen, Joshua E; Crowder, Roslyn N; Crowder, Roslyn; El-Deiry, Wafik S

2015-01-01

We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer.

First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent

PubMed Central

Allen, Joshua E.; Crowder, Roslyn; El-Deiry, Wafik S.

2015-01-01

We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer. PMID:26580220

Mechanical remodeling of normally sized mammalian cells under a gravity vector.

PubMed

Zhang, Chen; Zhou, Lüwen; Zhang, Fan; Lü, Dongyuan; Li, Ning; Zheng, Lu; Xu, Yanhong; Li, Zhan; Sun, Shujin; Long, Mian

2017-02-01

Translocation of the dense nucleus along a gravity vector initiates mechanical remodeling of a cell, but the underlying mechanisms of cytoskeletal network and focal adhesion complex (FAC) reorganization in a mammalian cell remain unclear. We quantified the remodeling of an MC3T3-E1 cell placed in upward-, downward-, or edge-on-orientated substrate. Nucleus longitudinal translocation presents a high value in downward orientation at 24 h or in edge-on orientation at 72 h, which is consistent with orientation-dependent distribution of perinuclear actin stress fibers and vimentin cords. Redistribution of total FAC area and fractionized super mature adhesion number coordinates this dependence at short duration. This orientation-dependent remodeling is associated with nucleus flattering and lamin A/C phosphorylation. Actin depolymerization or Rho-associated protein kinase signaling inhibition abolishes the orientation dependence of nucleus translocation, whereas tubulin polymerization inhibition or vimentin disruption reserves the dependence. A biomechanical model is therefore proposed for integrating the mechanosensing of nucleus translocation with cytoskeletal remodeling and FAC reorganization induced by a gravity vector.-Zhang, C., Zhou, L., Zhang, F., Lü, D., Li, N., Zheng, L., Xu, Y., Li, Z., Sun, S., Long, M. Mechanical remodeling of normally sized mammalian cells under a gravity vector. © FASEB.

Corticocortical feedback increases the spatial extent of normalization.

PubMed

Nassi, Jonathan J; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T

2014-01-01

Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a "normalization pool." Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing.

Corticocortical feedback increases the spatial extent of normalization

PubMed Central

Nassi, Jonathan J.; Gómez-Laberge, Camille; Kreiman, Gabriel; Born, Richard T.

2014-01-01

Normalization has been proposed as a canonical computation operating across different brain regions, sensory modalities, and species. It provides a good phenomenological description of non-linear response properties in primary visual cortex (V1), including the contrast response function and surround suppression. Despite its widespread application throughout the visual system, the underlying neural mechanisms remain largely unknown. We recently observed that corticocortical feedback contributes to surround suppression in V1, raising the possibility that feedback acts through normalization. To test this idea, we characterized area summation and contrast response properties in V1 with and without feedback from V2 and V3 in alert macaques and applied a standard normalization model to the data. Area summation properties were well explained by a form of divisive normalization, which computes the ratio between a neuron's driving input and the spatially integrated activity of a “normalization pool.” Feedback inactivation reduced surround suppression by shrinking the spatial extent of the normalization pool. This effect was independent of the gain modulation thought to mediate the influence of contrast on area summation, which remained intact during feedback inactivation. Contrast sensitivity within the receptive field center was also unaffected by feedback inactivation, providing further evidence that feedback participates in normalization independent of the circuit mechanisms involved in modulating contrast gain and saturation. These results suggest that corticocortical feedback contributes to surround suppression by increasing the visuotopic extent of normalization and, via this mechanism, feedback can play a critical role in contextual information processing. PMID:24910596

30 CFR 18.23 - Limitation of external surface temperatures.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction... external surfaces of mechanical or electrical components shall not exceed 150 °C. (302 °F.) under normal...

Selection of relatively exact reference genes for gene expression studies in goosegrass (Eleusine indica) under herbicide stress.

PubMed

Chen, Jingchao; Huang, Zhaofeng; Huang, Hongjuan; Wei, Shouhui; Liu, Yan; Jiang, Cuilan; Zhang, Jie; Zhang, Chaoxian

2017-04-21

Goosegrass (Eleusine indica) is one of the most serious annual grassy weeds worldwide, and its evolved herbicide-resistant populations are more difficult to control. Quantitative real-time PCR (qPCR) is a common technique for investigating the resistance mechanism; however, there is as yet no report on the systematic selection of stable reference genes for goosegrass. This study proposed to test the expression stability of 9 candidate reference genes in goosegrass in different tissues and developmental stages and under stress from three types of herbicide. The results show that for different developmental stages and organs (control), eukaryotic initiation factor 4 A (eIF-4) is the most stable reference gene. Chloroplast acetolactate synthase (ALS) is the most stable reference gene under glyphosate stress. Under glufosinate stress, eIF-4 is the best reference gene. Ubiquitin-conjugating enzyme (UCE) is the most stable reference gene under quizalofop-p-ethyl stress. The gene eIF-4 is the recommended reference gene for goosegrass under the stress of all three herbicides. Moreover, pairwise analysis showed that seven reference genes were sufficient to normalize the gene expression data under three herbicides treatment. This study provides a list of reliable reference genes for transcript normalization in goosegrass, which will facilitate resistance mechanism studies in this weed species.

Quantification of Age-Related Lung Tissue Mechanics under Mechanical Ventilation.

PubMed

Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

2017-09-29

Elderly patients with obstructive lung diseases often receive mechanical ventilation to support their breathing and restore respiratory function. However, mechanical ventilation is known to increase the severity of ventilator-induced lung injury (VILI) in the elderly. Therefore, it is important to investigate the effects of aging to better understand the lung tissue mechanics to estimate the severity of ventilator-induced lung injuries. Two age-related geometric models involving human bronchioles from generation G10 to G23 and alveolar sacs were developed. The first is for a 50-year-old (normal) and second is for an 80-year old (aged) model. Lung tissue mechanics of normal and aged models were investigated under mechanical ventilation through computational simulations. Results obtained indicated that lung tissue strains during inhalation (t = 0.2 s) decreased by about 40% in the alveolar sac (G23) and 27% in the bronchiole (G20), respectively, for the 80-year-old as compared to the 50-year-old. The respiratory mechanics parameters (work of breathing per unit volume and maximum tissue strain) over G20 and G23 for the 80-year-old decreased by about 64% (three-fold) and 80% (four-fold), respectively, during the mechanical ventilation breathing cycle. However, there was a significant increase (by about threefold) in lung compliance for the 80-year-old in comparison to the 50-year-old. These findings from the computational simulations demonstrated that lung mechanical characteristics are significantly compromised in aging tissues, and these effects were quantified in this study.

Antioxidant activity and induction of mechanisms of resistance to stresses related to the inoculation with Azospirillum brasilense.

PubMed

Fukami, Josiane; Ollero, Francisco Javier; de la Osa, Clara; Valderrama-Fernández, Rocio; Nogueira, Marco Antonio; Megías, Manuel; Hungria, Mariangela

2018-06-07

We investigated the effects of Azospirillum brasilense strains Ab-V5 and Ab-V6 in the induction of mechanisms of systemic acquired resistance (SAR) and induced system resistance (ISR) on maize (Zea mays L.) plants. Under normal growth conditions, the treatments consisted of the standard inoculation of cells at sowing, and leaf spray of cells or their metabolites at the V2.5 growth stage; under saline stress (170 mM NaCl), the treatment consisted of standard single and co-inoculation of A. brasilense and Rhizobium tropici. The main compounds in the Azospirillum metabolites were identified as indole-3-acetic acid (IAA) and salicylic acid (SA). Under normal conditions, A. brasilense cells applied at sowing or by leaf spray increased the activities of catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) in leaves, and of ascorbate peroxidase (APX) in roots; however, interestingly, in general the highest activities were observed by leaf spray of metabolites. Under normal conditions, the highest levels of salicylic acid (SA) and jasmonic acid (JA) were achieved in leaves by leaf spray of metabolites, of SA in roots by leaf spray of cells, and of JA in roots by standard inoculation and leaf spray of metabolites. Under saline stress, plant protection occurred via SA and abscisic acid (ABA), but not JA. In general, inoculation resulted in further increases in SA in leaves and roots, and ABA in leaves. We hypothesize that A. brasilense confers protection to maize plants by simultaneous induction of JA and SA pathways, and, under saline stressing conditions, by SA and ABA pathways.

Cardiac mechanics: Physiological, clinical, and mathematical considerations

NASA Technical Reports Server (NTRS)

Mirsky, I. (Editor); Ghista, D. N.; Sandler, H.

1974-01-01

Recent studies concerning the basic physiological and biochemical principles underlying cardiac muscle contraction, methods for the assessment of cardiac function in the clinical situation, and mathematical approaches to cardiac mechanics are presented. Some of the topics covered include: cardiac ultrastructure and function in the normal and failing heart, myocardial energetics, clinical applications of angiocardiography, use of echocardiography for evaluating cardiac performance, systolic time intervals in the noninvasive assessment of left ventricular performance in man, evaluation of passive elastic stiffness for the left ventricle and isolated heart muscle, a conceptual model of myocardial infarction and cardiogenic shock, application of Huxley's sliding-filament theory to the mechanics of normal and hypertrophied cardiac muscle, and a rheological modeling of the intact left ventricle. Individual items are announced in this issue.

Symptomatic Hypercalcemia in a Patient with B-cell Chronic Lymphocytic Leukemia - A Case Report and Review of the Literature.

PubMed

Koutroumpakis, Efstratios; Lobe, Montgomery; McCarthy, Lezah; Mehdi, Syed

Hypercalcemia due to malignancy is well described in the literature and a common paraneoplastic finding in certain solid tumors. Hematologic malignancies, however, are less frequently associated with hypercalcemia with the exception of myelomas and T-cell lymphomas. This case report describes a patient with B-cell chronic lymphocytic leukemia (B-CLL) who developed symptomatic hypercalcemia. None of the pathogenetic mechanisms of malignancy-associated hypercalcemia already described in the literature could explain the pathogenesis of hypercalcemia in our patient. Calcium levels were normalized after initial treatment and remained within normal limits following treatment of the underlying B-CLL. The follow-up period was 26 months. The normalization of calcium levels was closely associated with the drop in the absolute lymphocyte count. Symptomatic hypercalcemia in B-CLL is exceedingly rare and only documented a few times in the literature. Hypercalcemia, in the present case, was not caused by any of the mechanisms already described in the literature and responded well to treatment of the underlying B-CLL. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Shear-coupled grain-boundary migration dependence on normal strain/stress

NASA Astrophysics Data System (ADS)

Combe, N.; Mompiou, F.; Legros, M.

2017-08-01

In specific conditions, grain-boundary (GB) migration occurs in polycrystalline materials as an alternative vector of plasticity compared to the usual dislocation activity. The shear-coupled GB migration, the expected most efficient GB based mechanism, couples the GB motion to an applied shear stress. Stresses on GB in polycrystalline materials seldom have, however, a unique pure shear component. This work investigates the influence of a normal strain on the shear coupled migration of a Σ 13 (320 )[001 ] GB in a copper bicrystal using atomistic simulations. We show that the yield shear stress inducing the GB migration strongly depends on the applied normal stress. Beyond, the application of a normal stress on this GB qualitatively modifies the GB migration: while the Σ 13 (320 )[001 ] GB shear couples following the 〈110 〉 migration mode without normal stress, we report the observation of the 〈010 〉 mode under a sufficiently high tensile normal stress. Using the nudge elastic band method, we uncover the atomistic mechanism of this 〈010 〉 migration mode and energetically characterize it.

Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

PubMed

Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

2015-04-01

Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

An integrative approach to the assessment of narcissism.

PubMed

Roche, Michael J; Pincus, Aaron L; Lukowitsky, Mark R; Ménard, Kim S; Conroy, David E

2013-01-01

Narcissism research is poorly calibrated across fields of study in part due to confusion over how to integrate normal and pathological descriptions of narcissism. We argue that pathological and normal narcissism can be integrated in a single model that organizes around self-regulation mechanisms. We present theoretical and empirical support for this interpretation, and demonstrate that modeling pathological and normal narcissism as 2 dimensions underlying the narcissistic character can help to resolve some of the inconsistencies in the field regarding how to best assess adaptive and maladaptive expressions of narcissism.

The Particularities of the Monologue Speech Type Manifestations in Stuttering Schoolchildren with Tatar-Russian Bilingualism Compared to the Normality

ERIC Educational Resources Information Center

Osipovskaya, Marina P.; Sharifzyanova, Kadriya Sh.; Zamaletdinova, Zalfira I.

2016-01-01

Actuality of studying of an issue on specific manifestations of a monologue speech type in bilingual schoolchildren with stutter has been stipulated by the necessity of elaboration of a constituent concept on central mechanisms underlying this kind of communication disorder, on the nature of disturbances of speech formation mechanisms in the…

An accurate and efficient method for piezoelectric coated functional devices based on the two-dimensional Green’s function for a normal line force and line charge

NASA Astrophysics Data System (ADS)

Hou, Peng-Fei; Zhang, Yang

2017-09-01

Because most piezoelectric functional devices, including sensors, actuators and energy harvesters, are in the form of a piezoelectric coated structure, it is valuable to present an accurate and efficient method for obtaining the electro-mechanical coupling fields of this coated structure under mechanical and electrical loads. With this aim, the two-dimensional Green’s function for a normal line force and line charge on the surface of coated structure, which is a combination of an orthotropic piezoelectric coating and orthotropic elastic substrate, is presented in the form of elementary functions based on the general solution method. The corresponding electro-mechanical coupling fields of this coated structure under arbitrary mechanical and electrical loads can then be obtained by the superposition principle and Gauss integration. Numerical results show that the presented method has high computational precision, efficiency and stability. It can be used to design the best coating thickness in functional devices, improve the sensitivity of sensors, and improve the efficiency of actuators and energy harvesters. This method could be an efficient tool for engineers in engineering applications.

Investigation of the mechanisms of membrane fouling by intracellular organic matter under different iron treatments during ultrafiltration.

PubMed

Huang, Weiwei; Qin, Xiao; Dong, Bingzhi; Zhou, Wenzong; Lv, Weiguang

2018-05-30

Iron is an important trace element in algal growth and water eutrophication. This study focused on the ultrafiltration (UF) membrane fouling mechanism by the intracellular organic matter (IOM) of Microcystis aeruginosa under different iron treatments. The results indicated that the membranes experienced faster flux decline and worse fouling reversibility when the IOM formed under low iron concentrations. In contrast, less IOM membrane fouling was found under normal and high iron concentrations. The mass balances of the dissolved organic carbon (DOC) content implied that the IOM in the low-iron treatment was associated with higher IOM retention and a higher capacity of reversibly deposited organics, whereas more IOM in the high-iron treatment passed through the UF membrane. The IOM in the low-iron treatment was composed of more biopolymer macromolecules, whereas the IOM in the high-iron treatment contained more UV-absorbing hydrophobic organics. The fluorescence excitation-emission matrix (EEM) spectra coupled with peak-fitting analysis implied that the fouling associated with protein-like components was more irreversible in the low-iron treatment than those in the normal- and high-iron treatments. Cake formation combined with intermediate blocking was identified as the main membrane fouling mechanism responsible for the flux decline caused by IOM solutions in the three iron treatments in this study. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neural control of renal tubular solute and water transport.

PubMed

DiBona, G F

1989-01-01

The neural control of renal tubular solute and water transport is recognized as an important physiological mechanism in the overall regulation of solute and water homeostasis by the mammalian organism. Recent studies have expanded the understanding of this mechanism concerning the transport of diverse solutes with beginning insight into the precise nature of the cellular transport processes involved. The modulatory roles of both circulating and intrarenal hormonal systems on the responses to alterations in the magnitude of efferent renal sympathetic nerve activity are being understood from the nerve terminal release of neurotransmitter to influences on cellular transport processes which determine the overall effect. When dietary sodium intake is normal or only modestly reduced, intact renal innervation is not essential for normal renal sodium conservation. However, when dietary sodium intake is severely restricted, there is maximum engagement of all mechanisms known to participate in renal sodium conservation and, under these conditions, intact renal innervation is essential for normal renal sodium conservation.

Unequal effects of speech and nonspeech contexts on the perceptual normalization of Cantonese level tones.

PubMed

Zhang, Caicai; Peng, Gang; Wang, William S-Y

2012-08-01

Context is important for recovering language information from talker-induced variability in acoustic signals. In tone perception, previous studies reported similar effects of speech and nonspeech contexts in Mandarin, supporting a general perceptual mechanism underlying tone normalization. However, no supportive evidence was obtained in Cantonese, also a tone language. Moreover, no study has compared speech and nonspeech contexts in the multi-talker condition, which is essential for exploring the normalization mechanism of inter-talker variability in speaking F0. The other question is whether a talker's full F0 range and mean F0 equally facilitate normalization. To answer these questions, this study examines the effects of four context conditions (speech/nonspeech × F0 contour/mean F0) in the multi-talker condition in Cantonese. Results show that raising and lowering the F0 of speech contexts change the perception of identical stimuli from mid level tone to low and high level tone, whereas nonspeech contexts only mildly increase the identification preference. It supports the speech-specific mechanism of tone normalization. Moreover, speech context with flattened F0 trajectory, which neutralizes cues of a talker's full F0 range, fails to facilitate normalization in some conditions, implying that a talker's mean F0 is less efficient for minimizing talker-induced lexical ambiguity in tone perception.

Selection of relatively exact reference genes for gene expression studies in goosegrass (Eleusine indica) under herbicide stress

PubMed Central

Chen, Jingchao; Huang, Zhaofeng; Huang, Hongjuan; Wei, Shouhui; Liu, Yan; Jiang, Cuilan; Zhang, Jie; Zhang, Chaoxian

2017-01-01

Goosegrass (Eleusine indica) is one of the most serious annual grassy weeds worldwide, and its evolved herbicide-resistant populations are more difficult to control. Quantitative real-time PCR (qPCR) is a common technique for investigating the resistance mechanism; however, there is as yet no report on the systematic selection of stable reference genes for goosegrass. This study proposed to test the expression stability of 9 candidate reference genes in goosegrass in different tissues and developmental stages and under stress from three types of herbicide. The results show that for different developmental stages and organs (control), eukaryotic initiation factor 4 A (eIF-4) is the most stable reference gene. Chloroplast acetolactate synthase (ALS) is the most stable reference gene under glyphosate stress. Under glufosinate stress, eIF-4 is the best reference gene. Ubiquitin-conjugating enzyme (UCE) is the most stable reference gene under quizalofop-p-ethyl stress. The gene eIF-4 is the recommended reference gene for goosegrass under the stress of all three herbicides. Moreover, pairwise analysis showed that seven reference genes were sufficient to normalize the gene expression data under three herbicides treatment. This study provides a list of reliable reference genes for transcript normalization in goosegrass, which will facilitate resistance mechanism studies in this weed species. PMID:28429727

Cognitive interventions for addiction medicine: Understanding the underlying neurobiological mechanisms

PubMed Central

Zilverstand, Anna; Parvaz, Muhammad A.; Moeller, Scott J.; Goldstein, Rita Z.

2016-01-01

Neuroimaging provides a tool for investigating the neurobiological mechanisms of cognitive interventions in addiction. The aim of this review was to describe the brain circuits that are recruited during cognitive interventions, examining differences between various treatment modalities while highlighting core mechanisms, in drug addicted individuals. Based on a systematic Medline search we reviewed neuroimaging studies on cognitive behavioral therapy, cognitive inhibition of craving, motivational interventions, emotion regulation, mindfulness, and neurofeedback training in addiction. Across intervention modalities, common results included the normalization of aberrant activity in the brain’s reward circuitry, and the recruitment and strengthening of the brain’s inhibitory control network. Results suggest that different cognitive interventions act, at least partly, through recruitment of a common inhibitory control network as a core mechanism. This implies potential transfer effects between training modalities. Overall, results confirm that chronically hypoactive prefrontal regions implicated in cognitive control in addiction can be normalized through cognitive means. PMID:26822363

Abnormal Neurocirculatory Control During Exercise in Humans with Chronic Renal Failure

PubMed Central

Park, Jeanie; Middlekauff, Holly R.

2014-01-01

Abnormal neurocirculatory control during exercise is one important mechanism leading to exercise intolerance in patients with both end-stage renal disease (ESRD) and earlier stages of chronic kidney disease (CKD). This review will provide an overview of mechanisms underlying abnormal neurocirculatory and hemodynamic responses to exercise in patients with kidney disease. Recent studies have shown that ESRD and CKD patients have an exaggerated increase in blood pressure (BP) during both isometric and rhythmic exercise. Subsequent studies examining the role of the exercise pressor reflex in the augmented pressor response revealed that muscle sympathetic nerve activity (MSNA) was not augmented during exercise in these patients, and metaboreflex-mediated increases in MSNA were blunted, while mechanoreflex-mediated increases were preserved under basal conditions. However, normalizing the augmented BP response during exercise via infusion of nitroprusside (NTP), and thereby equalizing baroreflex-mediated suppression of MSNA, an important modulator of the final hemodynamic response to exercise, revealed that CKD patients had an exaggerated increase in MSNA during isometric and rhythmic exercise. In addition, mechanoreflex-mediated control was augmented, and metaboreceptor blunting was no longer apparent in CKD patients with baroreflex normalization. Factors leading to mechanoreceptor sensitization, and other mechanisms underlying the exaggerated exercise pressor response, such as impaired functional sympatholysis, should be investigated in future studies. PMID:25458430

Resveratrol increases nucleus pulposus matrix synthesis through activating the PI3K/Akt signaling pathway under mechanical compression in a disc organ culture.

PubMed

Han, Xiaorui; Leng, Xiaoming; Zhao, Man; Wu, Mei; Chen, Amei; Hong, Guoju; Sun, Ping

2017-12-22

Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc function. Mechanical overloading seriously decreases matrix synthesis and increases matrix degradation. The present study aims to investigate the effects of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude mechanical compression and the potential mechanism underlying this process. Porcine discs were perfusion-cultured and subjected to a relatively high-magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once per day) for 7 days in a mechanically active bioreactor. The non-compressed discs were used as controls. Resveratrol was added along with culture medium to observe the effects of resveratrol on NP matrix synthesis under mechanical load respectively. NP matrix synthesis was evaluated by histology, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix macromolecules (aggrecan and collagen II). Results showed that this high-magnitude mechanical compression significantly decreased NP matrix content, indicated by the decreased staining intensity of Alcian Blue and biochemical content (GAG and HYP), and the down-regulated expression of NP matrix macromolecules (aggrecan and collagen II). Further analysis indicated that resveratrol partly stimulated NP matrix synthesis and increased activity of the PI3K/Akt pathway in a dose-dependent manner under mechanical compression. Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical overloading, and the activation of the PI3K/Akt pathway may participate in this regulatory process. Resveratrol may be promising to regenerate mechanical overloading-induced disc degeneration. © 2017 The Author(s).

Beyond Correlation: Do Color Features Influence Attention in Rainforest?

PubMed Central

Frey, Hans-Peter; Wirz, Kerstin; Willenbockel, Verena; Betz, Torsten; Schreiber, Cornell; Troscianko, Tomasz; König, Peter

2011-01-01

Recent research indicates a direct relationship between low-level color features and visual attention under natural conditions. However, the design of these studies allows only correlational observations and no inference about mechanisms. Here we go a step further to examine the nature of the influence of color features on overt attention in an environment in which trichromatic color vision is advantageous. We recorded eye-movements of color-normal and deuteranope human participants freely viewing original and modified rainforest images. Eliminating red–green color information dramatically alters fixation behavior in color-normal participants. Changes in feature correlations and variability over subjects and conditions provide evidence for a causal effect of red–green color-contrast. The effects of blue–yellow contrast are much smaller. However, globally rotating hue in color space in these images reveals a mechanism analyzing color-contrast invariant of a specific axis in color space. Surprisingly, in deuteranope participants we find significantly elevated red–green contrast at fixation points, comparable to color-normal participants. Temporal analysis indicates that this is due to compensatory mechanisms acting on a slower time scale. Taken together, our results suggest that under natural conditions red–green color information contributes to overt attention at a low-level (bottom-up). Nevertheless, the results of the image modifications and deuteranope participants indicate that evaluation of color information is done in a hue-invariant fashion. PMID:21519395

Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres

PubMed Central

Song, Shufei

2018-01-01

Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging. These include DNA methylation, histone modifications, nucleosome positioning, and telomere regulation, including how these are influenced by environmental factors such as diet. Here we focus on two interconnected categories of chromatin-based mechanisms impacting aging: those involving changes in the levels of histones or in the functions of telomeres. PMID:29642537

The Relationship Between Fusion, Suppression, and Diplopia in Normal and Amblyopic Vision.

PubMed

Spiegel, Daniel P; Baldwin, Alex S; Hess, Robert F

2016-10-01

Single vision occurs through a combination of fusion and suppression. When neither mechanism takes place, we experience diplopia. Under normal viewing conditions, the perceptual state depends on the spatial scale and interocular disparity. The purpose of this study was to examine the three perceptual states in human participants with normal and amblyopic vision. Participants viewed two dichoptically separated horizontal blurred edges with an opposite tilt (2.35°) and indicated their binocular percept: "one flat edge," "one tilted edge," or "two edges." The edges varied with scale (fine 4 min arc and coarse 32 min arc), disparity, and interocular contrast. We investigated how the binocular interactions vary in amblyopic (visual acuity [VA] > 0.2 logMAR, n = 4) and normal vision (VA ≤ 0 logMAR, n = 4) under interocular variations in stimulus contrast and luminance. In amblyopia, despite the established sensory dominance of the fellow eye, fusion prevails at the coarse scale and small disparities (75%). We also show that increasing the relative contrast to the amblyopic eye enhances the probability of fusion at the fine scale (from 18% to 38%), and leads to a reversal of the sensory dominance at coarse scale. In normal vision we found that interocular luminance imbalances disturbed binocular combination only at the fine scale in a way similar to that seen in amblyopia. Our results build upon the growing evidence that the amblyopic visual system is binocular and further show that the suppressive mechanisms rendering the amblyopic system functionally monocular are scale dependent.

Priming of Short-Term Potentiation and Synaptic Tagging/Capture Mechanisms by Ryanodine Receptor Activation in Rat Hippocampal CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Li, Qin; Abraham, Wickliffe C.; Xiao, Zhi Cheng

2009-01-01

Activity-dependent changes in synaptic strength such as long-term potentiation (LTP) and long-term depression (LTD) are considered to be cellular mechanisms underlying learning and memory. Strengthening of a synapse for a few seconds or minutes is termed short-term potentiation (STP) and is normally unable to take part in the processes of synaptic…

5 Things To Know About Relaxation Techniques for Stress

MedlinePlus

... 5 Things To Know About Relaxation Techniques for Stress Share: When you’re under stress, your body reacts by releasing hormones that produce ... vessels narrow (restricting the flow of blood). Occasional stress is a normal coping mechanism. But over the ...

Mechanical properties of tank car steels retired from the fleet

DOT National Transportation Integrated Search

2008-08-31

As a consequence of several recent tank car accidents, the structural integrity of railroad tank cars has come under greater scrutiny, especially the older portion of the fleet fabricated prior to steel normalization requirements. The purpose of this...

Relating Mechanical Behavior and Microstructural Observations in Calcite Fault Gouge

NASA Astrophysics Data System (ADS)

Carpenter, B. M.; Di Stefano, G.; Viti, C.; Collettini, C.

2013-12-01

Many important earthquakes, magnitude 5-7, nucleate and/or propagate through carbonate-dominated lithologies. Additionally, the presence of precipitated calcite in (cement) and near (vein fill) faults indicates that the mechanical behavior of carbonate-dominated material likely plays an important role in shallow- and mid-crustal faulting. We report on laboratory experiments designed to explore the mechanical behavior of calcite and relate that behavior to post experiment microstructural observations. We sheared powdered gouge of Carrara Marble, >98% CaCO3, at constant normal stresses between 1 and 50 MPa under saturated conditions at room temperature. We performed velocity-stepping tests, 0.1-1000 μm/s, to evaluate frictional stability, and slide-hold-slide tests, 1-10,000 seconds, to measure the amount of frictional healing. Small subsets of experiments were performed under different environmental conditions and shearing velocities to better elucidate physicochemical processes and their role in the mechanical behavior of calcite fault gouge. All experimental samples were collected for SEM analysis. We find that the frictional healing rate is 7X higher under saturated conditions than under nominally dry conditions. We also observe a divergence between the rates of creep relaxation (increasing) and frictional healing (decreasing) as shear velocity is increased from 1 to 3000 μm/s. Our highest healing rates are observed at our lowest normal stresses. We observe a frictional strength of μ = 0.64, consistent with previous data under similar conditions. Furthermore, although we observe velocity-weakening frictional behavior in both the saturated and dry cases, rate- and-state friction parameters are distinctly different for each case. Our combined observations of rapid healing and of velocity-weakening frictional behavior indicate that faults where calcite-dominated gouge is present are likely to be seismic and have the ability to regain their strength quickly. Furthermore, our mechanical results highlight the important role of fluids in the evolution of frictional strength and thus fault behavior.

In Vitro Tissue Differentiation using Dynamics of Tissue Mechanical Properties

NASA Astrophysics Data System (ADS)

Lin, Wei-Chiang; Phillips, Paul J.

2002-03-01

Dynamics of tissue mechanical properties of various human tissue types were studied at macroscopic as well as microscopic level in vitro. This study was conducted to enable the development of a feedback system based on dynamics of tissue mechanical properties for intraoperative guidance for tumor treatment (e.g., RF ablation of liver tumor) and noninvasive tumor localization. Human liver tissues, including normal, cancerous, and cirrhotic tissues, were obtained from patients receiving liver transplant or tumor resection at Vanderbilt University Medical Center with the approval of the Vanderbilt Institutional Review Board. Tissue samples, once resected from the patients, were snap-frozen using liquid nitrogen and stored at -70 oC. Measurements of the mechanical properties of these tissue samples were conducted at the University of Tennessee at Knoxville. Dynamics of tissue mechanical properties were measured from both native and thermally coagulated tissue samples at macroscopic and microscopic level. Preliminary results suggest the dynamics of mechanical properties of normal liver tissues are very different from those of cancerous liver tissues. The correlation between the dynamics of mechanical properties at macroscopic level and those at microscopic level is currently under investigation.

Biomarkers identified for prostate cancer patients through genome-scale screening.

PubMed

Wang, Lei-Yun; Cui, Jia-Jia; Zhu, Tao; Shao, Wei-Hua; Zhao, Yi; Wang, Sai; Zhang, Yu-Peng; Wu, Ji-Chu; Zhang, Le

2017-11-03

Prostate cancer is a threat to men and usually occurs in aged males. Though prostate specific antigen level and Gleason score are utilized for evaluation of the prostate cancer in clinic, the biomarkers for this malignancy have not been widely recognized. Furthermore, the outcome varies across individuals receiving comparable treatment regimens and the underlying mechanism is still unclear. We supposed that genetic feature may be responsible for, at least in part, this process and conducted a two-cohort study to compare the genetic difference in tumorous and normal tissues of prostate cancer patients. The Gene Expression Omnibus dataset were used and a total of 41 genes were found significantly differently expressed in tumor tissues as compared with normal prostate tissues. Four genes (SPOCK3, SPON1, PTN and TGFB3) were selected for further evaluation after Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and clinical association analysis. MIR1908 was also found decreased expression level in prostate cancer whose target genes were found expressing in both prostate tumor and normal tissues. These results indicated that these potential biomarkers deserve attention in prostate cancer patients and the underlying mechanism should be further investigated.

Notes on Some Schizoid Mechanisms

PubMed Central

KLEIN, MELANIE

1996-01-01

I propose to summarize some of the conclusions presented in this paper. One of my main points was the suggestion that in the first few months of life anxiety is predominantly experienced as fear of persecution and that this contributes to certain mechanisms and defenses which characterize the paranoid and schizoid positions. Outstanding among these defenses is the mechanism of splitting internal and external objects, emotions, and the ego. These mechanisms and defenses are part of normal development and at the same time form the basis for later schizophrenic illness. I described the processes underlying identification by projection as a combination of splitting off parts of the self and projecting them on to another person, and some of the effects this identification has on normal and schizoid object relations. The onset of the depressive position is the juncture at which by regression schizoid mechanisms may be reinforced. I also suggested a close connection between the manic-depressive and schizoid disorders, based on the interaction between the infantile schizoid and depressive positions. PMID:22700275

Dynamic analysis of elastic rubber tired car wheel breaking under variable normal load

NASA Astrophysics Data System (ADS)

Fedotov, A. I.; Zedgenizov, V. G.; Ovchinnikova, N. I.

2017-10-01

The purpose of the paper is to analyze the dynamics of the braking of the wheel under normal load variations. The paper uses a mathematical simulation method according to which the calculation model of an object as a mechanical system is associated with a dynamically equivalent schematic structure of the automatic control. Transfer function tool analyzing structural and technical characteristics of an object as well as force disturbances were used. It was proved that the analysis of dynamic characteristics of the wheel subjected to external force disturbances has to take into account amplitude and phase-frequency characteristics. Normal load variations impact car wheel braking subjected to disturbances. The closer slip to the critical point is, the higher the impact is. In the super-critical area, load variations cause fast wheel blocking.

Normalization regulates competition for visual awareness

PubMed Central

Ling, Sam; Blake, Randolph

2012-01-01

Summary Signals in our brain are in a constant state of competition, including those that vie for motor control, sensory dominance and awareness. To shed light on the mechanisms underlying neural competition, we exploit binocular rivalry, a phenomenon that allows us to probe the competitive process that ordinarily transpires outside of our awareness. By measuring psychometric functions under different states of rivalry, we discovered a pattern of gain changes that are consistent with a model of competition in which attention interacts with normalization processes, thereby driving the ebb and flow between states of awareness. Moreover, we reveal that attention plays a crucial role in modulating competition; without attention, rivalry suppression for high-contrast stimuli is negligible. We propose a framework whereby our visual awareness of competing sensory representations is governed by a common neural computation: normalization. PMID:22884335

Influence of Soil Moisture on Litter Respiration in the Semiarid Loess Plateau

PubMed Central

Zhang, Yanjun; Guo, Shengli; Liu, Qingfang; Jiang, Jishao

2014-01-01

Understanding the response mechanisms of litter respiration to soil moisture in water-limited semi-arid regions is of vital importance to better understanding the interplay between ecological processes and the local carbon cycle. In situ soil respiration was monitored during 2010–2012 under various conditions (normal litter, no litter, and double litter treatments) in a 30-year-old artificial black locust plantation (Robinia pseudoacacia L.) on the Loess Plateau. Litter respiration with normal and double litter treatments exhibited similar seasonal variation, with the maximum value obtained in summer (0.57 and 1.51 μmol m−2 s−1 under normal and double litter conditions, respectively) and the minimum in spring (0.27 and 0.69 μmol m−2 s−1 under normal and double litter conditions, respectively). On average, annual cumulative litter respiration was 115 and 300 g C m−2 y−1 under normal and double litter conditions, respectively. Using a soil temperature of 17°C as the critical point, the relationship between litter respiration and soil moisture was found to follow quadratic functions well, whereas the determination coefficient was much greater at high soil temperature than at low soil temperature (33–35% vs. 22–24%). Litter respiration was significantly higher in 2010 and 2012 than in 2011 under both normal litter (132–165 g C m−2 y−1 vs. 48 g C m−2 y−1) and double litter (389–418 g C m−2 y−1 vs. 93 g C m−2 y−1) conditions. Such significant interannual variations were largely ascribed to the differences in summer rainfall. Our study demonstrates that, apart from soil temperature, moisture also has significant influence on litter respiration in semi-arid regions. PMID:25474633

Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization.

PubMed

Vucic, Steve; Kiernan, Matthew C

2008-03-01

Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.

Strongly Modulated Friction of a Film-Terminated Ridge-Channel Structure.

PubMed

He, Zhenping; Hui, Chung-Yuen; Levrard, Benjamin; Bai, Ying; Jagota, Anand

2016-05-26

Natural contacting surfaces have remarkable surface mechanical properties, which has led to the development of bioinspired surface structures using rubbery materials with strongly enhanced adhesion and static friction. However, sliding friction of structured rubbery surfaces is almost always significantly lower than that of a flat control, often due to significant loss of contact. Here we show that a film-terminated ridge-channel structure can strongly enhance sliding friction. We show that with properly chosen materials and geometrical parameters the near surface structure undergoes mechanical instabilities along with complex folding and sliding of internal interfaces, which is responsible for the enhancement of sliding friction. Because this structure shows no enhancement of adhesion under normal indentation by a sphere, it breaks the connection between energy loss during normal and shear loading. This makes it potentially interesting in many applications, for instance in tires, where one wishes to minimize rolling resistance (normal loading) while maximizing sliding friction (shear loading).

Biaxial Normal Strength Behavior in the Axial-Transverse Plane for Human Trabecular Bone—Effects of Bone Volume Fraction, Microarchitecture, and Anisotropy

PubMed Central

Sanyal, Arnav; Keaveny, Tony M.

2013-01-01

The biaxial failure behavior of the human trabecular bone, which has potential relevance both for fall and gait loading conditions, is not well understood, particularly for low-density bone, which can display considerable mechanical anisotropy. Addressing this issue, we investigated the biaxial normal strength behavior and the underlying failure mechanisms for human trabecular bone displaying a wide range of bone volume fraction (0.06–0.34) and elastic anisotropy. Micro-computer tomography (CT)-based nonlinear finite element analysis was used to simulate biaxial failure in 15 specimens (5 mm cubes), spanning the complete biaxial normal stress failure space in the axial-transverse plane. The specimens, treated as approximately transversely isotropic, were loaded in the principal material orientation. We found that the biaxial stress yield surface was well characterized by the superposition of two ellipses—one each for yield failure in the longitudinal and transverse loading directions—and the size, shape, and orientation of which depended on bone volume fraction and elastic anisotropy. However, when normalized by the uniaxial tensile and compressive strengths in the longitudinal and transverse directions, all of which depended on bone volume fraction, microarchitecture, and mechanical anisotropy, the resulting normalized biaxial strength behavior was well described by a single pair of (longitudinal and transverse) ellipses, with little interspecimen variation. Taken together, these results indicate that the role of bone volume fraction, microarchitecture, and mechanical anisotropy is mostly accounted for in determining the uniaxial strength behavior and the effect of these parameters on the axial-transverse biaxial normal strength behavior per se is minor. PMID:24121715

Micromechanics of ice friction

NASA Astrophysics Data System (ADS)

Sammonds, P. R.; Bailey, E.; Lishman, B.; Scourfield, S.

2015-12-01

Frictional mechanics are controlled by the ice micro-structure - surface asperities and flaws - but also the ice fabric and permeability network structure of the contacting blocks. Ice properties are dependent upon the temperature of the bulk ice, on the normal stress and on the sliding velocity and acceleration. This means the shear stress required for sliding is likewise dependent on sliding velocity, acceleration, and temperature. We aim to describe the micro-physics of the contacting surface. We review micro-mechanical models of friction: the elastic and ductile deformation of asperities under normal loads and their shear failure by ductile flow, brittle fracture, or melting and hydrodynamic lubrication. Combinations of these give a total of six rheological models of friction. We present experimental results in ice mechanics and physics from laboratory experiments to understand the mechanical models. We then examine the scaling relations of the slip of ice, to examine how the micro-mechanics of ice friction can be captured simple reduced-parameter models, describing the mechanical state and slip rate of the floes. We aim to capture key elements that they may be incorporated into mid and ocean-basin scale modelling.

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

PubMed

Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

2011-01-01

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding

PubMed Central

Varshney, Ankita; Rehan, Mohd; Subbarao, Naidu; Rabbani, Gulam; Khan, Rizwan Hasan

2011-01-01

Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state. PMID:21386972

Elimination of endogenous toxin, creatinine from blood plasma depends on albumin conformation: site specific uremic toxicity & impaired drug binding.

PubMed

Varshney, Ankita; Rehan, Mohd; Subbarao, Naidu; Rabbani, Gulam; Khan, Rizwan Hasan

2011-02-28

Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state.

Bronchial hyper-reactivity in migraine without aura: is it a new clue for inflammation?

PubMed

Kaleagasi, Hakan; Özgür, Eylem; Özge, Cengiz; Özge, Aynur

2011-03-01

We attempted to investigate the relationship between migraine without aura (MwoA) and bronchial hyper-reactivity to postulate inflammation as an underlying mechanism in migraine. Comorbidity of migraine and atopic diseases such as asthma has been an argument for suspected immune system dysfunction in migraineurs. Twenty patients with MwoA and 5 control subjects without history of atophy and asthma were included in study. Subjects with abnormal physical examination and chest radiographs were excluded. After a normal spirometry, methacholine bronchoprovocation test was performed in all subjects and controls according to 5 breath dosimeter methods. Sixteen of 20 patients and 2 of 5 control subjects were women. Mean ages were 37.5 (19-56) and 33.8 (26-43) years, respectively. Methacholine bronchoprovocation test was positive in 3 patients (15%) but was normal in all controls (0%). The relationship between MwoA and bronchial hyper-reactivity may help to postulate the inflammation in migraine as an underlying mechanism. © 2010 American Headache Society.

A dual closed-loop control system for mechanical ventilation.

PubMed

Tehrani, Fleur; Rogers, Mark; Lo, Takkin; Malinowski, Thomas; Afuwape, Samuel; Lum, Michael; Grundl, Brett; Terry, Michael

2004-04-01

Closed-loop mechanical ventilation has the potential to provide more effective ventilatory support to patients with less complexity than conventional ventilation. The purpose of this study was to investigate the effectiveness of an automatic technique for mechanical ventilation. Two closed-loop control systems for mechanical ventilation are combined in this study. In one of the control systems several physiological data are used to automatically adjust the frequency and tidal volume of breaths of a patient. This method, which is patented under US Patent number 4986268, uses the criterion of minimal respiratory work rate to provide the patient with a natural pattern of breathing. The inputs to the system include data representing CO2 and O2 levels of the patient as well as respiratory compliance and airway resistance. The I:E ratio is adjusted on the basis of the respiratory time constant to allow for effective emptying of the lungs in expiration and to avoid intrinsic positive end expiratory pressure (PEEP). This system is combined with another closed-loop control system for automatic adjustment of the inspired fraction of oxygen of the patient. This controller uses the feedback of arterial oxygen saturation of the patient and combines a rapid stepwise control procedure with a proportional-integral-derivative (PID) control algorithm to automatically adjust the oxygen concentration in the patient's inspired gas. The dual closed-loop control system has been examined by using mechanical lung studies, computer simulations and animal experiments. In the mechanical lung studies, the ventilation controller adjusted the breathing frequency and tidal volume in a clinically appropriate manner in response to changes in respiratory mechanics. The results of computer simulations and animal studies under induced disturbances showed that blood gases were returned to the normal physiologic range in less than 25 s by the control system. In the animal experiments understeady-state conditions, the maximum standard deviations of arterial oxygen saturation and the end-tidal partial pressure of CO2 were +/- 1.76% and +/- 1.78 mmHg, respectively. The controller maintained the arterial blood gases within normal limits under steady-state conditions and the transient response of the system was robust under various disturbances. The results of the study have showed that the proposed dual closed-loop technique has effectively controlled mechanical ventilation under different test conditions.

Comparison of Tibiofemoral Contact Mechanics After Various Transtibial and All-Inside Fixation Techniques for Medial Meniscus Posterior Root Radial Tears in a Porcine Model.

PubMed

Chung, Kyu Sung; Choi, Choong Hyeok; Bae, Tae Soo; Ha, Jeong Ku; Jun, Dal Jae; Wang, Joon Ho; Kim, Jin Goo

2018-04-01

To compare tibiofemoral contact mechanics after fixation for medial meniscus posterior root radial tears (MMPRTs). Seven fresh knees from mature pigs were used. Each knee was tested under 5 conditions: normal knee, MMPRT, pullout fixation with simple sutures, fixation with modified Mason-Allen sutures, and all-inside fixation using Fastfix 360. The peak contact pressure and contact surface area were evaluated using a capacitive sensor positioned between the meniscus and tibial plateau, under a 1,000-N compression force, at different flexion angles (0°, 30°, 60°, and 90°). The peak contact pressure was significantly higher in MMPRTs than in normal knees (P = .018). Although the peak contact pressure decreased significantly after fixation at all flexion angles (P = .031), it never recovered to the values noted in the normal meniscus. No difference was observed among fixation groups (P = .054). The contact surface area was significantly lower in MMPRTs than in the normal meniscus (P = .018) and increased significantly after fixation at all flexion angles (P = .018) but did not recover to within normal limits. For all flexion angles except 60°, the contact surface area was significantly higher for fixation with Mason-Allen sutures than for fixation with simple sutures or all-inside fixation (P = .027). At 90° of flexion, the contact surface area was significantly better for fixation with simple sutures than for all-inside fixation (P = .031). The peak contact pressure and contact surface area improved significantly after fixation, regardless of the fixation method, but did not recover to the levels noted in the normal meniscus after any type of fixation. Among the fixation methods evaluated in this time 0 study, fixation using modified Mason-Allen sutures provided a superior contact surface area compared with that noted after fixation using simple sutures or all-inside fixation, except at 60° of flexion. However, this study had insufficient power to accurately detect the differences between the outcomes of various fixation methods. Our results in a porcine model suggest that fixation can restore tibiofemoral contact mechanics in MMPRT and that fixation with a locking mechanism leads to superior biomechanical properties. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

An efficient finite element with layerwise mechanics for smart piezoelectric composite and sandwich shallow shells

NASA Astrophysics Data System (ADS)

Yasin, M. Yaqoob; Kapuria, S.

2014-01-01

In this work, we present a new efficient four-node finite element for shallow multilayered piezoelectric shells, considering layerwise mechanics and electromechanical coupling. The laminate mechanics is based on the zigzag theory that has only seven kinematic degrees of freedom per node. The normal deformation of the piezoelectric layers under the electric field is accounted for without introducing any additional deflection variables. A consistent quadratic variation of the electric potential across the piezoelectric layers with the provision of satisfying the equipotential condition of electroded surfaces is adopted. The performance of the new element is demonstrated for the static response under mechanical and electric potential loads, and for free vibration response of smart shells under different boundary conditions. The predictions are found to be very close to the three dimensional piezoelasticity solutions for hybrid shells made of not only single-material composite substrates, but also sandwich substrates with a soft core for which the equivalent single layer (ESL) theories perform very badly.

Numerical analysis of the effects induced by normal faults and dip angles on rock bursts

NASA Astrophysics Data System (ADS)

Jiang, Lishuai; Wang, Pu; Zhang, Peipeng; Zheng, Pengqiang; Xu, Bin

2017-10-01

The study of mining effects under the influences of a normal fault and its dip angle is significant for the prediction and prevention of rock bursts. Based on the geological conditions of panel 2301N in a coalmine, the evolution laws of the strata behaviors of the working face affected by a fault and the instability of the fault induced by mining operations with the working face of the footwall and hanging wall advancing towards a normal fault are studied using UDEC numerical simulation. The mechanism that induces rock burst is revealed, and the influence characteristics of the fault dip angle are analyzed. The results of the numerical simulation are verified by conducting a case study regarding the microseismic events. The results of this study serve as a reference for the prediction of rock bursts and their classification into hazardous areas under similar conditions.

Retentivity, selectivity and thermodynamic behavior of polycyclic aromatic hydrocarbons on charge-transfer and hypercrosslinked stationary phases under conditions of normal phase high performance liquid chromatography.

PubMed

Jiang, Ping; Lucy, Charles A

2016-03-11

Charge-transfer and hypercrosslinked polystyrene phases offer retention and separation for polycyclic aromatic hydrocarbons (PAHs) and thus have potential for petroleum analysis. The size, shape and planarity selectivity for PAH standards on charge-transfer (DNAP column) and hypercrosslinked polystyrene (HC-Tol and 5HGN columns) phases are different under normal phase liquid chromatography (NPLC). The HC-Tol column behaves like a conventional NPLC column with low retention of PAHs. Retention of PAHs on the DNAP and 5HGN are strong and increases with the number of aromatic rings. The main retention mechanism is through π-π interactions and dipole-induced dipole interaction. Thermodynamics indicates that the retention mechanism of PAHs remains unchanged over the temperature range 20-60°C. In addition, on either DNAP or 5HGN column, both linear and bent PAHs are retained through the same mechanism. But DNAP possesses smaller π-π interaction and higher planarity selectivity than 5HGN for PAHs. This is suggestive that DNAP interacts with PAHs through a disordered phase arrangement, while 5HGN behaves as an ordered adsorption phase. Copyright © 2016 Elsevier B.V. All rights reserved.

Fluid-structure interaction modeling of aneurysmal arteries under steady-state and pulsatile blood flow: a stability analysis.

PubMed

Sharzehee, Mohammadali; Khalafvand, Seyed Saeid; Han, Hai-Chao

2018-02-01

Tortuous aneurysmal arteries are often associated with a higher risk of rupture but the mechanism remains unclear. The goal of this study was to analyze the buckling and post-buckling behaviors of aneurysmal arteries under pulsatile flow. To accomplish this goal, we analyzed the buckling behavior of model carotid and abdominal aorta with aneurysms by utilizing fluid-structure interaction (FSI) method with realistic waveforms boundary conditions. FSI simulations were done under steady-state and pulsatile flow for normal (1.5) and reduced (1.3) axial stretch ratios to investigate the influence of aneurysm, pulsatile lumen pressure and axial tension on stability. Our results indicated that aneurysmal artery buckled at the critical buckling pressure and its deflection nonlinearly increased with increasing lumen pressure. Buckling elevates the peak stress (up to 118%). The maximum aneurysm wall stress at pulsatile FSI flow was (29%) higher than under static pressure at the peak lumen pressure of 130 mmHg. Buckling results show an increase in lumen shear stress at the inner side of the maximum deflection. Vortex flow was dramatically enlarged with increasing lumen pressure and artery diameter. Aneurysmal arteries are more susceptible than normal arteries to mechanical instability which causes high stresses in the aneurysm wall that could lead to aneurysm rupture.

Proteogenomic analysis reveals alternative splicing and translation as part of the abscisic acid response in Arabidopsis seedlings.

PubMed

Zhu, Fu-Yuan; Chen, Mo-Xian; Ye, Neng-Hui; Shi, Lu; Ma, Kai-Long; Yang, Jing-Fang; Cao, Yun-Ying; Zhang, Youjun; Yoshida, Takuya; Fernie, Alisdair R; Fan, Guang-Yi; Wen, Bo; Zhou, Ruo; Liu, Tie-Yuan; Fan, Tao; Gao, Bei; Zhang, Di; Hao, Ge-Fei; Xiao, Shi; Liu, Ying-Gao; Zhang, Jianhua

2017-08-01

In eukaryotes, mechanisms such as alternative splicing (AS) and alternative translation initiation (ATI) contribute to organismal protein diversity. Specifically, splicing factors play crucial roles in responses to environment and development cues; however, the underlying mechanisms are not well investigated in plants. Here, we report the parallel employment of short-read RNA sequencing, single molecule long-read sequencing and proteomic identification to unravel AS isoforms and previously unannotated proteins in response to abscisic acid (ABA) treatment. Combining the data from the two sequencing methods, approximately 83.4% of intron-containing genes were alternatively spliced. Two AS types, which are referred to as alternative first exon (AFE) and alternative last exon (ALE), were more abundant than intron retention (IR); however, by contrast to AS events detected under normal conditions, differentially expressed AS isoforms were more likely to be translated. ABA extensively affects the AS pattern, indicated by the increasing number of non-conventional splicing sites. This work also identified thousands of unannotated peptides and proteins by ATI based on mass spectrometry and a virtual peptide library deduced from both strands of coding regions within the Arabidopsis genome. The results enhance our understanding of AS and alternative translation mechanisms under normal conditions, and in response to ABA treatment. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Dynamic Response and Failure Mechanism of Brittle Rocks Under Combined Compression-Shear Loading Experiments

NASA Astrophysics Data System (ADS)

Xu, Yuan; Dai, Feng

2018-03-01

A novel method is developed for characterizing the mechanical response and failure mechanism of brittle rocks under dynamic compression-shear loading: an inclined cylinder specimen using a modified split Hopkinson pressure bar (SHPB) system. With the specimen axis inclining to the loading direction of SHPB, a shear component can be introduced into the specimen. Both static and dynamic experiments are conducted on sandstone specimens. Given carefully pulse shaping, the dynamic equilibrium of the inclined specimens can be satisfied, and thus the quasi-static data reduction is employed. The normal and shear stress-strain relationships of specimens are subsequently established. The progressive failure process of the specimen illustrated via high-speed photographs manifests a mixed failure mode accommodating both the shear-dominated failure and the localized tensile damage. The elastic and shear moduli exhibit certain loading-path dependence under quasi-static loading but loading-path insensitivity under high loading rates. Loading rate dependence is evidently demonstrated through the failure characteristics involving fragmentation, compression and shear strength and failure surfaces based on Drucker-Prager criterion. Our proposed method is convenient and reliable to study the dynamic response and failure mechanism of rocks under combined compression-shear loading.

Effects of mechanical stretching on the morphology of extracellular polymers and the mRNA expression of collagens and small leucine-rich repeat proteoglycans in vaginal fibroblasts from women with pelvic organ prolapse.

PubMed

Wang, Sumei; Lü, Dongyuan; Zhang, Zhenyu; Jia, Xingyuan; Yang, Lei

2018-01-01

To determine the effect of mechanical stretching load and the efficacy of postmenopausal estrogen therapy (ET) on pelvic organ prolapse (POP), vaginal fibroblasts isolated from postmenopausal women with or without POP were subjected to 0.1-Hz uniaxial cyclic mechanical stretching (CS) with 10% elongation and 10-8 M 17-β-estradiol (E2) treatment. We investigated the morphological characteristics of extracellular polymers using scanning electron microscopy (SEM) and monitored the mRNA expression of type I collagen (COL I) and type III collagen (COL III) as well as the small leucine-rich proteoglycan (SLRP) family members decorin (DCN), biglycan (BGN), fibromodulin (FMO), and lumican (LUM), using real-time quantitative polymerase chain reaction (RT-PCR). Using SEM, certain viscoelastic polymers were found to be randomly distributed among fibroblasts, which for normal fibroblasts formed clusters of plum flower-like patterns under static-culture conditions and resembled stretched strips when stretched in culture, whereas polymers among POP fibroblasts resembled stretched strips under static-cultured conditions and presented broken networks when stretched in culture. RT-PCR revealed that COL I, DCN, BGN, FMO, and LUM mRNA expression was significantly higher in POP than in normal fibroblasts under static-culture condition. Following CS, COL I and BGN mRNA expression was significantly up-regulated in normal fibroblasts, and DCN and FMO mRNA expression was down-regulated in POP fibroblasts. Following concomitant CS and E2 treatment, significantly elevated COL I and DCN mRNA expression was observed in normal fibroblasts, and significantly elevated COL I and BGN mRNA expression was observed in POP fibroblasts. COL III mRNA expression was not significantly different between the POP and normal group, and CS did not significantly affect expression in either group, though COL III was down-regulated in normal fibroblasts concomitantly treated with E2 and CS. We conclude that the morphological distribution of extracellular polymers in POP fibroblasts exhibited higher sensitivity and lower tolerance to stretching loads than do normal fibroblasts. These mechanical properties were further reflected in the transcription of COL I. Defects in the compensatory function of BGN for DCN and LUM for FMO exist in POP fibroblasts, which further affect the structure and function of COL I in response to stretching load, ultimately resulting in abnormal reconstruction of pelvic supportive connective tissues and the occurrence of POP. ET can maintain stretching-induced elevations in COL I and DCN transcription in healthy women and improve stretching-induced COL I, DCN, BGN, and FMO transcriptional changes in POP women to prevent and improve POP. Only down-regulated COL III transcription was observed upon concomitant CS and E2 treatment in normal fibroblasts, which suggests that the tensile strength, not the elasticity, of the supportive connective tissues is damaged in POP and that the higher tensile strength induced by ET in healthy fibroblasts prevents POP. These findings confirm the role of higher sensitivity and lower tolerance to mechanical stretching in the pathogenesis of POP and further provide evidence supporting the use of ET to prevent and inhibit POP in postmenopausal women.

Systems and Methods for Implementing Bulk Metallic Glass-Based Macroscale Compliant Mechanisms

NASA Technical Reports Server (NTRS)

Hofmann, Douglas C. (Inventor); Agnes, Gregory (Inventor)

2017-01-01

Systems and methods in accordance with embodiments of the invention implement bulk metallic glass-based macroscale compliant mechanisms. In one embodiment, a bulk metallic glass-based macroscale compliant mechanism includes: a flexible member that is strained during the normal operation of the compliant mechanism; where the flexible member has a thickness of 0.5 mm; where the flexible member comprises a bulk metallic glass-based material; and where the bulk metallic glass-based material can survive a fatigue test that includes 1000 cycles under a bending loading mode at an applied stress to ultimate strength ratio of 0.25.

The effect of heart failure and left ventricular assist device treatment on right ventricular mechanics: a computational study.

PubMed

Park, Jun I K; Heikhmakhtiar, Aulia Khamas; Kim, Chang Hyun; Kim, Yoo Seok; Choi, Seong Wook; Song, Kwang Soup; Lim, Ki Moo

2018-05-22

Although it is important to analyze the hemodynamic factors related to the right ventricle (RV) after left ventricular assist device (LVAD) implantation, previous studies have focused only on the alteration of the ventricular shape and lack quantitative analysis of the various hemodynamic parameters. Therefore, we quantitatively analyzed various hemodynamic parameters related to the RV under normal, heart failure (HF), and HF incorporated with continuous flow LVAD therapy by using a computational model. In this study, we combined a three-dimensional finite element electromechanical model of ventricles, which is based on human ventricular morphology captured by magnetic resonance imaging (MRI) with a lumped model of the circulatory system and continuous flow LVAD function in order to construct an integrated model of an LVAD implanted-cardiovascular system. To induce systolic dysfunction, the magnitude of the calcium transient function under HF condition was reduced to 70% of the normal value, and the time constant was reduced by 30% of the normal value. Under the HF condition, the left ventricular end systolic pressure decreased, the left ventricular end diastolic pressure increased, and the pressure in the right atrium (RA), RV, and pulmonary artery (PA) increased compared with the normal condition. The LVAD therapy decreased the end-systolic pressure of the LV by 41%, RA by 29%, RV by 53%, and PA by 71%, but increased the right ventricular ejection fraction by 52% and cardiac output by 40%, while the stroke work was reduced by 67% compared with the HF condition without LVAD. The end-systolic ventricular tension and strain decreased with the LVAD treatment. LVAD enhances CO and mechanical unloading of the LV as well as those of the RV and prevents pulmonary hypertension which can be induced by HF.

Friction mechanism of individual multilayered nanoparticles.

PubMed

Tevet, Ofer; Von-Huth, Palle; Popovitz-Biro, Ronit; Rosentsveig, Rita; Wagner, H Daniel; Tenne, Reshef

2011-12-13

Inorganic nanoparticles of layered [two-dimensional (2D)] compounds with hollow polyhedral structure, known as fullerene-like nanoparticles (IF), were found to have excellent lubricating properties. This behavior can be explained by superposition of three main mechanisms: rolling, sliding, and exfoliation-material transfer (third body). In order to elucidate the tribological mechanism of individual nanoparticles in different regimes, in situ axial nanocompression and shearing forces were applied to individual nanoparticles using a high resolution scanning electron microscope. Gold nanoparticles deposited onto the IF nanoparticles surface served as markers, delineating the motion of individual IF nanoparticle. It can be concluded from these experiments that rolling is an important lubrication mechanism for IF-WS(2) in the relatively low range of normal stress (0.96 ± 0.38 GPa). Sliding is shown to be relevant under slightly higher normal stress, where the spacing between the two mating surfaces does not permit free rolling of the nanoparticles. Exfoliation of the IF nanoparticles becomes the dominant mechanism at the high end of normal stress; above 1.2 GPa and (slow) shear; i.e., boundary lubrication conditions. It is argued that the modus operandi of the nanoparticles depends on their degree of crystallinity (defects); sizes; shape, and their mechanical characteristics. This study suggests that the rolling mechanism, which leads to low friction and wear, could be attained by improving the sphericity of the IF nanoparticle, the dispersion (deagglomeration) of the nanoparticles, and the smoothness of the mating surfaces.

Friction mechanism of individual multilayered nanoparticles

PubMed Central

Tevet, Ofer; Von-Huth, Palle; Popovitz-Biro, Ronit; Rosentsveig, Rita; Wagner, H. Daniel; Tenne, Reshef

2011-01-01

Inorganic nanoparticles of layered [two-dimensional (2D)] compounds with hollow polyhedral structure, known as fullerene-like nanoparticles (IF), were found to have excellent lubricating properties. This behavior can be explained by superposition of three main mechanisms: rolling, sliding, and exfoliation-material transfer (third body). In order to elucidate the tribological mechanism of individual nanoparticles in different regimes, in situ axial nanocompression and shearing forces were applied to individual nanoparticles using a high resolution scanning electron microscope. Gold nanoparticles deposited onto the IF nanoparticles surface served as markers, delineating the motion of individual IF nanoparticle. It can be concluded from these experiments that rolling is an important lubrication mechanism for IF-WS2 in the relatively low range of normal stress (0.96±0.38 GPa). Sliding is shown to be relevant under slightly higher normal stress, where the spacing between the two mating surfaces does not permit free rolling of the nanoparticles. Exfoliation of the IF nanoparticles becomes the dominant mechanism at the high end of normal stress; above 1.2 GPa and (slow) shear; i.e., boundary lubrication conditions. It is argued that the modus operandi of the nanoparticles depends on their degree of crystallinity (defects); sizes; shape, and their mechanical characteristics. This study suggests that the rolling mechanism, which leads to low friction and wear, could be attained by improving the sphericity of the IF nanoparticle, the dispersion (deagglomeration) of the nanoparticles, and the smoothness of the mating surfaces. PMID:22084073

Softened Mechanical Properties of Graphene Induced by Electric Field.

PubMed

Huang, Peng; Guo, Dan; Xie, Guoxin; Li, Jian

2017-10-11

The understanding on the mechanical properties of graphene under the applications of physical fields is highly relevant to the reliability and lifetime of graphene-based nanodevices. In this work, we demonstrate that the application of electric field could soften the mechanical properties of graphene dramatically on the basis of the conductive AFM nanoindentation method. It has been found that the Young's modulus and fracture strength of graphene nanosheets suspended on the holes almost stay the same initially and then exhibit a sharp drop when the normalized electric field strength increases to be 0.18 ± 0.03 V/nm. The threshold voltage of graphene nanosheets before the onset of fracture under the fixed applied load increases with the thickness. Supported graphene nanosheets can sustain larger electric field under the same applied load than the suspended ones. The excessively regional Joule heating caused by the high electric current under the applied load is responsible for the electromechanical failure of graphene. These findings can provide a beneficial guideline for the electromechanical applications of graphene-based nanodevices.

Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation.

PubMed

Arenaza-Urquijo, Eider M; Bejanin, Alexandre; Gonneaud, Julie; Wirth, Miranka; La Joie, Renaud; Mutlu, Justine; Gaubert, Malo; Landeau, Brigitte; de la Sayette, Vincent; Eustache, Francis; Chételat, Gaël

2017-11-01

The brain mechanisms underlying the effect of intellectual enrichment may evolve along the normal aging Alzheimer's disease (AD) cognitive spectrum and may include both protective and compensatory mechanisms. We assessed the association between early intellectual enrichment (education, years) and average cortical florbetapir standardized uptake value ratio as well as performed voxel-wise analyses in a total of 140 participants, including cognitively normal older adults, mild cognitive impairment (MCI), and AD patients. Higher education was associated with lower cortical florbetapir positron emission tomography (florbetapir-PET) uptake, notably in the frontal lobe in normal older adults, but with higher uptake in frontal, temporal, and parietal regions in MCI after controlling for global cognitive status. No association was found in AD. In MCI, we observed an increased fluorodeoxyglucose positron emission tomography (FDG-PET) uptake with education within the regions of higher florbetapir-PET uptake, suggesting a compensatory increase. Early intellectual enrichment may be associated with protection and compensation for amyloid beta (Aβ) deposition later in life, before the onset of dementia. Previous investigations have been controversial as regard to the effects of intellectual enrichment variables on Aβ deposition; the present findings call for approaches aiming to evaluate mechanisms of resilience across disease stages. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparing Risk- and Non-Risk-Groups Is a Favored Approach in Developmental Psychopathology. Commentary on: "Variations in Early Attachment Mechanisms Contribute to Attachment Quality: Case Studies Including Babies Born Preterm"

ERIC Educational Resources Information Center

Suess, Gerhard J.

2016-01-01

In this commentary, Suess opines that comparing risk- and non-risk-groups, as is done in the study by Witting, Ruiz, and Ahnert (2016), is a favored approach in developmental psychopathology in order to learn more about underlying mechanisms of normal development, as well as developmental deviations. Witting and colleagues followed up this…

Real-time quantification of xeroderma pigmentosum mRNA from the mammalian cochlea

PubMed Central

Guthrie, O'neil W.; Carrero-Martínez, Franklin A.

2010-01-01

Short Summary Xeroderma pigmentosum (XP) is a genetic disease that results in poor genomic defense from endogenous and exogenous stressors. Patients with mutations in the XPC and XPA genes exhibit cochlear hearing loss and to date, the underlying molecular mechanism is unknown. However, recent evidence suggests that the cochlea experiences persistent oxidative stress under normal conditions. In the current study, XPC and XPA gene products were purified from the cochlea and quantitative polymerase chain reaction was used to study the kinetics and magnitude of their expression. Additionally, immunohistochemistry was used to locate their respective polypeptides in the cochlea. The results revealed a significant demand for XP genes in the mammalian cochlea, which suggest that XP genomic defenses contribute in counterbalancing endogenous stress in the peripheral end-organ under normal conditions. PMID:20539233

Different Facets of Copy Number Changes: Permanent, Transient, and Adaptive

PubMed Central

Mishra, Sweta

2016-01-01

Chromosomal copy number changes are frequently associated with harmful consequences and are thought of as an underlying mechanism for the development of diseases. However, changes in copy number are observed during development and occur during normal biological processes. In this review, we highlight the causes and consequences of copy number changes in normal physiologic processes as well as cover their associations with cancer and acquired drug resistance. We discuss the permanent and transient nature of copy number gains and relate these observations to a new mechanism driving transient site-specific copy gains (TSSGs). Finally, we discuss implications of TSSGs in generating intratumoral heterogeneity and tumor evolution and how TSSGs can influence the therapeutic response in cancer. PMID:26755558

Piezo2 senses airway stretch and mediates lung inflation-induced apnoea

PubMed Central

Nonomura, Keiko; Woo, Seung-Hyun; Chang, Rui B.; Gillich, Astrid; Qiu, Zhaozhu; Francisco, Allain G.; Ranade, Sanjeev S.; Liberles, Stephen D.; Patapoutian, Ardem

2017-01-01

Respiratory dysfunction is a notorious cause of perinatal mortality in infants and sleep apnoea in adults, but the mechanisms of respiratory control are not clearly understood. Mechanical signals transduced by airway-innervating sensory neurons control respiration; however, the physiological significance and molecular mechanisms of these signals remain obscured. Here we show that global and sensory neuron-specific ablation of the mechanically activated ion channel Piezo2 causes respiratory distress and death in newborn mice. Optogenetic activation of Piezo2+ vagal sensory neurons causes apnoea in adult mice. Moreover, induced ablation of Piezo2 in sensory neurons of adult mice causes decreased neuronal responses to lung inflation, an impaired Hering–Breuer mechanoreflex, and increased tidal volume under normal conditions. These phenotypes are reproduced in mice lacking Piezo2 in the nodose ganglion. Our data suggest that Piezo2 is an airway stretch sensor and that Piezo2-mediated mechanotransduction within various airway-innervating sensory neurons is critical for establishing efficient respiration at birth and maintaining normal breathing in adults. PMID:28002412

Crash simulation of hybrid structures considering the stress and strain rate dependent material behavior of thermoplastic materials

NASA Astrophysics Data System (ADS)

Hopmann, Ch.; Schöngart, M.; Weber, M.; Klein, J.

2015-05-01

Thermoplastic materials are more and more used as a light weight replacement for metal, especially in the automotive industry. Since these materials do not provide the mechanical properties, which are required to manufacture supporting elements like an auto body or a cross bearer, plastics are combined with metals in so called hybrid structures. Normally, the plastics components are joined to the metal structures using different technologies like welding or screwing. Very often, the hybrid structures are made of flat metal parts, which are stiffened by a reinforcement structure made of thermoplastic materials. The loads on these structures are very often impulsive, for example in the crash situation of an automobile. Due to the large stiffness variation of metal and thermoplastic materials, complex states of stress and very high local strain rates occur in the contact zone under impact conditions. Since the mechanical behavior of thermoplastic materials is highly dependent on these types of load, the crash failure of metal plastic hybrid parts is very complex. The problem is that the normally used strain rate dependent elastic/plastic material models are not capable to simulate the mechanical behavior of thermoplastic materials depended on the state of stress. As part of a research project, a method to simulate the mechanical behavior of hybrid structures under impact conditions is developed at the IKV. For this purpose, a specimen for the measurement of mechanical properties dependet on the state of stress and a method for the strain rate depended characterization of thermoplastic materials were developed. In the second step impact testing is performed. A hybrid structure made from a metal sheet and a reinforcement structure of a Polybutylenterephthalat Polycarbonate blend is tested under impact conditions. The measured stress and strain rate depended material data are used to simulate the mechanical behavior of the hybrid structure under highly dynamic load with impact velocities up to 5 m/s. The mechanical behavior of the plastics structure is simulated using a quadratic yield surface, which takes the state of stress and the strain rate into account. The FE model is made from mid surface elements to reduce the computing time.

Ion acceleration via TNSA near and beyond the relativistic transparency limit

NASA Astrophysics Data System (ADS)

Schumacher, Douglass; Poole, Patrick; Cochran, Ginevra; Willis, Christopher

2017-10-01

Ultra-intense laser-based ion acceleration can proceed via several mechanisms whose fundamental operation and interplay with each other are still not well understood. The details of Relativistically Induced Transparency (RIT) and its impact on ultra-thin target acceleration are of interest for fundamental studies and to progress toward applications requiring controlled, high energy secondary radiation, e.g. hadron cancer therapy. Liquid crystal film targets formed in-situ with thickness control between 10 nm and > 50 μm uniquely allow study of how ion acceleration varies with target thickness. Several recent studies have investigated Target Normal Sheath Acceleration (TNSA) down to the thickness at which RIT occurs, with a wide range of laser conditions (energy, pulse duration, and contrast), using various ion and optical diagnostics to ascertain acceleration mechanisms and quality. Observation of target-normal directed ion acceleration enhancement at the RIT thickness onset will be discussed, including analysis of ion spatial and spectral features as well as particle-in-cell simulations investigating the underlying physical processes. This material is based upon work supported by the AFOSR under Award Number FA9550-14-1-0085, by the NNSA under DE-NA0003107, and by computing time from the Ohio Supercomputer Center.

Disadvantages of interfragmentary shear on fracture healing--mechanical insights through numerical simulation.

PubMed

Steiner, Malte; Claes, Lutz; Ignatius, Anita; Simon, Ulrich; Wehner, Tim

2014-07-01

The outcome of secondary fracture healing processes is strongly influenced by interfragmentary motion. Shear movement is assumed to be more disadvantageous than axial movement, however, experimental results are contradictory. Numerical fracture healing models allow simulation of the fracture healing process with variation of single input parameters and under comparable, normalized mechanical conditions. Thus, a comparison of the influence of different loading directions on the healing process is possible. In this study we simulated fracture healing under several axial compressive, and translational and torsional shear movement scenarios, and compared their respective healing times. Therefore, we used a calibrated numerical model for fracture healing in sheep. Numerous variations of movement amplitudes and musculoskeletal loads were simulated for the three loading directions. Our results show that isolated axial compression was more beneficial for the fracture healing success than both isolated shearing conditions for load and displacement magnitudes which were identical as well as physiological different, and even for strain-based normalized comparable conditions. Additionally, torsional shear movements had less impeding effects than translational shear movements. Therefore, our findings suggest that osteosynthesis implants can be optimized, in particular, to limit translational interfragmentary shear under musculoskeletal loading. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Erosion of a grooved surface caused by impact of particle-laden flow

NASA Astrophysics Data System (ADS)

Jung, Sohyun; Yang, Eunjin; Kim, Ho-Young

2016-11-01

Solid erosion can be a life-limiting process for mechanical elements in erosive environments, thus it is of practical importance in many industries such as construction, mining, and coal conversion. Erosion caused by particle-laden flow occurs through diverse mechanisms, such as cutting, plastic deformation, brittle fracture, fatigue and melting, depending on particle velocity, total particle mass and impingement angle. Among a variety of attempts to lessen erosion, here we investigate the effectiveness of millimeter-sized grooves on the surface. By experimentally measuring the erosion rates of smooth and triangular-grooved surfaces under various impingement angles, we find that erosion can be significantly reduced within a finite range of impingement angles. We show that such erosion resistance is attributed to the swirls of air within grooves and the differences in erosive strength of normal and slanted impact. In particular, erosion is mitigated when we increase the effective area under normal impact causing plastic deformation and fracture while decreasing the area under slanted impact that cuts the surface to a large degree. Our quantitative model for the erosion rate of grooved surfaces considering the foregoing effects agrees with the measurement results.

Functional Esophageal Disorders.

PubMed

Aziz, Qasim; Fass, Ronnie; Gyawali, C Prakash; Miwa, Hiroto; Pandolfino, John E; Zerbib, Frank

2016-02-15

Functional esophageal disorders consist of a disease category that present with esophageal symptoms (heartburn, chest pain, dysphagia, globus) not explained by mechanical obstruction (stricture, tumor, eosinophilic esophagitis), major motor disorders (achalasia, EGJ outflow obstruction, absent contractility, distal esophageal spasm, jackhammer esophagus), or gastroesophageal reflux disease (GERD). While mechanisms responsible are unclear, it is theorized that visceral hypersensitivity and hypervigilance play an important role in symptom generation, in the context of normal or borderline function. Treatments directed at improving borderline motor dysfunction or reducing reflux burden to sub-normal levels have limited success in symptom improvement. In contrast, strategies focused on modulating peripheral triggering and central perception are mechanistically viable and clinically meaningful. However, outcome data from these treatment options are limited. Future research needs to focus on understanding mechanisms underlying visceral hypersensitivity and hypervigilance so that appropriate targets and therapies can be developed. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

[Study of red tide spectral characteristics and its mechanism].

PubMed

Cui, Ting-Wei; Zhang, Jie; Ma, Yi; Sun, Ling

2006-05-01

In situ spectral data of different red tide, whose dominant species are leptocylindrus danicus, chattonella marina, skeletonema costatum, and mesodinium rubrum, were acquired by above water method utilizing spectrometer manufactured by FieldSpec Dual VNIR (USA). It is emphasized that the characteristic reflectance peak lying between 687 and 728 nm can be used to distinguish between red tide and normal sea water. Also the spectral discrepancy between different dominant species of red tide is pointed out, which could be utilized to identify certain red tide species by remote sensing technique. Mechanisms of phytoplankton red tide spectra peaks and vales are given. Spectral characteristics of mesodinium rubrum, a kind of protozoan, may be related to its symbiotic alga in its body and phytoplankton pigment crumb. So, research on ingestion preference, symbiotic property with algae, and fluorescence emission character of such symbiotic algae under normal temperature may be helpful for the deep understanding of mechanism of mesodinium rubrum spectra.

Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis.

PubMed

Goldring, Mary B; Goldring, Steven R

2010-03-01

The articular surface plays an essential role in load transfer across the joint, and conditions that produce increased load transfer or altered patterns of load distribution accelerate the development of osteoarthritis (OA). Current knowledge segregates the risk factors into two fundamental mechanisms related to the adverse effects of "abnormal" loading on normal cartilage or "normal" loading on abnormal cartilage. Although chondrocytes can modulate their functional state in response to loading, their capacity to repair and modify the surrounding extracellular matrix is limited in comparison to skeletal cells in bone. This differential adaptive capacity underlies the more rapid appearance of detectable skeletal changes, especially after acute injuries that alter joint mechanics. The imbalance in the adaptation of the cartilage and bone disrupts the physiological relationship between these tissues and further contributes to OA pathology. This review focuses on the specific articular cartilage and skeletal features of OA and the putative mechanisms involved in their pathogenesis.

Quantifying the underlying landscape and paths of cancer

PubMed Central

Li, Chunhe; Wang, Jin

2014-01-01

Cancer is a disease regulated by the underlying gene networks. The emergence of normal and cancer states as well as the transformation between them can be thought of as a result of the gene network interactions and associated changes. We developed a global potential landscape and path framework to quantify cancer and associated processes. We constructed a cancer gene regulatory network based on the experimental evidences and uncovered the underlying landscape. The resulting tristable landscape characterizes important biological states: normal, cancer and apoptosis. The landscape topography in terms of barrier heights between stable state attractors quantifies the global stability of the cancer network system. We propose two mechanisms of cancerization: one is by the changes of landscape topography through the changes in regulation strengths of the gene networks. The other is by the fluctuations that help the system to go over the critical barrier at fixed landscape topography. The kinetic paths from least action principle quantify the transition processes among normal state, cancer state and apoptosis state. The kinetic rates provide the quantification of transition speeds among normal, cancer and apoptosis attractors. By the global sensitivity analysis of the gene network parameters on the landscape topography, we uncovered some key gene regulations determining the transitions between cancer and normal states. This can be used to guide the design of new anti-cancer tactics, through cocktail strategy of targeting multiple key regulation links simultaneously, for preventing cancer occurrence or transforming the early cancer state back to normal state. PMID:25232051

Frictional properties of low-angle normal fault gouges and implications for low-angle normal fault slip

NASA Astrophysics Data System (ADS)

Haines, Samuel; Marone, Chris; Saffer, Demian

2014-12-01

The mechanics of slip on low-angle normal faults (LANFs) remain an enduring problem in structural geology and fault mechanics. In most cases, new faults should form rather than having slip occur on LANFs, assuming values of fault friction consistent with Byerlee's Law. We present results of laboratory measurements on the frictional properties of natural clay-rich gouges from low-angle normal faults (LANF) in the American Cordillera, from the Whipple Mts. Detachment, the Panamint range-front detachment, and the Waterman Hills detachment. These clay-rich gouges are dominated by neoformed clay minerals and are an integral part of fault zones in many LANFs, yet their frictional properties under in situ conditions remain relatively unknown. We conducted measurements under saturated and controlled pore pressure conditions at effective normal stresses ranging from 20 to 60 MPa (corresponding to depths of 0.9-2.9 km), on both powdered and intact wafers of fault rock. For the Whipple Mountains detachment, friction coefficient (μ) varies depending on clast content, with values ranging from 0.40 to 0.58 for clast-rich material, and 0.29-0.30 for clay-rich gouge. Samples from the Panamint range-front detachment were clay-rich, and exhibit friction values of 0.28 to 0.38, significantly lower than reported from previous studies on fault gouges tested under room humidity (nominally dry) conditions, including samples from the same exposure. Samples from the Waterman Hills detachment are slightly stronger, with μ ranging from 0.38 to 0.43. The neoformed gouge materials from all three localities exhibits velocity-strengthening frictional behavior under almost all of the experimental conditions we explored, with values of the friction rate parameter (a - b) ranging from -0.001 to +0.025. Clast-rich samples exhibited frictional healing (strength increases with hold time), whereas clay-rich samples do not. Our results indicate that where clay-rich neoformed gouges are present along LANFs, they provide a mechanically viable explanation for slip on faults with dips <20°, requiring only moderate (Pf <σ3) overpressures and/or correcting for ∼5° of footwall tilting. Furthermore, the low rates of frictional strength recovery and velocity-strengthening frictional behavior we observe provide an explanation for the lack of observed seismicity on these structures. We suggest that LANFs in the upper crust (depth <8 km) slip via a combination of a) reaction-weakening of initially high-angle fault zones by the formation of neoformed clay-rich gouges, and b) regional tectonic accommodation of rotating fault blocks.

A Range-Normalization Model of Context-Dependent Choice: A New Model and Evidence

PubMed Central

Camerer, Colin

2012-01-01

Most utility theories of choice assume that the introduction of an irrelevant option (called the decoy) to a choice set does not change the preference between existing options. On the contrary, a wealth of behavioral data demonstrates the dependence of preference on the decoy and on the context in which the options are presented. Nevertheless, neural mechanisms underlying context-dependent preference are poorly understood. In order to shed light on these mechanisms, we design and perform a novel experiment to measure within-subject decoy effects. We find within-subject decoy effects similar to what have been shown previously with between-subject designs. More importantly, we find that not only are the decoy effects correlated, pointing to similar underlying mechanisms, but also these effects increase with the distance of the decoy from the original options. To explain these observations, we construct a plausible neuronal model that can account for decoy effects based on the trial-by-trial adjustment of neural representations to the set of available options. This adjustment mechanism, which we call range normalization, occurs when the nervous system is required to represent different stimuli distinguishably, while being limited to using bounded neural activity. The proposed model captures our experimental observations and makes new predictions about the influence of the choice set size on the decoy effects, which are in contrast to previous models of context-dependent choice preference. Critically, unlike previous psychological models, the computational resource required by our range-normalization model does not increase exponentially as the set size increases. Our results show that context-dependent choice behavior, which is commonly perceived as an irrational response to the presence of irrelevant options, could be a natural consequence of the biophysical limits of neural representation in the brain. PMID:22829761

Mechanisms underlying perceptual learning of contrast detection in adults with anisometropic amblyopia

PubMed Central

Huang, Chang-Bing; Lu, Zhong-Lin; Zhou, Yifeng

2010-01-01

What underlies contrast sensitivity improvements in adults with anisometropic amblyopia following perceptual learning in grating contrast detection? In this paper, we adopted the external noise approach (Z.-L. Lu & B. A. Dosher, 1998) to identify the mechanisms underlying perceptual learning in adults with anisometropic amblyopia. By measuring contrast thresholds in a range of external noise conditions at two performance levels (79.3% and 70.7%), we found that a mixture of internal additive noise reduction and external noise exclusion underlay training induced contrast sensitivity improvements in adults with anisometropic amblyopia. In comparison, normal adults exhibited only small amount of external noise exclusion under the same training conditions. The results suggest that neural plasticity may be more robust in amblyopia, lending further support of perceptual learning as a potential treatment for adult amblyopia. PMID:20053087

Effects of hypoxia and non-lethal shell damage on shell mechanical and geochemical properties of a calcifying polychaete

NASA Astrophysics Data System (ADS)

Leung, Jonathan Y. S.; Cheung, Napo K. M.

2018-06-01

Calcification is a vital biomineralization process where calcifying organisms construct their calcareous shells for protection. While this process is expected to deteriorate under hypoxia, which reduces the metabolic energy yielded by aerobic respiration, some calcifying organisms were shown to maintain normal shell growth. The underlying mechanism remains largely unknown, but may be related to changing shell mineralogical properties, whereby shell growth is sustained at the expense of shell quality. Thus, we examined whether such plastic response is exhibited to alleviate the impact of hypoxia on calcification by assessing the shell growth and shell properties of a calcifying polychaete in two contexts (life-threatening and unthreatened conditions). Although hypoxia substantially reduced respiration rate (i.e., less metabolic energy produced), shell growth was only slightly hindered without weakening mechanical strength under unthreatened conditions. Unexpectedly, hypoxia did not undermine defence response (i.e., enhanced shell growth and mechanical strength) under life-threatening conditions, which may be attributed to the changes in mineralogical properties (e.g., increased calcite / aragonite) to reduce the energy demand for calcification. While more soluble shells (e.g., increased Mg / Ca in calcite) were produced under hypoxia as the trade-off, our findings suggest that mineralogical plasticity could be fundamental for calcifying organisms to maintain calcification under metabolic stress conditions.

Preservation of kinematics with posterior cruciate-, bicruciate- and patient-specific bicruciate-retaining prostheses in total knee arthroplasty by using computational simulation with normal knee model

PubMed Central

Koh, Y-G.; Son, J.; Kwon, S-K.; Kim, H-J.; Kang, K-T.

2017-01-01

Objectives Preservation of both anterior and posterior cruciate ligaments in total knee arthroplasty (TKA) can lead to near-normal post-operative joint mechanics and improved knee function. We hypothesised that a patient-specific bicruciate-retaining prosthesis preserves near-normal kinematics better than standard off-the-shelf posterior cruciate-retaining and bicruciate-retaining prostheses in TKA. Methods We developed the validated models to evaluate the post-operative kinematics in patient-specific bicruciate-retaining, standard off-the-shelf bicruciate-retaining and posterior cruciate-retaining TKA under gait and deep knee bend loading conditions using numerical simulation. Results Tibial posterior translation and internal rotation in patient-specific bicruciate-retaining prostheses preserved near-normal kinematics better than other standard off-the-shelf prostheses under gait loading conditions. Differences from normal kinematics were minimised for femoral rollback and internal-external rotation in patient-specific bicruciate-retaining, followed by standard off-the-shelf bicruciate-retaining and posterior cruciate-retaining TKA under deep knee bend loading conditions. Moreover, the standard off-the-shelf posterior cruciate-retaining TKA in this study showed the most abnormal performance in kinematics under gait and deep knee bend loading conditions, whereas patient-specific bicruciate-retaining TKA led to near-normal kinematics. Conclusion This study showed that restoration of the normal geometry of the knee joint in patient-specific bicruciate-retaining TKA and preservation of the anterior cruciate ligament can lead to improvement in kinematics compared with the standard off-the-shelf posterior cruciate-retaining and bicruciate-retaining TKA. Cite this article: Y-G. Koh, J. Son, S-K. Kwon, H-J. Kim, O-R. Kwon, K-T. Kang. Preservation of kinematics with posterior cruciate-, bicruciate- and patient-specific bicruciate-retaining prostheses in total knee arthroplasty by using computational simulation with normal knee model. Bone Joint Res 2017;6:557–565. DOI: 10.1302/2046-3758.69.BJR-2016-0250.R1. PMID:28947604

High concentration of vitamin E decreases thermosensation and thermotaxis learning and the underlying mechanisms in the nematode Caenorhabditis elegans.

PubMed

Li, Yiping; Li, Yinxia; Wu, Qiuli; Ye, Huayue; Sun, Lingmei; Ye, Boping; Wang, Dayong

2013-01-01

α-tocopherol is a powerful liposoluble antioxidant and the most abundant isoform of vitamin E in the body. Under normal physiological conditions, adverse effects of relatively high concentration of vitamin E on organisms and the underlying mechanisms are still largely unclear. In the present study, we used the nematode Caenorhabditis elegans as an in vivo assay system to investigate the possible adverse effects of high concentration of vitamin E on thermosensation and thermotaxis learning and the underlying mechanisms. Our data show that treatment with 100-200 µg/mL of vitamin E did not noticeably influence both thermosensation and thermotaxis learning; however, treatment with 400 µg/mL of vitamin E altered both thermosensation and thermotaxis learning. The observed decrease in thermotaxis learning in 400 µg/mL of vitamin E treated nematodes might be partially due to the moderate but significant deficits in thermosensation, but not due to deficits in locomotion behavior or perception to food and starvation. Treatment with 400 µg/mL of vitamin E did not noticeably influence the morphology of GABAergic neurons, but significantly decreased fluorescent intensities of the cell bodies in AFD sensory neurons and AIY interneurons, required for thermosensation and thermotaxis learning control. Treatment with 400 µg/mL of vitamin E affected presynaptic function of neurons, but had no remarkable effects on postsynaptic function. Moreover, promotion of synaptic transmission by activating PKC-1 effectively retrieved deficits in both thermosensation and thermotaxis learning induced by 400 µg/mL of vitamin E. Therefore, relatively high concentrations of vitamin E administration may cause adverse effects on thermosensation and thermotaxis learning by inducing damage on the development of specific neurons and presynaptic function under normal physiological conditions in C. elegans.

[Radiation-induced genomic instability: phenomenon, molecular mechanisms, pathogenetic significance].

PubMed

Mazurik, V K; Mikhaĭlov, V F

2001-01-01

The recent data on the radiation-induced genome instability as a special state of progeny of cells irradiated in vitro as well as after a whole body exposure to ionizing radiation, that make these cells considerably different from normal, unirradiated cells, were considered. This state presents a number of cytogenetical, molecular-biological, cytological and biochemical manifestations untypical for normal cells. The state is controlled by the mechanisms of regulation of checkpoints of cell cycle, and apoptosis, that is under gene p53 control. The proof has been found that this state transfers from irradiated maternal cells to their surviving progeny by the epigenetical mechanisms and would exist until the cells restore the original state of response on the DNA damage. From the point of view of the genome instability conception, that considers the chromatine rearrangement as the adaptive-evolution mechanism of adaptation of the species to changeable environmental conditions, the radiation-induced genome instability may be considered as transition of irradiated progeny to the state of read these to adaptation changes with two alternative pathways. The first leads to adaptation to enviromental conditions and restoring of normal cell functions. The second presents the cell transition into the transformed state with remain genome instability and with increase of tumour growth probability.

Effect of intra-aortic balloon pump on coronary blood flow during different balloon cycles support: A computer study.

PubMed

Aye, Thin Pa Pa; Htet, Zwe Lin; Singhavilai, Thamvarit; Naiyanetr, Phornphop

2015-01-01

Intra-aortic balloon pump (IABP) has been used in clinical treatment as a mechanical circulatory support device for patients with heart failure. A computer model is used to study the effect on coronary blood flow (CBF) with different balloon cycles under both normal and pathological conditions. The model of cardiovascular and IABP is developed by using MATLAB SIMULINK. The effect on coronary blood flow has been studied under both normal and pathological conditions using different balloon cycles (balloon off; 1:4; 1:2; 1:1). A pathological heart is implemented by reducing the left ventricular contractility. The result of this study shows that the rate of balloon cycles is related to the level of coronary blood flow.

Modified floating-zone growth of organic single crystals

NASA Astrophysics Data System (ADS)

Kou, S.; Chen, C. P.

1994-04-01

For organic materials floating-zone crystal growth is superior to other melt growth processes in two significant respects: (1) the absence of crucible-induced mechanical damage and (2) minimum heating-induced chemical degradation. Due to the rather low surface tension of organic melts, however, floating-zone crystal growth under normal gravity has not been possible so far but microgravity is ideal for such a purpose. With the help of a modified floating-zone technique, organic single crystals of small cross-sections were test grown first under normal gravity. These small crystals were round and rectangular single crystals of benzil and salol, up to about 7 cm long and 6 mm in diameter or 9 mm × 3 mm in cross-section.

Fault Frictional Stability in a Nuclear Waste Repository

NASA Astrophysics Data System (ADS)

Orellana, Felipe; Violay, Marie; Scuderi, Marco; Collettini, Cristiano

2016-04-01

Exploitation of underground resources induces hydro-mechanical and chemical perturbations in the rock mass. In response to such disturbances, seismic events might occur, affecting the safety of the whole engineering system. The Mont Terri Rock Laboratory is an underground infrastructure devoted to the study of geological disposal of nuclear waste in Switzerland. At the site, it is intersected by large fault zones of about 0.8 - 3 m in thickness and the host rock formation is a shale rock named Opalinus Clay (OPA). The mineralogy of OPA includes a high content of phyllosilicates (50%), quartz (25%), calcite (15%), and smaller proportions of siderite and pyrite. OPA is a stiff, low permeable rock (2×10-18 m2), and its mechanical behaviour is strongly affected by the anisotropy induced by bedding planes. The evaluation of fault stability and associated fault slip behaviour (i.e. seismic vs. aseismic) is a major issue in order to ensure the long-term safety and operation of the repository. Consequently, experiments devoted to understand the frictional behaviour of OPA have been performed in the biaxial apparatus "BRAVA", recently developed at INGV. Simulated fault gouge obtained from intact OPA samples, were deformed at different normal stresses (from 4 to 30 MPa), under dry and fluid-saturated conditions. To estimate the frictional stability, the velocity-dependence of friction was evaluated during velocity steps tests (1-300 μm/s). Slide-hold-slide tests were performed (1-3000 s) to measure the amount of frictional healing. The collected data were subsequently modelled with the Ruina's slip dependent formulation of the rate and state friction constitutive equations. To understand the deformation mechanism, the microstructures of the sheared gouge were analysed. At 7 MPa normal stress and under dry conditions, the friction coefficient decreased from a peak value of μpeak,dry = 0.57 to μss,dry = 0.50. Under fluid-saturated conditions and same normal stress, the friction coefficient decreased from a peak value of μpeak,sat = 0.45 to μss,sat = 0.34. Additionally, it has been observed that the weakening distance Dw is smaller under fluid- saturated conditions (˜4 mm) compared to dry conditions (˜6 mm). Results showed a linear decrease of both peak friction and steady state friction when normal stress increases. When fluid- saturation degree of gouges is reduced, gouge samples underwent a transition from velocity strengthening to velocity weakening behaviour, thus indicating a potentially unstable frictional behaviour of the fault. Furthermore, under both saturated and dry conditions, the frictional healing rate showed a low recovery of the friction coefficient under different holding times. Our experiments indicate that the frictional behaviour of Opalinus Clay is characterized by complex processes depending upon normal stress, sliding velocity, and saturation degree of the samples. This complexity highlights the need for further experiments in order to better evaluate the seismic risk during long-term nuclear waste disposal within the OPA clay formation.

Laminin and Matrix metalloproteinase 11 regulate Fibronectin levels in the zebrafish myotendinous junction.

PubMed

Jenkins, Molly H; Alrowaished, Sarah S; Goody, Michelle F; Crawford, Bryan D; Henry, Clarissa A

2016-01-01

Remodeling of the extracellular matrix (ECM) regulates cell adhesion as well as signaling between cells and their microenvironment. Despite the importance of tightly regulated ECM remodeling for normal muscle development and function, mechanisms underlying ECM remodeling in vivo remain elusive. One excellent paradigm in which to study ECM remodeling in vivo is morphogenesis of the myotendinous junction (MTJ) during zebrafish skeletal muscle development. During MTJ development, there are dramatic shifts in the primary components comprising the MTJ matrix. One such shift involves the replacement of Fibronectin (Fn)-rich matrix, which is essential for both somite and early muscle development, with laminin-rich matrix essential for normal function of the myotome. Here, we investigate the mechanism underlying this transition. We show that laminin polymerization indirectly promotes Fn downregulation at the MTJ, via a matrix metalloproteinase 11 (Mmp11)-dependent mechanism. Laminin deposition and organization is required for localization of Mmp11 to the MTJ, where Mmp11 is both necessary and sufficient for Fn downregulation in vivo. Furthermore, reduction of residual Mmp11 in laminin mutants promotes a Fn-rich MTJ that partially rescues skeletal muscle architecture. These results identify a mechanism for Fn downregulation at the MTJ, highlight crosstalk between laminin and Fn, and identify a new in vivo function for Mmp11. Taken together, our data demonstrate a novel signaling pathway mediating Fn downregulation. Our data revealing new regulatory mechanisms that guide ECM remodeling during morphogenesis in vivo may inform pathological conditions in which Fn is dysregulated.

Parameterization of 18th January 2011 earthquake in Dalbadin Region, Southwest Pakistan

NASA Astrophysics Data System (ADS)

Shafiq-Ur-Rehman; Azeem, Tahir; Abd el-aal, Abd el-aziz Khairy; Nasir, Asma

2013-12-01

An earthquake of magnitude 7.3 Mw occurred on 18th January 2011 in Southwestern Pakistan, Baluchistan province (Dalbadin Region). The area has complex tectonics due to interaction of Indian, Eurasian and Arabian plates. Both thrust and strike slip earthquakes are dominant in this region with minor, localized normal faulting events. This earthquake under consideration (Dalbadin Earthquake) posed constraints in depth and focal parameters due to lack of data for evaluation of parameters from Pakistan, Iran or Afghanistan region. Normal faulting mechanism has been proposed by many researchers for this earthquake. In the present study the earthquake was relocated using the technique of travel time residuals. Relocated coordinates and depth were utilized to calculate the focal mechanism solution with outcome of a dominant strike slip mechanism, which is contrary to normal faulting. Relocated coordinates and resulting mechanism are more reliable than many reporting agencies as evaluation in this study is augmented by data from local seismic monitoring network of Pakistan. The tectonics in the area is governed by active subduction along the Makran Subduction Zone. This particular earthquake has strike slip mechanism due to breaking of subducting oceanic plate. This earthquake is located where oceanic lithosphere is subducting along with relative movements between Lut and Helmand blocks. Magnitude of this event i.e. Mw = 7.3, re evaluated depth and a previous study of mechanism of earthquake in same region (Shafiq et al., 2011) also supports the strike slip movement.

Material processing of convection-driven flow field and temperature distribution under oblique gravity

NASA Technical Reports Server (NTRS)

Hung, R. J.

1995-01-01

A set of mathematical formulation is adopted to study vapor deposition from source materials driven by heat transfer process under normal and oblique directions of gravitational acceleration with extremely low pressure environment of 10(exp -2) mm Hg. A series of time animation of the initiation and development of flow and temperature profiles during the course of vapor deposition has been obtained through the numerical computation. Computations show that the process of vapor deposition has been accomplished by the transfer of vapor through a fairly complicated flow pattern of recirculation under normal direction gravitational acceleration. It is obvious that there is no way to produce a homogeneous thin crystalline films with fine grains under such a complicated flow pattern of recirculation with a non-uniform temperature distribution under normal direction gravitational acceleration. There is no vapor deposition due to a stably stratified medium without convection for reverse normal direction gravitational acceleration. Vapor deposition under oblique direction gravitational acceleration introduces a reduced gravitational acceleration in vertical direction which is favorable to produce a homogeneous thin crystalline films. However, oblique direction gravitational acceleration also induces an unfavorable gravitational acceleration along horizontal direction which is responsible to initiate a complicated flow pattern of recirculation. In other words, it is necessary to carry out vapor deposition under a reduced gravity in the future space shuttle experiments with extremely low pressure environment to process vapor deposition with a homogeneous crystalline films with fine grains. Fluid mechanics simulation can be used as a tool to suggest most optimistic way of experiment with best setup to achieve the goal of processing best nonlinear optical materials.

Genes and signaling pathways involved in memory enhancement in mutant mice

PubMed Central

2014-01-01

Mutant mice have been used successfully as a tool for investigating the mechanisms of memory at multiple levels, from genes to behavior. In most cases, manipulating a gene expressed in the brain impairs cognitive functions such as memory and their underlying cellular mechanisms, including synaptic plasticity. However, a remarkable number of mutations have been shown to enhance memory in mice. Understanding how to improve a system provides valuable insights into how the system works under normal conditions, because this involves understanding what the crucial components are. Therefore, more can be learned about the basic mechanisms of memory by studying mutant mice with enhanced memory. This review will summarize the genes and signaling pathways that are altered in the mutants with enhanced memory, as well as their roles in synaptic plasticity. Finally, I will discuss how knowledge of memory-enhancing mechanisms could be used to develop treatments for cognitive disorders associated with impaired plasticity. PMID:24894914

Salt-tolerant and -sensitive alfalfa (Medicago sativa) cultivars have large variations in defense responses to the lepidopteran insect Spodoptera litura under normal and salt stress condition

PubMed Central

Lei, Yunting; Liu, Qing; Hettenhausen, Christian; Cao, Guoyan; Tan, Qing; Zhao, Weiye; Lin, Honghui

2017-01-01

In nature, plants are often exposed to multiple stress factors at the same time. Yet, little is known about how plants modulate their physiology to counteract simultaneous abiotic and biotic stresses, such as soil salinity and insect herbivory. In this study, insect performance bioassays, phytohormone measurements, quantification of transcripts, and protein determination were employed to study the phenotypic variations of two alfalfa (Medicago sativa) cultivars in response to insect Spodoptera litura feeding under normal and salt stress condition. When being cultivated in normal soil, the salt-tolerant alfalfa cultivar Zhongmu-1 exhibited lower insect resistance than did the salt-sensitive cultivar Xinjiang Daye. Under salinity stress, the defense responses of Xinjiang Daye were repressed, whereas Zhongmu-1 did not show changes in resistance levels. It is likely that salinity influenced the resistance of Xinjiang Daye through suppressing the accumulation of jasmonic acid-isoleucine (JA-Ile), which is the bioactive hormone inducing herbivore defense responses, leading to attenuated trypsin proteinase inhibitor (TPI) activity. Furthermore, exogenous ABA supplementation suppressed the insect herbivory-induced JA/JA-Ile accumulation and levels of JAR1 (jasmonate resistant 1) and TPI, and further decreased the resistance of Xinjiang Daye, whereas Zhongmu-1 showed very little response to the increased ABA level. We propose a mechanism, in which high levels of abscisic acid induced by salt treatment may affect the expression levels of JAR1 and consequently decrease JA-Ile accumulation and thus partly suppress the defense of Xinjiang Daye against insects under salt stress. This study provides new insight into the mechanism by which alfalfa responds to concurrent abiotic and biotic stresses. PMID:28719628

Salt-tolerant and -sensitive alfalfa (Medicago sativa) cultivars have large variations in defense responses to the lepidopteran insect Spodoptera litura under normal and salt stress condition.

PubMed

Lei, Yunting; Liu, Qing; Hettenhausen, Christian; Cao, Guoyan; Tan, Qing; Zhao, Weiye; Lin, Honghui; Wu, Jianqiang

2017-01-01

In nature, plants are often exposed to multiple stress factors at the same time. Yet, little is known about how plants modulate their physiology to counteract simultaneous abiotic and biotic stresses, such as soil salinity and insect herbivory. In this study, insect performance bioassays, phytohormone measurements, quantification of transcripts, and protein determination were employed to study the phenotypic variations of two alfalfa (Medicago sativa) cultivars in response to insect Spodoptera litura feeding under normal and salt stress condition. When being cultivated in normal soil, the salt-tolerant alfalfa cultivar Zhongmu-1 exhibited lower insect resistance than did the salt-sensitive cultivar Xinjiang Daye. Under salinity stress, the defense responses of Xinjiang Daye were repressed, whereas Zhongmu-1 did not show changes in resistance levels. It is likely that salinity influenced the resistance of Xinjiang Daye through suppressing the accumulation of jasmonic acid-isoleucine (JA-Ile), which is the bioactive hormone inducing herbivore defense responses, leading to attenuated trypsin proteinase inhibitor (TPI) activity. Furthermore, exogenous ABA supplementation suppressed the insect herbivory-induced JA/JA-Ile accumulation and levels of JAR1 (jasmonate resistant 1) and TPI, and further decreased the resistance of Xinjiang Daye, whereas Zhongmu-1 showed very little response to the increased ABA level. We propose a mechanism, in which high levels of abscisic acid induced by salt treatment may affect the expression levels of JAR1 and consequently decrease JA-Ile accumulation and thus partly suppress the defense of Xinjiang Daye against insects under salt stress. This study provides new insight into the mechanism by which alfalfa responds to concurrent abiotic and biotic stresses.

Changes in Mechanics and Composition of Human Talar Cartilage Anlagen During Fetal Development

PubMed Central

Mahmoodian, Roza; Leasure, Jeremi; Philip, Phitha; Pleshko, Nancy; Capaldi, Franco; Siegler, Sorin

2011-01-01

Objective Fetal cartilage anlage provides a framework for endochondral ossification and organization into articular cartilage. We previously reported differences between mechanical properties of talar cartilage anlagen and adult articular cartilage. However, the underlying development-associated changes remain to be established. Delineation of the normal evolvement of mechanical properties and its associated compositional basis provides insight into the natural mechanisms of cartilage maturation. Our goal was to address this issue. Materials and methods Human fetal cartilage anlagen were harvested from the tali of normal stillborn fetuses from 20 to 36 weeks of gestational age. Data obtained from stress relaxation experiments conducted under confined and unconfined compression configurations were processed to derive the compressive mechanical properties. The compressive mechanical properties were extracted from a linear fit to the equilibrium response in unconfined compression, and by using the nonlinear biphasic theory to fit to the experimental data from the confined compression experiment, both in stress-relaxation. The molecular composition was obtained using FTIR, and spatial maps of tissue contents per dry weight were created using FTIR imaging. Correlative and regression analyses were performed to identify relationships between the mechanical properties and age, compositional properties and age, and mechanical versus compositional parameters. Results All of the compositional quantities and the mechanical properties excluding the Poisson’s ratio changed with maturation. Stiffness increased by a factor of ~2.5 and permeability decreased by 20% over the period studied. Collagen content and degree of collagen integrity increased with age by ~3-fold, while the proteoglycan content decreased by 18%. Significant relations were found between the mechanical and compositional properties. Conclusion The mechanics of fetal talar cartilage is related to its composition, where the collagen and proteoglycan network play a prominent role. An understanding of the mechanisms of early cartilage maturation could provide a framework to guide tissue-engineering strategies. PMID:21843650

The Mechanisms of Psychedelic Visionary Experiences: Hypotheses from Evolutionary Psychology

PubMed Central

Winkelman, Michael J.

2017-01-01

Neuropharmacological effects of psychedelics have profound cognitive, emotional, and social effects that inspired the development of cultures and religions worldwide. Findings that psychedelics objectively and reliably produce mystical experiences press the question of the neuropharmacological mechanisms by which these highly significant experiences are produced by exogenous neurotransmitter analogs. Humans have a long evolutionary relationship with psychedelics, a consequence of psychedelics' selective effects for human cognitive abilities, exemplified in the information rich visionary experiences. Objective evidence that psychedelics produce classic mystical experiences, coupled with the finding that hallucinatory experiences can be induced by many non-drug mechanisms, illustrates the need for a common model of visionary effects. Several models implicate disturbances of normal regulatory processes in the brain as the underlying mechanisms responsible for the similarities of visionary experiences produced by psychedelic and other methods for altering consciousness. Similarities in psychedelic-induced visionary experiences and those produced by practices such as meditation and hypnosis and pathological conditions such as epilepsy indicate the need for a general model explaining visionary experiences. Common mechanisms underlying diverse alterations of consciousness involve the disruption of normal functions of the prefrontal cortex and default mode network (DMN). This interruption of ordinary control mechanisms allows for the release of thalamic and other lower brain discharges that stimulate a visual information representation system and release the effects of innate cognitive functions and operators. Converging forms of evidence support the hypothesis that the source of psychedelic experiences involves the emergence of these innate cognitive processes of lower brain systems, with visionary experiences resulting from the activation of innate processes based in the mirror neuron system (MNS). PMID:29033783

Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

2015-11-01

Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

Experimental Analysis of the Mechanism of Hearing under Water

PubMed Central

Chordekar, Shai; Kishon-Rabin, Liat; Kriksunov, Leonid; Adelman, Cahtia; Sohmer, Haim

2015-01-01

The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC). PMID:26770975

Thermo-mechanical mechanism of laser-assisted alteration and stabilization of micro pore structure in eye-sclera

NASA Astrophysics Data System (ADS)

Baum, Olga; Wachsmann-Hogiu, Sebastian; Sobol, Emil

2018-02-01

Thermo-mechanical effect of laser radiation is a basis of new method of normalization of intraocular pressure in glaucomatous eyes due to laser-assisted pore formation in eye sclera. Laser-induced creation of pores in sclera increases hydraulic permeability. Stability of laser-induced pore system is achieved via gas nano-bubbles arisen in the sclera under laser radiation as a result of temperature dependency of gas solubility. The stabilization of laser-induced gas and pore systems in the tissue is an important mechanism for a long lasting healing of glaucoma observed in clinical trials with one year follow-up.

Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics

PubMed Central

Cao, Xuan; van Oosten, Anne; Shenoy, Vivek B.; Janmey, Paul A.; Wells, Rebecca G.

2016-01-01

Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G’ and G” and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver. PMID:26735954

A preliminary study of differentially expressed genes in expanded skin and normal skin: implications for adult skin regeneration.

PubMed

Yang, Mei; Liang, Yimin; Sheng, Lingling; Shen, Guoxiong; Liu, Kai; Gu, Bin; Meng, Fanjun; Li, Qingfeng

2011-03-01

In adults, severely damaged skin heals by scar formation and cannot regenerate to the original skin structure. However, tissue expansion is an exception, as normal skin regenerates under the mechanical stretch resulting from tissue expansion. This technique has been used clinically for defect repair and organ reconstruction for decades. However, the phenomenon of adult skin regeneration during tissue expansion has caused little attention, and the mechanism of skin regeneration during tissue expansion has not been fully understood. In this study, microarray analysis was performed on expanded human skin and normal human skin. Significant difference was observed in 77 genes, which suggest a network of several integrated cascades, including cytokines, extracellular, cytoskeletal, transmembrane molecular systems, ion or ion channels, protein kinases and transcriptional systems, is involved in the skin regeneration during expansion. Among these, the significant expression of some regeneration related genes, such as HOXA5, HOXB2 and AP1, was the first report in tissue expansion. Data in this study suggest a list of candidate genes, which may help to elucidate the fundamental mechanism of skin regeneration during tissue expansion and which may have implications for postnatal skin regeneration and therapeutic interventions in wound healing.

The mechanical properties of stored red blood cells measured by a convenient microfluidic approach combining with mathematic model.

PubMed

Wang, Ying; You, Guoxing; Chen, Peipei; Li, Jianjun; Chen, Gan; Wang, Bo; Li, Penglong; Han, Dong; Zhou, Hong; Zhao, Lian

2016-03-01

The mechanical properties of red blood cells (RBCs) are critical to the rheological and hemodynamic behavior of blood. Although measurements of the mechanical properties of RBCs have been studied for many years, the existing methods, such as ektacytometry, micropipette aspiration, and microfluidic approaches, still have limitations. Mechanical changes to RBCs during storage play an important role in transfusions, and so need to be evaluated pre-transfusion, which demands a convenient and rapid detection method. We present a microfluidic approach that focuses on the mechanical properties of single cell under physiological shear flow and does not require any high-end equipment, like a high-speed camera. Using this method, the images of stretched RBCs under physical shear can be obtained. The subsequent analysis, combined with mathematic models, gives the deformability distribution, the morphology distribution, the normalized curvature, and the Young's modulus (E) of the stored RBCs. The deformability index and the morphology distribution show that the deformability of RBCs decreases significantly with storage time. The normalized curvature, which is defined as the curvature of the cell tail during stretching in flow, suggests that the surface charge of the stored RBCs decreases significantly. According to the mathematic model, which derives from the relation between shear stress and the adherent cells' extension ratio, the Young's moduli of the stored RBCs are also calculated and show significant increase with storage. Therefore, the present method is capable of representing the mechanical properties and can distinguish the mechanical changes of the RBCs during storage. The advantages of this method are the small sample needed, high-throughput, and easy-use, which make it promising for the quality monitoring of RBCs.

Proteomic Adaptations to Starvation Prepare Escherichia coli for Disinfection Tolerance

PubMed Central

Du, Zhe; Nandakumar, Renu; Nickerson, Kenneth; Li, Xu

2015-01-01

Despite the low nutrient level and constant presence of secondary disinfectants, bacterial re-growth still occurs in drinking water distribution systems. The molecular mechanisms that starved bacteria use to survive low-level chlorine-based disinfectants are not well understood. The objective of this study is to investigate these molecular mechanisms at the protein level that prepare starved cells for disinfection tolerance. Two commonly used secondary disinfectants chlorine and monochloramine, both at 1 mg/L, were used in this study. The proteomes of normal and starved Escherichia coli (K12 MG1655) cells were studied using quantitative proteomics. Over 60-min disinfection, starved cells showed significantly higher disinfection tolerance than normal cells based on the inactivation curves for both chlorine and monochloramine. Proteomic analyses suggest that starvation may prepare cells for the oxidative stress that chlorine-based disinfection will cause by affecting glutathione metabolism. In addition, proteins involved in stress regulation and stress responses were among the ones up-regulated under both starvation and chlorine/monochloramine disinfection. By comparing the fold changes under different conditions, it is suggested that starvation prepares E. coli for disinfection tolerance by increasing the expression of enzymes that can help cells survive chlorine/monochloramine disinfection. Protein co-expression analyses show that proteins in glycolysis and pentose phosphate pathway that were up-regulated under starvation are also involved in disinfection tolerance. Finally, the production and detoxification of methylglyoxal may be involved in the chlorine-based disinfection and cell defense mechanisms. PMID:25463932

Proteomic adaptations to starvation prepare Escherichia coli for disinfection tolerance.

PubMed

Du, Zhe; Nandakumar, Renu; Nickerson, Kenneth W; Li, Xu

2015-02-01

Despite the low nutrient level and constant presence of secondary disinfectants, bacterial re-growth still occurs in drinking water distribution systems. The molecular mechanisms that starved bacteria use to survive low-level chlorine-based disinfectants are not well understood. The objective of this study is to investigate these molecular mechanisms at the protein level that prepare starved cells for disinfection tolerance. Two commonly used secondary disinfectants chlorine and monochloramine, both at 1 mg/L, were used in this study. The proteomes of normal and starved Escherichia coli (K12 MG1655) cells were studied using quantitative proteomics. Over 60-min disinfection, starved cells showed significantly higher disinfection tolerance than normal cells based on the inactivation curves for both chlorine and monochloramine. Proteomic analyses suggest that starvation may prepare cells for the oxidative stress that chlorine-based disinfection will cause by affecting glutathione metabolism. In addition, proteins involved in stress regulation and stress responses were among the ones up-regulated under both starvation and chlorine/monochloramine disinfection. By comparing the fold changes under different conditions, it is suggested that starvation prepares E. coli for disinfection tolerance by increasing the expression of enzymes that can help cells survive chlorine/monochloramine disinfection. Protein co-expression analyses show that proteins in glycolysis and pentose phosphate pathway that were up-regulated under starvation are also involved in disinfection tolerance. Finally, the production and detoxification of methylglyoxal may be involved in the chlorine-based disinfection and cell defense mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Research on the porous flow of the mechanism of viscous-elastic fluids displacing residual oil droplets in micro pores

NASA Astrophysics Data System (ADS)

Dong, Guanyu

2018-03-01

In order to analyze the microscopic stress field acting on residual oil droplets in micro pores, calculate its deformation, and explore the hydrodynamic mechanism of viscous-elastic fluids displacing oil droplets, the viscous-elastic fluid flow equations in micro pores are established by choosing the Upper Convected Maxwell constitutive equation; the numerical solutions of the flow field are obtained by volume control and Alternate Direction Implicit methods. From the above, the velocity field and microscopic stress field; the forces acting on residual oil droplets; the deformations of residual oil droplets by various viscous-elastic displacing fluids and at various Wiesenberg numbers are calculated and analyzed. The result demonstrated that both the normal stress and horizontal force acting on the residual oil droplets by viscous-elastic fluids are much larger compared to that of inelastic fluid; the distribution of normal stress changes abruptly; under the condition of the same pressure gradient in the system under investigation, the ratio of the horizontal forces acting on the residual oil droplets by different displacing fluids is about 1:8:20, which means that under the above conditions, the driving force on a oil droplet is 20 times higher for a viscous-elastic fluid compared to that of a Newtonian Fluid. The conclusions are supportive of the mechanism that viscous-elastic driving fluids can increase the Displacement Efficiency. This should be of help in designing new chemicals and selecting Enhanced Oil Recovery systems.

REACTOR CONTROL MECHANISM

DOEpatents

Lane, J.A.; Engberg, R.E.; Welch, J.M.

1959-05-12

A quick-releasing mechanism is described which may be used to rapidiy drop a device supported from beneath during normal use, such as a safety rod in a nuclear reactor. In accordance with this invention an electrical control signal, such as may be provided by radiation detection or other alarm condition sensing devices, is delivered to an electromagnetic solenoid, the armature of which is coupled to an actuating mechanism. The solenoid is energized when the mechanism is in its upper or cocked position. In such position, the mechanism engages a plurality of retaining balls, forcing them outward into engagement with a shoulder or recess in a corresponding section of a tubular extension on the upheld device. When the control signal to the solenoid suddenly ceases, the armature drops out, allowing the actuating mechanism to move slightly but rapidly under the force of a compressed spring. The weight of the device will urge the balls inward against a beveled portion of the actuating mechanism and away from the engaging section on the tubular extension, thus allowing the upheld device to fall freely under the influence of gravity.

Effects of neuroinflammation on the regenerative capacity of brain stem cells.

PubMed

Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

2011-03-01

In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the lipopolysaccharide-model to study the effects of inflammation and reactive-microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Aspects of body self-calibration

NASA Technical Reports Server (NTRS)

Lackner, J. R.; DiZio, P. A.

2000-01-01

The representation of body orientation and configuration is dependent on multiple sources of afferent and efferent information about ongoing and intended patterns of movement and posture. Under normal terrestrial conditions, we feel virtually weightless and we do not perceive the actual forces associated with movement and support of our body. It is during exposure to unusual forces and patterns of sensory feedback during locomotion that computations and mechanisms underlying the ongoing calibration of our body dimensions and movements are revealed. This review discusses the normal mechanisms of our position sense and calibration of our kinaesthetic, visual and auditory sensory systems, and then explores the adaptations that take place to transient Coriolis forces generated during passive body rotation. The latter are very rapid adaptations that allow body movements to become accurate again, even in the absence of visual feedback. Muscle spindle activity interpreted in relation to motor commands and internally modeled reafference is an important component in permitting this adaptation. During voluntary rotary movements of the body, the central nervous system automatically compensates for the Coriolis forces generated by limb movements. This allows accurate control to be maintained without our perceiving the forces generated.

No evidence that skewing of X chromosome inactivation patterns is transmitted to offspring in humans

PubMed Central

Bolduc, Véronique; Chagnon, Pierre; Provost, Sylvie; Dubé, Marie-Pierre; Belisle, Claude; Gingras, Marianne; Mollica, Luigina; Busque, Lambert

2007-01-01

Skewing of X chromosome inactivation (XCI) can occur in normal females and increases in tissues with age. The mechanisms underlying skewing in normal females, however, remain controversial. To better understand the phenomenon of XCI in nondisease states, we evaluated XCI patterns in epithelial and hematopoietic cells of over 500 healthy female mother-neonate pairs. The incidence of skewing observed in mothers was twice that observed in neonates, and in both cohorts, the incidence of XCI was lower in epithelial cells than hematopoietic cells. These results suggest that XCI incidence varies by tissue type and that age-dependent mechanisms can influence skewing in both epithelial and hematopoietic cells. In both cohorts, a correlation was identified in the direction of skewing in epithelial and hematopoietic cells, suggesting common underlying skewing mechanisms across tissues. However, there was no correlation between the XCI patterns of mothers and their respective neonates, and skewed mothers gave birth to skewed neonates at the same frequency as nonskewed mothers. Taken together, our data suggest that in humans, the XCI pattern observed at birth does not reflect a single heritable genetic locus, but rather corresponds to a complex trait determined, at least in part, by selection biases occurring after XCI. PMID:18097474

Different Effects of Hypoxia on Mental Rotation of Normal and Mirrored Letters: Evidence from the Rotation-Related Negativity.

PubMed

Ma, Qingguo; Hu, Linfeng; Li, Jiaojie; Hu, Yue; Xia, Ling; Chen, Xiaojian; Hu, Wendong

2016-01-01

The present study explored the neural mechanism underlying the effect of moderate and transient hypoxic exposure on mental rotation of two-dimensional letters in both normal and mirror versions. Event-related potential data and behavioral data were acquired in the task of discrimination between normal and mirrored versions separately in conditions of normoxia (simulated sea level) and hypoxia conditions (simulated 5000 meter altitude). The behavioral results revealed no significant difference between the normoxia and hypoxia conditions both in response time and error rate. However, obvious differences between these two conditions in ERP were found. First, enlarged P300 and Rotation-related Negativity (RRN) were observed in the hypoxia condition compared to the normoxia condition only with normal letters. Second, the angle effect on the amplitude of RRN was more evident with normal letters in the hypoxia condition than that in the normoxia condition. However, this angle effect nearly disappeared with the mirrored letters in the hypoxia condition. Third, more bilateral parietal activation was observed in the hypoxia condition than the normoxia condition. These results suggested that the compensation mechanism existed in the hypoxia condition and was effective with normal letters but had little effect on the mirrored letters. This study extends the research about the hypoxic effect on spatial ability of humans by employing a mental rotation task and further provides neural evidence for this effect.

Different Effects of Hypoxia on Mental Rotation of Normal and Mirrored Letters: Evidence from the Rotation-Related Negativity

PubMed Central

Ma, Qingguo; Hu, Linfeng; Li, Jiaojie; Hu, Yue; Xia, Ling; Chen, Xiaojian; Hu, Wendong

2016-01-01

The present study explored the neural mechanism underlying the effect of moderate and transient hypoxic exposure on mental rotation of two-dimensional letters in both normal and mirror versions. Event-related potential data and behavioral data were acquired in the task of discrimination between normal and mirrored versions separately in conditions of normoxia (simulated sea level) and hypoxia conditions (simulated 5000 meter altitude). The behavioral results revealed no significant difference between the normoxia and hypoxia conditions both in response time and error rate. However, obvious differences between these two conditions in ERP were found. First, enlarged P300 and Rotation-related Negativity (RRN) were observed in the hypoxia condition compared to the normoxia condition only with normal letters. Second, the angle effect on the amplitude of RRN was more evident with normal letters in the hypoxia condition than that in the normoxia condition. However, this angle effect nearly disappeared with the mirrored letters in the hypoxia condition. Third, more bilateral parietal activation was observed in the hypoxia condition than the normoxia condition. These results suggested that the compensation mechanism existed in the hypoxia condition and was effective with normal letters but had little effect on the mirrored letters. This study extends the research about the hypoxic effect on spatial ability of humans by employing a mental rotation task and further provides neural evidence for this effect. PMID:27144444

AGEs Induce Apoptosis in Rat Osteoblast Cells by Activating the Caspase-3 Signaling Pathway Under a High-Glucose Environment In Vitro.

PubMed

Liu, Jiaqiang; Mao, Jing; Jiang, Yi; Xia, Lunguo; Mao, Lixia; Wu, Yong; Ma, Pan; Fang, Bing

2016-03-01

Advanced glycation end products (AGEs) accumulate under high-glucose conditions and affect the healing of bone damage through various pathways; however, the detail mechanisms underlying these changes are unknown. In this study, we investigated the effects of AGEs on the apoptosis of in vitro-cultured rat osteoblasts under high-glucose conditions and explored the underlying mechanisms of these effects. First, we cultured rat osteoblasts and determined the accumulation of AGEs in the culture medium under high-glucose conditions. Then, we cultured rat osteoblasts under a high glucose concentration (35 mM), a normal glucose concentration (5.5 mM), and a normal glucose concentration (5.5 mM) in the presence of AGEs. We examined the effects of high glucose and AGEs on the apoptosis of rat osteoblasts at different time points and further analyzed the activity and changes in the levels of procaspase-3, caspase-3, and the caspase-3 substrate poly ADP-ribose polymerase (PARP). Finally, we added sRAGE (soluble RAGE) (an AGE inhibitor) or DEVD (a caspase-3 inhibitor) to each culture group and examined apoptosis under each culture condition and the changes in the levels of procaspase-3, caspase-3, and its substrate PARP. The results showed that the high-glucose condition and the addition of AGEs increased the apoptosis of rat osteoblast cells and simultaneously increased the activity and quantity of caspase-3. These increases could be inhibited by the AGE inhibitor sRAGE or the caspase-3 inhibitor DEVD. The above results demonstrate that high-glucose conditions lead to the accumulation of AGEs and activation of the caspase-3 signaling pathway, resulting in the increased apoptosis of cultured rat osteoblast cells.

Mechanisms for pituitary tumorigenesis: the plastic pituitary

PubMed Central

Melmed, Shlomo

2003-01-01

The anterior pituitary gland integrates the repertoire of hormonal signals controlling thyroid, adrenal, reproductive, and growth functions. The gland responds to complex central and peripheral signals by trophic hormone secretion and by undergoing reversible plastic changes in cell growth leading to hyperplasia, involution, or benign adenomas arising from functional pituitary cells. Discussed herein are the mechanisms underlying hereditary pituitary hypoplasia, reversible pituitary hyperplasia, excess hormone production, and tumor initiation and promotion associated with normal and abnormal pituitary differentiation in health and disease. PMID:14660734

Investigation of Mechanisms Associated with Nucleate Boiling Under Microgravity Conditions

NASA Technical Reports Server (NTRS)

Dhir, Vijay K.

1996-01-01

The focus of the present work is to experimentally study and to analytically/numerically model the mechanisms of growth of bubbles attached to, and sliding along, a heated surface. To control the location of the active cavities, the number, the spacing, and the nucleation superheat, artificial cavities will be formed on silicon wafers. In order to study the effect of magnitude of components of gravitational acceleration acting parallel to, and normal to the surface, experiments will be conducted on surfaces inclined at different angles including a downward facing surface. Information on the temperature field around bubbles, bubble shape and size, and bubble induced liquid velocities will be obtained through the use of holography, video/high speed photography and hydrogen bubble techniques, respectively. Analytical/numerical models will be developed to describe the heat transfer including that through the micro-macro layer underneath and around a bubble. In the micro layer model capillary and disjoining pressures will be included. Evolution of the interface along with induced liquid motion will be modelled. Subsequent to the world at normal gravity, experiments will be conducted in the KC-135 or the Lear jet especially to learn about bubble growth/detachment under low gravity conditions. Finally, an experiment will be defined to be conducted under long duration of microgravity conditions in the space shuttle. The experiment in the space shuttle will provide microgravity data on bubble growth and detachment and will lead to a validation of the nucleate boiling heat transfer model developed from the preceding studies performed at normal and low gravity (KC-135 or Lear jet) conditions.

Effect of Deep Cryogenic treatment on AISI A8 Tool steel & Development of Wear Mechanism maps using Fuzzy Clustering

NASA Astrophysics Data System (ADS)

Pillai, Nandakumar; Karthikeyan, R., Dr.

2018-04-01

Tool steels are widely classified according to their constituents and type of thermal treatments carried out to obtain its properties. Viking a special purpose tool steel coming under AISI A8 cold working steel classification is widely used for heavy duty blanking and forming operations. The optimum combination of wear resistance and toughness as well as ease of machinability in pre-treated condition makes this material accepted in heavy cutting and non cutting tool manufacture. Air or vacuum hardening is recommended as the normal treatment procedure to obtain the desired mechanical and tribological properties for steels under this category. In this study, we are incorporating a deep cryogenic phase within the conventional treatment cycle both before and after tempering. The thermal treatments at sub zero temperatures up to -195°C using cryogenic chamber with liquid nitrogen as medium was conducted. Micro structural changes in its microstructure and the corresponding improvement in the tribological and physical properties are analyzed. The cryogenic treatment leads to more conversion of retained austenite to martensite and also formation of fine secondary carbides. The microstructure is studied using the micrographs taken using optical microscopy. The wear tests are conducted on DUCOM tribometer for different combinations of speed and load under normal temperature. The wear rates and coefficient of friction obtained from these experiments are used to developed wear mechanism maps with the help of fuzzy c means clustering and probabilistic neural network models. Fuzzy C means clustering is an effective algorithm to group data of similar patterns. The wear mechanisms obtained from the computationally developed maps are then compared with the SEM photographs taken and the improvement in properties due to this additional cryogenic treatment is validated.

Physicochemical Processes and the Evolution of Strength in Calcite Fault Gouge at Room Temperature

NASA Astrophysics Data System (ADS)

Carpenter, B. M.; Viti, C.; Collettini, C.

2015-12-01

The presence of calcite in and near faults, as the dominant material, cement, or vein fill, indicates that the mechanical behavior of carbonate-dominated material likely plays an important role in shallow- and mid-crustal faulting. Furthermore, a variety of physical and chemical processes control the evolution of strength and style of slip along seismogenic faults and thus play a critical role in the seismic cycle. Determining the role and contributions of these types of mechanisms is essential to furthering our understanding of the processes and timescales that lead to the strengthening of faults during interseismic periods and their behavior during the earthquake nucleation process. To further our understanding of these processes, we performed laboratory-shearing experiments on calcite gouge at normal stresses from 1 to 100 MPa, under conditions of saturation and at room temperature. We performed velocity stepping (0.1-1000μm/s) and slide-hold-slide (1-3000s) tests, to measure the velocity dependence of friction and the amount of frictional strengthening respectively, under saturated conditions with pore fluid that was in equilibrium with CaCO3. At 5 MPa normal stress, we also varied the environmental conditions by performing experiments under conditions of 5% RH and 50 % RH, and saturation with: silicone oil, demineralized water, and the equilibrated solution combined with 0.5M NaCl. Finally, we collected post experimental samples for microscopic analysis. Our combined analyses of rate-dependence, strengthening behavior, and microstructures show that calcite fault gouge transitions from brittle to semi-brittle behavior at high normal stress and low sliding velocities. Furthermore, our results also highlight how changes in pore water chemistry can have significant influence on the mechanical behavior of calcite gouge in both the laboratory and in natural faults. Our observations have important implications for earthquake nucleation and propagation on faults in carbonate-dominated lithologies.

Nonepileptic seizures under levetiracetam therapy: a case report of forced normalization process.

PubMed

Anzellotti, Francesca; Franciotti, Raffaella; Zhuzhuni, Holta; D'Amico, Aurelio; Thomas, Astrid; Onofrj, Marco

2014-01-01

Nonepileptic seizures (NES) apparently look like epileptic seizures, but are not associated with ictal electrical discharges in the brain. NES constitute one of the most important differential diagnoses of epilepsy. They have been recognized as a distinctive clinical phenomenon for centuries, and video/electroencephalogram monitoring has allowed clinicians to make near-certain diagnoses. NES are supposedly unrelated to organic brain lesions, and despite the preponderance of a psychiatric/psychological context, they may have an iatrogenic origin. We report a patient with NES precipitated by levetiracetam therapy; in this case, NES was observed during the disappearance of epileptiform discharges from the routine video/electroencephalogram. We discuss the possible mechanisms underlying NES with regard to alternative psychoses associated with the phenomenon of the forced normalization process.

Nonepileptic seizures under levetiracetam therapy: a case report of forced normalization process

PubMed Central

Anzellotti, Francesca; Franciotti, Raffaella; Zhuzhuni, Holta; D’Amico, Aurelio; Thomas, Astrid; Onofrj, Marco

2014-01-01

Nonepileptic seizures (NES) apparently look like epileptic seizures, but are not associated with ictal electrical discharges in the brain. NES constitute one of the most important differential diagnoses of epilepsy. They have been recognized as a distinctive clinical phenomenon for centuries, and video/electroencephalogram monitoring has allowed clinicians to make near-certain diagnoses. NES are supposedly unrelated to organic brain lesions, and despite the preponderance of a psychiatric/psychological context, they may have an iatrogenic origin. We report a patient with NES precipitated by levetiracetam therapy; in this case, NES was observed during the disappearance of epileptiform discharges from the routine video/electroencephalogram. We discuss the possible mechanisms underlying NES with regard to alternative psychoses associated with the phenomenon of the forced normalization process. PMID:24926197

Crossover from ballistic to normal heat transport in the ϕ4 lattice: If nonconservation of momentum is the reason, what is the mechanism?

NASA Astrophysics Data System (ADS)

Xiong, Daxing; Saadatmand, Danial; Dmitriev, Sergey V.

2017-10-01

Anomalous (non-Fourier) heat transport is no longer just a theoretical issue since it has been observed experimentally in a number of low-dimensional nanomaterials, such as SiGe nanowires, carbon nanotubes, and others. To understand these anomalous behaviors, exploring the microscopic origin of normal (Fourier) heat transport is a fascinating theoretical topic. However, this issue has not yet been fully understood even for one-dimensional (1D) model chains, in spite of a great amount of thorough studies done to date. From those studies, it has been widely accepted that the conservation of momentum is a key ingredient to induce anomalous heat transport, while momentum-nonconserving systems usually support normal heat transport where Fourier's law is valid. But if the nonconservation of momentum is the reason, what is the underlying microscopic mechanism for the observed normal heat transport? Here we carefully revisit a typical 1D momentum-nonconserving ϕ4 model, and we present evidence that the mobile discrete breathers, or, in other words, the moving intrinsic localized modes with frequency components above the linear phonon band, can be responsible for that.

Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning.

PubMed

Matsuzaki, Satoshi; Szweda, Pamela A; Szweda, Luke I; Humphries, Kenneth M

2009-11-30

Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

Active transfer fault zone linking a segmented extensional system (Betics, southern Spain): Insight into heterogeneous extension driven by edge delamination

NASA Astrophysics Data System (ADS)

Martínez-Martínez, José Miguel; Booth-Rea, Guillermo; Azañón, José Miguel; Torcal, Federico

2006-08-01

Pliocene and Quaternary tectonic structures mainly consisting of segmented northwest-southeast normal faults, and associated seismicity in the central Betics do not agree with the transpressive tectonic nature of the Africa-Eurasia plate boundary in the Ibero-Maghrebian region. Active extensional deformation here is heterogeneous, individual segmented normal faults being linked by relay ramps and transfer faults, including oblique-slip and both dextral and sinistral strike-slip faults. Normal faults extend the hanging wall of an extensional detachment that is the active segment of a complex system of successive WSW-directed extensional detachments which have thinned the Betic upper crust since middle Miocene. Two areas, which are connected by an active 40-km long dextral strike-slip transfer fault zone, concentrate present-day extension. Both the seismicity distribution and focal mechanisms agree with the position and regime of the observed faults. The activity of the transfer zone during middle Miocene to present implies a mode of extension which must have remained substantially the same over the entire period. Thus, the mechanisms driving extension should still be operating. Both the westward migration of the extensional loci and the high asymmetry of the extensional systems can be related to edge delamination below the south Iberian margin coupled with roll-back under the Alborán Sea; involving the asymmetric westward inflow of asthenospheric material under the margins.

Integration of mechanical, structural and electrical imaging to understand response to cardiac resynchronization therapy.

PubMed

Silva, Etelvino; Bijnens, Bart; Berruezo, Antonio; Mont, Lluis; Doltra, Adelina; Andreu, David; Brugada, Josep; Sitges, Marta

2014-10-01

There is extensive controversy exists on whether cardiac resynchronization therapy corrects electrical or mechanical asynchrony. The aim of this study was to determine if there is a correlation between electrical and mechanical sequences and if myocardial scar has any relevant impact. Six patients with normal left ventricular function and 12 patients with left ventricular dysfunction and left bundle branch block, treated with cardiac resynchronization therapy, were studied. Real-time three-dimensional echocardiography and electroanatomical mapping were performed in all patients and, where applicable, before and after therapy. Magnetic resonance was performed for evaluation of myocardial scar. Images were postprocessed and mechanical and electrical activation sequences were defined and time differences between the first and last ventricular segment to be activated were determined. Response to therapy was defined as a reduction in left ventricular end-systolic volume ≥ 15% after 12 months of follow-up. Good correlation between electrical and mechanical timings was found in patients with normal left ventricular function (r(2) = 0.88; P = .005) but not in those with left ventricular dysfunction (r(2) = 0.02; P = not significant). After therapy, both timings and sequences were modified and improved, except in those with myocardial scar. Despite a close electromechanical relationship in normal left ventricular function, there is no significant correlation in patients with dysfunction. Although resynchronization therapy improves this correlation, the changes in electrical activation may not yield similar changes in left ventricular mechanics particularly depending on the underlying myocardial substrate. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Structural and mechanical properties of glassy water in nanoscale confinement.

PubMed

Lombardo, Thomas G; Giovambattista, Nicolás; Debenedetti, Pablo G

2009-01-01

We investigate the structure and mechanical properties of glassy water confined between silica-based surfaces with continuously tunable hydrophobicity and hydrophilicity by computing and analyzing minimum energy, mechanically stable configurations (inherent structures). The structured silica substrate imposes long-range order on the first layer of water molecules under hydrophobic confinement at high density (p > or = 1.0 g cm(-3)). This proximal layer is also structured in hydrophilic confinement at very low density (p approximately 0.4 g cm(-3)). The ordering of water next to the hydrophobic surface greatly enhances the mechanical strength of thin films (0.8 nm). This leads to a substantial stress anisotropy; the transverse strength of the film exceeds the normal strength by 500 MPa. The large transverse strength results in a minimum in the equation of state of the energy landscape that does not correspond to a mechanical instability, but represents disruption of the ordered layer of water next to the wall. In addition, we find that the mode of mechanical failure is dependent on the type of confinement. Under large lateral strain, water confined by hydrophilic surfaces preferentially forms voids in the middle of the film and fails cohesively. In contrast, water under hydrophobic confinement tends to form voids near the walls and fails by loss of adhesion.

Blue Again: Perturbational Effects of Antidepressants Suggest Monoaminergic Homeostasis in Major Depression

PubMed Central

Andrews, Paul W.; Kornstein, Susan G.; Halberstadt, Lisa J.; Gardner, Charles O.; Neale, Michael C.

2011-01-01

Some evolutionary researchers have argued that current diagnostic criteria for major depressive disorder (MDD) may not accurately distinguish true instances of disorder from a normal, adaptive stress response. According to disorder advocates, neurochemicals like the monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) are dysregulated in major depression. Monoamines are normally under homeostatic control, so the monoamine disorder hypothesis implies a breakdown in homeostatic mechanisms. In contrast, adaptationist hypotheses propose that homeostatic mechanisms are properly functioning in most patients meeting current criteria for MDD. If the homeostatic mechanisms regulating monoamines are functioning properly in these patients, then oppositional tolerance should develop with prolonged antidepressant medication (ADM) therapy. Oppositional tolerance refers to the forces that develop when a homeostatic mechanism has been subject to prolonged pharmacological perturbation that attempt to bring the system back to equilibrium. When pharmacological intervention is discontinued, the oppositional forces cause monoamine levels to overshoot their equilibrium levels. Since depressive symptoms are under monoaminergic control, this overshoot should cause a resurgence of depressive symptoms that is proportional to the perturbational effect of the ADM. We test this prediction by conducting a meta-analysis of ADM discontinuation studies. We find that the risk of relapse after ADM discontinuation is positively associated with the degree to which ADMs enhance serotonin and norepinephrine in prefrontal cortex, after controlling for covariates. The results are consistent with oppositional tolerance, and provide no evidence of malfunction in the monoaminergic regulatory mechanisms in patients meeting current diagnostic criteria for MDD. We discuss the evolutionary and clinical implications of our findings. PMID:21779273

Microscopic Origin of Strain Hardening in Methane Hydrate

PubMed Central

Jia, Jihui; Liang, Yunfeng; Tsuji, Takeshi; Murata, Sumihiko; Matsuoka, Toshifumi

2016-01-01

It has been reported for a long time that methane hydrate presents strain hardening, whereas the strength of normal ice weakens with increasing strain after an ultimate strength. However, the microscopic origin of these differences is not known. Here, we investigated the mechanical characteristics of methane hydrate and normal ice by compressive deformation test using molecular dynamics simulations. It is shown that methane hydrate exhibits strain hardening only if the hydrate is confined to a certain finite cross-sectional area that is normal to the compression direction. For normal ice, it does not present strain hardening under the same conditions. We show that hydrate guest methane molecules exhibit no long-distance diffusion when confined to a finite-size area. They appear to serve as non-deformable units that prevent hydrate structure failure, and thus are responsible for the strain-hardening phenomenon. PMID:27009239

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

Smith, Kandler A; Santhanagopalan, Shriram; Yang, Chuanbo

Computer models are helping to accelerate the design and validation of next generation batteries and provide valuable insights not possible through experimental testing alone. Validated 3-D physics-based models exist for predicting electrochemical performance, thermal and mechanical response of cells and packs under normal and abuse scenarios. The talk describes present efforts to make the models better suited for engineering design, including improving their computation speed, developing faster processes for model parameter identification including under aging, and predicting the performance of a proposed electrode material recipe a priori using microstructure models.

Immunomodulation of allergic autocytotoxicity in bronchial asthma by a bacterial lysate--Broncho-Vaxom.

PubMed

Podleski, W K

1985-01-01

The direct and antibody-dependent allergic autocytotoxicity (ACT) response, mediated by food antigens and its immunoregulation with bacterial lysate of the eight most common pathogens of the upper respiratory tract--Broncho-Vaxom (BX), was investigated in fifteen bronchial asthma patients and eight normal control individuals. Under the described experimental conditions, the BX inhibits ACT response in vitro. In analyzing the mechanism of this effect, the enhancement of T suppressor cells by BX was under consideration.

Regional ADC values of the normal brain: differences due to age, gender, and laterality.

PubMed

Naganawa, Shinji; Sato, Kimihide; Katagiri, Toshio; Mimura, Takeo; Ishigaki, Takeo

2003-01-01

The purpose of this study was to evaluate the stability of measurement for apparent diffusion coefficient (ADC) values in normal brain, to clarify the effect of aging on ADC values, to compare ADC values between men and women, and to compare ADC values between right and left sides of the brain. To evaluate the stability of measurements, five normal volunteers (four men and one woman) were examined five times on different days. Then, 294 subjects with normal MR imaging (147 men and 147 women; age range 20-89 years) were measured. The ADC measurement in normal volunteers was stable. The ADC values stayed within the 5% deviation of average values in all volunteers (mean+/-standard deviation 2.3+/-1.2%). The ADC values gradually increased by aging in all regions. In thalamus, no significant difference was seen between right and left in the subjects under 60 years; however, right side showed higher values in the subjects over 60 years (p<0.01). In the subjects under 60 years, women showed higher values in right frontal, bilateral thalamus, and temporal (p<0.01); however, in the subjects over 60 years, no region showed difference between men and women. The knowledge obtained in this study may be helpful to understand the developmental and aging mechanisms of normal brain and may be useful for the future quantitative study as a reference.

Evaluation of passive and active vibration control mechanisms in a microgravity environment

NASA Technical Reports Server (NTRS)

Ellison, J.; Ahmadi, G.; Grodsinsky, C.

1993-01-01

The behavior of equipment and their light secondary attachments in large space structures under orbital excitation is studied. The equipment is modeled as a shear beam and its secondary attachment is treated as a single-degree-of-freedom lumped mass system. Peak responses of the equipment and its secondary system for a variety of vibration control mechanisms are evaluated. A novel active friction control mechanism, by varying the normal force, is suggested. The device uses a magnetic field control to minimize the stick condition, thereby reducing the overall structural response. The results show that the use of the passive vibration control devices could reduce the peak equipment responses to a certain extent. However, major reduction of vibration levels could be achieved only by the use of active devices. Using active control of the interface normal force, the peak responses of the equipment and its attachment are reduced by a factor of 10 over the fixed-base equipment response.

Closed-form analysis of fiber-matrix interface stresses under thermo-mechanical loadings

NASA Technical Reports Server (NTRS)

Naik, Rajiv A.; Crews, John H., Jr.

1992-01-01

Closed form techniques for calculating fiber matrix (FM) interface stresses, using repeating square and diamond regular arrays, were presented for a unidirectional composite under thermo-mechanical loadings. An Airy's stress function micromechanics approach from the literature, developed for calculating overall composite moduli, was extended in the present study to compute FM interface stresses for a unidirectional graphite/epoxy (AS4/3501-6) composite under thermal, longitudinal, transverse, transverse shear, and longitudinal shear loadings. Comparison with finite element results indicate excellent agreement of the FM interface stresses for the square array. Under thermal and longitudinal loading, the square array has the same FM peak stresses as the diamond array. The square array predicted higher stress concentrations under transverse normal and longitudinal shear loadings than the diamond array. Under transverse shear loading, the square array had a higher stress concentration while the diamond array had a higher radial stress concentration. Stress concentration factors under transverse shear and longitudinal shear loadings were very sensitive to fiber volume fraction. The present analysis provides a simple way to calculate accurate FM interface stresses for both the square and diamond array configurations.

Tumor suppressor p53 negatively regulates glycolysis stimulated by hypoxia through its target RRAD

PubMed Central

Wu, Rui; Liang, Yingjian; Lin, Meihua; Liu, Jia; Chan, Chang S.; Hu, Wenwei; Feng, Zhaohui

2014-01-01

Cancer cells display enhanced glycolysis to meet their energetic and biosynthetic demands even under normal oxygen concentrations. Recent studies have revealed that tumor suppressor p53 represses glycolysis under normoxia as a novel mechanism for tumor suppression. As the common microenvironmental stress for tumors, hypoxia drives the metabolic switch from the oxidative phosphorylation to glycolysis, which is crucial for survival and proliferation of cancer cells under hypoxia. The p53's role and mechanism in regulating glycolysis under hypoxia is poorly understood. Here, we found that p53 represses hypoxia-stimulated glycolysis in cancer cells through RRAD, a newly-identified p53 target. RRAD expression is frequently decreased in lung cancer. Ectopic expression of RRAD greatly reduces glycolysis whereas knockdown of RRAD promotes glycolysis in lung cancer cells. Furthermore, RRAD represses glycolysis mainly through inhibition of GLUT1 translocation to the plasma membrane. Under hypoxic conditions, p53 induces RRAD, which in turn inhibits the translocation of GLUT1 and represses glycolysis in lung cancer cells. Blocking RRAD by siRNA greatly abolishes p53's function in repressing glycolysis under hypoxia. Taken together, our results revealed an important role and mechanism of p53 in antagonizing the stimulating effect of hypoxia on glycolysis, which contributes to p53's function in tumor suppression. PMID:25114038

Normal vision can compensate for the loss of the circadian clock

PubMed Central

Schlichting, Matthias; Menegazzi, Pamela; Helfrich-Förster, Charlotte

2015-01-01

Circadian clocks are thought to be essential for timing the daily activity of animals, and consequently increase fitness. This view was recently challenged for clock-less fruit flies and mice that exhibited astonishingly normal activity rhythms under outdoor conditions. Compensatory mechanisms appear to enable even clock mutants to live a normal life in nature. Here, we show that gradual daily increases/decreases of light in the laboratory suffice to provoke normally timed sharp morning (M) and evening (E) activity peaks in clock-less flies. We also show that the compound eyes, but not Cryptochrome (CRY), mediate the precise timing of M and E peaks under natural-like conditions, as CRY-less flies do and eyeless flies do not show these sharp peaks independently of a functional clock. Nevertheless, the circadian clock appears critical for anticipating dusk, as well as for inhibiting sharp activity peaks during midnight. Clock-less flies only increase E activity after dusk and not before the beginning of dusk, and respond strongly to twilight exposure in the middle of the night. Furthermore, the circadian clock responds to natural-like light cycles, by slightly broadening Timeless (TIM) abundance in the clock neurons, and this effect is mediated by CRY. PMID:26378222

Plant perception and response to the signal in gravity resistance

NASA Astrophysics Data System (ADS)

Hoson, Takayuki; Soga, Kouichi; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Zhang, Yan; Otomi, Yasuhiro; Hashimoto, Takashi; Iida, Hidetoshi

2012-07-01

Gravity resistance, mechanical resistance to the gravitational force, is a principal graviresponse in plants, distinct from gravitropism. Plants increase the rigidity of their cell walls in the final step of gravity resistance. We studied cellular events leading to or related to the cell wall changes under hypergravity conditions produced by centrifugation and under microgravity conditions in space. The involvement of mechanosensitive ion channels (mechanoreceptors) in signal perception in gravity resistance has been suggested by experiments with inhibitors. As a candidate for the mechanoreceptor, we identified MCA1 and MCA2 in Arabidopsis. mca-null and MCA-overexpressing seedlings were normal in growth in the dark at 1 g. However, suppression by hypergravity of elongation growth was reduced in hypocotyls of mca-null seedlings. On the contrary, MCA-overexpressing seedlings were hypersensitive to hypergravity. These results suggest that MCAs act as the mechanoreceptor in signal perception of gravity resistance. Cortical microtubules play an essential role in maintenance of normal growth phenotype under hypergravity conditions. In Space Seed experiment in the Kibo Module (PI: S. Kamisaka), we examined the effects of microgravity on growth phenotypes of Arabidopsis tubulin mutant, tua6. Inflorescences of the mutant emerged earlier and elongated rapidly under microgravity conditions than under on-orbit or ground 1 g conditions. Also, the inflorescences grown under microgravity conditions showed higher cell wall extensibilities than the controls. The tubulin mutant thus grew and developed more or less normally under microgravity conditions, supporting the principal role of microtubules also in plant resistance to 1 g gravity. On the other hand, the cellular osmotic properties, as well as the cell wall properties, are important factors determining the rigidity of plant body. Azuki bean epicotyls were capable of maintaining osmoregulation even under hypergravity conditions for a short period. By long-term hypergravity treatment, the increase in level of total osmotic solutes was suppressed, which was accounted by suppression of translocation of organic solutes, such as sugars and amino acids, from seed to epicotyl. Nevertheless, the ATP content per epicotyl or fresh weight was kept constant even under hypergravity conditions for a long period. The maintenance of osmoregulation may contribute to plant resistance to hypergravity. Space experiments on the International Space Station will further clarify the mechanism of gravity resistance.

Mechanical Fatigue Testing of High Burnup Fuel for Transportation Applications

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

Wang, Jy-An John; Wang, Hong

This report describes testing designed to determine the ability of high burnup (HBU) (>45 GWd/MTU) spent fuel to maintain its integrity under normal conditions of transportation. An innovative system, Cyclic Integrated Reversible-bending Fatigue Tester (CIRFT), has been developed at Oak Ridge National Laboratory (ORNL) to test and evaluate the mechanical behavior of spent nuclear fuel (SNF) under conditions relevant to storage and transportation. The CIRFT system is composed of a U-frame equipped with load cells for imposing the pure bending loads on the SNF rod test specimen and measuring the in-situ curvature of the fuel rod during bending using amore » set up with three linear variable differential transformers (LVDTs).« less

Mechanical Fatigue Testing of High-Burnup Fuel for Transportation Applications

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

Wang, Jy-An; Wang, Hong

This report describes testing designed to determine the ability of high burnup (HBU) (>45 GWd/MTU) spent fuel to maintain its integrity under normal conditions of transportation. An innovative system, Cyclic Integrated Reversible-bending Fatigue Tester (CIRFT), has been developed at Oak Ridge National Laboratory (ORNL) to test and evaluate the mechanical behavior of spent nuclear fuel (SNF) under conditions relevant to storage and transportation. The CIRFT system is composed of a U-frame equipped with load cells for imposing the pure bending loads on the SNF rod test specimen and measuring the in-situ curvature of the fuel rod during bending using amore » set up with three linear variable differential transformers (LVDTs).« less

Sleep and Human Aging

PubMed Central

Mander, Bryce A.; Winer, Joseph R.; Walker, Matthew P.

2017-01-01

Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need? PMID:28384471

Sleep and Human Aging.

PubMed

Mander, Bryce A; Winer, Joseph R; Walker, Matthew P

2017-04-05

Older adults do not sleep as well as younger adults. Why? What alterations in sleep quantity and quality occur as we age, and are there functional consequences? What are the underlying neural mechanisms that explain age-related sleep disruption? This review tackles these questions. First, we describe canonical changes in human sleep quantity and quality in cognitively normal older adults. Second, we explore the underlying neurobiological mechanisms that may account for these human sleep alterations. Third, we consider the functional consequences of age-related sleep disruption, focusing on memory impairment as an exemplar. We conclude with a discussion of a still-debated question: do older adults simply need less sleep, or rather, are they unable to generate the sleep that they still need? Copyright © 2017. Published by Elsevier Inc.

Influences of trunk flexion on mechanical energy flow in the lower extremities during gait.

PubMed

Takeda, Takuya; Anan, Masaya; Takahashi, Makoto; Ogata, Yuta; Tanimoto, Kenji; Shinkoda, Koichi

2016-05-01

[Purpose] The time-series waveforms of mechanical energy generation, absorption, and transfer through the joints indicate how movements are produced and controlled. Previous studies have used these waveforms to evaluate and describe the efficiency of human movements. The purpose of this study was to examine the influence of trunk flexion on mechanical energy flow in the lower extremities during gait. [Subjects and Methods] The subjects were 8 healthy young males (mean age, 21.8 ± 1.3 years, mean height, 170.5 ± 6.8 cm, and mean weight, 60.2 ± 6.8 kg). Subjects walked at a self-selected gait speed under 2 conditions: normal gait (condition N), and gait with trunk flexion formed with a brace to simulate spinal curvature (condition TF). The data collected from initial contact to the mid-stance of gait was analyzed. [Results] There were no significant differences between the 2 conditions in the mechanical energy flow in the knee joint and negative mechanical work in the knee joint. However, the positive mechanical work of the knee joint under condition TF was significantly less than that under condition N. [Conclusion] Trunk flexion led to knee flexion in a standing posture. Thus, a strategy of moving of center of mass upward by knee extension using less mechanical energy was selected during gait in the trunk flexed posture.

Impacts of You Gui Wan on the expression of estrogen receptors and angiogenic factors in OVX‑rat vagina: a possible mechanism for the trophic effect of the formula on OVX‑induced vaginal atrophy.

PubMed

Yin, Qiao-Zhi; Lu, Hua; Li, Li-Min; Yie, Shang-Mian; Hu, Xiang; Liu, Zhi-Bin; Zheng, Xiao; Cao, Sheng; Yao, Zou-Ying

2013-11-01

The administration of You Gui Wan (YGW) decoction has been observed to improve vaginal atrophy induced by ovariectomy (OVX) in rats. The aim of the current study was to explore the possible mechanisms underlying this effect. Following OVX, 37 Sprague Dawley female rats were randomly divided into three groups which were orally administered with YGW decoction, saline or estrogen for 11 weeks. In parallel with this, 19 normal and 17 rats with sham-surgery were used as controls. The effects of these treatments on estrogen receptors (ER) and various angiogenic factors, including vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-1 (VEGFR-1), angiopoietin (Ang)1 and 2 and basic fibroblast growth factor (bFGF) in the vagina were compared using immunohistochemistry or quantitative polymerase chain reaction (qPCR). OVX was found to induce significant vaginal atrophy and decrease the expression of ER and various angiogenic factors when compared with the normal and sham-surgery animals (all P<0.05). Estrogen replacement and the administration of YGW decoction reversed the vaginal atrophic process. The hormonal replacement and YGW treatment recovered the protein expression of ER-α and -β, VEGF and VEGFR-1 and the mRNA levels of ER-α, VEGF, VEGFR-1, Ang1 and 2, and bFGF when compared with OVX-rats with saline, normal and sham-surgery treatments (all P<0.05). Thus, it may be concluded that a possible mechanism underlying the effect of YGW on OVX-induced vaginal atrophy may be the upregulated expression of ER and various angiogenic factors in the vaginal tissue.

An integrated mathematical model of the human cardiopulmonary system: model development.

PubMed

Albanese, Antonio; Cheng, Limei; Ursino, Mauro; Chbat, Nicolas W

2016-04-01

Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics. Copyright © 2016 the American Physiological Society.

Eucalyptus tolerance mechanisms to lanthanum and cerium: subcellular distribution, antioxidant system and thiol pools.

PubMed

Shen, Yichang; Zhang, Shirong; Li, Sen; Xu, Xiaoxun; Jia, Yongxia; Gong, Guoshu

2014-12-01

Guanglin 9 (Eucalyptus grandis × Eucalyptus urophlla) and Eucalyptus grandis 5 are two eucalyptus species which have been found to grow normally in soils contaminated with lanthanum and cerium, but the tolerance mechanisms are not clear yet. In this study, a pot experiment was conducted to investigate the tolerance mechanisms of the eucalyptus to lanthanum and cerium. Cell walls stored 45.40-63.44% of the metals under lanthanum or cerium stress. Peroxidase and catalase activities enhanced with increasing soil La or Ce concentrations up to 200 mg kg(-1), while there were no obvious changes in glutathione and ascorbate concentrations. Non-protein thiols concentrations increased with increasing treatment levels up to 200 mg kg(-1), and then decreased. Phytochelatins concentrations continued to increase under La or Ce stress. Therefore, the two eucalyptus species are La and Ce tolerant plants, and the tolerance mechanisms include cell wall deposition, antioxidant system response, and thiol compound synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Single-shot measurements of low emittance beams from laser-plasma accelerators comparing two triggered injection methods

NASA Astrophysics Data System (ADS)

van Tilborg, Jeroen

2017-10-01

The success of laser plasma accelerator (LPA) based applications, such as a compact x-ray free electron laser (FEL), relies on the ability to produce electron beams with excellent 6D brightness, where brightness is defined as the ratio of charge to the product of the three normalized emittances. As such, parametric studies of the emittance of LPA generated electron beams are essential. Profiting from a stable and tunable LPA setup, combined with a carefully designed single-shot energy-dispersed emittance diagnostic, we present a direct comparison of charge dependent emittance measurements of electron beams generated by two different injection mechanisms: ionization injection and shock-induced density down-ramp injection. Both injection mechanisms have gained in popularity in recent years due to their demonstrated stable LPA performance. For the down-ramp injection configuration, normalized emittances a factor of two lower were recorded: less than 1 micron at spectral charge densities up to 2 pC/MeV. For both injection mechanisms, a contributing correlation of space charge to the emittance was identified. This measurement technique in general, and these results specifically, are critical to the evaluation of LPA injection methods and development of high-quality LPA beam lines worldwide. This work is supported by the U.S. DOE under Contract No. DE-AC02-05CH11231, by the U.S. DOE NNSA, DNN R&D (NA22), by the National Science Foundation under Grant No. PHY-1415596, and by the Gordon and Betty Moore Foundation under Grant ID GBMF4898.

Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance

PubMed Central

Liston, Conor; Cichon, Joseph M; Jeanneteau, Freddy; Jia, Zhengping; Chao, Moses V; Gan, Wen-Biao

2013-01-01

Excessive glucocorticoid exposure during chronic stress causes synapse loss and learning impairment. Under normal physiological conditions, glucocorticoid activity oscillates in synchrony with the circadian rhythm. Whether and how endogenous glucocorticoid oscillations modulate synaptic plasticity and learning is unknown. Here we show that circadian glucocorticoid peaks promote postsynaptic dendritic spine formation in the mouse cortex after motor skill learning, whereas troughs are required for stabilizing newly formed spines that are important for long-term memory retention. Conversely, chronic and excessive exposure to glucocorticoids eliminates learning-associated new spines and disrupts previously acquired memories. Furthermore, we show that glucocorticoids promote rapid spine formation through a non-transcriptional mechanism by means of the LIM kinase–cofilin pathway and increase spine elimination through transcriptional mechanisms involving mineralocorticoid receptor activation. Together, these findings indicate that tightly regulated circadian glucocorticoid oscillations are important for learning-dependent synaptic formation and maintenance. They also delineate a new signaling mechanism underlying these effects. PMID:23624512

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

PubMed

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-09-30

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

Late Miocene extensional systems in northern Tunisia and their relation with SE directed delamination of the African subcontinental mantle lithosphere

NASA Astrophysics Data System (ADS)

Booth-Rea, Guillermo; Gaidi, Seif; Melki, Fetheddine; Pérez-Peña, Vicente; Marzougui, Wissem; Azañón, Jose Miguel; Galve, Jorge Pedro

2017-04-01

Recent work has proposed the delamination of the subcontinental mantle lithosphere under northern Tunisia during the late Miocene. This process is required to explain the present location of the Tunisian segment of the African slab, imaged by seismic tomography, hanging under the Gulf of Gabes to the south of Tunisia. Thus, having retreated towards the SE several hundred km from its original position under the Tellian-Atlas nappe contact that crops out along the north of Tunisia. However, no tectonic structures have been described which could be related to this mechanism of lithospheric mantle peeling. Here we describe for the first time extensional fault systems in northern Tunisia that strongly thinned the Tellian nappes, exhuming rocks from the Tunisian Atlas in the core of folded extensional detachments. Two normal fault systems with sub-orthogonal extensional transport occur. These were active during the late Miocene associated to the extrusion of 13 Ma granodiorite and 9 Ma rhyodacite in the footwall of the Nefza detachment. We have differentiated an extensional system formed by low-angle normal faults with NE- and SW-directed transport cutting through the Early to Middle Miocene Tellian nappen stack and a later system of low and high-angle normal faults that cuts down into the underlying Tunisian Atlas units with SE-directed transport, which root in the Nefza detachment. Both normal fault systems have been later folded and cut by thrusts during Plio-Quaternary NW-SE directed compression. These findings change the interpretation of the tectonic evolution of Tunisia that has always been framed in a transpressive to compressive setting, manifesting the extensional effects of Late Miocene lithospheric mantle delamination under northern Tunisia.

Failure mechanisms of uni-ply composite plates with a circular hole under static compressive loading

NASA Technical Reports Server (NTRS)

Khamseh, A. R.; Waas, A. M.

1992-01-01

The objective of the study was to identify and study the failure mechanisms associated with compressive-loaded uniply graphite/epoxy square plates with a central circular hole. It is found that the type of compressive failure depends on the hole size. For large holes with the diameter/width ratio exceeding 0.062, fiber buckling/kinking initiated at the hole is found to be the dominant failure mechanism. In plates with smaller hole sizes, failure initiates away from the hole edge or complete global failure occurs. Critical buckle wavelengths at failure are presented as a function of the normalized hole diameter.

Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

PubMed

Zhang, Wei; Chen, Lulu; Zhang, Luqing; Xiao, Ming; Ding, Jiong; Goltzman, David; Miao, Dengshun

2015-02-19

Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Integrative genome-wide analysis of the determinants of RNA splicing in kidney renal clear cell carcinoma.

PubMed

Lehmann, Kjong-Van; Kahles, André; Kandoth, Cyriac; Lee, William; Schultz, Nikolaus; Stegle, Oliver; Rätsch, Gunnar

2015-01-01

We present a genome-wide analysis of splicing patterns of 282 kidney renal clear cell carcinoma patients in which we integrate data from whole-exome sequencing of tumor and normal samples, RNA-seq and copy number variation. We proposed a scoring mechanism to compare splicing patterns in tumor samples to normal samples in order to rank and detect tumor-specific isoforms that have a potential for new biomarkers. We identified a subset of genes that show introns only observable in tumor but not in normal samples, ENCODE and GEUVADIS samples. In order to improve our understanding of the underlying genetic mechanisms of splicing variation we performed a large-scale association analysis to find links between somatic or germline variants with alternative splicing events. We identified 915 cis- and trans-splicing quantitative trait loci (sQTL) associated with changes in splicing patterns. Some of these sQTL have previously been associated with being susceptibility loci for cancer and other diseases. Our analysis also allowed us to identify the function of several COSMIC variants showing significant association with changes in alternative splicing. This demonstrates the potential significance of variants affecting alternative splicing events and yields insights into the mechanisms related to an array of disease phenotypes.

Deformation micromechanisms of collagen fibrils under uniaxial tension

PubMed Central

Tang, Yuye; Ballarini, Roberto; Buehler, Markus J.; Eppell, Steven J.

2010-01-01

Collagen, an essential building block of connective tissues, possesses useful mechanical properties due to its hierarchical structure. However, little is known about the mechanical properties of collagen fibril, an intermediate structure between the collagen molecule and connective tissue. Here, we report the results of systematic molecular dynamics simulations to probe the mechanical response of initially unflawed finite size collagen fibrils subjected to uniaxial tension. The observed deformation mechanisms, associated with rupture and sliding of tropocollagen molecules, are strongly influenced by fibril length, width and cross-linking density. Fibrils containing more than approximately 10 molecules along their length and across their width behave as representative volume elements and exhibit brittle fracture. Shorter fibrils experience a more graceful ductile-like failure. An analytical model is constructed and the results of the molecular modelling are used to find curve-fitted expressions for yield stress, yield strain and fracture strain as functions of fibril structural parameters. Our results for the first time elucidate the size dependence of mechanical failure properties of collagen fibrils. The associated molecular deformation mechanisms allow the full power of traditional material and structural engineering theory to be applied to our understanding of the normal and pathological mechanical behaviours of collagenous tissues under load. PMID:19897533

Separation of lymphocytes by electrophoresis under terrestrial conditions and at zero gravity

NASA Technical Reports Server (NTRS)

Rubin, A. L.

1977-01-01

Electrophoretic mobility (EPM) of human peripheral lymphocytes were examined with the following objectives: To determine differences in EPM of lymphocytes under immuno-stimulated and immuno-suppressed states. To define the conditions necessary for the separation of lymphocyte sub-populations in normal and pathological conditions; To investigate immunological active, charged chemical groups on lymphocyte surfaces; and to investigate pathophysiological mechanisms of immune responsiveness, as reflected by alterations in EPM. To evaluate the potential of lymphocyte electrophoresis as: (1) a means of monitoring the immune status of kidney transplant recipients, (2) in predicting the outcome of kidney transplants, and (3) as a method for separation of lymphocyte sub-populations, the EPM was studied for unfractionated human peripheral lymphocytes and of populations enriched with T and "B" cells from normal adults, hemodialysis patients and kidney transplant recipients.

Nonlinear Laser Lithography implementation for both ``normal'' and ``anomalous'' laser induced periodic structuring

NASA Astrophysics Data System (ADS)

Pavlov, Ihor; Tokel, Onur; Yavuz, Ozgun; Makey, Ghaith; Ilday, Omer; Omer Ilday Team

Laser Induced Periodic Surface Structuring (LIPSS) is one of the most prominent directions in laser-material interaction due to both practical and theoretical importance, especially after the discovery of Nonlinear Laser Lithography (NLL), which opens new area for industrial application of LIPSS as an effective tool for controllable, highly ordered large area nanostructuring. LIPSS appear on the surface under laser beam in the form of periodical lines. The LIPSS, that appear perpendicular to laser polarization are called ``normal'', in contrast to ``anomalous'' LIPSS appearing parallel to the polarization. Although, NLL technique was already demonstrated for ``normal'' and ``anomalous'' LIPSS separately, up to now, there is no clear understanding of switching mechanism between these two modes. In presented paper we have shown that the mechanism relies on interplay between two feedbacks: long range, low intensity dipole-like scattering of light along the surface, and short range, high intensity plasmon-polariton wave. For the first time, we are able to create both types of LIPSS on the same surface by controlling these two feedbacks, obtaining highly-ordered large-area structured patterns in both modes.

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate

PubMed Central

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2017-01-01

Background Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (NMR, 3′-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance, and a well validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Methods Sixty-nine treatment-seeking smokers (30 slow, 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once following 24 hours of smoking abstinence. Results In whole brain analysis, normal (compared to slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were even more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Conclusion Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. PMID:26805583

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

PubMed

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2016-08-01

Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (3'-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance and a well-validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Treatment-seeking smokers (N = 69; 30 slow metabolizers and 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once after 24 hours of smoking abstinence. In whole-brain analysis, normal (compared with slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Investigation of Nucleate Boiling Mechanisms Under Microgravity Conditions

NASA Technical Reports Server (NTRS)

Dhir, V. K.; Qiu, D. M.; Ramanujapu, N.; Hasan, M. M.

1999-01-01

The present work is aimed at the experimental studies and numerical modeling of the bubble growth mechanisms of a single bubble attached to a heating surface and of a bubble sliding along an inclined heated plate. Single artificial cavity of 10 microns in diameter was made on the polished Silicon wafer which was electrically heated at the back side in order to control the surface nucleation superheat. Experiments with a sliding bubble were conducted at different inclination angles of the downward facing heated surface for the purpose of studying the effect of magnitude of components of gravity acting parallel to and normal to the heat transfer surface. Information on the bubble shape and size, the bubble induced liquid velocities as well as the surface temperature were obtained using the high speed imaging and hydrogen bubble techniques. Analytical/numerical models were developed to describe the heat transfer through the micro-macro layer underneath and around a bubble formed at a nucleation site. In the micro layer model the capillary and disjoining pressures were included. Evolution of the bubble-liquid interface along with induced liquid motion was modeled. As a follow-up to the studies at normal gravity, experiments are being conducted in the KC-135 aircraft to understand the bubble growth/detachment under low gravity conditions. Experiments have been defined to be performed under long duration of microgravity conditions in the space shuttle. The experiment in the space shuttle will provide bubble growth and detachment data at microgravity and will lead to validation of the nucleate boiling heat transfer model developed from the preceding studies conducted at normal and low gravity (KC-135) conditions.

A mechanism for decoupling within the oceanic lithosphere revealed in the Troodos ophiolite

USGS Publications Warehouse

Agar, Susan M.; Klitgord, Kim D.

1995-01-01

Contrasting kinematic histories recorded in the sheeted dykes and underlying plutonic rocks of the Troodos ophiolite provide a new perspective on the mechanical evolution of oceanic spreading centres. The kinematic framework of the decoupling zone that partitions deformation between the sheeted dykes and plutonics contrasts with low-angle detachment models for slow-spreading ridges based on continental-rift analogues. A model for the generation of multiple, horizontal decoupling horizons, linked by planar normal faults, demonstrates new possibilities for the kinematic and rheological significance of seismic reflectors in oceanic lithosphere.

Stress Corrosion Cracking of Basalt/Epoxy Composites under Bending Loading

NASA Astrophysics Data System (ADS)

Shokrieh, Mahmood M.; Memar, Mahdi

2010-04-01

The purpose of this research is to study the stress corrosion behavior of basalt/epoxy composites under bending loading and submerged in 5% sulfuric acid corrosive medium. There are limited numbers of research in durability of fiber reinforced polymer composites. Moreover, studies on basalt fibers and its composites are very limited. In this research, mechanical property degradation of basalt/epoxy composites under bending loading and submerged in acidic corrosive medium is investigated. Three states of stress, equal to 30%, 50% and 70% of the ultimate strength of composites, are applied on samples. High stress states are applied to the samples to accelerate the testing procedure. Mechanical properties degradation consists of bending strength, bending modulus of elasticity and fracture energy of samples are examined. Also, a normalized strength degradation model for stress corrosion condition is presented. Finally, microscopic images of broken cross sections of samples are examined.

Modelling of deformation process for the layer of elastoviscoplastic media under surface action of periodic force of arbitrary type

NASA Astrophysics Data System (ADS)

Mikheyev, V. V.; Saveliev, S. V.

2018-01-01

Description of deflected mode for different types of materials under action of external force plays special role for wide variety of applications - from construction mechanics to circuits engineering. This article con-siders the problem of plastic deformation of the layer of elastoviscolastic soil under surface periodic force. The problem was solved with use of the modified lumped parameters approach which takes into account close to real distribution of normal stress in the depth of the layer along with changes in local mechanical properties of the material taking place during plastic deformation. Special numeric algorithm was worked out for computer modeling of the process. As an example of application suggested algorithm was realized for the deformation of the layer of elasoviscoplastic material by the source of external lateral force with the parameters of real technological process of soil compaction.

Research on the Mechanism of In-Plane Vibration on Friction Reduction

PubMed Central

Wang, Peng; Ni, Hongjian; Wang, Ruihe; Liu, Weili; Lu, Shuangfang

2017-01-01

A modified model for predicting the friction force between drill-string and borehole wall under in-plane vibrations was developed. It was found that the frictional coefficient in sliding direction decreased significantly after applying in-plane vibration on the bottom specimen. The friction reduction is due to the direction change of friction force, elastic deformation of surface asperities and the change of frictional coefficient. Normal load, surface topography, vibration direction, velocity ratio and interfacial shear factor are the main influence factors of friction force in sliding direction. Lower driving force can be realized for a pair of determinate rubbing surfaces under constant normal load by setting the driving direction along the minimum arithmetic average attack angle direction, and applying intense longitudinal vibration on the rubbing pair. The modified model can significantly improve the accuracy in predicting frictional coefficient under vibrating conditions, especially under the condition of lower velocity ratio. The results provide a theoretical gist for friction reduction technology by vibrating drill-string, and provide a reference for determination of frictional coefficient during petroleum drilling process, which has great significance for realizing digitized and intelligent drilling. PMID:28862679

[Study of the phase transformation of TiO2 with in-situ XRD in different gas].

PubMed

Ma, Li-Jing; Guo, Lie-Jin

2011-04-01

TiO2 sample was prepared by sol-gel method from chloride titanium. The phase transformation of the prepared TiO2 sample was studied by in-situ XRD and normal XRD in different gas. The experimental results showed that the phase transformation temperatures of TiO2 were different under in-situ or normal XRD in different kinds of gas. The transformation of amorphous TiO2 to anatase was controlled by kinetics before 500 degrees C. In-situ XRD showed that the growth of anatase was inhibited, but the transformation of anatase to rutile was accelerated under inactive nitrogen in contrast to air. Also better crystal was obtained under hydrogen than in argon. These all showed that external oxygen might accelerate the growth of TiO2, but reduced gas might partly counteract the negative influence of lack of external oxygen. The mechanism of phase transformation of TiO2 was studied by in-situ XRD in order to control the structure in situ.

Loss‐of‐function mutation of rice SLAC7 decreases chloroplast stability and induces a photoprotection mechanism in rice

PubMed Central

Fan, Xiaolei; Wu, Jiemin; Chen, Taiyu; Tie, Weiwei; Chen, Hao; Zhou, Fei

2015-01-01

Abstract Plants absorb sunlight to power the photochemical reactions of photosynthesis, which can potentially damage the photosynthetic machinery. However, the mechanism that protects chloroplasts from the damage remains unclear. In this work, we demonstrated that rice (Oryza sativa L.) SLAC7 is a generally expressed membrane protein. Loss‐of‐function of SLAC7 caused continuous damage to the chloroplasts of mutant leaves under normal light conditions. Ion leakage indicators related to leaf damage such as H2O2 and abscisic acid levels were significantly higher in slac7‐1 than in the wild type. Consistently, the photosynthesis efficiency and Fv/Fm ratio of slac7‐1 were significantly decreased (similar to photoinhibition). In response to chloroplast damage, slac7‐1 altered its leaf morphology (curled or fused leaf) by the synergy between plant hormones and transcriptional factors to decrease the absorption of light, suggesting that a photoprotection mechanism for chloroplast damage was activated in slac7‐1. When grown in dark conditions, slac7‐1 displayed a normal phenotype. SLAC7 under the control of the AtSLAC1 promoter could partially complement the phenotypes of Arabidopsis slac1 mutants, indicating a partial conservation of SLAC protein functions. These results suggest that SLAC7 is essential for maintaining the chloroplast stability in rice. PMID:25739330

Investigating the mechanism(s) underlying switching between states in bipolar disorder

PubMed Central

Young, Jared W.; Dulcis, Davide

2015-01-01

Bipolar Disorder (BD) is a unique disorder that transcends domains of function since the same patient can exhibit depression or mania, states with polar opposite mood symptoms. During depression, people feel helplessness, reduced energy, and risk aversion, while with mania behaviors include grandiosity, increased energy, less sleep, and risk preference. The neural mechanism(s) underlying each state are gaining clarity, with catecholaminergic disruption seen during mania, and cholinergic dysfunction during depression. The fact that the same patient cycles/switches between these states is the defining characteristic of BD however. Of greater importance therefore, is the mechanism(s) underlying cycling from one state - and its associated neural changes - to another, considered the ‘holy grail’ of BD research. Herein, we review studies investigating triggers that induce switching to these states. By identifying such triggers, researchers can study neural mechanisms underlying each state and importantly how such mechanistic changes can occur in the same subject. Current animal models of this switch are also discussed, from submissive- and dominant-behaviors to kindling effects. Focus however, is placed on how seasonal changes can induce manic and depressive states in BD sufferers. Importantly, changing photoperiod lengths can induce local switches in neurotransmitter expression in normal animals, from increased catecholaminergic expression during periods of high activity, to increased somatostatin and corticotrophin releasing factor during periods of low activity. Identifying susceptibilities to this switch would enable the development of targeted animal models. From animal models, targeted treatments could be developed and tested that would minimize the likelihood of switching. PMID:25814263

Existence and stability of periodic solutions of quasi-linear Korteweg — de Vries equation

NASA Astrophysics Data System (ADS)

Glyzin, S. D.; Kolesov, A. Yu; Preobrazhenskaia, M. M.

2017-01-01

We consider the scalar nonlinear differential-difference equation with two delays, which models electrical activity of a neuron. Under some additional suppositions for this equation well known method of quasi-normal forms can be applied. Its essence lies in the formal normalization of the Poincare - Dulac obtaining quasi-normal form and the subsequent application of the theorems of conformity. In this case, the result of the application of quasi-normal forms is a countable system of differential-difference equations, which can be turned into a boundary value problem of the Korteweg - de Vries equation. The investigation of this boundary value problem allows us to draw a conclusion about the behaviour of the original equation. Namely, for a suitable choice of parameters in the framework of this equation is implemented buffer phenomenon consisting in the presence of the bifurcation mechanism for the birth of an arbitrarily large number of stable cycles.

The Effect of Radiation on the Normal and Oestrone-treated Mouse Vagina Grown in vitro

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

Lasnitzki, Ilse

1961-06-01

The effect of radiation on the differentiation of normal and oestrone- treated organ cultures of the mouse vagina was studied during growth in natural and in chemically defined medium. After explanation into either type of medium without addition of the hormone the vaginal epithelium spontaneously forms new squamous keratinising epithelium which displaces the original secretory epithelium. Addition of oestrone to the medium stimulates the growth of the new cells and hastens and increases keratin synthesis. Exposure to 200 r of x rays given one day after explanation inhibits the squamous development, suppresses keratin formation and preserves the original epithelium inmore » both normal and oestrone-treated explants grown in natural medium. Radiation of cultures kept in defined medium fails to influence the normal squamous differentiation and keratinisation. The mechanism of radiation action is discussed in the light of the differnet results obtained under the two conditions. (auth)« less

Spurious heat conduction behavior of finite-size graphene nanoribbon under extreme uniaxial strain caused by the AIREBO potential

NASA Astrophysics Data System (ADS)

Yang, Xueming; Wu, Sihan; Xu, Jiangxin; Cao, Bingyang; To, Albert C.

2018-02-01

Although the AIREBO potential can well describe the mechanical and thermal transport of the carbon nanostructures under normal conditions, previous studies have shown that it may overestimate the simulated mechanical properties of carbon nanostructures in extreme strains near fracture. It is still unknown whether such overestimation would also appear in the thermal transport of nanostructrues. In this paper, the mechanical and thermal transport of graphene nanoribbon under extreme deformation conditions are studied by MD simulations using both the original and modified AIREBO potential. Results show that the cutoff function of the original AIREBO potential produces an overestimation on thermal conductivity in extreme strains near fracture stage. Spurious heat conduction behavior appears, e.g., the thermal conductivity of GNRs does not monotonically decrease with increasing strain, and even shows a ;V; shaped reversed and nonphysical trend. Phonon spectrum analysis show that it also results in an artificial blue shift of G peak and phonon stiffening of the optical phonon modes. The correlation between spurious heat conduction behavior and overestimation of mechanical properties near the fracture stage caused by the original AIREBO potential are explored and revealed.

Rough fibrils provide a toughening mechanism in biological fibers.

PubMed

Brown, Cameron P; Harnagea, Catalin; Gill, Harinderjit S; Price, Andrew J; Traversa, Enrico; Licoccia, Silvia; Rosei, Federico

2012-03-27

Spider silk is a fascinating natural composite material. Its combination of strength and toughness is unrivalled in nature, and as a result, it has gained considerable interest from the medical, physics, and materials communities. Most of this attention has focused on the one to tens of nanometer scale: predominantly the primary (peptide sequences) and secondary (β sheets, helices, and amorphous domains) structure, with some insights into tertiary structure (the arrangement of these secondary structures) to describe the origins of the mechanical and biological performance. Starting with spider silk, and relating our findings to collagen fibrils, we describe toughening mechanisms at the hundreds of nanometer scale, namely, the fibril morphology and its consequences for mechanical behavior and the dissipation of energy. Under normal conditions, this morphology creates a nonslip fibril kinematics, restricting shearing between fibrils, yet allowing controlled local slipping under high shear stress, dissipating energy without bulk fracturing. This mechanism provides a relatively simple target for biomimicry and, thus, can potentially be used to increase fracture resistance in synthetic materials. © 2012 American Chemical Society

Tudor-SN, a component of stress granules, regulates growth under salt stress by modulating GA20ox3 mRNA levels in Arabidopsis

PubMed Central

Yan, Chunxia; Yan, Zongyun; Wang, Yizheng; Yan, Xiaoyuan; Han, Yuzhen

2014-01-01

The Tudor-SN protein (TSN) is universally expressed and highly conserved in eukaryotes. In Arabidopsis, TSN is reportedly involved in stress adaptation, but the mechanism involved in this adaptation is not understood. Here, we provide evidence that TSN regulates the mRNA levels of GA20ox3, a key enzyme for gibberellin (GA) biosynthesis. The levels of GA20ox3 transcripts decreased in TSN1/TSN2 RNA interference (RNAi) transgenic lines and increased in TSN1 over-expression (OE) transgenic lines. The TSN1 OE lines displayed phenotypes that may be attributed to the overproduction of GA. No obvious defects were observed in the RNAi transgenic lines under normal conditions, but under salt stress conditions these lines displayed slower growth than wild-type (WT) plants. Two mutants of GA20ox3, ga20ox3-1 and -2, also showed slower growth under stress than WT plants. Moreover, a higher accumulation of GA20ox3 transcripts was observed under salt stress. The results of a western blot analysis indicated that higher levels of TSN1 accumulated after salt treatment than under normal conditions. Subcellular localization studies showed that TSN1 was uniformly distributed in the cytoplasm under normal conditions but accumulated in small granules and co-localized with RBP47, a marker protein for stress granules (SGs), in response to salt stress. The results of RNA immunoprecipitation experiments indicated that TSN1 bound GA20ox3 mRNA in vivo. On the basis of these findings, we conclude that TSN is a novel component of plant SGs that regulates growth under salt stress by modulating levels of GA20ox3 mRNA. PMID:25205572

Reduced levels of brain-derived neurotrophic factor contribute to synaptic imbalance during the critical period of respiratory development in rats

PubMed Central

Gao, Xiu-ping; Liu, Qiuli; Nair, Bindu; Wong-Riley, Margaret T.T.

2014-01-01

Previously, our electrophysiological studies revealed a transient imbalance between suppressed excitation and enhanced inhibition in hypoglossal motoneurons of rats on postnatal days (P) 12–13, a critical period when abrupt neurochemical, metabolic, ventilatory, and physiological changes occur in the respiratory system. The mechanism underlying the imbalance is poorly understood. We hypothesized that the imbalance was contributed by a reduced expression of brain-derived neurotrophic factor (BDNF), which normally enhances excitation and suppresses inhibition. We also hypothesized that exogenous BDNF would partially reverse this synaptic imbalance. Immunohistochemistry/single neuron optical densitometry, real-time quantitative polymerase chain reaction, and whole-cell patch-clamp recordings were done on hypoglossal motoneurons in brain stem slices of rats during the first three postnatal weeks. Our results indicated that: 1) the levels of BDNF and its high-affinity TrkB receptor mRNAs and proteins were relatively high during the first 1-1½ postnatal weeks, but dropped precipitously at P12–13 before rising again afterwards; 2) exogenous BDNF significantly increased the normally lowered frequency of spontaneous excitatory postsynaptic currents (sEPSCs) but decreased the normally heightened amplitude and frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) during the critical period; 3) exogenous BDNF also decreased the normally heightened frequency of miniature IPSCs (mIPSCs) at P12–13; and 4) the effect of exogenous BDNF was partially blocked by K252a, a TrkB receptor antagonist. Thus, our results are consistent with our hypothesis that BDNF and TrkB play an important role in the synaptic imbalance during the critical period. This may have significant implications for the mechanism underlying Sudden Infant Death Syndrome (SIDS). PMID:24666389

Viewing strategies for simple and chimeric faces: an investigation of perceptual bias in normals and schizophrenic patients using visual scan paths.

PubMed

Phillips, M L; David, A S

1997-11-01

Left hemi-face (LHF) perceptual bias of chimeric faces in normal right-handers is well-documented. We investigated mechanisms underlying this by measuring visual scan paths in right-handed normal controls (n = 9) and schizophrenics (n = 8) for simple, full-face photographs and schematic, happy-sad chimeric faces over 5 s. Normals viewed the left side/ LHF first, more so than the right of all stimuli. Schizophrenics viewed the LHF first more than the right of stimuli for which there was a LHF choice of predominant affect. Neither group demonstrated an overall LHF perceptual bias for the chimeric stimuli. Readjustment of the initial LHF bias in controls was probably a result of increased attention to stimulus detail with scanning, whereas the schizophrenics demonstrated difficulty in redirection of the initial focus of attention. The study highlights the role of visual scan paths as a marker of normal and abnormal attentional processes. Copyright 1997 Academic Press.

TRPV2 KNOCKOUT MICE ARE SUSCEPTIBLE TO PERINATAL LETHALITY BUT DISPLAY NORMAL THERMAL AND MECHANICAL NOCICEPTION

PubMed Central

Park, Una; Vastani, Nisha; Guan, Yun; Raja, Srinivasa N.; Koltzenburg, Martin; Caterina, Michael J.

2011-01-01

TRPV2 is a nonselective cation channel expressed prominently in medium- to large-diameter sensory neurons that can be activated by extreme heat (>52°C). These features suggest that TRPV2 might be a transducer of noxious heat in vivo. TRPV2 can also be activated by hypoosmolarity or cell stretch, suggesting potential roles in mechanotransduction. To address the physiological functions of TRPV2 in somatosensation, we generated TRPV2 knockout mice and examined their behavioral and electrophysiological responses to heat and mechanical stimuli. TRPV2 knockout mice showed reduced embryonic weight and perinatal viability. As adults, surviving knockout mice also exhibited a slightly reduced body weight. TRPV2 knockout mice showed normal behavioral responses to noxious heat over a broad range of temperatures and normal responses to punctate mechanical stimuli, both in the basal state and under hyperalgesic conditions such as peripheral inflammation and L5 spinal nerve ligation. Moreover, behavioral assays of TRPV1/TRPV2 double knockout mice or of TRPV2 knockout mice treated with resiniferatoxin to desensitize TRPV1-expressing afferents revealed no thermosensory consequences of TRPV2 absence. In line with behavioral findings, electrophysiological recordings from skin afferents showed that C-fiber responses to heat and C- and Aδ-fiber responses to noxious mechanical stimuli were unimpaired in the absence of TRPV2. The prevalence of thermosensitive Aδ-fibers was too low to permit comparison between genotypes. Thus, TRPV2 is important for perinatal viability but is not essential for heat or mechanical nociception or hypersensitivity in the adult mouse. PMID:21832173

Isolated and modulated effects of topology and material type on the mechanical properties of additively manufactured porous biomaterials.

PubMed

Hedayati, R; Ahmadi, S M; Lietaert, K; Pouran, B; Li, Y; Weinans, H; Rans, C D; Zadpoor, A A

2018-03-01

In this study, we tried to quantify the isolated and modulated effects of topological design and material type on the mechanical properties of AM porous biomaterials. Towards this aim, we assembled a large dataset comprising the mechanical properties of AM porous biomaterials with different topological designs (i.e. different unit cell types and relative densities) and material types. Porous structures were additively manufactured from Co-Cr using a selective laser melting (SLM) machine and tested under quasi-static compression. The normalized mechanical properties obtained from those structures were compared with mechanical properties available from our previous studies for porous structures made from Ti-6Al-4V and pure titanium as well as with analytical solutions. The normalized values of elastic modulus and yield stress were found to be relatively close to each other as well as in agreement with analytical solutions regardless of material type. However, the material type was found to systematically affect the mechanical properties of AM porous biomaterials in general and the post-elastic/post-yield range (plateau stress and energy absorption capacity) in particular. To put this in perspective, topological design could cause up to 10-fold difference in the mechanical properties of AM porous biomaterials while up to 2-fold difference was observed as a consequence of changing the material type. Copyright © 2017 Elsevier Ltd. All rights reserved.

A sorting mechanism for a riffle-pool sequence

Treesearch

Thomas Lisle

1979-01-01

Transport of coarse, heterogeneous debris in a natural stream under a wide range of flows usually results in a remarkably stable, undulatory bed profile, which manifests an in transit sorting process of the bed material. In general, finer material representative of the bulk of the normal bed load resides in the deep sections, or pools, below flood stages. At high...

Downhill Cycling Symmetry Breaking: How the Rider Foils Experiment

ERIC Educational Resources Information Center

Abu, Yuval Ben; Wolfson, Ira; Bran, Gil; Yizhaq, Hezi

2017-01-01

In high-school teaching of mechanics, we deal, among other things, with the nature of static and kinetic friction, forces that are proportional to the normal force. Under the influence of frictional forces, a body moves down a rough sloped decline at a fixed rate of acceleration that is independent of its mass. This situation does not apply to…

A Failure of Left Temporal Cortex to Specialize for Language Is an Early Emerging and Fundamental Property of Autism

ERIC Educational Resources Information Center

Eyler, Lisa T.; Pierce, Karen; Courchesne, Eric

2012-01-01

Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend…

International Education Policy: Its Influence on the Conception of VET and the VET System in Germany

ERIC Educational Resources Information Center

Deissinger, Thomas

2015-01-01

Inquiries into vocational education and training (VET) systems are normally characterised by looking at institutions and steering mechanisms. That aside, however, it is culture which underlies both the practice and the theory as well as the policy of VET in various countries. Specific problems arise when it comes to harmonising VET systems through…

Adolescent Alcohol Exposure: Burden of Epigenetic Reprogramming, Synaptic Remodeling, and Adult Psychopathology

PubMed Central

Kyzar, Evan J.; Floreani, Christina; Teppen, Tara L.; Pandey, Subhash C.

2016-01-01

Adolescence represents a crucial phase of synaptic maturation characterized by molecular changes in the developing brain that shape normal behavioral patterns. Epigenetic mechanisms play an important role in these neuromaturation processes. Perturbations of normal epigenetic programming during adolescence by ethanol can disrupt these molecular events, leading to synaptic remodeling and abnormal adult behaviors. Repeated exposure to binge levels of alcohol increases the risk for alcohol use disorder (AUD) and comorbid psychopathology including anxiety in adulthood. Recent studies in the field clearly suggest that adolescent alcohol exposure causes widespread and persistent changes in epigenetic, neurotrophic, and neuroimmune pathways in the brain. These changes are manifested by altered synaptic remodeling and neurogenesis in key brain regions leading to adult psychopathology such as anxiety and alcoholism. This review details the molecular mechanisms underlying adolescent alcohol exposure-induced changes in synaptic plasticity and the development of alcohol addiction-related phenotypes in adulthood. PMID:27303256

Cholinergic regulation of epithelial ion transport in the mammalian intestine

PubMed Central

Hirota, C L; McKay, D M

2006-01-01

Acetylcholine (ACh) is critical in controlling epithelial ion transport and hence water movements for gut hydration. Here we review the mechanism of cholinergic control of epithelial ion transport across the mammalian intestine. The cholinergic nervous system affects basal ion flux and can evoke increased active ion transport events. Most studies rely on measuring increases in short-circuit current (ISC = active ion transport) evoked by adding ACh or cholinomimetics to intestinal tissue mounted in Ussing chambers. Despite subtle species and gut regional differences, most data indicate that, under normal circumstances, the effect of ACh on intestinal ion transport is mainly an increase in Cl- secretion due to interaction with epithelial M3 muscarinic ACh receptors (mAChRs) and, to a lesser extent, neuronal M1 mAChRs; however, AChR pharmacology has been plagued by a lack of good receptor subtype-selective compounds. Mice lacking M3 mAChRs display intact cholinergically-mediated intestinal ion transport, suggesting a possible compensatory mechanism. Inflamed tissues often display perturbations in the enteric cholinergic system and reduced intestinal ion transport responses to cholinomimetics. The mechanism(s) underlying this hyporesponsiveness are not fully defined. Inflammation-evoked loss of mAChR-mediated control of epithelial ion transport in the mouse reveals a role for neuronal nicotinic AChRs, representing a hitherto unappreciated braking system to limit ACh-evoked Cl- secretion. We suggest that: i) pharmacological analyses should be supported by the use of more selective compounds and supplemented with molecular biology techniques targeting specific ACh receptors and signalling molecules, and ii) assessment of ion transport in normal tissue must be complemented with investigations of tissues from patients or animals with intestinal disease to reveal control mechanisms that may go undetected by focusing on healthy tissue only. PMID:16981004

Alteration of a motor learning rule under mirror-reversal transformation does not depend on the amplitude of visual error.

PubMed

Kasuga, Shoko; Kurata, Makiko; Liu, Meigen; Ushiba, Junichi

2015-05-01

Human's sophisticated motor learning system paradoxically interferes with motor performance when visual information is mirror-reversed (MR), because normal movement error correction further aggravates the error. This error-increasing mechanism makes performing even a simple reaching task difficult, but is overcome by alterations in the error correction rule during the trials. To isolate factors that trigger learners to change the error correction rule, we manipulated the gain of visual angular errors when participants made arm-reaching movements with mirror-reversed visual feedback, and compared the rule alteration timing between groups with normal or reduced gain. Trial-by-trial changes in the visual angular error was tracked to explain the timing of the change in the error correction rule. Under both gain conditions, visual angular errors increased under the MR transformation, and suddenly decreased after 3-5 trials with increase. The increase became degressive at different amplitude between the two groups, nearly proportional to the visual gain. The findings suggest that the alteration of the error-correction rule is not dependent on the amplitude of visual angular errors, and possibly determined by the number of trials over which the errors increased or statistical property of the environment. The current results encourage future intensive studies focusing on the exact rule-change mechanism. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Effects of TiO2 nanoparticles on wheat (Triticum aestivum L.) seedlings cultivated under super-elevated and normal CO2 conditions.

PubMed

Jiang, Fuping; Shen, Yunze; Ma, Chuanxin; Zhang, Xiaowen; Cao, Weidong; Rui, Yukui

2017-01-01

Concerns over the potential risks of nanomaterials to ecosystem have been raised, as it is highly possible that nanomaterials could be released to the environment and result in adverse effects on living organisms. Carbon dioxide (CO2) is one of the main greenhouse gases. The level of CO2 keeps increasing and subsequently causes a series of environmental problems, especially for agricultural crops. In the present study, we investigated the effects of TiO2 NPs on wheat seedlings cultivated under super-elevated CO2 conditions (5000 mg/L CO2) and under normal CO2 conditions (400 mg/L CO2). Compared to the normal CO2 condition, wheat grown under the elevated CO2 condition showed increases of root biomass and large numbers of lateral roots. Under both CO2 cultivation conditions, the abscisic acid (ABA) content in wheat seedlings increased with increasing concentrations of TiO2 NPs. The indolepropioponic acid (IPA) and jasmonic acid (JA) content notably decreased in plants grown under super-elevated CO2 conditions, while the JA content increased with increasing concentrations of TiO2 NPs. Ti accumulation showed a dose-response manner in both wheat shoots and roots as TiO2 NPs concentrations increased. Additionally, the presence of elevated CO2 significantly promoted Ti accumulation and translocation in wheat treated with certain concentrations of TiO2 NPs. This study will be of benefit to the understanding of the joint effects and physiological mechanism of high-CO2 and nanoparticle to terrestrial plants.

Method and apparatus for single-stepping coherence events in a multiprocessor system under software control

DOEpatents

Blumrich, Matthias A.; Salapura, Valentina

2010-11-02

An apparatus and method are disclosed for single-stepping coherence events in a multiprocessor system under software control in order to monitor the behavior of a memory coherence mechanism. Single-stepping coherence events in a multiprocessor system is made possible by adding one or more step registers. By accessing these step registers, one or more coherence requests are processed by the multiprocessor system. The step registers determine if the snoop unit will operate by proceeding in a normal execution mode, or operate in a single-step mode.

Drosophila hematopoiesis under normal conditions and in response to immune stress.

PubMed

Letourneau, Manon; Lapraz, Francois; Sharma, Anurag; Vanzo, Nathalie; Waltzer, Lucas; Crozatier, Michèle

2016-11-01

The emergence of hematopoietic progenitors and their differentiation into various highly specialized blood cell types constitute a finely tuned process. Unveiling the genetic cascades that control blood cell progenitor fate and understanding how they are modulated in response to environmental changes are two major challenges in the field of hematopoiesis. In the last 20 years, many studies have established important functional analogies between blood cell development in vertebrates and in the fruit fly, Drosophila melanogaster. Thereby, Drosophila has emerged as a powerful genetic model for studying mechanisms that control hematopoiesis during normal development or in pathological situations. Moreover, recent advances in Drosophila have highlighted how intricate cell communication networks and microenvironmental cues regulate blood cell homeostasis. They have also revealed the striking plasticity of Drosophila mature blood cells and the presence of different sites of hematopoiesis in the larva. This review provides an overview of Drosophila hematopoiesis during development and summarizes our current knowledge on the molecular processes controlling larval hematopoiesis, both under normal conditions and in response to an immune challenge, such as wasp parasitism. © 2016 Federation of European Biochemical Societies.

Drain current enhancement induced by hole injection from gate of 600-V-class normally off gate injection transistor under high temperature conditions up to 200 °C

NASA Astrophysics Data System (ADS)

Ishii, Hajime; Ueno, Hiroaki; Ueda, Tetsuzo; Endoh, Tetsuo

2018-06-01

In this paper, the current–voltage (I–V) characteristics of a 600-V-class normally off GaN gate injection transistor (GIT) from 25 to 200 °C are analyzed, and it is revealed that the drain current of the GIT increases during high-temperature operation. It is found that the maximum drain current (I dmax) of the GIT is 86% higher than that of a conventional 600-V-class normally off GaN metal insulator semiconductor hetero-FET (MIS-HFET) at 150 °C, whereas the GIT obtains 56% I dmax even at 200 °C. Moreover, the mechanism of the drain current increase of the GIT is clarified by examining the relationship between the temperature dependence of the I–V characteristics of the GIT and the gate hole injection effect determined from the shift of the second transconductance (g m) peak of the g m–V g characteristic. From the above, the GIT is a promising device with enough drivability for future power switching applications even under high-temperature conditions.

Statistical State Dynamics Based Study of the Role of Nonlinearity in the Maintenance of Turbulence in Couette Flow

NASA Astrophysics Data System (ADS)

Farrell, Brian; Ioannou, Petros; Nikolaidis, Marios-Andreas

2017-11-01

While linear non-normality underlies the mechanism of energy transfer from the externally driven flow to the perturbation field, nonlinearity is also known to play an essential role in sustaining turbulence. We report a study based on the statistical state dynamics of Couette flow turbulence with the goal of better understanding the role of nonlinearity in sustaining turbulence. The statistical state dynamics implementations used are ensemble closures at second order in a cumulant expansion of the Navier-Stokes equations in which the averaging operator is the streamwise mean. Two fundamentally non-normal mechanisms potentially contributing to maintaining the second cumulant are identified. These are essentially parametric perturbation growth arising from interaction of the perturbations with the fluctuating mean flow and transient growth of perturbations arising from nonlinear interaction between components of the perturbation field. By the method of selectively including these mechanisms parametric growth is found to maintain the perturbation field in the turbulent state while the more commonly invoked mechanism associated with transient growth of perturbations arising from scattering by nonlinear interaction is found to suppress perturbation variance. Funded by ERC Coturb Madrid Summer Program and NSF AGS-1246929.

An update on oxidative stress-mediated organ pathophysiology.

PubMed

Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

2013-12-01

Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multiscale modeling and characterization for performance and safety of lithium-ion batteries

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

Pannala, Sreekanth; Turner, John A.; Allu, Srikanth

Lithium-ion batteries are highly complex electrochemical systems whose performance and safety are governed by coupled nonlinear electrochemical-electrical-thermal-mechanical processes over a range of spatiotemporal scales. In this paper we describe a new, open source computational framework for Lithium-ion battery simulations that is designed to support a variety of model types and formulations. This framework has been used to create three-dimensional cell and battery pack models that explicitly simulate all the battery components (current collectors, electrodes, and separator). The models are used to predict battery performance under normal operations and to study thermal and mechanical safety aspects under adverse conditions. The modelmore » development and validation are supported by experimental methods such as IR-imaging, X-ray tomography and micro-Raman mapping.« less

Multiscale modeling and characterization for performance and safety of lithium-ion batteries

DOE PAGES

Pannala, Sreekanth; Turner, John A.; Allu, Srikanth; ...

2015-08-19

Lithium-ion batteries are highly complex electrochemical systems whose performance and safety are governed by coupled nonlinear electrochemical-electrical-thermal-mechanical processes over a range of spatiotemporal scales. In this paper we describe a new, open source computational framework for Lithium-ion battery simulations that is designed to support a variety of model types and formulations. This framework has been used to create three-dimensional cell and battery pack models that explicitly simulate all the battery components (current collectors, electrodes, and separator). The models are used to predict battery performance under normal operations and to study thermal and mechanical safety aspects under adverse conditions. The modelmore » development and validation are supported by experimental methods such as IR-imaging, X-ray tomography and micro-Raman mapping.« less

Transcriptome profiling of the floating-leaved aquatic plant Nymphoides peltata in response to flooding stress.

PubMed

Wu, Jinwei; Zhao, Hua-Bin; Yu, Dan; Xu, Xinwei

2017-01-31

Waterlogging or flooding is one of the most challenging abiotic stresses experienced by plants. Unlike many flooding-tolerant plants, floating-leaved aquatic plants respond actively to flooding stress by fast growth and elongation of its petioles to make leaves re-floating. However, the molecular mechanisms of this plant group responding to flood have not been investigated before. Here, we investigated the genetic basis of this adaptive response by characterizing the petiole transcriptomes of a floating-leaved species Nymphoides peltata under normal and flooding conditions. Clean reads under normal and flooding conditions with pooled sampling strategy were assembled into 124,302 unigenes. A total of 8883 unigenes were revealed to be differentially expressed between normal and flooding conditions. Among them, top ranked differentially expressed genes were mainly involved in antioxidant process, photosynthesis process and carbohydrate metabolism, including the glycolysis and a modified tricarboxylic acid cycle - alanine metabolism. Eight selected unigenes with significantly differentiated expression changes between normal and flooding conditions were validated by qRT-PCR. Among these processes, antioxidant process and glycolysis are commonly induced by waterlogging or flooding environment in plants, whereas photosynthesis and alanine metabolism are rarely occurred in other flooding-tolerant plants, suggesting the significant contributions of the two processes in the active response of N. peltata to flooding stress. Our results provide a valuable genomic resource for future studies on N. peltata and deepen our understanding of the genetic basis underlying the response to flooding stress in aquatic plants.

Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease.

PubMed

McMurray, Cynthia T

2008-07-01

Mammalian cells have evolved sophisticated DNA repair systems to correct mispaired or damaged bases and extrahelical loops. Emerging evidence suggests that, in some cases, the normal DNA repair machinery is "hijacked" to become a causative factor in mutation and disease, rather than act as a safeguard of genomic integrity. In this review, we consider two cases in which active MMR leads to mutation or to cell death. There may be similar mechanisms by which uncoupling of normal MMR recognition from downstream repair allows triplet expansions underlying human neurodegenerative disease, or cell death in response to chemical lesion.

Genetic Diversity of Salt Tolerance in Miscanthus

PubMed Central

Chen, Chang-Lin; van der Schoot, Hanneke; Dehghan, Shiva; Alvim Kamei, Claire L.; Schwarz, Kai-Uwe; Meyer, Heike; Visser, Richard G. F.; van der Linden, C. Gerard

2017-01-01

Miscanthus is a woody rhizomatous C4 grass that can be used as a CO2 neutral biofuel resource. It has potential to grow in marginal areas such as saline soils, avoiding competition for arable lands with food crops. This study explored genetic diversity for salt tolerance in Miscanthus and discovered mechanisms and traits that can be used to improve the yield under salt stress. Seventy genotypes of Miscanthus (including 57 M. sinensis, 5 M. sacchariflorus, and 8 hybrids) were evaluated for salt tolerance under saline (150 mM NaCl) and normal growing conditions using a hydroponic system. Analyses of shoot growth traits and ion concentrations revealed the existence of large variation for salt tolerance in the genotypes. We identified genotypes with potential for high biomass production both under control and saline conditions that may be utilized for growth under marginal, saline conditions. Several relatively salt tolerant genotypes had clearly lower Na+ concentrations and showed relatively high K+/Na+ ratios in the shoots under salt stress, indicating that a Na+ exclusion mechanism was utilized to prevent Na+ accumulation in the leaves. Other genotypes showed limited reduction in leaf expansion and growth rate under saline conditions, which may be indicative of osmotic stress tolerance. The genotypes demonstrating potentially different salt tolerance mechanisms can serve as starting material for breeding programs aimed at improving salinity tolerance of Miscanthus. PMID:28261243

Hitting a Moving Target: Basic Mechanisms of Recovery from Acquired Developmental Brain Injury

PubMed Central

Giza, Christopher C.; Kolb, Bryan; Harris, Neil G.; Asarnow, Robert F.; Prins, Mayumi L.

2009-01-01

Acquired brain injuries represent a major cause of disability in the pediatric population. Understanding responses to developmental acquired brain injuries requires knowledge of the neurobiology of normal development, age-at-injury effects and experience-dependent neuroplasticity. In the developing brain, full recovery cannot be considered as a return to the premorbid baseline, since ongoing maturation means that cerebral functioning in normal individuals will continue to advance. Thus, the recovering immature brain has to ‘hit a moving target’ to achieve full functional recovery, defined as parity with age-matched uninjured peers. This review will discuss the consequences of developmental injuries such as focal lesions, diffuse hypoxia and traumatic brain injury (TBI). Underlying cellular and physiological mechanisms relevant to age-at-injury effects will be described in considerable detail, including but not limited to alterations in neurotransmission, connectivity/network functioning, the extracellular matrix, response to oxidative stress and changes in cerebral metabolism. Finally, mechanisms of experience-dependent plasticity will be reviewed in conjunction with their effects on neural repair and recovery. PMID:19956795

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling

PubMed Central

Engström, Wilhelm; Darbre, Philippa; Eriksson, Staffan; Gulliver, Linda; Hultman, Tove; Karamouzis, Michalis V.; Klaunig, James E.; Mehta, Rekha; Moorwood, Kim; Sanderson, Thomas; Sone, Hideko; Vadgama, Pankaj; Wagemaker, Gerard; Ward, Andrew; Singh, Neetu; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A. Ivana; Raju, Jayadev; Hamid, Roslida A.; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K.; Ryan, Elizabeth; Brown, Dustin G.; Bisson, William H.

2015-01-01

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span. PMID:26106143

Orchestrating brain-cell renewal: the role of immune cells in adult neurogenesis in health and disease.

PubMed

Ziv, Yaniv; Schwartz, Michal

2008-11-01

Immune cells and immune molecules have recently been shown to support neurogenesis from neural stem and progenitor cells in the adult brain. This non-classical immune activity takes place constantly under normal physiological conditions and is extended under acute pathological conditions to include the attraction of progenitor cells and induction of neurogenesis in regions of the adult central nervous system (CNS) in which formation of new neurons does not normally occur. We suggest that the immune system should be viewed as a novel player in the adult neural stem cell niche and a coordinator of cell renewal processes after injury. We discuss these notions in light of the well-known facts that both immune-cell activity and cell renewal are inherently limited in the adult CNS and that immune and stem cells provide the body's mechanisms of repair.

Sliding contact fracture of dental ceramics: Principles and validation

PubMed Central

Ren, Linlin; Zhang, Yu

2014-01-01

Ceramic prostheses are subject to sliding contact under normal and tangential loads. Accurate prediction of the onset of fracture at two contacting surfaces holds the key to greater long-term performance of these prostheses. In this study, building on stress analysis of Hertzian contact and considering fracture criteria for linear elastic materials, a constitutive fracture mechanics relation was developed to incorporate the critical fracture load with the contact geometry, coefficient of friction and material fracture toughness. Critical loads necessary to cause fracture under a sliding indenter were calculated from the constitutive equation, and compared with the loads predicted from elastic stress analysis in conjunction with measured critical load for frictionless normal contact—a semi-empirical approach. The major predictions of the models were calibrated with experimentally determined critical loads of current and future dental ceramics after contact with a rigid spherical slider. Experimental results conform with the trends predicted by the models. PMID:24632538

Microgravity as a novel environmental signal affecting Salmonella enterica serovar Typhimurium virulence

NASA Technical Reports Server (NTRS)

Nickerson, C. A.; Ott, C. M.; Mister, S. J.; Morrow, B. J.; Burns-Keliher, L.; Pierson, D. L.

2000-01-01

The effects of spaceflight on the infectious disease process have only been studied at the level of the host immune response and indicate a blunting of the immune mechanism in humans and animals. Accordingly, it is necessary to assess potential changes in microbial virulence associated with spaceflight which may impact the probability of in-flight infectious disease. In this study, we investigated the effect of altered gravitational vectors on Salmonella virulence in mice. Salmonella enterica serovar Typhimurium grown under modeled microgravity (MMG) were more virulent and were recovered in higher numbers from the murine spleen and liver following oral infection compared to organisms grown under normal gravity. Furthermore, MMG-grown salmonellae were more resistant to acid stress and macrophage killing and exhibited significant differences in protein synthesis than did normal-gravity-grown cells. Our results indicate that the environment created by simulated microgravity represents a novel environmental regulatory factor of Salmonella virulence.

Obesity and cancer: inflammation bridges the two

PubMed Central

Kolb, Ryan; Sutterwala, Fayyaz S.; Zhang, Weizhou

2016-01-01

Obesity is a growing public health problem and affects 35% US adults. Obesity increases the risk of many cancer types and is associated with poor outcomes. Clinical management of cancer patients has been essentially the same between normal weight and obese individuals. Understanding causal mechanisms by which obesity drives cancer initiation and progression is essential for the development of novel precision therapy for obese cancer patients. One caveat is that various mechanisms have been proposed for different cancer types for their progression under obesity. Since obesity is known to have global impact on inflammation, here we will summarize recent literature and discuss the potential of inflammation being the common causal mechanism to promote cancer promotion across cancer types. PMID:27429211

Hypothalamic Dysfunction of the Thrombospondin Receptor α2δ-1 Underlies the Overeating and Obesity Triggered by Brain-Derived Neurotrophic Factor Deficiency

PubMed Central

Cordeira, Joshua W.; Felsted, Jennifer A.; Teillon, Sarah; Daftary, Shabrine; Panessiti, Micaella; Wirth, Jena; Sena-Esteves, Miguel

2014-01-01

Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, are critical components of the neural circuitry controlling appetite and body weight. Diminished BDNF signaling in mice results in severe hyperphagia and obesity. In humans, BDNF haploinsufficiency and the functional Bdnf Val66Met polymorphism have been linked to elevated food intake and body weight. The mechanisms underlying this dysfunction are poorly defined. We demonstrate a chief role of α2δ-1, a calcium channel subunit and thrombospondin receptor, in triggering overeating in mice with central BDNF depletion. We show reduced α2δ-1 cell-surface expression in the BDNF mutant ventromedial hypothalamus (VMH), an energy balance-regulating center. This deficit contributes to the hyperphagia exhibited by BDNF mutant mice because selective inhibition of α2δ-1 by gabapentin infusion into wild-type VMH significantly increases feeding and body weight gain. Importantly, viral-mediated α2δ-1 rescue in BDNF mutant VMH significantly mitigates their hyperphagia, obesity, and liver steatosis and normalizes deficits in glucose homeostasis. Whole-cell recordings in BDNF mutant VMH neurons revealed normal calcium currents but reduced frequency of EPSCs. These results suggest calcium channel-independent effects of α2δ-1 on feeding and implicate α2δ-1–thrombospondin interactions known to facilitate excitatory synapse assembly. Our findings identify a central mechanism mediating the inhibitory effects of BDNF on feeding. They also demonstrate a novel and critical role for α2δ-1 in appetite control and suggest a mechanism underlying weight gain in humans treated with gabapentinoid drugs. PMID:24403154

FASTGRASS: A mechanistic model for the prediction of Xe, I, Cs, Te, Ba, and Sr release from nuclear fuel under normal and severe-accident conditions

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

Rest, J.; Zawadzki, S.A.

The primary physical/chemical models that form the basis of the FASTGRASS mechanistic computer model for calculating fission-product release from nuclear fuel are described. Calculated results are compared with test data and the major mechanisms affecting the transport of fission products during steady-state and accident conditions are identified.

Genetic and Environmental Relationships between Head Circumference Growth in the First Year of Life and Sociocognitive Development in the Second Year: A Longitudinal Twin Study

ERIC Educational Resources Information Center

Fujisawa, Keiko K.; Ozaki, Koken; Suzuki, Kunitake; Yamagata, Shinji; Kawahashi, Ikko; Ando, Juko

2012-01-01

Although growth in head circumference (HC) during infancy is known to predict later childhood outcomes, the mechanisms underlying this association with later sociocognitive abilities remain undetermined. Thus, using a sample of 241 pairs of normally developing Japanese twins, this study investigated the underpinnings of the association between HC…

Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

PubMed

Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

2009-07-15

Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

Experimental Investigation of the Peak Shear Strength Criterion Based on Three-Dimensional Surface Description

NASA Astrophysics Data System (ADS)

Liu, Quansheng; Tian, Yongchao; Ji, Peiqi; Ma, Hao

2018-04-01

The three-dimensional (3D) morphology of joints is enormously important for the shear mechanical properties of rock. In this study, three-dimensional morphology scanning tests and direct shear tests are conducted to establish a new peak shear strength criterion. The test results show that (1) surface morphology and normal stress exert significant effects on peak shear strength and distribution of the damage area. (2) The damage area is located at the steepest zone facing the shear direction; as the normal stress increases, it extends from the steepest zone toward a less steep zone. Via mechanical analysis, a new formula for the apparent dip angle is developed. The influence of the apparent dip angle and the average joint height on the potential contact area is discussed, respectively. A new peak shear strength criterion, mainly applicable to specimens under compression, is established by using new roughness parameters and taking the effects of normal stress and the rock mechanical properties into account. A comparison of this newly established model with the JRC-JCS model and the Grasselli's model shows that the new one could apparently improve the fitting effect. Compared with earlier models, the new model is simpler and more precise. All the parameters in the new model have clear physical meanings and can be directly determined from the scanned data. In addition, the indexes used in the new model are more rational.

Effects of insulin under normal and low glucose on retinal electrophysiology in the perfused cat eye.

PubMed

Lansel, N; Niemeyer, G

1997-04-01

To investigate the short-term effects of fast-acting insulin on the electroretinogram-b-wave, optic nerve response, standing potential, and flow rate in the arterially perfused cat eye under normal conditions and during low glucose levels. Enucleated cat eyes were perfused with a glucose- and insulin-free tissue culture medium, to which glucose was applied at normal (5.5 mM) and reduced (2 and 1 mM) concentrations. Photic stimulation was performed in the rod-matched intensity range before, during, and after insulin application at postprandial (5 ng/ml) and at 10 and 20 x higher concentrations. Insulin failed to affect retinal signals at normal glucose levels. However, insulin enhanced the low glucose-induced decrease in rod-driven b-wave amplitude (P < 0.05 at 2 mM; P < 0.01 at 1 mM) without affecting the corresponding changes in the optic nerve response. The standing potential increased by as much as 0.75 mV in response to insulin. The perfusate flow rate was not altered by insulin. Insulin was not required for normal retinal function as observed during 10 hours of perfusion. The differential responsiveness to insulin under low glucose of the b-wave versus the optic nerve response is thought to reflect suppression of glucose use by Müller (glial) cells rather than neuromodulation, as the neuronal optic nerve response is unaffected. The postulated insulin sensitivity of Müller cells (changes in b-wave amplitude) indicates a possible difference in the mechanism of glucose metabolism of glia versus neurons. The electrophysiological effect of insulin under low glucose suggests its passage across the blood-retina barrier. The increase in the standing potential is likely to be a receptor-mediated retinal pigment epithelium effect. These results provide evidence in the retina for the reported multifunctional nature of the insulin receptor.

A tale of two mechanisms. Strain-softening versus strain-hardening in single crystals under small stressed volumes

DOE PAGES

Bei, Hongbin; Xia, Yuzhi; Barabash, Rozaliya; ...

2015-08-10

Pre-straining defect-free single crystals will introduce heterogeneous dislocation nucleation sources that reduce the measured strength from the theoretical value, while pre-straining bulk samples will lead to strain hardening. Their competition is investigated by nanoindentation pop-in tests on variously pre-strained Mo single crystals with several indenter radii (~micrometer). Pre-straining primarily shifts deformation mechanism from homogeneous dislocation nucleation to a stochastic behavior, while strain hardening plays a secondary role, as summarized in a master plot of pop-in strength versus normalized indenter radius.

Mechanics of the Unusual Basilar Membrane in Gerbil

NASA Astrophysics Data System (ADS)

Kapuria, Santosh; Steele, Charles R.; Puria, Sunil

2011-11-01

The basilar membrane in gerbil differs from most other mammals, since its width and thickness show little variation from base to apex, and tympanic fiber layer in the pectinate zone forms a pronounced arch. Measurements indicate a quadratically increasing stiffness under point loading, which is contrary to the expected behavior of an arch. The plateau value has been considered to be the physiologically relevant stiffness, but it only occurs after 10-25 μm of deflection, whereas the normal physiological deflection is in the submicron range. The present work aims to resolve these contradictions by considering the mechanics of the geometric configuration.

Mechanical deterioration underlies malignant behavior of aneurysmal human ascending aorta.

PubMed

Koullias, George; Modak, Raj; Tranquilli, Maryann; Korkolis, Dimitris P; Barash, Paul; Elefteriades, John A

2005-09-01

The human ascending aorta becomes markedly prone to rupture and dissection at a diameter of 6 cm. The mechanical substrate for this malignant behavior is unknown. This investigation applied engineering analysis to human ascending aortic aneurysms and compared their structural characteristics with those of normal aortas. We measured the mechanical characteristics of the aorta by direct epiaortic echocardiography at the time of surgery in 33 patients with ascending aortic aneurysm undergoing aortic replacement and in 20 control patients with normal aortas undergoing coronary artery bypass grafting. Six parameters were measured in all patients: aortic diameter in systole and diastole, aortic wall thickness in systole and diastole, and blood pressure in systole and diastole. These were used to calculate mechanical characteristics of the aorta from standard equations. Aortic distensibility reflects the elastic qualities of the aorta. Aortic wall stress reflects the disrupting force experienced within the aortic wall. Incremental elastic modulus indicates loss of elasticity reserve. Aortic distensibility falls to extremely low levels as aortic dimension rises toward 6 cm (3.02 mm Hg(-1) for small aortas versus 1.45 mm Hg(-1) for aortas larger than 5 cm, P < .05). Aortic wall stress rises to 157.8 kPa for the aneurysmal aorta, compared with 92.5 kPa for normal aortas. For 6-cm aortas at pressures of 200 mm Hg or more, wall stress rises to 857 kPa, nearly exceeding the known maximal tensile strength of human aneurysmal aortic wall. Incremental elastic modulus deteriorates (1.93 +/- 0.88 MPa vs 1.18 +/- 0.21 MPa, P < .05) in aneurysmal aortas relative to that in normal aortas. The mechanical properties of the aneurysmal aorta deteriorate dramatically as the aorta enlarges, reaching critical levels associated with rupture by a diameter of 6 cm. This mechanical deterioration provides an explanation in engineering terms for the malignant clinical behavior (rupture and dissection) of the aorta at these dimensions. This work adds to our fundamental understanding of the biology of aortic aneurysms and promises to permit future application of engineering measurements to supplement aneurysm size in clinical decision making in aneurysmal disease.

Flux pinning mechanism in codoped-MgB2 with Al2O3 and SiC

NASA Astrophysics Data System (ADS)

Kiafiroozkoohi, Narjess Sadat; Ghorbani, Shaban Reza; Arabi, Hadi

2018-05-01

MgB2 superconductor samples, co-doped with 0.02 wt of Al2O3 and 0.02 wt SiC, have been examined by M-H loop measurements and calculation of the critical current density based on the Bean model. Normalized volume pinning force, f = F/Fmax, as a function of the reduced magnetic field, h = H/Hmax has been obtained at each temperature. Hughochi flux pinning model, which was included the normal point pinning, the normal surface pinning, and the pinning based on spatial variation in the Ginzburg-Landau parameter, was used to study the flux pinning mechanisms. It was found that the Δκ effect and the normal point pinning mechanisms play the main role in the flux pinning at the magnetic field lower than Hmax and the contribution of the Δκ mechanism increases with the increasing temperature, while the contribution of normal point pinning mechanism decreases. At magnetic field larger than Hmax, the only mechanism that acts as the flux pinning was the normal surface pinning mechanism.

Mechanism underlying berberine's effects on HSP70/TNFα under heat stress: Correlation with the TATA boxes.

PubMed

Jiang, Jing-Fei; Lei, Fan; Yuan, Zhi-Yi; Wang, Yu-Gang; Wang, Xin-Pei; Yan, Xiao-Jin; Yu, Xuan; Xing, Dong-Ming; DU, Li-Jun

2017-03-01

Heat stress can stimulate an increase in body temperature, which is correlated with increased expression of heat shock protein 70 (HSP70) and tumor necrosis factor α (TNFα). The exact mechanism underlying the HSP70 and TNFα induction is unclear. Berberine (BBR) can significantly inhibit the temperature rise caused by heat stress, but the mechanism responsible for the BBR effect on HSP70 and TNFα signaling has not been investigated. The aim of the present study was to explore the relationship between the expression of HSP70 and TNFα and the effects of BBR under heat conditions, using in vivo and in vitro models. The expression levels of HSP70 and TNFα were determined using RT-PCR and Western blotting analyses. The results showed that the levels of HSP70 and TNFα were up-regulated under heat conditions (40 °C). HSP70 acted as a chaperone to maintain TNFα homeostasis with rising the temperature, but knockdown of HSP70 could not down-regulate the level of TNFα. Furthermore, TNFα could not influence the expression of HSP70 under normal and heat conditions. BBR targeted both HSP70 and TNFα by suppressing their gene transcription, thereby decreasing body temperature under heat conditions. In conclusion, BBR has a potential to be developed as a therapeutic strategy for suppressing the thermal effects in hot environments. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Collision processes at the northern margin of the Black Sea

NASA Astrophysics Data System (ADS)

Gobarenko, V. S.; Murovskaya, A. V.; Yegorova, T. P.; Sheremet, E. E.

2016-07-01

Extended along the Crimea-Caucasus coast of the Black Sea, the Crimean Seismic Zone (CSZ) is an evidence of active tectonic processes at the junction of the Scythian Plate and Black Sea Microplate. A relocation procedure applied to weak earthquakes (mb ≤ 3) recorded by ten local stations during 1970-2013 helped to determine more accurately the parameters of hypocenters in the CSZ. The Kerch-Taman, Sudak, Yuzhnoberezhnaya (South Coast), and Sevastopol subzones have also been recognized. Generalization of the focal mechanisms of 31 strong earthquakes during 1927-2013 has demonstrated the predominance of reverse and reverse-normal-faulting deformation regimes. This ongoing tectonic process occurs under the settings of compression and transpression. The earthquake foci with strike-slip component mechanisms concentrate in the west of the CSZ. Comparison of deformation modes in the western and eastern Crimean Mountains according to tectonophysical data has demonstrated that the western part is dominated by strike-slip and normal- faulting, while in the eastern part, reverse-fault and strike-slip deformation regimes prevail. Comparison of the seismicity and gravity field and modes of deformation suggests underthusting of the East Black Sea Microplate with thin suboceanic crust under the Scythian Plate. In the Yuzhnoberezhnaya Subzone, this process is complicated by the East Black Sea Microplate frontal part wedging into the marginal part of the Scythian Plate crust. The indentation mechanism explains the strong gravity anomaly in the Crimean Mountains and their uplift.

Characterization of reward and effort mechanisms in apathy

PubMed Central

Bonnelle, Valerie; Veromann, Kai-Riin; Burnett Heyes, Stephanie; Lo Sterzo, Elena; Manohar, Sanjay; Husain, Masud

2015-01-01

Apathy is a common but poorly understood condition with a wide societal impact observed in several brain disorders as well as, to some extent, in the normal population. Hence the need for better characterization of the underlying mechanisms. The processes by which individuals decide to attribute physical effort to obtain rewards might be particularly relevant to relate to apathy traits. Here, we designed two paradigms to assess individual differences in physical effort production and effort-based decision-making and their relation to apathy in healthy people. Apathy scores were measured using a modified version of the Lille Apathy Rating Scale, suitable for use in a non-clinical population. In the first study, apathy scores were correlated with the degree to which stake (reward on offer) and difficulty level impacts on physical effort production. Individuals with relatively high apathy traits showed an increased modulation of effort while more motivated individuals generally exerted greater force across different levels of stake. To clarify the underlying mechanisms for this behavior, we designed a second task that allows independent titration of stake and effort levels for which subjects are willing to engage in an effortful response to obtain a reward. Our results suggest that apathy traits in the normal population are related to the way reward subjectively affects the estimation of effort costs, and more particularly manifest as decreased willingness to exert effort when rewards are small, or below threshold. The tasks we introduce here may provide useful tools to further investigate apathy in clinical populations. PMID:24747776

A finite element model of myocardial infarction using a composite material approach.

PubMed

Haddad, Seyyed M H; Samani, Abbas

2018-01-01

Computational models are effective tools to study cardiac mechanics under normal and pathological conditions. They can be used to gain insight into the physiology of the heart under these conditions while they are adaptable to computer assisted patient-specific clinical diagnosis and therapeutic procedures. Realistic cardiac mechanics models incorporate tissue active/passive response in conjunction with hyperelasticity and anisotropy. Conventional formulation of such models leads to mathematically-complex problems usually solved by custom-developed non-linear finite element (FE) codes. With a few exceptions, such codes are not available to the research community. This article describes a computational cardiac mechanics model developed such that it can be implemented using off-the-shelf FE solvers while tissue pathologies can be introduced in the model in a straight-forward manner. The model takes into account myocardial hyperelasticity, anisotropy, and active contraction forces. It follows a composite tissue modeling approach where the cardiac tissue is decomposed into two major parts: background and myofibers. The latter is modelled as rebars under initial stresses mimicking the contraction forces. The model was applied in silico to study the mechanics of infarcted left ventricle (LV) of a canine. End-systolic strain components, ejection fraction, and stress distribution attained using this LV model were compared quantitatively and qualitatively to corresponding data obtained from measurements as well as to other corresponding LV mechanics models. This comparison showed very good agreement.

The Pharmacological Basis of Cannabis Therapy for Epilepsy.

PubMed

Reddy, Doodipala Samba; Golub, Victoria M

2016-04-01

Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

A methodology for the characterization and diagnosis of cognitive impairments-Application to specific language impairment.

PubMed

Oliva, Jesús; Serrano, J Ignacio; del Castillo, M Dolores; Iglesias, Angel

2014-06-01

The diagnosis of mental disorders is in most cases very difficult because of the high heterogeneity and overlap between associated cognitive impairments. Furthermore, early and individualized diagnosis is crucial. In this paper, we propose a methodology to support the individualized characterization and diagnosis of cognitive impairments. The methodology can also be used as a test platform for existing theories on the causes of the impairments. We use computational cognitive modeling to gather information on the cognitive mechanisms underlying normal and impaired behavior. We then use this information to feed machine-learning algorithms to individually characterize the impairment and to differentiate between normal and impaired behavior. We apply the methodology to the particular case of specific language impairment (SLI) in Spanish-speaking children. The proposed methodology begins by defining a task in which normal and individuals with impairment present behavioral differences. Next we build a computational cognitive model of that task and individualize it: we build a cognitive model for each participant and optimize its parameter values to fit the behavior of each participant. Finally, we use the optimized parameter values to feed different machine learning algorithms. The methodology was applied to an existing database of 48 Spanish-speaking children (24 normal and 24 SLI children) using clustering techniques for the characterization, and different classifier techniques for the diagnosis. The characterization results show three well-differentiated groups that can be associated with the three main theories on SLI. Using a leave-one-subject-out testing methodology, all the classifiers except the DT produced sensitivity, specificity and area under curve values above 90%, reaching 100% in some cases. The results show that our methodology is able to find relevant information on the underlying cognitive mechanisms and to use it appropriately to provide better diagnosis than existing techniques. It is also worth noting that the individualized characterization obtained using our methodology could be extremely helpful in designing individualized therapies. Moreover, the proposed methodology could be easily extended to other languages and even to other cognitive impairments not necessarily related to language. Copyright © 2014 Elsevier B.V. All rights reserved.

Creep behaviour and creep mechanisms of normal and healing ligaments

NASA Astrophysics Data System (ADS)

Thornton, Gail Marilyn

Patients with knee ligament injuries often undergo ligament reconstructions to restore joint stability and, potentially, abate osteoarthritis. Careful literature review suggests that in 10% to 40% of these patients the graft tissue "stretches out". Some graft elongation is likely due to creep (increased elongation of tissue under repeated or sustained load). Quantifying creep behaviour and identifying creep mechanisms in both normal and healing ligaments is important for finding clinically relevant means to prevent creep. Ligament creep was accurately predicted using a novel yet simple structural model that incorporated both collagen fibre recruitment and fibre creep. Using the inverse stress relaxation function to model fibre creep in conjunction with fibre recruitment produced a superior prediction of ligament creep than that obtained from the inverse stress relaxation function alone. This implied mechanistic role of fibre recruitment during creep was supported using a new approach to quantify crimp patterns at stresses in the toe region (increasing stiffness) and linear region (constant stiffness) of the stress-strain curve. Ligament creep was relatively insensitive to increases in stress in the toe region; however, creep strain increased significantly when tested at the linear region stress. Concomitantly, fibre recruitment was evident at the toe region stresses; however, recruitment was limited at the linear region stress. Elevating the water content of normal ligament using phosphate buffered saline increased the creep response. Therefore, both water content and fibre recruitment are important mechanistic factors involved in creep of normal ligaments. Ligament scars had inferior creep behaviour compared to normal ligaments even after 14 weeks. In addition to inferior collagen properties affecting fibre recruitment and increased water content, increased glycosaminoglycan content and flaws in scar tissue were implicated as potential mechanisms of scar creep. Similarly, ligament autografts had persistently abnormal creep behaviour and creep recovery after 2 years likely due to infiltration by scar tissue. Short-term immobilization of autografts had long-term detrimental consequences perhaps due to re-injury of the graft at remobilization. Treatments that restore normal properties to these mechanistic factors in order to control creep would improve joint healing by restoring joint kinematics and maintaining normal joint loading.

An Electromechanical Left Ventricular Wedge Model to Study the Effects of Deformation on Repolarization during Heart Failure

PubMed Central

Rocha, B. M.; Toledo, E. M.; Barra, L. P. S.; dos Santos, R. Weber

2015-01-01

Heart failure is a major and costly problem in public health, which, in certain cases, may lead to death. The failing heart undergo a series of electrical and structural changes that provide the underlying basis for disturbances like arrhythmias. Computer models of coupled electrical and mechanical activities of the heart can be used to advance our understanding of the complex feedback mechanisms involved. In this context, there is a lack of studies that consider heart failure remodeling using strongly coupled electromechanics. We present a strongly coupled electromechanical model to study the effects of deformation on a human left ventricle wedge considering normal and hypertrophic heart failure conditions. We demonstrate through a series of simulations that when a strongly coupled electromechanical model is used, deformation results in the thickening of the ventricular wall that in turn increases transmural dispersion of repolarization. These effects were analyzed in both normal and failing heart conditions. We also present transmural electrograms obtained from these simulations. Our results suggest that the waveform of electrograms, particularly the T-wave, is influenced by cardiac contraction on both normal and pathological conditions. PMID:26550570

Carbon Nanotubes Preserve Normal Phenotypes Under Cancer-Promoting Conditions

NASA Astrophysics Data System (ADS)

Wailes, Elizabeth; Levi-Polyachenko, Nicole

2015-03-01

Tumor-associated fibroblasts and cancer cells have long been known to create a feedback loop that further stimulates the cancer. While this has been explored from a molecular biology standpoint, little is known about the physical relationship of the cell types even though both sets of cells are known to be mechanosensitive. Indeed, for both fibroblasts and cancer, mechanical signals can make the difference between a normal or pathological cell. To evaluate this relationship and test if it can be manipulated to favor normal cells, atomic force microscopy (AFM) and confocal microscopy was performed on fibroblast and breast cancer cell co-cultures with a collagen gel matrix to simulate the extracellular matrix. Pathological behavior was encouraged through the addition of transforming growth factor beta (TGF- β) . In a separate group, this behavior was discouraged through the doping of the collagen gel with multi-walled carbon nanotubes (MWNT). Significant differences were observed both in the elastic moduli of each cell type and the cancer cells' propensity to migrate through the gel as a model for metastasis. These results shed new light on how cancer progresses and promote the further investigation of nano-mechanical solutions to cancer.

Out-of-the-groove transport of lipids by TMEM16 and GPCR scramblases.

PubMed

Malvezzi, Mattia; Andra, Kiran K; Pandey, Kalpana; Lee, Byoung-Cheol; Falzone, Maria E; Brown, Ashley; Iqbal, Rabia; Menon, Anant K; Accardi, Alessio

2018-06-20

Phospholipid scramblases externalize phosphatidylserine to facilitate numerous physiological processes. Several members of the structurally unrelated TMEM16 and G protein-coupled receptor (GPCR) protein families mediate phospholipid scrambling. The structure of a TMEM16 scramblase shows a membrane-exposed hydrophilic cavity, suggesting that scrambling occurs via the ‟credit-card" mechanism where lipid headgroups permeate through the cavity while their tails remain associated with the membrane core. Here we show that afTMEM16 and opsin, representatives of the TMEM16 and GCPR scramblase families, transport phospholipids with polyethylene glycol headgroups whose globular dimensions are much larger than the width of the cavity. This suggests that transport of these large headgroups occurs outside rather than within the cavity. These large lipids are scrambled at rates comparable to those of normal phospholipids and their presence in the reconstituted vesicles promotes scrambling of normal phospholipids. This suggests that both large and small phospholipids can move outside the cavity. We propose that the conformational rearrangements underlying TMEM16- and GPCR-mediated credit-card scrambling locally deform the membrane to allow transbilayer lipid translocation outside the cavity and that both mechanisms underlie transport of normal phospholipids.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities

PubMed Central

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-01-01

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal–occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention. PMID:26419418

Timescales and Mechanisms of Sigh-Like Bursting and Spiking in Models of Rhythmic Respiratory Neurons.

PubMed

Wang, Yangyang; Rubin, Jonathan E

2017-12-01

Neural networks generate a variety of rhythmic activity patterns, often involving different timescales. One example arises in the respiratory network in the pre-Bötzinger complex of the mammalian brainstem, which can generate the eupneic rhythm associated with normal respiration as well as recurrent low-frequency, large-amplitude bursts associated with sighing. Two competing hypotheses have been proposed to explain sigh generation: the recruitment of a neuronal population distinct from the eupneic rhythm-generating subpopulation or the reconfiguration of activity within a single population. Here, we consider two recent computational models, one of which represents each of the hypotheses. We use methods of dynamical systems theory, such as fast-slow decomposition, averaging, and bifurcation analysis, to understand the multiple-timescale mechanisms underlying sigh generation in each model. In the course of our analysis, we discover that a third timescale is required to generate sighs in both models. Furthermore, we identify the similarities of the underlying mechanisms in the two models and the aspects in which they differ.

Nanoarchitectured materials composed of fullerene-like spheroids and disordered graphene layers with tunable mechanical properties.

PubMed

Zhao, Zhisheng; Wang, Erik F; Yan, Hongping; Kono, Yoshio; Wen, Bin; Bai, Ligang; Shi, Feng; Zhang, Junfeng; Kenney-Benson, Curtis; Park, Changyong; Wang, Yanbin; Shen, Guoyin

2015-02-04

Type-II glass-like carbon is a widely used material with a unique combination of properties including low density, high strength, extreme impermeability to gas and liquid and resistance to chemical corrosion. It can be considered as a carbon-based nanoarchitectured material, consisting of a disordered multilayer graphene matrix encasing numerous randomly distributed nanosized fullerene-like spheroids. Here we show that under both hydrostatic compression and triaxial deformation, this high-strength material is highly compressible and exhibits a superelastic ability to recover from large strains. Under hydrostatic compression, bulk, shear and Young's moduli decrease anomalously with pressure, reaching minima around 1-2 GPa, where Poisson's ratio approaches zero, and then revert to normal behaviour with positive pressure dependences. Controlling the concentration, size and shape of fullerene-like spheroids with tailored topological connectivity to graphene layers is expected to yield exceptional and tunable mechanical properties, similar to mechanical metamaterials, with potentially wide applications.

Nanoarchitectured materials composed of fullerene-like spheroids and disordered graphene layers with tunable mechanical properties

NASA Astrophysics Data System (ADS)

Zhao, Zhisheng; Wang, Erik F.; Yan, Hongping; Kono, Yoshio; Wen, Bin; Bai, Ligang; Shi, Feng; Zhang, Junfeng; Kenney-Benson, Curtis; Park, Changyong; Wang, Yanbin; Shen, Guoyin

2015-02-01

Type-II glass-like carbon is a widely used material with a unique combination of properties including low density, high strength, extreme impermeability to gas and liquid and resistance to chemical corrosion. It can be considered as a carbon-based nanoarchitectured material, consisting of a disordered multilayer graphene matrix encasing numerous randomly distributed nanosized fullerene-like spheroids. Here we show that under both hydrostatic compression and triaxial deformation, this high-strength material is highly compressible and exhibits a superelastic ability to recover from large strains. Under hydrostatic compression, bulk, shear and Young’s moduli decrease anomalously with pressure, reaching minima around 1-2 GPa, where Poisson’s ratio approaches zero, and then revert to normal behaviour with positive pressure dependences. Controlling the concentration, size and shape of fullerene-like spheroids with tailored topological connectivity to graphene layers is expected to yield exceptional and tunable mechanical properties, similar to mechanical metamaterials, with potentially wide applications.

Redox Regulation in Amyotrophic Lateral Sclerosis

PubMed Central

Parakh, Sonam; Spencer, Damian M.; Halloran, Mark A.; Soo, Kai Y.; Atkin, Julie D.

2013-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS. PMID:23533690

Strength of Gamma Rhythm Depends on Normalization

PubMed Central

Ray, Supratim; Ni, Amy M.; Maunsell, John H. R.

2013-01-01

Neuronal assemblies often exhibit stimulus-induced rhythmic activity in the gamma range (30–80 Hz), whose magnitude depends on the attentional load. This has led to the suggestion that gamma rhythms form dynamic communication channels across cortical areas processing the features of behaviorally relevant stimuli. Recently, attention has been linked to a normalization mechanism, in which the response of a neuron is suppressed (normalized) by the overall activity of a large pool of neighboring neurons. In this model, attention increases the excitatory drive received by the neuron, which in turn also increases the strength of normalization, thereby changing the balance of excitation and inhibition. Recent studies have shown that gamma power also depends on such excitatory–inhibitory interactions. Could modulation in gamma power during an attention task be a reflection of the changes in the underlying excitation–inhibition interactions? By manipulating the normalization strength independent of attentional load in macaque monkeys, we show that gamma power increases with increasing normalization, even when the attentional load is fixed. Further, manipulations of attention that increase normalization increase gamma power, even when they decrease the firing rate. Thus, gamma rhythms could be a reflection of changes in the relative strengths of excitation and normalization rather than playing a functional role in communication or control. PMID:23393427

[Examining the developing brain in Dutch child and adolescent psychiatry].

PubMed

Popma, A

2015-01-01

Research on the developing brain in children and adolescents is delivering new insights into the underlying mechanisms of childhood psychiatric disorders. To provide important information about the role that departments of Dutch child and adolescent psychiatry are playing in this international field that is expanding rapidly. This article provides an overview of recent, mainly Dutch neuro-imaging studies on the developing brain. A large number of studies from Dutch research centers have greatly increased our knowledge about normal and abnormal brain development in relation to the development of psychiatric disorders. Neuro-developmental research can help us to understand the underlying mechanisms of developing psychiatric disorders. This is likely to lead to new preventive measures and to more effective treatment in the future. Policy-makers should therefore commit a larger proportion of their neuroscience research budgets to neurodevelopmental studies in children.

Control rod drive

DOEpatents

Hawke, Basil C.

1986-01-01

A control rod drive uses gravitational forces to insert one or more control rods upwardly into a reactor core from beneath the reactor core under emergency conditions. The preferred control rod drive includes a vertically movable weight and a mechanism operatively associating the weight with the control rod so that downward movement of the weight is translated into upward movement of the control rod. The preferred control rod drive further includes an electric motor for driving the control rods under normal conditions, an electrically actuated clutch which automatically disengages the motor during a power failure and a decelerator for bringing the control rod to a controlled stop when it is inserted under emergency conditions into a reactor core.

Hypoxia and Coriolis Illusion in Pilots During Simulated Flight.

PubMed

Kowalczuk, Krzysztof P; Gazdzinski, Stefan P; Janewicz, Michał; Gąsik, Marek; Lewkowicz, Rafał; Wyleżoł, Mariusz

2016-02-01

Pilots' vision and flight performance may be impeded by spatial disorientation and high altitude hypoxia. The Coriolis illusion affects both orientation and vision. However, the combined effect of simultaneous Coriolis illusion and hypoxia on saccadic eye movement has not been evaluated. A simulated flight was performed by 14 experienced pilots under 3 conditions: once under normal oxygen partial pressure and twice under reduced oxygen partial pressures, reflecting conditions at 5000 m and 6000 m (16,404 and 19,685 ft), respectively. Eye movements were evaluated with a saccadometer. At normal oxygen pressure, Coriolis illusion resulted in 55% and 31% increases in mean saccade amplitude and duration, respectively, but a 32% increase in mean saccade frequency was only noted for saccades smaller than the angular distance between cockpit instruments, suggesting an increase in the number of correction saccades. At lower oxygen pressures a pronounced increase in the standard deviation of all measures was noticed; however, the pattern of changes remained unchanged. Simple measures of saccadic movement are not affected by short-term hypoxia, most likely due to compensatory mechanisms.

Autophagic activity in the mouse urinary bladder urothelium as a response to starvation.

PubMed

Erman, Andreja; Resnik, Nataša; Romih, Rok

2013-02-01

The urinary bladder urothelium is subjected to mechanical forces during cycles of distension and contraction, and its superficial cells are constantly flushed by toxic urine. Yet, the urothelium shows a very slow turnover of cells and superficial cells are extremely long lived. Autophagy has a well-known role in tissue homeostasis and serves as a protective mechanism against cellular stress. Therefore, the presence of autophagy as one of possible processes of survival in an unpleasant environment and during long lifetime of superficial cells was examined in mouse urothelium. We detected and evaluated autophagic activity of superficial urothelial cells under normal and stress conditions, caused by short-term starvation of newborn and 24-h-starved adult mice. Immunolabeling and Western blotting of essential effectors of autophagy, LC3 and Beclin 1, showed a weak signal in superficial urothelial cells. On the other hand, ultrastructural analysis, which proved to be the most reliable method in our study, revealed the presence of autophagic vacuoles, some of them containing specific urothelial structures, fusiform vesicles. Quantitative analysis showed increased autophagy in newborn and starved mice in comparison to a low basic level of autophagy in the urothelium of normal mice. Interestingly, some superficial cells of adults and neonates exhibit intense immunoreactions against LC3 and Beclin 1 and the typical ultrastructural characteristics of autophagy-dependent cell death. We conclude that autophagy, despite low basic activity under physiological conditions, plays an important role in urothelial homeostasis and stability under stress.

Improved Methods for Electroacupuncture and Electromyographic Recordings in Normal and Parkinsonian Rhesus Monkeys

PubMed Central

Zhao, Feng; Fan, Xiaotong; Grondin, Richard; Edwards, Ramsey; Forman, Eric; Moorehead, Jennifer; Gerhardt, Greg; Wang, Xiaomin; Zhang, Zhiming

2010-01-01

Although acupuncture has been widely and routinely used in healthcare in the USA, its use has been based more on empirical observation than on scientific knowledge. Therefore, there is a great need for better understanding the underlying mechanism(s) of action. A great body of evidence supports that nonhuman primates are a candidate for studying human diseases. However, the use of nonhuman primates in neurophysiological, neuroimaging and neurochemical studies is extremely challenging, especially under fully conscious, alert conditions. In the present study, we developed a protocol for safely performing acupuncture, electro-acupuncture (EA) and electromyography (EMG) in both normal nonhuman primates and animals with parkinsonian-like symptoms. Four normal and four hemiparkinsonian middle-aged rhesus monkeys were extensively trained, behaviorally monitored, and received both EA and EMG for several months. The results demonstrated that (1) all rhesus monkeys used in the study could be trained for procedures including EA and EMG; (2) all animals tolerated the procedures involving needle/electrode insertion; (3) EA procedures used in the study did not adversely alter the animal’s locomotor activities; rather, MPTP-treated animals showed a significant improvement in movement speed; and (4) EMG detected significant differences in muscle activity between the arms with and without MPTP-induced rigidity. Our results support that rhesus monkeys can be used as an experimental animal model to study EA and that EMG has the potential to be used to objectively assess the effects of antiparkinsonian therapies. The results also indicate that animals, especially those with parkinsonian-like symptoms, could benefit from long-term EA stimulations. PMID:20654649

Vulnerability of an epileptic case to psychosis: sodium valproate with lamotrigine, forced normalization, postictal psychosis or all?

PubMed

Turan, A B; Seferoglu, M; Taskapilioglu, O; Bora, I

2012-10-01

Patients with epilepsy can be considered to be at high risk for developing psychotic disorders. Furthermore, there is association between seizure freedom or the disappearance of the interictal epileptiform events from the EEG record and the occurrence of psychotic symptoms. Also, several newer antiepileptic drugs have been reported to induce psychotic symptoms. We present a patient with epilepsy who developed psychotic symptoms under the treatment of valproic acid (VPA) and lamotrigine (LTG) combination. The mechanism underlying the association between LTG, seizure control and development of psychosis are discussed in the light of the literature.

[Melatonin production in hypertonic patients during magnetic storms].

PubMed

Rapoport, S I; Shatalova, A M; Oraevskiĭ, V N; Malinovskaia, N K; Vetterberg, L

2001-01-01

To study mechanisms of action of natural magnetic field of the Earth on arterial pressure (AP) and melatonin production in patients with essential hypertension (EH) stage II. Clinical, laboratory and device investigations covered 52 men with EH stage II (mean age 42 +/- 0.92 years) and 11 healthy men (mean age 23 +/- 1.46 years). Mean 24-hour, mean daytime, mean night systolic and diastolic pressures, 24-h index, time hypertensive index, standard deviation were registered. Melatonin was measured in the urine by radioimmunoassay. Geomagnetic situation was assessed by K-index (quiet--under 15, disturbed--15-25, magnetic storm--above 25). In hypertensive patients AP grew with growth of geomagnetic activity. In normal subjects AP remained normal. The 24-h rhythm of AP variability in hypertensives was normal. Magnetic storm affected melatonin production in EH patients noticeably: night and daytime production of melatonin was low. In normal subjects night melatonin production was high. AH stage II patients respond to magnetic storm with maladaptation, i.e. a rise in AP and low melatonin production.

Basal-like Breast Cancers: From Pathology to Biology and Back Again.

PubMed

Gusterson, Barry; Eaves, Connie J

2018-06-05

Human breast cancers referred to as "basal-like" are of interest because they lack effective therapies and their biology is poorly understood. The term basal-like derives from studies demonstrating tumor gene expression profiles that include some transcripts characteristic of the basal cells of the normal adult human mammary gland and others associated with a subset of normal luminal cells. Elucidating the mechanisms responsible for the profiles of basal-like tumors is an active area of investigation. More refined molecular analysis of patients' samples and genetic strategies to produce breast cancers de novo from defined populations of normal mouse mammary cells have served as complementary approaches to identify relevant pathway alterations. However, both also have limitations. Here, we review some of the underlying reasons, including the unifying concept that some normal luminal cells have both luminal and basal features, as well as some emerging new avenues of investigation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Experimental Program to Stimulate Competitive Research (EPSCoR)

NASA Technical Reports Server (NTRS)

Dingerson, Michael R.

1997-01-01

Report includes: (1) CLUSTER: "Studies in Macromolecular Behavior in Microgravity Environment": The Role of Protein Oligomers in Protein Crystallization; Phase Separation Phenomena in Microgravity; Traveling Front Polymerizations; Investigating Mechanisms Affecting Phase Transition Response and Changes in Thermal Transport Properties in ER-Fluids under Normal and Microgravity Conditions. (2) CLUSTER: "Computational/Parallel Processing Studies": Flows in Local Chemical Equilibrium; A Computational Method for Solving Very Large Problems; Modeling of Cavitating Flows.

Study of metabolism and energetics in hypogravity: Degenerative effects of prolonged hypogravity

NASA Technical Reports Server (NTRS)

Siegel, S. M.

1976-01-01

The role of gravity in the formation of rigid, lignified plant cell walls hence to the development of the erect land plant body is examined. An experiment was proposed with a general hypothesis that a chosen plant, a dwarf marigold, would display degenerative changes in mechanical supportive systems under hypogravity because normal lignin-cellulose wall structure fails to develop. Observational and experimental results are given.

Experimental Studies on the Mechanical Behaviour of Rock Joints with Various Openings

NASA Astrophysics Data System (ADS)

Li, Y.; Oh, J.; Mitra, R.; Hebblewhite, B.

2016-03-01

The mechanical behaviour of rough joints is markedly affected by the degree of joint opening. A systematic experimental study was conducted to investigate the effect of the initial opening on both normal and shear deformations of rock joints. Two types of joints with triangular asperities were produced in the laboratory and subjected to compression tests and direct shear tests with different initial opening values. The results showed that opened rock joints allow much greater normal closure and result in much lower normal stiffness. A semi-logarithmic law incorporating the degree of interlocking is proposed to describe the normal deformation of opened rock joints. The proposed equation agrees well with the experimental results. Additionally, the results of direct shear tests demonstrated that shear strength and dilation are reduced because of reduced involvement of and increased damage to asperities in the process of shearing. The results indicate that constitutive models of rock joints that consider the true asperity contact area can be used to predict shear resistance along opened rock joints. Because rock masses are loosened and rock joints become open after excavation, the model suggested in this study can be incorporated into numerical procedures such as finite-element or discrete-element methods. Use of the model could then increase the accuracy and reliability of stability predictions for rock masses under excavation.

Repressed SIRT1/PGC-1α pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration.

PubMed

Golestaneh, Nady; Chu, Yi; Cheng, Shuk Kei; Cao, Hong; Poliakov, Eugenia; Berinstein, Daniel M

2016-12-20

Study of age related macular degeneration (AMD) has been hampered by lack of human models that represent the complexity of the disease. Here we have developed a human in vitro disease model of AMD to investigate the underlying AMD disease mechanisms. Generation of iPSCs from retinal pigment epithelium (RPE) of AMD donors, age-matched normal donors, skin fibroblasts of a dry AMD patient, and differentiation of iPSCs into RPE (AMD RPE-iPSC-RPE, normal RPE-iPSC-RPE and AMD Skin-iPSC-RPE, respectively). Immunostaining, cell viability assay and reactive oxygen species (ROS) production under oxidative stress conditions, electron microscopy (EM) imaging, ATP production and glycogen concentration assays, quantitative real time PCR, western blot, karyotyping. The AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE present functional impairment and exhibit distinct disease phenotypes compared to RPE-iPSC-RPE generated from normal donors (Normal RPE-iPSC-RPE). The AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE show increased susceptibility to oxidative stress and produced higher levels of reactive oxygen species (ROS) under stress in accordance with recent reports. The susceptibility to oxidative stress-induced cell death in AMD RPE-iPSC-RPE and Skin-iPSC-RPE was consistent with inability of the AMD RPE-iPSC-RPE and Skin-iPSC-RPE to increase SOD2 expression under oxidative stress. Phenotypic analysis revealed disintegrated mitochondria, accumulation of autophagosomes and lipid droplets in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE. Mitochondrial activity was significantly lower in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE compared to normal cells and glycogen concentration was significantly increased in the diseased cells. Furthermore, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial biogenesis and function was repressed, and lower expression levels of NAD-dependent deacetylase sirtuin1 (SIRT1) were found in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE as compared to normal RPE-iPSC-RPE. Our studies suggest SIRT1/PGC-1α as underlying pathways contributing to AMD pathophysiology, and open new avenues for development of targeted drugs for treatment of this devastating neurodegenerative disease of the visual system.

Vapor-Gas Bubble Evolution and Growth in Extremely Viscous Fluids Under Vacuum

NASA Technical Reports Server (NTRS)

Kizito, John; Balasubramaniam, R.; Nahra, Henry; Agui, Juan; Truong, Duc

2008-01-01

Formation of vapor and gas bubbles and voids is normal and expected in flow processes involving extremely viscous fluids in normal gravity. Practical examples of extremely viscous fluids are epoxy-like filler materials before the epoxy fluids cure to their permanent form to create a mechanical bond between two substrates. When these fluids flow with a free liquid interface exposed to vacuum, rapid bubble expansion process may ensue. Bubble expansion might compromise the mechanical bond strength. The potential sources for the origin of the gases might be incomplete out-gassing process prior to filler application; regasification due to seal leakage in the filler applicator; and/or volatiles evolved from cure reaction products formed in the hardening process. We embarked on a study that involved conducting laboratory experiments with imaging diagnostics in order to deduce the seriousness of bubbling caused by entrained air and volatile fluids under space vacuum and low gravity environment. We used clear fluids with the similar physical properties as the epoxy-like filler material to mimic the dynamics of bubbles. Another aspect of the present study was to determine the likelihood of bubbling resulting from dissolved gases nucleating from solution. These experimental studies of the bubble expansion are compared with predictions using a modified Rayleigh- Plesset equation, which models the bubble expansion.

Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night.

PubMed

Mathew, Robin; White, Eileen

2011-02-01

Autophagy is the mechanism by which cells consume parts of themselves to survive starvation and stress. This self-cannibalization limits cell death and tissue inflammation, recycles energy and biosynthetic substrates and removes damaged proteins and organelles, accumulation of which is toxic. In normal tissues, autophagy-mediated damage mitigation may suppress tumorigenesis, while in advanced tumors macromolecular recycling may support survival by buffering metabolic demand under stress. As a result, autophagy-activation in normal cells may suppress tumorigenesis, while autophagy inhibition may be beneficial for the therapy of established tumors. The mechanisms by which autophagy supports cancer cell metabolism are slowly emerging. As cancer is being increasingly recognized as a metabolic disease, how autophagy-mediated catabolism impacts cellular and mammalian metabolism and tumor growth is of great interest. Most cancer therapeutics induce autophagy, either directly by modulating signaling pathways that control autophagy in the case of many targeted therapies, or indirectly in the case of cytotoxic therapy. However, the functional consequence of autophagy induction in the context of cancer therapy is not yet clear. A better understanding of how autophagy modulates cell metabolism under various cellular stresses and the consequences of this on tumorigenesis will help develop better therapeutic strategies against cancer prevention and treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis.

PubMed

Gu, Jinping; Hu, Xiaomin; Shao, Wei; Ji, Tianhai; Yang, Wensheng; Zhuo, Huiqin; Jin, Zeyu; Huang, Huiying; Chen, Jiacheng; Huang, Caihua; Lin, Donghai

2016-09-13

Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression.

Conception on the cell mechanisms of bone tissue loss under spase flight conditions

NASA Astrophysics Data System (ADS)

Rodionova, Natalia; Oganov, Victor; Kabitskaya, Olga

Basing on the analysis of available literature and the results of our own electron microscopic and radioautographic researches the data are presented about the morpho-functional peculiarities and succession of cellular interactions in adaptive remodeling of bone structures under normal conditions and after exposure of animals (rats, monkeys, mice) to microgravity (SLS-2, Bion-11, BionM-1). The probable cellular mechanisms of the development of osteopenia and osteoporosis are considered. Our conception on remodeling proposes the following sequence in the development of cellular interactions after decrease of the mechanical loading: a primary response of osteocytes (mechanosensory cells) to the mechanical stimulus; osteocytic remodeling (osteolysis); transmission of the mechanical signals through a system of canals and processes to functionally active osteoblasts and surface osteocytes as well as to the bone-marrow stromal cells and to those lying on bone surfaces. As a response to the mechanical stimulus (microgravity) the system of stromal cell-preosteoblast-osteoblast shows a delay in proliferation, differentiation and specific functioning of the osteogenetic cells, some of the osteoblasts undergo apoptosis. Then the osteoclastic reaction occurs (attraction of monocytes and formation of osteoclasts and bone matrix resorption in the loci of apoptosis of osteoblasts and osteocytes). The macrophagal reaction is followed by osteoblastogenesis, which appears to be a rehabilitating process. However, during prolonged absence of mechanical stimuli (microgravity, long-time immobilization) the adaptive activization of osteoblastogenesis doesn’t occur (as it is the case during the physiological remodeling of bone tissue) or it occurs to a smaller degree. The loading deficit leads to an adaptive differentiation of stromal cells to fibroblastic cells and adipocytes in these remodeling loci. These cell reactions are considered as adaptive-compensatory, but they don’t result in rehabilitation of the resorbed bone tissue. This sequence of events is considered as a mechanism of bone tissue loss which underlies the development of osteopenia and osteoporosis under the mechanical loading deficit.

Adaptation of the white shrimp Litopenaeus vannamei to gradual changes to a low-pH environment.

PubMed

Han, Si-Yin; Wang, Bao-Jie; Liu, Mei; Wang, Meng-Qiang; Jiang, Ke-Yong; Liu, Xin-Wei; Wang, Lei

2018-03-01

pH variation could cause a stress response in euryhaline penaeids, we evaluated the mortality, growth performance, osmoregulation gene expression, digestive enzyme activity, histology, and resistance against Vibrio parahemolyticus of white shrimp Litopenaeus vannamei reared under conditions of gradual changes to a low-pH environment (gradual-low pH, 6.65-8.20) or a high-pH environment (gradual-high pH, 8.20-9.81) versus a normal pH environment (8.14-8.31) during a 28-d experiment. Consequently, under gradual-high pH, the cumulative mortality rate (CMR) rose with time until 39.9% on days 28; the weight gain percentage (WGP) and length gain percentage (LGP) decreased continuously. However, under gradual-low pH, the CMR of shrimp stabilized at 6.67% during 7-28 d; the WGP and LGP decreased first and then returned to normal. These results indicated that L. vannamei displayed a moderate tolerance to gradual-low pH, compared with gradual-high pH. Under gradual-low pH, the Na + /K + -ATPase, cytoplasmic carbonic anydrase (CAc), and glycosyl-phosphatidylinositol-linked carbonic anhydrase (CAg) transcripts of shrimp increased continuously or then back to normal; the amylase, lipase, and trypsin activities decreased first and then returned to normal or increased; the hepatopancreases and midguts showed histopathological lesions first and then got remission. Thus, the major adaptation mechanism of shrimp to gradual-low pH might be its high osmoregulation ability, which made shrimp achieve a new, balanced steady-state, then promoted longer intestinal villi and recuperative hepatopancreases of shrimp with enhanced digestive enzyme activities to increase nutrient absorption after long-term exposure. Meanwhile, the enhanced resistance against V. parahemolyticus under gradual-low pH would probably inhibit disease outbreak in the shrimp farming. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence for initiation of frictional partial slip as the mechanism behind nonlinear stress-strain hysteresis in rock fractures under seismic-frequency torsion

NASA Astrophysics Data System (ADS)

Saltiel, S.; Bonner, B. P.; Delbridge, B. G.; Ajo Franklin, J. B.

2016-12-01

We have adapted a low-frequency (0.1 - 64 Hz) torsional apparatus to explore the pure shear behavior of rock fractures under low normal stresses, simulating low effective stress environments - shallow depths and/or under high pore pressures. The instrument is unique in this ability to measure under very low confinement as well as to probe partial slip on the outside of asperities, before full slip nucleation occurs. Using a sinusoidal oscillation around this condition, we can probe the stress-strain constitutive relation at a range of strain amplitudes and the rate-dependence of the initiation of asperity slip. We find different, nonlinear, stress-strain constitutive relations for dolomite, rhyolite, and granite fractured samples, but all show softening at high strain amplitudes (above microstrain or micron-scale displacement). All measured samples exhibit qualitatively similar time-series hysteresis loops and frequency-dependence. The low frequency stress-strain loops stiffen at the high strain static end of the sinusoidal oscillation. This shape is determined by harmonic generation in the strain, while the stress signal has low power in harmonics, confirming that the driver and electronics are not the source of this nonlinearity. We also observe that this stiffening cusp does not occur as frequency increases above 8 Hz (opposite to normal dispersion seen at higher normal stresses). We monitor the fracture surface wear with repeated cycles to show the extent of slip on mapped asperities. These observations suggest that a rate dependent, healing, process causes the nonlinear responce of fracture faces under low normal stress to periodic shear. We propose that static friction at the low strain-rate part of the cycle, when given enough time at low oscillation frequencies, causes this stiffening cusp shape in the hysteretic stress-strain curve. An analytic model with idealized contact area is used to constrain the rate-state friction constitutive model parameters needed to provide this dynamic behavior.

The cell cycle.

PubMed

Singh, N; Lim, R B; Sawyer, M A

2000-07-01

The cell cycle and the cell cycle control system are the engines that drive life. They allow for the processes of cell renewal and the growth of organisms, under controlled conditions. The control system is essential for the monitoring of normal cell growth and replication of genetic material and to ensure that normal, functional daughter cells are produced at completion of each cell cycle. Although certain clinical applications exist which take advantage of the events of the cell cycle, our understanding of its mechanisms and how to manipulate them is infantile. The next decades will continue to see the effort of many researchers focused upon unlocking the mysteries of the cell cycle and the cell cycle control system.

An investigation during the system test phase of the GOES spacecraft

NASA Technical Reports Server (NTRS)

Mallette, L. A.

1983-01-01

Spurious RF oscillations were noted during the system test phase of the Geostationary Operational Environmental Satellite (GOES). A space qualified data collection platform report (DCPR) transmitter was subsequently found to have a cracked load resistor in its output isolator. The failure mechanism was caused by heat from the output power of a 20 watt transmitter being reflected into the DCPR transmitter through a sneak path. The reflection from a high VSWR at the rotary joint was not part of the normal operation but was due to unusual circumstances. The reliability of the load resistor under normal operation (low VSWR) over the life of the satellite was determined to be high.

Experimental evidence of non-Amontons behaviour at a multi-contact interface

NASA Astrophysics Data System (ADS)

Scheibert, J.; Prevost, A.; Frelat, J.; Rey, P.; Debrégeas, G.

2008-08-01

We report on normal stress field measurements at the multicontact interface between a rough elastomeric film and a smooth glass sphere under normal load, using an original MEMS-based stress-sensing device. These measurements are compared to Finite-Elements Method (FEM) calculations with boundary conditions obeying locally Amontons' rigid-plastic-like friction law with a uniform friction coefficient. In dry contact conditions, significant deviations are observed which decrease with increasing load. In lubricated conditions, the measured profile recovers almost perfectly the predicted profile. These results are interpreted as a consequence of the finite compliance of the multicontact interface, a mechanism which is not taken into account in Amontons' law.

Control mechanisms of circadian rhythms in body composition: Implications for manned spaceflight

NASA Technical Reports Server (NTRS)

Moore-Ede, M. C.

1976-01-01

The mechanisms underlying the internal synchronization of the circadian variations in electrolyte content in body compartments were investigated, and the significance of these oscillations for manned spaceflight were examined. The experiments were performed with a chair-acclimatized squirrel monkey system, in which the animal sits in a chair, restrained only around the waist. The following information was given: (1) experimental methodology description, (2) summary of results obtained during the first contract year, and (3) discussion of the research performed during the second contract year. This included the following topics: physiological mechanisms promoting normal circadian internal synchronization, factors precipitating internal desynchronization, pathophysiological consequences of internal desynchronization of particular relevance to spaceflight, and validation of a chair-acclimatized system.

The concept of the mechanically active guideway as a novel approach to maglev

NASA Technical Reports Server (NTRS)

Horwath, T. G.

1992-01-01

A maglev system that is suitable for operation in the United States will have to meet unique requirements which determine the major systems characteristics. Maglev configurations presently developed in Germany and Japan are based on conventional maglev concepts and as such do not meet all of the requirements. A novel maglev guideway concept is introduced as a solution. This concept, the mechanically active guideway, is articulated in three degrees of freedom and assumes system functions which normally reside in the maglev vehicle. The mechanically active guideway contains spatially distributed actuators which are energized under computer control at the time of vehicle passage to achieve bank angle adjustment and ride quality control. A typical realization of the concept is outlined.

Stability and tribological performances of fluid phospholipid bilayers: effect of buffer and ions.

PubMed

Dekkiche, F; Corneci, M C; Trunfio-Sfarghiu, A-M; Munteanu, B; Berthier, Y; Kaabar, W; Rieu, J-P

2010-10-15

We have investigated the mechanical and tribological properties of supported Dioleoyl phosphatidylcholine (DOPC) bilayers in different solutions: ultrapure water (pH 5.5), saline solution (150 mM NaCl, pH 5.8), Tris buffer (pH 7.2) and Tris saline buffer (150 mM NaCl, pH 7.2). Friction forces are measured using a homemade biotribometer. Lipid bilayer degradation is controlled in situ during friction tests using fluorescence microscopy. Mechanical resistance to indentation is measured by force spectroscopy with an atomic force microscope. This study confirms that mechanical stability under shear or normal load is essential to obtain low and constant friction coefficients. In ultrapure water, bilayers are not resistant and have poor lubricant properties. On the other hand, in Tris saline buffer, they fully resist to indentation and exhibit low (micro=0.035) and stable friction coefficient with no visible wear during the 50 min of the friction test. The unbuffered saline solution improves the mechanical resistance to indentation but not the lubrication. These results suggest that the adsorption of ions to the zwiterrionic bilayers has different effects on the mechanical and tribological properties of bilayers: higher resistance to normal indentation due to an increase in bilayer cohesion, higher lubrication due to an increase in bilayer-bilayer repulsion. Copyright (c) 2010 Elsevier B.V. All rights reserved.

A Protective Mechanism of Visible Red Light in Normal Human Dermal Fibroblasts: Enhancement of GADD45A-Mediated DNA Repair Activity.

PubMed

Kim, Yeo Jin; Kim, Hyoung-June; Kim, Hye Lim; Kim, Hyo Jeong; Kim, Hyun Soo; Lee, Tae Ryong; Shin, Dong Wook; Seo, Young Rok

2017-02-01

The phototherapeutic effects of visible red light on skin have been extensively investigated, but the underlying biological mechanisms remain poorly understood. We aimed to elucidate the protective mechanism of visible red light in terms of DNA repair of UV-induced oxidative damage in normal human dermal fibroblasts. The protective effect of visible red light on UV-induced DNA damage was identified by several assays in both two-dimensional and three-dimensional cell culture systems. With regard to the protective mechanism of visible red light, our data showed alterations in base excision repair mediated by growth arrest and DNA damage inducible, alpha (GADD45A). We also observed an enhancement of the physical activity of GADD45A and apurinic/apyrimidinic endonuclease 1 (APE1) by visible red light. Moreover, UV-induced DNA damages were diminished by visible red light in an APE1-dependent manner. On the basis of the decrease in GADD45A-APE1 interaction in the activating transcription factor-2 (ATF2)-knockdown system, we suggest a role for ATF2 modulation in GADD45A-mediated DNA repair upon visible red light exposure. Thus, the enhancement of GADD45A-mediated base excision repair modulated by ATF2 might be a potential protective mechanism of visible red light. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Acoustic emission from trabecular bone during mechanical testing: the effect of osteoporosis and osteoarthritis.

PubMed

Leichter, I; Bivas, A; Margulies, J Y; Roman, I; Simkin, A

1990-01-01

This study examines the relation between the nature of acoustic emission signals emitted from cancellous bone under compression and the mechanical properties of the tissue. The examined bone specimens were taken from 12 normal, 31 osteoporotic and six osteoarthritic femoral heads. The mechanical behaviour of the osteoporotic bone specimens was found to be significantly different from that of the normal specimens both in the pre-yield and post-yield ranges. In the osteoarthritic bones only the elastic behaviour was significantly different. The rates of acoustic events before yield and beyond it were found to be significantly higher both in the osteoporotic and osteoarthritic bone specimens. The average peak amplitude of the signals was also significantly higher in the diseased bones. Stepwise regression analysis showed that a combination of the acoustic emission parameters could significantly predict some mechanical properties of the bone. The energy absorbed during compression and the ultimate compressive stress of the specimens could be estimated from the rate of pre-yield acoustic events, the average amplitude of the signals and the rate of post-yield events. However, the explanation power of the acoustic emission parameters was only moderate. The nature of acoustic emission signals was thus demonstrated to be a potential tool for assessing bone quality.

Mechanobiology in Lung Epithelial Cells: Measurements, Perturbations, and Responses

PubMed Central

Waters, Christopher M.; Roan, Esra; Navajas, Daniel

2015-01-01

Epithelial cells of the lung are located at the interface between the environment and the organism and serve many important functions including barrier protection, fluid balance, clearance of particulate, initiation of immune responses, mucus and surfactant production, and repair following injury. Because of the complex structure of the lung and its cyclic deformation during the respiratory cycle, epithelial cells are exposed to continuously varying levels of mechanical stresses. While normal lung function is maintained under these conditions, changes in mechanical stresses can have profound effects on the function of epithelial cells and therefore the function of the organ. In this review, we will describe the types of stresses and strains in the lungs, how these are transmitted, and how these may vary in human disease or animal models. Many approaches have been developed to better understand how cells sense and respond to mechanical stresses, and we will discuss these approaches and how they have been used to study lung epithelial cells in culture. Understanding how cells sense and respond to changes in mechanical stresses will contribute to our understanding of the role of lung epithelial cells during normal function and development and how their function may change in diseases such as acute lung injury, asthma, emphysema, and fibrosis. PMID:23728969

Assessment of duration of the drive operation in the mode of kinetic energy recovery under power supply voltage sags in electrical grids of mechanical engineering enterprises

NASA Astrophysics Data System (ADS)

Shonin, O. B.; Novozhilov, N. G.

2017-02-01

Voltage sags in electric grids of mechanical engineering enterprises may lead to disconnection of important power consumers with variable frequency drives from the power grid and further interruption of the production process. The paper considers a sensorless V/f control system of еру induction motor drive under normal conditions and under voltage sags on the basis of a computer model of the drive and derivation of a formula for assessment of possible duration of the drive operation in the mode of controlled recovery of kinetic energy accumulated in rotating mass of the drive. Results of simulations have been used to validate results of calculations of the rotor velocity deceleration made in a closed form obtained from the equation reflecting the balance of torques. It is shown that results of calculations practically coincide with results of simulations in the range up to 5% of the velocity initial value. The proposed formula may be useful for estimation of the duration of the drive operation in the mode of recovery of kinetic energy depending on parameters of the motor and driven mechanisms.

Cellular Mechanosensing: Getting to the nucleus of it all

PubMed Central

Fedorchak, Gregory R.; Kaminski, Ashley; Lammerding, Jan

2014-01-01

Cells respond to mechanical forces by activating specific genes and signaling pathways that allow the cells to adapt to their physical environment. Examples include muscle growth in response to exercise, bone remodeling based on their mechanical load, or endothelial cells aligning under fluid shear stress. While the involved downstream signaling pathways and mechanoresponsive genes are generally well characterized, many of the molecular mechanisms of the initiating ‘mechanosensing’ remain still elusive. In this review, we discuss recent findings and accumulating evidence suggesting that the cell nucleus plays a crucial role in cellular mechanotransduction, including processing incoming mechanoresponsive signals and even directly responding to mechanical forces. Consequently, mutations in the involved proteins or changes in nuclear envelope composition can directly impact mechanotransduction signaling and contribute to the development and progression of a variety of human diseases, including muscular dystrophy, cancer, and the focus of this review, dilated cardiomyopathy. Improved insights into the molecular mechanisms underlying nuclear mechanotransduction, brought in part by the emergence of new technologies to study intracellular mechanics at high spatial and temporal resolution, will not only result in a better understanding of cellular mechanosensing in normal cells but may also lead to the development of novel therapies in the many diseases linked to defects in nuclear envelope proteins. PMID:25008017

Thermo-mechanical pressurization of experimental faults in cohesive rocks during seismic slip

NASA Astrophysics Data System (ADS)

Violay, M.; Di Toro, G.; Nielsen, S.; Spagnuolo, E.; Burg, J. P.

2015-11-01

Earthquakes occur because fault friction weakens with increasing slip and slip rates. Since the slipping zones of faults are often fluid-saturated, thermo-mechanical pressurization of pore fluids has been invoked as a mechanism responsible for frictional dynamic weakening, but experimental evidence is lacking. We performed friction experiments (normal stress 25 MPa, maximal slip-rate ∼3 ms-1) on cohesive basalt and marble under (1) room-humidity and (2) immersed in liquid water (drained and undrained) conditions. In both rock types and independently of the presence of fluids, up to 80% of frictional weakening was measured in the first 5 cm of slip. Modest pressurization-related weakening appears only at later stages of slip. Thermo-mechanical pressurization weakening of cohesive rocks can be negligible during earthquakes due to the triggering of more efficient fault lubrication mechanisms (flash heating, frictional melting, etc.).

Sensitive periods in epigenetics: bringing us closer to complex behavioral phenotypes.

PubMed

Nagy, Corina; Turecki, Gustavo

2012-08-01

Genetic studies have attempted to elucidate causal mechanisms for the development of complex disease, but genome-wide associations have been largely unsuccessful in establishing these links. As an alternative link between genes and disease, recent efforts have focused on mechanisms that alter the function of genes without altering the underlying DNA sequence. Known as epigenetic mechanisms, these include DNA methylation, chromatin conformational changes through histone modifications, ncRNAs and, most recently, 5-hydroxymethylcytosine. Although DNA methylation is involved in normal development, aging and gene regulation, altered methylation patterns have been associated with disease. It is generally believed that early life constitutes a period during which there is increased sensitivity to the regulatory effects of epigenetic mechanisms. The purpose of this review is to outline the contribution of epigenetic mechanisms to genomic function, particularly in the development of complex behavioral phenotypes, focusing on the sensitive periods.

Sensitive Periods in Epigenetics: bringing us closer to complex behavioral phenotypes

PubMed Central

Nagy, Corina; Turecki, Gustavo

2017-01-01

Genetic studies have attempted to elucidate causal mechanisms for the development of complex disease but genome-wide associations have been largely unsuccessful in establishing these links. As an alternative link between genes and disease, recent efforts have focused on mechanisms that alter the function of genes without altering the underlying DNA sequence. Known as epigenetic mechanisms, these include: DNA methylation, chromatin conformational changes through histone modifications, non-coding RNAs, and most recently, 5-hydroxymethylcytosine. Though DNA methylation is involved in normal development, aging and gene regulation, altered methylation patterns have been associated with disease. It is generally believed that early life constitutes a period during which there is increased sensitivity to the regulatory effects of epigenetic mechanisms. The purpose of this review is to outline the contribution of epigenetic mechanisms to genomic function, particularly in the development of complex behavioral phenotypes, focusing on the sensitive periods. PMID:22920183

HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise.

PubMed

Park, Bong-Sup; Henning, Paul C; Grant, Samuel C; Lee, Won Jun; Lee, Sang-Rok; Arjmandi, Bahram H; Kim, Jeong-Su

2013-12-01

To investigate the efficacy and underlying mechanisms of β-hydroxy-β-methylbutyrate (HMB) on body composition, muscle mass and physical performance under catabolic versus normal training conditions. Mice were divided into four groups (n=10/group): (1) ALT=ad libitum+trained (1 h/d for 3 d/wk); (2) ALTH=ALT+HMB (0.5 g/kg BW/d); (3) C=calorie restricted (-30%)+trained (6 h/d, 6 d/wk); and (4) CH=C+HMB. Repeated in vivo assessments included body composition, grip strength and sensorimotor coordination before and after the experimental protocol, while in vitro analyses included muscle wet weights, expression of selected genes and proteins regulating muscle mass, and myofiber cross-sectional area. ANOVAs were used with significance set at p<0.05. ALTH had greater lean mass than ALT and sensorimotor function increased in ALTH, but decreased in ALT under normal training conditions. Grip strength decreased only in C, but was maintained in CH. Gastrocnemius mass and myofiber CSA were greater in CH than C following catabolic conditions. Gastrocnemius atrogin-1 mRNA expression was elevated in C but not in CH compared to all other groups whereas atrogin-1 protein levels showed no significant changes. HMB improves body composition and sensorimotor function during normal training and attenuates muscle mass and strength loss during catabolic conditions. © 2013.

Marangoni Effects in the Boiling of Binary Fluid Mixtures

NASA Technical Reports Server (NTRS)

Ahmed, Sayeed; Carey, Van P.; Motil, Brian

1996-01-01

Results of very recent experimental studies indicate that during nucleate boiling in some binary mixture, Marangoni effects augment the gravity driven flow of liquid towards the heated surface. With gravity present, it is impossible to separate the two effects. The reduced gravity environment gives an unique opportunity to explore th role of Marangoni effects on the boiling mechanisms free of gravitational body forces that obscure the role of such effects. However, recent experimental results suggest that under reduced gravity conditions, Marangoni effects is the dominant mechanism of vapor-liquid exchange at the surface for some binary mixture. To further explore such effects, experiments have been conducted with water/2-propanol mixtures at three different concentrations under normal gravity with different orientations of the heater surface and under reduce gravity aboard the DC-9 aircraft at NASA Lewis Research Center. The system pressure was sub atmospheric (approx. 8 kP at 1g(n)) and the bulk liquid temperature varied from low subcooling to near saturation. The molar concentrations of 2-propanol tested were 0.015, 0.025, and 0.1. Boiling curves were obtained both for high gravity (approx. 2g(n)) and reduce gravity (approx. 0.01g(n)). For each concentration of 2-propanol, the critical heat flux has been determined in the flight experiments only for reduced gravity conditions. Comparison of boiling curves and CHF obtained under l-g(n) an reduced gravity indicates that boiling mechanism in this mixtures is nearly independent of gravity. The results also indicate that the Marangoni mechanism is strong enough in these mixtures to sustain the boiling under reduced gravity conditions.

Electromechanical Coupling Factor of Breast Tissue as a Biomarker for Breast Cancer.

PubMed

Park, Kihan; Chen, Wenjin; Chekmareva, Marina A; Foran, David J; Desai, Jaydev P

2018-01-01

This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor. The design of a portable diagnostic tool and a microelectromechanical systems (MEMS)-based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced. To verify that electromechanical coupling factor can be used as a biomarker for breast cancer, the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma (IDC) samples in the 25-45 temperature range. While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature. From the two-sample -test, the electromechanical coupling factor under compression shows statistically significant differences ( 0.0039) between the two groups. The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue, using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple parameters of breast tissue allowing for practical application.

Trabecular bone adaptation to low-magnitude high-frequency loading in microgravity.

PubMed

Torcasio, Antonia; Jähn, Katharina; Van Guyse, Maarten; Spaepen, Pieter; Tami, Andrea E; Vander Sloten, Jos; Stoddart, Martin J; van Lenthe, G Harry

2014-01-01

Exposure to microgravity causes loss of lower body bone mass in some astronauts. Low-magnitude high-frequency loading can stimulate bone formation on earth. Here we hypothesized that low-magnitude high-frequency loading will also stimulate bone formation under microgravity conditions. Two groups of six bovine cancellous bone explants were cultured at microgravity on a Russian Foton-M3 spacecraft and were either loaded dynamically using a sinusoidal curve or experienced only a static load. Comparable reference groups were investigated at normal gravity. Bone structure was assessed by histology, and mechanical competence was quantified using μCT and FE modelling; bone remodelling was assessed by fluorescent labelling and secreted bone turnover markers. Statistical analyses on morphometric parameters and apparent stiffness did not reveal significant differences between the treatment groups. The release of bone formation marker from the groups cultured at normal gravity increased significantly from the first to the second week of the experiment by 90.4% and 82.5% in response to static and dynamic loading, respectively. Bone resorption markers decreased significantly for the groups cultured at microgravity by 7.5% and 8.0% in response to static and dynamic loading, respectively. We found low strain magnitudes to drive bone turnover when applied at high frequency, and this to be valid at normal as well as at microgravity. In conclusion, we found the effect of mechanical loading on trabecular bone to be regulated mainly by an increase of bone formation at normal gravity and by a decrease in bone resorption at microgravity. Additional studies with extended experimental time and increased samples number appear necessary for a further understanding of the anabolic potential of dynamic loading on bone quality and mechanical competence.

Circadian gene expression regulates pulsatile gonadotropin-releasing hormone (GnRH) secretory patterns in the hypothalamic GnRH-secreting GT1-7 cell line.

PubMed

Chappell, Patrick E; White, Rachel S; Mellon, Pamela L

2003-12-03

Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1-7 mouse hypothalamic cell line as a model for GnRH secretion, because these cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1-7 cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1-7 cells by transient expression of the dominant-negative Clock-Delta19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1-7 cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.

Attention-related changes in correlated neuronal activity arise from normalization mechanisms

PubMed Central

Verhoef, Bram-Ernst; Maunsell, John H.R.

2017-01-01

Attention is believed to enhance perception by altering the correlations between pairs of neurons. How attention changes neuronal correlations is unknown. Using multi-electrodes in primate visual cortex, we measured spike-count correlations when single or multiple stimuli were presented, and stimuli were attended or unattended. When stimuli were unattended, adding a suppressive, non-preferred, stimulus beside a preferred stimulus increased spike-count correlations between pairs of similarly-tuned neurons, but decreased spike-count correlations between pairs of oppositely-tuned neurons. These changes are explained by a stochastic normalization model containing populations of oppositely-tuned, mutually-suppressive neurons. Importantly, this model also explains why attention decreased (attend preferred stimulus) or increased (attend non-preferred stimulus) correlations: as an indirect consequence of attention-related changes in the inputs to normalization mechanisms. Our findings link normalization mechanisms to correlated neuronal activity and attention, showing that normalization mechanisms shape response correlations and that these correlations change when attention biases normalization mechanisms. PMID:28553943

TGF-ß Regulates Cathepsin Activation during Normal and Pathogenic Development.

PubMed

Flanagan-Steet, Heather; Christian, Courtney; Lu, Po-Nien; Aarnio-Peterson, Megan; Sanman, Laura; Archer-Hartmann, Stephanie; Azadi, Parastoo; Bogyo, Matthew; Steet, Richard A

2018-03-13

Cysteine cathepsins play roles during development and disease beyond their function in lysosomal protein turnover. Here, we leverage a fluorescent activity-based probe (ABP), BMV109, to track cysteine cathepsins in normal and diseased zebrafish embryos. Using this probe in a model of mucolipidosis II, we show that loss of carbohydrate-dependent lysosomal sorting alters the activity of several cathepsin proteases. The data support a pathogenic mechanism where TGF-ß signals enhance the proteolytic processing of pro-Ctsk by modulating the expression of chondroitin 4-sulfate (C4-S). In MLII, elevated C4-S corresponds with TGF-ß-mediated increases in chst11 expression. Inhibiting chst11 impairs the proteolytic activation of Ctsk and alleviates the MLII phenotypes. These findings uncover a regulatory loop between TGF-ß signaling and Ctsk activation that is altered in the context of lysosomal disease. This work highlights the power of ABPs to identify mechanisms underlying pathogenic development in living animals. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Disrupted cortical function underlies behavior dysfunction due to social isolation

PubMed Central

Miyazaki, Tomoyuki; Takase, Kenkichi; Nakajima, Waki; Tada, Hirobumi; Ohya, Daisuke; Sano, Akane; Goto, Takahisa; Hirase, Hajime; Malinow, Roberto; Takahashi, Takuya

2012-01-01

Stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. However, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. Here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. Neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors normally occurring during circuit formation in the rodent barrel cortex. This inhibition of AMPA receptor trafficking was mediated by an increase of the stress glucocorticoid hormone and was associated with reduced calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling, resulting in attenuated whisker sensitivity at the cortex. These effects led to defects in whisker-dependent behavior in juvenile animals. These results indicate that neonatal social isolation alters neuronal plasticity mechanisms and perturbs the initial establishment of a normal cortical circuit, which potentially explains the long-lasting behavioral effects of neonatal stress. PMID:22706303

Structure of suicide-inactivated. beta. -hydroxydecanoyl-thioester dehydrase

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

Schwab, J.M.; Ho, C.K.; Li, W.B.

..beta..-Hydroxydecanoylthioester dehydrase, the key enzyme in biosynthesis of unsaturated fatty acids under anaerobic conditions, equilibrates thioesters of (R)-3-hydroxydecanoic acid, E-2-decenoic acid, and Z-3-decenoic acid. Dehydrase is irreversibly inactivated by the N-acetylcysteamine thioester of 3-decynoic acid (3-decynoyl-NAC), via dehydrase-catalyzed isomerization to 2,3-decadienoyl-NAC. To probe the relationship between normal catalysis and suicide inactivation, the structure of the inactivated enzyme has been studied. 3-(2-/sup 13/C)Decynoyl-NAC was synthesized and incubated with dehydrase. /sup 13/C NMR showed that attack of 2,3-decadienoyl-NAC by the active site histidine gives 3-histidinyl-3-decenoyl-NAC, which slowly rearranges to the more stable ..delta../sup 2/ isomer. Model histidine-allene adducts have been made andmore » characterized. Analysis of NMR data show that the C=C configuration of the decenoyl moiety of enzyme-bound inactivator is E. The suggestion that the mechanism of dehydrase inactivation parallels its normal mechanism of action is supported these findings.« less

Compression of Probabilistic XML Documents

NASA Astrophysics Data System (ADS)

Veldman, Irma; de Keijzer, Ander; van Keulen, Maurice

Database techniques to store, query and manipulate data that contains uncertainty receives increasing research interest. Such UDBMSs can be classified according to their underlying data model: relational, XML, or RDF. We focus on uncertain XML DBMS with as representative example the Probabilistic XML model (PXML) of [10,9]. The size of a PXML document is obviously a factor in performance. There are PXML-specific techniques to reduce the size, such as a push down mechanism, that produces equivalent but more compact PXML documents. It can only be applied, however, where possibilities are dependent. For normal XML documents there also exist several techniques for compressing a document. Since Probabilistic XML is (a special form of) normal XML, it might benefit from these methods even more. In this paper, we show that existing compression mechanisms can be combined with PXML-specific compression techniques. We also show that best compression rates are obtained with a combination of PXML-specific technique with a rather simple generic DAG-compression technique.

Effect of high pressure hydrogen on the mechanical characteristics of single carbon fiber

NASA Astrophysics Data System (ADS)

Jeon, Sang Koo; Kwon, Oh Heon; Jang, Hoon-Sik; Ryu, Kwon Sang; Nahm, Seung Hoon

2018-02-01

In this study, carbon fiber was exposed to a pressure of 7 MPa for 24 h in high pressure chamber. The tensile test for carbon fiber was conducted to estimate the effect on the high pressure hydrogen in the atmosphere. To determine the tensile strength and Weibull modulus, approximately thirty carbon fiber samples were measured in all cases, and carbon fiber exposed to high pressure argon was evaluated to verify only the effect of hydrogen. Additionally, carbon fiber samples were annealed at 1950 °C for 1 h for a comparison with normal carbon fiber and then tested under identical conditions. The results showed that the tensile strength scatter of normal carbon fiber exposed to hydrogen was relatively wider and the Weibull modulus was decreased. Moreover, the tensile strength of the annealed carbon fiber exposed to hydrogen was increased, and these samples indicated a complex Weibull modulus because the hydrogen stored in the carbon fiber influenced the mechanical characteristic.

Novel Regulation of Ski Protein Stability and Endosomal Sorting by Actin Cytoskeleton Dynamics in Hepatocytes*

PubMed Central

Vázquez-Victorio, Genaro; Caligaris, Cassandre; Del Valle-Espinosa, Eugenio; Sosa-Garrocho, Marcela; González-Arenas, Nelly R.; Reyes-Cruz, Guadalupe; Briones-Orta, Marco A.; Macías-Silva, Marina

2015-01-01

TGF-β-induced antimitotic signals are highly regulated during cell proliferation under normal and pathological conditions, such as liver regeneration and cancer. Up-regulation of the transcriptional cofactors Ski and SnoN during liver regeneration may favor hepatocyte proliferation by inhibiting TGF-β signals. In this study, we found a novel mechanism that regulates Ski protein stability through TGF-β and G protein-coupled receptor (GPCR) signaling. Ski protein is distributed between the nucleus and cytoplasm of normal hepatocytes, and the molecular mechanisms controlling Ski protein stability involve the participation of actin cytoskeleton dynamics. Cytoplasmic Ski is partially associated with actin and localized in cholesterol-rich vesicles. Ski protein stability is decreased by TGF-β/Smads, GPCR/Rho signals, and actin polymerization, whereas GPCR/cAMP signals and actin depolymerization promote Ski protein stability. In conclusion, TGF-β and GPCR signals differentially regulate Ski protein stability and sorting in hepatocytes, and this cross-talk may occur during liver regeneration. PMID:25561741

Study on the Correlation Between Dynamical Behavior and Friction/Wear Mechanism Under the Effect of Grooves

NASA Astrophysics Data System (ADS)

Zhu, Z. Y.; Mo, J. L.; Wang, D. W.; Zhao, J.; Zhu, M. H.; Zhou, Z. R.

2018-04-01

In this work, the interfacial friction and wear and vibration characteristics are studied by sliding a chromium bearing steel ball (AISI 52100) over both multi-grooved and single-grooved forged steel disks (20CrMnMo) at low and high rotating speeds in order to reveal the effect mechanism of groove-textured surface on tribological behaviors. The results show that the grooves modify the contact state of the ball and the disk at the contact interface. This consequently causes variations in the normal displacement, normal force, and friction force signals. The changes in these three signals become more pronounced with increasing groove width at a low speed. The collision behavior between the ball and the groove increase the amplitude of vibration acceleration at a high speed. The test results suggest that grooves with appropriate widths could trap wear debris on the ball surface while avoiding a strong collision between the disk and the ball, resulting in an improvement in the wear states.

Connexin 43 and ATP-sensitive potassium channels crosstalk: a missing link in hypoxia/ischemia stress.

PubMed

Ahmad Waza, Ajaz; Ahmad Bhat, Shabir; Ul Hussain, Mahboob; Ganai, Bashir A

2018-02-01

Connexin 43 (Cx43) is a gap junction protein expressed in various tissues and organs of vertebrates. Besides functioning as a gap junction, Cx43 also regulates diverse cellular processes like cell growth and differentiation, cell migration, cell survival, etc. Cx43 is critical for normal cardiac functioning and is therefore abundantly expressed in cardiomyocytes. On the other hand, ATP-sensitive potassium (K ATP ) channels are metabolic sensors converting metabolic changes into electrical activity. These channels are important in maintaining the neurotransmitter release, smooth muscle relaxation, cardiac action potential repolarization, normal physiology of cellular repolarization, insulin secretion and immune function. Cx43 and K ATP channels are part of the same signaling pathway, regulating cell survival during stress conditions and ischemia/hypoxia preconditioning. However, the underlying molecular mechanism for their combined role in ischemia/hypoxia preconditioning is largely unknown. The current review focuses on understanding the molecular mechanism responsible for the coordinated role of Cx43 and K ATP channel protein in protecting cardiomyocytes against ischemia/hypoxia stress.

Twinning in magnesium under dynamic loading

NASA Astrophysics Data System (ADS)

Dixit, Neha; Hazeli, Kavan; Ramesh, Kaliat T.

2015-09-01

Twinning is an important mode of deformation in magnesium (Mg) and its alloys at high strain rates. Twinning in this material leads to important effects such as mechanical anisotropy, texture evolution, tension-compression asymmetry, and sometimes non-Schmid effects. Extension twins in Mg can accommodate significant plastic deformation as they grow, and thus twinning affects the overall rate of plastic deformation. We use an experimental approach to study the deformation twinning mechanism under dynamic loading. We perform normal plate impact recovery experiments (with microsecond pulse durations) on pure polycrystalline Mg specimens. Estimates of average TB velocity under the known impact stress are obtained by characterization of twin sizes and aspect ratios developed within the target during the loading pulse. The measured average TB velocities in our experiments are of the order of several m s-1. These velocities are several orders of magnitude higher than those so far measured in Mg under quasi-static loading conditions. Electron back-scattered diffraction (EBSD) is then used to characterize the nature of the twins and the microstructural evolution. Detailed crystallographic analysis of the twins enables us to understand twin nucleation and growth of twin variants under dynamic loading.

The impact of systemic cortical alterations on perception

NASA Astrophysics Data System (ADS)

Zhang, Zheng

2011-12-01

Perception is the process of transmitting and interpreting sensory information, and the primary somatosensory (SI) area in the human cortex is the main sensory receptive area for the sensation of touch. The elaborate neuroanatomical connectivity that subserves the neuronal communication between adjacent and near-adjacent regions within sensory cortex has been widely recognized to be essential to normal sensory function. As a result, systemic cortical alterations that impact the cortical regional interaction, as associated with many neurological disorders, are expected to have significant impact on sensory perception. Recently, our research group has developed a novel sensory diagnostic system that employs quantitative sensory testing methods and is able to non-invasively assess central nervous system healthy status. The intent of this study is to utilize quantitative sensory testing methods that were designed to generate discriminable perception to objectively and quantitatively assess the impacts of different conditions on human sensory information processing capacity. The correlation between human perceptions with observations from animal research enables a better understanding of the underlying neurophysiology of human perception. Additional findings on different subject populations provide valuable insight of the underlying mechanisms for the development and maintenance of different neurological diseases. During the course of the study, several protocols were designed and utilized. And this set of sensory-based perceptual metrics was employed to study the effects of different conditions (non-noxious thermal stimulation, chronic pain stage, and normal aging) on sensory perception. It was found that these conditions result in significant deviations of the subjects' tactile information processing capacities from normal values. Although the observed shift of sensory detection sensitivity could be a result of enhanced peripheral activity, the changes in the effects of adaptation most likely reflect changes in central nervous system. The findings in this work provide valuable information for better understanding the underlying mechanisms involved in the development and maintenance of different neurological conditions.

Atomic resolution of structural changes in elastic crystals of copper(II) acetylacetonate

NASA Astrophysics Data System (ADS)

Worthy, Anna; Grosjean, Arnaud; Pfrunder, Michael C.; Xu, Yanan; Yan, Cheng; Edwards, Grant; Clegg, Jack K.; McMurtrie, John C.

2018-01-01

Single crystals are typically brittle, inelastic materials. Such mechanical responses limit their use in practical applications, particularly in flexible electronics and optical devices. Here we describe single crystals of a well-known coordination compound—copper(II) acetylacetonate—that are flexible enough to be reversibly tied into a knot. Mechanical measurements indicate that the crystals exhibit an elasticity similar to that of soft materials such as nylon, and thus display properties normally associated with both hard and soft matter. Using microfocused synchrotron radiation, we mapped the changes in crystal structure that occur on bending, and determined the mechanism that allows this flexibility with atomic precision. We show that, under strain, the molecules in the crystal reversibly rotate, and thus reorganize to allow the mechanical compression and expansion required for elasticity and still maintain the integrity of the crystal structure.

Study of coherent structures of turbulence with large wall-normal gradients in thermophysical properties using direct numerical simulation

NASA Astrophysics Data System (ADS)

Reinink, Shawn K.; Yaras, Metin I.

2015-06-01

Forced-convection heat transfer in a heated working fluid at a thermodynamic state near its pseudocritical point is poorly predicted by correlations calibrated with data at subcritical temperatures and pressures. This is suggested to be primarily due to the influence of large wall-normal thermophysical property gradients that develop in proximity of the pseudocritical point on the concentration of coherent turbulence structures near the wall. The physical mechanisms dominating this influence remain poorly understood. In the present study, direct numerical simulation is used to study the development of coherent vortical structures within a turbulent spot under the influence of large wall-normal property gradients. A turbulent spot rather than a fully turbulent boundary layer is used for the study, for the coherent structures of turbulence in a spot tend to be in a more organized state which may allow for more effective identification of cause-and-effect relationships. Large wall-normal gradients in thermophysical properties are created by heating the working fluid which is near the pseudocritical thermodynamic state. It is found that during improved heat transfer, wall-normal gradients in density accelerate the growth of the Kelvin-Helmholtz instability mechanism in the shear layer enveloping low-speed streaks, causing it to roll up into hairpin vortices at a faster rate. It is suggested that this occurs by the baroclinic vorticity generation mechanism which accelerates the streamwise grouping of vorticity during shear layer roll-up. The increased roll-up frequency leads to reduced streamwise spacing between hairpin vortices in wave packets. The density gradients also promote the sinuous instability mode in low-speed streaks. The resulting oscillations in the streaks in the streamwise-spanwise plane lead to locally reduced spanwise spacing between hairpin vortices forming over adjacent low-speed streaks. The reduction in streamwise and spanwise spacing between hairpin vortices causes them to interact more frequently by merging together and by breaking apart into smaller turbulence structures.

Study of coherent structures of turbulence with large wall-normal gradients in thermophysical properties using direct numerical simulation

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

Reinink, Shawn K.; Yaras, Metin I., E-mail: Metin.Yaras@carleton.ca

2015-06-15

Forced-convection heat transfer in a heated working fluid at a thermodynamic state near its pseudocritical point is poorly predicted by correlations calibrated with data at subcritical temperatures and pressures. This is suggested to be primarily due to the influence of large wall-normal thermophysical property gradients that develop in proximity of the pseudocritical point on the concentration of coherent turbulence structures near the wall. The physical mechanisms dominating this influence remain poorly understood. In the present study, direct numerical simulation is used to study the development of coherent vortical structures within a turbulent spot under the influence of large wall-normal propertymore » gradients. A turbulent spot rather than a fully turbulent boundary layer is used for the study, for the coherent structures of turbulence in a spot tend to be in a more organized state which may allow for more effective identification of cause-and-effect relationships. Large wall-normal gradients in thermophysical properties are created by heating the working fluid which is near the pseudocritical thermodynamic state. It is found that during improved heat transfer, wall-normal gradients in density accelerate the growth of the Kelvin-Helmholtz instability mechanism in the shear layer enveloping low-speed streaks, causing it to roll up into hairpin vortices at a faster rate. It is suggested that this occurs by the baroclinic vorticity generation mechanism which accelerates the streamwise grouping of vorticity during shear layer roll-up. The increased roll-up frequency leads to reduced streamwise spacing between hairpin vortices in wave packets. The density gradients also promote the sinuous instability mode in low-speed streaks. The resulting oscillations in the streaks in the streamwise-spanwise plane lead to locally reduced spanwise spacing between hairpin vortices forming over adjacent low-speed streaks. The reduction in streamwise and spanwise spacing between hairpin vortices causes them to interact more frequently by merging together and by breaking apart into smaller turbulence structures.« less

Pathophysiology of immobilization osteoporosis

NASA Technical Reports Server (NTRS)

Doty, S. B.; DiCarlo, E. F.

1995-01-01

The reduction of gravity-related forces on the skeleton creates a type of osteoporosis that is unique because its severity is dependent on the mechanical stress bearing function of the skeleton as well as the length of time that the forces are absent or reduced. Bones that bear weight under normal conditions are more affected than bones that normally do not bear weight. The cytokine environment and the cells in the affected bones are altered in time so that stem cells produce fewer new cells and the differentiated cells tend to be less active. These alterations in the local environment of the affected parts appear to resemble those of age- and disease-associated systemic forms of osteoporosis. The osteoporosis produced as a result of the loss of normal activity however, appears to be at least partially reversible through remobilization, strenuous exercise, and--possibly in the future--cytokine therapy.

Role of 4-hydroxynonenal in chemopreventive activities of sulforaphane

PubMed Central

Sharma, Rajendra; Sharma, Abha; Chaudhary, Pankaj; Sahu, Mukesh; Jaiswal, Shailesh; Awasthi, Sanjay; Awasthi, Yogesh C.

2012-01-01

Chemoprevention of cancer via herbal and dietary supplements is a logical approach to combat cancer and presently it is an attractive area of research investigations. Over the years, the use of isothiocyanates, such as sulforaphane (SFN) found in cruciferous vegetables, has been advocated as chemopreventive agents and their efficacy has been demonstrated in cell lines and animal models. In-vivo studies with SFN suggest that besides protecting normal healthy cells from environmental carcinogens it also exhibits cytotoxicity and apoptotic effects against various cancer cell types. Among several mechanisms for the chemopreventive activity of SFN against chemical carcinogenesis, its effect on drug metabolizing enzymes that causes activation/ neutralization of carcinogenic metabolites is well established. Recent studies suggest that SFN exerts its selective cytotoxicity to cancer cells via reactive oxygen species (ROS)-mediated generation of lipid peroxidation (LPO) products particularly 4-hydroxynonenal (HNE). Against the background of the known biochemical effects of SFN on normal and cancer cells, in this article we have reviewed the underlying molecular mechanisms responsible for the overall chemopreventive effects of SFN focusing on the role of HNE in these mechanisms that may also contribute to its selective cytotoxicity to cancer cells. PMID:22579574

Reprogramming to developmental plasticity in cancer stem cells.

PubMed

O'Brien-Ball, Caitlin; Biddle, Adrian

2017-10-15

During development and throughout adult life, sub-populations of cells exist that exhibit phenotypic plasticity - the ability to differentiate into multiple lineages. This behaviour is important in embryogenesis, is exhibited in a more limited context by adult stem cells, and can be re-activated in cancer cells to drive important processes underlying tumour progression. A well-studied mechanism of phenotypic plasticity is the epithelial-to-mesenchymal transition (EMT), a process which has been observed in both normal and cancerous cells. The epigenetic and metabolic modifications necessary to facilitate phenotypic plasticity are first seen in development and can be re-activated both in normal regeneration and in cancer. In cancer, the re-activation of these mechanisms enables tumour cells to acquire a cancer stem cell (CSC) phenotype with enhanced ability to survive in hostile environments, resist therapeutic interventions, and undergo metastasis. However, recent research has suggested that plasticity may also expose weaknesses in cancer cells that could be exploited for future therapeutic development. More research is needed to identify developmental mechanisms that are active in cancer, so that these may be targeted to reduce tumour growth and metastasis and overcome therapeutic resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Particle irradiation induces FGF2 expression in normal human lens cells

NASA Technical Reports Server (NTRS)

Chang, P. Y.; Bjornstad K, A.; Chang, E.; McNamara, M.; Barcellos-Hoff, M. H.; Lin, S. P.; Aragon, G.; Polansky, J. R.; Lui, G. M.; Blakely, E. A.

2000-01-01

Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells. Particle radiations, including both proton and helium-ion beams, have been used to successfully treat choroidal melanoma, but with the complication of radiation-induced cataract. We have investigated a role for radiation-induced changes in the expression of basic fibroblast growth factor (FGF2) gene expression as part of the mechanism(s) underlying lens cell injury associated with cataract. Normal human lens epithelial (HLE) cells were cultured in vitro on extracellular matrix (ECM) originated from bovine corneal endothelial cells. This study reports evidence for rapid but transient induction of FGF2 transcripts, an increase of between 5- and 8-fold, within 0.5 h after exposure to particle radiation, followed by another wave of increased transcription at 2-3 h postirradiation. Immunofluorescence results confirm the enhanced levels of FGF2 protein rapidly after exposure to protons or helium ions, followed by another wave of increased activity unique to helium at 6 h postirradiation. This second wave of increased immunoreactivity was not observed in the proton-irradiated samples. Total FGF2 protein analysis after helium-ion exposures shows induced expression of three FGF2 isoforms, with an increase of up to 2-fold in the 18-kDa low-molecular-weight species. Studies of the effects of protons on individual FGF2 protein isoforms are in progress. Several mechanisms involving a role for FGF2 in radiation-induced cataract are discussed.

Spectral Sequences of Type Ia Supernovae. I. Connecting Normal and Subluminous SNe Ia and the Presence of Unburned Carbon

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

Heringer, E.; Kerkwijk, M. H. van; Sim, S. A.

2017-09-01

Type Ia supernovae (SNe Ia) are generally agreed to arise from thermonuclear explosions of carbon–oxygen white dwarfs. The actual path to explosion, however, remains elusive, with numerous plausible parent systems and explosion mechanisms suggested. Observationally, SNe Ia have multiple subclasses, distinguished by their light curves and spectra. This raises the question of whether these indicate that multiple mechanisms occur in nature or that explosions have a large but continuous range of physical properties. We revisit the idea that normal and 91bg-like SNe can be understood as part of a spectral sequence in which changes in temperature dominate. Specifically, we findmore » that a single ejecta structure is sufficient to provide reasonable fits of both the normal SN Ia SN 2011fe and the 91bg-like SN 2005bl, provided that the luminosity and thus temperature of the ejecta are adjusted appropriately. This suggests that the outer layers of the ejecta are similar, thus providing some support for a common explosion mechanism. Our spectral sequence also helps to shed light on the conditions under which carbon can be detected in premaximum SN Ia spectra—we find that emission from iron can “fill in” the carbon trough in cool SNe Ia. This may indicate that the outer layers of the ejecta of events in which carbon is detected are relatively metal-poor compared to events in which carbon is not detected.« less

Liquid and gel electrodes for transverse free flow electrophoresis

DOEpatents

Jung, Byoungsok; Rose, Klint A; Shusteff, Maxim; Persat, Alexandre; Santiago, Juan

2015-04-07

The present invention provides a mechanism for separating or isolating charged particles under the influence of an electric field without metal electrodes being in direct contact with the sample solution. The metal electrodes normally in contact with the sample are replaced with high conductivity fluid electrodes situated parallel and adjacent to the sample. When the fluid electrodes transmit the electric field across the sample, particles within the sample migrate according to their electrophoretic mobility.

Molecular Mechanisms Underlying Genomic Instability in Brca-Deficient Cells

DTIC Science & Technology

2014-03-01

in BRCA1, which is required for homologous recombination, or in any of the Fanconi anaemia complementation group ( FANC ) genes , which excise DNA...The Brca1 gene is required for DNA repair by homologous recombination and normal embryonic development. The protein 53BP1 promotes ligation and...in the right panel. Key Research Accomplishments • Deletion of the DNA damage response gene RIF1 mimics 53BP1 deficiency with respect to

The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions

PubMed Central

Mastrogiannaki, Maria; Matak, Pavle

2013-01-01

Although earlier, seminal studies demonstrated that the gut per se has the intrinsic ability to regulate the rates of iron absorption, the spotlight in the past decade has been placed on the systemic regulation of iron homeostasis by the hepatic hormone hepcidin and the molecular mechanisms that regulate its expression. Recently, however, attention has returned to the gut based on the finding that hypoxia inducible factor-2 (HIF-2α) regulates the expression of key genes that contribute to iron absorption. Here we review the current understanding of the molecular mechanisms that regulate iron homeostasis in the gut by focusing on the role of HIF-2 under physiological steady-state conditions and in the pathogenesis of iron-related diseases. We also discuss implications for adapting HIF-2–based therapeutic strategies in iron-related pathological conditions. PMID:23678007

Lab-On-Chip Clinorotation System for Live-Cell Microscopy Under Simulated Microgravity

NASA Technical Reports Server (NTRS)

Yew, Alvin G.; Atencia, Javier; Chinn, Ben; Hsieh, Adam H.

2013-01-01

Cells in microgravity are subject to mechanical unloading and changes to the surrounding chemical environment. How these factors jointly influence cellular function is not well understood. We can investigate their role using ground-based analogues to spaceflight, where mechanical unloading is simulated through the time-averaged nullification of gravity. The prevailing method for cellular microgravity simulation is to use fluid-filled containers called clinostats. However, conventional clinostats are not designed for temporally tracking cell response, nor are they able to establish dynamic fluid environments. To address these needs, we developed a Clinorotation Time-lapse Microscopy (CTM) system that accommodates lab-on- chip cell culture devices for visualizing time-dependent alterations to cellular behavior. For the purpose of demonstrating CTM, we present preliminary results showing time-dependent differences in cell area between human mesenchymal stem cells (hMSCs) under modeled microgravity and normal gravity.

Lab-On-Chip Clinorotation System for Live-Cell Microscopy Under Simulated Microgravity

NASA Technical Reports Server (NTRS)

Yew, Alvin G.; Atencia, Javier; Chinn, Ben; Hsieh, Adam H.

1980-01-01

Cells in microgravity are subject to mechanical unloading and changes to the surrounding chemical environment. How these factors jointly influence cellular function is not well understood. We can investigate their role using ground-based analogues to spaceflight, where mechanical unloading is simulated through the time-averaged nullification of gravity. The prevailing method for cellular microgravity simulation is to use fluid-filled containers called clinostats. However, conventional clinostats are not designed for temporally tracking cell response, nor are they able to establish dynamic fluid environments. To address these needs, we developed a Clinorotation Time-lapse Microscopy (CTM) system that accommodates lab-on- chip cell culture devices for visualizing time-dependent alterations to cellular behavior. For the purpose of demonstrating CTM, we present preliminary results showing time-dependent differences in cell area between human mesenchymal stem cells (hMSCs) under modeled microgravity and normal gravity.

Hyperthyroidism and cardiovascular complications: a narrative review on the basis of pathophysiology

PubMed Central

Cicero, Arrigo F.

2013-01-01

Cardiovascular complications are important in hyperthyroidism because of their high frequency in clinical presentation and increased mortality and morbidity risk. The cause of hyperthyroidism, factors related to the patient, and the genetic basis for complications are associated with risk and the basic underlying mechanisms are important for treatment and management of the disease. Besides cellular effects, hyperthyroidism also causes hemodynamic changes, such as increased preload and contractility and decreased systemic vascular resistance causes increased cardiac output. Besides tachyarrythmias, impaired systolic ventricular dysfunction and diastolic dysfunction may cause thyrotoxic cardiomyopathy in a small percentage of the patients, as another high mortality complication. Although the medical literature has some conflicting data about benefits of treatment of subclinical hyperthyroidism, even high-normal thyroid function may cause cardiovascular problems and it should be treated. This review summarizes the cardiovascular consequences of hyperthyroidism with underlying mechanisms. PMID:24273583

HSF1 critically attunes proteotoxic stress sensing by mTORC1 to combat stress and promote growth.

PubMed

Su, Kuo-Hui; Cao, Junyue; Tang, Zijian; Dai, Siyuan; He, Yishu; Sampson, Stephen Byers; Benjamin, Ivor J; Dai, Chengkai

2016-05-01

To cope with proteotoxic stress, cells attenuate protein synthesis. However, the precise mechanisms underlying this fundamental adaptation remain poorly defined. Here we report that mTORC1 acts as an immediate cellular sensor of proteotoxic stress. Surprisingly, the multifaceted stress-responsive kinase JNK constitutively associates with mTORC1 under normal growth conditions. On activation by proteotoxic stress, JNK phosphorylates both RAPTOR at S863 and mTOR at S567, causing partial disintegration of mTORC1 and subsequent translation inhibition. Importantly, HSF1, the central player in the proteotoxic stress response (PSR), preserves mTORC1 integrity and function by inactivating JNK, independently of its canonical transcriptional action. Thereby, HSF1 translationally augments the PSR. Beyond promoting stress resistance, this intricate HSF1-JNK-mTORC1 interplay, strikingly, regulates cell, organ and body sizes. Thus, these results illuminate a unifying mechanism that controls stress adaptation and growth.

An Experimental Study on Normal Stress and Shear Rate Dependency of Basic Friction Coefficient in Dry and Wet Limestone Joints

NASA Astrophysics Data System (ADS)

Mehrishal, Seyedahmad; Sharifzadeh, Mostafa; Shahriar, Korosh; Song, Jae-Jon

2016-12-01

Among all parameters that affect the friction of rocks, variable normal stress and slip rate are the most important second-order parameters. The shear-rate- and normal-stress-dependent friction behavior of rock discontinuities may significantly influence the dynamic responses of rock mass. In this research, two limestone rock types, which were travertine and onyx marble with slickenside and grinded #80 surfaces, were prepared and CNL direct shear tests were performed on the joints under various shear conditions. The shearing rate varied from 0.1 to 50 mm/min under different normal stresses (from 2 to 30 % of UCS) in both dry and wet conditions. Experiments showed that the friction coefficient of slickensided and ground #80 surfaces of limestone increased with the increasing shear velocity and decreased with the increasing normal stress. Micro-asperity interlocking between ground #80 surfaces showed higher wear and an increase in friction coefficient ( µ) compared to slickensided surfaces. Slickensided samples with moist surfaces showed an increase in the coefficient of friction compared to dry surfaces; however, on ground #80 surfaces, the moisture decreased the coefficient of friction to a smaller value. Slickenside of limestone typically slides stably in a dry condition and by stick-slip on moist surfaces. The observed shear-rate- and normal-stress-dependent friction behavior can be explained by a similar framework to that of the adhesion theory of friction and a friction mechanism that involves the competition between microscopic dilatant slip and surface asperity deformation. The results have important implications for understanding the behavior of basic and residual friction coefficients of limestone rock surfaces.

A comparative study on the mechanical energy of the normal, ACL, osteoarthritis, and Parkinson subjects.

PubMed

Bahreinizad, Hossein; Salimi Bani, Milad; Hasani, Mojtaba; Karimi, Mohammad Taghi; Sharifmoradi, Keyvan; Karimi, Alireza

2017-08-09

The influence of various musculoskeletal disorders has been evaluated using different kinetic and kinematic parameters. But the efficiency of walking can be evaluated by measuring the effort of the subject, or by other words the energy that is required to walk. The aim of this study was to identify mechanical energy differences between the normal and pathological groups. Four groups of 15 healthy subjects, 13 Parkinson subjects, 4 osteoarthritis subjects, and 4 ACL reconstructed subjects have participated in this study. The motions of foot, shank and thigh were recorded using a three dimensional motion analysis system. The kinetic, potential and total mechanical energy of each segment was calculated using 3D markers positions and anthropometric measurements. Maximum value and sample entropy of energies was compared between the normal and abnormal subjects. Maximum value of potential energy of OA subjects was lower than the normal subjects. Furthermore, sample entropy of mechanical energy for Parkinson subjects was low in comparison to the normal subjects while sample entropy of mechanical energy for the ACL subjects was higher than that of the normal subjects. Findings of this study suggested that the subjects with different abilities show different mechanical energy during walking.

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.

PubMed

Engström, Wilhelm; Darbre, Philippa; Eriksson, Staffan; Gulliver, Linda; Hultman, Tove; Karamouzis, Michalis V; Klaunig, James E; Mehta, Rekha; Moorwood, Kim; Sanderson, Thomas; Sone, Hideko; Vadgama, Pankaj; Wagemaker, Gerard; Ward, Andrew; Singh, Neetu; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A Ivana; Raju, Jayadev; Hamid, Roslida A; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K; Ryan, Elizabeth P; Brown, Dustin G; Bisson, William H

2015-06-01

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Suppression of seizures based on the multi-coupled neural mass model.

PubMed

Cao, Yuzhen; Ren, Kaili; Su, Fei; Deng, Bin; Wei, Xile; Wang, Jiang

2015-10-01

Epilepsy is one of the most common serious neurological disorders, which affects approximately 1% of population in the world. In order to effectively control the seizures, we propose a novel control methodology, which combines the feedback linearization control (FLC) with the underlying mechanism of epilepsy, to achieve the suppression of seizures. The three coupled neural mass model is constructed to study the property of the electroencephalographs (EEGs). Meanwhile, with the model we research on the propagation of epileptiform waves and the synchronization of populations, which are taken as the foundation of our control method. Results show that the proposed approach not only yields excellent performances in clamping the pathological spiking patterns to the reference signals derived under the normal state but also achieves the normalization of the pathological parameter, where the parameters are estimated from EEGs with Unscented Kalman Filter. The specific contribution of this paper is to treat the epilepsy from its pathogenesis with the FLC, which provides critical theoretical basis for the clinical treatment of neurological disorders.

Light trapping for emission from a photovoltaic cell under normally incident monochromatic illumination

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

Takeda, Yasuhiko, E-mail: takeda@mosk.tytlabs.co.jp; Iizuka, Hideo; Mizuno, Shintaro

2014-09-28

We have theoretically demonstrated a new light-trapping mechanism to reduce emission from a photovoltaic (PV) cell used for a monochromatic light source, which improves limiting conversion efficiency determined by the detailed balance. A multilayered bandpass filter formed on the surface of a PV cell has been found to prevent the light generated inside by radiative recombination from escaping the cell, resulting in a remarkable decrease of the effective solid angle for the emission. We have clarified a guide to design a suitable configuration of the bandpass filter and achieved significant reduction of the emission. The resultant gain in monochromatic conversionmore » efficiency in the radiative limit due to the optimally designed 18-layerd bandpass filters is as high as 6% under normally incident 1064 nm illumination of 10 mW/cm²~ 1 kW/cm², compared with the efficiency for the perfect anti-reflection treatment to the surface of a conventional solar cell.« less

A Method for Preparation, Storage and Activation of Large Populations of Immotile Sea Urchin Sperm

NASA Technical Reports Server (NTRS)

Bracho, Geracimo E.; Fritch, Jennifer J.; Tash, Joseph S.

1997-01-01

Reversible protein phosphorylation is associated with initiation and modulation of sperm flagellar motility. Many studies aimed at examining the signal transduction mechanisms underlying the expression of motility have relied on detergent-permeabilized sperm reactivated with exogenous 32 P-ATP. However, the reactivation conditions allow variable levels of motility to be expressed and phosphorylation of many proteins that appear to be unrelated to sperm motility. Thus, identification of the few relevant proteins is difficult. We have developed a method to collect and keep sperm immotile until reactivated for analysis to normal motility levels. Artificial sea water (ASW) buffered with 5 mM 2-[N-morpholino]ethanesulfonic acid at pH 6.0 and containing 50 mM KCI, allows collection and storage of immotile sea urchin sperm for up to 96 h at 4-5 C. Motility under these conditions is essentially zero, but sperm is rapidly reactivated to normal motility by diluting with ASW to standard pH (8.0) and KCI concentration (10 mM).

EDAC: Epithelial defence against cancer-cell competition between normal and transformed epithelial cells in mammals.

PubMed

Kajita, Mihoko; Fujita, Yasuyuki

2015-07-01

During embryonic development or under certain pathological conditions, viable but suboptimal cells are often eliminated from the cellular society through a process termed cell competition. Cell competition was originally identified in Drosophila where cells with different properties compete for survival; 'loser' cells are eliminated from tissues and consequently 'winner' cells become dominant. Recent studies have shown that cell competition also occurs in mammals. While apoptotic cell death is the major fate for losers in Drosophila, outcompeted cells show more variable phenotypes in mammals, such as cell death-independent apical extrusion and cellular senescence. Molecular mechanisms underlying these processes have been recently revealed. Especially, in epithelial tissues, normal cells sense and actively eliminate the neighbouring transformed cells via cytoskeletal proteins by the process named epithelial defence against cancer (EDAC). Here, we introduce this newly emerging research field: cell competition in mammals. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Pathogenesis of rhegmatogenous retinal detachment: predisposing anatomy and cell biology.

PubMed

Mitry, Danny; Fleck, Brian W; Wright, Alan F; Campbell, Harry; Charteris, David G

2010-01-01

The pathogenesis of rhegmatogenous retinal detachment is complex, and our knowledge of the exact mechanism of vitreoretinal attachment and detachment remains incomplete. We performed a Medline, Ovid, and EMBASE search using search words rhegmatogenous, retinal detachment, vitreous, and retinal adhesion. All appropriate articles were reviewed, and the evidence was compiled. Cortical vitreous contains fibrillar collagens type II, V/XI, and IX. The inner limiting membrane of the retina contains collagens type I, IV, VI, and XVIII as well as numerous other glycoproteins and potential adhesion molecules. The distribution and age-related changes in the structure of these molecules play an important role in the formation of a retinal break, which may compromise and disrupt the normal mechanisms of neurosensory retinal adhesion. Rhegmatogenous retinal detachment development is intimately related to changes in the fibrillar structure of the aging vitreous culminating in posterior vitreous detachment with regions of persistent and tangential vitreoretinal traction predisposing to retinal tear formation. A complex interplay of factors such as weakening of vitreoretinal adhesion, posterior migration of the vitreous base, and molecular changes at the vitreoretinal interface are important in predisposing to focal areas of vitreoretinal traction precipitating rhegmatogenous retinal detachment. Once formed, the passage of liquefied vitreous through a retinal break may overwhelm normal neurosensory-retinal pigment epithelium adhesion perpetuating and extending detachment and causing visual loss. To understand the molecular events underlying rhegmatogenous retinal detachment so that new therapies can be developed, it is important to appreciate the structural organization of the vitreous, the biology underlying vitreous liquefaction and posterior vitreous detachment, and the mechanisms of vitreoretinal attachment and detachment.

Mysterious coloring: structural origin of color mixing for two breeds of Papilio butterflies.

PubMed

Diao, Ying-Ying; Liu, Xiang-Yang

2011-05-09

The structural origin of the coloration mechanisms and related extraordinary optical properties of the wing scales of two breeds of Papilio butterflies, namely, Papilio ulysses and Papilio blumei, are explored. The precise ordered biophotonic nanostructures of the wing scales are characterized by scanning electron microscopy (SEM). Despite their structural similarities, the two breeds of Papilio butterflies do not exhibit any analogy in their optical performances. When illuminated with UV-Vis light, P. ulysses gives rise to two reflection peaks: one is from concavities, and the other is from ridges. These two spectral peaks shift their positions under different illumination angles (normal and 45° incident light). In contrast, the spectra for the green scales of P. blumei give one broad reflection peak, and the peak remains the same under normal and 45° incident light. The optical microscopy images indicate that the cap-shaped concavities on P. blumei's wing scales generate an abnormal bicolor reflection with a strong polarization effect. Both of these two breeds of butterflies take advantage of color mixing strategy: the blue color of P. ulysses is mixed by the colors reflected from concavities and ridges; the green color of P. blumei is produced by the biocolor reflection from concavities. The differences of their coloration mixing mechanisms and optical performances are due to the variations of their nanostructures. The investigation of the color mixing mechanisms of these biologically photonic nanostructures may offer a convenient way for fabricating optical devices based on biomimicry. © 2011 Optical Society of America

Sudden cardiac death: the pro-arrhythmic interaction of an acute loading with an underlying substrate.

PubMed

Sutherland, George R

2017-10-21

Sudden cardiac death (SCD) is a complex phenomenon, occurring either in apparently normal individuals or in those where there is a recognized underlying cardiac abnormality. In both groups, the lethal arrhythmia has frequently been related to the physiologic trigger of either exercise or stress. Prior research into SCD has focused mainly on a combination of identifying either vulnerable myocardial substrates; pharmacological approaches to altering electrical activation/repolarisation in substrates; or the suppression of induced lethal arrhythmias with implantable defibrillators. However, it has been suggested that in a significant number of cases, the interaction of a transient induced trigger with a pre-existing electrical or mechanical substrate is the basis for the induction of the sustained lethal arrhythmia. In this manuscript we will discuss the precise mechanisms whereby one of such potential physiologic trigger: an acute change in systolic blood pressure, can induce a sequence of alterations in global and local cardiac mechanics which in turn result in regional left ventricular post-systolic deformation which, mediated (through stretch-induced changes in local mechano-electrical coupling) provokes local electrical after-depolarisations which can spill over into complex runs of premature ventricular beats. These local acute pressure/stretch induced runs of ventricular ectopy originate in either basal or apical normal myocardium and, in combination with a co-existing distal pro-arrhymic substrate, can interact to induce a lethal arrhythmia. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

Deregulated angiogenesis in chronic lung diseases: a possible role for lung mesenchymal progenitor cells (2017 Grover Conference Series)

PubMed Central

Kropski, Jonathan A.; Richmond, Bradley W.; Gaskill, Christa F.; Foronjy, Robert F.

2017-01-01

Chronic lung disease (CLD), including pulmonary fibrosis (PF) and chronic obstructive pulmonary disease (COPD), is the fourth leading cause of mortality worldwide. Both are debilitating pathologies that impede overall tissue function. A common co-morbidity in CLD is vasculopathy, characterized by deregulated angiogenesis, remodeling, and loss of microvessels. This substantially worsens prognosis and limits survival, with most current therapeutic strategies being largely palliative. The relevance of angiogenesis, both capillary and lymph, to the pathophysiology of CLD has not been resolved as conflicting evidence depicts angiogenesis as both reparative or pathologic. Therefore, we must begin to understand and model the underlying pathobiology of pulmonary vascular deregulation, alone and in response to injury induced disease, to define cell interactions necessary to maintain normal function and promote repair. Capillary and lymphangiogenesis are deregulated in both PF and COPD, although the mechanisms by which they co-regulate and underlie early pathogenesis of disease are unknown. The cell-specific mechanisms that regulate lung vascular homeostasis, repair, and remodeling represent a significant gap in knowledge, which presents an opportunity to develop targeted therapies. We have shown that that ABCG2pos multipotent adult mesenchymal stem or progenitor cells (MPC) influence the function of the capillary microvasculature as well as lymphangiogenesis. A balance of both is required for normal tissue homeostasis and repair. Our current models suggest that when lymph and capillary angiogenesis are out of balance, the non-equivalence appears to support the progression of disease and tissue remodeling. The angiogenic regulatory mechanisms underlying CLD likely impact other interstitial lung diseases, tuberous sclerosis, and lymphangioleiomyomatosis. PMID:29040010

Tenascin-C and mechanotransduction in the development and diseases of cardiovascular system

PubMed Central

Imanaka-Yoshida, Kyoko; Aoki, Hiroki

2014-01-01

Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain tissue structure. ECM is also important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Among ECM molecules, increased attention has been focused on matricellular proteins. Matricellular proteins are a growing group of non-structural ECM proteins highly up-regulated at active tissue remodeling, serving as biological mediators. Tenascin-C (TNC) is a typical matricellular protein, which is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion. The expression is tightly regulated, dependent on the microenvironment, including various growth factors, cytokines, and mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted manner during early stages of development, sparsely detected in normal adults, but transiently re-expressed at restricted sites associated with tissue injury and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated during embryonic development and under pathological conditions with an increase in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular system develops normally in TNC knockout mice. However, deletion of TNC causes acute aortic dissection (AAD) under strong mechanical and humoral stress. Accumulating reports suggest that TNC may modulate the inflammatory response and contribute to elasticity of the tissue, so that it may protect cardiovascular tissue from destructive stress responses. TNC may be a key molecule to control cellular activity during development, adaptation, or pathological tissue remodeling. PMID:25120494

Circadian preference modulates the neural substrate of conflict processing across the day.

PubMed

Schmidt, Christina; Peigneux, Philippe; Leclercq, Yves; Sterpenich, Virginie; Vandewalle, Gilles; Phillips, Christophe; Berthomier, Pierre; Berthomier, Christian; Tinguely, Gilberte; Gais, Steffen; Schabus, Manuel; Desseilles, Martin; Dang-Vu, Thanh; Salmon, Eric; Degueldre, Christian; Balteau, Evelyne; Luxen, André; Cajochen, Christian; Maquet, Pierre; Collette, Fabienne

2012-01-01

Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that these preferences are not a simple by-product of socio-professional timing constraints, but can be driven by inter-individual differences in the expression of circadian and homeostatic sleep-wake promoting signals. Chronotypes thus constitute a unique tool to access the interplay between those processes under normally entrained day-night conditions, and to investigate how they impinge onto higher cognitive control processes. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on conflict processing-related cerebral activity throughout a normal waking day. Sixteen morning and 15 evening types were recorded at two individually adapted time points (1.5 versus 10.5 hours spent awake) while performing the Stroop paradigm. Results show that interference-related hemodynamic responses are maintained or even increased in evening types from the subjective morning to the subjective evening in a set of brain areas playing a pivotal role in successful inhibitory functioning, whereas they decreased in morning types under the same conditions. Furthermore, during the evening hours, activity in a posterior hypothalamic region putatively involved in sleep-wake regulation correlated in a chronotype-specific manner with slow wave activity at the beginning of the night, an index of accumulated homeostatic sleep pressure. These results shed light into the cerebral mechanisms underlying inter-individual differences of higher-order cognitive state maintenance under normally entrained day-night conditions.

[The mechanism of phenoptosis: 2. Hayflick limit is caused by the programmed attenuation of bioenergetics].

PubMed

Trubitsin, A G

2010-01-01

This article continues earlier started theme on a substantiation of the programmed aging mechanism (phenoptosis). The concept underlying this mechanism is that the life represents a lot of the interconnected physical and chemical processes moving by the bioenergetics. The gradual programmed decrease of the level of bioenergetics causes the slow and coordinated attenuation of all physiological functions, i.e. aging. For a convincing substantiation of such mechanism it is necessary to show, how attenuation of bioenergetics causes the basic nocuous processes accompanying aging. It is shown earlier that the age dependent decrease in level of bioenergetics causes increase in production of reactive oxygen species by mitochondria and decrease in overall level of protein synthesis. The proof that Hayflick limit is also caused by the decrease in level of bioenergetics is presented in this article. Decrease in level of bioenergetics below certain critical level deprives a cell the ability to pass the restriction point of G1-phase of proliferative cycle. The inhibitor of cyclin-dependent kinase, p27, prevents the passage through this critical point in all normal cells. During division of normal somatic cells p27 is removed by cyclin E-Cdk2 complex. Interaction p27 with cyclin E-Cdk2 complex can have two consequences. At the normal physiological level of bioenergetics the cyclin E-Cdk2 phosphorylates p27, then the latter is destroyed by proteolytic enzymes--the cell enters in S-phase. When the programme decreases the bioenergetics level below certain value the cyclin E-Cdk2 becomes the target for p27. As a result the inhibitor evacuation stops and restriction point becomes closed--a cell enters irreversible proliferative rest.

Fluid involvement in normal faulting

NASA Astrophysics Data System (ADS)

Sibson, Richard H.

2000-04-01

Evidence of fluid interaction with normal faults comes from their varied role as flow barriers or conduits in hydrocarbon basins and as hosting structures for hydrothermal mineralisation, and from fault-rock assemblages in exhumed footwalls of steep active normal faults and metamorphic core complexes. These last suggest involvement of predominantly aqueous fluids over a broad depth range, with implications for fault shear resistance and the mechanics of normal fault reactivation. A general downwards progression in fault rock assemblages (high-level breccia-gouge (often clay-rich) → cataclasites → phyllonites → mylonite → mylonitic gneiss with the onset of greenschist phyllonites occurring near the base of the seismogenic crust) is inferred for normal fault zones developed in quartzo-feldspathic continental crust. Fluid inclusion studies in hydrothermal veining from some footwall assemblages suggest a transition from hydrostatic to suprahydrostatic fluid pressures over the depth range 3-5 km, with some evidence for near-lithostatic to hydrostatic pressure cycling towards the base of the seismogenic zone in the phyllonitic assemblages. Development of fault-fracture meshes through mixed-mode brittle failure in rock-masses with strong competence layering is promoted by low effective stress in the absence of thoroughgoing cohesionless faults that are favourably oriented for reactivation. Meshes may develop around normal faults in the near-surface under hydrostatic fluid pressures to depths determined by rock tensile strength, and at greater depths in overpressured portions of normal fault zones and at stress heterogeneities, especially dilational jogs. Overpressures localised within developing normal fault zones also determine the extent to which they may reutilise existing discontinuities (for example, low-angle thrust faults). Brittle failure mode plots demonstrate that reactivation of existing low-angle faults under vertical σ1 trajectories is only likely if fluid overpressures are localised within the fault zone and the surrounding rock retains significant tensile strength. Migrating pore fluids interact both statically and dynamically with normal faults. Static effects include consideration of the relative permeability of the faults with respect to the country rock, and juxtaposition effects which determine whether a fault is transmissive to flow or acts as an impermeable barrier. Strong directional permeability is expected in the subhorizontal σ2 direction parallel to intersections between minor faults, extension fractures, and stylolites. Three dynamic mechanisms tied to the seismic stress cycle may contribute to fluid redistribution: (i) cycling of mean stress coupled to shear stress, sometimes leading to postfailure expulsion of fluid from vertical fractures; (ii) suction pump action at dilational fault jogs; and, (iii) fault-valve action when a normal fault transects a seal capping either uniformly overpressured crust or overpressures localised to the immediate vicinity of the fault zone at depth. The combination of σ2 directional permeability with fluid redistribution from mean stress cycling may lead to hydraulic communication along strike, contributing to the protracted earthquake sequences that characterise normal fault systems.

Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns

PubMed Central

Camley, Brian A.; Zhang, Yunsong; Zhao, Yanxiang; Li, Bo; Ben-Jacob, Eshel; Levine, Herbert; Rappel, Wouter-Jan

2014-01-01

Pairs of endothelial cells on adhesive micropatterns rotate persistently, but pairs of fibroblasts do not; coherent rotation is present in normal mammary acini and kidney cells but absent in cancerous cells. Why? To answer this question, we develop a computational model of pairs of mammalian cells on adhesive micropatterns using a phase field method and study the conditions under which persistent rotational motion (PRM) emerges. Our model couples the shape of the cell, the cell’s internal chemical polarity, and interactions between cells such as volume exclusion and adhesion. We show that PRM can emerge from this minimal model and that the cell-cell interface may be influenced by the nucleus. We study the effect of various cell polarity mechanisms on rotational motion, including contact inhibition of locomotion, neighbor alignment, and velocity alignment, where cells align their polarity to their velocity. These polarity mechanisms strongly regulate PRM: Small differences in polarity mechanisms can create significant differences in collective rotation. We argue that the existence or absence of rotation under confinement may lead to insight into the cell’s methods for coordinating collective cell motility. PMID:25258412

The effect of glycation on arterial microstructure and mechanical response.

PubMed

Stephen, Elizabeth A; Venkatasubramaniam, Arundhathi; Good, Theresa A; Topoleski, L D T

2014-08-01

Like engineered materials, an artery's biomechanical behavior and function depend on its microstructure. Glycation is associated with both normal aging and diabetes and has been shown to increase arterial stiffness. In this study we examined the direct effect of glycation on the mechanical response of intact arteries and on the mechanical response and structure of elastin isolated from the arteries. Samples of intact arteries and isolated elastin were prepared from porcine aortas and glycated. The mechanical response of all samples was completed using a uniaxial material test system. Glycation levels were measured using ELISA. A confocal microscope was used to image differences in the structure of the glycated and untreated elastin fibers. We found that, under the conditions used in this study, glycation led to decreased stiffness of elastin isolated from arteries, which was associated with a thinning of elastin fibers as imaged by confocal microscopy. We observed no effect of glycation on collagen fibers under our treatment conditions. These results suggest that glycation leads to weakening of the elastin component of arteries that could contribute to vascular defects seen in diabetes and aging. Prevention of glycation reactions may be an important consideration for vascular health later in life. © 2013 Wiley Periodicals, Inc.

Issues in development, evaluation, and use of the NASA Preflight Adaptation Trainer (PAT)

NASA Technical Reports Server (NTRS)

Lane, Norman E.; Kennedy, Robert S.

1988-01-01

The Preflight Adaptation Trainer (PAT) is intended to reduce or alleviate space adaptation syndrome by providing opportunities for portions of that adaptation to occur under normal gravity conditions prior to space flight. Since the adaptation aspects of the PAT objectives involve modification not only of the behavior of the trainee, but also of sensiomotor skills which underly the behavioral generation, the defining of training objectives of the PAT utilizes four mechanisms: familiarization, demonstration, training and adaptation. These mechanisms serve as structural reference points for evaluation, drive the content and organization of the training procedures, and help to define the roles of the PAT instructors and operators. It was determined that three psychomotor properties are most critical for PAT evaluation: reliability; sensitivity; and relevance. It is cause for concern that the number of measures available to examine PAT effects exceed those that can be properly studied with the available sample sizes; special attention will be required in selection of the candidate measure set. The issues in PAT use and application within a training system context are addressed through linking the three training related mechanisms of familiarization, demonstration and training to the fourth mechanism, adaptation.

Facial bone fragmentation in blind cavefish arises through two unusual ossification processes.

PubMed

Powers, Amanda K; Kaplan, Shane A; Boggs, Tyler E; Gross, Joshua B

2018-05-03

The precise mechanisms underlying cranial bone development, evolution and patterning remain incompletely characterised. This poses a challenge to understanding the etiologies of craniofacial malformations evolving in nature. Capitalising on natural variation, "evolutionary model systems" provide unique opportunities to identify underlying causes of aberrant phenotypes as a complement to studies in traditional systems. Mexican blind cavefish are a prime evolutionary model for cranial disorders since they frequently exhibit extreme alterations to the skull and lateral asymmetries. These aberrations occur in stark contrast to the normal cranial architectures of closely related surface-dwelling fish, providing a powerful comparative paradigm for understanding cranial bone formation. Using a longitudinal and in vivo analytical approach, we discovered two unusual ossification processes in cavefish that underlie the development of 'fragmented' and asymmetric cranial bones. The first mechanism involves the sporadic appearance of independent bony elements that fail to fuse together later in development. The second mechanism involves the "carving" of channels in the mature bone, a novel form of post-ossification remodeling. In the extreme cave environment, these novel mechanisms may have evolved to augment sensory input, and may indirectly result in a trade-off between sensory expansion and cranial bone development.

Digest of NASA earth observation sensors

NASA Technical Reports Server (NTRS)

Drummond, R. R.

1972-01-01

A digest of technical characteristics of remote sensors and supporting technological experiments uniquely developed under NASA Applications Programs for Earth Observation Flight Missions is presented. Included are camera systems, sounders, interferometers, communications and experiments. In the text, these are grouped by types, such as television and photographic cameras, lasers and radars, radiometers, spectrometers, technology experiments, and transponder technology experiments. Coverage of the brief history of development extends from the first successful earth observation sensor aboard Explorer 7 in October, 1959, through the latest funded and flight-approved sensors under development as of October 1, 1972. A standard resume format is employed to normalize and mechanize the information presented.

Synaptic mechanisms underlying persistent cocaine craving

PubMed Central

Wolf, Marina E.

2017-01-01

Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction. PMID:27150400

Cardiac Mechano-Gated Ion Channels and Arrhythmias

PubMed Central

Peyronnet, Remi; Nerbonne, Jeanne M.; Kohl, Peter

2015-01-01

Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, are exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intra-cardially, and are thus maintained even in heart transplant recipients. Although mechano-sensitivity of heart rhythm has been described in the medical literature for over a century, its molecular mechanisms are incompletely understood. Thanks to modern biophysical and molecular technologies, the roles of mechanical forces in cardiac biology are being explored in more detail, and detailed mechanisms of mechano-transduction have started to emerge. Mechano-gated ion channels are cardiac mechano-receptors. They give rise to mechano-electric feedback, thought to contribute to normal function, disease development, and, potentially, therapeutic interventions. In this review, we focus on acute mechanical effects on cardiac electrophysiology, explore molecular candidates underlying observed responses, and discuss their pharmaceutical regulation. From this, we identify open research questions and highlight emerging technologies that may help in addressing them. Cardiac electrophysiology is acutely affected by the heart’s mechanical environment. Mechano-electric feedback affects excitability, conduction, and electrical load, and remains an underestimated player in arrhythmogenesis. The utility of therapeutic interventions targeting acute mechano-electrical transduction is an open field worthy of further study. PMID:26838316

Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

PubMed

Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

2015-03-01

The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

Phototropic bending of non-elongating and radially growing woody stems results from asymmetrical xylem formation.

PubMed

Matsuzaki, Jun; Masumori, Masaya; Tange, Takeshi

2007-05-01

Active phototropic bending of non-elongating and radially growing portion of stems (woody stems) has not been previously documented, whereas negative gravitropic bending is well known. We found phototropic bending in woody stems and searched for the underlying mechanism. We inclined 1-year-old Quercus crispula Blume seedlings and unilaterally illuminated them from a horizontal direction perpendicular to ('normal' illumination) or parallel to ('parallel' illumination) the inclination azimuth. With normal illumination, active phototropic bending and xylem formation could be evaluated separately from the negative gravitropic response and vertical deflection resulting from the weight of the seedlings. One-year-old stems with normal illumination bent significantly, with asymmetrical xylem formation towards the illuminated upper surface and side of the stem, whereas those with parallel illumination showed non-significant lateral bending, with asymmetrical xylem formation only on the upper side. A mechanical model was built on the assumption that a bending moment resulted from the asymmetrical xylem formation during phototropic bending of the woody stems. The model fitted the relationship between the observed spatial distributions of the xylem and the observed lateral bending, and thus supported the hypothesis that phototropic bending of woody stems results from asymmetrical xylem formation, as such occurs during gravitropism.

[The effect of 5-HD on expression of PKC-alpha in rats of chronic hypoxic pulmonary hypertension].

PubMed

Shu, Ying; Li, Qiu; Li, Yun-lei; Zhang, Li-ping; Chen, Cheng-shui

2011-08-01

To investigate the effect of mito chondrial K(ATP) channels (mitoK(ATP)) inhibitor 5-hydroxydecanoate(5-HD) on chronic hypoxic pulmonary artery hypertension (CHPAH) rats and its underlying mechanisms. Forty-eight male SD rats were equally divided into 4 groups randomly (n=12): normal group, hypoxia group, hypoxia + 5-HD group, hypoxia + Diazoxide group. Except the first group, the other three groups were put into hypoxic [O2 (10.0% +/- 0.3%] and nonrmobaric chamber for four weeks to establish chronic hypoxic model and received different interference. When the interference completed, right heart catheter was used to detect the mean pulmonary arterial pressure (mPAP) of each rat and PKC-alpha mRNA expression in pulmonary arteries was detected by reverse transcription-polymerase chain reaction (RT-PCR) and protein expression by Western blot. (mPAP was much higher in hypoxia group than that in normal group (P < 0.01) while in hypoxia + 5-HD group and hypoxia + diazoxide were decreased significantly compared to hypoxia group (P < 0.01). (2) The protein and mRNA levels of PKC-alpha in the hypoxic group were higher than those in normal group (P < 0.05). 5-HD plays a protective role on CHPAH. The mechanism of its effect may be attributed to inhibiting MitoK(ATP).

Deformation along the leading edge of the Maiella thrust sheet in central Italy

NASA Astrophysics Data System (ADS)

Aydin, Atilla; Antonellini, Marco; Tondi, Emanuele; Agosta, Fabrizio

2010-09-01

The eastern forelimb of the Maiella anticline above the leading edge of the underlying thrust displays a complex system of fractures, faults and a series of kink bands in the Cretaceous platform carbonates. The kink bands have steep limbs, display top-to-the-east shear, parallel to the overall transport direction, and are brecciated and faulted. A system of pervasive normal faults, trending sub-parallel to the strike of the mechanical layers, accommodates local extension generated by flexural slip. Two sets of strike-slip faults exist: one is left-lateral at a high angle to the main Maiella thrust; the other is right-lateral, intersecting the first set at an acute angle. The normal and strike-slip faults were formed by shearing across bed-parallel, strike-, and dip-parallel pressure solution seams and associated splays; the thrust faults follow the tilted mechanical layers along the steeper limb of the kink bands. The three pervasive, mutually-orthogonal pressure solution seams are pre-tilting. One set of low-angle normal faults, the oldest set in the area, is also pre-tilting. All other fault/fold structures appear to show signs of overlapping periods of activity accounting for the complex tri-shear-like deformation that developed as the front evolved during the Oligocene-Pliocene Apennine orogeny.

Metasurfaced Reverberation Chamber.

PubMed

Sun, Hengyi; Li, Zhuo; Gu, Changqing; Xu, Qian; Chen, Xinlei; Sun, Yunhe; Lu, Shengchen; Martin, Ferran

2018-01-25

The concept of metasurfaced reverberation chamber (RC) is introduced in this paper. It is shown that by coating the chamber wall with a rotating 1-bit random coding metasurface, it is possible to enlarge the test zone of the RC while maintaining the field uniformity as good as that in a traditional RC with mechanical stirrers. A 1-bit random coding diffusion metasurface is designed to obtain all-direction backscattering under normal incidence. Three specific cases are studied for comparisons, including a (traditional) mechanical stirrer RC, a mechanical stirrer RC with a fixed diffusion metasurface, and a RC with a rotating diffusion metasurface. Simulation results show that the compact rotating diffusion metasurface can act as a stirrer with good stirring efficiency. By using such rotating diffusion metasurface, the test region of the RC can be greatly extended.

Mechanics of load-drag-unload contact cleaning of gecko-inspired fibrillar adhesives.

PubMed

Abusomwan, Uyiosa A; Sitti, Metin

2014-10-14

Contact self-cleaning of gecko-inspired synthetic adhesives with mushroom-shaped tips has been demonstrated recently using load-drag-unload cleaning procedures similar to that of the natural animal. However, the underlying mechanics of contact cleaning has yet to be fully understood. In this work, we present a detailed experiment of contact self-cleaning that shows that rolling is the dominant mechanism of cleaning for spherical microparticle contaminants, during the load-drag-unload procedure. We also study the effect of dragging rate and normal load on the particle rolling friction. A model of spherical particle rolling on an elastomer fibrillar adhesive interface is developed and agrees well with the experimental results. This study takes us closer to determining design parameters for achieving self-cleaning fibrillar adhesives.

Friction and Wear Behavior of Plasma-Sprayed Al2O3-13 wt.%TiO2 Coatings Under the Lubrication of Liquid Paraffin

NASA Astrophysics Data System (ADS)

Zhao, Xiaoqin; An, Yulong; Hou, Guoliang; Zhou, Huidi; Chen, Jianmin

2014-04-01

Two types of ceramic composite coatings (denoted as N-AT13 coating and M-AT13 coating) were fabricated on 1Cr18Ni9Ti stainless steel substrate from ultra-fine and coarse Al2O3-13%TiO2 feedstocks by air plasma spraying. The friction and wear behavior of as-prepared coatings sliding against Al2O3 and stainless steel balls under the lubrication of liquid paraffin was evaluated with an SRV friction and wear tester (Optimol, Germany). The fractured and worn surfaces of the coatings were observed using a scanning electron microscope and a field-emission scanning electron microscope; and the wear mechanisms of the coatings were discussed based on scanning electron microscopic analysis and energy dispersive spectrometric analysis. Results show that N-AT13 coating possesses a unique microstructure and strong inter-splat bonding, thereby showing increased microhardness and bonding strength as well as much better friction-reduction and wear resistance than M-AT13 coating. Moreover, there exist differences in the wear mechanisms of N-AT13 and M-AT13 coatings which slide against ceramic and stainless steel balls under the lubrication of liquid paraffin. Namely, with the increase of normal load, the burnishing of N-AT13 coating coupled with Al2O3 ball is gradually transformed to grain-abrasion and deformation, while M-AT13 coating is dominated by grain-pullout and brittle fracture in the whole range of tested normal load.

Convergent synaptic and circuit substrates underlying autism genetic risks.

PubMed

McGee, Aaron; Li, Guohui; Lu, Zhongming; Qiu, Shenfeng

2014-02-01

There has been a surge of diagnosis of autism spectrum disorders (ASD) over the past decade. While large, high powered genome screening studies of children with ASD have identified numerous genetic risk factors, research efforts to understanding how each of these risk factors contributes to the development autism has met with limited success. Revealing the mechanisms by which these genetic risk factors affect brain development and predispose a child to autism requires mechanistic understanding of the neurobiological changes underlying this devastating group of developmental disorders at multifaceted molecular, cellular and system levels. It has been increasingly clear that the normal trajectory of neurodevelopment is compromised in autism, in multiple domains as much as aberrant neuronal production, growth, functional maturation, patterned connectivity, and balanced excitation and inhibition of brain networks. Many autism risk factors identified in humans have been now reconstituted in experimental mouse models to allow mechanistic interrogation of the biological role of the risk gene. Studies utilizing these mouse models have revealed that underlying the enormous heterogeneity of perturbed cellular events, mechanisms directing synaptic and circuit assembly may provide a unifying explanation for the pathophysiological changes and behavioral endophenotypes seen in autism, although synaptic perturbations are far from being the only alterations relevant for ASD. In this review, we discuss synaptic and circuit abnormalities obtained from several prevalent mouse models, particularly those reflecting syndromic forms of ASD that are caused by single gene perturbations. These compiled results reveal that ASD risk genes contribute to proper signaling of the developing gene networks that maintain synaptic and circuit homeostasis, which is fundamental to normal brain development.

An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development

PubMed Central

Boman, Bruce M.; Fields, Jeremy Z.

2013-01-01

APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes. PMID:24224156

Thymoquinone, a bioactive component of Nigella sativa, normalizes insulin secretion from pancreatic β-cells under glucose overload via regulation of malonyl-CoA

PubMed Central

Gray, Joshua P.; Zayasbazan Burgos, Delaine; Yuan, Tao; Seeram, Navindra; Rebar, Rebecca; Follmer, Rebecca

2015-01-01

Thymoquinone (2-isopropyl-5-methylbenzo-1,4-quinone) is a major bioactive component of Nigella sativa, a plant used in traditional medicine to treat a variety of symptoms, including elevated blood glucose levels in type 2 diabetic patients. Normalization of elevated blood glucose depends on both glucose disposal by peripheral tissues and glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. We employed clonal β-cells and rodent islets to investigate the effects of thymoquinone (TQ) and Nigella sativa extracts (NSEs) on GSIS and cataplerotic metabolic pathways implicated in the regulation of GSIS. TQ and NSE regulated NAD(P)H/NAD(P)+ ratios via a quinone-dependent redox cycling mechanism. TQ content was positively correlated with the degree of redox cycling activity of NSE extracts, suggesting that TQ is a major component engaged in mediating NSE-dependent redox cycling. Both acute and chronic exposure to TQ and NSE enhanced GSIS and were associated with the ability of TQ and NSE to increase the ATP/ADP ratio. Furthermore, TQ ameliorated the impairment of GSIS following chronic exposure of β-cells to glucose overload. This protective action was associated with the TQ-dependent normalization of chronic accumulation of malonyl-CoA, elevation of acetyl-CoA carboxylase (ACC), fatty acid synthase, and fatty acid-binding proteins following chronic glucose overload. Together, these data suggest that TQ modulates the β-cell redox circuitry and enhances the sensitivity of β-cell metabolic pathways to glucose and GSIS under normal conditions as well as under hyperglycemia. This action is associated with the ability of TQ to regulate carbohydrate-to-lipid flux via downregulation of ACC and malonyl-CoA. PMID:26786775

Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer.

PubMed

Kwon, Youngjoo; Godwin, Andrew K

2017-04-01

Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC.

Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer

PubMed Central

Kwon, Youngjoo; Godwin, Andrew K.

2016-01-01

Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC. PMID:27170665

Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

PubMed Central

2011-01-01

Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile) to those of lower birth weight (5-25th centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk. PMID:21999700

Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression

PubMed Central

Zhang, Kuo; Pan, Xing; Wang, Fang; Ma, Jie; Su, Guangyue; Dong, Yingxu; Yang, Jingyu; Wu, Chunfu

2016-01-01

Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation. PMID:27502757

Mechanisms underlying the cooling observed within the TTL during the active spells of organized deep convection of the Indian Summer Monsoon with COSMC RO and In-situ Measurements

NASA Astrophysics Data System (ADS)

Rao, Kusuma; Reddy, Narendra

Climate impact of the Asian monsoon as a tropical phenomena has been studied for decades in the past for its tropospheric component. However, the effort towards assessing the role of the Asian summer monsoon in the climate system with focus on the Upper Troposphere into the Lower Stratosphere (UTLS) is being addressed only in the recent times. Deep convective vertical fluxes of water and other chemical species penetrate and ventilate the TTL for redistribution of species in to stratosphere. However, the mechanisms underlying such convective transports are yet to be understood. Our specific goal here is to investigate the impact of organized deep moist convection of the Indian summer monsoon on thermal structure of UTLS, and to understand the underlying mechanisms. Since active monsoon spells are manifestations of organized deep convection embedded with overshooting convective elements, it becomes absolutely imperative to understand the impact of organized monsoon convection on three time scales, namely, (i) super synoptic scales of convectively intense active monsoon spells, (ii) on synoptic time scales of convectively disturbed conditions, and finally on (iii) cloud scales. Impact of deep convection on UTLS processes is examined here based on analysis of COSMIC RO and the METEOSAT data for the period, 2006-2011 and the in-situ measurements available from the national programme, PRWONAM during 2009-10 over the Indian land region and from the International field programme, JASMINE during 1999 over the Bay of Bengal. On all the three time scales during (i) the active monsoon spells, (ii) the disturbed periods and (iii) during the passage of deep core of MCSs, we inferred that the Coldpoint Tropopause Temperatures (CPT) lower at relatively lower CPT Altitudes (CPTA) unlike in the cases determined by normal temperature lapse rates; these unusual cases are described here as ‘Unlike Normal’ cases. TTL thickness shrinks during the convective conditions. During the passage of deep core of MCSs, cooling observed within the TTL is significantly higher than the cooling occuring on the other two time scales. The result that ‘Unlike Normal cases’ are associated with higher CAPE and higher surface equivalent potential temperatures lead to explain the possible mechanisms underlying the CPT cooling at relatively lower altitudes.

Origin and Timing of Dauphiné Twins Using Fluid Inclusions in Quartz-Cement Fractures in Sandstones from Diagenetic Environments

NASA Astrophysics Data System (ADS)

Fall, A.; Ukar, E.; Laubach, S.

2016-12-01

Dauphiné twins in quartz are widespread in many tectonometamorphic environments. Under diagenetic temperatures (<200°C) and burial depths less than 5 km Dauphiné twins are also common in isolated fracture quartz deposits spanning between fracture walls in low-porosity quartz-cemented sandstones. The twin boundaries coincide with fracture wall-normal fluid inclusion trails. The association of Dauphiné twins and fluid inclusion trails from which temperature and possibly timing can be inferred provides a way to research mechanism and timing of twinning, and potentially the magnitude of paleostrain and stress in some diagenetic settings. Using examples from East Texas and Colorado cores, we show that twins are associated with crack-seal microstructure and fluid inclusions. Fracture wall-parallel and wall-normal inclusion trails contain coexisting aqueous and hydrocarbon gas inclusions, so homogenization temperatures of aqueous inclusions, ranging from 130°C to 159°C in the East Texas Basin, and from 162°C to 176°C in the Piceance Basin, record true trapping temperatures. Inclusions in wall-normal trails are large and irregularly shaped compared to those in wall-parallel trails, but both show similar liquid-to-vapor ratios. Trapping temperatures for wall-normal inclusion trails are usually higher than those in the wall-parallel trails. Wall-normal fluid inclusion assemblage temperatures typically match the highest temperatures of wall-parallel assemblages trapped during sequential widening, but not necessarily the most recent. In context of burial histories for these samples, this temperature pattern implies that wall-normal assemblages form at discrete times during or after crack-seal fracture widening. Stacking transmitted light images with scanning electron microscope cathodoluminescence (SEM-CL) and electron backscattered diffraction (EBSD) images demonstrates that the twin boundaries are localized along wall-normal inclusion trails. Localization in isolated, potentially high-stress quartz deposits in fractures is compatible with a mechanical origin for these Dauphiné twins. Punctuated temperature values and discrepant sizes and shapes of inclusions in wall-normal trails imply that twinning is a by-product of the formation of the wall-normal inclusion trails.

Molecular mechanisms of decomposition of hydrated Na+Cl- ion pairs under planar nanopore conditions

NASA Astrophysics Data System (ADS)

Shevkunov, S. V.

2017-02-01

The decomposition of Na+Cl- ion pairs under the conditions of a nanoscopic planar pore with structureless walls in a material contact with water vapor at 298 K is simulated by Monte Carlo method. The transition from the state of a contact ion pair (CIP) to the state of solvent-separated ion pair (SSIP) is shown to occur as a result of an increase in the vapor pressure over a pore after exceeding the threshold number of molecules in a hydrate shell. It is found that the planar form of a molecular cluster under the conditions of a narrow pore does not level an abrupt structural transition and the formation of hydrogen bonds in the hydrate shell starts after three molecules are added. The hydrogen bond length under pore conditions is found to be resistant to variations in the hydrate shell size and coincides with that in water under normal conditions.

Nonlinear and Stochastic Dynamics in the Heart

PubMed Central

Qu, Zhilin; Hu, Gang; Garfinkel, Alan; Weiss, James N.

2014-01-01

In a normal human life span, the heart beats about 2 to 3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems. PMID:25267872

What choline metabolism can tell us about the underlying mechanisms of fetal alcohol spectrum disorders.

PubMed

Zeisel, Steven H

2011-10-01

The consequences of fetal exposure to alcohol are very diverse and the likely molecular mechanisms involved must be able to explain how so many developmental processes could go awry. If pregnant rat dams are fed alcohol, their pups develop abnormalities characteristic of fetal alcohol spectrum disorders (FASD), but if these rat dams were also treated with choline, the effects from ethanol were attenuated in their pups. Choline is an essential nutrient in humans, and is an important methyl group donor. Alcohol exposure disturbs the metabolism of choline and other methyl donors. Availability of choline during gestation directly influences epigenetic marks on DNA and histones, and alters gene expression needed for normal neural and endothelial progenitor cell proliferation. Maternal diets low in choline alter development of the mouse hippocampus, and decrement memory for life. Women eating low-choline diets have an increased risk of having an infant with a neural tube or orofacial cleft birth defect. Thus, the varied effects of choline could affect the expression of FASD, and studies on choline might shed some light on the underlying molecular mechanisms responsible for FASD.

Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

PubMed Central

2017-01-01

The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. PMID:28567415

Hard-hard coupling assisted anomalous magnetoresistance effect in amine-ended single-molecule magnetic junction

NASA Astrophysics Data System (ADS)

Tang, Y.-H.; Lin, C.-J.; Chiang, K.-R.

2017-06-01

We proposed a single-molecule magnetic junction (SMMJ), composed of a dissociated amine-ended benzene sandwiched between two Co tip-like nanowires. To better simulate the break junction technique for real SMMJs, the first-principles calculation associated with the hard-hard coupling between a amine-linker and Co tip-atom is carried out for SMMJs with mechanical strain and under an external bias. We predict an anomalous magnetoresistance (MR) effect, including strain-induced sign reversal and bias-induced enhancement of the MR value, which is in sharp contrast to the normal MR effect in conventional magnetic tunnel junctions. The underlying mechanism is the interplay between four spin-polarized currents in parallel and anti-parallel magnetic configurations, originated from the pronounced spin-up transmission feature in the parallel case and spiky transmission peaks in other three spin-polarized channels. These intriguing findings may open a new arena in which magnetotransport and hard-hard coupling are closely coupled in SMMJs and can be dually controlled either via mechanical strain or by an external bias.

Molecular mechanism of mast cell–mediated innate defense against endothelin and snake venom sarafotoxin

PubMed Central

Schneider, Lars A.; Schlenner, Susan M.; Feyerabend, Thorsten B.; Wunderlin, Markus; Rodewald, Hans-Reimer

2007-01-01

Mast cells are protective against snake venom sarafotoxins that belong to the endothelin (ET) peptide family. The molecular mechanism underlying this recently recognized innate defense pathway is unknown, but secretory granule proteases have been invoked. To specifically disrupt a single protease function without affecting expression of other proteases, we have generated a mouse mutant selectively lacking mast cell carboxypeptidase A (Mc-cpa) activity. Using this mutant, we have now identified Mc-cpa as the essential protective mast cell enzyme. Mass spectrometry of peptide substrates after cleavage by normal or mutant mast cells showed that removal of a single amino acid, the C-terminal tryptophan, from ET and sarafotoxin by Mc-cpa is the principle molecular mechanism underlying this very rapid mast cell response. Mast cell proteases can also cleave ET and sarafotoxin internally, but such “nicking” is not protective because intramolecular disulfide bridges maintain peptide function. We conclude that mast cells attack ET and sarafotoxin exactly at the structure required for toxicity, and hence sarafotoxins could not “evade” Mc-cpa's substrate specificity without loss of toxicity. PMID:17923505

The Type VI Secretion System Engages a Redox-Regulated Dual-Functional Heme Transporter for Zinc Acquisition.

PubMed

Si, Meiru; Wang, Yao; Zhang, Bing; Zhao, Chao; Kang, Yiwen; Bai, Haonan; Wei, Dawei; Zhu, Lingfang; Zhang, Lei; Dong, Tao G; Shen, Xihui

2017-07-25

The type VI secretion system was recently reported to be involved in zinc acquisition, but the underlying mechanism remains unclear. Here, we report that Burkholderia thailandensis T6SS4 is involved in zinc acquisition via secretion of a zinc-scavenging protein, TseZ, that interacts with the outer membrane heme transporter HmuR. We find that HmuR is a redox-regulated dual-functional transporter that transports heme iron under normal conditions but zinc upon sensing extracellular oxidative stress, triggered by formation of an intramolecular disulfide bond. Acting as the first line of defense against oxidative stress, HmuR not only guarantees an immediate response to the changing environment but also provides a fine-tuned mechanism that allows a gradual response to perceived stress. The T6SS/HmuR-mediated active zinc transport system is also involved in bacterial virulence and contact-independent bacterial competition. We describe a sophisticated bacterial zinc acquisition mechanism affording insights into the role of metal ion transport systems. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Mechanism-based modeling of solute strengthening: application to thermal creep in Zr alloy

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

Tome, Carlos; Wen, Wei; Capolungo, Laurent

2017-08-01

This report focuses on the development of a physics-based thermal creep model aiming to predict the behavior of Zr alloy under reactor accident condition. The current models used for this kind of simulations are mostly empirical in nature, based generally on fits to the experimental steady-state creep rates under different temperature and stress conditions, which has the following limitations. First, reactor accident conditions, such as RIA and LOCA, usually take place in short times and involve only the primary, not the steady-state creep behavior stage. Moreover, the empirical models cannot cover the conditions from normal operation to accident environments. Formore » example, Kombaiah and Murty [1,2] recently reported a transition between the low (n~4) and high (n~9) power law creep regimes in Zr alloys depending on the applied stress. Capturing such a behavior requires an accurate description of the mechanisms involved in the process. Therefore, a mechanism-based model that accounts for the evolution with time of microstructure is more appropriate and reliable for this kind of simulation.« less

The function and failure of sensory predictions.

PubMed

Bansal, Sonia; Ford, Judith M; Spering, Miriam

2018-04-23

Humans and other primates are equipped with neural mechanisms that allow them to automatically make predictions about future events, facilitating processing of expected sensations and actions. Prediction-driven control and monitoring of perceptual and motor acts are vital to normal cognitive functioning. This review provides an overview of corollary discharge mechanisms involved in predictions across sensory modalities and discusses consequences of predictive coding for cognition and behavior. Converging evidence now links impairments in corollary discharge mechanisms to neuropsychiatric symptoms such as hallucinations and delusions. We review studies supporting a prediction-failure hypothesis of perceptual and cognitive disturbances. We also outline neural correlates underlying prediction function and failure, highlighting similarities across the visual, auditory, and somatosensory systems. In linking basic psychophysical and psychophysiological evidence of visual, auditory, and somatosensory prediction failures to neuropsychiatric symptoms, our review furthers our understanding of disease mechanisms. © 2018 New York Academy of Sciences.

Sleep and circadian rhythm disruption in neuropsychiatric illness.

PubMed

Jagannath, Aarti; Peirson, Stuart N; Foster, Russell G

2013-10-01

Sleep and circadian rhythm disruption (SCRD) is a common feature in many neuropsychiatric diseases including schizophrenia, bipolar disorder and depression. Although the precise mechanisms remain unclear, recent evidence suggests that this comorbidity is not simply a product of medication or an absence of social routine, but instead reflects commonly affected underlying pathways and mechanisms. For example, several genes intimately involved in the generation and regulation of circadian rhythms and sleep have been linked to psychiatric illness. Further, several genes linked to mental illness have recently been shown to also play a role in normal sleep and circadian behaviour. Here we describe some of the emerging common mechanisms that link circadian rhythms, sleep and SCRD in severe mental illnesses. A deeper understanding of these links will provide not only a greater understanding of disease mechanisms, but also holds the promise of novel avenues for therapeutic intervention. Copyright © 2013. Published by Elsevier Ltd.

Initial survey of the wave distribution functions for plasmaspheric hiss observed by ISEE 1

NASA Technical Reports Server (NTRS)

Storey, L. R. O.; Lefeuvre, F.; Parrot, M.; Cairo, L.; Anderson, R. R.

1991-01-01

The generation mechanism of hiss observed by ISEE 1 satellite in the earth magnetosphere is investigated by analyzing the ELF/VLF wave data obtained from four passes of ISEE 1, all of which occurring during magnetically quiet periods. The results of these measurements, together with those published earlier, indicate that the generation mechanisms proposed by Kennel alnd Petschek (1966), by Thorne et al. (1979), and by Solomon et al. (1988, 1989) are all physically possible and can come into action whenever the necessary conditions exist. However, plasmaspheric hiss was observed by ISEE even when the conditions for any of these mechanisms existed; under these conditions, hiss appears to be generated near the equatorial plane over a wide range of L values, with the wave normals at large angles to the field. The generation mechanism that applies in such cases is still unknown.

Effects of bioleaching on the mechanical and chemical properties of waste rocks

NASA Astrophysics Data System (ADS)

Yin, Sheng-Hua; Wu, Ai-Xiang; Wang, Shao-Yong; Ai, Chun-Ming

2012-01-01

Bioleaching processes cause dramatic changes in the mechanical and chemical properties of waste rocks, and play an important role in metal recovery and dump stability. This study focused on the characteristics of waste rocks subjected to bioleaching. A series of experiments were conducted to investigate the evolution of rock properties during the bioleaching process. Mechanical behaviors of the leached waste rocks, such as failure patterns, normal stress, shear strength, and cohesion were determined through mechanical tests. The results of SEM imaging show considerable differences in the surface morphology of leached rocks located at different parts of the dump. The mineralogical content of the leached rocks reflects the extent of dissolution and precipitation during bioleaching. The dump porosity and rock size change under the effect of dissolution, precipitation, and clay transportation. The particle size of the leached rocks decreased due to the loss of rock integrity and the conversion of dry precipitation into fine particles.

New insights into the formation mechanism of Ag, Au and AgAu nanoparticles in aqueous alkaline media: alkoxides from alcohols, aldehydes and ketones as universal reducing agents.

PubMed

Gomes, Janaina F; Garcia, Amanda C; Ferreira, Eduardo B; Pires, Cleiton; Oliveira, Vanessa L; Tremiliosi-Filho, Germano; Gasparotto, Luiz H S

2015-09-07

In this report we present new insights into the formation mechanism of Ag, Au and AgAu nanoparticles with alcohols, aldehydes and ketones in alkaline medium at room temperature. We selected methanol, ethanol, glycerol, formaldehyde, acetaldehyde and acetone to demonstrate their capability of reducing gold and silver ions under the above-mentioned conditions. We showed that the particles are also formed with potassium tert-butoxide in the absence of hydroxides. Our results strongly suggest that alkoxides, formed from any molecule containing a hydroxyl or a functional group capable of generating them in alkaline medium, are the actual and universal reducing agent of silver and gold ions, in opposition to the currently accepted mechanisms. The universality of the reaction mechanism proposed in this work may impact on the production of noble nanoparticles with simple chemicals normally found in standard laboratories.

Mechanisms of Resistance to Chemotherapies Targeting BRCA-Mutant Breast Cancer

DTIC Science & Technology

2016-12-01

such as 53BP1, restored normal HR activity in BRCA1 deficient cells and rendered these cells resistant to chemotherapeutic agents. Under the aegis...NHEJ (defined as NHEJ conducted during S phase which typically results in genome instability). We found that the anti-resection activities of 53BP1...for the recruitment of the PALB2/BRCA2 complex that may be dependent on the ubiquitin ligase activity of RNF168. Specifically, we are interested in

[Neurophysiology and neuropsychology of recognition confabulation in hospitalized schizophrenic patients].

PubMed

Salazar Fraile, J; Tabarés Seisdedos, R; Selva Vera, G; Balanzá Martínez, V; Leal Cercós, C; Vilela Soler, C; Vallet Mas, M

1998-01-01

Recognition confabulation was studied in 16 schizoprhenic patients and 16 normal controls. Half of the schizophrenics presented recognition confabulation, while the remaining 8 and 16 controls did not. This type of confabulation was associated to attentional deficiency, difficulties in perceptual follow-up and perceptive changes. These test satisfactorily discriminated confabulating schizoprhenics and both ill and healthy non-confabulating subjects. The possible mechanisms underlying this type of confabulation are discussed, in relation to the deficiences observed.

427th Brookhaven Lecture

ScienceCinema

Gene-Jack Wang

2017-12-09

The increasing number of obese individuals in the U.S. and other countries world-wide adds urgency to the need to understand the mechanisms underlying pathological overeating. Research by the speaker and others at Brookhaven National Laboratory and elsewhere is compiling evidence that the brain circuits disrupted in obesity are similar to those involved in drug addiction. Using positron emission tomography (PET), the speaker and his colleagues have implicated brain dopamine in the normal and the pathological intake of food by humans.

Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring.

PubMed

Reynolds, Clare M; Segovia, Stephanie A; Vickers, Mark H

2017-01-01

Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut-brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.

YiXin-Shu, a ShengMai-San-based traditional Chinese medicine formula, attenuates myocardial ischemia/reperfusion injury by suppressing mitochondrial mediated apoptosis and upregulating liver-X-receptor α.

PubMed

Zhao, Yichao; Xu, Longwei; Qiao, Zhiqing; Gao, Lingchen; Ding, Song; Ying, Xiaoying; Su, Yuanyuan; Lin, Nan; He, Ben; Pu, Jun

2016-03-11

Positive evidence from clinical trials has fueled growing acceptance of traditional Chinese medicine (TCM) for the treatment of cardiac diseases; however, little is known about the underlying mechanisms. Here, we investigated the nature and underlying mechanisms of the effects of YiXin-Shu (YXS), an antioxidant-enriched TCM formula, on myocardial ischemia/reperfusion (MI/R) injury. YXS pretreatment significantly reduced infarct size and improved viable myocardium metabolism and cardiac function in hypercholesterolemic mice. Mechanistically, YXS attenuated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway (as reflected by inhibition of mitochondrial swelling, cytochrome c release and caspase-9 activity, and normalization of Bcl-2 and Bax levels) without altering the death receptor and endoplasmic reticulum-stress death pathways. Moreover, YXS reduced oxidative/nitrative stress (as reflected by decreased superoxide and nitrotyrosine content and normalized pro- and anti-oxidant enzyme levels). Interestingly, YXS upregulated endogenous nuclear receptors including LXRα, PPARα, PPARβ and ERα, and in-vivo knockdown of cardiac-specific LXRα significantly blunted the cardio-protective effects of YXS. Collectively, these data show that YXS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and oxidative stress and by upregulating LXRα, thereby providing a rationale for future clinical trials and clinical applications.

An equivalent-time-lines model for municipal solid waste based on its compression characteristics.

PubMed

Gao, Wu; Bian, Xuecheng; Xu, Wenjie; Chen, Yunmin

2017-10-01

Municipal solid waste (MSW) demonstrates a noticeable time-dependent stress-strain behavior, which contributes greatly to the settlement of landfills and therefore influences both the storage capacity of landfills and the integrity of internal structures. The long-term compression tests for MSW under different biodegradation conditions were analyzed. It showed that the primary compression can affect the secondary compression due to the biodegradation and mechanical creep. Based on the time-lines model for clays and the compression characteristics of MSW, relationships between MSW's viscous strain rate and equivalent time were established, and then the viscous strain functions of MSW under different biodegradation conditions were deduced, and an equivalent-time-lines model for MSW settlement for two biodegradation conditions was developed, including the Type I model for the enhanced biodegradation condition and the Type II model for the normal biodegradation condition. The simulated compression results of laboratory and field compression tests under different biodegradation conditions were consistent with the measured data, which showed the reliability of both types of the equivalent-time-lines model for MSW. In addition, investigations of the long-term settlement of landfills from the literature indicated that the Type I model is suitable for predicting settlement in MSW landfills with a distinct biodegradation progress of MSW, a high content of organics in MSW, a short fill age or under an enhanced biodegradation environment; while the Type II model is good at predicting settlement in MSW landfills with a distinct progress of mechanical creep compression, a low content of organics in MSW, a long fill age or under a normal biodegradation condition. Furthermore, relationships between model parameters and the fill age of landfills were summarized. Finally, the similarities and differences between the equivalent-time-lines model for MSW and the stress-biodegradation model for MSW were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Outlets on Cracking Risk and Integral Stability of Super-High Arch Dams

PubMed Central

Hu, Hang

2014-01-01

In this paper, case study on outlet cracking is first conducted for the Goupitan and Xiaowan arch dams. A nonlinear FEM method is then implemented to study effects of the outlets on integral stability of the Xiluodu arch dam under two loading conditions, i.e., normal loading and overloading conditions. On the basis of the case study and the numerical modelling, the outlet cracking mechanism, risk, and corresponding reinforcement measures are discussed. Furthermore, the numerical simulation reveals that (1) under the normal loading conditions, the optimal distribution of the outlets will contribute to the tensile stress release in the local zone of the dam stream surface and decrease the outlet cracking risk during the operation period. (2) Under the overloading conditions, the cracks initiate around the outlets, then propagate along the horizontal direction, and finally coalesce with those in adjacent outlets, where the yield zone of the dam has a shape of butterfly. Throughout this study, a dam outlet cracking risk control and reinforcement principle is proposed to optimize the outlet design, select the appropriate concrete material, strengthen the temperature control during construction period, design reasonable impounding scheme, and repair the cracks according to their classification. PMID:25152907

Comparison of animal discs used in disc research to human lumbar disc: torsion mechanics and collagen content.

PubMed

Showalter, Brent L; Beckstein, Jesse C; Martin, John T; Beattie, Elizabeth E; Espinoza Orías, Alejandro A; Schaer, Thomas P; Vresilovic, Edward J; Elliott, Dawn M

2012-07-01

Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these with the human disc. To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar discs, and cow, rat, and mouse caudal discs. Collagen content was measured and normalized by dry weight for the same discs except the rat and the mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human discs. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Disc torsion mechanics are comparable with human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented are useful for selecting and interpreting results for animal disc models. Structural organization of the fiber angle may explain the differences that were noted between species after geometric normalization.

Comparison of Animal Discs Used in Disc Research to Human Lumbar Disc: Torsion Mechanics and Collagen Content

PubMed Central

Showalter, Brent L.; Beckstein, Jesse C.; Martin, John T.; Beattie, Elizabeth E.; Orías, Alejandro A. Espinoza; Schaer, Thomas P.; Vresilovic, Edward J.; Elliott, Dawn M.

2012-01-01

Study Design Experimental measurement and normalization of in vitro disc torsion mechanics and collagen content for several animal species used in intervertebral disc research and comparing these to the human disc. Objective To aid in the selection of appropriate animal models for disc research by measuring torsional mechanical properties and collagen content. Summary of Background Data There is lack of data and variability in testing protocols for comparing animal and human disc torsion mechanics and collagen content. Methods Intervertebral disc torsion mechanics were measured and normalized by disc height and polar moment of inertia for 11 disc types in 8 mammalian species: the calf, pig, baboon, goat, sheep, rabbit, rat, and mouse lumbar, and cow, rat, and mouse caudal. Collagen content was measured and normalized by dry weight for the same discs except the rat and mouse. Collagen fiber stretch in torsion was calculated using an analytical model. Results Measured torsion parameters varied by several orders of magnitude across the different species. After geometric normalization, only the sheep and pig discs were statistically different from human. Fiber stretch was found to be highly dependent on the assumed initial fiber angle. The collagen content of the discs was similar, especially in the outer annulus where only the calf and goat discs were statistically different from human. Disc collagen content did not correlate with torsion mechanics. Conclusion Disc torsion mechanics are comparable to human lumbar discs in 9 of 11 disc types after normalization by geometry. The normalized torsion mechanics and collagen content of the multiple animal discs presented is useful for selecting and interpreting results for animal models of the disc. Structural composition of the disc, such as initial fiber angle, may explain the differences that were noted between species after geometric normalization. PMID:22333953

Between destiny and disease: genetics and molecular pathways of human central nervous system aging.

PubMed

Glorioso, Christin; Sibille, Etienne

2011-02-01

Aging of the human brain is associated with "normal" functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human post-mortem brain microarray studies, which we hypothesize, point to a potential genetically controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

Placental expression of D6 decoy receptor in preeclampsia

PubMed Central

Cho, Geum Joon; Lee, Eun Sung; Jin, Hye Mi; Lee, Ji Hye; Kim, Yeun Sun; Seol, Hyun-Joo; Hong, Soon-Cheol; Kim, Hai-Joong

2015-01-01

Objective The purpose of this study was to investigate the expression of the D6 decoy receptor that can bind chemokines and target them for degradation, resulting in inhibition of inflammation in placentas from preeclamptic and normal pregnancies. Methods The current study was carried out in 35 pregnant women (23 patients with preeclampsia and 12 healthy, normotensive pregnant women) during the third trimester of pregnancy. The expressions of D6 decoy receptor in the placenta were determined with real time reverse transcriptase polymerase chain reaction and western blotting. Results The mRNA and protein of D6 decoy receptor were detected in all of placentas from preeclamptic and normal pregnancies. Placental D6 decoy receptor mRNA expression was significantly lower in patients with preeclampsia than in patients with normal pregnancies. Western blot analyses revealed decreased protein expression in cases of preeclampsia. Conclusion The expression of the D6 decoy receptor in preeclamptic placentas was significantly lower than in normal placentas. Further studies are needed to clarify the underlying mechanisms that link decreased expression of placental D6 decoy receptor and preeclampsia. PMID:26430656

Salivary glucose concentration and excretion in normal and diabetic subjects.

PubMed

Jurysta, Cedric; Bulur, Nurdan; Oguzhan, Berrin; Satman, Ilhan; Yilmaz, Temel M; Malaisse, Willy J; Sener, Abdullah

2009-01-01

The present report aims mainly at a reevaluation of salivary glucose concentration and excretion in unstimulated and mechanically stimulated saliva in both normal and diabetic subjects. In normal subjects, a decrease in saliva glucose concentration, an increase in salivary flow, but an unchanged glucose excretion rate were recorded when comparing stimulated saliva to unstimulated saliva. In diabetic patients, an increase in salivary flow with unchanged salivary glucose concentration and glucose excretion rate were observed under the same experimental conditions. Salivary glucose concentration and excretion were much higher in diabetic patients than in control subjects, whether in unstimulated or stimulated saliva. No significant correlation between glycemia and either glucose concentration or glucose excretion rate was found in the diabetic patients, whether in unstimulated or stimulated saliva. In the latter patients, as compared to control subjects, the relative magnitude of the increase in saliva glucose concentration was comparable, however, to that of blood glucose concentration. The relationship between these two variables was also documented in normal subjects and diabetic patients undergoing an oral glucose tolerance test.

Retinal degeneration increases susceptibility to myopia in mice

PubMed Central

Park, Hanna; Tan, Christopher C.; Faulkner, Amanda; Jabbar, Seema B.; Schmid, Gregor; Abey, Jane; Iuvone, P. Michael

2013-01-01

Purpose Retinal diseases are often associated with refractive errors, suggesting the importance of normal retinal signaling during emmetropization. For instance, retinitis pigmentosa, a disease characterized by severe photoreceptor degeneration, is associated with myopia; however, the underlying link between these conditions is not known. This study examines the influence of photoreceptor degeneration on refractive development by testing two mouse models of retinitis pigmentosa under normal and form deprivation visual conditions. Dopamine, a potential stop signal for refractive eye growth, was assessed as a potential underlying mechanism. Methods Refractive eye growth in mice that were homozygous for a mutation in Pde6b, Pde6brd1/rd1 (rd1), or Pde6brd10/rd10 (rd10) was measured weekly from 4 to 12 weeks of age and compared to age-matched wild-type (WT) mice. Refractive error was measured using an eccentric infrared photorefractor, and axial length was measured with partial coherence interferometry or spectral domain ocular coherence tomography. A cohort of mice received head-mounted diffuser goggles to induce form deprivation from 4 to 6 weeks of age. Dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured with high-performance liquid chromatography in each strain after exposure to normal or form deprivation conditions. Results The rd1 and rd10 mice had significantly greater hyperopia relative to the WT controls throughout normal development; however, axial length became significantly longer only in WT mice starting at 7 weeks of age. After 2 weeks of form deprivation, the rd1 and rd10 mice demonstrated a faster and larger myopic shift (−6.14±0.62 and −7.38±1.46 diopter, respectively) compared to the WT mice (−2.41±0.47 diopter). Under normal visual conditions, the DOPAC levels and DOPAC/dopamine ratios, a measure of dopamine turnover, were significantly lower in the rd1 and rd10 mice compared to the WT mice, while the dopamine levels were similar or higher than WT in the rd10 mice. Lower basal levels of DOPAC were highly correlated with increasing myopic shifts. Conclusions Refractive development under normal visual conditions was disrupted toward greater hyperopia from 4 to 12 weeks of age in these photoreceptor degeneration models, despite significantly lower DOPAC levels. However, the retinal degeneration models with low basal levels of DOPAC had increased susceptibility to form deprivation myopia. These results indicate that photoreceptor degeneration may alter dopamine metabolism, leading to increased susceptibility to myopia with an environmental visual challenge. PMID:24146540

Molecular inflammation: underpinnings of aging and age-related diseases.

PubMed

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2009-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) upregulation of pro-inflammatory mediators (e.g., TNF-alpha, IL-1beta, IL-6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-kappaB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity.

Molecular Inflammation: Underpinnings of Aging and Age-related Diseases

PubMed Central

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2013-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) up-regulation of pro-inflammatory mediators (e.g., TNF-α, IL-1β, 6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-κB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity. PMID:18692159

Insights into the Mechanisms Underlying Boron Homeostasis in Plants

PubMed Central

Yoshinari, Akira; Takano, Junpei

2017-01-01

Boron is an essential element for plants but is toxic in excess. Therefore, plants must adapt to both limiting and excess boron conditions for normal growth. Boron transport in plants is primarily based on three transport mechanisms across the plasma membrane: passive diffusion of boric acid, facilitated diffusion of boric acid via channels, and export of borate anion via transporters. Under boron -limiting conditions, boric acid channels and borate exporters function in the uptake and translocation of boron to support growth of various plant species. In Arabidopsis thaliana, NIP5;1 and BOR1 are located in the plasma membrane and polarized toward soil and stele, respectively, in various root cells, for efficient transport of boron from the soil to the stele. Importantly, sufficient levels of boron induce downregulation of NIP5;1 and BOR1 through mRNA degradation and proteolysis through endocytosis, respectively. In addition, borate exporters, such as Arabidopsis BOR4 and barley Bot1, function in boron exclusion from tissues and cells under conditions of excess boron. Thus, plants actively regulate intracellular localization and abundance of transport proteins to maintain boron homeostasis. In this review, the physiological roles and regulatory mechanisms of intracellular localization and abundance of boron transport proteins are discussed. PMID:29204148

Comparative Developmental Staging of Female and Male Water Fleas Daphnia pulex and Daphnia magna During Embryogenesis.

PubMed

Toyota, Kenji; Hiruta, Chizue; Ogino, Yukiko; Miyagawa, Shinichi; Okamura, Tetsuro; Onishi, Yuta; Tatarazako, Norihisa; Iguchi, Taisen

2016-02-01

The freshwater crustacean genus Daphnia has been used extensively in ecological, developmental and ecotoxicological studies. Daphnids produce only female offspring by parthenogenesis under favorable conditions, but in response to various unfavorable conditions and external stimuli, they produce male offspring. Although we reported that exogenous exposure to juvenile hormones and their analogs can induce male offspring even under female-producing conditions, we recently established a male induction system in the Daphnia pulex WTN6 strain simply by changing day-length. This male and female induction system is suitable for understanding the innate mechanisms of sexual dimorphic development in daphnids. Embryogenesis has been described as a normal plate (developmental staging) in various daphnid species; however, all studies have mainly focused on female development. Here, we describe the developmental staging of both sexes during embryogenesis in two representative daphnids, D. pulex and D. magna, based on microscopic time-course observations. Our findings provide the first detailed insights into male embryogenesis in both species, and contribute to the elucidation of the mechanisms underlying sexual differentiation in daphnids.

Compression Stiffening of Brain and its Effect on Mechanosensing by Glioma Cells

NASA Astrophysics Data System (ADS)

Pogoda, Katarzyna

The stiffness of tissues, often characterized by their time-dependent elastic properties, is tightly controlled under normal condition and central nervous system tissue is among the softest tissues. Changes in tissue and organ stiffness occur in some physiological conditions and are frequently symptoms of diseases such as fibrosis, cardiovascular disease and many forms of cancer. Primary cells isolated from various tissues often respond to changes in the mechanical properties of their substrates, and the range of stiffness over which these responses occur appear to be limited to the tissue elastic modulus from which they are derived. Our goal was to test the hypotheses that the stiffness of tumors derived from CNS tissue differs from that of normal brain, and that transformed cells derived from such tumors exhibit mechanical responses that differ from those of normal glial cells. Unlike breast and some other cancers where the stroma and the tumor itself is substantially stiffer than the surrounding normal tissue, our data suggest that gliomas can arise without a gross change in the macroscopic tissue stiffness when measured at low strains without compression. However, both normal brain and glioma samples stiffen with compression, but not in elongation and increased shear strains. On the other hand, different classes of immortalized cells derived from human glioblastoma show substantially different responses to the stiffness of substrates in vitrowhen grown on soft polyacrylamide and hyaluronic acid gels. This outcome supports the hypothesis that compression stiffening, which might occur with increased vascularization and interstitial pressure gradients that are characteristic of tumors, effectively stiffens the environment of glioma cells, and that in situ, the elastic resistance these cells sense might be sufficient to trigger the same responses that are activated in vitro by increased substrate stiffness.

The role of eggshell and underlying vitelline membrane for normal pattern formation in the early C. elegans embryo.

PubMed

Schierenberg, Einhard; Junkersdorf, Bernd

1992-12-01

The embryo of the nematode Caenorhabditis elegans is surrounded by an inconspicuous inner vitelline membrane and a prominent outer chitinous eggshell proper. We demonstrate that the complete removal of the chitinous eggshell does not interfere with successful development to yield a normal worm. The same result can be obtained when the vitelline membrane is penetrated with laser microbeam irradiation of only the eggshell proper, gently enough to permit its resealing after a while. However, when large holes are made into the eggshell the concomitantly penetrated vitelline membrane does not reseal. While early development is quite normal under these conditions, gastrulation is defective in that gut precursor cells do not migrate in properly, eventually leading to embryonic arrest. This suggests a crucial role for pattern formation of the "micro-environment" around the embryo preserved by the intact vitelline membrane. Removing both eggshell and vitelline membrane results in a string-like arrangement of founder cells and subsequent grossly abnormal cell patterns. Our experiments support the idea that the prominent eggshell proper just functions as a mechanical protection while the thin vitelline membrane directly or indirectly serves as a necessary control element affecting the positions of cells which to begin with are determined by the orientation of the cleavage spindle.

Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.

PubMed

Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

2012-08-15

Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Regulation and function of mTOR signalling in T cell fate decision

PubMed Central

Chi, Hongbo

2012-01-01

The evolutionary conserved kinase mTOR couples cell growth and metabolism to environmental inputs in eukaryotes. T cells depend on mTOR signalling to integrate immune signals and metabolic cues for their proper maintenance and activation. Under steady-state conditions, mTOR is actively controlled by multiple inhibitory mechanisms, and this enforces normal T cell homeostasis. Antigen recognition by naïve CD4+ and CD8+ T cells triggers mTOR activation, which in turn programs their differentiation into functionally distinct lineages. This Review focuses on the signalling mechanisms of mTOR in T cell homeostatic and functional fates and therapeutic implications of targeting mTOR in T cells. PMID:22517423

Use of natural clinoptilolite for the removal of lead, copper and zinc in fixed bed column.

PubMed

Stylianou, Marinos A; Hadjiconstantinou, Michalis P; Inglezakis, Vasilis J; Moustakas, Konstantinos G; Loizidou, Maria D

2007-05-08

This work deals with the removal of lead, copper and zinc from aqueous solutions by using natural zeolite (clinoptilolite). Fixed bed experiments were performed, using three different volumetric flow rates of 5, 7 and 10bed volume/h, under a total normality of 0.01N, at initial pH of 4 and ambient temperature (25 degrees C). The removal efficiency increased when decreasing the flow rate and the following selectivity series was found: Pb(2+)>Zn(2+)> or =Cu(2+). Conductivity measurements showed that lead removal follows mainly ion exchange mechanism, while copper and zinc removal follows ion exchange and sorption mechanism as well.

Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia.

PubMed

Huang, M H; Horackova, M; Negoescu, R M; Wolf, S; Armour, J A

1996-09-01

To determine the response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. Extracellular recordings were made from 54 spontaneously active and 5 normally quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest dogs under control conditions and during epicardial mechanical or chemical stimulation and myocardial ischaemia. The activity of 78% of spontaneously active and all quiescent neurones with left ventricular sensory fields was modified by left ventricular ischaemia. Forty-six spontaneously active neurones (85%) were polysensory with respect to mechanical and chemical stimuli. The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active neurones associated with left ventricular mechanosensory endings (37 neurones) generated four different activity patterns in response to similar mechanical stimuli (high or low pressure active, high-low pressure active, high-low pressure inactive). A fifth group generated activity which was not related to chamber dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively. Maximum local mechanical or chemical stimuli enhanced activity to similar degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique activity patterns in response to similar mechanical or chemical stimuli. Most myocardial ischemia-sensitive dorsal root ganglion neurones associated with epicardial neurites sense mechanical and multiple chemical stimuli, a small population sensing only mechanical or chemical stimuli. Activity patterns generated by these neurones depend on their primary sensory characteristics or those of other neurones that may converge on them, as well as the type and magnitude of the stimuli that impinge upon their sensory fields, both normally and during ischaemia.

Association between left ventricular mechanics and diffuse myocardial fibrosis in patients with repaired Tetralogy of Fallot: a cross-sectional study.

PubMed

Haggerty, Christopher M; Suever, Jonathan D; Pulenthiran, Arichanah; Mejia-Spiegeler, Abba; Wehner, Gregory J; Jing, Linyuan; Charnigo, Richard J; Fornwalt, Brandon K; Fogel, Mark A

2017-12-11

Patients with repaired tetralogy of Fallot (TOF) have progressive, adverse biventricular remodeling, leading to abnormal contractile mechanics. Defining the mechanisms underlying this dysfunction, such as diffuse myocardial fibrosis, may provide insights into poor long-term outcomes. We hypothesized that left ventricular (LV) diffuse fibrosis is related to impaired LV mechanics. Patients with TOF were evaluated with cardiac magnetic resonance in which modified Look-Locker (MOLLI) T1-mapping and spiral cine Displacement encoding (DENSE) sequences were acquired at three LV short-axis positions. Linear mixed modeling was used to define the association between regional LV mechanics from DENSE based on regional T1-derived diffuse fibrosis measures, such as extracellular volume fraction (ECV). Forty patients (26 ± 11 years) were included. LV ECV was generally within normal range (0.24 ± 0.05). For LV mechanics, peak circumferential strains (-15 ± 3%) and dyssynchrony indices (16 ± 8 ms) were moderately impaired, while peak radial strains (29 ± 8%) were generally normal. After adjusting for patient age, sex, and regional LV differences, ECV was associated with log-adjusted LV dyssynchrony index (β = 0.67) and peak LV radial strain (β = -0.36), but not LV circumferential strain. Moreover, post-contrast T1 was associated with log-adjusted LV diastolic circumferential strain rate (β = 0.37). We observed several moderate associations between measures of fibrosis and impaired mechanics, particularly the LV dyssynchrony index and peak radial strain. Diffuse fibrosis may therefore be a causal factor in some ventricular dysfunction in TOF.

ProNormz--an integrated approach for human proteins and protein kinases normalization.

PubMed

Subramani, Suresh; Raja, Kalpana; Natarajan, Jeyakumar

2014-02-01

The task of recognizing and normalizing protein name mentions in biomedical literature is a challenging task and important for text mining applications such as protein-protein interactions, pathway reconstruction and many more. In this paper, we present ProNormz, an integrated approach for human proteins (HPs) tagging and normalization. In Homo sapiens, a greater number of biological processes are regulated by a large human gene family called protein kinases by post translational phosphorylation. Recognition and normalization of human protein kinases (HPKs) is considered to be important for the extraction of the underlying information on its regulatory mechanism from biomedical literature. ProNormz distinguishes HPKs from other HPs besides tagging and normalization. To our knowledge, ProNormz is the first normalization system available to distinguish HPKs from other HPs in addition to gene normalization task. ProNormz incorporates a specialized synonyms dictionary for human proteins and protein kinases, a set of 15 string matching rules and a disambiguation module to achieve the normalization. Experimental results on benchmark BioCreative II training and test datasets show that our integrated approach achieve a fairly good performance and outperforms more sophisticated semantic similarity and disambiguation systems presented in BioCreative II GN task. As a freely available web tool, ProNormz is useful to developers as extensible gene normalization implementation, to researchers as a standard for comparing their innovative techniques, and to biologists for normalization and categorization of HPs and HPKs mentions in biomedical literature. URL: http://www.biominingbu.org/pronormz. Copyright © 2013 Elsevier Inc. All rights reserved.

Seismicity and Seismotectonic Properties of The Sultandağı Fault Zone (Afyonkarahisar-Konya): Western Anatolia,Turkey

NASA Astrophysics Data System (ADS)

Kalafat, D.; Gunes, Y.; Kekovali, K.; Kara, M.; Gorgun, E.

2017-12-01

n this study we investigated seismicity and source characteristics of the Sultandağı Fault Zone (SFZ). As known Western Anatolia is one of the most important seismically active region in Turkey. The relative movement of the African-Arabian plates, it causes the Anatolian Plate to movement to the west-Southwest direction 2.5 cm per year and this result provides N-S direction with extensional regime in the recent tectonic. In this study, especially with the assessment of seismic activity occurring in Afyon and around between 200-2002 years, we have been evaluated to date with seismic activity as well as fault mechanism solution. We analyzed recent seismicity and distribution of earthquakes in this region. In the last century, 3 important earthquakes occurred in the Sultandağı Fault zone (Afyon-Akşehir Graben), this result shown it was seismic active and broken fault segments caused stress balance in the region and it caused to occur with short intervals of earthquakes in 2000 and 2002, triggering each other. The scope of this tudy, we installed new BB stations in the region and we have been done of the fault plane solutions for important earthquakes. The focal mechanisms clearly exhibit the activation of a NE-SW trending normal faulting system along the SFZ region. The results of stress analysis showed that the effective current tectonic evolution of normal faulting in this region. This study is supported by Bogazici University Research Projects Commission under SRP/BAP project No. 12280. Key Words: Sultandağı fault zone, normal faulting, seismicity, fault mechanism

Friendly Fire: War-Normalizing Metaphors in the Israeli Political Discourse

ERIC Educational Resources Information Center

Gavriely-Nuri, Dalia

2009-01-01

Combining principles of peace education and political discourse analysis, this study dwells on one powerful metaphorical mechanism engaged in by Israeli political leaders: war-normalizing metaphors, a mechanism for framing war as part of human nature and normal life. Six core semantic fields were identified as particularly useful "raw…

Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function.

PubMed

Wang, Vicky Y; Lam, H I; Ennis, Daniel B; Cowan, Brett R; Young, Alistair A; Nash, Martyn P

2009-10-01

The majority of patients with clinically diagnosed heart failure have normal systolic pump function and are commonly categorized as suffering from diastolic heart failure. The left ventricle (LV) remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions, which in turn can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element (FE) model was customized to geometric data segmented from in vivo tagged magnetic resonance images (MRI) data and myofibre orientation derived from ex vivo diffusion tensor MRI (DTMRI) of a canine heart using nonlinear finite element fitting techniques. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion in each voxel of a DTMRI directly corresponds to the local myocardial fibre orientation. Due to differences in myocardial geometry between in vivo and ex vivo imaging, myofibre orientations were mapped into the geometric FE model using host mesh fitting (a free form deformation technique). Pressure recordings, temporally synchronized to the tagging data, were used as the loading constraints to simulate the LV deformation during diastole. Simulation of diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. Integrated physiological modelling of this kind will allow more insight into mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction under pathological conditions.

Mechanical Ventilation–associated Lung Fibrosis in Acute Respiratory Distress Syndrome A Significant Contributor to Poor Outcome

PubMed Central

Cabrera-Benitez, Nuria E.; Laffey, John G.; Parotto, Matteo; Spieth, Peter M.; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S.

2016-01-01

One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. The role of mechanical stress as an inciting factor for lung fibrosis versus its role in lung homeostasis and the restoration of normal pulmonary parenchymal architecture is poorly understood. In this review, the authors explore recent advances in the field of pulmonary fibrosis in the context of acute respiratory distress syndrome, concentrating on its relevance to the practice of mechanical ventilation, as commonly applied by anesthetists and intensivists. The authors focus the discussion on the thesis that mechanical ventilation—or more specifically, that ventilator-induced lung injury—may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress–induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis. PMID:24732023

Mechanical ventilation-associated lung fibrosis in acute respiratory distress syndrome: a significant contributor to poor outcome.

PubMed

Cabrera-Benitez, Nuria E; Laffey, John G; Parotto, Matteo; Spieth, Peter M; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S

2014-07-01

One of the most challenging problems in critical care medicine is the management of patients with the acute respiratory distress syndrome. Increasing evidence from experimental and clinical studies suggests that mechanical ventilation, which is necessary for life support in patients with acute respiratory distress syndrome, can cause lung fibrosis, which may significantly contribute to morbidity and mortality. The role of mechanical stress as an inciting factor for lung fibrosis versus its role in lung homeostasis and the restoration of normal pulmonary parenchymal architecture is poorly understood. In this review, the authors explore recent advances in the field of pulmonary fibrosis in the context of acute respiratory distress syndrome, concentrating on its relevance to the practice of mechanical ventilation, as commonly applied by anesthetists and intensivists. The authors focus the discussion on the thesis that mechanical ventilation-or more specifically, that ventilator-induced lung injury-may be a major contributor to lung fibrosis. The authors critically appraise possible mechanisms underlying the mechanical stress-induced lung fibrosis and highlight potential therapeutic strategies to mitigate this fibrosis.

Tibiofemoral contact mechanics following posterior root of medial meniscus tear, repair, meniscectomy, and allograft transplantation.

PubMed

Kim, Jin Goo; Lee, Yong Seuk; Bae, Tae Soo; Ha, Jeong Ku; Lee, Dong Hoon; Kim, Young Jae; Ra, Ho Jong

2013-09-01

The purposes of this study were to evaluate the effect on tibiofemoral contact mechanics of repair of the posterior root of the medial meniscus and the effect of meniscal allograft transplantation (MAT) with medial collateral ligament (MCL) release at different flexion angles. Ten fresh-frozen human cadaveric knees (five pairs) were used. A digital pressure sensor was inserted by capsulotomy, and experiments were performed serially under the following six conditions, that is, with an intact medial meniscus (normal controls), with a root tear, after root repair, after total meniscectomy, after MAT, and after MAT plus MCL release. During each experiment, knees were positioned at 0°, 30°, 60°, and 90° of flexion, and peak pressure (kPa) and contact area (cm2) were measured. At 0° of flexion, contact pressure did not differ among the six experimental settings. However, at 30° and 60° of flexion, contact pressure differed significantly between root tear and root repair specimens (p = 0.04 and 0.03, respectively), and between total meniscectomy and MAT specimens (p = 0.02 and 0.03, respectively). On the other hand, mean contact pressures were different between normal (476.7 ± 473.1 and 573.3 ± 479.1 kPa) and root repair (575.7 ± 357.8 and 598.6 ± 415.8), and between normal and MAT (635.7 ± 437.4 and 674.3 ± 533.2). At 0°, 30°, 60°, and 90° of flexion, contact areas differed significantly between normal and total meniscectomy specimens (p = 0.02, 0.01, 0.02, and 0.02, respectively), and between MAT and total meniscectomy specimens (p = 0.03, 0.02, 0.02, and 0.03, respectively). Contact areas differed significantly between root tear and root repair specimens at 60° of flexion (p = 0.04), and between normal control and root repair specimens at 60° and 90° of flexion (p = 0.03 and 0.04, respectively). The effects of MAT plus MCL release on contact mechanics were not different from the effects of MAT alone (n.s.). Both meniscal root repair and transplantation of meniscus improved contact mechanics, but it did not appear that repair of the meniscal root or transplantation of meniscus restores the biomechanical function back to normal level. The MAT plus MCL release was similar to those after MAT alone. Therefore, it is better to preserve meniscus and MCL release could be done during the MAT.

Failure and fatigue characteristics of adhesive athletic tape.

PubMed

Bragg, Richard W; Macmahon, John M; Overom, Erin K; Yerby, Scott A; Matheson, Gordon O; Carter, Dennis R; Andriacchi, Thomas P

2002-03-01

Athletic tape has been commonly reported to lose much of its structural support after 20 min of exercise. Although many studies have addressed the functional performance characteristics of athletic tape, its mechanical properties are poorly understood. This study examines the failure and fatigue properties of several commonly used athletic tapes. A Web-based survey of professional sports trainers was used to select the following three tapes for the study: Zonas (Johnson & Johnson), Leukotape (Beiersdorf), and Jaylastic (Jaybird & Mais). Using a hydraulic material testing system (MTS), eight samples of each tape were compared in three different mechanical tests: load-to-failure, fatigue testing under load control, and fatigue testing under displacement control. Differences in tape microstructure were used to interpret the results of the mechanical tests. Significant differences (P < 0.001) in failure load, elongation at failure, and stiffness were found from failure tests. Significant differences were also found (P < 0.001) in fatigue behavior under both modes of control. As a representative example, in one normalized displacement control fatigue test after 20 min of cycling, 21% (Zonas), 29% (Leukotape), and 57% (Jaylastic) of the mechanical support was lost. After cycling, all tapes loaded to failure showed increased stiffness (P < 0.001), indicating significant energy absorption during cycling. Observed differences in the tapes' microstructure were qualitatively consistent with the measured differences in their mechanical properties. In understanding the shortcomings of currently available tapes, the results of these tests can now be used as benchmarks with which to compare and develop future tape designs. Ultimately, these improved tapes should reduce ankle injuries among athletes.

Is eye damage caused by stereoscopic displays?

NASA Astrophysics Data System (ADS)

Mayer, Udo; Neumann, Markus D.; Kubbat, Wolfgang; Landau, Kurt

2000-05-01

A normal developing child will achieve emmetropia in youth and maintain it. Thereby cornea, lens and axial length of the eye grow astonishingly coordinated. In the last years research has evidenced that this coordinated growing process is a visually controlled closed loop. The mechanism has been studied particularly in animals. It was found that the growth of the axial length of the eyeball is controlled by image focus information from the retina. It was shown that maladjustment can occur by this visually-guided growth control mechanism that result in ametropia. Thereby it has been proven that e.g. short-sightedness is not only caused by heredity, but is acquired under certain visual conditions. It is shown that these conditions are similar to the conditions of viewing stereoscopic displays where the normal accommodation convergence coupling is disjoint. An evaluation is given of the potential of damaging the eyes by viewing stereoscopic displays. Concerning this, different viewing methods for stereoscopic displays are evaluated. Moreover, clues are given how the environment and display conditions shall be set and what users shall be chosen to minimize the risk of eye damages.

Application of laser therapy in the treatment of brain ischemia

NASA Astrophysics Data System (ADS)

Zalesskaya, G. A.; Nechipurenko, N. I.; Musienko, J. I.; Kuchinsky, A. V.

2007-06-01

Intravenous laser irradiation of blood (ILIB) by helium-neon laser (HNL) with λ=632.8 nm, 2.5-4.5 mW at the light guide outlet was employed to investigate ILIB influence on blood oxygen transport (BOT), hydro-ion balance for normal rabbits and after modeling of local ischemia of brain (LIB). Marked improvement of disturbances typical for ischemia was revealed for both hydro-ion balance characteristics and BOT parameters such as oxygen tension (p vO II), oxygen hemoglobin saturation (s vO II), p vO II of blood under its 50% saturation by O II (p50) and tendency was found to their normalization. To identify the molecular photoacceptors and the mechanisms of primary photoreactions the spectral data were used both in visible and infrared regions. On the basis of spectral analysis hemoglobin was discussed as a possible photoacceptor when blood is irradiated with HNL radiation. Variations in the redox properties of respiratory chain components were considered as primary mechanisms of light action on photoacceptor molecules that initiated a cascade of secondary reactions controlling cellular homeostasis parameters.

Forced Normalization: Antagonism Between Epilepsy and Psychosis.

PubMed

Kawakami, Yasuhiko; Itoh, Yasuhiko

2017-05-01

The antagonism between epilepsy and psychosis has been discussed for a long time. Landolt coined the term "forced normalization" in the 1950s to describe psychotic episodes associated with the remission of seizures and disappearance of epileptiform activity on electroencephalograms in individuals with epilepsy. Since then, neurologists and psychiatrists have been intrigued by this phenomenon. However, although collaborative clinical studies and basic experimental researches have been performed, the mechanism of forced normalization remains unknown. In this review article, we present a historical overview of the concept of forced normalization, and discuss potential pathogenic mechanisms and clinical diagnosis. We also discuss the role of dopamine, which appears to be a key factor in the mechanism of forced normalization. Copyright © 2017 Elsevier Inc. All rights reserved.

Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

PubMed Central

Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-01-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

Stress path dependent hydromechanical behaviour of heterogeneous carbonate rock

NASA Astrophysics Data System (ADS)

Gland, N.; Dautriat, J.; Dimanov, A.; Raphanel, J.

2010-06-01

The influence of stress paths, representative of reservoir conditions, on the hydromechanical behavior of a moderately heterogeneous carbonate has been investigated. Multiscale structural heterogeneities, common for instance in carbonate rocks, can strongly alter the mechanical response and significantly influence the evolution of flow properties with stress. Using a triaxial cell, the permeability evolutions during compression and the effects of brittle (fracture) and plastic (pore collapse) deformations at yield, were measured. A strong scattering was observed on the mechanical response both in term of compressibility and failure threshold. Using the porosity scaling predicted by an adapted effective medium theory (based on crack growth under Hertzian contact), we have rescaled the critical pressures by the normalized porosity deviation. This procedure reduces efficiently the scattering, revealing in the framework of proportional stress path loading, a linear relation between the critical pressures and the stress path parameter through all the deformation regimes. It leads to a new formulation for the critical state envelope in the 'mean stress, deviatoric stress' diagram. The attractive feature of this new yield envelope formulation relies on the fact that only the two most common different mechanical tests 'Uniaxial Compression' and 'Hydrostatic Compression', are needed to define entirely the yield envelope. Volumic strains and normalized permeabilities are finally mapped in the stresses diagram and correlated.

Behavior of B-type natriuretic peptide during mechanical ventilation and spontaneous breathing after extubation.

PubMed

Principi, T; Falzetti, G; Elisei, D; Donati, A; Pelaia, P

2009-04-01

The behavior of B-type natriuretic peptide (BNP) is assessed during mechanical ventilation (MV) and spontaneous breathing after extubation in critical patients. Thirty patients admitted in the Intensive Care Unit (ICU) were enrolled. BNP, fluid balance (FB), airway pressure (AP) and dobutamine infusion needing (DP) were registered in three stages: T0, admission to ICU; T1, before extubation; T2, 24 h after extubation. Patients with congestive heart failure (CHF) had BNP values higher than other patients. The value of BNP during MV was greater than normal in all patients. The cut-off to discriminate patients with heart failure during MV was 286 pgxmL(-1)(sensitivity: 86%; specificity: 90%). The increase of BNP during MV directly correlated with FB and inversely correlated with AP and DP. The plasmatic level of BNP remained higher than normal values 24 h after extubation. The underlying disease of an ICU patient seems to play a relevant role for BNP production and is probably linked to different aspects of therapeutic approach required by the patient. Our data suggest a cut-off value of BNP higher than the usual is necessary to discriminate mechanically-ventilated patients without CHF. This study should be repeated with an enlarged population.

Excitatory, inhibitory and facilitatory frequency response areas in the inferior colliculus of hearing impaired mice.

PubMed

Felix, Richard A; Portfors, Christine V

2007-06-01

Individuals with age-related hearing loss often have difficulty understanding complex sounds such as basic speech. The C57BL/6 mouse suffers from progressive sensorineural hearing loss and thus is an effective tool for dissecting the neural mechanisms underlying changes in complex sound processing observed in humans. Neural mechanisms important for processing complex sounds include multiple tuning and combination sensitivity, and these responses are common in the inferior colliculus (IC) of normal hearing mice. We examined neural responses in the IC of C57Bl/6 mice to single and combinations of tones to examine the extent of spectral integration in the IC after age-related high frequency hearing loss. Ten percent of the neurons were tuned to multiple frequency bands and an additional 10% displayed non-linear facilitation to the combination of two different tones (combination sensitivity). No combination-sensitive inhibition was observed. By comparing these findings to spectral integration properties in the IC of normal hearing CBA/CaJ mice, we suggest that high frequency hearing loss affects some of the neural mechanisms in the IC that underlie the processing of complex sounds. The loss of spectral integration properties in the IC during aging likely impairs the central auditory system's ability to process complex sounds such as speech.

Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

PubMed Central

Pan, Zhi; Avila, Andrew; Gollahon, Lauren

2014-01-01

Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis. PMID:24549172

Cooperation between brain and islet in glucose homeostasis and diabetes

PubMed Central

Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

2014-01-01

Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

Oligosilylarylnitrile: The Thermoresistant Thermosetting Resin with High Comprehensive Properties.

PubMed

Wang, Mingcun; Ning, Yi

2018-04-11

One of the highest thermoresistant thermosetting resins ever studied so far, oligosilylarylnitrile resin, was investigated first in this study. Oligosilylarylnitrile was synthesized by lithium-reduced Wurtz-Fittig condensation reaction, and the prepared viscous resin exhibited moderate rheological behaviors while heated purely or together with 20% polysilazane as a cross-linking agent. The thermal curing temperatures were found by differential scanning calorimetry at 268 °C (pure) and 158 °C (with the polysilazane cross-linking agent), which is comparably close to that of polysilylarylacetylene resin (normally at 220-250 °C) but much lower than those of polyimide and phthalonitrile resins (normally >300 °C), indicating the admirable material processability of oligosilylnitrile. The cured oligosilylarylnitrile resins have extremely high thermal resistance, indicated by the results of thermogravimetric analysis (the mass residue at 800 °C is >90% under N 2 ) and dynamic mechanical analysis (the glass-transition temperature is >420 °C). The mechanical property of the oligosilylarylnitrile-matrixed silica-cloth reinforced laminate is comparably close to those of polyimide and phthalonitrile but much higher than that of polysilylarylacetylene, indicating the enviable thermal and mechanical properties of oligosilylnitrile. Thus, among the high-temperature resins ever studied so far, the oligosilylarylnitrile resin was found to have the almost best comprehensive characteristics of processability and properties.

A self-photoprotection mechanism helps Stipa baicalensis adapt to future climate change

PubMed Central

Song, Xiliang; Zhou, Guangsheng; Xu, Zhenzhu; Lv, Xiaomin; Wang, Yuhui

2016-01-01

We examined the photosynthetic responses of Stipa baicalensis to relative long-term exposure (42 days) to the predicted elevated temperature and water availability changes to determine the mechanisms through which the plant would acclimate to future climate change. Two thermal regimes (ambient and +4 °C) and three irrigation levels (partial, normal and excess) were used in environmental control chambers. The gas exchange parameters, light response curves and A/Ci curves were determined. The elevated temperature and partial irrigation reduced the net photosynthetic rate due to a limitation in the photosynthetic capacity instead of the intercellular CO2 concentration. Partial irrigation decreased Rubisco activation and limited RuBP regeneration. The reduction in Vcmax increased with increasing temperature. Excess irrigation offset the negative effect of drought and led to a partial recovery of the photosynthetic capacity. Although its light use efficiency was restricted, the use of light and dark respiration by Stipa baicalensis was unchanged. We concluded that nonstomatal limitation was the primary reason for photosynthesis regulation in Stipa baicalensis under relative long-term climate change conditions. Although climate change caused reductions in the light use efficiency and photosynthetic rate, a self-photoprotection mechanism in Stipa baicalensis resulted in its high ability to maintain normal live activities. PMID:27161934

Stress granule formation via ATP depletion-triggered phase separation

NASA Astrophysics Data System (ADS)

Wurtz, Jean David; Lee, Chiu Fan

2018-04-01

Stress granules (SG) are droplets of proteins and RNA that form in the cell cytoplasm during stress conditions. We consider minimal models of stress granule formation based on the mechanism of phase separation regulated by ATP-driven chemical reactions. Motivated by experimental observations, we identify a minimal model of SG formation triggered by ATP depletion. Our analysis indicates that ATP is continuously hydrolysed to deter SG formation under normal conditions, and we provide specific predictions that can be tested experimentally.

The cell biology of polycystic kidney disease

PubMed Central

Chapin, Hannah C.

2010-01-01

Polycystic kidney disease is a common genetic disorder in which fluid-filled cysts displace normal renal tubules. Here we focus on autosomal dominant polycystic kidney disease, which is attributable to mutations in the PKD1 and PKD2 genes and which is characterized by perturbations of renal epithelial cell growth control, fluid transport, and morphogenesis. The mechanisms that connect the underlying genetic defects to disease pathogenesis are poorly understood, but their exploration is shedding new light on interesting cell biological processes and suggesting novel therapeutic targets. PMID:21079243

[Comparative study of unidirectional transducers for invasive blood pressure monitoring].

PubMed

Matzek, F; Boenick, U; Frucht, U; Schroeder, P M

1989-03-01

This paper reports on the results of a study in which the offset drift, sensitivity error and drift, as well as the linearity error of six DPT's were investigated under normal ambient conditions and varying conditions of temperature, light, operating time and variation of supply voltage. In addition, the dynamic response, and the influence of storage at extreme temperatures, and resterilisation, was examined. The electrical and mechanical safety/reliability of DPT's was also investigated. The results obtained are compared.

Melt layer erosion of metallic armour targets during off-normal events in tokamaks

NASA Astrophysics Data System (ADS)

Bazylev, B.; Wuerz, H.

2002-12-01

Melt layer erosion by melt motion is the dominating erosion mechanism for metallic armours under high heat loads. A 1-D fluid dynamics simulation model for calculation of melt motion was developed and validated against experimental results for tungsten from the e-beam facility JEBIS and beryllium from the e-beam facility JUDITH. The driving force in each case is the gradient of the surface tension. Due to the high velocity which develops in the Be melt considerable droplet splashing occurs.

Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells.

PubMed

Gudasheva, T A; Koliasnikova, K N; Antipova, T A; Seredenin, S B

2016-07-01

It was shown for the first time that the endogenous cyclic dipeptide cycloprolylglycine (CPG) at concentrations of 10(-7) and 10(-3) M and piracetam at a concentration of 10(-3) M increased the content of brainderived neurotrophic factor (BDNF) in the culture of neuronal cells in normal state and under conditions of glutamate and 6-oxydopamine neurotoxicity. This may indicate the possible involvement of BDNF in the mechanism of action of neuropeptide CPG and piracetam.

Role of Endoplasmic Reticulum Stress in Metabolic Disease and Other Disorders

PubMed Central

Ozcan, Lale; Tabas, Ira

2012-01-01

Perturbations in the normal functions of the endoplasmic reticulum (ER) trigger a signaling network that coordinates adaptive and apoptotic responses. There is accumulating evidence implicating prolonged ER stress in the development and progression of many diseases, including neurodegeneration, atherosclerosis, type 2 diabetes, liver disease, and cancer. With the improved understanding of the underlying molecular mechanisms, therapeutic interventions that target the ER stress response would be potential strategies to treat various diseases driven by prolonged ER stress. PMID:22248326

Identification of Pro-Differentiation p53 Target Genes and Evaluation of Expression in Normal and Malignant Mammary Gland

DTIC Science & Technology

2009-04-01

progenitor cells ’ ability to survive under non-attachment culture conditions, which is composed of primary mammoshpere and secondary mammosphere. Both... cell lineages in early mouse development depend on SOX2 function. Genes Dev, 17: 126-140, 2003 8. Chambers, I., Colby, D., Robertson, M., Nichols, J...Rivett, D., Jones, K., and Dalton, S. LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development , 132: 885-896

Moisture-Induced Delamination Video of an Oxidized Thermal Barrier Coating

NASA Technical Reports Server (NTRS)

Smialek, James L.; Zhu, Dongming; Cuy, Michael D.

2008-01-01

PVD TBC coatings were thermally cycled to near-failure at 1150 C. Normal failure occurred after 200-300 1-hr cycles with only moderate weight gains (0.5 mg/cm2). Delamination and buckling was often delayed until well after cooldown (desktop spallation), but could be instantly induced by the application of water drops, as shown in an accompanying video-recording. Moisture therefore plays a primary role in delayed desktop TBC failure. Hydrogen embrittlement is proposed as the underlying mechanism.

Attention and normalization circuits in macaque V1

PubMed Central

Sanayei, M; Herrero, J L; Distler, C; Thiele, A

2015-01-01

Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. PMID:25757941

Effect of Test Parameters on the Friction Behaviour of Anodized Aluminium Alloy

PubMed Central

Khalladi, A.; Elleuch, K.; De-Petris Wery, M.; Ayedi, H. F.

2014-01-01

The tribological behaviour of anodic oxide layer formed on Al5754, used in automotive applications, was investigated against test parameters. The friction coefficient under different normal loads, sliding speeds, and oxide thicknesses was studied using a pin on disc tribometer. Results show that the increase of load and sliding speed increase the friction coefficient. The rise of contact pressure and temperature seems to cause changes in wear mechanism. Glow-discharge optical emission spectroscopy (GDOES) was used to investigate the chemical composition of the oxide layer. Morphology and composition of the wear tracks were analyzed by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). On the basis of these characterization techniques, a wear mechanism was proposed. The observed mechanical properties can be related to the morphology and the chemical composition of the layer. PMID:27437452

Lineage plasticity-mediated therapy resistance in prostate cancer.

PubMed

Blee, Alexandra M; Huang, Haojie

2018-06-12

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

The effect of an external mechanical compression on in vivo optical properties of human skin

NASA Astrophysics Data System (ADS)

Nakhaeva, I. A.; Mohammed, M. R.; Zyuryukina, O. A.; Sinichkin, Yu. P.

2014-09-01

We have studied the influence of an external mechanical compression on diffuse reflection spectra of skin tissue under in vivo conditions. An analysis of these spectra based on the diffusion approximation of the radiation transfer theory has allowed us to find that the application of the external compression weakens absorbing and scattering properties of skin tissue. After the removal of the compression, the recovery time of the skin tissue (on the order of 1 h) considerably exceeds the stabilization time of its parameters after application of external mechanical compression (several minutes). In this case, at the initial moment of time after the removal of the compression, the fullness of blood vessels and the degree of oxygenation of blood hemoglobin in the skin tissue increase considerably compared to normal skin.

A biomechanical model of the craniomandibular complex and cervical spine based on the inverted pendulum.

PubMed

Gillies, G T; Broaddus, W C; Stenger, J M; Taylor, A G

1998-01-01

The head and neck constitute an inverted pendulum that is stabilized during consciousness by neuromuscular restoring forces. An analysis of the dynamics of this inverted pendulum suggests that the mechanics of the mandible and temporomandibular joint might couple into those of the pendulum's stabilization process. In this article, physical principles of the inverted pendulum model as these apply to the head and neck are explored, and the authors describe implications of mandibular mechanics for the forces acting on the head and neck at equilibrium. This novel application of the inverted pendulum model predicts that alteration or pathology of temporomandibular mechanics would lead to perturbations of the normal forces acting in the head and neck. Under certain circumstances, these perturbations could be expected to contribute to symptoms and result in additional or accelerated degenerative effects.

The Randle cycle revisited: a new head for an old hat

PubMed Central

Hue, Louis; Taegtmeyer, Heinrich

2009-01-01

In 1963, Lancet published a paper by Randle et al. that proposed a “glucose-fatty acid cycle” to describe fuel flux between and fuel selection by tissues. The original biochemical mechanism explained the inhibition of glucose oxidation by fatty acids. Since then, the principle has been confirmed by many investigators. At the same time, many new mechanisms controlling the utilization of glucose and fatty acids have been discovered. Here, we review the known short- and long-term mechanisms involved in the control of glucose and fatty acid utilization at the cytoplasmic and mitochondrial level in mammalian muscle and liver under normal and pathophysiological conditions. They include allosteric control, reversible phosphorylation, and the expression of key enzymes. However, the complexity is formidable. We suggest that not all chapters of the Randle cycle have been written. PMID:19531645

Anti-tumor effects of osthole on ovarian cancer cells in vitro.

PubMed

Jiang, Guoqiang; Liu, Jia; Ren, Baoyin; Tang, Yawei; Owusu, Lawrence; Li, Man; Zhang, Jing; Liu, Likun; Li, Weiling

2016-12-04

Cnidium monnieri (L.) Cusson is a commonly used traditional Chinese medicine to treat gynecological disease in some countries. Osthole, an active O-methylated coumadin isolated from Cnidium monnieri (L.) Cusson, has been shown to induce various beneficial biochemical effects such as anti-seizure and anti-inflammatory effects. However, the anti-tumor mechanism of osthole is not well known. Here, we show that osthole inhibited the proliferation and migration of two widely used ovarian cancer cell lines, A2780 and OV2008 cells, in a dose-dependent manner. The study investigated the molecular mechanisms underlying ovarian cancer cells proliferation, apoptosis, cell cycle arrest and migration triggered by osthole. Ovarian cancer cell lines A2780, OV2008 and normal ovarian cell line IOSE80 were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry assays were performed to confirm apoptosis and cell cycle. We employed wound healing and transwell assays to delineate invasive and migratory potential triggered by osthole. MTT assays indicated that cell viability significantly decreased in ovarian cancer cells treated with osthole without effect on normal ovarian cells. Flow cytometric analysis revealed that osthole suppressed cells proliferation by promoting G2/M arrest and inducing apoptosis. The underlying mechanisms involved were regulation of the relative apoptotic protein Bcl-2, Bax and Caspase 3/9. In addition, wound healing and transwell assays revealed that the migratory potential and activity of matrix metalloproteinase MMP-2 and MMP-9 were markedly inhibited when cells were exposed to osthole. Our findings suggested that osthole has the potential to be used in novel anti-cancer therapeutic formulations for ovarian cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Good news–bad news: the Yin and Yang of immune privilege in the eye

PubMed Central

Forrester, John V.; Xu, Heping

2012-01-01

The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialized function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because its natural defenses are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood–ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics, and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumor-related IP can combine to permit extensive tumor growth and increased risk of metastasis thus threatening the survival of the host. PMID:23230433

A mathematical model of cancer stem cell driven tumor initiation: implications of niche size and loss of homeostatic regulatory mechanisms.

PubMed

Gentry, Sara N; Jackson, Trachette L

2013-01-01

Hierarchical organized tissue structures, with stem cell driven cell differentiation, are critical to the homeostatic maintenance of most tissues, and this underlying cellular architecture is potentially a critical player in the development of a many cancers. Here, we develop a mathematical model of mutation acquisition to investigate how deregulation of the mechanisms preserving stem cell homeostasis contributes to tumor initiation. A novel feature of the model is the inclusion of both extrinsic and intrinsic chemical signaling and interaction with the niche to control stem cell self-renewal. We use the model to simulate the effects of a variety of types and sequences of mutations and then compare and contrast all mutation pathways in order to determine which ones generate cancer cells fastest. The model predicts that the sequence in which mutations occur significantly affects the pace of tumorigenesis. In addition, tumor composition varies for different mutation pathways, so that some sequences generate tumors that are dominated by cancerous cells with all possible mutations, while others are primarily comprised of cells that more closely resemble normal cells with only one or two mutations. We are also able to show that, under certain circumstances, healthy stem cells diminish due to the displacement by mutated cells that have a competitive advantage in the niche. Finally, in the event that all homeostatic regulation is lost, exponential growth of the cancer population occurs in addition to the depletion of normal cells. This model helps to advance our understanding of how mutation acquisition affects mechanisms that influence cell-fate decisions and leads to the initiation of cancers.

A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall.

PubMed

Mei, Ling; Chen, Jin; Zong, Liang; Zhu, Yan; Liang, Chun; Jones, Raleigh O; Zhao, Hong-Bo

2017-12-01

Digenic Connexin26 (Cx26, GJB2) and Cx30 (GJB6) heterozygous mutations are the second most frequent cause of recessive deafness in humans. However, the underlying deafness mechanism remains unclear. In this study, we created different double Cx26 and Cx30 heterozygous (Cx26 +/- /Cx30 +/- ) mouse models to investigate the underlying pathological changes and deafness mechanism. We found that double Cx26 +/- /Cx30 +/- heterozygous mice had hearing loss. Endocochlear potential (EP), which is a driving force for hair cells producing auditory receptor current, was reduced. However, unlike Cx26 homozygous knockout (Cx26 -/- ) mice, the cochlea in Cx26 +/- /Cx30 +/- mice displayed normal development and had no apparent hair cell degeneration. Gap junctions (GJs) in the cochlea form two independent networks: the epithelial cell GJ network in the organ of Corti and the connective tissue GJ network in the cochlear lateral wall. We further found that double heterozygous deletion of Cx26 and Cx30 in the epithelial cells did not reduce EP and had normal hearing, suggesting that Cx26 +/- /Cx30 +/- may mainly impair gap junctional functions in the cochlear lateral wall and lead to EP reduction and hearing loss. Most of Cx26 and Cx30 in the cochlear lateral wall co-expressed in the same gap junctional plaques. Moreover, sole Cx26 +/- or Cx30 +/- heterozygous mice had no hearing loss. These data further suggest that digenic Cx26 and Cx30 mutations may impair heterozygous coupling of Cx26 and Cx30 in the cochlear lateral wall to reduce EP, thereby leading to hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic investigations on 8 patients affected by ring 20 chromosome syndrome

PubMed Central

2010-01-01

Background Mosaic Chromosome 20 ring [r(20)] is a chromosomal disorder associated with a rare syndrome characterized by a typical seizure phenotype, a particular electroclinical pattern, cognitive impairment, behavioural problems and absence of a consistent pattern of dysmorphology. The pathogenic mechanism underlying seizures disorders in r(20) syndrome is still unknown. We performed a detailed clinical and genetic study on 8 patients with r(20) chromosome, aimed at detecting the genetic mechanism underlying r(20) syndrome. Methods We submitted 8 subjects with a previous diagnosis of ring 20 chromosome mosaicism to a clinical re-evaluation, followed by cytogenetic, FISH, array-CGH and molecular analyses. The genetic study was also extended to their available parents. Results FISH and array-CGH experiments indicate that cryptic deletions on chromosome 20 are not the cause of the r(20) chromosome associated disease. Moreover, no evidence of chromosome 20 uniparental disomy was found. Analysis of FISH signals given by variant in size alphoid tandem repeats probes on the normal chromosome 20 and the r(20) chromosome in the mosaic carriers suggests that the r(20) chromosome is the same chromosome not circularized in the "normal" cell line. Conclusions Higher percentages of r(20) chromosome cells were observed to be related with precocious age at seizure onset and with resistance to antiepileptic drug treatment. Behavioural problems also seem to be associated with higher percentages of r(20) chromosome cells. Our results suggest that an epigenetic mechanism perturbing the expression of genes close to the telomeric regions, rather than deletion of genes located at the distal 20p and/or 20q regions, may underlie the manifestation of r(20) syndrome. PMID:20939888

Non-enzymatic antioxidant accumulations in BR-deficient and BR-insensitive barley mutants under control and drought conditions.

PubMed

Gruszka, Damian; Janeczko, Anna; Dziurka, Michal; Pociecha, Ewa; Fodor, Jozsef

2017-12-07

Drought is one of the most adverse stresses that affect plant growth and yield. Disturbances in metabolic activity resulting from drought cause overproduction of reactive oxygen species. It is postulated that brassinosteroids (BRs) regulate plant tolerance to the stress conditions, but the underlying mechanisms remain largely unknown. An involvement of endogenous BRs in regulation of the antioxidant homeostasis is not fully clarified either. Therefore, the aim of this study was to elucidate the role of endogenous BRs in regulation of non-enzymatic antioxidants in barley (Hordeum vulgare) under control and drought conditions. The plant material included the 'Bowman' cultivar and a group of semi-dwarf near-isogenic lines (NILs), representing mutants deficient in BR biosynthesis or signaling. In general, accumulations of 11 compounds representing various types of non-enzymatic antioxidants were analyzed under both conditions. The analyses of accumulations of reduced and oxidized forms of ascorbate indicated that the BR mutants contain significantly higher contents of dehydroascorbic acid under drought conditions when compared with the 'Bowman' cultivar. The analysis of glutathione accumulation indicated that under the control conditions the BR-insensitive NILs contained significantly lower concentrations of this antioxidant when compared with the rest of genotypes. Therefore, we postulate that BR sensitivity is required for normal accumulation of glutathione. A complete accumulation profile of various tocopherols indicated that functional BR biosynthesis and signaling are required for their normal accumulation under both conditions. Results of this study provided an insight into the role of endogenous BRs in regulation of the non-enzymatic antioxidant homeostasis. © 2017 Scandinavian Plant Physiology Society.

Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells*

PubMed Central

Hwang, Ji-Sun; Kwon, Mi-Youn; Kim, Kyung-Hong; Lee, Yunkyoung; Lyoo, In Kyoon; Kim, Jieun E.; Oh, Eok-Soo; Han, Inn-Oc

2017-01-01

We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. However, GlcN suppressed NO/iNOS production under high glucose culture conditions. Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. Glucose itself dose dependently increased LPS-induced iNOS expression. LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess. PMID:27927986

Protein S-nitrosylation as a therapeutic target for neurodegenerative diseases

PubMed Central

Nakamura, Tomohiro; Lipton, Stuart A.

2015-01-01

At physiological levels, nitric oxide (NO) contributes to the maintenance of normal neuronal activity and survival, thus serving as an important regulatory mechanism in the central nervous system. In contrast, accumulating evidence suggests that exposure to environmental toxins or the normal aging process can trigger excessive production of reactive oxygen/nitrogen species (such as NO), contributing to the etiology of several neurodegenerative diseases. Here we highlight protein S-nitrosylation, resulting from covalent attachment of an NO group to a cysteine thiol of the target protein, as a ubiquitous effector of NO signaling in both health and disease. We review our current understanding of this redox-dependent posttranslational modification under neurodegenerative conditions, and evaluate how targeting dysregulated protein S-nitrosylation can lead to novel therapeutics. PMID:26707925

Need telomere maintenance? Call 911.

PubMed

Francia, Sofia; Weiss, Robert S; d'Adda di Fagagna, Fabrizio

2007-01-17

"Natura non facit saltum" (nature makes no leap) the Latins used to say, meaning that nature does not like discontinuities. Cells make no exception and indeed any discontinuity in the DNA double helix is promptly detected, triggering an alteration of cell proliferation and an attempt to repair. Yet, linear chromosomes bear DNA ends that are compatible with normal cell proliferation and they escape, under normal conditions, any repair. How telomeres, the chromosomes tips, achieve that is not fully understood. We recently observed that the Rad9/Hus1/Rad1 (911) complex, previously known for its functions in DNA metabolism and DNA damage responses, is constitutively associated with telomeres and plays an important role in their maintenance. Here, we summarize the available data and discuss the potential mechanisms of 911 action at telomeres.

Need telomere maintenance? Call 911

PubMed Central

Francia, Sofia; Weiss, Robert S; d'Adda di Fagagna, Fabrizio

2007-01-01

"Natura non facit saltum" (nature makes no leap) the Latins used to say, meaning that nature does not like discontinuities. Cells make no exception and indeed any discontinuity in the DNA double helix is promptly detected, triggering an alteration of cell proliferation and an attempt to repair. Yet, linear chromosomes bear DNA ends that are compatible with normal cell proliferation and they escape, under normal conditions, any repair. How telomeres, the chromosomes tips, achieve that is not fully understood. We recently observed that the Rad9/Hus1/Rad1 (911) complex, previously known for its functions in DNA metabolism and DNA damage responses, is constitutively associated with telomeres and plays an important role in their maintenance. Here, we summarize the available data and discuss the potential mechanisms of 911 action at telomeres. PMID:17229321

Effectiveness of surgical reconstruction to restore radiocarpal joint mechanics after scapholunate ligament injury: an in vivo modeling study.

PubMed

Johnson, Joshua E; Lee, Phil; McIff, Terence E; Toby, E Bruce; Fischer, Kenneth J

2013-05-31

Disruption of the scapholunate ligament can cause a loss of normal scapholunate mechanics and eventually lead to osteoarthritis. Surgical reconstruction attempts to restore scapholunate relationship show improvement in functional outcomes, but postoperative effectiveness in restoring normal radiocarpal mechanics still remains a question. The objective of this study was to investigate the benefits of surgical repair by observing changes in contact mechanics on the cartilage surface before and after surgical treatment. Six patients with unilateral scapholunate dissociation were enrolled in the study, and displacement driven magnetic resonance image-based surface contact modeling was used to investigate normal, injured and postoperative radiocarpal mechanics. Model geometry was acquired from images of wrists taken in a relaxed position. Kinematics were acquired from image registration between the relaxed images, and images taken during functional loading. Results showed a trend for increase in radiocarpal contact parameters with injury. Peak and mean contact pressures significantly decreased after surgery in the radiolunate articulation and there were no significant differences between normal and postoperative wrists. Results indicated that surgical repair improves contact mechanics after injury and that contact mechanics can be surgically restored to be similar to normal. This study provides novel contact mechanics data on the effects of surgical repair after scapholunate ligament injury. With further work, it may be possible to more effectively differentiate between treatments and degenerative changes based on in vivo contact mechanics data. Copyright © 2013 Elsevier Ltd. All rights reserved.

Vibrational Spectroscopic Studies of Reduced-Sensitivity RDX under Static Compression

NASA Astrophysics Data System (ADS)

Wong, Chak

2005-07-01

Explosives formulations with Reduced- Sensitivity RDX showed reduced shock sensitivity using NOL Large Scale Gap Test, compared with similar formulations using normal RDX. Molecular processes responsible for the reduction of sensitivity are unknown and are crucial for formulation development. Vibrational spectroscopy at static high pressure may shed light to the mechanisms responsible for the reduced shock sensitivity as shown by the NOL Large Scale Gap Test. SIRDX, a form of Reduced- Sensitivity RDX, was subjected to static compression at ambient temperature in a Merrill-Bassett sapphire cell from ambient to about 6 GPa. The spectroscopic techniques used were Raman and Fourier-Transformed IR (FTIR). The pressure dependence of the Raman mode frequencies of SIRDX was determined and compared with that of normal RDX. The behavior of SIRDX near the pressure at which normal RDX, at ambient temperature, undergoes a phase transition from the α to the γ polymorph will be presented. Implications to the reduction in sensitivity will be discussed.

Nrf2: bane or blessing in cancer?

PubMed

Xiang, MingJun; Namani, Akhileshwar; Wu, ShiJun; Wang, XiaoLi

2014-08-01

The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element pathway serves a major function in endogenous cytoprotection in normal cells. Nrf2 is a transcription factor that mainly regulates the expression of a wide array of genes that produce the antioxidants and other proteins responsible for the detoxification of xenobiotics and reactive oxygen species. Nrf2 mediates the chemoprevention of cancer in normal cells. Growing body of evidence suggests that Nrf2 is not only involved in the chemoprevention of normal cells but also promotes the growth of cancer cells. However, the mechanism underlying the function of Nrf2 in oncogenesis and tumor protection in cancer cells remains unclear and thus requires further study. This review aims to rationalize the existing functions of Nrf2 in chemoprevention and tumorigenesis, as well as the somatic mutations of Nrf2 and Keap1 in cancer and Nrf2 cross talk with miRNAs. This review also discusses the future challenges in Nrf2 research.

The spleen can influence the metastasis of AH130 hepatoma cells in rats.

PubMed

Toyonaga, M; Hiraoka, T; Tanaka, H; Miyauchi, Y

1993-06-01

The effect of pathophysiological conditions due to disturbance of the spleen is still unclear. We studied the effects of splenectomy in normal and methylcellulose-induced hypersplenic rats on the development of pulmonary metastases created by intravenous injection of ascites containing AH130 hepatoma cells from male Hos-Donryu rats. Growth of metastatic lesions in the lung was not affected by splenectomy in normal rats, but was increased by splenectomy in hypersplenic rats. Overall, there were fewer pulmonary metastases in rats with hypersplenism, but after splenectomy rats with hypersplenism had a significantly greater number of metastases than did normal rats. The metastases rate correlated somewhat with changes in the blood coagulation and T lymphocyte profile. There is a relationship between the spleen and formation of metastases in cancer. Formation of metastases in the lung was affected most by splenectomy in hypersplenism. To elucidate the mechanism by which metastases are formed in the lung under these pathologic conditions, further studies on the exact role of the spleen are required.

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

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

Marks, Shawn M.; Lockhart, Samuel N.; Baker, Suzanne L.

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turnmore » associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.« less

[Role of placental apoptosis in fetal growth restriction].

PubMed

Liu, Yuan; Gao, Peng; Xie, Yingbo; Wang, Shuyun; Dai, Minsheng; Jiang, Sen

2002-12-01

To determine the relationship of placental cellular apoptosis and pathophysiology of fetal growth restriction (FGR). Placental samples were obtained from 18 pregnancies complicated by FGR and 14 normal pregnancies. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and transmission electron microscopy were used to confirm the occurrence of apoptosis. In FGR group the placental apoptosis rate was (n = 18) 12.1 per thousand, the average placental weight was (236 +/- 24) g, the average birth weight was (2,071 +/- 428) g; In normal group (n = 14), the placental apoptosis rate was 7.3 per thousand, the average placental weight was (354 +/- 63) g, the average birth weight was (3,411 +/- 588) g (P < 0.05). The incidence of apoptosis was significantly higher in placental samples from pregnancies with FGR compared with normal placental samples (P < 0.05). Under transmission election microscopy, apoptosis was obviously compact and the chromatins were formed as mass. These results suggest that apoptosis may play a role in the pathophysiologic mechanisms of FGR.

Black phosphorus as a saturable absorber for generating mode-locked fiber laser in normal dispersion regime

NASA Astrophysics Data System (ADS)

Latiff, A. A.; Rusdi, M. F. M.; Hisyam, M. B.; Ahmad, H.; Harun, S. W.

2016-11-01

This paper reports a few-layer black phosphorus (BP) as a saturable absorber (SA) or phase-locker in generating modelocked pulses from a double-clad ytterbium-doped fiber laser (YDFL). We mechanically exfoliated the BP flakes from BP crystal through a scotch tape, and repeatedly press until the flakes thin and spread homogenously. Then, a piece of BP tape was inserted in the cavity between two fiber connectors end facet. Under 810 mW to 1320 mW pump power, stable mode-locked operation at 1085 nm with a repetition rate of 13.4 MHz is successfully achieved in normal dispersion regime. Before mode-locked operation disappears above maximum pump, the output power and pulse energy is about 80 mW and 6 nJ, respectively. This mode-locked laser produces peak power of 0.74 kW. Our work may validates BP SA as a phase-locker related to two-dimensional nanomaterials and pulsed generation in normal dispersion regime.

Frictional heating processes during laboratory earthquakes

NASA Astrophysics Data System (ADS)

Aubry, J.; Passelegue, F. X.; Deldicque, D.; Lahfid, A.; Girault, F.; Pinquier, Y.; Escartin, J.; Schubnel, A.

2017-12-01

Frictional heating during seismic slip plays a crucial role in the dynamic of earthquakes because it controls fault weakening. This study proposes (i) to image frictional heating combining an in-situ carbon thermometer and Raman microspectrometric mapping, (ii) to combine these observations with fault surface roughness and heat production, (iii) to estimate the mechanical energy dissipated during laboratory earthquakes. Laboratory earthquakes were performed in a triaxial oil loading press, at 45, 90 and 180 MPa of confining pressure by using saw-cut samples of Westerly granite. Initial topography of the fault surface was +/- 30 microns. We use a carbon layer as a local temperature tracer on the fault plane and a type K thermocouple to measure temperature approximately 6mm away from the fault surface. The thermocouple measures the bulk temperature of the fault plane while the in-situ carbon thermometer images the temperature production heterogeneity at the micro-scale. Raman microspectrometry on amorphous carbon patch allowed mapping the temperature heterogeneities on the fault surface after sliding overlaid over a few micrometers to the final fault roughness. The maximum temperature achieved during laboratory earthquakes remains high for all experiments but generally increases with the confining pressure. In addition, the melted surface of fault during seismic slip increases drastically with confining pressure. While melting is systematically observed, the strength drop increases with confining pressure. These results suggest that the dynamic friction coefficient is a function of the area of the fault melted during stick-slip. Using the thermocouple, we inverted the heat dissipated during each event. We show that for rough faults under low confining pressure, less than 20% of the total mechanical work is dissipated into heat. The ratio of frictional heating vs. total mechanical work decreases with cumulated slip (i.e. number of events), and decreases with increasing confining pressure and normal stress. Our results suggest that earthquakes are less dispersive under large normal stress. We linked this observation with fault roughness heterogeneity, which also decreases with applied normal stress. Keywords: Frictional heating, stick-slip, carbon, dynamic rupture, fault weakening.

Role of various hormones in photosynthetic responses of green plants under environmental stresses.

PubMed

Poonam; Bhardwaj, Renu; Kaur, Ravdeep; Bali, Shagun; Kaur, Parminder; Sirhindi, Geetika; Thukral, Ashwani K; Ohri, Puja; Vig, Adarsh P

2015-01-01

Environmental stress includes adverse factors like water deficit, high salinity, enhanced temperature and heavy metals etc. These stresses alter the normal growth and metabolic processes of plants including photosynthesis. Major photosynthetic responses under various stresses include inhibition of photosystems (I and II), changes in thylakoid complexes, decreased photosynthetic activity and modifications in structure and functions of chloroplasts etc. Various defense mechanisms are triggered inside the plants in response to these stresses that are regulated by plant hormones or plant growth regulators. These phytohormones include abscisic acid, auxins, cytokinins, ethylene, brassinosteroids, jasmonates and salicylic acid etc. The present review focuses on stress protective effects of plants hormones on the photosynthetic responses.

Triggered intracellular calcium waves in dog and human left atrial myocytes from normal and failing hearts.

PubMed

Aistrup, Gary L; Arora, Rishi; Grubb, Søren; Yoo, Shin; Toren, Benjamin; Kumar, Manvinder; Kunamalla, Aaron; Marszalec, William; Motiwala, Tej; Tai, Shannon; Yamakawa, Sean; Yerrabolu, Satya; Alvarado, Francisco J; Valdivia, Hector H; Cordeiro, Jonathan M; Shiferaw, Yohannes; Wasserstrom, John Andrew

2017-11-01

Abnormal intracellular Ca2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca2+ waves in left atria from normal and failing dog hearts. Intracellular Ca2+ cycling was studied using confocal microscopy during rapid pacing of atrial myocytes (36 °C) isolated from normal and failing canine hearts (ventricular tachypacing model). In normal atrial myocytes (NAMs), Ca2+ waves developed during rapid pacing at rates ≥ 3.3 Hz and immediately disappeared upon cessation of pacing despite high sarcoplasmic reticulum (SR) load. In heart failure atrial myocytes (HFAMs), triggered Ca2+ waves (TCWs) developed at a higher incidence at slower rates. Because of their timing, TCW development relies upon action potential (AP)-evoked Ca2+ entry. The distribution of Ca2+ wave latencies indicated two populations of waves, with early events representing TCWs and late events representing conventional spontaneous Ca2+ waves. Latency analysis also demonstrated that TCWs arise after junctional Ca2+ release has occurred and spread to non-junctional (cell core) SR. TCWs also occurred in intact dog atrium and in myocytes from humans and pigs. β-adrenergic stimulation increased Ca2+ release and abolished TCWs in NAMs but was ineffective in HFAMs making this a potentially effective adaptive mechanism in normals but potentially arrhythmogenic in HF. Block of Ca-calmodulin kinase II also abolished TCWs, suggesting a role in TCW formation. Pharmacological manoeuvres that increased Ca2+ release suppressed TCWs as did interventions that decreased Ca2+ release but these also severely reduced excitation-contraction coupling. TCWs develop during the atrial AP and thus could affect AP duration, producing repolarization gradients and creating a substrate for reentry, particularly in HF where they develop at slower rates and a higher incidence. TCWs may represent a mechanism for the initiation of atrial fibrillation particularly in HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

[Research of anti-aging mechanism of ginsenoside Rg1 on brain].

PubMed

Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

2014-11-01

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.

NFE2 Induces miR-423-5p to Promote Gluconeogenesis and Hyperglycemia by Repressing the Hepatic FAM3A-ATP-Akt Pathway.

PubMed

Yang, Weili; Wang, Junpei; Chen, Zhenzhen; Chen, Ji; Meng, Yuhong; Chen, Liming; Chang, Yongsheng; Geng, Bin; Sun, Libo; Dou, Lin; Li, Jian; Guan, Youfei; Cui, Qinghua; Yang, Jichun

2017-07-01

Hepatic FAM3A expression is repressed under obese conditions, but the underlying mechanism remains unknown. This study determined the role and mechanism of miR-423-5p in hepatic glucose and lipid metabolism by repressing FAM3A expression. miR-423-5p expression was increased in the livers of obese diabetic mice and in patients with nonalcoholic fatty liver disease (NAFLD) with decreased FAM3A expression. miR-423-5p directly targeted FAM3A mRNA to repress its expression and the FAM3A-ATP-Akt pathway in cultured hepatocytes. Hepatic miR-423-5p inhibition suppressed gluconeogenesis and improved insulin resistance, hyperglycemia, and fatty liver in obese diabetic mice. In contrast, hepatic miR-423-5p overexpression promoted gluconeogenesis and hyperglycemia and increased lipid deposition in normal mice. miR-423-5p inhibition activated the FAM3A-ATP-Akt pathway and repressed gluconeogenic and lipogenic gene expression in diabetic mouse livers. The miR-423 precursor gene was further shown to be a target gene of NFE2, which induced miR-423-5p expression to repress the FAM3A-ATP-Akt pathway in cultured hepatocytes. Hepatic NFE2 overexpression upregulated miR-423-5p to repress the FAM3A-ATP-Akt pathway, promoting gluconeogenesis and lipid deposition and causing hyperglycemia in normal mice. In conclusion, under the obese condition, activation of the hepatic NFE2/miR-423-5p axis plays important roles in the progression of type 2 diabetes and NAFLD by repressing the FAM3A-ATP-Akt signaling pathway. © 2017 by the American Diabetes Association.

Molecular mechanisms underlying the protective effects of hydrogen-saturated saline on noise-induced hearing loss.

PubMed

Chen, Liwei; Han, Mingkun; Lu, Yan; Chen, Daishi; Sun, Xuejun; Yang, Shiming; Sun, Wei; Yu, Ning; Zhai, Suoqiang

2017-10-01

This study aimed to explore the molecular mechanism of the protective effects of hydrogen-saturated saline on NIHL. Guinea pigs were divided into three groups: hydrogen-saturated saline; normal saline; and control. For saline administration, the guinea pigs were given daily abdominal injections 3 d before and 1 h before noise exposure. ABR were tested to examine cochlear physiology changes. The changes of 8-hydroxy-desoxyguanosine (8-HOdG), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), intercellular cell adhesion molecule-1 (ICAM-1) and high mobility group box-1 protein (HMGB1) in the cochlea were also examined. The results showed that pre-treatment with hydrogen-saturated saline could significantly attenuate noise-induced hearing loss. The concentration of 8-HOdG was also significantly decreased in the hydrogen-saturated saline group compared with the normal saline group. After noise exposure, the concentrations of IL-1, IL-6, TNF-α, and ICAM-1 in the cochlea of guinea pigs in the hydrogen-saturated saline group were dramatically reduced compared to those in the normal saline group. The concentrations of HMGB-1 and IL-10 in the hydrogen-saturated saline group were significantly higher than in those in the normal saline group immediately and at 7 d after noise exposure. This study revealed for the first time the protective effects of hydrogen-saturated saline on noise-induced hearing loss (NIHL) are related to both the anti-oxidative activity and anti-inflammatory activity.

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

Li, Mo; Nakshatrala, Kalyana; William, Kasper

The objective of this project is to develop a new class of multifunctional concrete materials (MSCs) for extended spent nuclear fuel (SNF) storage systems, which combine ultra-high damage resistance through strain-hardening behavior with distributed multi-dimensional damage self-sensing capacity. The beauty of multifunctional concrete materials is two-fold: First, it serves as a major material component for the SNF pool, dry cask shielding and foundation pad with greatly improved resistance to cracking, reinforcement corrosion, and other common deterioration mechanisms under service conditions, and prevention from fracture failure under extreme events (e.g. impact, earthquake). This will be achieved by designing multiple levels ofmore » protection mechanisms into the material (i.e., ultrahigh ductility that provides thousands of times greater fracture energy than concrete and normal fiber reinforced concrete; intrinsic cracking control, electrochemical properties modification, reduced chemical and radionuclide transport properties, and crack-healing properties). Second, it offers capacity for distributed and direct sensing of cracking, strain, and corrosion wherever the material is located. This will be achieved by establishing the changes in electrical properties due to mechanical and electrochemical stimulus. The project will combine nano-, micro- and composite technologies, computational mechanics, durability characterization, and structural health monitoring methods, to realize new MSCs for very long-term (greater than 120 years) SNF storage systems.« less

Salinity Tolerance Mechanism of Economic Halophytes From Physiological to Molecular Hierarchy for Improving Food Quality

PubMed Central

Xu, Chongzhi; Tang, Xiaoli; Shao, Hongbo; Wang, Hongyan

2016-01-01

Soil salinity is becoming the key constraints factor to agricultural production. Therefore, the plant especially the crops possessing capacities of salt tolerance will be of great economic significance. The adaptation or tolerance of plant to salinity stress involves a series of physiological, metabolic and molecular mechanisms. Halophytes are the kind of organisms which acquire special salt tolerance mechanisms to respond to the salt tress and ensure normal growth and development under saline conditions in their lengthy evolutionary adaptation, so understanding how halophytes respond to salinity stress will provide us with methods and tactics to foster and develop salt resistant varieties of crops. The strategies in physiological and molecular level adopted by halophytes are various including the changes in photosynthetic and transpiration rate, the sequestration of Na+ to extracellular or vacuole, the regulation of stomata aperture and stomatal density, the accumulation and synthesis of the phytohormones as well as the relevant gene expression underlying these physiological traits, such as the stress signal transduction, the regulation of the transcription factors, the activation and expression of the transporter genes, the activation or inhibition of the synthetases and so on. This review focuses on the research advances of the regulating mechanisms in halophytes from physiological to molecular, which render the halophytes tolerance and adaption to salinity stress. PMID:27252587

Preventive Effects of Poloxamer 188 on Muscle Cell Damage Mechanics Under Oxidative Stress.

PubMed

Wong, Sing Wan; Yao, Yifei; Hong, Ye; Ma, Zhiyao; Kok, Stanton H L; Sun, Shan; Cho, Michael; Lee, Kenneth K H; Mak, Arthur F T

2017-04-01

High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure. In this study, we investigated the preventive effect of poloxamer 188 (P188) on skeletal muscle cells against extrinsic oxidative challenges (H 2 O 2 ). It was found that with 1 mM P188 pre-treatment for 1 h, skeletal muscle cells could maintain their compressive damage threshold. The actin polymerization dynamics largely remained stable in term of the expression of cofilin, thymosin beta 4 and profilin. Laser photoporation demonstrated that membrane sealing ability was preserved even as the cells were challenged by H 2 O 2 . These findings suggest that P188 pre-treatment can help skeletal muscle cells retain their normal mechanical integrity in oxidative environments, adding a potential clinical use of P188 against the combined challenge of mechanical-oxidative stresses. Such effect may help to prevent deep tissue ulcer development.

Torsional bridge setup for the characterization of integrated circuits and microsensors under mechanical shear stress.

PubMed

Herrmann, M; Gieschke, P; Ruther, P; Paul, O

2011-12-01

We present a torsional bridge setup for the electro-mechanical characterization of devices integrated in the surface of silicon beams under mechanical in-plane shear stress. It is based on the application of a torsional moment to the longitudinal axis of the silicon beams, which results in a homogeneous in-plane shear stress in the beam surface. The safely applicable shear stresses span the range of ±50 MPa. Thanks to a specially designed clamping mechanism, the unintended normal stress typically stays below 2.5% of the applied shear stress. An analytical model is presented to compute the induced shear stress. Numerical computations verify the analytical results and show that the homogeneity of the shear stress is very high on the beam surface in the region of interest. Measurements with piezoresistive microsensors fabricated using a complementary metal-oxide-semiconductor process show an excellent agreement with both the computational results and comparative measurements performed on a four-point bending bridge. The electrical connection to the silicon beam is performed with standard bond wires. This ensures that minimal forces are applied to the beam by the electrical interconnection to the external instrumentation and that devices with arbitrary bond pad layout can be inserted into the setup.

Precise Synaptic Efficacy Alignment Suggests Potentiation Dominated Learning.

PubMed

Hartmann, Christoph; Miner, Daniel C; Triesch, Jochen

2015-01-01

Recent evidence suggests that parallel synapses from the same axonal branch onto the same dendritic branch have almost identical strength. It has been proposed that this alignment is only possible through learning rules that integrate activity over long time spans. However, learning mechanisms such as spike-timing-dependent plasticity (STDP) are commonly assumed to be temporally local. Here, we propose that the combination of temporally local STDP and a multiplicative synaptic normalization mechanism is sufficient to explain the alignment of parallel synapses. To address this issue, we introduce three increasingly complex models: First, we model the idealized interaction of STDP and synaptic normalization in a single neuron as a simple stochastic process and derive analytically that the alignment effect can be described by a so-called Kesten process. From this we can derive that synaptic efficacy alignment requires potentiation-dominated learning regimes. We verify these conditions in a single-neuron model with independent spiking activities but more realistic synapses. As expected, we only observe synaptic efficacy alignment for long-term potentiation-biased STDP. Finally, we explore how well the findings transfer to recurrent neural networks where the learning mechanisms interact with the correlated activity of the network. We find that due to the self-reinforcing correlations in recurrent circuits under STDP, alignment occurs for both long-term potentiation- and depression-biased STDP, because the learning will be potentiation dominated in both cases due to the potentiating events induced by correlated activity. This is in line with recent results demonstrating a dominance of potentiation over depression during waking and normalization during sleep. This leads us to predict that individual spine pairs will be more similar after sleep compared to after sleep deprivation. In conclusion, we show that synaptic normalization in conjunction with coordinated potentiation--in this case, from STDP in the presence of correlated pre- and post-synaptic activity--naturally leads to an alignment of parallel synapses.

Intestinal absorption of water-soluble vitamins in health and disease.

PubMed

Said, Hamid M

2011-08-01

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. © The Authors Journal compilation © 2011 Biochemical Society

Intestinal absorption of water-soluble vitamins in health and disease

PubMed Central

Said, Hamid M.

2014-01-01

Our knowledge of the mechanisms and regulation of intestinal absorption of water-soluble vitamins under normal physiological conditions, and of the factors/conditions that affect and interfere with theses processes has been significantly expanded in recent years as a result of the availability of a host of valuable molecular/cellular tools. Although structurally and functionally unrelated, the water-soluble vitamins share the feature of being essential for normal cellular functions, growth and development, and that their deficiency leads to a variety of clinical abnormalities that range from anaemia to growth retardation and neurological disorders. Humans cannot synthesize water-soluble vitamins (with the exception of some endogenous synthesis of niacin) and must obtain these micronutrients from exogenous sources. Thus body homoeostasis of these micronutrients depends on their normal absorption in the intestine. Interference with absorption, which occurs in a variety of conditions (e.g. congenital defects in the digestive or absorptive system, intestinal disease/resection, drug interaction and chronic alcohol use), leads to the development of deficiency (and sub-optimal status) and results in clinical abnormalities. It is well established now that intestinal absorption of the water-soluble vitamins ascorbate, biotin, folate, niacin, pantothenic acid, pyridoxine, riboflavin and thiamin is via specific carrier-mediated processes. These processes are regulated by a variety of factors and conditions, and the regulation involves transcriptional and/or post-transcriptional mechanisms. Also well recognized now is the fact that the large intestine possesses specific and efficient uptake systems to absorb a number of water-soluble vitamins that are synthesized by the normal microflora. This source may contribute to total body vitamin nutrition, and especially towards the cellular nutrition and health of the local colonocytes. The present review aims to outline our current understanding of the mechanisms involved in intestinal absorption of water-soluble vitamins, their regulation, the cell biology of the carriers involved and the factors that negatively affect these absorptive events. PMID:21749321

Defining the cause of skewed X-chromosome inactivation in X-linked mental retardation by use of a mouse model.

PubMed

Muers, Mary R; Sharpe, Jacqueline A; Garrick, David; Sloane-Stanley, Jacqueline; Nolan, Patrick M; Hacker, Terry; Wood, William G; Higgs, Douglas R; Gibbons, Richard J

2007-06-01

Extreme skewing of X-chromosome inactivation (XCI) is rare in the normal female population but is observed frequently in carriers of some X-linked mutations. Recently, it has been shown that various forms of X-linked mental retardation (XLMR) have a strong association with skewed XCI in female carriers, but the mechanisms underlying this skewing are unknown. ATR-X syndrome, caused by mutations in a ubiquitously expressed, chromatin-associated protein, provides a clear example of XLMR in which phenotypically normal female carriers virtually all have highly skewed XCI biased against the X chromosome that harbors the mutant allele. Here, we have used a mouse model to understand the processes causing skewed XCI. In female mice heterozygous for a null Atrx allele, we found that XCI is balanced early in embryogenesis but becomes skewed over the course of development, because of selection favoring cells expressing the wild-type Atrx allele. Unexpectedly, selection does not appear to be the result of general cellular-viability defects in Atrx-deficient cells, since it is restricted to specific stages of development and is not ongoing throughout the life of the animal. Instead, there is evidence that selection results from independent tissue-specific effects. This illustrates an important mechanism by which skewed XCI may occur in carriers of XLMR and provides insight into the normal role of ATRX in regulating cell fate.

Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

PubMed Central

Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

2013-01-01

Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

Mechanisms of three-dimensional growth of thyroid cells during long-term simulated microgravity

PubMed Central

Kopp, Sascha; Warnke, Elisabeth; Wehland, Markus; Aleshcheva, Ganna; Magnusson, Nils E.; Hemmersbach, Ruth; Juhl Corydon, Thomas; Bauer, Johann; Infanger, Manfred; Grimm, Daniela

2015-01-01

Three-dimensional multicellular spheroids (MCS) of human cells are important in cancer research. We investigated possible mechanisms of MCS formation of thyroid cells. Both, normal Nthy-ori 3–1 thyroid cells and the poorly differentiated follicular thyroid cancer cells FTC-133 formed MCS within 7 and 14 days of culturing on a Random Positioning Machine (RPM), while a part of the cells continued to grow adherently in each culture. The FTC-133 cancer cells formed larger and numerous MCS than the normal cells. In order to explain the different behaviour, we analyzed the gene expression of IL6, IL7, IL8, IL17, OPN, NGAL, VEGFA and enzymes associated cytoskeletal or membrane proteins (ACTB, TUBB, PFN1, CPNE1, TGM2, CD44, FLT1, FLK1, PKB, PKC, ERK1/2, Casp9, Col1A1) as well as the amount of secreted proteins (IL-6, IL-7, IL-8, IL-17, OPN, NGAL, VEGFA). Several of these components changed during RPM-exposure in each cell line. Striking differences between normal and malignant cells were observed in regards to the expression of genes of NGAL, VEGFA, OPN, IL6 and IL17 and to the secretion of VEGFA, IL-17, and IL-6. These results suggest several gravi-sensitive growth or angiogenesis factors being involved in 3D formation of thyroid cells cultured under simulated microgravity. PMID:26576504

Network recruitment to coherent oscillations in a hippocampal computer model

PubMed Central

Krieger, Abba; Litt, Brian

2011-01-01

Coherent neural oscillations represent transient synchronization of local neuronal populations in both normal and pathological brain activity. These oscillations occur at or above gamma frequencies (>30 Hz) and often are propagated to neighboring tissue under circumstances that are both normal and abnormal, such as gamma binding or seizures. The mechanisms that generate and propagate these oscillations are poorly understood. In the present study we demonstrate, via a detailed computational model, a mechanism whereby physiological noise and coupling initiate oscillations and then recruit neighboring tissue, in a manner well described by a combination of stochastic resonance and coherence resonance. We develop a novel statistical method to quantify recruitment using several measures of network synchrony. This measurement demonstrates that oscillations spread via preexisting network connections such as interneuronal connections, recurrent synapses, and gap junctions, provided that neighboring cells also receive sufficient inputs in the form of random synaptic noise. “Epileptic” high-frequency oscillations (HFOs), produced by pathologies such as increased synaptic activity and recurrent connections, were superior at recruiting neighboring tissue. “Normal” HFOs, associated with fast firing of inhibitory cells and sparse pyramidal cell firing, tended to suppress surrounding cells and showed very limited ability to recruit. These findings point to synaptic noise and physiological coupling as important targets for understanding the generation and propagation of both normal and pathological HFOs, suggesting potential new diagnostic and therapeutic approaches to human disorders such as epilepsy. PMID:21273309

Transcriptional analysis of the conidiation pattern shift of the entomopathogenic fungus Metarhizium acridum in response to different nutrients.

PubMed

Wang, Zhenglong; Jin, Kai; Xia, Yuxian

2016-08-09

Most fungi, including entomopathogenic fungi, have two different conidiation patterns, normal and microcycle conidiation, under different culture conditions, eg, in media containing different nutrients. However, the mechanisms underlying the conidiation pattern shift are poorly understood. In this study, Metarhizium acridum undergoing microcycle conidiation on sucrose yeast extract agar (SYA) medium shifted to normal conidiation when the medium was supplemented with sucrose, nitrate, or phosphate. By linking changes in nutrients with the conidiation pattern shift and transcriptional changes, we obtained conidiation pattern shift libraries by Solexa/Illumina deep-sequencing technology. A comparative analysis demonstrated that the expression of 137 genes was up-regulated during the shift to normal conidiation, while the expression of 436 genes was up-regulated at the microcycle conidiation stage. A comparison of subtractive libraries revealed that 83, 216, and 168 genes were related to sucrose-induced, nitrate-induced, and phosphate-induced conidiation pattern shifts, respectively. The expression of 217 genes whose expression was specific to microcycle conidiation was further analyzed by the gene expression profiling via multigene concatemers method using mRNA isolated from M. acridum grown on SYA and the four normal conidiation media. The expression of 142 genes was confirmed to be up-regulated on standard SYA medium. Of these 142 genes, 101 encode hypothetical proteins or proteins of unknown function, and only 41 genes encode proteins with putative functions. Of these 41 genes, 18 are related to cell growth, 10 are related to cell proliferation, three are related to the cell cycle, three are related to cell differentiation, two are related to cell wall synthesis, two are related to cell division, and seven have other functions. These results indicate that the conidiation pattern shift in M. acridum mainly results from changes in cell growth and proliferation. The results indicate that M. acridum shifts conidiation pattern from microcycle conidiation to normal conidiation when there is increased sucrose, nitrate, or phosphate in the medium during microcycle conidiation. The regulation of conidiation patterning is a complex process involving the cell cycle and metabolism of M. acridum. This study provides essential information about the molecular mechanism of the induction of the conidiation pattern shift by single nutrients.

Catch-up Growth: Cellular and Molecular Mechanisms

PubMed Central

Finkielstain, GP; Lui, JC; Baron, J

2012-01-01

In mammals, after a period of growth inhibition, body growth often does not just return to a normal rate but actually exceeds the normal rate, resulting in catch-up growth. Recent evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms that normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age. There is evidence that this mechanism contributes both to catch-up growth in terms of body length, which involves proliferation in the growth plate, and to catch-up growth in terms of organ mass, which involves proliferation in multiple non-skeletal tissues. PMID:23428687

Color constancy of color-deficient observers under illuminations defined by individual color discrimination ellipsoids.

PubMed

Ma, Ruiqing; Kawamoto, Ken-Ichiro; Shinomori, Keizo

2016-03-01

We explored the color constancy mechanisms of color-deficient observers under red, green, blue, and yellow illuminations. The red and green illuminations were defined individually by the longer axis of the color discrimination ellipsoid measured by the Cambridge Colour Test. Four dichromats (3 protanopes and 1 deuteranope), two anomalous trichromats (2 deuteranomalous observers), and five color-normal observers were asked to complete the color constancy task by making a simultaneous paper match under asymmetrical illuminations in haploscopic view on a monitor. The von Kries adaptation model was applied to estimate the cone responses. The model fits showed that for all color-deficient observers under all illuminations, the adjustment of the S-cone response or blue-yellow chromatically opponent responses modeled with the simple assumption of cone deletion in a certain type (S-M, S-L or S-(L+M)) was consistent with the principle of the von Kries model. The degree of adaptation was similar to that of color-normal observers. The results indicate that the color constancy of color-deficient observers is mediated by the simplified blue-yellow color system with a von Kries-type adaptation effect, even in the case of brightness match, as well as by a possible cone-level adaptation to the S-cone when the illumination produces a strong S-cone stimulation, such as blue illumination.

Ignition and combustion of bulk metals at normal, elevated and reduced gravity

NASA Technical Reports Server (NTRS)

Branch, Melvyn C.; Daily, John W.; Abbud-Madrid, Angel

1995-01-01

Knowledge of the oxidation, ignition, and combustion of bulk metals is important for fire safety in the production, management, and utilization of liquid and gaseous oxygen for ground based and space applications. This proposal outlines studies in continuation of research initiated earlier under NASA support to investigate the ignition and combustion characteristics of bulk metals under varying gravity conditions. Metal ignition and combustion have not been studied previously under these conditions and the results are important not only for improved fire safety but also to increase knowledge of basic ignition and combustion mechanisms. The studies completed to date have led to the development of a clean and reproducible ignition source and diagnostic techniques for combustion measurements and have provided normal, elevated, and reduced gravity combustion data on a variety of different pure metals. The research conducted under this grant will use the apparatus and techniques developed earlier to continue the elevated and low gravity experiments, and to develop the overall modeling of the ignition and combustion process. Metal specimens are to be ignited using a xenon short-arc lamp and measurements are to be made of the ignition energy, surface temperature history, burning rates, spectroscopy of surface and gas products, and surface morphology and chemistry. Elevated gravity will be provided by the University of Colorado Geotechnical Centrifuge and microgravity will be obtained in NASA's DC-9 Reduced Gravity aircraft.

Normalization and extension of single-collector efficiency correlation equation

NASA Astrophysics Data System (ADS)

Messina, Francesca; Marchisio, Daniele; Sethi, Rajandrea

2015-04-01

The colloidal transport and deposition are important phenomena involved in many engineering problems. In the environmental engineering field the use of micro- and nano-scale zerovalent iron (M-NZVI) is one of the most promising technologies for groundwater remediation. Colloid deposition is normally studied from a micro scale point of view and the results are then implemented in macro scale models that are used to design field-scale applications. The single collector efficiency concept predicts particles deposition onto a single grain of a complex porous medium in terms of probability that an approaching particle would be retained on the solid grain. In literature, many different approaches and equations exist to predict it, but most of them fail under specific conditions (e.g. very small or very big particle size and very low fluid velocity) because they predict efficiency values exceeding unity. By analysing particle fluxes and deposition mechanisms and performing a mass balance on the entire domain, the traditional definition of efficiency was reformulated and a novel total flux normalized correlation equation is proposed for predicting single-collector efficiency under a broad range of parameters. It has been formulated starting from a combination of Eulerian and Lagrangian numerical simulations, performed under Smoluchowski-Levich conditions, in a geometry which consists of a sphere enveloped by a control volume. In order to guarantee the independence of each term, the correlation equation is derived through a rigorous hierarchical parameter estimation process, accounting for single and mutual interacting transport mechanisms. The correlation equation provides efficiency values lower than one over a wide range of parameters and is valid both for point and finite-size particles. A reduced form is also proposed by elimination of the less relevant terms. References 1. Yao, K. M.; Habibian, M. M.; Omelia, C. R., Water and Waste Water Filtration - Concepts and Applications. Environ Sci Technol 1971, 5, (11), 1105-&. 2. Tufenkji, N., and M. Elimelech, Correlation equation for predicting single-collector efficiency in physicochemical filtration in saturated porous media. Environmental Science & Technology 2004 38(2):529-536. 3. Boccardo, G.; Marchisio, D. L.; Sethi, R., Microscale simulation of particle deposition in porous media. J Colloid Interface Sci 2014, 417, 227-37

Microbial production of metabolites and associated enzymatic reactions under high pressure.

PubMed

Dong, Yongsheng; Jiang, Hua

2016-11-01

High environmental pressure exerts an external stress on the survival of microorganisms that are commonly found under normal pressure. In response, many growth traits alter, including cell morphology and physiology, cellular structure, metabolism, physical and chemical properties, the reproductive process, and defense mechanisms. The high-pressure technology (HP) has been industrially utilized in pressurized sterilization, synthesis of stress-induced products, and microbial/enzymatic transformation of chemicals. This article reviews current research on pressure-induced production of metabolites in normal-pressure microbes and their enzymatic reactions. Factors that affect the production of such metabolites are summarized, as well as the effect of pressure on the performance of microbial fermentation and the yield of flavoring compounds, different categories of induced enzymatic reactions and their characteristics in the supercritical carbon dioxide fluid, effects on enzyme activity, and the selection of desirable bacterial strains. Technological challenges are discussed, and future research directions are proposed. Information presented here will benefit the research, development, and application of the HP technology to improve microbial fermentation and enzymatic production of biologically active substances, thereby help to meet their increasing demand from the ever-expanding market.

Study on Excitation-triggered Damage Mechanism in Perilous Rock

NASA Astrophysics Data System (ADS)

Chen, Hongkai; Wang, Shengjuan

2017-12-01

Chain collapse is easy to happen for perilous rock aggregate locating on steep high slope, and one of the key scientific problems is the damage mechanism of perilous rock under excitation action at perilous rock rupture. This paper studies excitation-triggered damage mechanism in perilous rock by wave mechanics, which gives three conclusions. Firstly, when only the normal incidence attenuation spread of excitation wave is considered, while the energy loss is ignored for excitation wave to spread in perilous rock aggregate, the paper establishes one method to calculate peak velocity when excitation wave passes through boundary between any two perilous rock blocks in perilous rock aggregate. Secondly, following by Sweden and Canmet criteria, the paper provides one wave velocity criterion for excitation-triggered damage in the aggregate. Thirdly, assuming double parameters of volume strain of cracks or fissures in rock meet the Weibull distribution, one method to estimate micro-fissure in excitation-triggered damage zone in perilous rock aggregate is established. The studies solve the mechanical description problem for excitation-triggered damage in perilous rock, which is valuable in studies on profoundly rupture mechanism.

Gut Microbiota and IGF-1.

PubMed

Yan, Jing; Charles, Julia F

2018-04-01

Microbiota and their hosts have coevolved for millions of years. Microbiota are not only critical for optimal development of the host under normal physiological growth, but also important to ensure proper host development during nutrient scarcity or disease conditions. A large body of research has begun to detail the mechanism(s) of how microbiota cooperate with the host to maintain optimal health status. One crucial host pathway recently demonstrated to be modulated by microbiota is that of the growth factor insulin like growth factor 1 (IGF-1). Gut microbiota are capable of dynamically modulating circulating IGF-1 in the host, with the majority of data suggesting that microbiota induce host IGF-1 synthesis to influence growth. Microbiota-derived metabolites such as short chain fatty acids are sufficient to induce IGF-1. Whether microbiota induction of IGF-1 is mediated by the difference in growth hormone expression or the host sensitivity to growth hormone is still under investigation. This review summarizes the current data detailing the interaction between gut microbiota, IGF-1 and host development.

Setting-up tension in the style of Marantaceae.

PubMed

Pischtschan, E; Classen-Bockhoff, R

2008-07-01

The Marantaceae stand out from other plant families through their unique style movement which is combined with a highly derived form of secondary pollen presentation. Although known for a long time, the mechanism underlying the movement is not yet understood. In this paper, we report an investigation into the biomechanical principles of this movement. For the first time we experimentally confirm that, in Maranta noctiflora, longitudinal growth of the maturing style within the 'straitjacket' of the hooded staminode involves both arresting of the style before tripping and building up of potential for the movement. The longer the style grows in relation to the enclosing hooded staminode, the more does its capacity for curling increase. We distinguish between the basic tension that a growing style builds up normally, even when the hooded staminode is removed beforehand, and the induced tension which comes about only under the pressure of a too short hooded staminode and which enables the movement. The results of our investigations are discussed in relation to previous interpretations, ranging from biomechanical to electrophysiological mechanisms.

Physical, Chemical, and Biological Methods for the Removal of Arsenic Compounds

PubMed Central

Lim, K. T.; Shukor, M. Y.; Wasoh, H.

2014-01-01

Arsenic is a toxic metalloid which is widely distributed in nature. It is normally present as arsenate under oxic conditions while arsenite is predominant under reducing condition. The major discharges of arsenic in the environment are mainly due to natural sources such as aquifers and anthropogenic sources. It is known that arsenite salts are more toxic than arsenate as it binds with vicinal thiols in pyruvate dehydrogenase while arsenate inhibits the oxidative phosphorylation process. The common mechanisms for arsenic detoxification are uptaken by phosphate transporters, aquaglyceroporins, and active extrusion system and reduced by arsenate reductases via dissimilatory reduction mechanism. Some species of autotrophic and heterotrophic microorganisms use arsenic oxyanions for their regeneration of energy. Certain species of microorganisms are able to use arsenate as their nutrient in respiratory process. Detoxification operons are a common form of arsenic resistance in microorganisms. Hence, the use of bioremediation could be an effective and economic way to reduce this pollutant from the environment. PMID:24696853

Molecular Mechanisms Underlying γ-Aminobutyric Acid (GABA) Accumulation in Giant Embryo Rice Seeds.

PubMed

Zhao, Guo-Chao; Xie, Mi-Xue; Wang, Ying-Cun; Li, Jian-Yue

2017-06-21

To uncover the molecular mechanisms underlying GABA accumulation in giant embryo rice seeds, we analyzed the expression levels of GABA metabolism genes and contents of GABA and GABA metabolic intermediates in developing grains and germinated brown rice of giant embryo rice 'Shangshida No. 5' and normal embryo rice 'Chao2-10' respectively. In developing grains, the higher GABA contents in 'Shangshida No. 5' were accompanied with upregulation of gene transcripts and intermediate contents in the polyamine pathway and downregulation of GABA catabolic gene transcripts, as compared with those in 'Chao2-10'. In germinated brown rice, the higher GABA contents in 'Shangshida No. 5' were parallel with upregulation of OsGAD and polyamine pathway gene transcripts and Glu and polyamine pathway intermediate contents and downregulation of GABA catabolic gene transcripts. These results are the first to indicate that polyamine pathway and GABA catabolic genes play a crucial role in GABA accumulation in giant embryo rice seeds.

Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

PubMed

Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

2017-10-01

Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications

PubMed Central

Liu, Chunlei; Wei, Hongjiang; Gong, Nan-Jie; Cronin, Matthew; Dibb, Russel; Decker, Kyle

2016-01-01

Quantitative susceptibility mapping (QSM) is a recently developed MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field is a result of the superposition of the dipole fields generated by all voxels and that each voxel has its unique magnetic susceptibility. QSM provides improved contrast to noise ratio for certain tissues and structures compared to its magnitude counterpart. More importantly, magnetic susceptibility is a direct reflection of the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism generating susceptibility contrast within tissues and some associated applications. PMID:26844301

Thermionic switched self-actuating reactor shutdown system

DOEpatents

Barrus, Donald M.; Shires, Charles D.; Brummond, William A.

1989-01-01

A self-actuating reactor shutdown system incorporating a thermionic switched electromagnetic latch arrangement which is responsive to reactor neutron flux changes and to reactor coolant temperature changes. The system is self-actuating in that the sensing thermionic device acts directly to release (scram) the control rod (absorber) without reference or signal from the main reactor plant protective and control systems. To be responsive to both temperature and neutron flux effects, two detectors are used, one responsive to reactor coolant temperatures, and the other responsive to reactor neutron flux increase. The detectors are incorporated into a thermionic diode connected electrically with an electromagnetic mechanism which under normal reactor operating conditions holds the the control rod in its ready position (exterior of the reactor core). Upon reaching either a specified temperature or neutron flux, the thermionic diode functions to short-circuit the electromagnetic mechanism causing same to lose its holding power and release the control rod, which drops into the reactor core region under gravitational force.

Putting tumours in context

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

Bissell, Mina J.; Radisky, Derek

2001-10-01

The interactions between cancer cells and their micro- and macroenvironment create a context that promotes tumor growth and protects it from immune attack. The functional association of cancer cells with their surrounding tissues forms a new 'organ' that changes as malignancy progresses. Investigation of this process might provide new insights into the mechanisms of tumorigenesis and could also lead to new therapeutic targets. Under normal conditions, ORGANS are made up of TISSUES that exchange information with other cell types via cell-cell contact, cytokines and the EXTRACELLULAR MATRIX (ECM). The ECM, which is produced by collaboration between STROMAL fibroblasts and EPITHELIALmore » cells, provides structural scaffolding for cells, as well as contextual information. The endothelial vasculature provides nutrients and oxygen, and cells of the immune system combat pathogens and remove apoptotic cells. Epithelial cells associate into intact, polarized sheets. These tissues communicate through a complex network of interactions: physically, through direct contact or through the intervening ECM, and biochemically, through both soluble and insoluble signalling molecules. In combination, these interactions provide the information that is necessary to maintain cellular differentiation and to create complex tissue structures. Occasionally, the intercellular signals that define the normal context become disrupted. Alterations in epithelial tissues can lead to movement of epithelial sheets and proliferation - for example, after activation of mesenchymal fibroblasts due to wounding.Normally, these conditions are temporary and reversible, but when inflammation is sustained, an escalating feedback loop ensues.Under persistent inflammatory conditions, continual upregulation of enzymes such as matrix metalloproteinases (MMPs) by stromal fibroblasts can disrupt the ECM, and invading immune cells can overproduce factors that promote abnormal proliferation. As this process progresses, the normal organization of the organ is replaced by a functional disorder. If there are pre-existing epithelial cells within this changing context that possess tumorigenic potential, they can start to proliferate. Alternatively, the abnormal interactions might lead to genomic instability within the epithelial cells and the acquisition of tumorigenic potential. The proliferating cancer cells can then interact with their microenvironment and enhance the abnormal interactions. At this point, the tumor has become its own organ, with a distinct context that now defines all its cellular responses. Here, we will examine how the mechanisms that contribute to the normal context also act to suppress developing tumors, how disruption of this context initiates and supports the process of tumorigenicity, and how some cells with a tumorigenic genotype can become phenotypically normal if the context is appropriately manipulated.« less

Distinct biological effects of low-dose radiation on normal and cancerous human lung cells are mediated by ATM signaling

PubMed Central

Li, Wei; Zhao, Yuguang; Wen, Xue; Liang, Xinyue; Zhang, Xiaoying; Zhou, Lei; Hu, Jifan; Niu, Chao; Tian, Huimin; Han, Fujun; Chen, Xiao; Dong, Lihua; Cai, Lu; Cui, Jiuwei

2016-01-01

Low-dose radiation (LDR) induces hormesis and adaptive response in normal cells but not in cancer cells, suggesting its potential protection of normal tissue against damage induced by conventional radiotherapy. However, the underlying mechanisms are not well established. We addressed this in the present study by examining the role of the ataxia telangiectasia mutated (ATM) signaling pathway in response to LDR using A549 human lung adenocarcinoma cells and HBE135-E6E7 (HBE) normal lung epithelial cells. We found that LDR-activated ATM was the initiating event in hormesis and adaptive response to LDR in HBE cells. ATM activation increased the expression of CDK4/CDK6/cyclin D1 by activating the AKT/glycogen synthase kinase (GSK)-3β signaling pathway, which stimulated HBE cell proliferation. Activation of ATM/AKT/GSK-3β signaling also increased nuclear accumulation of nuclear factor erythroid 2-related factor 2, leading to increased expression of antioxidants, which mitigated cellular damage from excessive reactive oxygen species production induced by high-dose radiation. However, these effects were not observed in A549 cells. Thus, the failure to activate these pathways in A549 cells likely explains the difference between normal and cancer cells in terms of hormesis and adaptive response to LDR. PMID:27708248

Gaussian fitting for carotid and radial artery pressure waveforms: comparison between normal subjects and heart failure patients.

PubMed

Liu, Chengyu; Zheng, Dingchang; Zhao, Lina; Liu, Changchun

2014-01-01

It has been reported that Gaussian functions could accurately and reliably model both carotid and radial artery pressure waveforms (CAPW and RAPW). However, the physiological relevance of the characteristic features from the modeled Gaussian functions has been little investigated. This study thus aimed to determine characteristic features from the Gaussian functions and to make comparisons of them between normal subjects and heart failure patients. Fifty-six normal subjects and 51 patients with heart failure were studied with the CAPW and RAPW signals recorded simultaneously. The two signals were normalized first and then modeled by three positive Gaussian functions, with their peak amplitude, peak time, and half-width determined. Comparisons of these features were finally made between the two groups. Results indicated that the peak amplitude of the first Gaussian curve was significantly decreased in heart failure patients compared with normal subjects (P<0.001). Significantly increased peak amplitude of the second Gaussian curves (P<0.001) and significantly shortened peak times of the second and third Gaussian curves (both P<0.001) were also presented in heart failure patients. These results were true for both CAPW and RAPW signals, indicating the clinical significance of the Gaussian modeling, which should provide essential tools for further understanding the underlying physiological mechanisms of the artery pressure waveform.

Computational modelling of left-ventricular diastolic mechanics: effect of fibre orientation and right-ventricle topology.

PubMed

Palit, Arnab; Bhudia, Sunil K; Arvanitis, Theodoros N; Turley, Glen A; Williams, Mark A

2015-02-26

Majority of heart failure patients who suffer from diastolic dysfunction retain normal systolic pump action. The dysfunction remodels the myocardial fibre structure of left-ventricle (LV), changing its regular diastolic behaviour. Existing LV diastolic models ignored the effects of right-ventricular (RV) deformation, resulting in inaccurate strain analysis of LV wall during diastole. This paper, for the first time, proposes a numerical approach to investigate the effect of fibre-angle distribution and RV deformation on LV diastolic mechanics. A finite element modelling of LV passive inflation was carried out, using structure-based orthotropic constitutive law. Rule-based fibre architecture was assigned on a bi-ventricular (BV) geometry constructed from non-invasive imaging of human heart. The effect of RV deformation on LV diastolic mechanics was investigated by comparing the results predicted by BV and single LV model constructed from the same image data. Results indicated an important influence of RV deformation which led to additional LV passive inflation and increase of average fibre and sheet stress-strain in LV wall during diastole. Sensitivity of LV passive mechanics to the changes in the fibre distribution was also examined. The study revealed that LV diastolic volume increased when fibres were aligned more towards LV longitudinal axis. Changes in fibre angle distribution significantly altered fibre stress-strain distribution of LV wall. The simulation results strongly suggest that patient-specific fibre structure and RV deformation play very important roles in LV diastolic mechanics and should be accounted for in computational modelling for improved understanding of the LV mechanics under normal and pathological conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Attention and normalization circuits in macaque V1.

PubMed

Sanayei, M; Herrero, J L; Distler, C; Thiele, A

2015-04-01

Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Quaternary ammonium-functionalized silica sorbents for the solid-phase extraction of aromatic amines under normal phase conditions.

PubMed

Vidal, Lorena; Robin, Orlane; Parshintsev, Jevgeni; Mikkola, Jyri-Pekka; Riekkola, Marja-Liisa

2013-04-12

Quaternary ammonium-functionalized silica materials were synthesized and applied for solid-phase extraction (SPE) of aromatic amines, which are classified as priority pollutants by US Environmental Protection Agency. Hexamethylenetetramine used for silica surface modification for the first time was employed as SPE sorbent under normal phase conditions. Hexaminium-functionalized silica demonstrated excellent extraction efficiencies for o-toluidine, 4-ethylaniline and quinoline (recoveries 101-107%), while for N,N-dimethylaniline and N-isopropylaniline recoveries were from low to moderate (14-46%). In addition, the suitability of 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica as SPE sorbent was tested under normal phase conditions. The recoveries achieved for the five aromatic amines ranged from 89 to 99%. The stability of the sorbent was evaluated during and after 150 extractions. Coefficients of variation between 4.5 and 10.2% proved a high stability of the synthesized sorbent. Elution was carried out using acetonitrile in the case of hexaminium-functionalized silica and water for 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica sorbent. After the extraction the analytes were separated and detected by liquid chromatography ultraviolet detection (LC-UV). The retention mechanism of the materials was primarily based on polar hydrogen bonding and π-π interactions. Comparison made with activated silica proved the quaternary ammonium-functionalized materials to offer different selectivity and better extraction efficiencies for aromatic amines. Finally, 1-alkyl-3-(propyl-3-sulfonate) imidazolium-functionalized silica sorbent was successfully tested for the extraction of wastewater and soil samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness.

PubMed

Blakely, E A; Kronenberg, A

1998-11-01

Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.

Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness

NASA Technical Reports Server (NTRS)

Blakely, E. A.; Kronenberg, A.; Chatterjee, A. (Principal Investigator)

1998-01-01

Shortly after the discovery of polonium and radium by Marie Curie and her husband and colleague, Pierre Curie, it was learned that exposure to these alpha-particle emitters produced deleterious biological effects. The mechanisms underlying the increased biological effectiveness of densely ionizing radiations, including alpha particles, neutrons and highly energetic heavy charged particles, remain an active area of investigation. In this paper, we review recent advances in several areas of the radiobiology of these densely ionizing radiations, also known as heavy ions. Advances are described in the areas of DNA damage and repair, chromosome aberrations, mutagenesis, neoplastic transformation in vitro, genomic instability, normal tissue radiobiology and carcinogenesis in vivo. We focus on technical innovations, including novel applications of pulsed-field gel electrophoresis, fluorescence in situ hybridization (FISH), linkage analysis, and studies of gene expression and protein expression. We also highlight the use of new cellular and animal systems, including those with defined DNA repair deficiencies, as well as epithelial cell model systems to assess neoplastic transformation both in vitro and in vivo. The studies reviewed herein have had a substantial impact on our understanding of the genotoxic effects of heavy ions as well as their distinct effects on tissue homeostasis. The use of these radiations in cancer therapy is also discussed. The use of both heavy-ion and proton therapy is on the upswing in several centers around the world, due to their unique energy deposition characteristics that enhance the therapeutic effect and help reduce damage to normal tissue.

Respiratory mechanics during sevoflurane anesthesia in children with and without asthma.

PubMed

Habre, W; Scalfaro, P; Sims, C; Tiller, K; Sly, P D

1999-11-01

We studied lung function in children with and without asthma receiving anesthesia with sevoflurane. Fifty-two children had anesthesia induced with sevoflurane (up to 8%) in a mixture of 50% nitrous oxide in oxygen and then maintained at 3% with children breathing spontaneously via face mask and Jackson-Rees modification of the T-piece. Airway opening pressure and flow were then measured. After insertion of an oral endotracheal tube under 5% sevoflurane, measurements were repeated at 3%, as well as after increasing to 4.2%. Respiratory system resistance (Rrs) and compliance during expiration were calculated using multilinear regression analysis of airway opening pressure and flow, assuming a single-compartment model. Data from 44 children were analyzed (22 asthmatics and 22 normal children). The two groups were comparable with respect to age, weight, ventilation variables, and baseline respiratory mechanics. Intubation was associated with a significant increase in Rrs in asthmatics (17% +/- 49%), whereas in normal children, Rrs slightly decreased (-4% +/- 39%). At 4.2%, Rrs decreased slightly in both groups with almost no change in compliance system resistance. We concluded that in children with mild to moderate asthma, endotracheal intubation during sevoflurane anesthesia was associated with increase in Rrs that was not seen in nonasthmatic children. Tracheal intubation using sevoflurane as sole anesthetic is possible and its frequency is increasing. When comparing children with and without asthma, tracheal intubation under sevoflurane was associated with an increase in respiratory system resistance in asthmatic children. However, no apparent clinical adverse event was observed.

Effects of pH and aggregation in the human prion conversion into scrapie form: a study using molecular dynamics with excited normal modes.

PubMed

Lima, Angelica Nakagawa; de Oliveira, Ronaldo Junio; Braz, Antônio Sérgio Kimus; de Souza Costa, Maurício Garcia; Perahia, David; Scott, Luis Paulo Barbour

2018-03-15

There are two different prion conformations: (1) the cellular natural (PrP C ) and (2) the scrapie (PrP Sc ), an infectious form that tends to aggregate under specific conditions. PrP C and PrP Sc are widely different regarding secondary and tertiary structures. PrP Sc contains more and longer β-strands compared to PrP C . The lack of solved PrP Sc structures precludes a proper understanding of the mechanisms related to the transition between cellular and scrapie forms, as well as the aggregation process. In order to investigate the conformational transition between PrP C and PrP Sc , we applied MDeNM (molecular dynamics with excited normal modes), an enhanced sampling simulation technique that has been recently developed to probe large structural changes. These simulations yielded new structural rearrangements of the cellular prion that would have been difficult to obtain with standard MD simulations. We observed an increase in β-sheet formation under low pH (≤ 4) and upon oligomerization, whose relevance was discussed on the basis of the energy landscape theory for protein folding. The characterization of intermediate structures corresponding to transition states allowed us to propose a conversion model from the cellular to the scrapie prion, which possibly ignites the fibril formation. This model can assist the design of new drugs to prevent neurological disorders related to the prion aggregation mechanism.

Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

PubMed

Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

2014-01-01

The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

Androgen Effects on Adipose Tissue Architecture and Function in Nonhuman Primates

PubMed Central

Varlamov, Oleg; White, Ashley E.; Carroll, Julie M.; Bethea, Cynthia L.; Reddy, Arubala; Slayden, Ov; O'Rourke, Robert W.

2012-01-01

The differential association of hypoandrogenism in men and hyperandrogenism in women with insulin resistance and obesity suggests that androgens may exert sex-specific effects on adipose and other tissues, although the underlying mechanisms remain poorly understood. Moreover, recent studies also suggest that rodents and humans may respond differently to androgen imbalance. To achieve better insight into clinically relevant sex-specific mechanisms of androgen action, we used nonhuman primates to investigate the direct effects of gonadectomy and hormone replacement on white adipose tissue. We also employed a novel ex vivo approach that provides a convenient framework for understanding of adipose tissue physiology under a controlled tissue culture environment. In vivo androgen deprivation of males did not result in overt obesity or insulin resistance but did induce the appearance of very small, multilocular white adipocytes. Testosterone replacement restored normal cell size and a unilocular phenotype and stimulated adipogenic gene transcription and improved insulin sensitivity of male adipose tissue. Ex vivo studies demonstrated sex-specific effects of androgens on adipocyte function. Female adipose tissue treated with androgens displayed elevated basal but reduced insulin-dependent fatty acid uptake. Androgen-stimulated basal uptake was greater in adipose tissue of ovariectomized females than in adipose tissue of intact females and ovariectomized females replaced with estrogen and progesterone in vivo. Collectively, these data demonstrate that androgens are essential for normal adipogenesis in males and can impair essential adipocyte functions in females, thus strengthening the experimental basis for sex-specific effects of androgens in adipose tissue. PMID:22547568

Integrative Analyses of miRNA-mRNA Interactions Reveal let-7b, miR-128 and MAPK Pathway Involvement in Muscle Mass Loss in Sex-Linked Dwarf Chickens

PubMed Central

Luo, Wen; Lin, Shumao; Li, Guihuan; Nie, Qinghua; Zhang, Xiquan

2016-01-01

The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. PMID:26927061

Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

PubMed Central

Hanson, M. A.; Gluckman, P. D.

2014-01-01

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention. PMID:25287859

Competition for Space Is Controlled by Apoptosis-Induced Change of Local Epithelial Topology.

PubMed

Tsuboi, Alice; Ohsawa, Shizue; Umetsu, Daiki; Sando, Yukari; Kuranaga, Erina; Igaki, Tatsushi; Fujimoto, Koichi

2018-06-11

During the initial stage of tumor progression, oncogenic cells spread despite spatial confinement imposed by surrounding normal tissue. This spread of oncogenic cells (winners) is thought to be governed by selective killing of surrounding normal cells (losers) through a phenomenon called "cell competition" (i.e., supercompetition). Although the mechanisms underlying loser elimination are increasingly apparent, it is not clear how winner cells selectively occupy the space made available following loser apoptosis. Here, we combined live imaging analyses of two different oncogenic clones (Yki/YAP activation and Ras activation) in the Drosophila epithelium with computer simulation of tissue mechanics to elucidate such a mechanism. Contrary to the previous expectation that cell volume loss after apoptosis of loser cells was simply compensated for by the faster proliferation of winner cells, we found that the lost volume was compensated for by rapid cell expansion of winners. Mechanistically, the rapid winner-dominated cell expansion was driven by apoptosis-induced epithelial junction remodeling, which causes re-connection of local cellular connectivity (cell topology) in a manner that selectively increases winner apical surface area. In silico experiments further confirmed that repetition of loser elimination accelerates tissue-scale winner expansion through topological changes over time. Our proposed mechanism for linking loser death and winner expansion provides a new perspective on how tissue homeostasis disruption can initiate from an oncogenic mutation. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

[Mechanism and Prospect of Radiotherapy Combined with Apotatinib
in the Treatment of Non-small Cell Lung Cancer].

PubMed

Liu, Guohui; Wang, Chunbo; E, Mingyan

2017-12-20

Non-small cell lung cancer is one of the most commom malignant tumor being harmful to people's life and health. Most of the patients have developed to the last stage which not suitable for surgical indications, so radiation and chemotherapy is the main treatment strategy. In recent years, with the theory of anti-angiogenesis therapy for malignant tumors, apatinib as a promising novel medicine to treat malignant tumors, represents synergistic antitumor effects in combination with radiotherapy. The underlying mechanisms may include make blood vessel normalization, alleviating inner hypoxia, and angiogenic factors regulation. Apatinib in combination with radiotherapy may become a new and effective treatment strategy of non-small cell lung cancer.

Learning, Memory, and Transcranial Direct Current Stimulation

PubMed Central

Brasil-Neto, Joaquim P.

2012-01-01

Transcranial direct current stimulation (tDCS) has been the subject of many studies concerning its possible cognitive effects. One of the proposed mechanisms of action for neuromodulatory techniques, such as transcranial magnetic stimulation and tDCS is induction of long-term potentiation (LTP) and long-term depression (LTD)-like phenomena. LTP and LTD are also among the most important neurobiological processes involved in memory and learning. This fact has led to an immediate interest in the study of possible effects of tDCS on memory consolidation, retrieval, or learning of various tasks. This review analyses published articles describing beneficial or disruptive effects of tDCS on memory and learning in normal subjects. The most likely mechanisms underlying these effects are discussed. PMID:22969734

Calcite Decarbonation and its Influence on the Mechanical Behaviour of Carbonate-bearing Faults

NASA Astrophysics Data System (ADS)

Carpenter, Brett; Collettini, Cristiano; Mollo, Silvio; Viti, Cecilia

2014-05-01

Calcite decarbonation has been identified as one of the important, thermally-activated physicochemical processes that are triggered by temperature rise during fast fault motion. This process has been observed in the laboratory during high-velocity friction experiments where the dynamic weakening that occurs for carbonate-rich gouges is strictly controlled by the thermal decomposition of calcite. Furthermore, this process has also been identified along ancient, exhumed faults and is an important indicator of seismic slip. The thermally-induced decarbonation (CaCO3 → CaO + CO2) and microcracking (due to thermal expansion) of calcite are likely to be primary mechanisms in controlling the mechanical and hydrologic properties of carbonate rocks. In addition, the process and products of decarbonation will likely exert significant influence on the behaviour of faults at both geologic and earthquake time scales by causing changes in (1) the effective normal stress on the fault and (2) the frictional behaviour of material within it. Due to the paucity of scientific information on the effects of decarbonation and thermal microcracking on the mechanical properties of carbonate fault rocks, we present results from experiments performed on portlandite (>90 wt.%), a hydrous mineral formed by the recombination of CaO and water, and stable product of the decarbonation reaction. We produced portlandite by thermally-treating powdered Carrara Marble (calcite >98 wt.%) in the laboratory at 1100 °C under air buffering conditions. We then sheared gouge layers of this water-reacted, decarbonation product under saturated conditions at room temperature. These tests were designed to evaluate the frictional strength, stability, and healing behaviour of portlandite-bearing rocks to better understand how its presence affects fault mechanics. Our data indicate that the conversion of calcite to portlandite, results in a distinct change in the mechanical behaviour of the fault gouge. The difference in frictional strength, between marble and portlandite, increases from 0µ to 0.4µ as the normal stress is increased from 1 to 50 MPa. Additionally, at the low shearing rates of 0.1 and 0.3 µm/s, portlandite fails through stick-slip motion whereas calcite slides stably. Furthermore, we observe power-law type healing in portlandite that results in a dramatic increase in static frictional strength of ~0.2 µ over a relatively short hold time of 3000s. We suggest that decarbonated fault patches are (1) frictionally weaker, (2) more frictionally unstable, and (3) likely to regain their frictional strength more quickly, than patches in pure carbonate rocks. Under water-saturated conditions, the occurrence of portlandite and other hydrous minerals is undoubtedly the key for interpreting changes in the mechanical behaviour, both transient and long-term, of decarbonated faults.

Fosfomycin and Tobramycin in Combination Downregulate Nitrate Reductase Genes narG and narH, Resulting in Increased Activity against Pseudomonas aeruginosa under Anaerobic Conditions

PubMed Central

McCaughey, Gerard; Gilpin, Deirdre F.; Schneiders, Thamarai; Hoffman, Lucas R.; McKevitt, Matt; Elborn, J. Stuart

2013-01-01

The activity of aminoglycosides, which are used to treat Pseudomonas aeruginosa respiratory infection in cystic fibrosis (CF) patients, is reduced under the anaerobic conditions that reflect the CF lung in vivo. In contrast, a 4:1 (wt/wt) combination of fosfomycin and tobramycin (F:T), which is under investigation for use in the treatment of CF lung infection, has increased activity against P. aeruginosa under anaerobic conditions. The aim of this study was to elucidate the mechanisms underlying the increased activity of F:T under anaerobic conditions. Microarray analysis was used to identify the transcriptional basis of increased F:T activity under anaerobic conditions, and key findings were confirmed by microbiological tests, including nitrate utilization assays, growth curves, and susceptibility testing. Notably, growth in subinhibitory concentrations of F:T, but not tobramycin or fosfomycin alone, significantly downregulated (P < 0.05) nitrate reductase genes narG and narH, which are essential for normal anaerobic growth of P. aeruginosa. Under anaerobic conditions, F:T significantly decreased (P < 0.001) nitrate utilization in P. aeruginosa strains PAO1, PA14, and PA14 lasR::Gm, a mutant known to exhibit increased nitrate utilization. A similar effect was observed with two clinical P. aeruginosa isolates. Growth curves indicate that nitrate reductase transposon mutants had reduced growth under anaerobic conditions, with these mutants also having increased susceptibility to F:T compared to the wild type under similar conditions. The results of this study suggest that downregulation of nitrate reductase genes resulting in reduced nitrate utilization is the mechanism underlying the increased activity of F:T under anaerobic conditions. PMID:23959314

What Choline Metabolism Can Tell Us About the Underlying Mechanisms of Fetal Alcohol Spectrum Disorders

PubMed Central

2013-01-01

The consequences of fetal exposure to alcohol are very diverse and the likely molecular mechanisms involved must be able to explain how so many developmental processes could go awry. If pregnant rat dams are fed alcohol, their pups develop abnormalities characteristic of fetal alcohol spectrum disorders (FASD), but if these rat dams were also treated with choline, the effects from ethanol were attenuated in their pups. Choline is an essential nutrient in humans, and is an important methyl group donor. Alcohol exposure disturbs the metabolism of choline and other methyl donors. Availability of choline during gestation directly influences epigenetic marks on DNA and histones, and alters gene expression needed for normal neural and endothelial progenitor cell proliferation. Maternal diets low in choline alter development of the mouse hippocampus, and decrement memory for life. Women eating low-choline diets have an increased risk of having an infant with a neural tube or or ofacial cleft birth defect. Thus, the varied effects of choline could affect the expression of FASD, and studies on choline might shed some light on the underlying molecular mechanisms responsible for FASD. PMID:21259123

Magnon drag thermopower and thermomagnetic properties of single-crystal iron

NASA Astrophysics Data System (ADS)

Watzman, Sarah; Jin, Hyungyu; Heremans, Joseph

2015-03-01

Lucassen et al. demonstrate that magnon drag involves a spin-transfer mechanism closely related to the recently discovered spin-Seebeck effect. This talk will first present results of experiments mapping out the thermopower and magnetothermopower of single-crystal iron and prove that its thermopower is indeed dominated by magnon drag, as suggested by Blatt et al. in 1967. Measurements will then be presented on the magnetic field and temperature dependence of the full thermomagnetic tensor of iron's thermopower in the xxx, xyx, and xyz geometries (the first index gives the direction of the heat flux, the second the measured electric field, the third the applied magnetic field). Results of magneto-thermopower and Nernst coefficients will be reported for single-crystal samples oriented with x =[100]. The Nernst coefficients of elemental iron contain a contribution of a direct spin-transfer mechanism, which should be present in the absence of an interface between a ferromagnet and a normal metal. This mechanism could be put to use in high temperature ferromagnetic metallic thermoelectric alloys. This work is supported by the NSF GRFP under Grant No. DGE-0822215 and the ARO MURI under Grant No. W911NF-14-1-0016.

Speech Motor Sequence Learning: Effect of Parkinson Disease and Normal Aging on Dual-Task Performance.

PubMed

Whitfield, Jason A; Goberman, Alexander M

2017-06-22

Everyday communication is carried out concurrently with other tasks. Therefore, determining how dual tasks interfere with newly learned speech motor skills can offer insight into the cognitive mechanisms underlying speech motor learning in Parkinson disease (PD). The current investigation examines a recently learned speech motor sequence under dual-task conditions. A previously learned sequence of 6 monosyllabic nonwords was examined using a dual-task paradigm. Participants repeated the sequence while concurrently performing a visuomotor task, and performance on both tasks was measured in single- and dual-task conditions. The younger adult group exhibited little to no dual-task interference on the accuracy and duration of the sequence. The older adult group exhibited variability in dual-task costs, with the group as a whole exhibiting an intermediate, though significant, amount of dual-task interference. The PD group exhibited the largest degree of bidirectional dual-task interference among all the groups. These data suggest that PD affects the later stages of speech motor learning, as the dual-task condition interfered with production of the recently learned sequence beyond the effect of normal aging. Because the basal ganglia is critical for the later stages of motor sequence learning, the observed deficits may result from the underlying neural dysfunction associated with PD.

Surfactant Effect on the Average Flow Generation Near Curved Interface

NASA Astrophysics Data System (ADS)

Klimenko, Lyudmila; Lyubimov, Dmitry

2018-02-01

The present work is devoted to the average flow generation near curved interface with a surfactant adsorbed on the surface layer. The investigation was carried out for a liquid drop embedded in a viscous liquid with a different density. The liquid flows inside and outside the drop are generated by small amplitude and high frequency vibrations. Surfactant exchange between the drop surface and the surrounding liquid is limited by the process of adsorption-desorption. It was assumed that the surfactant is soluble in the surrounding liquid, but not soluble in the liquid drop. Surrounding liquid and the liquid in the drop are considered incompressible. Normal and shear viscous stresses balance at the interface is performed under the condition that the film thickness of the adsorbed surfactant is negligible. The problem is solved under assumption that the shape of the drop in the presence of adsorbed surfactant remains spherical symmetry. The effective boundary conditions for the tangential velocity jump and shear stress jump, describing the above generation have been obtained by matched asymptotic expansions method. The conditions under which the drop surface can be considered as a quasi-solid are determined. It is shown that in the case of the significant effect of surfactant on the surface tension, the dominant mechanism for the generation is the Schlichting mechanisms under vibrations.

Resistivity changes in conductive silicone sheets under stretching.

PubMed

González-Correa, C A; Screaton, G; Hose, D R; Brown, B H; Avis, N J; Kleinermann, F

2002-02-01

This paper reports a preliminary finding associated with an investigation of how tissues respond to mechanical stress. The stress distribution within the tissue may be the result of normal function, for example, joint forces, or it may result from interventions such as tissue suturing during or after surgery. We sought to combine electrical and mechanical computational models in order to better understand the interaction between the two. For example, if mechanical stress is applied to tissue this may change the cell arrangements within the tissue matrix and hence change the electrical properties. If this interaction could be determined, then it should be possible to use electrical impedance tomography measurements to identify stress patterns in tissues. Measurements of resistivity changes have been made in conductive silicone rubber sheets when subject to a uniaxial stress of up to 10%. Relatively large changes in resistivity are produced (up to 200%). These changes are far larger than those predicted arising from topological changes alone. It is suggested that under stress the conductive islands of carbon within the silicone rubber sheet undergo a reversible disassociation from their neighbours and that the material's electrical properties change under load. If similar stress-resistivity relationships occur within biological materials it may be possible to recover the stress fields within tissues from transfer impedance measurements and thereby predict if actions such as inappropriate suture tension will compromise tissue viability.

Structural and Mechanical Properties of Intermediate Filaments under Extreme Conditions and Disease

NASA Astrophysics Data System (ADS)

Qin, Zhao

Intermediate filaments are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that intermediate filament proteins play key roles to reinforce cells subjected to large-deformation as well as participate in signal transduction. However, it is still poorly understood how the nanoscopic structure, as well as the biochemical properties of these protein molecules contribute to their biomechanical functions. In this research we investigate the material function of intermediate filaments under various extreme mechanical conditions as well as disease states. We use a full atomistic model and study its response to mechanical stresses. Learning from the mechanical response obtained from atomistic simulations, we build mesoscopic models following the finer-trains-coarser principles. By using this multiple-scale model, we present a detailed analysis of the mechanical properties and associated deformation mechanisms of intermediate filament network. We reveal the mechanism of a transition from alpha-helices to beta-sheets with subsequent intermolecular sliding under mechanical force, which has been inferred previously from experimental results. This nanoscale mechanism results in a characteristic nonlinear force-extension curve, which leads to a delocalization of mechanical energy and prevents catastrophic fracture. This explains how intermediate filament can withstand extreme mechanical deformation of > 1 00% strain despite the presence of structural defects. We combine computational and experimental techniques to investigate the molecular mechanism of Hutchinson-Gilford progeria syndrome, a premature aging disease. We find that the mutated lamin tail .domain is more compact and stable than the normal one. This altered structure and stability may enhance the association of intermediate filaments with the nuclear membrane, providing a molecular mechanism of the disease. We study the nuclear membrane association with intermediate filaments by focusing on the effect of calcium on the maturation process of lamin A. Our result shows that calcium plays a regulatory role in the post-translational processing of lam in A by tuning its molecular conformation and mechanics. Based on these findings we demonstrate that multiple-scale computational modeling provides a useful tool in understanding the biomechanical property and disease mechanism of intermediate filaments. We provide a perspective on research opportunities to improve the foundation for engineering the mechanical and biochemical functions of biomaterials. (Copies available exclusively from MIT Libraries, libraries.mit.edu/docs - docs@mit.edu)

Entropy generation and momentum transfer in the superconductor-normal and normal-superconductor phase transformations and the consistency of the conventional theory of superconductivity

NASA Astrophysics Data System (ADS)

Hirsch, J. E.

2018-05-01

Since the discovery of the Meissner effect, the superconductor to normal (S-N) phase transition in the presence of a magnetic field is understood to be a first-order phase transformation that is reversible under ideal conditions and obeys the laws of thermodynamics. The reverse (N-S) transition is the Meissner effect. This implies in particular that the kinetic energy of the supercurrent is not dissipated as Joule heat in the process where the superconductor becomes normal and the supercurrent stops. In this paper, we analyze the entropy generation and the momentum transfer between the supercurrent and the body in the S-N transition and the N-S transition as described by the conventional theory of superconductivity. We find that it is not possible to explain the transition in a way that is consistent with the laws of thermodynamics unless the momentum transfer between the supercurrent and the body occurs with zero entropy generation, for which the conventional theory of superconductivity provides no mechanism. Instead, we point out that the alternative theory of hole superconductivity does not encounter such difficulties.

Impaired neurogenesis and neurite outgrowth in an HIV-gp120 transgenic model is reversed by exercise via BDNF production and Cdk5 regulation

PubMed Central

Lee, Myoung-Hwa; Amin, Niranjana D.; Venkatesan, Arun; Wang, Tongguang; Tyagi, Richa; Pant, Harish C.; Nath, Avindra

2013-01-01

Human immunodeficiency virus (HIV) infection associated neurocognitive disorders (HAND) is accompanied with brain atrophy. In these patients, impairment of adult neurogenesis and neurite outgrowth in the hippocampus may contribute to the cognitive dysfunction. Although running exercises can enhance neurogenesis and normalize neurite outgrowth, the underlying molecular mechanisms are not well understood. The HIV envelope protein, gp120, has been shown to impair neurogenesis. Using a gp120 transgenic mouse model, we demonstrate that exercise stimulated neural progenitor cell (NPC) proliferation in the hippocampal dentate gyrus and increased the survival rate and generation of newborn cells. However sustained exercise activity was necessary since the effects were reversed by detraining. Exercise also normalized dendritic outgrowth of neurons. Furthermore, it also increased the expression of hippocampal brainderived neurotrophic factor (BDNF) and normalized hyperactivation of cyclin-dependent kinase 5 (Cdk5). Hyper-activated Cdk5 or gp120 treatment led to aberrant neurite outgrowth and BDNF treatment normalized the neurite outgrowth in NPC cultures. These results suggest that sustained exercise has trophic activity on the neuronal lineage which is mediated by Cdk5 modulation of the BDNF pathway. PMID:23982957

Effects of acetylcysteine and probucol on contrast medium-induced depression of intrinsic renal glutathione peroxidase activity in diabetic rats.

PubMed

Yen, Hsueh-Wei; Lee, Hsiang-Chun; Lai, Wen-Te; Sheu, Sheng-Hsiung

2007-04-01

Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity. Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ). We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD. These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity.